7.32 Nutritional glaucoma

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

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

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

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

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

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

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.