Ocular Graft Versus Host Disease

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Assigned status Update Pending by Vatinee Bunya, MD on December 17, 2015.

Disease Entity

Ocular Graft Versus Host Disease (GVHD) occurs in patients who have undergone allogenic hematological stem cell transplantation. It can occur in patients who have acute or chronic GVHD, though it is more common in patients with the chronic form. Approximately 40-90% of patients with chronic GVHD will develop ocular symptoms. Ocular manifestations can include moderate to severe keratoconjuncitvitis sicca, bilateral marginal keratitis, anterior uveitis, corneal ulceration or neovascularization.

Risk Factors

Patients who have undergone allogenic stem cell transplantation are at risk for developing GVHD. 

General Pathology

Histology demonstrates decreased conjunctival goblet cell density, increased conjunctival squamous metaplasia and inflammatory cells. Often a lymphocytic infiltration with epithelial cell necrosis and lymphocytic exocytosis can be seen.


Ocular GVHD occurs when donor lymphocytes attack host histocompatibility angitens. It is a T-cell medieated process that leads to  infiltration and inflammation of the lacrimal gland, conjunctiva and ocular surface. The inflammation can eventually cause a decrease in the density of conjunctival goblet cells as well as scarring of the lacrimal gland and conjunctiva.



A history of allogenic bone marrow transplant is present in all patients with this disease.

Physical examination

A complete ophthalmologic examination is required including visual acuity testing, refraction, slit lamp examination with the use of flourscein and rose bengal stains. A Schirmer tests can be done to determine tear production and evaluation of tear break-up time can be used to determine the quality of tears. Infectious etiologies must always be ruled out.


Ocular GVHD is associated with meibomian gland obstruction, anterior and posterior blepharitis. There is often associated scaring of the lacrimal gland leading to decreased tear production. Conjunctival hyperemia with pseudomembrane and membrane formation can also be see. Chronic inflammation can lead to conjuncitval necrosis and cicatrical scaring and fibrosis. Patients often have corneal manifestations including punctate epithelial keratopathy, filamentary keratitis. Severe disease can lead to corneal erosions, thinning, ulcerations and possible perforations.


Ocular GVHD mimics other immunologically mediated ocular inflammatory diseases. Symptoms are not unique to this disease entity and can include dry eye, foreign body sensation, redness, irritation. It can also cause epiphora, photophobia, blurred vision and severe pain. Children with a history of bone marrow transplantation can also develop ocular symptoms but do not complain of the same symptoms as adults. Often children are noted to have excessive eye rubbing and light sensitivity as their predominant symptoms.

Clinical diagnosis

A grading criteria for ocular manifestations of chronic GVHD was introduced in 2004 by Robinson et al. See table below.

Grading criteria for chronic GVHD
Grade Manifestation
Grade 1 Conjunctival hyperemia of the bulbar or palpebral conjunctiva 
Grade 2 Fibrovascular changes of the palpebral conjunctiva involving <25% of the total surface are of at least 1 eyelid
Grade 3 Fibrovascular changes of the palpebral conjunctiva involuving 25-75% of at least 1 eyelid. 
Grade 4 Involves >75% of the conjuncitval with or without cicatrical entropion in at least 1 eyelid. 

Diagnostic procedures

A Schirmer Test can be done to determine the amount of tear production. See Physical Exam for other diagnostic testing.


Systemic treatment of the GVHD is important, but often ocular symptoms do not improve with system treatment. Treatment includes topical lubricants including preservative free artificial tears, autologous serum tears and other topical and systemic immunosuppressive treatments. Systemic steroids have been found to be helpful. Topical cyclosporine 0.5% is now a mainstay of treatment. Cyclosporine A is a T-cell inhibitor that helps to downregulate inflammatory cytokines in the conjunctiva. Malta et al. (Cornea 2010;29:1392-1236) advocate initiation of topical cyclosporine 0.5% 1 month prior to bone marrow transplantation to reduce the severity of ocular symptoms associated with GVHD. However, these recommendations have not been validated by a large double-blinded, placebo controlled trial.

General treatment

See Management of Ocular Graft vs Host page


If untreated, cicatrical scarring of the lacrimal gland and conjunctiva can occur. Additionally, severe corneal disease can lead to epithelial breakdown, thinning, infection, and possible perforation. Scarring and neovascularization can also cause decreased vision in these patients. 

Additional Resources


  1. Deitrich-Ntoukas T, Cursiefen C, Westekemper H, et al. Diagnosis and treatment of ocular chronic graft-versus-host disease: report from the German-Austrian-Swiss Consensus Conference on Clinical Practice in Chronic GVHD. Cornea 2012; 31:299-310.
  2. Malta JB, Soong HK, Shtein RM, et al. Treatment of Ocular Graft-Versus-Host-Disease with Topical Cyclosproine 0.05%. Cornea 2010; 29:1392-1396.
  3. Townley JR, Dana R, Jacobs DS, Keratoconjunctivitis Sicca Manifestations in Ocular Graft Versus Host Disease: Pathogenesis, Presentation, Prevention, and Treatment. Seminars in Ophthalmology 2011; 26:251-260.