4.1 Not-so-routine exams

Preventive care is a wonderful idea. This naturally applies to eyecare as well.

A routine eye exam is supposed to be yearly or biannually depending on what your insurance policy allows. It involves a physical exam of the eyes to make sure your eye sight is still 20/20. And any deviation from the previous exams is subject to additional testing and/or referral to a specialist. This specialist then also determines if any need for more treatments. What a system!

In reality, while many do enjoy routine care, others - young or middle-aged patients - show up in an eye doctor’s office often with a myriad of chief complaints, starting from blurred vision both far and near especially when driving at night, to diabetes and high blood pressure/cholesterol that are being treated, to frequent pain, tearing and photophobia, plus family history of glaucoma and AMD. And by the way: “I also need some new contacts.” In less affluent areas, even in a developed country such as the US, this is not an unusual scenario - yes, the all-inclusive not-so-routine exams. The cause? IMHO, the managed-care maze which both the patients and the doctors often must navigate together. It is a system so inflexible as to impede providing and receiving of proper care. As as result, the patients' health problems multiply.

So what do the doctors see in addition to changes in refraction, incipient cataracts, glaucoma suspects, and background diabetic retinopathy? Well, quite a bit. An interesting list, starting from the most common to somewhat rare, is shown below:

1. Dry eye and subconjunctival hemorrhage
2. Contact lens over-wear and keratoconjunctivitis
3. Medicine-induced mydriasis in children
4. Allergic conjunctivitis
5. Early arcus senilis
6. Pterygium and non-UV pinguecula
7. Undiagnosed keratoconus
8. Herpes simplex keratitis
9. Corneal dystrophy

In addition, patients who often self-refer because of alarming visual disturbances. A few common complaints are listed below:

1. Diplopia
2. Floaters/flashes/vitreous hemorrhage
3. Visual field loss/blood vessel occlusion
4. Retinal detachment
5. Macular hole/pucker

Interesting cases deserve serious comments which I will now start to post.

3.3.2 Squint (noun)

Childhood squint, i.e., strabismus or tropia is different from phoria. The latter refers to the eyes assuming a natural position when they are artificially dissociated. They resume fixation at the same point when both eyes now see at the same time. The angle of deviation, in prism diopters, can be measured quite accurately, e.g., with rotating prisms. And frequently, small amounts of prisms are prescribed to relieve extraocular-muscular strains from the need to actively maintain the binocular alignment.

In squint, the two eyes remain dissociated and misaligned, also known as crossed- or walled-eyes when the affected eye turns in or out, respectively. The deviation can be horizontal, vertical, or mixed. It can be constant or it can vary with gaze. And it can involve one or both eyes. The main cause can be either central involving the brain, or a local neuromuscular problem. So the diagnosis is best left to a professional. The deviated eye either has already developed amblyopia or has the potential to become so. Proper therapy, either patching or atropine eyedrops, must be initiated in conjunction with orthoptic re-alignment of the eyes. Often strabismus requires surgery to re-arrange the positions of the extraocular muscles; although mostly for cosmetic reasons.

There is a special case, accommodative esotropia. It is from relatively high hyperopia and when the child tries to see even at distance, accommodation kicks in and the eyes converge (cross) as a result. A pair of properly prescribed glasses or contacts can re-align the eyes without the need for surgery or orthoptics.

Also in Asian babies, because of the flat nose bridge and the thick epicanthal skin covering more of the nasal part of the eyes, there is an optical illusion of esotropia or pseudo-esotropia. You can shine a penlight about 3m away into the baby's eyes and observe the reflexes on the corneas. If the reflexes appear at the same position in each eye, then the eyes are aligned.

You may have heard of the term “vision therapy” and its putative efficacy. Historically, “vision therapy” is not very well-defined and in fact quite confusing. This much we do know: In two 2005 studies, comparing intensive office-based therapy and in-home pencil push-up exercise, the former seems to better resolve symptoms from convergence insufficiency, e.g., headaches, eye fatigue, blurred and double vision from near work. This conclusion is not without controversies, though. The claim of remedying learning disability, on the other hand, is unsupported.

More recent versions of “vision therapy” include training of re-focusing and visual perception, improvement of oculo-motor coordination and eye tracking. In fact, some professional athletes are enthusiastic supporters of this type of therapy.

As in other fields of medicine, the effectiveness of any treatment must be evidence-based. Let’s just say, much more needs to be done in the field of vision therapy.

3.3.1 Who's being lazy?

Amblyopia is commonly known as the lazy eye. Except for congenital opacities, a lazy eye is absolutely normal in structure, both inside and out, yet its vision is poor. The other eye, on the other hand, has good vision. To a child, the visual world would appear normal. And to others, nothing unusual about this child's eyes, either. For this reason, the discovery of amblyopia is almost all by accident, first noticed by an observant parent or a pediatrician.

There are three types of amblyopia:

Deprivational: this happens when there are cataracts or corneal opacities blocking the path of light into the eye. Naturally the opacities must be removed first.

Refractive: this type occurs due to a large difference between the refractive errors of the two eyes. For example, if one eye is normal or near-sighted and the other is very far-sighted, then the latter will remain unused to avoid diplopia - this then results in amblyopia. There is a subtype due to high astigmatism. It usually involves both eyes. And because part of the retina is never used fully, that part will become amblyopic and the vision will not achieve 20/20 even with the best correction.

Strabismic: In this type, the eye positions are not aligned or coordinated, so the less dominating eye becomes disused or suppressed on order of the brain. This eye then becomes amblyopic.

A “lazy” eye therefore is not an eye that does not want to contribute but rather it is prevented from doing so.

The treatment of amblyopia is really to force the amblyopic eye to see, by means of patching of the good eye, or by using atropine eyedrops to reduce the usage of the good eye. The earlier the treatment starts, the better the outcome.

The major problem with patching is the children’s resistance often from discomfort or teasing from their peers. Compliance using the atropine drops (once a day) is certainly easier and in fact the results are as good as that with eye patching. This was supported by a recent clinical study comparing these two methods: The improvement was 3.7 lines (on the visual acuity chart) in the patching group and 3.6 lines in the atropine group. And about half of each group can achieve a visual acuity of 20/25 or better.

So these are the two choices, both equally effective. Amblyopia in fact should not remain untreated. Unfortunately, we still see these cases from time to time.

3.2.3 Young-old eyes

"Tear flooded his young, old eyes..." (Calvin's Stones, Magnetic Poetry's Journal, Jan 4, 2006)

Unfortunately in the young eyes, we can find older people's problems, e.g., cataract and glaucoma. Congenital cataract and congenital glaucoma, that is. By far, these are the two major congenital anomalies of the eye.

There are inherent difficulties in examining the eyes of a tiny infant. A good example is the visual acuity which cannot be assessed accurately. Yet another is the measurement of the intraocular pressure. And often sedation is needed in order to perform a complete exam, and which often must be done in an OR setting. Refraction, on the other hand, can be done with trial-lens retinoscopy or a hand-held auto-refractor. The latter, however, is less useful if nystagmus is present. And contact lens fitting naturally requires full parental participation. Routine interactive tests, e.g., subjective refraction and visual field testing must be postponed until much later for obvious reasons.

Congenital cataract is diagnosed at birth or it can develop soon after. In 1/3 of the cases, cataract is present in only one eye. If in both eyes, then 23% of the patients have a family history in an autosomal dominant pattern. This type of congenital cataracts is frequently associated with metabolic/systemic diseases (e.g., hypolycemia, trisomy, and myotonic dystrophy). Some congenital cataracts are a result of infection in-utero, most commonly from rubella; although it can also be from a host of others including rubeola, chicken pox, cytomegalovirus, herpes simplex/zoster, poliomyelitis, influenza, Epstein-Barr virus, syphilis, and toxoplasmosis. In under-developed countries, it can be from poisons in the drinking water contaminated by industrial wastes.

Because of the early presentation, if the opacity obstructs vision and left untreated, amblyopia can develop in the affected eye, and permanent vision loss if both eyes are cataractous. The usual guideline is if the opacity is 3mm or greater and located in the path of the visual axis, then the lens must be extracted. Smaller opacities do not necessarily cause vision issues. They are often discovered by chance during an adulthood routine eye exam, to the patient's greatest surprise.

Congenital glaucoma is also present at birth; although most cases are detected during early infancy/childhood. It is caused by a malformation in the fluid drainage channels, known as the trabecular meshwork, in the eye. Very rarely it is hereditary; although it won't be surprising if some cases are. It can affect only one eye; however, in 70% of the cases, both eyes. And more in boys (65%). The increase in the intraocular pressure from fluid build-up can rupture the corneal endothelium causing entry of water into the cornea. And the eye itself enlarges in size as well. Like glaucoma in the adults, the retina can be permanently damaged.

Congenital glaucoma is treated with surgical creation of a drainage pathway. Often multiple surgeries are needed to finally stablize the intraocular pressure. As you can imagine, this requires the expertise of a pediatric ophthalmologist specializing in congenital glaucoma. A video from the University of Iowa demonstrating trabeculotomy is shown below:

http://webeye.ophth.uiowa.edu/eyeforum/cases/case42-Primary-Congenital-
Glaucoma-(Infantile-Glaucoma).htm

The eye is of course only a small part of the body which, while still in the developmental stage in the uterus, is subject to all sorts of assaults. Proper prenatal care, a healthy pregnancy, and full-term birth, can certainly go a long way towards avoiding all congenital diseases, not just cataract and glaucoma.

3.2.2 ROP

ROP, or retinopathy of prematurity, surprisingly is still quite prevalent. In older ophthalmology textbooks, ROP was referred to as retrolental fibroplasia and the cause was traced to excessive oxygen in the incubator. This occurred in the 1940s and 50s and was thought to be under control. However, with the recent advent of in-vitro fertilization and fertility drugs based on follicle-stimulating hormone and luteinizing hormone, multiple births have become relatively common. And with that, an increase of preemies. We often see on TV evening news, palm-sized infants inside the incubators with beaming parents looking on. While all lives must be celebrated, often unreported is a multitude of complications from pre-term births. The surviving babies often face a lifetime of health problems. And one of the problems is ROP.

In this day and age, excess oxygen in the incubator is no longer an issue, which is very carefully monitored. However, the development of the retina in pre-term babies is incomplete and for some reason, further development outside the womb is met with confusion. Often the blood vessels, reaching from the optic nerve to the peripheral retina, become fibrous that can pull off the retina (see the video below).

(Courtesy of National Eye Institute, NIH)

ROP is divided into 5 stages of increasing severity. Stage 5 is the most advanced that usually involves total retinal detachment. The video above illustrates such a case.

The treatment of ROP is essentially a repair, using laser, cryotherapy, or open-sky vitrectomy. We favor the more efficacious open-sky procedure in which the cornea is opened and the crystalline lens removed to expose the rest of the eye to the sky. Then the fibrous tissues are removed and the retina re-attached. The resulting aphakia, unlike that of the age-related cataract, is corrected with a contact lens first, then an IOL later in life. The visual acuity is usually quite good, often in the 20/40 - 20/60 range.

To avoid ROP and related health problems, perhaps higher-order births should be discouraged. Certainly multiple births should be managed by OBs and pediatric nurses with specialty training. They must not yet be treated as normal births.

3.2.1 Stargardt et al

There are several frequently encountered hereditary eye diseases. Most of them are autosomal recessive, i.e., both parents are carriers. They include Stargardt's Disease, Usher Syndrome, and Leber's Congenital Amaurosis (LCA), among others. Still another common occurrence is retinoblastoma, caused by a deletion of the tumor suppressor gene Rb. Rb codes for a protein crucial in the regulation of the cell cycle.

These diseases each affects a different tissue of the eye:

Stargardt's disease can be regarded as juvenile macular degeneration. Similar to AMD, the end result is a dense central scotoma. And the gene culprit is abca4. The starting age of Stargardt's is usually around adolescence. Fortunately, these patients will never lose vision entirely. Their central vision may decrease to around 20/100 - 20/400, the peripheral vision is still quite normal. So proper optical aids can be of tremendous help to these children.

Usher Syndrome involves a form of retinitis pigmentosa, together with deafness. There are three types from the most severe USH1, to less severe USH2, and more moderate USH3. So far 12 loci are known to cause Usher Syndrome and seven of them and their proteins also have been identified. For your info: Genes for USH1 are MY07A, USH1C, CDH23, PCDH15, and SANS; for USH2: USH2A; and for USH3: USH3A. It is important to differentiate the types for counseling purposes. For example, USH1 patients with profound deafness will need to learn Braille prior to age 10 before their vision totally deteriorates.

Another of the worst possible cases is LCA, in which, there is no detectable photoreceptor activity at all. And the disease usually starts at birth or during early infancy. There are now 11 types identified, each associated with a mutation. And 14 genes are now known to be involved. There is a bright side: More recently, clinical trials of gene therapy for LCA caused by mutations in the RPE65 have begun. This is based on previous successful animal studies (dogs with the same RPE65 mutations) and should be very promising. This may pave the way for future treatment of genetic eye diseases. We shall find out soon enough.

And retinoblastoma is a cancer of the pediatric eye caused by deletions or mutation of Rb in the q14 band of chromosome 13. There are two types, the first is the familial retinoblastoma, in which both copies of defective Rb are present (i.e., one from each parent). There is another, unilateral retinoblastoma which is non-hereditary and not as severe; although no less cancerous. The treatment of retinoblastoma is similar to other cancers. Often the eyes must be removed to preserve life.

Here, I should point out that the practice of pediatric eyecare carries an enormous responsibility. Indeed, in all cases, accurate diagnosis is absolutely essential.

At present, not all clinics have access to PCR machines and the tests are quite costly as well. So genetic analysis is still not as widely available as it should. We hope this situation changes in the future. For now, by studying family history and examining symptoms, and signs, the latter through ophthalmoscopic observation, fundus photography, visual fields, etc, in conjunction with electrophysiological testing, such as ERG and VER, we can still draw very accurate road maps. Furthermore, in almost all cases with residual sights, the children can also be managed successfully through low-vision care.

3.1 Pediatrics

Some babies are born with eye problems. It seems unfair. Well, it is unfair because some problems are hereditary while others are induced in-utero or from premature birth. Fortunately, with loving parental care and societal support, most if not all grow up to be well-adjusted boys and girls.

In every nation, there are schools for the blind. While some pupils indeed were born blind and require special education, many others simply need powerful optical aids such as magnifiers and telescopes to carry on visual tasks. With gene therapy and electrode implants in the offing, even those with no vision at all may one day see again. We hope, in not so distant future, schools for the blind will all close for lack of students.

We will now discuss the etiology of more prevalent eye diseases that cause vision loss in the pediatric population, e.g.,
1. Hereditary
2. Prematurity
3. Infection and poison

And in a separate category, we will examine children with compromised binocularity:
1. Amblyopia (lazy eye)
2. Strabismus

In these cases, higher-order functions such as depth perception and stereopsis are lost. While not as debilitating as the vision loss, it is still a barrier for children aspiring to many professions that require binocularity, e.g., airline pilots. Early intervention is therefore crucial.