Developing a new grading system of ocular surface disease after allogeneic hematopoietic stem cell transplantation (HSCT).

Background and Study Objective: ocular surface disease (OSD) resembling the dry eye syndrome is a common chronic GVHD-associated late complication of allogeneic HSCT and a cause of significant morbidity. Diagnosis of OSD is usually based on the measurement of tear production through the Schirmer test (ST): however, this test has low sensitivity and does not allow patient stratification. In this study we develop a more detailed grading system for OSD following allogeneic HSCT. Patients and Methods: starting on april 2004, we enrolled 30 consecutive patients complaining of OSD symptoms (dryness, burning, hypersecretion, pain or photophobia) after allogeneic HSCT. All enrolled patients underwent analysis of ocular surface function based on the following parameters: tear production (based on ST, scored positive if <5 in at least one eye); tear composition (scored positive based on either a positive Ferning test or on a tear break-up time of <5 seconds); corneal epithelial damage (scored positive based on slit lamp examination and by staining the cornea with fluorescein when possible); conjunctival inflammation (scored positive based on a conjunctival smear cytology score of >5). Each patient received a score (0 through 4) based on the number of positive parameters. Results: patients were enrolled after a median follow up of 397 days (68-3737). Two patients had a score of 0 (no OSD) and were therefore excluded from further analysis. Of the remaining 28 patients, 4 had a score of 1; 5 had a score of 2 (including 1 patient with a positive ST): for purposes of analysis, these two cohorts were grouped together as low risk patients; 7 had a score of 3 (including 3 with a positive ST) (intermediate risk); and 12 had a score of 4 (all with a positive ST) (high risk). Patient and transplant characteristics were similar in the three groups, with the exception of myeloablative conditioning, that was more common in the intermediate and high risk group (7/7 and 10/12, respectively) than in the low risk group (4/9). Among low risk patients 5/9 had cGVHD (3 extensive), whereas 5/7 had cGVHD in intermediate risk patients (4 extensive) and 12/12 in high risk patients (8 extensive). After a median follow up of 499 days following enrollment (range 0-1057, including two patients who did not receive follow up visits yet), the number of experimental treatments (including topical cyclosporine, autologous serum, plugs or protective lenses) that had been administered was 1 in the low risk group, 4 (all in 1 patient) in the intermediate risk and 14 (in 6 patients) in the high risk group. At last follow up, 5/9 patients in the low risk group had cGVHD (2 extensive), including 2 patients with persistent OSD; 5/6 in the intermediate risk group had cGVHD (3 extensive), including 4 persistent OSD; and 11/11 in the high risk group had cGVHD (7 extensive), including 9 persistent OSD. Conclusion: patients with a score of >3 based on our OSD scoring system have a higher risk of persistent OSD requiring experimental treatment in association with refractory extensive cGVHD. The development of a more detailed OSD scoring system may allow better patients stratification and help monitor responses in clinical trials.