Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Corneal thickness changes during herpes simplex virus disciform keratitis.

OBJECTIVE: To describe the changes in corneal thickness determined by ultrasonic pachymetry during follow-up of herpes simplex virus disciform corneal edema. METHODS: Thirty-five patients with herpetic keratitis underwent slit-lamp biomicroscopy and ultrasonic pachymetry. Measurements during follow-up and at clinical resolution of corneal inflammation were compared with the initial corneal thickness. RESULTS: Corneal thickness of disciform stromal keratitis decreased 15% (95% confidence interval 10% to 20%) during follow-up, and 65% (95% confidence interval 43% to 88%) of this decrease occurred during the first 2 weeks. Increased central corneal thickness measured by pachymetry was associated with biomicroscopic detection of corneal edema (P = 0.03). CONCLUSIONS: Corneal pachymetry supplements clinical assessment of herpetic disciform edema.

Slitlamp biomicroscopy and photographic image analysis of herpes simplex virus stromal keratitis.

OBJECTIVE: To validate photographic bioimaging for evaluating the severity of herpes simplex virus keratitis. METHODS: Stromal keratitis of patients in the Herpetic Eye Disease Study was clinically measured with a slitbeam micrometer and then photographed at trial entry. Calibrated images of 169 eyes were analyzed for the size, location, and density of stromal keratitis and endotheliitis, with shape factor as a function of area and perimeter. Validity was assessed by comparing clinical and computerized measurements and by correlating the keratitis area with visual acuity. Logistic regression explored characteristics associated with larger or denser corneal inflammation. RESULTS: Stromal keratitis had a median area of 22.4 mm(2) (interquartile range, 12.8-31.6 mm(2)) with a median shape factor of 0.69 (interquartile range, 0.56-0.79); 126 eyes (75%) had their midpoint within 2 mm of the cornea's geometric center. Photoanalytical area estimates of herpetic stromal keratitis correlated closely with clinical measurements (correlation coefficient, 0.83). Eyes with larger stromal keratitis had worse vision (correlation coefficient, 0.32) and were more likely to have iritis (P = .01). Necrotizing stromal keratitis was significantly whiter (P = .02). CONCLUSIONS: Image analysis validly assesses the disciform geometry of herpetic stromal keratitis and confirms that increased severity is associated with uveitis and reduced vision.