Anatomy and Physiology of Cornea powerpoint.pptx

Ophthalmology basic science

1. Anatomy And Physiology of Cornea

2. Cornea is a transparent, avascular tissue which covers the iris and pupil. Forms the anterior 1/6 th of the outer fibrous coat of eyeball.

3. Structure Derived from Corneal epithelium Surface ectoderm Stroma Paraxial mesoderm Descemet’s membrane Paraxial mesoderm Endothelium Paraxial mesoderm Embryology Of Cornea

4. Epithelium develops from the surface ectoderm 40 days of gestation Superficial squamous cell layer Basal cuboidal layer 3 months 3 layered 5 -6 months of gestation Corneal epithelium attains adult appearance Corneal Epithelium

5. Bowman’s layer, Stroma, Descemet’s Membrane and Endothelium 40 days of gestation Corneal endothelium – 2 layer of flattened cells 3 rd month Centre of endothelium become single layer of flattened cells Rest on their interrupted basal lamina – future descemets membrane Bowmans layer starts forming by condensation of superficial acellular part of corneal stroma Middle of 4 th month Apices of endothelial cells are joined by zonulae occludentes 5 months corneal nerves present 6 th month of gestation Descemets membrane demarcated clearly All of them are derived from the mesenchyme

6. Embryotoxon - thickening at the periphery of descemet’s membrane Embryological Malformations Corneal leucoma - due to failure of keratinocytes to produce collagen fibres

7. Micro cornea When horizontal corneal diameter is less than 10 mm Megalo cornea When horizontal corneal diameter is more than 13 mm Systemic associations with Marfan’s , Ehler Danlos and Down’s syn Cornea plana B/l flat cornea since birth a/w astigmatic refractive error.

8. Anterior surface Elliptical horizontal diameter of 11.7 mm vertical diameter of 11 mm . Posterior surface Circular avg diameter of 11.5mm Pachymetry 0.5mm thick at the centre and gradually increases in thickness towards the periphery Radius of curvature Central 5mm – powerful refracting surface Anterior and posterior radii of curvature at centre are 7.8mm and 6.5mm . Topography of Cornea

9. Radius of curvature Central 5mm – powerful refracting surface Anterior and posterior radii of curvature at centre are 7.8mm and 6.5mm respectively . Refractive power Anterior surface = +48D Posterior surface = -5D Net = + 43D (forms 3/4 th of the total power of the eyeball) Refractive index 1.37 Shape Prolate

10. Layers of Cornea Epithelium Bowman’s membrane. Substantia propria (corneal stroma) Dua’s layer ( Pre Descemet’s layer) Descemet’s membrane Endothelium

11. Epithelium Composed of non keratinized stratified squamous epithelium Forms 10% of total corneal thickness Presence of desmosomes and hemidesmosomes 5 – 7 layers of cells Deep layer – Basal cells ( columnar in shape and capable of mitosis) Mid epithelial 2-3 layer – wing cells (umbrella shaped) Superficial 2 layers – flattened cells Microvilli with glycocalyx helps in adhesion and stabilization of the tear film

12. Images of how the different layers of epithelium appear under a confocal microscope

13. Limbal Stem Cells The pluripotent limbal stem cells are found in the limbal basal epithelium of the Palisades Of Vogt Damage to limbal stem cells – chemical burns , steven-Johnson syndrome pemphigoid , trachoma – epithelial surface defect – invasion of conjunctival epithelium on to cornea

14. Epithelial Basement Membrane Desmosomes connect the cells to one another and hemidesmosomes attach the cells to basal lamina In Traumatic recurrent corneal erosion hemidesmosomes unimpaired, split occurs between epithelial basement membrane and bowman’s layer Epithelial Basement membrane dystrophies the hemidesmosomes are affected

15. If there is an epithelial defect and basal lamina is intact – 7days needed for regeneration. But if the basal lamina is damaged then 6 weeks needed for regeneration. Important Points to Remember

16. Bowman ’s Membrane Not a true membrane but an acellular condensate of the anterior most part of the stroma. When disrupted, it does not regenerate rather scars. Randomly packed type I and type V collagen fibres , enmeshed with proteoglycan and glycoprotein

17. Clinical correlation- In anterior stromal puncture, we puncture upto the Bowman’s so that the epithelium scars and hence there are no epithelial bullae.

18. Stroma 90% of corneal thickness is contributed by the stroma Composed of collagen fibrils, keratocytes and extra cellular ground substance Collagen Fibrils Arranged in flat bundles called lamellae (approx. 300 lamellae ) Type I (predominant) , III , V and VI. Type VII forms anchoring fibrils

19. Transparency of cornea Collagen fibres have a uniform diameter of around 25-35nm Distance between 2 corneal fibres is highly uniform 41.5 nm. Ground Substance of stroma Hydrated matrix of proteoglycan Keratin sulphate and chondroitin sulphate in ratio 3:1 Function : forms rigid frame for IOP

20. The packing density is higher in the anterior lamellae than in the posterior stroma. Collagen fibrils in the prepupillary region are more closely packed in the peripheral cornea- necessary for maintaining corneal strength and hence curvature in a region of reduced corneal thickness. Prevents changes in the morphology of the stromal region even after edema. Proteoglycan distribution- Anterior stroma has higher ratio of dermatan sulphate to keratan sulphate.

21. Numerous keratocytes Minimal keratocytes

22. Reasons for Corneal Transparency Optically smooth tear film Role of corneal epithelium Arrangement of stromal fibres Avascularity of cornea Absence of myelination in corneal fibres .

23. Theories behind corneal transparency 2 major theories – a. Maurice theory b. Goldman theory Maurice theory states that there the corneal fibres are arranged in a regular lattice arrangement such that the distance between the 2 fibres is less than wavelength of light. This ensures that the scattering of light is cancelled by destructive interference.

24. Goldman theory It states that the lattice arrangement is not important. As long as the size of the lamellae is less than half the wavelength of light. How Maurice theory explains corneal edema ? According to the Maurice theory, there are fluid pockets that are created in between the corneal lamellae which increases the distance between the lamellae which leads to nullification of the phenomenon of destructive interference. Hence the cornea will appear hazy .

25. Pre Descemet layer / Dua layer Discovered by Dr.Harminder Dua , an Ophthalmologists of Indian origin. 15 µm thick acellular structure, very strong , impervious to air. Composed of type I collagen (primarily), collagen 4 and 6 are also present. No keratocyte present. Discovery of this layer has lead to description of new surgical techniques Pre Descemets Endothelial keratoplasty DALK

26. Types of big bubble

27. Elastic layer made of collagen and glycoprotein but no elastic fibres Thickness: 3µm at birth and 10-12µm in young adults Resistant to enzymatic degradation by toxins and phagocytes On EM ant. 1/3 rd is vertically banded pattern (develops in utero ) and post 2/3 rd amorphous and granular (develops after birth ) Descemet’s Membrane

28. Mono layer of flat polygonal cells Density: 6000cells/sq.mm. (at birth), 2400-3000cells/sq.mm. (young adults) Best evaluated by specular microscopy Adjacent cells share extensive lateral inter digitations and possess gap and tight junctions along lateral border Lateral membrane contains high density of Na+ K+ Atpase pump Basal surface of endothelium contains numerous hemidesmosomes that promote adhesion to Descemet’s Endothelium

29. Endothelial cells cannot replicate or divide With ageing the cell density of the endothelium decreases and is compensated by increase in size ( Polymegathism ) or shape (Pleomorphism) As endothelial cells are responsible for corneal hydration, endothelial cell density below 800 cells/mm2 leads to corneal decompensation

30. Normal hexagonal cells (honey comb ) Change in shape Increase in size but no change in shape

31. Endothelial Pump Osmotic gradient is created by pushing Na+ into the aqueous which will cause the water to move out as well Corneal hydration is 80%

32. The 2 most important ion transport systems are the membrane-bound NaC and KC-ATPase sites and the intracellular carbonic anhydrase pathway. Activity in both these pathways produces a net flux of ions from the stroma to the aqueous humor. The barrier portion of the endothelium is unique in that it is permeable to some degree, permitting the ion flux necessary to establish the osmotic gradient

33. Physiology of corneal edema The forces responsible for corneal edema Endothelial pumps IOP-Optimal iop needed to pump out the water from stromal lamellae. If IOP increases there is corneal edema The tight junctions present at the epithelium and endothelium do not allow cornea to hydrate Once tear film evaporates from the epithelial surface it increases the osmolarity of the surface thereby allowing it to maintain its dehydrated state.

34. Swelling Pressure- is the tendency of the stroma to swell due to the presence of interfibrillary proteoglycans and other proteins within in. Normal stromal pressure is 55mmHg. Imbibition pressure (IP) is a negative pressure exerted by glycosaminoglycans by which fluid is drawn into the cornea. Intraocular pressure (IOP) = SP + IP Relationship between Swelling Pressure, Imbibition pressure and IOP

35. Cornea’s Response to injury Epithelium-responds immediately to establish barrier action and protect the underlying structure. Bowman’s layer- no repair mechanism Stroma – Keratocytes produce reparative collagen and proteoglycan but transparency is compromised. Descemet – Resecreted by the corneal endothelium Endothelium- No repair mechanism

36. Types of corneal opacity

37. Blood Supply of Cornea In normal condition, cornea does not contain any blood vessels. Anterior ciliary artery, b/o ophthalmic artery, forms a vascular arcade in the limbal region and helps in corneal metabolism and wound repair by providing nourishment. Absence of blood vessels in the cornea is one of the contributors for the transparency of cornea.

38. Nerve Supply of cornea Cornea is a highly sensitive tissue of the body Density of nerve endings in cornea is 300 times more than the skin Sensory supply is by the nasociliary branch of trigeminal nerve. The nasociliary nerve in turn divides into the long and short posterior ciliary nerves and then pierce the sclera close to the limbus. Corneal nerve fibres are not myelinated.

39. Corneal nerve plexus There are 3 main nerve plexus 1. Stromal plexus – present in stromal 2 . Subepithelial/ subbasal plexus - present below the epithelium 3. Intraepithelial plexus- Traverses the epithelial layer Loss of corneal epithelium produces severe pain due to exposure of the corneal nerve fibres . Infection or reactivation of latent herpes simplex virus in the trigeminal nerve reduces corneal sensation due to damage to the nerve fibres

40. While doing slit lamp examination, the corneal nerve fibres might be visible in the periphery as diameters of the nerves are larger at periphery than at the centre .

41. Enlarged Corneal nerves Keratoconus Fuchs corneal epithelial dystrophy Congenital glaucoma Corneal graft failure Reis Buckler corneal dystrophy Acanthamoeba keratitis Prominent Corneal Nerves MEN 2A Refsum disease Icthyosis Primary amyloidosis Leprosy Neurofibromatosis 1

42. CELL TURNOVER AND WOUND HEALING EPITHELIUM Migration Mitosis differentiation Begins after 5 – 6 hours of injury Rate – 60-80 micro M / hr

43. Migration is also dependent on the matrix induced intracellular signaling Adhesion of epithelium is achieved by hemisdesmosomes Most mitotic activity takes place at limbus Conjunctival cells , limbal stem cells , and normal corneal epithelial cells can be distinguished by cytokeratin profile

44. Stromal healing

45. Corneal endothelial healing Repaired by migration , no mitosis Endothelial defects are repaired by migration and enlargement of surrounding cells. Old age – decline in endothelial cells number  wounding leads to cell slide cell layer can’t perform its pumping action cornea imbibes water  opaque

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