Medical interventions for traumatic hyphema.

BACKGROUND: Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications. OBJECTIVES: To assess the effectiveness of various medical interventions in the management of traumatic hyphema. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022. SELECTION CRITERIA: Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose.  The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest. AUTHORS' CONCLUSIONS: We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Epidemiology, methods of diagnosis, and clinical management of patients with arginase 1 deficiency (ARG1-D): A systematic review.

BACKGROUND: Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels. It typically presents in early childhood with spasticity (predominately affecting the lower limbs), mobility impairment, seizures, developmental delay, and intellectual disability. This systematic review aims to identify and describe the published evidence outlining the epidemiology, diagnosis methods, measures of disease progression, clinical management, and outcomes for ARG1-D patients. METHODS: A comprehensive literature search across multiple databases such as MEDLINE, Embase, and a review of clinical studies in ClinicalTrials.gov (with results reported) was carried out per PRISMA guidelines on 20 April 2020 with no date restriction. Pre-defined eligibility criteria were used to identify studies with data specific to patients with ARG1-D. Two independent reviewers screened records and extracted data from included studies. Quality was assessed using the modified Newcastle-Ottawa Scale for non-comparative studies. RESULTS: Overall, 55 records reporting 40 completed studies and 3 ongoing studies were included. Ten studies reported the prevalence of ARG1-D in the general population, with a median of 1 in 1,000,000. Frequently reported diagnostic methods included genetic testing, plasma arginine levels, and red blood cell arginase activity. However, routine newborn screening is not universally available, and lack of disease awareness may prevent early diagnosis or lead to misdiagnosis, as the disease has overlapping symptomology with other diseases, such as cerebral palsy. Common manifestations reported at time of diagnosis and assessed for disease progression included spasticity (predominately affecting the lower limbs), mobility impairment, developmental delay, intellectual disability, and seizures. Severe dietary protein restriction, essential amino acid supplementation, and nitrogen scavenger administration were the most commonly reported treatments among patients with ARG1-D. Only a few studies reported meaningful clinical outcomes of these interventions on intellectual disability, motor function and adaptive behavior assessment, hospitalization, or death. The overall quality of included studies was assessed as good according to the Newcastle-Ottawa Scale. CONCLUSIONS: Although ARG1-D is a rare disease, published evidence demonstrates a high burden of disease for patients. The current standard of care is ineffective at preventing disease progression. There remains a clear need for new treatment options as well as improved access to diagnostics and disease awareness to detect and initiate treatment before the onset of clinical manifestations to potentially enable more normal development, improve symptomatology, or prevent disease progression.

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.

Outcome choice and definition in systematic reviews leads to few eligible studies included in meta-analyses: a case study.

BACKGROUND: There is broad recognition of the importance of evidence in informing clinical decisions. When information from all studies included in a systematic review ("review") does not contribute to a meta-analysis, decision-makers can be frustrated. Our objectives were to use the field of eyes and vision as a case study and examine the extent to which authors of Cochrane reviews conducted meta-analyses for their review's pre-specified main outcome domain and the reasons that some otherwise eligible studies were not incorporated into meta-analyses. METHODS: We examined all completed systematic reviews published by Cochrane Eyes and Vision, as of August 11, 2017. We extracted information about each review's outcomes and, using an algorithm, categorized one outcome as its "main" outcome. We calculated the percentage of included studies incorporated into meta-analyses for any outcome and for the main outcome. We examined reasons for non-inclusion of studies into the meta-analysis for the main outcome. RESULTS: We identified 175 completed reviews, of which 125 reviews included two or more studies. Across these 125 reviews, the median proportions of studies incorporated into at least one meta-analysis for any outcome and for the main outcome were 74% (interquartile range [IQR] 0-100%) and 28% (IQR 0-71%), respectively. Fifty-one reviews (41%) could not conduct a meta-analysis for the main outcome, mostly because fewer than two included studies measured the outcome (21/51 reviews) or the specific measurements for the outcome were inconsistent (16/51 reviews). CONCLUSIONS: Outcome choice during systematic reviews can lead to few eligible studies included in meta-analyses. Core outcome sets and improved reporting of outcomes can help solve some of these problems.

Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.

Anti-vascular endothelial growth factor for neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. OBJECTIVES: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. MAIN RESULTS: We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up. AUTHORS' CONCLUSIONS: Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.

Interventions to slow progression of myopia in children.

BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents. OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children. SEARCH METHODS: We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25 diopters (D) spherical equivalent myopia. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: We included 41 studies (6772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15 D (95% confidence interval [CI] -0.29 to 0.00; n = 142; low-certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95% CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95% CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95% CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95% CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95% CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95% CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95% CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95% CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and sperical aberration SCLs.

Development, implementation and evaluation of an online course on evidence-based healthcare for consumers.

BACKGROUND: Evidence-based healthcare (EBHC) principles are essential knowledge for patient and consumer ("consumer") engagement as research and research implementation stakeholders. The aim of this study was to assess whether participation in a free, self-paced online course affects confidence in explaining EBHC topics. The course comprises six modules and evaluations which together take about 6 h to complete. METHODS: Consumers United for Evidence-based Healthcare (CUE) designed, tested and implemented a free, online course for consumers, Understanding Evidence-based Healthcare: A Foundation for Action ("Understanding EBHC"). The course is offered through the Johns Hopkins Bloomberg School of Public Health. Participants rated their confidence in explaining EBHC topics on a scale of 1 (lowest) to 5 (highest), using an online evaluation provided before accessing the course ("Before") and after ("After") completing all six course modules. We analyzed data from those who registered for the course from May 31, 2007 to December 31, 2018 (n = 15,606), and among those persons, the 11,522 who completed the "Before" evaluation and 4899 who completed the "After" evaluation. Our primary outcome was the overall mean of within-person change ("overall mean change") in self-reported confidence levels on EBHC-related topics between "Before" and "After" evaluations among course completers. Our secondary outcomes were the mean within-person change for each of the 11 topics (mean change by topic). RESULTS: From May 31, 2007 to December 31, 2018, 15,606 individuals registered for the course: 11,522 completed the "Before" evaluation, and 4899 of these completed the "After" evaluation (i.e., completed the course). The overall mean change in self-reported confidence levels (ranging from 1 to 5) from the "Before" to "After" evaluation was 1.27 (95% CI, 1.24-1.30). The mean change by topic ranged from 1.00 (95% CI, 0.96-1.03) to 1.90 (95% CI, 1.87-1.94). CONCLUSION: Those who seek to involve consumer stakeholders can offer Understanding EBHC as a step toward meaningful consumer engagement. Future research should focus on long-term impact assessment of online course such as ours to understand whether confidence is retained post-course and applied appropriately.

Intrastromal corneal ring segments for treating keratoconus.

BACKGROUND: Keratoconus is a degenerative condition of the cornea that profoundly affects vision and vision-specific quality of life. The axial cornea thins and protrudes, resulting in irregularity and, eventually, scarring of the cornea. There are multiple options available for treating keratoconus. Intrastromal corneal ring segments are small, crescent-shaped plastic rings that are placed in the deep, peripheral corneal stroma in order to flatten the cornea. They are made of polymethylmethacrylate (PMMA). The procedure does not involve corneal tissue nor does it invade the central optical zone. Intrastromal corneal ring segments are approved for use when contact lenses or spectacles are no longer adequate. OBJECTIVES: To evaluate the effectiveness and safety of intrastromal corneal ring segments as a treatment for keratoconus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not implement any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 January 2018. SELECTION CRITERIA: Two review authors independently assessed records from the electronic searches to identify randomized controlled trials (RCTs). Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: We planned for two authors to independently review full-text reports, using standard methodological procedures expected by Cochrane. MAIN RESULTS: We found no RCTs comparing intrastromal corneal ring segments with spectacles or contact lenses. AUTHORS' CONCLUSIONS: In the absence of eligible RCTs to review, no conclusions can be drawn.

Routine preoperative medical testing for cataract surgery.

BACKGROUND: Cataract surgery is practiced widely, and substantial resources are committed to an increasing cataract surgical rate in low- and middle-income countries. With the current volume of cataract surgery and future increases, it is critical to optimize the safety and cost-effectiveness of this procedure. Most cataracts are performed on older individuals with correspondingly high systemic and ocular comorbidities. It is likely that routine preoperative medical testing will detect medical conditions, but it is questionable whether these conditions should preclude individuals from cataract surgery or change their perioperative management. OBJECTIVES: 1. To investigate the evidence for reductions in adverse events through preoperative medical testing2. To estimate the average cost of performing routine medical testing SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS BIREME, the metaRegister of Controlled Trials (mRCT) (last searched 5 January 2012); ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 June 2018, with the exception of mRCT which is no longer in service. We searched the references of reports from included studies for additional relevant studies without restrictions regarding language or date of publication. SELECTION CRITERIA: We included randomized clinical trials in which routine preoperative medical testing was compared to no preoperative or selective preoperative testing prior to age-related cataract surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed abstracts to identify possible trials for inclusion. For each included study, two review authors independently documented study characteristics, extracted data, and assessed risk of bias. MAIN RESULTS: We identified three randomized clinical trials that compared routine preoperative medical testing versus selective or no preoperative testing for 21,531 cataract surgeries. The largest trial, in which 19,557 surgeries were randomized, was conducted in Canada and the USA. Another study was conducted in Brazil and the third in Italy. Although the studies had some issues with respect to performance and detection bias due to lack of masking (high risk for one study, unclear for two studies), we assessed the studies as at overall low risk of bias.The three randomized clinical trials included in this review reported results for 21,531 total cataract surgeries with 707 total surgery-associated medical adverse events, including 61 hospitalizations and three deaths. Of the 707 medical adverse events reported, 353 occurred in the pre-testing group and 354 occurred in the no-testing group (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.86 to 1.16; high-certainty evidence). Most events were cardiovascular and occurred during the intraoperative period. Routine preoperative medical testing did not reduce the risk of intraoperative (OR 0.99, 95% CI 0.71 to 1.38) or postoperative ocular adverse events (OR 1.11, 95% CI 0.74 to 1.67) when compared to selective or no testing (2 studies; 2281 cataract surgeries; moderate-certainty evidence). One study evaluated cost savings, estimating the costs to be 2.55 times higher in those with preoperative medical testing compared to those without preoperative medical testing (1 study; 1005 cataract surgeries; moderate-certainty evidence). There was no difference in cancellation of surgery between those with preoperative medical testing and those with selective or no preoperative testing, reported by two studies with 20,582 cataract surgeries (OR 0.97, 95% CI 0.78 to 1.21; high-certainty evidence). No study reported outcomes related to clinical management changes (other than cancellation) or quality of life scores. AUTHORS' CONCLUSIONS: This review has shown that routine preoperative testing does not increase the safety of cataract surgery. Alternatives to routine preoperative medical testing have been proposed, including self administered health questionnaires, which could substitute for health provider histories and physical examinations. Such avenues may lead to cost-effective means of identifying those at increased risk of medical adverse events due to cataract surgery. However, despite the rare occurrence, adverse medical events precipitated by cataract surgery remain a concern because of the large number of elderly patients with multiple medical comorbidities who have cataract surgery in various settings. The studies summarized in this review should assist recommendations for the standard of care of cataract surgery, at least in low- and middle-income settings. Unfortunately, in these settings, medical history questionnaires may be useless to screen for risk because few people have ever been to a physician, let alone been diagnosed with any chronic disease.

Omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products. OBJECTIVES: To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms. SEARCH METHODS: CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated. SELECTION CRITERIA: We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54). AUTHORS' CONCLUSIONS: Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.

Medical interventions for traumatic hyphema.

BACKGROUND: Traumatic hyphema is the entry of blood into the anterior chamber (the space between the cornea and iris) subsequent to a blow or a projectile striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma, optic atrophy, etc.) may seriously affect vision. Such complications can lead to permanent impairment of vision. People with sickle cell trait/disease may be particularly susceptible to increases of elevated intraocular pressure. If rebleeding occurs, the rates and severity of complications increase. OBJECTIVES: To assess the effectiveness of various medical interventions in the management of traumatic hyphema. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase.com; PubMed (1948 to June 2018); the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 28 June 2018. SELECTION CRITERIA: Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. In this review, we included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical intervention or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions regarding age, gender, severity of the closed-globe trauma, or level of visual acuity at the time of enrollment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data for the primary outcomes, visual acuity and time to resolution of primary hemorrhage, and secondary outcomes including: secondary hemorrhage and time to rebleed; risk of corneal blood staining, glaucoma or elevated intraocular pressure, optic atrophy, or peripheral anterior synechiae; adverse events; and duration of hospitalization. We entered and analyzed data using Review Manager 5. We performed meta-analyses using a fixed-effect model and reported dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD). MAIN RESULTS: We included 20 randomized and seven quasi-randomized studies with a total of 2643 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest.We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Eight trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty.Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60) as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two studies with 121 participants. We assessed the certainty of these findings as low and very low, respectively. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.31, 95% CI 0.17 to 0.55) in five trials with 578 participants, as did aminomethylbenzoic acid as reported in one study (RR 0.10, 95% CI 0.02 to 0.41). The evidence to support an associated reduction in the risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect in the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention.The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials.We found no evidence of an effect between a single versus binocular patch or ambulation versus complete bed rest on the risk of secondary hemorrhage or time to rebleed. AUTHORS' CONCLUSIONS: We found no evidence of an effect on visual acuity by any of the interventions evaluated in this review. Although evidence was limited, it appears that people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema took longer clear in people treated with systemic aminocaproic acid.There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision. OBJECTIVES: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 µm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes. AUTHORS' CONCLUSIONS: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

Cyclodestructive procedures for non-refractory glaucoma.

BACKGROUND: Glaucoma is a leading cause of blindness worldwide. It results in a progressive loss of peripheral vision and, in late stages, loss of central vision leading to blindness. Early treatment of glaucoma aims to prevent or delay vision loss. Elevated intraocular pressure (IOP) is the main causal modifiable risk factor for glaucoma. Aqueous outflow obstruction is the main cause of IOP elevation, which can be mitigated either by increasing outflow or reducing aqueous humor production. Cyclodestructive procedures use various methods to target and destroy the ciliary body epithelium, the site of aqueous humor production, thereby lowering IOP. The most common approach is laser cyclophotocoagulation. OBJECTIVES: To assess the effectiveness and safety of cyclodestructive procedures for the management of non-refractory glaucoma (i.e. glaucoma in an eye that has not undergone incisional glaucoma surgery). We also aimed to compare the effect of different routes of administration, laser delivery instruments, and parameters of cyclophotocoagulation with respect to IOP control, visual acuity, pain control, and adverse events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 8); Ovid MEDLINE; Embase.com; LILACS; the metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov. The date of the search was 7 August 2017. We also searched the reference lists of reports from included studies. SELECTION CRITERIA: We included randomized controlled trials of participants who had undergone cyclodestruction as a primary treatment for glaucoma. We included only head-to-head trials that had compared cyclophotocoagulation to other procedural interventions, or compared cyclophotocoagulation using different types of lasers, delivery methods, parameters, or a combination of these factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, assessed risks of bias, extracted data, and graded the certainty of the evidence in accordance with Cochrane standards. MAIN RESULTS: We included one trial (92 eyes of 92 participants) that evaluated the efficacy of diode transscleral cyclophotocoagulation (TSCPC) as primary surgical therapy. We identified no other eligible ongoing or completed trial. The included trial compared low-energy versus high-energy TSCPC in eyes with primary open-angle glaucoma. The trial was conducted in Ghana and had a mean follow-up period of 13.2 months post-treatment. In this trial, low-energy TSCPC was defined as 45.0 J delivered, high-energy as 65.5 J delivered; it is worth noting that other trials have defined high- and low-energy TSCPC differently. We assessed this trial to have had low risk of selection bias and reporting bias, unclear risk of performance bias, and high risk of detection bias and attrition bias. Trial authors excluded 13 participants with missing follow-up data; the analyses therefore included 40 (85%) of 47 participants in the low-energy group and 39 (87%) of 45 participants in the high-energy group.Control of IOP, defined as a decrease in IOP by 20% from baseline value, was achieved in 47% of eyes, at similar rates in the low-energy group and the high-energy groups; the small study size creates uncertainty about the significance of the difference, if any, between energy settings (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.64 to 1.65; 79 participants; low-certainty evidence). The difference in effect between energy settings based on mean decrease in IOP, if any exists, also was uncertain (mean difference (MD) -0.50 mmHg, 95% CI -5.79 to 4.79; 79 participants; low-certainty evidence).Decreased vision was defined as the proportion of participants with a decrease of 2 or more lines on the Snellen chart or one or more categories of visual acuity when unable to read the eye chart. Twenty-three percent of eyes had a decrease in vision. The size of any difference between the low-energy group and the high-energy group was uncertain (RR 1.22, 95% CI 0.54 to 2.76; 79 participants; low-certainty evidence). Data were not available for mean visual acuity and proportion of participants with vision change defined as greater than 1 line on the Snellen chart.The difference in the mean number of glaucoma medications used after cyclophotocoagulation was similar when comparing treatment groups (MD 0.10, 95% CI -0.43 to 0.63; 79 participants; moderate-certainty evidence). Twenty percent of eyes were retreated; the estimated effect of energy settings on the need for retreatment was inconclusive (RR 0.76, 95% CI 0.31 to 1.84; 79 participants; low-certainty evidence). No data for visual field, cost effectiveness, or quality-of-life outcomes were reported by the trial investigators.Adverse events were reported for the total study population, rather than by treatment group. The trial authors stated that most participants reported mild to moderate pain after the procedure, and many had transient conjunctival burns (percentages not reported). Severe iritis occurred in two eyes and hyphema occurred in three eyes. No instances of hypotony or phthisis bulbi were reported. The only adverse outcome that was reported by the treatment group was atonic pupil (RR 0.89 in the low-energy group, 95% CI 0.47 to 1.68; 92 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to evaluate the relative effectiveness and safety of cyclodestructive procedures for the primary procedural management of non-refractory glaucoma. Results from the one included trial did not compare cyclophotocoagulation to other procedural interventions and yielded uncertainty about any difference in outcomes when comparing low-energy versus high-energy diode TSCPC. Overall, the effect of laser treatment on IOP control was modest and the number of eyes experiencing vision loss was limited. More research is needed specific to the management of non-refractory glaucoma.

Neuroprotection for treatment of glaucoma in adults.

BACKGROUND: Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. OBJECTIVES: The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (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 on 16 August 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until study investigators provide additional study details. We documented reasons for excluding studies from the review. MAIN RESULTS: We included one multicenter RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was progression of visual field loss after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, the investigators excluded 12 (6.3%) after randomization; 77 participants (40.5%) did not complete four years of follow-up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%).Of those remaining in the study at four years, participants assigned to brimonidine showed less progression of visual field loss than participants assigned to timolol (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.14 to 0.86; 101 participants). Because of high risk of attrition bias and potential selective outcome reporting, we graded the certainty of evidence for this outcome as very low. At the four-year follow-up, the mean IOP was similar in both groups among those for whom data were available (mean difference 0.20 mmHg, 95% CI -0.73 to 1.13; 91 participants; very low-certainty evidence). The study authors did not report analyzable data for visual acuity or any data related to vertical cup-disc ratio, quality of life, or economic outcomes. The most frequent adverse event was ocular allergy to the study drug, which affected more participants in the brimonidine group than the timolol group (RR 5.32, 95% CI 1.64 to 17.26; 178 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Although the only trial we included in this review found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that we can draw no conclusions from this finding. Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG. Such research should focus on outcomes important to patients, such as preservation of vision, and how these outcomes relate to cell death and optic nerve damage. As OAG is a chronic, progressive disease with variability in symptoms, RCTs designed to measure the effectiveness of neuroprotective agents require a long-term follow-up of five years or longer to detect clinically meaningful effects.

Non-surgical interventions for acute internal hordeolum.

BACKGROUND: A hordeolum is a common, painful inflammation of the eyelid margin that is usually caused by a bacterial infection. The infection affects oil glands of the eyelid and can be either internal or external. In many cases, the lesion drains spontaneously and resolves without treatment; however, the inflammation can spread to other ocular glands or tissues, and recurrences are common. If unresolved, an acute internal hordeolum can become chronic, or can develop into a chalazion. External hordeola, also known as styes, were not included in the scope of this review. OBJECTIVES: The objective of this review was to investigate the effectiveness, and when possible, the safety, of non-surgical treatments for acute internal hordeola compared with observation or placebo. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 12)), MEDLINE Ovid, MEDLINE Ovid Epub Ahead of Print, MEDLINE Ovid In-Process & Other Non-Indexed Citations, MEDLINE(R) Ovid Daily (January 1946 to December 2016), Embase (January 1947 to December 2016), PubMed (1948 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the metaRegister of Controlled Trials (mRCT; www.controlled-trials.com (last searched 26 July 2012)), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 December 2016. SELECTION CRITERIA: The selection criteria for this review included randomized or quasi-randomized clinical trials of participants diagnosed with an acute internal hordeolum. Studies of participants with external hordeola (styes), chronic hordeola, or chalazia were excluded. Non-surgical interventions of interest included the use of hot or warm compresses, lid scrubs, antibiotics, or steroids compared with observation, placebo, or other active interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the references identified by electronic searches for inclusion in this review. No relevant studies were found. The reasons for exclusion were documented. MAIN RESULTS: No trials were identified for this review. Most of the references identified through our search reported on external hordeola or chronic internal hordeola. The few references specific to acute internal hordeola reported recommendations for treatment, were reports of interventional case series, case studies, or other types of observational study designs, and were published more than 20 years ago. AUTHORS' CONCLUSIONS: We did not find any evidence for or against the effectiveness of non-surgical interventions for the treatment of an internal hordeolum. Controlled clinical trials would be useful to determine which interventions are effective for the treatment of acute internal hordeola.

Surgery for cataracts in people with age-related macular degeneration.

BACKGROUND: Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract surgery is an effective treatment for cataract-induced visual loss, some clinicians suspect that such an intervention may increase the risk of worsening of underlying AMD and thus have deleterious effects on vision. OBJECTIVES: The objective of this review was to evaluate the effectiveness and safety of cataract surgery compared with no surgery in eyes with AMD. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (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 on 2 December 2016. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized trials that enrolled participants whose eyes were affected by both cataract and AMD in which cataract surgery was compared with no surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated the search results against the inclusion and exclusion criteria. Two review authors independently extracted data, assessed risk of bias for included studies, and graded the certainty of evidence. We followed methods as recommended by Cochrane. MAIN RESULTS: We included two RCTs with a total of 114 participants (114 study eyes) with visually significant cataract and AMD. We identified no ongoing trials. Participants in each RCT were randomized to immediate cataract surgery (within two weeks of enrollment) or delayed cataract surgery (six months after enrollment). The risk of bias was unclear for most domains in each study; one study was registered prospectively.In one study conducted in Australia outcomes were reported only at six months (before participants in the delayed-surgery group had cataract surgery). At six months, the immediate-surgery group showed mean improvement in best-corrected visual acuity (BCVA) compared with the delayed-surgery group (mean difference (MD) -0.15 LogMAR, 95% confidence interval (CI) -0.28 to -0.02; 56 participants; moderate-certainty evidence). In the other study, conducted in Austria, outcomes were reported only at 12 months (12 months after participants in the immediate-surgery group and six months after participants in the delayed-surgery group had cataract surgery). There was uncertainty as to which treatment group had better improvement in distance visual acuity at 12 months (unit of measure not reported; very low-certainty evidence).At 12 months, the mean change from baseline between groups in cumulated drusen or geographic atrophy area size was small and there was uncertainty which, if either, of the groups was favored (MD 0.76, 95% CI -8.49 to 10.00; 49 participants; low-certainty evidence). No participant in one study had exudative AMD develop in the study eye during 12 months of follow-up; in the other study, choroidal neovascularization developed in the study eye of 1 of 27 participants in the immediate-surgery group versus 0 of 29 participants in the delayed-surgery group at six months (risk ratio 3.21, 95% CI 0.14 to 75.68; 56 participants; very low-certainty evidence). Quality of life was measured using two different questionnaires. Scores on the Impact of Vision Impairment (IVI) questionnaire suggested that the immediate-surgery group fared better regarding vision-related quality of life than the delayed-surgery group at six months (MD in IVI logit scores 1.60, 95% CI 0.61 to 2.59; low-certainty evidence). However, we could not analyze scores from the Visual Function-14 (VF-14) questionnaire from the other study due to insufficient data. No postoperative complication was reported from either study. AUTHORS' CONCLUSIONS: At this time, it is not possible to draw reliable conclusions from the available data as to whether cataract surgery is beneficial or harmful in people with AMD after 12 months. Although cataract surgery provides short-term (six months) improvement in BCVA in eyes with AMD compared with no surgery, it is unclear whether the timing of surgery has an effect on long-term outcomes. Physicians must make recommendations to their AMD patients regarding cataract surgery based on experience and clinical judgment until large controlled trials are conducted and their findings published.There is a need for prospective RCTs in which cataract surgery is compared with no surgery in people with AMD to better evaluate whether cataract surgery is beneficial or harmful in all or a subset of AMD patients. However, ethical considerations preclude withholding surgery, or delaying it for several years, if it may be a potentially beneficial treatment. Designers of future trials are encouraged to utilize existing standardized systems for grading cataract and AMD and for measuring key outcomes: visual acuity, change in visual acuity, worsening of AMD, quality of life measures, and adverse events.

Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery.

BACKGROUND: Endophthalmitis is a severe inflammation of the anterior or posterior (or both) chambers of the eye that may be sterile or associated with infection. It is a potentially vision-threatening complication of cataract surgery. Prophylactic measures for endophthalmitis are targeted against various sources of infection. OBJECTIVES: To evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery compared with no prophylaxis or other form of prophylaxis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to December 2016),the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 6 December 2016. We also searched for additional studies that cited any included trials using the Science Citation Index. SELECTION CRITERIA: We included randomized controlled trials that enrolled adults undergoing cataract surgery (any method and incision type) for lens opacities due to any origin. We included trials that evaluated preoperative antibiotics, intraoperative (intracameral, subconjunctival or systemic), or postoperative antibiotic prophylaxis for acute endophthalmitis. We excluded studies that evaluated antiseptic preoperative preparations using agents such as povidone iodine or antibiotics for treating acute endophthalmitis after cataract surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and full-text articles for eligibility, assessed the risk of bias for each included study, and abstracted data. MAIN RESULTS: Five studies met the inclusion criteria for this review, including 101,005 adults and 132 endophthalmitis cases. While the sample size was very large, the heterogeneity of the study designs and modes of antibiotic delivery made it impossible to conduct a formal meta-analysis. Interventions investigated included the utility of adding vancomycin and gentamycin to the irrigating solution compared with standard balanced saline solution irrigation alone, use of intracameral cefuroxime with or without topical levofloxacin perioperatively, periocular penicillin injections and topical chloramphenicol-sulfadimidine drops compared with topical antibiotics alone, and mode of antibiotic delivery (subconjunctival versus retrobulbar injections; fixed versus separate instillation of gatifloxacin and prednisolone). The risk of bias among studies was low to unclear due to information not being reported. We identified one ongoing study.Two studies compared any antibiotic with no antibiotic. One study, which compared irrigation with antibiotics in balanced salt solution (BSS) versus BSS alone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). One study found reduced risk of endophthalmitis when combining intracameral cefuroxime and topical levofloxacin (risk ratio (RR) 0.14, 95% confidence interval (CI) 0.03 to 0.63; 8106 participants; high-certainty evidence) or using intracameral cefuroxime alone (RR 0.21, CI 0.06 to 0.74; 8110 participants; high-certainty evidence) compared with placebo, and an uncertain effect when using topical levofloxacin alone compared with placebo (RR 0.72, CI 0.32 to 1.61; 8103 participants; moderate-certainty evidence).Two studies found reduced risk of endophthalmitis when combining antibiotic injections during surgery and topical antibiotics compared with topical antibiotics alone (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.12 to 0.92 (periocular penicillin and topical chloramphenicol-sulfadimidine; 6618 participants; moderate-certainty evidence); and RR 0.20, 95% CI 0.04 to 0.91 (intracameral cefuroxime and topical levofloxacin; 8101 participants; high-certainty evidence)).One study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). Another study found no evidence of a difference in endophthalmitis when comparing subconjunctival versus retrobulbar antibiotic injections (RR 0.85, 95% CI 0.55 to 1.32; 77,015 participants; moderate-certainty evidence).Two studies reported any visual acuity outcome; one study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, reported only that mean visual acuity was the same for both groups at 20 days postoperation. In the other study, the difference in the proportion of eyes with final visual acuity greater than 20/40 following endophthalmitis between groups receiving intracameral cefuroxime with or without topical levofloxacin compared with no intracameral cefuroxime was uncertain (RR 0.69, 95% CI 0.22 to 2.11; 29 participants; moderate-certainty evidence).Only one study reported adverse events (1 of 129 eyes had pupillary membrane in front of the intraocular lens and 8 eyes showed posterior capsule opacity). No study reported outcomes related to quality of life or economic outcomes. AUTHORS' CONCLUSIONS: Multiple measures for preventing endophthalmitis following cataract surgery have been studied. High-certainty evidence shows that injection with cefuroxime with or without topical levofloxacin lowers the chance of endophthalmitis after surgery, and there is moderate-certainty evidence to suggest that using antibiotic eye drops in addition to antibiotic injection probably lowers the chance of endophthalmitis compared with using injections or eye drops alone. Clinical trials with rare outcomes require very large sample sizes and are quite costly to conduct; thus, it is unlikely that many additional clinical trials will be conducted to evaluate currently available prophylaxis. Practitioners should rely on current evidence to make informed decisions regarding prophylaxis choices.

Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews?

PURPOSE: Are existing systematic reviews of interventions for age-related macular degeneration incorporated into clinical practice guidelines? DESIGN: High-quality systematic reviews should be used to underpin evidence-based clinical practice guidelines and clinical care. We examined the reliability of systematic reviews of interventions for age-related macular degeneration (AMD) and described the main findings of reliable reviews in relation to clinical practice guidelines. METHODS: Eligible publications were systematic reviews of the effectiveness of treatment interventions for AMD. We searched a database of systematic reviews in eyes and vision without language or date restrictions; the database was up to date as of May 6, 2014. Two authors independently screened records for eligibility and abstracted and assessed the characteristics and methods of each review. We classified reviews as reliable when they reported eligibility criteria, comprehensive searches, methodologic quality of included studies, appropriate statistical methods for meta-analysis, and conclusions based on results. We mapped treatment recommendations from the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for AMD to systematic reviews and citations of reliable systematic reviews to support each treatment recommendation. RESULTS: Of 1570 systematic reviews in our database, 47 met inclusion criteria; most targeted neovascular AMD and investigated anti-vascular endothelial growth factor (VEGF) interventions, dietary supplements, or photodynamic therapy. We classified 33 (70%) reviews as reliable. The quality of reporting varied, with criteria for reliable reporting met more often by Cochrane reviews and reviews whose authors disclosed conflicts of interest. Anti-VEGF agents and photodynamic therapy were the only interventions identified as effective by reliable reviews. Of 35 treatment recommendations extracted from the PPPs, 15 could have been supported with reliable systematic reviews; however, only 1 recommendation cited a reliable intervention systematic review. No reliable systematic review was identified for 20 treatment recommendations, highlighting areas of evidence gaps. CONCLUSIONS: For AMD, reliable systematic reviews exist for many treatment recommendations in the AAO PPPs and should be cited to support these recommendations. We also identified areas where no high-level evidence exists. Mapping clinical practice guidelines to existing systematic reviews is one way to highlight areas where evidence generation or evidence synthesis is either available or needed.

Comparative Effectiveness of First-Line Medications for Primary Open-Angle Glaucoma: A Systematic Review and Network Meta-analysis.

TOPIC: Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first-line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. CLINICAL RELEVANCE: Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. METHODS: We included randomized controlled trials (RCTs) that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. RESULTS: We included 114 RCTs with data from 20 275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67). CONCLUSIONS: All active first-line drugs are effective compared with placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost, should be considered in selecting a drug for a given patient.