Antibiotics Versus Placebo for Acute Bacterial Conjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. DESIGN: Systematic review and meta-analysis. METHODS: We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis. RESULTS: Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low. CONCLUSIONS: Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.

Topical ophthalmic anesthetics for corneal abrasions.

BACKGROUND: Despite potential analgesic benefits from topical ophthalmic amides and esters, their outpatient use has become of concern because of the potential for abuse and ophthalmic complications. OBJECTIVES: To assess the effectiveness and safety of topical ophthalmic anesthetics compared with placebo or other treatments in persons with corneal abrasions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase.com; Latin American and Caribbean Health Sciences (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The search was performed on 10 February 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of topical ophthalmic anesthetics alone or in combination with another treatment (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs)) versus a non-anesthetic control group (e.g. placebo, non-treatment, or alternative treatment). We included trials that enrolled participants of all ages who had corneal abrasions within 48 hours of presentation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included nine parallel-group RCTs with a total of 556 participants (median number of participants per study: 45, interquartile range (IQR) 44 to 74), conducted in eight countries: Australia, Canada, France, South Korea, Turkey, New Zealand, UK, and USA. Study characteristics and risk of bias Four RCTs (314 participants) investigated post-traumatic corneal abrasions diagnosed in the emergency department setting. Five trials described 242 participants from ophthalmology surgery centers with post-surgical corneal defects: four from photorefractive keratectomy (PRK) and one from pterygium surgery. Study duration ranged from two days to six months, the most common being one week (four RCTs). Treatment duration ranged from three hours to one week (nine RCTs); the majority were between 24 and 48 hours (five RCTs). The age of participants was reported in eight studies, ranging from 17 to 74 years of age. Only one participant in one trial was under 18 years of age. Of four studies that reported funding sources, none was industry-sponsored. We judged a high risk of bias in one trial with respect to the outcome pain control by 48 hours, and in five of seven trials with respect to the outcome complications at the furthest time point. The domain for which we assessed studies to be at the highest risk of bias was missing or selective reporting of outcome data. Findings The treatments investigated included topical anesthetics compared with placebo, topical anesthetic compared with NSAID (post-surgical cases), and topical anesthetics plus NSAID compared with placebo (post-surgical cases). Pain control by 24 hours In all studies, self-reported pain outcomes were on a 10-point scale, where lower numbers represent less pain. In post-surgical trials, topical anesthetics provided a moderate reduction in self-reported pain at 24 hours compared with placebo of 1.28 points on a 10-point scale (mean difference (MD) -1.28, 95% confidence interval (CI) -1.76 to -0.80; 3 RCTs, 119 participants). In the post-trauma participants, there may be little or no difference in effect (MD -0.04, 95% CI -0.10 to 0.02; 1 RCT, 76 participants). Compared with NSAID in post-surgical participants, topical anesthetics resulted in a slight increase in pain at 24 hours (MD 0.82, 95% CI 0.01 to 1.63; 1 RCT, 74 participants). One RCT compared topical anesthetics plus NSAID to placebo. There may be a large reduction in pain at 24 hours with topical anesthetics plus NSAID in post-surgical participants, but the evidence to support this large effect is very uncertain (MD -5.72, 95% CI -7.35 to -4.09; 1 RCT, 30 participants; very low-certainty evidence). Pain control by 48 hours Compared with placebo, topical anesthetics reduced post-trauma pain substantially by 48 hours (MD -5.68, 95% CI -6.38 to -4.98; 1 RCT, 111 participants) but had little to no effect on post-surgical pain (MD 0.41, 95% CI -0.45 to 1.27; 1 RCT, 44 participants), although the evidence is very uncertain. Pain control by 72 hours One post-surgical RCT showed little or no effect of topical anesthetics compared with placebo by 72 hours (MD 0.49, 95% CI -0.06 to 1.04; 44 participants; very low-certainty evidence). Proportion of participants with unresolved epithelial defects When compared with placebo or NSAID, topical anesthetics increased the number of participants without complete resolution of defects in trials of post-trauma participants (risk ratio (RR) 1.37, 95% CI 0.78 to 2.42; 3 RCTs, 221 participants; very low-certainty evidence). The proportion of placebo-treated post-surgical participants with unresolved epithelial defects at 24 to 72 hours was lower when compared with those assigned to topical anesthetics (RR 0.14, 95% CI 0.01 to 2.55; 1 RCT, 30 participants; very low-certainty evidence) or topical anesthetics plus NSAID (RR 0.33, 95% CI 0.04 to 2.85; 1 RCT, 30 participants; very low-certainty evidence). Proportion of participants with complications at the longest follow-up When compared with placebo or NSAID, topical anesthetics resulted in a higher proportion of post-trauma participants with complications at up to two weeks (RR 1.13, 95% CI 0.23 to 5.46; 3 RCTs, 242 participants) and post-surgical participants with complications at up to one week (RR 7.00, 95% CI 0.38 to 128.02; 1 RCT, 44 participants). When topical anesthetic plus NSAID was compared with placebo, no complications were reported in either treatment arm up to one week post-surgery (risk difference (RD) 0.00, 95% CI -0.12 to 0.12; 1 RCT, 30 participants). The evidence is very uncertain for safety outcomes. Quality of life None of the included trials assessed quality of life outcomes. AUTHORS' CONCLUSIONS: Despite topical anesthetics providing excellent pain control in the intraoperative setting, the currently available evidence provides little or no certainty about their efficacy for reducing ocular pain in the initial 24 to 72 hours after a corneal abrasion, whether from unintentional trauma or surgery. We have very low confidence in this evidence as a basis to recommend topical anesthetics as an efficacious treatment modality to relieve pain from corneal abrasions. We also found no evidence of a substantial effect on epithelial healing up to 72 hours or a reduction in ocular complications when we compared anesthetics alone or with NSAIDs versus placebo.

Corneal Culture and Antibiotic Susceptibility Results for Microbial Keratitis in the Mid-Atlantic Region of the United States, 2016 to 2020.

OBJECTIVE: To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States. METHODS: Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020. RESULTS: Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; ∼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin. CONCLUSIONS: Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.

Satellite Faculty in an Academic Ophthalmology Department: Junior, Clinical, and Female.

Purpose: To evaluate the perception of physicians at satellite offices of a large academic ophthalmology department. Methods: A survey was sent to the 32 physician faculty members working at the satellite offices in the Ophthalmology Department of the University of Michigan. The ophthalmologists answered 44 survey questions on staffing, wait times, physician satisfaction, patient satisfaction, compensation, administrative help, research, and operations management. Results: Seventeen (53%) satellite ophthalmologists responded. The majority were satisfied with work at satellites, which they felt operated efficiently and believed to feature high patient satisfaction. A minority of ophthalmologists had concerns about salary, volume, marketing support, and geographic location. Some respondents did not understand the compensation structure, satellites' finances, or contribution to the overall department. Most described a lack of research and resident teaching opportunities at satellites. Conclusions: The perceptions of ophthalmologists who work in satellite offices are important because of the growth of these offices in academic medical centers and the ability for satellite doctors to offer care comparable with and sooner than doctors at the main hospital at locations convenient for patients. Satellite ophthalmologists at this academic center would appreciate increased transparency of compensation and financial structures; administrative help with marketing and maintaining efficiency, which doctors and patients enjoy at satellite offices; and more teaching and research opportunities, which are the basis of academic advancement. Such efforts may help retain satellite doctors, who tend to be junior in rank, female, nontenured faculty, and who experience a higher turnover rate than faculty at the main campus.

Antibiotics versus placebo for acute bacterial conjunctivitis.

BACKGROUND: Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on the basis that they may speed recovery, reduce persistence, and prevent keratitis. However, many cases of acute bacterial conjunctivitis are self-limited, resolving without antibiotic therapy. This Cochrane Review was first published in The Cochrane Library in 1999, then updated in 2006, 2012, and 2022. OBJECTIVES: To assess the benefits and side effects of antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2022, Issue 5), MEDLINE (January 1950 to May 2022), Embase (January 1980 to May 2022), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www. CLINICALTRIALS: gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases in May 2022.   SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which any form of antibiotic treatment, with or without steroid, had been compared with placebo/vehicle in the management of acute bacterial conjunctivitis. This included topical and systemic antibiotic treatments. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts of identified studies. We assessed the full text of all potentially relevant studies and determined the included RCTs, which were further assessed for risk of bias using Cochrane methodology. We performed data extraction in a standardized manner and conducted random-effects meta-analyses using RevMan Web. MAIN RESULTS: We included 21 eligible RCTs, 10 of which were newly identified in this update. A total of 8805 participants were randomized. All treatments were topical in the form of drops or ointment. The trials were heterogeneous in terms of their eligibility criteria, the nature of the intervention (antibiotic drug class, which included fluoroquinolones [FQs] and non-FQs; dosage frequency; duration of treatment), the outcomes assessed and the time points of assessment. We judged one trial to be of high risk of bias, four as low risk of bias, and the others as raising some concerns. Based on intention-to-treat (ITT) population, antibiotics likely improved clinical cure (resolution of clinical symptoms or signs) by 26% (RR 1.26, 95% CI 1.09 to 1.46; 5 trials, 1474 participants; moderate certainty) as compared with placebo. Subgroup analysis showed no differences by antibiotic class (P = 0.67) or treatment duration (P = 0.60). In the placebo group, 55.5% (408/735) of participants had spontaneous clinical resolution by days 4 to 9 versus 68.2% (504/739) of participants treated with an antibiotic. Based on modified ITT population, in which participants were analyzed after randomization on the basis of positive microbiological culture, antibiotics likely increased microbiological cure (RR 1.53, 95% CI 1.34 to 1.74; 10 trials, 2827 participants) compared with placebo at the end of therapy; there were no subgroup differences by drug class (P = 0.60). No study evaluated the cost-effectiveness of antibiotic treatment. Patients receiving antibiotics had a lower risk of treatment incompletion than those in the placebo group (RR 0.64, 95% CI 0.52 to 0.78; 13 trials, 5573 participants; moderate certainty) and were 27% less likely to have persistent clinical infection (RR 0.73, 95% CI 0.65 to 0.81; 19 trials, 5280 participants; moderate certainty). There was no evidence of serious systemic side effects reported in either the antibiotic or placebo group (very low certainty). When compared with placebo, FQs (RR 0.70, 95% CI 0.54 to 0.90) but not non-FQs (RR 4.05, 95% CI 1.36 to 12.00) may result in fewer participants with ocular side effects. However, the estimated effects were of very low certainty. AUTHORS' CONCLUSIONS: The findings of this update suggest that the use of topical antibiotics is associated with a modestly improved chance of resolution in comparison to the use of placebo. Since no evidence of serious side effects was reported, use of antibiotics may therefore be considered to achieve better clinical and microbiologic efficacy than placebo. Increasing the proportion of participants with clinical cure or increasing the speed of recovery or both are important for individual return to work or school, allowing people to regain quality of life. Future studies may examine antiseptic treatments with topical antibiotics for reasons of cost and growing antibiotic resistance.

Survey of state conjunctivitis policies for school-age students.

PURPOSE: To examine state policies regarding school-age students with conjunctivitis. METHODS: Analysis included the following evidence: publicly available policies for disposition of affected students; indications for exclusion and return to classroom; and completeness of information, including mention of different etiologies of conjunctivitis; signs and symptoms of viral versus bacterial conjunctivitis; student disposition and treatment based on etiology; internally consistent recommendations; reference to credible resources; and mention of the possibility of a conjunctivitis outbreak. RESULTS: Fifteen of 50 states have no policies. Ten states allow students to remain in school, 5 allow return 24 hours after initiation of antibiotic treatment, and 5 require physician approval. Seventeen states and Washington, DC, offer little detail or internally inconsistent recommendations, such as choice of antibiotic use or provider note. Twelve policies are thoroughly presented. Twenty-three states refer to sources like the Centers for Disease Control and Prevention and the American Academy of Pediatrics. No policy references the American Academy of Ophthalmology. CONCLUSIONS: State policies on conjunctivitis in students vary widely. Antibiotic use as a prerequisite for return to school has drawbacks of cost to parents, increasing antibiotic resistance, and lack of efficacy against nonbacterial etiologies, for example, viral conjunctivitis. Publicly available information and guidelines could be improved, aiming for fewer absentee days, reduced outbreak risk, and reduced risk of antibiotic resistance.

Topical Pharmacologic Interventions Versus Active Control, Placebo, or No Treatment for Epidemic Keratoconjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or placebo for epidemic keratoconjunctivitis (EKC). DESIGN: Systematic review. METHODS: We included randomized controlled trials that compared antiseptic agents, virustatic agents, or immune-modulating topical therapies with placebo or an active control. We adhered to Cochrane methods for trial selection, data extraction, risk of bias evaluation, and data synthesis. RESULTS: Ten randomized controlled trials with 892 participants with acute or chronic EKC were included. Eight trials compared interventions with artificial tears or saline (n = 4) or with steroids (n = 4); two 3-arm trials contributed data to both comparisons. Estimates suggested that compared with tears, after povidone-iodine (PVP-I) alone (2 studies, 409 participants) more participants with acute EKC had resolution of symptoms (risk ratio [RR] 1.15 [95% confidence interval {CI} 1.07-1.24]) and signs (RR 3.19 [95% CI 2.29-4.45]) within 10 days. In 2 trials comparing treatments with steroid alone or steroid with levofloxacin, fewer eyes treated with PVP-I or polyvinyl alcohol iodine (PVA-I) plus steroid developed subepithelial infiltrates within 21 days (RR 0.08 [95% CI 0.01-0.55]; 69 eyes). No treatment was shown to improve resolution of infiltrates. CONCLUSIONS: Low- to very low-level certainty of evidence suggested that PVP-I or PVA-I with steroid may confer some benefit in acute EKC, but imprecision from small sample sizes, the potential risk of bias from inadequate reporting or trial design, and variability in participant selection, outcome measurement, and reporting limit the amount and quality of evidence.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

BACKGROUND: Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care. OBJECTIVES: To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021. SELECTION CRITERIA: We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty. AUTHORS' CONCLUSIONS: The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.

Clinical Experience of an American Academic Ophthalmology Department During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: To describe the experience of a large American academic ophthalmology department from the start of the COVID-19 pandemic to the early recovery phase in Summer 2020. METHODS: Retrospective review; description of approaches taken by our academic medical center and department regarding supply chain issues, protection of doctors and staff, elimination of nonurgent care, calls for staff and faculty deployment, and reopening. Comparison of surgical and clinic volumes in suburban locations versus the main campus; analysis of volumes compared with pre-pandemic periods. RESULTS: At our medical center, screening and precautions (such as the mask policy) continued to evolve from March through August 2020. Ophthalmologists were not allowed to use N95 respirators except in rare circumstances. Surgical and clinic volume dropped at both urban and suburban locations, but surgery rebounded more quickly at suburban surgery centers once elective procedures resumed. Mandates from administration were not always attainable. CONCLUSIONS: During respiratory pandemics such as COVID-19, medical centers should adopt protective measures that are consistent across inpatient and outpatient sectors and consistent with other institutions. Our department's large presence outside the urban center where the main hospital is located allowed faster return of clinical care overall. In the event of another pandemic, a central budget rather than individual divisional budgets should be used for purchase of protective equipment for health care workers of an academic center. Because outpatient care provides important continuity of care and keeps patients away from emergency departments and hospitals, perhaps outpatient care does not have to be curtailed to the extent it was in Spring-Summer 2020, provided that outpatient health care workers have sufficient staff and equipment and the above measures are in place.

Transepithelial Versus Epithelium-Off Corneal Crosslinking for Progressive Keratoconus: Findings From a Cochrane Systematic Review.

PURPOSE: The purpose of this study was to summarize key findings from a systematic review of the effectiveness and safety of transepithelial corneal crosslinking (CXL) compared with epithelium-off CXL for progressive keratoconus. DESIGN: Cochrane systematic review. METHODS: We included in our review only randomized controlled trials (RCTs) in which transepithelial and epithelium-off CXL had been compared among participants with progressive keratoconus. The primary outcome was keratoconus stabilization based on post-operative maximum keratometry (Kmax). We adhered to Cochrane methods for trial selection, data extraction, risk of bias evaluation, and data synthesis. RESULTS: Thirteen RCTs with 567 participants (661 eyes) were included; 11 studies compared non-iontophoresis-assisted transepithelial with epithelium-off CXL. Keratoconus stabilization was described as an outcome in 2 studies. The estimated difference in Kmax means (ie, the "mean difference," MD) from meta-analysis of 177 eyes in 5 RCTs indicated that there were no differences between intervention groups in Kmax at 12 months or later (MD: 0.99 diopter [D]; 95% confidence interval: -0.11 to 2.09). Meta-analysis of keratometry and visual acuity outcomes at 12 months or longer after surgery from 2 studies that had compared transepithelial CXL using iontophoresis provided no conclusive evidence of an advantage over epithelium-off CXL. CONCLUSIONS: Lack of precision due to small sample sizes, indeterminate risk of bias due to inadequate reporting, and inconsistency in how outcomes were measured and reported among studies make it difficult to state with confidence whether transepithelial CXL confers an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to stabilization of keratoconus, visual acuity, or patient-reported outcomes based on available data.

Cost Savings From a Policy to Diagnose and Prevent Transmission of Adenoviral Conjunctivitis in Employees of a Large Academic Medical Center.

IMPORTANCE: Adenoviral conjunctivitis is highly contagious, can be associated with systemic infections, and can cause chronic visual impairment. It accounts for a large proportion of acute conjunctivitis. Outbreaks of epidemic keratoconjunctivitis (EKC) are costly in terms of productivity loss from work furloughs and spread to patients and have resulted in clinic and departmental closures. OBJECTIVE: To examine the institutional cost savings of a policy to diagnose adenoviral conjunctivitis and triage and furlough medical center employees with this condition to prevent outbreaks. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed Johns Hopkins Medicine employees with red eye from November 1, 2011, through October 31, 2018, who were triaged at the occupational health clinic whose conditions were diagnosed using polymerase chain reaction (PCR) validated for adenoviral conjunctivitis. INTERVENTIONS: Only employees with positive PCR test results were furloughed, with furlough length tailored to subtype (a minimum of 2 weeks for EKC and 1 week otherwise). MAIN OUTCOMES AND MEASURES: Total number of furloughs avoided and cost savings associated with reducing unnecessary furloughs. RESULTS: Of 2142 employees with red eye, 1520 (71.0%) underwent PCR testing; 130 (8.6%) had positive adenoviral PCR test results, of whom 41 (31.5%) had EKC. Furloughing 130 employees with positive PCR test results vs furloughing all 1520 employees clinically suspected of having adenoviral conjunctivitis represented an estimated annual savings of $442 073, or $3 094 511 during 7 years. The cost of performing PCR on employees suspected of having adenoviral conjunctivitis was 5.0% of the cost associated with furloughing all employees with red eye. No outbreaks occurred. CONCLUSIONS AND RELEVANCE: In this quality improvement study, this policy, notable for development and use of PCR for adenoviral conjunctivitis on a large scale, resulted in substantial cost savings from fewer work furloughs compared with the number of employees who would have been furloughed based on clinical diagnosis. These results may provide impetus for policy adoption by other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.

Transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus.

BACKGROUND: Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze. OBJECTIVES: To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus. SEARCH METHODS: To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I2 = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I2 = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I2 = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported. AUTHORS' CONCLUSIONS: Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.

Detection of SARS-CoV-2 RNA in the corneal epithelium of a patient after recovery from COVID-19.

PURPOSE: To report a case of a patient presenting with unilateral keratouveitis associated with ocular hypertension six weeks after being discharged from the hospital for COVID-19. Ocular specimens were obtained for testing. OBSERVATIONS: A 69-year-old African American woman developed poor vision while hospitalized for COVID-19 in April but did not seek ophthalmic care until end of May. She had an edematous cornea, stromal keratitis, and highly elevated intraocular pressure by June. After lack of response to oral valacyclovir, aqueous fluid and swabs of her conjunctiva and limbal epithelium with corneal epithelium anterior to the limbus were sent for real-time polymerase chain reaction (PCR) for herpes simplex virus, herpes zoster virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epithelium from the cornea and limbus was positive for SARS-CoV-2 by PCR; specimens from the other two ocular sites were negative. All specimens were negative for herpes simplex virus and varicella zoster virus. The patient refused further treatment despite intraocular pressure above 50 mm Hg at last follow-up. CONCLUSIONS AND IMPORTANCE: Although SARS-CoV-2 and severe acute respiratory syndrome coronavirus (SARS-CoV) have been detected by PCR in the conjunctiva and tears of patients with acute respiratory infection, presence in corneal tissue has not been described. In addition, no one has studied whether ocular tissues in convalesced patients can harbor viral RNA. Here we describe unilateral keratouveitis in a convalesced patient whose corneal epithelium/limbal tissue was positive for SARS-CoV-2 by PCR. Further investigation is required to determine whether active viral replication or viral remnants account for this result.

Review of Gamma-Irradiated Sterile Cornea: Properties, Indications, and New Directions.

ABSTRACT: Gamma-irradiated sterile cornea (GISC) is a relatively new graft tissue that follows the 30-year success of irradiation to other tissues (bone and sclera) to lessen antigenic load and infection transmission. It can serve as a graft to cover glaucoma drainage devices, as graft tissue for frank or impending corneal perforations in tectonic keratoplasty, as graft tissue in lamellar keratoplasty, and as carrier tissue for keratoprosthesis. With the limited availability of fresh corneal tissue in less developed countries, GISC may fill a need for corneal tissue worldwide. It can be used in situations where corneal endothelium is not needed and with a greatly reduced risk of rejection and infection because of the effect of irradiation on corneal tissue.