Ocular Surface Alteration after Long-term Treatment with an Antiglaucomatous Drug Jose M. Herreras, MD,]. Carlos Pastor, MD, Margarita Calonge, MD, Victor M. Asensio, MD Background: This study was undertaken to see whether long-term locally applied ocular medications produced any alterations in the ocular surface, and, in particular, whether it caused damage to the mucus layer of the tear film. Methods: The authors studied the ocular surface of 40 control subjects (group 1), 21 patients (group 2) chronically treated with a commercial preparation of 0.5% timolol maleate, and 20 previously untreated glaucomatous patients (group 3) in need of treat- ment with the same drug. Parameters studied were Schirmer's test, lacrimal meniscus height, break-up time, fluorescein and rose Bengal stains, conjunctival impression cy- tology, mucus staining, and the ferning test. Results: Patients in groups 2 and 3 showed a significant decrease (P < 0.001) in the number of normal Schirmer's and break-up time tests. All had positive vital stains. Results showed a significant decrease (P < 0.001) in goblet-cell density, mucus granules, and reticular sheets, and an increase (P < 0.001) in pathologic crystallization patterns. Conclusion: These results demonstrate that chronic application of a commercial preparation of timolol maleate damaged the ocular surface, especially the mucus layer of the tear film. Ophthalmology 1992;99:1082-1088 In a previous study,' we demonstrated that it was neces- sary to damage the mucus layer of the tear film to allow the enhancement of an experimental allergicconjunctivitis elicited by topical challenge. Because it was our clinical impression that patients undergoing chronic topical treatment had a higher inci- dence of ocular allergic reactions, we postulated that long- term, locally applied ocular medications damaged the mucus layer of the tear film and subsequently facilitated local allergic reactions. Originally received: October 18, 1991. Revision accepted: February 25, 1992. From the Ocular Immunology Unit of the Instituto de Oftalmobiologia Aplicada (IOBA) and Hospital Clinico Universitario, Universidad de Valladolid, Valladolid, Spain. Presented as a poster at the Association for Research in Vision and Oph- thalmology Annual Meeting, Sarasota, May 1991. Supported by Laboratorios Cusi S.A., Barcelona, Spain. The authors have no financial interest in this drug. Reprint requests to Jose M. Herreras, MD, Instituto de Oftalmobiologia Aplicada, FacuItad de Medicina, Universidad de Valladolid, Ramon y Cajal 7, Valladolid 47005, Spain. 1082 As a first approach to this hypothesis, we have at- tempted to determine if chronic application of a com- mercial preparation of 0.5% timolol maleate produced microscopic alterations of the ocular surface, with special emphasis on the mucus layer. Materials and Methods Patient Groups We studied three groups of patients. Informed consent was obtained from all subjects after the procedure was fully explained. The protocol was approved by the Com- mittee of Clinical Assay of the Hospital Clinico Univer- sitario, in Valladolid, Spain. Group 1 included 40 control subjects (40 eyes) and was subdivided by age into 2 groups of 20 subjects each as follows: group lA included subjects between 41 and 60 years and group IB included subjects between 61 and 80 years. In each group, 10 subjects were male and 10 were female. To be included in the study, patients were required to have a normal slit-lamp examination, a lac-