7.3 Aji-no-moto

Aji-no-moto, the "essence of flavor", commonly known as MSG (monosodium glutamate), has been a fixture in kitchens of all sizes, all over Asia, since 1909. A few grains of the chemical turns "clear water into chicken soup" as the advertisement goes. And in fact, no ill physical effects have been noted until 1968, when reports surfaced in the US about physical discomfort suffered by some, after consuming Chinese food. Despite conflicting data from several studies later on, the label of "Chinese Restaurant Syndrome" stuck. To this day, in American culture, any discomfort, including postprandial stupor, from eating out, is automatically attributed to CRS. And restaurants began to offer MSG-free meals since that time, even though the replacement, the soup stock, is quite rich in MSG.

Generally, the symptoms are mild that include transient headaches, flushing and sweating. It is unknown if some patients are ultra-sensitive to even a small dose of MSG; although it does not make sense why any reasonable immune system should attack glutamic acid, which is actually one of the 20+ essential amino acids, the building blocks of protein - unless it is something neurological as some have noticed later (see below). In any case, a normal dose of vitamin B6 seems effective in preventing or staving off CRS.

What's MSG, or more accurately, glutamic acid, got to do with the eye? Let's make a long story suitably short:

Glutamate is actually a major excitatory neurotransmitter in the brain. It is involved in the very complex behavior of NMDA (N-Methyl-D-Aspartate) glutamate receptors. It turns out that excessive glutamate can damage these receptors. In fact, excitotoxicity due to glutamic acid has been proposed to be the cause of neuron destruction in patients with strokes (and other forms of brain ischemia).

Maybe this toxicity can explain the CRS? No, not really, because there is a blood-brain barrier, aji-no-moto cannot enter the brain without invitation/breach. The source of the endogenous glutamate is the injured local cells, causing excessive neuronal excitation of their neighbors, hence the increasing tissue damage. The real culprit of CRS still remains unknown; although it is most likely not dietary MSG.

But wait, since someone has mentioned ischemia and the retina is part of the central nervous system, i.e., the brain, doesn't it make sense that glaucoma/diabetes related damages to the retina also can be blamed on glutamate excitotoxicity? Maybe so. And a lot of research projects are examining all facets of this issue. Already neuro-protection is a topic of major interest in the management of POAG. For example, drugs for treating Parkinson's disease are being used/tested in a number of advanced cases.

On the other hand, it is also very important to realize that as part of the blood-brain barrier, there is the blood-ocular barrier, which prevents the entry of exogenous glutamate (e.g., MSG in Chinese food) into the retina. And even in the lab, an extremely high concentration of glutamate is needed to produce direct cellular damages to the retina. Again, we can rule out dietary MSG in all ischemia-related retinopathies.

Often in the lay press, a few keywords are lumped together to create a seemingly scientific report. In the above case, putting MSG and neurotoxicity together in an uncritically written article can lead the reader to erroneously conclude that "eating out at a Chinese restaurant can damage your brain/retina". On the other hand, without the press coverage and the ensuing publicity, research on glutamate and its excitotoxicity would not have advanced so far. Ultimately, the patients benefit, so the system does work despite its many flaws. Readers must still exercise their own judgment, of course.

Merry Christmas

Merry Christmas to All !!

7.2 Harder who?

Next time, when you visit your eye doctor, casually mention that you would like to have your Harderian gland checked. The doctor will look at you quizzically, "Harder who?"

With the long and rich history of human anatomy, you'd think that everything in the human body, big and small, young and old, have all been discovered and carefully documented. Not so. The Harderian gland has escaped attention, even though its existence in other mammals has long been known. In fact, it was first described in 1694 by an obstetrics professor in Basel, Johann Jacob Harder (1656-1711).

Indeed, one time, an excited nuclear medicine research group, who have just developed PET microscopy, informed us a large uptake of a certain compound (we are sworn to secrecy as to its identity) by the posterior portion of the eye, in a living rat. And they have traced it to the Gland of Harder. This uptake was later confirmed and quantified with another study. The excitement, however, was somewhat dampened when told that there was no such gland in the humans, at least not the ones we saw. In our collective knowledge, only one person recalled reading about this gland in non-primate mammals - in the comparative anatomy chapter of Wolfe's Anatomy of the Eye. This gland is hiding posterior to and underneath the eye ball, blended into the fatty tissues of the orbit. Easily missed if you are not looking for it intentionally.

What a shame - as PET (Positron Emission Tomography) microscopy is nothing to sneeze at. PET scans usually show low-resolution whole-body/brain images, to see images of a 3-mm rat eye is no small feat.

In 2006, two biologists in Pennsylvania finally published a paper: "Primate Harderian gland: Does it really exist?" in Annals of Anatomy - Anatomischer Anzeiger Volume 188, Issue 4, 3 July 2006, Pages 319-327. The finding? Indeed the Harderian gland is found in fetal and neonatal stages in humans but is largely absent from adults. And of course, its role is still unknown. (In contrast, numerous functions have been proposed for the Harderian gland in non-primates.)

Who knows why the humans do not have a functioning Gland of Harder, but then we don't have the nictating membrane, either.

Sometimes we run into an unknown. And to have found the answer is like discovering some new species in the deep jungles of Indonesia. Sometimes, however, the findings are to be filed away perhaps for another day. All part of the fun and game of research.

7.1 Cold fish eye

A patient once remarked that her post-LASIK vision seemed to change for the worse but only during the winter time. An examination and a comparison with past records indeed confirmed her self-observation. Since no other similar reports have surfaced, we have regarded this case as anecdotal. Although, it is entirely possible that structural change of a thinner cornea in response to a lower ambient temperature did occur. It'll be interesting to study post-LASIK Alaskans' visual stability, for example.

So how does the eyes keep warm - or cool, for that matter. Human corneal temperature is normally 34.2°C. Then there is a temperature gradient from the cornea all the way deep into the orbit, reaching the body temp. This indicates that the anterior segment, including the cornea, iris, and the crystalline lens, is kept cool through blood and aqueous circulation. Normal corneas seem to be quite comfortable with the temperature change and can stay transparent. Even solar keratitis affects mostly only the epithelium, the rest is still clear.

The crystalline lens is a different story. In a simulation, when a model human eye is exposed to an infrared radiation source of 1500°C, the lens temperature increase can reach 1-2°C, which seems enough to cause infrared cataracts.

Hmm, what if you live in a cold environment? There are the experimental "cold cataracts" seen in the lenses of newborn cows, rats, and mice; although, luckily, not in that of human babies. What about fish living in the -2°C Arctic/Antarctic ocean. Well, they have a glycoprotein antifreeze in their body systems and, most interestingly, cold-resistant lens proteins. These proteins are actually gamma-crystallins. It seems that in some cold-adapted fish, these crystallins are more tightly packed than the mammalian kinds, and are therefore far more resistant to protein-water phase separation (hence the opacities). That does make sense, or the chance of survival for a cataractous fish would not be so great.

Next time, when you look at a fish in the eye, do remember the remarkable biochemistry contained within.

What if you are an eagle flying up in the cold air and needs to hunt for a rabbit a mile away? The eagles do have an extra eyelid, as that in a rabbit, called nictating membrane. In the eagles, this membrane is transparent which swings into action during hunt. Their retinal cell density is about 5 times that of the humans. So we can safely assume the eagles have much better visual acuity than the humans. Cold cataracts? Not a chance. In the eagle eye, within the vitreous, there is a structure called pecten body. It is a vascularized feathery structure with the function of a heat radiator. That is how the eagle eye is kept warm even flying through frigid air, and, some say, pecten body also provides oxygen to the ocular structures. It turns out that all birds, including the lowly chicken, have it, too. Surprise, surprise.

It pays to strike up a conversation with a veterinarian sometimes.

6.6 Unexpectedly...

In major academic institutions, case reports do not rate as formal papers. The rationale is simple: each patient responds to a treatment differently, so they should not be reported piecemeal - case by case. With enough cases to show a trend and a strategy for reversing this trend, then they can be presented in toto as a research paper, so that others can learn from the experience.

In fact, very often the surgical procedure itself is described as being a big success, but then things start to go wrong. In very general terms, a quick description of some (not all) post-op problems is shown below:

1. Refractive surgery

Take, for example, LASIK:

Obviously if the correction is inaccurate, e.g., under- or over-correction, residual astigmatism, or regression, then the post-op vision won't be as good as advertised.

There are also glare, haze, and halo that can result from off-centered ablation, pupil size larger than the ablated zone, or folds in the flap.

Post-op dry eye, epithelial growth, inflammation, and infections are all possibilities.

2. Cataract extraction

Cataract surgery has a 95% success rate. It is still possible to develop catastrophic infection (known as endophthalmitis), intraocular hemorrhage, cystoid macular edema, or even retinal detachment.

3. Glaucoma shunts

After previously failed glaucoma surgeries, the last resort is a shunt implant. The principal complication after implanting the shunts is hypotony (low intraocular pressure). Healthy eyes will produce enough aqueous humor to fill up the shunt reservoirs. And the eye then re-pressurizes. However, choroidal detachments or hemorrhages can occur if the eye is not healthy (e.g., from diabetes).

4. Vitrectomy

Most patients experience improved vision after vitrectomy. However, about 18% of patients develop complications with half of them having zero improvement in vision, and the other half, actually permanent vision loss from, e.g., neovascular glaucoma (the main reason why the glaucoma shunts are needed).

5. EOM re-alignment (strabismus surgery)

The most common complications are under- and over-correction, so the eyes are still not straight post-operatively. Sometimes these are transient, but other times, another surgical correction is needed. Other complications include:

Perforation of the sclera
Lost and slipped muscles
Infection
Anterior segment ischemia (from damage to the ciliary arteries)
Diplopia
Conjunctival granulomas and cysts

6. Corneal transplant

As in all transplants, the biggest problem for cornea transplant is tissue rejection. This is treated with immunosuppressants at the early stage. Other possible complications include infection, hemorrhage, retina detachment, and glaucoma. Still other problems are optical, for example, irregular astigmatism can be a result. Irregular astigmatism cannot be corrected with spectacles at all; only RGP hard contacts can cover up the irregularity.

Fortunately, most if not all of the above post-op complications can be successfully repaired or treated; although the outcome will be somewhat less than that expected before the surgery.

6.5 Vision rehab setup

(from ablezone.com)

Traditionally, low vision care is a major component of tertiary eyecare. Patients, in general, have already exhausted most if not all medical and surgical options and their vision may still be deteriorating. These patients are usually found in eye hospitals and large retina practices. For them, stabilization of ocular conditions coupled with maximal/optimal vision correction remains a life-long process.

The definition of low vision is, however, rapidly changing. It no longer denotes legal blindness or worse, rather it now includes patients with BCVA of 20/80 or less and whose vision cannot be further restored. For example, patients with cataracts plus AMD or diabetic retinopathy, or patients with post-RK ghosting and/or polypolia. Thus low vision cases are now often seen in a primary care office.

A common misconception is that since the patients cannot achieve 20/20 vision, the accuracy of refraction is no longer crucial. In fact, having lost some vision, the patients are extremely sensitive to changes, however small. Any loss is potentially devastating and gain a cause for celebration. Part of this maybe psychological; however, the change can often be attributed to the development of another sensitized areas (outside of the macula/fovea) for vision. It is the doctor's responsibility to identify these areas and maximize the patients’ vision accordingly.

The ultimate goal of low vision care is really the improvement of the patient’s quality of life. For some patents, it is also crucial to integrate vision rehab with occupational therapy, so that they can be productive again.

Low vision care is an extension of refraction including contact lens application. The main principle is magnification without compromising the available field of view. In other words, if the magnification is such that it allows the patient to read, but only one word or even only one character at a time, then it will be very difficult to scan the whole line of text, let alone reading at a reasonable speed.

The availability of low vision devices has also increased from optical magnifiers and telescopes to computerized readers, self-focusing telescopes, satellite-guided navigators, all the way to macular relocation, implanted telescopes, and ocular and cerebral electro-implants. The increasingly bionic approach can benefit patients with profound loss of vision, whether it can serve or is accepted by low vision patients remains to be seen.

Here, we will describe a typical set up of a low vision care office:

Patient flow: Wherever applicable, Braille signs must be posted. For example, in the elevators, Braille floor number signs must be posted next to the push-buttons. Also, Braille directions to the clinic should be affixed onto the walls at waist level along the way to the clinic. The clinic also must be wheel-chair accessible. The patient then enters the front desk and waiting area and proceeds to register.

Pre-test room: An Ophthlamic Technician should then take history, both visual and medical. Especially important is previous history of eye treatments and/or surgeries. Previous records are important, in fact, crucial for further evaluation. Record patients’ current low vision devices and their effectiveness. And what the patients’ expectations for the visit.

Visual acuities, both aided and unaided and most important pin-hole acuity must then be taken. This is done with standard Snellen charts or equivalent. Patients should NOT be dilated at this point. Dilate only if the patient needs a retinal exam. Also, no applanation/indentation tonometry (this may distort the cornea), save this for later. Patients with POAG and silicone oil must have tonometry before conclusion of each visit.

Do auto-refraction/keratometry (note the shape of the mires) if practical. A hand-held auto-refractor may be needed for children.

Visual analysis/eye exam room: A skilled refractionist then evaluates the patients. For this room, in addition to the standard Snellen charts, a low-vision chart designed for 1m testing distance is required. For children, a childrens’ chart for 1-3m will suffice. For infants, use a separate preferential looking chart.

Accurate refraction is key to successful management of low vision cases. The following equipment is required:

Phoropter with chair and stand together with a slit-lamp
Complete set of trial lenses (including prisms) and a trial frame
Retinoscope with halogen lamp
Direct opthalmoscope with halogen lamp
Binocular indirect ophthalmoscope
Volk lenses (at least one +78D lens)
Complete set of LV trials (for example, that from Eschenbach)

Record best correctable vision and reasons for sub-optimal vision. Propose low vision aids and/or further tests.

Low vision aids: for example, telescopes, microscopes
Special optical aids: for example, prism for eccentric viewing or avoiding diplopia
Specialty contact lenses that include lenses for aphakia, aniridia, keratoconus, complications after corneal transplants or refractive surgery, contact-lens telescope
Electronic devices: for example, desk or head-mounted CCTVs

Special testing room: This room should be equipped with a special visual field testing instrument, ideally a scanning laser ophthalmoscope. In severe visual loss, SLO provides information on areas of preferential viewing and the angle of deviation from the macula, so that the amount and axis of prism correction can be determined.

A high percentage of patients suffer from glare sensitivity. A glare testing device is also needed in order to quantify the need for shields.

Education room: An ophthalmic assistant teaches the patients how to use the low vision aids. Most patients will require instructions or the devices often go unused.

Occupational therapy room: For those with severe loss of vision, an Occupational Therapist teaches assistive living with the goal of achieving independence. This room is equipment with a kitchen with utensils designed for LV patients.

A computer area for learning skills for navigating the Internet and improving office productivity.

For the immediate future, assistive technologies should be developed for the use of ATMs, PDAs, and cell phones. These are, not surprisingly, what the low-visoin patients have the most difficulty with at present time. Some never even have the opportunity to access these devices.

6.4 (Non-)Contacts

Strictly speaking, a contact lens (CL) is not in direct contact with the corneal epithelium. Instead, it floats on top of the tear film. This is, however, only academic.

There are simple steps for fitting contacts:

1. Corneal evaluation:

Maintaining corneal health remains the most important goal in contact lens fitting. It is now known that the corneal endothelium can change its cell density, size and shape after contact lens wear. The endothelium is responsible for the maintenance of water content in the cornea (too much water causes corneal edema hence haze which occurs in eyes with improperly fitted CLs). Healthy cornea of course is a must for the eye to receive the CL. Eyes with corneal defects such as the dry eye will be incompatible with CL wear. The epithelial defects can be readily seen with fluorescein staining when observed under the cobalt (blue) light. Specular microscopy is needed for the evaluation of the endothelium; although this is not commonly done.

2. Parameters needed for CL fitting:

(1) The most important one is corneal curvature measured with keratometry. The curvature in mm (known as the “K”) is the basis for the selection of CLs. In other words, the base curve of the CL must be based on that of the cornea. For example, in hard lens fitting, the base curve can be on mixed K, on flat K, or slightly flatter than the flattest K, and in soft lens fitting, the base-curve is usually flatter than the flattest K. This allows CL movement that facilitates tear (essentially oxygen and nutrient) exchange. It should always be remembered that CLs are NEVER fitted steeper than K as this will cause “central pooling” (immobile CL with tears trapped underneath) leading very quickly to corneal damage. It also should be noted that the K-readings are those of the central 2-3 mm of the cornea. Trial lens fitting therefore remains the most practical approach in the selection of CL base curve.
(2) The palpebral fissure or the gap between the upper and lower eyelids when the eyes are in the normal open position can be a determining factor in the selection of lens diameter (i.e., size). This is based on the assumption that the portion of the cornea covered by the lids does not receive enough oxygen already, larger-diameter lens therefore will deprive the cornea of even more oxygen.
(3) The corneal diameter also can be a determining factor in the selection of CL size. Again, this is based on the area of corneal coverage by the CL. In general, the smaller the CL diameter the better for cornea health. Furthermore, smaller CL diameter has the same effect as increasing the base curve, i.e., smaller CLs will appear flatter than large CLs. However, it also should be noted that sometimes the patients will experience glare and unstable vision because the CL diameter is too small. And by the same token, eyes with extremely large pupils also will experience peripheral disturbances if the CL is too small.
(4) In addition to CL base curve and diameter, it is also necessary to adjust the lens power because of the difference in the vertex distance (which is the distance between the back of the spectacle lens and the cornea/eye). Notice that refraction either with the trial frame or with the phoropter, is done at a distance away from the eye of around 13 mm. The CLs are fitted directly onto the eye, so the power actually needed will be less minus (or more plus) especially when the spectacle lens power is more than 4 diopters. For example, a spectacle lens power of -5.00D requires a CL power of –4.50D. A conversion chart or software is generally available online.

Notice in the very high myopia (malignant myopia) and hyperopia (pseudophakics), the adjustments may have to be made through over-refraction as even slight change in the vertex distance can cause large differences.

3. CL Selection:

(1) Soft lenses are HEMA-based that contain 30-70% water. There are now daily wear, 3-month extended wear, daily disposable, and 1-2 weekly disposable lenses. Selection is based more on the patient’s life style and sometimes on economic concerns.
(2) Hard lenses are now silicone-based RGP lenses. The classical PMMA lens is no longer or very seldom in use. The fitting principle for RGP lenses is the same as that developed for the PMMA lens, i.e., fitting on K or more frequently, flatter than K to allow CL movements. However, because of the high oxygen transmission, RGPs can be fitted on-K for better stability. (3) Special lenses are those with toric design as well as the bifocals. They are also available in hard- and soft-forms. Because of the necessity to limit lens rotation from blinking motion, a prism ballast or similar must be built-in to anchor the lens in a fixed orientation. Nonetheless, lens rotation sometimes is still too extensive to allow stable vision. There is a momentary blur after each blink that some patients cannot seem to tolerate at all.

4. Situations that require extensive management:

(1) Dry eye – deficient tear production and poor tear quality
(2) Severe allergic conjunctivitis – chronic inflammation and discomfort (“itchy” eyes)
(3) Pregnancy and use of birth control pills – these change tear chemistry that can reduce the wear time
(4) Diabetes mellitus – general intolerance to ischemia
(5) POAG – CL wear may mask glaucoma-related corneal change
(6) Chronic and acute infectious keratitis

5. Complications from CL wear:

(1) Punctate stains – epithelial defects due to desiccation and/or oxygen deprivation often in the 3-9 o’clock position
(2) Corneal edema – from severe oxygen deficit detectable by limbal trans-illumination as central corneal clouding (ccc)
(3) GPC (giant papillary conjunctivitis) – response to allergens embedded in the CL; cobble-stone type
(4) Infectious keratitis – improper wear habit (often over-wear and poor CL hygiene) causing breakdown of corneal resistance to micro-organisms, mostly bacteria (e.g., Pseudomonas aruginosa)

6.Remedies for problems in CL wear:

(1) Proper blinking pattern and adequate blinking rate
(2) Use of wetting solutions and lubricants
(3) Shorten CL wear time
(4) Proper cleaning and disinfecting of contact lenses
(5) Use alternative types of CLs (CAUTION: hard CL re-fitting is quite difficult especially if the patient is a long-term CL wearer. It often necessitates suspension of CL wear for 3 months before the re-fit.)

Conclusions:

From the doctors' point of view, Good Vision, Ocular Comfort, plus Adequate Lens Movement are the three hallmarks of a successful contact lens fit. However, it should be noted that thorough dispensing/teaching sessions and periodic follow-ups are also required to ensure maintenance of the patients’ corneal health.