CASE PRESENTATION:Corneal Dystrophy

Dr. Nilay Nitin Patel

Dr. Nita Shanbhag

D Y Patil University, School of Medicine

Nerul, Navi Mumbai

Case History• A 45 year old woman came with complaints of Gradual

Progressive Diminision of Vision in both eyes since 10 years of

age

• Patient was apparently alright before that with good visual acuity

• No H/o Photophobia, Coloured halos, Watering and Pain

• No H/o Trauma, Viral infection

• No relevant family history

• No H/o of any systemic illness

• No known drug allergy

Ocular ExaminationRIGHT EYE LEFT EYE

V/A 6/36 6/60

Pin hole Vn 6/36 NI 6/60 NI

Retinoscopy +1.25 / +1.25 +1.0 / +1.0

IOP Digitally normal Digitally normal

Lids / lashes Normal Normal

Sclera / Conjunctiva

Not congested Not congested

Cornea Multiple white dots about 0.5mm in diameter eroding out of the epithelium, studding the stroma not involving the endothelium, spread over 8mm area, with interdigitating network of filaments

Anterior chamber Normal in depth. No KPs, flares and cells.

Iris / Pupil CPN / CCRTL CPN / CCRTL

Lens Clear Clear

EOM Free and full Free and full

Dil. Fundus Examination

Media: ClearDisc:0.3 cup with normal NRRVessels: WNL; Macula: Normal FR: +

Media: ClearDisc:0.3 cup with normal NRRVessels: WNL; Macula: Normal FR: +

Gonioscopy Open angles Open angles

RE LE

Characteristics Lattice Granular Macular

Genetics Autosomal Dominant Autosomal Dominant Autosomal Recessive

Onset 1st decade of life Early Adolescence 1st decade

VisionEarly reduction with

obvious cloudingGood until middle age

Reduced by 30-40 years, FC by 50 years

SymptomsSevere recurrent

erosionsMinimal inflammation

and irritationMild recurrent erosions

Opacites

Grayish ‘ pipe cleaner’ linear, branching, threads; dots and

flakes; distinct borders

Grayish opaque granules; bread

crumbs; sharp borders

Grayish opaque spots; indisctinct borders

Intervening Stroma Relatively clear Clear Diffusely clear

Distribution of Opacities

Entire cornea with dots; linear opacities central;periphery usually clear;

Progress to central disciform by middle age

Axial only; periphery clear

Entire cornea; but most dense centrally

Histopathology

Large hyaline lesions with scattered fibrillar

material; also subepithelial

Discrete, hyaline, granulated

Diffuse, granular, nonhyaline,

Asso with keratocytes

DefectStructural protein:

primary amyloidosis of cornea

Structural proteins: hyaline degeneration of

collagen

Metabolic: defective acid

mucopolysaccharide metabolism

Corneal Stromal Dystrophy

Types of Lattice Corneal dystrophy

CharacteristicsType I ( Biber-Haab-Dimme)

Type II ( Meretoja Syndrome )

Type III

Usual age of onset <10 years >20 years >40 years

Visual acuity Impaired by age 40-60 Good until age 65 Impaired after 60

Systemic amyloidosis No Yes No

Faces Normal

Masklike facial expression, blepharochalasis, floppy ears, protruding lips

Normal

Nervous system NormalCranial and peripheral nerve palsies

Normal

Skin NormalDry, itchy, and lax with amyloid deposits

Normal

Cornea

Delicate interdigitating network of filaments; no lines present at early stages

Thick and radially oriented linesExtending to periphery

Thick lines

Episodic corneal erosions

Yes Yes No

Granular Dystrophy Type 2 (Avellino /Granular- Lattice Dystrophy)

• Gen: Autosomal Dominant related to the TGFBI gene, locus 5q31

• Recurrent erosions are more common

• Biomicroscopically, granular deposits are more superficial; as the disease progresses, a snowflake appearance deeper in the stroma can be noted.

• The linear refractile deposits tend to be deeper than the granular deposits, but with progression these lines coalesce with the round opacities.

• Pathology: mixed deposits of hyaline and amyloid; hyaline stains with Masson Trichrome and amyloid stains with Congo Red

Stains Lattice Granular Macular Avellino

PAS (Periodic acid schiff) + + +

Trichrome Masson + + +

Congo red (Under polarization) + +

Alcian blue +

Stains used for Histopathological diagnosis of the Stromal Corneal Dystrophy

InvestigationsOcular

• IOP

• Sac syringing

• Corneal Topography

• Anterior Segment OCT

• UBM

• Pachymetry

• Posterior segment I/O to r/o

any retinal Pathology

Systemic

• Diabetes

• Hypertension

• Systemic Amyloidosis

• Peripheral and cranial

nerve involvement

Initial medical management

• Lubricating drops, or autologous serum

therapy

• Punctal plugs

• Bandage Contact Lenses +/- antibiotics for

recurrent

erosions

DiscussionIf Epithelium & Stroma involved

• Common

• DALK

– Manual

– Excimer donor lenticule giving better approximation with lesser astigmatism

– Femto donor Lenticule with more optimal results

If Endothelium involved

• Very Rarely

• PKP is the only Mx option

– With good visual prognosis

– Recurrences of primary

dystrophy are known in

the graft

In this case PKP is preferred over DALK because dissection of the stroma would be difficult as the stromal involvement is extensive.

Differential Diagnosis

• Lattice Corneal Dystrophy - Type I, III, IIIa, IV:  these dystrophies typically present with central anterior stromal corneal lattice lines at variable stages in life, recurrent corneal erosions, and no systemic features

• Granular Corneal Dystrophy – Avellino, Reis Bückler

• Macular Corneal Dystrophy – Type I, Type Ia, Type II

• Schnyder Corneal Crystalline Dystrophy (SCCD)IMPRESSION: Avellino Corneal Dystrophy

THANK YOU

Dystrophy vs Degeneration

Dystrophies:

• Genetic (usually Aut Dom) with

onset in childhood/early

adulthood

• Not associated with systemic

disease

•  Bilateral

• Centrally located within the

cornea

• Typically involve only one layer of

the cornea

Degenerations: •  Progressive (onset typically after

age 40)

• Usually unrelated to family history

or genetic predisposition

• Commonly associated with

systemic disease (rheumatologic,

infectious)

• Usually unilateral, asymmetric if

bilateral, and peripherally located

on the cornea

• Can involve one or multiple layers

of the cornea

• Often associated with

neovascularization

TGFβ1 and Corneal Dystrophies

• Transforming Growth Factor Beta Induced Protein (gene product of TGFβ1) is very abundant in cornea

- >30 mutations in TGFβ1 gene that result in corneal dystrophies - 68 kDa protein known as keratoepithelin

• It is secreted by corneal epithelial cells and is found in normal stroma bound to type VI collagen

- Mutations in theTGFβ1 gene protein aggregation in the cornea 2/2 protein misfolding

• TGFβ1 induced protein accumulates as insoluble products in various forms. The severity, clinicopathologic variations , age of onset, and location of deposits all depend in the type of amino acid alterations in the protein