Peter R. Laibson

Dysfunctional Tear Syndrome A Delphi Approach to Treatment Recommendations

Purpose: To develop current treatment recommendations for dry eye disease from consensus of expert advice. Methods: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. Results: A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. Conclusion: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

Spectrum of fungal keratitis at Wills Eye Hospital, Philadelphia, Pennsylvania.

Purpose. To report the spectrum of fungal keratitis at Wills Eye Hospital, Philadelphia. Methods. We reviewed the records of 24 cases of culture-positive fungal keratitis treated from January 1991 to March 1999 at Wills Eye Hospital. Risk factors, fungal identification, antifungal treatment, and outcomes were evaluated. Results. The study included 24 eyes (24 patients). Fourteen patients (58.3%) were female. The mean age was 59 years (range, 19–86 years). Predisposing factors included chronic ocular surface disease (41.7%), contact lens wear (29.2%), atopic disease (16.7%), topical steroid use (16.7%), and ocular trauma (8.3%). Early identification of fungal elements was achieved by staining of corneal scrapings in 18 cases (75%). Half of the cases (12 eyes) had corneal infections caused by yeast, and the other half by filamentous fungi. Candida albicans was the most commonly isolated organism (45.8%), followed by Fusarium sp (25%). Natamycin and amphotericin B were the topical antifungals most frequently used, while systemic treatment commonly used included fluconazole, ketoconazole, or itraconazole. Six patients (25%) had penetrating keratoplasty during the acute stage of infection. After a mean follow-up of nine months, 13 eyes (54.1%) had the best corrected visual acuity 20/100 or better. Conclusions. In contrast to other studies from the northern United States, we found Fusarium sp the most commonly isolated filamentous fungus. In our series, C. albicans was the most frequent cause of fungal keratitis, and a past history of ocular trauma was uncommon.

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.

Boston keratoprosthesis outcomes and complications.

Purpose: To evaluate the outcomes of the Boston Keratoprosthesis (KPro) at our institution. Methods: A computerized database retrospectively identified all patients who received a Boston KPro from August 2005 to October 2007. Results: There were 37 patients, 24 (65%) were male. Mean age was 66.3 years (median 69 years, range: 24-93 years; SD = 18.1 years). Mean follow-up was 16 months (range: 6-28 months; SD = 6.0 months). There were 36 type 1 (97%) and 1 type 2 (3%) KPros. The primary indication was failed penetrating keratoplasty in 29 patients (78%)-22 (59%) from multiple failures. Preoperative comorbidities included glaucoma [27 patients (73%)] and limbal stem cell deficiency [13 patients (35%)]. No intraoperative complications occurred. Postoperative complications included retroprosthetic membrane [24 patients (65%)], increased intraocular pressure [14 patients (38%)], glaucoma progression [5 patients (13.5%)], and endophthalmitis [4 patients (11%)-3 who discontinued prophylactic antibiotics secondary to compliance]. Thirty-six KPros (97%) were retained-1 type 2 KPro (3%) in a patient with ocular cicatricial pemphigoid extruded and was replaced. Mean best-corrected visual acuities were counting fingers preoperatively (range: light perception to 20/100) and 20/90 at last follow-up (range: light perception to 20/25). At last follow-up, 31 patients (84%) improved 2 lines or greater-3 patients (8%) had worse vision. Conclusions: Retention rates were excellent, and best-corrected visual acuities improved in the vast majority of patients. Complications can occur and require frequent follow-up to monitor and treat glaucoma progression, endophthalmitis, and inflammation. Patient compliance is of paramount importance. Despite the potential complications, the Boston KPro provides visual improvement in patients with an otherwise poor prognosis.

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.

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.

Clinically Atypical Granular Corneal Dystrophy with Pathologic Features of Lattice-like Amyloid Deposits: A Study of Three Families

Four patients from families in Pennsylvania, Massachusetts, and Argentina were diagnosed clinically as having granular dystrophy. Results of pathologic examination of the corneal buttons from each patient after penetrating keratoplasty confirmed granular deposits in the anterior third of the stroma. Amyloid was demonstrated within some of these granular deposits by Congo red staining with birefringence and dichroism and by electron microscopy. In addition to the morphologically granular deposits, numerous fusiform deposits identified as amyloid by histochemistry and electron microscopy and morphologically identical to those seen in lattice corneal dystrophy were detected deep to the granular deposits. It was further shown that the histochemical pattern of staining of the granular material by a series of lectins was similar to that present in corneas with lattice dystrophy. Although a relationship between these patients cannot be definitively proven, each family traces its origins to the Italian province of Avellino.

Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy1

BACKGROUND Excimer laser phototherapeutic keratectomy (PTK) can be useful to treat anterior corneal dystrophies both before and after penetrating keratoplasty. OBJECTIVE To evaluate the recurrence of corneal dystrophies after excimer laser PTK. DESIGN Retrospective case series. PARTICIPANTS Fifty excimer laser PTK procedures were performed in 43 eyes of 33 patients with corneal dystrophies. Preoperative diagnoses included Reis-Bücklers dystrophy (13 eyes), granular dystrophy (11 eyes), anterior basement membrane (ABM) dystrophy (11 eyes), lattice dystrophy (7 eyes), and Schnyder crystalline dystrophy (1 eye). INTERVENTION Two excimer lasers (VISX 20/20 model B and VISX Star) were used to perform all PTKs. MAIN OUTCOME MEASURES After PTK, patients were followed on a regular basis with measurement of best-corrected visual acuity and biomicroscopic examination. Evidence of recurrent dystrophy was noted according to specific criteria. RESULTS Follow-up range was from 1.1 to 71.2 months (mean, 19.5 months). Clinically significant recurrent dystrophy occurred in 17 eyes. The ABM dystrophy recurred in the form of recurrent corneal erosions in 5 (42%) of the 12 eyes within 6 to 9 months of PTK. Four of these five eyes had mild erosions, which were treated successfully with topical medications while one eye required an additional PTK for an erosion outside the initial treatment area. Eight (47%) of 17 eyes with Reis-Bücklers dystrophy developed clinically significant recurrence an average of 21.6 months after PTK. Three (23%) of 13 eyes with granular dystrophy were found to have a significant recurrence a mean of 40.3 months after PTK. Only one (14%) of seven eyes with lattice dystrophy developed a significant recurrence at 6 months after PTK. Six eyes with significant recurrence after PTK were retreated successfully with additional PTK. Three eyes later developed recurrence of granular and Reis-Bücklers dystrophy after the second PTK. The probability of recurrence of these dystrophies after PTK was calculated using the Kaplan-Meier survival analysis. CONCLUSION Phototherapeutic keratectomy can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful retreatment with PTK is possible.

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study Five Years after Surgery

In the Prospective Evaluation of Radial Keratotomy (PERK) Study, 793 eyes of 435 patients with 2 to 8 diopters (D) of myopia received a standardized surgery consisting of 8 incisions with a diamond-bladed knife set at 100% of the thinnest paracentral ultrasonic corneal thickness measurement and a diameter of the clear zone of 3.0 to 4.5 mm; 97 eyes (12%) received an additional 8 incisions. There were 757 eyes (95%) followed for 3 to 6.3 years. After surgery, uncorrected visual acuity was 20/40 or better in 88% of eyes. The refractive error was within 1 D of emmetropia for 64% of eyes; 19% were myopic and 17% were hyperopic by more than 1 D. Between 6 months and 5 years after surgery, 22% of the eyes had a refractive change of 1 D or more in the hyperopic direction. For 25 eyes (3%) there was a loss of 2 or more lines of best spectacle-corrected visual acuity.

Indications for Penetrating Keratoplasty and Associated Procedures, 2001–2005

Purpose. To identify current indications and trends in indications for penetrating keratoplasty (PKP) and associated procedures. Methods. Retrospective chart review of all patients who underwent PKP at Wills Eye Institute from January 1, 2001, to December 31, 2005. Results. A total of 1,162 cases were performed in this 5-year period. Leading indications for PKP were pseudophakic corneal edema (PCE) in 330 (28.4%) cases, followed by regraft in 250 (22.0%), keratoconus in 186 (16%), and Fuchs’ endothelial dystrophy in 126 (10.8%) cases. Of the 330 cases of PCE, 232 (70.3%) were associated with posterior chamber intraocular lenses (PCIOLs) and 96 (29.1%) with anterior chamber lenses. In 330 eyes with PCE, the lens was not exchanged in 246 (74.5%) cases and was exchanged in 76 (23%) cases. Seventy of the exchanged lenses were anterior chamber intraocular lenses (ACIOLs) and six lenses were PCIOLs. In cases of ACIOL exchanges, 10 were for scleral sutured IOLs, 18 for PCIOLS, and 42 for another ACIOL. Conclusions. Pseudophakic corneal edema remains the leading indication for PKP at our institution followed by regraft, continuing a trend noted in our previous studies. Although the percentage of cases of PCE associated with PCIOLS increased, fewer lenses were exchanged, perhaps reflecting increased confidence in biocompatibility of newer IOLs. The decrease in overall number of corneal transplants in these 5 years continues a trend noted in our previous study and mirrors the national decline in PKP.