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Background The incidence of herpes zoster (HZ) has been on the rise for decades in the United States. Clinical trials for the recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of over 90% in preventing herpes zoster. However, there is limited information on its effectiveness outside of a clinical trial setting, as well as its effectiveness against herpes zoster ophthalmicus (HZO). Methods A de-identified electronic health records database from Kaiser Permanente Hawaii (KPH) was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against HZ and HZO in immunocompetent, vaccine age-eligible individuals without a prior history of HZ, who were continuously enrolled in KPH for ≥365 days prior to becoming age-eligible for RZV between January 1, 2018, through December 31, 2019. Results A total of 78 356 adults were included in this study, with 11 864 (15.1%) adults receiving two valid doses of the recombinant zoster vaccine. The incidence rate of HZ was 325.6 (95% CI: 217.7 to 464.4) cases per 100 000 person-years in vaccinated persons compared to 1063.3 cases per 100 000 person-years (95% CI: 1006.0 to 1122.8) in the unvaccinated group. The incidence rate of HZO was 11.9 (95% CI: 0.7 to 52.3) cases per 100 000 person-years in the vaccinated group compared to 72.1 (95% CI: 58.0 to 88.3) in the unvaccinated group. RZV was 83.5% (95% CI: 74.9% to 89.2%) effective against HZ and 93.3% (95% CI: 48.7% to 99.1%) effective against HZO. Conclusions RZV has demonstrated high effectiveness against both HZ and HZO outside of a clinical trial setting in the United States. Vaccine coverage is low, emphasizing the need for public health efforts to increase vaccination to reduce morbidity from HZ and HZO.

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

To explore the effectiveness of "off-the-shelf" dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) as an alternative to sodium EDTA as chelation therapy in removal of calcific band keratopathy (CBK).This study was a retrospective case series involving 4 patients with CBK who underwent superficial keratectomy and subsequent chelation therapy with K2-EDTA in a single center (Coastal Eye Clinic) by the same surgeon. Visual acuity and symptomatic relief were the main outcomes measured in our study.All 4 participants in this study were female with an average age of 80.3 years. Three of the patients with reasonable baseline visual acuity experienced improved visual acuity at 1 month. The other patient with multiple ocular comorbidities and severely reduced visual potential reported symptomatic pain relief at 1-month follow-up after the intervention.K2-EDTA seems to be an effective alternative to disodium EDTA in its ability to clear calcific plaques and restore visual function. Because of the logistical difficulties associated with acquiring disodium EDTA, and the relative abundance of K2-EDTA in health-care facilities, we believe that our findings warrant further investigation into its use as a more accessible and cost-effective chelating agent in CBK.

Erythromycin enol ether is a potent mimic of the peptide hormone motilin. To understand its biological activity, its three-dimensional structure in CD(2)Cl(2) was determined from constrained molecular mechanics using constraints derived from NMR spectra. The structure of the enol ether is well defined by 10 structures that minimize the energy and satisfy the NMR data. We infer the molecular basis for its activity as a motilide from a comparison of its structure with that of motilin. The macrolide ring of the enol ether is a beta-turn mimic of the peptide. Furthermore, a superposition of the structures of the enol ether and motilin shows a striking overlap of the sugar rings attached to the macrolide ring with essential aromatic side chains in the peptide.

Purpose To report choroidal detachment following tamsulosin (Flomax, an α 1A -adrenoceptor antagonist) treatment of benign prostatic hyperplasia (BPH). Design Case report. Methods Chart review, serial examination. Results A 65-year-old man underwent uncomplicated cataract extraction and placement of a posterior chamber intraocular lens. The patient subsequently developed three separate episodes of choroidal detachments in the operated eye. Each episode was preceded by treatment with an α 1 -adrenoceptor antagonist. Conclusions Tamsulosin may cause adverse ocular effects including recurrent choroidal detachments. α 1A is the dominant α-adrenoceptor in the rabbit choroid, and the mechanism for choroidal detachment in this patient could include some effect of antagonists like tamsulosin on these receptors.

Purpose To evaluate the microbial flora of eyes with a Boston Keratoprosthesis (K-Pro). Methods A prospective study was performed for 17 eyes of 15 patients who underwent a K-Pro implantation between September 2005 and June 2011. Preoperative diagnoses included failed corneal grafts, limbal stem cell deficiency, chemical burns, and Stevens-Johnson Syndrome. The patients used topical antibiotics after their surgery including a fluoroquinolone, polymyxin-trimethoprim, vancomycin, or a combination of the 3. The conjunctiva in the study eye was swabbed and cultured. A separate culture was taken of the contralateral eye as well. If available, the bandage contact lens was removed, and half of it was placed in thioglycolate broth, and half in 5 mL of a sterile balanced salt solution. The contact lens in the balanced salt solution was sonicated using a QSonica Q125 sonicator (Newtown, CT) for 1 minute, at an amplitude of 20%. Ten microliters of fluid was subsequently cultured. Results Of the patients who underwent the K-Pro surgery during that time period, 15 patients with 17 eyes were able to participate in the data collection. Nine of the 17 eyes implanted with the K-Pro (53%) had positive cultures. Two of the 13 (15%) of the control swabs exhibited bacterial growth. Eight percent (1/12) of the sonicated lenses were positive on culture, whereas 4/12 (33%) of the lenses placed in thioglycolate broth were positive for organisms. Conclusions Despite being on antibiotics, eyes implanted with the K-Pro were more likely to have a positive conjunctival culture in our cohort as compared with that of fellow eyes.

Purpose: To report the results of imaging using high-resolution, Fourier domain anterior segment optical coherence tomography (AS-OCT) to evaluate patients with a type 1 Boston Keratoprosthesis (KPro). Methods: We performed a retrospective comparative study of patients in whom we implanted the Boston KPro. A total of 26 eyes of 23 patients from the Cornea Service at the University of California Davis Eye Center were included. Subjects were evaluated with the Spectralis AS-OCT (Heidelberg Engineering GmbH). Results: Preoperative diagnoses for KPro surgery included failed corneal transplant (69%), chemical burn (23%), and aniridia (8%). The average age of patients was 63.2 years (range, 17-88 years). Fifty-four percent of the patients were female. The mean duration between the KPro surgery and the acquisition of high-resolution AS-OCT imaging was 35.8 months (range, 2-90 months). The most commonly observed finding was retroprosthetic membrane formation, which we found in 77% of KPro eyes. In 65% of KPro eyes, we identified epithelium behind the front plate, and in 54%, we identified an epithelial lip over the anterior surface of the KPro front plate. In 31% of KPro eyes, we identified periprosthetic cysts, gaps or spaces, and thinning in the corneal carrier graft. Conclusions: Fourier domain AS-OCT is a useful noninvasive imaging technique in patients with a KPro and provides the ability to identify changes that are sometimes difficult to appreciate by clinical evaluation. The higher resolution Fourier domain systems may aid in the clinical diagnosis and management of pathology that might not be imaged with instruments of lower resolution. AS-OCT has the potential for monitoring the anatomic stability of an implanted KPro and may also help to monitor for complications. Moreover, highresolution imaging may enhance our understanding of periprosthetic anatomy.© 2013 by Lippincott Williams & Wilkins.

Infectious keratitis is a major cause of monocular blindness worldwide.1 Although fungal ulcers are relatively uncommon in developed nations, they occur frequently in developing countries, especially those in tropical regions. In South India, up to half of infectious ulcers are fungal.2 Fungal ulcers are notoriously difficult to treat compared with bacterial ulcers, and physicians frequently use combination therapy.3 Amphotericin B and natamycin are two commonly used topical agents to treat filamentous fungal keratitis.3 However, combination therapy may increase the risk of potential drug toxicity as well as the cost of therapy. Currently, there are no data on whether natamycin and amphotericin B interact synergistically in vitro against filamentous fungi. Here, we investigate whether amphotericin B and natamycin interact synergistically in vitro when tested against Fusarium and Aspergillus spp. isolated from patients with fungal keratitis. Ten Fusarium spp. and ten Aspergillus spp. isolates were randomly selected from 98 consecutive cases of culture-positive fungal keratitis treated at Aravind Eye Hospital in South India. All patients underwent cornea culture and were treated with natamycin, …

Role of randomised clinical trials in public health: distribution of mass antibiotics for trachoma control In this issue, Wright et al 1 discuss the role of randomised clinical trials (RCTs) in public health. They suggest that not all decisions can be based on evidence from RCTs, and they use the distribution of mass antibiotics for trachoma control as an example. The authors refer to several reports in which the prevalence of infection was dramatically lower after mass azithromycin distributions, but which had no control groups for comparison.2–5 They contend that a large RCT which randomised communities to different treatment strategies would be too difficult, too expensive and too unethical to conduct, and that treatment recommendations are needed immediately to prevent blindness. The particular example that the authors choose is an interesting one. Antibiotics are clearly effective in eliminating chlamydia.6–8 Infection has stayed low for months, if not years, after a single community-wide antibiotic distribution.2–4 But the long-term efficacy of mass treatment had not been rigorously shown in a group-randomised trial, at least not in time for a Cochrane Collaboration report on the topic (most recently updated in 2005).9,10 The report highlighted the fact that many studies have been uncontrolled and non-blinded. For an outcome, several have relied on clinical activity, which has never been shown to be a particularly good marker for ocular chlamydial infection.11–13 Those trials that did randomise by group typically included far too few …

CONTEXT: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. OBJECTIVE: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. INTERVENTION: A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. MAIN OUTCOME MEASURE: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. RESULTS: Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P

Fungal keratitis causes significant morbidity, especially in tropical climates, and is notoriously difficult to manage. The choice of antifungal agent for fungal keratitis remains largely empirical, with no consensus on the role of susceptibility testing in guiding therapy. Studies suggest that susceptibility and outcome may be associated in systemic fungal infections with some dimorphic fungi,1 but this correlation may not exist for filamentous fungi or in ocular disease because of frequent topical dosing and high drug concentration. Given the availability of new topical medications, tailoring antifungal therapy based on microbial sensitivity is important.2 Here, we assess whether fungal susceptibility testing correlates with clinical outcomes in cases of fungal keratitis. This study was a retrospective case review of consecutive patients with culture proven fungal keratitis presenting to the Aravind Eye Hospital cornea clinic between March and July 2004. Of 98 consecutive patients, minimum inhibitory concentration (MIC) data was available for 90.3 Eighty-one corresponding charts were available, and 54 charts had follow-up of at least 3 weeks to allow determination of healing. All cases were …

To characterize the susceptibility of filamentous fungi isolated from keratitis to amphotericin B, natamycin, caspofungin acetate, itraconazole, voriconazole, and posaconazole.Ninety isolates from fungal keratitis cases at Aravind Eye Hospital in South India were tested using macrobroth dilution for susceptibility to amphotericin B, natamycin, caspofungin, itraconazole, voriconazole, and posaconazole. The minimum inhibitory concentration (MIC) median and 90th percentile were determined.The 90 isolates included 41 Aspergillus species, 38 Fusarium species, and 11 others. The triazoles and caspofungin had the lowest MICs against Aspergillus species; voriconazole, amphotericin B, and posaconazole had the lowest MICs against Fusarium species, and none of the Fusarium species were inhibited by itraconazole or caspofungin. Amphotericin B had significantly lower MICs compared with natamycin, but after correcting for the typical prescription dose, natamycin was superior.No single agent was universally most effective, but voriconazole and other triazoles demonstrated the broadest spectrum. Itraconazole and caspofungin were not effective against Fusarium species.Fungal ulcers are commonly treated empirically; drugs are typically selected without regard to susceptibility data. The nonocular infectious disease literature suggests modern fungal susceptibility methods are clinically relevant, but ocular studies are limited. Our results suggest antifungal therapy might be tailored to individual organisms.