Contributing to this article, Shahzad I. Mian, MD, Professor, Ophthalmology and Visual Sciences, Vice Chair, Clinical Sciences and Learning, Kellogg Eye Center, Michigan Medicine
Previous research has shown that patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic malignancies, such as leukemia and lymphoma, are at a high risk of developing graft-versus-host disease (GVHD). Chronic GVHD involves various organs, including the eyes, and it profoundly affects the quality of life of long-term survivors of HSCT. Recent advances in allogeneic HSCT has helped to increase long-term survivorship of patients with hematologic malignancies, but studies show that the incidence of chronic GVHD has increased in recent years.
Ocular GVHD affects 40% to 60% of allogeneic SCT recipients, according to published data. The most common ocular manifestation of GVHD is dry eye disease (DED), a condition for which clinical management remains problematic despite ongoing research. “Ocular GVHD can lead to DED that results from reduced tear production and excessive evaporation of tears,” says Shahzad I. Mian, MD from the Kellogg Eye Center at Michigan Medicine. He notes that dry eye in chronic GVHD can significantly decrease quality of life by causing symptoms such as photophobia, foreign body sensation, blurred vision, and pain.
Taking a Closer Look
Recent studies have indicated that vitamin A deficiency appears to be associated with the severity of ocular manifestations in patients with chronic GVHD, including DED, but this relationship between remains unclear. At the 2020 American Academy of Ophthalmology Annual Meeting, Dr. Mian and Kyeong Hwan Kim, MD, PhD, from Inje University Haeundae Paik Hospital in South Korea presented data from a study that sought to determine if serum vitamin A levels was associated with the incidence and severity of DED resulting from chronic GVHD.
The study included data on 51 patients who underwent allogeneic HSCT and had their serum vitamin A levels measured at follow-up visits. Primary outcomes were the development of grade 4 DED and changes in Ocular Surface Disease Index (OSDI) score. According to the results, the average time to developing Grade 4 DED after allogeneic HSCT was 10.0 months in patients with low vitamin A levels, compared with 28.1 months for those with normal vitamin A levels. DED of any grade developed at an average of 2.3 months in the low vitamin A group, compared with 10.0 months in the normal vitamin A group. Mean changes in OSDI scores from baseline were 24.0 for patients with low vitamin A levels compared with 17.7 for those with normal vitamin A levels.
Studies have shown that vitamin A is essential to the development of mucosal tolerance and to the shift of target organ tropism of donor T cells, which is important in the pathogenesis of GVHD. “Based on our results, low levels of vitamin A may increase risks for DED associated with GVHD,” says Dr. Mian. “It’s possible that vitamin A supplementation may improve ocular surface disease in patients who have undergone HSCT.”
Of note, therapies aimed at increasing vitamin A levels on the ocular surface of patients with chronic GVHD are in the pipeline. There is optimism that future studies on these treatments and a better understanding of the role of vitamin A in ocular manifestations of chronic GVHD will provide new strategies for the management of DED in this patient population.
Kim KH, et al. Association of Serum Vitamin A With Incidence of Severe DED Associated With Chronic GVHD. Presented at: American Academy of Ophthalmology 2020 Virtual Congress. Session: PO068. November 2020. Available at: https://aaommg.apprisor.org/apsSession.cfm?id=PO068.
Yin J, Kheirkhah A, Dohlman T, Saboo U, Dana R. Reduced efficacy of low-dose topical steroids in dry eye disease associated with graft-versus-host disease. Am J Ophthalmol. 2018;190:17-23.
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1.
Tong J, Hu R, Zhao Y, Xu Y, Zhao X, Jin X. Serum vitamin A levels may affect the severity of ocular graft-versus-host disease. Front Med (Lausanne). 2017;4:67.