Corneal dystrophies
- 1. Corneal dystrophies DR NAJARA THAPA 1ST YEAR RESIDENT LEI, NAMS
- 2. Objective To understand different types of corneal dystrophy, their clinical features and management. 2
- 3. Layout Introduction Classification Epithelial corneal dystrophies Corneal dystrophies of Bowmans layer Stromal corneal dystrophies Descemet membrane and endothelial dystrophies 3
- 4. History Gr. dys meaning ‘wrong’or ‘difficult’ ;and trophe meaning ‘nourishment’ Introduced into the medical literature by Wilhelm Erb (1840–1921) in 1884 Arthur Groenouw Noduli Corneae (1890) 4
- 5. Introduction Non- inflammatory corneal opacifying disorders. Characteristic features: Usually have a strong pattern of inheritance Bilateral and symmetric Little to no relationship with systemic and environmental factors Begin early in life but clinically apparent later in life Slowly progressive 5
- 6. 6 Features Degeneration Dystrophy Onset Presents later in life, associated with aging Present early in life, hereditary Laterality Unilateral Bilateral; May be asymmetric Bilateral & symmetric Family history Uncommon Common Vascularization Common Uncommon Location often peripherally located Centrally located Progression Progression can be very slow or rapid Progression usually slow
- 7. Classification: Based on anatomic location Epithelial and Subepithelial dystrophy Bowman layer dystrophy Stromal dystrophy Descemet membrane and Endothelial Dystrophy 7
- 8. According to anatomic level affected, genetic basis, clinical and pathologic information, we have International Committee for the Classification of Corneal Dystrophy (IC3D) 8
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- 11. EPITHELIAL BASEMENT MEMBRANE DYSTROPHY Syn. Map-dot fingerprint dystrophy or Cogan microcystic dystrophy or Anterior basement membrane dystrophy Most common dystrophy Often sporadic; AD Genetics: locus 5q31, gene TGFB1 in minority 11
- 12. Clinical findings Women, age > 50 Grey patches, fine lines and microcysts Best seen with retro- illumination, sclerotic scatter Recurrent epithelial erosions Transient blurred vision Can also cause irregular astigmatism and inaccurate IOL calculations 12
- 13. 13 Geographic map likeFingerprint lines
- 14. HISTOPATHOLOGY: Thickening of basement membrane. Deposition of fibrillary protein between BM and basement membrane TREATMENT: 5% NaCl drops or ointment Lubricating drops/ointment Debridement of the loosened epithelium Excimer laser phototherapeutic keratectomy (PTK) 14
- 15. MEESMAN EPITHELIAL DYSTROPHY Syn. Juvenile hereditary epithelial dystrophy AD Slowly progressive (gene epithelial keratins; Locus 12q13) SYMPTOMS: Asymptomatic Recurrent erosion and blurring (mild) SIGNS: Myriad tiny intraepithelial cysts (centrally, extends to limbus) Whorled and wedge-shaped epithelial patterns 15
- 16. HISTOLOGY: Irregular thickening of epithelial basement membrane and intra- epithelial cysts (PAS positive). Intracytoplasmic ‘‘peculiar substance’’: focal collection of fibrogranular material surrounded by tangles of cytoplasmic filaments (EM) TREATMENT: Lubrication for minute erosions Soft contact lenses 16
- 17. LISCH EPITHELIAL CORNEAL DYSTROPHY Syn. Band-shaped and whorled microcystic dystrophy • X-linked dominant • Onset- Childhood Diffuse grayish epithelial opacities Densely packed microcysts 17 Histology: Pronounced vacuolization of epithelial cells
- 18. CORNEAL DYSTROPHIES OF BOWMAN'S LAYER 18
- 19. REIS- BUCKLERS CORNEAL DYSTROPHY Syn. Corneal basement dystrophy type 1 AD, TGFB1 gene Severe recurrent corneal erosion; visual impairment 19
- 20. HISTOLOGY: Replacement of corneal BM by connective tissue bands Eosinophilic and fibrotic material beneath the epithelium and in anterior stroma Electron microscopic- rod shaped deposition 20
- 21. THIEL- BEHNKE CORNEAL DYSTROPHY Syn. Honeycomb shaped corneal dystrophy or corneal basement dystrophy type 2; Waardenburg and Jonkers dystrophy Less severe than REIS-BUCKLERS AD; TGFB1 gene Recurrent erosions in childhood 21
- 22. HISTOPATHOLOGY: Wavy, sub-epithelial fibrosis with disruption of BM and of epithelial basement membrane(saw tooth appearance). Electron- microscopy: Curly collagen filaments replace the BM. 22
- 23. Treatment: T/t of recurrent erosion Superficial keratectomy; Excimer laser phototherapeutic keratectomy Lamelar keratoplasty Penetrating keratoplasty 23
- 25. The Stromal Dystrophies 25 Granularcorneal dystrophy Type 1 (classic) Type 2 (granular-lattice) Type 3 (Reis-Bücklers) LATTICE corneal dystrophy MACULAR corneal dystrophy CLASSIC FORM GELSOLIN TYPE
- 26. GRANULAR CORNEAL DYSTROPHY (Type 1) AD Gene TGFB1; locus 5q31 Deposition of small, discrete, sharply demarcated opacities Grayish-white opacities in the anterior central stroma Spare limbus 26
- 27. HISTOPATHOLOGY: Masson's trichrome stain: Eosinophilic, rod, or trapezoidal- shaped hyaline deposits in the stroma TREATMENT: PK / Deep lamellar keratoplasty 27
- 28. GRANULAR CORNEAL DYSTROPHY (Type 2) Syn. Avellino corneal dystrophy; Combined granular-lattice dystrophy AD; gene TGFB1 Recurrent erosions, visual impairment (1) Anterior, stromal, discrete gray-white granular deposits (2) Mid to posterior stromal lattice lesions (3) Anterior stromal haze 28
- 29. HISTOLOGY: Hyaline(Masson trichrome) and amyloid (Congo Red) 29
- 30. treatment Therapeutic contact lenses Artificial tears Epithelial erosions SURGERY Superficial Superficial keratectomy Lamellar keratoplasty Phototherapeutic keratectomy (PTK) Deep PK- recurrence as early as 1 year 30
- 31. MACULAR CORNEAL DYSTROPHY Inheritance: AR Genetcis: gene CHST6; locus: 16q22 Clinical findings: Least common Clear at birth and cloud between age 3-9 ( decrease vision between 10-30) Focal gray- white opacities with indistinct edges Stroma between opacities is diffusely cloudy 31
- 32. Pathology: GAGs that stain with Alcian blue and colloidal iron Treatment: Treat erosions PKP/ DALK Recurrence 32 Thick deposition of GAG Diffuse deposition of GAG
- 33. 33
- 34. treatment Therapeutic contact lenses Artificial tears Epithelial erosions SURGERY Superficial keratectomy Lamellar keratoplasty Phototherapeutic keratectomy (PTK) PK 34
- 35. AD Bilateral Primary, localized corneal amyloidosis 35LATTICE DYSTROPHY small refractile glass like filamentary lines
- 36. anterior stromal white dots diffuse central anterior stromal haze 36
- 37. 37 Characteristi s Lattice Type 1 Lattice Type 2 (Meretoja syndrome) Inheritance AD AD Gene 5q31; TGFB1 9q34; gelsolin Onset 10yrs 20-35yrs Visual Acquity Poor after 40 Good until 65 Erosions Frequent Infrequent Cornea Numerous glass like delicate lines, amorphous deposits, periphery clear Few thick lines extend to periphery, few amorphous deposits Systemic None Amyloidosis involving skin, arteries and other organs Face Normal Facial paresis, typical dermatochalasis, lagophthalmous,pedulous ears, dry lax skin
- 38. Pathology Amyloid deposits concentrated in anterior stroma Stains pink with Congo red, metachromatically with crystal violet, and exhibits birefringence with polarized light Management Patching, hypertonic agents, contact lens, superficial keratectomy or PTK Severe cases with visual loss treated with DALK or PKP Recurrence is more common than other stromal dystrophies 38
- 39. SCHNYDER CORNEAL DYSTROPHY Inheritance: AD Genetics: locus 1p36; gene UBIAD1 Clinical findings: Rare and slow progressive (predictable progression) Central opacification (20s);dense arcus (30s) Mid peripheral full thickness opacification (40s) Decreased corneal sensation 39
- 40. Pathology: Accumulations of cholesterol and phospholipids Oil-red- O stains the phospholipids red. Management: Most have PKP by the age 50. Can recur Many have abnormal lipid panel 40 Polychromatic cholesterol crystals deposits- geographic, annular, or disciform pattern
- 41. Treatment : Lipid profile PTK Lamellar keratoplasty PK 41
- 42. DESCEMET’S MEMBRANE AND ENDOTHELIAL DYSTROPHY 42
- 43. FUCHS ENDOTHELIAL CORNEAL DYSTROPHY Syn. Endoepithelial corneal dystrophy Inheritance: sporadic; occasional AD Gene locus: 13pTel –13q12.13, 15q, 18q21.2 –q21.32. Early-onset variant:1p34.3 – p32 G Female preponderance Onset >50yrs (early onset variant-3rd decade) 43
- 44. Symptoms: Decrease in vision (edema) Pain (ruptured bullae); pain subsides once fibrosis occurs Clinical Findings: Corneal guttae (central to periphery) Decompensated cornea with stromal edema(DM folds) Epithelial edema, microcystic edema (epithelial bullae) Subepithelial fibrosis 44
- 45. stages Stage 1: asymptomatic, central corneal guttae with fine pigment dusting, vision and corneal thickness normal Stage 2: Stromal edema, painless decreased vision glare and haloes Stage 3: Persistent epithelial edema leading to microcysts and bullae pain upon rupture Stage 4 – Growth of avascular subepithelial connective tissue, scarring, pain diminished but severely reduced vision 45
- 46. Pathogenesis: Abnormal production of collagenous material by the affected endothelial cells Marked thickening of descemet’s membrane guttae Deposition of collagen and extracellular matrix in Descemet’s membrane Na+/K- pump 46
- 47. Treatment: - Reduce edema with NaCl drops - Lower IOP - Bandage Contact Lenses to protect exposed nerve endings - PK 47
- 48. POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY Syn. Posterior polymorphous dystrophy (PPMD); Schlichting dystrophy Inheritance: AD Unilateral Clinical features: (any or all of following) Isolated group vesicles Geographic-shaped, discrete, gray leisons Broad bands with scalloped edges 48
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- 50. Pathogenesis: - Focal metaplasia of endothelial cells into keratinized epithelial-like cells. - Loss of stromal deturgesence - Tendency towards synechiae formation Treatment: Majority require no treatment Keratoplasty for corneal opacification. 50
- 51. CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY AD/AR Onset is perinatal Focal or diffuse thickening of Descemet membrane and endothelial degeneration Blue-gray with ground glass appearance to total opacification 51
- 52. CHED 1 CHED 2 Autosomal dominant (chr 20p11) Autosomal recessive (20p13) Clear cornea at birth Corneal clouding at birth Photophobia and epiphora common No Photophobia and epiphora Vision better Vision poor Nystagmus uncommon Nystagmus common 52 Diagnosing corneal dystrophies in the pediatric patient remains a challenge.
- 53. … take home messages… Inherited, bilateral and symmetric, slowly progressive Not related to environmental or systemic factors Early than degeneration (fuchs’ dystrophy which occurs in 40s- 50s) Positive family history Mostly autosomal dominant ( macular corneal dystrophy, CHAD 2- AR) PPMD and fuchs’ dystrophy raised IOP Treatment- symptomatic. Surgery if vision impaired. Recurrence in graft common 53
- 54. References AAO. External disease and cornea. 2013-2014 Kanski. Clinical ophthalmology, 8th edition Jayne S et al. IC3D classification of corneal dystrophies- Edition-2. cornea. Vol 32, feb 2015 Yanoff and Ducker Ophthalmology, 3rd edition Internet sources, www.corneasociety.org 54
- 55. 55 THANKYOU !!!
Editor's Notes
- #5: the term is most commonly used to describe an inherited disorder affecting cells, tissues, or organs, alone or in combination. Arthur Groenouw (1862–1945) published his classic paper describing 2 patients with ‘‘noduli corneae,’’ with 1 patient having granular corneal dystrophy and the other, macular corneal dystrophy.
- #6: exceptions to each of these definitions have been noted. patients with epithelial basement membrane dystrophy: no hereditary pattern. patients with posterior polymorphous corneal dystrophy manifest unilaterally. In macular dystrophy, the level of antigenic serum keratan sulfate correlates with the immunophenotypes of the disease, indicating that systemic abnormalities are integral to the development of the characteristic corneal changes.
- #12: The most common dystrophy seen in clinical practice; Onset in the 2nd decade
- #13: Signs: lesions besat visualized in retroillumination Dot like and microcystic epithelial lesion; subepithelial map laike pattern; whorled fingerprint like lines; bleb like subepithelial pebbled glass pattern
- #14: Thin, relucent hair like lines (fingerprint) thicker irregular surrounded by fine haze (map like) Dot like and microcystic epithelial lesion; subepithelial map laike pattern; whorled fingerprint like lines; bleb like subepithelial pebbled glass pattern
- #15: Extra sheets of basement membrane material grow into the epithelium. Masson trichrome; F, PAS,
- #16: It has been linked to mutations in corneal keratin (K3 and K12) that are specifically expressed in the epithelium and not in other layers.
- #17: EM: ELECTRON MICROSCO Degenerated epithelial cell products with cytoplasmic and nuclear debris
- #20: Confluent irregular and coarse geographic opacities with varying densities at Bowman layer and superficial stroma
- #21: Masson trichrome stains keratohyalin intensely red beneath the epithelium and between superficial stromal lamellae. Note characteristic destruction of the Bowman layer
- #22: Symmetric subepithelial reticular opacities sparing peripheral cornea (thus the name honeycomb)
- #23: There is varying thickness of the epithelium due to a thickened abnormal subepithelial fibrous layer (arrowheads) that replaces the Bowman layer and has a characteristic sawtooth-like surface
- #27: Crumb like opacities in the superficial cornea. On direct illumination, it appears white, indirect illumitnation, it appears small translucent dots with vacuoles (crushed bread crumb appearance) Drop-shaped; Crumb-shaped; Ringshaped
- #28: Noncollagenous protein derived from keratocytes
- #29: Stellate shaped snowflake like opacities Fine superficial opacities, stellate or annular lesions
- #30: Dashes in GCD2 appear whiter, and lattice lines in LCD are more refractile. 2. Dashes in GCD2 rarely cross each other, while lattice lines in LCD characteristically intersect to result in the pathognomonic lattice configuration.
- #31: TREATMENT: Lamellar Keratoplasty or PK (PTK is not recommended as it results in increased opacification)
- #32: Involves entire stroma and periphery Carbohydrate sulfotransferase 6
- #33: Colloidal iron stain
- #36: Congo red stain
- #39: This same section viewed with polarized light confirms deposits are birefringent
- #40: Disproportionately reduces photopic vision with excellent scotopic vision UbiA prenyltransferase domain containing protein
- #41: Oil Red O stains innumerable tiny lipid droplets within the corneal stroma in a frozen section Sine crystals
- #45: Corneal thickness increases to nearly 1mm (normal is 0.52-0.56mm) Symptoms worsens upon awakening because of the decreased surface evaporation during sleep
- #46: Stage 1 at this stage patients vision is nrmal; stroma n epithelium uninvolved
- #47: Guttae, Latin for "drops," are excrescences of collagen produced by stressed corneal endothelial cells.
- #49: this rare dystrophy has a clinical spectrum that ranges from congenital corneal edema to late-onset corneal edema in middle age. Many cases are subclinical and have good vision Broad peripheral synechia Increased intraocular pressure Iris atrophy/corectopia
- #50: Pic1: isolated vesicles bilaterally, which appear as circular or oval transparent cysts with a gray halo at the level of Descemet’s membrane, best viewed by retroillumination Pic2: band-shaped or “snail track” areas, which typically have scalloped edges Pic3: rounded dark area with central cell detail (doughnut like pattern)
- #52: other features: corneal thickness two to three times normal (>1mm centrally), normal IOP, and normal corneal diameter. Associated features are corneal pannus, nystagmus, and esotropia.
- #53: t/t: these patients require keratoplasty due to the bilateral nature of the corneal edema. despite significant corneal haze and absence of a red reflex, patients often seem to see much better than expected.