Study Suggests Ocular GVHD Is Underdiagnosed in Patients After Hematopoietic Stem Cell Transplantation

A survey of blood and bone marrow transplant patients found that many who fit current criteria for ocular graft-versus-host disease have not been diagnosed.

Ocular graft-versus-host disease (oGVHD) is estimated to occur in more than half of patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies. However, it frequently goes undiagnosed. A recent study surveyed blood and bone marrow transplant patients to gain a better understanding of the degree and causes of oGVHD underdiagnosis in this population.

Of the 3 forms of GVHD — acute, chronic, and overlap syndrome — all 3 can manifest as oGVHD. The current study, published in Clinical Ophthalmology, focused on chronic oGVHD, which is the most common form in ambulatory patients and can occur months to decades post–allo-HSCT. Potential symptoms, including constant discomfort and corneal ulceration, melt, and perforation, can significantly impact patient quality of life.

A relatively small population has undergone allo-HSCT, and the diagnostic criteria for oGVHD have changed over the years. Therefore, it is often underdiagnosed, especially when no other organ systems are involved. Until recently, at least one other organ involvement was necessary for the diagnosis of oGVHD. The International Chronic Ocular GVHD Consensus Group (ICCGVHD) pioneered a 4-part scoring system that was validated in 2017, but it is not widely used in clinical practice. Still, strictly ocular symptoms sans other organ involvement are now enough to diagnose oGVHD.

Avoiding underdiagnosis of oGVHD is imperative, as it also leads to underdiagnosis of chronic GVHD overall. Therefore, authors of the current study created a 15-question survey to assess patients’ history of GVHD; eye-related symptoms; oGVHD diagnosis; previous treatments; and use of scleral lenses and prosthetic replacement of the ocular surface ecosystem devices (SL/PD), which are FDA approved for oGVHD treatment but are typically only used in severe cases.

The survey was sent to 6032 members of the Blood and Marrow Transplant Information Network via email, and 371 patients completed and returned the survey. All patients confirmed having undergone allo-HSCT, and 335 respondents had one or more of the ocular symptoms listed in the questionnaire. The most common symptoms were gritty and/or dry eyes, light sensitivity, and burning and/or stinging.

Of the 335 patients with ocular symptoms, 6 reported that their symptoms were present before HSCT and remained mild afterward. Twenty-three patients reported having symptoms pre-HSCT that worsened afterward, and 306 patients did not have symptoms until after HSCT. Most of the patients who did not experience symptoms until afterward experienced 3 or more symptoms.

Of the 306 symptomatic participants who had no previous symptoms, 107 (35%) experienced onset within 6 months of allo-HSCT, 87 (28.4%) experienced onset between 6 and 12 months post-HSCT, and 112 (36.6%) experienced onset more than 1 year post-transplant. Of the participants with pre-existing symptoms whose condition worsened post-HSCT, 9 (39.1%) reported symptoms worsening within 6 months after HSCT, 3 (13%) experienced worse symptoms 7 to 12 months afterward, and 11 (47.8%) experienced worse symptoms more than 1 year post-HSCT.

Overall, 286 (85.4%) of the systematic respondents reportedly had a diagnosis of systemic chronic GVHD. A total of 167 had been diagnosed with both oGVHD and systemic GVHD, 119 were solely diagnosed with chronic systemic GVHD, 9 were diagnosed with oGVHD only, and 40 respondents had neither diagnosis. Despite meeting the NIH criteria as of 2014 and being highly likely to have oGVHD, a total of 154 respondents were never diagnosed with it.

The survey results showed that oGVHD diagnosis was not associated with the level of symptom control patients reported. But patients were more likely to be diagnosed with oGVHD when they reported more symptoms or having undergone more treatments. The median number of symptoms undiagnosed patients reported was 3, versus a median of 7 reported symptoms in the respondents who were diagnosed.

The study’s main limitations included its reliance on patient recollection for data and the inherent bias in conducting the survey via email, since those who responded were more likely to have ocular issues than those who chose not to respond. Even so, the findings suggest that in spite of updated NIH and ICCGVHD recommendations for diagnosis, oGVHD remains underdiagnosed.

“We hope to raise the awareness of oGVHD in patients as well as providers,” the authors wrote. “We hope to point direction for future studies to establish better and earlier diagnosis and treatment.”

Reference

Colarusso BA, Bligdon SM, Ganjei AY, Kwok A, Brocks D, Luo ZK. Ocular graft-versus-host disease underdiagnosis: a survey study. Clin Ophthalmol. Published May 3, 2022. doi:10.2147/OPTH.S359539