Ocular Manifestations of Graft vs. Host Disease

Symptoms of GVHD can mimic those of dry eye disease.

By Steven Sorkin, OD, FSLS

Ocular manifestations of graft-versus-host disease (GVHD) are occurring with increasing frequency in patients who have undergone allogeneic hematologic stem cell transplantation.1 Clinicians should be aware of these manifestations so they can choose appropriate management strategies for this potentially debilitating condition.

Allogeneic hematopoietic stem cell transplantation is a potential curative therapy for a variety of malignant or benign hematologic diseases, including leukemias and lymphomas.2,3 As survival rates among patients with these life-threatening diseases has increased, therapy has caused an increase in chronic complications.4 Unfortunately, the ocular side effects of bone marrow transplantation and peripheral blood stem cell transplantation therapy are frequently overlooked. These side effects can manifest with potentially devastating consequences on the ocular surface. Approximately 40% to 60% of patients with chronic GVHD will develop ocular symptoms.

There are two forms of GVHD, acute and chronic, of which the latter is the more common. Chronic GVHD has historically been defined as occurring 100 days after treatment, but a new definition of chronic GVHD was proposed several years ago. A US National Institutes of Health consensus document from a working group on diagnosis and staging of GVHD suggested in 2005 that chronic GVHD requires the presence of at least one diagnostic manifestation of chronic GVHD.3

The ocular manifestations of GVHD include keratoconjunctivitis sicca, keratitis, uveitis, corneal neovascularization, and corneal scarring. Ocular GVHD occurs when T cells infiltrate the lacrimal glands, conjunctiva, and ocular surface. The meibomian glands are typically affected as well, and decreased goblet cell density is also frequently present.5 Ocular manifestations of GVHD may be a precursor to systemic GVHD and are poor prognostic factors for mortality.6

Of note, there are no specific symptoms unique to ocular GVHD; its presentation can mirror that of any other patient with dry eye disease (DED), which we are all familiar with and see on a daily basis. Symptoms can include a gritty foreign-body sensation, irritation, burning, redness, photophobia, pain, and fluctuating vision.


As the symptoms of ocular GVHD are similar to those of typical DED, so too are the therapies similar to those we use in practice on a daily basis for our patients with DED. Optimizing the ocular surface is very important in preventing further damage. Frequent lubrication, maximizing the quality of tears, and preventing tear evaporation are of utmost importance.

Repeated use of preservative-free artificial tears, gels, and ointments to aggressively lubricate the ocular surface helps to prevent breakdown of the epithelium, which can lead to keratitis. Punctal occlusion may also be incorporated to maximize the retention of tears on the ocular surface.

Aggressive treatment of meibomian gland dysfunction with hot compresses, hypochlorous lid scrubs, omega-3 fatty acid supplementation, and meibomian gland treatment with Lipiflow (Johnson & Johnson Vision) are also important to reduce the evaporative component of DED.

For persistent epithelial defects, application of amniotic membranes can be used, as can surgical tarsorrhaphy when necessary.

Prescription topical medications such as cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) and lifitegrast ophthalmic solution 5% (Xiidra, Shire) and topical steroids also are important in the treatment of DED resulting from ocular GVHD. Autologous serum is frequently used as well.7 Autologous serum is preservative-free and contains vital tear components and nutrients. Moisture goggles and environmental modifications such as the use of a humidifier may also be helpful.


The use of contact lenses in the treatment of ocular GVHD has become more common with the advent of modern large-diameter gas permeable scleral lenses. Scleral lenses act as protection for the ocular surface and create a tear reservoir between the lens and ocular surface that promotes constant lubrication of the cornea.

A secondary benefit of scleral lenses is improvement in quality of vision, as many patients with ocular GVHD have irregular corneas due to scarring and epithelial defects. Separate studies by Schornack et al and Takahide et al found that gas permeable scleral lenses improved comfort and reduced symptoms in patients with ocular GVHD.8,9

It is important to discuss with patients that compromised corneas may not allow full-time contact lens wear. Lenses may have to be removed during the day and refilled with preservative-free saline solution because the ocular surface is not optimized. Frequent follow-up visits to monitor the health of the ocular surface are important.

These patients are also prone to posterior lens tear film fogging and front surface filming. New lens treatments such as Tangible Hydra-PEG (Tangible Science) may be helpful in optimizing the lens surface.

Meticulous care of scleral lenses is vital. Use of a preservative-free hydrogen peroxide lens care solution is recommended. Lenses also may have to be replaced frequently.

As with any patient, lens fit must be optimized to allow successful scleral lens wear. Minimizing lens vault and ensuring proper alignment of the lens haptic landing zone will help to prevent lens complications.


GVHD can have a significant effect on the ocular surface of the affected patient and lead to devastating corneal surface morbidity. It can also cause a significant decrease in patients’ quality of life. A comprehensive evaluation is required, and frequent follow-up examinations are necessary throughout treatment. Numerous therapies are available to help maximize the ocular surface and prevent further damage and loss of vision. Working together in a multidisciplinary fashion with hematology and oncology can help to improve management outcomes.

1. Deitrich-Ntoukas, T, et al. Diagnosis and Treatment of ocular graft vs host disease. Cornea. 2012: 31:299-310.

2. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-56.

3. Munir SZ, Aylward J. A review of graft-versus-host disease. Optom Vis Sci. 2017; 94(5):545-555

4. Shikari H, Antin, JH, Dana R, Ocular graft versus host, a review. Surv Ophthalmol. 2013; 58:233-251.

5. Nassiri N, Eslani M, Panahi et al. Ocular graft versus host disease following allogenic stem cell transplantation: a review of common knowledge and recommendations. J Ophthalmic Vis Res. 2013:8(4):351-8

6. Townley JR, Dana R, Jacobs DS. Keratoconjunctivitis sicca manifestations in ocular graft versus host disease: pathogenesis, presentation, prevention, and treatment. Semin Ophthalmol. 2011;26(4-5):251-260.

7. Ogawa Y, Okamoto S, Mori T, et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2003;31(7):579-583.

8. Schornack MM, Baratz KH, Patel SV, Maguire LJ. Jupiter scleral lenses in the management of chronic graft versus host disease. Eye Contact Lens. 2008;34(6):302-305.

9. Takahide K, Parker PM, Wu M, et al. Use of fluid-ventilated, gas-permeable scleral lens for management of severe keratoconjunctivitis sicca secondary to chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2007;13(9):1016-1021.

Steven Sorkin, OD, FSLS
• director, specialty contact lens services, Corneal Associates of New Jersey, Fairfield, N.J.; president, Essex County Optometric Society, Essex County, N.J.
• financial disclosure: none relevant
• 973-439-3937; ssorkin@cornealassociates.com