Clinical Manifestations and Prognostic Factors of Chronic Ocular Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Wang Lan Y , Chiu Gloria B , Young Rachel A , Akhtari Mojtaba 
Published: October 2019

Abstract
Introduction:
Ocular graft-versus-host disease (GvHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHSCT), typically affecting 40-60% of patients within 3 years after alloHSCT. The most common clinical manifestation is dry eye disease (DED), which may lead to secondary epithelial changes in the cornea such as filamentary keratitis, and contribute to ocular discomfort and further complications. Patients with DED typically require a complete ophthalmologic examination, including a slit lamp exam to look at punctate epithelial erosions (PEEs) and other ocular surface findings. Treatment for chronic ocular GvHD typically ranges from artificial tears and lid hygiene, to anti-inflammatory agents such as corticosteroids or cyclosporine A, and BostonSight Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) or other scleral lens therapy. Here, we retrospectively describe the clinical manifestations and look at potential prognostic factors of ocular GvHD at our institution.
Methods:
We identified 113 patients who had undergone alloHSCT by a single hematologist at the Norris Comprehensive Cancer Center from 1/14/2014 to 12/26/2017. Patients were excluded if they had no documented ocular symptoms or no eye exam performed. We created a final cohort of 26 patients whose demographics, transplant-related factors, clinical manifestations, and treatment outcomes were collected. PEE, from the optometrist's perspective, was graded from 0 - 4 with 4 being the most severe, and ocular surface disease index (OSDI), from the patient's perspective, was graded from 0 to 100 with 100 being the most severe. Descriptive statistics were used to characterize the cohort. The T-test was used to describe groups with continuous outcomes and the Fisher's exact test was used to describe groups with categorical outcomes. A p-value of < 0.05 was considered statistically significant.
Results:
The incidence of ocular symptoms in our study was 30.1%. A total of 26 patients (mean age 43 years old) with 84.6% Hispanic, 11.5% non-Hispanic Whites (NHWs), and 3.8% African American, were included in statistical analysis. The primary disease included 50% acute myeloid leukemia (AML), 30.7% acute lymphoid leukemia (ALL), 7.7% severe aplastic anemia (sAA), chronic myelomonocytic leukemia (CMML), myelofibrosis, and hemophagocytic lymphohistiocytosis (HLH). 50% of the patients underwent alloHSCT with a match related donor (MRD), 34.6% with a match unrelated donor (MUD), and 15.4% of patients with a haploidentical donor (HAPLO). 65.4% of patients had evidence of acute GvHD and 100% of patients had evidence of chronic GvHD in other organs.
The most common symptom was DED (73%), followed by light sensitivity (34.6%), gritty sensation (30.8%), eye pain (30.8%), itchy eyes, mucus discharge, foreign body sensation, and tearing. There was a significantly higher PEE score for patients with the A blood type compared to the other blood types (2.0 vs. 0.98; p < 0.0046) and a not statistically significant trend towards higher OSDI scores as well (50.1 vs. 27.3; p = 0.071). There also was a significantly higher OSDI score in patients with donors > 50 years old (65.0 vs. 32.2; p = 0.045) and a significantly higher proportion of filamentary keratitis (66.6% vs. 5%; p = 0.0047), with a statistically insignificant trend towards higher PEE scores (1.92 vs. 1.36; p = 0.2). No prognostic impact was seen with primary disease type, race, age of recipient at transplant, gender of donor or recipient, recipient blood type, type of transplant, CMV status of donor or recipient, recipient CMV reactivation post-transplant, prior acute GvHD or concurrent systemic chronic GvHD.
Artificial tears/conservative therapy was recommended in 15.4% of patients, anti-inflammatory eye drops in 42.3% and scleral lens/PROSE therapy in 42.3% of patients. Compliance was poor and only 14 patients had visual acuity data with treatment. There was an improvement in LogMar score of average 0.14 in both eyes (0.08 in right eye and 0.19 in left eye).
Conclusions:
Ocular GvHD is an important complication in patients undergoing alloHSCT. Patients who had type A blood type had a significantly higher PEE score than those with other blood types. There was also a significantly higher OSDI score in patients who had donors > 50 years of age, as well as a significantly higher proportion of filamentary keratitis, which can lead to severe corneal complications.

Disclosures
No relevant conflicts of interest to declare.