Cross-Linking Assisted Infection Reduction (CLAIR): A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Bacterial Keratitis.

PURPOSE: To determine whether there is a benefit to adjuvant corneal cross-linking (CXL) for bacterial keratitis. METHODS: This is an outcome-masked, randomized controlled clinical trial. Consecutive patients presenting with a smear-positive bacterial ulcer at Aravind Eye Hospitals at Madurai, Pondicherry, and Coimbatore in India were enrolled. Study eyes were randomized to topical moxifloxacin 0.5% or topical moxifloxacin 0.5% plus CXL. The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle corrected visual acuity at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 weeks and 3 months, infiltrate and/or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL had 0.60 decreased odds of culture positivity at 24 hours (95% confidence interval [CI]: 0.10-3.50; P = 0.65), 0.9 logarithm of the minimum angle of resolution lines worse visual acuity (95% CI: -2.8 to 4.6; P = 0.63), and 0.41-mm larger scar size (95% CI: -0.48 to 1.30; P = 0.38) at 3 months. We note fewer corneal perforations or need for therapeutic penetrating keratoplasty in the CXL group. CONCLUSIONS: We were unable to confirm a benefit to adjuvant CXL in the primary treatment of moderate bacterial keratitis. However, CXL may reduce culture positivity and complication rates; therefore, a larger trial to fully evaluate this is warranted. TRIAL REGISTRATION: NCT02570321.

Cross-Linking-Assisted Infection Reduction: A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Outcomes in Fungal Keratitis.

PURPOSE: To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis. DESIGN: Outcome-masked, 2×2 factorial design, randomized controlled clinical trial. PARTICIPANTS: Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India. METHODS: Study eyes were randomized to 1 of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. MAIN OUTCOME MEASURES: The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 days, 3 weeks, and 3 months, infiltrate or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL regardless of medication (topical natamycin or amphotericin) had 1.32-fold increased odds of 24-hour culture positivity, although this was not statistically significant (95% confidence interval [CI], 0.57-3.06; P = 0.51). We were also unable to find a difference in 24-hour culture positivity between those randomized to amphotericin and those randomized to natamycin when evaluating as a group regardless of whether or not they received CXL (coefficient 1.10; 95% CI, 0.47-2.54; P = 0.84). The BSCVA was approximately 0.22 logarithm of the minimum angle of resolution (logMAR) (2.2 Snellen lines) worse on average at 3 weeks among those receiving CXL regardless of medication (95% CI, -0.04 to 0.40; P = 0.04) and 0.32 logMAR (3.2 Snellen lines) worse visual acuity at 3 months after controlling for baseline visual acuity (95% CI, 0.03-0.54; P = 0.02). There was no difference in infiltrate or scar size, percentage of epithelialized or adverse events when comparing CXL with no CXL or the 2 topical medications. CONCLUSIONS: There appears to be no benefit of adjuvant CXL in the primary treatment of moderate filamentous fungal ulcers, and it may result in decreased visual acuity.

Colonization of therapeutic contact lens by dematiaceous fungi.

PURPOSE: To report 2 patients with colonization of therapeutic contact lens with dematiaceous fungi. METHODS: Case report. RESULTS: The first patient had a retained soft contact lens on an opaque cornea for 4 years with brownish black multiple colonies on the soft contact lens and culture grew Bipolaris spp. The second patient was on therapeutic contact lens for pseudophakic bullous keratopathy for 4 months and developed a brownish colonization of contact lens with unidentified dematiaceous fungi. Both the patients had conjunctivitis but did not develop fungal keratitis. CONCLUSION: Judicious use of therapeutic contact lens is required in agrarian countries with adequate emphasis on strict adherence to the standard protocols and frequent replacement of the lens.

Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis.

PURPOSE: To assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial. DESIGN: Experimental study using data from a randomized comparative trial. PARTICIPANTS: Of the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis. METHODS: The Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed. MAIN OUTCOME MEASURES: The primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization. RESULTS: A 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95% CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15-0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97; P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study. CONCLUSIONS: Decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome.

Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial.

PURPOSE: To analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole and to assess the relationship between organism, MIC, and clinical outcome. METHODS: Data were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity, infiltrate/scar size, time to reepithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole were done according to Clinical and Laboratory Standards Institute standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC were assessed. RESULTS: Of the 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly isolated organisms. MIC was significantly different across the groups of organisms (P = 0.0001). A higher MIC was significantly associated with an increased likelihood of perforation [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.02-4.04; P = 0.04]. There was no significant association between MIC and 3-week visual acuity (OR, 0.058; 95% CI, -0.01 to 0.13; P = 0.11), 3-month visual acuity (OR, 0.01; 95% CI,-0.08 to 1.04; P = 0.79), 3-week infiltrate/scar size (OR, 0.12, 95% CI, -0.02 to 0.27; P = 0.10), 3-month infiltrate/scar size (OR, 0.12; 95% CI, -0.02 to 0.25; P = 0.09), or time to reepithelialization (hazards ratio, 1.19; 95% CI, 0.98-1.45; P = 0.08). CONCLUSION: A higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.

Antioxidants in prevention of cataracts in South India: methodology and baseline data*.

PURPOSE: To describe the methodology and baseline data for the Antioxidants in Prevention of Cataracts (APC) study in South India. METHODS: The APC study is a prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based clinical trial to examine the effect of antioxidants (combination tablet of vitamins A, C, and E) on progression of cataract. The primary outcome variable is cataract progression (nuclear opalescence), evaluated with the slit-lamp biomicroscope by the Lens Opacification Classification System III method. Secondary outcome variables are progression in cortical and posterior subcapsular opacity and nuclear color, change in best corrected visual acuity, myopic shift, and treatment failure (progression to cataract surgery or best corrected vision worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a diagnosis of diabetes mellitus or nonfasting blood glucose level>7.8 mmol/L, history or presence of various ocular conditions or treatment forms, or current use of vitamin supplements. Baseline ophthalmic, demographic, and potential cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were compared between groups on an intent-to-treat basis. RESULTS: Of 954 people screened, 798 were enrolled, a sample size which exceeded the required estimate. More than 80% of subjects had 20/20 or better vision in at least one eye, and baseline prevalence of significant cataract according to the LOCS III grading scale was high. The two treatment groups were comparable for all baseline measures except alcohol intake. CONCLUSION: The sample size and group baseline characteristics will provide sufficient power to detect a change in cataract progression within 5 years.

Visual experience during phacoemulsification under topical versus retrobulbar anesthesia: results of a prospective, randomized, controlled trial.

PURPOSE: To compare the subjective visual experience of cataract patients during phacoemulsification and intraocular lens implantation under topical anesthesia (TA) vs retrobulbar anesthesia (RA). DESIGN: Prospective, randomized, controlled trial. METHODS: Three hundred six cataract patients eligible for phacoemulsification and intraocular lens implantation were randomized to receive either TA or RA during surgery by one of three surgeons. The surgeons were familiar with both anesthetic techniques and operated on the patients using the technique to which the patients were randomized. A masked interviewer conducted in-person interviews with the patients using a standardized questionnaire about their intraoperative visual experience and their reaction to their visual experience between 30 minutes and 4 hours after the surgery. RESULTS: Two patients (one in each group) had intraoperative posterior capsule rupture and were excluded from analysis. There was no statistically significant difference between TA (n = 154) and RA (n = 150) groups, except that more males compared with females had TA (P = .03). More patients who had TA reported perception of light (P < .001) and colors (P < .001) and a change (either increase or decrease) in light brightness during the course of the surgery (P < .001). There was no statistically significant difference in the proportions of patients who saw movements, flashes, instruments, or the surgeon or medical staff during the operation and who found their visual sensations frightening in the two groups. However, 10.4% in the TA group and 9.3% in the RA group found their visual experience frightening. CONCLUSIONS: More patients undergoing cataract surgery under TA compared with RA reported perception of light, colors, and a change in light brightness. A significant proportion of patients in both groups found the visual experience frightening.