Eccentric Viewing Training for Age-Related Macular Disease: Results of a Randomized Controlled Trial (the EFFECT Study).

Purpose: Eccentric viewing training for macular disease has been performed for > 40 years, but no large studies including control groups have assessed the benefits of this training. The EFFECT (Eccentric Fixation From Enhanced Clinical Training) study is a large randomized controlled trial of 2 types of eccentric viewing training. Design: Randomized controlled trial. Participants: Two hundred adults with age-related macular disease. Methods: Participants were randomized to either of the following: (1) a control group; (2) a group receiving supervised reading support; (3) a group receiving 3 sessions of training to optimize the use of their own preferred retinal locus; or (4) a group receiving 3 sessions of biofeedback training of a theoretically optimal trained retinal locus. All participants received standard low-vision rehabilitation. Main Outcome Measures: The primary outcome was patient-reported visual task ability measured on the Activity Inventory instrument at goal level. Secondary outcomes included reading performance and fixation stability. Results: There was no difference between groups on change in task ability (F(3,174) = 1.48, P = 0.22) or on any of the secondary outcome measures. Visual acuity and contrast sensitivity fell in all groups, suggesting that disease progression outweighed any benefit of training. Conclusions: Eccentric viewing training did not systematically improve task ability, reading performance, or fixation stability in this study. Our results do not support the routine use of eccentric viewing training for people with progressing age-related macular disease, although this training may help people with end-stage disease. Rehabilitation of an inherently progressive condition is challenging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Test-Retest Variability and Discriminatory Power of Measurements From Microperimetry and Dark Adaptation Assessment in People With Intermediate Age-Related Macular Degeneration - A MACUSTAR Study Report.

Purpose: The purpose of this study was to assess test-retest variability and discriminatory power of measures from macular integrity assessment (S-MAIA) and AdaptDx. Methods: This is a cross-sectional study of 167 people with intermediate age-related macular degeneration (iAMD), no AMD (controls; n = 54), early AMD (n = 28), and late AMD (n = 41), recruited across 18 European ophthalmology centers. Repeat measures of mesopic and scotopic S-MAIA average (mean) threshold (MMAT decibels [dB] and SMAT [dB]) and rod intercept time (RIT [mins]) at 2 visits 14 (±7) days apart were recorded. Repeat measures were assessed by Bland-Altman analysis, intra-class correlation coefficients (ICCs) and variability ratios. Secondary analysis assessed the area under the receiver operating characteristic curves (AUC) to determine the ability to distinguish people as having no AMD, early AMD, or iAMD. Results: Data were available for 128, 131, and 103 iAMD participants for the mesopic and scotopic S-MAIA and AdaptDx, respectively. MMAT and SMAT demonstrate similar test-retest variability in iAMD (95% confidence interval [CI] ICC of 0.79-0.89 and 0.78-0.89, respectively). ICCs were worse in RIT (95% CI ICC = 0.55-0.77). All tests had equivalent AUCs (approximately 70%) distinguishing between subjects with iAMD and controls, whereas early AMD was indistinguishable from iAMD on all measures (AUC = <55%). A learning effect was not seen in these assessments under the operating procedures used. Conclusions: MMAT, SMAT, and RIT have adequate test-retest variability and are all moderately good at separating people with iAMD from controls. Translational Relevance: Expected levels of test-retest variability and discriminatory power of the AdaptDx and MAIA devices in a clinical study setting must be considered when designing future trials for people with AMD.

Problem-Solving Treatment for People Recently Diagnosed with Visual Impairment: Pilot Randomised Controlled Trial.

BACKGROUND: Problem-Solving Treatment (PST) has been used to treat and prevent depression in a variety of settings. However, the impact of PST on improving psychological well-being in those with recent vision loss remains unknown. The aim of this study was to evaluate whether PST may lead to better psychological well-being in people with recent vision loss through a pilot parallel-group randomised controlled trial. METHODS: Participants who were diagnosed with visual impairment during the previous 3 months were randomly allocated to either an 8-week PST or treatment as usual (N = 61). Outcome measures were administered at baseline, 3, 6, and 9-months. RESULTS: A linear mixed model demonstrated that PST significantly improved psychological well-being (measured by the Warwick Edinburgh Mental Well-being Scale) (treatment effect = 2.44; 95% CI = 0.40-4.47; p = 0.019). Significant improvements in the PST group for symptoms of distress, quality of life and self-efficacy were also observed. There was no significant difference in mobility. The treatment effect was consistent at all follow-ups. Attrition rate was low (13%). CONCLUSIONS: PST was associated with a significant and sustained improvement in a range of outcomes in people with recent vision loss. Further large scale RCT is now required.

Cross-sectional comparison of age- and gender-related comorbidities in people living with HIV in Canada.

Because antiretroviral therapy (ART) is allowing people living with human immunodeficiency virus (PLWH) to survive longer, they are developing more age-related comorbidities. We evaluated the effects of age and gender on the burden of age-related comorbidities among PLWH. In this retrospective real-world study, de-identified data were extracted from the medical charts of 2000 HIV-positive adults on ART across 10 sites in Canada. The prevalence of age-related comorbidities was determined in 6 age subgroups (<30, 30-39, 40-49, 50-59, 60-69, and ≥70 years). The effects of gender on these comorbidities were also examined. Risks of cardiovascular disease and chronic kidney disease (CKD) were calculated using the Framingham and D:A:D equations. Most persons were White (68%), male (87%), and virologically suppressed (94%). The mean age was 50.3 years (57% aged ≥50 years), and mean CD4+ T-cell count was 616 cells/mm3. The most common comorbidities were neuropsychiatric symptoms (61%), overweight/obesity (43%), liver disease (37%), and dyslipidemia (37%). The mean number of comorbidities increased across age subgroups (P < .001). Across all age subgroups, the prevalence of hypertension (P = .04), dyslipidemia (P = .04), CKD (P = .03), bone fragility (P = .03), and depression (P = .02) differed between males and females. Both age (P < .001) and gender (P < .001) impacted cardiovascular disease and CKD risk. Age and gender influenced the burden, types, and risks of age-related comorbidities in PLWH in this Canadian cohort. These comorbidities should be diagnosed and treated in routine clinical practice.

Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report.

Importance: There is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment. Objective: To assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD). Design, Setting, and Participants: This international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity [BCVA], low-luminance visual acuity [LLVA], Moorfields Acuity Test [MAT], Pelli-Robson Contrast Sensitivity [CS], and International Reading Speed Test [IReST]) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited. Main Outcomes and Measures: Intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states. Results: A total of 301 participants (mean [SD] age, 71 [7] years; 187 female participants [62.1%]) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61). Conclusions and Relevance: BCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.

Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials: Recommendations from the International HOVER Taskforce.

Translational research in vision prosthetics, gene therapy, optogenetics, stem cell and other forms of transplantation, and sensory substitution is creating new therapeutic options for patients with neural forms of blindness. The technical challenges faced by each of these disciplines differ considerably, but they all face the same challenge of how to assess vision in patients with ultra-low vision (ULV), who will be the earliest subjects to receive new therapies. Historically, there were few tests to assess vision in ULV patients. In the 1990s, the field of visual prosthetics expanded rapidly, and this activity led to a heightened need to develop better tests to quantify end points for clinical studies. Each group tended to develop novel tests, which made it difficult to compare outcomes across groups. The common lack of validation of the tests and the variable use of controls added to the challenge of interpreting the outcomes of these clinical studies. In 2014, at the bi-annual International "Eye and the Chip" meeting of experts in the field of visual prosthetics, a group of interested leaders agreed to work cooperatively to develop the International Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials (HOVER) Taskforce. Under this banner, more than 80 specialists across seven topic areas joined an effort to formulate guidelines for performing and reporting psychophysical tests in humans who participate in clinical trials for visual restoration. This document provides the complete version of the consensus opinions from the HOVER taskforce, which, together with its rules of governance, will be posted on the website of the Henry Ford Department of Ophthalmology (www.artificialvision.org). Research groups or companies that choose to follow these guidelines are encouraged to include a specific statement to that effect in their communications to the public. The Executive Committee of the HOVER Taskforce will maintain a list of all human psychophysical research in the relevant fields of research on the same website to provide an overview of methods and outcomes of all clinical work being performed in an attempt to restore vision to the blind. This website will also specify which scientific publications contain the statement of certification. The website will be updated every 2 years and continue to exist as a living document of worldwide efforts to restore vision to the blind. The HOVER consensus document has been written by over 80 of the world's experts in vision restoration and low vision and provides recommendations on the measurement and reporting of patient outcomes in vision restoration trials.

Validation of a Vision-Guided Mobility Assessment for RPE65-Associated Retinal Dystrophy.

Purpose: To validate a vision-guided mobility assessment for individuals affected by RPE65-associated retinal dystrophy (RPE65-RD). Methods: In this comparative cross-sectional study, 29 subjects, comprising 19 subjects with RPE65-RD and 10 normally-sighted subjects undertook three assessments of mobility: following a straight line, navigating a simple maze, and stepping over a sidewalk "kerb." Performance was quantified as the time taken to complete each assessment, number of errors made, walking speed, and percent preferred walking speed, for each assessment. Subjects also undertook assessments of visual acuity, contrast sensitivity, full-field static perimetry, and age-appropriate quality of life questionnaires. To identify the most relevant metric to quantify vision-guided mobility, we investigated repeatability, as well as convergent, discriminant, and criterion validity. We also measured the effect of illumination on mobility. Results: Walking speed through the maze assessment best discriminated between RPE65-RD and normally-sighted subjects, with both convergent and discriminant validity. Walking speed also approached statistical significance when assessed for criterion validity (P = 0.052). Subjects with RPE65-RD had quantifiably poorer mobility at lower illumination levels. A relatively small mean difference (-0.09 m/s) was identified in comparison to a relatively large repeatability coefficient (1.10 m/s). Conclusions: We describe a novel, quantifiable, repeatable, and valid assessment of mobility designed specifically for subjects with RPE65-RD. The assessment is sensitive to the visual impairment of individuals with RPE65-RD in low illumination, identifies the known phenotypic heterogeneity and will furthermore provide an important outcome measure for RPE65-RD. Translational Relevance: This assessment of vision-guided mobility, validated in a dedicated cohort of subjects with RPE65-RD, is a relevant and quantifiable outcome measure for RPE65-RD.

Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR.

BACKGROUND: There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials. METHODS: The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part's primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part's primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities. DISCUSSION: The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017.

Individualizing Therapy for Neovascular Age-Related Macular Degeneration with Aflibercept (VITAL): A Two-Year Prospective, Interventional Single-Centre Trial.

AIMS: To report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections. METHODS: A prospective, open-label, interventional non-randomised case series with 24 months' duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment. RESULTS: Fifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm. CONCLUSIONS: Aflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02441816, the VITAL study.

Femtosecond Laser-Assisted Cataract Surgery Versus Phacoemulsification Cataract Surgery (FACT): A Randomized Noninferiority Trial.

PURPOSE: To report the 3-month results of a randomized trial (Femtosecond Laser-Assisted Cataract Trial [FACT]) comparing femtosecond laser-assisted cataract surgery (FLACS) with standard phacoemulsification cataract surgery (PCS). DESIGN: Multicenter, randomized controlled trial funded by the UK National Institute of Health Research (HTA 13/04/46/). PARTICIPANTS: Seven hundred eighty-five patients with age-related cataract. METHODS: This trial took place in 3 hospitals in the UK National Health Service (NHS). Randomization (1:1) was stratified by site, surgeon, and 1 or both eyes eligible using a secure web-based system. Postoperative assessments were masked to the allocated intervention. The primary outcome was unaided distance visual acuity (UDVA) in the study eye at 3 months. Secondary outcomes included corrected distance visual acuity, complications, and patient-reported outcomes measures. The noninferiority margin was 0.1 logarithm of the minimum angle of resolution (logMAR). ISRCTN.com registry, number ISRCTN77602616. MAIN OUTCOME MEASURES: We enrolled 785 participants between May 2015 and September 2017 and randomly assigned 392 to FLACS and 393 to PCS. At 3 months postoperatively, mean UDVA difference between treatment arms was -0.01 logMAR (-0.05 to 0.03), and mean corrected distance visual acuity difference was -0.01 logMAR (95% confidence interval [CI], -0.05 to 0.02). Seventy-one percent of both FLACS and PCS cases were within ±0.5 diopters (D) of the refractive target, and 93% of FLACS and 92% of PCS cases were within ±1.0 D. There were 2 posterior capsule tears in the PCS arm and none in the FLACS arm. There were no significant differences between arms for any secondary outcome. CONCLUSIONS: Femtosecond laser-assisted cataract surgery is not inferior to conventional PCS surgery 3 months after surgery. Both methods are as good in terms of vision, patient-reported health, and safety outcomes at 3 months. Longer-term outcomes of the clinical effectiveness and cost-effectiveness are awaited.

New Technologies for Outcome Measures in Glaucoma: Review by the European Vision Institute Special Interest Focus Group.

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.

New Technologies for Outcome Measures in Retinal Disease: Review from the European Vision Institute Special Interest Focus Group.

Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.

Binocular Inhibition of Reading in Macular Telangiectasia Type 2.

Purpose: To assess the presence of binocular gain in macular telangiectasia type 2 (MacTel) and its correlation to paracentral scotomas. Methods: Sixty-eight patients with MacTel were consecutively recruited for a cross-sectional analysis. Best-corrected visual acuity (BCVA), reading acuity, and reading speed were tested monocularly and binocularly. Macular retinal sensitivity was examined with fundus-controlled perimetry (microperimetry). Scotomas were quantified by their size, their depth, and their proximity to the fovea. Results: Binocular reading speed and acuity were lower than monocular reading speed and acuity in the functionally better eye (142 vs. 159 words per minute and 0.43 vs. 0.28 log reading acuity determination, P < 0.001). Magnitude of binocular inhibition of reading speed was correlated to the degree of interocular functional difference (R2 = 0.61, P < 0.001). This correlation was not found for reading acuity or BCVA (R2 < 0.03). Binocular reading speed was negatively correlated to size of right and left eye scotomas, with bigger effect size for left eye scotomas. The magnitude of binocular inhibition was correlated to size of left eye scotomas, but not of right eye scotomas. When both eyes had similar scotoma characteristics, the right eye was more frequently the better reading eye. Conclusions: We provide evidence for the presence of binocular inhibition of reading performance in MacTel, likely due to binocular rivalry. This may result from the characteristic paracentral scotomas in noncorresponding retinal fields and, in particular, a disruptive projection of scotomas in reading direction arising from the left eyes. Patients may benefit from occluding one eye while reading.

Selective laser trabeculoplasty versus drops for newly diagnosed ocular hypertension and glaucoma: the LiGHT RCT.

BACKGROUND: Newly diagnosed open-angle glaucoma (OAG) and ocular hypertension (OHT) are habitually treated with intraocular pressure (IOP)-lowering eyedrops. Selective laser trabeculoplasty (SLT) is a safe alternative to drops and is rarely used as first-line treatment. OBJECTIVES: To compare health-related quality of life (HRQoL) in newly diagnosed, treatment-naive patients with OAG or OHT, treated with two treatment pathways: topical IOP-lowering medication from the outset (Medicine-1st) or primary SLT followed by topical medications as required (Laser-1st). We also compared the clinical effectiveness and cost-effectiveness of the two pathways. DESIGN: A 36-month pragmatic, unmasked, multicentre randomised controlled trial. SETTINGS: Six collaborating specialist glaucoma clinics across the UK. PARTICIPANTS: Newly diagnosed patients with OAG or OHT in one or both eyes who were aged ≥ 18 years and able to provide informed consent and read and understand English. Patients needed to qualify for treatment, be able to perform a reliable visual field (VF) test and have visual acuity of at least 6 out of 36 in the study eye. Patients with VF loss mean deviation worse than -12 dB in the better eye or -15 dB in the worse eye were excluded. Patients were also excluded if they had congenital, early childhood or secondary glaucoma or ocular comorbidities; if they had any previous ocular surgery except phacoemulsification, at least 1 year prior to recruitment or any active treatment for ophthalmic conditions; if they were pregnant; or if they were unable to use topical medical therapy or had contraindications to SLT. INTERVENTIONS: SLT according to a predefined protocol compared with IOP-lowering eyedrops, as per national guidelines. MAIN OUTCOME MEASURES: The primary outcome was HRQoL at 3 years [as measured using the EuroQol-5 Dimensions, five-level version (EQ-5D-5L) questionnaire]. Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness and safety. RESULTS: Of the 718 patients enrolled, 356 were randomised to Laser-1st (initial SLT followed by routine medical treatment) and 362 to Medicine-1st (routine medical treatment only). A total of 652 (91%) patients returned the primary outcome questionnaire at 36 months. The EQ-5D-5L score was not significantly different between the two arms [adjusted mean difference (Laser-1st - Medicine-1st) 0.01, 95% confidence interval (CI) -0.01 to 0.03; p = 0.23] at 36 months. Over 36 months, the proportion of visits at which IOP was within the target range was higher in the Laser-1st arm (93.0%, 95% CI 91.9% to 94.0%) than in the Medicine-1st arm (91.3%, 95% CI 89.9% to 92.5%), with IOP-lowering glaucoma surgery required in 0 and 11 patients, respectively. There was a 97% probability of Laser-1st being more cost-effective than Medicine-1st for the NHS, at a willingness to pay for a quality-adjusted life-year of £20,000, with a reduction in ophthalmology costs of £458 per patient (95% of bootstrap iterations between -£585 and -£345). LIMITATION: An unmasked design, although a limitation, was essential to capture any treatment effects on patients' perception. The EQ-5D-5L questionnaire is a generic tool used in multiple settings and may not have been the most sensitive tool to investigate HRQoL. CONCLUSIONS: Compared with medication, SLT provided a stable, drop-free IOP control to 74.2% of patients for at least 3 years, with a reduced need for surgery, lower cost and comparable HRQoL. Based on the evidence, SLT seems to be the most cost-effective first-line treatment option for OAG and OHT, also providing better clinical outcomes. FUTURE WORK: Longitudinal research into the clinical efficacy of SLT as a first-line treatment will specify the long-term differences of disease progression, treatment intensity and ocular surgery rates between the two pathways. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32038223. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 31. See the NIHR Journals Library website for further project information.

Glaucoma is an eye condition in which the optic nerve becomes damaged and, if left untreated, will lead to loss of vision. Ocular hypertension (OHT) is the medical name for high pressure in the eye that increases the risk of getting glaucoma. Lowering the eye pressure is the only known way to prevent glaucoma from getting worse. Before this trial, the standard initial treatment of these conditions was the prescription of eyedrops to lower the pressure in the eye. An alternative is a laser therapy that is known to reduce the eye pressure. This study investigated if starting treatment of glaucoma or OHT with laser therapy (using eyedrops later, if needed) affected the patients' quality of life (QoL) more or less than starting treatment with eyedrops alone. The study also investigated if initial treatment with laser and initial treatment with eyedrops are equally good at controlling eye pressure and are equally safe and how much they cost the NHS. Patients were randomly assigned to starting treatment with either laser or eyedrops and the two groups were then compared. The study found that for the first 3 years QoL was similar regardless of treatment. However, three-quarters of patients initially treated with laser did not need any eyedrops to control their eye pressure for 3 years. Patients initially treated with laser were less likely to require cataract surgery, and none needed any glaucoma surgery in the first 3 years. In contrast, among those patients treated with eyedrops, glaucoma surgery was required in 11 eyes (out of 622 eyes). Initial treatment with laser was cheaper than initial treatment with eyedrops. The results of this study suggest that laser is an efficient, safe and cheaper alternative to eyedrops, and that three-quarters of the patients initially treated with laser do not need any eyedrops for the first 3 years of treatment.

Productivity Losses and Their Explanatory Factors Amongst People with Impaired Vision.

Purpose: To estimate productivity losses amongst people with impaired vision in Portugal and to investigate explanatory factors associated with non-participation in the labour market.Methods: A total of 546 visually impaired individuals participated in face-to-face interviews. Participants were asked about their workforce participation to determine productivity (employment status questionnaire), their health-related quality of life - HRQoL (EQ-5D) and their visual acuity and visual ability (Activity Inventory). Productivity losses included absenteeism and reduction in workforce participation. Logistic regression was used to determine independent factors associated with participation in the labour market.Results: From the 546 participants, 50% were retired, 47% were of working age and 3% were students. The employment rate was 28%, and the unemployment rate was 21% for the working age sample. For those of working age, productivity losses were estimated at €1.51 million per year, mean of €5496 per participant. The largest contributor to productivity losses was reduced workforce participation, estimated from 159 early retired or unemployed participants. After controlling for visual acuity and ability, younger individuals, with more years of education, without comorbidities and high HRQoL had a higher probability of being employed.Conclusions: Our findings show a high unemployment rate and high productivity losses amongst people with impaired vision. The probability of being employed was associated with education, HRQoL and comorbidities. We speculate that promoting education and health through effective visual rehabilitation programs may help to increase participation in the labour market. These findings can inform decisions to intervene to reduce the burden of vision loss.

Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial.

BACKGROUND: Primary open angle glaucoma and ocular hypertension are habitually treated with eye drops that lower intraocular pressure. Selective laser trabeculoplasty is a safe alternative but is rarely used as first-line treatment. We compared the two. METHODS: In this observer-masked, randomised controlled trial treatment-naive patients with open angle glaucoma or ocular hypertension and no ocular comorbidities were recruited between 2012 and 2014 at six UK hospitals. They were randomly allocated (web-based randomisation) to initial selective laser trabeculoplasty or to eye drops. An objective target intraocular pressure was set according to glaucoma severity. The primary outcome was health-related quality of life (HRQoL) at 3 years (assessed by EQ-5D). Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness, and safety. Analysis was by intention to treat. This study is registered at controlled-trials.com (ISRCTN32038223). FINDINGS: Of 718 patients enrolled, 356 were randomised to the selective laser trabeculoplasty and 362 to the eye drops group. 652 (91%) returned the primary outcome questionnaire at 36 months. Average EQ-5D score was 0·89 (SD 0·18) in the selective laser trabeculoplasty group versus 0·90 (SD 0·16) in the eye drops group, with no significant difference (difference 0·01, 95% CI -0·01 to 0·03; p=0·23). At 36 months, 74·2% (95% CI 69·3-78·6) of patients in the selective laser trabeculoplasty group required no drops to maintain intraocular pressure at target. Eyes of patients in the selective laser trabeculoplasty group were within target intracoluar pressure at more visits (93·0%) than in the eye drops group (91·3%), with glaucoma surgery to lower intraocular pressure required in none versus 11 patients. Over 36 months, from an ophthalmology cost perspective, there was a 97% probability of selective laser trabeculoplasty as first treatment being more cost-effective than eye drops first at a willingness to pay of £20 000 per quality-adjusted life-year gained. INTERPRETATION: Selective laser trabeculoplasty should be offered as a first-line treatment for open angle glaucoma and ocular hypertension, supporting a change in clinical practice. FUNDING: National Institute for Health Research, Health and Technology Assessment Programme.

MACUSTAR: Development and Clinical Validation of Functional, Structural, and Patient-Reported Endpoints in Intermediate Age-Related Macular Degeneration.

PURPOSE: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. PROCEDURES: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. RESULTS: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). CONCLUSIONS: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD.

Microperimetry and swept-source optical coherence tomography in the assessment of the preferred retinal locus in a child with macular retinoblastoma in the remaining eye.

Assessing the visual capabilities that remain to children affected with bilateral retinoblastoma has relied on psychophysical tests based on recognition visual acuity. We report a case in which fundus-driven perimetry and swept-source optical coherence tomography was performed in a patient with a macular tumor in the remaining eye as a novel way of further assessing fixation after oncological disease and treatment.

Visual functioning in adults with Idiopathic Infantile Nystagmus Syndrome (IINS).

PURPOSE: IINS is associated with mild/moderate visual impairment, strabismus and compensatory head postures (CHP), which can negatively impact quality of life. Standard visual acuity assessments tend to underestimate the effect of IINS on visual functioning. Published evidence on the effect of INS on quality of life is slowly emerging. Our study examines visual functioning of adults with IINS using the National Eye Institute Visual Function Questionairre-25 (VFQ-25). METHODS: 38 participants were recruited to participate in the study. All participants underwent detailed clinical examination, as well as appropriate investigations and were asked to complete the self administered VFQ-25. RESULTS: 35/38 participants completed the questionnaire. The mean age of the population was 35.1 years (range 17-64). Mean overall VFQ-25 score at baseline was 65 (SD 13, range 34-91). Participants specifically demonstrated lowest scores for the impact of IINS on mental health, role limitations and dependency. 26/35 of participants were not driving, either due to sub-normal vision, lack of confidence or difficulties with contrast sensitivity. CONCLUSIONS: IINS can have a greater than expected impact on an individual's quality of life, without necessarily causing markedly reduced visual acuity. Our study showed lowest scores in the domains of mental health and wellbeing. Patients also reported reduced visual functioning in driving, which can impact adversely on employability and independence. Visual functioning questionnaires such as the VFQ-25 may provide more functional information on the impact of nystagmus on an individual's quality of life than objective measures such as high contrast Snellen and/or LogMAR visual acuity.

A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis.

Purpose: RPE65-associated Leber congenital amaurosis (RPE65-LCA) is an early-onset severe retinal dystrophy associated with progressive visual field loss. Phase I/II and III gene therapy trials have identified improved retinal sensitivity but little is known about the natural history of retinal sensitivity in RPE65-LCA. Methods: A total of 19 subjects (aged 9 to 23 years) undertook monocular full-field static perimetry of which 13 subjects were monitored longitudinally. Retinal sensitivity was measured as mean sensitivity (MS) and volumetrically quantified (in decibel-steradian) using visual field modeling and analysis software for the total (VTOT), central 30° (V30) and central 15° (V15) visual field. Correlation was evaluated between retinal sensitivity and age, best-corrected visual acuity (BCVA), contrast sensitivity, vision-related quality of life, and genotype. Test-retest reliability was also investigated. Results: V30 was identified to have a strong, weak, and moderate correlation with age, BCVA and contrast sensitivity respectively. Furthermore, V30 was identified as having a weak linear relationship with the mobility and independence domains of the vision-related quality of life questionnaire. Longitudinal analysis demonstrated a slow loss of retinal sensitivity in this cohort. Subjects with at least one RPE65 nonsense variant appeared to show greater progressive loss of retinal sensitivity in the second decade of life than those without. Conclusions: Volumetric assessment of central 30° visual field sensitivity, V30, is a useful independent measure of retinal function and, in our data, represented the best metric to monitor deterioration of retinal sensitivity in RPE65-LCA. Furthermore, functional correlation with genotype may enable more informed prognostic counseling. (ClinicalTrials.gov number, NCT02714816.)