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We report our experience of anterior stromal puncture (ASP) in symptomatic chronic corneal edema patients awaiting penetrating keratoplasty (PK) and hypothesize the mechanism of action of ASP in bullous keratopathy (BK).We reviewed the medical records of 28 patients with BK who underwent ASP between November 1996 and September 1999 with at least 1 month of follow-up. In all these patients, approximately 200 punctures were given with a bent 26-gauge needle sparing the peripheral cornea. Patients were examined on days 1 and 7, 1 month, and every 3 months after the procedure. The symptoms, corneal findings, and visual acuity of the patients at last follow-up were noted and compared with the preprocedure findings. For 11 patients who underwent PK, histopathologic study of corneal buttons was performed and a clinicopathologic correlation was attempted.Of the 28 patients, there were 15 men and 13 women with a mean age of 61.1 years. The clinical diagnosis was pseudophakic BK in 11 (39.3%), aphakic BK in 11 (39.3%), Fuchs' dystrophy in 4 (14.3%), failed graft in 1 (3.6%), and chronic corneal edema of unknown etiology in 1 (3.6%). The follow-up ranged from 1 to 33 months with a mean of 9.5 ± 7.5 months. Symptomatic relief was noted in all. Twenty patients (71.4%) had complete relief, whereas eight patients (28.6%) experienced mild symptoms such as tearing and occasional pain. Visual acuity improved in 7 patients (25%), decreased in 12 (42.8%), and remained the same in 9 (32.4%). Objective evidence of scarring after ASP was noted in all patients. Complete regression of epithelial bullae and epithelial edema was found in 10 (35.7%) and partial regression in 18 (62.25%) patients. There was no progression or appearance of new blood vessels except in one patient (3.6%). Histologically, puncture marks and superficial stromal scarring were noted in all corneal buttons. Adhesion of epithelium with varying degrees of subepithelial fibrosis was seen in six, whereas in the remaining five buttons, there was complete denudation of the epithelium. Vascularization was seen in five and inflammation in two buttons. Clinicopathologic correlation revealed that symptomatic patients had persistent edema and loose adhesion of the epithelium to the stroma, resulting in detachment.ASP is a simple, safe, and cost-effective outpatient procedure for symptomatic relief in patients with BK. The possibility of decreased visual acuity after the procedure should be explained to all patients. Although ASP promoted subepithelial fibrosis in all cases, its subsequent adhesion is variable and probably has clinical relevance. Further studies could be directed toward identifying specific mediators that promote epithelial–stromal interaction and firm anchoring of epithelium to the underlying stroma.