Ocular Pathology: Glaucoma, Cataract, Retina & Uveitis

Aqueous Humor and Glaucoma

Production and outflow. The nonpigmented ciliary epithelium secretes aqueous humor into the posterior chamber by a carbonic anhydrase-dependent process modulated by β and α2 receptors. Aqueous passes through the pupil into the anterior chamber and leaves at the iridocorneal angle: most drains through the trabecular meshwork into the canal of Schlemm and episcleral veins, and the rest exits by the uveoscleral route through the ciliary muscle. Normal intraocular pressure (IOP) is about 10–21 mmHg.

Glaucoma is an optic neuropathy: progressive loss of retinal ganglion cell axons, seen as cupping of the optic disc with matching visual field loss, usually but not always with raised IOP.

Primary open-angle glaucoma. The angle is open, but trabecular outflow resistance rises. Damage is painless, bilateral, and silent: peripheral (arcuate) field defects come first and central acuity is lost last. The disc shows an enlarged cup-to-disc ratio. Risk factors are older age, African ancestry, family history, myopia, and elevated IOP. In normal-tension glaucoma the same damage occurs with normal IOP.

Acute angle-closure glaucoma. In a shallow anterior chamber (hyperopia, older age with a thickening lens, Asian ancestry), a mid-dilated pupil lets the peripheral iris bow forward (pupillary block) and seal the trabecular meshwork. IOP rises abruptly, causing severe eye pain, frontal headache, nausea and vomiting, blurred vision with halos, a red eye with a steamy edematous cornea, a fixed mid-dilated pupil, and a rock-hard globe. Anything that dilates the pupil can trigger it: dim light, anticholinergics (atropine, scopolamine, tricyclics, first-generation antihistamines), sympathomimetics, and dilating drops. Topiramate can cause a secondary, often bilateral, angle closure.

Glaucoma Pharmacology

Two strategies. Drugs either reduce ciliary secretion or increase outflow; prostaglandin analogs are usual first-line therapy for open-angle glaucoma.

Eye drops drain through the nasolacrimal duct into the nasal mucosa and bypass first-pass metabolism, so timolol drops can cause bronchospasm in asthma and bradycardia or heart block.

Cataract

Presentation. A cataract is opacification of the lens. It causes painless, gradually progressive blurring, glare, and halos around lights at night, with a diminished red reflex. Cataract is the leading cause of blindness worldwide, yet it is reversible with lens extraction and intraocular lens implantation. In infants, a congenital cataract presents as leukocoria, which must be distinguished from retinoblastoma.

• Age, smoking, alcohol, and ultraviolet light exposure
• Long-term corticosteroids (posterior subcapsular cataract)
• Diabetes: aldose reductase converts glucose to sorbitol, which traps water in lens fibers
• Classic galactosemia and galactokinase deficiency: galactose is converted to galactitol, causing infant cataracts
• Trauma, radiation, and chronic uveitis
• Congenital rubella, myotonic dystrophy, Wilson disease (sunflower cataract), and hypocalcemia

Macular Degeneration, Diabetic and Hypertensive Retinopathy

Age-related macular degeneration. AMD is the leading cause of irreversible central vision loss in older adults in developed countries; risks are age, smoking, and family history. The dry (atrophic) form, over 80% of cases, shows yellow drusen between the retinal pigment epithelium and Bruch membrane and later geographic atrophy, with slow central loss. AREDS supplements (vitamins C and E, zinc, copper, lutein/zeaxanthin) slow progression; β-carotene was removed from the formula because it raises lung cancer risk in smokers. In the wet (neovascular) form, choroidal neovascularization breaks through Bruch membrane and leaks fluid and blood beneath the macula, causing rapid central loss and metamorphopsia (wavy lines on an Amsler grid). It is a minority of cases but causes most severe vision loss, and intravitreal anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) are first-line.

Nonproliferative diabetic retinopathy. Hyperglycemia causes pericyte loss and basement membrane thickening. Microaneurysms are the earliest sign, followed by dot-blot hemorrhages, hard exudates (leaked lipoprotein), cotton-wool spots (nerve fiber layer infarcts), and venous beading. Diabetic macular edema can occur at any stage and is the most common cause of vision loss.

Proliferative diabetic retinopathy. Capillary closure leaves ischemic retina that releases VEGF, driving fragile new vessels on the disc, retina, and iris. These bleed into the vitreous, contract into tractional retinal detachment, and block the angle (neovascular glaucoma). Treatment is panretinal laser photocoagulation and/or intravitreal anti-VEGF, plus glucose and blood pressure control.

Hypertensive retinopathy. Chronic hypertension narrows arterioles and thickens their walls (copper and silver wiring), with AV nicking where arterioles compress venules. Severe elevations add flame-shaped hemorrhages, cotton-wool spots, and hard exudates in a macular star; optic disc swelling marks hypertensive emergency.

Vascular Occlusion, Detachment, and Other Retinopathies

Central retinal artery occlusion. The central retinal artery, a branch of the ophthalmic artery, is usually blocked by an embolus from carotid atherosclerosis (a refractile cholesterol Hollenhorst plaque) or by giant cell arteritis. Vision is lost suddenly and painlessly in one eye. The ischemic inner retina turns white and edematous, while the fovea, which lacks inner layers, shows the intact choroidal circulation as a cherry-red spot; arterioles may show boxcar segmentation. CRAO is a stroke equivalent that warrants carotid and cardiac evaluation, and in older patients ESR and CRP for giant cell arteritis. A cherry-red spot also occurs in Tay-Sachs and Niemann-Pick disease, where lipid-laden ganglion cells whiten the surrounding retina.

Central retinal vein occlusion. Thrombosis of the central retinal vein, favored by age, hypertension, diabetes, glaucoma, and hypercoagulable states, causes painless monocular blurring with a blood-and-thunder fundus: hemorrhages in all four quadrants, dilated tortuous veins, cotton-wool spots, and disc swelling. Macular edema is treated with anti-VEGF, and ischemic disease can produce neovascular glaucoma.

Retinal detachment. The neurosensory retina separates from the retinal pigment epithelium. The rhegmatogenous type follows a retinal tear (high myopia, trauma, cataract surgery, posterior vitreous detachment); tractional detachment complicates proliferative diabetic retinopathy; exudative detachment follows fluid leakage. Photopsia and a shower of floaters precede a painless curtain across the field, and the retina appears gray and elevated. Prompt surgical repair, before the macula detaches, preserves central vision.

Retinitis pigmentosa. Inherited photoreceptor degeneration (for example, rhodopsin mutations; dominant, recessive, or X-linked) affects rods before cones: night blindness in youth, then progressive tunnel vision. The fundus shows bone-spicule pigmentation, attenuated arterioles, and waxy disc pallor. Similar retinopathy occurs in abetalipoproteinemia (vitamin A and E malabsorption), Refsum disease, Usher syndrome (with deafness), and Kearns-Sayre syndrome.

CMV retinitis. In AIDS with CD4 counts below 50/mm³, CMV causes painless floaters and field loss with fluffy yellow-white perivascular necrosis and hemorrhages ("pizza pie") and little vitreous inflammation. Treatment is ganciclovir or valganciclovir (foscarnet for resistance), sometimes intravitreal, plus antiretroviral therapy. Toxoplasma retinochoroiditis differs: a focal white lesion with dense vitritis ("headlight in the fog"), often beside an old pigmented scar, treated with pyrimethamine and sulfadiazine.

Uveitis and the Swollen Optic Disc

Uveitis. Inflammation of the iris and ciliary body (anterior), pars plana (intermediate), or choroid and retina (posterior). Anterior uveitis causes a painful red eye with photophobia, ciliary flush, cells and flare in the anterior chamber, sometimes a hypopyon, and a small irregular pupil from posterior synechiae. Treatment is topical corticosteroids plus a cycloplegic to relieve ciliary spasm and prevent synechiae.

• HLA-B27 disease: ankylosing spondylitis, reactive arthritis, inflammatory bowel disease, psoriatic arthritis (acute unilateral anterior uveitis)
• Sarcoidosis: granulomatous, often bilateral, anterior or posterior uveitis
• Juvenile idiopathic arthritis: silent chronic anterior uveitis in ANA-positive oligoarticular disease, so children need routine slit-lamp screening
• Behçet disease (HLA-B51): hypopyon and retinal vasculitis with oral and genital ulcers

Papilledema vs optic neuritis. Papilledema is optic disc swelling caused by raised intracranial pressure from a mass, idiopathic intracranial hypertension, venous sinus thrombosis, or malignant hypertension. Optic neuritis is inflammatory demyelination of the optic nerve, often the first sign of multiple sclerosis; high-dose IV methylprednisolone speeds recovery.