3,549 research outputs found

    In Synch but Not in Step: Circadian Clock Circuits Regulating Plasticity in Daily Rhythms

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    The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one another to produce emergent properties of the network. Here we review the current understanding of communication among SCN clock cells and highlight a collection of formal assays where changes in SCN interactions provide for plasticity in the waveform of circadian rhythms in behavior. Future studies that pair analytical behavioral assays with modern neuroscience techniques have the potential to provide deeper insight into SCN circuit mechanisms

    Hospital admissions in older people with visual impairment in Britain.

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    BACKGROUND: We aimed to assess the risk of hospital admission associated with visual impairment in a representative sample of older people living in the community in Britain. METHODS: DESIGN: Prospective study of hospital admission in a population-based sample of community dwelling people aged 75 years and above in Britain. SETTING: 53 general practices. PARTICIPANTS: 14,394 participants in the MRC Trial of Assessment and Management of Older people in the Community. MAIN OUTCOME MEASURE: Hospital admission. RESULTS: Visually impaired older people had 238.7 admissions/1000 person-years compared to 169.7 admissions/1000 person-years in people with good vision: age and sex adjusted rate ratio (RR) 1.32 (95% CI 1.19 to 1.47). Adjusting for a wide range of potential explanatory factors largely eliminated this association: RR 1.06 (95% CI 0.94 to 1.20). However, adjusting for a more limited range of confounding factors, excluding those factors possibly a consequence of reduced vision, left a modest increased risk: RR 1.19 (95% CI 1.06 to 1.34). CONCLUSION: The association between visual impairment and rate of hospital admission can be attributed to higher levels of co-morbidity and reduced functional ability among people with reduced vision. Visual impairment is likely to be an important contributor to reduced functional ability, but other factors may also be involved

    Ivermectin for onchocercal eye disease (river blindness).

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    BACKGROUND: It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear. OBJECTIVES: The aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary aim was to assess the effects of ivermectin on lesions affecting the eye in onchocerciasis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to April 2012), EMBASE (January 1980 to April 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 April 2012. SELECTION CRITERIA: We included randomised controlled trials with at least one year of follow-up comparing ivermectin with placebo or no treatment. Participants in the trials were people normally resident in endemic onchocercal communities with or without one or more characteristic signs of ocular onchocerciasis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. As trials varied in design and setting, we were unable to perform a meta-analysis. MAIN RESULTS: The review included four trials: two small studies (n = 398) in which people with onchocercal infection were given one dose of ivermectin or placebo and followed up for one year; and two larger community-based studies (n = 4941) whereby all individuals in selected communities were treated every six or 12 months with ivermectin or placebo, whether or not they were infected, and followed for two to three years. The studies provide evidence that treating people who have onchocerciasis with ivermectin reduces the number of microfilariae in their skin and eye(s) and reduces the number of punctate opacities. There was weaker evidence that ivermectin reduced the risk of chorioretinitis. The studies were too small and of too short a duration to provide evidence for an effect on sclerosing keratitis, iridocyclitis, optic nerve disease or visual loss. One community-based study in communities mesoendemic for the savannah strain of O.volvulus provided evidence that annual mass treatment with ivermectin reduces the risk of new cases of optic nerve disease and visual field loss. The other community-based study of mass biannual treatment of ivermectin in communities affected by the forest strain of O.volvulus demonstrated reductions in microfilarial load, punctate keratitis and iridocyclitis but not sclerosing keratitis, chorioretinitis, optic atrophy or visual impairment. The study was underpowered to estimate the effect of ivermectin on visual impairment and other less frequent clinical signs. The studies included in this review reported some adverse effects, in particular an increased risk of postural hypotension in people treated with ivermectin. AUTHORS' CONCLUSIONS: The lack of evidence for prevention of visual impairment and blindness should not be interpreted to mean that ivermectin is not effective, however, clearly this is a key question that remains unanswered. The main evidence for a protective effect of mass treatment with ivermectin on visual field loss and optic nerve disease comes from communities mesoendemic for the savannah strain of O.volvulus. Whether these findings can be applied to communities with different endemicity and affected by the forest strain is unclear. Serious adverse effects were rarely reported. None of the studies, however, were conducted in areas where people are infected with Loa loa (loiasis)

    Antibiotics for trachoma.

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    BACKGROUND: Trachoma is the world's leading infectious cause of blindness. In 1997 the World Health Organization (WHO) launched an Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective) and on Chlamydia trachomatis (C. trachomatis) infection of the conjunctiva (secondary objective). SEARCH STRATEGY: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 11), MEDLINE (January 1950 to December 2010), EMBASE (January 1980 to December 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (December 2010) and ClinicalTrials.gov (www.clinicaltrials.gov) (December 2010). We used the Science Citation Index to look for articles that cited the included studies. We searched the reference lists of identified articles and we contacted authors and experts for details of further relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 12 December 2010. SELECTION CRITERIA: We included randomised trials that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. A subdivision of particular interest was trials in which topical tetracycline or chlortetracycline and oral azithromycin were compared with each other, or in which one of these treatments was compared with placebo or no treatment, as these are the two WHO recommended antibiotics. We considered individually randomised and cluster-randomised trials separately. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted investigators for missing data. Where appropriate, the effect estimates from the individual studies (risk ratios) were pooled using a random-effects model. MAIN RESULTS: A total of 14 trials randomised individuals with trachoma to oral antibiotic, topical antibiotic, both, or control (no treatment or placebo) and were eligible for inclusion in this review (n = 3587). Overall, the quality of the evidence provided from these trials was low. Nine of the trials compared antibiotic treatment to control. Most of the studies found a beneficial effect of treatment on active trachoma and ocular chlamydial infection at three and 12 months follow up. There was considerable clinical and statistical heterogeneity between trials, which meant that it was difficult to reliably estimate the size of the treatment effect. It is likely to be in the region of a 20% relative risk reduction. Seven of the 14 trials compared the effectiveness of oral and topical antibiotics. There was no consistent evidence as to whether oral or topical antibiotics were more effective, although one trial suggested that a single dose of oral azithromycin was significantly more effective than unsupervised use of topical tetracyclineA further eight trials assessed the effectiveness of community-based treatment. In five trials antibiotic treatment was compared to no (or delayed) treatment (57 communities), and in three trials oral antibiotic was compared to topical treatment (12 communities). The quality of the evidence provided by these trials was variable but at least one trial was considered to provide high quality evidence. There was evidence that community-based antibiotic treatment reduced the prevalence of active trachoma and ocular infection 12 months after single-dose treatment. There was some evidence that oral azithromycin was more effective than topical tetracycline as a community treatment. Data on adverse effects were not consistently reported however there were no reported serious adverse events associated with treatment with oral azithromycin or topical tetracycline; in one sample survey of 671 people treated with azithromycin between 10% and 15% experienced gastrointestinal adverse effects (nausea or vomiting, or both). AUTHORS' CONCLUSIONS: Antibiotic treatment reduces the risk of active trachoma and ocular chlamydial infection in people infected with C. trachomatis, but we do not know for certain the size of the treatment effect in individuals. Mass antibiotic treatment with single-dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities

    Medical interventions for fungal keratitis.

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    BACKGROUND: Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear. OBJECTIVES: To assess the effects of different antifungal drugs in the management of fungal keratitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), 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 March 2015. SELECTION CRITERIA: We included randomised controlled trials of medical therapy for fungal keratitis. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion in the review, assessed trials for risk of bias and extracted data. The primary outcome was clinical cure at two to three months. Secondary outcomes included best-corrected visual acuity, time to clinical cure, compliance with treatment, adverse outcomes and quality of life. MAIN RESULTS: We included 12 trials in this review; 10 trials were conducted in India, one in Bangladesh and one in Egypt. Seven of these trials were at high risk of bias in one or more domains, two of these studies were at low risk of bias in all domains. Participants were randomised to the following comparisons: topical 5% natamycin compared to topical 1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical 5% natamycin compared to topical chlorhexidine gluconate (0.05%, 0.1% and 0.2%); topical 1% voriconazole compared to intrastromal voriconazole 50 g/0.1 mL (both treatments combined with topical 5% natamycin); topical 1% voriconazole combined with oral voriconazole compared to both oral voriconazole and oral itraconazole (both combined with topical 5% natamycin); topical 1% itraconazole compared to topical 1% itraconazole combined with oral itraconazole; topical amphotericin B compared to topical amphotericin B combined with subconjunctival injection of fluconazole; intracameral injection of amphotericin B with conventional treatment compared to conventional treatment alone (severe fungal ulcers); topical 0.5% and 1% silver sulphadiazine compared to topical 1% miconazole. Overall the results were inconclusive because for most comparisons only one small trial was available. The exception was the comparison of topical natamycin and topical voriconazole for which three trials were available. In one of these trials clinical cure (healed ulcer) was reported in all 15 people allocated to natamycin and in 14/15 people allocated to voriconazole (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.89 to 1.28, low quality evidence). In one trial people randomised to natamycin were more likely to have a microbiological cure at six days (RR 1.64; 95% CI 1.38 to 1.94, 299 participants). On average, people randomised to natamycin had better spectacle-corrected visual acuity at two to three months compared to people randomised to voriconazole but the estimate was uncertain and the 95% confidence intervals included 0 (no difference) (mean difference -0.12 logMAR, 95% CI -0.31 to 0.06, 434 participants; 3 studies, low quality evidence) and a decreased risk of corneal perforation or therapeutic penetrating keratoplasty, or both (RR 0.61; 95% CI 0.40 to 0.94, 434 participants, high quality evidence). There was inconclusive evidence on time to clinical cure. Compliance with treatment and quality of life were not reported. One trial comparing natamycin and voriconazole found the effect of treatment greater in Fusarium species, but this subgroup analysis was not prespecified by this review. AUTHORS' CONCLUSIONS: The trials included in this review were of variable quality and were generally underpowered. There is evidence that natamycin is more effective than voriconazole in the treatment of fungal ulcers. Future research should evaluate treatment effects according to fungus species

    Reducing inequity of cataract blindness and vision impairment is a global priority, but where is the evidence?

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    Throughout the world, people who are socially or economically disadvantaged disproportionately experience blindness and vision impairment caused by cataract. Reducing vision loss from cataract and its unequal distribution must be a priority if the WHO's aim of 'universal eye health' is to be realised. To help achieve this, decision-makers and service planners need evidence on which strategies improve access to cataract services among disadvantaged populations, and under what circumstances. Unfortunately, despite many strategies to improve cataract services being implemented in recent decades, evidence of what works, for who and in what circumstances is not readily available. This paper summarises the extent of the evidence on interventions to reduce inequity of vision loss from cataract and makes suggestions for how the evidence base can be strengthened

    Manual small incision cataract surgery (MSICS) with posterior chamber intraocular lens versus extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens for age-related cataract.

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    BACKGROUND: Age-related cataract is the opacification of the lens, which occurs as a result of denaturation of lens proteins. Age-related cataract remains the leading cause of blindness globally, except in the most developed countries. A key question is what is the best way of removing the lens, especially in lower income settings. OBJECTIVES: To compare two different techniques of lens removal in cataract surgery: manual small incision surgery (MSICS) and extracapsular cataract extraction (ECCE). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to September 2014), EMBASE (January 1980 to September 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2014), Web of Science Conference Proceedings Citation Index- Science (CPCI-S), (January 1990 to September 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), 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 23 September 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) only. Participants in the trials were people with age-related cataract. We included trials where MSICS with a posterior chamber intraocular lens (IOL) implant was compared to ECCE with a posterior chamber IOL implant. DATA COLLECTION AND ANALYSIS: Data were collected independently by two authors. We aimed to collect data on presenting visual acuity 6/12 or better and best-corrected visual acuity of less than 6/60 at three months and one year after surgery. Other outcomes included intraoperative complications, long-term complications (one year or more after surgery), quality of life, and cost-effectiveness. There were not enough data available from the included trials to perform a meta-analysis. MAIN RESULTS: Three trials randomly allocating people with age-related cataract to MSICS or ECCE were included in this review (n = 953 participants). Two trials were conducted in India and one in Nepal. Trial methods, such as random allocation and allocation concealment, were not clearly described; in only one trial was an effort made to mask outcome assessors. The three studies reported follow-up six to eight weeks after surgery. In two studies, more participants in the MSICS groups achieved unaided visual acuity of 6/12 or 6/18 or better compared to the ECCE group, but overall not more than 50% of people achieved good functional vision in the two studies. 10/806 (1.2%) of people enrolled in two trials had a poor outcome after surgery (best-corrected vision less than 6/60) with no evidence of difference in risk between the two techniques (risk ratio (RR) 1.58, 95% confidence interval (CI) 0.45 to 5.55). Surgically induced astigmatism was more common with the ECCE procedure than MSICS in the two trials that reported this outcome. In one study there were more intra- and postoperative complications in the MSICS group. One study reported that the costs of the two procedures were similar. AUTHORS' CONCLUSIONS: There are no other studies from other countries other than India and Nepal and there are insufficient data on cost-effectiveness of each procedure. Better evidence is needed before any change may be implemented. Future studies need to have longer-term follow-up and be conducted to minimize biases revealed in this review with a larger sample size to allow examination of adverse events

    Multifocal versus monofocal intraocular lenses after cataract extraction.

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    BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. METHODS: SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register), The Cochrane Library 2012, Issue 2, MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio, RR for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval, CI 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses

    Accommodative intraocular lens versus standard monofocal intraocular lens implantation in cataract surgery.

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    BACKGROUND: Following cataract surgery and intraocular lens (IOL) implantation, loss of accommodation or postoperative presbyopia occurs and remains a challenge. Standard monofocal IOLs correct only distance vision; patients require spectacles for near vision. Accommodative IOLs have been designed to overcome loss of accommodation after cataract surgery. OBJECTIVES: To define (a) the extent to which accommodative IOLs improve unaided near visual function, in comparison with monofocal IOLs; (b) the extent of compromise to unaided distance visual acuity; c) whether a higher rate of additional complications is associated the use of accommodative IOLs. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 October 2013. SELECTION CRITERIA: We include randomised controlled trials (RCTs) which compared implantation of accommodative IOLs to implantation of monofocal IOLs in cataract surgery. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, assessed risk of bias and extracted data. All included trials used the 1CU accommodative IOL (HumanOptics, Erlangen, Germany) for their intervention group. One trial had an additional arm with the AT-45 Crystalens accommodative IOL (Eyeonics Vision). We performed a separate analysis comparing 1CU and AT-45 IOL. MAIN RESULTS: We included four RCTs, including 229 participants (256 eyes), conducted in Germany, Italy and the UK. The age range of participants was 21 to 87 years. All studies included people who had bilateral cataracts with no pre-existing ocular pathologies. We judged all studies to be at high risk of performance bias. We graded two studies with high risk of detection bias and one study with high risk of selection bias.Participants who received the accommodative IOLs achieved better distance-corrected near visual acuity (DCNVA) at six months (mean difference (MD) -3.10 Jaeger units; 95% confidence intervals (CI) -3.36 to -2.83, 2 studies, 106 people, 136 eyes, moderate quality evidence). Better DCNVA was seen in the accommodative lens group at 12 to 18 months in the three trials that reported this time point but considerable heterogeneity of effect was seen, ranging from 1.3 (95% CI 0.98 to 1.68; 20 people, 40 eyes) to 6 (95% CI 4.15 to 7.85; 51 people, 51 eyes) Jaeger units and 0.12 (95% CI 0.05 to 0.19; 40 people, binocular) logMAR improvement (low quality evidence). The relative effect of the lenses on corrected distant visual acuity (CDVA) was less certain. At six months there was a standardised mean difference of -0.04 standard deviations (95% CI -0.37 to 0.30, 2 studies, 106 people, 136 eyes, low quality evidence). At long-term follow-up there was heterogeneity of effect with 18-month data in two studies showing that CDVA was better in the monofocal group (MD 0.12 logMAR; 95% CI 0.07 to 0.16, 2 studies, 70 people,100 eyes) and one study which reported data at 12 months finding similar CDVA in the two groups (-0.02 logMAR units, 95% CI -0.06 to 0.02, 51 people) (low quality evidence).The relative effect of the lenses on reading speed and spectacle independence was uncertain, The average reading speed was 11.6 words per minute more in the accommodative lens group but the 95% confidence intervals ranged from 12.2 words less to 35.4 words more (1 study, 40 people, low quality evidence). People with accommodative lenses were more likely to be spectacle-independent but the estimate was very uncertain (risk ratio (RR) 8.18; 95% CI 0.47 to 142.62, 1 study, 40 people, very low quality evidence).More cases of posterior capsule opacification (PCO) were seen in accommodative lenses but the effect of the lenses on PCO was uncertain (Peto odds ratio (OR) 2.12; 95% CI 0.45 to 10.02, 91 people, 2 studies, low quality evidence). People in the accommodative lens group were more likely to require laser capsulotomy (Peto OR 7.96; 95% CI 2.49 to 25.45, 2 studies, 60 people, 80 eyes, low quality evidence). Glare was reported less frequently with accommodative lenses but the relative effect of the lenses on glare was uncertain (RR any glare 0.78; 95% CI 0.32 to 1.90, 1 study, 40 people, and RR moderate/severe glare 0.45; 95% CI 0.04 to 4.60, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate-quality evidence that study participants who received accommodative IOLs had a small gain in near visual acuity after six months. There is some evidence that distance visual acuity with accommodative lenses may be worse after 12 months but due to low quality of evidence and heterogeneity of effect, the evidence for this is not clear-cut. People receiving accommodative lenses had more PCO which may be associated with poorer distance vision. However, the effect of the lenses on PCO was uncertain.Further research is required to improve the understanding of how accommodative IOLs may affect near visual function, and whether they provide any durable gains. Additional trials, with longer follow-up, comparing different accommodative IOLs, multifocal IOLs and monofocal IOLs, would help map out their relative efficacy, and associated late complications. Research is needed on control over capsular fibrosis postimplantation.Risks of bias, heterogeneity of outcome measures and study designs used, and the dominance of one design of accommodative lens in existing trials (the HumanOptics 1CU) mean that these results should be interpreted with caution. They may not be applicable to other accommodative IOL designs

    Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty.

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    BACKGROUND: Penetrating keratoplasty is a corneal transplantation procedure in which a full-thickness cornea from the host is replaced by a graft from a donor. The use of various immunosuppressants to prevent graft rejection, the most common cause of graft failure in the late postoperative period, is increasing. OBJECTIVES: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high- and normal-risk keratoplasty. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2015), EMBASE (January 1980 to May 2015), China National Knowledge Infrastructure (CNKI) (January 1913 to February 2015), VIP database (January 1989 to February 2015), Wanfang Data (www.wanfangdata.com) (January 1990 to February 2015), 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 English language databases on 18 May 2015 and the Chinese language databases on 20 February 2015. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) assessing the use of immunosuppressants in the prevention of graft rejection, irrespective of publication language. DATA COLLECTION AND ANALYSIS: We used standard procedures expected by Cochrane. The primary outcome was clear graft survival at 12 months after penetrating keratoplasty. Secondary outcomes included graft rejection, best-corrected visual acuity, and quality of life. We defined 'high-risk keratoplasty' as repeat keratoplasty and other indications of reduced graft survival. MAIN RESULTS: We included six studies conducted in Germany (three studies), Iran, India, and China. Three studies were conducted in people undergoing high-risk keratoplasty and investigated three different comparisons: systemic mycophenolate mofetil (MMF) versus no MMF; systemic MMF versus systemic cyclosporine A (CsA); and topical CsA versus placebo. One study compared topical tacrolimus to topical steroid in people with normal-risk keratoplasty, and two studies compared topical CsA to placebo in people experiencing graft rejection after normal-risk keratoplasty. Overall, we considered the trials to be at unclear or high risk of bias.MMF may not improve clear graft survival (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.84 to 1.33, 1 RCT, 87 participants, low-quality evidence) but may reduce the risk of graft rejection (RR 0.49, 95% CI 0.22 to 1.08, 1 RCT, 87 participants, low-quality evidence) compared to no MMF. Visual acuity was not reported.In 1 study of 52 people comparing systemic MMF and systemic CsA, there were no graft failures in the first year of follow-up. Data from the longest follow-up (three years) suggest that there may be little difference in the effect of these two treatments on clear graft survival (RR 1.10, 95% CI 0.90 to 1.35, low-quality evidence). There was low-quality evidence of an increased risk of graft rejection with systemic MMF compared to systemic CsA, but with wide CIs compatible with increased risk with systemic CsA (RR 1.48, 95% CI 0.56 to 3.93, low-quality evidence). Visual acuity was not reported.One study of 84 people comparing topical CsA to placebo did not report clear graft survival at 1 year, which suggests that all grafts survived to 1 year. This study suggests that the use of topical CsA probably leads to little or no difference in graft rejection (RR 1.00, 95% CI 0.39 to 2.58, moderate-quality evidence). At one year, the mean difference (MD) between the two groups in visual acuity was 0.07 (95% CI -0.01 to 0.15, moderate-quality evidence).Topical CsA probably does not have an effect on clear graft survival in people experiencing graft rejection after normal-risk keratoplasty compared to placebo (RR 1.03, 95% CI 0.96 to 1.10, 2 RCTs, 283 participants, moderate-quality evidence). There were inconsistent findings on graft rejection, with one study reporting a reduced incidence of graft rejection in the CsA group (RR 0.35, 95% CI 0.14 to 0.87, 230 participants) but the other study reporting a higher average number of episodes of graft rejection in people treated with CsA (MD 1.30, 95% CI 0.39 to 2.21, 43 participants). Overall, we judged this to be low-quality evidence due to risk of bias and inconsistency. There was no evidence for a difference in visual acuity between the 2 groups at final follow-up (approximately 18 months, range 2 to 33 months) (MD 0.04, 95% CI -0.10 to 0.18, 1 RCT, 43 participants, low-quality evidence).In 1 study comparing topical tacrolimus to topical steroid, the graft survived in all of the 12 treated participants and 20 control participants at 6 months. Graft rejection was rare (0 out of 12 versus 2 out of 20) (RR 0.32, 95% CI 0.02 to 6.21, low-quality evidence). Visual acuity was not reported.None of the studies reported on quality of life. We identified an unpublished trial of basiliximab (Simulect) (NCT00409656), probably completed in 2005. AUTHORS' CONCLUSIONS: Current evidence on the effect of immunosuppressants in the prevention of graft failure and rejection after high- and normal-risk keratoplasty is largely low quality because the number of trials was limited, and, in general, the trials were small and at risk of bias. Future trials should be large enough to detect important clinical effects, conducted with a view to minimising the risk of bias, and they should measure outcomes important to patients
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