Randomised, single-masked non-inferiority trial of femtosecond laser-assisted versus manual phacoemulsification cataract surgery for adults with visually significant cataract: the FACT trial protocol.

INTRODUCTION: Cataract is one of the leading causes of low vision in the westernised world, and cataract surgery is one of the most commonly performed operations. Laser platforms for cataract surgery are now available, the anticipated advantages of which are broad and may include better visual outcomes through greater precision and reproducibility, and improved safety. FACT is a randomised single masked non-inferiority trial to establish whether laser-assisted cataract surgery is as good as or better than standard manual phacoemulsification. METHODS AND ANALYSIS: 808 patients aged 18 years and over with visually significant cataract will be randomised to manual phacoemulsification cataract surgery (standard care) or laser-assisted cataract surgery (intervention arm). Outcomes will be measured at 3 and 12 months after surgery. The primary clinical outcome is uncorrected distance visual acuity (UDVA, logMAR) at 3 months in the study eye recorded by an observer masked to the trial group. Secondary outcomes include UDVA at 12 months, corrected distance visual acuity at 3 and 12 months, complications, endothelial cell loss, patient-reported outcome measures and a health economic analysis conforming to National Institute for Health and Care Excellence standards. ETHICS AND DISSEMINATION: Research Ethics Committee Approval was obtained on 6 February 2015, ref: 14/LO/1937. Current protocol: v2.0 (08/04/2015). Study findings will be published in peer-reviewed journals. ISRCTN: 77602616.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Developing an algorithm to convert routine measures of vision into utility values for glaucoma.

PURPOSE: Measures of quality of life called utility values (UVs) are needed to deliver the most cost-effective health care for glaucoma patients. UVs are rarely measured in clinical research and practice whereas clinical outcomes such as visual field are routinely collected. The aim of this study was to develop an algorithm that calculates UVs directly from combinations of routine measures of binocular visual field, visual acuity, and contrast sensitivity. METHODS: A total of 132 outpatients with primary open angle glaucoma were recruited. The Time Trade-off (TTO) question was administered during face-to-face interviews. Binocular ETDRS logMAR visual acuity (VA(B)), binocular Pelli-Robson contrast sensitivity (CS(B)), and Humphrey 24-2 monocular visual field tests were performed on the same day. Integrated (binocular) visual field (IVF) scores were derived. Tobit regression analyses were used to model utility values based on combinations of IVF, VA(B), CS(B) and other controlling factors. RESULTS: UVs recorded for 123 cases correlated significantly with both clinical measures of binocular visual function (r = -0.47, IVF; r = -0.48, VA(B); r = 0.50, CS(B); P <0.0001) and measures of vision-specific quality of life (r = 0.54-0.6, P <0.0001). Two final models incorporate terms for IVF and VA(B), with or without living arrangements, and explain 22% and 31% of variation in utilities. CS(B) was not included in either model due to co-linearity between CS(B) and VA(B) confounding the models. CONCLUSION: The models provide preliminary algorithms for predicting the expected UVs for glaucoma populations directly from clinical outcomes collected routinely in clinical practice.

Glaucoma.

INTRODUCTION: Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure, but 40% of people with glaucoma have normal intraocular pressure and only 10% of people with raised intraocular pressure are at risk of optic-nerve damage. Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people than in white populations. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? What are the effects of treatment for acute angle-closure glaucoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: laser trabeculoplasty (alone or plus topical medical treatment), topical medical treatments, and surgical trabeculectomy.

Depression and anxiety in visually impaired older people.

PURPOSE: To investigate the association between visual impairment and depression and anxiety in older people in Britain. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Thirteen thousand nine hundred people aged 75 years and older in 49 family practices in Britain. METHODS: Vision was measured in 13 900 people aged 75 years and older in 49 family practices taking part in a randomized trial of health screening that included depression (Geriatric Depression Scale [GDS-15]) and anxiety (General Health Questionnaire [GHQ-28]). Cause of visual impairment (binocular acuity less than 6/18) was assessed from medical records. Analysis was by logistic regression (odds ratio [OR] and 95% confidence interval [CI]), taking account of potential health and social confounders. MAIN OUTCOME MEASURES: Levels of depression and anxiety. RESULTS: Visually impaired people had a higher prevalence of depression compared with people with good vision. Of visually impaired older people, 13.5% were depressed (GDS-15 score of 6 or more) compared with 4.6% of people with good vision (age- and gender-adjusted OR, 2.69; 95% CI, 2.03-3.56). Controlling for potential confounding factors, particularly activities of daily living, markedly attenuated the association between visual impairment and depression (OR, 1.26; 95% CI, 0.94-1.70). There was little evidence for any association between visual impairment and anxiety. On the GHQ-28 scale, 9.3% of visually impaired people had 2 or more symptoms of anxiety compared with 7.4% of people with good vision. CONCLUSIONS: Although cause and effect cannot be established in a cross-sectional study, it is plausible that people with visual impairment are more likely to experience problems with functioning, which in turn leads to depression.

Increased crystalline lens thickness and phacomorphic glaucoma in patients with Fanconi anemia.

We describe 2 siblings with Fanconi anemia (FA). One developed phacomorphic glaucoma, and both had increased crystalline lens thickness, features that have not been reported in patients with FA. The possible pathogenesis and clinical implications of the findings are discussed.

Is the NEI-VFQ-25 a useful tool in identifying visual impairment in an elderly population?

BACKGROUND: The use of self-report questionnaires to substitute for visual acuity measurement has been limited. We examined the association between visual impairment and self reported visual function in a population sample of older people in the UK. METHODS: Cross sectional study of people aged more than 75 years who initially participated in a trial of health screening. The association between 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores and visual impairment (defined as an acuity of less than 6/18 in the better eye) was examined using logistic regression. RESULTS: Visual acuity and NEI-VFQ scores were obtained from 1807 participants (aged 77 to 101 years, 36% male), from 20 general practices throughout the UK. After adjustment for age, gender, practice and NEI-VFQ sub-scale scores, those complaining of poor vision in general were 4.77 times (95% CI 3.03 to 7.53) more likely to be visually impaired compared to those who did not report difficulty. Self-reported limitations with social functioning and dependency on others due to poor vision were also associated with visual impairment (odds ratios, 2.52, 95% CI 1.55 to 4.11; 1.73, 95% CI 1.05 to 2.86 respectively). Those reporting difficulties with near vision and colour vision were more likely to be visually impaired (odds ratios, 2.32, 95% CI 1.30 to 4.15; 2.25, 95% CI 1.35 to 3.73 respectively). Other NEI-VFQ sub-scale scores were unrelated to measures of acuity. Similar but weaker odds ratios were found with reduced visual acuity (defined as less than 6/12 in the better eye). Although differences in NEI-VFQ scores were small, scores were strongly associated with visual acuity, binocular status, and difference in acuity between eyes. CONCLUSION: NEI-VFQ questions regarding the quality of general vision, social functioning, visual dependency, near vision and colour vision are strongly and independently associated with an objective measure of visual impairment in an elderly population.

Cause-specific visual impairment and mortality: results from a population-based study of older people in the United Kingdom.

OBJECTIVE: To assess the association between mortality and cause-specific visual impairment in older people. METHODS: Visual acuity and causes of visual impairment were collected in 13 569 participants 75 years and older participating in a randomized trial of health screening. Participants were followed up for mortality for a median of 6.1 years. RESULTS: Compared with those with 6/6 (or 20/20 Snellen) or better visual acuity, the age- and sex-adjusted rate ratio for visually impaired people (binocular visual acuity <6/18 or <20/60 Snellen) was 1.60 (95% confidence interval, 1.47-1.74), which was markedly attenuated (rate ratio, 1.17; 95% confidence interval, 1.07-1.27) after adjustment for confounding factors. People whose visual impairment was due to cataract or age-related macular degeneration had excess risks of all-cause and cardiovascular mortality, which disappeared after adjustment. People with refractive error remained at small risk, despite adjustment, probably owing to residual confounding from factors associated with minimal use of eye services rather than underlying eye disease. There were no associations with cancer mortality. CONCLUSION: Associations reported for visual impairment and mortality or for specific causes of visual impairment reflect confounding by comorbidities, risk factors, and other factors related to susceptibility to death rather than an independent biological association of vision problems or specific eye diseases.

Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology.

BACKGROUND: There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT. METHODS: National postal questionnaire survey of clinicians with potential responsibility for PDT provision. The survey explored reported local provision, beliefs about the effectiveness of PDT and what sources of opinion might influence attitudes towards providing PDT. RESULTS: The response rate was 73% (111/150). Almost half of the surveyed ophthalmology units routinely provided PDT, as part of a trend of steady growth in provision. The proportion of respondents who believed that further proof of effectiveness was required has also declined despite the absence of any new substantial evidence. Attitudes towards providing PDT were positive, on average, and were more strongly associated with perceived social pressure from local colleagues than from other sources. Local colleagues were seen as being most approving of PDT. CONCLUSION: Those responsible for implementing the NICE guidance need to address ophthalmologists' beliefs about the evidence of effectiveness for PDT and draw upon supportive local individuals or networks to enhance the credibility of the guidance.

Photodynamic therapy for neovascular age-related macular degeneration

Objectives: The aim of this review was to examine the effects of PDT in the treatment of neovascular ARMD.

Age-related macular degeneration causing visual impairment in people 75 years or older in Britain: an add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community.

PURPOSE: Age-related macular degeneration (AMD) is the most commonly occurring cause of visual loss in people registered as blind or partially sighted. There are no nationally representative data on the prevalence of AMD in the British population. We aimed to estimate the prevalence of AMD causing visual impairment in people 75 years or older in Britain. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Thirteen thousand nine hundred people 75 years or older in 49 practices taking part in the Medical Research Council Trial of the Assessment and Management of Older People in the Community. METHODS: Trial nurses tested visual acuity in everyone 75 years or older in participating practices. We collected data on the cause of visual loss for everyone who was visually impaired. We obtained these data from review of the general practice medical notes and by sending a questionnaire to the hospital ophthalmologist. Visual impairment was defined as a binocular acuity of less than 6/18. MAIN OUTCOME MEASURE: Prevalence of AMD causing visual impairment. RESULTS: There were 976 visually impaired people for whom a cause of visual loss was established. Of these, 516 (53%) had AMD as a cause of visual loss. We estimate that 3.7% (95% confidence interval, 3.2%-4.2%) of the population 75 years or older and 14.4% (11.6%-17.2%) of the population 90 years or older are visually impaired due to AMD. There are an estimated 192 000 people 75 years or older visually impaired due to AMD in the United Kingdom (95% confidence interval, 144 000-239 000). CONCLUSION: Our results, from the largest and most representative study of the causes of vision loss in older people in the British population, confirm the substantial burden of AMD in people 75 years and older. As the population ages, this problem will get worse. The needs of this group for vision aids and other support in the community should be addressed; research on the causes of AMD and possible preventive measures should be given priority.

Factors associated with success in first-time trabeculectomy for patients at low risk of failure with chronic open-angle glaucoma.

PURPOSE: To examine the relationships between study factors and trabeculectomy outcome in a representative sample of United Kingdom ophthalmology surgeons and patients. DESIGN: Cross-sectional observational study by questionnaire. PARTICIPANTS: All ophthalmic surgeons performing trabeculectomy in the National Health Service were invited to select their 4 most recent consecutive trabeculectomy cases satisfying study eligibility criteria before June 1996. Three hundred eighty-two surgeons supplied baseline data for 1450 patients and 1-year follow-up data for 1240 (85.3%) patients. All patients had undergone first-time trabeculectomy for chronic open-angle glaucoma. METHODS: Data were collected by self-administered questionnaires at baseline and 6 and 12 months postoperatively. Univariate analysis of the relationships between study factors and success was performed by chi-square test (categorical variables) and Student's t or Mann-Whitney U tests (continuous variables). Multiple logistic regression modeling of explanatory variables significant at a P value of