Ophthalmic Pathology & Intraocular Tumors

Front 1

SCLERA: ANATOMY
-From which cells is the sclera derived?
-Thickness of sclera?
-Posterior scleral anatomy?

Back 1

-Neural crest derived
-Thickness: 1.0 mm posteriorly - 0.3 mm anteriorly (just posterior to insertion of recti)
-Posterior outer 2/3 of sclera merge with optic nerve dura; inner 1/3 continues as lamina cribosa

Front 2

SCLERA: ANATOMY
-What is episclera?

Back 2

-Thin fibrovascular membrane covering outer scleral stroma
-Composed of loose collagen fibers and vascular plexus

Front 3

SCLERA: ANATOMY
-Describe stromal fibers
-What types of transmural emisserial channels are in sclera?
-What is an Axenfeld nerve loop?

Back 3

-Stroma: sparsely vascularized, dense, type I collagen, randomly arranged, may branch and curl
-scleral collagen fibers are thicker and more variable in thickness/orientation than corneal
-Transmural emissarial channels:
-posterior sclera: post ciliary arteries/nerves
-equatorial sclera: vortex veins
-anterior sclera: ant ciliary arteries, nerves, veins
-Axenfeld nerve loop: pigmentation on epibulbar surface that represents pigmented melanocytes along ciliary nerve sheaths

Front 4

SCLERA: ANATOMY
-What is lamina fusca?

Back 4

-Thin network of bridging collagen fibers that loosely binds uvea to sclera
-Strongest along major emissarial canals and anterior base of ciliary body
-contains melanocytes

Front 5

SCLERA: Congenital Anomalies
-Describe episcleral osseous choristoma
-Nanophthalmos

Back 5

-Episcleral osseous choristoma: superotemporal region, single stationary hard white plaqueup to 1 cm diameter, below conjunctiva, histo shows mature lamellar bony trabeculae
-Nanophthalmos: eye reduced in size except for nl/slightly enlarged lens, severe hyperopia, abnormally thick sclera, bilateral, predisposed to glaucoma (decreased venous outflow, angle closure, etc)

Front 6

SCLERA: Episcleritis
-What is simple episcleritis?
(location, epidemiology, histology, treatment)

Back 6

-Slightly tender, movable, sectorial red area
-M=F, 3-5th decades, no asociation with trauma/systemic disease
-Histo: vascular congestion, stromal edema,chronic perivascular lymphocytic inflammation
-Resolves with/without topical steroids, may be recurrent --> scarring

Front 7

SCLERA: Episcleritis
-What is nodular episcleritis?
(location, histology, epidemiology, treatment)

Back 7

-tender, elevated, round, pink nodules on anterior episclera
-F>M, associated with rheumatoid arthritis
-Histo: central necrotic collagen core surrounded by palisading epithelioid histiocytes (like rheumatoid nodules)
-Spontaneous resolution

Front 8

SCLERA: Scleritis
-Describe types of scleritis
(anterior, posterior, necrotizing, non-necrotizing)

Back 8

-Painful and progressive
-High association with systemic autoimmune disease
-Anterior: severe pain, sectoral inflammation of sclera and episclera, photophobia, bilateral in 50%
-Posterior: unilateral proptosis, retrobulbar pain, gaze restriction, VF loss, may have contiguous optic neuritis or retinal/choroidal detachments, thickened sclera
-Necrotizing: can be nodular or diffuse, necrosis surrounded by palisading epithelioid histiocytes and multinucleated giant cells with rim of lymphocytes and plasma cells
-Scleromalacia perforans: severe ectasia of scleral shell after recurrent disease, predisposes to herniation of uveal tissue
-Nonnecrotizing: perivascular lymphocytic and plasma cell infiltrate, NO granulomatous reaction, treat with NSAIDs

Front 9

SCLERA: Degenerations
-What are senile calcific plaques?
-What are scleral staphylomas?

Back 9

-Senile plaques: elderly, flat/firm/gray rectangular to oval patches < 1 cm, anterior to rectus muscle inserations, +von Kossa stain
-Staphylomas: ectasias lined by uveal tissue at points of weakness in scleral shell (i.e., posterior to muscle insertion or areas of scarring), in peds: may be 2/2 long standing increased IOP or axial myopia, look like variably sized blue/purple patches of sclera (due to underlying uveal pigment)

Front 10

LENS: Anatomy
-What is the size and tissue derivation of the lens?
-Describe the size, thickness and funtion of the lens capsule

Back 10

-Lens: biconvex, derived from surface ectoderm, 9-10mm diameter and 3.5mm AP thickness
-Capsule: made of thickened BM elaborated by epithelial cells; thickest anteriorly (12-21 um) and thinnest posteriorly (2-9 um); helps mold lens shape

Front 11

LENS: Anatomy
-Describe epithelium
-Describe lens cortex/nucleus
-What is the location of zonules?

Back 11

-Epithelium: centrally located cells do not divide; peripheral/equatorial cells actively divide
-anterior/axial cells: single cuboidal layer
-equatorial cells: elongated
-Cortex/nucleus: new lens fibers laid by epithelial cells make up cortex; oldest fibers are embryonic and fetal lens nuclei
-Zonules: attach to anterior and posterior lens capsule in periphery

Front 12

LENS: Congenital anomalies
-Distinguish b/w subluxation & luxation
-Describe systemic disorders associated with ectopia lentis

Back 12

-Subluxation: partial dislocation
-Luxation: complete dislocation
-Marfan: upward/superotemporal dislocation of lens, axial myopia, fibrillin gene defect (ch 15)
-Homocystinuria: inferonasal or ant/post dislocation, auto recessive, defect in cystathionine b-synthase
-Others: Weill-Marchesani, Ehlers-Danlos, hyperlysinemia, Crouzon disease, oxycephaly

Front 13

LENS: Congenital cataract
-When do congenital cataracts develop?
-What is the epidemiology of these cataracts?
-What are posterior polar cataracts?
-What causes rubella cataracts?

Back 13

-Congenital cataracts: present at birth or 1st yr (infantile cat: not seen at birth)
-unilateral or bilateral
-1/3 associated with other diseases, 1/3 are inherited, 1/3 unknown causes
-Post polar cataracts: variable presentation (Mittendorf dot --> large plaque 2/2 persistent fetal vasculature)
-Rubella cataract: exposed to virus in 1st or 2nd trimester, associated with microspherophakia

Front 14

LENS: Inflammations
-Phacoantigenic endophthalmitis (cause, histology)

Back 14

-Phacoantigenic endophthalmitis: IgG against lens protein, may follow accidental/surg trauma
-Histo: central nidus of degenerating lens surrounded by concentric layers of inflammatory cells (inner: multinucleated giant cells, PMNs; outer: lymphocytes, histiocytes)

Front 15

LENS: Inflammations
-Phacolytic glaucoma (mechanism, histology)

Back 15

-Hypermature cataract --> liquefied cortex may leak through capsule into AC
-Histo: nongranulomatous inflammation 2/2 macrophages phagocytizing lens protein --> these macs and lens protein material clog TM
-Macs will have eosinophilic lens material in them

Front 16

LENS: Inflammations
-P. Acnes endophthalmitis: clinical features

Back 16

-granulomatous KPs, small hypo yon, vitritis, small plaque in capsular bag with bacteria and residual lens material
-may follow YAG cap ( allows release of sequestered organisms )

Front 17

LENS: Capsular degenerations
-Describe coronary (cerulean) cataract
-Describe posterior lenticonus
-Describe exfoliation syndrome

Back 17

-Coronary cataract: wartlike excrescences on capsule --> over time these are replaced by clumps of epithelium (look like granular debris in cortex)
-Posterior lenticonus: abnormally thin lens capsule --> lens bulges into anterior vitreous (anterior lenticonus is more rare)
-Exfoliation: fibrillary protein-like material deposited on anterior lens capsule (like iron filings standing on surface of magnet on histology)

Front 18

LENS: Epithelial degenerations
-What are glaukomflecken?
-What are effects of chronic iritis on lens epithelium?

Back 18

-Glaukomflecken: patches of white flecks beneath lens capsule after chronic severe IOP elevation (injures epithelial cells)
-Chronic iritis: epithelial hyperplasia and metaplasia into collagen-producing cells; lens epithelium may produce another capsule surrounding the fibrous plaque after resolution of inflamm.

Front 19

LENS: Epithelial degenerations
-Describe PSC
-What are Elschnig pearls?
-What is a Soemmerring ring?

Back 19

-PSC: most common lens epithelial abnormality; caused by epithelial disarray at equator --> posterior migration of lens epithelium --> enlargement/swelling of cels to 5-6x normal size (bladder/Wedl cells)
-Causes of PSC: vitreal inflammation, ionizing radiation, steroid use
-Elschnig pearls: after disruption of capsule, lens epithelial cells proliferate and cover iner surface of post capsule --> form partially transparent, globular masses (see with retroillumination)
-Soemmerring ring: equatorial sequestration of proliferating lens fibers --> creates doughnut shaped configuration

Front 20

LENS: Cortical degenerations
-What happens with focal cortical opacification/degeneration?
-What are morgagnian globules?
-What is a morgagnian cataract?

Back 20

-Earliest sign of focal cortical degeneration: hydropic swelling of lens fibers, increased eosinophilic staining
-Morgagnian globules: eosinophilic globules accumlate between lens fibers in slitlike spaces
-Morgagnian cataract: liquefaction of entire cortex --> nucleus sinks down and capsule wrinkles

Front 21

LENS: Nuclear degenerations
-What causes nuclear sclerotic cataracts?
-What are signs of nuclear sclerosis on histology?
-What is the consequence of nuclear sclerotic cataracts?

Back 21

-Causes of NS: continued lens fiber proliferation during life causes mechanical compression on nucleus --> hardening of nuclear material
-Histology: loss of cellular laminations --> increased homogenous appearance of nucleus (less artifactual fracturing during sectioning)
-Consequence of NS: increased index of refraction of lens, myopic shift

Front 22

LENS: Systemic causes of cataract
-What systemic diseases are associated with cataracts?

Back 22

-Diabetes
-Galactosemia
-Hypercupremia
-Fabry disease
-Downs syndrome
-Steroid use

Front 23

VITREOUS: Anatomy
-What is the volume and composition of the vitreous?

Back 23

-volume: 4 cc
-99% water
-macromolecules: types II, IX collagen, GAGs, soluble proteins, glycoproteins

Front 24

VITREOUS: Anatomy
-Describe the structure of different parts of the vitreous
-What are the most firm sites of attachment of the vitreous?

Back 24

-Vitreous cortex (hyaloid face): outer portion of vitreous, has greater number of collagen fibrils
-Hyaloideocapsular ligament: attaches vitreous to lens capsule
-Most firm site of attachment: vitreous base (360 deg band straddling ora serrata, width of 2 - 6 mm)
-Other firm attachment sites of vitreous: optic nerve head, margins of lattice degenerations, along course of major retinal vessels, foveal area

Front 25

VITREOUS: Anatomy
-What are the primary, secondary and tertiary vitreous?

Back 25

-Primary vitreous: fibrillar material, mesenchymal cells, vascular components (hyaloid artery, vasa hyaloidea propria, tunica vasculosa lentis)
-Secondary vitreous: forms at 9th wk GA, destined to become main portion of vitreous, primary vitreous atrophies when secondary vitreous forms
-Remnants of primary vitreous: Bergmeister papillae, Mittendorf dot, Cloquet's canal
-Tertiary vitreous: zonular fibers

Front 26

VITREOUS: Congenital anomalies
-What is persistent fetal vasculature (PHPV)?
-What are associations/complications of PHPV?

Back 26

-PHPV: persistence of variable components of primary vitreous, usually unilateral
-May appear as fibrovascular plaque posterior to lens extending laterally to ciliary processes (elongated ciliary processes) and posteriorly to optic nerve head via remnant of hyaloid artery
-Consequences/associations: tractional RD of peripapillary retina, cataract, microophthalmos

Front 27

VITREOUS: Congenital anomalies
-What is a Bergmeister papilla?
-What is a Mittendorf dot?
-What are peripapillary vascular loops?

Back 27

-Bergmeister papilla: persistence of small part of posterior portion of hyaloid artery (veil or finger-like structure extending from surface of disc)
-Mittendorf dot: focal lens opacity inferiorly/nasal to center, vestigial remnant of attachment of hyaloid artery to tunica vasculosa lentis
-Peripapillary vascular loops: growth of retinal vessels into Bergmeister papilla and then return back to optic nerve head (looks like vascular loop)

Front 28

VITREOUS: Inflammations
-What are causes and consequences of vitreal inflammation?

Back 28

-Causes: secondary inflammation from infection with toxocaria, toxoplasma, CMV; inflammatory conditions (sarcoid, ARN, pars planitis)
-Consequences: liquefaction and PVD, formation of fibrocellular membranes (retinal traction)

Front 29

VITREOUS: Degenerations
-What is vitreous syneresis and what are some etiologies?
-What is the pathophysiology of vitreous hemorrhage?

Back 29

-Vitreous syneresis: liquefaction of vitreous gel, caused by pathologic myopia, aging, inflammation and hemorrhage
-Vit heme: after 3-10 days, clots undergo fibrinolysis --> RBCs diffuse into vitreous
-loss of Hgb from cells causes ghost cells to form (can lead to ghost cell glaucoma)
-macrophages phagocytose RBCs

Front 30

VITREOUS: Degenerations
-What material makes up asteroids in asteroid hyalosis?
-What material makes up amyloid in vitreous amyloidosis?

Back 30

-Asteroid hyalosis: asteroid bodies are similar to hydroxyapatite, stain with Alcian blue and with stains for neutral fats, phospholipids and Ca; no associated inflammatory reaction
-Amyloidosis: vitreous amyloid occurs when the amyloid protein is transthyretin (prealbumin), proteins form beta-pleated sheets

Front 31

VITREOUS: Degenerations
-What is the mechanism of a PVD?
-Where are retinal tears most likely to form?
-What are histopathologic features of RD?
-What is the pathophysiology of PVR?

Back 31

-PVD: dehiscence in vitreous cortex --> leakage of fluid from syneretic cavity into posterior subhyaloid space --> remaining vitreous cortex stripped from ILM
-PVD occurs rapidly (hours to days) until vitreous remains attached only at base
-Retinal tears: seen during/after PVD (2/2 vitreous traction), trauma, at sites of strong vitreoretinal adhesions
-RD: degeneration of photoreceptor outer segments --> eventual loss of photoreceptor cells; migration of Muller cells, proliferation/migration of RPE
-PVR: cellular membranes form on anterior and/or posterior surface of detached retina 2/2 proliferation of RPE and other cells

Front 32

VITREOUS: Degenerations
-What is the pathophysiology of a macular hole?
-Describe stages of macular hole (1a,1b, 2, 3)
-What are associated conditions?

Back 32

-Pathophysiology: vitreous degeneration --> localized parafoveal detachment (primary pathophysiologic event) --> anterior traction on fovea
-Stage 1a: foveal pseudocyst
-Stage 1b: disruption of outer retina
-Stage 2: full-thickness dehiscence of retina
-Stage 3: full thickness defect with rounded tissue margins
-Epiretinal membrane and CME can form in parafoveal retina adjacent to full thickness macular holes

Front 33

VITREOUS: Intraocular lymphoma
-What is the presentation of primary intraocular lymphoma?
-What are the cellular characteristics of PIOL?
-Is the choroid involved in PIOL?

Back 33

-Presentation: posterior uveitis (most common) with sub-RPE infiltrates (look like speckled pigmentation over tumor detachments of retina), 50% of pts with eye findings have concomitant CNS involvement
-Cells: usually monoclonal B cell population with heterogeneous vitreal infiltrate (largeatypical lymphoid cells and small lymphocytes which are mostly reactive T cells)
-Choroid is usually not involved, but can be the primary site of involvement in systemic lymphoma with mets to eye

Front 34

RETINA/RPE: Anatomy
-What embryonic tissues are the retina/RPE derived from?
-What is the topography of the retina/RPE?

Back 34

-RPE: outer layer of optic cup
-Retina: inner layer of optic cup
-RPE: anteriorly continuous with pigmented CB epithelium, posteriorly terminates at optic nerve
-Retina: anteriorly continuous with nonpigmented CB epithelium, posteriorly terminates at optic nerve (nuclear, photoreceptor and synaptic layers only --> NFL continues to form optic nerve)

Front 35

RETINA/RPE: Anatomy
-What are the 9 layers of the retina (from vitreous to choroidal side)?

Back 35

-ILM (true basement membrane synthesized by Muller cells)
-NFL
-Ganglion cell layer
-Inner plexiform layer
-Inner nuclear layer
-Outer plexiform layer
-Outer nuclear layer
-ELM (not a true BM)
-Photoreceptors

Front 36

RETINA/RPE: Anatomy
-Describe the blood supply of the retina (retinal vs choroidal vessels)

Back 36

-Retinal blood vessels supply: NFL, ganglion cell layer, inner plexiform layer, inner 2/3 of inner nuclear layer
-Choroidal vessels supply: outer 1/3 of inner nuclear layer, outer plexiform layer, outer nuclear layer, photoreceptors, RPE
-Watershed area: inside inner nuclear layer

Front 37

RETINA/RPE: Anatomy
-What is the structure of RPE in macula, equator/midperipheral regions?
-What are some aging-related changes in RPE?
-What are the functions of the RPE?

Back 37

-RPE structure: monolayer of hexagonal cells; taller/narrower/more pigmented in macula; wider, thinner in equator/midperiphery
-Aging changes: increased cytoplasmic pigment (lipofuscin) in macular RPE
-Functions: vit A metabolism, light absorption, phagocytosis of photoreceptor outer segments, heat exchange, maintanance of blood-retina barrier, forms basal lamina of inner Bruch's membrane, active transport of materials into/out of subretinal space

Front 38

RETINA/RPE: Anatomy
-What is the cellular structure of the macula and fovea?
-Describe the orientation of NFL in macula and it's clinic relevance
-Why does the macula appear yellow?

Back 38

-Cellular structure: macula = area of retina where ganglion cell layer is thicker than 1 cell
-Fovea: only photoreceptors present (only cones)
-Macular nerve fibers in outer plexiform layer (NFL of Henle) run obliquely --> cause flower-petal shape of CME and star-shaped pattern of exudate in macula
-Yellow color of macula 2/2 presence of xanthophyll pigment

Front 39

RETINA/RPE: Congenital anomalies
-What is the difference between oculocutaneous and ocular albinism?
-What are the 2 clinical ocular patterns of albinism (either ocular or oculocutaneous forms)? Which of these is true albinism and which is albinoidism?

Back 39

-Oculocutaneous albinism: decreased amount of melanin in each melanosome
-Ocular albinism: decreased amount of melanosomes
-Clinical patterns:
1) congenital subnormal VA, nystagmus (true albinism)
2) normal/min reduced VA, no nystagmus (albinoidism)

Front 40

RETINA/RPE: Congenital anomalies
-What are common clinical features of albinism & albinoidism?
-What is one distinguishing feature between albinism and albinoidism?
-What are two types of ocular albinism that have important systemic associations?

Back 40

-Common features: photophobia, iris TI defects, hypopigmented fundus
-Distinguishing feature: foveal hypoplasia (albinism) vs normal fovea (albinoidism)
-Hermansky-Pudlak: albinism + platelet defect (easy bleeding)
-Chediak-Higashi: albinism + PMN abnormality (frequent infections)

Front 41

RETINA/RPE: Congenital anomalies
-Describe myelinated NFL (cells that produce myelin, location, clinical significance)

Back 41

-Normal myelination of optic nerve terminates at lamina cribosa
-myelinated NFL usually contiguous with optic nerve head (but not always)
-myelin produced by oligodendoglial cells within NFL
-If large, myelinated NFL produce significant scotoma

Front 42

RETINA/RPE: Congenital anomalies
-What is the clinical presentation and histology of CHRPE?
-What is an important systemic association with CHRPE?

Back 42

-Clinical: flat, dark/black lesion from few - 10 mm; may have central lacunae and peripheral zone of less dense pigmentation
-Histology: enlarged RPE cells with densely packed, larger than normal spherical melanin granules
-CHRPE may rarely give rise to RPE adenocarcinoma
-Associated with Gardner syndrome (FAP): bilateral/multiple (>4) areas of RPE hypertrophy --> if seen in patient with +FHx, increased risk for colon cancer
-CHRPE associated with FAP usually 2/2 hyperplasia (not hypertrophy) of RPE

Front 43

RETINA/RPE: Viral infections
-What is the etiology, clinical presentation and histological appearance of ARN?
-What are systemic associations and histologic appearance of CMV retinitis?

Back 43

-ARN: 2/2 HSV-1 or 2, VZV (rarely CMV also); presents with diffuse uveitis, vitritis, retinal vasculitis and necrotizing retinitis
-ARN electron microscopy: viral inclusions in retinal cells
-CMV retinitis: seen in 37% of AIDS pts, looks like retinal necrosis --> leads to thin fibroglial scar after healing
-CMV histology: large neurons (20-30 um) with large eosinophilic inclusions

Front 44

RETINA/RPE: Fungal infections
-What patient population typically gets fungal retinitis?
-What are the most common etiologies?
-What is the histologic appearance of fungal retinitis?

Back 44

-Almost exclusively occurs in immunocompromised pts
-Common organisms: Candida, Aspergillus, Crypto
-Histo: necrotizing granulomatous inflammation, heals with fibrous scar

Front 45

RETINA/RPE: Toxoplasmosis infection
-What is the most common cause of retinal toxo?
-What is the histologic appearance of toxo?

Back 45

-Most cases 2/2 reactivation of transplacentally acquired retinal infection
-May also see acquired retinal infection in immunosuppressed patients
-Histo: retinal necrosis, PMN/lymphocytic infiltrates, cysts & tachyzoites, lymphocytic infiltrate of vitreous/AC

Front 46

RETINA/RPE: Sarcoidosis
-What are clinical findings associated with retinal sarcoidosis?
-What is the typical histologic appearance?

Back 46

-Associated with retinal periphlebitis (candlewax drippings), CME, vascular occlusion, neovascularization
-Histo: noncaseating granulomas without demonstratable infectious cause

Front 47

RETINA/RPE: Degenerations
-Distinguish between typical & reticular peripheral cystoid degeneration (by area of retina affected, location, progression to degenerative retinoschisis, epidemiology)

Back 47

-Typical peripheral cystoid degeneration: cystic spaces in outer plexiform layer --> when these spaces coalesce, forms typical degenerative retinoschisis (space should be >1.5 mm diameter)
-Reticular peripheral cystoid degeneration: cystic spaces in NFL --> progresses to reticular degenerative retinoschisis
-Incidence: TPCD near universal in adults > 20 yo, RPCD less common
-Incidence: TDR: 1% of adults, RDR: 1.6% of adults
-Location: TPCD usually more anterior to RPCD
-Location: TDR usually inferotemporal in location, RDR more posterior in location and tends to be associated with outer layer retinal breaks

Front 48

RETINA/RPE: Degenerations
-What is the epidemiology of lattice degeneration?
-What are histologic features of lattice?

Back 48

-Occurs in 8-10% of all eyes, but seen in 20-40% of all RRDs
-Histology:
1) discontinuity of ILM
2) liquefied vitreous overlying lesion
3) condensed vitreous adherent to margins of lesion (predisposes to breaks)
4) sclerosis of retinal vessels
5) variable atrophy of inner retinal layers
6) atrophic holes may form within lattice but do not lead to RD because overlying vitreous is liquefied (no traction)

Front 49

RETINA/RPE: Degenerations
-What is radial perivascular lattice degeneration?
-What is the pathophysiology, histology and clinical appearance of paving stone degeneration?

Back 49

-RPLD: same as lattice, but occurs more posterioly along course of retinal vessels, can be assoc with severe forms of RD
-Paving stone (cobblestone): caused by occlusion of peripehral choriocapillaris --> loss of outer retinal layers and RPE; looks like well demarcated, flat, pale lesions
-Histology: outer retinal layers atrophy --> remaining inner layers adhere to Bruch's membrane

Front 50

RETINA/RPE: Cellular responses to ischemia
-What are the causes of inner ischemic retinal atrophy and outer ischemic retinal atrophy, respectively?
-What are cytoid bodies?
-What happens to glial cells after ischemic injury?
-What are microglial cells and what is their function?

Back 50

-Inner ischemic retinal atrophy: caused by retinal vascular occlusion
-Outer ischemic retinal atrophy: caused by choroidal vascular occlusion
-Cytoid bodies: swollen axons of ganglion cells (represent localized accumulation of axoplasmic material)
-Glial cells: proliferate in areas adjacent to infarction/ischemia --> cause glial scar formation
-Microglia: are actually tissue macrophages, phagocytose necrotic cells/debris, resistant to ischemia

Front 51

RETINA/RPE: Vascular responses to ischemia
-What is the histologic appearance of hard exudates?
-What types of hemorrhages are likely to be seen in each of the following parts of the retina: inner nuclear/outer plexiform layers, NFL, pre-retinal?

Back 51

-Hard exudates: eosinophilic, sharply circumscribed spaces within retina
-Dot-blot: middle layers (inner nuclear/outer plexiform)
-Flame: NFL
-Boat-shaped: pre-retinal (subhyaloid)

Front 52

RETINA/RPE: Vascular responses to ischemia
-What causes the white areas in white-centered hemorrhages (Roth spots)?
-What are IRMAs and MAs and how are they best seen histologically?
-What characterizes retinal neovascularization?

Back 52

-Roth spots: white centers caused by aggregates of WBC/plts/fibrin or retinal light reflexes
-IRMAs and MAs: dilated irregular vascular channels appearing adjacent to acellular areas; best seen using PAS-stained trypsin digest preparations
-Retinal NV: characterized by new blood vessels growing on the vitreous side of the ILM --> hemorrhage is 2/2 vitreous traction on fragile new vessels

Front 53

RETINA/RPE: CRAO/BRAO
-What are 3 causes of a CRAO?
-Why does a cherry-red spot develop in CRAO?
-What is the classic histologic picture of CRAO?
-What causes a BRAO?

Back 53

-CRAO is 2/2 localized arteriosclerotic changes, embolic events or vasculitis (rare, i.e., GCA)
-Cherry red spot: ischemia causes edema and loss of transparency of retina --> the fovea contains only photoreceptors and does not exhibit edema, so the normal color of choroid shows through fovea but not through rest of retina --> cherry red spot
-Histo: inner ischemic retinal atrophy
-BRAO: most commonly 2/2 emboli lodging at bifurcation of retinal arteriole
-Types of emboli: Hollenhorst plaque (cholesterol emboli, carotid disease), calcific emboli (cardiac valvular disease), platelet-fibrin emboli (thromboembolism)

Front 54

RETINA/RPE: CRVO/BRVO
-What is the pathophysiologic mechanism of both CRVO and BRVO?
-Where is the site of compression in CRVO? BRVO?

Back 54

-Both CRVO and BRVO caused by compression of vein --> turbulent flow --> thrombosis and occlusion
-Compression in CRVO occurs at lamina cribosa (2/2 changes in lamina cribosa and CRA)
-Compression in BRVO occurs at sites of AV crossing (artery and vein share common adventitial sheath --> atherosclerotic arterial changes compress the vein)

Front 55

RETINA/RPE: CRVO/BRVO
-What are diseases that predisopose to CRVO? BRVO?
-What is the relationship between papillophlebitis and CRVO?

Back 55

-CRVO: HTN, DM, arteriosclerosis, glaucoma
-BRVO: arteriosclerosis, HTN
-Papillophlebitis is thought to be a CRVO in a patient with good collateral circulation (only clinical sign of CRVO is optic disc edema)

Front 56

RETINA/RPE: CRVO/BRVO
-What is the clinical appearance of CRVO?
-Describe ischemic CRVO by clinical and histologic appearance

Back 56

-Clinical: prominent optic disc edema, dilation of retinal veins, heme in 4 quadrants, CWS, macular edema
-Ischemic CRVO: >10 disc areas of nonperfusion on IVFA
-Histo: significant retinal edema, focal necrosis, subretinal/intraretinal/preretinal heme
-Ischemia in CRVO stimulates gliosis, disorganization of retinal architecture, hemorrhage, formation of collaterals at optic nerve head, NVI

Front 57

RETINA/RPE: CRVO/BRVO
-Where does BRVO most commonly occur?
-What is the visual prognosis for pts with BRVO?

Back 57

-63% of BRVO occurs in superotemporal quadrant
-50-60% of pts have VA 20/40 or better after 1 yr

Front 58

RETINA/RPE: Diabetic Retinopathy
-What are three abnormalities that occur early in the course of DR?

Back 58

-Impaired retinal vasculature autoregulation
-Altered retinal blood flow
-Blood-retinal barrier breakdown

Front 59

RETINA/RPE: Diabetic retinopathy
-What are primary changes in the retinal microcirculation in DR?

Back 59

-thickened retinal capillary basement membrane
-loss of pericytes (more than loss of capillary endothelial cells)
-microaneurysms
-closure of capillaries
-formation of telangiectatic vessels, IRMAs
-Consequences of these changes: intraretinal edema, exudates, hemorrhages, microinfarcts --> atrophy

Front 60

RETINA/RPE: Diabetic retinopathy
-What are other histologic changes in DR? (cornea, CB, lens)

Back 60

-Thickened corneal epithelial BM, inadequate adherence of epithelium to Bowman's --> predisposition to K abrasions, poor wound healing
-Iris: formation of glycogen-containing vacuoles in iris pigment epithelium
-CB: thickening of ciliary epithelial BM
-Lens: cataract formation

Front 61

RETINA/RPE: ROP
-What is the pathophysiology of ROP?
-What are some differences between ROP and other retinal ischemic states?
-What are the consequences of neovascularization in ROP?

Back 61

-Pathophysiology: absent retinal vessels in incompletely developed retinal periphery & decreased blood flow from oxygen-induced vasoconstriction
-ROP: no retinal edema or exudates; neovascularization forms only in most severe cases (i.e., plus disease) --> at border of perfused and non-perfused retina
-NV leads to: tractional RD, high myopia, macular heterotopia

Front 62

RETINA/RPE: AMD
-What antioxidants are associated with decreased risk of progression of AMD?
-What is the difference between basal linear and basal laminar deposits?
-What are drusen?

Back 62

-Antioxidants: beta carotene, vitamin C, vitamin E, zinc
-Basal linear: between RPE BM and elastic portion of Bruch's
-Basal laminar: between RPE plasma membrane and RPE BM
-Drusen: large PAS-positive deposits between RPE and Bruch's

Front 63

RETINA/RPE: AMD
-What are the sizes of small, intermediate and large drusen?
-What are basal laminar/cuticular drusen?
-What are calcific drusen?

Back 63

-Small: <63 um
-Intermediate: 63-125 um
-Large: >125 um
-Cuticular drusen: diffuse, small, regular deposits of drusen-like material in macula
-Calcific drusen: sharply demarcated, glistening, refractile lesions associated w/ RPE atrophy

Front 64

RETINA/RPE: AMD
-Where does CNV form?
-What is the consequence of CNV?

Back 64

-CNV = fibrovascular tissue b/w inner and outer layer of Bruch's, beneath RPE or in subretinal space
-CNV leads to leakage of fluid from new vessels --> serous RD, subretinal/intraretinal hemorrhages

Front 65

RETINA/RPE: AMD
-Distinguish between Type 1 and Type 2 CNV

Back 65

-Type 1: NV within Bruch's membrane in sub-RPE space --> more common in AMD
-Type 2: NV in subretinal space, small defect in which RPE is abnormally oriented/absent --> more common in ocular histoplasmosis

Front 66

RETINA/RPE: Polypoidal choroidal vasculopathy
-What is the pathophysiology of PCV?
-What is the clinical appearance?
-What is the epidemiology?

Back 66

-Pathophysiology: dilated, thin walled vascular channels that arise from short posterior ciliary arteries penetrate Bruch's --> associated CNV occurs
-Clinical: elevated red-orange polyplike/tubular subretinal lesions with associated serosanguinous RD
-Japanese/Chinese: 80% men, 85% unilateral
-Europe/America: 96% female, 68% male, affects darker skinned people (79%), HTN (43%)

Front 67

RETINA/RPE: Macular dystrophies
-What are 4 characteristics common to both fundus flavimaculatus and Stargardt disease?
-What is the most common mutation in Stargardt disease?
-What does this gene encode?
-What is the most striking histologic feature of Stargardt disease?

Back 67

-Common features: yellow flecks at RPE, vermillion color to fundus, dark choroid on IVFA, gradually decreasing VA, autosomal recessive (mostly)
-ABCA4 gene mutation
-encodes RIM protein (ATP-binding cassette transporter)
-Histo: engorgement of RPE cells with lipofuscin-like, PAS+ material

Front 68

RETINA/RPE: Best Disease
-What are the clinical characteristics of Best disease?
-What are the genetics?

Back 68

-Vitelliform (egg-yolk) macular lesion
-abnormal light peak to dark trough on EOG
-Histo: lipiofuscin-containing pigment cells in subretinal space and outer neurosensory retina
-VMD2 gene on ch11q13 --> bestrophin protein (chloride ion channel)

Front 69

RETINA/RPE: Pattern dystrophies
-What is the most common genetic mutation associated with pattern dystrophies?
-Describe the histopathologic appearance of pattern dystrophies
-What is the clinical appearance of butterfly pattern dystrophy?
-What is the clinical appearance of adult-onset foveomacular vitelliform dystrophy?

Back 69

-RDS/Peripherin gene mutation
-Histo: loss of RPE/photoreceptor layer in center of lesion with lipofuscin containin RPE to either side
-BPD: butterfly-shaped irregular depigmented lesion at RPE
-AFMVD: slightly elevated, symmetric, solitary, oval yellow RPE lesions

Front 70

RETINA/RPE: RP
-What genes contribute the greatest number of known mutations assoc with RP?
-Which of these is the most common cause of auto dominant RP?
-What cells are affected by RP?
-What is the clinical appearance of RP?

Back 70

-Most common genes: RHO, RP1, RPGR
-Of these, RHO (Rhodopsin) mutations most commonly cause AD RP
-Pathophysiology: Loss of rod cells by apoptosis (cones usually degenerate secondarily to rods, not directly affected)
-Appearance: bone spicule pigment changes, arteriolar narrowing, optic disc atrophy

Front 71

RETINA/RPE: RB
-What are the cells of origin of RB?
-What stains can be used to identify RB cells?
-What is the pathophysiology of RB?

Back 71

-Cells of origin: neuroblasts (nucleated cells of the retina) --> may be a neoplasm of cone cells
-Stains: neuron-specific enolase, rod-outer segment photoreceptor-specific S antigen, rhodopsin
-Cells secrete interphotoreceptor retinoid-binding protein
-Pathophys: RB gene is a tumor suppressor gene --> RB develops when both homologous loci of this gene are nonfunctional
-Single nl gene and abnormal gene = unstable situation

Front 72

RETINA/RPE: RB
-What are the most common histologic features of RB?
-What is the most common route of spread of RB?

Back 72

-Histo: cells with round/oval/spindle nuclei approx 2x size of lymphocyte (little cytoplasm)
-Characteristic necrosis pattern:(alternating zones of necrosis and tumor cells) with viable cells closer to blood vessels (ischemic necrosis begins 90-120 um from vessels)
-Spreads via direct extension by invasion of optic nerve --> brain (poor prognostic sign)
-Uveal invasion --> hematogenous spread to regional nodes

Front 73

RETINA/RPE:RB
-Distinguish between Flexner-Wintersteiner rosettes and Homer Wright rosettes?
-What is a fleurette?

Back 73

-Flexner-Wintersteiner rosette: characteristic of RB (doesn't occur in other neuroblastic tumors); central lumen lined by refractile structure (corresponds to retinal ELM); cells are columnar with eosinophilic cytoplasm and peripheral nuclei
-Homer Wright rosette: can be seen in other neuroblastic tumors, lumen filled with tangle of eosinophilic cytoplasmic processes
-Fleurette: curvilinear clusters of cells made up of rod/cone inner segments, exhibit greater differentiation than Flexner-Wintersteiner rosette

Front 74

RETINA/RPE: Other retina, tumors
-what is the histological appearance of a retinocytoma?
-what are some features that distinguish retinocytoma and RB?

Back 74

-histo: numerous fleurettes + cells with photoreceptor differentiation
-retinocytoma: no mitoses, cells with more cytoplasm and more evenly dispersed nuclear chromatin, no necrosis

Front 75

RETINA/RPE: Other retinal tumors
-What is the most common secondary malignancy in genetic retinoblastoma?
-What is the cell of origin of a medulloepithelioma?
-What is the histologic appearance of medulloepithelioma?

Back 75

-Most common secondary malignancy: Osteosarcoma (inc risk with ext beam radiation)
-Medulloepithelioma: originates from primary medullary epithelium, found in ciliary body (lightly/non-pigmented cystic mass)
-Histo: ribbon-like organization of cells that are round-oval with little cytoplasm (similar morphology as CB epithelium); Homer Wright rosettes, may see heteroplastic tissues (cartilage, smooth muscle --> teratoid medulloepithelioma)

Front 76

RETINA/RPE: Other retinal tumors
-Fuchs adenoma: location, acquired vs congenital, histology

Back 76

-Fuchs adenoma: acquired tumor of nonpigmented CB epithelium, assoc with sectoral cataract
-Histo: hyperplastic, nonpigmented ciliary epithelium in sheets/tubules

Front 77

RETINA/RPE: Other retinal tumors
-What is the clinical appearance of a combined hamartoma of the retina/RPE?

Back 77

-Combined hamartoma: slightly elevated, variably pigmented mass of RPE, peripapillary retina, optic nerve and overlying vitreous
-increased vascularity of affected area

Front 78

UVEAL TRACT: Anatomy
-From which embryonic tissues is the uveal tract derived?
-What are the 3 points of firmest attachment between the uveal tract and sclera?

Back 78

-Derived from mesoderm and neural crest
-3 points of firmest attachment: scleral spur, exit points of vortex veins, optic nerve

Front 79

UVEAL TRACT: Anatomy
-What cells compose the iris stroma?
-Describe the arrangement of the posterior iris epithelium

Back 79

-Iris stroma: blood vessels, nerves, melanocytes, clump cells
-Clump cells type I (clump cells of Koganei): macrophages containing phagocytosed pigment
-Clump cells type II: smooth muscle cell variants
-Posterior iris has anterior and posterior pigment epithelium (double layer, arranged in apex-to-apex configuration)

Front 80

UVEAL TRACT: Anatomy
-What are the boundaries of the CB and what are it's two areas called?
-Describe the anatomy of the CB

Back 80

-CB extends from base of iris to ora serrata (where it becomes continuous with choroid)
-2 areas: pars plicata (contains ciliary processes), pars plana
-Structure: double epithelium (inner nonpigmented layer, outer pigmented layer), processes attach to zonular fibers, 3 types of muscle fibers (longitudinal - Brucke, radial, circular inner muscle - Muller)

Front 81

UVEAL TRACT: Anatomy
-What are the boundaries of the choroid?
-What are the 3 principal layers of the choroid?

Back 81

-Choroid extends from ora serrata anteriorly to optic nerve posterioly
-3 layers: lamina fusca (suprachoroid), stroma, choriocapillaris (provides nutrients for RPE/outer retina)

Front 82

UVEAL TRACT: Congenital anomalies
-What is aniridia and what other ocular abnormalities is it associated with?
-What other systemic abnormality is aniridia associated with and what are the genetics of this syndrome?

Back 82

-Aniridia = absence of iris (usually incomplete and bilateral)
-Associated with incomplete formation of angle and PAS with overgrowth of corneal endothelium
-Associated with Wilm's tumor (WAGR): 11p13 deletion and PAX6 gene mutations

Front 83

UVEAL TRACT: Inflammations
-Describe the pattern of inflammation and areas of involvement of sympathetic ophthalmia?
-What are mutton-fat KPs and Dalen Fuch's nodules composed of?
-What is the proposed pathogenesis of SO?

Back 83

-SO: bilateral, granulomatous, panuveitis
-4-8 weeks latency most common
-Choriocapillaris is spared
-Mutton-fat KPs: collections of histiocytes on K epithelium
-Dalen Fuch's nodules: collections of epitheliod histiocytes and lymphocytes between RPE and Bruch's
-Pathogenesis: hypersensitivity to melanin pigment, retinal S-antigen or other retinal/uveal proteins --> penetrating eye injury allows these antigens to gain access to lymphatics --> sensitization occurs

Front 84

UVEAL TRACT: Inflammations
-What is the epidemiology of VKH syndrome?
-What are systemic manifestations?
-What is the pattern of inflammation and areas of involvement in VKH?
-What is the most common genetic association?

Back 84

VKH
-Epidemiology: Asians, Native Americans; 30-50 yo
-Systemic findings: alopecia, vitiligo, poliosis (loss of pigmentation of brows/lashes), dysacusis, HA, seizues
-Granulomatous diffuse inflammation, entire choroid involved (no sparing of choriocapillaris), can also involve retina
-HLA-DR4

Front 85

UVEAL TRACT: Inflammations
-What is the composition of inflammatory nodules in sarcoidosis?
-Distinguish between Koeppe and Busacca nodules
-What are candlewax drippings?
-What are asteroid bodies and Schaumann bodies?

Back 85

Sacroidosis
-Inflammatory nodules composed of epithelioid histiocytes and lymphocytes, noncaseating
-Iris nodules: Koeppe nodules are at pupillary margin, Busacca nodules are elsewhere on iris
-Candlewax drippings: appearance of periphlebitis exudates in Sarcoidosis
-Giant cells may contain asteroid bodies (star-shaped, acidophilic) or Schaumann bodies (spherical, basophilic, calcified)

Front 86

UVEAL TRACT: Degenerations
-Where does rubeosis iridis most commonly occur?
-What is ectropion uveae?
-Describe the non-progressive form of rubeosis and it's systemic associations

Back 86

-Rubeosis most commonly occurs at anterior surface of iris
-If occurs on posterior surface, can lead to ectropion uveae (dragging of posterior iris pigment epithelium anterior to level of sphincter muscle)
-Nonprogressive form of rubeosis: small neovascular tufts at pupillary margin --> seen in DM and myotonic dystrophy

Front 87

UVEAL TRACT: Degenerations
-What is hyalinization of the ciliary body?
-What is it's clinical significance?

Back 87

-Hyalinization = thin, delicate ciliary processes become blunted and attenuated with time, stroma more eosinophilic
-Normal aging change, functionally associated with presbyopia

Front 88

UVEAL TRACT: Iris nevus
-What anatomical changes can be associated with an iris nevus?
-What is one systemic disease associated with iris nevi?
-What is the histologic pattern of an iris nevus?

Back 88

Iris nevus
-May be associated with distortion of pupil or sectoral cataract
-Neurofibromatosis = increased incidence of nevi
-Histo: accumulations of branching dendritic cells or collections of bland-looking spindle cells (no cellular atypia or mitoses)

Front 89

UVEAL TRACT: Iris Melanoma
-What is the general clinical course of iris melanomas compared to posterior melanomas?
-What is the epidemiology of iris melanoma?
-What is one case in which iris melanomas behave more aggressively?

Back 89

Iris melanomas
-non-aggressive clinical course
-may cause spontaneous hyphema
-Average age of presentation is 10-20 yrs younger than pts with choroidal melanoma
-Rarely metastasize, except when diffusely involves iris stroma --> can extend into angle and CB (ring melanoma forms)

Front 90

UVEAL TRACT: Melanocytoma (magnocellular nevus)
-Describe the typical clinical appearance of melanocytoma
-Describe the histology

Back 90

-Clinical appearance: jet black lesions in peripapillary region
-Histo: plump polyhedral cells with small nuclei, abundant cytoplasm, heavy pigmetnation
-cystic degeneration/necrosis possible

Front 91

UVEAL TRACT: Melanoma
-What is the most common intraocular malignancy in adults?
-What are some clinical signs of a CB melanoma?
-What is a ring melanoma?

Back 91

-Choroidal melanoma = most common intraocular malignancy in adults
-Clinical signs of CB melanoma: sectoral cataract, peripheral iris mass, epibulbar mass, lens displacement
-Ring melanoma: circumferential growth of tumor to involve entire CB

Front 92

UVEAL TRACT: Melanoma
-What is the clinical appearance of a choroidal melanoma?
-What are the 2 most important variables associated with survival in choroidal melanoma?

Back 92

-Clinical: brown, elevated, dome-shaped subretinal mass, variable pigmentation, clumps of overlying lipofuscin at RPE (orange pigment), localized serous RD
-Looks like mushroom-shaped mass as it breaks through Bruch's
-2 important variables assoc with survival: size of largest tumor dimension in contact with sclera & cell type of tumor

Front 93

UVEAL TRACT: Melanoma
-What is the modified Callender classification of uveal melanoma and which has the best/worst prognosis?

Back 93

-Callender classification: spindle cell nevus (only Spindle A cells), spindle cell melanoma (both Spindle A & B cells), epithelioid melanoma, mixed-cell type (both spindle and epithelioid cells)
-Best prognosis: spindle cell
-Worst prognosis: epithelioid cell

Front 94

UVEAL TRACT: Melanoma
-Describe the histologic appearance of Spindle A, Spindle B and Epithelioid cells

Back 94

-Spindle A: low nuclear:cytoplasm ratio, no mitoses, central stripe may be visible down long axis of nucleus
-Spindle B: higher n:c ratio, coarse granular chromatin, larger nuceli, mitoses present
-Epitheloid cells: abundant eosinophilic cytoplasm, enlarged oval/polygonal nuclei, marked pleuomorphism including multinucleated tumor giant cells

Front 95

UVEAL TRACT: Melanoma
-What is the pathophysiology of melanomalytic glaucoma?

Back 95

-Melanomalytic glaucoma: tumor necrosis --> liberation of melanin pigment --> trapped in AC angle --> secondary glaucoma
(note: direct tumor invasion can also lead to secondary glaucoma)

Front 96

UVEAL TRACT: Melanoma
-How does melanoma metastasize and where does it most often go?

Back 96

-Hematogenous metastasis
-Most common location: liver (more than 95% of tumor related deaths have liver involvement, 1/3 of these have liver as sole site of metastasis)

Front 97

UVEAL TRACT: Metastatic tumors
-What is the epidemiology of metastatic tumors and what are the most common primary malignancies?
-What is the clinical appearance of mets?

Back 97

-Metastatic tumors are THE MOST COMMON INTRAOCULAR TUMOR IN ADULTS
-Most common primaries: breast (females) and lung (males)
-Clinical: multiple, bilateral tumors with flattened growth pattern
-Other primary tumors: cutaneous melanoma, prostate ca, renal cell ca, carcinoid

Front 98

UVEAL TRACT: Hemangioma
-What are the differences between localized and diffuse choroidal hemangiomas?
-What is the most common complication of a choroidal hemangioma and what is the typical treatment?

Back 98

Choroidal Hemangioma:
-Localized: no systemic disease association, red-orange tumor in postequatorial fundus, may affect overlying RPE and cause cystoid degen of outer retina
-Diffuse: associated with Sturge-Weber syndrome, diffuse reddish hue to entire fundus (tomato catstup fundus) --> spectrum of disease ranges from predominantly capillary --> cavernous --> mixed)
-Most common complication: serous RD --> treat with laser demarcation (argon)

Front 99

LIDS: Anatomy
-What are the 4 main histologic layers of the eyelid at the level of the tarsus?
-What type of epithelium does eyelid skin have?
-What are the structues present in the eyelid dermis?

Back 99

-4 histologic layers: skin, orbicularis oculi, tarsus, palpebral conjunctiva
-eyelid epithelium: keratinizing stratified squamous
-eyelid dermis: cilia and assoc sebaceous glands (Zeis), apocrine sweat glands (Moll), eccrine sweat glands, pilosebaceous units

Front 100

LIDS: Anatomy
-What is the function of the conjunctival goblet cells?
-What is the function of the accessory lacrimal glands of Krause and Wolfring? Where are these located?
-What is the function of the Meibomian glands? Where are these located?

Back 100

-Goblet cells: mucin secretion, enhances K wetting
-Krause/Wolfring glands: secrete aqueous layer of tear film (Krause: conj fornices, Wolfring: superior tarsal plate)
-Meibomian glands: secrete lipid layer of tear film to retard evaporation; located in tarsus

Front 101

LIDS: Anatomy
Define the following terms:
-acanthosis
-hyperkeratosis
-parakeratosis

Back 101

-acanthosis: inc thickness of stratum malpighii of epidermis
-hyperkeratosis: inc thickness of stratum corneum
-parakeratosis: retention of nuclei within stratum corneum, absence of stratum granulosum

Front 102

LIDS: Anatomy
Define the following terms:
-papillomatosis
-dyskeratosis
-acantholysis
-spongiosis

Back 102

-papillomatosis: finger-like upward projections of epidermis
-dyskeratosis: premature individual cell keratinization within stratum malpighii (lower layers of epidermis)
-acantholysis: loss of cohesion b/w adjacent epithelial cells
-spongiosis: widening of intercellular spaces between cells 2/2 edema

Front 103

LIDS: Congenital anomalies
-What is distichiasis and how is it inherited?
-What is another name for a phakomatous choristoma and what is it?

Back 103

-Distichiasis: aberrant formation of cilia within the tarsus --> exit eyelid margin through meibomian gland orifices; autosomal dominant
-Phakomatous choristoma: aka Zimmerman tumor, aberrant location of lens epithelium within inferonasal portion of lower eyelid

Front 104

LIDS: Inflammations
-What is the etiology of a papilloma and what is the histologic appearance?
-What patient population develops molluscum contagiosum and what is the clinica/histologic appearance?

Back 104

-Papilloma: HPV 6,11; pedunculated growths along lid margins
-Histology: acanthotic, hyperkeratotic epidermis lining papillary fibrovascular cores
-Molluscom: young/immunocompromised pts, dome-shaped, waxy nodule with central umbilication, secondary follicular conjunctivitis
-Histology: nodular epithelial proliferation move up along epithelium till they are extruded on skin surface, progress from eosinophilic --> basophilic as nodule moves up through epidermis

Front 105

LIDS: Inflammations
-What is the pathophysiology of a chalazion?
-What glands are most often involved?
-What type inflammatory reaction is present?
-What glands are typically involved in a hordeolum?

Back 105

-Chalazion: lipid secretions of meibomian glands (less often, glands of Zeis) discharged into surrounding tissues
-Lipogranulomatous reaction results (histiocytes, multinucleated plasma cells)
-Hordeolum: glands of Zeis > meibomian glands, focal inflammation with collections of PMNs and necrotic debris

Front 106

LIDS: Degenerations
Xanthelasma
-What is the clinical appearance?
-Epidemiology?
-Histologic appearance?

Back 106

Xanthelasma:
-soft yellow plaques on nasal aspect of upper & lower lids
-middle-aged or elderly F>M, may have assoc hyperlipidemia (30-40%)
-Histo: collections of histiocytes with foamy cytoplasm, cluster around vessels and adnexal dermal structures

Front 107

LIDS: Degenerations
Amyloid
-What does the term "amyloid" refer to?
-What is the protein configuration of amyloid deposits?
-Distinguish between the clinical significance of amyloid lesions of the eyelid vs elsewehre in the ocular adnexa
-What is the histologic appearance?
-What stains are useful for highlighting amyloid?

Back 107

-Amyloid = heterogenous group of extracellular proteins, exhibit dichroism and birefringence under polarized light with Congo red stain
-Beta-pleated sheet configuration
-Skin amyloid: suggests systemic disease process, multiple bilateral symmetric waxy yellow-white nodules, increased vascular fragility --> purpura
-Ocular adnexal amyloid: localized disease process
-Histo: amorphous, fibrogranular, eosinophilic extracellular deposit within vessel walls, around periph nerves/sweat glands
-Stains: Congo red, cystal violet, thioflavin T

Front 108

LIDS: Seborrheic keratosis
-What is the clinical appearance?
-What are histologic features? and what is one characteristic feature?
-What is the Leser-Trelat sign?

Back 108

Seborrheic keratosis
-oval, well circumscribed, "stuck-on" papule, may be dome-shaped or verrucoid
-Histo: acanthosis, hyperkeratosis, some papillomatosis, no dysplasia
-Pseudohorn cysts = characteristic finding: concentrically laminated collections of surface keratin within infoldings of epidermis
-Leser-Trelat sign: sudden onset multiple seborrheic keratoses --> may represent evolving acanthosis nigricans, assoc with malignancy (usu. GI adenocarcinoma)

Front 109

LIDS: Keratocanthoma
-What is the clinical appearance and pattern of progression?
-What is the histologic appearance?
-What is the diagnosis with which keratocanthoma is most often confused?

Back 109

Keratocanthoma
-Rapidly growing dome-shaped nodule with keratin-filled crater
-spontaneous involution over several months --> scar
-Histo: cup-shaped invagination of well-differentiated squamous cells forming irregular nests/strands, lymphocytes/plasma cell response
-May have mitotic activity/nuclear atypia at deep aspect of nodule
-Confused with squamous cell carcinoma --> excision needed

Front 110

LIDS: Actinic keratosis
-What is the clinical appearance?
-What type of cancer can develop?
-What are 5 characteristic histologic features?
-What are characteristic dermal changes?
-What is a histologic marker of UV-light induced damage?

Back 110

Actinic keratosis (solar keratosis)
-Erythematous, scaly macules/papules on sun-exposed skin, middle age pts
-Can give rise to squamous cell carcinoma
-5 histologic abnormalities: nuclear dysplasia/enlargement/hyperchromasia, nuclear membrane irregularity, increased N:C ratio
-Dermis shows solar elastosis (fragmentation, clumping, loss of eosinophils,chronic inflamamtory infiltrate)
-Histologic marker of UV-light induced damage: collagen of dermis appears blue instead of pink on H&E staining

Front 111

LIDS: Keratocanthoma
-What is the clinical appearance and pattern of progression?
-What is the histologic appearance?
-What is the diagnosis with which keratocanthoma is most often confused?

Back 111

Keratocanthoma
-Rapidly growing dome-shaped nodule with keratin-filled crater
-spontaneous involution over several months --> scar
-Histo: cup-shaped invagination of well-differentiated squamous cells forming irregular nests/strands, lymphocytes/plasma cell response
-May have mitotic activity/nuclear atypia at deep aspect of nodule
-Confused with squamous cell carcinoma --> excision needed

Front 112

LIDS: Squamous cell carcinoma
-What eye area is most frequently involved?
-What is the histologic appearance?

Back 112

Squamous cell carcinoma
-arises in sun-damaged skin, lower eyelid most common
-Histo: atypical squamous cells forming nests/strands, extend beyond epidermal basmenet membrane
-look for presence of intercellular bridges between tumor cells when diagnosis in question

Front 113

LIDS: Actinic keratosis
-What is the clinical appearance?
-What type of cancer can develop?
-What are 5 characteristic histologic features?
-What are characteristic dermal changes?
-What is a histologic marker of UV-light induced damage?

Back 113

Actinic keratosis (solar keratosis)
-Erythematous, scaly macules/papules on sun-exposed skin, middle age pts
-Can give rise to squamous cell carcinoma
-5 histologic abnormalities: nuclear dysplasia/enlargement/hyperchromasia, nuclear membrane irregularity, increased N:C ratio
-Dermis shows solar elastosis (fragmentation, clumping, loss of eosinophils,chronic inflamamtory infiltrate)
-Histologic marker of UV-light induced damage: collagen of dermis appears blue instead of pink on H&E staining

Front 114

LIDS: Basal cell carcinoma
-What percent of eyelid malignancies are accounted for by BCC?
-Where do lesions most commonly occur and where are lesions most likely to be invasive?
-What is the characteristic clinical appearance?
-What are histologic patterns of BCC?

Back 114

Basal cell carcinoma
-Accounts of 90% of all eyelid malignancies
-Lower eyelid most commonly involved
-Medial canthal tumors most likely to be deeply invasive,involve orbit
-Clinical: slowly enlarging ulcer with pearly/raised/rolled edges (exception: morpheaform looks like flat plaque)
-Growth patterns: nodular, multicentric, morpheaform
-Histo: bland, monomorphous nuclei with high N:C ratio, form cohesive nests with palisading of peripheral cell layer

Front 115

LIDS: Keratocanthoma
-What is the clinical appearance and pattern of progression?
-What is the histologic appearance?
-What is the diagnosis with which keratocanthoma is most often confused?

Back 115

Keratocanthoma
-Rapidly growing dome-shaped nodule with keratin-filled crater
-spontaneous involution over several months --> scar
-Histo: cup-shaped invagination of well-differentiated squamous cells forming irregular nests/strands, lymphocytes/plasma cell response
-May have mitotic activity/nuclear atypia at deep aspect of nodule
-Confused with squamous cell carcinoma --> excision needed

Front 116

LIDS: Squamous cell carcinoma
-What eye area is most frequently involved?
-What is the histologic appearance?

Back 116

Squamous cell carcinoma
-arises in sun-damaged skin, lower eyelid most common
-Histo: atypical squamous cells forming nests/strands, extend beyond epidermal basmenet membrane
-look for presence of intercellular bridges between tumor cells when diagnosis in question

Front 117

LIDS: Basal cell carcinoma
-What percent of eyelid malignancies are accounted for by BCC?
-Where do lesions most commonly occur and where are lesions most likely to be invasive?
-What is the characteristic clinical appearance?
-What are histologic patterns of BCC?

Back 117

Basal cell carcinoma
-Accounts of 90% of all eyelid malignancies
-Lower eyelid most commonly involved
-Medial canthal tumors most likely to be deeply invasive,involve orbit
-Clinical: slowly enlarging ulcer with pearly/raised/rolled edges (exception: morpheaform looks like flat plaque)
-Growth patterns: nodular, multicentric, morpheaform
-Histo: bland, monomorphous nuclei with high N:C ratio, form cohesive nests with palisading of peripheral cell layer

Front 118

LIDS: Actinic keratosis
-What is the clinical appearance?
-What type of cancer can develop?
-What are 5 characteristic histologic features?
-What are characteristic dermal changes?
-What is a histologic marker of UV-light induced damage?

Back 118

Actinic keratosis (solar keratosis)
-Erythematous, scaly macules/papules on sun-exposed skin, middle age pts
-Can give rise to squamous cell carcinoma
-5 histologic abnormalities: nuclear dysplasia/enlargement/hyperchromasia, nuclear membrane irregularity, increased N:C ratio
-Dermis shows solar elastosis (fragmentation, clumping, loss of eosinophils,chronic inflamamtory infiltrate)
-Histologic marker of UV-light induced damage: collagen of dermis appears blue instead of pink on H&E staining

Front 119

LIDS: Squamous cell carcinoma
-What eye area is most frequently involved?
-What is the histologic appearance?

Back 119

Squamous cell carcinoma
-arises in sun-damaged skin, lower eyelid most common
-Histo: atypical squamous cells forming nests/strands, extend beyond epidermal basmenet membrane
-look for presence of intercellular bridges between tumor cells when diagnosis in question

Front 120

LIDS: Basal cell carcinoma
-What percent of eyelid malignancies are accounted for by BCC?
-Where do lesions most commonly occur and where are lesions most likely to be invasive?
-What is the characteristic clinical appearance?
-What are histologic patterns of BCC?

Back 120

Basal cell carcinoma
-Accounts of 90% of all eyelid malignancies
-Lower eyelid most commonly involved
-Medial canthal tumors most likely to be deeply invasive,involve orbit
-Clinical: slowly enlarging ulcer with pearly/raised/rolled edges (exception: morpheaform looks like flat plaque)
-Growth patterns: nodular, multicentric, morpheaform
-Histo: bland, monomorphous nuclei with high N:C ratio, form cohesive nests with palisading of peripheral cell layer

Front 121

LIDS: Capillary hemangioma
-What is the clinical presentation?
-What is the clinical course?
-When should treatment be considered?
-What is the histologic appearance?

Back 121

Capillary hemangiomas
-Seen in children either at or shortly after birth
-red-purple nodule
-Course: spontaneous involution most common (by school age)
-Treatment considered when vision affected by proptosis or astigmatism --> amblyopia
-Histo: well-developed, flattened endothelium-lined capillary channels in lobular configuration

Front 122

LIDS: Sebaceous carcinoma
-Where does it most commonly arise?
-What does it mimic clinically?
-What is the histologic appearance and which stains are typically used?
-What is pagetoid spread?
-What is the prognosis and pattern of metastasis?

Back 122

Sebaceous carcinoma
-Elderly patients, upper eyelid
-Arises within tarsal meibomian glands, Zeis glands in skin or sebaceous gland of caruncle
-Mimics chalazion/chronic blepharitis
-Histo: tumors have microvesicular, foamy cytoplasm reflective of lipid within cytoplasm
-Special stains: Sudan black, oil red O (lipid stains)
-Pagetoid spread: dissemination of individual tumor cells/clusters of cells within epidermis or conj epithelium
-Prognosis: worse than for squamous cell ca; mets usually go to lymph nodes first

Front 123

LIDS: Melanocytic lesions
-What are clinical characteristics of congenital nevi?

Back 123

Congenital nevi:
-usually larger than nevi that appear in childhood
-Giant congenital nevus: up to 20 cm diameter
-risk of melanoma development is proportional to nevus size
-congen nevi usually have nevus cells within/around adnexal structures, vessel walls, perineurium

Front 124

LIDS: Melanocytic lesions
-Distinguish between junctional, compound and intradermal nevi
-What is the morphology of nevus cells within the superficial, mid-portion and deepest level of the nevus?

Back 124

-Junctional nevi: nests (theques) of melanocytes along dermal-epidermal junction
-Compound nevi: theques begin to migrate into superficial dermis (both junctional and intradermal components present); nevus looks dome-shaped or papillomatous
-Intradermal nevi: junctional component disappears
-Superficial nevus cells: polygonal, epitheliod cells (type A)
-Midportion of nevus: smaller cells with less cytoplasm (resemble lymphocytes) (type B)
-Deeper nevus cells: spindled appearance, look like Schwann cells of peripheral nerves (type C)

Front 125

LIDS: Melanocytic lesions
-What are 4 histological characteristics favoring a benign lesion?
-What is a Spitz nevus and what is the histologic appearance?

Back 125

-Benign characteristics: no intraepidermal migration of cells, no mitotic activity within dermal component, no nuclear enlargement/prominent nucleoli, melanin content of cells greatest in superficial layers and absent in deeper layers
-Spitz nevus: late childhood, pink-red color, can be up to 1 cm
-Histo: compound nevus, nuclear & cytoplasmic enlargement w/ pleomorphism

Front 126

LIDS: Melanocytic lesions
-What are clinical, architectural and cytologic features of dysplastic nevi?

Back 126

Dysplastic nevi:
-Clinically, >0.5 cm size, irregular margins and pigmentation pattern
-Histo: lentiginous (single-cell) melanocytic hyperplasia
-Cytology: atypical cells (enlarged nucleus, mitotic figures, hyperchromasia)
-Multiple dysplastic nevi: risk of melanoma, may indicate possible genetic susceptibility

Front 127

LIDS: Melanocytic lesions
-What are the most common types of cutaneous melanoma and which of these does not involve the eyelids?
-What are histologic features of melanoma?
-Where does metastasis typically occur?

Back 127

-Superficial spreading melanoma = most common type, radial growth pattern
-Lentigo maligna: long pre-invasive face, occurs on face of elderly pts
-Acral-lentiginous: does not occur on eyelid (extremities only)
-Histo: pagetoid intraepidermal spread, nuclear abnormalities, no maturation of deeper portions, atypical mitoses, lymphocytic host response
-Mets usually go to regional lymph nodes first

Front 128

ORBIT: Anatomy
-What 7 bones make up the boundary of the orbit?
-What is the volume of the orbit?
-What divides the two lobes of the lacrimal gland?
-What is the histologic structure of the acini and the ducts of the lacrimal gland?

Back 128

-7 bones that make up the orbit: frontal, zygoma, maxillary, ethmoid, lacrimal, sphenoid, palatine
-volume: 30 cc
-Lacrimal gland divided into orbital and palpebral lobes by aponeurosis of levator palpebrae superioris
-Acini: low cuboidal epithelium
-Ducts: low cuboidal epithelium and second outer layer of flat myoepithelial cells

Front 129

ORBIT: Congenital anomalies
-What is the pathophysiology and typical location of dermoid cysts?
-What reaction is caused by rupture of a dermoid cyst?
-What is the histologic appearance of a dermoid?

Back 129

Dermoid cysts
-Arise from embryonic epithelial nests that become trapped during embryogenesis
-Superotemporal mass
-Rupture leads to granulomatous reaction
-Histo: encapsulated, lined by keratinzed stratified squamous epithelium, contains hair/keratin and adnexal structures (if no adnexal structures, called an epidermal cyst)

Front 130

ORBIT: Inflammations
-What is the typical patient population of mucormycosis and how is diagnosis confirmed?
-Histologic appearance of mucor?

Back 130

Mucormycosis:
-Poorly controlled diabetics or immunosuppressed pts
-Dx: biopsy of necrotic appearing tissues in nasopharynx
-Histo: acute & chronic inflammation and necrosis, GMS and PAS stain with nonseptate hyphae
-Thrombosing vasculitis can be seen if fungi invade vessel walls

Front 131

ORBIT: Inflammations
-What is the epidemiology and course of orbital aspergillus infection?
-What is the branching pattern of hyphae?

Back 131

Aspergillus
-Immunocompromised OR otherwise healthy
-Slowly progressive and insidious course
-Sclerosing granulomatous disease
-Septate hyphae with 45 deg angle branching

Front 132

ORBIT: Inflammations
-What is the most common cause of unilateral or bilateral exophthalmos in adults?
-What is the histologic appearance?
-What is the pattern of muscle involvement?

Back 132

Thyroid-associated orbitopathy
-Most common cause of unilateral or bilateral exophthalmos in adults
-Histo: mononuclear cells, lymphocytes, plasma cells, mast cells and fibroblasts in EOM (inferior and medial rectus most common)
-Inflammation spares tendons, cause fusiform enlargement of muscle
-Progressive fibrosis --> restriction of EOM

Front 133

ORBIT: Inflammations
-What is the clinical course of orbital inflammatory syndrome?
-What percentage of orbital lesions is accounted for by this diagnosis?
-What is orbital myositis?
-What is the histology for early and later stage lesions?
-Treatment?

Back 133

Orbital inflammatory syndrome
-Abrupt course, painful, children OR adults
-Accounts for 5% of orbital lesions
-Orbital myositis: localized to extraocular muscle
-Early histo: polymorphous inflammation, perivascular, infiltrates muscle and causes fat necrosis
-Later histo: fibrous reaction predominates with lymphoid follicles bearing germinal centers
-Inflammation does not spare muscle tendons (unlike Graves')
-Early inflammation responds to steroids

Front 134

ORBIT: Neoplasia
-What are the two most common primary orbital neoplasms?
-What is the most common origin of secondary orbital tumors?
-What are the most common benign and malignant orbital tumors in children?
-What percent of orbital tumors in children are benign?

Back 134

-2 most common primary orbital neoplasms: hemangioma, lymphoma
-Secondary tumors are usually extensions from adjacent sinus tumors
-90% of pediatric orbital tumors are benign (cystic)
-most common malignant pediatric orbital tumor: rhabdomyosarcoma

Front 135

ORBIT: Neoplasia
-What is the most common epithelial tumor of the lacrimal gland?
-What is cortication?
-Is the tumor encapsulated and is there erosion of adjacent bone?
-What is the epidemiology?

Back 135

Pleomorphic adenoma
-Most common epithelial lacrimal gland tumor
-M>F, 35 yo
-Painless
-Cortication: tumor growth stimulates adjacent bone periosteum to deposit thin layer of new bone
-No erosion of adjacent bone
-Tumor is initially encapsulated

Front 136

ORBIT: Neoplasia
-What is the histologic appearance of pleomorphic adenoma of the lacrimal gland?
-Does the capsule function as an anatomic barrier separating the tumor from the other orbital contents?
-What are 2 important surgical principles of excision?
-Is there risk of malignant transformation in this tumor?

Back 136

Pleomorphic adenoma
-Histo: mixture of epithelial and stromal elements, nests/tubules lined by 2 layers of cells, stroma contains heterogenous structures (cartilage, bone)
-Capsule is not an anatomic barrier --> microscopic tumor lobules can prolapse through the capusle
-Surgical principles: 1) excise tumor with thin rim of normal orbital tissue to avoid recurrence, 2) avoid incisional biopsies (prevent seeding)
-There is risk of malignant transformation to carcinoma

Front 137

ORBIT: Neoplasia
-What is the epidemiology of adenoid cystic carcinoma of the lacrimal gland?
-Is the tumor encapsulated?
-What is the clinical appearance and presentation?
-What is the histologic appearance?
-What pattern is associated with the worst prognosis?
-What is the general long term prognosis?

Back 137

Adenoid cystic carcinoma of lacrimal gland
-F>M, 40 yo
-Not encapsulated --> tends to erode through bone and invade orbit
-Painful orbital mass (erodes through orbital nerves), looks like grayish white firm nodule
-Histo: Swiss cheese (cribiform) pattern is common
-Basaloid pattern associated with worst prognosis
-Exenteration recommended, poor long term prognosis

Front 138

ORBIT: Neoplasia
-What is the incidence of orbital involvement in systemic lymphomas?
-What type of lymphoma makes up the majority of primary malignant orbital lymphomas?
-What is the most common LOW grade orbital lymphoma?
-What is the immunophenotype of low grade lymphomas?

Back 138

Orbital lymphoma
-1.3% incidence of orbital involvement with systemic lymphoma
-Most primary malignant orbital lymphomas: Non-Hodgkins B cell
-Most common low grade orbital lymphoma: MALT --> B cell phenotype, CD5 and CD10 negative

Front 139

ORBIT: Neoplasia
-What are the most common high grade orbital lymphomas?
-What type of orbital lesion is most likely to be associated with systemic involvement?
-What is the clinical presentation of orbital lymphoma?
-How is orbital lymphoma treated?

Back 139

Orbital lymphoma
-Most common high grade lymphomas: large cell, lymphoblastic, Burkitt's
-Eyelid lesions have 67% rate of systemic involvement (highest)
-Clinical presentation: gradual, painless proptosis
-Must investigate all lesions for systemic involvement: CBC, lymph node exam, chest/abd imaging
-If confined to orbit --> radiation

Front 140

ORBIT: Neoplasia
-What is the typical presentation of a lymphangioma?
-What are differences between adult and pediatric hemangioma?
-What are features of hemangiopericytoma (pt population, presentation, histo)

Back 140

Lymphangioma: pediatric patients, p/w fluctuating proptosis, unencapsulated and diffusely infiltrating tumors
Adult hemangioma: encapsulated, cavernous spaces (cavernous hemangioma)
Pediatric hemangioma: unencapsulated, capillary sized vessels (capillary hemangioma)
Hemangioperictyoma: adults, p/w painless proptosis/diplopia/dec vision, staghorn/branching vascular pattern, reticulun stain for tumor cells wrapped in collagenous material

Front 141

ORBIT: Neoplasia
-What is the most common primary malignant orbital tumor of childhood?
-What is the clinical presentation?
-What are 3 histologic tumor types and which is most common?
-What are 2 immunohistochemical stains?

Back 141

Rhabdomyosarcoma
-Clinical: rapidly progressive, age 7-8 avg onset, reddish discoloration of lids but no local warmth or systemic fever like cellulitis
-3 histologic types: embryonal (most common), alveolar, differentiated (pleomorphic)
-Immunohistochemical stains: desmin, muscle-specific actin

Front 142

ORBIT: Neoplasia
-What is the clinical presentation of a fibrous histiocytoma?

Back 142

Fibrous histiocytoma (fibroxanthoma)
-Most common mesenchymal tumor of orbits in adults
-Avg age 43, upper nasal orbit, benign

Front 143

ORBIT: Neoplasia
-What is the most common type of nerve sheath tumor?
-What is the histology?
-What disease is the plexiform type of this tumor associated with?

Back 143

Neurofibroma
-Most common nerve sheath tumor
-Histo: spindle-shaped cels arranged in cords/ribbons in matrix of myxoid tissue and collagen, also contains axons
-Plexiform neurofibroma is assoc with NF 1

Front 144

ORBIT: Neoplasia
-From what cells does a neurilemoma arise?
-What are the two histologic patterns?

Back 144

Neurilemoma
-Arises from Schwann cells
-May be associated with neurofibromatosis
-Antoni A spindle cells: interlacing cords, whorls, palisades; may form Verocay bodies
-Antoni B: stellate cells with mucoid stroma

Front 145

OPTIC N: Anatomy
-from which embryonic structure is the optic nerve derived?
- what is the full length of the nerve and how long are the intraocular, intracanalicular and the intraorbital portions?
-what is the diameter of the nerve?

Back 145

-derived from optic stalk embrologically
-length: 35-55mm (intraocular 0.7-1mm, intracanalicular 4-10mm, intraorbital 25-30mm)
-diameter: 3-3.5mm (tapers to 1.5 mm In scleral canal

Front 146

OPTIC N: Anatomy
-Which artery supplies the intraorbital and intraocular portions of the nerve?
-Which fibers are supplied by the CRA?
-Which meningeal layers is continuous with the sclera?

Back 146

-Ophthalmic artery supplies optic nerve (intraorbital, intraocular)
-Axial fibers are supplied by CRA
-Dura is continuous with sclera

Front 147

OPTIC N: Congenital anomalies
-What causes an optic pit, where is it usually seen and what other conditions is it associated with in the eye?
-What causes a coloboma and where is it typically located?

Back 147

OPTIC PIT: Defect in closure of fetal fissure
-located temporally on nerve head
-assoc with VF defects, serous RD, coloboma in fellow eye
COLOBOMA: failure of closure of fetal fissure
-located inferiorly to the nerve head

Front 148

OPTIC N: Inflammations
-What is the pathophysiology of optic nerve damage 2/2 multiple sclerosis and acute disseminated myelitis?
-What is the pathophysiology of GCA-mediated optic nerve injury? Sarcoid?

Back 148

-MS and acute disseminated myelitis produce loss of myelin --> damaged myelin removed my macrophages --> astroctes produce glial scar (plaque)
-GCA: granulomatous mural inflammation, occlusion of posterior ciliary vessels, liquefactive necrosis of optic n.
-Sarcoid: optic nerve lesions may feature caseating granulomas (elsewhere only noncaseating granulomas are seen)

Front 149

OPTIC N: Degenerations
-Distinguish between ascending and descending optic atrophy
-What is "cavernous optic atrophy of Schnabel"?

Back 149

Optic atrophy:
-ascending: loss of retinal ganglion cells (glaucoma, infarction) --> axons degenerate
-descending: pathology within cranial cavity --> axonal degeneration, loss of myelin and oligodendocytes
-Cavernous optic atrophy of Schnabel: large cystic spaces with mucopolysaccharide material (stains with alcian blue) post to lamina cribosa
-most common causes of cavernous optic atrophy: acute IOP inc in glaucoma, elderly pts with atherosclerotic disease

Front 150

OPTIC N: Degenerations
-What are disc drusen and how do they form (on a cellular level)?
-What are complications of disc drusen?
-What can disc drusen be mistaken for on exam?
-What conditions are giant drusen associated with?
-What are ways to diagnose disc drusen clinically?

Back 150

Disc drusen
-Hyaline-like calcified material in disc substance, tends to be bilateral
-Thought to be 2/2 intracellular mitochondrial calcification within axons
-Complications: VF defects, neovascularization, hemorrhage
-DDx: papilledema (pseudopapilledema)
-Giant drusen: assoc with phakomatoses (tuberous sclerosis, NF)
-Diagnosis: B-scan, fundus photography with autofluorescence

Front 151

OPTIC N: Neoplasia
-What is the clinical appearance of a melanocytoma?
-What is the histologic appearance?

Back 151

Melanocytoma
-Benign, deeply pigmented melanocytic tumor
-Eccentrically located on disc, projects <2mm into vitreous
-Can extend to lower temporal retina and posteriorly beyond lamina cribosa
-Histo: plump uniform cells with abundant cytoplasm, small regular nuclei and nucleoli, ++pigmentation

Front 152

OPTIC N: Neoplasia
-What is the most common cell of origin in glioma?
-What is the most common systemic association?
-What are Rosenthal fibers?
-What are some of the changes in the meninges in a glioma?
-Are high grade gliomas common in the optic nerve?

Back 152

Glioma
-Most common cell of origin: spindle-shaped/hairlike (pilocytic) astrocytoma
-Assoc with NF1 (ch17q11)
-Rosenthal fibers: enlarged, deeply eosinophilic filaments (degenerating cell processes)
-Meninges: show reactive hyperplasia, dura is intact so nerve appears tubular/sausage shaped
-High grade tumors (i.e. glioblastoma multiforme) rarely primarily involve optic n.

Front 153

OPTIC N: Neoplasia
-Compare primary vs secondary optic n meningiomas: which is more common, what is the area of origin for each, which one has better prognosis?
-What is the histologic appearance?
-What systemic disease can meningioma rarely be associated with?

Back 153

Meningioma
-Primary: less common, originate from arachnoid of optic n., longer survival
-Secondary: more common, extends from intracranial primary site into orbit and optic n., shorter survival
-Micro: plump cells arranged in whorls
-Rarely assoc with NF1 (less common than glioma)

Front 154

PIGM TUMORS: Nevi
-What 2 clinical findings can an iris nevus be assoc with?
-What is the clinical appearance of a choroidal nevus?

Back 154

Iris nevus: can be assoc with slight ectropion iridis and sectoral cataract (look at angle to r/o CB melanoma)
-Choroidal nevus: flat/min elevated, pigmented, indistinct margins
**may see overlying serous RD, RPE disturbances, drusen, CNV or orange pigment

Front 155

PIGM TUMORS: Nevi
-What tumor thickness and diameter is suggestive of melanoma? of nevus?
-What are clinical risk factors for enlargement of melanocytic lesions of the choroid?

Back 155

Choroidal nevus:
-If > 3 mm thickness and/or > 10 mm basal diameter --> almost always malignant
-If < 1 mm thickness and/or < 10 mm diamter --> almost always benign
-Risk factors for enlargement: visual symptoms, orange pigmentation, SRF, juxtapapillary location, no drusen/RPE changes, homogenous on U/S, hot spots on IVFA, larger size at presentation

Front 156

PIGM TUMORS: Iris melanoma
-What percentage of all uveal melanomas are iris melanomas?
-What are signs suggestive of malignancy?
-What is the mortality rate for iris melanomas?

Back 156

Iris melanoma
-3-10% of all uveal melanomas
-Signs of malignancy: extensive ectropion iridis, prominent vessels, sectoral cataract, secondary glaucoma, seeding of angle, extrascleral extension, progressive growth
-Prognosis: 1-4% mortality rate (better than for CB/choroidal melanomas)

Front 157

PIGM TUMORS: CB/Choroidal melanomas
-What are risk factors for these melanomas?
-What are clinical signs of a CB melanoma?

Back 157

CB/Choroidal melanomas
-Risk factors: light pigmentation, 50-60s, genetic predisposition (dysplastic nevus syndrome), smoking, melanosis oculi or oculodermal melanocytosis
-Signs of CB melanoma: dilated episcleral sentinel vessels, sectoral/diffuse cataract, lens subluxation, secondary glaucoma, RD, NVI

Front 158

PIGM TUMORS: CB/Choroidal melanomas
-What is a ring melanoma?
-What are clinical features of a choroidal melanoma?

Back 158

CB/Choroidal melanomas
-Ring melanoma: diffuse growth pattern, extends 180-360 around CB
-Choroidal melanoma: pigmented, elevated, dome-shaped mass, looks like mushroom when erupts through Bruch's, can lead to exudative RD or secondary angle closure

Front 159

PIGM TUMORS: CB/Choroidal melanoma
-What study is the most useful ancillary study for evaluating CB/choroidal tumors?
-What is the ancillary test of choice to detect orbital extension assoc with intraocular malignancy?
-What is the typical A-scan pattern for choroidal melanoma?
-What IVFA patterns are helpful for dx of choroidal melanoma?

Back 159

-Ultrasound: most impt ancillary study for eval of CB/choroidal melanomas & for detection of orbital extension of tumor
-A scan: solid tumor pattern with high amplitude initial echoes and low amplitude internal reflections (low internal reflectivity) --> better for differentiating between tumor types than B-scan
-No IVFA pattern is pathognomonic for choroidal melanoma

Front 160

PIGM TUMORS: CB/Choroidal melanoma
-How can ARMD be distinguished from choroidal melanoma?

Back 160

ARMD vs choroidal melanoma
-ARMD: commonly see hemorrhages, IVFA pathognomonic (early blockage from hemorrhage, late hyperfluorescence in CNV distribution)
-Melanoma does not have hemorrhage unless tumor extends thru Bruch's

Front 161

PIGM TUMORS: CB/Choroidal melanoma
-What is the clinical appearance and significance of CHRPE?
-Histology of CHRPE?

Back 161

CHRPE
-Well-defined, flat, dark pigmentated lesion of variable size
-Pts usually young (teens-20s)
-Older pts: focal areas of depigmentation (lacunae) may form within lesion
-Histo: tall, melanin-containing pigment epithelial cells with large speherical pigment granules
-If pt with CHRPE has family member with Gardener syndrome --> risk of colon cancer

Front 162

PIGM TUMORS: Mgmt
-What is the predominant organ involved in metastatic uveal melanoma?
-Which is the first organ typically involved in metastasis?
-What other areas are more frequently involved in mets?
-What 3 tests make up the metastatic evaluation?
-What 3 tests should be done if any of the first 3 tests are abnormal?

Back 162

Metastatic uveal melanoma
-Liver: predominant site of metastasis and usually first site of metastasis
-Other organs: liver (89%), lung (24%), bone (17%), subcut tissue (12%)
-Metastatic workup: liver imaging (ultrasound), LFTs, CXR
-If any of the above abnormal: triphasic liver CT, CT-PET of chest/abd, MRI chest/abd

Front 163

PIGM TUMOR: Mgmt
-When is enucleation considered?
-How is brachytherapy delivered and what are the most commonly used isotypes?
-What are risks of regrowth and radiation complications with brachytherapy?

Back 163

-Enucleation: radioactive plaque applied to sclera in area overlying tumor site
-Most commonly used isotypes: iodine 125, ruthenium 106
-Regrowth: 4-5% of tumors
-Radiation complications: optic neuropathy, retinopathy --> occur in 50% of pts

Front 164

PIGM TUMORS: Mgmt
-What are advantages to using charged particle radiation?
-What radiation complications are associated with this technique?
-What is the utility of external beam radiation?

Back 164

Charged particle radiation
-more homogenous dose of radiation delivered to tumor compared to brachytherapy
-less lateral spread of radiation energy
-higher dose of radiation delivered to anterior segment --> increased complications such as glaucoma (10% of treated eyes)
-Ext beam radiation: not effective as single modality tx --> can use in conjunction with enucleation

Front 165

PIGM TUMORS: Mgmt
-What is the utility of photocoagulation, diathermy, chemotx and transpupillary thermotherapy in the mgmt of these tumors?
-What is the utility of exenteration?

Back 165

-Photocoagulation: can cause increased tumor growth (ruptures Bruch's) --> limited role
-TTT: can also be assoc with increased tumor recurrence but can be successful
-Diathermy: contraindicated --> scleral damage may provide route for extrascleral tumor extension
-Chemo: not effective for primary or met disease
-Exenteration: today, replaced by enculeation + limited tenonectomy + local radiotherapy

Front 166

PIGM TUMORS: Mgmt
-What is the 5 yr mortality rate for small, medium and large choroidal melanoma?
-What are clinical risk factors for mortality?
-What are histologic features assoc with greater risk of mortality?

Back 166

-5 yr mortality: 50% (large), 30% (medium), 12% (small)
-Clinical risk factors: anterior location, older age, regrowth or rapid dec in size after globe conserving tx, juxtapapillary location
-Histo: epithelioid cells, complex microvascular patterns, mean of 10 largest nuclei, tumor-infiltrating lymphocytes, monosomy 3, trisomy 8

Front 167

PIGM TUMORS: COMS
-Describe the purpose of the large melanoma COMS trial and major findings
-Describe the purpose of the medium melanoma trial and major findings
-Describe the major findings of the small melanoma trial

Back 167

Collaborative Ocular Melanoma Study (COMS)
-Large melanoma trial: compared enucleation alone vs enucleation preceded by ext beam radiation
-Findings: adjunct radiotherapy does NOT improve overall survival (primary enucleation alone is appropriate)
-Medium melanoma trial: compared standardized enucleation vs iodine 125 brachythearpy
-Findings: Similar rate of metastasis with both forms of therapy
-Secondary findings: 0.3% misdiagnosis in enucleated eyes
-Secondary findings re: brachytherapy: 10.3% local tumor recurrence at 5 yrs, 12.5% risk of enuc after brachytherapy at 5 yrs, 43% of pts had declined VA to 20/200 at 3 yrs
-Small melanoma trial: observational study, melanoma specific mortality was 1% at 5 yrs

Front 168

PIGM TUMORS: Adenomas
-What is the clinical appearance and prognosis of an RPE adenoma?
-What is the clinical and histologic appearance of a Fuch's adenoma?

Back 168

RPE Adenomas
-clinical: oval, deeply melanocytic lesions arising abruptly from RPE; rarely enlarge or become malignant
-Fuch's adenoma: incidental finding, glistening/white/irreg tumor arising from ciliary crest
-Histo: benign prolif of nonpigmented ciliary epithelium with accum BM-like material

Front 169

ANGIO TUMORS: Choroidal hemangioma
-Describe differences between diffuse & circumscribed choroidal hemangiomas (systemic associations, clinical appearance)
-What are the 4 considerations in the DDx of a circumscribed choroidal hemangioma?

Back 169

Choroidal hemangioma
-Circumscribed: no other systemic disorders, red/orange tumor in posterior pole near macula, can lead to secondary RD
-Diffuse: assoc with Sturge-Weber syndrome, diffuse reddish/orange thickening of entire fundus (tomato catsup fundus), assoc with RD/glaucoma
-DDx: choroidal osteoma, choroidal granuloma, choroidal metastasis, amelanotic choroidal melanoma

Front 170

ANGIO TUMORS: Choroidal hemangioma
-What is the IVFA pattern?
-What does A-scan show?
-What does B-scan show?

Back 170

Choroidal hemangioma
-IVFA: large choroidal vessels in prearterial/arterial phases with late staining of tumor and overlying retina --> not pathognomonic
-A-scan: high internal reflectivity (high amplitude initial echo and high amplitude broad internal echoes)
-B-scan: localized/diffuse thickening of choroid, prominient internal reflections (acoustic heterogeneity), no choroidal excavation or orbital shadowing

Front 171

ANGIO TUMORS: Choroidal hemangioma
-Is there any associated retinal damage typically?
-What is the most common complication?
-What are treatment options?

Back 171

Choroidal hemangioma
-Assoc with damage to overlying RPE and degeneration of outer retinal layers
-Most common complication: serous RD involving fovea
-Rx: Laser (may need repeated tx), PDT, brachytherapy, charged-particle radiation, external beam radiation also described

Front 172

ANGIO TUMORS: Retinal capillary angioma
-How is this condition inherited?
-What is the clinical appearance?
-What is the term for the solitary variant of disease and the term for the systemic variant?
-What other tumors is the systemic variant associated with?

Back 172

Retinal capillary hemangioma
-Autosomal dominant
-Clinical: Red/orange tumor, large caliber tortuous afferent/efferent vessels with assoc yellow-white retinal/subretinal exudate (often involves fovea)
-Can lead to exudative RD
-If solitary finding: von Hippel disease (familial in 20%, bilateral in 50%)
-If assoc with cerebral hemangioblastoma, von Hippel-Lindau syndrome: chromosome 3
-Other tumors in this syndrome: renal cell carcinoma, pheochromocytoma

Front 173

ANGIO TUMORS: Retinal capillary hemangioma
-What is the typical IVFA appearance?
-What are potential treatments and associated complications of treatment?

Back 173

Retinal capillary hemangioma
-IVFA: rapid AV transit, immediate filling of feeding arteriole, subsequent filling of small blood vessels of tumor, then drainage by dilated venule
-Can see massive fluorescein leakage of dye into tumor/vitreous
-Rx: photocoagulation, cryo --> can lead to vascular decompensation --> massive exudative RD

Front 174

ANGIO TUMORS: Retinal cavernous hemangioma
-What is the clinical appearance?
-What is the IVFA appearance?
(contrast with retinal capillary hemangiomas, Coats disease)

Back 174

Retinal cavernous hemangioma
-Clinical: cluster of grapes appearance, NO assoc exudates (unlike Coats, capillary hemangioma), may see small hemorrhages and areas of gliosis/fibrosis on surface
-IVFA: diagnostic; SLOW filling (unlike capillary hemangioma), pooling of fluorescein in upper part of vascular space while lower part filled with cellular elements, fluorescein remains in vascular space for extended period, NO leakage (unlike Coats, capillary hemangioma)

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ANGIO TUMORS: Retinal cavernous hemangioma
-What is the histologic appearance?
-What is Wyburn-Mason syndrome?

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Retinal cavernous hemangioma
-Histo: Dilated, thin walled vascular channels interconnected by small orifices
Wyburn Mason
-Retinal racemose hemangioma (artery-to-vein anastomosis, AVM) assoc with midbrain AVMs

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RETINOBLASTOMA: Overview
-How common is RB?
-What is the epidemiology?
-How frequently is it bilateral?

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RB
-Most common primary intraocular malignancy of childhood; second most common primary intraocular malignancy in all ages (first is uveal melanoma)
-Epi: M=F, 90% of pts <3 yo
-Mean age at dx: 4 months (known +FHx), 14 mo (bilateral), 24 mo (unilateral)
-30-40% of cases bilateral

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RETINOBLASTOMA: Genetics
-What gene is implicated and where is it located?
-What percent of pts have +FHx?
-What is the likelihood of a germline mutation in bilateral RB?
-In sporadic cases, what is the likelihood of unilateral disease with no germline mutation?
-What is the chance of having an affected child if pt has bilateral vs unilateral disease?

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RB Genetics
-RB1 gene on ch13q14
-Both copies need to be mutated to develop tumor
-6% of pts have +FHx (94% sporadic)
-98% with bilat disease have germline mutation
-60% of sporadic pts have unilat disease, no germline mutation (15% of these pts do have a germline mutation)
-45% risk of having affected child if pt is a bilateral RB survivor, 7% risk if unilateral RB survivor

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RETINOBLASTOMA: Diagnosis
-What are the most common presenting signs in the US?
-What is the clinical appearance?

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RB: Dx
-Presentation: leukocoria, strabismus, ocular inflammation
-Clinical: initially a translucent, gray-white intraretinal tumor, fed/drained by dilated tortuous retinal vessels; later shows foci of calcification, chalky white appearance, assoc serous RD
-Endophytic tumor: more likely to have vitreous seeding --> tumor implants throughout eye

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RETINOBLASTOMA: Dx
-What is diffuse infiltrating RB and what is the DDx?
-How does RB escape the eye?
-What is the preferred imaging modality?
-What is the DDx for leukocoria + RD?

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RB: Dx
-Diffuse infiltrating RB: rare variant, detected at older age, usually unilateral --> can be mistaken for intermediate uveitis
-Metastasis: optic nerve invasion (most common), through sclera into orbit, through TM into conj lymphatics --> palpable preauricular/cervical LN
-MRI: preferred for imaging optic n, orbits, brain
-DDx: Coats disease, PFV, ocular toxocariasis, ROP, RB

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RETINOBLASTOMA: DDx
-Coats disease: describe epidemiology, clinical appearance, IVFA, tx

Back 180

RB: DDx - Coats disease
-Epi: 1st decade, boys
-Clinical: unilateral retinal telangiectasia + exudation, no distinct mass
-IVFA: classic telangiectatic vessels
-Rx: laser or cryo to vascular abnormalities

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RETINOBLASTOMA: DDx
-PFV: describe laterality, assoc conditions, preferred imaging modality, tx.

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RB: DDx - PFV
-Unilateral in 2/3
-Assoc with: microophthalmos, shallow/flat AC, hypoplastic iris with prominent vessels, retrolenticular fibrovascular mass
-May see vascular stalk arising from optic n head, attaching to post lens capsule
-Ultrasound confirms Dx
-Rx: combined lensectomy, vitrectomy

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RETINOBLASTOMA: DDx
-Ocular toxocariasis: describe epidemiology, typical exposures, clinical manifestations

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RB: DDx - Ocular toxocariasis
-Epi: older children
-Exposure: soil ingestion, exposure to puppies
-Clinical: posterior, peripheral granulomas, assoc uveitis, vitreoretinal traction, cataracts

Front 183

RETINOBLASTOMA: DDx
-Astrocytoma: describe clinical appearance, assoc with giant drusen, assoc with systemic conditions

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RB: DDx - Astrocytoma
-Clinical: small, smooth, white glistening tumor in NFL; can increase and become calcified --> mulberry appearance
-Giant drusen: astrocytomas arising from optic disc
-Systemic assoc: tuberous sclerosis (most common), NF

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RETINOBLASTOMA: Classification
-What is the most common method of classification?
-What factors does it take into account?
-How are tumors grouped?
-Does this classification provide prognostic info?

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RB: Classification
-Reese-Ellsworth
-Does not classify extraocular RB
-Takes into account number, size, location of tumors, presence of vitreous seeds
-Grouped into I - V (very favorable to unfavorable) based on probability of preservation w/ ext beam radiation alone
-No prognostic info

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RETINOBLASTOMA: Assoc conditions
-What are similarities and differences between retinocytoma and RB?
-What is a trilateral RB?
-When does it usually present?
-Is it assoc with metastases elswhere in body?
-What % of pts with germline mutation have this variant?
-How can one screen for this disease?

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Retinocytoma
-Clinically indistinguishable from RB
-Histologically benign but has same genetic implications as RB (child with RB in one eye and retinocytoma in other can pass faulty tumor suppressor gene to offspring)
-Trilateral RB: bilateral RB + ectopic intracranial RB (pinealoblastoma)
-Affects 2-5% of pts with germline RB1 mutation
-Presents months-years after initial intraocular RB treatment
-No other metastatic disease elsewhere
-Image all RB pts with serial MRI w/o contrast (no radiation)

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RETINOBLASTOMA: Tx
-When is enucleation considered appropriate treatment?
-When is primary systemic chemotherapy used and what are the 4 typical agents?

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RB: Tx
-Enucleation (definitive tx): when 1) tumor involved in >50% of globe, 2) orbital or optic n involvement suspected, 3) ant segment involved (+/- NVG)
-Chemo: for bilateral intraocular RB, decreases tumor volume, use carboplatin/vincristine/etoposide/cyclosporine