Corneal Endothelium & Applied Aspects.pptx

Explains corneal endothelium

1. CORNEAL ENDOTHELIUM AND APPLIED ASPECTS By Dr. Nitya Reddy Ophthal PG 1 st Year

2. MICROSCOPIC STRUCTURE OF CORNEA-6 LAYERS

3. The  corneal endothelium  is the  innermost layer  of the cornea, composed of a  single layer of flattened, hexagonal endothelial cells  lining the posterior surface of the cornea, adjacent to the aqueous humor in the anterior chamber. These cells possess abundant  mitochondria , reflecting their high metabolic activity focused on fluid regulation.

4. Appears as a mosaic on specular microscopy. Origin: neural crest mesenchyme.

5. EMBRYOLOGY OF CORNEAL ENDOTHELIUM The  corneal endothelium is derived from the neural crest , a population of multipotent cells that migrate from the edges of the neural tube during early embryogenesis. Neural crest cells contribute to various ocular structures, including: Corneal endothelium Corneal stroma Iris stroma Trabecular meshwork

6. DEVELOPMENT OF CORNEAL ENDOTHELIUM Early Gestation (Weeks 5–7) During the  fifth to sixth week of gestation , a  wave of neural crest cells  migrates between the newly forming lens vesicle and surface ectoderm. These cells form the  primitive corneal endothelium , which becomes the  inner layer of the cornea . Initially, the cells are irregular and loosely arranged.

7. Formation of Descemet’s Membrane As endothelial cells differentiate, they begin to  secrete Descemet’s membrane , the basement membrane of the endothelium. This structure continues to thicken throughout life, with two components: Anterior banded layer  (embryonic origin) Posterior non-banded layer  (postnatal addition)

8. Maturation (Weeks 7–15) The endothelial cells become  more organized  into a  monolayer of hexagonal cells . By  15 weeks of gestation , the corneal endothelium is functionally active, capable of fluid regulation. The cell layer becomes  non-mitotic  by mid-gestation—this limited mitotic activity continues to decline postnatally.

9. Postnatal Development 1. At Birth The corneal endothelial cell density is relatively  high , typically around: 4,000 to 6,000 cells/mm²  at birth. 2. Early Childhood There is a  gradual decline  in cell density as the eye grows. Cell density reduces due to  natural cell loss ; no significant new cell proliferation occurs. Decline rate during childhood is more noticeable but still relatively slow.

10. 3. Adulthood Cell density stabilizes somewhat but continues to decline slowly. Typical adult density ranges between: 2,500 to 3,000 cells/mm² . Annual decline rate is about  0.3% to 0.6% per year  due to normal aging and cell attrition. 4. Mechanism of Density Change No mitosis  in human corneal endothelial cells postnatally. Loss of cells is compensated by: Enlargement of remaining cells ( polymegathism ) Change in cell shape (pleomorphism) This helps maintain the  integrity and function  of the endothelial layer despite decreased cell numbers.

11. Neural Crest Cells (Ectodermal origin) ↓ Migration between surface ectoderm & lens vesicle (Starts around 5–6 weeks of gestation) ↓ Formation of Primitive Corneal Endothelium(First wave of neural crest cells) ↓ Cell Differentiation & Organization (Cells become a monolayer by 7–8 weeks gestation) ↓ Secretion of Descemet's Membrane(Begins around 8 weeks; continues through life) ↓ Functional Maturation of Endothelial Cells By 15 weeks gestation; fluid regulation begins) ↓ Loss of Mitotic Activity (Endothelial cells become non-replicative mid-gestation) ↓ Postnatal Development(Cell density highest at birth → gradual decline with age) ↓ Adult Endothelium(Non-regenerative; wound healing by cell spreading/enlargement)

12. Cell density: ~6000 cells/mm²at birth → ~2500 in young adults. • Falls by 26% in first year, another 26% by 11 years. • Little/no mitotic potential – cell loss compensated by polymegathism & pleomorphism.

13. FUNCTIONS OF CORNEAL ENDOTHELIUM Functionally vital: maintains corneal transparency by controlling stromal hydration Barrier via tight junctions; pump via Na⁺/K⁺ ATPase to move ions and water. The lateral membranes contain a high density of Na+/K+ ATPase pump. These sites actively pumps Na(osmotically followed by water)from the stroma into anterior chamber. This helps in maintaining cornea in Relatively DehydratedState(70% water content.

14. Threshold for decompensation: <500 cells/mm². Clinical importance: endothelial dysfunction → corneal edema (bullous keratopath y) . Evaluated by specular microscopy.

15. Factors maintaining Corneal Transparency. Relatively Dehydrated state of cornea. Avascularity of cornea. Regular and parallel arrangement of collagen fibrils and within the corneal stromal cells that reduce the backscatter of light. Absence of myelin sheath of corneal nerves. Uniform refractive index throughout cornea.

16. Specular microscopy  is a non-invasive imaging technique used to evaluate the  corneal endothelium , which is the innermost layer of the cornea. It is especially useful in diagnosing and monitoring  corneal endothelial disorders , such as  Fuchs’ endothelial dystrophy ,  pseudophakic bullous keratopathy , or damage following  intraocular surgery .

17. It provides high-resolution images and quantitative data on: Parameter Description Endothelial cell density (ECD) Number of cells per mm². Normal: ~2,500–3,000 cells/mm² in adults. Cell morphology (pleomorphism) Variation in cell shape—normal cells are mostly hexagonal. Cell size variation (polymegathism) Variation in cell size. Increased variation can indicate stress or damage. Central corneal thickness (CCT) Measured in microns; indirectly reflects endothelial function.

18. NORMAL SPECULAR MICROSCOPY PROFILE ECD ~2,500–3,000 cells/mm² Hexagonality ≥ 60% hexagonal cells CV ( Polymegathism ) ≤ 30% (ideally ~22–27%) Cell Area ~280–400 µm² (depending on age)

19. Confocal microscopy  is an advanced, high-resolution imaging technique used in ophthalmology to  visualize the layers of the cornea , especially at the  cellular level

20. Clinical Applications Corneal Dystrophies Detects early  Fuchs endothelial dystrophy : guttae, cell dropout. Assesses  stromal dystrophies : granular, lattice, macular dystrophies. Corneal Infections Identifies  Acanthamoeba cysts ,  fungal filaments ,  bacterial infiltrates . Non-invasive confirmation in  infectious keratitis . Post-Surgery Monitoring After LASIK, PRK, DMEK, or corneal transplant: evaluate healing, cell health, and scarring.

21. Dry Eye & Neuropathy Evaluates  sub-basal nerve plexus  in conditions like  diabetes ,  neurotrophic keratitis , or  Sjogren's . Contact Lens Complications Detects microtrauma, inflammation, or cell changes due to long-term wear.

22. Layer Appearance on IVCM Superficial Epithelium Polygonal cells, bright borders, visible nuclei, perinuclear dark ring Wing Cells Less reflective, bright borders and nucleus Basal Epithelium Mosaic of dark bodies with bright edges Sub‑Basal Nerves Bright, branching nerve fibers Bowman’s Layer Homogeneous; may show nerve bundles or dendritic cells Stroma Bright keratocyte nuclei on a dark background Endothelium Hexagonal bright cells with dark borders; can be counted semi/automatically

23. Pachymetry  is the  measurement of corneal thickness , typically in  micrometers (µm) . While it doesn't directly assess endothelial cells, it is  clinically important  in evaluating  endothelial function , especially in diseases that affect corneal hydration. Condition Pachymetry Change Cause Fuchs Endothelial Dystrophy ↑ Thickening (>600 µm) Guttae and cell loss → poor pump function Post-cataract surgery Transient ↑ Endothelial trauma during surgery Glaucoma surgeries Possible ↑ Surgical damage or elevated IOP Keratoplasty Monitored for rejection or failure ECC and thickness monitored over time

24. ↓ Endothelial cells  → ↓ Pump function →  ↑ Stromal hydration  →  ↑ Pachymetry Monitoring  corneal thickness trends over time  helps detect  early endothelial failure , even before vision is affected. Location Average Thickness Central Cornea ~540–550 µm Mid-periphery ~600–650 µm Limbus ~700 µm

25. Fuchs Endothelial Dystrophy (FECD) A  progressive, bilateral corneal dystrophy  that affects the  endothelium , leading to  corneal edema ,  visual impairment , and in advanced stages,  painful bullous keratopathy . Pathophysiology Loss of endothelial cells  → impaired fluid pump function. Accumulation of fluid in stroma and epithelium  → corneal thickening, haze. Formation of  guttae  (collagenous excrescences on Descemet’s membrane). Progressive endothelial dysfunction →  corneal decompensation.

26. Age of onset Common after age 40 (late-onset type) Gender More common in females Inheritance Usually autosomal dominant Gene mutations COL8A2, TCF4 ( trinucleotide repeats) Stage Findings Symptoms 1 (Early) Central guttae, normal vision Often asymptomatic 2 Enlarging guttae, endothelial cell loss Mild blurred vision, especially in AM 3 Stromal and epithelial edema , Descemet folds Blurred vision, halos, glare 4 (Advanced) Bullous keratopathy, epithelial erosions Pain, foreign body sensation, severe vision loss

27. Slit Lamp “Beaten metal” or “hammered silver” appearance (guttae), epithelial bullae Specular Microscopy ↓ endothelial cell density, polymegathism, pleomorphism, guttae Confocal Microscopy Dark guttae, disrupted endothelial mosaic Pachymetry ↑ central corneal thickness (may exceed 640–700 μ m) OCT/AS-OCT Corneal edema , epithelial bullae , Descemet thickening

28. DMEK (Descemet Membrane Endothelial Keratoplasty). Treatment Purpose Hypertonic saline (5%) drops/ointment Draws fluid out of cornea Hair dryer technique Dehydrates cornea overnight Lubricants Soothes epithelium

29. POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY PPCD is a rare,  bilateral ,  non-inflammatory  dystrophy affecting the  Descemet's membrane and corneal endothelium . It is unique because the  endothelial cells undergo metaplasia , acquiring  epithelial-like characteristics  (they can proliferate and migrate). Inheritance Autosomal dominant (most common) Genes involved ZEB1, COL8A2, TCF8, and others Onset Often detected in childhood or young adulthood, though usually asymptomatic for years

30. PATHOPHYSIOLOGY Endothelial cells become  epithelial-like , producing abnormal basement membrane. They can migrate across the  trabecular meshwork , causing  secondary angle-closure glaucoma . In advanced cases, they lead to  corneal edema .

31. Aspect Description Laterality Bilateral (but may be asymmetric) Symptoms Often asymptomatic; may have blurred vision or glare Corneal findings Vesicular, band-like, or diffuse lesions at posterior corneal surface Endothelial changes Vesicle-like lesions, scalloped borders, train-track appearance Glaucoma Seen in ~15–20% of cases, especially if angle is involved

32. SLITLAMP FINDINGS Lesion Type Appearance Vesicular Small blister-like lesions on Descemet’s membrane Band-like Horizontal gray lines Diffuse opacities Broad, indistinct haze “Railroad track” sign Parallel bands with intervening lucency

33. Specular Microscopy Shows abnormal endothelial morphology Confocal Microscopy Details vesicle-like changes at Descemet's level Pachymetry To monitor for corneal thickening Gonioscopy Check for peripheral anterior synechiae and angle closure Tonometry Monitor intraocular pressure (IOP) regularly

34. Treatment Purpose Hypertonic saline (5% NaCl drops/ointment) Reduces corneal edema by drawing fluid out of the stroma Lubricating drops Alleviate irritation from epithelial changes Hair dryer therapy (low heat) May help reduce corneal swelling in the morning Procedure Description DMEK (Descemet Membrane Endothelial Keratoplasty) Best visual results, preferred in most PPCD cases DSEK/DSAEK Easier handling, good outcomes Penetrating Keratoplasty (PK) Reserved for complex or failed EK cases

35. CONGENITAL HEREDITARY ENDOTHELIAL DYSTROPHY CHED  is a rare, non-inflammatory, bilateral,  inherited dystrophy of the corneal endothelium , leading to  diffuse corneal edema  and  thickening from birth or early childhood . It results in  impaired vision due to corneal clouding . Type Inheritance Onset Severity Gene Notes CHED1 Autosomal Dominant First few years of life Mild Unknown Very rare, slowly progressive CHED2 Autosomal Recessive Present at birth More severe SLC4A11 Most common form

36. The  corneal endothelium  is responsible for  maintaining corneal deturgescence  by pumping excess fluid out of the stroma. In CHED: endothelial cells  are either absent or severely dysfunctional. This leads to  fluid accumulation in the corneal stroma , causing: Corneal  edema . Thickening  of the cornea. Loss of  transparency  and visual acuity.

37. Feature Description Laterality Bilateral (both eyes) Corneal opacity Diffuse, non-inflammatory, milky-white from birth or early infancy Corneal thickness Markedly increased No vascularization or scarring Unlike other causes of congenital corneal clouding Visual impairment From birth (CHED2) or progressive (CHED1) Nystagmus May be present in severe cases due to sensory deprivation No systemic abnormalities CHED is isolated to the eyes

38. Test Findings Slit-lamp exam Hazy cornea without vascularization Pachymetry Significantly increased corneal thickness Specular microscopy Reduced or absent endothelial cells Ultrasound B-scan Done if cornea too hazy to view posterior segment Genetic testing Identifies SLC4A11 mutations (for CHED2)

39. Dystrophy Management Notes Fuchs Endothelial Corneal Dystrophy (FECD) - Early: Observation, hypertonic saline drops/ointment - Advanced: Endothelial keratoplasty (DSEK/DSAEK, DMEK) Most common endothelial dystrophy; gradual progression Congenital Hereditary Endothelial Dystrophy (CHED) - Early surgery (Penetrating keratoplasty or DSEK/DSAEK) - Supportive: lubricants, amblyopia treatment Presents in infancy; corneal clouding from birth Posterior Polymorphous Corneal Dystrophy (PPCD) - Usually observation - Surgery (keratoplasty) if edema or vision loss occurs Often asymptomatic; may develop edema or glaucoma

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