Globe pathology Notes

NOTES NOTES GLOBE PATHOLOGY GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Disorders affecting eye structures; if untreated → severe visual impairment ▪ Due to damage to cornea, retina, lens, optic nerve ▪ Inherited/acquired COMPLICATIONS ▪ Impaired vision, blindness SIGNS & SYMPTOMS ▪ Early stages often asymptomatic ▪ Visual changes DIAGNOSIS DIAGNOSTIC IMAGING Direct/indirect fundoscopy ▪ Visualize retina OTHER DIAGNOSTICS ▪ Clinical presentation: history; visual acuity, field loss Slit lamp ▪ Visualize sclera, conjunctiva, iris, lens, cornea 598 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Corneal ulcer ▫ Antimicrobial, steroid eye drops; analgesics ▪ Age-related macular degeneration (ARMD)/ diabetic retinopathy (DR) ▫ Intravitreal injections of vascular endothelial growth factor (VEGF) antagonists ▪ Glaucoma ▫ Beta blockers, alpha agonists SURGERY ▪ Cataract ▫ Small incision; removal of opacified lens ▫ Alternative: leaving lens capsule intact (extracapsular cataract extraction), eye without lens (aphakic eye) ▪ DR ▫ Laser photocoagulation of peripheral retina, vitrectomy ▪ Glaucoma ▫ Laser surgery, trabeculectomy, peripheral iridotomy OTHER INTERVENTIONS ▪ ARMD ▫ Vitamin, antioxidant supplements; smoking cessation ▪ DR ▫ Glucose, blood pressure control

Chapter 77 Globe Pathlogy AGE-RELATED MACULAR DEGENERATION (ARMD) osms.it/macular-degeneration PATHOLOGY & CAUSES ▪ Acquired degenerative disease of macula → loss of central vision; peripheral vision preserved; most common cause of severe visual impairment in older adults in highincome countries ▪ Results from damage to photoreceptors of macula ▪ Unilateral/bilateral; contralateral eye at high risk TYPES Nonexudative ARMD ▪ AKA dry/atrophic; most common ▪ Drusen: extracellular deposits between Bruch membrane, retinal pigment epithelium (RPE) ▫ ↑ size, number of soft drusen → ↑ risk of progression to advanced ARMD ▪ RPE changes: geographic atrophy, detachments, subretinal clumping Exudative ARMD ▪ AKA wet/neovascular; less common ▪ Neovascularization: abnormal vessel formation under retina originating from choroidal circulation, penetrating through Bruch membrane beneath RPE → leakage of serous fluid, blood → collections, fibrosis RISK FACTORS ▪ ↑ age; > 65 most common ▪ Family history: associated with polymorphisms in complement regulatory genes, esp. complement factor H (CFH) ▪ More common in individuals who are biologically female, white people of Ashkenazi Jewish descent ▪ Smoking, intense light exposure, heavy alcohol use, obesity, hypertension, hyperlipidemia COMPLICATIONS ▪ Severe visual impairment: impacts functional status, quality of life; complete loss of vision rare SIGNS & SYMPTOMS ▪ Early stages: often asymptomatic; blurred vision; metamorphopsia (straight lines seen curved) ▪ Loss of central vision; gradual progression in nonexudative, rapid over weeks/months in exudative DIAGNOSIS DIAGNOSTIC IMAGING Fluorescein dye retinal angiography ▪ Fluorescein leaks from abnormal vessels Optical coherence tomography ▪ Retinal edema/subretinal fluid Amsler grid ▪ Individual holds grid at 36–41cm/14–16in, looks at center dot ▫ Curvy lines, blurry spots, scotomas Direct/indirect fundoscopy ▪ Nonexudative ARMD ▫ Drusen: white-yellowish, round/oval deposits ▫ Retinal atrophy: round patches of depigmentation ▫ RPE clumping: increased pigmentation ▪ Exudative ARMD ▫ Neovascularization: gray discoloration ▫ Subretinal fluid/hemorrhage OSMOSIS.ORG 599

OTHER DIAGNOSTICS ▪ Clinical presentation: history; ↓ visual acuity, visual fields (central vision loss) TREATMENT MEDICATIONS ▪ Exudative ARMD ▫ Intravitreal injections of VEGF antagonists to reduce neovascularization ▫ Alternative: photodynamic therapy; injection of photosensitive dye verteporfin → damages neovascular endothelium; application of photoactivating laser Figure 77.1 Drusen in the macula of individual with age-related macular degeneration. OTHER INTERVENTIONS ▪ No curative method; therapy aimed at slowing progression ▪ Vitamin, antioxidant supplements ▪ Nonexudative ARMD ▫ Smoking cessation CATARACT osms.it/cataract PATHOLOGY & CAUSES ▪ Painless, gradual decline in vision due to opacification of lens ▪ Proteins deposit on lens → reduce transmission of light to retina → decrease in vision ▪ Often bilateral but asymmetrical; congenital/ acquired TYPES Nuclear ▪ Opacification of lens nucleus ▪ Slow progression of vision loss Cortical ▪ Opacification of lens fibers surrounding 600 OSMOSIS.ORG nucleus (cortex) ▪ Mild degradation of vision Posterior subcapsular ▪ Opacification in posterior cortical layer under lens capsule ▪ Rapid progression RISK FACTORS ▪ Age-related cataract; usually > 60 ▪ Smoking, excessive alcohol use, prolonged drug use (esp. glucocorticoids), exposure to UV light, eye trauma/infections, radiation of intraocular tumor, trisomies (13, 18, 21) ▪ Metabolic diseases: diabetes mellitus, Wilson disease, galactosemia, myotonic dystrophy

Chapter 77 Globe Pathlogy COMPLICATIONS ▪ Blindness (if untreated) ▪ Secondary posterior subcapsular cataract due to migration of lens epithelium posterior cortical layer Secondary glaucoma ▪ Phacolytic ▫ Lysed lens proteins clog trabecular meshwork → ↑ pressure ▪ Phacoanaphylactic ▫ Autoimmune reaction to proteins → ↑ pressure ▪ Phacomorphic ▫ Swollen lens → closed angle glaucoma Surgery ▪ Residual lens epithelial cells migrate over capsule → opacification, reduction in vision ▪ Endophthalmitis, bullous keratopathy, intraocular lens dislocation, cystoid macular edema, retinal detachment ▪ Toxic anterior segment syndrome ▫ Inflammation of anterior segment due to noninfectious contaminants of surgical equipment SIGNS & SYMPTOMS ▪ Painless visual impairment; progresses slowly over many years ▪ Myopic shift: improvement in nearsightedness before decline in vision; lens sclerosis → increase in refractive power ▪ Blurry vision, poor vision at night, dullness of colors ▪ Glare, halos around bright lights; predominant in cortical cataract DIAGNOSIS DIAGNOSTIC IMAGING Slit lamp ▪ Loss of lens transparency Indirect/direct fundoscopy ▪ Degree of lens opacity ▪ Obscuration of fundus details ▪ Darkening of normal red reflex from fundus OTHER DIAGNOSTICS ▪ Clinical presentation: history; ↓ visual acuity TREATMENT SURGERY Figure 77.2 The eye of a 50-year-old male with a cataract. ▪ Small incision ▫ Phacoemulsification of lens, implantation of synthetic intraocular lens ▪ Removal of opacified lens (alternative) ▫ Leaving lens capsule intact (extracapsular cataract extraction), eye without lens (aphakic eye) OSMOSIS.ORG 601

CORNEAL ULCER osms.it/corneal-ulcer PATHOLOGY & CAUSES TREATMENT ▪ Inflammatory condition of cornea; usually infectious → dissolution of corneal stroma ▪ Presents as open corneal sore ▪ AKA ulcerative keratitis ▪ Exudate, cells leak into anterior chamber → form hypopyon if sufficient quantity MEDICATIONS CAUSES SURGERY ▪ Bacteria, fungi, viruses (esp. herpes simplex, zoster), protozoa (e.g. Acanthamoeba) ▪ Antimicrobial eye drops ▪ Analgesics for pain control ▪ Steroid eye drops after treatment of infection to reduce swelling, prevent scarring ▪ Corneal transplantation to replace damaged cornea if scarring decreases vision RISK FACTORS ▪ Improper usage of contact lens, corneal abrasions, eye burns, xerophthalmia (i.e. dry eye), eyelid disorders, steroid eye drops, vitamin A deficiency SIGNS & SYMPTOMS ▪ Red eye, severe pain, soreness, discharge (tearing, pus), eyelid swelling, blurred vision, vision loss, photophobia DIAGNOSIS DIAGNOSTIC IMAGING ▪ Slit lamp ▪ Reveals corneal ulcer/hypopyon ▪ Fluorescein dye ▫ Ulcer margins (absorbed by exposed corneal stroma, appears green) ▪ Herpes simplex ulcers ▫ Typical dendritic/geographic pattern OTHER DIAGNOSTICS ▪ Clinical presentation: history; ↓ visual acuity 602 OSMOSIS.ORG Figure 77.3 A corneal ulcer caused by herpes simplex keratitis viewed with fluorescein under a UV lamp. The ulcer has a classical dendritic pattern.

Chapter 77 Globe Pathlogy DIABETIC RETINOPATHY (DR) osms.it/diabetic-retinopathy PATHOLOGY & CAUSES ▪ Type of retinopathy affecting individuals with diabetes mellitus → vision loss ▪ Long-standing diabetes mellitus/poor glycemic control → chronic hyperglycemia → retinal vascular changes (e.g. abnormal vascular permeability, vascular occlusions) → ischemia → production of VEGF → formation of abnormal blood vessels (neovascularization) microaneurysms, microocclusions, exudates, nerve-fiber layer infarcts (cotton wool spots), intraretinal hemorrhage, macular edema OTHER DIAGNOSTICS ▪ Ophthalmologic screening: annual screening suggested for individuals with diabetes ▪ Clinical presentation: ↓ visual acuity TYPES Proliferative DR ▪ Presence of neovascularization Nonproliferative DR ▪ Absence of neovascularization; majority of cases; can progress to proliferative; hypertension, fluid retention exacerbate condition COMPLICATIONS ▪ Visual loss due to ▫ Macular edema (most common); vitreal hemorrhage from neovascularization; retinal detachment; neovascular glaucoma Figure 77.4 A retinal photograph demonstrating proliferative diabetic retinopathy. There are cotton wool spots and as well as neovascularisation of the retina. SIGNS & SYMPTOMS ▪ Usually asymptomatic until late stages ▪ Decreased/fluctuating vision; presence of floaters, flashes of lights (photopsias); scotomas DIAGNOSIS DIAGNOSTIC IMAGING Direct/indirect fundoscopy ▪ Thickening of basement membrane, TREATMENT MEDICATIONS ▪ Intravitreal VEGF inhibitors for proliferative DR, significant macular edema SURGERY ▪ Laser photocoagulation of peripheral retina ▪ Vitrectomy for vitreous hemorrhage/ severe proliferative DR nonresponsive to photocoagulation OSMOSIS.ORG 603

OTHER INTERVENTIONS ▪ Glucose, blood pressure control to reduce progression of nonproliferative DR GLAUCOMA osms.it/glaucoma PATHOLOGY & CAUSES ▪ Group of eye disorders; intraocular hypertension damages optic nerve → progressive peripheral visual field loss ▪ Aqueous humour drainage pathway becomes partially/completely blocked → fluid cannot easily drain out → pressure of anterior chamber builds up → intraocular hypertension (pressure > 21mmHg/2.8kPa) → affects eye structures → atrophy of outer rim of optic nerve → peripheral vision loss ▪ Intraocular pressure increases → continued damage to optic nerve → ganglion cell loss → loss of central vision TYPES Open Angle Glaucoma ▪ Angle between cornea, iris; most common ▪ Increased aqueous production/decreased outflow ▪ Secondary to uveitis, vitreous hemorrhage, retinal detachment Closed Angle Glaucoma ▪ Narrowing/closure of anterior chamber angle → inadequate drainage of aqueous humor → increased intraocular pressure → optic nerve damage ▪ Acute: rapid buildup of pressure Normal Tension Glaucoma ▪ Genetic hypersensitivity to intraocular pressures in normal range RISK FACTORS Open angle ▪ ↑ age, black people of African descent, 604 OSMOSIS.ORG family history Closed angle ▪ ↑ age, family history, biologically-female individuals of Asian descent, hyperopia, medications (e.g. mydriatic eye drops), pseudoexfoliation COMPLICATIONS ▪ If untreated, blindness SIGNS & SYMPTOMS Open angle ▪ Asymptomatic Closed angle ▪ Chronic: often asymptomatic, peripheral vision loss ▪ Acute (ophthalmic emergency): abrupt onset of severe eye pain, redness, blurry vision/vision loss, headache, nausea, halos around lights, fixed mid-dilated pupil, conjunctival redness, corneal edema DIAGNOSIS DIAGNOSTIC IMAGING Tonometry ▪ ↑ intraocular pressure Direct/indirect fundoscopy ▪ Cupping: hollowed-out appearance of optic nerve (thinning of outer rim) ▪ Increased cup-to-disc ratio; > 0.5 suggestive of glaucoma Slit lamp ▪ Special lens to visualize angle (gonioscopy)

Chapter 77 Globe Pathlogy OTHER DIAGNOSTICS ▪ Clinical presentation: history, ↓ visual acuity, visual field (peripheral vision loss; central loss at late stages) TREATMENT MEDICATIONS Open angle ▪ Beta-adrenergic receptor antagonists, carbonic anhydrase inhibitors, alpha adrenergic agonists ▫ ↓ production of aqueous humor ▪ Prostaglandin analogs, alpha adrenergic agonists ▫ ↑ outflow of aqueous humor ▫ Open trabecular meshwork, increase aqueous outflow (trabeculoplasty); destroy humor producing cells; create new channel for aqueous humour drainage ▪ Surgical trabeculectomy ▫ Create alternate drainage pathway Acute closed angle ▪ Peripheral iridotomy with laser ▫ Small hole through iris for aqueous humor drainage Acute closed angle ▪ Eye drops (e.g. beta-blockers, alpha agonists); systemic (e.g. acetazolamide, urea, mannitol, glycerol) SURGERY Open angle ▪ Laser surgery Figure 77.5 A photograph of the eye of an individual with acute angle closure glaucoma. There is ciliary flush and a hazy cornea. RETINAL DETACHMENT (RD) osms.it/retinal-detachment PATHOLOGY & CAUSES ▪ Separation of retinal photoreceptors from underlying retinal pigment epithelium (RPE), choroid; if untreated leads → vision loss ▪ Detachment of neurosensory retinal layer from underlying layers → ischemia, progressive degeneration of photoreceptors → vision loss TYPES Rhegmatogenous ▪ Most common ▪ Full thickness retinal break → vitreous fluid passes into subretinal space → retinal detachment ▪ Causes ▫ Posterior vitreous detachment: most common, age 50–75, separation of OSMOSIS.ORG 605

posterior vitreous membrane from retina due to natural age-related liquefaction of vitreous → retinal breaks can occur in areas of strong vitreoretinal attachment ▫ Ocular trauma Nonrhegmatogenous ▪ Vitreous traction ▫ Abnormally strong vitreoretinal adhesion → contraction → detachment; proliferative diabetic retinopathy, retinopathy of prematurity ▪ Exudative ▫ Fluid accumulation between layers; inflammatory conditions, choroidal neoplasms RISK FACTORS Rhegmatogenous ▪ High myopia; lattice degeneration (thinning of retinal periphery); family history; history of retinal detachment; ocular trauma; previous intraocular surgery (e.g. cataract surgery) COMPLICATIONS ▪ Vision loss, proliferative retinopathy SIGNS & SYMPTOMS ▪ Sudden onset: floaters/flashes of light; if preceded by posterior vitreous detachment ▪ Monocular vision loss: curtain drawn over vision field ▪ Tractional: smooth concave retinal surface; minimal shifting with eye movements ▪ Exudative: smooth retinal surface, shifting fluid LAB RESULTS ▪ Diabetes: traction, exudative RD; find underlying cause OTHER DIAGNOSTICS ▪ Clinical history, physical examination TREATMENT SURGERY ▪ Laser photocoagulation/cryoretinopexy: seal retinal breaks, prevent retinal detachment ▪ Rhegmatogenous RD ▫ Pneumatic retinopexy: intraocular injection of gas to tamponade retinal break (along with laser or cryoretinopexy) ▫ Scleral buckles: silicone bands placed are sewed to sclera under rectus muscles (along with laser or cryoretinopexy) ▫ Vitrectomy: removal of vitreous body to reduce the effect of vitreous traction to retina ▪ Tractional RD ▫ Vitrectomy with scleral buckling DIAGNOSIS DIAGNOSTIC IMAGING ▪ ↓ visual acuity Ocular ultrasound ▪ E.g. choroidal masses ▪ Traction, exudative RD; find underlying cause Direct/indirect fundoscopy ▪ Rhegmatogenous: wavy appearance, changes with eye movements, changes in vessel direction 606 OSMOSIS.ORG Figure 77.6 An MRI scan of the head in the axial plane demonstrating detachment of the right retina.

Chapter 77 Globe Pathlogy RETINOBLASTOMA osms.it/retinoblastoma PATHOLOGY & CAUSES ▪ Intraocular malignant tumor; affects children; presents as leukocoria ▪ Most common primary intraocular malignancy of childhood; usually < two years ▪ Associated with intracranial tumor ▫ Pinealoblastoma (trilateral retinoblastoma) ▪ Mutational inactivation of both alleles of retinoblastoma (RB1) gene located in chromosome 13 ▫ Blood → lungs, bones, liver ▫ Lymphatic vessels → conjunctiva, eyelids, extraocular tissue ▪ Heritable retinoblastoma ▫ Secondary malignancy (e.g. bone, soft tissue sarcomas) TYPES Heritable (40%) ▪ Germline mutations: inherited/de novo ▪ Presents at early age; bilateral/multifocal; 50% risk of passing to offspring Nonheritable (60%) ▪ Somatic mutations in both alleles; negative family history ▪ Presents later in life; unilateral Figure 77.7 The gross pathological appearance of a retinoblastoma. RISK FACTORS ▪ Family history ▪ 13q14 deletion syndrome ▫ Microdeletions in region 1 band 4 located in large arm (q) of chromosome 13 COMPLICATIONS ▪ Fatal if untreated; with prompt treatment, survival > 95% ▪ Spreads via ▫ Choroid → sclera, orbit → destruction of globe → vision loss ▫ Optic nerve → brain ▫ Subarachnoid space → contralateral optic nerve, brain Figure 77.8 A child with retinblastoma causing whitening of the right pupil known as leukocoria. OSMOSIS.ORG 607

SIGNS & SYMPTOMS ▪ Leukocoria (abnormal white reflexion from retina) ▪ Strabismus, nystagmus, red eye DIAGNOSIS DIAGNOSTIC IMAGING MRI (brain, orbits) ▪ T1-weighted: bright ▪ T2-weighted: dark compared to vitreous ▪ Detect optic nerve involvement, associated intracranial tumor Direct/indirect fundoscopy ▪ Well-circumscribed, translucent, white intraretinal mass Ocular ultrasound ▪ Normal globe size, calcification LAB RESULTS Figure 77.9 An MRI scan of the head in the axial plane demonstrating a retinoblastoma of the left globe. ▪ Genetic testing ▫ Estimate risk in family members, future offspring OTHER DIAGNOSTICS ▪ Metastasis evaluation (e.g. bone marrow aspiration, lumbar puncture) TREATMENT MEDICATIONS ▪ Local/systemic chemotherapy ▫ Preserve vision, optimize survival SURGERY ▪ Cryopexy, laser photoablation, enucleation ▫ Preserve vision, optimize survival 608 OSMOSIS.ORG Figure 77.10 A retinoblastoma as seen on fundoscopy.

Chapter 77 Globe Pathlogy RETINOPATHY OF PREMATURITY osms.it/retinopathy-of-prematurity PATHOLOGY & CAUSES ▪ AKA retrolental fibroplasia ▪ Proliferative retinopathy, occurs in preterm infants; if untreated → vision loss ▪ Common cause of childhood blindness ▪ Premature birth interrupts development → ↑ risk of vascular insult ▪ Supplemental oxygen administration → disruption of normal angiogenesis → abnormal growth of blood vessels, fibrous tissue affecting temporal part of retinal periphery ▪ Regress spontaneously in most cases RISK FACTORS ▪ Gestational age < 30 weeks; birth weight ≤ 1.5kg/3.3lbs; excessive oxygen therapy; supplemental oxygen COMPLICATIONS ▪ Retinal bleeding, scarring ▪ Contraction of fibrovascular tissue → retinal detachment → blindness ▪ Refractive errors: myopia, anisometropia ▪ Squint/strabismus ▪ Glaucoma SIGNS & SYMPTOMS ▪ Blindness due to retinal detachment, if untreated ▪ Classification ▫ Location: three concentric zones from optic disc to periphery ▫ Extent: retina divided in 12 parts (hours of a clock) ▫ Stage I: thin white demarcation line separating vascularized from avascular retina ▫ Stage II: ridge of fibrous tissue into vitreous between vascularized, avascular retina ▫ Stage III: abnormal growth of fibrovascular tissue on ridge; extension into vitreous ▫ Stage IV: partial retinal detachment ▫ Stage V: total retinal detachment ▫ Plus disease: increased venous dilation, tortuosity of posterior retinal vessels, vitreous haze OTHER DIAGNOSTICS ▪ Screening of preterm infants TREATMENT MEDICATIONS ▪ Intravitreal injection of VEGF antagonists SURGERY ▪ Ablation of retina with laser photocoagulation DIAGNOSIS DIAGNOSTIC IMAGING Fundoscopy ▪ Direct/indirect following pupil dilation ▫ Disorganized growth of vessels, fibrous tissue OSMOSIS.ORG 609

Figure 77.11 A CT scan of the head in the axial plane demonstrating increased density and asymmetry of the globes in a one year old biologically-female individual. The increase in density is caused by retinal detachment and subsequent fibrous reorganisation of the vitreous. 610 OSMOSIS.ORG