Graft-versus-Host Disease (GVHD) and the Cornea

The cornea bears the greatest burden of ocular GVHD because it depends entirely on a healthy tear film and a functioning epithelial surface to maintain its transparency. The most common corneal finding in ocular GVHD is superficial punctate keratopathy (SPK), a pattern of scattered microscopic erosions across the corneal epithelium. Studies report SPK in up to 91% of patients with ocular GVHD. These tiny defects cause irritation, foreign body sensation, and light sensitivity, and they serve as an early indicator that the ocular surface is under significant stress.

In more advanced cases, strands of mucus and dead epithelial cells adhere to the corneal surface, forming filaments that pull with each blink and cause sharp pain. Filamentary keratitis develops when the tear film is so deficient that the epithelium becomes rough and dehydrated, allowing debris to stick and accumulate. Treatment involves carefully removing the filaments in the office and aggressively addressing the underlying dryness to prevent recurrence.

Chronic tear deficiency and persistent inflammation weaken the corneal epithelium, the protective outer cell layer. When the epithelium breaks down, the underlying stroma is exposed, leaving the cornea vulnerable to thinning, infection, and in severe cases perforation. Patients with band keratopathy or other degenerative corneal changes may face compounding surface challenges that further complicate healing. Persistent epithelial defects that fail to close within two weeks require escalated treatment to prevent irreversible structural damage.

When the cornea is chronically inflamed and oxygen-deprived, new blood vessels can grow into the normally avascular tissue, a process called corneal neovascularization. These vessels bring additional inflammatory cells into the stroma and can deposit lipids and scar tissue, permanently reducing corneal clarity. Once established, corneal scarring from GVHD may require surgical intervention such as a corneal transplant to restore vision, though the inflammatory environment of GVHD makes graft survival more challenging than in other conditions.

Treatment follows a stepwise approach based on severity. Mild cases are managed with frequent preservative-free artificial tears and lubricating ointments at night. When lubrication alone is insufficient, topical anti-inflammatory agents are added, most commonly cyclosporine A eye drops or short courses of topical corticosteroids. Punctal plugs help retain whatever natural or supplemental tears are present. For moderate to severe disease, autologous serum tears have been shown to improve corneal nerve density and reduce corneal staining. In cases where the corneal surface remains unstable, bandage contact lenses or scleral lenses may be recommended to protect the epithelium.

Yes. Prolonged inflammation, recurrent epithelial breakdown, and corneal neovascularization can all lead to stromal scarring that permanently reduces corneal clarity. Scarring tends to develop in patients whose ocular GVHD is diagnosed late or inadequately treated. Once significant scarring is established, a corneal transplant may be the only option for visual rehabilitation. Patients with endothelial compromise from other causes, such as Fuchs dystrophy, face additional surgical considerations if transplantation is needed.

Scleral lenses are large-diameter rigid gas-permeable lenses that vault over the entire cornea and rest on the surrounding sclera. The fluid reservoir trapped between the lens and the cornea continuously bathes the ocular surface, providing constant lubrication that artificial tears cannot match. Studies show that mini-scleral lenses improve visual acuity, reduce corneal staining, and significantly improve eye-related quality of life in patients with ocular GVHD who have not responded adequately to conventional therapy.

Acute GVHD typically appears within the first 100 days after transplant and primarily causes inflammation, conjunctival irritation, and pseudomembrane formation. Chronic GVHD, which usually develops after 100 days, produces a more progressive and fibrotic process that leads to lasting lacrimal and meibomian gland damage, cicatricial conjunctival changes, and the severe dry eye that defines most long-term ocular GVHD. Chronic disease is responsible for the corneal complications that make ongoing ophthalmologic monitoring essential.

Systemic immunosuppressive therapy prescribed by the transplant team for chronic GVHD, such as corticosteroids, calcineurin inhibitors, or newer agents like ruxolitinib, can reduce the overall inflammatory burden and may indirectly benefit the eyes. However, systemic treatment alone is rarely sufficient to control ocular GVHD. Coordination between the transplant physician and the ophthalmologist ensures that topical and systemic therapies work together. Oral pilocarpine or cevimeline may also be prescribed to stimulate residual tear gland function.

Current expert recommendations call for a baseline comprehensive eye examination before the stem cell transplant to document pre-existing ocular surface conditions. After transplant, any new onset of dryness, redness, light sensitivity, or blurred vision should prompt referral to an ophthalmologist experienced in ocular surface disease. Even patients without symptoms benefit from scheduled evaluations at three, six, and twelve months post-transplant, and annually thereafter, because subclinical corneal changes often precede noticeable symptoms.