Anatomy of cornea and sclera

A very helpful concise summary of the anatomy, embryology and histology of cornea for ophthalmology residents!

1. Dr. Henok Samuel (R1) Moderator: Dr. Yonas Tilahun (Consultant Ophthalmologist & Cornea surgeon) Anatomy of Cornea and Sclera

2. Outline Gross Anatomy Structural Layers Embryology Blood supply Nerve Supply Function References

3. Cornea

4. 4 Gross Anatomy Anterior 1 /6 of outer coat Curved & Domshaped Fibrous, Transparent & No BVs Diameter (Ant.) : Horizontal 12mm Vertical 11mm Posteriorily : 11.7mm Radius of Curvature : Anterior 8 mm Posterior 7 mm

5. 5 Thickness: Central 0.5 - 0.6mm Peripheral 0.8 – 1.0mm Refractive Index : 1.37 Refractive Power : 42 D

6. Charts & Infographics

7. Zones of the cornea Central zone Para central zone Peripheral zone 7

8. Charts & Infographics Corneal epithelium (Anterior epithelium) Bowman’s membrane Corneal Stroma Descement’s Membrane Endothelium (Posterior epithelium) Structural Layers

9. 9 Epithelium Stratified Squamous Nonkeratinised (5-6 layers) Surface layer Flat cells (2-3 layers) fewer cellular organelles than deeper cells Microvilli and microplicae Tight junctions (zonula occludens ) and numerous desmosomes

10. 10 Intermed . Layer Wing/umbrella cells - Polyhedral (2-3 layers Desmosomes and gap junctions join wing cells to each other

11. 11 Basal layer Tall, columnar, polygonal cells (one layer) Stand in palisade-like manner on basal lamina Basal cells have density of approx. 6000 cells per square mm. Oval nuclei, few organelles germinal layer where mitosis occurs. joined to the basement membrane by hemidesmosomes anchoring fibrils Renewing cycle≈7 days

12. 12 Proliferation of Stem cells to desquamation of superficial corneal epithelial cells

13. 13 Bowman’s membrane Also called anterior limiting membrane No cell (Acellular) 10 to 12 micrometer. Dense mass of collagen fibers Acts barrier—spread of infection Damaged—can’t regenerate Ends as a round border

14. Charts & Infographics 3. Stroma 90% corneal thickness - 500 μ m thick Composed of : –Collagen fibrils(type I) (lamellae) –cells (keratocytes) – ground substance (proteoglycans) Bundles of collagen fibers—highly ordered

15. 15 Arranged in many layers 200—230 sequentially arranged lamellae Parallel to each other and corneal surface Adjacent lamellae lie at angles to one another Each lamella extends across the entire cornea, and each fibril runs from limbus to limbus. Stroma cont’d Lamellae

16. 16 Occupy 2.5-5% of stromal volume Long, thin, flattened cells running parallel to corneal surface eccentric nucleus long branching processes Synthesis of stromal collagen and proteoglycan during development and injury Keratocytes (Corneal fibroblasts)

17. Besides keratocytes, some other cells are also found in corneal stroma: - Wandering macrophages - Histiocytes - Lymphocytes - Polymorphonuclear leucocytes (very rarely) 17

18. 18 Descemet’s membrane (Posterior limiting layer): basement membrane of the endothelium Thickness varies with age: 3µm at birth 10-12µm in adults Posteriorly endothelium & DM are attached by modified hemidesmosomes exhibits an elastic property

19. 19 Descemet’s membrane Cont’d Composed of: -collagen (type IV ) -glycoproteins Resistant to trauma, chemical agents & pathological processes( barrier to perforation in deep corneal ulcer) Normally, it stays in tension & curls if torn Regenerable

20. 20 5. Endothelium Endothelial cells are polyhedral , cuboidal, single layer Regular arrangement of these cells is described as the endothelial mosaic

21. 21 The cell density (cells per unit area) of the endothelium decreases normally with aging because of cell disintegration; density ranges from 3000 to 4000 cells/mm2 in children to 1000 to 2000 cells/mm2 at age 80 years. The minimum cell density necessary for adequate function (functional reserve) is in the range of 400 to 700 cells/mm. Defect left by dying cells is filled by enlargement of remaining cells : polymegathism - increase in the variability of cell shape (pleomorphism) or size ( polymegathism )

22. 22 Cells of endothelium are firmly bound together by cell junctions including maculae adhaerentes , maculae occludentes Endothelial cells are attached to DM by hemidesmosomes These linkage maintains barrier function of endothelium Maintains an effective barrier from aqueous humour

23. 23 The separation of the lens vesicle from the surface ectoderm initiates the development of cornea There are three waves of successive in growth of neural crest cells in anterior segment differentiation - endothelium - stroma - keratocytes Embryology of the cornea

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25. 25 The fibrous layer of mesenchyme surrounding the anterior part of optic cup forms the cornea By 9 weeks Sclera and cornea differentiate Corneal diameter is about 10 mm at birth &adult size is attained by 2 years of age.

26. 26 Epithelium Is formed from the surface ectoderm at about 40 days of gestation It attains its adult appearance at 5-6 months of gestation Endothelium & Descemet’s membrane formed from mesenchymal cells derived from neural crest cells at the margin of optic cup Descemet’s membrane is demarcated clearly at 6 th month of gestation

27. 27 Stroma & bowman’s layer Are derived from the mesenchymal cells between the surface ectoderm & the developing lens BM is formed by condensation of superficial part of stroma. It is fully developed at birth.

28. 28 Blood Supply Avascular structures Corneoscleral limbus is generously supplied by anterior conjuntival branches of the anterior ciliary arteries Aqueous humor, the conjunctival and episcleral capillary networks located in the limbus and tear film provides nutrients Important factor in corneal transparency

29. 29 Helps to establish “ Immune Privilege ” that gives some protection against rejection of grafts Corneal Neovascularisation : Sproutting of new vessels from the perilimbal capillaries(in response oxygen deprivation)

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31. 31 Combined theory Demonstrated by Maurice et al

32. 32 Densely innervated with sensory fibers 5 TH C.N OPHTH. division NASOCILIARY N 2 Long CILIARY N Nerve Supply

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36. 36 As sensory nerves pass through bowman’s layer, Schwann cell covering is lost & fibers terminate as free nerve endings No nerve endings are located in posterior stroma Descemet’s membrane or the endothelium Density of sensory nerve endings in the epithelium is approx.400 times than that of epidermis of skin. Individuals with corneal anesthesia & loss of nerve endings may have increased epithelial permeability, reduced mitosis, decreased cell adhesion & impaired wound healing .

37. 37 Corneal function/Physiology NUTRITION ( cornea is avascular ) By diffusion Tear Film Aqueous humour Limbal capillaries CORNEAL TRANSPARENCY ( WHY ? ) Anatomical Factors : Cornea is avascular Epithelium is nonkeratinized Stromal lamellae are regular Nerves are nonmyelinated Precorneal tear film

38. 38 Physiological Factors : Corneal hydration Uniform refractive indices of corneal tissue

39. 39 Corneal hydration Cornea has the highest water content than any other connective tissue in the body i.e. 78% Four Factors are responsible for keeping the water content constant Factor which draws in water stromal swelling pressure Factor preventing inflow of water Barrier mechanism Factor which pump out water from cornea Metabolic pump Evaporation of water from corneal surface

40. 40 Stromal swelling pressure Pressure exerted by GAG in corneal stroma (60mm Hg) These have anionic effect on the tissue & therefore sucking the fluid with equal negative pressure. IMBIBITION PRESSURE In vitro : IP=SP In vivo : IP changes with IOP IP=IOP-SP(17-60=-43) Therefore, corneal edema is imminent when IOP>SP

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42. 42 Barrier mechanism Barrier function is exerted by both Epithelium and endothelium Barrier to excessive flow of water & electrolytes into stroma due to semipermeable nature.

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44. 44 Active pump mechanism mainly in endothelium Na+/K+ ATPase pump system Na+/H+ pump system Bicarbonate dependent ATPase Carbonic anhydrase enzyme

45. 45 Evaporation of water from corneal surface Evaporation leads to increased osmolarity of precorneal tear film Hyperosmolarity of pre-corneal tear film draws in water from cornea Helps maintaining dehydration of cornea

46. 46 Drug permeability across cornea Factors affecting drug penetration through the cornea are : Lipid and water solubility of the drug Molecular size, weight and concentration of drug Ionic form of the drug pH of the solution Surface active agent Tonicity of the solution Pro drug form

47. 47 Posterior 5 ／6 of fibrous mem White , opaque, firm and fibrous Outer surface is covered by tenon's capsule and also by bulbar conjunctiva in the anterior part Inner surface lies in contact with the choroid with a potential suprachoroidal space in between Composed primarily of type I,III,V&VI collagen and proteoglycans SCLERA

48. 48 Thickness of the sclera Thickness of the sclera varies considerably in different individuals It is blue (thinner) - In children than adult - females than males - in pathological conditions where uvea shines through it It may be yellow in old age due to fat deposition

49. Thinnest (0.3 mm) just behind the insertions of the rectus muscles thickest (1.0mm) at the posterior pole around the optic nerve head It is 0.4–0.5 mm thick at the equator 0.6mm thick anterior to the muscle insertions Adjacent to limbus 0.8mm thick 49

50. Formed from neural crest cells and Small temporal portion of it from mesoderm The differentiation occurs by week 6 of development in the region anterior to the equator The development progresses from anterior to posterior & from inner to outer By 3 rd month well formed sclera completely envelops the eye By 4 th month circularly oriented scleral fiber form scleral spur and 5 th month scleral fibers around axon of optic nerve form lamina cribrosa 50 Development of sclera

51. Tenons capsule Fascial sheath of eye ball and supports eye ball with in orbit separating it from orbital fat permit eye ball movement produced by extraocular muscles Thin at limbus become thicker about 3mm backwards until tendinous insertion of muscle Posteriorly envelops and fuses with optic nerve dural sheath and with sclera around exit of optic nerve 51

52. Scleral sulcus Scleral spur Lamina cribrosa 52 Special regions of the sclera

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54. posterior apertures Middle aperture Anterior aperture 54 Scleral apertures

55. Microscopic structures/Histology Episclera Stroma proper Lamina fusca 55

56. 56 Episclera Stroma proper Lamina fusca

57. Blood supply - Relatively avascular - Anterior ciliary arteries and episcleral plexus - Short posterior ciliary arteries - Choroidal vascular network 57 Vascular & Nerve supply

58. The sclera is supplied by branches from the long ciliary nerves anteriorly and short ciliary nerves behind the equator Branches of the ciliary nerves that supply the cornea sometimes leave the sclera to form loops posterior to the nasal and temporal limbus. 58 Nerve supply of sclera

59. References BCSC 2016-2017,(section 2&8) Duane`s ophthalmology,2012 Khurana, comprehensive ophthalmology, fourth edition 59

60. T hank Y ou!