Corneal EdemaCorneal EdemaOthman Al-Abbadi, M.D

The common denominator for all of the conditions is clinical stromal +/- epithelial edema

May be caused by endothelial dysfunction or by physiologic situations that exceed the barrier and pump capacity of the endothelium

Persistent Epithelial Persistent Epithelial DefectsDefectsThe epithelium is 200x more

impermeable than the endothelium◦loss of the epithelial barrier◦pH alterations (due to infective

keratitis)◦stromal collagenolysis (tear film

enzymes)

Increased IOPIncreased IOPelevated IOP combined with

normal stromal SP can create an increase in corneal thickness

persistent elevated IOP drives fluid across the endothelium, creating edema of both the epithelium and stroma◦acute angle-closure glaucoma

Primary Endothelial Primary Endothelial diseasesdiseasesCan compromise endothelial

function by reducing the effectiveness of both the barrier and the endothelial pump function

These conditions may result from a decrease in endothelial ◦cell function, ◦cell number, ◦or both

Fuch’s dystrophyFuch’s dystrophy

Introduction Introduction dystrophia epithelialis corneae

◦bilateral central corneal clouding in 13 elderly patients in 1910

Inherited, bilateral, asymmetric, non-inflammatory disorder

Characterized by varying degrees of epithelial and stromal edema, pain, decreased vision, and corneal guttae

GuttaeGuttae• Described by Vogt at 1921• Droplike excrescences of the

posterior surface of the cornea• Seen in:–Fuch’s dystrophy– Inflammatory conditions of the cornea–Hassal-Henle warts; • peripheral corneal guttae• without corneal edema nor decreased

endothelial cell count• With aging

Clinical featuresClinical features

Usually starts on the fourth decade of life

Grouped into four stages

Stage 1Stage 1Marked by the onset of corneal guttaeSigns:

◦central corneal guttae◦pigment dusting on the posterior corneal

surface◦thickened, beaten-metal appearance of

Descemet's membrane◦guttae spread to the periphery while

progressing◦only recognized retrospectively because

patients have no corneal edema and are asymptomatic

Stage 2Stage 2Symptoms:

◦painless decrease in vision ◦glare and halos around lights◦more severe on awakening

Signs:◦varying degrees of epithelial and

stromal edema ◦Epithelial edema can be seen as small

droplets (bedewing) on slit lamp retroillumination

Stage 3Stage 3Epithelial microcysts coalesce to

form bullae which eventually burst (bullous keratopathy)

Wrinkles in Descemet's membrane(striae) develop

Signs:◦Recurrent corneal erosions◦microbial ulceration◦persistent pain & FB sensation

Stage 4Stage 4subepithelial pannusMarked reduction of V/AReduction of painReduction of epithelial edemaPersistence of stromal edemaMarkedly thickened cornea

Epidemiology Epidemiology Autosomal dominant with

variable expressivity3-1 female-male30% of population <40 y/o have

guttae70% of population >40 y/o have

guttae◦3.8% have more than stage 1◦0.1% have epithelial edema or bullae

Descement membraneDescement membraneNormally

◦Type IV collagen◦Anterior banded portion

Fixed thickness 3 μm

◦Posterior non-banded portion Variable thickness 3μm at age 20 & 10 μm at age 80 Average 9μm

Histopathology Histopathology Dysfunctional & diseased endotheliumPosterior nonbanded portion becomes

bandedOn specular microscopy, the

endothelial cells are large and lose their hexagonal appearance

studies suggest that diminished pump function, rather than increased permeability, is the cause of corneal edema in Fuchs' endothelial dystrophy.

Posterior Polymorphous Posterior Polymorphous DystrophyDystrophy

Introduction Introduction Autosomal dominantBilateralVariable expressionMajority are asymptomaticSome may develop stromal

edema and secondary epithelial edema that causes severe and permanent impairment in visual acuity

Presentation Presentation 1. Small asymptomatic, discrete,

round gray vesicular lesion within an otherwise clear cornea (most common)◦On high magnification… appear as an

indentation or “pox mark” on the endothelium

2. Band lesions & small, diffuse gray endothelial opacities

3. Larger geographic lesions or a coalescence of grouped vesicles

HistopathologyHistopathologyPresence of epithelial-like cells

within focal areas of the endothelium◦These cells possess multiple

characteristics of epithelial cellsThe posterior zone resembles the

anterior banded zone

Congenital Hereditary Congenital Hereditary Endothelial DystrophyEndothelial Dystrophy

Introdution Introdution “corneitis interstitialis in utero” in

1893“congenital hereditary

endothelial dystrophy” in 1960BilateralSYMMETRICcauses corneal opacification from

limbus to limbus, without clear regions

Clinical manifestationClinical manifestationGray-white diffuse corneal cloudingWithin the first 6 months of lifeCorneal diameter and IOP are

normalNo signs of inflammation or

vascularizationNo associated systemic diseaseRarely unilateral with good vision

in the non-involved eye

Histopathology Histopathology Abnormal collagen tissue is found

between the normal Descemet's membrane and the endothelium

Anterior banded layer is thickPosterior collagenous material

that is much more disorganized than the nonbanded collagen

Inheritance Inheritance Inherited in an autosomal dominant

or autosomal recessive fashion Recessive form presents at birth,

rarely progresses, is asymptomatic, and is associated with nystagmus

Dominant form appears at age 1-2, slowly progressive, lacks nystagmus, and is commonly associated with photophobia and tearing

Iridocorneal Endothelial Iridocorneal Endothelial SyndromeSyndrome

Introduction Introduction Continuum of one disease that

includes the iris nevus (Cogan-Reese) syndrome, Chandler's syndrome, and essential iris atrophy

UnilateralAcquired disorder of the corneal

endotheliumYoung adults

Clinical manifestationsClinical manifestationsIris nodulesVarying degrees of iris atrophyPeripheral anterior synechiaeCorrectopiaElevated IOPCorneal edema

Chronicity Chronicity Abnormal corneal endotheliumGrow in a membraneCover the angleGlaucomaGrow onto the anterior surface of

the irisIris “nevus” syndromeContraction of the membraneAnterior synechiaeCorrectopia & Iris atrophy

Treatment Treatment Bimodal

◦Glaucoma◦Corneal edema

Cataract surgery inducedCataract surgery inducedMost common cause of iatrogenic

corneal edemaRevesible:

◦high hydrostatic pressure from the flow◦manipulation of instruments in the eye

may cause localized edema at the incision site as well

◦inadvertent touch of instruments to the endothelium may cause localized cell lysis

Preexisting endothelial Preexisting endothelial diseasediseaseCataract extraction is usually successful as

long as epithelial edema is not present and stromal thickness is <600 μm

Corneal edema should be evident on examination and the patient should report symptoms of morning blurring before the ophthalmologist considers combined corneal transplantation and cataract surgery

Controversy exists as to whether the best postoperative results occur with combined PKP and cataract extraction, PKP before or after

Surgical traumaSurgical traumaPseudophakic corneal edema is the

leading indication for PKP in US since mid 80s… before was keratoconus

Vitreous touch to the cornea can cause corneal edema by mechanical ballottement of the endothelium

Vitreous incarcerated into the cataract wound may cause incisional corneal edema that may progress over the entire cornea

Cataract surgery +/- PC/IOL is currently associated with 2-5% endothelial loss

Closed-loop IOLs was blamed for 24-62% endothelial loss previously due to repeated endothelial touch leading to stimulated inflammation, bleeding +/- glaucoma

BSS Plus is considered more endothelial friendly, with ingredients such as glutathione, sodium bicarbonate, and glucose

Brown-McLean syndromeBrown-McLean syndromeCorneal edema involving the peripheral 2

to 3 mm of the corneaStarts inferiorly sparing the central

portionAssociated with a punctate orange-brown

pigmentation on the endotheliumCentral cornea guttata is frequently seenMost frequently after ICCEMay occur following ECCE, phaco & PPVMay progress to complete endothelial

decompensation

Decreasing iatrogenic Decreasing iatrogenic corneal edemacorneal edemaImproved surgical techniquebetter microsurgical instrumentationmore biocompatible irrigating

solutionsacceptance of viscoelastic materials

increasing number of cataract surgery cases and an enlarging elderly population will likely make pseudophakic corneal edema a problem for some time

Vitreoretinal surgery

Refractive surgery intraocular FB

VR surgeryVR surgerySilicone oil and perfluorocarbon

cause edemaMigration of oil or gas into A/C

◦Mechanically damage the endothelium◦Block aqueous nutrients

Phakic and pseudophakic vs aphakicInferior iridectomy in cases of

silicone oil retention & aphakia can limit access of silicone oil into A/C by allowing normal aqueous flow through the iridectomy site

Refractive surgeryRefractive surgeryRadial keratotomy may be associated

with diurnal variation in corneal thickness

PRK on rats showed increased apoptosis of corneal keratocytes and endothelial cells

Corneal endothelial analysis following LASIK verified pleomorphism with definite loss of endothelial cells and altered cell morphology acutely manifesting as corneal edema

Corneal trauma (FB)Corneal trauma (FB)External & penetrating traumas

can induce corneal edemaWhen a penetrating object lodge in

the angle, it may be difficult to see with gonioscopy or through the microscope at the time of surgery

Optimum treatment for metallic foreign bodies is surgical removal ASAP

Chemical injuryChemical injuryNormal pH of endothelium= 6.8-

8.2Damages the plasma membrane

reducing the effectiveness of the barrier function

Chemical injuries alter the pH decreasing the amount of stromal Bicarbonate buffer reducing the pump function

Inflammation Inflammation Corneal edema depends on the

severity of the inflammatory process, its duration, and the health of the endothelium

Can be induced by uveitis, herpes simplex, herpes zoster, sarcoidosis & post-op when the endothelium is more vulnerable

Increased IOPIncreased IOPIf the endothelium is already

stressed and diseased, a relatively low IOP can cause corneal edema increasing the threshold ◦postoperative cataract surgery◦postoperative PKP◦severe Fuchs' dystrophy

Contact lensesContact lensesWhen covered with a contact lens, the

cornea can receive oxygen from three sources: ◦oxygen dissolved in tears that float behind

the lens◦oxygen that passes directly through the lens◦oxygen that passes into areas of the cornea

not covered by the lensOxygen transmission of CL= Dk/L

◦L is lens thickness◦Dk of CL is the oxygen transmissibility

coefficient

Contact lens hypoxia often presents as epithelial microcysts in the central portion of the cornea

Corneal edema results from depletion of glycogen and accumulation of lactic acid within the cornea... The pH changes of lactic acid further exacerbate the endothelial barrier capacity