Herbert E. Kaufman

Specular Microscopy of Human Corneal Endothelium in VIVO

A clinical specular microscope used in the routine examination fo the corneal endothelium of 40 patients at high magnification, without inconvenience or discomfort to the patients, detected endothelial damage or disease that was not seen by slit-lamp examination. A statistically significant decrease (P less than .001) in the number of central endothelial cells with age was documented.

Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease

BACKGROUND Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatment can prevent recurrences of ocular HSV disease. METHODS We randomly assigned 703 immunocompetent patients who had had ocular HSV disease within the preceding year to receive 400 mg of acyclovir or placebo orally twice daily. The study outcomes were the rates of development of ocular or nonocular HSV disease during a 12-month treatment period and a 6-month observation period. RESULTS The cumulative probability of a recurrence of any type of ocular HSV disease during the 12-month treatment period was 19 percent in the acyclovir group and 32 percent in the placebo group (P<0.001). Among the 337 patients with a history of stromal keratitis, the most common serious form of ocular HSV disease, the cumulative probability of recurrent stromal keratitis was 14 percent in the acyclovir group and 28 percent in the placebo group (P=0.005). The cumulative probability of a recurrence of nonocular (primarily orofacial) HSV disease was also lower in the acyclovir group than in the placebo group (19 percent vs. 36 percent, P<0.001). There was no rebound in the rate of HSV disease in the six months after treatment with acyclovir was stopped. CONCLUSIONS After the resolution of ocular HSV disease, 12 months of treatment with acyclovir reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. Long-term antiviral prophylaxis is most important for patients with a history of HSV stromal keratitis, since it can prevent additional episodes and potential loss of vision.

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study One Year After Surgery

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between -2.00 and -8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within +/- 1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, -4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between -2.00 and -4.25 diopters. Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by greater than 0.50 diopters in 19% of eyes.

Central Photorefractlve Keratectomy for Myopia: Partially Sighted and Normally Sighted Eyes

Ten partially sighted and 19 normally sighted eyes underwent excimer laser photorefractive keratectomy for the correction of myopia. Nine of the partially sighted and 17 of the normally sighted eyes had 12 months of follow-up. Epithelial healing was complete in all eyes by day 6. None of the eyes had recurrent erosions, infections, or other medical complications. An increase in corneal haze after surgery was followed by a slow trend toward clearing. Average uncorrected visual acuity in the 7 normally sighted eyes with attempted corrections of 5 diopters (D) or less was 20/40 from month 2 on; the eyes with greater than 5 D attempted corrections had an average of 20/80--at month 2, which declined to 20/200--by month 6. Best spectacle-corrected visual acuity was within +/- 1 Snellen line of preoperative values in 14 of the normally sighted eyes, improved 2 or more lines in 2 eyes, and worsened two or more lines in two eyes. Hard contact lens overcorrection restored all of the two-line loss in 1 eye and 1 line of the 3-line loss in the other. Refraction and keratometry indicated corneal flattening without induced astigmatism.

Endothelial Damage Associated with Intraocular Lenses

We examined the corneal endothelium of five patients with the clinical specular microscope before and at intervals after combined cataract extraction and intraocular lens implantation. There was a severe loss of endothelial cells postoperatively in all five patients despite clear, thin corneas. We observed no significant endothelial regeneration (increased number of cells) or continued cell loss during 15 weeks of postoperative observation. The clinical specular microscope was useful in assessing the endothelial effects of ocular surgical procedures.

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-controlled, 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.

Changes in Corneal Topography after Excimer Laser Photorefractive Keratectomy for Myopia

Computer-assisted analysis of corneal topography was performed in 17 normally sighted human eyes during the first year after excimer laser photorefractive keratectomy (PRK) for myopia. Laser ablation of the central cornea produced an optical zone with a smooth power transition to the peripheral cornea. Decentration of the ablation was noted in some eyes (less than 0.5 mm in 3 eyes, 0.5 to 1.0 mm in 10 eyes, 1 to 1.5 mm in 3 eyes, and 2.1 mm in 1 eye), suggesting that careful alignment of the laser beam is critical. Improved methods to align the ablation within the center of the entrance pupil are needed. In 12 of 17 eyes, the topographic pattern appeared to stabilize between 3 and 7 months after PRK. In the remaining five eyes, central ablation power changed by more than 0.5 diopters (D) between the 6- and 12-month examinations. Regression was more common and more pronounced in eyes with intended corrections more than 5 D, whereas the majority of eyes with intended corrections of 5 D or less showed good correspondence between the final change in central ablation power and the attempted correction. Two eyes had a loss of at least two lines of best spectacle-corrected visual acuity that was attributable to irregular astigmatism, decentration of the ablation, and/or corneal opacification.

Herpetic Eye Disease Study: A Controlled Trial of Oral Acyclovir for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study

PURPOSE To investigate whether conjunctival inflammation represents a primary event in the pathogenesis of keratoconjunctivitis sicca or whether it is a secondary inflammatory reaction caused by enhanced mechanical irritation as a result of surface dryness and whether anti-inflammatory drops (corticosteroids and nonsteroidal anti-inflammatory) have therapeutic effects and are similar. DESIGN Single-masked, randomized, prospective clinical trial. METHODS Thirty-two keratoconjuctivitis patients with or without Sjögren syndrome were included in the study. The patients were randomized to three groups. Group 1 patients received a topical artificial tear substitute (ATS); group 2 received ATS plus nonsteroidal anti-inflammatory drops (NSAID); and group 3 received ATS plus topical corticosteroidal drops. The eye symptom severity scores, Schirmer test values, rose bengal and fluorescein staining scores were evaluated before treatment and 15 and 30 days after start of treatment. Impression cytology specimens were stained using immunohistochemical methods to detect the percentages of human leukocyte antigen II (HLA-DR) positive, Apo 2.7 positive, and periodic acid-Schiff positive cells. Statistical analyses were performed within and between groups. Group 3 patients had significantly lower symptom severity scores, fluorescein and rose bengal staining, and HLA-DR positive cells on days 15 and 30 compared with patients in other groups. They also had a significantly higher number of periodic acid-Schiff positive (goblet) cells in their impression cytology specimens on days 15 and 30 compared with the other patients. On day 30, group 3 patients had significant differences compared with their baseline measurements in terms of above-mentioned parameters. However, we did not detect a significant effect of any treatment schedule on the Shirmer test value and the numbers of Apo 2.7 cells in impression cytology specimens. CONCLUSION Topical corticosteroids had a clearly beneficial effect both on the subjective and objective clinical parameters of moderate-to-severe dry eye patients. These effects were associated with the reduction of inflammation markers of conjunctival epithelial cells.

Herpetic Stromal Keratitis—Evidence for Cell-Mediated Immunopathogenesis

Immunofluorescence, histological, and electron microscopic observations were made on rabbit corneas from animals with experimentally induced stromal keratitis following intracorneal injection with the RE strain of herpes simplex virus. Electron microscopic observations were also made on human corneas obtained from patients with a history of herpetic stromal disease. Viral antigens were demonstrated by immunofluorescence in keratocytes of rabbit corneas with herpetic stromal keratitis. Electron microscopic observations and viral culture failed to reveal the presence of viral particles in these tissues. Lymphocytes, a major infiltrating cell type found in both the rabbit and human corneas, were often found in intimate contact with degenerating keratocytes.