{22180} keratoconus

Leukocoria: White instead of the normal red pupillary light reflection. Think of retinoblastoma!

Limbus: The junction between the cornea and the sclera

Marcus Gunn pupil: Descriptions vary, but this is an indicator for optic nerve damage in the involved eye. The pupil is larger than the other one ("to let in more light"), and constricts more slugglishly than the other on both direct and consensual testing.

Myopia: Nearsightedness, convergence of focus anterior to the retina. Often, but not always, due to an elongated eyeball.

Panophthalmitis: Inflammation of the whole eye. Usually bacterial, after trauma.

Papilledema: Changes in the optic disk seen in increased intracranial pressure. Mechanisms are complex and reviewed in "Big Robbins"; longstanding papilledema damages the optic nerve.

{22092} papilledema

Phaco-, phako-: Pertaining to the lens of the eye

Photophobia: Pain on exposure to light

Phthisis bulbi: End-stage, shrunken, often painful eye

Presbyopia: Loss of the ability of the lens to alter its shape; one result of advancing age. The usual reason people get bifocal eyeglasses.

Proptosis: Forward protrusion of the eye

Retinal dysplasia: Persistence of many little tubules and/or "rosettes", like in embryonic eye or classic retinoblastomas. Seen, usually with other abnormalities, in certain birth defects.

Scotoma: A blind spot

Strabismus: Eyes pointed in different directions, the result of eye muscle balance problems. Several interesting synonyms exist, including (for some reason) "squint".

Synechiae: As elsewhere, fibrous adhesions resulting from healing

Uvea / Uveal tract: Term for the vascular coat of the eye, i.e., the choroid, ciliary body, and iris.

Xerophthalmia: Dry eyes

BIRTH DEFECTS: A selection

Trisomy 13 ("Trisomy D", "Patau's")

You're already familiar with the other stigmata of this illness. The eyes are almost never normal. They may be single ("cyclops") or fused (cyclops variant); even if there are the correct number, they present an array of abnormalities described in "Big Robbins".

Future eye pathologists: A coloboma with cartilage suggests Patau's.

Trisomy 21 ("Down's", etc.)

Brushfield's spots are areas where the iris is hypoplastic.

{15608} Brushfield's spots

A variety of other abnormalities are common. Remember esotropia and epicanthic folds.

Congenital rubella syndrome

Again, you are familiar with the other features of this syndrome.

Rubella cataract results from retention of nuclei in the center of the lens. This is pretty distinctive.

*The iris epithelium is largely necrotic, there may be granulomas, and so forth. The result is leather iris.

*The pigment layer of the retina alternates between hypertrophic ("pepper") and atrophic ("salt") areas.

* Congenital rubella syndrome with blindness is still rampant where immunization is not practiced, or where people refuse (Arch. Ophth. 122: 541, 2004; J. Inf. Dis. 187(S1): S-146 & S-191 & S-223 & S-235, 2003; Am. J. Pub. Health 90: 1555, 2000).

Congenital syphilis

Again, you are familiar with the extra-ocular features.

The characteristic eye finding is inflammation of corneal stroma (interstitial keratitis). This appears in youth, but is not present at birth.

There are likely to be other abnormalities in the eyes.

Tay-Sach's

In this and a few other inborn errors of metabolism, the normal red of the macula forms the "cherry" in the pale, lipid-laden retina.

{20115} cherry red spot

* Lisch nodules, little hamartomas, are usual in the iris of neurofibromatosis I patients.

LID PROBLEMS

Sty (hordeolum) is suppuration (usually staphylococcal) of the hair follicle, sebaceous glands (* "Zeis's glands"), and/or apocrine glands (* "Moll's glands").

Chalazion (* Greek for hailstone) is chronic, usually granulomatous, inflammation of the sebaceous (* "Meibomian") glands.

{13143} chalazion

Of course, infections that involve the bulbar conjunctiva often involve the conjunctiva of the lid, too. See below.

VITAMIN A DEFICIENCY (still around: Br. Med. J. 310: 1051, 1995)

The basic problem (at the front of the eye) is excessive squamous differentiation of the corneal epithelium ("xerophthalmia"). Bitot's spots are actually just the thickened, hyperkeratotic epithelium, typically at the limbus.

As you'd also expect, the cornea mucus cells are lost.

When keratomalacia is said to be present, it means the hyperkeratotic epithelium has become soft. It may become secondarily infected (* Corynebacterium xerosis, others) and even perforate.

Remember that in the absence of vitamin A, you can't make the pigment for rods. Night blindness results.

Many governments, for their own dark reasons, fail to implement or even allow public health measures that would do a lot of good for very little money spent. Over half of the boys in rural Ethiopia have Bitot's spots (East African Medical Journal 76: 590, 1999); of course their growth is stunted and their vitamin A levels very low. Cambodia: Arch. Ophth. 122: 517, 2004.

An amateur vegan family blinds its six-year-old son: Arch. Ophth. 122: 1228, 2004. More about vegans: Clin. Ped. 43: 107, 2004.

* After years of delay because of anti-biotech activism, vitamin-A enriched rice is now widely used and being welcomed by the world's poor: Nature Biotech. 21: 971, 2003.

TRACHOMA (Br. Med. J. 362: 223, 2001; Lancet 362: 223, 2003)

We've already discussed Chlamydia trachomatis, an important cause of blindness worldwide.

The pathology mostly involves lymphoid follicles on the conjunctival membrane. Later there is scarring.

If there is coexistent vitamin A deficiency, the infection is likely to be worse (Lancet 357: 1676, 2001).

McCallan's stages of trachoma:

I: Follicles (i.e., lymphoid infiltrates) on the cornea, with early fibrosis

II: Debris-laden macrophages ("Leber cells") appear

III: Severe scarring; contraction produces an entropion

IV: The actual infection self-cures, since the damaged, opacified eye surface is no longer vulnerable to infection.

The World Health Organization "plans to eliminate trachoma by the year 2020" by mass antibiotic use, twice a year in areas where the disease is prevalent (Nat. Med. 5: 572, 1999).

CONJUNCTIVITIS

Trachoma's lesser chlamydial counterpart in the U.S. is swimming pool conjunctivitis (inclusion conjunctivitis). Look for the characteristic inclusions on smears (* we suggest a Giemsa stain).

Bacterial conjunctivitis generally produces a red eye with purulent discharge. Think of gonorrhea, pneumococci, staph (* I once endured this), and Hemophilus.

Classic ophthalmia neonatorum was gonococcal infection acquired in the birth canal. Silver nitrate, erythromycin, and (now) povidone iodine (great for the poor nations) are prophylaxis (NEJM 332: 562 & 600, 1995).

Conjunctivitis can also be viral (remember adenovirus and measles), IgE-mediated (vernal conjunctivitis, i.e., in the springtime allergy season; look for eosinophils), due to delayed hypersensitivity (often cosmetics), due to injury or a foreign body, or due to ultraviolet light (remember "snow blindness").

Remember that conjunctivitis from most causes can involve the cornea (keratoconjunctivitis). See below. Unless you know the cause of the conjunctivitis, don't share towels....

PINGUECULA AND PTERYGIUM

Pinguecula is fatty deposits in the conjunctiva, especially in people who've had lots of sun exposure. Look near the nasal aspect of the limbus on both sides.

{5932} pinguecula

Pterygium ("wing") is more of the same, but extending over the cornea, obliterating Bowman's membrane.

{21874} pterygium, gross
{21876} pterygium, gross
{21879} pterygium, micro, oil red O stain for lipid

CORNEAL DISEASE

Remember the layers (from out to in): Epithelium, Bowman's membrane, stroma, Descemet's membrane, endothelium.

Because there are no vessels here, once the cornea gets infected, it's serious. Especially in parts of the world where treatment is not available, blindness often results.

Herpes simplex produces the familiar dendritic ulcers.

{14127} herpes keratitis
{21931} herpes keratitis
{22055} herpes, inclusion bodies

Acanthamoeba recently produced an epidemic among users of certain contact-lens solutions.

{22192} red eye from acanthamoeba

Kayser-Fleischer ring: copper deposit in Wilson's disease. Band keratopathy: Hypercalcemia.

{21992} Kayser-Fleischer ring
{21927} band keratopathy, gross
{21928} band keratopathy, micro, calcium dark blue

*The corneal dystrophies, which render the cornea opalescent due to faulty chemistry, include several hereditary problems.

Granular dystrophy -- autosomal dominant -- opacities

Lattice dystrophy -- autosomal dominant -- amyloid

Macular dystrophy -- autosomal recessive -- mucopolysaccharide

Also worth knowing: Fuch's -- leaky backside epithelium, with water bubbles on the inner surface

Here's an example of one locus for several illnesses: BIGH3 can cause lattice, granular, or other corneal dystrophies depending on the mutation (Am. J. Hum. Genet. 62: 320, 1998). Why is this not surprising, especially in the cornea?

{21935} granular dystrophy
{21938} granular dystrophy
{21920} lattice dystrophy
{21957} lattice dystrophy, congo red
{21929} macular dystrophy, histology
{21932} macular dystrophy, histology
{22117} corneal transplant
{22121} corneal transplant

If for some reason you wish to know more about amyloid on the cornea and elsewhere in the eye, refer to Am. J. Ophth. 117: 529, 1994.

UVEAL DISEASE

Aniridia: No iris. Lots of problems with the eyes; many of these patients have a gene deletion that extends to the nearby Wilms tumor locus (chromosome 11).

Albinism: The major problem these people face is excessive sensitivity of the eye to light.

Non-granulomatous uveitis is usually idiopathic, chronic inflammation.

Granulomatous uveitis (by contrast) has a long differential...

Infection

Bacteria: tularemia, syphilis, gonorrhea

Viruses: CMV, zoster

Fungi: various

Other: toxoplasmosis. (NOTE: Toxoplasmosis is an important disease of the eye. In the worst cases, pathologists find patches of coagulation necrosis in retina and choroid.)

Odd immune diseases

Sarcoidosis

Ulcerative colitis and Crohn's disease

Reiter's and Behçet's syndromes

Sympathetic ophthalmia is probably an autoimmune reaction against one's own pigment epithelium and retinal neurons following penetrating injury of one eye. Unfortunately, it involves both eyes, and does great harm. Thankfully it is rare, but the only sure prevention is to enucleate the injured eye within a week or two. A white-knuckle management problem for ophthalmologists. The anatomic pathology: Am. J. Ophth. 138: 475, 2004.

All about uveitis: Lancet 338: 1498 & 1501, 1991. Since material is seldom obtainable for study, the antigens involved in the (surely immune-mediated) havoc remain largely unknown.

CATARACTS

A variety of opacities in the lens; nuclear sclerosis is the most common type seen in the aging lens.

{12428} cataract
{22009} cataract
{22209} cataract
{22212} cataract
{22251} cataract
{22254} cataract; nuclear sclerosis

Remember as causes of cataract:

radiation

long-term glucocorticoid therapy

hypoparathyroidism

congenital rubella

trauma

diabetes ("sorbitol snowflake cataract", others)

galactosemia

genes (* two loci, the crystallins, are known)

heavy sunlight exposure (Ophth. 108: 1400, 2001, minor risk)

While we're on the subject of lens disease, a displaced lens ("ectopia lentis") is one problem faced by Marfan types.

{21999} ectopia lentis

RETROLENTAL FIBROPLASIA ("retinopathy of prematurity"; Ped. Clin. N.A. 50: 77, 2003)

The developing fetal retinal circulation, especially at its temporal margin, is selectively damaged by high concentrations of oxygen. The vessels, which are sprouting from the optic disk, at first constrict, then obliterate, so that the peripheral retina fails to vascularize. Several weeks after cessation of oxygen therapy, vessels begin sprouting willy-nilly from the edge, and grow into the vitreous; scar may contract and detach the retina, and there may be other problems.

* Not surprisingly, the mechanism turns out to be suppression of VEGF-A production in the retina. The details are being worked out (J. Clin. Invest. 112: 50, 2003).

This is a classic cause of blindness in premature infants treated with high concentrations of oxygen. It became a major public health problem in the 1940's and early 1950's (my grammar school had a girl a few years older than myself who had a full-time amanuensis). It became less troublesome when oxygen concentrations were reduced, but has recurred now that very small babies are surviving (a 600 gm baby tolerates even 90 mmHg of oxygen poorly).

HYPERTENSIVE AND ARTERIOSCLEROTIC (better, "arteriolosclerotic") RETINOPATHY

A common subject for discussion on rounds. Here's the system:

Hypertensive retinopathy: High blood pressure is bad for the vessels.

Grade I: The arterioles are a bit narrowed

Grade II: The arterioles are going into spasm somewhere

Grade III: There are bleeds

Grade IV: There is also edema of the optic disk, i.e., the hypertension has resulted in increased intracranial pressure

{22018} hypertensive retinopathy with hemorrhages

Arteriosclerotic retinopathy: Due to progressive opacification of the arteries

Grade I: Widened light reflex due to "hyaline arteriolosclerosis", which renders the vessels opalescent

Grade II: AV crossing defects; the hyaline wall of the artery makes it hard to see the vein underneath

Grade III: Copper wires; the blood doesn't show clearly through the arterial wall

Grade IV: Silver wires. The blood fails to show at all.

{22034} don't forget diabetic retinopathy, too

RETINITIS PIGMENTOSA

A heterogeneous group of diseases, mostly hereditary, in which the photoreceptor cells gradually die off. Patients are first troubled by loss of peripheral vision, and later lose all sight. The rods are typically lost before the cones ("night blindness", again).

There is proliferation of the pigment cells of the retina, typically along the vessels.

The molecular biology for the major autosomal dominant forms were worked out in the early 1990's. Around 1/3 of cases have a defective rhodopsin gene; some people with simple autosomal-dominant night-blindness have the same thing (Nature 367: 639, 1994), and vitamin A in fairly big doses can help these folks.

*Other autosomal dominant syndromes are known (RP1, peripherin, NRL: Br. J. Ophth. 86: 328, 2002).

In common (rhodopsin) retinitis pigmentosa, the defective rhodopsin accumulates and kills the cells. Gene therapy now works in mice, and involves administering a ribozyme (via a virus) that cleaves the defective gene's mRNA (Nat. Med. 4: 967, 1998.)

Usher syndrome (retinitis pigmentosa and congenital nerve deafness) is often the myosin VII-A locus.

Consider night blindness in children with unexplained fear of the dark.

{22074} retinitis pigmentosa

Retinitis pigmentosa
Prize photograph
Institute of Medical Illustrators

Stationary night blindness, i.e., the rods don't work but the cones work fine, has a variety of genetic causes (Nat. Genet. 13: 358, 1996; update Am. J. Ophth. 135: 733, 2003).

Vitamin A deficiency is of course a better-known cause of night blindness, but thankfully it is no longer common in the U.S.

Night-vision goggles are now coming into use for people with night-blidness (Inv. Op. 45: 1725, 2004).