Eye Pathology PDF

Eye Pathology Michael Yakubovskyy, MD, PhD 1  Content and LOs Content LOs Intro: Functional LO1. Explain the most clinically relevant structural aspects of the eye Anatomy...

Eye Pathology Michael Yakubovskyy, MD, PhD 1  Content and LOs Content LOs Intro: Functional LO1. Explain the most clinically relevant structural aspects of the eye Anatomy of the Eye LO2. Describe etiology, pathogenesis, and clinicopathologic presentation of cataract Disorders of the Anterior Segment LO3. Define glaucoma and list its types; describe etiology, pathogenesis, and clinicopathologic presentation of each type of glaucoma LO4. Describe etiology, pathogenesis, and clinicopathologic/fundoscopic presentation of the Disorders of the Optic following disorders Nerve Disc – Optic disc swelling – Glaucomatous nerve damage – Optic neuritis LO5. Describe etiology, pathogenesis, and clinicopathologic/fundoscopic presentation of the following disorders – Age-related macular degeneration (dry and wet) Disorders of the – Retinitis pigmentosa Retina – Hypertensive retinopathy (benign HTN, HTN urgency and emergency) – Diabetic retinopathy (background and proliferative) – Retinal vein occlusion – Retinal artery occlusion – Retinopathy in lipid storage diseases LO6. Describe etiologic/genetic factors Tumors of the Eye recognize their clinicopathologic presentationof eye melanoma and retinoblastoma, and  Functional Anatomy of the Eye LO1. Explain the most clinically relevant structural aspects of the eye 3 Eye Compartments. Diagram, Micro Anterior and Posterior Chambers of Anterior Segment. Diagram Retina. Diagram, Micro Bruch membrane  Optic Nerve Sensory nerve Excavated optic disc (head of the nerve) Surrounded by meninges Bathed by CSF Pathology: similar to CNS pathology 7  Disorders of the Anterior Segment LO2. Describe etiology, pathogenesis, and clinicopathologic presentation of cataract LO3. Define glaucoma and list its types; describe etiology, pathogenesis, and clinicopathologic presentation of each type of glaucoma 8  Cataract Cataract = lens opacification – Latin “cataracta” – waterfall Major cause of blindness worldwide Classification – Acquired cataract – Congenital cataract (galactosemia, rubella embryopathy, Wilson disease, etc.) 9  Acquired Cataract: Risk Factors Increasing age —> age-related cataract – The most common type in the US Diabetes mellitus Prolonged corticosteroid use Excessive exposure to sunlight Previous eye trauma, inflammation, or surgery Other: obesity, smoking, excessive alcohol consumption 10  Cataract: Pathogenesis and Presentation 1. Influence of etiologic factor 2. Degeneration of lens fibers – Decreased metabolism – Protein modification and aggregation – Oxidative stress 3. Lens fiber compaction (sclerosis) 4. Loss of optic translucency of the lens 11  Glaucoma Definition: elevated intraocular pressure (r.r.: 10 – 20 mm Hg) with atrophy of the retina and cupping of the optic disk Cause: obstruction of aqueous humor outflow into the Schlemm canal Complications: blindness 12  Glaucoma: Approach to Classification 1. Condition of the anterior chamber angle: open vs closed/narrow 2. Etiology: primary vs secondary – Primary: a genetic or unknown cause – Secondary: the cause is known 13  Glaucoma, Four Types Angle Open Angle Closed Primary open-angle Primary closed-angle Primary glaucoma glaucoma Secondary open- Secondary closed- Secondary angle glaucoma angle glaucoma  Open-Angle Glaucoma, Primary and Secondary Obstruction is distal to the anterior chamber angle Types – Primary, the most common type of glaucoma in the US Genetic abnormalities in trabecular meshwork – Secondary, due to angular accumulation of RBC fragments after eye trauma Tumor debris in retinoblastoma and melanoma 15 Open-Angle Glaucoma: Diagram  Closed-Angle Glaucoma, Primary Syn.: primary narrow angle glaucoma, acute angle closure glaucoma (AACG) Common in Asians Causes/provoking factors – Pupil dilation: low light conditions, increased sympathetic tone, emotional excitement, drugs – Shallow anterior chamber: hyper(metr)opia 17  Primary Closed-Angle Glaucoma (AACG), Pupil Dilation Pupil dilation (mydriasis) Widening of the iris Iris apposition to the cornea Closure of the angle  Primary Closed-Angle Glaucoma (AACG), Shallow Anterior Chamber Short optical axis with shallow anterior chamber Iris apposition to the lens (“pupillary block”) Obstruction to aqueous humor flow Bulging of the iris into the anterior chamber Apposition of the iris to the cornea Closure of the angle  Acute Primary Closed-Angle Glaucoma (AACG) = Medical Emergency Symptoms – Eye pain – Blurred vision with halos – Headache – Nausea Signs – Steamy cornea – Injected conjunctiva – Mid-dilated non-reactive pupil 20  Secondary Closed-Angle Glaucoma Formation of neovascular membrane over the iris with following closure of the angle Causes: diabetes mellitus and retinal vein occlusion Mechanism: release of VEGF —>… 21 Disorders of the Optic Nerve Disc LO4. Describe etiology, pathogenesis, and clinicopathologic/fundoscopic presentation of the following disorders - Optic disc swelling - Glaucomatous nerve damage - Optic neuritis 22  Optic Disc Swelling Causes – Increased intracranial pressure —> bilateral optic disk swelling (papilledema) Cerebrovascular diseases: hemorrhage, infarct Infections: meningitis, encephalitis, abscess Brain tumors – Central retinal vein occlusion – Optic neuritis (intraocular) No loss of vision 23  Optic Disc Swelling: Fundoscopy Hyperemic disc: capillary engorgement Blurred margins Reduced/absent physiologic cup Dusky veins Control 24  Optic Disc Swelling. Micro Control  Glaucomatous Optic Nerve Damage 1. Intraocular pressure elevation (>20 mm Hg) 2. Atrophy and loss of ganglion cells 3. Thinning of the nerve fiber layer 4. Excavation/cupping of the optic disc 26  Cupping Optic Disc. Fundoscopy Control  Optic Neuritis Definition: inflammation with demyelination Major cause: multiple sclerosis – Minor causes: tuberculosis, syphilis, Lyme disease, viral infections, etc. Symptoms, usually unilateral – Diminished vision: from blurring to blindness – Eye pain associated with eye movement – Extraocular pain associated with orbital muscles – Reduced color vision Fundoscopy: papillitis = optic disc swelling – NB: no disc swelling with retrobulbar optic neuritis 28  Optic Disc, (Severe) Optic Neuritis. Fundoscopy Control  Disorders of the Retina LO5. Describe etiology, pathogenesis, and clinicopathologic/fundoscopic presentation of the following disorders - Age-related macular degeneration (dry and wet) - Retinitis pigmentosa - Hypertensive retinopathy (benign HTN, HTN urgency and emergency) - Diabetic retinopathy (background and proliferative) - Retinal vein occlusion - Retinal artery occlusion - Retinopathy in lipid storage diseases 30 Age-Related Macular Degeneration (AMD) The mostly area affected: the fovea – Loss of central vision Major risk factors – Polymorphism/mutations in complement factor H (CFH) gene – Other: smoking, hypercholesterolemia, advanced age (> 65 yrs) Two forms – Dry AMD (atrophic) – Wet AMD (exudative) 31  Dry AMD 80% of all AMD cases Atrophy of the retinal pigment epithelium (RPE) in the macular area Accumulation of non-degraded remnants of RPE (drusen) above Bruch membrane in the macular area 32  Wet AMD, Natural History Angiogenesis in choriocapillaris Penetration of Bruch membrane by new vessels Growth of neovascular membrane between RPE and photoreceptor area in the macular area Edema and hemorrhages in the macular area Retinal detachment Macular scarring with loss of vision  Dry ADM, Drusen (A); Wet AMD, Hemorrhage (B). Fundoscopy A B  Retinitis Pigmentosa Hereditary: X-linked, ADD, or ARD Apoptosis of both rods and cones – Loss of rods —> night blindness and constricted visual fields (tunnel blindness) – Loss of cones —> loss of central visual acuity Migration and accumulation of RPE and macrophages laden with melanin in the affected areas —> “pigmentosa” 35 Retinitis Pigmentosa: Pigment Accumulation Early stage Late stage  Hypertensive Retinopathy Mild in benign HTN Moderate in hypertensive urgency and hypertensive emergency Severe in hypertensive emergency 37  Mild Hypertensive Retinopathy Vascular changes: hyaline arteriolosclerosis Retinal changes (fundoscopy) – Arteriolar narrowing – Arteriolar wall thickening: normal red arteriole —> copper wire —> silver wire Vein compression at the point of arterio- venous crossing —> venous stasis and AV nicking 38  Mild Hypertensive Retinopathy, Arteriolar Narrowing (A), “Copper and Silver Wire” Arteries and AV Nicking (B). Fundoscopy A B  Moderate Hypertensive Retinopathy Vascular changes: hyaline arteriolosclerosis Retinal changes (fundoscopy) – Cotton-wool spots (areas of ischemic axonal injury in nerve fiber layer) – Dots-and-blots and flames (vessel rupture — > hemorrhages) – Exudates (accumulation of transudate due to ↑vascular permeability) 40  Severe Hypertensive Retinopathy Vascular changes: fibrinoid arteriolonecrosis and hyperplastic arteriolosclerosis Retinal changes (fundoscopy) – Papilledema – Cotton-wool spots – Dots-and-blots and flames – Exudates Macular star: exudates radiating from the macula41 Severe Hypertensive Retinopathy. Diagram and Fundoscopy  Two Types of Diabetic Retinopathy Background/preproliferative retinopathy – Collagen glycation —> ↑vascular permeability Proliferative retinopathy – Proliferation of capillaries with formation of neovascular membrane NB: diabetic non-retinal ocular pathology: cataract, glaucoma, Argyll-Robertson pupil, mucormycosis of the orbit 43  DM, Background Retinopathy. Fundoscopy Macular edema (1) – Large and dark macule Exudates (2) 1 3 2 Dot and blot hemorrhages (3) 4 Cotton wool spots (4) 5 Microaneurysms (5) 44  DM, Proliferative Retinopathy, Neovascular Membrane (A), New Capillaries and Small Hemorrhages (B). Micro, Fundoscopy A B  Retinal Vein Occlusion Cause: occlusive thrombosis – Virchow triad —> occlusion of central retinal vein – HTN with hyaline arteriolosclerosis and vein compression at the AV nicking —> occlusion of retinal vein branches Morphology/pathogenesis – Severe edema and hemorrhages – Low blood flow velocity —> mild/moderate retinal ischemia —> subtle ganglion cell injury 46  Retinal Vein Occlusion: Fundoscopy Multiple and large flame-shaped hemorrhages – “Blood and thunder” fundus Optic disc edema Exudates (macular edema) 47  Central (A) and Branch (B) Retinal Vein Occlusion, Flames. Fundoscopy A B  Retinal Vein Occlusion: Clinical Correlates Clinical manifestations: sudden painless loss of vision (usually) in one eye – Vision may recover Complication: severe glaucoma – Slowly developing retinal ischemia —> VEGF release —> neovascularization of both posterior and anterior segments of the anterior chamber 49  Retinal Artery Occlusion Causes: atherosclerosis, thrombosis, and embolism/thromboembolism Location – Central retinal artery – Retinal artery branches Cholesterol embolus in a small retinal artery: Hollenhorst plaque Sudden onset —> ischemic injury —> retinal infarct 50  Central Retinal Artery Occlusion Pale retina – Ischemia in the area of the central retinal artery supply – Swelling of ganglion cells Pale optic disc (1, next slide) Empty arteries (2, next slide) Cherry-red fovea (3, next slide) – Thinnest part of the retina – No ganglion cells – Blood supply from the posterior ciliary arteries (branches of the ophthalmic a. that supply the choroid) 51  Central Retinal Artery Occlusion (A) and Hollenhorst Plaque (B). Fundoscopy A B 3 1 2 52  Retinal Artery Occlusion: Clinical Manifestations Sudden loss of vision – Usually unilateral – With retinal infarct, will progress to permanent unilateral blindness Retinal artery embolism (Hollenhorst plaque) may cause loss of vision lasting few seconds/minutes – Amaurosis fugax = fugitive darkening (Greek) Lysis of the embolus —> restoration of vision 53  Retinopathy in Storage Diseases Causes (in the order of descending frequency) – Tay-Sachs disease: genetic hexosaminidase A deficiency with accumulation of GM2 gangliosides – Niemann-Pick disease: genetic sphingomyelinase deficiency with accumulation of sphingomyelin – Gaucher disease: genetic glucocerebrosidase deficiency with accumulation of glucocerebroside Fundoscopy: cherry-red fovea  Cherry-Red Fovea in Storage Diseases The fovea by itself is not affected but looks bright- red in contrast with pale peripheral macula due to accumulation of lipids or carbohydrates in the ganglion cells around the fovea  Tumors of the Eye LO6. Describe etiologic/genetic factors of eye melanoma and retinoblastoma, and recognize their clinicopathologic presentation 56  Eye Tumors Primary tumors – Melanoma (similar to skin melanoma) Uveal melanoma in the iris, ciliary body, and choroid Conjunctival melanoma – Retinoblastoma Sporadic Familial – Retinal lymphoma (similar to primary brain lymphoma covered in CNS Tumors) Secondary tumors (metastases): more common than primary tumors  Retinoblastoma: Flexner-Wintersteiner (Left) and Homer-Wright (Right) Rosettes The End 59