What are the clinical recommendations for patients with reduced endothelial cell density and corneal thinning?

From the Guidelines

Patients with reduced endothelial cell density and corneal thinning should be managed with a stepwise approach focusing on both preservation of remaining endothelial cells and addressing corneal thinning, with the most recent evidence from 2024 suggesting the use of preservative-free lubricating eye drops, hypertonic saline drops, and potentially Rho kinase inhibitors to reduce corneal edema 1.

Initial Management

Initial management includes:

• Preservative-free lubricating eye drops 4-6 times daily (such as Systane Ultra or Refresh Optive) to maintain ocular surface integrity
• Hypertonic saline drops (5% sodium chloride) for corneal edema if present
• Avoiding eye rubbing and discontinuing contact lens wear to prevent further endothelial damage

Medical Management

Medical management may also involve:

• Topical corticosteroids like prednisolone acetate 1% for short-term use (1-2 weeks) to reduce inflammation, with careful monitoring due to potential intraocular pressure elevation
• Rho kinase inhibitors, which may play a role in reducing corneal edema in Fuchs corneal dystrophy, although randomized controlled trials are needed to establish efficacy and safety 1

Surgical Intervention

Definitive treatment often requires surgical intervention, with:

• Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) or Descemet's Membrane Endothelial Keratoplasty (DMEK) being preferred over full-thickness corneal transplantation due to faster visual recovery and lower rejection rates
• Scleral lenses may be useful to provide improved visual outcomes and symptom improvement in severe cases with advanced edema or scarring 1

Key Considerations

Key considerations in managing patients with reduced endothelial cell density and corneal thinning include:

• Lowering intraocular pressure (IOP) when elevated or at the upper end of the normal range, while avoiding prostaglandin analogues and topical carbonic anhydrase inhibitors due to their potential inflammatory character and interference with endothelial function, respectively 1
• Controlling inflammation with topical corticosteroids, while monitoring for potential side effects such as intraocular pressure elevation 1

From the FDA Drug Label

WARNINGS ... In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The clinical recommendations for patients with reduced endothelial cell density and corneal thinning are to use corticosteroids with caution, as prolonged use may increase the risk of perforations in diseases that cause corneal thinning 2.

• Key considerations:
  • Caution with corticosteroid use in patients with corneal thinning
  • Risk of perforations with prolonged corticosteroid use
  • Monitor for signs of infection or exacerbation of existing conditions

From the Research

Clinical Recommendations for Patients with Reduced Endothelial Cell Density and Corneal Thinning

• Patients with reduced endothelial cell density and corneal thinning should be closely monitored for signs of corneal edema and decreased visual acuity 3.
• The minimum (critical) endothelial cell density required to maintain the pumping function of the endothelium is 400-500 cells/mm2, and patients with densities below this threshold are at risk of developing corneal edema and reduced visual acuity 3.
• Endothelial cell transplantation by various endothelial keratoplasty techniques may be considered in cases of significant compromise 4.
• Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy, and patients with dry eye disease (DED) may be at higher risk of accelerated corneal endothelial cell loss 4, 5, 6.
• Patients with DED and low subbasal nerve density are at high risk for accelerated corneal endothelial cell loss, and close monitoring and management of DED may be necessary to slow the progression of endothelial cell loss 6.

Management Strategies

• Management of underlying systemic diseases, such as diabetes or atherosclerosis, and eye diseases, such as uveitis or DED, may be necessary to slow the progression of endothelial cell loss 3, 5.
• Avoidance of therapeutic ophthalmological interventions that may damage the corneal endothelium, such as intraocular pressure-lowering surgeries, may be necessary in patients with reduced endothelial cell density 3.
• Corneal endothelial cell regeneration and rehabilitation may be possible in the future, and patients with reduced endothelial cell density may benefit from emerging therapies 4.

Corneal Thinning Considerations

• Corneal thinning may be associated with reduced endothelial cell density, and patients with corneal thinning should be closely monitored for signs of corneal edema and decreased visual acuity 7.
• The paracellular pathway of corneal endothelial cell monolayers may be altered in cases of low density, leading to increased permeability and decreased barrier function 7.