anatomyandphysiologyofcornea and applied .pptx

Anatomy and physiology of cornea

1. Anatomy and physiology of cornea with applied aspect Dr. Sandeep Panwar

2. Anatomy

3. The word cornea has come from “Kerato”. The term “Kerato” in greek means horn or shield like.

4. The Cornea The cornea is a transparent avascular tissue with smooth, convex outer surface and concave inner surface. To meet the diverse functional demands the cornea must be: - Transparent - Refract light - Contain the intraocular pressure - Provide a protective interface

5. Microcornea: when HCD is less than 10mm Macrocornea when HCD is more than 13 mm  

6. Shape : -prolate Surface area: - About 1.3 cm² (one-sixth of the globe) Radius of curvature: - Anterior surface – about 7.8 mm - Post. Surface – about 6.5 mm Refractive power: +43 to +43.5D Refractive index: 1.376

7. Composition of human cornea Water: 78 % Collagen: 15 % Type-I : 50-55 % Type-III : 1 % Type-IV : 8-10 % Type-VI : 25-30 % Other protein: 5 % Keratan sulphate: 0.7 % Condroitin/dermatan sulphate: 0.3 % Hyaluronic acid: + Salts: 1 %

8. Layers of cornea

9. Embryonic origin of Cornea: Structure      Derived from Corneal epithelium Surface ectoderm Bowman’s membrane, Stroma, Descmet’s membrane,endothelium Neural crest

10. Structure

11. Epithelium: Stratified, nonkeratinized and squamous Three types of cells are seen a.Superficial cells b.Wing cells c.Basal cells

12. Superficial cells: - Microvilli + - Helps in glycocalyx formation and stability of tear film. Wing cells( umbrella cells): Polyhedral cells with wing like extensions Basal cells: - Germinative layer of the epithelium Single layer of Columnar cells - O nly epithelial layer with mitotic activity

13. Adhesion is achieved by – desmosomes And hemidesmosomes Desmosomes are tight junctions between cells Hemidesmosomes are tight junctions between cell and basal lamina Langerhans cells (cells of immune recognition system) present near periphery. They are almost absent at central cornea but aggregate in response to infection

14. Epithelial Turnover: - G erminative region lies at the limbus - The stem cells migrate at a very slower rate (123 µm/week) to the center of the cornea XYZ hypothesis: - Thoft R. and Friend J. (1983) proposed that both limbal basal and corneal basal cells are the source for corneal epithelial cells, and there is a balance among division, migration & shedding.

15. Epithelial Repair: I njury ( abrasion) Cells at wound edge retract, thicken and lose attachment Travel in an amoeboid movement to cover the defect Cells at wound edge ruffle and send out filopodia and lamellipodia towards the center of wound

16. Migration process is halted by contact inhibition They then anchor Mitosis resumes to re-establish epithelial thickness Surface tight junctions re-establised Adhesion with Bowman’s layer within 7 days (if basal lamina intact)

17. Bowman’s layer: (Ant. Limiting lamina) - Modified region of anterior stroma - 8 – 14 µm thick - It delineates the anterior junction between cornea and limbus Compact arrangement of collagen gives it great strength and relatively resistant to trauma both mechanical and infective.

18. Stroma: (Substantia propria) 1. About 500 µm thick (about 90% of corneal thickness) 2. Consists of regularly arranged lamellae of collagen bundles, lie in proteoglycan ground substance 3. keratocytes - 2.4million, 5% of stromal volume

19. Arrangement of lamellae – - Lamellae are arranged in layers, parallel with each other & corneal surface - In deeper stroma the lamellae form strap-like ribbons which run at angles to those in consecutive layers - There is remarkable regularity of separation both within and between lamella - At the limbus the bundles appeared to take a circular course

20. Fig.: Arrangement of stromal lamellae

21. - The keratocytes occupy 5 % of total stromal volume - Responsible for synthesis and maintaining of collagen & proteoglycan substance of stroma. - There are stellate processes which extends with other keratocytes in same plane forming gap junctions

22. Stromal repair: - Repair of stroma after small injuries involves: - Keratocytes activation Migration & transformation into fibroblasts Production of scar tissue Initial fibrils are large & irregular

23. Remodelling of scar tissue occurs, it ensues – 1. Thinning of fibrils 2. Reformation of lamellae over months 3. Increase in transparency - Larger wounds provoke rapid vascular response and leaving a vascularised scar .

24. Clinical aspect - The parallel arrangement of lamellae allows an easy interlamellar dissection during superficial keratectomy - Regular organization of stroma fibrils is necessary for optical properties, curvature and strength of cornea. - Alteration of this stromal structure in refractive and cataract surgery leads to postoperative refractive error. - In keratoconus stromal thinning occur

25. Descemet’s membrane: (Post. Limiting layer) - It is the basal lamina of corneal endothelium - First appears at 2nd month of gestation and synthesis continue throughout adult life

26. - Thickness – at birth :- 3 – 4 µm at childhood :- about5µm at adult :- 10 – 12 µm - It is a strong resistant sheet - Major protein of DM is Type IV collagen - It has two zones: Anterior 1/3 zone - developed in utero - irregular banded zone Posterior 2/3 zone - developed after birth - Homogenous fibrillo-granular material

27. Haab’s striae - Curvilinear breaks in Descemet's membrane - Resulting acutely from stretching of the cornea in primary congenital glaucoma. (Healed breaks in descemet membrane)

28. Schwalbe’s line: • The peripheral rim of DM, internal landmark of corneal limbus and the anterior limit of drainage angle Posterior embryotoxon: Schwalbe’s line may hypertrophied in congenital anomalies and appears as visible shelf on gonioscopy

29. Repair of Descemet’s layer: Traumatic interruption of DM (Path./Mech.) Endothelium spread its cells to resurface the defect Synthesis of fresh basal lamina which is structurally identical to normal descemet’s layer

30. Clinical aspect: •Peripheral projections of the Descemet membrane, known as Hassall-Henle warts. •Central projections (cornea guttae) appears with increasing age. •In corneal ulcer, Descemet’s membrane remains intact and often herniates out as a result of increased intraocular pressure, which known as Descematocele.

31. Endothelium : - It is a single layer of hexagonal, cuboidal cells attached to posterior aspect of DM - It is mesenchymal in origin - Can be seen by specular microscopy using a slit lamp (Mosaic Pattern)

32. Endothelial cells density - If cells density falls below 500 cells/mm² corneal oedema devlops and transparency reduced

33. Endothelium is rich in subcellular organeles – - Rich in mitochondria, endoplasmic reticulum and ribozomes These reflects that endothelium is extremely active metabolically Nutrition to endothelium: - Endothelium gets its nutrition & O₂ from aqueous - Essential nutrients (such as glucose & amino acids) pass across its surface to supply all the corneal layers

34. Endothelial Repair: - Physical & chemical damage to endothelium results in loss of cells - Neighboring cells move over to fill the gap by sliding process and enlargement of cells occur (polymegathism) - Thus, after injury, 1. The endothelial cell densit y falls 2. The cell area increases 3. The cell height decreases

35. Limbal Stem Cells: Only 5% to 15% of the cells in the limbus Basal cells of limbal epithelium Precursor for other cells Self maintaining population High potential to proliferate in cell culture They can not be differentiated

36. Dua’s Layer • Dua's group at the University of Nottingham • It is hypothetically 15 micrometers thick, located between the corneal stroma and Descemet’s membrane • L ayer is very strong and impervious to air. • It is strong enough to withstand up to 2 bars (200 kPa) of pressure.

37. Significance- •Knowledge of Dua's Layer could improve outcomes for patients undergoing corneal grafts and transplants •In SMILE: The lenticule is dissected within the stroma, likely sparing Dua’s layer. • In FS-LASIK: The flap cut may disrupt Dua’s layer, potentially affecting corneal strength.

38. Blood supply to cornea: Relatively avascular structure Peripheral cornea receives some nutrient supply from the vascular arcade of the limbus Vascular arcade in the limbal region supplied by the anterior ciliary arteries and long posterior ciliary arteries Absence of blood vessel in cornea is one of the contributing factors for its transparency

39. Nerve supply of Cornea: The ophthalmic division of the trigeminal nerve has three parts: the frontal nerve, the lacrimal nerve, and the nasociliary nerve. Density of the nerve ending in cornea is about 300 times of that of skin. The nasociliary nerve provides sensory innervation to cornea.

40. Applied anatomy - •Cornea is immunologically privileged for keratoplasty due to avascularity, absence of lymphatics •Degree and depth of corneal vascularization are prognostic in keratoplasty. •Deep vascularization of more than 2 quadrants is considered as high risk of graft rejection following keratoplasty

41. • Unmyelination contributes to corneal transparency • Conditions which lead to loss of corneal epithelium, cause severe pain due to exposure of corneal nerve ending. • Infection or reactivation of latent herpes virus located in trigeminal ganglion, reduces corneal sensation due to damage to the nerve endings.

42. Corneal Nutrition & Metabolism Cornea requires energy for normal metabolic activities, maintaining transparency and dehydration Energy is generated by the breakdown of glucose in the form of ATP Most actively metabolizing layers are epithelium & endothelium

43. Sources of Nutrients: - Oxygen – mainly from atmosphere through tear film - Normal Po₂ in tears is 155 mm Hg - In aqueous is about 40 mm Hg - Minimum 25 mm Hg Po₂ is needed for maintaining deturgescence state and transparency

44. - Glucose, amino acid, vitamins, and other nutrients supplied to cornea by aqueous humor - Glucose can also derived from glycogen stores in corneal epithelium. - Epithelium consumes O₂ 10 times faster than stroma.

45. Corneal Transparency The cornea transmits nearly 100% of the light that enters it. Transparency achieved by – 1. Arrangement of stromal lamellae Two theories – i) Maurice (1957): The transparency of the strom a is due to the regular lattice arrangement of collagen fibrils. ii) Goldman et al. (1968): The collagen fibrils are separated by a distance which is less than the wavelength of light so that irregular refracted rays of light are eliminated by destructive interference.

46. Other factors of corneal transparency – 2. Corneal epithelium & tear film • Epithelial non-keratinization • Regular & uniform arrangement of corneal epithelium • Junctions between cells & its compactness 3. Relative deturgescence state of normal cornea. 4. Corneal avascularity 5. Non myelinated nerve fibres

47. Drug permeability across the Cornea Factors affecting drug penetration through the cornea are – 1. Lipid and water solubility of the drug 2. Molecular size and concentration of drug 3. Ionic form of the drug 4. pH of the solution 5. Tonicity of the solution 6. Surface active agents 7. Pro-drug form

48. 1. Lipid and water solubility of the drug Drug should be amphipathic,should have both lipid and water soluble properties. Epithelium and endothelium – lipophilic Stroma - hydrophilic

49. 2. Molecular size, weight and concentration of the drug lipid soluble molecules can cross the corneal epithelium irrespective of their molecular size Substances with molecular weight less than 100 Da can pass but more than 500 Da can not.

50. 3. Ionic form of the drug Capacity to exist in both ionic and non-ionic forms, because only non-ionised drugs can penetrate epithelium and ionised drugs can pass through stroma. Fluorescein dye test- Fluorescein is a water-soluble dye that does not penetrate an intact corneal epithelium but easily enters areas where the epithelium is disrupted.

51. 4. PH of the solution Normal range – 4 to 10 Any solution outside this range increases irritation, reflex tearing and blinking Weak bases (e.g., beta-blockers, timolol) More lipophilic at alkaline pH → better epithelial penetration. Weak acids (e.g., NSAIDs, prostaglandins) More lipophilic at acidic pH → better penetration.

52. Functions of cornea- •The most important refractive media of the eye. •Maintains the integrity of eyeball •Formation of glycocalyx layer of the tear film •Cornea is richly supplied by nerves hence it protects the eye as any noxious stimuli to the cornea causes reflex blinking. •The epithelium of the cornea forms a protective barrier against the pathogenic microorganisms.

53. Congenital Anomalies of Cornea

54. Microcornea •Horizontal corneal diameter is less than 9 mm in newborn or it is 10 mm or less over 2 yrs of age.

55. Megalocornea •Corneal diameter more than 12mm at birth or more than 13mm after 2 years.

56. Cornea Plana •Refers to flat cornea where the radius of curvature <43D

57. Keratectasia •characterized by protuberance between the eyelids of a severely opacified and vascularized cornea

58. Sclerocornea •Peripheral corneal opacification, with no visible border between the sclera and cornea

59. References : ●American Academy of Ophthalmology, 2014-15 ●Yanoff and Duker’s Ophthalmology, 3rd Ed. ELSEVIER, 2008. ●Brad Rowling, Kanski’s Clinical Ophthalmology, 8th Ed. ELSEVIER, 2016

60. Thank you