Delayed diagnosis of ocular graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

To investigate the delayed diagnosis of chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT), and further analyze potential confounding factors. This cross-sectional study included 118 patients newly diagnosed as coGVHD after alloHCT at Zhongshan Ophthalmic Center, Sun Yat-sen University. All participants finished the flow path of medical history taking, detailed ophthalmological examination and questionnaire-based survey. coGVHD was diagnosed and graded by International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Lag time of diagnosis was defined as interval between noting of ocular symptoms and confirmed diagnosis of coGVHD (TN-D). We further compared the clinical parameters between groups categorized by the median TN-D as medium and long delay groups. The median TN-D was 6.3 [IQR 2.8-14.5] months. Most coGVHD patients underwent delayed diagnosis of coGVHD longer than 3 months (70%, 83 of 118), with 90 of 118 diagnosed as severe coGVHD (76%). The long delay group exhibited higher ICOGCG scores (10 [IQR 9-10.5] vs. 9 [IQR 8-10], P=0.039) and more pronounced ocular signs, including conjunctival injection, meibomian gland loss, fibrotic tarsal conjunctiva, symblepharon, and corneal complications (all P <0.05). Delayed diagnosis was strikingly correlated with seeking ophthalmic medical care twice or more prior to diagnosis (adjusted OR=5.42, 95%CI: 1.40-21.06, P=0.015) and accurate knowledge of ocular discomfort symptoms in coGVHD (adjusted OR=0.29, 95%CI: 0.08-1.00, P=0.050). Delayed diagnosis of coGVHD, associated with disease severity, was common among alloHCT recipients in southern China. Improving patient education and the awareness of ophthalmologists may facilitate early diagnosis of coGVHD.