Pathological changes of the cornea,.pptx, congenital cornea defects

this presentation talks about some of the different pathological changes on the cornea

1. Pathological changes of the cornea Dr Jean de Dieu Ntivuguruzwa PGY 1 RIIO 10/17/2024 1

2. Outlines Introduction Review on embryology Review of normal histology Congenital anomalies Developmental anomalies Infectious conditions Non infectious conditions Degenerative disease Corneal dystrophies 10/17/2024 2

3. Introduction The normal cornea is clear, avascular and contains 5 layers epithelium Bowman layer stroma Descemet membrane Endothelium It covers 1/6 of the surface of the globe Average radius of curvature is7.8mm 10/17/2024 3

4. Intro At birth, horizontal cornea diameter~9.5-10mm In adults, the cornea measure ~12mm in horizontal meridian and 11mm in the vertical median The central 3 rd is nearly spherical and measures ~4mm in diameter. The posterior surface is more curved than the anterior The central cornea is thinner ~0.5mm than the peripheral ~1.0mm It flattens peripherally, more nasally and superiorly than temporally and inferiorly. 10/17/2024 4

5. N ormal histology Normal cornea On high magn with PAS 10/17/2024 5

6. Normal histology High magnification, H&E, can see pre descemet stroma. 10/17/2024 6

7. Embryology/Congenital defects Embryology The cornea is derived from 3 embriological sources Surface ectoderm : ext corneal epith . Mesoderm : conective tissue w/c is cont’with sclera Neural crest cells : corneal endothelium Corneal abscence Very rare and doesn’t occur in isolation. Usually absence of other parts of the eye from prim.ectoderm Severe dysgenesis of anterior segmnt or entire eye 10/17/2024 7

8. Microcornea < 11mm in greatest diameter, the eye usually is structurally normal. May be inherited as an autosomal dominant trait. Hist. the cornea is usually normal except for its size. In conjunction with microphthalmos and often associated with colobomas : iris, retina, choroid & optic n. Colobomatous micropthalmos 10/17/2024 8

9. Megalocornea >12 mm at birth or >13mm after age 2. Isolated finding, b/l and non progressive. Do not cause sympt . Themselves excpt refr.error Rec. X linked inheritance pattern(xq21-q26) Iris transillumination , pigment dispersion, lens subluxation,… 10/17/2024 9

10. Developmental anomaly Dermoids : kind of choristoma that may involve the cornea Peters anomaly: represent severe end of the spectrum of anterior segment dysgenesis sd Neural crest cells do not migrate or differenciate during e mbryologic development. Prevents cleavage of lens from the corneal epithelium. The condition is b/l and sporadic but a utosomal dominant and recessive have been reported . Mutations in genes PAX6, PITX2, FOXC1 = anterior sgment dysgenesis . 10/17/2024 10

11. Peters anomaly The iris strands adhere to the posterior corneal surface In severe cases of peters, the lens adhere to the corneal surface The AC may be malfomed --- congenital glaucoma. Associated with sclerocornea and cornea plana and systemic abnormalities. Internal ulcer of von Hippel is a localized defect of endothelium and descemet membrane. It is central or paracentral and differ in peters’ as no lens abnormalities are present. 10/17/2024 11

12. Peters anomaly Central corneal opacity with attached iris strand Adherent leukoma in B. Von Hippel ulcer with attached iris strands in C 10/17/2024 12

13. Infectious keratitis Infectious process caused by a number of microorganism May result in corneal inflammation Severe corneal inflammation may lead to necrosis, culceration and perforation. Bacterial infections HSV keratitis Fungal, herpes zoster virus,HIV , 10/17/2024 13

14. Bacterial infection Often follows a disruption of the corneal integrity Contact lenses, trauma, alteration in immunologic defenses. Pre existing corneal diseases. Ocular medics toxicity or contamination P. aeruginosa , S. Aureus , Strep. Pneumonia & enterobacteriaceae . Hyperemia of the conjunctiva, ciliary injection and purulent d/c Epithelial defect with creamy white infiltration Cells and flare in AC Fibrin or hypopyon Folds in decemet me with edema Stromal thinning in Pseudomonas infection—poor prognosis 10/17/2024 14

15. Bacterial infection Clinical picture Stain with H&E, acute necrotizing ulcerative kerititis , numerous neutr infiltrating the stroma Gram stain, shows numerous gram+ cocci A scar from healed keratitis, note loss of Bowman’s layer, stromal thinning with fibrosis and compansatory ep. thickening 10/17/2024 15

16. HSV keratitis Usually self ltd corneal epithelial infection and may have recurrent or chronic form The most common cause of central corneal ulcer It presents as epithelial infection with dendritic pattern Dendrites reflect viral reactivation in the corneal nerves 10/17/2024 16

17. HSV keratitis Stromal keratitis with loss of bowman’s layer Stromal scarring and vascularization scattered chronic inflammatory cells granulomatous reaction in the region of Descemet membrane the fibrous retrocorneal membrane scattered chronic inflammatory cells, and blood vessel. 10/17/2024 17

18. HSV keratits Multinucleated giant cells located just anterior to Descemet membrane Postherpetic neurotrophic keratopathy. A featureless corneal stroma with very few keratocytes (F) 10/17/2024 18

19. Fungal / fusarium keratitis A complication of trauma Micro trauma in contact lens wearers Topical corticosteroids use Can penetrate and extend into AC Aspergillus , fusarium and yeast candida. Grey white stromal infiltrates and satelite lesions Hist. (GMS)demonstrates frequent fungal hyphae. 10/17/2024 19

20. Acantamoeba keratitis Commonly in soft contact lens wearers with poor adherence to precautions Severe eye pain due to radial keratoneuritis . Corneal ring infiltrate may present late stage and hypopyon Microrganisms penetrate deeper in stromal layers. Hist. cysts and trophozoids in the stroma 10/17/2024 20

21. Interstitial keratitis( IK) Nonsuppurative inflammatory cells infiltrate stromal interlamelar spaces . Often with vascularization, stromal opacity, the epith . remains intact Transplacental infection by T.pallidum (congenital syphilis ). Hist. shows stromal ghost vessels with surrounding fibrosis and a variable degree of chronic inflammation. Bowman’s layer and descemet me. are intact . 10/17/2024 21

22. Infectious crystalline keratopathy . I n patients who are on long-term topical corticosteroid therapy. E.g : following penetrating keratoplasty (PK ). Most common microorganism is Streptococcus viridans ( b-hemolytic Strep). The infection arose along a suture track following repair of a corneal laceration . feathery stromal infiltrate with intact overlying epithelium. Gram stain demonstrates sequestrations of gram-positive cocci interposed between stromal collagen lamellae without an appreciable inflammatory response. 10/17/2024 22

23. Non infectious keratitis Keratitis may also result from many other non infectious processes. Autoimmune disease: RA and graft vs host disease may also associate with interstitial keratitis and sterile corneal ulceration. Topical medications toxicity( anaesthetics , NSAIDs and antivirals may cause corneal melting. The histology varies depending on the cause The unifying feature is the absence of organisms 10/17/2024 23

24. P eripheral ulcerative keratitis A form of unilateral crescent-shaped stromal inflammation. I nvolves the juxtalimbal cornea. C haracterized by sectorial thinning of the affected area . always associated with an overlying epithelial defect and progressive loss of the corneal stroma. often contiguous with adjacent conjunctival , episcleral , and scleral inflammation. The presence of adjacent tissue inflammation complicate to corneal perforation. PUK w/o systemic association is known as Mooren's ulcer (MU) and contributes to 31.5% of PUK causes. 10/17/2024 24

25. PUK Slit lamp photograph of a patient with juvenile RA demonstrates sectorial corneal thinning and overlying epithelial defect. ( B ) The clinical appearance following corneal transplantation for tectonic purpose. 10/17/2024 25

26. PUK Crescent-shaped peripheral corneal thinning with superficial vascularization and infiltration, which is specific for PUK . 10/17/2024 26

27. Degenerative diseases 2ndry changes that occur in previously normal tissue. Often associated with aging, not necessarily bilateral, not inherited. Salzmann Nodular Degeneration Calcific Band Keratopathy Actinic Keratopathy Bullous Keratopathy Pinguecula and Pterygium Keratoconus 10/17/2024 27

28. Salzmann Nodular Degeneration S lowly progressive degenerative condition and often asymptomatic Usually the condition is bilateral and occurs in middle aged and adult individuals with female predominance C haracterized by the appearance of nodular gray-white to bluish , flat or raised opacities that vary in number and size and are located in the central or paracentral cornea. A, Clinical photograph. Note the gray-white to bluish elevated superficial opacities . B, Hist. of a superficial keratectomy specimen (PAS stain ): irregular epith . thickness and loss of B. layer which is replaced by disorganized collagenous tissue. 10/17/2024 28

29. Calcific Band Keratopathy Seen as a band-shaped calcific plaque in the interpalpebral zone Spares the peripheral clear cornea Deposition of calcium at the level of Bowman layer and the anterior stroma. 10/17/2024 29

30. Calcific Band Keratopathy May develop in chronically inflamed or traumatized eye or following intraocular therapy Less commonly associated with systemic hypercalcemia B , The ca2+ deposits at the level of Bowman layer, appearing deeply basophilic on H&E stain C, Calcium deposits appear black with von Kossa stain 10/17/2024 30

31. Actinic Keratopathy Also known as spheroidal keratopathy, Labrador keratopathy or climatic droplet keratopathy T ranslucent , golden-brown spheroidal deposits in the interpalpebral superficial cornea Generally bilateral and more common in males. The deposits develop from UV radiation or synthesis of abnrml extracellular material at the limbal conjunctiva( controversial). The condition is more prevalent in dry equatorial regions . 10/17/2024 31

32. Actinic Keratopathy Hist. irregular, pale, basophilic, globules extending from epith to superficial stroma. 10/17/2024 32

33. Corneal pannus The growth of fibro-vascular , fibro-inflammatory , or fibrous tissue btn the epithelium and Bowman layer Frequently seen in cases of chronic corneal disease. The Bowman layer remains intact under the fibrous or fibro-vascular tissue . Hist. fibro-vascular degenerative pannus interposed between the epithelium and Bowman layer. 10/17/2024 33

34. keratoconus Inferior conical deformity of the cornea . Typically diagnosed during adolescence or young adulthood. Characterized by inferior or inferotemporal corneal stromal ectasia . Loss of stromal structural integrity, leading to keratoectasia , or stretching and thinning of the corneal stroma. Familial inheritance, other ocular or systemic conditions( atopy Down sd , Ehlers- Danlos sd ) 10/17/2024 34

35. keratoconus B, Low-magnification photomicrograph showing apical stromal thinning C, Masson trichrome stain demonstrating focal disruption of Bowman layer 10/17/2024 35

36. keratoconus D, Prussian blue stain demonstrates focal intraepithelial iron deposition (Fleischer ring ) E, In a patient with prior hydrops , PAS stain highlights the rupture of Descemet me with rolled edges on either side 10/17/2024 36

37. Corneal dystrophies A group of non inflammatory, inherited, b/l disorders of the cornea. Characterized by pathognomonic pattern of cornea deposition and morphological changes. Primarily affect the stroma Over time can extent into anterior cornea layers and descemt membrane and endothelium Classified into 4 main groups of major corneal dystrophies: epithelial and sub-epithelial dystrophies epithelial–stromal TGFBI dystrophies stromal dystrophies endothelial dystrophies 10/17/2024 37

38. Epithelial and Sub-epithelial Dystrophies 10/17/2024 38

39. Epithelial basement membrane dystrophy Also called map-dot-fingerprint dystrophy patterns resembling maps, dots, and fingerprints in the superficial cornea . Regional thickening of the epithelial basement membrane look like a continent on the map Intraepithelial pseudo cysts that contain degenerated epithelial debris appear as dots. Rib like intraepithelial extensions of basal laminar material give rise to patterns resembling fingerprints. It may result in impaired adhesion of EBM to Bowman layer 10/17/2024 39

40. EBMD Recurrent epithelial erosions Ttt is superfiacial keratectomy or phototherapeutic keratectomy A. fine lacy opacities B. retroillumination showing wavy line and dot like lesions 10/17/2024 40

41. EBMD The intraepithelial BM and degenerating epithelial cells trapped within cystoid spaces ( C). irregular, wavy thickening of the epithelial basement membrane 10/17/2024 41

42. Epithelial–Stromal TGFBI Dystrophies Caused by mutation in the TGFBI gene located at 5q31 TGFBI encodes keratoepithelin , TGFBIp which is involved in pathogenesis of TGFBI-dystrophies. These dystrophies are arise in the stroma and epithelium The mechanism is not well elucidated 10/17/2024 42

43. Reis- Bücklers corneal dystrophy Formerly called corneal dystrophy of the Bown layer type 1 Autosomal dominant disorder Confluent irregular, coarse, and angulated like geographic opacities at the level of Bowman layer and superficial stroma. OCT shows homogeneous layer of hyper-reflective deposits at the Bowman layer and anterior stroma Hist. Bowman layer is replaced by a multilayered pannus which stains red with Masson trichrome. Ultra structural studies show crystalloid that stain deeply black with osmium tetroxide. 10/17/2024 43

44. RBCD The picture A shows coarse opacities ressembling geographic map in superficial cornea. In B, diffuse loss of Bowman layer superficial stromal fibrosis and numerous red deposits( M asson trichrome stain) 10/17/2024 44

45. Thiel- Behnke corneal dystrophy A.k.a corneal dystrophy of Bowman layer type 2 Irregularly shaped, scattered opacities at B. layer that progresses to sub-epithelial honey comb opacities. OCT: Sawtooth pattern of of hyper reflective material at the level of Bowman layer, extending into epithelium. Hist. = replacement of Bowman layer by fibrous pannus and the sawtooth pattern. The abnormal material is composed of curly collagen fibers ~10nm of diameter distinctly different from RBCD. 10/17/2024 45

46. TBCD Masson trichrome stain demonstrate diffuse replacement of B.L by by a thick fibrous pannus Swatooht pattern of overlying epith . The underlying stroma appears unaffected 10/17/2024 46

47. Lattice corneal dystrophy type 1 Also know as  Biber - Haab -Dimmer corneal dystrophy, TGFBI type Lattice Dystrophy, or Classic Lattice Dystrophy. Autosomal dominant inheritance of stromal dystrophy Corneal lines forming a lattice configuration in anterior stroma The peripheral cornea is clear and limbus is not involved Focal thinning or loss of Bowman layer Hist. poorly demarcated, fusiform amyloid deposits in the anterior stroma and Bowman layer. The deposits stain red –orange with Congo red on microscopy and exhibit apple green birefrignent on polarized light 10/17/2024 47

48. LCD 1 Fine lattice lines scattered fusiform, eosinophilic deposits in the anterior and mid stroma on H&E Congo red stain (red orange) demonstrates that the fusiform deposits are amyloid With Congo red stain, under polarized light, amyloid deposits exhibit apple-green birefringence 10/17/2024 48

49. LCD2 Dominantly inherited, of the Gelsolin gene on 9q34. Familial form of systemic paramyloidosis or 2ndry corneal amyloidosis. Mainly in people of Finnish origin Consist of Lattice corneal changes more peripheral and less less dense than in LCD1 Most lesions are in the anterior stroma Progressive cranial neuropathy and skin changes 10/17/2024 49

50. Granular corneal dystrophy type 1 &2 Autosomal dominant disorder Sharply demarcated central corneal stromal deposits separated by clear intervening stroma. Hist. irregular shaped well circumscribed crumb like deposits of hyaline materials in the stroma, which stain red on M asson trichrome. GCD 2 a.k.a Avelino dystrophy It demonstrates clinical, histologic and ultrastructural features of both GCD 1 and LCD1 10/17/2024 50

51. GCD type 1 10/17/2024 51

52. GCD type 2/ Avelino dystrophy Both lattice and lines and granular deposits Trichrome stain of deep anterior lamella keratoplasty , hyaline deposits at the level of Bowman layer, and anterior stroma. And other darker blue deposits in the stromal background 10/17/2024 52

53. Stromal dystrophy 10/17/2024 53

54. Macular corneal dystrophy An autosomal recessive corneal stromal dystrophy. mutations in the carbohydrate sulfotransferase 6 gene (CHST6), located at 16q22. Diffuse stromal haze from limbus to limbus Poorly demarcated focal opacities( macules) H&E stain: subtle eosinophilic stromal deposits. Colloidal iron stains: non sulfated GAG deposits in stromal keratocytes , endothelium and in the stroma. Pathologic changes in the endothelium are frequently accompanied by guttae in the Descemet membrane. 10/17/2024 54

55. MCD 10/17/2024 55

56. Descemet membrane and endothelial dystrophies 10/17/2024 56

57. Fuchs endothelial corneal dystrophy Can be inherited in an autosomal dominant pattern but the mode of inheritance is unknown in most cases. Early stage present with guttae along Descemet me with beaten metal appearance. Progressive endothelial cell loss leading to significant corneal edema and bullous keratopathy. Hist. irregular thickened Descemet me. is studded with drop like guttae which protrude into the AC or buried in new layer of BM. 10/17/2024 57

58. FECD Slit-lamp shows the “beaten metal” appearance of Descemet membrane B. Corneal button from PK shows endothelial cell loss, with a few surviving endothelial cells (E ). diffuse stromal edema (loss of interlamellar clefts) and epithelial bulla (asterisk ). C. Specimen from EK shows scant endothelial cells (E) and numerous guttae . 10/17/2024 58

59. Congenital hereditary endothelial dystrophy Autosomal recessive variant of endothelial dystrophy A mutation in the SLC4A11 gene, located at 20p13, has been implicated Diffuse/ground glass, milky corneal clouding associated with marked corneal thickening. It is thought to be a degeneration of the endothelial cells during/after 5 th weeks gestation. Hist. Descemet membrane is diffusely thickened and occasionally multilaminated. Bullous keratopathy , DM diffusely thickened w/o guttae . Endoth cells absent Marked loss of endothelial cells. 10/17/2024 59

60. CHED 10/17/2024 60

61. Posterior polymorphous corneal dystrophy Autosomal dominant that typically manifest early in life. Frequently with asymmetric opacities of various shapes at the level of Descemet membrane. Includes nummular, vesicular ( blisterlike ), and railroad track like lesions/ opacities. It can progress and be associated with corneal edema, peripheral iridocorneal adhesions and elevated IOP. Hist. Descemet me is thickened and multilaminated with focal nodular and fusiform outgrowths. 10/17/2024 61

62. PPCD A, Clinical photograph showing nummular and linear opacities on the endothelial surface . B, Histology showing overlapping and multilayered aggregates of endothelial cells 10/17/2024 62

63. Ophthalmic pathology and intraocular tumors BSCS 2022-2023 Ocular pathology 5 th ed Eye wiki-corneal stromal dystrophies National library of medicine, update on peripheral ulcerative kerititis ELSEVIER: pathogenesis and treatement of corneal dystrophies Ento Key : Fastest Otolaryngology & Ophthalmology Insight Engine 10/17/2024 63

64. Thank you for your attention 10/17/2024 64