Ocular Pathology
Fundamentals
Congenital abnormalities
Conjunctiva
Cornea
Eyelids
Intraocular Tumors
Lens
Optic Nerve
Orbit
Phacomatoses
Retina and Vitreous
Trauma
Ocular Pathology Fundamentals
Changes with Aging
Pathologic changes
Deposits
Inflammatory Cells
Immunologic Responses
Granulomatous Inflammation
Chronic inflammation and Phithisis
Ocular Changes with Aging
Cornea changes with Aging
- Thickening of Decemets layer
- Hassal-Henle warts= guttata in aging cornea
Sclera changes with Aging
- senile calcified plaques over recti muscles
- calcification of Bruchs membrane under macula
- calcification of internal elastic lamina
Lens changes with Aging
Ciliary body changes with Aging
- decreased cellularity of ciliary muscles
- processes become blunt and less vascular
Retina changes with Aging
- Langes folds- artifact folding of retina in infant eyes
- lag in vascularization of temporal retina after birth
- perepherial cystoid degeneration
Optic nerve changes with Aging
- decreased arachnoid cellularity with age
Pathologic ocular changes
Metaplasia- replacement of one adult cell type for another
- osseous metaplasia of pigment epithelium
- anterior subcapsular cataract
- Displasia-
disorderly maturation
- retinal dysplasia in Trisomy 13
- conjunctival dysplasia
- benign- well differentiated, enlarge by expansion, capsule, compression
- malignant-
variably differentiated, infiltrative, metastasis (discontinuous spread)
- eyelid, conjunctiva- lymphatic spread
- intraocular-hematogenous (no lymphatics)
- uveal melanomas-bypass lymph nodes-go to liver
- intraocular tumor with local spread to conjunctiva-lymphatic spread possible
- retinoblastoma-growth into optic nerve-spread to brain
- Other types of pathologic growth
- Hamartomas focal growth of tissue normally found in
that location
- Choristomas
= tissue not found in given location (heterotopic)
Deposits
Hyaline
Amyloid
Acid mucopolysaccharide
Urate
Calcium oxalate
Copper
Iron
Hyaline
Amyloid
Acid mucopolysaccharide
Urate
Calcium oxalate
- lens of morganian cataract
- chronic retinal detachment
- necrotic uveal melanomas
- methoxflurane anesthesia
- oxalosis
Copper
Iron
- corneal "blood staining"
- Fleischer ring- corneal epithelial iron in keratoconus
Inflammatory Cells
- usually first to respond-except in viral and some inflammations like Bechets
disease
- form abscess, nuclear fragments= nuclear dust
- in cornea appear flattened- look at nuclei to differentiate from fibroblasts
- attracted to immediate hypersensitvity reactions, immune complex deposition and
parasites (toxocara, trichinosis)
- bilobed nucleus
- same as basophils but in tissue
- round central nucleus in blue cytoplasm
- immediate hypersensitivity reactions
- small,round, little cytoplasm
- t-cells
- b-cells
- plasma cells
- eccentric, clock face nuclei
- produce antibodies
Russell bodies, Dutcher bodies = cytoplasmic collections of immunoglobulin
Macrophage, Monocyte, Histiocyte
abundant cytoplasm, eccentiric bean shaped nucleus
seen in AC in phacolytic glaucoma
form epitheloid cells when full of stuff they cant digest
congregation of macrophages (often in epitheloid form) = a granuloma
Giant cells
- fusion of epitheloid cells
- Langhans type- horseshoe of nuclei
- Tuton type- "two-tone" cytoplasm, ring of nuclei
- Foreign Body type central, random nuclei
- in epithelium, branching processes
- Birbeck or Langerhans granule
= organelle in cytoplasm
- involved in corneal graft rejection
- Langerhans cell histiocytosis (Histiocytosis X) eosinophilic granuloma
- Hand-Schuller-Christian Disease
- Letterer-Siwe disease
Ocular Immunologic Responses
- Type I: immediate (anaphylactic) hypersensistivity
- mast cell degranulation in response to antigen also eosinophils and plasma cells
involved
- example: vernal conjunctivitis
- TypeII
: antibody-dependant, cytotoxic hypersensitivity
- antibody targets tissue enciting inflammation
- example: pemphigoid
- Type III: immune-complex mediated
hypersensitivity
- antibody-antigen complex deposit in tissue enciting compliment response
- example: phacoantigenic(phacoanaphylactic) endophthalmitis possibly related to P.acnes
- Type IV
: cell-mediated hypersensitivity
- macrophages present antigen to senstitized t-lymphocytes, create lymphokines
- example: sympathetic ophthalmia
- Type V
: Antibody stimulation or supression
- antibody stimulation via receptors. eg.Graves Disease
- antibody supression via receptors. eg. Myasthenia Gravis
Granulomatous inflammation
- Sympathetic Ophthalmia
- Bilateral, spares choriocapillaris
- Dalen-Fuchs nodules- granulomas between
Bruchs membrane and RPE
- HLA A-11 association
- If inflammation occurs in sympathazing eye will occur in one year in 90%
- Phacoanaphylactic Endophthalmitis-zonal abscess
- Voght-Koyanagi-Haradas
Disease
- vitiligo, poliosis, dysacusis, tinnitis, CSF pleocytosis
- involves choriocapillaris and leaves chorioretinal scars
- Sarcoid
- Busacca nodule: perepherial iris granuloma
- Koeppe nodule: iris margin granuloma
- PAS, CPS, cataract
- phlebitis-vein occlusion
- Dalen-Fuchs-like nodules
- Optic nerve granuloma=possible CNS
- biopsy visible lesions in conjunctiva
- Tuberculosis
- Toxoplasmosis- acquired or congenital retinitis
Results of chronic
inflammation and phthisis
- band keratopathy
- cataract
- chronic retinal detachment, suprachoroidal hemorrhage
- RPE hyperplasia, osseous metaplasia of RPE
- cholesterol deposition following hemorrhage
Trauma
Surgical
Non-Surgical:
Acid Burns
Alkali Burns
Electrical Injury
Intraocular Foreign Bodies
Tear Gas
Thermal Injury
Radiation
Signs of Non-Ocular Trauma in the
Eyes
Surgical Trauma
- Iris stroma doesnt heal, iris pigment epithelium can close small holes
- Lens epithelium can seal small rents in lens capsule
- Sclera doesnt heal either, episcleral tissue grows down into wound or uveal
fibrous tissue grows up into wound
Cataract Surgery
- epithelial downgrowth
- implantation cyst- epithelium implanted in AC
- stromal fibrous ingrowth
- vitreous wick
- sputtering hyphema-vessels in wound
- Sommerings ring cataract-after ECCE
- Elschnig pearls-lens epithelium along posterior capsule
- CME- swelling in outer plexiform layer
Retinal Laser Scars- surrounding pigment-RPE
hypertropy or hyperplasia
Penetrating Keratoplasy
- primary graft failure- first post-operative day #1 graft unclear-endothelial cell
loss; poor graft, improper handling of tissue
- secondary graft failure-loss of endothelium, membrane formation
- endothelial rejection
- vascularization, rejection line, inflammation
- epithelial rejection
- epithelium repopulated by host cells
- supepithelial infiltrates, rejection line, Langerhans cells play a role
Blunt Non-Surgical Trauma
Corneal abrasion
- recurrent erosions from faulty reconnection of hemi-desmosomes to basement membrane
- if Bowmans layer compromised, facette results
Corneal edema with Descemets folds
- if Decemets ruptures- corneal hydrops, renewal of endothelial barrier resolves
edema
- forceps injury-usually unilateral, vertical or diagonal striae
- Haabs striae (congenital glaucoma) are usually bilateral and horizontal
- healing of Decemets occurs in scrolls- clinically lines
Lens subluxation or dislocation
- subluxation-partial zonular dehiscence, lens partially out of position
- dislocation (luxation)- complete zonular dehiscence-lens in AC or vitreous
- refractive error, PAS, pupillary block with lens in AC
- Other causes of lens malposition
Other lens alterations from Blunt
Trauma
- Vossius ring-imprint of iris pigment on anterior capsule
- Cataract- petaloid pattern
Iris changes from Blunt Trauma
- Iridodialysis- associated with hyphema
- Sphincter tear
Angle changes from Blunt Trauma
- Trabecular Meshwork
- endothelium deposits glycosaminoglycans and additional collagen
- endothelial cells engulf pigment and debris and can clog meshwork
- corneal endothelial cells may grow over meshwork-a secondary ICE syndrome
- Angle Recession
- tear through face of ciliary body, through longitudinal and meridional muscles
- clinically; prominent ciliary body band
- histologically; if line parallel to visual axis drawn through scleral spur is anterior
to angle= recession
- glaucoma in 6%
- PAS can form
- Cyclodialysis
- disinsertion of ciliary body from scleral spur
- uvea attached to sclera at scleral spur, vortex veins and optic nerve
- clinically see sclera posterior to scleral spur or enlargement of scleral spur
Posterior Segment Injury from
Blunt Trauma
- Vitreous Hemorrhage
- cholesterol bulbi-cholesterol crystals from degenerated RBCs (contrast with
asteroid hyalosis is usually bilateral although very asymmetric)
- Hemosiderosis bulbi-build up of hemosiderin leading to retinal damage
- Ghost cell glaucoma can occur if anteior
hyloid face is defective. Ghost cells may appear khaki or white. Treat with AC washout or
vitrectomy if meds ineffective
- Retinal Dialysis- separation of perepherial retina from ora
- can occur after blunt or penetrating trauma, inflammation or even spontaneously
- Commotio Retinae
- macular edema or photoreceptor disorganization,
- complicated by macular cysts progressing to macular hole
- pigment mottling
- Retinal Necrosis- posttraumatic pigmentary retinopathy "pseudoretinitis
pigmentosa"
- Retinal/ subretinal hemorrhage
- Choroidal rupture
- indirect injury (contre-coup) concentric to optic nerve
- associated with tear of overlying retina
- Retinitis sclopeteria- overlying the area of impact
- Avulson of optic nerve
- early- blood in optic nerve sheath
- late-fibrous tissue replaces optic nerve, this may extend into globe for a short
distance
- Globe rupture
- globe weakest posterior to recti insertions, at limbus and around optic nerve.
Penetrating Trauma
Penetrating Trauma- Definitions
- penetrate-enter structure
- perforate- through and through
Thermal injury
- blink provides some protection
- results in coagulative necrosis of cornea
Electrical injury
- perepherial anterior subcapsular lens vacuoles
- progression to anterior subcapsular cataract
- lightening- both anterior and posterior lens changes
Acid burns
- precipitation of tissue proteins creates barrier for further damage
- tears buffer
- coagulative necrosis of epithelium
Alkali burns
- denature proteins and saponify lipids therefore penetrate deeper
- extensive necrosis and damage to intraocular tissues
- chemical cautery cause focal blanching of vessels
- late corneal perforation maybe caused by collagenases released by neutrophiles
- late consequences
- symblepharon with dry eye
- entropion
- corneal scar and vascularization
- chronic non-granulomatous anterior uveitis
- cataract
- glaucoma
- phthisis
Tear Gas
- fumes: epithelial defects that heal well
- powder: severe keratitis if direcly in contact with eye
Radiation
Non-ionizing Radiation
- Radio, TV: no ocular effects
- Microwave: cataracts
- Infrared (770nm-12,000nm)
- true exfoliation(spliting) of lens epithelium
- longer the wavelength more cataractogenic
- Ultraviolet (180nm-390nm)
Ionizing Radiation
- x-rays (artificially produced), gamma rays(naturally occuring)
- electromagnetic
- high tissue penetration (feet)
- alpha rays: ionized helium
- beta rays
- charged electrons
- used to prevent pterygium recurrence
- low penetration
- protons
- hydrogen nuclei
- medium low penetration
- theraputic modality eg. uveal melanomas
- effects
- lid erythema ,chronic radiodermatitis, entropion, ectropion
- conjunctival teleangectasis
- corneal keratinization, vascularization, scarring, necrosis
- cataract
- obliteration of retinal vessels-endothelium very sensitive
- pre-retinal membrane, tractional retinal detachment, retinal neovascularization
- late optic atropy
- post-radiation orbital sarcomas esp. in retinoblastoma
patient
Ocular manifiestations of
non-ocular trauma
- Terson's Syndrome
- Retinal fat emboli
- chest, pelvis and long bone fracture
- retinal hemorrhage, exudate, edema
- Shake injury
Tersons syndrome
- Retinal hemorrhage over optic nerve-associated with subdural hemorrhage,
- Increased cerebral spinal fluid pressure causes compromise of venous flow around optic
nerve and rupture of vessels around the surface of the disk and peripapillary retina
- Blood may collect under internal limiting membrane
Corneal Pathology
Anatomy and Pathologic responses: Epithelium, Bowman's layer, Stroma,
Decemet's membrane, Endothelium
Disease that change corneal shape
Dystrophies
Infections
Limbal pathology
Neoplasia
Epithelium: Anatomy and Pathologic Responses
- PAS stain highlights epithelium basement membrane
- reduplication of basement membrane seen in bullous keratopathy or Map-Dot-Fingerprint
dystrophy
- hydropic degeration= epithelial edema, bullous detachement
- Depositions
- Immunoglobulins- in macroglobulinemia
- Iron
- Fleisher ring- surrounds cone in Keratoconus
- Ferry line- near filtering bleb
- Stocker line- at the advancing edge of a pterygium
- Hudson-Stahli line- horizonal
- Urate in gout
- Cystinosis- refractive crystals in epithelium
- Amiodarone-vortex pattern
- Thioridazine (mellaril)
- Chloroquine
- Cysts in Meesmans dystrophy
- Degenerative pannus
- avascular tissue
- non-specific response to corneal inflammation and edema
- deposition of connective tissue in supepithelal space
- possible sources
- limbus
- stroma through holes in Bowmans that normally transmit nerves
- fibrous metaplasia of epithelial cells
- Inflammatory pannus
- vascular tissue from limbus
- inflammatory cells present
- often destroys Bowmans
Bowmans layer: Anatomy and
Pathologic responses
- condensation of anterior layers of stroma
- no keratocytes, doesnt regenerate
- focal defects filled in by epithelium= facette
- PAS doesnt stain it
- Band Keratopathy
- calcification of Bowmans layer in interpalpebral fissure
- Calcific: calcium salts in Bowmans layer
- Actinic= Labrador keratopathy= Droplet Keratopathy= Spheroidal Degeneration
- solar elastosis of Bowmans and anterior stoma
- altered collagen from UV damage stains more blue on H&E
- appears more like elastic tissue but isnt digested with elastase
- Fracturing/Fragmenting: diagnostic of keratoconus
Corneal Stroma: Anatomy and Pathologic Responses
- fibroblasts (keratocytes) populate and lay down collagen fibers into lamellae
- artifact of parafin embedding causes clefts in lamellae, corneal edema causes fewer
clefts
- collagen misalignment leads to stromal whitening = scarring
- excessive scarring= keloid
- Congenital white cornea DDx: (see glaucoma
notes)
- Sclerocornea: congenital misalignment of corneal collagen
- Congenital Glaucoma
- Peters Anomaly: absence
of Decemets membrane centrally, =/- adhesions of iris or lens to cornea
- Mucopolysaccharidoses: accumulation of intra- and extra-cellular
mucopolysaccharides
- Corneal ulcer: involves stromal loss, inflammation, edema, necrosis
- necrosis
- keratocytes absent
- inflammatory cells unless aseptic necrosis (eg. radiation)
- loss of collagen fibril structures
- seen in:
- inflammation/infection
- radiation
- chemical injury
- anterior segment ischemia
- healing involves, scarring, vascularization
Deposits
- Hylaine: stains red with Trichrome stain
- Amyloid: stains red with Congo Red
- Mucopolysaccharide:
-
- Hemoglobin:
- corneal blood staining-hemoglobin in stroma
- iron found in keratocytes not in collagen in late blood staining
- Iron: late corneal blood staining can find iron in the form of hemosiderin in
keratocytes
- Lipid: Oil-red-O stain
- deposited in triangles with base towards Bowmans or Decemets and apeces in
center of stroma
- corneal arcus= lipid
- Cholesterol
- Immunoglobulins: macroglobulinemia
Decemets membrane: Anatomy
and Pathologic Responses
- endothelial basement membrane
- Two layers
- anterior banded: deposited in utero
- posterior non-banded: deposited after birth: thickens throughout life
- Guttata or Hassal-Henle warts
- focal thickening of Decemets
- Fuchs
endothelial dystrophy: guttata plus loss of endothelial cells plus corneal edema
- can have pigment settle on them-pigmented guttata
- strings of guttata or large scrolls of Decemets seen in congenital syphillis
- Decemetocele-herniation of Decemets through ulcer. Tensile strengh prevents
Decemets rupture in ulcer
- Hydrops in keratoconus, forceps injury, congenital glaucoma (Haabs
striae), trisomy 21
- Peters Anomly: central absence of
Decemets this causes scarring of stroma. Possible adhesion of iris or lens to cornea
- Detachment- a result of surgery or trauma
- Granulomatous inflammation: inflammation in HSV infection
- Deposits
Corneal Endothelium: Anatomy and Pathologic
Responses
- derived from neural crest cells
- maintains stromal dehydration
- regenerates poorly
- halts downgrowth of epithelium
- Endothelium can grow over angle (forming "neo-Decemets") in response to:
- Fibrous retrocorneal membrane can cover endothelium
- from iris after PAS
- from corneal stroma through gap in Decemets
- fibrous metaplasia of endothelium-deposition of posterior collagenous layer of
Decemets membrane
- Pigment deposition
- pigment can deposit on endothelium. eg. pigmented guttata
- endothelium can take up pigment. eg. Krukenburg spindle in pigment
dispersion syndrome
Corneal Changes in size and shape
- Megalocornea
- X-linked non-progressive enlargement of cornea
- 13-18 mm in diameter
- Microcornea
- less than 10 mm in diameter
- may be complicated by glaucoma
- Keratoconus
- bilateral ectasia, often asymmetric, leads to irregular corneal curvature
- thinning to a conical or irregular shape
- Vogt striae- stress lines in cornea that disappear with pressure on cornea
- fracturing or fragmentation of Bowmans layer
- rupture of Decemets= hydrops
- Keratoglobus
- bilateral ectasia leading to uniform corneal thinning
- Staphyloma
- a bulging lined by uveal tissue
- corneal staphyloma is lined by iris
Selected Corneal Infections
- Fungi
- Decemets doesnt offer a barrier to fungi
- seen on GMS (silver) stain
- Herpes Simplex
- Dendrites
- Geographic ulcers
- Disciform keratitis
- stromal inflammation and superficial scarring
- fragmented Bowmans layer
- granulomatous reaction to Decemets membrane
- Acanthamoeba
- resembles herpetic disciform keratitis
- ring infiltrates, spoke infiltrates along nerves
- Calcoflour white with flourescence highlights cysts
- Trophozoite seen on routine stains as well
- Corneal scraping or biopsy
Corneal Dystrophies
- Epithelium
- Bowmans Layer
- Stroma
- Endothelium
Perepherial Cornea and Limbus
Pathology
- Limbal Dermoid: a choristoma- heterotropic rest of
tissue
- Degenerations
- Pelucid Marginal Degeneration: perepherial, usually inferior ectasia
- Terrians Marginal Degeneration
- thinning of perepherial cornea
- perepherial corneal staphylomas
- astigmatism
- risk of rupture with blunt trauma
- Inflammations
- Staphlyococcal marginal infiltrate: hypersensitivity to staphylococcal exotoxins
- Phlyctenular keratoconjunctivitis: hypersensitivity to systemic staphylococcus or
turberculosis at limbus or in conjunctiva
- Limbal vernal keratoconjunctivitis: papillary reaction, Horner-Trantas dots- degenerative
products of eosinophiles
- Superior Limbic keratoconjunctivitis: injection and superior conjunctival
thickening
Corneal Neoplasia: conjuctival tumors
tend to arise at the limbus (see conjunctiva section)
Conjunctival Pathology
Anatomy
Pathologic responses
Deposits
Choristomas
Color Changes
Epithelial Lesions/ Squamous Cell Carcinoma
Inflammation
Lymphoid Lesions
Nevi
Melanosis-Congenital
Melanosis-Acquired
Melanoma
Biopsy
Conjunctival Anatomy
- Bulbar
- non-keratinizing stratified squamous epithelium
- goblet cells not usually near surface
- substantia propria (aka stroma)
- sclera under substantial propria
- Fornix
- pseudostratified columnar epithelium with goblet cells
- substantia propria (aka stroma)
- Palpebral
- pseudostratified columnar epithelium with goblet cells
- substantia propria (aka stroma)
- Tarsus
- dermis
- epidermis
- Accessory lacrimal tissue
- Krause and Wolfring glands: produces aqueous layer of tear film
- Lymphoid tissue
- lymphocytes and plasma cells
- part of Mucosa Associted Lymphoid Tissue (MALT)
- form IgA
- Forms lymphoid follicles in: follicular conjunctivitis, lymphoid
hyperplasia
- Diffusely infiltrates substantia propria in lymphoma
Conjunctival Pathologic Responses
- loss of goblet cells (keratitis sicca, vitamin A deficency)
- conjunctival scarring (alkali burns, pemphigoid)
- increase in goblet cells (ocular irritations: pterygium)
- keratin production
- Bitot spot in vitamin A deficency,
- diptheroids produce gas in keratin and give bubbly appearance,
- Dry eye
- Exposure
- squamous metaplasia
- replacement of pseudostratified columnar epithelium in fornix or palpebral conjuctiva
with squamous epithelium
- epidermidalization
- formation of rete ridges
- seen often with keratinization
- follicles- formation of germinal centers by lymphoid tissues
- papillae- substantia propria is loosly organized causing redundancy and folding, usually
increase in goblet cells
- cysts- chronic conjunctivitis, compound nevi, rarely seen in melanomas that arise from
compound nevi
- bullae
- pemphigus: intraepithelial bullae, antibodies directed to intercellular substance
- acantholysis-epithelial cells separate from each other
- bullae can rupture and become infected
- pemphigoid: subepithelial bullae, antibodies against epithelial basement membrane
- rupture of bullae leads to scarring, symblepharon, obliteration of orifices of lacrimal
glands and accessory lacramal gland- tear deficency
- loss of goblet cells- decreased corneal wettablility
- Solar elastosis
- marker of damage by UV light
- sub-epithelial elastoic collagen- stains blue on H&E but doesnt digest with
elastase
- seen in penguecula, pterygium, (recurrent pterygium is granulation tissue and scarring
not solar elastosis)
Conjunctival Deposits
- urate in gout
- cystinosis- refractive crystals in epithelium
- immunoglobulins
- drugs
- epinepherine
- silver
- tetracycline
- amyloid: reflects local disease
- pseudoexfoliation material
Conjunctival Choristomas
- limbal dermoid
- lipodermoid
- superior temporal quadrant
- adipose tissue with elements of solid dermoid tumor
- carilage and secretory glands can be present
- osseous choristoma: usually involves epislera in superior temoral quadrant
Conjunctival Color Changes
- Red: vascular injection or blood
- conjunctivitis
- episcleritis (more violet color)
- scleritis (more dusky red)
- polycythemia
- blood
- subconjunctival hemorrhage
- trauma
- Kaposis sarcoma
- appears as chronic non resolving hemorrhage in skin or eyelid
- histologically-slit like spaces between spindle shaped cells and
RBCs confined to these spaces
- Blue
- hemosiderin
- melanin in episclera or sclera
- congenital ocular melanosis
- Nevus of Ota- accompanying blue pigmentation of periocular skin
- Brown or black
- yellow
- lipid of sebacious carcinoma
- solar elastosis
- "scleral" icterus is really bilirubin deposits in conjunctiva not sclera
- gray or white
Conjuncitval
Epithelial and Supepithelial Lesions (Neoplastic and other)
- epithelium: abrupt elevations and irregular surfaces characterize lesions arising
from epithelium
- Squamous Papilloma
- papillary fronds
- core of fibrovascular tissue surrounded by hyperplastic epithelium
- dysplasia
- carcinoma in situ: thickening of epithelium appears gelatinous and translucent
- supepithelial compartment: tend to elevate and streach normal epithelium
- pinguecula
- lymphoid lesions- "salmon patch"
- cysts
- chronic conjunctivitis
- compound nevus
- lymphatics
- lymphangiectasia
- lymphangioma
Conjunctival Inflammation
- Actinic granuloma: Granulomatous inflammation
- Sardoid
- Cat Scratch
- follicular conjunctivitis with or with out a granulomatous mass
- granulomas with central abscess characteristic
- excision of the granulomatous mass may hasten recovery
- if enlarged lymph nodes- cat scratch fever
- one of Parinauds Oculoglandular Fever
- DDx: tularemia, syphilis, sporotrichosis, tuberculosis, other rare infections
Conjunctival Lymphoid lesions
- Features:
- Typically unilateral, 60s-70s
- can be subepithelial and space occupying "salmon patch"
- can involve orbit
- tend to be hyperplastic, benign
- bilaterality doesnt mean malignancy
- Classification
- benign reactive lymphoid hyperplasia
- atypical lymphoid hyperplasia
- malignant lymphoma
- lymphoasmacytic proliferations
- Management
- systemic workup by oncologist
- CBC
- serum electrophoresis
- bone marrow aspirate and biopsy
- liver & spleen scan
- thoracic and abdominal CT
- radiation with shielding of eye
- lesions respond poorly to steroids
Conjunctival Squamous Cell Carcinoma
- Definitions
- acanthosis- epithelium thickened (hyperplastic)
- hyperkeratosis- any keratin in conjunctiva
- dyskeratosis- individual cell keratinization within epithelium
- dysplasia- abnormal maturation of partial thickness epithelium
- cytoplasmic atypia
- abnormal mitosis
- loss of polarity
- carcinoma in situ- full thickness dysplasia
- no invasion into stroma (substantia propria)
- Heriditary benign intraepithelial dyskeratosis (HBID)
- autosomal dominant
- Haliwa indians-from Halifax and Washington
- triracal families- white, african-american and american indian
- Conjunctival intraepithelia neoplasia (CIN)- dysplasia & carcinoma in situ
- Clinical features
- may have solid elevated appearance
- may have papillary appearance
- may resemble a pterygium
- may look like a thin hazy membrane creaping across corneal epithelium
- commonly at limbus but can occur elseware
- Histologic features
- exophytic (out growth) as in papillary squamous cell carcinoma (scleral invasion absent
in this type)
- invasion into substantia propria and sclera
- intraocular invasion rare
- metastisis rare
Conjunctival Nevi
- Features
- pigmented or nonpigmented
- affect bulbar conjunctiva, fornix or caruncle rarely palpebral conjunctiva
- circumscribed
- often contain small cysts in compound nevus
- Types
- Junctional
- children or adolescents
- proliferation of nevus cells at juction of epithelium and stroma
- nesting may be prominent
- may be indistinguishable from primary acquired melanosis with atypia
- Compound
- contain cysts usually
- lie in the epithelium and subepithelial substantia propria
- Subepithelial
- may have nests and cysts
- confined to substantia propria
Conjunctival Melanosis: Congenital - more
blue in color, scleral or episcleral melanin
- Congenital ocular melanosis
- Nevus of Ota
- accompanying blue pigmentation of periocular skin
- clinical differentiation of congenital ocular melanosis and conjunctival melanin
- conjunctival melanin will move with movement of conjuctiva
Conjunctival Melanosis: Acquired
- Primary (PAM)
- Features
- unilateral, flat, in light complected individuals
- discontinuous foci of pigmentation
- can involve, bulbar, palpebral, fornix epithelium
- can also involve caruncle and corneal epithelium
- may wax and wane, spread, or disappear
- PAM without atypia
- hyperpigmentation without hyperplasia or
- hyperplasia without cytologic atypia
- little risk of progression to melanoma
- PAM with atypia
- atypical melanocytes confined to epithelium
- risk of developing melanomal approches 50%
- features linked to progression to melanoma
- any growth pattern other than basilar hyperplasia
- epitheloid cells present
- Management
- biopsy all patients with PAM
- if atypia present, lesion should be extirpated by excision, cryotherapy, laser or
topical chemotherapy
- Secondary
- no predilection for melanoma
- conjunctival pigmentation in african-americans
- Addisons disease
- drugs such as epinepherine, silver, tetracycline
Conjunctival Melanoma
- Features
- 25% overall mortality rate
- spreads to regional lymph nodes (in contrast to uveal melanoma which first spreads to
liver)
- most develop from PAM
- PAM with upward invasion into conjunctival epithelium (Pagetoid spread) has worse
prognosis
- tumors thicker than 0.85 mm have worse prognosis
- tumors of caruncle have worse prognosis
Conjunctival Biopsy
- spread tissue on flat absorbant surface such as paper wrapping for gloves, the file-card
envelope for sutures or filter paper
- allow tissue to become adherent to mount
- float in formalin, sample will sink to bottom in proper orientation
Eyelid Pathology
Epidermis pathology
Dermis pathology
Sub-cutaneous fat pathology
Definition of terms
Clinical clues to underlying
pathology
Specific Conditions:
Epidermis- by layers
- keratin layer
- granular layer
- basophilic keratohylain granules in cytoplasm
- eventually nucleus is lost
- prickle cell layer
- spines represent sites of desmosomal attachment
- acanthosis- thickening of this layer
- germative layer
- only layer with mitotic figures
- sits on basement membrane
- other cells
- melanocytes
- derived from neural crest
- reside in basal layer
- inject melanin into overlying prickle cells by way of dendritic processes
- Langerhans cells
- capture antigens, process them and present them to dendritic reticulum cells or
lymphocytes in the dermis
Dermis
- hair tumors
- pilar cyst
- trichoepithelioma
- trichofolliculoma
- tricholemmoma
- pilomatrixoma
- glands
- eccrine glands
- apocrine glands (glands of Mol)
- hidrocystomas
- sebaceous glands
- sebacious hyperplasia
- adenoma
- carcinoma
- vessels
- capillary hemangioma
- nevus flammeus
- artrio-venous hemangioma
- Kaposis sarcoma
- nerves
- schwannoma (neurolemmoma)
- neurofibroma
Sub-cutaneous fat
- absent in eyelid
- dermis rests on obicularis
- fat on eyelid biopsy represents orbital fat
Terminology-Skin
- Acanthosis
- epidermal thickening by hyperplasia
- prickle cell hyperplasia
- acanth= "spines"
- element of seborrheic keratosis
- Hyperkeratosis
- increased amount of keratin
- clinically grey or white scale
- abundant amounts appear waxy and yellowish. generic term for this is "cutaneous
horn"
- causes
- actinic keratosis
- squamous cell carcinoma
- inverted follicular keratosis
- sebacious carcinoma
- removal of lesion involves removal of epidermis under lesion
- Parakeratosis
- a type of keratosis with retention of nuclei in keratin layer
- granular layer is thin or absent
- sign of shortented epidermal turnover time
- Dyskeratosis
- individual cell keritinization occurs within epidermis rather than at the surface
- Dysplasia
- abnormal maturation of an epithelium
- cells lose polarity
- atypical cytologically
- partial thickness
- Carcinoma-in-situ
- full thickness dysplasia of epithelium (epidermis)
- does not invade dermis
- Squamous cell carcinoma
- dysplasia with evasion through basement membrane
- invasive component may have:
- dyskeratosis
- keratin pearls- aggregates of keratin
- atypical mitotic figures
- nuclear atypia
- infiltrative borders
- Elastosis
- assoicated with actinic keratosis, squamous cell carcinoma, basal cell carcinoma,
melanoma
- Keratosis
- non specific term meaning a lesion in the epidermis
- examples:
- seborrheic keratosis
- actinic keratosis
- Actinic Keratosis
- epidermal dysplasia
- elastosis
- inflammation
- hyperkeratosis, parakeratosis
- clinically: raised, scaly, sometimes erythematous
- precursor of squamous cell carcinoma
Clinical clues to underlying
pathology
Color of Skin Lesions
- Red or pink- increased quanities of oxygenated RBCs
- nevus flammeus:
- Sturge-Weber syndrome
- telangiectatic vessels in dermis
- capillary hemangioma of childhood
- may be present at birth or develop rapidly in first six months
- most cases regress by age 6 or 7
- pyogenic granuloma- inflammatory granulation tissue
- dacryocystitis
- swelling does not extend above medial canthal ligament. tumors may
project above this mark
- pre-septal cellulitis
- inflammation that dissects through tissue planes
- chalazion
- Blue- hemosiderin or deep melanin
- Brown or black- superficial melanin
- nevi
- melanoma precursors and melanoma
- abundant keratin in keratoacanthoma
- Grey or white- increased keratin
- Yellow- lipid or elastic tissue
- Xanthalasma
- Necrobiotic Xanthogranuloma
- yellow deposits and skin necrosis
- may harbor or later develop multiple myleoma
- immunoelectrophoresis and bone marrow biopsy necessary
- Pseudoxanthoma elasticum
- associated with angioid streaks
- prone to have GI bleeds
Surface topography of Skin
Lesions
Lesions arising from epidermis
- edges abruptly elevated
- epidermal topography exaggerated
- eg. squamous papilloma, seborrheic keratosis
Lesions arising from dermis
- streach of overlying epidermis giving a smooth surface
- edges slope and blend with adjacent tissue
- dermal deposits
- amyloid
- waxy plaques
- purpuric hemorrhage from deposits around vessels causing them to be
fragile
- reflects systemic pathology as opposed to conjunctival amyloid
- lipoid protenosis
- waxy nodules usually at eyelid margins
- hyalin material
- similar lesions around vocal cords can cause hoarsness
- xanthalasma
- yellow plaques on upper and lower eyelids
- dermal lipid filled macrophages around venules
- dont necessarily have elevated serum lipids
- tumors
- syringoma
- small nodules beneath eyelids
- arise from eccrine sweat glands
- neurofibroma
- plexiform neurofibroma
- can occur in eyelid
- follows a nerve trunk
- "S"-shaped ptosis of upper lid
- diagnostic for neurofibromatosis type I (von Recklinghousen disease)
- solitary neurofibromas not associated with
neurofibromatosis
- cysts
Skin Lesions that
dont follow the rules
Basal Cell Carcinoma
- arise from epithelium but does not thicken this layer
- invades the dermis and occupies space in the dermis
- sloping, curved edges, central umbilication
- may be nodular or cystic
Squamous Cell Carcinoma
- epithelium thickened
- AND infiltration into dermis causing dermal space occupying pattern as well
Specific Eyelid Skin Conditions
Lid Lesions-
Inflammations
Chalazion
- inflammation of tarsus sometimes breaking through to the skin
- sebacious carcinoma may mimic clinical appearance
- pink skin and dermal mass lesion
- granulomatous inflammation around lipid with giant cells
Hordeolum (Stye)
- suppurative (acute) inflammation
- usually centered around glands of Zeis associated with an eyelash
Cellulitis
- inflammation passing through tissue planes
Abscess
- localized zone of suppurative inflammation frequently assoicated with necrosis
Herpes Simplex and Zoster
- intact and crusted vesicles
- vesicles form within the epidermis
- lysis of acanthocyte layer (prickle cells) "acantholysis"
- characteristic intranuclear inclusion bodies
Molluscum Contagiosum
- solitary or multiple elevated white umbilicated lesions
- seen in children commonly and in immunocompromised adults
- viral particles may shed into conjuntival cul-de-sac causing a follicular conjunctivitis
- epidermal thickening- acanthosis
- cells infected with DNA poxvirus
- basophilic and eosinophilic inclusion bodies
Lid Lesions- Cysts
Epidermal inclusion cyst
- subepidermal (in dermis)
- freely mobile, opaque
- filled with white, maloderous, greasy material
- lined by stratified squamous epithelium, no dermal elements
- filled with keratin
- may spontaneously rupture leading to a granulomatous inflammation to the keratin
Dermoid cyst
- example of choristoma- heterotopic rest of tissue
- lined by keratinizing stratified squamous epithelium
- cyst wall also contains other dermal elements eg. hair and sebacious glands
Sudoriferous cyst
- at lid margin or near canthi
- contain secretions of sweat glands
- transmit light well
- formed by eccrine or apocrine glands
- lined by bilayer of flattened epithelium
Cystic basal cell carcinoma
- basal cell carcinoma that has undergone central necrosis
- can clinically mimic epithelial inclusion cyst
- tumor may be attached to adjacent tissue making shelling out of contents difficult
- doesnt transilluminate
- hemosiderin accounts for blue color
- perepherial palasading nuclei
- cracking artifiact- separation of tumor from dermis
- Benign lesions arrising from epidermis
Lid Lesions-
Other Epidermal lesions
Squamous papilloma
- prominent hyperkeratosis
- fronds may be seen with magnification
- similar to verruca (true viral verruca rare on eyelids)
- acanthosis (hyperplasia) of epitheithelium and thrown into folds over cores of dermal
fibrovascular connective tissue
Seborrheic keratosis
- complex groved surface, "stuck on" appearance
- may be pigmented especially in dark races
- appearance of sudden multiple lesions may be marker of internal malignancy
- acanthosis
- base of lesion flat- noninvasive
- no dysplasia
- lamellar hyperkeratosis
- pseudo keratin inclusions- formed by grooves on surface of lesion
- variable papillomatosis
Inverted follicular keratosis
- presents as a "cutaneous horn"
- some call them irritated seborrheic keratosis
- may be some acantholysis just above basal layer
- squamous eddies- whorls of benign squamous cells just above acanthocytes
Keratoacanthoma
- rapid growth of cup shaped lesion (weeks to months)
- frequently central black plug of keratin causing central crater
- usually regresses without treatment
- sometimes hard to distinguish from squamous cell carcinoma
- SCC usually lacks central crater and come on less quickly and dont resolve
spontaneously
- SCC has infiltration at base of lesion
- biopsy should include edge of lesion and central crater
- acanthosis, hyperkeratosis, dyskeratosis, mitotic figures, some cytologic atypia
possible, no infiltration at base, inflammation at base
- biologically could be a self-regressing squamous cell carcinoma
- a.k.a- squamous cell carcinoma-keratoacanthoma type
Non-pigmented malignancies of epidermis
Actinic keratosis (pre-malignant)
- acanthosis, hyperkeratosis, parakeratosis, dysplasia, small lymphocytic infiltrate
possible
Squamous cell carcinoma
- may occur anywhere on eyelid skin
- 40 times less common than basal cell carcinoma
- hyperkeratosis may cause grey-white scale
- low potential for regional lymph node metastasis
- atypical squamous cells infiltrate dermis
Basal cell carcinoma
- clinical features
- usually lower eyelids
- metastasis extremely rare
- local invasion into orbit, sinus, frontal cranial fossa
- nodular
- nodular-ulcerative
- cystic
- sclerosing- borders difficult to identifiy
- pigmented- melanin elaborated by benign melanocytes entrapped in tumor
- pathology
- islands, nests and chords of cells with scant basophilic cytoplasm
- perepherial palasading nuclei
- cracking artifact- separation of tumor from stroma
- arborizing strands of tumor within stroma with abundant fibrous stroma may represent
sclerosing variant
- nevoid basal cell carcinoma syndrome
- autosomal dominant
- multiple basal cell carcinomas at a young age
- systemic associations
- bifid ribs
- ovarian lesions
- odontogenic jaw cysts
- pitting of the palms
- management
- do incisional biopsy before planning surgery to establish diagnosis
- completely remove tumor
- if margins contain tumor recurrance rate 8-10%
- can observe or excise scar
- check margins with frozen section (Mohs)
Tumors arising in sub-epidermal
Lid tissues
Sebaceous carcinoma
- Clinical Features
- may present as nodule in eyelid and mimic chalazion
- biopsy and submit recurrent chalazion material
- may present as nodule in caruncle
- may present as chronic unilateral (blepahro) conjunctivitis
- may be accompanied by madarosis (loss of eyelashes)
- marker of internal malignancy
- Pathology
- arise from meibomian glands, glands of Zeis (assoicated with eyelash), or sebacious
glands in caruncle
- may be multicentric
- Pagetoid spread (upward spread to epithelium, also seen in melanoma)
- can be mistaken for carcinoma-in-situ or chronic inflammation
- bubbly cytoplasm, not foamy lipid-filled cytoplasm
- full thickness lid biopsy to look at meibomian glands and Zeis glands may be necessary
- Oil-red-O stain on fresh or formalin fixed tissues can identify fat
- Prognostic parameters
- size
- orgin (better if from glands of Zeis)
- differentiation
- presence or absence of infiltration
- location (better if from lower lid)
Syringoma
- multiple small (2-3mm) plaques on or beneath lower lids in young or middle aged women
- benign tumor of eccrine glands
- fibrous stroma and glandular elements
Lid Lesions-Nevi
Congenital
- split nevus of eyelid
- melanocytes migrate over eyelid before separation of eyelids in utero
- may add bulk to eyelid and cause ambylopia
- tendancy for cutaneous melanoma to develop at this site
Acquired
- stages of maturation
- junctional nevus
- nests of nevus cells at juction of dermis and epidermis
- clinically flat
- compound nevus
- cells drop off epidermis
- nests in dermis and epidermis
- lesion becomes elevated
- intradermal nevus
- all cells in dermis
- lesion elevated
- smooth, dome shaped lesions
- may be pigmented or not
- hairs frequently protrude from surface
- posterior surface molds or contours to surface of eyelid
Lid Melanoma
Lentigo maligna
- seen in older patients after extreme sun exposure
- flat, irregular borders, variable pigmentation
- may overlap into adjacent conjunctiva
Superficial spreading type
Nodular type
Acral lentigiinous type (rare around eyes)
Optic Nerve Pathology
Optic Nerve-Anatomic relationships
Contrast
Optic nerve to peripheral nerve
optic nerve
mylenated by olgiodendroglia
tumors are glioma and meningioma
no regeneration
scarring and repair: gliosis
gliosis= glial cells proliferate and produce
intracellular material. Also occurs in retina
perepherial nerve
- mylenated by Schwann cells
- tumors are Schwannoma, neurofibroma
- regeneration possible following transection
- scarring and repair: fibrosis
- fibrosis= fibroblasts secrete extracellular material (i.e., collagen)
Laminar Optic Nerve Zones
- Prelaminar
- lamina retinalis and lamina choroidalis
- some blood supply from choroidal vessels
- Intralaminar
- Retrolaminar
- mylenated by oliodendroglia
Cross-sectional
Optic Nerve Anatomy
- continuous anteriorly with the sclera and posteriorly with the periosteum of orbital
bones
subdural space
- continuous with same space in brain
- subdural hemorrhage of brain can track back along optic nerve in this space (as in
shaken baby syndrome)
arachnoid
- continuous with arachnoid of brain
- contains arachnoid epithelium forming "granulations"
- have "clearing"of nuclei
- meningiomas form from epithelium
subarachnoid space
- continuous with same space in brain
pia
- intimately surrounds nerve
- compartmentalize nerve and carry small vessels into it
Axoplasmic transport
- axons originate from ganglion cells and terminate in lateral geniculate body
- orthograde transport- flow of material from cell body down axon
- when transport is interrupted, axoplasmic flow procedes from cell body to site of
interruption. Organelles especially mitochondria pool next to the interruption. cytoplasm
swells.
Optic Nerve
Pathologic changes
- Nerve fiber layer infarct
- collection of cytoid bodies in layer= pink on H&E
- usually occur in retina but can occur in lamina retinalis of optic nerve
- clinically a cotton wool spot
- Papilledema
- swelling of optic nerve head associated with increased intracranial pressure
- lamina retinalis swells due to stasis of axoplasmic transport
- photoreceptors displaced laterally
- dilation of epipapillary vessels
- fluid accumulates in extracellular compartment
- lamina scleralis position
- anterior bowing
- elevated intracranial pressure
- compression of optic nerve from orbital or optic nerve tumor
- ocular hypotony
- posterior bowing in acute IOP elevations
- Drusen
- calcific masses, usually anterior to lamina scleralis
- focal burried masses
- sharp optic nerve border
- often vessel anomalities
- absence of cup
- "giant drusen" in tuberous sclerosis
are calcified astrocytic hamartomas
- scleral canal may be congenitally narrowed which may lead to stasis of axoplasmic
transport
- calcified mitochondria may be extruded from axons causing calcific masses
- 75% get visual field defects
- Optic atropy and gliosis
- cells or tissues already present decrease in size or mass
- loss of axons
- widening of subdural space
- hypoplasia
- structure not formed completely
- double ring sign = ring of sclera around small optic nerve
- crushed nerve may appear histologically as atrophy or gliosis. some of the nerve
contents can also be squeezed subretinally and into blood vessels "myelin
artifact"
Tumors of the optic nerve
Optic nerve head Tumors
- Tumors associated with phacomytoses
- Astrocytic Aamartoma
- Hemangioblastoma
- can mimic a hemorrhage
- seen in Von Hippel-Lindau disease
Melanocytoma
- jet black lesions of optic nerve head
- feathery borders often
- more prevalent in black patients
- may increase in size
- benign
- may develop elsewhere in uveal tract
- nevus cells densly packed with melanin granules
- spindle and large polygonal cells seen after melanin bleaching
Secondary
Tumors arising
from the Optic Nerve
Optic Nerve Meningioma
- middle aged women most common
- prognosis usually good for primary optic nerve meningioma of adulthood
- can be seen in children
- tumors usually more aggressive in children
- optociliary shunt vessels
- optic nerve head edema can occur
- irregular distention of optic nerve sheath on imaging
- arise from meningothelial cells in arachnoid
- may invade into and beyond dura
- psammoma body- mengiothelial cells form sand like granules of focal calcifications
- tend to grow around and compress optic nerve causing atrophy
Optic Nerve Glioma
- axial proptosis
- associated with neurofibromatosis
- indolent in childhood and more aggressive in adulthood
- develops from and expands the substance of the optic nerve
- meningial hyperplasia may accompany glioma
- can be histologically indistinguishable from meningioma
- doesnt spread outside the dura as opposed to meningioma
- tend to be intradural
Pilocytic Astrocytoma
- proliferating glia are delicate and elongated like hairs
- Rosenthal fibers= degenerated eosinophilic glial fibers
- microcysts may form and coalesce suddenly leading to sudden proptosis and doesnt
indicate malignancy
Retina and Vitreous Pathology
Retinal anatomy and pathologic response to injury
Retinal Layers
- internal limiting (ILM)
- true basement membrane- PAS positive
- produced by Mueller cells
- normally no cells or tissue line ILM
- new vessels break through in neovascularization
- membranes lie over ILM in proliferative vitreoretinopathy and may wrinkle retina
underneath
- extenal limiting
- not a true basement membrane
- adhesions of Mueller cells with photoreceptors
- defines lumen in Flexner-Wintersteiner rosettes
- at level of inner and outer segments of photoreceptors
nerve fiber layer
- contains axons of ganglion cells
- hemorrhage appears flame shaped in this layer
- thins in end-stage glaucoma
ganglion cell layer
- nuclei of axons contined in nerve fiber layer
- multiple cells thick in macula
- accumulation of storage material in neuronal storage diseases such as Tay-Sachs disease
- loss of nuclei in end-stage glaucoma
inner plexiform layer
- cell processes between ganglion cells and inner nuclear layer
inner nuclear layer
- nuclei of Mueller cells
- astrocytes
- bipolar cells
- other neurons
outer plexiform layer
- aka. Henles layer
- oriented obliquely in normal macula causing appearance of macular "star" when
exudates accumulate here
- cell processes between photoreceptors and inner nucelar layer
- hemorrhage here appears dot-like
- well circumscribed ("hard") exudate occur here
outer nuclear layer
- nuclei of the photoreceptors
photoreceptor layer
- inner and outer segments separated by outer limiting membrane
retinal pigment epithelium (RPE)
- phagocytosis of outer segments of photoreceptors
- blood retinal barrier
- exchange of light and heat energy
- derived from outer layer of optic cup
- responds to injury by hyperplasia
- hexagonal cells
- form drusen
- contributes to formation of pre- and retro-retinal membranes
- osseous metaplasia-RPE can deposit bone in phthisis
Bruchs membrane
- basement membrane of RPE
- inner aspect of choriocapillaris
- middle elastic layer may calcify and fragment in
- angioid streaks
- macular degeneration
- aging
choroid
- derived from mesoderm; fibroblasts and vessels
- populated by melanocytes; neural crest
- melanocytes are capable of neoplastic responses
Regional variations in
retinal anatomy
- thickness of ganglion cell layer
- oblique orientation of Henles layer
- thickening of RPE
perepherial retina
- non-pigmented ciliary epithelium merges into retina
- vitreous base straddles perepherial retina and pars plana
Retinal Blood Supply
- supply up to inner 2/3 of inner nuclear layer
- interruption in BRAO causes retinal necrosis and atrophy only in these areas
- in contrast glaucoma causes only atrophy in nerve fiber and ganglion cell layers
choriocapillaris -supplies outer 1/3 of inner nuclear layer and outer layers
- no cross communication between retina and choroidal circulation
Retinal vascular diseases
Retinal Vascular Fundamentals
Arteriosclerosis
- generic term meaning "hardening of arteries"
- encompases the following
- athrosclerosis
- narrowing of lumen,
- athrosclerotic plaque (athroma)
- inside internal elastic lamina
- made of cholesterol and can calcify
- arteriolosclerosis
- thickening of walls of arterioles
- copper wiring
- silver wiring
- calcific medial sclerosis
- deposition of clacium at level of internal elastic lamina and/or media
- vessel may become palpable
- associated with aging
Vascular Occlusion
- thrombosis
- intravascular clotting
- thromboembolism- piece of clot breaks off and travels distally
- clot
- extravascular blood and blood products
- hyphema is an example
- embolus
- material that has been carried through the vessels to a distant intravascular site
- calcific
- originate from calcific heart valves or calcified athromatous plaques
- intravascular white refractile bodies
- stain dark red on H&E
- athromatous or cholesterol
- yellow intravascular plaques
- seen ophthalmologically as Hollenhorst plaques
- usually originate from carotid athrosclerotic plaques
- thromboemboli
- source cardiac or cartoid arteries
- seen as small intravascular grey-white opacities
- referred to as "fibrin-platelet" emboli
- fat
- complicate trauma to long bones
- oil-red-o stain
- talc- seen in IV drug abusers
Hypertension
- affects major vessels as well as microcirculation of retina and choroid
- arteriolosclerosis with sustained mild to moderate
hypertension
- malignant hypertension
- retinal hemorrhages in outer retinal layers
- exudates- fibrin and other proteins collect in retina especially in outer plexiform
layer (Henles layer)
- nerve fiber layer infarcts
- Eschnig spots- choroidal infarct
- optic nerve head edema lateral displacement of photoreceptors
- serous retinal detachment
- macular star with oblique orientation of exudates in Henles layer
Neovascularization
- response to conditions that produce retinal ischemia
- vascular endothelial growth factor (VEGF) is upregulated in retinal hypoxia
- intraretinal vascular proliferation precedes neovascularization
- growth of blood vessels into the vitreous side of internal limiting membrane
- with no posterior vitreous detachment (PVD) and intact hyloid face vessels remain in
the plane between the hyloid and ILM
- if a PVD occurs the vessels can be streached and bleed
- if hyloid face is not intact vessels can grow into vitreous
- may lead to tractional retinal detachment because
- myofibroblasts in membrane contract
- blood from the membrane organizes and contracts
- neovascularization of the disc
- optic nerve head lined by membrane analogous to the ILM
- vessels on vitreous side of this membrane are noevascularization
- iris neovascularization
- ectropion uveae
- fine vessels at pupil margin
- eccentric pupil
- effacement of iris crypts
- tissue lining anterior border of iris leaving iris border flat
- myofibroblasts may contract causing perpeherial anterior synechais and neovascular
glaucoma
- are fragile and may bleed producing hyphema
Vascular occlusive disorders
Retinal artery occlusion
- first leads to death of retinal neuronal elements
- retinal becomes opaque rather than transparent
- cherry red spot
- color of normal choroid is transmitted through fovea
- surrounding retina is thick and edematous
- in Tay-Sachs disease spot is due to acclumulation of acclumulation of material in
ganglion cells and relative lack of ganglion cells in fovea transmits choroidal color
- box carring of arterioles- result of stagnant flow
- post necrotic retinal atrophy of inner retinal layers
- no reactive gliosis
Retinal vein occlusion
- arteriole and venule share same adventitia in optic nerve and retina
- arterolosclerosis compresses venule resulting in stasis
- gradual progression to poor perfusion, ischemia
- ischemia of the pericytes and endothelial cells of microcirculation leads to weakness
and retinal hemorrhages of nearly full retinal thickness
- leakage of fluid occurs causing exudation and edema
- retinal ischema may lead to neovascularization of iris, disc or retina
Diseases of microcirculation
Diabetes
- basement membranes
- increased amounts of basement material is layed down throughout body. Thickening of
basement membrane of ciliary body epithelium in pars plicata retinal vessels and choroidal
vessesl is characteristic
- interface between corneal epithelium and basement membrane my be disturbed causing
recurrent erosions
- microcirculation changes
- decreased number of pericytes
- microaneurysms
- often too small to see ophthalmologically
- most of what is called microaneurysm is dot heme
- better seen by flourscein angiography
- increase permeability leading to
- macular edema
- exudates- tend to settle in outer plexifom layer
- hemorrhages
- neovascularization
- lacy vacuolization of iris pigment epithelium accompanies hyperglycemic states
Sickle cell disease
- retinopathy unusual in SS disease but occurs in SC, Sthal and in S trait
- neovascularization
- may produce "sea-fans" that may produce vitreous hemorrhage
- hemorrahges
- salmon patches- fresh intraretinal hemorrhage
- iridescent spots- hemosiderin from previous hemorrhage
- black sunburst- subretinal hemorrhage with RPE hyperplasia
Retinopathy of Prematurity
- temporal retinal circulation incompletely developed at term
- elevated levels of oxygen may lead to vasospasm then distal retinal ischema.
- Retinal neovascularization can occur leading to tractional retinal
detachment
Coats Disease
- usually unilateral exudative retinal detachment
- retinal telangiectasis- very leaky
- no neovascularization
- foam cells and cholesterol clefts in subretinal space- not specific
Peripheral retinal degenerations
Langes fold
- artifact in infants
- rolled up retina at the ora
Pavingstone degeration (cobble stone)
- presumably related to abnormalties in choroidal circulation
- clinical features
- common in later life
- up to 25% of autopsy eyes
- bilateral in 30%
- well demarcated circular areas 0.5 to 2 disc diameters in size
- center pale, edges have variable pigmentation
- histologic features
- atropy of outer retinal layer, RPE and choriocapillaris
- RPE hypertrophy may be seen at the edges
Lattice degeneration
clinical features
- linear, circumferentially oriented zones of retinal thinning between ora and equator
- most commonly occur superiorly, unusual in horizontal meridians
- 6-11% of population
- may be pigmented
- may be crossed by fine white lines and sclerotic vessels
- liquefaction of ovelying vitreous
- may contain atrophic holes that arent predisposed to retinal detachment
- traction by vitreous after PVD can cause a horseshoe tear and rhegmatogenous retinal
detachment (RRD)
- 30% of RRD associated with lattice although it is uncommon for someone with lattice to
develop an RRD
histologic features
- involves the vitreoretinal interface
- focal discontinuity of ILM
- thinning of inner retinal layers leading to round atrophic holes
- sclerotic vessels
- liquifaction pocket of vitreous overlying lattice
- strong adhesions of vitreous to margins of lattice
Pars plana cysts
- seen in up to 16% of normal population
- increase in incidence with age
- more numerous in patinets with myleoma or other dysproteinemic states
- clear in vivo
- opaque after formalin fixation
histologic features
- may contain hyaluronic acid
- may immunoglobulins in myleoma
Perepherial cystoid degeneration
- typical cystoid degeneration
- clinical features
- very common; up to 87% in autopsy series
- pathology located immediately posterior to ora
- colescence of cysts may lead to typical retinoschisis
- histologic features
- cyst-like spaces at level of outer plexiform layer
- demarcated by columns of Mueller cells
- contain hyaluronic acid
reticular perepherial cystoid degeneration
- seen in 18% of the population
- located posterior to a zone of typical cystoid degeneration
- may appear to follow course of retinal vessels
- may predispose to reticular (bullous) retinoschisis
- split in the neve fiber layer as opposed to outer plexiform layer
Retinoschisis
- a split within the layers of the retina as opposed to a retinal detachment with is a
split between the neurosensory retina and RPE
- Typical degenerative retinoschisis
- present in 1% of population
- bilateral in 35% of affected
- affects inferior temporal quadrant usually
- adjacent to area of typical cystoid degneration
- smooth surface with domed elevation, cavity is optically negative
- histologic features
- split in outer plexiform layer
Reticular (bullous) retinoschisis
- ususally found in assoication with reticular cystoid degeneration
- bullous intraretinal cavity
histologic features
- split in nerve fiber layer of retina
Congenital X-linked retinoschisis
- x-linked
- most common inferior temporally
- may involve macula
- wide split in retina may be mistaken for vitreous veils
- blood vessels bridging schisis cavitiy can bleed
- macular stellate lesion
histologic features
- split within nerve fiber layer
Retinal detachment
- Separation between neurosensory retina and RPE
- Categories
-
non-rhegmatogenous
- not caused by a retinal break
- types:
- exudative- caused by retinal vascular anomalies
- solid- caused by choroidal neoplasms
-
rhegmatogenous
- caused by a retinal break
- pathophysiology
- vitreous adherent to retina in three zones
-
vitreous base
-
optic nerve
-
along major vessels
- in certain conditions, vitreous more adherant e.g. lattice
degeneration
- in a PVD clean separation usually happens but retina can tear along areas of strong
attachment
- the edge of the tear is held open by the anteriorly displaced vitreous
- Retinal breaks
- tears- caused by traction
- holes
- Atrophic changes: usually dont cause detachment
- Traction
- Preretinal membranes- can cause either rhegmatogeous or non-rhegmatogenous retinal
detachments
- Artifact vs. Real
-
artifact
- good presentation of photoreceptor
- pigment adherent to photoreceptors
- subretinal fluid is usually missing. (subretinal fluid is a variable finding in RD)
- sharp edges
-
real
- rounded edges
- photoreceptors missing- indicating chronic RD
- subretinal fluid is a variable finding
- retinal changes in detachment
-
early:
photoreceptor degeneration
-
later
- gliosis
- intraretinal cysts
Proliferative vitreoretinopathy
- preretinal membranes over the ILM derived from glial cells that have migrated through breaks in ILM
- RPE cells that have migrated through a full thickness retinal break
- "hylocytes" of the cortical vitreous
- myleofibroblastic elements contract distorting retina and cause fixed retinal folds
- retroretinal membranes- just under photoreceptor layer
Macular Diseases
Age-related macular degeneration (AMD)
- Clinical aspects
- most common cause of blindness in elderly in USA
- atrophic changes
- drusen
- loss of macular reflex
- pigment epithelial atrophy
- exudative and hemorrhagic changes- choroidal neovascular membrane
- organization of blood with scar
- glial elements
- fibroblasts from choroid, through break in Bruchs membrane
- hyperplastic and metaplastic RPE
- Pathology
- Age-related changes
- the phagocytosed photoreceptor elements are digested and the by-products deposited
in Bruchs membrane by the RPE causing thickening of Bruchs membrane
- collagen and basement membrane material is layed down by the choriocapillaris leading
to compression and partial dropout of the vascular layer
- with age Bruchs may calcifiy and crack
- RPE and choriocapillaris function as a unit
- destruction of the RPE can lead to atropy of choriocapillaris
- widespread atrophy of choriocapillaris can lead to atropy of RPE
- Atrophic macular degeneration
- Exudative macular degeneration
- neovascularization from choriocapillaris breaks through Bruchs membrane leaking
fluid into sub-RPE space= serous pigment epithelial detachment (PED)
- physiologic barrier between sub-RPE space and sub-retinal space may become disrupted
causing a serous retinal detachment
- Hemorrhagic macular degeneration
- neovascularization in the sub-RPE space may hemorrhage and break into the sub-retinal
space or even vitreous
- sub-RPE hemorrhage can be mistaken for a melanoma
- Disciform degeneration
- organized scar partially by RPE
- color of scar depends upon amount of RPE reaction
- bone may be deposited by osseous metaplasia of the RPE
Cystoid macular edema
related to intraocular inflammation
post-surgery (Irvine-Gass
syndrome)
secondary to perepherial retinal anomalities or tumors
Histologic features- cyst-like spaces in outer plexiform layer seen in late cases
Pathogenesis- two theories:
- vascular instability leads to leakage of intravascular fluids into the retina which
pool in the outer plexiform layer
- focal hydropic degeneration of the Mueller cells in th e region of the macula,
colescence of these degenerating cells leads to cyst-like spaces
Pathology of vitreous
- syneresis cavities
- posterior vitreous separation
- asteroid bodies
- calcified saponified fats
- usually bilateral but may be asymmetrical
- vision loss uncommon
- synchesis scintillans (cholsesterolosis bulbi)
- result of vitreous hemorrhage
- usually unilateral
Intraocular tumors
Uveal nevus and melanoma
arise from uveal melanocytes
uveal melanocytes vs. RPE
uveal melanocytes
derived from neural crest
rare hyperplasia
form nevi and melanoma
RPE
derived from optic vesicle
frequent hyperplasia
rarely form adenomatous neoplasms
cell types
normal uveal melanocytes are spindle shaped and dendritic
nevus cells
spindle shaped like normal melanocytes
nuclei lack nucleoli
spindle A cells
lack conspicuous nucleoli
basophilic stripe along long axis of elongated nucleus
lesions composed exclusively of spindle A are considered nevi
spindle B cells
have conspicuous nuclei
elongated nuclei
epithelioid cells
not spindled
look the least like normal uveal melanocytes
abundant cytoplasm
large nuclei with prominent nucleoli
uveal melanoma classification based on cell type (modified Callender classification)
grouped with nevi
all spindle A
excellent prognosis
spindle cell melanomas
composed of spindle B or mixture of spindle A and B
good prognosis
mixed cell type
both spindle cells and epithelioid cells
intermediate prognosis
necrotic cell
cell type cannot be determined
intermediate prognosis
epitheloid melanomas
composed of epithelioid cells
worst prognosis
fasicular melanoma
variant of spindle cell melanoma
resembles Antoni A pattern of Schwanomma
no prognostic significance
metastasis- likelyhood increases with increasing proportion of epitheloid cells
clinicopathologic correlations
cutaneous/conjunctival nevi vs. uveal nevi
cutaneous/conjunctival nevus
derived from melanocytes
stages of development; junctional, compound, intradermal
congential nevi are larger than acquired nevi and have greater tendancy to give rise to
melanoma
most acquired nevi will not evolve to melanoma
uveal nevi
derived from melanocytes
grow without stages of development
most are acquired
congeniatal ocular melanosis more diffuse than focal nevus and may be prone to develop
uveal melanoma
most acquired nevi will never develop into melanoma
iris nevi
tend to develop in blue-eyed people in inferior one-half of iris
may distort the pupil
may grow but usually not progressively and they dont usually encroach on the
angle
iris melanoma probably have little risk of metastasis
choroidal nevi
clinical features
relatively flat and small
may be associated with overlying drusen or small subretinal fluid pockets
histologic features
no scleral invasion or extraocular extension
contain bland spindle cells and no spindle B or epithelioid cells
uveal melanoma
metastasis generally first appear in liver
rarely gain access to sub-conjunctival space and spread to lymph nodes via lymphatics
iris melanomas
excellent prognosis because they are usually found early and probably dont
metastasize often
if they invade into the angle, may cause elevation of intraocular pressure
ciliary body and choroidal melanomas
may arise from pre-existing nevi, congenital ocular melanosis or de novo
prognosis for life depends upon
size- maximum basal diameter is more important than elevation in predicting survival
location- prognosis worsens with more anterior location
extraocular extension- usually follow an aggressive course
extention into voretx veins
around ciliary nerves
into or through sclera
escape into subconjunctival space
rarely spread into optic nerve as opposed to retinoblastoma
Axenfelds nerve loop should not be confused with anterior extraocular extension
of ciliary body melanoma
growth pattern- the following patterns have a more serious prognosis
ring melanoma- tumor grows circumferentially around the major circle of the iris
diffuse melanoma- covers the majority of the posterior pole
cytology- the likelyhood of metastasis increases with greater proportion of epitheloid
cells
mitotic activity- prognosis worsens with increasing numbers of mitoses
changes to other ocular structures
Bruchs membrane can rupture leading to mushroom or collar-button appearance
RPE- accumulation of drusen, lipofucin (orange pigment), and fibrous metaplasia of
overlying RPE
retina- overlying non-rhegmatogenous (serous) detachments, photoreceptor degeneration,
tumor may also invade overlying retina
inflammation- may complicate necrotic melanoma
elevation of IOP by:
direct invasion of angle
mass effect of ciliary body melanoma causing secondary angle closure
neovascular glaucoma
melanomalytic glaucoma- pigment released by tumors is phagocytosed by macrophages, the
pigment or macrophages clogs meshwork
Retinoblastoma
most common intraocular tumor of childhood
shows no predilection for race, gender or laterality
up to 30% of cases are bilateral
clinical presentations
leukocoria
differential diagnosis- congenital cataract, PHPV, Coats disease, coloboma,
retinopathy of prematurity, toxocara
strabismus- exotropia or esotropia
heterchromia- secondary to iris neovascularization
genetics
heritable
all cells in the body contain the gene mutation
may or may not have family history
seconday primary tumors may develop within or outside field of radiation treatment
retinoblastoms may appear as a solitary tumor, multiple tumors, unilateral, bilateral,
or trilateral (involving pineal gland)
bilateral and trilateral are markers of heritable disease
tumors appear 13-16 months
non-heritable
mutation confined to retina
no family history
not transmissable
second primary tumors do not develop
solitary tumor confined to one eye
tumors appear 20-27 months
molecular genetics
gene: long arm chromosome 13, two alleles
normal functioning gene supresses tumor formation
development of retinoblastoma requires both alleles to be abnormal
when one allele is inherited higher likelyhood of developing tumor from a new mutation
in the other allele
the mutation in the second allele must have occurred early in embryogenesis in order
for the second allele to be passed on to offspring.
Gross pathology
endophytic- growth of tumor into vitreous
exophytic- growth into the subretinal space
tumors may display elements of both endophytic and exophytic growth
seeding into vitreous and even anterior chamber simulating hypopion
may grow into choroid or optic nerve and travel through CSF and seed in the
subarachnoid space
may also grow outside the eye
may undergo partial or complete regression
calcium can be seen in the tumor by ultrasonography
Microscopic pathology
alternating zones of viable tumor centered around blood vessels and necrosis
basophilic layer around tumor vessels is DNA from dead tumor cells, this layering can
be seen in blood vessels away from the tumor
calcium deposition
poorly differentiated cells as well as more differentiated zones can be seen
Homer Wright rosettes
no central lumen, center occupied by a neurofibrillary tangle
not specific to retinoblastoma, also seen in meduloepithelioma and neuroblastoma
Flexner-Wintersteiner rosettes
one row of cells with a central clearing
contrast to dysplastic retina which has multiple layers of cells forming rosettes
specific for retinoblastoma
Fleurettes
marker of photoreceptor differentiation
tumors with fleurettes may be more resistant to radiation
Secondary effects on the eye
non-rhegmatogenous retinal detachment
iris neovascularization- acquired heterochromia and hyphema may develop
eye fills with tumor
Prognostic features for life
most important: presence or absence of tumor outside of eye
tumor to surgical margin of resection of optic nerve
orbital extension
worse if tumor invades sclera, choroid or optic nerve even if margins are clear
tumor may spread along optic nerve into CNS
undergo hematogenous spread to other organs
spread through lymphatic system if extends into subconjunctival space
retinoma or retinocytoma- possibly benign variant of retinoblastoma or a well
differentiated retinoblastoma
Prognostic features for vision
depends upon size, location and presence or absence of seeding
Reese-Ellsworth classification
Metastasis
metastasis to the choroid as a group is most common intraocular tumor in adults
most common sources: breast in women, lung in men
more common in the posterior pole but may affect the iris
prognosis for life is poor after metastisis to the eye
Tumors of pigmented and non-pigmented epithelium
RPE is more prone to hyperplasia than neoplasia
occasionally RPE responses may simulate melanoma
Lymphoid lesions of retina and choroid
Primary lymphoma of the retina and CNS
presents as unilateral or bilateral uvetitis but eye is not red
ocular findings may precede development of lymphoma in the brain
less commonly primary CNS lymphoma precedes retinal involvement
retina is primarily involved but there is often spillover into the vitreous making
vitreous biopsy a way to make a diagnosis
vitreous biopsy shows atypical lymphocytes that are almost always B-lymphocytes
lymphocytes aggreagate in retina and sub-RPE space
cells in the choroid are usually benign lymphocytes
treatment: palliative radiation of the eye and brain
prognosis for life is poor
Secondary involvement of the Choroid in systemic lymphoma
involves primarly the choroid not the retina
Reactive lymphoid hyperplasia of the choroid
diffuse uveal thickeing by mature lymphocytes
germinal centers may be present
may spill over into epi-scleral tissues
clinically may mimic metastatic lesions, uveal melanoma, or posterior scleritis
usually follows a benign course
Phacomatoses
Neurofibromatosis (see Neuro notes: Neurofibromatosis)
von-Recklinghausen disease
autosomal dominant with irregular penetrance
some sporatic cases
systemic features
café-au-lait spots
six or more
greater than 1.5mm in dameter
axillary freckling
neurofibromas
benign overgrowth of Schwann cells, endoneural fibroblasts and axons in perepherial
nerves
an isolated neurofibroma doesnt make diagnosis
however plexiform neurofibroma is sufficent to make diagnosis of neurofibromatosis
scoliosis
schwannoma or malignant schwannoma
pheochromocytoma
malignant neurofibrosarcoma
ophthalmic features
prominent corneal nerves
glaucoma with possible buphthalmos- possible causes:
involvement of angle structures by neurofibroma
defective innervation of angle structures
immature angle
Lisch nodules
nevi of anterior iris stroma
diagnostic
may appear in childhood and be an early manifistation
neurofibromas and schwannomas of the uvea
optic nerve glioma
malignant schwannoma of orbit
hypoplasia of greater wing of sphenoid
permits transmission of pulsations of CSF
pulsating proptosis
Tuberous Sclerosis
Bournevilles diesease
autosomal dominant
Systemic features
adenoma sebaceum
angiofibroma of the sebaceous glands
commonly seen on cheeks and around nasolabial folds
may be mistaken for acne
Shagreen patch
roughened skin, like an orange peel
frequently seen on the back
periungual fibromas
ash-leaf spot
areas of skin hypopigmentation frequently on the back
lesion in the shape of an ash-leaf
may be the earliest sign
others
rhabdomyomas of the heart
angiomyolipomas of the kidney (an example of a hamartoma)
brain frequently involved by:
astrocytic hamartoma
overgrowth of astrocytes (glial cells)
including sub-ependymal giant astrocytoma
may be shaped like potatoes- "tuberous"
may account for seizures
may be partially calcified and recongnizable radiographically
some are mentally retarded
ophthalmic features
retinal astrocytic hamartomas (astrocytoma)
focal overgrowth of astrocytes (glial cells) in the retina
optic nerve astrocytoma
sometimes incorrectly identified as giant drusen of optic nerve
Angiomatosis Retinae
when no CNS involvement called: von Hippels disease
when CNS is involved called: von Hippel-Lindau disease
autosomal dominant
systemic features
hemangioblastoma of cerebellum or spinal cord
contain capillaries with foamy stromal cells of uncertain origin
cysts of pancreas, kidneys and epididymis
renal cell carcinoma
pheochromocytoma
ophthalmic features
retinal hemangioblastomas
bilateral in 50%
have feeding vessels; arteriole and vein
retinal exudation
contain capillaries and foamy stromal cells of uncertain origin
may involve the optic nerve head
-hemangiomas in the retina and ONH
-spherical, orange-red c/ feeder and drainage vessel
-mult and bilat 50%
-leakage? serous RD
-aut dom (incomplete pen) vs. sporadic.
-20% c/ CNS hemang (c-bell, pons, spinal)
-cysts of kidneys, panc, liver, ovary, epidyd
-renal cell CA, Pheo, meningiomas
-die young from renal cell or c-bell tumor.
-Tx: laser of hemangiomas, careful f/u.
Encephalotrigeminal angiomatosis
Sturge-Weber syndrome
no inheritance pattern
Associated with glaucoma (see Sturge-Weber
in Glaucoma notes)
systemic features
port-wine stain
skin lesion
telangiectasis, not an angioma
involment of the skin in distribution of first division of cranial nerve V suggests
intraocular involvement
angiomatous malformations of the meningies
may cause seizures
meningeal calcification seen radiographically
ophthalmic features
angiomas
choroidal, diffuse cavernous hemangiomas
episcleral vascular malformations
may lead to elevated episcleral venous pressure and glaucoma
congenital glaucoma
malformation of angle
Congenital Abnormalities
Defects of embryologic development
Chromosomal Syndromes
Secondary to infection
Defects of embryologic development
- Aplasia: total failure of a structure to form
- Anophthalmos: absence of the globe
- Primary: optic vessicle doesnt envaginate, rare and sporadic.
serial sections through orbit needed to confirm absence of eye
- Secondary: malformation in the anterior portion of the neural tube
resulting in failure of optic vessicle to form, lethal malformation
- Consecutive: optic vessicle forms then degenerates.
- Not to be confused with cryptopththalmia which may involve: absence of separate eyelids,
microphthalmia, smooth skin over globe, corneal fusion to skin over globe
- Hypoplasia: incomplete development of a structure, contrast with atrophy- loss of a
substance
- Abnormality of fusion
- Cyclopia: total fusion of globes, associated with holoprosencephaly (failure of
lobes of brain to separate-a lethal condition)
- Synophthalmia: abnormal fusion of the eyes, more common than cyclopia, also
associated with holoprosencephaly,
- Failure of an embryonic structure to close
- Coloboma: cleft or defect in the normal continuity of a
structure
- typical coloboma: occurs along the inferionasal portion of eye
- iris or ciliary body: ciliary body coloboma may occur with formation of
cartilage, usually found in Trisomy 13
- retinal-choroidal coloboma: retinal detachment at edge of coloboma
may be difficult to repair, absence of uvea and RPE, retina remains as a thin overlying
glial membrane
- Often associated with a cyst which can be larger than the eye itself
- atypical coloboma: occur outside the inferonasal portion of the eye and location of the
embryonic fissure. May result from congenital infections such as toxoplasmosis
- Failure of an embryonic structure to regress
- hyloid system: regression normally begins centrally and continues both anteriorly
and posteriorly
- Bergmeisters papilla: failure of posterior portion of hyloid system to regress,
comes off optic nerve head
- Mittendorfs dot: failure of anterior portion of hyloid system to regress
- Abnormal development of a structure
- Retinal dysplasia: multilayered rosettes, accompanies Trisomy 13
- Anterior chamber
- Designated as anterior chamber cleavage syndrome or "mesodermal" dysgenesis
syndrome
- May be from abnromal migration of neural crest tissues
- Posterior embryotoxin: prominent anterior position of Schwalbes line (in up to 15%
normal)
- Anterior embryotoxin is the same as juvenile arcus- deposition of lipid
- Axenfelds anomality: posterior embryotoxin + prominent iris processes, glaucoma in
up to 50%, displaced pupil
- Reigers anomality: posterior embryotoxin + prominent iris processes + hypoplasia
of iris
- Reigers syndrome: Reigers anomality plus dental and skeletal anomalies
- Peters anomality: central absence of Decemets membrane and endothelium,
associated with adhesions of iris or lens to posterior corneal defect
Chromosomal Syndromes
- Trisomy 21
- Epicanthal folds
- Brushfield spots: seen in as many as 85%
- may be seen in the normal population
- normal or hypercellular areas of iris stroma adjacent to areas of stromal hypoplasia
- Keratoconus with a tendancy for hydrops
- Retinoblastoma
- Cataracts
- Trisomy 13
Congenital anomalities
secondary to infection
- Congenital syphilis
- Systemic findings
- mental retardation
- saddle deformity of the nose
- Saber shins
- dental malformations
- Ocular findings
- chorioretinal scars
- optic atrophy
- interstitial keratitis (delayed finding) and assoiciated glaucoma
- Congenital rubella
- Systemic findings: congential heart disease, deafness
- Ocular findings
- congenital cataract
- retention of lens epithelial nuclei in nucleus of lens
- virus can be harbored in the lens
- congenital glaucoma
- hypoplasia of the iris dilator- meiosis
- "salt and pepper" pigmentary retinopathy- alternating hypertrophy and atrophy
of RPE
- Cytomegalic inclusion disease
- Systemic findings
- intracranial calcifications
- hepatosplenomegaly
- anemia
- Ocular findings: chorioretinitis
- Congenital toxoplasmosis
- Sytemic findings
- intracranial calcifications
- seizures
- mental retardation
- Ocular findings: bilateral chorioretinal macular scars secondary to
chorioretinitis
Lens Pathology
Anatomy
closed epithelial system
lens epithelium basement membrane is the lens capsule
lens epithelium "infoliates" instead of exfoliates
constant accumulation of lens epithelium causes continued lens thickening and cataract
of maturity
nuclear sclerotic cataract- accumulation of urochrome pigment in nucleus
homogeniztion of lens neucleus is histologic marker of nucelar sclerosis
vision cannont be predicted by histologic appearance of the lens
avascular
epithelium is totally dependant upon acqueous for nutrition
high IOP can shut down acqueous flow and cause focal necrosis of lens epithelium
seen in acute angle closure glaucoma
glaucomflecken- antrior evanescent lens opacities that resolve with lowering IOP
posterior synechias may cover lens epithelium walling off acqueous causing epithelial
necrosis
lens sensitive to abnormalities in chemical composition of acqueous
high levels of glucose as in diabetes can lead to sorbitol accumulation through the
aldose reductase pathway, high levels of sorbital may play a role in diabetic cataract
formation by altering the osmolarity of the lens
high levels of galactose in galactosemia leads to an accumulation of galactitol which
may lead to cataract by same pathway as in diabetes
lens proteins are sequestered from the immune system perhaps explaining the
pathogenesis if phacoantigenic (a.k.a phacoanaphylactic) endophthalmitis
changes in size and shape
excessive lens thickening may lead to pupillary block and glaucoma- phacomorphic
glaucoma
microspherophakia
increased risk of pupillary block with iris miotics
laxity of zonules allows lens to become incarcerated in the pupillary aperature
nanophthalmos- lens is normal size but the globe is small, therefore the lens is too
big for the eye- inappropriate size of lens may lead to pupillary block and glaucoma
lens zonules
originate from the pars plana and insert on lens capsule
physiology of accomodation involves anterior/posterior shortning of zonules rather than
circumferential constriction of a ring
may weaken leading to subluxation- malpositioning of the lens in the posterior chamber
or luxation (dislocation) of the lens into the anterior chamber or vitreous.
subluxation/luxation seen in:
syphilis
Marfans syndrome
Weill-Marchesani syndrome
homocystinuria
sulfite oxidase deficency
sectoral absence of zonules can be seen in coloboma
Pathophysiologic responses to injury
capsule
thins causing either anterior or posterior bulging = anterior or posterior lenticonus
true exfoliation - capsule may split in response to infrared radiation
pseudoexfoliation
basement membrane material deposits
this material accumulates on iris, ciliary body, zonules as well as throughout the body
it accumulates even after lens is removed
may cause glaucoma and weaken zonules
pigment may deposit on capsule
copper may deposit within lens capsule
sunflower cataract- Wilsons disease
intraocular foreign body
may be focally thickened- "excrescence" on internal surface of lens seen in
Lowes syndrome, Down syndrome and Miller syndrome
epithelium
necrosis- as in glaukomflecken
fibrous metaplasia-
anterior subcapsular cataract
often after posterior synechias induce pupillary block and decreased acqueous flow to
lens epithelium
iron accumulation- siderosis bulbi
normally lens epithelium not seen posterior to equator
epithelial cells can migrate posterior to equator, lose contact inhibition and assume
an altered morphology = Wadl cells or balloon cells in posterior subcapsular
cataract
posterior subcapsular opacity- epithelium may grow over capsule after cataract
extraction
Sommerrings ring cataract- accumulation of corticle material in fornices of
capsule after cataract extraction
Elschnigs pearls- accumulation of lens material on lens capsule after
cataract extraction
cortex
liqifaction
may partially liquify leading to bubbles or clefts
seen histologically as fragmented lens fibers
artifactitious cracking has squared off edges to the clefts
Morganian cataract
cortex totally liquifies
opacification of nucleus by nuclear sclerosis
sinking of nucleus inferiorly
calcium oxalate may accumulate in nucleus
liquified cortical material is non-antigenic but may seep though capsule and be
engulfed by macrophages which can clog the trabecular meshwork leading to phacolytic
glaucoma
lens protien laden macrophages may be demonstrated by examining aqueous from anterior
chamber paracentesis- macrophages have a granular eosinophilic cytoplasm
the denatured lens protein itself can also clog the meshwork
phacolytic glaucoma v. phacoantigenic endophthalmitis
phacolytic glaucoma
cortex is liquified and non-antigenic
capsule intact
cortical material in macrophages
phacoantigenic endophthalmitis
cotex is intact and antigenic
capsule is frequently ruptured
zonal granulomatous response, including PMN"s, lymphocytes and macrophages with
giant cells
see typeIII hypersensitivity
hypermature catract
cortical material has liquified and escaped
lens becomes shrunken and possibly calcified
nucleus
thickens through process of "infoliation" leading to nuclear sclerosis
accumulation of urochrome gives brown color
homogenization of nucleus is a marker of nuclear sclerosis
cataracts
any opacity of the lens
pathogenesis
metabolic
diabetes and galactosemia
heriditary
drug induced
prolonged corticosteroid use in posterior subcapsular cataract
infections
congenital rubella (Greggs syndrome)
can see retention of epithelial nuclei in anatomic nucleus of lens
also seen in trisomy 13 and Leighs necrotizing encephalopathy
cataracts of maturity
may be related to antioxidants, light exposure, diet
Orbit Pathology
Inflammations
sinus related
Orbital cellulitis
ethmoid sinusitis most common source of infection
preseptal cellulitis can progress to orbital cellulitis but less commonly than from
sinus disease
may result in orbital absecess
proptosis and erythema
CT scan can show sinus disease and abscesses
Mucocele
chronic sinusitis results in blockage of sinus drainage channels
sinus becomes distended with pressure and may erode into orbit
frontal, ethmoid and rarely sphenoid sinuses affected in adults
Mucormycosis
usually develops as a sinus infection in a debilitated patient
diabetics in DKA, leukemics, immunocompromised
however patient need not be debilitated
organism tends to invade vessels causing infarction of tissues
organism is non-septate with branching hyphae of variable widths that form branches at
90 degrees, wider than aspergillosis
systemic conditions
Graves orbitopathy
orbital involvement can occur in hypo-, hyper- or euthyoid Graves disease
most common cause of unilateral or bilateral proptosis
disease is bilateral but may be very asymmertric
lid retraction and injection around rectus muscle insertions
may result in massive enlargement of rectus muscles, most typically inferior rectus
histologically muscles are infiltrated by lymphocytes and plasma cells, expanded by
fibrosis and accumulation of acid mucopolysaccharides
thickening of muscles at the orbital apex may cause compressive optic neuropathy
Wegners granulomatosis
may present in the orbit in conjunction with pulmonary and renal involvement or may be
confined to the eye and orbit at the time of presentation
histologically vasculitis is prominent feature accompanied by granulomatous reaction to
necrotic collagen
Sjogrens Syndrome
lesions consist of lymphoepithelial lesions of the lacrimal gland with following
characteristics
destruction of acini of gland
lymphoid stromal infiltrate frequently with lymphoid follicles
lesion may evolve into lymphoma
hyperplasia of myoepithelial cells-epimyoepithelial islands
Orbital pseudotumor
may be generalized or localized to a portion of the orbit
onset
abrupt onset characterized by pain. Graves and lymphoid lesions appear gradually
children
both pseudotumor and Graves can affect children
lymphoma is a disease of adults, except Burkitts lymphoma
corticosteroids
pseudotumor responds promptly to high dose steroids
Graves and lymphoid hyperplasia/ neoplasia do not respond as dramatically
pathologic findings
depend upon stage of disease
early
dominant element may be lymphoid follicles mixed with other cells including
eosinophiles
T-cells are present in higher porportions than B-cells
vasculitis may be prominent
later
repair becomes noticable feature
deposition of fibrous connective tissue
inflammation still present
very late
lymphoid component diminishes and fibrous component dominates
at this point sometimes called "sclerosing" pseudotumor
orbital myositis
could be a co
mpartmentalized form of orbital pseudotumor
inflammation of muscle involves the tendon which is not the case in Graves
disease
histologically there is inflammation between surrounding muscle fibers
sclerosing dacryoadenitis
pseudotumor localized to the lacrimal gland
localization to Tenons capsule is visible on echo or CT
Lymphoid lesions
clinical presentation
middle-aged adults most common except in Burkitts lymphoma
onset gradual, no pain
predilection for involvement of lacrimal gland
lesions tend to "mold" around contour of globe
spectrum of pathology
benign reactive lymphoid hyperplasia
reactive lymphoid follicles with germinal centers and surrounding mature lymphocytes
no reactive scarring, as opposed to pseudotumor
predominance of T-lymphocytes
B-lymphocytes demonstrate a polyclonal proliferation
15-25% may develop systemic lymphoma
malignant lymphoma
most are B-cell tumors
Hodgkins disease and mycosis fungoides have been reported in the orbit
diffuse or follicular (nodular) patterns
frequently monoclonal proliferations detectable by testing for immunoglobulin markers
or gene rearrangement studies
75% of cytologically malignant orbital lymphoma will develop systemic lymphoma
atypical lymphoid lesion
not benign but not clearly lymphoma
since there is no normal lymphoid architecture in the orbit to compare with so these
lesions can be hard to sort out
marker studies used to differentiate these tumors
up to 50% will develop systemic lymphoma before obtaining a biopsy
lymphoplasmacytoid lesion
sheets of well differentiated lymphocytes many of which have cytologic features
suggestive of plasma cells
Dutsher bodies may be prominent
PAS positive intranuclear inclusions
a cytoplasmic invagination into the nucleus
germinal centers may be seen
dysproteinemia, immunoglobulin electrophoresis recommended
difficult to predict on an individual basis but some of these lesions progress to
systemic lymphoma
fresh frozen tissue is prefered for immunohistochemisty and is required for gene
rearrangement studies
workup/treatment
evalution by hematologist-oncologist
general physical exam to detect lymphadenopathy
CBC and diff
immunoglobulin electrophoresis
thoracic and abdominal CT or liver and spleen scans
bone marrow biopsy
peritrabecular lymphoid aggregates may indicate systemic lymphoma
not bone marrow aspirate
radiation therapy
shield the globe
2500-3500 rads
Introduction to orbital tumors
separate by age of presentation
tumors of adulthood do not commonly affect children
some orbital tumors of childhood are distinctive for this group
the behavior of the same neoplasm may be different in a child and an adult
therefore one can make the following generalizations:
Adults
most common vascular tumor of adulthood is cavernous hemangioma which does not affect
children
schwannomas and neurofibromas tend to affect adults
tumors of the lacrimal gland epithelium are seen in adults and are rare in childhood
secondary tumors of the orbit (metastatic tumors and invasion of orbit by sinus tumors)
are seen in adults not children
optic nerve meningioma is indolent in middle age
Children
most common vascular tumor of childhood is capillary hemangioma
orbital rhabdomyosarcoma is a tumor of childhood
lesions of orbital bones; eosinophilic granuloma and fibrous displasia tend to appear
in childhood
congenital tumors of the orbit; dermoid cyst and orbital teratoma
secondary tumors of orbit reflect tumors of childhood; metastatic neuroblastoma,
Ewings sarcoma, granulocytic sarcoma
optic nerve meningioma is aggressive in childhood
Orbital tumors of childhoold
vascular origin
capillary hemangioma
clinical features
1/3 present at birth and most clinically evident by 6 months old
frequently associated with a cutaneous component which appears red
blanches with pressure unlike nevus flammus (Sturge-Weber syndrome)
rarely presents with proptosis- unlike cavernous hemangioma of adults
most commoly presents with rapid enlargement of the mass without displacement of the
globe or proptosis
growth may be rapid up to six months and taper off
mass may be more prominent when child cries
nearly 80% regress with some signs of regression in the first year, most have regressed
by age 7
ambylopia is important consideration
tumor may press on cornea causing astigmatism and anisometropic ambylopia
pathology
follows clinical course
during rapid growth, sheets of proliferating endothelial cells may be seen
mitoses seen- not a marker of malignancy in this tumor
not encapsulated, unlike cavernous hemangioma, but infiltrative, often frustrating
total surgical excision
during period of cessation of growth, capillary like lumina are more apparent
during the phase of regression, cellularity deminishes and more vascular spaces become
apparent, collagen is deposited in and around tumor
lymphangioma
clinical features
may present in the eyelids, conjunctiva, or orbit
growth is slowly progressive
may have hemorrhage into lesion (chocolate cyst) suddenly worsening proptosis
doesnt reqress
may enlarge during bouts of upper respiratory infections because of increase in
accompaying lymphoid tissue
pathology
there are capillary, cavernous and cystic lymphangiomas
spaces are lined by endothelial cells without pericytes or smooth muscle
associated lymphoid follicles
muscle origin
rhabomyosarcoma
clinical features
rapid evolving proptosis with our without ptosis
subconjunctival mass in botryoid type
average age of onset 7.8 years
rare over age 20
may arise de novo in the orbit or invade orbit from paranasal sinuses
biopsy should be done as quickly as urgently as possible
tumor may grow within days to weeks
combination radiation and chemotherapy should be started immediately after diagnosis is
made
with radiation and chemotherapy the survival rate is 90% but if tumor has spread from
orbit to paranasal sinuses survival drops to 55%
pathology
doesn't arise from extraocular muscles but thought to arise from "mesenchymal
rests"
types
pleomorphic
probably doesn't affect the orbit
forms in skeletal muscles of adults
alveolar
tumor with bright eosinophilic cytoplasm are shed into spaces lined by fibrous tissue-
resemble "alveoli"
numerous tumor giant cells
worse prognosis than embryonal type
embryonal
loose arrangement of tumor cells, many with scant cytoplasm
cells appear to be falling apart from each other
difficult to make diagnosis by light microscopy alone
rhabdomyoblasts seen on trichrome stain
cross striations
primitive Z bands by electron microscopy
muscle specific actin and myosin by immunohistochemisty
if above tests don't confirm tumor as myleoblastic, designated "embryonal sarcoma,
type undetermined"
botryoid
subconjunctival variant of embryonal rhabdomyosarcoma
neural origin
plexiform neurofibroma
orbital involvement by neurofibromatosis more common in childhood
unencapsulated proliferation of Schwann cells, axons and endoneural fibroblasts
see neurofibromatosis
fibro-osseous lesions of bone
fibrous dysplasia (monostotic variant)
dysplasia of any of the orbital or facial bones leading to facial asymmetry
optic foramen may be narrowed
fibrous stroma with spicules of woven bone often in a "c" shape or resembling
Chinese characters
osteoblasts are inconspicuous
malignancy is rare unless lesion is radiated
ossifying fibroma
tends to involve the cortex rather than than medulla as in fibrous dysplasia
expansion of mass from within bone, ground glass appearance on CT scan
fibrous stroma with spicules of lamellar bone
osteoblasts are conspicuous near spicules
hematologic disorders
Langerhans cell granulomatosis (histiocytosis X)-
eosinophilic granuloma
tends to be located superior temporally
lesion is lytic radiographically
skin is erythematous and indurated
"histiocytosis X" is antequated idea, cell of origin is not a histiocyte but
a Langerhans cell with distinctive cell markers
langerhans cell has abundant eosinophilic cytoplasm and a groved nucleus
eosinophiles may be present in varying quantities
leukemia- granulocytic sarcoma
mean age 7 years old
not limited to children but much more common in children
most reported cases are from Africa
orbital lesion preceds overt leukemia in most patients and develops within several
months
tumor cells infiltrate orbital tissues
chloroma- some of these tumors show a green color on the cut surface that fades with
time
von Leders esterase stain may help with diagnosis (positive with myeloid
precursors and high maginification mast cells)
metastasis to orbit
metastatic neuroblastoma
in most cases the primary tumor has been diagnosed before the orbital metastasis
primary is usually an abdominal tumor
metastasis tend to affect the zygoma
bilateral in 50%
lid ecchymosis may develop because the tumor is very vascular
Homer Write rosettes exist in tumor
Ewings sarcoma
metastasis tends to occur following diagnosis of primary tumor rarely the lesion occurs
primarily in the orbit
small cells that contain glycogen
affects orbital bones
congenital lesions
cysts
develop in the superior and superior temporal aspect of the orbit and anterior to the
orbital septum
dermoid cyst, epidermoid cyst, and cysts lined by
conjunctival epithelium
dermoid cyst
painless, palpable masses
may be attached to a defect in the adjacent orbital bone
lined by epidermis with dermis-like stroma containing adenexal structures like hair
follicles and sebaceous glands
epidermoid cyst- lined by epidermis but no dermis structures found
Orbital tumors of adulthood
vascular origin
cavernous hemangioma
clinical features
most common vascular tumor of the orbit in adults
usually arises in the intraconal space causing axial proptosis
encapsulated and thus easier to excise than childhood capillary hemangioma
histiologic features
well encapsulated mass composed of large endothelial lined blood containing spaces and
intervening thin connective septa
hemangiopericytoma
uncommon tumor seen in adults
more rapid developmemt of proptosis than in cavernous hemangioma
proliferating pericytes located outside endothelial cells
on low mag; gaping, staghorn or pouting vascular spaces
potentially malignant but no reliable clues to separate benign from malignant tumors
fibrous tissue origin
fibrous histiocytoma
most common mesenchymal orbital tumor of adulthood
most are benign
10% have locally aggressive features and uncertain capacity for metastasis thus treated
as malignant
grows by expansion compressing surrounding tissue forming a sort of capsule
microscopically spindle shaped cells form a cartwheel (storiform) arrangement.
frequent lipid laden macrophages
neural origin
Schwannoma
a.k.a. neurilemoma
may be isolated or found in conjunction with neurofibromatosis
tend to be encapsulated
grow at margin of a nerve
usually present with proptosis
tumor patterns
Antoni A- spindle shaped Schwann cells form a picket-fence (palisading) pattern
often contain Verocay bodies- collection of cells resembling sensory corpuscles
Antoni B- looser, more diffuse pattern representing degenerative change
cystic degeneration
usually benign tumors, malignant Schwannomas do exist but are very rare
neurofibroma
unencapsulated
most common nerve sheath tumor
see neurofibromatosis
hematologic
spectrum of lesions
benign reactive lymphoid hyperplasia
atypical lesions
malignant lymphoma
must be differentiated from pseudotumor clinically and histologically
see lymphoid lesions
lacrimal gland tumors
general principles
50% of lacrimal masses will be inflammatory or lymphoid lesions
50% will be epitheial derived tumors
clinical history and radiologic findings narrow diagnosis
avoid biopsy of a benign mixed tumor because of possible seeding of the orbit with
tumor cells and risk of aggressive recurrences
benign mixed tumor (pleomorphic adenoma)
clinical features
presents with painless gradual onset of fullness in the lacrimal fossa
eventually the globe may become displaced
because of slow growth, the periosteum is irritated not destroyed, a thin layer of new
bone may be deposited in the lacrimal fossa (cortication)
excivation of lacrimal fossa occurs as well
growth by expansion causes compression of surrounding tissue creating a capsule
tumor cells may however occur in the capsule tissues thus the tumor should never be
shelled out
a sudden change in the degree of proptosis in a patinet with many years of stability
may signal the development of malignant mixed tumor
adenocarcinoma and adenoid cystic carcinoma may be found within these masses
histologic features
composed of epithelial elements from the lacrimal ducts
proliferation of myoepithelial cells that produce a stroma that resembles cartilage
hence the term "mixed tumor"- a combination of epithelial and mesenchymal
elements
treatment
incision into the capsule can result in seeding and subsequent recurrences that can be
aggressive
treatment consists of complete excision of gland with rim of healty normal tissue
adenoid cystic carcinoma
clinical features
more rapid clinical course than benign mixed tumor
fequent complaint of pain
adjacent bone in invaded rather than compressed showing lacrimal fossa erosion
histologic features
infiltrative not encapsulated
patterns
baseloid
tubular
"swiss-cheese"
tends to invade surrounding nerves- probably accounts for pain felt by patients
treatment- definitive treatment may requrire orbital exenteration and resection of
adjacent orbital bone
orbital metastasis
most common
lung- men
breast- women
metastatic breast carcinoma may result in intense fibrous reaction in the stroma
(scirrhous carcinoma) that contracts and leads to enophthalmos and restriction of motility