Congenital corneal disorders

Various corneal disorders, their clinical presentation and management.

1. CONGENITAL ANOMALIES OF CORNEA Dr. Sneha Thapliyal

2. Embryology....

3. 4-5 weeks: surface ectodermal cells cover the defect  primitive corneal epithelium Primary acellular stroma or post epithelial layer (random fibrils) ~5 th week : 1 st wave of mesenchymal cells just beneath the primitive epithelium  primitive endothelium (double layer) ~7 th week: 2 nd wave b/w endothelium and epi cellular stroma ( keratocan ) 7-10 th week: mesenchymal cells differentiate into sclera/cornea + corneal curvature> scleral curvature

4. 8 th week: endothelium becomes monolayer and starts producing decemets membrane 12-26 weeks: epi  stratified squamous epi 20 weeks: Condensation of acellular anterior stroma  bowman’s membrane 3 rd month: corneal nerves invade stroma 5 th month: tight junction around endothelial cells 5-7 th month: transparent in utero Na-k ATP pump

5. CORNEA Forms the anterior 1/6 th of the globe DIA: H 11.5-12, V 10.5-11 CURVATURE: Anterior: 7.8mm; Posterior: 6.5mm REFRACTIVE POWER:43D CORNEAL THICKNESS : Central: 0.52mm Peripheral: 0.67mm

6. LAYERS OF CORNEA

7. EPITHELIUM

8. INTER CELLULAR JUNCTIONS DESMOSOMES ADHERENS JUNCTIONS TIGHT JUNCTIONS GAP JUNCTIONS CYTOPLASMIC FILAMENTS KERATIN ACTIN MICROTUBULES SOURCE OF CORNEAL EPITHELIAL CELL: Limbal progenitor epithelial cell k/a adult corneal epithelial cell Located peripherally in palisades of vogt

9. BOWMAN’S MEMBRANE Acellular ,forms an interface between basal lamina of epithelium and the lamellar stroma Secreted by both epithelial cells and stromal keratocytes Randomly arranged collagen fibrils Considerable resistance to infection and injury. Once destroyed can not regenerate Collagen types:type1 and type 5

10. STROMA 90% thickness of the cornea Predominantly water Structural network of insoluble and soluble ECM and cellular components CELLULAR COMPONENTS Collagen Keratocytes Proteoglycans and GAG Histiocytes /wandering macrophages Corneal nerves

11. FUNCTIONS OF THE STROMA Maintain proper curvature Mechanical resistance to IOP CORNEAL TRANSPARENCY

12. CORNEAL LAMELLAE Randomly arranged in anterior stroma Orthogonal to one another in posterior stroma ANTERIOR 1/3 RD POSTERIOR2/3 RD The type 1 fibrils and corneal lamellae stretch across the cornea from limbus to limbus in a belt like fashion where they turn and for a circumferential annulus 1-2.5mm wide around the cornea maintaining the curvature of the cornea

13. PROTEOGLYCANS CORE PROTIEN DECORIN LUMICAN KERATOCAN MIMECAN Attached covalently to GAG’S Non covalently to collagen fibrils

14. FUNCTIONS Tissue volume Maintain the spatial order of collagen fibrills Resist compressive forces Viscoelastic properties to tissue GAG: Keratan sulphate (60%)  posterior stroma Dematan sulphate (40%)  anterior stroma

15. KERATOCYTES Are fibroblasts found through out stroma Are active in neonatal life and during trauma Large nucleus and less cell organelles KERATOCYTE PROGENITOR CELLS  subpopulation of adult stromal stem cell present in periphery near the limbus

16. Dua’s layer Also known as pre descemets layer Simulating DALK air bubbles were injected into the cornea after descemets membrane was surgically removed It formed two types of air bubbles type 2 which dissipated and type 1 which did not. Further experiments showed that all air bubble free specimens could be reinflated with a type 1 bubble Indicating bubble was being trapped by a distinct layer of material which is not a normal variation of corneal stroma Results were studied by optical and electron microscopy that revealed a thin layer of corneal collagen between corneal stroma and descemets membrane

17. DESCEMET’S MEMBRANE Anterior banded zone is present at birth Posterior 2/3 rd is the non banded zone formed by endothelium Regenerates post trauma Highly elastic Consists of collagen type4 , laminin , fibronectin and collagen type 8 Schwalbe’s line Hassel henle bodies Guttae

18. ENDOTHELIUM Single layer of flat polygonal cells Hexagonal cells attached to descemet’s membrane via hemidesmosomes and to each other by desmosomes Metabolically active with abundant granules 6000 at birth  falls by 26% in 1 st year falls by 26% in next 11 yearsstable , 2400-3000cells/ sqmm Polymegathism 70-80%cells are hexagonal if not is none as pleomorphism

19. Blood supply AVASCULAR Small loops derived from anterior cilliary vessels that invade periphery for about 1mm and provide nourishment

20. Corneal nerves

21. Congenital anomalies of cornea.....

22. Congenital anomalies Anomalies of size and shape Mesenchymal dysgenesis of anterior ocular segment- anterior cleavage syndrome Corneal dystrophies

23. Developmental corneal anomalies of size and shape Absence of the cornea Anomalies of corneal size Anomalies of corneal shape

24. Absence of cornea True absence True cryptophthalmos / ablepharon Pseudocryptophthalmos

25. True absence Very rare Always accompanied by agenesis of various other anterior segment structures

26. Cryptophthalmos AR, B/L Skin ( dermoid transformation) replaces normal eyelid architecture Connect to the underlying globe and anterior segment  grossly abnormal Absence of lashes, brows, lacrimal gland and cannaliculi Small or absent AC

27. Diagnostic criteria for cryptophthalmos syndrome FRASER SYNDROME Major criteria Minor criteria Cryptophthalmos Synctactyly Abnormal genital Sibling with cryptophthalmos syndrome Congenial malformation of the nose Congenital malformation of the ears Congenital malformation of the larynx Cleft lip and/or palate Skeletal defects Umbilical hernia Renal agenesis Mental retardation Atleast 2 major criteria and one minor criteria or one major and 4 minor criteria

28. Pseudocryptophthalmos Total ankyloblephron Eyelids form but fail to separate Normal cornea and conjunctiva covered by skin Both lashes and brows are present Vision restored by surgery creating a palpebral fissure

29. Anomalies of Size Microcornea ‡ Megalocornea ‡

30. Microcornea C lear cornea of normal thickness H Diameter is < 10 mm (or 9.5-10 mm in a newborn 10-12.5 MM IN ADULTHOOD) Non progressive, u/l or b/l , no sex predilection ‡  Anterior microphthalmos : whole anterior segment is small ‡ Microphthalmos : entire eye is small and malformed Nanophthalmos : eye is small but otherwise normal MIDAS: DELETION OF SHORT ARM OF X P 22 MICRO+ DERMA APLASIA+ SCLEROCORNEA

31. Pathogenesis ‡Cause unknown Fetal arrest of growth of the cornea in the 5 th month ‡Overgrowth of the anterior tips of the optic cup, which leaves less space for the cornea to develop.

32. Clinical Findings ‡ Autosomal dominant or recessive Equal sex predilection ‡Cornea relatively flat: hyperopia & increased incidence of angle-closure glaucoma

33. Clinical Findings Associated ocular anomalies: ‡Persistent fetal vasculature ‡Congenital catarcts ‡Anterior segment dysgenesis ‡Optic nerve hypoplasia Associated systemic conditions: ‡ Myotonic dystrophy ‡ Fetal alcohol syndrome ‡ Achondroplasia ‡Ehlers- Danlos syndrome

34. Management ‡Excellent visual prognosis if an isolated finding ‡Spectacles to treat the hyperopia resulting from the flat cornea ‡Specific treatment for concurrent ocular pathology

35. Megalocornea ‡Bilateral, nonprogressive corneal enlargement ‡X-linked recessive ‡ Histologically normal cornea measuring >=12MM AT BIRTH AND AFTERV 2 YRS >13.0 mm ‡Males are more typically affected

36. Pathogenesis ‡ Failure of the optic cup to grow and of its anterior tips to close, leaving a larger space for the cornea to fill

37. Three patterns Simple megalocornea Anterior megaophthalmos Buphthalmos

38. Simple megalocornea Normal cornealdiameter >13mm Non progressive AD inheritance

39. Anterior megaophthalmos X linked recessive Central cornea usually clear but may contain mosaic stromal opacity Corneal curvature is normal Deep anterior chamber Hypoplastic iris stroma Excess mesenchymal tissue in angle  increased IOP Lens subluxation and cataracts before 40 years

40. Buphthalmos Triad of: haab’s striae , increaesd IOP and optic disk changes Milder case can be differentiated by sharply demarcated limbal region seen in megalocornea A-scan : to measure axial length in which entire globe is increased along with cornea

41. Clinical Findings Associated ocular anomalies: Iris translucency ( diaphany ) ‡ Miosis ‡ Goniodysgenesis ‡Cataract ‡ Ectopia lentis ‡ Arcus juvenilis ‡Mosaic corneal dystrophy ‡Glaucoma Craniosynostosis ‡Frontal bossing ‡ Hypertelorism ‡Facial anomalies Associated systemic conditions‡ Dwarfism ‡Facial hemiatrophy ‡Mental retardation ‡ Hypotonia ‡Down Syndrome ‡ Marfan Syndrome ‡ Alport Syndrome ‡ Osteogenesis imperfecta Mucolipidosis type II

42. Management Intraocular pressure testing and slit lamp biomicroscopy : to rule out congenital glaucoma ‡ Ultrasonography : to determine short vitreous length , deep lens and iris position, and normal axial length that distinguish megalocornea from buphthalmos caused by congenital glaucoma ‡ Careful cataract surgery: to implant the IOL in the lens capsular bag

43. Anomalies of shape of cornea Cornea plana / sclerocornea Posterior keratoconus : generalized/circumscribed Keratoglobus Congenital staphyloma and keratectasia

44. Cornea Plana ‡Flat cornea, where the radius of curvature is less than 43 D, and readings of 30-35D are common ‡Corneal curvature that is the same as the adjacent cornea is pathognomic All cases have some degree of peripheral or central scleralization

45. Sclerocornea ‡ Nonprogressive , noninflammatory scleralization of the cornea, may be limited to the corneal periphery, or the entire cornea may be involved.

46. Pathogenesis ‡ Autosomal recessive and dominant forms of cornea plana and sclerocornea , AR having more severe manifestation 7 th -8 th gestational weeks when mesenchymal cells differentiate into sclera and cornea and also allows corneal curvature to exceed scleral curvature.

47. Clinical Findings Associated ocular anomalies: ‡ Sclerocornea ‡ Microcornea ‡Cataracts ‡Anterior and posteriorcolobomas ‡ Hyperopia ‡Angle-closure glaucoma ‡Open-angle glaucoma Associated systemic condition: ‡Ehlers- Danlos Syndrome

48. Management ‡Refractive errors are corrected ‡Loss of central clarity may indicate penetrating keratoplasty , but cornea plana increases the risk of graft rejection and post keratoplasty glaucoma.

49. Generalized posterior keratoconus Increased posterior corneal curvature with a short radius of curvature Normal anterior corneal surface Central cornea is thinned but clear Sporadic as a result of developmental arrest. Less common

50. Circumscribed Posterior Keratoconus ‡More common Localized central or paracentral indentation of the posterior cornea without any protrusion of the anterior surface, as seen in typical keratoconus

51. Pathogenesis Abnormal migration of the 2 nd wave of mesenchymal cells that normally form corneal stroma Represent mild variant of Peter’s anomaly therefore implying some intrauterine inflammation or anterior segment dysgenesis

52. Clinical Findings ‡ Variable amount of overlying stromal haze ‡Loss of stromal substance can lead to corneal thinning approaching one third of normal. ‡ Descemet’s membrane and endothelium are usually present in the area of defect ‡Focal deposits of pigmentation and guttae are often present at the margins of opacity. ‡Astigmatism and/ or amblyopia may occur

53. Keratectasia and Congenital Anterior Staphyloma ‡ Unilateral conditions that are both characterized by protrusion of the opaque cornea between the eyelids at birth. ‡Differ only in the presence of a uveal lining of the cornea in congenital anterior staphyloma

54. Pathogenesis ‡ Secondary failure of neutral crest cell migration results in dermoid transformation of the cornea to stratified squamous epithelium, sparing the eyelids and conjunctiva.

55. ‡ Histopathologically , Descemet’s membrane and endothelium are absent , and a uveal lining is present (except in keratectasia ). ‡The cornea is variably thinned and scarred and the anterior segment disorganized, with the lens occasionally adherent to the posterior cornea , resembling unilateral Peters anomaly

56. Management ‡Except in very mild cases, visual prognosis is poor because of associated severe damage to the anterior segment. Penetrating keratoplasty is rarely warranted, and enucleation may be required for a blind, glaucomatous, painful eye

57. Keratoglobus b/l , non inflammatory Entire cornea is thinned out ( 1/3 rd -1/5 th the normal thickness) and takes globular shape Keratomertry readings: 60-70 D Strong association with Ehler-Danlos syndrome type VI

58. Histopathology Absent/fragmented Bowman’s membrane Thinned stroma with normal lamellar orientation Thin Decemet’s membrane with focal breaks Normal endothelium Thin sclera

59. Clinical features Globular shape of cornea Thinning more pronounced in mid-periphery Very deep anterior chamber Otherwise normal anterior segment structures

60. Management Spectacle correction for high myopia to avoid amblyopia . 2 stage procedure : epikeratplasty or tectonic lamellar corneo-scleral graft followed by penetrating keratoplasty weeks to months later Protective eye wear is strongly encouraged and enforced.

61. Anterior chamber cleavage syndrome Posterior embryotoxon Axenfeld-Rieger syndrome Peter’s anomaly Iridogoniodysgenesis

62. Posterior Embryotoxon ‡ Thickened and centrally displaced anterior border ring of Schwalbe ‡ Schwalbe’s ring represents the junction of the trabecular meshwork with the termination of  Descemet’s membranes. ‡Usually inherited as a dominant trait

63. Axenfeld-Rieger Syndrome ‡ Represents a spectrum of disorders characterized by an anteriorly displaced Schwalbe’s ring ( posterior embryotoxon ), with attached iris strands , iris hypoplasia , and glaucoma in 50% of the cases occurring in late childhood or adulthood Associated skeletal, cranial, facial, and dental abnormalities are often present

64. Transmission is usually dominant (75%) for the Axenfeld-Rieger group, but it can be sporadic . ‡Spectrum of mutations of transcription factors located in chromosome region 6p25 , known as forkhead genes , are responsible for many developmental defects of the anterior chamber of the eye

65. Peters Anomaly ‡3 anatomic components Central posterior corneal defect in endo and DM with overlying corneal opacity Keratoiridial adhesion Corneaolenticular contact or cataract Defective neural crest cell migration in 6 th -8 th week of gestation.

66. ‡80% bilateral Inheritance is mostly sporadic ‡Associated ocular anomalies present in ~50%of cases Associated with systemic malformations in60% of cases

67. Clinical Findings Associated ocular anomalies: ‡ Keratolenticular touch ‡Cataract ‡Congenital glaucoma ‡ Microphthalmos ‡ Aniridia ‡Persistent fetal vasculature Associated systemic malformations ‡craniofacial anomalies ‡External ear abnormalities Hearing loss ‡ ‡Peter’s plus’: short-limbed dwarfism, cleft lip/ palate,learning difficulties

68. Histopathologic Findings Localized absence of the corneal endothelium and Descemet’s membrane beneath the area of opacity

69. Corneal Dystrophies ‡Congenital hereditary stromal dystrophy ‡Posterior amorphous corneal dystrophy ‡Congenital hereditary endothelial dystrophy

70. Congenital Hereditary Stromal Dystrophy (CHSD) ‡Extremely rare AD stationary dystrophy presents at birth with bilateral central superficial corneal clouding. Anterior corneal stroma exhibits an ill-defined flaky or feathery opacity. ‡ Cornea is clear peripherally ‡ No edema , photopobia or tearing, but the opacities can be sufficiently dense to cause a reduction in vision

71. Posterior Amorphous Corneal Dystrophy ‡ Rare autosomal dominant stromal dystrophy is bilaterally symmetric. Appears early in life and may be congenital Grouped vesicles, refractile geographic lesions, scalloped bands and peripheral iridocorneal adhesions

72. ‡Gray-white, sheet like stromal opacities concentrated in the posterior stroma . ‡Epithelium appears normal, but Descemet’s membranes shows involvement, with focal areas of endothelial disruption ‡Central corneal thinning ‡ Hyperopia ‡Flattened corneal topography ‡Anterior iris abnormalities ‡Fine iris process extending to Schwalbe’s line for 360 degree.

73. Congenital hereditary endothelial dystrophy (CHED) ‡A cause of bilateral congenital corneal edema ‡Due to primary dysfunction of the corneal endothelium, characterized by increased permeability and abnormal Descemet’s membrane secretion ‡No consistent associations with other systemic abnormalities

74. Dominant form (CHED 1) ‡Presents in the first or second year of life ‡Slowly progressive ‡Accompanied by pain, photophobia, and tearing but nystagmus is not present ‡Cornea exhibits a diffuse, blue-gray, ground-glass appearance ‡Primary abnormality: degeneration of endothelial cells during or after the 5th month

75. Autosomal Recessive Type(CHED 2) ‡Presents at birth, remains stationary and A ccompanied by nystagmus ‡Bluish white cornea may be 2-3 times normal thickness and have a ground-glass appearance, but this finding is not associated with tearing or photopobia ‡Diffuse non bullous epithelial edema ‡ Uniform thickening of Descemet’s membrane may be seen, but no guttae changes are present

76. Iridocorneal Endothelial Syndrome ‡Spectrum of disorders characterized by varying degrees of corneal edema , glaucoma and iris abnormalities Corneal edema that precluded visualization of the posterior cornea

77. Pathogenesis ‡Unknown but appears to involve an abnormal clone of endothelial cells that takes on ultrastructural characteristics of epithelial cells ‡Varying degrees of endothelialization take place in the anterior chamber angle and on the iris surface .

78. Clinical Findings Iris atrophy, corectopia , polycoria (hallmarks of the essential iris atrophy variant) Cogan-Reese (iris-nevus variant)   Chandler variant : hammered silver endothelium

79. Management ‡Penetrating keratoplasty ‡Long-term graft clarity depends on the successful control of the IOP