Retina & RPE Histopathology
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Normal Retinal Anatomy
Color fundus photo of the retina
Histologic appearance of retinal layers
- Layers
- Internal limiting membrane
- Formed by footplates of Müller cells
- Nerve fiber layer
- Ganglion cell layer
- Inner plexiform layer
- Inner nuclear layer
- Contains bipolar cells, Müller cells, amacrine cells and horizontal cells
- Müller cells are microglial cells that provide both functional and structural support
- Interconnections between amacrine and horizontal cells are important in the initial stages of visual processing
- Outer plexiform layer
- Outer nuclear layer
- External limiting membrane
- Formed by junctions between photoreceptors and Mueller cells
- Photoreceptor layer
- Composed of rods and cones
- High metabolic activity with nourishment obtained from choroid
- Retinal pigment epithelium
- Internal limiting membrane
- Light transduction pathway
- Rhodopsin of rod cells and iodopsins of cone cells absorb photons, causing the molecule to change from the cis to trans conformation
- The hyperpolarization at photoreceptor membrane is transmitted by bipolar cells in the inner nuclear layer to ganglion cells, which project to the lateral geniculate body.
- Histologically, the macula is defined as the area where the ganglion cell layer is greater than one cell layer thick. Clinically, this corresponds to the area between the superior and inferior arcades.
Histologic appearance of the fovea
Oblique orientation of axons in outer plexiform layer forming Henle’s layer
- Fovea
- Cones are the predominant photoreceptor in the fovea and are connected to ganglion cells in a 1:1 ratio
- Ganglion cells are concentrated outside of the central fovea, allowing more light to reach the central photoreceptors
- Foveal photoreceptor axons form Henle’s layer run in an oblique fashion due to the peripheral concentration of ganglion cells
Hypertensive Retinopathy
Fundus photo of hypertensive retinopathy
- Chronically elevated blood pressure leads to arteriosclerotic changes and vascular damage
- Initial changes include vasoconstriction and vasospasm
- Sclerotic intimal wall thickening manifests as AV nicking and silver and copper wiring
- Eventually, disruption of the blood-retinal barrier leads to hemorrhage and plasma exudation into the retina
- Severe cases can cause swelling of the optic nerve
- Findings
- Flame-shaped hemorrhages: in nerve fiber layer
- Dot-blot hemorrhages: in inner nuclear or outer plexiform layers
- Hard exudates: extracellular protein and lipid deposits left in chronic edema after water component has been removed, star-shaped due to location in Henle’s layer
Silver-wiring from hypertensive retinopathy
Optic disc swelling from hypertensive retinopathy
Central Retinal Artery Occlusion (CRAO)
- Caused by arteriosclerosis, embolism, and vasculitis
- Clinical appearance: “Cherry-red spot” signifying redness of underlying choroid in fovea
- Edema of ganglion cell layer and NFL, which are thickest in macula but absent in fovea
- Ischemia of inner 2/3 of retina to Outer Nuclear Layer
- Histopathology shows inner ischemic retinal atrophy (NFL, GCL, inner plexiform layer, inner nuclear layer) after occlusion of retinal circulation
- Outer ischemic retinal atrophy is indicative of an occlusion of choroidal circulation
Branch Retinal Artery Occlusion (BRAO)
- Partial retinal ischemia
- Usually from embolic phenomenon
- Hollenhorst plaque: cholesterol emboli
- Important clue for a systemic disorder, such as carotid vascular disease (Hollenhorst plaque), cardiac valvular disease (calcific emboli), or thromboembolism (platelet-fibrin emboli)
- Histology: inner ischemic atrophy of retina downstream of occluded arteriole
Central Retinal Vein Occlusion (CRVO)
Cross-section of atherosclerotic central retinal artery
Gross photo of sagittally cut globe
Retinal architecture disrupted from CRVO
- Structural changes in central retinal artery and lamina cribrosa à central retinal vein compression à turbulent flow à thrombosis
- Usually occur in setting of arteriosclerosis, hypertension, diabetes, glaucoma
- Papillophlebitis: clinical features of CRVO, no history of vascular disease, patients under age 50, retinal vein occlusion due to inflammation of retinal vessels at the optic disc
- Clinical signs:
- Retinal hemorrhages in all four quadrants
- Prominent optic nerve head edema
- Retinal vein dilation
- Cotton-wool spots
- Macular Edema
- Nonperfused CRVO: >10 disc areas show nonperfusion on FA, extensive retinal edema & hemorrhage, marked venous dilation, cotton-wool spots
- Histology: hemorrhage, hemosiderosis, disorganized retinal architecture, cystic spaces with blood and proteinaceous exudate, nodular hyperplasia of RPE, gliosis
- Microaneurysms and neovascularization follows ischemic CRVO
Branch Retinal Vein Occlusion (BRVO)
- Arteriovenous crossing causes occlusion of branch retinal vein
- Artery & vein share common adventitial sheath; arteriosclerosis leads to compression of venule
- More common in arteriosclerosis and hypertension
- Clinical findings: retinal hemorrhages, cotton-wool spots
- Neovascularization unlikely unless >5 disc diameters of ischemia
- If permanent vision loss: CME, retinal nonperfusion, pigmentary changes, macular edema with hard exudate, subretinal fibrosis, epiretinal membrane
- Histology: similar to CRVO but localized to distribution of vein
- Microaneurysms and dilated collaterals may be present
Diabetic Retinopathy
Trypsin-digest showing microaneurysms from loss of pericytes
- Primary histologic changes in diabetes:
- Thickened retinal capillary basement membrane
- Selective loss of capillary pericytes
- Microaneurysms
- Fusiform or saccular outpouchings of retinal capillaries
- Best seen histologically with PAS-stained trypsin digest preparation
- Acellular capillary beds
Fundus photo of diabetic retinopathy
- Clinical findings and late histologic changes: hard exudates, cotton-wool spots, dot-blot & flame hemorrhages, neovascularization
Histopathology of hard exudates
- Hard exudates: eosinophilic-staining extracellular protein and lipid deposits left in chronic edema after water component has been removed
- Histologically are distinctly-bordered eosinophilic spaces
Fundus photo of cotton-wool spots
Cotton-wool spots in Ganglion Cell and Nerve-fiber layers
Swollen ganglion cells in cotton-wool spot
- Cotton-wool spot: focal areas of ischemia in Ganglion Cell Layer and Nerve Fiber Layer
-
- Can see swollen ischemic ganglion cells
- Cytoid bodies are the histopathologic hallmark of cotton-wool spots
- Cytoid body- eosinophilic accumulation of ganglion cell axoplasmic material that develops during an ischemic event of the NFL
- Leaves atrophic retina after they resolve
- Categorized as proliferative if neovascularization in the eye present or non-proliferative if neovascularization is absent
- Proliferative diabetic retinopathy is further categorized by the location of neovascularization: neovascularization of the disc (NVD) and neovascularization elsewhere (NVE)
- Chronic retinal ischemia results in the release of vascular endothelial growth factor (VEGF), which stimulates the growth of new, incompetent blood vessels and increases vascular permeability
Fundus photo of neovascularization elsewhere (NVE)
Neovascularization of the disc (NVD)
Scarring and hemorrhage from neovascularization
Boat-shaped, pre-retinal hemorrhage in proliferative diabetic retinopathy
- Boat-shaped hemorrhage: blood in potential space between posterior hyaloid and internal limiting membrane
Neovascularization of iris (NVI), also known as rubeosis iridis
Neovascularization of the angle
- Other diabetic changes elsewhere in the eye:
- Thickened corneal epithelium basement membrane: increases risk of corneal abrasion and causes poor corneal epithelial healing
Lacy vacuolization of iris pigment epithelium
- Lacy vacuolization of iris pigment epithelium: glycogen-filled intraepithelial vacuoles (PAS-positive, diastase-sensitive) in focal areas
PAS stain showing thickened basement membrane of ciliary body epithelium
-
- Thickened pigmented ciliary body epithelium basement membrane
- Increased incidence of cataracts
- Argon laser photocoagulation: destroys outer retina and RPE, occludes choriocapillaris
- Heal by proliferation of adjacent RPE and glial scarring
Sickle Cell Retinopathy
Fluorescein angiogram of Sickle cell or Eales disease
Sickled RBCs in retinal vasculature
- Most severe in sickle cell hemoglobin C disease (SC disease)
- Can also occur in sickle thalassemia, sickle disease, and occasionally sickle cell trait
- Classification:
- Stage I: peripheral arteriolar occlusion between equator and ora serrata
- Stage II: peripheral arteriolar-venular anastomoses, usually in temporal quadrant
- Stage III: neovascular and fibrous proliferation
- Leakage of neovascular patch on FA produces characteristic sea-fan pattern
- Stage IV: vitreous hemorrhage, usually from neovascular patch
- Stage V: Retinal Detachment (RD)
- Clinical and histologic signs of retinal ischemia due to local hypoxia from occlusion of retinal vasculature by sickled RBCs
Macular Holes
Fundus photo of full-thickness macular hole
Magnified fundus photo of macular hole with fixation rod
Edge of macular hole showing edema
-
- Formed by anterior-posterior traction and localized perifoveal traction
- Several stages have been identified
Stage 1a – Foveal pseudocyst
Stage 1b – Disruption of outer retina
Stage 2 – Full thickness dehiscence
Stage 3 – Full thickness defect w/ rounded edges
- Epiretinal membrane often associated.
- CME common
Epiretinal Membranes (ERM)
- Fibrocellular membrane on the inner surface of the retina associated with increased age and posterior vitreous detachment
- Usually idiopathic but can occur secondarily to retinal vascular diseases and ocular trauma
- Theorized to be caused by glial cells such as astrocytes and Müller cells that facilitate remodeling on the surface of the retina
- On exam, ERM appears as a sheen or wrinkling overlying the macula
Fundus photo of epiretinal membrane
Fundus photo of epiretinal membrane
Red-free fundus photo of epiretinal membrane
OCT showing wrinkling of the macula
Histology of epiretinal membrane
Dry Age-related Macular Degeneration
- 60% cases associated with single nucleotide polymorphisms in complement factor H (CFH) gene
- Risk factors: elderly, smoking, family history, cardiovascular disease, lack of antioxidant supplementation
- Drusen: PAS-positive deposits of eosinophilic material
- Basal linear deposits: between RPE basement membrane and elastic layer of Bruch
- Basal laminar deposits: between RPE cell membrane and basement membrane
- Only visible by EM
- Hard (hyaline) drusen: discrete, yellow, PAS-positive nodules, composed of hyaline, can cause RPE drop-out
- Bruch membrane is a 5-layered structure that mediates interactions between the retinal pigment epithelium and choroid
- Layers from innermost to outermost: RPE basement membrane, inner collagenous layer, elastic layer, outer collagenous layer, choriocapillaris basement membrane
- Retinal pigment epithelium functions:
- Transport of nutrients and waste to and from the retina
- Recycling of rhodopsin via the reisomerization of the retinal molecule from the trans to cis conformation
- Absorption of light by the pigment
- Physical barrier formed by tight junctions
- Soft drusen: amorphous, poorly-demarcated, result from cleavage of deposits from Bruch
Fundus photo of confluent drusen around the fovea
- Diffuse drusen: confluent deposits, visible by light microscopy, can affect vision, can be pre-cursor to subretinal neovascularization
- Basal laminar or cuticular drusen: diffuse, small, regular, nodular, in macula
- Calcific drusen: sharp borders, glistening, refractile, associated with RPE atrophy
- Photoreceptor atrophy likely secondary to RPE and Bruch membrane changes
Fundus photo of geographic atrophy
RPE atrophy in geographic atrophy
- Geographic atrophy (GA) or central areolar atrophy of the RPE: large, central zones of RPE atrophy
- Dry (nonexudative AMD): drusen, photoreceptor atrophy, RPE atrophy
- Abrupt transition zone from atrophic to more normal appearing retina and RPE on histology
Wet Age-related Macular Degeneration
Sub-RPE and subretinal neovascularization
Larger sub-RPE and subretinal neovascularization
Histopathology of sub-RPE neovascularization
Photo reference: Harper RA. Basic Ophthalmology. Amer Academy of Ophthalmology; 2010.
- Neovascularization in Wet AMD
- Also called neovascular or exudative AMD
- Choroidal neovascularization between inner and outer layers of Bruch, under RPE, or in subretinal space
- Vessel leakage can cause: macular edema, serous RD, subretinal and intraretinal hemorrhage
Retinal Neovascularization
- Type 1 neovascularization: within Bruch in sub-RPE space
- RPE abnormally oriented or completely missing in large area along inner portion of Bruch
- Associated with basal laminar deposits and diffuse drusen
- More typical in AMD
- Type 2 neovascularization: occurs in subretinal space
- Only small area of abnormally oriented or missing RPE
- More typical in ocular histoplasmosis
- More amenable to surgical removal
- Histology shows vascular channels, photoreceptor outer segments, basal laminar and linear deposits, hyperplastic RPE, and inflammatory cells
Gliosis
Disciform scar from neovascularization
- Glial scar: glial cells like astrocytes proliferate is areas adjacent to infarct or ischemia
- Microglial cells are resistant to ischemia and phagocytose necrotic cells and extracellular material
Retinal Neovascularization
- Type 1 neovascularization: within Bruch in sub-RPE space
- RPE abnormally oriented or completely missing in large area along inner portion of Bruch
- Associated with basal laminar deposits and diffuse drusen
- More typical in AMD
- Type 2 neovascularization: occurs in subretinal space
- Only small area of abnormally oriented or missing RPE
- More typical in ocular histoplasmosis
- More amenable to surgical removal
- Histology shows vascular channels, photoreceptor outer segments, basal laminar and linear deposits, hyperplastic RPE, and inflammatory cells
Cystoid Macular Edema
- Disruption of the blood-retinal barrier leads to the accumulation of transudate in the outer plexiform layer (Henle’s layer), creating the classic flower-petal pattern
Fundus photo of cystoid macular edema (CME)
Histopathology of CME in Henle’s layer
Bull’s Eye Maculopathy
- Unique appearance of the macula seen in patients with chronic medication use (chloroquine or hydroxychloroquine), cone dystrophy, or Stargardt disease
- Finding is not specific and is associated with other conditions as well
Fundus photo of bull’s eye maculopathy
Best Disease
Sub-RPE deposit in Best disease
- Also known as vitelliform macular dystrophy when seen in an adult
- Early-onset macular degenerative disease
- Diagnosis: egg-yolk lesion or pigmentary changes in central macula
- Electro-oculogram: reduced ratio of light peak to dark trough
- Deposits found under RPE in the macula
- Autosomal dominant inheritance
- Mutation in VMD2 on chromosome 11q13, which encodes bestrophin protein
- Bestrophin localizes to basolateral RPE plasma membrane, represents chloride ion channel family
- Bestrophins volume sensitive and may help regulate RPE cell volume
Stargardt Disease
Hypertrophic RPE cells filled with lipofuscin-like material
- Typically autosomal recessive, but autosomal dominant reported
- Genetic mutations in ABCA4, STGD4, ELOV4, RDS/peripherin
- ABCA4 codes for RIM protein, which is expressed on photoreceptors and transports vitamin A to RPE
- Juvenile onset, rapid progression
- Clinical appearance:
- Yellow flecks around the macula at level of RPE in pisciform (fish-like) distribution
- Reddish or vermillion fundus
- Dark choroid on FA
- Gradually decreasing visual acuity
- Geographic RPE atrophy and photoreceptor loss seen in advanced stages
- Histology: markedly engorged RPE cells filled with lipofuscin-like, PAS-positive material with apical displacement of RPE melanin granules
- Hypertrophic RPE cells correspond with flecks seen clinically
Fundus Flavimaculatus
- Milder subset of Stargardt disease
- Later disease onset and slower progression
- Fundus photos may show more diffuse retinal involvement compared to Stargardt disease, but macula is less involved
Pattern Dystrophy
- Group of inherited macular disorders with various patterns of macular pigment deposition at the RPE
- Common genetic mutation of RDS/peripherin gene
- Histology: central RPE and photoreceptor loss, pigment-containing macrophages in subretinal space and outer retina, RPE distended with lipofuscin
- Butterfly-shaped pattern dystrophy: irregular, butterfly-shaped lesion of depigmentation
- Adult-onset foveomacular vitelliform dystrophy: slightly raised, symmetric, round to oval, yellow lesions
- Smaller than lesion of Best disease
- OCT shows elevation of photoreceptor layer
- Dystrophic material between photoreceptors and RPE
- Also includes reticular dystrophy and fundus pulverulentus
Fungal Chorioretinitis
Presumed ocular histoplasmosis
- Uncommon, occurs almost always in immunosuppressed patients due to fungemia
- Most common pathogen: candida
- Less common pathogens: aspergillus, cryptococcus
- Histology: central necrosis surrounded by granulomatous inflammation and lymphocytic infiltrate
- After treatment, heal with fibrous scar
- Identify pathogen by vulture or fungal features on histopathology
- Typical fungal stain: Gomori methenamine-silver nitrate (GMS), stains fungi black
Toxoplasmosis
Fundus photo of active toxoplasmosis
Chorioretinal scar in quiescent disease containing toxoplasma
Destruction of retina, RPE, and choroid form toxoplasmosis
- Most common infectious retinitis
- Due to either reactivation of congenitally acquired disease or acquired Toxoplasma in healthy or immunocompromised
- Clinical appearance – acute: “headlights in the fog”
- Whitish lesion and disc seen through hazy vitreous
- Can wipe out retina, RPE, and choroid
- Lack of chorioretinal scar suggests newly acquired disease
- Clinical appearance – Quiescent disease: pigmented lesion containing toxoplasmosis pathogen, may reactivate
- Histopathology – acute: necrosis, infiltrate of PMNs and lymphocytes, cysts and released tachyzoites
- Vitreous and anterior chamber with significant lymphocytic infiltrate
- Inner choroid with granulomatous inflammation
- Histopathology – healed: inflammatory infiltrate, cysts of organisms in retina at edge of chorioretinal scar
CMV Retinitis
Intracytoplasmic and intranuclear inclusions
- Opportunistic infection in immunosuppressed patients (i.e. AIDS)
- Clinical appearance: “pizza pie with tomato ketchup”
- Hemorrhages with areas of ischemia and whitening
- Histology: retinal necrosis followed by thin fibroglial scar with healing
- Acute lesions: large eosinophilic intranuclear and intracytoplasmic inclusions within enlarged neurons (ganglion cells)
- Can infect vascular endothelium, retinal neurons, and macrophages
Acute Retinal Necrosis (ARN)
- Causes: HSV1, HSV2, VZV, rarely CMV
- Progressive, necrotizing retinitis
- Occurs in both healthy and immunocompromised
- Histology: anterior chamber and vitreous inflammation, significant obliterative retinal vasculitis, retinal necrosis
- Viral inclusions in retinal cells seen on EM
- PCR of aqueous or vitreous quickly identifies viral cause
Bacterial Chorioretinitis
- Infectious endophthalmitis: vitreous inflammation due to infectious agents (bacteria, fungi)
- Bacterial endophthalmitis: neutrophilic infiltration of vitreous
- Leads to liquefaction of vitreous and then posterior vitreous detachment
- Severe inflammation may lead to fibrocellular membrane in the retrolental space, causing traction on the peripheral retina
- Gross opacification and infiltration of vitreous
- Histology: cellular infiltration of vitreous
Pseudoxanthoma Elasticum (PXE)
- Rare genetic disease that causes calcification and fragmentation of elastic tissue
- Angioid streaks are focal breaks in Bruch membrane
Angioid streaks in pseudoxanthoma elasticum
Flexural creases in pseudoxanthoma elasticum
Retinitis Pigmentosa
Fundus photo of classic triad of features in retinitis pigmentosa
Histopathology of retinitis pigmentosa
- Group of inherited retinal diseases featuring photoreceptor and RPE dysfunction leading to progressive visual field loss
- Inheritance can be sporadic, autosomal dominant, autosomal recessive, or X-linked
- Rhodopsin gene (RHO) mutation is most common cause in autosomal dominant disease
- Clinical triad of pallorous disc, attenuated vasculature, and bony spicules
- Bony spicules formed when pigment released from RPE deposits along vessels
- Rod photoreceptors lost by apoptosis
- Cone photoreceptors rarely affected directly by identified mutations, but degenerate secondarily to rods
- Histology: photoreceptor loss, RPE hyperplasia, migration of RPE pigment around retinal vessels
- Late findings: vessel wall thickening and hyalinization, diffuse or sectoral optic nerve atrophy, gliosis
Typical Peripheral Cystoid Degeneration (TPCD)
- Found in all people over age 20
- Development of cystic spaces in outer plexiform layer
- Typical Degenerative Retinoschisis: forms when these cystic spaces coalesce and the retina splits along the outer plexiform layer
- Usually in inferotemporal retina
- Occurs in 1% of adults
Reticular Degenerative Retinoschisis
- Originates from Reticular Peripheral Cystoid Generation (RPCD)
- RPCD: cystic spaces in nerve fiber layer, less common than TPCD, usually posterior to sites of TPCD
- Reticular Degenerative Retinoschisis: retina splits along nerve fiber layer
- Higher risk of RD
Lattice Degeneration
- Occurs in up to 10% of general population, very few of whom develop RD
- Possibly a familial condition
- 40% of rhegmatogenous detachments occur in the setting of lattice degeneration
- Histopathology:
- Discontinuous internal limiting membrane (ILM)
- Overlying vitreous liquefaction
- Sclerotic, but physiologically patent, retinal vessels
- Vitreous condensation and adherence at margins
- Some degree of atrophy of underlying retina
- Atrophic holes often develop in center of lattice, but rarely causes RD due to lack of vitreous traction
- RD with lattice usually due to vitreous traction at lesion margin
- Radial perivascular degeneration: lattice degeneration posteriorly along course of retinal vessels
- Associated with Stickler’s and severe RD
Paving Stone Degeneration
- AKA cobblestone degeneration
- Ischemia of outer retina and RPE from occlusion of choriocapillaris
- Clinical findings: well-demarcated, flat, pale lesions in peripheral retina near ora serrata
- Histopathology: atrophy of outer retina and RPE, inner nuclear layer adherent to Bruch membrane, sharp boundary between normal and abnormal retina
Retinopathy of Prematurity (ROP)
External photo of bilateral leukocoria
Fundus photo of dragged disc in resolved ROP
Gross photo of exudative retinal detachment
Scleral buckle used in funnel retinal detachment
- Incomplete development of retinal vasculature in periphery contributes to retinal ischemia
- Oxygen-induced vasoconstriction may also contribute
- No edema, no exudates
- Part of differential diagnosis of bilateral leukocoria along with congenital cataracts
- Hemorrhages and vessel dilation only in severe cases (ie. Plus or Rush disease)
- Neovascularization at border of vascularized and avascular retina
- Fibrovascular proliferation into vitreous à tractional RD, macular heterotopia (ectopic macula), high myopia
Retinoblastoma
Fundus photo of calcified intraocular mass
- Most common primary intraocular malignancy in childhood
- Neuroblastic origin from nucleated retinal cells
- Small amounts of glial tissue present within retinoblastoma suggests ability to differentiate into astroglia or a glial response to primary neoplastic cells
- Retinoblastoma gene (RB) on chromosome 13 suppresses tumor development
- Loss of both genes required for tumor development
- Starting as heterozygous may promote mutation of normal gene
Gross photo with sagittal cut of exophytic retinoblastoma
Gross photo of exophytic retinoblastoma with exudate
Retinoblastoma with both exophytic and endophytic growth
- Endophytic: grow into vitreous
- Exophytic: grow under retina
- Histology
- Cells with round, oval, or spindle-shaped nuclei
- Hyperchromatic nuclei with very little cytoplasm
- High mitotic activity
Pseudorosettes in retinoblastoma
- Pseudorosette formation due to necrosis from outgrowing blood supply
- Pseudorosette: tumor cells surrounding blood vessel
- Calcification common in areas of necrosis, AKA dystrophic calcification
- Neovascularization of iris can occur from high oxygen demand and tumor ischemia
- Shed tumor cells in vitreous and subretinal space can implant elsewhere in the eye
Flexner-Wintersteiner rosettes in retinoblastoma
Alcian blue stain of Flexner-Wintersteiner rosettes
- Flexner-Wintersteiner rosettes: cells surround central lumen lined by refractile structure comprised of external limiting membrane of retina
- Represents retinal differentiation, arise from primitive retinal tissue
- Single row of columnar cells with eosinophilic cytoplasm and peripheral nuclei
- Rarely seen in some pinealoblastomas and ectopic intracranial retinoblastomas
- Homer Wright rosette: lumen contains eosinophilic cytoplasmic processes (neurofibrillary tangle)
- Also seen in neuroblastoma and medulloblastoma
- Fleurette:
- curvilinear clusters of rod and cone inner segments with evidence of aborted outer segments
- Represents greater degree of retinal differentiation than Flexner-Wintersteiner
- Differentiation not an important prognostic factor
Vitreous seeding of retinoblastoma
- Intra-arterial chemotherapy ineffective for vitreous seeding, so intra-vitreal injections required
Retinoblastoma invading optic nerve
- Most commonly escapes eye via optic nerve
- Direct infiltration or leptomeninges can extend to brain and subarachnoid space
- Worst prognostic sign
- Uveal invasion increases risk of hematogenous spread
- Involvement of anterior segment and conjunctival substantia propria promotes spread to regional lymph nodes, especially if trabecular meshwork affected
- Tumor cells in anterior chamber can clinically appear like a hypopyon, therefore called a pseudohypopyon
Retinocytoma
- AKA retinoma
- Numerous fleurettes mixed with cells of variable degrees of photoreceptor differentiation
- Different from spontaneous regression of retinoblastoma from coagulative necrosis
- Differences from retinoblastoma
- More cytoplasm
- Nuclear chromatin more evenly dispersed
- No mitoses
- Necrosis usually absent, but calcification may be present
Combined Hamartoma of the Retina and RPE
- Clinical appearance: slightly elevated and variably pigmented mass, thickened optic nerve head, thickened peripapillary retina, increased number of vessels, hyperplastic RPE
- Preretinal membrane often distorts tumor’s inner surface
- Condensed vitreous and fibroglial proliferation may be on tumor surface
- Typically diagnosed in childhood
- Possible that vascular changes primary and adjacent RPE changes secondary
RPE Adenoma
- RPE neoplasia uncommon
- Unlike RPE hyperplasia, no history of or findings suggesting prior ocular trauma or disease
- Adenoma: RPE retains characteristics of normal RPE (basement membrane, cell junctions, microvilli)
RPE Adenocarcinoma
- Greater anaplasia, mitotic activity, invasion of choroid or retina
- No documented metastases in patients with RPE adenocarcinomas
Myelinated Nerve Fibers
- Normally, nerve fibers in the optic nerve are myelinated only up to lamina cribrosa
- Nerve fibers myelinated by oligodendrocytes
- Myelination of NFL usually, but not always, continuous with optic nerve head
- If isolated and large, can produce significant scotoma
- Associated with myopia, amblyopia, strabismus, nystagmus
Congenital Hypertrophy of the RPE (CHRPE)
- Common congenital lesion
- Clinical appearance: flat, dark black, few to 10mm in diameter
- With central lacunae and peripheral area of less dense pigmentation
- Histology: enlarge RPE cells, large and tightly packed melanin granules
- Rarely, adenoma and adenocarcinoma of RPE may develop
- CHRPE-like lesions seen in Gardner syndrome or familial adenomatous polyposis
- RPE changes in Gardner syndrome more hyperplasia than hypertrophy
- More like hamartoma
Ocular Albinism
- Albinism: congenital decrease in pigmentation of skin and/or eyes
- Features: photophobia, iris transillumination, hypopigmented fundus
- Ocular albinism defined as reduced number of melanosomes
- Some mild cutaneous involvement typically still present
- X-linked recessive inheritance
- On histopathology, little or no pigmentation in iris stroma, RPE, choroid stroma
Oculocutaneous Albinism
- Oculocutaneous albinism: less melanin within each melanosome
- Autosomal recessive inheritance
- On histopathology, nuclei of melanosomes can be seen due to decreased pigment
References
Harper RA. Basic Ophthalmology. Amer Academy of Ophthalmology; 2010.
Yanoff M, Fine BS. Ocular Pathology, A Text and Atlas. Lippincott Williams & Wilkins; 1989.