Eye Pathologies - Cataracts

Cataracts are any opacity of the lens
Worldwide, cataracts are the most common reversible cause of blindness
Cataract appearance depends on the location of the opacity within the lens
Cortical cataracts are radial or spoke-like opacities, found in the anterior or posterior cortex of the lens
Nuclear sclerosis cataracts have a yellow-brown discoloration of the central lens
Posterior subcapsular cataracts are located next to the capsule, in the posterior aspect of the lens

Cataracts - Clinical Features

Cataracts cause a gradual, painless, progressive decrease in visual acuity (VA)
Symptoms include glare or dimness, halos around lights, and monocular diplopia (double vision)
Some patients experience a "second sight" phenomenon, becoming more myopic due to increased lens refractive power (in nuclear sclerosis only)
Opacities of the lens can be seen with an ophthalmoscopic examination
Surgery or laser therapy are the typical treatments.
Post-surgery, a proportion of patients experience posterior subcapsular cataracts.

Cataracts - Causes

90% of cataracts are due to age-related changes within the lens
These changes lead to nuclear sclerosis, leading to a yellow-brown tint to vision which reduces blue light transmission.
The lens cortex can liquefy, causing cortical cataracts
Systemic diseases and certain medications can also contribute to cataract formation such as diabetes, Wilson's disease, hypocalcemia, or systemic steroid use
Eye-specific conditions like trauma, radiation, or uveitis can also lead to cataracts.

Uveitis

Uveitis is inflammation of the choroid layer
Categories include: iritis, iridocyclitis, posterior uveitis, and endophthalmitis.
Endophthalmitis is associated with bacterial infection of the entire eye
Uveitis is mostly divided into anterior and posterior uveitis
Anterior uveitis is more common, roughly about 8 cases per 100,000 people a year, where 90% are anterior
Uveitis can cause various complications such as macular edema and destruction, glaucoma, corneal damage, cataracts, and destruction of the entire eye.

Uveitis - Etiology

About 90% of anterior uveitis cases are idiopathic
Other possible causes include seronegative spondyloarthropathies (e.g., ankylosing spondylitis), inflammatory bowel diseases (IBD), sarcoidosis, juvenile idiopathic arthritis (JIA), lupus, Behcet's disease, AIDS, and herpes
Most common causes of anterior uveitis are idiopathic, sarcoidosis, and autoimmune
Posterior uveitis is frequently associated with infections, most commonly Toxoplasmosis and CMV infections.
Autoimmune and sarcoidosis are also associated with posterior uveitis

Uveitis - History & Physical

Acute anterior uveitis causes pain, redness, photophobia, excessive tearing, and decreased vision. Pain typically develops over a few hours or days, except in cases of trauma.
Chronic anterior uveitis mostly presents with blurred vision, mild redness, little pain, or photophobia, except in acute episodes.
Posterior uveitis may present with blurred vision and floaters.
In general, anterior uveitis symptoms include pain, redness, and photophobia; these symptoms are absent in posterior uveitis
Conjunctival injection, where the limbus is more inflamed than the periphery, may occur. In conjunctivitis, the periphery is still fairly erythematous compared to the limbus.
Physical examination can reveal reduced visual acuity and a funny-looking iris and pupil. The iris may be stuck to the lens (synechiae), with white cells (flare) present in the anterior chamber. Increased intraocular pressure is another possible sign.
Hypopyon and hyphema are associated conditions seen in some cases

Aqueous Humor Production

Aqueous humor production is a three step process: secretion into posterior chamber, movement to the anterior chamber, and reabsorption through the scleral venous sinus.
Impaired drainage of aqueous humor can lead to increased intraocular pressure

Glaucoma

Glaucoma is a progressive, pressure-sensitive optic neuropathy characterized by structural changes to the optic nerve head and visual field changes.
Most glaucomas are associated with elevated intraocular pressure (IOP), but some can occur with normal or low IOP.
Normal IOP typically ranges between 10-21 mmHg.
Glaucoma is a major cause of blindness, with approximately 1.6 million people in the USA experiencing visual impairment.

Types of Glaucoma

Glaucoma can be categorized into open-angle and closed-angle types. Open-angle is more common (95%).
Open-angle glaucoma involves complete physical access of the aqueous humor to the trabecular meshwork. In contrast, closed-angle glaucoma is characterized by an inability for the aqueous humor to reach and drain through the trabecular meshwork
Primary open-angle glaucoma occurs with normal or slightly elevated IOP, while closed angle typically is associated with markedly elevated IOP

Primary Open-Angle Glaucoma

Possible causes include obstruction of trabecular meshwork, loss of trabecular endothelial cells, reduced pore size of endothelial cells, reduced phagocytic activity, and neurological feedback mechanisms
Many patients have normal IOP but increased IOP between 30-40 mmHg is a significant risk factor for progression.
Clinical manifestations include asymptomatic bilateral (but one side often worse) insidious (gradual) loss of vision. Temporal field loss occurs first.
Physical examination typically reveals increased IOP, flame-shaped hemorrhages, increased cup-disk ratio, and optic nerve atrophy.

Secondary Open-Angle Glaucoma

Caused by trabecular meshwork clogging. This can be due to high-molecular-weight lens proteins, red blood cells after trauma, iris epithelial pigment granules, and necrotic tumors. It can develop quickly with similar symptoms to acute angle-closure glaucoma.

Primary Angle-Closure Glaucoma

Risk factors for this condition include race (Asian, Southeast Asian, Inuit), hyperopia, female sex, environmental factors (e.g., situations such as watching movies or confined spaces, the use of certain medications e.g. antihistamines, dim lighting).
Key characteristic is the transient apposition of the pupillary margin of the iris to the anterior surface of the lens, blocking aqueous humor flow. This leads to elevated intraocular pressure, which can damage the lens and retina. Marked elevation in IOP usually exceeds 40 mmHg.

Primary Angle-Closure Glaucoma - Clinical Features

Typically very painful, photophobic, unilateral (one side), redness of the eye. Redness of the eye includes peripheral conjunctiva, and can encroach on the limbus.
Pupil may be fixed in mid-dilation with decreased visual acuity and the presence of haloes around lights.
Other symptoms can include subcapsular opacities in the lens, corneal edema, and degeneration. A characteristic symptom is irreversible vision loss in hours or days

Secondary Angle-Closure Glaucoma

Typically related to diabetes-associated neovascularization and the growth of a neovascular membrane over the trabecular meshwork. Uveitis (anterior) can cause synechia (constricting membranes) to adhere iris to lens, closing angle

Glaucoma - Treatment

Acute closed-angle glaucoma often requires acute interventions like laser iridotomy, or surgery (if necessary).
Medications reduce aqueous humor production and increase aqueous outflow
Medications include topical alpha 2-adrenergic agonists, topical beta 1-blockers, miotics (pilocarpine), prostaglandin analogues, and carbonic anhydrase inhibitors (e.g. acetazolamide)
Primary open-angle glaucoma typically uses similar medications, and laser trabeculoplasty may be considered for certain patients.

Retinal Detachment

Separation of neurosensory retina from retinal pigment epithelium
Rhegmatogenous retinal detachment (caused by tear) - most common type
Possible secondary causes (without a retinal break) - Complication of a variety of conditions (e.g., vascular disorders, trauma, hypertension, tumors, autoimmune diseases etc.)
Symptoms may include the sensation of a flashing light (photopsia), floaters, and the appearance of a shadow in the peripheral visual field that may expand to cover the entire visual field
The appearance of floaters and a shadowy peripheral visual field (or "curtain-like") spread are characteristic symptoms
Immediate referral for ophthalmological consultation and diagnosis are required

Retinal Vascular Disease - Diabetes Mellitus

Hyperglycemia's effects on the lens and iris have already been described. This can cause cataracts, and neovascular membranes that lead to glaucoma.
Diabetic retinopathy is classified into background (preproliferative) and proliferative types.
Background retinopathy involves thickened basement membranes, microaneurysms, macular edema, and hemorrhagic exudates.
Proliferative retinopathy features the appearance of new vessels (neovascularization) sprouting from existing vessels. These new vessels can appear on the optic nerve head or the surface of the retina.
Diabetic retinopathy is a leading cause of new cases of blindness in the USA resulting in 8000 people becoming legally blind yearly (due to complications such as retinal detachment).

Background (Preproliferative) Diabetic Retinopathy

Thickening of the retinal blood vessel basement membrane
Common occurrence of microaneurysms (dilated blood vessels)
Macular edema (swelling of the macula)
Hemorrhagic exudates (bleeding and leaks from blood vessels)

Proliferative Diabetic Retinopathy

Formation of new blood vessels that grow on the optic nerve head or retinal surface
Potential complications include neovascularization (growth of new vessels), hemorrhages, and retinal detachment

Diabetic Retinopathy - Clinical Features

Initial stages are generally asymptomatic
More advanced stages can present with: floaters, blurred vision, distortion, and progressive vision loss
Symptoms can appear as microaneurysms in early stages
Other features can include hemorrhages (dot and flame), general retinal edema, hard exudates, cotton wool spots, macular edema.
Retinal detachment is a potential late complication.

The Cotton-Wool Spot

Axoplasmic transport in the nerve fiber layer is interrupted, leading to axonal damage.
Accumulation of mitochondria (cytoid bodies) at the ends of damaged axons
Collections of cytoid bodies appear on ophthalmoscopic examination as cotton-wool spots
Detection of cotton-wool spots is seen in a variety of retinal occlusive vasculopathies. Diabetes and hypertension are common causes

Macular Degeneration

Macular degeneration is the damage to the macula, which is responsible for central vision
Early stages characterized by the appearance of drusen (small, round, beneath retina). They generally do not affect vision significantly.
Late stages are usually associated with vision loss, most often presenting in one eye first.
Dry (atrophic) ARMD is an irreversible form of the disease, which commonly causes difficulty in situations such as reading or recognizing faces in early stages, and eventually severe vision loss worldwide.
Wet (exudative, neovascular) ARMD progresses quicker and is characterized by the development of neovascular membranes, blood vessels below the retina, which can penetrate the retinal pigment epithelium and underlying neurosensory retina.
The exudate (blood) from the vessels may organize into retinal pigment epithelial cells, which may lead to macular scars.

ARMD - Pathogenesis

Etiology (cause) is largely unclear.
Associated causes include smoking, dietary issues/nutritional factors, sometimes treated with high-dose antioxidants, atherosclerosis, and hypertension.
Familial causes exist with some difficulty identifying the associated genes, with some related to the complement component (complement factor H)