Corneal Disorders Epi to Endo

Transcription

1 Corneal Disorders Epi to Endo Christine W Sindt OD FAAO University of Iowa Director, Contact Lens Service Associate Professor of Clinical Ophthalmology 1

2 Corneal Epithelium: Anatomy Thickness of epi? Time to turnover? Time for production of basement membrane? Components of b.m.? Collagen IV Laminin Fibronectin (during active epithelial injury) 40-50u 7-10 days 6 weeks 2

3 Corneal Epithelium: Wound Healing Healing from injury: immediate immediate cell migration and spreading in smaller injuries, delay of hours in larger injuries migrates migrates at rate of up to 60-80um/hr mitosis mitosis and proliferation begins at 24hrs for smaller injuries, up to 96hrs for larger injuries X, X, Y, Z hypothesis: proliferate, migrate, desquamate all all this is affected by ocular surface disease 3

4 Corneal Epithelium: Wound Healing diabetes: diabetes: thickened b.m. neurotrophic:: lack of substance P? DDx? DDx AFIP-CC Amiodarone Fabry s Dx. Indomethacin Plaquenil Chloroquine Chlorpromazine 4

5 Corneal Epithelium: Wound Healing Factors effective in wound healing: growth growth factors? fibronectin:: from plasma and fresh wounds effective in some PEDs but not others tretinoin:: promotes proper differentiation of proliferating epi cells 5

6 Corneal Epithelium: RES 2 Types 1. Primary Corneal dystrophies. 2. Secondary after minor trauma. Most common reason for recurrent erosion syndrome Usually lasts weeks, but can be years Cornea may be normal in between episodes other: e.g., diabetes 6

7 Corneal Epithelium: Dystrophies Map Fingerprint Dot 7

8 Corneal Epithelium: Dystrophies Map-Dot Dot-Fingerprint most most common anterior corneal dystrophy 33 main findings: thickening of b.m. with extensions into epithelium intraepithelial microcysts from degenerated, trapped epi cells fibrillar material between b.m. and underlying Bowman s associated associated with recurrent erosions in 10% found found in 50% of people with recurrent erosions 8

9 Corneal Epithelium: Dystrophies Meesman s Epithelial Dystrophy autosomal autosomal dominant, bilateral, seen in childhood multiple multiple intraepithelial vesicles 9

10 Corneal Epithelium: Dystrophies Meesman s Epithelial Dystrophy asymptomatic until middle age with irritation, photophobia, RES 10

11 Corneal Epithelium: Dystrophies Meesman s Epithelial Dystrophy histopath:: thickened epi, projections of b.m. into epi, intracytoplasmic fibrillogranular peculiar substance 11

12 Corneal Epithelium: RES Treatment Medical lubrication hypertonic solutions Surgical anterior stromal micropuncture superficial keratectomy PTK 12

13 Stromal Dystrophies and Ectasias 1. Anterior membrane dystrophies 2. Stromal dystrophies 3. Corneal ectasias 13

14 Anterior Membrane Dystrophies Reis-Bücklers Dystrophy Thiel-Behnke Honeycomb Dystrophy Subepithelial Mucinous Corneal Dystrophy Lot of confusion between first two. 14

15 Reis-Bücklers Alternative Names CDB I (Corneal Dystrophy of Bowman s s I) SVGD (Superficial Variant of Granular Dystrophy) Granular dystrophy Type III AD, 5q31 (BIGH3) 15

16 Reis-Bücklers Clinical Features RES beginning in first few years of life early and marked visual loss (earlier than CDB II) superficial ring or map- shaped opacities 16

17 Reis-Bücklers 17

18 Reis-Bücklers Pathology subepithelial/anterior stromal fibrosis destruction of Bowman s Masson-positive granular subepithelial deposits (similar to granular dystrophy) Electron Microscopy: rod- shaped bodies (similar to granular dystrophy) NOT curly fibers sawtooth shape in region of Bowman s s from scarring 18

19 Reis-Bücklers Treatment SK PTK Penetrating Keratoplasty can recur in grafts 19

20 Thiel-Behnke Alternative Names CDB II (Corneal Dystrophy of Bowman s s II) Honeycomb Dystrophy AD, 5q31 (BIGH3) 20

21 Thiel-Behnke Clinical Features RES begins later in life, in 1 st /2 nd decades superficial reticular corneal scarring honeycomb or ring- shaped opacities 21

22 Thiel-Behnke Pathology subepithelial/anterior stromal fibrosis destruction of Bowman s only equivocally positive with Masson Electron Microscopy: curly fibers sawtooth shape in region of Bowman s s from scarring (same as Reis-Bücklers cklers) 22

23 Thiel-Behnke Treatment SK PTK Penetrating Keratoplasty Can recur in grafts 23

24 Subepithelial Mucinous Corneal Dystrophy AD, very rare. Clinical Features: RES in 1 st decade of life, subside over next decade progressive visual loss dense, subepithelial, gray-white patches densest centrally intervening generalized subepithelial haze to limbus 24

25 Subepithelial Mucinous Corneal Dystrophy Pathology: eosinophilic,, PAS + subepithelial deposits anterior to Bowman s stain with Alcian Blue consist of chondroitin sulfate and dermatan sulfate (mucopolysaccharides) 25

26 Subepithelial Mucinous Corneal Dystrophy Treatment SK Penetrating Keratoplasty 26

27 Stromal Dystrophies 1. Lattice Dystrophy 2. Granular Dystrophy 3. Avellino Dystrophy 4. Macular Dystrophy 5. Gelatinous Drop-Like Dystrophy 6. Schnyder Crystalline Dystrophy 7. Central Cloudy Dystrophy of Francois 8. Fleck Dystrophy 9. Cornea Farinata 10. Pre-Descemet Descemet s Dystrophy 11. Posterior Amorphous Corneal Dystrophy 12. Congenital Hereditary Stromal Dystrophy 13. Primary Band Keratopathy 27

28 Lattice Dystrophy 3 Types: I: Primary corneal II: Secondary, systemic III, IIIA: Primary corneal Types I, III: AD, 5q31 (BIGH3) encodes for keratoepithelin,, found in corneal epithelial cells and stromal keratocytes Type II: AD, 9q34 28

29 Lattice Dystrophies Type I Type II (Meretoja) Type III Characteristic Inheritance Autosomal dominant Autosomal dominant Autosomal recessive? Onset <10 years 20 to 35 years >40 years Visual acuity Poor after age 40 Good until age 65 Impaired after 60 yo Erosions Frequent Infrequent None Cornea Systemic involvmnt Numerous, delicate lines, many amorphous deposits; periphery clear None Few thick lines; periphery involved; few amorphous deposits Amyloidosis involving skin, arteries, and other organs Face Normal Facial paresis and blepharochalasis after age 40 Thick lines None Normal 29

30 Lattice Dystrophy Type I Most common type. Clinical Features: bilateral, may be asymmetric fine, rod-like, glassy opacities in anterior stroma begin in 1 st /2 nd decade RES central anterior stromal haze may develop 30

31 Lattice Dystrophy Type I Pathology: amyloid deposits stain with Congo red, PAS, and Masson s trichrome 31

32 Lattice Dystrophy Type I Pathology: amyloid deposits stain with Congo red, PAS, and Masson s trichrome dichroism and birefringence seen with polarized light 32

33 Lattice Dystrophy Type II Secondary corneal amyloidosis. associated with Meretoja syndrome ie,, Familial Amyloid Polyneuropathy Type IV (Finnish type) cranial neuropathy, including bilateral facial n. systemic amyloid deposition 33

34 Lattice Dystrophy Type II lattice lines greater in periphery fine lines, more radial clear intervening stroma RES less frequent visual changes less severe higher incidence of glaucoma and PXF 34

35 Lattice Dystrophy Type III thick, ropy lines no RES later in life (>40 yo) IIIA: French variant: autosomal dominant, with RES Lattice Type IIIA 35

36 Granular Dystrophy 3 Types: I: Classic granular dystrophy II: Avellino dystrophy III: Reis-Bücklers dystrophy AD, 5q31 (BIGH3) 36

37 Granular Dystrophy Type I AD, chrom.. 5q (BIGH3) discrete corneal opacities (bread- crumbs) whitish or glassy clear intervening stroma often asymptomatic RES in some (?SVGD) 37

38 Granular Dystrophy Type I Pathology: stains red with Masson trichrome EM: rod-like bodies Treatment: PKP recurs superficially in grafts can be treated with PTK 38

39 Avellino Dystrophy autosomal dominant, chromosome 5q (BIGH3) combines features of both granular and lattice dystrophies majority of patients from the Avellino region of Italy Clinical Features: granular deposits in anterior stroma develop first lattice lines deeper in the stroma develop later gray, subepithelial haze centrally RES vision loss 39

40 Macular Dystrophy Least common and most severe of the 3 classic stromal dystrophies. AR, 16q21. 3 Types: I: no detectable antigenic keratan sulfate (aks( aks) ) in serum or cornea II: normal amounts of aks in serum and cornea corneal deposits react with anti-ks antibody IA: no detectable aks in serum, but keratocytes react with antibodies to keratan sulfate 40

41 Macular Dystrophy Clinical Features: faint, white, anterior stromal opacities early in life become denser with ground-glass glass haze throughout anterior stroma severe photophobia, RES, and vision loss by 2 nd to 3 rd decades 41

42 Macular Dystrophy Pathology: glycosaminoglycan accumulation within and outside keratocytes, beneath epithelium, and within endothelial cells stains with alcian blue, colloidal iron, and PAS Treatment: PKP: low recurrence in grafts 42

43 Gelatinous Drop-Like Dystrophy =Familial subepithelial amyloidosis. Autosomal recessive, 1p. Japan >> U.S., Africa, India. Symptoms: severe photophobia tearing decreased vision 43

44 Gelatinous Drop-Like Dystrophy Clinical Features: gray/white/yellow subepithelial nodules in central cornea appear in 1 st to 2 nd decades become confluent over time, giving mulberry surface to cornea later: superficial vascularization with deeper amyloid deposition 44

45 Gelatinous Drop-Like Dystrophy Pathology: subepithelial and anterior stromal accumulation of amyloid Treatment: SK recurs in 2 years PKP early recurrences 45

46 Corneal Amyloidoses 46

47 Schnyder Crystalline Dystrophy Autosomal dominant, variable expressivity. Associated with hypercholesterolemia. Clinical Features: central subepithelial crystals often in ring pattern progresses to more diffuse haze and arcus diminished corneal sensation decreased vision after 4 th decade 47

48 Schnyder Crystalline Dystrophy Pathology: oil-red O staining material (phospholipid( phospholipid, cholesterol) throughout stroma,, most prominent peripherally in Bowman s just anterior to Descemet s cholesterol clefts Treatment: PKP 48

49 Central Cloudy Dystrophy of Francois Same appearance as posterior crocodile shagreen. Autosomal dominant. Pathology sawtooth disarray of corneal stromal lamellae 49

50 Fleck Dystrophy =speckle or Francois-Neeten dystrophy. Autosomal dominant. Usually found incidentally. Discrete, small, white, comma-shaped opacities scattered throughout all levels of stroma. No epithelial involvement. Usually asymptomatic, but may have photophobia. 50

51 Fleck Dystrophy Pathology: distention of keratocytes vacuoles filled with lipid and acid MPS stains with oil-red O Treatment not necessary. 51

52 Cornea Farinata A degeneration (not a dystrophy). Associated with aging. Numerous, small, dust-like or flour-like like particles anterior to Descemet's membrane. No clinical significance. 52

53 Pre-Descemet Descemet s Dystrophy Probably autosomal dominant or degenerative. Bilateral, symmetric. Onset after age 30. Vision usually not affected. 53

54 Pre-Descemet Descemet s Dystrophy Clinical features: focal, fine gray dots in posterior stroma variety of punctate and linear shapes less commonly large circular, comma, boomerang, wormlike, and dendritic shapes may be diffuse, central, or form a ring 54

55 Pre-Descemet Descemet s Dystrophy Variant: punctiform and polychromatic pre-descemet Descemet s dystrophy Similar Entities polymorphic amyloid degeneration cornea farinata deep filiform dystrophy Pre-Descemet Descemet s opacities also seen in: pseudoxanthoma elasticum X-linked recessive ichthyosis keratoconus 55

56 Posterior Amorphous Corneal Dystrophy Rare, autosomal dominant, onset 1 st decade. Bilateral, symmetric, slow to not progressive. Findings: central and peripheral, deep, gray, broad sheets of corneal opacification some have only peripheral changes extending to limbus associated corneal flattening central thinning (can be 300 microns) iridocorneal adhesions have been reported 56

57 Posterior Amorphous Corneal Dystrophy Pathology: irregular disorganization of the corneal lamellae anterior to Descemet's membrane lipid deposition within some keratocytes Usually vision affected only minimally. Treatment is unnecessary. 57

58 Congenital Hereditary Stromal Dystrophy Non-progressive, rare, autosomal dominant anomaly. Clinical Features: bilateral, white, diffuse stromal clouding, most prominent centrally absence of corneal edema, normal pachymetry and IOP rule out glaucoma and CHED. Pathology: separation of normal lamellae with loosely packed, irregular layers of collagen thinner collagen fibrils (half of normal) lack of banding of anterior portion of Descemet s Treatment: PKP 58

59 Primary Band Keratopathy Rare, autosomal recessive form of the normally acquired band keratopathy seen in adults. Presents in childhood. 59

60 Corneal Ectasias 1. Keratoconus 2. Pellucid Marginal Degeneration 3. Keratoglobus 4. Posterior Keratoconus 60

61 Keratoconus Progressive corneal ectasia associated with corneal thinning and usually inferior corneal steepening. Probably autosomal dominant one gene mapped to chromosome 21 family history in only 10% Etiology unknown: may be related to epithelial enzyme dysregulation. Prevalence 1/2000 in general population. Topographic signs seen in up to 5% of those seeking refractive surgery for myopia. 61

62 Keratoconus Clinical Features: inferior corneal steepening Munson s s sign Rizutti s sign Charleaux s sign Other signs pulsation of mires on tonometry or keratometry secondary to ocular pulse transmitted through thin cornea 62

63 Keratoconus Clinical Features: Fleischer ring Vogt s striae apical thinning protrusion at apex hydrops fibrosis 63

64 Keratoconus Topographic Features: inferior corneal steeping paracentral anterior & posterior corneal elevation thinning corresponding to above region oblique axis of astigmatism 64

65 Keratoconus Diagnosis: Rabinowitz suggested following criteria: keratometry > 47.20D steepening of inferior cornea of >1.2D compared to superior cornea skewing of radial axis of astigmatism >21º Sensitivity 98%, specificity 99.5% 65

66 Keratoconus Ocular Associations: Leber s congenital amaurosis retinitis pigmentosa retinopathy of prematurity Systemic Associations: atopy vernal keratoconjunctivitis Down s s syndrome eye rubbing Marfan s Ehlers-Danlos 66

67 Keratoconus Pathology: breaks in Bowman s fibrosis extending into stroma breaks in Descemet s with hydrops inward curling of Descemet s 67

68 Keratoconus Treatment: spectacles contact lens penetrating keratoplasty Urrets-Zavalia syndrome epikeratoplasty lamellar keratoplasty 68

69 Pellucid Marginal Degeneration Bilateral, peripheral, usually inferior corneal ectasia. Inheritance unknown. Thinning is inferior to apex of cornea. begins mm from inferior limbus thin zone is mm wide x 6-88 mm long no iron line or striae usually clear ( pellucid( pellucid ) may develop hydrops,, which may lead to scarring & vessels 69

70 Pellucid Marginal Degeneration Against the rule astigmatism centrally. With the rule astigmatism inferiorly. 70

71 Pellucid Marginal Degeneration Horizontal mires closer together centrally. Vertical mires closer together inferiorly. (egg-shaped) 71

72 Pellucid Marginal Degeneration Classic bent bowtie on topography. 72

73 Pellucid Marginal Degeneration Treatment: large or eccentric PKP large LKP, possibly followed by PKP Easy to differentiate from other peripheral thinning disorders. 73

74 Age at onset Pellucid marginal degeneration Second to fifth decade Terrien's marginal degeneration Usually middle-aged to elderly Mooren's ulcer Adult to elderly Furrow degeneration Elderly Thinning Laterality Bilateral Bilateral Unilateral and Bilateral bilateral types Sex Male = female Males predominate Males more common Male = female Astigmatism Common Common Sometimes None Inflammation Epithelial defect Vascularization Lipid deposits Perforation Inferior band 1-2 mm wide Usually starts superiorly Starts within lid fissure None Occasionally Typical; worse in bilateral type None Usually none Typical None None None Hydrops more common Crosses area of thinning Common; central to thinning Unusual Peripheral edge of thinning Not acutely Common in bilateral type Occurs with arcus None None Corneal arcus Never 74

75 Keratoglobus Bilateral, usually nonprogressive or minimally progressive corneal ectasia. May be part of autosomal recessive syndromes: Ehlers-Danlos Type VI brittle cornea syndrome (blue sclera, red hair) 75

76 Keratoglobus Clinical Features: diffuse thinning greatest in periphery may be associated with scleral thinning normal or slightly increased corneal diameter 76

77 Keratoglobus Clinical Features: no iron line minimal if any corneal scarring less likely to develop hydrops than in KCN more likely to rupture after minimal trauma 77

78 Keratoglobus Treatment: protect from trauma epikeratoplasty large LKP, possibly followed by PKP large PKP 78

79 Posterior Keratoconus Congenital corneal anomaly with protrusion of posterior corneal surface usually localized region Usually sporadic and unilateral. probably a variant of anterior segment dysgenesis Clinical Features: often stromal scarring anterior to Descemet s in area of protrusion Treatment is usually not necessary. 79

80 Age at onset Iron line Keratoglobus Frequency Laterality Thinning Protrusion Scarring Most common Usually bilateral Pellucid marginal degeneration Keratoconus Posterior Keratoconus Less common Rare Least common Bilateral Bilateral Usually unilateral Puberty Age 20 to 40 years Usually at birth Inferior paracentral Thinnest at apex Fleischer ring Inferior band 1 to 2 mm wide Superior to band of thinning Greatest in periphery Generalized Birth Paracentral posterior excavation Usually none Sometimes None Sometimes Common Only after hydrops Mild Common Striae Common Sometimes Sometimes None 80

81 Corneal Endothelium: Anatomy Endothelial cells cells/mm 2 at birth, declines by 0.5%/yr. to % hexagonal early in life, decreasing to 60% Descemet s membrane banded layer secreted in utero starts 3um thick, banded ends 10um thick, anterior banded, posterior not banded 81

82 Corneal Endothelium: Physiology Maintenance of stromal deturgescence: passive gradient of flow from hypo-osmotic osmotic cornea to hyperosmotic aqueous endothelial cells function to pump fluid out of stroma and into aqueous via 2 mechanisms: Na +, K +, -ATPase:: membrane-bound bound carbonic anhydrase: : intracellular 82

83 Corneal Endothelial Injury Endothelial stressors: metabolic: hypoxia, hyperglycemia toxic: drugs, preservatives alterations in ph, ionization, or osmolarity trauma from surgery Changes to endothelium can appear locally, and therefore not seen on randomly selected specular microscopy photographs. 83

84 Corneal Endothelial Injury Hypoxia: contact lens wear possible permanent changes to endothelium variation in cell size increases percentage of hexagonal cells decreases 84

85 Corneal Endothelial Injury Hyperglycemia: changes in endothelium compared to age- matched controls variation in cell size increases percentage of hexagonal cells decreases doesn t t appear to affect function clinically 85

86 Endothelial Disorders Fuchs dystrophy CHED congenital hereditary endothelial dystrophy PPMD posterior polymorphous dystrophy Endothelial trauma 86

87 Endothelial Disorders: Fuchs Epidemiology most common corneal dystrophy requiring transplantation autosomal dominant with variable expressivity female:male 4:1 Caucasian=African-American>Asians American>Asians symptoms in middle age 87

88 Endothelial Disorders: Fuchs Pathogenesis altered Na +,K + -ATPase pump activity normal barrier function 88

89 Endothelial Disorders: Fuchs Guttae: excrescences of Descemet s membrane not pathognomonic for Fuchs 11% of people over 50yo have guttae seen in other conditions, including uveitis pathologically identical to Hassall-Henle Henle bodies seen in periphery 89

90 Endothelial Disorders: Fuchs Guttae: start discretely in center, advance to periphery and coalesce ( beaten( metal ) 90

91 Endothelial Disorders: Fuchs Staging 1. Endothelial changes only, vision not affected 2. Stromal swelling, especially in mornings, with affected vision. 3. Progressive stromal and epithelial microcystic edema, recurrent erosions, pannus formation, anterior stromal haze. 91

92 Endothelial Disorders: Fuchs Exam Specular microscopy Sclerotic scatter Pachymetry Retro-illumination 92

93 Endothelial Disorders: Fuchs Pathology: guttae thickened, abnormal Descemet s abnormal posterior banded layer fibrillar layer Descemet s changes can be seen before guttae paucity of endothelial cells 93

94 Endothelial Disorders: CHED One of the many causes of bilateral congenital corneal clouding. Inheritance: AD, AR, or sporadic corneal thickness two to three times the normal normal IOP normal horizontal corneal diameter associated features: corneal pannus, nystagmus, esotropia usually requires penetrating keratoplasty 94

95 Endothelial Disorders: CHED Onset: corneal clouding may be maximal at birth or progress over a period of years CHED 1: AD inheritance: progressive onset of corneal edema years postpartum with associated photophobia, but without nystagmus Genetic locus 20p11.2 q11.2 CHED 2: AR inheritance: presence at birth of bilateral corneal edema without photophobia, but with nystagmus Genetic locus 20p13 95

96 Endothelial Disorders: CHED Pathogenesis abnormal neural crest cell terminal induction during the late term to perinatal period failure to complete final differentiation of the endothelial monolayer results in a dysfunctional endothelium with faulty growth regulation mechanisms leads to formation of abnormal, thickened posterior nonbanded Descemet's membrane 96

97 Endothelial Disorders: CHED Findings diffuse stromal gray-blue ground-glass glass coloring uniform density anterior to posterior within a given region variable density across cornea where stromal opacification is less dense, Descemet's membrane appears gray and on specular reflection may have a 'peau d'orange' ' texture irregular texture of epithelial surface with diffuse pigskin- like roughness recurrent epithelial erosions are uncommon discrete white dots may be seen in the stroma fine corneal pannus may be seen 97

98 Endothelial Disorders: CHED Prognosis usually requrire penetrating keratoplasty 5-year graft survival rate about 50% usually left with haze/opaque grafts 98

99 Endothelial Disorders: PPMD Definition rare, bilateral, usually autosomal dominant with variable penetrance,, cases of autosomal recessive polymorphic posterior corneal surface irregularities widely variable degrees of corneal decompensation majority of patients are asymptomatic with subtle findings can present with congenital corneal clouding Genetic locus: PPCD1 20p11.2-q11.2 PPCD2 10p

100 Endothelial Disorders: PPMD 3 types of endothelial changes: vesicles mm diameter curvilinear irregularities band-shaped or snail track areas with scalloped edges, 1mm wide, 2-10 mm long placoid irregularities rare, diffuse corneal presentation hazy Descemet s and posterior stroma assoc. with corneal edema and iridocorneal adhesions Usually normal vision in vesicular & curvilinear, compromised in placoid. 100

101 Endothelial Disorders: PPMD Other Features: endothelial changes best seen in retroillumination with dilated pupil rounded dark areas with cells that give a doughnut-like pattern on specular microscopy reduced endothelial cell counts iridocorneal adhesions, peripheral anterior synechiae,, & glaucoma most commonly in placoid type tendency to recur in grafts 101

102 Endothelial Disorders: PPMD Pathogenesis focal transformation of endothelial cells into fibroblast-like like and epithelial-like like cells transformation of endothelial monolayer into multilayer epithelium-like like tissue 102

103 Endothelial Disorders: PPMD Pathology pits of the posterior corneal surface which correspond to the vesicles seen on exam attenuated Descemet's membrane in these areas multilayered endothelium in other areas, Descemet's membrane appears multilayered, of variable thickness, and with attenuation or loss of endothelium 103

104 Endothelial Disorders: PPMD Pathology features of abnormal endothelial cells: surface microvilli multilayered contain numerous desmosomes and intracytoplasmic filaments 104

105 Endothelial Disorders: PPMD Course believed to be nonprogressive usually without vision impairment penetrating keratoplasty for those with vision impairment risk for recurrence in the grafted cornea risk for development of severe post-transplant transplant glaucoma 105

106 Endothelial Disorders: Trauma Blunt trauma: 2 mechanisms of injury 1. Mechanical deformation of cornea buckling of cornea from blunt or surgical trauma causes annular endothelial stress with focal destruction of cells grayish swelling of endotheial cells gives snail track appearance and dark spots at level of Descemet s dark spots may resemble guttae,, but are more regular in size, not pigmented, and are reversible surrounding cells migrate rapidly usually no changes evident beyond days 106

107 Endothelial Disorders: Trauma Blunt trauma: 2 mechanisms of injury 2. Rupture of Descemet s membrane severe blunt trauma, forceps delivery Descemet s curls in toward stroma causes acute hydrops surrounding cells migrate and produce new Descemet s corneal edema resolves as new endothelial cells fill in 107

108 Isolated Congenital Corneal Anomalies 1. Anomalies of corneal size: a. microcornea b. megalocornea c. congenital corneal ectasia 2. Anomalies of corneal clarity a. anterior embryotoxon b. posterior embryotoxon c. corneal keloids d. Peters anomaly e. sclerocornea 108

109 Isolated Congenital Corneal Anomalies of Size Normal horizontal corneal diameter: mm at birth mm in adulthood 109

110 Isolated Congenital Corneal Anomalies of Size Microcornea: 110

111 Isolated Congenital Corneal Anomalies of Size Microcornea: HCD <9 mm at birth, <10 mm in adult mostly sporadic some autosomal recessive and dominant (autosomal dominant assoc. with cataract and anterior segment anomalies) remainder of eye normal, unlike microphthalmos can lead to angle closure glaucoma as lens enlarges 111

112 Isolated Congenital Corneal Anomalies of Size Megalocornea: 112

113 Isolated Congenital Corneal Anomalies of Size Megalocornea: HCD >12 mm at birth, >13 mm after 2 years of age bilateral anterior segment enlargement IOP and overall globe size normal, unlike buphthalmos and megalophthalmos usually myopic Genetic forms: X-linked recessive: more common, associated with TIDs,, pigment dispersion, lens subluxation, arcus,, & central crocodile shagreen; normal endothelial cell density, corneal thickness, and clarity autosomal dominant least common, no other ocular abnormalities other forms associated with congenital miosis, ectopia lentis et pupillae,, and mental retardation 113

114 Isolated Congenital Corneal Anomalies of Size Congenital Corneal Ectasia: = congenital anterior staphyloma often seen with Peters anomaly marked corneal thinning and bulging (worse than in usual Peters cases) usually unilateral often associated with iris developmental defects etio: : inflammatory or infectious corneal thinning in utero? 114

115 Isolated Congenital Corneal Anomalies of Clarity Developmental Correlate: lens vesicle separates from surface ectoderm at 5 th week gestation mesenchymal neural crest cells migrate between surface ectoderm and optic cup in 3 waves 1 st wave: corneal endothelium, trabecular meshwork 2 nd wave: stromal keratocytes 3 rd wave: anterior iris stroma separation of these waves of cells forms the anterior chamber alterations in these steps leads to abnormalities of specified structures 115

116 Isolated Congenital Corneal Anomalies of Clarity 116

117 Isolated Congenital Corneal Anomalies of Clarity Anterior Embryotoxon term used to describe a congenital broad limbus superiorly with an otherwise normal anterior segment merely represents a broad transition from sclera to cornea also used to describe an appearance similar to arcus senilis (arcus juvenilis) ) present at birth often sporadic, some autosomal dominant and autosomal recessive 117

118 Isolated Congenital Corneal Anomalies of Clarity Posterior Embryotoxon most frequently seen isolated corneal anomaly thickening and anterior displacement of Schwalbe's line most easily seen in the temporal cornea toxon derived from the Greek word for bow, referring to the crescent of Schwalbe's line no clinical significance when present in isolation 118

119 Isolated Congenital Corneal Anomalies of Clarity Corneal Keloids white, glistening, protuberant lesions that involve all or part of the cornea usually acquired from trauma or ocular inflammation congenital variant exists, usually bilateral histopathology: hypertrophic scar with irregularly arrayed collagen bundles, fibroblasts, and capillaries arising in the corneal stroma may be progressive sometimes associated with disorders that involve oculodigital manipulation (e.g. Lowe's syndrome) treatment: keratoplasty if no other ocular abnormalities if other abnormalities, consider dissection of the lesion from the t cornea followed by covering with a conjunctival flap to halt progression 119

120 Isolated Congenital Corneal Anomalies of Clarity Peters Anomaly Type I: Primary usually unilateral central or paracentral corneal opacity with iris strands attaching to the periphery of the opacity a defect in corneal endothelium and Descemet's membrane is present initially, often with marked corneal edema that can extend well beyond the defect over time the surrounding endothelium covers the defect, produces new basement membrane, and the edema regresses to leave the corneal opacity only 120

121 Isolated Congenital Corneal Anomalies of Clarity Peters Anomaly Type II: Secondary usually bilateral lens involvement: lens adherence to the posterior cornea, failure of complete separation of the lens from the cornea, and/or cataract usually other ocular associations usually other systemic associations (can be severe) 121

122 Isolated Congenital Corneal Anomalies of Clarity Peters Anomaly ocular associations: include chorioretinal coloboma,, iris coloboma,, PHPV, microphthalmos,, and optic nerve hypoplasia systemic associations: Krause-Kivlin Kivlin syndrome: short stature, facial dysmorphism,, developmental delay, and delayed skeletal maturation; autosomal recessive Peters'-plus syndrome: Peters' anomaly with syndactyly,, genitourinary anomalies, brachycephaly,, central nervous system anomalies, cardiac disease, or deafness; FOXC1? fetal alcohol syndrome posterior keratoconus and posterior ulcer of von Hippel might be thought of as Peters' anomaly without iris adhesions 122

123 Isolated Congenital Corneal Anomalies of Clarity Peters Anomaly Pathology absence of Descemet's membrane and endothelium in the area of opacity initially endothelial cells and Descemet's membrane defects are replaced by surrounding cells residual fibrosis in the posterior stroma usually absent central Bowman's membrane Treatment treat associated glaucoma penetrating keratoplasty for bilateral corneal opacification visual outcomes often are not ideal 123

124 Isolated Congenital Corneal Anomalies of Clarity Sclerocornea scleral-like like clouding of cornea can be peripheral or diffuse may be associated with cornea plana (flat cornea) may be associated with most other anterior segment anomalies glaucoma is common usually sporadic, bilateral X-linked form: microphthalmia,, dermal aplasia, sclerocornea treat: control glaucoma; penetrating keratoplasty poor outcomes often secondary to severe glaucoma 124