Clin Med: Eye Manifestations of Internal Disease

Episcleritis

Acute, typically benign and self-limited inflammation of the episclera, the vascular connective tissue located between the conjunctiva and sclera, which is most commonly idiopathic (~65–75%) or associated with systemic autoimmune conditions (~25%). Pathophysiology involves superficial episcleral vascular inflammation where vessels remain mobile over the sclera and blanch upon application of topical phenylephrine. Clinical presentation features acute onset of sectoral or diffuse eye redness, mild tenderness or irritation, tearing, and a foreign-body sensation, while visual acuity remains normal without severe pain or prominent photophobia.

Scleritis

Severe, vision-threatening inflammation of the deep scleral tissue, with approximately 50% of cases linked to systemic autoimmune or inflammatory diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, or systemic lupus erythematosus. Pathophysiology involves deep scleral vascular engorgement causing tissue edema and a characteristic deep bluish or violet hue. Clinical presentation features severe, deep, boring or piercing ocular pain that often awakens the patient from sleep and worsens with extraocular movements, along with scleral tenderness and potential visual loss.

Posterior Scleritis

Severe inflammation involving the sclera posterior to the insertion of the rectus muscles. Pathophysiology involves retrobulbar scleral edema and fluid accumulation, often producing a "T-sign" on B-scan ultrasonography. Clinical presentation includes deep ocular pain, decreased or blurred vision, pain during eye movement, and possible proptosis, diplopia, optic disc edema, or choroidal abnormalities, frequently with a normal external eye appearance.

Anterior Uveitis

Inflammation of the anterior uveal tract (iris and ciliary body), which is mostly idiopathic but can stem from autoimmune conditions (such as spondyloarthritis, inflammatory bowel disease, or sarcoidosis) or infections (such as HSV, VZV, or syphilis). Pathophysiology involves inflammatory breakdown of the blood-ocular barrier, causing white blood cells and protein to leak into the anterior chamber. Clinical presentation features eye pain, prominent photophobia, a red eye with ciliary flush around the cornea, blurred vision, a constricted or irregular pupil (miosis), and slit-lamp findings of anterior chamber cells and flare.

Intermediate and Posterior Uveitis

Inflammation predominantly affecting the vitreous humor (intermediate) or the retina and choroid (posterior). Pathophysiology involves intraocular inflammatory or infectious processes involving the posterior ocular structures. Clinical presentation is characterized primarily by floaters and decreased visual acuity, often with little to no eye pain or external redness.

Amaurosis Fugax

Sudden, transient monocular vision loss caused by temporary retinal ischemia, acting as a retinal transient ischemic attack (TIA). Pathophysiology involves temporary blockage of retinal arterial blood flow, most commonly from an embolus originating from ipsilateral carotid artery atherosclerosis. Clinical presentation features a sudden, painless visual deficit classically described as a "curtain" or "shade" descending over the eye lasting seconds to minutes with complete resolution, with physical examination sometimes revealing a Hollenhorst plaque

Hollenhorst plaque

a bright cholesterol embolus in retinal arteriole

Central Retinal Artery Occlusion (CRAO)

Acute ischemic stroke of the retina caused by embolic occlusion of the central retinal artery, constituting an ophthalmic and neurologic emergency. Pathophysiology involves complete arrest of arterial perfusion to the inner retinal layers, producing rapid cellular ischemia and infarction. Clinical presentation presents as sudden, severe, painless monocular vision loss, a relative afferent pupillary defect (RAPD), and funduscopic findings including diffuse retinal whitening/pallor, a "cherry-red spot" at the fovea, attenuated retinal arteries, and "boxcarring" of retinal blood flow.

Branch Retinal Vein Occlusion (BRVO)

Obstruction of a branch retinal vein, most frequently at an arteriovenous crossing where a sclerotic arteriole compresses the underlying vein within a shared sheath. Pathophysiology involves elevated venous capillary pressure distal to the blockage, leading to localized vascular leakage, ischemia, and edema. Clinical presentation features variable painless vision loss depending on macular involvement, with funduscopy demonstrating sectoral intraretinal hemorrhages, dilated tortuous veins, cotton-wool spots, and macular edema restricted to the involved retinal sector.

Central Retinal Vein Occlusion (CRVO)

Blockage of the main central retinal vein near the lamina cribrosa, strongly associated with hypertension, diabetes, hyperlipidemia, and glaucoma. Pathophysiology involves widespread venous stasis and hydrostatic pressure elevation throughout the retinal vasculature, causing global capillary breakdown and hypoxia. Clinical presentation includes sudden, painless, extensive vision loss, with funduscopy revealing diffuse "blood and thunder" intraretinal hemorrhages across all four quadrants, dilated and tortuous veins, cotton-wool spots, optic disc edema, and macular edema.

Nonproliferative Diabetic Retinopathy (NPDR)

Early retinal microvascular disease resulting from chronic hyperglycemia, which damages retinal capillary walls. Pathophysiology involves capillary hyperpermeability and progressive microvascular breakdown and closure without new vessel growth. Clinical presentation is often asymptomatic early on, showing funduscopic signs such as microaneurysms (the earliest visible sign), dot-blot retinal hemorrhages, hard exudates (lipid deposits from leaking vessels), cotton-wool spots, and potential diabetic macular edema.

Proliferative Diabetic Retinopathy (PDR)

Advanced stage of diabetic retinopathy driven by persistent, severe retinal microvascular ischemia. Pathophysiology involves retinal hypoxia causing marked elevation of vascular endothelial growth factor (VEGF), which stimulates abnormal neovascularization on the optic disc or retina that can bleed or contract via fibrovascular tissue growth. Clinical presentation includes severe vision threat or sudden vision loss caused by vitreous hemorrhage or tractional retinal detachment.

Hypertensive Retinopathy

Damage to the retinal microvasculature secondary to acute or chronic elevated systemic blood pressure. Pathophysiology involves arteriolosclerosis and vascular remodeling in chronic hypertension, progressing to blood-retinal barrier disruption and ischemia in severe elevations. Clinical presentation ranges from chronic arteriolar narrowing, copper wiring, and AV nicking to flame-shaped hemorrhages in the superficial nerve fiber layer, cotton-wool spots, hard exudates, and optic disc edema (signaling hypertensive emergency).

flame-shaped hemorrhages

hemorrhage occurs in the superficial nerve fiber layer where nerve fibers run parallel to retinal surface

AV nicking

thickened arteriole compresses the underlying vein where they cross

copper wiring

thickened/sclerotic arteriole causes an increased light reflex

HIV Retinopathy

Retinal microvascular disease associated with advanced HIV infection and severe immunosuppression. Pathophysiology involves HIV-related microvasculopathy and capillary occlusion. Clinical presentation is typically asymptomatic and discovered on fundus examination as cotton-wool spots, occasionally accompanied by retinal hemorrhages and microaneurysms.

CMV Retinitis

Opportunistic viral infection of the retina occurring in severely immunocompromised individuals, classically in patients with AIDS having a CD4 count under 50 cells/mm³. Pathophysiology involves full-thickness viral retinal necrosis and necrotizing vasculitis. Clinical presentation includes floaters, flashes, blurred vision, and visual field defects, with funduscopy showing yellow-white areas of retinal necrosis combined with extensive hemorrhages ("pizza pie" or "cheese and ketchup" pattern) that can lead to retinal detachment and permanent blindness.

Optic Neuritis

Demyelinating inflammation of the optic nerve, classically occurring in young adults and strongly associated with multiple sclerosis. Pathophysiology involves immune-mediated axonal demyelination interrupting optic nerve conduction. Clinical presentation features acute or subacute unilateral vision loss, characteristic eye pain that worsens with extraocular movement, decreased color vision (especially red desaturation), a relative afferent pupillary defect (RAPD), and central visual field defects, while early funduscopy is frequently normal.

Uhthoff phenomenon

a worsening of symptoms temporarily due to increased body temperature

Thyroid Eye Disease (Graves Ophthalmopathy)

Autoimmune inflammatory condition affecting orbital tissues and extraocular muscles, strongly linked to Graves disease and exacerbated by smoking. Pathophysiology involves orbital fibroblasts producing glycosaminoglycans that draw water into the retrobulbar space, causing muscle expansion and tissue edema. Clinical presentation includes proptosis (exophthalmos), lid retraction, lid lag, dry/irritated eyes, conjunctival chemosis, periorbital edema, restricted eye movement causing diplopia, and risk of dysthyroid optic neuropathy from optic nerve compression.

Papilledema

Optic disc swelling specifically caused by increased intracranial pressure (ICP), typically affecting both eyes. Pathophysiology involves elevated cerebrospinal fluid pressure transmitted through the optic nerve sheath, impeding axoplasmic flow and venous drainage. Clinical presentation features headache, nausea, vomiting, transient visual obscurations, pulsatile tinnitus, diplopia from cranial nerve VI palsy, and funduscopic signs of elevated discs with blurred margins, venous engorgement, and peripapillary hemorrhages, while early visual acuity is usually preserved.

Nystagmus

Involuntary, rhythmic oscillation of the eyes categorized into jerk (slow drift followed by fast corrective beat) or pendular forms. Pathophysiology stems from dysfunction in vestibular, cerebellar, or brainstem pathways, or drug/toxin toxicity. Clinical presentation involves abnormal, rhythmic eye movements; peripheral vestibular nystagmus is typically horizontal, accompanied by vertigo, and suppressed by visual fixation, whereas central nystagmus may be vertical or direction-changing, accompanied by additional neurologic deficits, and not suppressed by fixation.

Presbyopia

Age-related impairment of ocular accommodation that generally becomes symptomatic between ages 40 and 45. Pathophysiology is caused by progressive loss of elasticity and stiffening of the crystalline lens. Clinical presentation involves difficulty focusing on near objects, blurry near vision, and a tendency to hold reading material at an increased distance, while distance vision remains unaffected