http://EyeSee-EyeTalk.blogspot.com

12.4 Contact lens 2100

2012-01-01T08:32:00.004-05:00

[Source: NPR/here]

"Imagine being able to access the Internet through the contact lenses on your eyeballs. Blink, and you'd be online. Meet someone, and you'd have the ability to immediately search their identity. And if your friend happens to be speaking a different language, an instantaneous translation could appear directly in front of you.

"That might sound farfetched, but it's something that might very well exist in 30 years or less, says theoretical physicist Michio Kaku.

"'The first people to buy these contact lenses will be college students studying for final exams,' he tells Fresh Air's Terry Gross. "They'll see the exam answers right in their contact lenses. ... In a cocktail party, you will know exactly who to suck up to, because you'll have a complete read out of who they are. President Barack Obama will buy these contact lenses, so he'll never need a teleprompter again. ... These already exist in some form [in the military]. You place [a lens] on your helmet, you flip it down, and immediately you see the Internet of the battlefield ... all of it, right on your eyeball."

Indeed, this may revolutionize contact lens industry and beyond. Those interested should take note.

Happy New Year to All!!

12.3 A cure for cataracts?

2011-11-03T14:30:00.007-04:00

[Above: The Second Cataract of the Nile, artist's rendition, 1841. Nothing to do with the cataracts in the eye, included here just for fun.]

According to a report in Time Healthland (11/3/2011)"Clearing Away Old Cells Delays Aging in Mice":
Source: http://healthland.time.com/2011/11/03/clearing-away-old-cells-delays-aging-in-mice/?hpt=hp_t2

"...Normally, these old cells are cleared by the body, but the process becomes less efficient with age. So researchers at the Mayo Clinic used a drug to target only senescent cells and force them to self-destruct, in a group of mice that were genetically engineered to age rapidly.

"In mice that were treated throughout their lifetimes, researchers said they saw a remarkable delay in the development of cataracts, muscle wasting and the type of fat loss that, in humans, causes skin wrinkling. Another group of mice was treated in older age, after cataracts had already set in. The drug didn't reverse the age-related changes that had already occurred, but it prevented further decline."

Comment: This study seems to suggest that cataractognesis is part of the aging process and that a certain drug is capable of targeting the underlying inflammatory factors [as indicated in the original article]. This is odd, the nucleus of the crystalline lens contains the oldest cells in the body and aggregation of the crystallins causes nuclear cataracts - not some inflammatory process. Even if so, how would the drug enter the lens, through the cortex and force the tightly packed, senescent nuclear lens fibers to self-destruct only to leave a huge central vacuole behind?

12.2 Cyclops shark

2011-10-18T11:29:00.005-04:00

A fetal shark cut from the belly of a pregnant shark caught in the Gulf of California. The shark, which would likely not have survived outside the womb, had only one eye.

This is the real deal, a one-eyed [cyclops] albino shark:

"The fisherman who discovered the Cyclops shark is reportedly hanging on to the preserved remains, news outlets reported. But scientists have recently examined and X-rayed the fish, authenticating the catch. According to Seth Romans, a spokesman for Pisces Fleet, Galvan Magana and his colleagues will publish a scientific paper about the find within the next several weeks." - Source: http://www.foxnews.com/scitech/2011/10/18/albino-cyclops-shark-is-real-experts-say/?test=faces

12.1 Number 1 health risk

2011-09-09T13:10:00.003-04:00

On a scale of one (no worries) to five (real consequences), which risks are a gamble?

Wearing Disposable Contact Lenses Past Expiration
Risk Rating: 5

Whether your lenses are supposed to last a day or a month, it's not a good idea to save a few bucks by stretching out their life span, says Thomas Steinemann, an associate professor of ophthalmology at Case Western Reserve Medical School, in Cleveland: "Even when you clean and disinfect them, lenses and lens cases become coated with germs and protein over time."

At the very least, wearing contacts past their prime can irritate your eyes, forcing you to wear clunky glasses while your eyes recover. At worst, you can develop an infectious corneal ulcer that leaves scar tissue, reducing your vision or―in extremely rare cases―causing permanent blindness. Replacing lenses with new ones as directed will ensure that you see clearly and avoid issues with your eyes.

[Source: http://www.foxnews.com/health/2011/09/06/which-health-shortcuts-are-ok/]

11.12 FAQ12 - Final Destination 5

2011-08-14T10:29:00.003-04:00

[Source of picture and text below: Boston Herald 8/14/2011]

“Final Destination 5” is the first movie to feature death by the common LASIK eye surgery procedure.

Question: For real?

Answer: “I think people are smart enough to know this is fiction,” said Dr. Samir Melki of Boston Laser in Brookline. “The machine cannot really turn itself on like in the movie. . . . The laser turns off if (the patient) can’t keep their eye on the tracker.”

11.11 FAQ11 - A new imager BAOSO

2011-06-10T06:45:00.007-04:00

[Source: http://www.foxnews.com/scitech/2011/06/09/historic-first-image-reveals-millions-light-sensors-in-human-eye/]

These images are from "Reflective afocal broadband adaptive optics scanning ophthalmoscope" by Alfredo Dubra and Yusufu Sulai, that has just appeared in
Biomedical Optics Express, Vol. 2, Issue 6, pp. 1757-1768 (2011) doi:10.1364/BOE.2.001757 [here].

Image on the left shows the cones in the fovea. And that on the right shows a more peripheral retinal location: the large bright dots with a dark ring around them are cones, and the surrounding smaller spots are rods.

Question: A historical first - as advertised?

Answer: Fundus photography has come a long way. This one, ultra-micro-imaging of the human retina, is absolutely astounding, indeed a historic first. It'll be interesting to see images of diseased retina. No doubt this is being actively pursued. Our congratulations to Drs Dubra and Sulai.

11.10 FAQ10 - Avastin vs Lucentis

2011-04-28T18:35:00.004-04:00

News from Boston Globe today:

A much cheaper drug has proved just as good as a $2,000 monthly shot at treating a common eye disorder that can lead to blindness, a long-awaited study has found. It also shows that patients can be treated less often, sparing them a lot of pain and expense.

The results are expected to lead many doctors and patients to turn away from the pricier Lucentis and instead use $50 shots of Avastin for an age-related condition called wet macular degeneration.

Question: What kind of shots?

Answer: Avastin has long been used to treat macular degeneration. The new study finally verifies the efficacy of this generic version of Lucentis. And if you must know, this drug is delivered through injection into the vitreous. Pain? Just a little needle prick, really.

11.9 FAQ9 - The other right eye

2011-04-20T17:00:00.003-04:00

News today on KTAU.com:

VANCOUVER, Wash. – When four-year-old Jesse Matlock went in for surgery last Wednesday, doctors were supposed to operate on his right eye to stop it from wandering. But his parents said that’s not what happened.

They said his eye surgeon first mistakenly operated on his left eye, realized her mistake and then repeated the same operation on his right eye – the correct eye.

“I have not noticed any improvement in the right eye and as far as I can tell the left is now wandering,” said Tasha Gaul, Jesse’s mother. Now Gaul is concerned about what this unnecessary surgery will do to his vision in the future.

The surgeon was Dr. Shawn Goodman of Lake Oswego. When KATU called her office on Monday a staff member said she was not in. She has not yet returned messages.

“My husband and I were in awe, we were like ‘can you repeat that again?” Gaul said. “She said, ‘frankly, I lost sense of direction and didn’t realize I had operated on the wrong eye until I was done operating on the eye.’”

The surgery was done at Legacy Emanuel Medical Center in Portland. The hospital’s Chief Administrative Officer, said they have procedures to help prevent mistakes like this.

“We have a critical incident team that will be responding to it, that will be interviewing all of our staff in the operating room as well as private practice physicians in the operating room that were involved,” said hospital CAO Dr. Lori Morgan. “Our hope is to never have it happen again in any of our hospitals.”

Dr. Goodman is not a Legacy employee but was using their operating facilities.

“Something went wrong with their checklist,” said Dale Matlock, Jesse’s father. “They came in and circled his eye, for which eye they were going to operate on. Then (Dr. Goodman) proceeded with the left, the wrong eye.”

Jesse’s parents have hired a lawyer and are considering a malpractice suit.

Question: Will the lawsuit be successful?

Answer: Probably not. This appears a case of strabismus surgery - to re-position the extraocular muscles of BOTH eyes so the two eyes can stay straight. Often multiple surgeries are needed. There is no damage to the eyeballs nor to patient's pre-op vision.

11.8 FAQ8 - More on 3D

2011-03-19T18:48:00.006-04:00

Because of a lack of substantial data, the pros and cons of children playing with the Nintendo 3DS have evolved into a controversy of sorts.

According to USA Today - 3/18/2011:

U.S. eye specialists are welcoming the Nintendo 3DS game device, dismissing the manufacturer's warnings that its 3-D screen shouldn't be used by children 6 or younger because it may harm their immature vision.

On the contrary, the optometrists say, it's a good idea to get your kids to try the 3-D screen, especially if they're younger than 6. It won't do any harm, they say, and it could help catch vision disorders that have to be caught early to be fixed.

"The 3DS could be a godsend for identifying kids under 6 who need vision therapy," said Michael Duenas, associate director for health sciences and policy for the American Optometric Association.

On the other hand,

David Hunter, a pediatric ophthalmologist affiliated with the Children's Hospital in Boston and the American Academy of Ophthalmology, said the idea that off-the-shelf 3-D games or movies could help screen for vision problems such as amblyopia is "a little perplexing."

Kids with amblyopia don't have much depth perception in real life, he said, so if they don't see depth in a 3-D screen, they might not say anything because that wouldn't be much different from what they see around them.

It's not impossible that it could help, but it's "all sort of exploration and speculation," said Hunter, who has started a company that's developing a device for childhood screening of vision disorders.

Question: Who's right?

Answer: Taking self-interest out of the arguments, it is still neither. More research on binocularity is still the key.

11.7 FAQ7 - Esotropia and diet

2011-01-31T12:48:00.013-05:00

So now we have an internet sensation: Heidi the resident "cross-eyed" opossum at Leipzig Zoo, complete with her own Facebook and YouTube appearances.

A spokeswoman at the Zoo has put forth the theory that Heidi's esotropia "could have come from a poor diet when she was young, causing large fat deposits to form behind her eyes". The white-haired marsupial has since been put on a diet and lost 400g of body weight.

Question: Are we witnessing a new type of strabismus?

Answer: Hardly. The photo above actually shows (1) corneal reflections are in the same 1 o'clock position, i.e., this is a case of pseudo-esotropia, commonly seen in babies in Asia; and (2) swollen conjunctiva in both eyes suggesting accumulation of fluids, or chemosis, which has further enhanced the esotropia illusion. Neither has anything to do with too much fat in the orbit. No crossed eyes here; instead, Heidi is probably suffering from some sort of allergies.

11.6 FAQ6 - 3D and children's eyes

2011-01-01T10:47:00.009-05:00

On its website, Nintendo announces:

"6歳以下の小さなお子様の視覚は発達段階にあると言われており、専門家は、『ニンテンドー3DS』だけでなく、3D映画や3Dテレビなども含め、左右の目に異なる映像を届ける3D映像は、小さなお子様の目の成長に影響を与える可能性があるという見解をもっています。"

Translation: No Nintendo 3DS for kids under 6.

Question: Now what?

Answer: Let's be clear on one point, we live in a 3D world. Kids and babies included. We are programmed to perceive 3D accurately during the first year of our lives. And stereo-acuity actually matures between 3-5 years of age.

The two eyes each receives the same image from a slightly different angle - the same principle used for 3D gadgets. Shouldn't 3D viewing then enhance the performance of the visual system? The common complaint of asthenopia [eyestrain and headaches] from viewing 3D is an entirely different matter. Instead of real research on convergence and fusion, Nintendo mimics 3D TV manufactures by issuing simplistic warnings.

Lest we forget: CYA is not a real solution, real solutions require real R&D.

11.5 FAQ5 - The Third I

2010-12-03T10:54:00.006-05:00

CNN reports on 12/2/2010:

* A New York University Professor [Wafaa Bilal] installed a thumb-sized camera in back of his head for art exhibit
* Iraqi born photography professor had the procedure done at a piercing studio last month
* The camera will take a single snap-shot each minute of everyday activities for one year

This is an implanted mini-camera, no less. Incredibly, the procedure was done at a "piercing studio", an accident, in many forms, waiting to happen. It also begs the question: "why not a head-mounted camera":

Just point it the other way?

Tentative answer: An artist's mind works differently from yours and mine?

11.4 FAQ4 - Gucci 3D glasses

2010-10-28T14:57:00.005-04:00

It finally happened. Time Magazine reports today:

3-D technology just got a whole lot sexier.

"Gucci has stamped out its own corner in the tech market with a new line of luxury 3-D glasses. The 80s-style aviator plastic specs will retail for $225, and feature that coveted (for some) Gucci logo. Technically speaking, the glasses feature 6-base curved lenses that operate with circular polarized technology, allowing images to trick your eyes into seeing a 3-dimensional picture, and a mirrored coating to help with color contrast. (Most complaints with modern 3-D film conversion focus on how dark or dingy the picture appears.)"

Questions: (1) 6-base curved lenses? And (2) Circular polarized technology allowing images to trick your eyes into seeing a 3-dimensional picture?

Answers: (1) Optician lingo referring to the curvature of a lens with no refractive power (i.e., a plano lens, used in sunglasses). A 0=totally flat, an 8=very curved, and a 6=cool-looking curved lens. And (2) A better way than linear polarization of allowing each eye to see a different image, or together, a stereo pair. The stereo view is retained even if you tilt your head a little, hence more comfortable when watching 3D movies. However, it is the brain (in the intraparietal sulcus area), not the eyes, that is tricked into seeing 3D.

We have no comments on the US$225 a pair price tag.

11.3 FAQ3 - Sunglasses

2010-10-13T06:37:00.005-04:00

CNN reports:

[Updated at 5:55 a.m. ET, 6:55 a.m. Chile time] Dawn is breaking in Copiapo, Chile and the miners will be facing a change in light as they emerge from the rescue chamber.
All of the miners now will likely be wearing sunglasses so they can adjust after being underground in darkness for more than two months.
So far, eight miners have been rescued, in a little under eight hours.

Our congratulations to the 33 miners for having survived 69 days underground and to the rescuers for accomplishing an almost impossible mission.

Q: Why the sunglasses?

A: Sunglasses are intended for protection from solar UV, both UV-A and UV-B. However, in the present case, they seem to be for acclimation to light from prolonged dark-adaptation. If so, then tinted goggles make more sense than sunglasses; the latter still allow lights from the sides. On the other hand, light-adaptation per se does not require much effort, the photo-receptors know what they are doing. Perhaps the purpose is simply for the miners to avoid photophobic irritation from sudden pupil constriction - again, a transient event - although it beats squinting into the sunlight/limelight.

In any case, it is apparent that a lot of thoughts have been put into preserving the well-being of the miners including their eyes. This deserves our appreciation and applause.

11.2 FAQ2 - gene of the week

2010-09-13T11:11:00.004-04:00

The "gene of the week" phenomenon finally catches up with myopia. In headlines around the world today, news under the heading, e.g., "Genes for Myopia discovered" spreads like wildfire.

According to Insciences.org:

"Researchers from the Department of Twin Research at King’s College London have identified genes associated with two common eye problems, myopia and glaucoma. The findings have been published in this week’s edition of Nature Genetics [see ‘A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25’. Pirro Hysi et al. Nature Genetics, 12 September 2010, doi:10.1038/ng.664]."

"In their study of over 4,000 twins, the researchers identified a myopia susceptibility gene called RASGRF1, which has been replicated in over 13,000 other people from the UK, the Netherlands and Australia."

According to Daily Mail, "Within just ten years, a drug that prevents short-sightedness or stops it in its tracks could be in widespread use."

However, "A second study, by Dutch researchers, identified a second short-sightedness gene. Ultimately, there could be dozens behind the condition."

There is more: "We hope that by understanding the mechanisms we can stop children from becoming shortsighted and stop short-sighted children from becoming more short-sighted."

Question: "Even though the mechanisms are still unknown, and yet, in 10 years, a drug can be developed to stop myopia?"

Answer: "Don't hold your breath."

11.1 FAQ1 - cataracts

2010-08-28T16:29:00.015-04:00

[Three major types of cataracts, cortical, nuclear, and subcapsular.
Occasionally, numerous vacuoles can be seen in the cortex that eventually evolve into opacities. In the image above, light comes in from the right. ]

Whenever a doctor informs an elderly patient of the presence of cataracts, the patient will inevitably asks "what do I do now?". His/her real question is "what can I do to reverse or remove the cataracts without surgery". And the honest answer is "nothing you can do". Since age-related cataracts are caused by cumulative events leading up to irreversible protein aggregation and disruption of cellular integrity, there is nothing in the form of eyedrops that can repair these damages.

What about preventing cataracts from further progression? Perhaps, if the current thinking of the causative factor of age-related cataracts, oxidative stress, holds up. Oxidative stress has been blamed for many human illnesses and is becoming a favorable catch phrase for the for-profit anti-aging industry. There is nothing wrong as far as oxidation and cataractogenesis. In fact, hydrogen peroxide in relatively high concentrations has been discovered in the aqueous humor of the human eye. And solar radiation of the lens, particularly that from the ultraviolet, starts soon after birth. Logically, anti-oxidants should then retard the progression of cataracts. The problem is: "which ones that work". This is where the unproven therapeutics with fraudulent claims come in. Any proof of efficacy must be based on large-scale clinical trials and yet, none have been done thus far. On the other hand, dietary intake balanced with natural food produce rich in anti-oxidants is not a bad idea. Stay out of the sun, if you remember to take your vitamin D or wear UVA and UVB-blocking sunglasses.

Surgery? Sure, when the decreasing visual acuity meets the screen guidelines. Cataract extraction is a low-risk highly effective procedure. However, the outcome will depend on (1) the skill and the experience of the surgeon; (2) the status of the macula/retina; (3) structural integrity of the eye globe; (4) underlying systemic diseases if any; (5) management of interim and final binocular vision; and (6) possible complications and treatments. A pre-op consultation with your trusted ophthalmic surgeon is of course indispensable.

10.16 Berklee adds a Braille beat

2010-08-09T09:35:00.002-04:00

Boston Globe Aug 9, 2010:

Wayne Pearcy, a Berklee College of Music student, sits hunched before a console buried under a mountain of keyboards, wires, computer monitors, and microphones. A thin 23-year-old Louisianan with strawberry-blond hair, Pearcy is enthusiastically explaining his plan to write the next number one hit single.

[Complete article here.]

10.15 Who needs eyes anyway?

2010-07-19T18:30:00.005-04:00

In the deep caves of Madagascar, absolute darkness led to the development of eye-less creatures, hence this:

Blind Shrimp Flee from Blind Cave Fish

10.14 EYE in Chicago

2010-06-17T08:52:00.005-04:00

EYE is a three-story tall eyeball sculpture that artist Tony Tasset will install in Chicago's Pritzker Park next month. You can see it, and it can see you, until the end of October. Some may find it creepy - Tasset acknowledged, calling it "surrealist-noir."

And the reason why it is a blue eye? Well, it is modeled after the artist's own eye. Is it anatomically correct? Most likely not. Would have been an educational opportunity if there is a door opening into a world of the intricate inner structure of the eye. One such model used to locate on the first floor of Singapore National Eye Centre. It may still be there. Check it out.

10.13 Bob Cousy on vision

2010-06-02T08:33:00.006-04:00

Bob Cousy in his heyday, now 81

There is a fascinating comment by Bob Cousy that appears in Boston Globe [6/2/2010]:

“Vision, I think, for a point guard, is the most important thing. I was constantly being told I had eyes behind my head. It would seem that way to people who didn’t know that much about basketball who couldn’t believe that I could see things I could see. It’s exceptional peripheral vision.

“People who have tunnel vision don’t usually become point guards. That happened with [Chauncey] Billups here before they traded him. I think it was the only thing [Rick] Pitino ever asked me. I didn’t think Billups would make a good point guard because he would penetrate and then run into people. Billups proved me and Pitino both wrong, but I still don’t see him as a great creator in the vein of Rondo.’’

Rondo is of course the 6-1, 175-pound Celtic point guard Rajon Rondo. And here we go again: Game 1 of NBA Championship - June 3, 2010.

Beat LA!!

10.12 Watch it at your own risk

2010-04-24T16:08:00.006-04:00

3D TV has finally arrived. In an apparent attempt to ward off potential lawsuits, Samsung has publicized the dangers of 3D TV watching:

Photosensitive Seizure Warning and Other

CNN has an analysis: "Can 3-D movies, television make you sick?". In part, it says

[Samsung] cautions that certain flashing images or lights could induce epileptic seizure or stroke, and that "motion sickness, perceptual aftereffects, disorientation, eye strain and decreased postural stability" may result.

In addition: As for long-term effects of watching 3-D television instead of regular television, no one knows for sure because it's too new. ...is concerned about serious consequences for children who watch 3-D television for long periods of time -- 'a continuous abnormal stimulus may possibly have long-term effects that are yet to be studied'...

So 3D TV watching can be hazardous to your health. Does it really? More research, please.

10.11 Avatar

2010-02-17T20:17:00.007-05:00

According to China Daily [see here], a middle-aged female developed acute angle-closure glaucoma after attending a 3D showing of the movie Avatar. Presumably, pupil dilation induced by the dark environment for a lengthy period of time precipitated this attack. Curiously, however, the patient must have been staring at the bright movie screen; this, by itself, should have caused pupil constriction unless totally negated by the Polaroid glasses worn for the 3D effect. Unfortunately, no experimental data are available for a reasonable explanation.

Ultimately, the deciding factor is the structure of the angle in the eyes of each individual. A patient with extremely narrow angle will have a higher risk that often can be confirmed with the darkroom test. Intermittent narrow angle glaucoma cases can be examined with the darkroom prone-position test in which the patient stays for 45 min without going to sleep. And the IOP measured immediately after. An increase of 8 mm Hg is considered positive.

Not only the movies, 3D TVs are rapidly moving into the consumer products arena. The common complaint of asthenopia owing to the contraction of medial recti can be resolved with the incorporation of base-out prisms in the 3D glasses. Strangely, no manufacturers have bothered with this implementation thus far even though the cost is minimal.

A recent report of stroke/death of a hypertensive man in Taiwan [see here] after watching Avatar is most likely coincidental. It could have been from seeing any exciting movies, not necessarily the 3D effect per se; although medical issues do await further investigation.

All new technologies will have unintended side-effects, real or imagined, e.g., the much disputed correlation between cell phone use and brain tumor (there is none, BTW). The introduction of the pseudo-3D visual world to the populace is no exception. This may spur some much-needed research. Very simply put: who wouldn't want to enjoy 3D in both comfort and safety.

10.10 Alzheimer's eye test

2010-01-17T10:53:00.006-05:00

[Source: http://lancastria.net/blog/?p=1794]

The headline of The Daily Mirror "High street eye test for Alzheimer's within five years" (Jan 14, 2010) is so tantalizing that prompts a further reading:

"A test for Alzheimer's could be carried out by shop opticians within five years. Scientists have found a way to detect the disease before any symptoms emerge during eye exams.

"By putting harmless fluorescent dye on the retina, they can spot dying cells - an early indication of Alzheimer's.

"The technique could end the need for costly MRI scans.

"Prof Francesca Coredeiro, of University College London, said: "Few people realise the retina is a direct, albeit thin, extension of the brain." and "It's entirely possible a visit to a high-street optician to check your eyesight in five years will also be a check on the state of your brain."

Wow, that is certainly progress; although a careful reading of the original research paper [here] raises some issues:

1. The high-street optician must own and be proficient in operating a confocal scanning laser ophthalmoscope to take the pictures of the retina through dilated pupils plus knowledge in interpreting the images;
2. To put the "harmless fluorescent dye on the retina" requires an intravenous injection of the dye, much like fluorescein angiography; the widely reported eye drops approach simply does not work; and
3. What evidence is there to support death and necrosis of the retinal photoreceptors in mice predates brain cell deaths, and even if true, does that apply to Alzheimer's in humans.

In five years? Maybe not.

Happy New Year !!

2009-12-31T10:36:00.002-05:00

A Happy New Year to All !!

(When you pop-open the champagne bottle, make sure the cork does not hit anyone in the eye .)

10.9 Perfect parking

2009-12-14T13:37:00.006-05:00

So you have trouble reverse parallel park your car? Relax, Prof Simon Blackburn of University of London's Royal Holloway College comes to rescue (The Telegraph 12/11/2009). He has devised a formula so you'll know when to turn the steering wheel at the precise moments:

Gee, and we have all thought that parallel parking is all about eye-hand-brain coordination.

10.8 Peripheral hyperopic defocus

2009-11-13T08:51:00.007-05:00

Recently, some diligent researchers have come up with a novel explanation of myopia progression in the human, i.e., the "peripheral hyperopic defocus".

In plain English, it means when you wear glasses to correct nearsightedness or more accurately the central vision, the side vision is actually still fuzzy with the clear focal points behind the eye (or being hyperopic, i.e., farsighted, by definition). This is illustrated in the picture here, in which the white arc behind the eye is the hyperopic focus. It is this blurriness at the retinal level that seems to cause the eyeball to grow or "elongate" in the anterior-posterior sense. Not only in the myopic eyes, potential myopic eyes also have the more prolate eyeball shape. So it would appear that the shape of the eyeball is predictive of myopia formation and progression.

With the new information,
(1) the instrument makers can develop new refractive devices;
(2) lens makers can design new spectacle and contact lenses;
(3) the doctors will have new myopia managing regimens to contemplate;
(4) the biochemists will propose and test new projects on the development of posterior sclera/choroid during myopization; and
(5) the drug makers can look into more targeted posterior pole growth inhibitors.

In other words, a whole new enterprise unveils right before our eyes. Naturally it remains to be seen if this defocus theory ultimately proves to be true.

10.7 Gordon Brown's eyes

2009-10-13T12:18:00.000-04:00

Have you ever noticed that Mr Brown's left eye is slightly recessed and is in a down and out position?

He has lost his vision in the left eye from retinal detachment - after being kicked in the head while playing rugby at age 16. Several attempts at repairing this eye had failed. When the right eye started to show the same symptoms and signs of RD two years later, the re-attachment was quite successful.

A routine annual eye exam on Oct 10 reveals that Mr Brown's right eye has two small retinal tears. For now, ophthalmologists at Moorfield Hospital where Mr Brown was seen have decided to continue observation rather than perform an operation. Presumably, 3-7% of Brits walk around unaware of retinal tears in their eyes. Mr Brown insists that his eye sight has not deteriorated; although he does read texts with large prints.

Quite a few take-home lessons here:

(1) contrary to common belief, low vision in fact does not affect a person's capabilities;
(2) the need for regular eye exams is clear - once every two years as a matter of principle, once every year when necessary;
(3) not all retinal tears must be patched;
(4) RD from head trauma is not uncommon - with long latency as well; and most important,
(5) retinal tears do not affect central vision - patients must instead pay attention to appearance of photopsia and floaters.

10.6 Reading glasses and bank robbery

2009-10-07T18:48:00.005-04:00

Guess what, now reading glasses are an accessory for committing a crime:

News from BROCKTON, MA, USA - Police are looking for a man who robbed a bank Monday (Oct 5, 2009) morning in Brockton.

The suspect, who was wearing reading glasses and a Red Sox hat, passed a note to the Community Bank teller demanding money, police said. The man fled from the Main Street bank in an unknown direction after taking money.

Police say the suspect was wearing a beige pullover, blue jeans and work boots. Anyone with information about this person is asked to call Brockton police at 1-(508)-941-0234.

Let's see, a male Caucasian with a pair of half-eyes suggesting he is 42 years-old with 20/20 distant vision. The glasses are apparently OTC, purchased for US$15 from a local drug store, probably one of the CVS Pharmacies. Most likely, these glasses are made with +1.25 to +1.50D lenses to be used for reading comfortably at 16 inches, if we know the height of the counter top at the bank, this robber's body height can be quickly estimated. On the other hand, the Boston Red Sox cap is not helpful, almost everybody has one.

Forensic optics can be fun, huh?

10.5 LCA repair

2009-08-13T08:36:00.004-04:00

After 2 years, the preliminary results of LCA (Leber congenital amaurosis) gene therapy are in [Aug 12, 2009].

This study is still ongoing at U of FL and UPenn (and other universities). The participants are a woman and two men between the ages of 21 and 24. After 12 months, the safety is maintained. More important is this:

"The tiny portions of the patients’ retinas that received gene therapy [RPE65] experienced restored function up to 1,000-fold during the day and 63,000-fold at night."

In other words, the patients have developed a preferential retinal locus at the injected (treated) area. The visual acuity will depend on the photoreceptor density, among other issues. And the field size will necessarily be limited to the locus. Still, it is a giant leap forward.

Let's hope this study continues to be successful.

10.4 Blue-eyed rodent

2009-07-30T01:34:00.006-04:00

Researchers at Univ of Rochester have discovered that Brilliant Blue G, a food dye, when injected IV can prevent secondary neuronal damages caused by an excess release of ATP into the spinal injury site.

The injection works only if it is done within 15 min after the injury and the skin turns blue for a while as a result.

The more interesting to us is the eyes now also appear blue (right). The pink hue of the paws, ears, nose, and the eyes (top left) is typical of the lack of pigmentation in this type of rats allowing the vascularity to show through.

Presumably then, a fair-skinned person, after consuming a large quantity of blue M&Ms, may develop dark blue eyes even if only briefly. The blue skin? We refer you to Star Trek (2009), Uhura's roomate (and Kirk's date) for more details.

10.3 Target: one million cases of cataracts

2009-06-24T16:58:00.007-04:00

This is a news report on June 24, 2009:

来源：荆楚网　(楚天都市报陈媛田静欣高翔向清)

记者昨从湖北省卫生厅获悉，我省于近日启动“贫困白内障患者复明工程”，近万名患者可从中受益。　　
今年，我国启动“百万贫困白内障患者复明工程”，计划利用3年时间，为100万名贫困白内障患者实施复明手术，湖北省今年的任务是9475例，每位患者将享受800元的费用减免。全省三级医院和大部分具备条件的二级医院都将成为项目医院。
昨日，中南医院开始接受手术报名，凡我省农业户口以及城镇下岗职工、低保、残疾人士等都可持相关证明到该院登记手术。
该院眼科主任蔡小军介绍，我国约有盲人1240多万，因白内障致盲人数约为699万，这其中又有15%的患者属于贫困阶层，无钱做手术。

Partial translation: "Hubei Province will soon institute a program, Cataract Vision Restoration for the Poor, and about 1 million patients will benefit. This is a 3-year program and for the current year, 9,475 patients will enjoy a $800 (about USD 100) discount for the surgery... It is estimated that there are 12.4 million blind in China. Of them, 6.99 million are cataract cases and 15% cannot afford to pay for the surgery [hence this program]."

Certainly a step in the right direction.

10.2 Blurred vision

2009-06-23T07:28:00.003-04:00

Lies all well disguised, masses all hypnotized
Terror's all you hear, war won't make it disappear
Leader's teach us, everything we shouldn't be
everyday people, this is no Democracy!

(a song in support of the Iranian people, try http://blurredvisionmusic.com or here)

10.1 Truth or Consequences

2009-04-04T21:57:00.005-04:00

Drug companies in Taiwan probably have sold the most atropine eyedrops than anywhere in the universe. You might wonder what it is used for. It turns out that atropine drops and other cycloplegics are used to control the progression of school myopia.

There has been a long history of cycloplegics used for this purpose; however, it has never gained any popularity elsewhere. In fact, atropine in particular is prescribed, if at all, only for the treatment of amblyopia. As it does appear as efficacious as eye patching; although the treatment is short-term. In contrast, atropine treatment for myopia goes on for years.

Since so many myopic children in Taiwan are treated with cycloplegics and who do not wear optical corrections in school, teachers are running out of front-row seats for these children and start to question this practice.

Do the cycloplegics work? Yes, if one considers less myopia progression a success and a goal by itself. What about the ultimate purpose? Unclear. Because cycloplegics do not reverse myopia, which merely slow down the progression. So, by late teens or early 20s when the myopization process naturally stops, patients are still left with moderate to high myopia. The atropine treatment appears to have based on the assumptions that (1) all myopia cases can become degenerative myopes and that (2) high myopia equals ocular diseases developed later in life such as glaucoma and various retinal integrity issues. And by lowering the degree of myopia, these diseases can be avoided. Unfortunately, so far there is no hard evidence to support this proposal. Perhaps a certain segment of the myopic population can indeed benefit from cycloplegia; again, there is no evidence.

And the downside of long-term atropine treatment? Let's see, cycloplegia causes loss of accommodation and prolonged pupil dilation, allows large amounts of UV into the eye, and potentiates chronic narrow-angle glaucoma. Worse, it is not known how long the treatment can continue without irreversible paralysis of ciliary and iris muscles.

There is something amiss here.

9.15 Looking upward and forward

2009-02-27T06:50:00.005-05:00

This is a fish named the barreleye (http://www.livescience.com/animals/090223-fish-head.html) from Indonesia. The two dots above the mouth are not the eyes, they actually are the nostrils. Where are the eyes? They are inside the see-through head looking upward. The two green caps are in fact lenses of the eyes. The tubular eyes can point forward as well when the barreleye has to find its way around. Why looking up? To see the silhouette/luminescence of an overhead jellyfish or a small fish, so that it can quickly attack.

Looking upward and forward - sounds like a very short lecture on life.

9.14 Galileo's eyes

2009-01-26T12:27:00.010-05:00

(Galileo Galilei [1564-1642], circa 1630)

Well, it is only inevitable in this age of TV CSI shows: Scientists from both UK and Italy are now seeking the Vatican's approval to exhume Galileo's body, so that they can do some DNA analysis to figure out what had ailed Galileo's eyes.

This news has been widely reported, see for example, here and here. The scientists' interest is to explain why Galileo described Saturn as having "lateral ears" rather than rings around the planet. And the theory is that poor eyesight was behind the error.

Galileo's drawings of Saturn are shown on the left:

The one on top was sketched in 1610, and the bottom, 1616.

These "arms" were clarified by Dutch astronomer, Christiaan Huygens, in 1659, as a ring system. He was able to do so because of improved telescope optics. [Note: Huygens also discovered Saturn's moon, Titan, and for this reason, the probe exploring Titan is named after him. And a few years later, Jean-Dominique Cassini discovered 4 other major moons of Saturn: Iapetus, Rhea, Tethys, and Dione.]

So what was wrong with Galileo's eyes and vision? It was actually quite well-documented. According to this site, for example:

"Galileo’s sight began to deteriorate in the middle of 1636 when he was 68 years old, and by the end of June 1637 he had lost the use of his right eye while his left eye was affected by a constant discharge. He described seeing a 'luminous halo' around candle flames. To date there has been little speculation by modern optometrists or physicians about the possible causes of Galileo’s blindness. In July 1636 he wrote to his friend, an Italian lawyer living in France, Elia Diodati, 'I have been in bed for five weeks oppressed with weakness and other infirmities. Added to the (proh dolor!) the sight of my right eye - that eye whose labours (I have no hesitation in saying) have had such glorious results, is lost forever. That of the left, which was and is imperfect, is rendered null by a continual running’. He became totally blind early in December 1637, a few months after using the telescope to discover that the moon wobbles on its axis ('lunar libration') which was quite a remarkable observation to make with only one useful eye. At this point he wrote to Father Castelli noting that 'The noblest eye is darkened which nature ever made, an eye so privileged and so gifted with rare qualities that it may with truth be said to have seen more than the eyes of all those who are gone, and to have opened the eyes of all those who are to come'."

The keywords are shown in red. The symptom/sign suggests active keratitis [discharge] accompanied by corneal edema [halo]. And since both eyes eventually lost vision, it would imply a chronic retinal problem, perhaps posterior uveitis. The left eye was probably further complicated by band keratopathy in his last years. His 20X telescope was actually a low-vision device - at least by 1616, Galilio appeared to still have retained enough vision (at least 20/400) to allow somewhat accurate observation of Saturn's rings/arms.

What the proposed DNA analysis can prove? Probably not much. The project is expected to cost around £282,000, by the way.

Year of Recovery

2009-01-23T20:33:00.008-05:00

Happy Lunar New Year

It is a year of 扭(牛)轉乾坤, i.e.,
a year of (bullish) recovery.

Enjoy.

9.13 Five-, 6-, 7-, 8-pointed stars

2009-01-05T10:26:00.020-05:00

How many points does a star emanate?

It depends on where you are from.

In the US, five (5). You see 5-pointed stars on a certain sidewalk in Hollywood (e.g., left). Even the Texaco logo has such a star. It is also the basic standard emblem of the US Military. The American flag has 50 such stars. And the national flags of Singapore, New Zealand, Pakistan, Turkey, China, Somalia, and many others all have the 5-pointed star(s) as part of the design.

There are of course the 6-pointed stars, e.g., the Marian star and the star of David.

The municipal flag of Chicago has four 6-pointed stars (right), each commemorating a specific event and each of the 6 points, a special meaning. A fifth star has been proposed on more than one occasion, but none has been realized thus far. Further, the white stripes = north, west and south sides of Chicago, and the two blue stripes = Lake Michigan and Chicago River, respectively.

Interestingly, the 6-pointed star is also a sacred Mongol symbol, seen, e.g., on the entry to Humayun's tomb in New Delhi (below):

Seven-pointed stars? Of course, the Australian flag has 5 of them:

It often puzzles the tourists: 6 states + 2 territories = 7, not 8 points? (Dared to be different, these Aussies?)

Actually, it is a bit more complicated than the simple math. The winner of the original flag design (contest conducted in 1901) had 5, 6, 7 and 8 points (below, left).

King Edward VII approved the current 5- and 7-pointed star version.

There have been many iterations on the significance of these designs which we'll leave to the real historians to contemplate.

The only national flag that has an 8-pointed star seems to be that of Azerbaijan (below). This star is supposed to be the symbol of Rub El Hizb (Arabic: رب الحزب‎). And the design here was modified in 1991:
Seriously, how many points of a real heavenly star are we supposed to see? Let's see:

In the human eye, the crystalline lens is composed of a single-cell-layer epithelium in the front and a cortex that envelopes the nucleus. The epithelial cells elongate into cortical fiber cells and the ends are jointed at the front and the back, known as the sutures. The front suture is shaped as an upright Y and the posterior, an inverted Y. Superimposing the two Ys, what do you get? Yes, 6-points. This is the basic pattern. Often there are branches off the basic Ys. In other words, stars (in effect, point sources of light) should appear 6-pointed (with/without branches) to most of us. If you see 5 or 7 points, have your eyes examined.

Occasionally, something goes wrong with the sutures, then you'd end up with sutural cataracts. A real bad case is shown here:

(From: http://www.eyesonline.com.au)

See the huge Y within the dilated pupil? Most sutural cataracts are, however, less dramatic than the one shown here. Most have no significant impact on vision except the 6-pointed stars look even more prominent.

You'll shoot your eye out

2008-12-23T19:19:00.005-05:00

(A Christmas Story, Warner Bros, 1983)

(Click arrow to start the video)

Merry Christmas and

Happy New Year!

9.12 Panda myopia

2008-12-23T09:55:00.006-05:00

Two giant pandas, Tuan-Tuan and Yuan-Yuan, both from Sichuan arrived in Taiwan today.

Panda-mania now begins. Kids are overjoyed. And adults are busy analyzing the political implications of such precious gifts.

The happiest people are the merchants who peddle everything panda, from cookies, candies, to clothing.

What, pandas are near-sighted? -4.00D? Based on cycloplegic refraction?

9.11 Lobster eyes

2008-12-05T06:40:00.025-05:00

On the left is a normal 2-clawed Maine lobster. Newport Daily News (12/3/2008) reports that a 1.5-lb 4-clawed lady lobster is caught this week by a Mr Patrick Marks in the waters 60 miles south of Newport, RI. It has one crusher claw and three pincher claws, all functional. After showing it off most of the day, Mr Marks let her go, explaining that he "sometimes lets lobsters go out of guilt when they look at him funny."

Yes!! Lobster vision at work.

Lobster eyes are structurally very different from that of other animals (including the mantis shrimp). The cornea actually contains an array of mirror-like reflectors, each arranged at a specific angle, that ultimately focus incoming light rays onto the retina.

The optics is reflection rather than the more conventional refraction.

Presumably in the dim deep sea where sharp vision is less important than acute sense of smell and touch, the lobsters do not rely on vision to hunt, they only need to detect motion.

Under bright lights, the lobsters probably cannot not see much as everything is blended into the background and "washed out". Lights reflected from their eyes, on the other hand, will give you an impression that you are being stared at, inquisitively. If you were a lobsterman, you'd probably let them go, too.

Earlier this summer, another 4-clawed lobster was caught by a Mr Jimmy Whitty based in Morell, PEI, Canada. It was nicknamed Mothra and kept in an aquarium at a restaurant. It was, alas, lost to follow-up.

And in Taiwan (local news, 11/25/2008, reported in www.nownews.com), fisherman Mr Chen caught a 3-kg male crab with a 50-cm "wing" span, estimated at 10 years old, at the mouth of Chen-wen Brook in Tainan Hsien (台南曾文溪河口). When caught with a net, it protested loudly with a hissing sound, fought gallantly with its claws, and with the eyes extending from the protective grooves, it was looking to escape at the same time. Mr Chen eventually let him go, so it can continue to propagate.

The first Thanksgiving

2008-11-26T05:58:00.003-05:00

(In November of 1621) when the Wampanoags helped the Pilgrims (who had arrived on the Mayflower, in 1620) bring in their first crop in the new world, there was a great feast during that harvest time. According to the Pilgrims, about 90 Wampanoags crashed the party and brought with them all sorts of delicacies. The Wampanoags usually celebrated their harvests, with food and rejoicing. They brought venison (deer meat), wild turkey, rabbit, woodchuck, lobster, clams, mussels, potatoes, sea bass, bluefish and many other delicious foods. Wampanogas also brought corn, beans, and squash to the feast, and even showed the Pilgrims how to cook the food. The Pilgrims were very appreciative of the gifts, and the 90 Wampanoags who crashed the party had a wonderful time (extracted from http://content.scholastic.com/browse/article.jsp?id=7587).

Thanksgiving is celebrated in the US on the 4th Thursday of November every year. Happy Thanksgiving !!

9.10 Eye popping

2008-11-21T11:01:00.025-05:00

Occasionally, patients claim they can do "crazy" things with their eyes. One of them can indeed move her eyes independently, for example. So much for coordinated binocularity. A burning question is: Can the eyes actually pop out of the eye sockets. The video below answers the question in part. It shows voluntary globe luxation, another of those crazy things, which presumably is a painless maneuver. Strictly speaking, it is a form of exophthalmos. Exophthalmos, as we all know, is most commonly seen in Graves disease.

Warning: The following video is a bit on the gruesome side:

(Click on arrow to start the video)

There are all kinds of catastrophic injuries involving the whole eyeglobes. One of them has the eyeball hanging outside of the socket with the eyelids closing behind the eyeball. This is not a pleasant topic; however, from the eyecare point of view, a review is still necessary.

As far as this type of involuntary eye popping, there are two varieties: (1) traumatic avulsion of the globe and (2) traumatic globe luxation. The difference between the two is really the extent of the damages: avulsion involves completely or partially severed extraocular muscles and the optic nerve, whereas in luxation, the muscles and the optic nerve are retained (hence a potentially total recovery after proper care). Luxation can be from a simple act of sneezing - often the patient has shallow eye sockets and weak ligaments.

With globe avulsion, there is very little or in fact zero chance of sight restoration. The 1999 movie, Oliver Stone's Any Given Sunday, has a scene that depicts some hapless football player's eyeball flying across the end-zone when tackled. This is actually probable despite common disbelief. There were indeed incidences of such injuries from through-the-windshield car accidents and blow-to-the-head martial-art competitions.

Perhaps the most disturbing are reports of eyeballs hanging by the threads (i.e., remnants of the optic nerve) in many A-bomb victims in Hiroshima on Aug 6, 1945. The blast force was a "mere" 15 kilo-tons, far less than the warheads in the arsenals of super-powers today, e.g., 300 kT. Destruction on such a scale is beyond imagination/comprehension. Let's not even try.

9.9 One-eyed dragons

2008-11-11T22:17:00.018-05:00

Ah, yes, this 1956 movie based on Leo Tolstoy's epic tome of the same title. And Audrey Hepburn (1929-1993) remains a perennial favor of many movie fans all over the world, even today.

One of the supporting characters in the movie, while in fact the chief architect of the Moscow defense, or more accurately, the Non-Defender of Moscow, General Mikhail Kutuzov had lost his right eye to head injuries, sustained while fighting against the Turks early in his career.

In 1812, France invaded Russia. With Kutuzov's scorched-earth strategy, Napoleon entered a deserted Moscow. His Grand Armée eventually succumbed to the bitter winter. Of the 450,000 men, only 10,000 returned to France, barely alive.

There were a few one-eyed generals. In the Eastern culture, they are known as one-eyed dragons (or 独眼竜 in Japanese and 獨眼龍 in Chinese). In the Chinese Red Army, there was General Liu Po-cheng (劉伯承, 1892-1986) who had also lost his right eye to a bullet wound. He led successful guerrilla warfare against the Nationalist Army in the late 1940s.

Beyond military operations, and far more interesting is the founding of Sendai City (仙台市) in the Northeast region of Japan in 1600 by Lord Da-Té Masa-Mu-né (伊達政宗, 1567-1636) who had also lost one eye. The right eye, of course.
In this case, however, the loss was not owing to war injuries but to an eye infection of unknown etiology. Some proposed small pox, others claim that he later gouged out his diseased eye on purpose. And it is doubtful that any anesthetic was used at that time.

Lord Daté was a patron of Christianity in Japan. He actually built sea-worthy ships and with which, sent emissaries to Rome to establish diplomatic relations with the Pope. Five members of the expedition stayed in Coria (now Seville) in Spain to avoid religious persecution ordered by the Tokugawa government back home. The descendants adopted a last name "Japón" who now number 600+.

It would appear that generals who had lost their right eyes were great visionaries.

To make the story complete, the earliest known one-eyed general was Antigonus I Monophthalmus (382BC - 301BC) under the command of Alexander the Great. Unfortunately, it is unknown as to which eye he had lost. Judging from his life-long military successes, probably the right eye as well. He finally lost a battle at age 81, killed by a javelin.

King Philip II (360-336BC, father of Alexander the Great) also had lost his right eye, but then he was not a general.

Happy Halloween!!

2008-10-21T13:51:00.009-04:00

It is that time of the year again... Temperatures start to drop. Leaves begin to turn colors and fall on the ground. And in the early evening of Oct 31, kids from around the neighborhood, dressed up as little goblins and ghouls, come and ring your doorbell. They'll yell "Trick or treat!!" when you open the door, and gleefully collect candies from your hands. [Mental note: one of them has peanut allergies.]

And a Jack-o'-lantern on your porch? Yes, a tradition around here in the Northeast (or wherever modern-day Celts congregate).

Why are the eyes triangular in shape? No one really knows. Maybe the all-seeing eye housed in a pyramid, an icon of the Freemasons, can tell us.

A Happy Halloween to all!!

9.8 Baby formula

2008-10-06T11:33:00.005-04:00

By now, 53,000 babies in China have been sickened by melamine-tainted milk and 4 have already died (left: a baby holding a can of Sanlu powdered milk). And milk products from China are now banned in many countries around the World.

Ideally, there should not be any melamine in any food anywhere. Unfortunately, melamine is ubiquitous. Chances are the favorite plastic dish/cup of yours or the counter top in your kitchen was made in part from melamine. The upper safety limit in food set by both the EU and the US is now 2.5 ppm (or 2.5 mg/kg). For babies, 1 ppm in China [in Taiwan, the upper limit for powder milk for babies is at a far more stringent 0.05 ppm]. In the US, the tolerable daily intake is set, for now, at 0.63 mg/kg body weight/day.

Let's do some simple math: Assuming you weigh 50 kg, the daily melamine limit is then 0.63 x 50 = 31.5 mg. Then even if you consume 31.5/2.5 = 12.6 kg of milk powder everyday, it is still "safe". And for a 12-month-old baby weighing 10 kg at the 1 ppm limit, it'll be a 1 kg consumption per day - still quite a lot of milk. Unfortunately, the melamine content in Sanlu powdered milk putatively was as high as a mind-boggling 2,560 ppm. So forget the math, the stuff is highly toxic all right.

The most logical alternative to powdered cow milk is of course mother's milk. While this may not always be possible, for those making the switch, more about milk and the eyes:

The following are extracted from an interesting article by Hoffman et al: "Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk". J Nutr 134:2307-2313, 2004:

The authors divided 6-month-old breast-feeding babies into two groups: (1) the DHA group that received each day, one jar of baby food (113 g) containing egg yolk enriched with 115 mg/100 g DHA (docosahexaenoic acid) and (2) the same but no DHA (i.e., the control group).

Both groups continuedto breast-feed for a mean of 9 months. In the control group, the red cell DHA levels decreasedsignificantly between 6 and 12 months (from 3.8 to 3.0 g/100 g totalfatty acids), whereas in the DHA group, the levels increasedfrom 4.1 to 5.5 g/100 g.VEP (visually evoked response) acuity at 6 months was 0.49 logMAR (minimum angle of resolution)which improved to 0.29 logMAR by 12 months in the control group. In the DHA group, VEP acuity was 0.48 logMAR at 6 months and which matured to 0.14logMAR at 12 months. In other words, 1.5 lines (on the eye chart) better visual acuity than the controls. So an adequatedietary supply of DHA throughout the first year of life maybe necessary for visual maturation. The stereo-acuity on the other hand was not affected by DHA.

Interestingly, DHA concentration in human milkvaries from as little as 0.1% of total fatty acids in women on Western diets to as much as 1.4% in Inuit women inNorth America and 2.78% in Chinese women from a fishing village,both of the latter consumed large amounts of marine animal foods.

Hmm... So the old-wives' tale of "fish is brain food", by way of DHA, is quite profound and is actually scientifically accurate! [We don't need to repeat that the brain is the extension of the eyes, do we.]

9.7 Beethoven's Symphony No 9 in D-minor

2008-09-20T17:40:00.018-04:00

It is a well-known story: When his 9th (the Choral) Symphony premiered on May 7, 1824, in the Kärntnertortheater in Vienna, the audience went wild. Ludwig van Beethoven (1770-1827) by then, however, was totally deaf. Contralto soloist, Karoline Unger, had to help turn him around to face the cheering crowd. There were 5 ovations all together, the ultimate respect for a common man (the police stopped further ovations in deference to the royalties who customarily were accorded three). It must have been quite a moving sight.

Beethoven indeed had put all his heart and soul into this symphony. In fact, despite the common belief that the vocal part of the 4th movement, Ode to Joy, was a poem borrowed from Frederich Schiller (1759-1805), Beethoven himself actually wrote portions of it. For example, at the very beginning of the vocal part, i.e., the baritone solo starting on bar 216:

O Freunde, nicht diese Töne!

Sondern laßt uns angenehmere anstimmen,

und freudenvollere.

Freude! Freude!

This symphony is of course remembered forever for its 4th movement. However, IMHO, the 3rd movement beginning with Adagio molto e cantabile is positively celestial that deserves even more attention.

Something about Beethoven's eyes? Ah, yes, we are just coming around to that.

The etiology of Beethoven's deafness has never been clear. Several possibilities have been put forth including otosclerosis, syphilis, noise trauma, Paget’s disease, sarcoidosis, and otitis media. None of them was conclusive, however.

It is known that Beethoven suffered from digestive diseases plus rheumatism, various skin abscesses and recurrent infections, ophthalmia, jaundice, and anemia. Ophthalmia? An old term for inflammation of the membranes/coats of the eye, i.e., iritis/uveitis. This, plus Beethoven's own admission of "constant belly aches, diarrhea and bloody stools" suggests that he might have a bad case of ulcerative colitis or Crohn's disease - both of which are associated episodically with deafness.

So the best guess is then: Beethoven's deafness was an immunopathic manifestation of Inflammatory Bowel Disease (IBD). And iritis/uveitis no doubt flared up from time to time. Unfortunately, after the autopsy, the coroner's report concentrated on the liver and the abdominal fluid, with nothing on the intestines. So we'll never know for sure.

There is a lesson here, though: Patients with IBD need to have their eyes (especially the retina) and ears (at least the hearing) examined regularly - particularly for musicians and composers.

9.6 Diving and retinal breaks

2008-09-12T09:19:00.009-04:00

Guo Jingjing is the Gold medalist of Women's 3-m springboard diving of the 2008 Olympics. She took up diving since age 7. And now at age 27, she is the most decorated Olympic female diver ever.

And the price she has paid as far as the eyes? Retinal tears or breaks:
They lead up to the more severe sight-threatening retinal detachment. Which was probably what has happened to Ms Guo. In 2002, a retinal break was discovered in her right eye. After a successful surgical repair, her vision or visual field dropped to 20% of normal anyway. In 2004, right before the Olympics in Athens, the retina apparently has re-detached. She went on to win two gold medals nonetheless. After the 2008 Games, both eyes now require surgery.

Sudden physical impacts or blunt trauma to the eyes in, e.g., boxing, car accidents, baseball or hockey games, can disrupt the retinal (and sometimes choroidal) structure. Even if there is no detectable blow-out detachment when the eyes are examined immediately after the injury, it does not mean that the patient is out of the woods. Unfortunately, the latency for retinal detachment is quite long, often in years. Diving apparently involves repetitive impacts on the top portion of the eye. In other words, when the diver's head enters the pool water, the contact force will have been transmitted to the eyeballs. And the latency of retinal detachment will have been considerably shortened. Even worse if there are other pre-disposing factors, e.g., high myopia and/or family history of retinal detachment.

Athletes in competitive diving should probably have their retinas examined at least once every 6 months.

9.5 You are left-eyed?

2008-09-02T10:37:00.015-04:00

No one can spin a better yarn about the eyes as the ancient Egyptians. In the Egyptian mythology, the right eye, aka the Eye of Re (or Ra), symbolizes the Sun. And the left eye, aka the Eye of Horus, is the Moon.

The Eye of Re has a mind of its own and frequently wanders around by itself. On one of the fun-filled outings, it refuses to return, so Re (the father of all gods) sends Shu and Tefnut, two underlings, to retrieve it. The eye stubbornly refuses. And in the ensuing struggle, the eye sheds tears and from which, men emerge.

Another story has it differently, Re actually sends Thoth to fetch it back. And upon returning, the eye discovers that it has been replaced by another eye and becomes quite indignant. To pacify it, Re places the right eye in the shape of the uraeus serpent on his own brow - to show that the eye is now the ruler of the world. This serpent is worn by all Egyptian Pharaohs on their headgears. The right eye later becomes an entity and its association with many goddesses is of course the basis of many other stories.

The story of the left eye, the Moon, is even more complex.

The lunar cycle actually represents the eternal battle between Horus and Seth. They are fighting for the inheritance of Horus's father, Osiris. Seth steals the eye and damages it - cuts it up into six pieces. Thoth, with the help of other gods, puts the eye back together on the 6th lunar day. The healed eye is known as Wadjet. It symbolizes a re-established order after disturbances. The lunar cycle is essentially a description of how the eye is injured and repaired. The latter performed by 14 gods.

For the mere mortals such as you and I, the two eyes also behave somewhat differently - in the form of ocular dominance. About 2/3 of the population sight with the right eye. Ocular dominance seems to correlate with the handedness, i.e., a right-handed person sights with the right eye. However, there are always exceptions; you can be right-handed but sight with the left eye and so on. The reason is simple, each retina is controlled by both hemispheres of the brain, whereas each limb by only one side.

Ocular dominance is actually quite interesting and practical at the same time. It is often why a patient notices a change in vision (i.e., when the dominant eye is seeing less well than the fellow eye) and seeks help. In monovision contact lens fitting, the first attempt is always to fit the dominant eye for distant vision and the fellow eye for reading. Sometimes, this does not work out and the patient actually does better with the dominant eye for reading. In monovision laser vision correction, the dominant eye is also selected for distant vision. You are of course stuck if this arrangement does not work.

Being very capable archers, the ancient Egyptians must have queried their eye doctors why some sighted with one eye vs the other. The mythology of the eyes, on the other hand, is a true testament to their vivid imagination.

Evidence of eye surgery in ancient Egypt? See the lower eyelid of the right eye in this mummy portrait:

An attempt at repairing entropion, it seems.

Exemplary Olympians

2008-08-23T17:49:00.006-04:00

In the wheelchair is Su Li-Wen of Chinese-Taipei (Taiwan). She competed with an injured left knee in the women's 57-kg Taekwondo and fought in excruciating pain to the end. In the last round, she fell 11 times yet refused to concede.

Robina Muqimyar of Afghanistan who competed in the 100 meters. She came to Beijing despite the mysterious disappearance of teammate Mehboba Ahadyar (around July 4, while training in Italy), who was to run in the women's 1500- and 3000-m events.

9.4 Valsalva retinopathy

2008-08-11T16:09:00.012-04:00

Lu Ying-Chi of Chinese Taipei won a bronze medal of women's 63kg weightlifting

event at Beijing 2008 Olympic Games, Aug 11, 2008.

Chen Xiexia (C) of China, Sibel Ozkan (L) of Turkey and Chen Wei-Ling (R) of Chinese Taipei wave to spectators at the awarding ceremony of the women's 48kg of weightlifting event at Beijing 2008 Olympic Games at the Beijing University of Aeronautics & Astronautics Gymnasium in Beijing, China, Aug 9, 2008. Chen Xiexia, Sibel Ozkan and Chen Wei-Ling won the gold, silver and bronze medals respectively. (From news/xinhuanet.com)

Weight-lifting can injure the eyes. No kidding.

Once a patient came in and complained that his vision in the right eye was suddenly lost when he tried to lift some heavy boxes in his basement. Valsalva retinal hemorrhage immediately comes to mind. However, fundus exam reveals a cellophane membrane over a "wrinkled" macula. A macular pucker, it turned out to be. This is entirely different from the first suspect which occurs when one holds breath performing physically strenuous tasks, e.g., heavy weight-lifting, giving birth, passing stool, etc. The increase in the intrathoracic/abdominal pressure raises the venous pressure which in turn causes rupture of retinal capillaries. The blood accumulates between the retina and the vitreous. And vision changes if the hemorrhages occur within the visual axis. Often the history and a retinal exam confirm the diagnosis:

(Image from Digital Ophthalmology)

The above is an unusually large pre-retinal hemorrhage in a case of Valsalva retinopathy. More common than not, the hemorrhages are much smaller of about 1 disc diameter often found near the disc itself; although they can extend into the macula and obscure vision.

Luckily, most cases of simple Valsalva retinopathy heal quickly, spontaneously, and completely. Some cases, usually those with pre-existing vascular disorders, may require the Nd:YAG laser/surgical intervention.

So who/why/what is "Valsalva"? Well, Mr Antonio Maria Valsalva (1666-1723) was an Italian physician specializing in ear anatomy. He had also described the (original) Valsalva maneuver (i.e., what happens physiologically when you forcibly exhale against a closed glottis). He also coined the term, the Eustachian tube (which connects the middle ear and the pharynx). When you travel by air, when the airplane descends for landing, your ears tend to "pop". The reason is the rapid increase in the atmospheric pressure causes the Eustachian tube to collapse (or become pinched). Gum-chewing works the best in opening this tube and restoring the pressure balance. If you don't have any chewing gums handy, try opening your jaws with the lips closed instead.

08-08-08

2008-08-08T14:51:00.002-04:00

9.3 Centrifuges and reading in space

2008-08-02T18:37:00.019-04:00

This is a standard desktop centrifuge. Each "hole" accommodates an Eppendorf centrifuge tube. The centrifugal force is about 2,000 x g, strong enough for separating most particulate matters from the solvents. For comparison, 1 x g is what most of us experience on the surface of Earth everyday.

Humans occasionally subject themselves to higher Gs. For example, most rides in amusement/theme parks are actually centrifuges or variations of centrifuges. While most are in the less than 2 x g range (an example is shown below), some in the form of roller-coasters, e.g., the Space Mountain in Disney World, can reach 4 x g.

(An amusement park centrifuge)

Momentary exposure to 4 x g (or even higher) is relatively harmless, unless there is an undiagnosed pre-existing medical condition - then it can end in tragedy. Indeed, heart attacks and brain hemorrhages are known to occur on some high-G rides.

NASA has the ultimate centrifuge for the humans:
This is NASA's 20 x g centrifuge used for testing the physiologic responses of astronauts. And this is where you see the astronauts' faces start to melt, among other things.

Technically, the g-force is calculated thus:

where g = Relative centrifugal force (RCF)
r = rotational radius (centimeters, cm)
N = rotating speed (revolutions per minute, rpm)

Of course, g is also the basic unit of the gravitational force. Without gravity (i.e., zero-g), as that in the outer space, some human reflexes that have worked previously now begin to unravel. And one of them is the simple vestibulo-ocular reflex (VOR).

Now pick one object in your room, stare at it, and then move/rotate your head to left and right, you'll notice the object remains in the same stable position. In other words, the image of the object is stabilized on your retina. This is the VOR at work.

The sensory aspect of VOR is handled in the inner ear by the semicircular canals (which sense angular acceleration to detect head rotation) and the otolith organs (which sense linear acceleration to detect both head translation and the position of the head relative to gravity). The information is processed centrally and the output sent to extraocular muscles.

In zero-G, the semicircular canals do not work well because the fluid contained within no longer convects effectively. So the coordination between head motion and eye movement is now disturbed. If you read too fast, the text lines will appear jerky. Effective reading can be achieved only at voice speed. Whether VOR eventually adapts to long periods of zero-G and normalizes is still yet to be tested. In a long journey to other galaxies, catching up on your reading will become an integral part of mental exercise. Certainly beats looking out of the window into darkness 24/7.

Of course, large centrifuges can be incorporated into space stations and star ships. The centrifugal force will provide simulated gravitation that can make the astronauts' lives easier.

The (presumably) rotating space station shown below is in 3D. You'll need to borrow a pair of red-green glasses from your eye doctor to see the effect.

(From http://farm3.static.flickr.com/2351/2130591814_53d9037897.jpg?v=0)

9.2 Mars

2008-07-14T17:57:00.010-04:00

No one can forget the excitement upon seeing this image, taken in 1976 by the Viking spacecraft then orbiting Mars. Clearly it is a face complete with eyes (well, at least one), nose, and mouth. Some claimed that computer enhancement showed an eyeball with the pupil (the right eye) plus a tear drop below the eye. In 1998, the Mars Global Surveyor re-photographed the same region and the face now looked somewhat different, the "eye", sadly, either was never there or had disappeared:

So the Martians most likely did not construct the site, if there had been Martians in the first place.

Now the Phoenix Mars Lander tells us, there is ice on Mars and the Martian soil is similar to that found in our backyards. For those who grew up with Ray Bradbury's the Martian Chronicles (1950), the new info is simply a re-affirmation of what maybe, even though no Martians are found just yet. Of course, Marvin the Martian (and his eyes) has been around to entertain us for a long long time:
Now, remember this 1990 movie, "Total Recall", starring Arnold
Fast forward your DVD to the part when Douglas Quaid and Melina get blown out of the enclosures onto the surface of Mars and are now exposed to the Martian environment, i.e., the vacuum. Their bodies begin to bloat. The change of their eyes is especially alarming as they begin to bulge out of the eye sockets. However, as soon as the alien machine starts to alter the Mars atmosphere to that resembling the Earth, both Quaid and Melina recover nicely. Their eyes look entirely normal with no loss in function - as if nothing untoward has happened. Right there is your clue that something is amiss in this explosive decompression episode. If the eyeball can expand at all, it'll only be the conjunctiva. The retina does not have the elasticity to allow stretching and is certain to disrupt, just like wet tissue paper. So an episode such as that depicted in the movie can lead to blindness.

It is often assumed that a person explodes when exposed to the non-pressure of the outer space. In reality, for a human being to decompress from 1 atm to zero, nothing much happens, because the skin is tough enough to withstand such a small change. The sclera of the eyeglobe is especially strong because it is constituted of overlaying collagen fibers. A slight inflation, yes. Explosion, no. Oh, the death is from asphyxiation, naturally.

There has been only one catastrophic explosive decompression of unimaginable force. That is the Byford Dolphin diving bell accident of 1983. In which, 4 divers inside the bell died from a sudden pressure drop from 8 to 1 atm owing to the sudden opening of a hatch (the diver who opened the hatch also died). The Byford Dolphin is a Norwegian oil exploration rig then operating in the North Sea. The divers were undergoing gradual decompression when the accident occurred. One of them closest to the hatch literally did explode. The others showed blood lipoprotein denaturation, organ hemorrhages, and large amount of gas in blood vessels. One diver had a large sub-conjunctival blister suggesting a separation of the conjunctiva from the sclera.

It is possible that the script writers of "Total Recall" had perused the Byford Dolphin forensic reports, hence the eye scene.

Unfortunately, in a world now starving for oil, we foresee a rush to off-shore oil exploration and deep-sea drilling. We must all remember that safety for the workers/divers is a first priority and deservedly so.

Happy 4th of July !!

2008-07-04T08:00:00.004-04:00

A quick report (11:00PM): Boston celebrates 4th of July in style, again. The Boston Pop under Keith Lockhart performs at the Half-Shell on the Esplanade for a crowd of half a million with music that combines country and pop, the 1812 Overture by Tchaikovsky complete with canon firing and church bell ringing, Puccini's Nessun Dorma from Tourandot, John Philip Sousa's Star and Stripes Forever - just to name a few. The event is MC'd by Craig Ferguson. And the fireworks are simply breathtaking that light up the dark summer sky with spectacular reflection from the Charles River.

It is a great city, Boston. Please come and visit.

Incidentally, Red Sox 6, Yankees 4, today.

9.1 Shrimp's auntie

2008-07-03T09:43:00.011-04:00

No, this is not a cockroach. It is a mantis shrimp (shown above is one of the less colorful varieties), also known as 蝦姑 (the shrimp's auntie) in Chinese.

A more colorful one is shown below:
It is more a crab than a shrimp. The taste is rather bland, though - probably the reason why it has never made it into the menu of Chinese restaurants. The Italians do have a way of preparing it (recipe below quoted from here):

Canocchie (or Panocchie) alla Pezza - Mantis Shrimp Pezza Style

To serve 4:
16 Mantis shrimp, about 2 1/4 pounds (1 k) in all
A small clove of garlic, minced
A small bunch parsley
A lemon (optional)
Olive oil
Salt to taste

Lightly oil a deep skillet large enough to contain all the shrimp, and lay them flat in it with the garlic and a pinch of salt. Sprinkle a little water over the shrimp, cover the skillet with a wet cloth, and cook over very high heat for 2-3 minutes. Serve the shrimp at once, garnished with sprigs of parsley and, if you like, lemon wedges.

Note: It goes without saying that it'll be a messy sitting, as the shrimp shell is a bit hard to crack.

There are always people who look at the shrimp differently. A few have noticed the unusual eyes:
And a close-up (by Roy Campbell, from www.wired.com):
In the 3/20/2008 issue of Current Biology, Cronin, Marshall, and Caldwell reported that the mantis shrimp had a 4th mode of vision. Really, unlike everybody else, it sees circular polarization light. (Note: the other three modes of vision: black & white, color, and linear polarization). So what does that mean? Let's look at the polarization process first (below quoted from here).

"Light in the form of a plane wave in space is said to be linearly polarized...If light is composed of two plane waves of equal amplitude by differing in phase by 90°, then the light is said to be circularly polarized. If two plane waves of differing amplitude are related in phase by 90°, or if the relative phase is other than 90° then the light is said to be elliptically polarized."

In other words, if one can see the tip of the vector, circularly (or elliptically) polarized light would appear to rotate. It can be produced by passing linearly polarized light through a quarter-wave plate at a 45° angle to the optic axis of the plate. For the transmission of electromagnetic waves, circular polarization has almost no signal loss. It will be a great way of cell phone communication - no more dropped signals. Of course, for the mantis shrimp, this "technology" has been in use for more than 400 million years. Human electrical engineers are still yet to catch up.

It is fair to assume that the mantis shrimp uses circularly polarized light to communicate for mating and/or staking territorial claims - as in other animals. Its shell then must be the source of the reflected polarization light. Its compound eyes already contain thousands of rows of light-detecting units called ommatidia - a mix of photoreceptors and filters.

If you think about it, the mantis shrimp will survive long pass other species on earth: It looks un-appetizing, in fact, not much taste, has a hard shell for protection, and communicates with polarized light which no one else can see. Not bad at all. In fact, it is also known as the shrimp from Mars.

Speaking of Mars...

8.7 Plastic brain

2008-06-23T11:29:00.015-04:00

(From ewake.wfubmc.edu. IMHO, a pickled sheep brain is more fun to play with.)

Actually, the topic here is Brain Plasticity (or the more authoritatively sounding "Neuroplasticity"), a red-hot theme in brain research today. This post will only give you a quick introduction of what it is. Ideally, another blog should be created to cover this subject in much greater detail. Perhaps in the future.

Only a few decades ago, it was generally agreed that the lower brain and neocortical areas were immutable/unchangeable. In other words, the brain functions are fixed in certain areas:

Indeed, developmentally, it has been shown that the sensory pathways are fixed after a certain critical period. However, it has gradually become clear that the continued re-wiring of the brain, throughout life, largely influenced by the environment, is also operational. (A grand unification theory is needed here.)

Simplistically speaking, beyond the basic developmental plasticity, there are at least two other types of plasticity: one induced by injury repair and the other simply from learning and memory. In brain repair, the functions can move to different locations, and in learning/memory, specific brain areas can expand.

Neurologists have long observed that spontaneous recovery from brain lesions is common. For example, in an fMRI study (Pantano et al, Brain 125: 1607-1615, 2002), MS patients who had suffered a single attackof hemiparesis, there are adaptive changes involving both the symptomatic and asymptomatic hemispheres - during a simplemotor task. And the extent of these changes increased with the lapsed time and the severity of damage .

There are simply too many such examples to cite, so we won't even attempt. Readers are encouraged to google their own.

And in this news article: "Taxi drivers' brains 'grow' on the job" (BBC News, 14 March, 2000): "...The hippocampus is at the front of the brain and was examined in Magnetic Resonance Imaging (MRI) scans on 16 London cabbies. The tests found the only area of the taxi drivers' brains that was different from the 50 other "control" subjects was the left and right hippocampus... One particular region of the hippocampus, the posterior or back, was bigger in the taxi drivers..."

These Knowledge Boys/Girls are special, aren't they.

Notice in the above, the research methodology was based on MRI yet again. In fact, both morphometric and functional MRI.

Let's not stray too far from the eye. If you recall "3.3.1 Who's being lazy" and "3.3.2 Squint", here is something extra that is relevant to brain plasticity:

"...The gray matter volume in strabismic adults was smaller than that in normal subjects at the areas consistent with the occipital eye field (OEF) and parietal eye field (PEF). However, greater gray matter volume was found in strabismic adults relative to normal controls at the areas consistent with the frontal eye field (FEF), the supplementary eye field (SEF), the prefrontal cortex (PFC), and subcortical regions such as the thalamus and the basal ganglia. These opposite gray matter changes in the visual and the oculomotor processing areas are compatible with a hypothesis of plasticity in the oculomotor regions to compensate for the cortical deficits in the visual processing areas..." (See Chan et al, Neuroimage 22:986-94, 2004.)

(Esotropia OS. From eye.ac.cn)

The next step is confirmation with fMRI. Time to write a grant application, then.

Maybe an introductory paragraph starting with:

"Visual deficits can be correlated to less gray matter at the striate and extra-striate visual cortex. In particular, visual motion deficits can be correlated to less gray matter at the parietal eye field, and normal saccade responses can be correlated to more gray matter at the rest of the oculomotor regions..."

Then again, maybe not.

2008-06-18T00:03:00.001-04:00

Now, 2008

8.6 Perivenous syndrome

2008-06-13T16:03:00.005-04:00

First, all sons and daughters, take your father out to dinner on Sunday.

Happy Father's Day!

We will now touch upon the "perivenous syndrome". Perhaps the best explanation is that in Prof Philip James's " Hyperbaric oxygenation in fluid microembolism", Neurol Res, 29(2): 156-161(6), 2007:

[Abstract] "...Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid..."

Having already gone over the principle and practice of NMR, now a quick review of the current treatment of multiple sclerosis (MS):

MS, despites years of research, still does not have an agreed upon etiology. Since the principal symptom is inflammation, treatments thus far have targeted it by using anti-inflammatories. For acute relapses, patients with relapse-remitting MS are treated with steroids usually intravenous methylprednisolone (IVMP). For longer-term maintenance, there are the interferons, IFN1a and INF1b, that can block immune factors known as class II MHC molecules. With this treatment, the T cells can no longer breach the blood-brain barrier to cause cerebral damages.

The search for a better alternative to interferons culminated in 2004 when natalizumab, a monoclonal antibody, was approved for MS treatment. However, shortly after, reports of a rare progressive multifocal leukoencephalopathy (PML) surfaced. This new drug was withdrawn from the market in Feb, 2005. And after extensive reviews, in June, 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. The benefits of natalizumab, either by itself or in conjunction with IFNa1 seem to outweigh the risks according to several 2006 reports. So MS patients actually do have treatment choices and many are well-managed by their neurologists.

Of course, there are always other drugs being developed and tested, for example, the immunosuppressants, the statins, estrogen, even the cannabinoids. Also being tested are stem-cell implants and plasmapheresis. Preliminary results are somewhat mixed in most if not all cases.

Most intriguing, however, is the hyperbaric oxygen treatment (HBOT) of MS. In fact, the efficacy of HBOT has been reported in as early as 1983 (for details, see: Fischer BH et al. Hyperbaric oxygen in the treatment of multiple sclerosis; a randomised placebo-controlled double-blind trial. New Eng J Med 1983;308:181-186).

Because of the venous leakage that causes inflammation in the surrounding area, the treatment principle is to provide the repairing process the best environment before sclerosis sets in. And one of the major environmental factors is indeed oxygen. Logically, then HBOT should be employed urgently as it it the best way of delivering oxygen.

Treating early stage MS is now possible with the advent of MRI and MRS (and eventually, the 4-dimensional NMR spectroscopy). To firmly establish HBOT as the treatment of choice, large-scale double-blind studies based on MR technology must be conducted. The focus will be on the level of lactate, the 1.35-ppm resonance [note: its chemical shift is pH-dependent], th index of anaerobic glucose metabolism.

In fact, all eye doctors should be on the lookout for patients with early MS - pay more attention to a complaint of diplopia for one thing, and do take retrobulbar pains seriously. A judicious referral for MRI scan is mandatory. The treatment choices also must be presented and explained to the patients.

Ideally, those microemboli that cause focal ischemia in MS in the first place should be definitely identified and the method for their removal developed. Something for the near future, perhaps.

Lest we forget: many devastating ocular diseases are ischemic in nature, for example, primary open-angle glaucoma, age-related macular degeneration, and diabetic retinopathy. Is there a role for HBOT in the treatment of these diseases? You tell me.

8.5 Optic neuritis

2008-05-28T19:50:00.018-04:00

(The above is a fundus photo of optic neuritis, notice the blurred disc margin. This is not always seen, however. Image from meded.ucsd.edu.)

Sometimes a patient's chief complaint is this: Over the past few weeks, vision fades in and out and the patient is now experiencing "pain behind the eye" especially when looking about. Also, there is now a loss of vision. A quick visual acuity test does confirm the patient's own observation. And the swinging penlight test also reveals an afferent pupillary defect. Ophthalmoscopy, however, shows a normal optic disc. You are entertaining a diagnosis of optic neuritis but how to confirm it in the absence of any obvious signs of disc change?

Contrast MRI, naturally:
The above is a T1-weighted coronal image of the brain after intravenous GdDTPA, a contrast agent, to provide enhancement of the lesion. And in this case, a hyperintense left optic nerve (on the right side of the image, the white spot next to the caption) suggesting a leaky optic nerve sheath resulting from, most likely, inflammation. In contrast, the right optic nerve shows no such enhancement. This clinches the diagnosis of left optic neuritis. A course of intravenous steroid treatment is then in order. Unfortunately for the patients, optic neuritis is often an early manifest of multiple sclerosis (MS):

In fact, 15 years after the onset of optic neuritis, ca 75% of women and ca 34% of men will have developed MS (see above, the hyperintense areas) which is characterized by exacerbations and remissions of motor and/or sensory functions over a period of time. Conversely, up to 50% of MS patients will develop one episode of optic neuritis. Both types of patients are seen in the eye doctor's office.

Metabolically, proton MRS of MS brain lesions shows a decrease in the NAA/Cr ratio and an increase in the Cho/Cr ratio. MRS in conjunction with MRI therefore can help distinguish early lesions that might respond to therapy from late irreversible ones. In theory, other resonances such as lipids, lactate, glutamate, and inositol, could potentially help in the staging of MS. Certainly, any successful treatment will be evidenced by the normalization of the NMR spectra.

A more specific water-suppressed proton MRS study of an MS patient (see Narayana et al. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 1998;43:56–71) is cited here:

The spectra shown above were obtained on Days 98 (A), 147 (B), 189 (C), and 259 (D) of a longitudinal study. The volume of interest is exhibited in the MR images. The resonance at 2 ppm is NAA. (A) is the baseline. (B) and (C) reflect transient changes, chiefly a decrease in NAA. And (D) total recovery back to baseline as that in (A).

Notice in (B), the resonance at 1.32 ppm, designated as lipids in the original report, is actually lactate [to be further verified of course]. This is consistent with the general observation that lactate accumulates abnormally during necrosis, inflammation, or other tissue injury. In other words, whenever ischemia occurs, cellular metabolism is forced into anaerobic glycolysis with lactate as the principal end-product.

We will next examine the etiology and treatment of MS.

8.4 Four-dimensional NMR spectroscopy

2008-05-22T06:33:00.012-04:00

Yes, everybody knows that: we all live in a magnetic field - the Earth. Its field strength is a mere 30-60 micro Tesla (depending on where you live). However, a large metal tube such as a submarine deep in the ocean can cause magnetic disturbances and is therefore detectable. Rumor has it that a certain U-Boat captain founded an NMR company, most likely inspired by his wartime experience evading MADs (magnetic anomaly detectors). A submarine can become electrically charged owing to the difference in the temperature of the upper and lower hull. This is enough to create a difference in salinity of the enclosing sea water, hence a dynamic electric field around "Das Boot". A stealth submarine will have to address this issue obviously. In NMR, shielding high-field magnets is a challenge even now. Incidentally, Mr Tom Clancy has much more on anti-submarine warfare in his classic "The Hunt for Red October" (which most people on Earth have already read):
Back to the issue at hand: At some point in the not so distant future, the full potential of biological NMR will finally be realized. And it will be in the form of 4-dimensional (three spatial and one chemical-shift) NMR spectroscopy. In other words, imaging of, not just the water-protons, but the far more informative metabolites. The limiting factor is, yep, you've guessed it, the magnetic field strength.

Now picture yourself inside a magnet with a set of antennas enclosing your head. And after a certain period of rf irradiation at proton Larmor frequency and FID signal collection and processing, you are ready for the result. And it'll be a spectrum with only a large water peak. That won't be so interesting at all, will it. So, how is an MR image constructed?

Very simple, the FIDs must be encoded in three dimensions. First, along the direction of the north-south direction (the z-axis) of the magnetic field, a field gradient (i.e., the z-gradient) is applied. This gradient causes the Larmor frequency to change linearly, and a slice is selected by choosing the rf frequency corresponding to the Larmor frequency of the center of that slice. For this slice, a preparation gradient, the y-gradient, is then applied for frequency encoding, followed by the x-gradient for phase-encoding. Finally, a 2D Fourier Transform is used to transform the encoded image into the spatial domain. Why the need for a slice? Answer: to make sure enough signals are generated. A single layer of nuclei will have almost negligible signals to work with. [Note: For more information on important aspects of MRI, we recommend this site: http://mritechnicianschools.net].

Present-day clinical MRI is mostly imaging of water-protons. For the ultimate 4-dimensional NMR spectroscopy, an example is shown below:

Again, using an old standby: a rabbit lens (10-mm diameter and 5-mm thickness) incubated for 28 hours in high glucose for maximal sorbitol production. ¹³C1-glucose was used as the substrate. And NMR experiments were performed using a 9.4-Tesla spectrometer.

Part 1. MR microscopy:

Top: Schematic diagrams of the lens. The two primary regions are the cortex and the nucleus. (Left): section through the anterior-posterior poles and (Right): section through the equatorial plane.

Bottom: A water-proton image, through the equatorial plane, acquired with a spin-echo pulse sequence with TE (echo time)/TR (repetition time) = 3.88/1000ms, a 126x128 matrix, and 32 averages. Image resolution was 40 x 40 x 500 micron.

Part 2. Chemical-shift ¹³C microscopy:

At the bottom is a ¹³C spectrum acquired at 100.61MHz without proton decoupling - hence the multiplets of the biochemicals.

And the top shows color-coded images of glucose (red), sorbitol (yellow), and lactate (purple), respectively. The images were acquired with spin-echo of TE/TR = 9/500ms over 8 hours. A narrow bandwidth selective pulse (4KHz) was used with z-gradient = 800Hz/mm (slice thickness = 5mm). All three metabolites resonated within this bandwidth. The in-plane resolution was 600 x 600 micron. From the images, it is clear that there is a glucose concentration gradient with higher glucose in the cortex. And in contrast, sorbitol appears to re-distribute into the nucleus even though it is produced mostly in the cortex.

Obviously the above still cannot be done on humans. However, 7-Tesla clinical imagers are now coming on line. It is really only a matter of time before the manufacturers start seeking FDA approval for these imagers. For now, an alternative is to collect NMR spectra from, e.g., selected areas of the brain. It is possible to acquire somewhat low-resolution ³¹P, water-suppressed proton, and even ¹³C spectra at 1.5 Tesla - the most common magnet field strength used in a clinical setting today.

(Source: http://www.ajnr.org/cgi/content/full/23/8/1387)

In the above example, Cho (choline), Cr (creatine), and NAA (N-acetyl aspartate) are clearly seen. Each spectrum is from a volume of interest of 100 x 80 x 15 mm with an acquisition time of 60 min. [Note: A little long, but not intolerable from personal experience. Despite the loud knocking noises from turning gradients, some are known to doze off in the magnet.]

So, here is the current situation: MRI using 1.5-Tesla body scanners has matured as a routine clinical procedure. However, to see the metabolites, the only practical approach is to acquire NMR spectra from a volume of interest in the brain (or other body parts). This is in-vivo NMR spectroscopy, also known as MRS (magnetic resonance spectroscopy). Again, with ultra-high-field clinical magnets now rapidly becoming available, we should expect high-resolution MRS and perhaps even chemical-shift imaging soon.

For the eye, we will need to make some adjustment. Instead of the body or the head coil, we use a home-made surface coil that transmits and receives rf. Typically, it is a single-turn 1-inch coil that covers the whole eyeglobe:
It is then possible to obtain high-resolution MR images of the eye and water-suppressed proton spectra of the vitreous. Again, for the time being.

8.3 For the first time in human history

2008-05-20T05:29:00.004-04:00

(A 4.7-Tesla horizontal-bore superconducting magnet for small animals)

Chemists have long used NMR spectroscopy to study the structure of chemicals. Usually (1) the samples are Pasteur-pipetted into a small diameter NMR tube (e.g., 5-mm or less), and (2) to improve S/N, the acquisition time is deliberately long to allow more signal averages. For the biochemists, the only possible application is to analyze PCA (perchloric acid) tissue extracts (through a procedure that requires a mortar and pestle and loads of liquid nitrogen and elbow grease). Studies of living tissues are obviously out of the question; although even PCA extracts can provide interesting NMR spectra.

It is unclear who first convinced manufacturers of NMR spectrometers that size did matter and that many biological applications were still waiting in the wings. By the mid-1980s, there was a proliferation of wide-bore high-field superconducting magnets, both vertical and horizontal. All of a sudden, in-vivo and ex-vivo experiments can now be performed. With the additional bore space, simple perfusion systems can be integrated that can maintain cell/tissue/organ viability inside the magnet. And anesthetized small animals, such as mice, rats, and rabbits, can be comfortably fitted into the bore of, e.g., a 4.7-Tesla magnet (see image at top). In time, spectrometers capable of imaging also become available thus completing the entire application of biological NMR. And whatever happened to the NMR jocks (those within our circle, of course)? As far as we know, some are still shimming (bigger and better) magnets, while others become neuroradiologists, and at least four are practicing ophthalmologists.

For eye doctors who happen to be interested in diabetic cataract formation, the 10-mm probe is ideal as it allows studies of intact rabbit lenses which coincidentally are each around 10mm in diameter. Or, 10-12 rat lenses can be grouped together and regarded as one lens. These lenses can be placed in a 10-mm NMR tube filled with incubating medium and they will stay viable during signal acquisition. Further, the medium can be prepared with normal (5.5mM) or high (35.5mM) glucose (or other sugar substrates), the latter to simulate hyperglycemia.

NMR spectroscopy not only confirms old findings but often provides new information. The latter is akin to witnessing the discovery of something new "for the first time in human history". Some examples are shown below:
The above is a ³¹P spectrum of normal rat lenses (age of the animals: 8-10 months). It shows low levels of S3P (sorbitol-3-phosphate), F3P (fructose-3-phosphate), and αGP (α-glycerophosphate), and relatively high levels of PCh (phosphorylcholine), Pi (inorganic phosphate), GPC (glycerophosphorylcholine), and ATP.

One week after diabetic induction (by using streptozotocin), there is a huge increase of S3P, F3P, and αGP:

And if the the diabetic rats are treated with an oral AR (aldose reductase) inhibitor to stop sorbitol production, then the spectrum normalizes. In fact, both S3P and F3P now disappear entirely.

S3P and F3P are both novel metabolites never seen before. In fact, to this day, we still don't know their roles in diabetic cataractogenesis. They are also present in the red cells of human diabetics for reasons unknown.

In addition, in rat lenses incubated in high glucose, there is production of sorbitol (and some fructose) with time as evidenced by the following ¹³C spectra (top: one-month-old rat lenses and bottom, old rat lenses):
On the other hand, no mannitol is produced in lenses incubated in high mannose:
Does this mean that mannose can be used as a sweetener for the diabetics? Perhaps. Mannose, in fact, does taste quite sweet. Although, as they often say: more studies are needed.

Structurally, mannose and glucose differ only in C-2, different enough for AR not to recognize and metabolize it:
Of course, there are numerous other ocular diseases that can be examined with NMR. For example, the much dreaded bacterial endophthalmitis after cataract surgery. In rabbits, intraocular Streptococcus pneumoniae caused appearance of lipids in the vitreous, suggesting a breakdown in the blood-ocular barrier:

On the left are proton spectra of the normal eye/vitreous dominated by the lactate resonance (at 1.35ppm). The infected eye/vitreous shows, in addition to lactate, methylene (1.15ppm) and methyl (0.83ppm) groups of lipids, over a span of 2-4 days. By the 10th day, the eye becomes phthitic.

Here we should point out that the concentration of water is 55.6M. Such a high concentration is great for MRI. In NMR spectroscopy, however, water-protons easily overwhelm other proton resonances. For the investigation of metabolites with a concentration in the mM range, water-suppression is therefore necessary. The above spectra were acquired by pre-saturating water signals, one of the half a dozen or so techniques.

So how do we go from NMR spectroscopy to MRI? Very simple, it is all in spatial encoding. To illustrate this point, we shall next examine MR microscopy and chemical-shift imaging.

8.2 NMR

2008-05-17T19:48:00.031-04:00

One wonders if both Felix Purcell (1912-1997) and Edward Bloch (1905-1983) had experimented with magnets (see above) when they were little. They did, however, share the Nobel Prize in Physics in 1952 for independently creating experiments for the observation of NMR (nuclear magnetic resonance).

The growth of NMR research especially in the past two decades is nothing short of spectacular. It is a field driven entirely by the magnetic field strength (B₀) which determines the operational frequency or Lamor frequency (_ω0) of the NMR nuclei. The equation central to NMR research is this:

ω₀ = γB₀

γ is of course the immutable gyromagnetic ratio (or magnetogyro ratio - depending on whether you are a physicist or a chemist) unique to each NMR nucleus. The table below is a quick glance of the Larmor Frequency at a field strength of 1 Tesla (last column on the right):

Particle	Spin	w_Larmor/B s^-1T^-1	n/B
Electron	1/2	1.7608 x 10¹¹	28.025 GHz/T
Proton	1/2	2.6753 x 10⁸	42.5781 MHz/T
Deuteron	1	0.4107 x 10⁸	6.5357 MHz/T
Neutron	1/2	1.8326 x 10⁸	29.1667 MHz/T
²³Na	3/2	0.7076 x 10⁸	11.2618 MHz/T
³¹P	1/2	1.0829 x 10⁸	17.2349 MHz/T
¹⁴N	1	0.1935 x 10⁸	3.08 MHz/T
¹³C	1/2	0.6729 x 10⁸	10.71 MHz/T
¹⁹F	1/2	2.518 x 10⁸	40.08 MHz/T

(Note: the study of electron spin is ESR - Electron Spin Resonance or now known as EPR - Electron Paramagnetic Resonance - an entirely different ballgame from NMR)

In the old days, field strength was represented by proton frequency. For example: what was a 400MHz (or megacycle) magnet is now known as a (400/42.5781=)9.4 Tesla magnet. Because of the notoriously low sensitivity of NMR nuclei, much improvement in signal generation relies on increasing the magnetic field strength. The higher the field strength, the more the signal intensity (or higher signal-to-noise ratio). For example, for proton, an increase from 300 to 400MHz yields an improvement in S/N of (400/300)²= 1.78 fold. Building ultra-high-field magnets is a competitive sport for the manufacturers of course.

What are these NMR nuclei? Well, any nucleus with an odd number of protons or neutrons (or combination) qualifies; for example, biologically relevant nuclei include ¹³C, ³¹P, ¹H (proton), ²³Na, ¹⁷O,¹⁵N, ¹⁹F, and deuterium (a nucleus with spin number I=1). Of these, ³¹P and ²³Na are both 100%, and ¹H 99.98% naturally abundant. The others are only a fraction of around 1% or less and are usually used as labels; for example,¹³C can be labeled at either C-1 or C-6 position of glucose and the glycolytic products can thus be traced. On the other hand, proton is part of the ubiquitous water molecule, and ³¹P that of ATP and other organophosphates.

All these nuclei when placed in a magnetic field will precess at certain ω₀: depending on the γ of each nucleus, as mentioned above:

(From: teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm)

If a radiofrequency (rf) perpendicular to the north-south direction, or conventionally, the z-axis of the magnetic field is applied at the frequency of a nucleus of interest, then this nucleus will be tipped into the x-y plane. When the rf is turned off, the nucleus will begin to return to its original ground state through a process, known as relaxation. Relaxation is defined by longitudinal relaxation time (T1) and transverse relaxation time (T2). And the signals produced in the rf field are known as the FIDs (free induction decays) which can be picked up by an antenna and processed (through Fourier Transform from time into frequency domain) to generate NMR spectra.

(Note: No Bruker share-holders here)

The above is a typical high-field vertical-bore superconducting magnet used in NMR spectroscopy. It requires periodic feeding of liquid nitrogen and liquid helium. A probe is inserted from the bottom and the sample (in an NMR tube) loaded from the top, controlled by compressed air. A computer console is situated nearby for shimming, pulse sequence delivery, signal collection, spectral generation and printing.

An NMR probe is the heart of the spectrometer, it fits vertically into the bore of the magnet. They come in different bore sizes as well, e.g., 2, 5, 10, and 20mm diameters are common. These probes can be broadband or single frequency.

Before insertion, it needs to be optimized by using tuning and matching rods with the aid of an oscilloscope. Tuning is simply to make sure the probe is set to the frequency of interest. And matching is to ensure the impedance is equal to the external electronic circuitry so that maximal power can be transferred. These two operations are actually inter-related:

Shimming is an art, its purpose is to maximize the magnetic field homogeneity which greatly affects spectral resolution. Some "NMR jocks" are known to take extraordinarily long time (e.g., forever) to shim the magnet - to perfection. And a lot of them know how to read the FIDs even before FT. The resulting spectra are often strikingly well-resolved. NMR jocks are a special breed. Much like computer hackers, NMR jocks also survive on pizza and coke, except the food and drink are paid for with cash, as their credit cards are usually erased by the magnets. (Try and explain this to the pizzeria owners.)

Next, we will examine a few examples of NMR spectroscopy of ocular tissues - before entering the field of MRI (magnetic resonance imaging).

8.1 Brain is an extension of the eyes

2008-05-13T17:55:00.010-04:00

(The visual pathway - looking from the base of the brain)

The visual pathway of course travels all the way from the eyes to the back of the brain (see above, in red). Anything untoward that occurs along the pathway will manifest as an ophthalmic problem. And in addition to the second cranial nerve, the extraocular muscles are innervated by the third, 4th and 6th cranial nerves. Plus, the pupillary responses are controlled by yet another set of nervous pathway. Neuro-ophthalmology is indeed a very interesting and challenging field. With very simple tools, such as a penlight, an occluder, a tangent screen and/or perimeter, definitive diagnosis often can be reached. With time, more tools become available. And brain imaging is now consisted of many modalities:

(From socialfiction.org)

These modalities include the old standby CT, the re-vamped PET, the anatomical MRI and the more powerful fMRI (f=functional), and a close relative of fMRI, the Optical Imaging of Intrinsic Signals (OIS). (Note: Cryo is imaging of frozen brain in slices, not for the living.)

Of these, we will go into more about MRI, in order to discuss important subjects such as "perivenous syndrome" and "brain plasticity". And to understand MRI, we will need to start from its humble beginning, NMR. Next post is therefore "8.2 NMR".

Happy Mother's Day

2008-05-10T11:22:00.005-04:00

a Happy Mother's Day to All

To my Burmese friends, SA and Moe: Hope you and your families are all OK.

Update (12 May 2008): Please remember the earthquake victims in Sichuan, China

7.33 Too much oxygen?

2008-05-04T11:28:00.008-04:00

The magnificent Brooklyn Bridge, the 5,989-ft long suspension bridge linking Brooklyn and Manhattan, opened for business on May 24, 1883, after 13 years of construction. To lay the foundation, the workers must work in caissons under the East River, with compressed air pumped in from the surface. A lot of workers suffered from decompression diseases, i.e., the "bends" which also afflict deep-sea divers if the decompression rate was too fast. Air bubbles are trapped especially in the joints causing severe pains and injuries. However, no one seemed to have complained of blurred vision during that time. Perhaps in a harsh working environment, vision was not a first priority issue. In fact, the complaint of blurred vision should probably have been noted and registered.

A 2002 report in Japan indeed shows myopia in some workers after completing 11 weeks (4 days/week) of work in pneumatic caissons. When they were examined 6 months later, a recovery towards hyperopia was found. The speculation was that this transient myopia was caused by excessive oxygen which somehow altered the structure(s) of the eye. In fact, the same myopia shift has been found in patients undergoing hyperbaric oxygen therapy.

(The inside of a hyperbaric chamber - from hyperchamber.com)

Hyperbaric oxygen therapy has a long history. It started as a treatment for the bends and logically for carbon monoxide poisoning. Now it is used to promote wound-healing and inhibit recalcitrant anaerobic bacterial infection (for example, in gangrenes). In another 2002 publication in Acta Ophthalmologica Scandinavica, with a regimen of 95-min sessions at > 95% oxygen at 2.5 atmospheres given daily Monday to Friday for a total of 30 sessions, the patients exhibited a 0.58D of myopia shift. There was no change in the axial length; although a "minimal" yet significant change in keratometric readings was noted. The investigators suspected alterations in lenticular refractive index and/or curvatures.

And in a 2006 case report from Norway: A 58-year-old man showed a hypermetropic shift, which followed the myopic shift after each of two series of treatments. The maximal refractive amplitude was 3.00 D (range -1.37 D to +1.62 D) in the right eye and 2.75 D (range -1.25 D to + 1.50 D) in the left eye. And refraction stabilized after 1.5 years to pretreatment values.

So what's going on? Given the paucity of experimental data, a reasonable speculation is a change principally in the refractive index of the lens nucleus.The best approach is probably photo-documentation with a Scheimpflug camera supplemented with ultrasound A-scan, corneal topography, and cycloplegic refraction. Scheimpflug images allow lens density as well as anterior lens thickness determination:

Some investigators have proposed that the high oxygen might have caused protein aggregation in the lens nucleus, as part of the oxidative damage, hence the increase in the refractive index. However, by and large, changes in lens protein structure are irreversible. This does not agree with the transient nature of the myopia. Alternatively, it may just be a simple increase in lens thickness owing to an increasing intake of sodium and/or loss of potassium, i.e., an ionic pump malfunction from oxygen toxicity.

All guesses. Someone out there should pick up this project.

7.32 Nutritional glaucoma

2008-04-28T15:46:00.008-04:00

The above is Mexican poppy (botanically: Argemone mexicana) or Satyanashi. Its seeds give out a poisonous oil, the argemone oil (aka the katkar oil), which is indistinguishable from dark mustard oil.

In northern India, mustard oil is used for cooking. If some unscrupulous merchants were to adulter mustard oil with argemone oil, then an epidemic poisoning would ensue (known as Epidemic Dropsy). In fact, the first case was reported in Bombay in 1877. And more recently in Delhi in 1998 when 2,552 cases were reported and 65 died.

Sanguinarine, one of the 2 alkaloids found in argemone oil causes dilation of blood vessels/capillaries. The patients suffer general edema (i.e., dropsy) owing to leakage of plasma into the surrounding tissues. This leakage also involves the blood vessels of the uvea, thereby hindering the uveal outflow. As a result, a special form of glaucoma develops, which persists even after the poison is excluded that often requires medical/surgical intervention.

Fortunately, Epidemic Dropsy is largely a thing of the past. However, nutritional glaucoma can appear in a totally unexpected manner. In a recent case reported in Taiwan (March, 2008), a 40-year-old lady developed blurred vision with high IOP (30mmHg) - after a one-root-per-day consumption of ginseng for one month. Medicinal ginseng is quite expensive, in fact, not everyone can afford such a regimen. So, there is no epidemic here. It was speculated that high-dose ginseng might have altered the viscosity of the aqueous humor causing a sluggish outflow.

(Korean ginseng, the ones with the highest quality - the"天字第一號 (Heaven No 1)" - can fetch USD10,000 per root.)

After the ginseng runs its cause, recovery, most likely total, is expected for this particular patient. Follow-ups are of course recommended.

Sometimes the eye doctors must connect the dots and become a capable medical sleuth.

7.31 Couching

2008-04-06T18:25:00.013-04:00

The above is the cover page of a 17th Century reprint of one of the Chinese ophthalmology textbooks, written presumably by Sun Shi Ni (孫思邈) in 682AD. In which, a form of cataract surgery, known as couching with a golden needle (金针拨障术), was laid out in great detail.

During the Tang Dynasty (618-907AD), this technique was practiced by physicians from India. And it was apparently quite well-accepted. In fact, Poet Bai Ju Yi (白居易, 772-846) was known to mull over whether to have his cataracts treated medically or surgically:
"案上漫铺龙树论,合中虚贮决明丸.人间方药应无益,争得金蓖试刮看."
(On my desk, there is this ophthalmology book,龙树论, next to it a box of pills, 决明丸. If the pills do not work, I'd have to go under the golden needle, 金蓖, quick.)

And around the same time, Philosopher Liu Yu Xi (刘禹锡, 772-842) wrote a thank-you poem to his cataract surgeon, a monk-ophthalmologist from India:
"看朱渐成碧,羞日不禁风.师有金蓖术,如何为发蒙."
(Everything red is turning blue, I am now also photophobic and sensitive to the wind. Thank you for the couching needles, how that cut through my fogginess.)

Couching of cataracts with a needle was reported by a Hindu surgeon Susruta at around 5th Century BC. The triangular lancet (for corneal incision) and the couching needles are shown here:
You can almost find some similarities to modern-day instruments for ophthalmic surgery:
Is the procedure safe? Relatively speaking, yes. Wounds from, e.g., paracentesis (puncture of the peripheral cornea with a needle, usually to withdraw some aqueous humor), or small-incision cataract surgery rarely require sutures. The corneas self-heal. And if the cataractous lens stays in one piece, with little or no injuries to the iris or the ciliary body. The outcome can be quite favorable. However, in most cases, the complication rates can reach as high as 50%.

One might imagine that couching was performed under unsanitary conditions. By modern-day standards, most likely yes. Yet in the Synopsis of Ophthalmology (目经大成) compiled by Huang Ting Jin (黄庭镜) in 1774, the procedures listed eight steps. And the very first one called for a thorough cleansing of the surgical area around the eye.

In areas with no access to formally-trained surgeons and operating facilities, or for simple economical reasons, couching is still being practiced today. In a 2001 review of the surgical outcome of 1,274 eyes in a rural area of China, it was found that with proper post-op care, couching was no less efficacious than extra-cap surgery. In fact, the prevalence of blindness dropped from 5 to 2% and low vision from 24 to 6%. The key is then post-op care. However, in remote areas of, e.g., West Africa, couching as practiced by traditional healers, even the safety maybe compromised.

There is such a long Sino-Indian history of cataract couching. It is therefore mystifying to note a Yale-educated missionary doctor practicing in China, Peter Parker, MD (1804-1888), who wrote that

"Diseases of the eye were selected as those the most common in China [in the late Qing Era]; and being a class in which the native practitioners were most impotent, the cures, it was supposed, would be as much appreciated as any other."

And one of his more successful "cures" was none other than cataract couching, the very same technique practiced by Susruta and his followers throughout the ages, on different continents, and in many cultures including China.

To complete the discussion, couching can be either sharp (more common, with a needle) or blunt (by massaging the anterior portion of the cataractous eye). Blunt couching works only if the lens zonules are almost all disrupted.

7.30 Poetic review

2008-03-25T20:23:00.021-04:00

It has been stated: "Science is for those who learn; poetry, for those who know." ~Joseph Roux (1725-1793), Meditations of a Parish Priest

Such a great topic for fMRI study of the brain, too. Perhaps when they think, scientists and poets activate different areas of their brains, and the areas do not usually overlap. If true, then Galileo would not have been able to do the following:

"If Galileo had said in verse that the world moved, the inquisition might have let him alone." ~Thomas Hardy OM (1840-1928)

Often the progress in science results in unintended cultural consequences. A good example is cited here:
The above is a poem celebrating the mid-autumn moon. It was written by Su Shi (蘇軾,1037-1101) invoking the Chinese folklore of Chang-Er (嫦蛾) who flew to and resided on the moon - after eating a Heavenly Peach. In 1969, Neil Armstrong's a "giant leap for mankind" moon-landing spoiled it for all, forever.
This poem still retains its popularity; however, now only the last stanza makes sense, i.e., the moon is seen/shared by all even if they are separated by a vast distance.

The eye in fact figures prominently in numerous poems. Let's see if science has changed anything. We'll now try some American poems:

"Thy fingers make early flowers" by e. e. cummings (1894-1962):
thy whitest feet crisply are straying.
Always
thy moist eyes are at kisses playing,
whose strangeness much
says; singing
(though love be a day)
for which girl art thou flowers bringing?

Moist eyes, huh? See "4.4 Dry eye" and "4.10 Itchy eyes" to understand why some eyes are overly "moist".

"Dust in the Eyes" by Robert Frost (1874-1963):
If, as they say, some dust thrown in my eyes
Will keep my talk from getting overwise,
I'm not the one for putting off the proof.
Let it be overwhelming, off a roof
And round a corner, blizzard snow for dust,
And blind me to a standstill if it must.

The immediate physiological response to dust in the eyes is profuse tearing. This condition often requires flushing the eyes with water or normal saline. Prophylactic antibiotic/anti-inflammatory eyedrops may be needed as well. And if the dust happens to be alkaline in nature, e.g., lime, a quick referral to an eye doctor is not an overwise next move. (On the other hand, blinding snow is obviously harmless, unless you are driving on I-93 North.) For more, see "7.17 Wink, wink".

Some poems about death and the eye are downright spooky:

"I’ve seen a dying eye" by Emily Dickinson (1830-1886):
I've seen a dying eye
Run round and round a room
In search of something, as it seemed,
Then cloudier become;
And then, obscure with fog,
And then be soldered down,
Without disclosing what it be,
'T were blessed to have seen.

Corneal edema immediately before death? This is quite unlikely. Fresh fish have clear eyes which become cloudy with prolonged storage on ice - perhaps this is what Dickinson was referring to? See also: "7.1 Cold fish eye".

"The Hollow Men" by T.S. Eliot (1888-1965):
The eyes are not here
There are no eyes here
In this valley of dying stars
In this hollow valley
This broken jaw of our lost kingdoms
In this last of meeting places
We grope together
And avoid speech
Gathered on this beach of the tumid river
Sightless, unless
The eyes reappear
As the perpetual star
Multifoliate rose
Of death’s twilight kingdom
The hope only
Of empty men.

Transplanting the whole eyes? See "7.21 Never say never?" for details. Plus "7.8 Now you see it, now you don't" just to cover all grounds.

What about poems from the East?

"Fallen flowers" by Li Shan Yin (李商隱, 812/3 - 858AD):
高閣客竟去, 小園花亂飛 (My best friend has just left, the flowers are flying/dispersing in the small garden)
參差連曲陌, 迢遞送斜暉 (From the tortuous paths, I now send off the evening sun)
腸斷未忍掃, 眼穿仍欲歸 (Too sad to sweep off the fallen flowers, still hoping to see the friend's return)
芳心向春盡, 所得是沾衣 (My heart is broken as the abrupt end of Spring, only the petals remain on my clothing)

It can be an accommodation/focusing issue to see so intently. See "7.20 Mr Sulu, take us home" for explanation.

"Wan Shi Sa (浣溪沙)" by Wang Guo Wei (王国维, 1877-1927):
山寺微茫背夕曛,鸟飞不到半山昏.上方孤罄定行云. (In the dim dusk, it was hard to make out the temple, for the birds to fly half-way up the hill; the fleeing clouds were anchored in place by a lone prayer drum)
试上高峰窥皓月,偶开天眼觑红尘,可怜身是眼中人. (I tried to climb up to the mountaintop to peek at the luminous moon, in a blink of the heaven's eye, I could see the world, and realized sadly that I was also part of this world.)

Heaven's eye? The Hubble telescope? Maybe this:
For less powerful telescopes, see "7.27 Thousand mile eye".

Clearly, the word "eye" sets off a reaction of clinical interpretation that overtakes the entire poetry. Essentially, the one-tracked mind at work. Although, we suppose Carl Sandburg (1878-1967) was being honest who said, "I've written some poetry I don't understand myself."

More to the point, though, is this:
"You can't write poetry on the computer." ~Quentin Tarantino (1963-present)
(Much less translate.)

In any case, we now call for an fMRI brain study. Poets are invited.

7.29 HAL 9000

2008-03-22T17:08:00.018-04:00

Of course you all recognize this scene from "2001: A Space Odyssey" with Frank Poole (l) and David Bowman both hiding in a pod, discussing HAL 9000's increasingly erratic behavior. Unfortunately, HAL was programmed to read lips and "he" was therefore able to learn the astronauts' intention of pulling his plug, and took steps to eliminate both humans. You can see the cyclopean HAL outside the oval window, and a close-up of HAL's eye:
Notice it does not has a clearly defined pupil, unnecessary in a controlled environment such as the interior of a spaceship, we suppose. In George Lucas's Star Wars, C3PO does not even have pupils only vertical slits.
On the other hand, the eyes of the Terminator (by James Cameron et al, 1984) are quite interesting:
A dying Terminator was actually shown with pupil reflexes gradually dimming with the ebbing (machine) life (when it was being crushed by a hydraulic press). It is quite obvious that careful thoughts have been put into the movie plot. Finally, in "I, Robot (2004, based on Issac Asimov's original work)", human-like eyes appeared:
The ultimate is of course an android named Commander Data of Star Trek TNG; although "he" is simply too human to be credible. It was probably too costly to construct a life-like robotic prop for the TV series.

In real-life, machine vision (MV) using artificial intelligence (AI) techniques, such as expert systems, fuzzy logic, inductive learning, neural networks, genetic algorithms, and swarm intelligence, is no longer a nascent field. For automation, MV has applications in manufacturing of semiconductors, electronics, pharmaceuticals, medical devices, automotive and consumer goods, and also in packaging and facial recognition.

The next challenge is the design and construction of autonomous robots (as opposed to "robots" remotely controlled by humans). In fact, true robots are beginning to make its presence felt. It is, however, a bit disconcerting to see Asimo (by Honda) possessing no discernible eye structures at all:
What gives, really.

Arthur C Clarke (1917-2008), the sci-fi visionary, was actually right - HAL-like lip-reading machines are now being developed. They will be capable of translating audio speech into visual speech, based on light reflected from the moving parts of human speech and the reflection collected by, naturally, machine vision. And the purpose for these machines? Hmm, a very good question.

Just to add more intrigue: Each letter of HAL (Heuristic Algorithmic Computer) is one alphabet before IBM, and the significance of which is still unclear.

7.28 Optic ischemia

2008-03-16T11:52:00.015-04:00

Did you know that Johann Sebastian Bach (1685-1750; portrait on a stamp, mit one of the Brandenburg Concertos, see above) was blinded by acute angle-closure glaucoma a few months before he died? Also, Messrs Jose Feliciano, Stevie Wonder, and the late Ray Charles all suffered from congenital glaucoma? And former Minnesota Twins baseball all-star, the Hall-of-Famer, Kirby Puckett (1960-2006) was blinded by glaucoma in his right eye?

What kind of damages you ask? Well, the definition of glaucoma especially that of OAG (open-angle glaucoma) keeps changing. It is a sign of progress; although, the answer to "what is glaucoma?" is no longer straightforward. Perhaps in the next few years, we'll know the whole story. For now, we can only work with what we have.

We'll narrow down the discussion a bit to only open-angle glaucoma: OAG has traditionally been regarded as a topical (as opposed to a systemic) issue. In other words, if the intraocular pressure (IOP) is high, then the eye may suffer pressure-induced damages to the retina and the optic nerve, in the form of ischemia. The treatment is then to normalize the pressure using pharmaceuticals. The problem is in some cases, medicine alone seems ineffective, the disease process continues nonetheless. In low-tension glaucoma, the IOP is actually normal, yet the glaucoma-related ocular damages still occur. So, something else apparently is going on, but what is it? Is it associated with systemic circulation? Shall we now institue systemic neuro-protection? And to complicate the situation even further: It also should be noted that a high IOP does not always lead to OAG.

Even more basic: How do we know optic ischemia is involved? Or more accurately, how do we measure the oxygen level in the optic nerve under high IOP? Short of inserting an oxygen-sensing electrode into the optic nerve itself, there isn't really any good way. One can opt to study animal models or examine post-mortal glaucomatous eyes. However, to perform the measurement in the humans in vivo, a special technique is needed. This is known as T2*(pronounced T2-star)-weighted or BOLD (Blood Oxygen Level Dependent) MRI - used in functional MRI of the brain. This technique takes advantage of de-oxygenated hemoglobin being a paramagnetic which disturbs the homogeneity of a magnetic field. And an increase in oxyhemoglobin, i.e., blood oxygenation, reduces this paramagnetic effect, hence an increase in the MR signal intensity.

We have invited some volunteers for a BOLD-MRI study. Using a home-made surface coil for the eye/orbit and T2* MRI performed before and after a bolus injection of Diamox, a vasodilator via its pH lowering effect. The change in MR signals in the optic nerve near the optic disc is then determined. The results are tabulated below:

Change in image intensity in the optic nerve of normal and glaucomatous patients

Diagnosis	Time after Dx	IOP (mmHg) at MRI	Treatment history	Residual Visual Field	Optic Nerve (% change)
Normal	--	15-16	none	--	+12.1 ± 2.2 (N=4)
POAG atypical, unilateral (IOP=48 at time of Dx)	2 years	17-27	0.25% Timolol	Upper temporal quadrant	+10.6
POAG	3 years	23-29	0.5% Timolol	Lower temporal quadrant	+0.0
POAG	18 years	20	0.5% Timolol	Cetral 10° +lower temporal quadrant	-10.5
POAG Secondary to trauma?	23 years	20	argon laser trabeculotomy + 0.5% Timolol	Central 5-10°	-14.9

Note: The 4 normal volunteers are all ultra-dedicated ophthalmology residents. And the study has been approved by the IRB.

Just look at the last column. Intriguing results, we might add. They essentially confirm that in the optic nerve of the living humans, as the glaucoma advances, blood oxygen level decreases. In other words, ischemia!!

Granted this is a small study. A large scale study will have to await further developments in MRI technology: (1) even higher magnetic fields (e.g., > 1.5 Tesla) to increase the signal intensity and shorten the scan time; and (2) much reduced scanning costs to justify the utilization of MRI of the eye/orbit. There has been a recent proposal that the glaucomatous changes go beyond the eye, all the way through the optic track, the LGN, ultimately to the visual cortex. Then T2* MRI will prove the only practical means for assessing ischemic changes in the whole visual pathway.

Note: For those interested, the seminal paper on fMRI (i.e., Echo-planar BOLD-MRI) is this one:

Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, Cheng HM, Brady TJ, Rosen BR: Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci (USA) 1992;89:5675-5679.

7.27 Thousand mile eye

2008-03-09T08:44:00.017-04:00

Baron Munchausen's friend Adolphus and one of the Southeastern Chinese deity Mazu's (媽祖) two guards, Chien Li Yan (千里眼), both can see objects miles away. These eyes are known as Thousand Mile Eyes. So telescopic vision is a common interest of sorts for both East and West. The real telescope did take a long while to become a reality, though.

Notice in this scene illustrated by Mr Winslow Homer (1836-1910) for Harper's Weekly April 25, 1863 Issue - The Approach of the British Pirate "Alabama" (picture from www.sonofthesouth.net) - the tall gentleman is looking through a Galilean telescope trying to spot the pirate ship.
Galilean? Somehow the invention of the telescope was credited to Galileo of the University of Padua. This is not historically correct because the first documented working telescope was delivered in the last week of September, 1608, by Hans Lippershey from Middelburg in Zeeland to Prince Maurice of Nassau in The Hague. It was not until May, 1609, Galileo was able to quickly fashion an 8X and a 20X telescope to show around publicly. And his reputation grew as a result.

The Galilean telescope is simple to construct. You can put together one, for example, by using a long cardboard mailing tube (5cm in diameter and 110cm long), a +0.75D convex (i.e., plus) lens as the "objective", and a concave (i.e., minus) lens as the "eyepiece/ocular" (power = -6.6 diopter). Cut the lens diameter down to around 5cm to fit in the tube. With some tinkering and adjustment of the focus, you got yourself an almost 9X telescope.

Telescopes are often used in the correction of low vision, obviously not what Galileo et al intended at first. Low vision simply means the patient's central visual field normally with a visual acuity of 20/20 or better is lost, only the para-central or the peripheral retina can now be used for vision. [Note: Patients with retinitis pigmentosa - true Night Blindness - retain a very restricted central visual field and the central vision can be poor as well]. In order to improve vision, for viewing distant objects, the magnification can be achieved through the use of the telescope. And for near tasks, an assortment of magnifiers are available. Magnification is of course what the para-central/peripheral retina needs in order to see well.

The example below is an adjustable 3X spectacle-mounted (clip-on) telescope which also can be used hand-held. It has a plastic casing for low weight. And with a reading cap, it doubled as a reading magnifier for a normal reading distance of around 14-16 inches.

Still kind of bulky, huh? Let's see: the Galilean telescope consists of only two lenses, what if we put one in a spectacle frame, and the other worn as a contact lens? This idea has not escaped the attention of some eye doctors. With the advent of high-index spectacle lenses and high-power soft contact lenses, this is now readily achievable. For those who are interested, this is how it is done:

Let's say you need an around 1.7X telescope, use a contact lens of -50D (i.e., -20mm focal length) and a spectacle lens of +30D (i.e., 33.3mm focal length), then the vertex distance is -20+33.3 = 13.3mm. The vertex distance is the distance between the spectacle lens and the cornea (normally around 13.5mm), and in the present case, give and take because of the lens thickness. And the magnification is 50/30 = 1.66X.

By lengthening the vertex distance just a bit, the power of the lenses can be reduced. The added advantage is lower power lenses are easier to make correctly. So, for a vertex distance of 15mm, the following combinations are possible (lens power in diopter):

Objective	Ocular	Magnification
+15.37	-20	1.3
+20.7	-30	1.45
+25	-40	1.6
+30	-50	1.75
+31.62	-60	1.9

You can play with the numbers and construct your own table.

Lens weight is a major concern - heavy lenses become mis-aligned quickly and the "Contact-lens Telescope" can no longer achieve the desired magnification. High-index light-weight spectacle lenses therefore must be used. RGP corneal contacts are not stable enough, scleral/macro lenses maybe a better alternative [to be verified]. Large-diameter soft lenses usually work out well; although the power must be as accurate as possible.

As usual, not all patients are suitable candidates.

Lest we forget, mini-telescopes also can be implanted in the center of the corneas - to restore vision of patients with retinal damages, such as AMD. A recent clinical trial has proved efficacious. However, the FDA eventually did not approve the device because of the concern of corneal endothelial cell loss - which occurred at a higher rate than the normal age-related loss.

Back to the drawing board.

7.26 Eye-tooth, tooth-eye

2008-03-02T12:03:00.019-05:00

News headline: "Blind Man Regains Sight After Doctors Implant Son's Tooth in His Eye" (Foxnews.com, 28 Feb, 2008)

So what is this all about? Well, there are always surgeries of the last-resort in any field.

As far as the eye, it is always a shame when only the cornea is messed up while the rest of the eye is intact. The logical next step is corneal transplant, typically around 90% success. What about the other 10%, though? They still need to see, don't they? Luckily, there are always surgeons who are willing to tinker, explore, invent, experiment, and cure. We will cite a few examples in this post.

Before we did that, a quick review on what could cause the corneal grafts to fail. Not surprisingly, the major one is allograft rejection, followed by increased intraocular pressure, infection (excluding endophthalmitis), and ocular surface problems. Pre-existing conditions such as diabetes and glaucoma increase the endothelial cell loss hastening the demise of the transplanted cornea. And chemical burn and end-stage dry eye (the latter as part of, e.g., Stevens-Johnson syndrome) both involving ocular surface changes also are major factors in graft failure. Any of the above leads to undesirable outcome, even multiple corneal transplants would not take.

The alternative is then to implant optically active prosthetics directly into the cornea. And if the retina is functioning well, then the patients can regain functional vision often at 20/40 or better.

First example is the Boston Keratoprosthesis developed by Dr Claes Dohlman of Massachusetts Eye and Ear Infirmary in Boston (a schematic is shown below):

The locking ring is titanium, it therefore does not interfere with MRI. This device is first fitted into a donor cornea, then the whole assembly is transplanted as that in normal penetrating keratoplasty. And a therapeutic contact lens is then fitted over the implant, together with life-long use of antibiotic eyedrops. The outcome is quite dramatic, interested readers can look up a news article "No time for tears" in the 5 Nov 2007 issue of Boston Globe.

The post-op appearance (without the contact lens) is shown below:

The second example is OOKP (osteo-odonto keratoprosthesis) developed by the late Dr GianCarlo Falcinelli of San Camillo Hospital in Rome. In patients with severe dry eyes, Boston Keratoprosthesis may not perform well owing to the need for a contact lens - hence the need for adequate tear fluid production. These patients will have to have an eye-tooth implant. Eye-tooth = the upper canine tooth because it situates near the eye. Only a few surgeons in the world are qualified to perform this procedure that include Drs Christopher Liu of Brighton, England, Günther Grabner in Salzburg, Austria, and Konrad Hille of Homburg/Saar, Germany. And a team led by Dr Donald Tan of Singapore National Eye Centre is also active in OOKP implantation. Other eye centers may have also followed suit, check your local listing.

OOKP implant is a two-stage process. The first involves the repair of ocular surfaces using mucosal linings from the patient's cheek, removal of a canine tooth with part of the jaw bone, the tooth is fashioned into a bolt-shaped structure or a flat lamina with a hole drilled in the center, an optical cylinder is then inserted and cemented in the hole. The whole assembly is then implanted in the patient's cheek or under the fellow eye to allow growth of blood vessels. The second stage involves removal of anterior ocular contents and finally replacement with the tooth-bone-cylinder complex, now the tooth-eye.

Not all patients are surgically eligible for the procedures described above. When done, these last-ditch efforts often yield miracle-like results. These surgeons are a special lot, so are the patients who often have already endured multiple surgeries.

7.25 Gee, I feel faint

2008-02-27T11:52:00.015-05:00

(Geronimo Mercuriale, 1530-1606 -from www.sahha.gov.mt)

In 1580, Geronimo Mercuriale formulated the concept of syncope and demonstrated that it was associated with a slow pulse rate: "Ubi pulsus sit rarus semper expectanda est syncope".

The precise cause of syncope, commonly known as fainting, is hard to pin down. The mechanisms, however, are quite well-known, for at least a few hundred years. Essentially, people faint because of a mixture of (1) cardiac inhibition from enhanced parasympathetic tone, and (2) vasodilation from sympathetic withdrawal. Simply put, a slowed heart rate that reduces blood flow to the brain thereby causing a patient to faint.

Like migraine headaches, there are many triggers for syncope - officially "vasovagal syncope", for example, stress, standing upright for too long [known to happen to the Guards at the Buckingham Palace], pain, the sight of blood, hunger, prolonged hyperthermia, just to name a major few. For a few seconds, the patient feels light-headed, experiences nausea, sweating, ringing in the ears, and visual disturbances, before losing consciousness. The patient then keels over and this is when the injuries occur.

(Changing of guards - before somebody fainted.)

(Avoiding the sight of blood, Mr Patroclus?)

Feeling faint in an eye doctor's office? Of course that happens. This is often confused with feeling dizzy or having blackouts; both of which need to be neurologically evaluated. And it is not quite the "true syncope" but the "near syncope". In other words, the patient has all the signs and symptoms but stops short of passing out. This occurs usually from four activities: (1) contact tonometry (both applanation and indentation - the instruments must touch the cornea to get IOP readings); (2) first-time contact lens trial; (3) slit-lamp biomicroscopy; and (4) insertion of punctal plugs. In all situations, once the patient's eyes or eyelids are touched by the tip of the tonometer, by the doctor or an assistant when inserting a contact lens, or by the doctor's pulling down the patient's lower eyelid for a closer view of the palpebral conjunctiva or the puncta, usually at the slit-lamp, vasovagal reflex kicks in within minutes. Interestingly, most patients are young and healthy, possibly for the first time in their lives, their eyes are now manipulated by a stranger. The eyes/eyelids are indeed under some mechanical pressure albeit quite minor yet the physical reaction is quite dramatic.

First aid is to have the patient lie down while raising his/her feet or at least lower the head, so the brain can get back some much-needed blood.

Call an ambulance? Nah. The patient recovers on his/her own within minutes. Although it is not unheard of that a complete cardiac work-up is ordered if the patient ends up in the ER. And at least one patient brought a lawsuit against one eye doctor for some unspecified damages and emotional stress (remember: this is the United States of America, home to many personal injury barristers).

Some patients are disappointed that they probably won't be able to wear contacts, ever. Some are a bit embarrassed yet are quite happy to have a tale for their loved ones. Fortunately, vasovagal syncope, true or near, is never fatal.

Think about this: For patients with a history of having trouble instilling eyedrops or inserting contacts, it may not be a matter of dexterity but a mild form of vasovagal reaction.

7.24 You have small eyes

2008-02-24T16:53:00.044-05:00

(A General Electric 1.5 Tesla Signa MR scanner with a head coil inside the bore)

Enough fun with the Singapore sling, now we move on to something intriguing.

Despite the outward appearance, all emmetropic and hyperopic eyeballs are pretty much the same in size. The myopic eyes are indeed a little bigger. And once in a while, we need to inform a patient, "You have small eyes." This is not being impolite, but to point out the presence of nanophthalmos (dwarf eye). Nanopthalmos is not to be confused with microphthalmia (small eye); the latter is a congenital malformation with other developmental issues, often from fetal alcohol syndrome or viral infection in utero. Patients with hereditary nanophthalmos may have a defective gene on Chromosome 11; otherwise, they are developmentally normal.

Nanophthalmos with uveal effusion is a nasty condition first described by Dr Robert Brockhurst of Boston, Massachusetts, in 1974. These patients often develop narrow-angle glaucoma that prompted surgical intervention. Unfortunately, this also results in secondary retinal and choroidal detachment - owing to uveal effusion. Further repair is ineffective and sometimes choroidal elevation can be mistaken as intraocular tumors. So the recognition of nanophthalmos is important in order to manage it correctly.

Maybe this is a good time to look at the size of human eyeballs. We have been able to convince some patients to volunteer for MR imaging of the eye:

Table I. Refractive error of patients and volunteers (5 eyes/group).

Type of Eye	Mean ± SD (diopter)	Range (diopter)
Nanophthalmos (phakic)	+10.42 ± 6.22	+4.50 – +18.50
Hyperopia	+3.42 ± 0.66	+3.00 - +4.50
Emmetropia	+0.21 ± 0.25	-0.25 - +0.50
Myopia	-10.25 ± 4.31	-6.25 - -15.50

Notice the nanophthalmic eyes all have very high hyperopia which in fact is one of the diagnostic indices.

And from MR images, it is possible to calculate the size of the eyeballs in 3D:

Table II. Ocular dimensions (mean ± SD mm) determined from MR images.

Type of Eye	Axial¹	Equatorial¹	Coronal(H)	Coronal(V)
Nanophthalmos	18.1 ± 2.0²	19.0 ± 2.6²	19.3 ± 3.0²	18.2 ± 2.5²
Hyperopia³	23.1 ± 1.0	24.1 ± 0.5	23.8 ± 0.3	23.3 ± 1.4
Emmetropia	22.9 ± 1.3	23.9 ± 1.2	23.9 ± 1.5	23.0 ± 1.9
Myopia⁴	28.5 ± 1.0	27.1 ± 1.5	28.3 ± 0.5	27.4 ± 0.7

¹The equatorial lengths are significantly greater than the axial lengths: paired t-test P=0.006 and 0.025 for emmetropia and hyperopia, respectively. For nanophthalmic eyes, P=0.1 and for myopia, P=0.2.
²Unpaired t-tests between nanophthalmos and emmetropia in all dimensions, P<0.02.

3No difference between hyperopia and emmetropia.
⁴Unpaired t-tests between myopia and emmetropia in all dimensions P<0.01.

Clearly, myopic eyes are big. And in contrast, nanophthalmic eyes are much smaller which is the hallmark of nanophthalmos.

If we look at the anterior segment closely:

Table III. Anterior segment dimensions (mean ± SD mm).

Type of Eye	Ant. Chamber Depth	Lens Thickness	Lens Diameter
Nanophthalmos	3.0 ± 0.1¹	5.3 ± 0.8²	8.5 ± 0.4
Hyperopia³	3.1 ± 0.3	4.6 ± 0.6	8.7 ± 0.4
Emmetropia	3.0 ± 0.2	5.0 ± 0.8	8.4 ± 0.4
Myopia⁴	2.6 ± 0.6	4.0 ± 0.3	9.4 ± 1.3

¹Unpaired t-test when calculated as % axial length between nanophthalmos (16.5±2.5) and emmetropia (13.0±1.1): P=0.025.
²Unpaired t-test when calculated as % axial length between nanophthalmos (29.5±7.2) and emmetropia (21.7±2.9): P=0.06.
³No significant difference between hyperopia and emmetropia.
⁴No significant difference between emmetropia and myopia.

Hmm, the anterior chamber depth and the lens size in nanophthalmos are both similar to normal emmetropic and hyperopic eyes. So what else has gone wrong?

Table IV. Choroidal and scleral thickness (mean ± SD mm).

	Axial		Vertical		Equatorial
Type of Eye	Choroid	Sclera	Choroid¹	Sclera	Choroid	Sclera²
Naophthalmos	0.7±0.3	0.7±0.3	0.7±0.3	0.5±0.2	0.6±0.3	0.7±0.3
Hyperopia³	1.0±0.0	0.7±0.3	0.4±0.2	0.4±0.2	0.5±0.3	0.4±0.3
Emmetropia	0.9±0.2	0.6±0.3	0.5±0.1	0.4±0.2	0.5±0.2	0.4±0.2
Myopia⁴	N.M.	N.M.	N.M.	N.M.	N.M.	N.M.

1Unpaired t-test between nanophthalmos and emmetropia: P<0.09; when calculated as % of total vertical axial length, nanophthalmos (4.0±1.8) vs. emmetropia (1.9±0.5): P<0.04. 2Unpaired t-test between nanophthalmos and emmetropia: P<0.08; when calculated as % of total equatorial axial length, nanophthalmos (3.4±1.4) vs. emmetropia (1.6±0.5): P=0.03. 3No difference between hyperopia and emmetropia. 4N.M. - Not measurable. Thicknesses less than the in-plane resolution of 0.31mm.

Ah, so that's it: the equatorial sclera is the thickest in the nanopthalmic eyes. It is almost like all eyes are given the same amount of building materials. Smaller eyes are constructed with thicker walls while larger (myopic) eyes with thinner walls. Thick equatorial sclera chokes off blood circulation through the vortex veins (each eye has 4 or 6 of these). The only effective treatment for relieving high eye pressure is therefore sclerostomy around the base of the vortex veins.

For those who have patiently read through the above, a bonus for you. We'll now show you how to perform high-resolution MRI of the eye (also the methodology used in the study described above):

MR imaging was conducted using General Electric 1.5 Tesla Signa body scanners. A home-made 1.25-inch receive-only surface coil tuned to the proton frequency of the imagers was placed over the eye of interest. [Note: the factory 3-inch TMJ coil also can be used.] The coil was constructed with variable capacitors that allowed tuning and matching. A sagittal head image series using an FOV of 20 mm or more was acquired to locate the eye. Slice selection in the axial plane was then determined using graphic prescription. Multi-slice images in the axial and coronal planes were obtained (usually 8-9 slices/plane/eye) using a T1-weighted spin-echo sequence with for example, TR/TE = 400/20 msec with an image resolution of 0.31 x 0.31 mm and a slice thickness of 3 mm (in this case, the image acquisition time was 4.5 min). Image slices was selected by aligning imaging planes as parallel to the antero-posterior axis as possible.

7.23 Singapore sling

2008-02-17T12:26:00.017-05:00

Please, Singapore is pronounced Sin-ga-po', not Sin-ga-poah. And Singapore sling is a "mysteriously refreshing drink" in the tropical sun, not a run-of-the-mill cocktail at your local pub. There are many imitations, though. For DIYers, this one, from drinkmixer.com, is quite genuine:

1 oz gin
1/2 oz cherry brandy
4 oz pineapple juice
1/2 oz lime juice
1/4 oz Cointreau® orange liqueur
1/4 oz benedictine herbal liqueur
1/3 oz grenadine syrup
1 dash Angostura® bitters
Combine all in a shaker, fill with ice and shake until the shaker is well frosted. Strain into a tall glass and garnish with a slice of pineapple and cherry. No tiny umbrellas of course.

Better yet, go down to the Long Bar at Raffles Hotel, sit in the rattan wicker chair and have the sling with roasted-in-shell peanuts. You'll forget where you are.

Ah, but we do remember: Singapore is a prefect place to investigate the pattern of cataract formation. The Merlion City is sitting practically on the equator (1°N) with 12 hours each of day and night, with an annual temperature average of 26.7°C and a UV index of 10-13. These couldn't be good for the eyes? Yet, sunglasses and broad-rimmed hats are apparently not in fashion (see image below).

See, only one guy with sunglasses and none wears a hat.

The Merlion? Here-lah:

So, in a study on 550 Chinese Singaporeans of older than 50 years, only 26.1% are found without cataracts. More specifically, 47.3% of the 50-60 age group are without cataracts; although the rate drops down to 11.7% in the 60-70 group. And everybody has cataracts if older than 70.

Compared with a group of Japanese (884 participants) residing in Noto Peninsula - which has an average temperature of 21.3°C with 1/2 the UV radiation of S'pore - cataract prevalence in the 50-60 Singaporeans is similar to that of the 70-80 age group in Japan, i.e., a decade earlier. In addition, nuclear cataract prevalence in the 50-60 Singaporeans was 9 times higher than the same age group in Japan. One can argue that besides geography, there are differences in culture, e.g., diet, outdoor activities, etc that may also be contributing factors. The principal factors are, however, still ambient temperature and UV index.

In fact, in cooler places like Iceland, with an average temperature of 4.4°C and 1/5 of UV index of S'pore, 39% of 60-70 year-olds are still cataract-free (study population=993). If race is a major factor, then all Caucasians no matter where they live should have identical cataract prevalence. This is not the case: Melbourne residents in fact have higher cataract prevalence than Icelanders.

Further, the prevalence of nuclear cataracts in Sumatra, another high temperature locale, is similar to that of S'pore suggesting the high ambient temperature, not race is a major factor.

Does it really matter to have high cataract prevalence? It does from the viewpoint of loss of productivity and the costs for cataract extraction. It is much simpler to practice prevention - clearly a job for the eye doctors.

Have another sip and plan.

(A more detailed version of this post, written in Chinese, is available here.)

7.22 One, two, or three eyes

2008-02-15T14:48:00.011-05:00

(Yang Jian, the 3-eyed god-general)

In Homer's Odyssey, Book 9, Mr Odysseus ran into Mr Polyphemus, a cyclops. The one-eyed giant ate a few of Odysseus's crew before losing his eye to Mr O's trickery. In Chinese mythology, The Investiture of the Gods (封神演義), Chapter 97, Yang Jian (楊戩) was born with three eyes; the third, sitting vertically on the forehead, can see beyond space and time.

While it is possible for a vertebrate embryo to develop only one eye, the three-eyed variety probably does not exist because this will require a fundamental re-structure of the cerebrum into three 1/3 brains. If we want to venture a guess, General Yang's third eye was most likely either a birthmark or a nevus that looked like an eye.

Cyclopes result from a problem with the prosencephalon which normally divides into right and left brains. Failing so, only one eye forms in the place where the nose is supposed to be. Cyclopes are mostly stillborns, so it was highly unusual for Polyphemus to even grow up, but then his Dad probably intervened (as far as life-support).

Actually, a close inspection reveals a complicated origin for each tissue in the eye. For those who for some reason must know, here is a quick summary:

Neuroectoderm: the retina, epithelium of the ciliary body/iris, and optic nerve
Surface ectoderm: the lens and corneal epithelium
The surrounding mesenchyme (neural crest origin): the sclera, the remainder of the cornea, the choroid, ciliary body/iris, and blood vessels

In the vertebrates, the development of the eye is through several invagination processes with precise timing. Any insults from microbes or toxins can of course cause mutations and congenital eye diseases. (See previous posts under Pediatrics.)

Here is something new and interesting: The development of the lens maybe controlled by the Six3 gene which in turn regulates Pax6, the master gene for eye development. The presence of gene product of Six3 does precede that of Pax6. In fact, problem with Six3 leads to holoprosencephaly. And the worse case? Yes, Mr Polyphemus the Cyclops and a kitten named Cy (see image below).

(Cy the kitten, the only living cyclops ever, even if for only one day - from cbsnews.com)

So Six3, in effect, initiates the whole cascade of gene activation in the development of the eye. We wonder why Poseidon did not see this coming.

7.21 Never say never?

2008-02-12T13:23:00.009-05:00

(Warner Bros, 1983)

After years of education by sci-fi movies and TV shows, some members of the general public actually believe eye transplant is a reality. Well, it is not, not yet anyway. And is it just a pipe dream or shall we quote Mr James Bond, "Never say never again" in view of the tremendous progress in recent medical research?

If it is possible to transplant anything at all, the candidates must have been blinded by an incurable eye disease yet still with some residual, functional neural (visual) activity. And the procedures must of course subject to the IRB approval.

Now, let's review what the major obstacles may be, one scenario at a time - an FAQ of sorts:

1. Transplant the whole eyeball?

Sure, assuming we can keep the donor eyeballs alive, or more important, for the tissues, especially the cornea, lens, and the retina, to remain functional after transplant. The eyeballs must be kept at 0-4°C; although the best way is probably to connect the arteries, branching from the ophthalmic artery, to a miniature circulator using oxygenated artificial blood enriched with 5.5mM glucose, so that the ocular group of arteries can continue to supply and sustain tissue metabolism.

Now we come to the second problem: how to reconnect the optic nerve.

Picture an undersea fiberoptic cable that got severed during a major earthquake. Do you then retrieve the cable, and reconnect the many thousands of fibers one by one? No, you'd replace the entire section. The optic nerve has 1 million nerve fibers. And at present, there is no way of joining two damaged nerve fibers to make it one functional unit. Also, unlike the undersea cables, the optic nerve is not an isolated section with connectors at both ends, so you cannot replace the optic nerve itself.

Assuming you can somehow coax the nerve fibers to repair their cell membranes and join end to end, it probably won't be the whole 1 million fibers. Then it depends on how many are revived which will then determine the visual field size and the attainable visual acuity.

After all the above, the visual cortex will need to exercise all its plasticity to interpret the images, since it now receives signals from most definitely mis-wired optic nerve fibers. Whether this is possible is still anybody's guess.

Last but not least, the extraocular muscles must be re-attached so that the eye can move according to the direction of gaze. This is cosmetically important as well.

So, transplanting the whole eyeball seems a bit impractical, at least for now.

2. Transplant the retina?

OK. The full-thickness retina or just the photoreceptor layer? The whole retina or just the macula?

First, the retinal viability and the reconnection of "wires" (this time with the optic nerve) are both still the major obstacles. The image below is a whole mount retina specially stained for the retinal ganglion cell fibers (downloaded from webvision.med.utah.edu). You can see numerous fibers all converging toward the optic disc (the black "hole" in the center) and each one must be re-connected with its corresponding fiber in the optic nerve. Technically, with open-sky vitrectomy, perhaps the whole thickness retina/macula can be replaced in toto, but not the photoreceptor layer itself (remember it faces posteriorly the pigment epithelium) - it is simply a humanly impossible task.

Still a bit unrealistic, this retinal transplant deal. But then as in eye transplant, it may just be a matter of figuring out how to fuse nerve fibers through some clever means. And other innovations may then follow.

3. What about electronics?

Ah, now we enter the realm of practicality. A project led by Dr Eberhart Zrenner of Tübingen and Regensburg universities in Germany has implanted retinal chips in patients with retinitis pigmentosa (see image below - from The Economist, 7 June, 2007).

This chip is composed of 1,540 photodiodes which, when stimulated by light, send electric pulses to retinal ganglion cells and the excitation is transmitted all the way to the visual cortex. So now we have roughly 40 x 40 pixels that cover most of the visual field. The patients can differentiate black and white as well as some shapes. For some, this is already a huge difference.

For patients without a semi-functional eye, the alternative is to implant electrodes directly into the visual cortex. The electrodes are connected to a spectacle-mounted digital camera which functions as the eye. As with retinal chips, the resolution is quite low (around 15 x 16 pixels) and the patients can only "see" white dots on black background.

These artificial sensors no doubt will further improve so that the resolution may become high enough with little power requirement and that each implanted chip can last a lifetime. There are also attempts to teach other senses such as auditory and taste to receive and interpret electronic visual signals - with varying degrees of success.

The electronics are not a bad first step towards bionic vision - a popular notion ever since the debut of the "Six Million Dollar Man" series (ABC TV) in 1978.

4. Stem cells?

Yes, this can be very promising especially for replenishing photoreceptor cells lost to retinal degeneration. Previous attempts of directly injecting retinal cells from young rabbits into the adult rabbit eyes have produced intriguing results: There was incorporation of the photoreceptors in the the retina that formed "rosettes". Photoreceptors were present at the luminal side of the rosettes surrounded by layers corresponding to inner layers of the normal retina. So the transplanted retinal "bits" appear to have a natural tendency to self re-organize. Stem cells grown into retinal cells, when implanted, will most likely behave the same way.

The potential problems in stem cell transplants are surgical injury, tumor formation, and vector-mediated infection. These can be avoided as the transplant process evolves. The biggest hurdle in stem cell research seems political, at least at the present time.

5. No more gene therapy?

Not at all. In fact, this research is proceeding in great earnest. As previously posted, gene therapy has already been tested in Leber's congenital amaurosis (LCA) to correct a defective RPE65 gene. This project was carried out last year at University College London Institute of Ophthalmology and Moorfields Eye Hospital, led by Prof Robin Ali with Drs James Bainbridge and Tony Moore. If successful, it will no doubt lead and change the way of genetic eye disease treatment.

Hmm, James Bond maybe right after all.

7.20 Mr Sulu, take us home

2008-02-11T12:22:00.003-05:00

(Star Trek IV, The Voyage Home, 1986)

You all remember the Star Trek movie, "The Wrath of Khan (1982)", in which Captain James Tiberius Kirk receives a pair of reading glasses as a birthday present from Dr Leonard (Bones) H McCoy. Kirk proceeds to lament rather unconvincingly the onslaught of old age. Presumably, by the 23rd Century, presbyopia has already been eradicated. Unfortunately, Capt Kirk is allergic to Retinax V - the medicine for treating Presbyopia, or "老花眼old blurry eyes" in Chinese and "老眼old eyes" in Japanese. The keyword: "old".

Funny the script did not follow the more creative vein as that for Captain Jean-Luc Picard who chooses to be bald (Ha!!) There is perhaps a lack of imagination on the screen writers' part. Because even now, there are invasive ways of manipulating presbyopia. Not that this is necessary, a pair of inexpensive OTC readers, bifocals including bifocal contacts, or monovision correction of various kinds (from LASIK to contact lenses, to spectacles) all can quickly resolve the issue.

Presbyopia is an age-related loss of crystalline lens deformability for focusing at near. This was described by Thomas Young (1773-1829) in 1793. To explain the process, he had invoked the elasticity theory. The Young's Modulus (stress = E x strain) is dependent on the material. In the case of accommodation, the lens capsule appears the candidate (see image below). Young's argument was that the capsule elasticity had diminished during aging. Indeed, recent measurements confirmed that the Modulus was about 6 × 10⁷ dyn/cm² in children which decreased to 3 × 10⁷ dyn/cm² at age 60, and to 1·5 × 10⁷ dyn/cm² in extreme old age. Similar to tired old rubber bands which cannot resume the original lengths when the tension is released.

(Lens capsule is the outer most layer which envelops the whole lens
- it is the faint band to the left (anterior to) the single-cell-layer epithelium in the above image)

That is not the whole story, though. There are three parts involved in the accommodation process (see below, 1-3):

(1: The zonules; 2: the crystalline lens; and 3: ciliary muscle)

The ciliary muscle must first contract to allow a decrease in the tension of the zonules, so the capsule can re-shape the lens. Does the ciliary muscle change with aging as well? Not the contractility. It appears the diameter of the ciliary muscle ring does decrease owing to a configurational change. The overall result is the zonules no longer have enough space to relax. And the weakened capsule also can no longer deform the lens as much as before. Did the lens diameter increase with aging also? Some say no; although the only way to make sure is to do a large-scale high-resolution MRI of the eye, because the lens is hiding behind the iris, inaccessible through optical means. The zonules? It is assumed, but never quantified, that the zonular fiber elasticity also changes with time.

Loose ends galore, indeed.

So, how can presbyopia be manipulated surgically? At least in theory, the ciliary muscle ring can be re-positioned to create more space for the zonules. This procedure has already been attempted; although the outcome is still unclear. Alternatively, Conductive Keratoplasty (CK), using radiofrequency to heat and shrink collagen fibers in the cornea, can be done. This to steepen the curvature of the appropriate area of the cornea, so that more plus power is produced for near tasks. CK takes about 3 min and is done to only one eye - a monovision correction as well. It seems to work for some, for a limited duration anyway (about 4-7 years). Interested parties are urged to consult their own eye doctors.

It's been 26 years since "The Wrath of Khan" and we still don't know the composition and the mechanism of effect of Retinax. Well, the sci-fi writers have already pointed the way, perhaps pharmacological researchers can now take us home - to a presbyopia-free world.

7.19 Headaches

2008-02-09T11:59:00.000-05:00

(Skrik, 1893, Edvard Munch - from headaches?)

Headaches are an interesting clinical entity. They are quite common yet with very few outward signs useful for diagnosis (except maybe temporal arteritis, see below). Plus the potential causative factors are many. Of course, we are talking real serious headaches, not those from muscular tension or sinus congestion; both of which most people are well aware of and who can often self-treat.

Most times, headaches can be diagnosed based on chief complaints, for example, in migraine and cluster headaches. One of the migraine prodromes, the occurrence of auras is quite well-known. [Note, however, in ocular migraines, auras do not lead to headaches.] And cluster headaches can last quite a few days; the patients often need to rest/recuperate in a dark and quiet place.

Patients with persistent headaches who show up in an eye doctor's office, are often referrals from the PCPs. The purpose is see if any of these apply: athenopia, angle-closure glaucoma, temporal arteritis, pseudotumor cerebri, pituitary tumor, etc. The PCPs may also plan, in addition to a complete physical to rule out hypertension, migraines, etc, neurological and radiological consults to ensure absence of space-occupying or vascular lesions, hemorrhages in the brain, or even meningitis. It is a multi-disciplinary process of elimination that can therefore be quite time-consuming.

From an eye doctor's perspective, any patients with headaches are suspected of having one of the following until proven otherwise:

Beyond the routine headaches checklist (throbbing/sharp/dull, where, when, how long, how bad, how treated), the first exam is to see if asthenopia is a contributing factor. Asthenopia is simply headaches caused by eye strain or uncorrected refractive error. The strain can occur when the eyes are forced to constantly re-focus, further worsened by insufficient accommodative reserve - typically in progressive hyperopia and/or incipient presbyopia, and much less well-known, in uncorrected astigmatism. The patient's complain of pain is usually vague; although it mostly refers to heaviness in and around the eyes. The symptoms disappear as soon as the refractive error is properly corrected. A good example is to switch from spherical equivalent to toric contact lenses for a full astigmatism correction. And the accommodative lag or insufficiency is remedied by applying more plus (or less minus) power. Asthenopia is, however, never truly debilitating, nor is it sight- or life-threatening.

Often the patient with acute angle-closure glaucoma attack ends up in the ER department of a hospital. Because the symptoms can include headaches, nausea, and vomiting. During attacks, the eyes show steamy corneas with limbal flush and often a distorted pupil as well (see image below):

As in acute angle-closure, patients with chronic narrow-angle glaucoma often complain of "brow aches". The cause is a true increase of pressure in the eye that can be readily measured with a tonometer. At the slit-lamp, gonioscopy is also performed to assess the angle - to see if the aqueous drainage is dangerously obstructed. Both hypotensive agents and laser iridotomy maybe needed to normalize the IOP to get to the origin of this type of headaches and prevent the visual field loss.

Temporal arteritis usually afflicts the elderly. It is a manifestation of a systemic giant cell arteritis that can sometimes lead to death. Usually the inflamed temporal artery can be seen snaking under the skin (shown in image below). The temple area is quite tender, certainly sensitive to touch, and painful while chewing. The blood supply to the optic nerve and the retina also can be compromised, causing irreversible loss of vision. Definitive diagnosis is based on erythrocyte sedimentation rate (ESR) and temporal artery biopsy. The treatment of choice is naturally the use of systemic steroids which can reduce the inflammation rather quickly.

Then we have the pseudotumor cerebri. As the name indicates, this is not a real tumor inside the cranium, but an increase in intracranial pressure owing to the presence of excess cerebrospinal fluid (CSF). Usually the patient is a slightly over-weight woman of child-bearing age. Birth control pills, vitamin A, and tetracyclines are all risk factors. Because of the increase in the intracranial pressure as in hypertension, sometimes papilledema is seen (shown below). Papilledema is a swelling of the optic disc, so the disc margin is now raised and the demarcation blurred. These can be seen very easily with a hand-held ophthalmoscope.

Definitive diagnosis is lumbar puncture together with neuro-imaging, the latter to rule out brain tumor. There are other visual disturbances such as blurred vision and diplopia. In fact, these visual symptoms are the reason why the patients are referred to the eye doctors in the first place.

Speaking of brain tumor, pituitary adenomas that impinge upon the optic chiasm can cause bilateral hemifield loss. Which can be picked up by performing simple confrontation visual field tests. Definitive diagnosis is brain MRI. The MR image below is a T1-weighted coronal scan showing a large hyperintense area (arrows), i.e., the pituitary tumor.

Headaches are of course a prominent feature of pituitary adenoma. They also can be the only manifest, and to the surprise of many eye doctors, without involving any visual field loss. Needless to say, pituitary tumors must be removed (usually through the nose to reach the base of the brain where the pituitary gland is).

Diagnosis and treatment of headaches can be exciting and rewarding - particularly if a potentially sight- and/or life-threatening lesion is the root cause. Fortunately, most cases are benign, stress-induced variety.

7.18 Nip and tuck

2008-02-06T10:33:00.001-05:00

(From pachealthholdings.com)

Cosmetic eye surgery has always been very popular. In Asia, for example, double-upper-lid surgery (see above) is a perennial ladies' favorite - for a more "spirited" look, allegedly. In the US, the low insurance reimbursement rates for other procedures have forced surgeons to seek additional sources of revenue. And medically unnecessary cosmetic surgery is paid out of pocket by the patients. It is therefore a perfect solution, especially if the surgical outcome meets the expectation of the patients. Botox injection to remove the wrinkles and thermo-lasers to re-surface the skin are now common place.

Medical necessity simply means whatever is "reasonable and necessary for the diagnosis or treatment of illness, injury, or to improve the function of a malformed body member" - according to Medicare. So the double-lid surgery cited above does not qualify. Also excluded is the "bags under the eyes" which are simply too common to merit any especial attention. They are essentially pockets of fatty tissues which can be removed and the skin tightened with the basic Z-plasty. Some of course opt for the procedure to look younger. Sometimes, however, the "bags" are from accumulation of fluids, as part of a general fluid retention, then the underlying problem(s) should be addressed instead.

There are many medically necessary cosmetic surgeries for the eye/orbit, usually performed by specially-trained hospital-based plastic surgeons. To name a few: ptosis repair, excision of cancer of the lid-margins, orbital decompression for Graves' Disease, patching of fractured orbital bones, prosthetics implants, reconstruction of facial deformity, repair of tear drainage system, and pterygium removal. This list probably should alert you that not all plastic surgeons are trained or qualified to operate on the eye and orbit.

A few examples of the eye plastics are presented below:

The most common procedure is probably that for repairing ptosis, i.e., drooping eyelids, that can interfere with vision.
In the case pictured above (notice also the bags under the eyes), clearly the visual field of the right eye is severely limited. The levator or Muller's muscle is therefore shortened to lift the upper lid. Ptosis can be bilateral. It can be congenital or acquired. The latter as a result of Cranial Nerve III palsy or myathenia gravis; both of which accompanied by double vision.

Very few people know how a prosthetic eye is fashioned. It actually requires the implant of a sphere made of porous polyethylene into the orbit to replace the enucleated eye - porous to allow migration of cells into it. Then the 4 straight rectus muscles are re-attached and the sphere covered with conjunctival tissue. After proper healing, an acrylic shell with the painted iris is then inserted (see image below).
The outcome is, without exception, quite striking. It is not uncommon for a novice eye doctor trying to examine the prosthetic eye, to the great bemusement of the patient.

Graves' disease, commonly known as hyperthyroidism, can cause enlargement of the extraocular muscles or increasing volume of the orbital fat (both within and without the EOM cone). This increase forces the eyeballs to bulge out - not only cosmetically undesirable but often the vision may be compromised. It is therefore necessary to decompress the orbit, by removing part of either the orbital bones or the fatty tissues, or both.

Very simplistically put, ocular/orbital plastics is practiced by very talented artists who happen to be skilled surgeons.

7.17 Wink, wink

2008-02-05T11:43:00.000-05:00

("The Wink" - Seinfeld: Season 7, Episode 114, 12 Oct 1995)

The fans of the 1990s "a [TV] show about nothing" known as "Seinfeld" will readily recall "the Wink" episode. In which, a bit of grapefruit juice was accidentally squirted into George Costanza's left eye causing George to wink at inopportune moments.

First, a little info on first-aid: Any time when acid or alkali is splashed onto the eye, the most important first action is to rinse the open eye with copious amount of normal saline, or tap water if saline solution is not available. A few liter or more is generally needed. Then seek immediate medical attention so that the anterior structure of the eye can be preserved. Acid and alkali burns are different. Acid causes protein denaturation on contact. The denatured protein sometimes can form a barrier to prevent further acid erosion. On the other hand, alkali can penetrate deep into ocular tissues. Alkali burn is long-lasting and far more difficult to manage. In either case, saline/water rinsing is the crucial first step.

Back to "Seinfeld". The pH of grapefruit juice is around 3, mild in comparison to, e.g., HCl; although it does cause some discomfort for the eye. Tear fluid in the eye is poorly buffered yet its pH usually stays at a comfortable 7.4, until disturbed. George's winking or twitching, known as myokymia, is from acidic irritation to the nerve endings of the orbicularis oculi muscle in the lower eyelid (occasionally, the upper eyelid can be affected). Myokymia usually resolves itself. In very annoying cases, anti-histamine eyedrops can be used to slow down the muscle contraction. The best one Livostin unfortunately is no longer in production, probably lost out to Botox injection?

There is another uncontrollable winking, know as the Marcus-Gunn jaw-winking syndrome, in which the patient's eye (or eyes) twitches when chewing or suckling. In this case, there is a wiring problem: the eyelid levator muscle, instead of being innervated by a branch of Cranial Nerve III, is now by the motor branch of Cranial Nerve V. It can be regarded as a birth defect; although nothing untoward is involved.

More persistent and chronic twitching of the eyelids of both eyes is known as blepharospasm. It has been noted for years that blepharospasm seems to predate the onset of Parkinson's disease. Recent findings suggest that indeed if there is a lesion in substantia nigra, then Parkinson's eventually does develop. Others report that L-DOPA used to treat Parkinson's can cause blepharospasm. Sort of a lose-lose situation. Other possibilities include the usual suspects: fatigue, dry eye, stress, too much caffeine, etc.

Truly debilitating eye twitching involves half the face, i.e., hemifacial spasm or Meige's Syndrome, that can severely curtail both speech and eating. It is usually a result of inflammation of the facial nerve (Cranial Nerve VII), a sequela of Bell's palsy, or from a tumor or blood vessel pressing on the facial nerve. This can be treated with muscle relaxants, Botox injection, or neurosurgical repair.

Indeed, a wink is not quite just twitching of the eyelid.

7.16 Organ donors

2008-02-03T22:06:00.001-05:00

(A post-op transplanted cornea - the zig-zag lines are the sutures)

Organ donation remains a voluntary act, at least in the US. The way it must be. Usually, at driver's license renewal, a question on whether you are willing to donate your organs is put forth. You can answer either yes or no and your wish is honored. Or you can carry a donor card with you (see picture below). In the hospitals, it is often a difficult task for physicians to request organ donation of a deceased from the grieving family; although who almost always give their consents.
Organ donation actually cuts through social, cultural and religious boundaries. It is a universal human act of giving and care.

Donated organs that can benefit many others include: Kidneys, heart, liver, pancreas, intestines, lungs; skin; bone and bone marrow; and the cornea. To keep these organs/tissues safe, both the FDA and the Health Resources and Services Administration (part of the HHS) have issued rules and guidelines - necessary for avoiding life-threatening infectious agents. Unfortunately, there are also unscrupulous operators who provide contaminated or cancerous organs that result in the death/injury of the recipients.

Here, we will touch upon the corneal issue. You can elect to donate only your corneas (see donor card above). They are a true gift of sight. The Sri Lanka Eye Donation Society is known to have collected tens of thousands of corneas, made available not only to Sri Lankans but also to numerous patients in other countries. These and all other donors deserve our special gratitude and respect.

It is estimated that in the US, between 30-50,000 corneal transplants are performed each year. And the reason for such an operation is to restore vision to patients with the following problems:

Keratoconus (cone-shaped cornea, see illustration below) and thinning of the cornea
Cornea scarring and ulcers (caused by, e.g., infection or injury)
Corneal opacities or severe edema

(Keratoconus - from ocularis.es)

Eye banks are now responsible for retrieving and preserving the donor eyes which are then provided to corneal surgeons. Since the eyes have limited "shelf life", unused (plus those deemed unsuitable) eyes can also be used for lab research. Essentially, there is no such thing as a wasted donor eye.

So can the donor corneas be preserved for as long as possible without losing their viability? In the olden days, the whole eyes were simply stored in a refrigerator and the corneas used within 2 days. Now, the excised corneas are placed in culture media such as Optisol GS or Eusol-C, which can preserve the cornea for up to 2 weeks (at 0-4°C). Other MEM-based modified culture media may also be used if needed. The corneas are inspected for the shape and count of the endothelial cells. The more cell loss the less viable/successful after transplantation.

Technically, there are three corneal transplant procedures. The most common is Penetrating Keratoplasty, in which the whole damaged cornea is replaced with the donor cornea. A trephine (similar to a miniature cookie cutter) is used to cut the donor and recipient corneal buttons, so the sizes match. Unexpectedly, the recent popularity of LASIK has actually reduced the donor cornea availability because the cornea now maybe too thin for penetrating keratoplasty. The alternative is to use only the endothelium, which is untouched by the LASIK procedure, for Deep Lamellar Transplant. Yet another procedure is the Surface Lamellar Transplant, in which, only the superficial layers of the cornea, in toto, are replaced. The corneal surgeon of course is the one who can decide which procedure works the best for you.

Corneal transplants have the usual surgical complications such as infection, bleeding, inflammation, and the occasional rejection (rare because the cornea is not a vascularized tissue). However, the success rate is quite high, e.g., 98% in keratoconus repair and more than 90% overall. We have just seen a case of of keratoconus that recurred after the transplant. This has been reported by others, in 11.7% of post-op cases. The causative factor is, however, still unknown.

By and large, corneal transplant, as cataract extraction, is a very safe way of replacing damaged corneas.

7.15 Go Pats!!

2008-02-01T05:54:00.002-05:00

What's in an American football game? Why, a display of the ultimate eye-limb coordination, of course. It is a major part of the American culture involving thousands of fans congregating in gigantic stadiums (i.e., bowls) every week (or separately in front of TV sets), cheering for their respective home teams. This season so far, Boston's own, the New England Patriots are a record 18-0, and are playing for a historical 19-0 this coming Sunday (3 Feb, 2008), against the New York Giants for the "World" Championship.

The game is essentially one team trying to march across a 100-yard field, by rushing or passing, to put the football in the end zone for 6 points (add 1 more point if the subsequent field goal is successful, for a total of 7 points). And the other team does its best to block the progress. The rules are quite simple. On each possession, a team has 4 chances to gain 10 yards (to reach another "first down") in order to try and gain the next 10 (i.e., a new "first down, 10 to go"). If the attempts fail, then the opposing team has the possession. Often the best part is to watch a harried quarterback tossing the ball up in the air across the field into the awaiting hands of a running receiver who somehow manages to keep both feet just inside the end zone.

The eye-limb coordination operates in this manner: Following a brief discussion of the game plan in a huddle, the ball is snapped to the quarterback who must then look for an open wide receiver and avoid being sacked at the same time. At this moment, both V1 and MT brain areas are highly activated. As soon as the distance to where the receiver maybe is calculated, the motor cortex goes into high gear directing the tossing arm to wind back and throw up the ball. The ball then sails through the often breezy, frigid autumn/winter air into the wide receiver (or a tightend if the star receiver is unavailable). The receiver while running upfield must also look back to see where the ball is and where the defenders are. MT, V1 and motor areas must all coordinate in order to complete the task at hand. All these are accomplished in a matter of seconds.

As far as the eye in football playing:

The players do lose their contacts during tackles; soft disposable lenses with an adequate supply of solution are therefore recommended. Since the game is often played in sub-freezing temperatures, it'll be interesting to know if the physical properties of the lenses are altered. And if the vision is affected as a result.

It is also known that strenuous physical activities, e.g., Marathon running, can significantly lower the intraocular pressure. No studies have been done to investigate any IOP changes from football (or the even more taxing basketball) playing.

Head-butts are also common despite heavily padded helmets. Whether the impacts aggravate pre-existing retinal breaks or holes thereby causing future retinal detachments is also unknown.

Much remains to be studied, isn't it. Nevertheless, do enjoy Super Bowl XLII wherever you may be.

Go Pats!!
_______
Post-game comment: "Nuts!!"

7.14 London 2012 and Pokémon

2008-01-27T11:17:00.001-05:00

(One of the official London 2012 Olympic Games logos)

After almost a decade of absence, photosensitive epilepsy re-surfaces in England. BBC News reports 1.5 alleged cases of seizure from watching a short animated segment of the Games promotion on TV (5 June, 2007). It involves a "diver diving into a pool which had a multi-colour ripple effect" according to a spokesperson. The segment was promptly removed from broadcasting and the london2012.org website.

It may not be a bad idea to give it a quick review, for video game designers/players and TV viewers alike.

Photosensitive epilepsy is a subset of epilepsy, involving 3-5% of all cases of epilepsy. Many cases, however, have no history of epilepsy at all. The most common trigger is the flickering light.

It has been established at the beginning of the TV age, that TV monitors with a refresh rate of 50Hz could provoke seizures. It was no longer a problem after the rate improved to 100Hz. During the the Disco era in the 1960s, the flashing strobe lights posed the same issue. Then in the late 1990s, with the immense popularity of TV-based video games, the occurrence of photosensitive seizures became alarmingly frequent. The trigger is still flickering light which is now software/game-specific. The London 2012 episode is, in fact, similar to that of the 700-1,000 children in Japan who suffered seizures after watching a Pokémon explosion cartoon 10 years ago. So it is really up to the video designers to carefully craft their products, e.g., 2 - 50Hz flickering is of course prohibited.

Nintendo Pokémon, i.e., Pocket Monster - ポケットモンスター

Photosensitive epilepsy is not a modern phenomenon. The Roman novelist and orator Apuleius (ca 125-170AD) noted that the spinning potter’s wheel could send onlookers into seizures. Others have reported that sunlight filtered through the leaves of a tree had the the same flickering effect when one passed under the tree. Even the whirling helicopter rotors, at low speed, has been reported to cause seizure. It is the periodicity heightened by contrast and brightness that can initiate aura which leads eventually to seizure.

If you are an avid video gamer (or a watcher for that matter), the following info maybe useful:

1. While playing TV-based video games, the viewing distance should be at least four times the monitor size (conventionally measured diagonally across the screen) - use a tape measure if necessary.
2. Eat and drink on a regular basis when playing.
3. No excessive play time - certainly not to continue when under stress (e.g., lack of sleep, running a fever, etc).
4. Do not play in a dark room, this to avoid high contrasts.
5. If episodes of photosensitivity, seek neurological consult, know how to manage the seizure, and dispose of the triggering games.

It is really a matter of common sense.

7.13 Computer vision syndrome

2008-01-26T09:55:00.000-05:00

(From www.fnal.gov)

Does this picture look familiar? Yes, a CPA who's been working on spreadsheets all day. It is the beginning of the tax season, you know. And he is already feeling the eye strain (not to mention the stress).

CPA or not, all ye who work with the computers, welcome to the world of CVS (computer vision syndrome).

No doubt most of you have searched high and low for CVS and its remedies. Here, we will try to explain what, physiologically, may lead up to CVS. Quite a few factors, actually:

First, the attention factor. The prefrontal cortex in the brain is responsible for attention (its development is delayed by ca 3 years in children with ADHD) - needed for analytical tasks such as computing. This area is also coded for eye blinking. With the attention turned on, the blinking rate changes from a normal of once every 4 sec to a whopping 20 sec. That is plenty of time for the tear fluid to evaporate, which is further aggravated if you work in a "sick" building or if you suffer from dry eyes in the first place. With the tear film (known as the tear lens) disturbed, vision also will be affected. Often if you blink a few times to refresh the tear film, then the vision improves.

You can remind yourself to blink more often; although this, much like the New Year's resolution, is usually forgotten after a few days. There is actually pop-up software to remind you to blink. Some may find it useful while others more a distraction. The more reasonable approach is to regard attention-induced non-blinking as a dry eye issue and treated as such.

Next, the "dark focus" factor. Computer work is a type of near work. This actually requires 3 activities working together: the two eyes turn inwards, pupils constrict, and the crystalline lenses focus. So we have the medial rectus muscles, the iris sphinctor muscle, and the ciliary muscle all working at the same time. Hacker-style computing is not without merits: by sitting away from the monitor (preferably in a well-padded sofa), these muscles will not have to work as hard as at close range (usually 17-18 inches) - perhaps the reason why the hackers can hack 24/7 non-stop. Until...

(From www.infosatellite.com)

There is, however, the "dark focus" factor. Computer screens, be they CRTs or LCDs, are all pixelated. Presumably the eyes have a difficult time remaining focussed on the pixels. And as a result, the accommodation tends to relax to a point farther away from the monitor, i.e., at the Resting Point of Accommodation (the "dark focus"). Since the eyes must constantly re-focus, the strain on the ciliary muscle can be a major source of eye strain.

How to avoid this strain? Well, if the refraction is done using a computer monitor as the visual target, then the final prescription may be different from that based on printed Snellen reading charts. Usually more plus power is needed and the two eyes may need different powers as well. The prescription is known as, what else, the computer glasses - although not to be confused with those US$5-15 OTC readers available at your local computer stores or pharmacies.

Sustained accommodation also can cause transient pseudo-myopia. In other words, after an 8-hour day, some people become (more) myopic. Driving home may become noticeably unsafe.

Then there is the glare factor. Glare generally refers to intolerance to bright lights, e.g., oncoming car headlights at night especially for people with early cataracts. In computer use, glare from the monitor can be a source of eye irritation as it is similar to staring at a light bulb all day long. Actually it's more than that, the refresh rate of a monitor in a way is a measure of how fast the lights flicker - similar to pulsating strobe lights or single fluorescent light tubes if you will. So now we have an uncomfortable repetitive on-and-off, as opposed to sustained continuous activation of retinal photoreceptors.

Of course, manufacturers of monitors do strive to provide you with glare-free, high-resolution, high-refresh-rate monitors. Well worth the purchase price, we might add. And anti-glare screens for CRTs may still be popular. Anti-reflection (AR) coating on your spectacles works quite well also.

Finally, the sick building factor. In office buildings with poorly-ventilated poorly-filtered arid air, ozone generated from the computers can be another source of eye irritation. This is, however, beyond the scope of eye care. Talk to your landlords.

Unfortunately, this is the digital age. No one escapes CVS.

7.12 I see 'little' people

2008-01-24T09:46:00.000-05:00

(Gulliver's Travels: Lilliput hallucination?)

Occasionally, an elderly patient with counting finger vision reports seeing black cats darting across the room, zig-zag lines, little people moving about (hence the term "Lilliput hallucination"), various pulsating geometric shapes, closing and opening curtains, etc. Needless to say, the patient is very anxious ("Am I losing my mind?") and family members are equally concerned - until it is explained that these are a form of visual hallucination.

A Swiss gentleman by the name of Charles Bonnet documented in 1760 that his grandfather, nearly blinded from cataracts, complained of seeing vivid phantom images - hence the name, Charles Bonnet Syndrome (CBS). If you have never heard of it, you are not alone.

First and foremost, patients with CBS are mentally healthy. The hallucination is not the pharmacologically-induced type or from psychosis/dementia, but are, in a way, similar to the phantom-limb syndrome. In the latter, amputees can still sense itch and pain in the now removed limbs.

What causes CBS? Theories abound, e.g., sensory deprivation, dream activation, creative visual cortex, etc. The only way to make sure is to map the brain with MEG or fMRI during hallucination, at least to see which brain area is activated. This will be extremely difficult, if not impossible.

Not everyone experiences CBS, though - in only about 15% of low-vision patients according to one study. There are other studies, statistical numbers may vary but all are in the low percentiles. Some clinicians have reported CBS in patients with recent vision loss. We have encountered only patients with long-term (i.e., years of) loss. So, the onset of CBS may be patient-specific. The cause of vision loss per se, however, does not appear important.

Unlike the real pain in phantom-limb syndrome, CBS cannot be or even needs to be treated. Just know that patients with CBS do not have any psychiatric issues. Instead, their vision needs to be re-evaluated and possibly further rehabilitated.

7.11 Flower child?

2008-01-20T08:35:00.000-05:00

No, iris and pupil, part of the eye. Not being insulting, this is just to refresh your memory: Iris is of course the colored part of the eye and the central opening is the pupil. And we all know the latter regulates the amount of light entering the eye.

The color of the iris is determined by the proportion of two pigments, melanin (brown, controlled by chromosome 15) and lipochrome (yellowish brown, chromosome 19). A blue eye looks blue is because it has less melanin than lipochrome and less pigments in general. And the more melanin, the darker the iris. An iris without pigments would appear pale pink. A cross section of the iris is shown below:

The cornea (not shown) is to the left. The dark vertical structure in this image is the iris proper and the pink area to its right is the crystalline lens. In the posterior part of the iris, the darker band is the pigment epithelium with all the pigments. Without shielding from much melanin, blue eyes are inherently more sensitive to bright lights. Dark irises are pharmacologically more resistant to dilating eyedrops, however.

You can have one hazel eye and the other brown, too - known as heterochromia. Presumably Alexander the Great (356-323 BC) was heterochromic. This happens when one iris fails to generate enough melanin. It can be hereditary or from childhood trauma to the sympathetic nerve along the carotid artery. One can imagine someone (King Philip II?) picked up little Al by the head in a Macedonian horseplay, thereby causing the said injury. To all the dads/uncles out there: please don't do this to the little ones.

Sometimes, however, the pigments can get dislodged, as seen below in a retro-illumination photo. In which the light is reflected through the backside of the iris. And in the posterior surface of the cornea, a vertical band of pigments also appears (i.e., the Krukenberg's spindle).

(From nature.com)

This is known as pigmentation dispersion syndrome. If the pigments clog up the aqueous outflow, the intraocular pressure can rise, then we have the pigmentary glaucoma. Often filtration surgery is needed.

The pupils of all humans are round. Animals are not all so. Some animals have vertical pupils while others horizontal ones. They can be slits, ovals, or even W-shaped. And the reason why all these different shapes? You can propose your own theory and whatever it is, is probably right. It is usually something like slit pupils can shut quicker than round ones, nocturnal animals have vertical pupils to detect a prey scurrying away, and horizontal slits are better for navigating rocky terrains, etc.

Here are a few examples:

Above: Vertically oval pupil in an alligator, also seen in cats and some lizards. And below: horizontal slits in a goat (also in octopuses).
And a W-shaped pupil found only in the cuttlefish:Other than it looks like a miniature Batman symbol, a reasonable explanation is still lacking.

In humans, some are born without the iris (i.e., aniridia). Supposedly, during Renaissance, the courtesans would take Belladonna extracts (rich in scopolamine and atropine) to maximally dilate their pupils - to make the eyes more attractive. And the pupils are sometimes re-shaped by trauma from, e.g., recoiling bungee cords with a metal hook, or playing paintballs without the goggles. Or more frequently by surgery, e.g., during cataract removal (see image below):
Then we may have a case of light and glare sensitivity because the iris no longer functions normally. And sometimes a small opening in the iris is created to facilitate aqueous flow as a treatment for chronic narrow-angle glaucoma (see the small hole, 11 o'clock position, from laser iridotomy):The iris is such an interesting structure, some have gone further and developed iris-reading (as in palm-reading):
Although it is still unclear, for example, why/how/where/when the iris sphinctor muscle area should be associated with the digestive tract (and so on).