Eye Pathology - Cumulative-1

8/7/2019 Eye Pathology - Cumulative-1

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Basic Pathology of the EyeBasic Pathology of the Eye

Nicola G. Ghazi

IntroductionIntroduction

A subspecialty on its own Focus on generalities and most common

conditions in each major disease category Suggested readings:

Spencer WH (ed): Ophthalmic pathology: An atlas and textbook,4 th ed. Philadelphia: WB Saunders, 1996.

Yanoff M, Fine BS: Ocular pathology, 5 th ed. St. Louis: Mosby-Year Book, 2002

Klintworth GK: The eye pathologist, an eye pathology tutor anddisease database. http://www.eyepathologist.com

The Eyelids,The Eyelids, BlepharitisBlepharitis

Blepharitis: Inflammation of the

eyelids Several types:

seborrheaic staphylococcal mixed meibomia gland

dysfunction (posterior) others

anterior

Anterior lamella

Posterior lamella

The Eyelids,The Eyelids, BlepharitisBlepharitis

anterior

posterior

The Eyelids,The Eyelids, HordeolumHordeolum

Hordeolum: Acute, purulent, focal

inflammatory lesion of the eyelid

Usually due to abacterial infection

May involve hair follicles or glandular structures

The Eyelids,The Eyelids, HordeolumHordeolum

Hordeolum: May be:

external: starts asfolliculitis

perifolliculitisnearby glands

internal: involvesmeibomian glands

Both may causeabscess formation


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The Eyelids,The Eyelids, ChalazionChalazion

Chalazion: Chronic localized

lipogranlomatous

inflammation Centered around the

sebaceous glands of the eyelid

Reaction to extrudedlipid

May also be external(marginal) or internal


External

External (marginal)

Internal


Chalazion: May be caused by

infectious,inflammatory or neoplastic processes

The common etiologyis obstruction of thesebaceous glandorifice

lipogranlomatousinflammation :

predominantly chronicinflammatory cellsaround lipid vacuoles

The Orbit, GravesThe Orbit, Graves

Exophthalmos or proptosis: forwardprotrusion of the eye

Thyroid orbitopathy inGraves disease is themost common causeof unilateral or bilateral eyeprotrusion in adults


Exophthalmos inGraves disease mayprecede or followother manifestationsof thyroid dysfunction

May manifest in anydysthyroid state of thedisease


Autoimmune disease Female: male= 4:1 Bilateral or unilateral

eye protrusion Upper lid retraction:

stare ( may indicatehyperthyroid state )


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Eyelid swelling Chemosis (conj

swelling)

EOM restriction withocular motilitydisturbance anddiplopia

Exposure keratopathy Compressive optic

neuropathyVision loss



swelling) EOM restriction with

ocular motilitydisturbance anddiplopia

Exposure keratopathy

Compressive opticneuropathy

Vision loss



swelling) EOM restriction with

ocular motilitydisturbance anddiplopia

Exposure keratopathy Compressive optic

neuropathyVision loss


Pathologically: Chronic inflammatory

cells, mainly

lymphocytes andplasma cells Mucopolysaccharide Involves EOM belly

but not the tendon

The Conjunctiva, ConjunctivitisThe Conjunctiva, Conjunctivitis

Most common of eyediseases

Hyperemic conj bloodvessels (pink eye)

Crusting Discharge Matting in the

morning

The Conjunctiva, ConjunctivitisThe Conjunctiva, Conjunctivitis

May be: Allergic (papillae) Infectious:

viral (follicles) bacterial


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The Conjunctiva, TrachomaThe Conjunctiva, Trachoma

Bilateral Chroniccicatricialconjunctivitis

Caused by Chlamydiatrachomatis serotypesA, B, and C

Highly contagious spread by fingers,

fomites and flies


Affects upper conjunctiva especiallythe palpebral part

Still the most commoncause of blindness inunderdevelopedareas in Asia, theMiddle East andAfrica


Pathology: Lymphocytic infiltrate Epithelial cells:

intracytoplasmicinclusion bodies


Pathology: Superior limbal

subepithelial

inflammatoryfibrovascular pannus

Inflamed pannus Non-inflamed pannus



subepithelialinflammatoryfibrovascular pannus



subepithelialinflammatoryfibrovascular pannus

Inflamed pannus Non-inflamed pannus


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Pathology: Herbert pits

The Conjunctiva,The Conjunctiva, PingueculumPingueculum

Yellowish conjunctivallump

Usually affects nasalconjunctiva

Sun-damaged collagen Pathology:

accumulations of amorphous, granular collagen fragments

Stain with elastin stains butare elastase resistant,elastotic degeneration of collagen

Giant cells may be seen

The Conjunctiva,The Conjunctiva, PterygiumPterygium

Pingueculum thatgrows onto thecornea

Insect wing shape(hence the name)

Forms a fold of vascularizedconjunctiva

The Cornea, DystrophiesThe Cornea, Dystrophies

Varied geneticdisorders

Non-inflammatory

Most are autosomaldominant

Most widely classifiedby the layer of thecornea primarilyinvolved

Many involve morethan one layer

The Cornea, DystrophiesThe Cornea, DystrophiesEpithelial dystrophies

Basement membranedystrophiesBowman layer dystrophies

Stromal dystrophies

Endothelial dystrophies

The Cornea, EpithelialThe Cornea, EpithelialDystrophiesDystrophies

Faulty maturation andturnover of epithelialcells: Microcysts

(cytoplasmic epithelialaccumulations)

Basement membraneduplication/migration

Faulty desmosomaland hemidesmosomaljunctions (recurrenterosions)

Meesmann Map-dot-fingerprint


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Faulty maturation andturnover of epithelialcells:

Microcysts(cytoplasmic epithelialaccumulations)


Faulty desmosomaland hemidesmosomaljunctions (recurrenterosions)



Faulty maturation andturnover of epithelialcells: Microcysts

(cytoplasmic epithelialaccumulations)


Faulty desmosomal

and hemidesmosomaljunctions (recurrenterosions)


The Cornea,The Cornea, StromalStromal DystrophiesDystrophies

Deposition of abnormal material inthe stroma amyloid (lattice) mucopolysaccharides

(macular) unidentified proteins,

hyaline (granular) Lipids (numerous) Some may be

associated withsystemicmanifestations


Granular: hyaline


Macular:mucopolysaccharide

Colloidal iron (may use Alcian Blue)


Lattice: amyloid

Congo red

Red-green

Plane polarized


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M arilyn: M acular M onroe: M ucopolysaccharide Always: Alcian Blue

G ets: G ranular H er: H yaline M en: M assson-Trichrome In LA: Lattice/ Amyloid C ounty: C ongo red

The Cornea, EndothelialThe Cornea, EndothelialDystrophiesDystrophies

Accompanied byDescemet membrane(DM) changes Fuchs:

Endothelial cell loss DM thickening DM wartlike excrescences

(guttata ) corneal edema with vision

loss Posterior polymorphous

dystrophy (PPD) Congenital hereditaryendothelial dystrophy(CHED)

The Lens, CataractThe Lens, Cataract

Most common cause of reversible vision loss inthe elderly

Opacification of thecrystalline lens

Possible role for ultraviolet light

Multiple ocular and non-ocular causes for secondary cases

Genetic, metabolic, toxic,physical and other conditions


Most commonlyassociated with age

Path: varies with type Lens fibers harden

and are compressedcentrally ( nuclear sclerosis )


Path: varies with type Peripheral cortical

fibers degenerate,fragment and formglobules ( Morgagniancorpuscles; corticalcataract )


Path: varies with type Anterior lens epithelial

cells migrateposteriorly and swellup ( bladder cells of Wedl; posterior subcapsular cataract )


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Path: varies with type Cortex liquefies

completely and

nucleus sinks down(morgagnian cataract )


May cause glaucoma: Phacomorphic : due to

continuous osmoticlens swelling whicheventually obstructsoutflow of aqueous

Phacolytic : due to lensdebris seeping outthrough lens capsuleand accumulating inmacrophages thateventually obstructoutflow ( phacolyticcells )










The Retina, hemorrhageThe Retina, hemorrhage

A feature of manyretinal disorders

Appearance varieswith location: Dot/blot (round): outer

retina (outer plexiformlayer)

Splinter (flame)-shaped: inner retina(nerve fiber layer)

Melanoma-like: sub-RPE or suprachoroidal


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The Retina, hemorrhageThe Retina, hemorrhage A feature of many

retinal disorders Appearance varies

with location: Blot (round): outer

retina (outer plexiformlayer)

Dot (round): inner plexiform

Splinter (flame)-shaped: inner retina(nerve fiber layer)

Melanoma-like: sub-RPE or suprachoroidal

The Retina, retinal occlusiveThe Retina, retinal occlusivediseasedisease

2 nd most commonretinal vascular disease after DR

May be: Arterial Venous


Venous: Central (CRVO) Branch (BRVO)

Arterial Central (CRAO) Branch (BRAO)

Effect depends: on size and location of

involved vessel degree of ischemia


Venous: Central (CRVO) Branch (BRVO)

Arterial Central (CRAO) Branch (BRAO)

Effect depends: on size and location of

involved vessel degree of ischemia

The Retina, arterial occlusionThe Retina, arterial occlusion

The etiology of bothbranch or centralartery occlusion: Embolic, thrombotic,

vasculitic, stenotic,vasospastic,compressive, andidiopathic

Embolic is maincause:

Carotid Heart Major vessels


Pathology: Early:

Cotton wool spots Retinal swelling Thin artery Cherry red spot (in

CRAO)

Late: Inner retinal atrophy Optic nerve atrophy

Cytoid bodies(micro-infarctswith impairedaxoplasmic flow)


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Pathology: Early:

Cotton wool spots

Inner retinalswelling/infarction Cherry red spot (in

CRAO)


Stenotic CRAO due to an atheromatous plaque

No inner retina


Pathology: Early:

Cotton wool spots Inner retinal

swelling/infarction Cherry red spot (in

CRAO)

Late: Inner retinal atrophy

Optic nerve atrophy

Stenotic CRAO due to an atheromatous plaque

No inner retina


Pathology: Early:

Cotton wool spots Retinal swelling Cherry red spot (in

CRAO)


Atrophy involves inner retina butspares the outer aspect of INL


Leads to permanent visual loss if circulation not restored within a short time

Amaurosis fugax: transient vision loss dueto micro-emboli to CRA

The Retina, venous occlusionThe Retina, venous occlusion

The etiology of occlusion not wellunderstood

Thought to be: thrombotic in CVO compressive in BVO


The etiology of occlusion not wellunderstood

Thought to be: thrombotic in CVO compressive in BVO


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Both have similar fundusfindings along thedistribution of occlusion: Venous/capillary tortuousity

Cotton-wool spots Retinal hemorrhages(splinter mainly)

Retinal and ONH swelling Cystoid macular edema

(CME) Retinal/ONH/anterior

segment neo-vascularization

Neovascular glaucoma(within 3 months)


CME: Leakage of fluid from

compromised retinalcapillaries

Patelloid appearanceon angiography

Pathology: fluidaccumulation mainly inouter plexiform layer (OPL)


Neovascular glaucoma (NVG): 90-day glaucoma Angle

neovascularization Open angle early Closed later on

(peripheral anterior synechiae)

Painful Worst prognosis

The Retina, hypertensiveThe Retina, hypertensiveretinopathyretinopathy

Chronic hypertensionaffects retinal andchoroidal arteriolesthrough the process of arteriosclerosis

This leads to thickeningof arteriolar wall andnarrowed lumen

Arterioles compress veinsat AV crossings Some believe that no

compression occurs butvenous sclerosis

Ophthalmoscopic findings: Arteriolar narrowing and sheathing (cupper and

silver wiring) due to arteriosclerosis AV nicking Retinal vascular occlusion, mainly venous Microaneurysms Flame shaped hemorrhages Cotton-wool spots

Exudates Macular star (exudates radiating from macula) ONH swelling in malignant hypertension



Ophthalmoscopicfindings: Exudates Macular star (exudates

radiating from macula) Malignant

hypertension ONH swelling Fibrinoid necrosis of

precapillary arterioles


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Ophthalmoscopicfindings: Exudates

Macular star (exudatesradiating from macula)

Malignanthypertension

ONH swelling Fibrinoid necrosis of

precapillary arterioles

Vascular disease 20-40% of diabetics develop ocular symptoms

and retinopathy The rate of proliferative DR correlates with:

Type of diabetes Degree of glycemic control

Almost all type 1 and most type 2 diabeticsdevelop some form of retinopathy by 15 years

The better the glycemic control the lower therate of retinopathy

Proliferative retinopathy (worse type) usuallyappears after 10 years of diabetes

The Retina, Diabetic retinopathyThe Retina, Diabetic retinopathy(DR)(DR)

Diabetes causes retinal ischemia : Narrowing/occlusion of retinal arterioles and

capillaries: Arteriosclerosis Platelet thrombi Lipid deposition in vessel wall

Narrowing of central retinal or ophthalmic arteriesfrom atherosclerosis

Diabetes causes incompetence of retinalcirculation with leakage : Endothelial cell damage Loss of pericytes (1:1 ratio disrupted)

The Retina, Diabetic retinopathyThe Retina, Diabetic retinopathy


2 types of DR: Non-proliferative

(NPDR)

Proliferative (PDR) The difference is

neovascularization

The Retina, Diabetic retinopathy,The Retina, Diabetic retinopathy,nonproliferativenonproliferative

Previously calledbackground Retinal dot/blot

hemorrhages Hard exudates Cotton-wools spots Retinal swelling Venous beading

Microaneurysms IRMA



hemorrhages Hard exudates Cotton-wools spots Retinal swelling Venous beading Microaneurysms IRMA


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hemorrhages Hard exudates Cotton-wools spots Retinal swelling



hemorrhages Hard exudates Cotton-wools spots Retinal swelling Venous beading

Microaneurysms IRMA



hemorrhages Hard exudates Cotton-wools spots Retinal swelling Venous beading Microaneurysms IRMA


These lesions do not affect vision unless: they involve the macula or PM bundle associated with macular edema

These lesions are more prominent in type2 DM

Hard exudates are rich in lipids due tolipoproteinemia of diabetics


Pathology: Microaneurysms: focal

capillary dilatations atareas of wall weakness


Pathology: IRMA:

close to areas of venous beeding rich in endothelium but rare to no pericytes


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The Retina, Diabetic retinopathy,The Retina, Diabetic retinopathy,proliferativeproliferative

Neovascularization: At the disc ( NVD) Elsewhere (NVE)

May be associatedwith vitreoushemorrhage

Tractions retinaldetachment

Iris neovessels


Neovascularization: At the disc (NVD) Elsewhere ( NVE ) May be associated

with vitreoushemorrhage


Iris neovessels


Neovascularization: At the disc (NVD) Elsewhere (NVE) May be associated



Iris neovessels


Neovascularization: At the disc (NVD) Elsewhere (NVE)

May be associatedwith vitreoushemorrhage


Iris neovessels


Neovascularization: At the disc (NVD) Elsewhere (NVE) May be associated



Iris neovessels


Neovascularization : Due to VEGF release

from ischemic retina Stimulates endothelial

cell and astrocyteproliferation

Fibrovascular proliferation


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Pathology: New blood vessels

with glial tissue(gliosis) from surfaceof retina or ONH intovitreous

NVE NVD

New blood vessels inthe iris ( rubeosis iridis )or angle


Pathology: New blood vessels

with glial tissue(gliosis) from surfaceof retina or ONH intovitreous

NVE NVD

New blood vessels inthe iris ( rubeosis iridis )or angle


Pathology: Retina NVE NVD Traction RD

AP forces (asterisk) Tangential forces

(arrowhead) Foci of VR attachments

at NVE (arrows)


Pathology: Iris Rubeosis iridis:

fibrovascular

membrane on the irissurface PAS with angle closure

(neovascular glaucoma) Posterior synecahiae Ectropion uveae Hyphema


Pathology: Iris Lacy vacuolization of

the iris pigmentepithelium (IPE):

Due to hyperglycemia Glycogen storage in

IPE, lost by processing


Pathology: DME:

May occur in NPDR or PDR

Main cause of visionloss in diabetics

Swelling/hard exudatesin or close to themacula

Patholohy: Lipoprotein and fluid

accumulation mainly inOPL


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Retinal ischemia and incompetence of retinalcirculation with leakage may explain all thesigns of DR


One of the 3 leadingcauses of irreversiblevision loss in the USA: DR AMD Glaucoma

Vision loss due to: DME Vitreous hemorrhage

Retinal detachment NVG

Vision loss from DRhas a bad prognosis Life expectancy < 6yrs Only 20% survive 10

yrs Death from RF/CAD

often follows

BS control can not be

overemphasized

Other ophthalmic manifestationsOther ophthalmic manifestationsof diabetesof diabetes

Snowflake cataract: White spoke-shaped

opacities Adjacent to lens

capsule Rapidly progressing

over days to week Due to an osmotic

effect of sorbitol in thelens

Earlier onset andfaster growing thanage-related NSC

The Retina, Retinal detachmentThe Retina, Retinal detachment(RD)(RD)

The Retina, Retinal detachmentThe Retina, Retinal detachment(RD)(RD)

Fluid leads to RD

The Retina, RDThe Retina, RD

3 types of RD Rhegmatogenous: Rhegma = break Common after trauma

and cataract surgery Most common type

Tractional: No break usually Due to pulling on retina PDR, ROP

Exudative: No break/traction Fluid accumulates

under retina Inflammation, tumors


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The Retina,The Retina, RhegmatogenousRhegmatogenous RDRD

Factors required for arhegmatogenous RDto occur:

Retinal break Traction Fluid


Pathology: Photoreceptor atrophy :

due to separation fromRPE and choroid

RPE demarcation line Cystic degeneration of

the retina Subretinal dense

proteinaceous material


Pathology: Photoreceptor atrophy:

due to separation fromRPE and choroid

RPE demarcation line Cystic degeneration of

the retina Subretinal dense

proteinaceous material

The Retina, AgeThe Retina, Age --related macular related macular degeneration (AMD)degeneration (AMD)

Most common causeof vision loss in theelderly (>60)

The macular center,the foveola, is: Point of maximal

visual acuity Highest cone

concentration


May be: Wet : subretinal

fibrovascular tissue Dry : drusen/RPE

atrophy



fibrovascular tissue Dry : drusen/RPE

atrophy


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fibrovascular tissue

Dry : drusen/RPEatrophy

The Optic Nerve, Optic nerveThe Optic Nerve, Optic nervehead (ONH) edemahead (ONH) edema

Swelling of the nervewhere it enters theglobe ( optic disc )

Increased ICP is themost important cause Usually bilateral Papilledema

Inflammation,

infarction, venousdrainage obstructionare other causes


Clinical findings: Optic disc swelling Disc elevation Blurred margins Dilated vessels Hemorrhages Exudates CWS Concentric folds of choroid

and retina Central vision is preserved

initially ( no syxs ) Vision loss, late (atrophic

stage)


The Optic Nerve, Optic atrophyThe Optic Nerve, Optic atrophy

Loss of optic nerve axons Many causes:

Chronic edema Optic neuritis Optic compression Retinal conditions Infarction Toxicity (ethambutol,

isoniazid)

Hereditary ( Leber ) GLAUCOMA

Clinically: Thin disc rim Pale ONH Flat ONH Excavated (cupped) in

GLAUCOMA


Atrophic papilledema

Glaucomatous excavation


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Post inflammation (optic neuritis) Glaucomatous excavation

Normal

GlaucomaGlaucoma

Collection of disorders: Optic neuropathy Characteristic ONH

excavation Progressive visual

field loss

GlaucomaGlaucoma

Most commonlyassociated withincreased intraocular pressure (IOP)

Normal tensionglaucoma (NTG) isone exception

Increased IOP doesnot always lead toglaucoma

GlaucomaGlaucoma

Aqueous flow: A delicate balance

between production

and filtration maintainsphysiologic IOP When aqueous

accumulates, IOPrises

Usually aqueousdrainage rather thanproduction involved

GlaucomaGlaucoma

High IOP may lead tovision loss: ONH damage Corneal edema

GlaucomaGlaucoma

Types: Congenital Acquired

Open angle Primary Secondary

Closed anglePrimarySecondary


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GlaucomaGlaucoma

Types: Congenital Acquired

Open angle Primary Secondary

Closed anglePrimarySecondary

Glaucoma, 1ry open angleGlaucoma, 1ry open angle

Normal AC and angle Most common type Major cause of

blindness 6 th decade Bilateral, asymmetric Asymptomatic,

insidious: ONH damage Irreversible field loss



Pathology: Increased resistance

to aqueous outflow

Usually in the vicinityof Schlems canal

Multiple genes maydeterminepredisposition toglaucoma

Glaucoma, 1ry closed angleGlaucoma, 1ry closed angle

Affects patients whohave an abnormallynarrow angle Without pupil block:

Peripheral iris displacedanteriorly

When pupil isconstricted ( miotic )angle widens

When dilated(mydriatic ) anglenarrows and IOPincreases


With pupil block: In patients with small

eyes or anterior segments

Pupil blocked by lens Peripheral iris pushed

forward ( iris bombe ) Angle obstructed and

IOP rises


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Symptoms: Decreased vision Ocular pain

Headache Nausea/vomiting Red eye Halos Light sensitivity


Ocular emergency Start treatment as

soon as possible(within 24-48 hrs)

Treat the other eyeprophylactically

Glaucoma, 2ry GlaucomaGlaucoma, 2ry Glaucoma

May be open or closed angle too

Many causes: Inflammation Hemorrhage Neovascularization Tumors Many others

Pigment dispersion syndrome

Glaucoma, LowGlaucoma, Low --tensiontensionGlaucomaGlaucoma

Also called normaltension glaucoma ONH glaucomatous

damage Visual field loss Normal IOP

May representpatients withhypersensitivity toIOP

GlaucomaGlaucoma

Effects of increasedIOP: ONH excavation, not

in infants Nasalization of blood

vessels Buphthalmos: in pts

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Eye Pathology - Cumulative-1