Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and while culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungal keratitis and Acanthameoba. Next generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However outcomes remain poor secondary to corneal melting, scarring and perforation. Adjuvant therapies aimed at reducing the immune response responsible for much of the morbidity associated with keratitis include topical corticosteroids. The large, randomized controlled Steroids for Corneal Ulcers trial found that while steroids provided no significant improvement overall, they did appear beneficial for ulcers that were central, deep or large, non-Nocardia or classically invasive P. aeruginosa, patients with low baseline vision, and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960’s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial showed a benefit of topical natamycin over topical voriconazole for fungal keratitis, particularly among those caused by Fusarium. The second Mycotic Ulcer Treatment Trial showed that oral voriconazole did not improve outcomes overall although there may have been some effect among Fusarium ulcers. Given an increase in non-serious adverse events the authors concluded that they could not recommend oral voriconazole at this time. Viral keratitis differs from bacterial and fungal cases in that is often recurrent and is common in developed countries. The first Herpetic Eye Disease Study (HEDS) showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of HSV keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

Objectives: Trachoma is the leading cause of infectious blindness worldwide. It is known to be highly correlated with poverty, limited access to healthcare services and water. In 2003, the WHO estimated that 84 million people were suffering from active trachoma, and 7.6 million were severely visually impaired or blind as a result of trachoma: this study provides an updated estimate of the global prevalence of trachoma based on the most recent information available. Methods: A literature search of recent published and unpublished surveys in the 57 endemic countries was carried out: the result of surveys that used the WHO trachoma grading system and additional information from regional and country experts served as a basis to determine the prevalence of trachoma in each country. Results: Population-based surveys provided recent information for 42 out of 57 endemic countries. 40.6 million people are estimated to be suffering from active trachoma, and 8.2 million are estimated to have trichiasis. Conclusions: The current estimate of prevalence of trachoma is lower than the previous WHO estimates: this can be explained by the success in implementing control strategy, by more accurate data, as well as by socioeconomic development in endemic countries.

Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

for the Mycotic Ulcer Treatment Trial II Group OBJECTIVE To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. DESIGN, SETTING, AND PARTICIPANTSThe Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis.INTERVENTIONS Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. MAIN OUTCOMES AND MEASURESThe primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use.RESULTS A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Šidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P < .001 after Holms-Šidák correction for multiple comparisons). CONCLUSIONS AND RELEVANCEThere appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00996736

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Gram-positive organisms are the most commonly identified etiology of microbial keratitis in this series. Approximately 35% of cultured organisms had variable susceptibility to moxifloxacin, and resistance seems to be increasing over time. The risk of culturing MRSA increased over time.

Purpose: To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). Design: Cohort study within a multicenter randomized clinical trial. Methods: 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0–7 days (N=675) or 8–14 days (N=655) and followed for three years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection. Results: Cumulative probability of definite graft rejection was 3.6% (99% CI 2.5% to 5.3%). Younger recipient age was associated with graft rejection [p<0.001; HR: 0.53 (0.33, 0.83) per decade]. PT, donor-recipient gender mismatch, recipient diagnosis, recipient race, graft size, discontinuation of topical corticosteroids, and immune-modulators, prior immunizations within three months, and prior glaucoma surgery were not associated with rejection (p>0.01). Among clear grafts with an ECD measurement at baseline and 3 years (N=913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (N=27) than in those that did not (N=886) (48% vs 38%, p=0.03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS. Conclusions: Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure.

; for the Cornea Preservation Time Study Group IMPORTANCE Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. OBJECTIVE To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. INTERVENTIONS The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. MAIN OUTCOMES AND MEASURES Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. RESULTS The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (−103 [−196 to −9] cells/mm 2), lower screening ECD (−234 [−331 to −137] per 500 cells/mm 2), recipient diagnosis of PACE (−257 [−483 to −31] in cells/mm 2), and operative complications (−324 [−516 to −133] in cells/mm 2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. CONCLUSIONS AND RELEVANCE Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.