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.

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.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PURPOSE: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. DESIGN: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). PARTICIPANTS: Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. METHODS: Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. MAIN OUTCOME MEASURES: The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. RESULTS: Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. CONCLUSIONS: Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation.

Test-Retest Reliability of Scotopic and Mesopic Fundus-Controlled Perimetry Using a Modified MAIA (Macular Integrity Assessment) in Normal Eyes.

PURPOSE: To assess the intrasession test-retest reliability of scotopic cyan and scotopic red fundus-controlled perimetry (FCP) in normal subjects using a modified MAIA "microperimeter" (macular integrity assessment) device. METHODS: Forty-seven normal eyes of 30 subjects (aged 33.8 years) underwent duplicate mesopic (achromatic stimuli, 400-800 nm), scotopic cyan (505 nm), and scotopic red (627 nm) FCP, using a grid of 49 stimuli over 14° of the central retina. Test-retest reliability for pointwise sensitivity (PWS), stability of fixation, reaction time and test duration were analyzed using mixed-effects models. RESULTS: PWS test-retest reliability was good among all 3 types of retinal sensitivity assessments (coefficient of repeatability of 4.75 dB for mesopic, 5.26 dB for scotopic cyan, and 4.06 dB for scotopic red testing). While the mean sensitivity decreased with eccentricity for both mesopic and scotopic red testing, it was highest at 7° eccentricity for the scotopic cyan assessment (p < 0.001). CONCLUSIONS: The modified MAIA device allows for reliable scotopic FCP in normal subjects. Our findings suggest that testing of scotopic cyan sensitivity largely reflects rod function.

Preserved retinotopic brain connectivity in macular degeneration.

PURPOSE: The eye disease macular degeneration (MD) is a leading cause of blindness worldwide. There is no cure for MD, but several promising treatments aimed at restoring vision at the level of the retina are currently under investigation. These treatments assume that the patient's brain can still process appropriately the retinal input once it is restored, but whether this assumption is correct has yet to be determined. METHODS: We used functional magnetic resonance imaging (fMRI) and connective field modelling to determine whether the functional connectivity between the input-deprived portions of primary visual cortex (V1) and early extrastriate areas (V2/3) is still retinotopically organised. Specifically, in both patients with juvenile macular degeneration and age-matched controls with simulated retinal lesions, we assessed the extent to which the V1-referred connective fields of extrastriate voxels, as estimated on the basis of spontaneous fMRI signal fluctuations, adhered to retinotopic organisation. RESULTS: We found that functional connectivity between the input-deprived portions of visual areas V1 and extrastriate cortex is still largely retinotopically organised in MD, although on average less so than in controls. Patients with stable fixation exhibited normal retinotopic connectivity, however, suggesting that for the patients with unstable fixation, eye-movements resulted in spurious, homogeneous signal modulations across the entire input-deprived cortex, which would have hampered our ability to assess their spatial structure of connectivity. CONCLUSIONS: Despite the prolonged loss of visual input due to MD, the cortico-cortical connections of input-deprived visual cortex remain largely intact. This suggests that the restoration of sight in macular degeneration can rely on a largely unchanged retinotopic representation in early visual cortex following loss of central retinal function.

Quality of vision after bilateral multifocal intraocular lens implantation: a randomized trial--AT LISA 809M versus AcrySof ReSTOR SN6AD1.

PURPOSE: To compare postoperative visual symptoms and spectacle freedom after bilateral implantation of the AT LISA 809M (Carl Zeiss Meditec, Jena, Germany) versus the AcrySof ReSTOR SN6AD1 (Alcon Laboratories, Irvine, CA) multifocal intraocular lens (IOL). DESIGN: Double-masked, prospective, randomized, controlled clinical trial. PARTICIPANTS: A total of 188 patients undergoing bilateral sequential cataract surgery or bilateral refractive lens exchange. METHODS: Patients were preoperatively randomized (allocation ratio 1:1) to bilateral implantation with the AT LISA 809M IOL or ReSTOR SN6AD1 IOL. Postoperative outcomes were assessed 4 to 8 months after second eye surgery. MAIN OUTCOME MEASURES: The primary outcome was visual symptoms evaluated with the Quality of Vision (QoV) questionnaire. Secondary outcomes included other questionnaire data (CatQuest-9SF, spectacle independence, vision satisfaction, and dysphotopsia) and visual function measures (near, intermediate, and distance visual acuity, binocular reading speed [International Reading Speed Texts], contrast sensitivity, and forward light scatter). Adverse events, including intraoperative and postoperative complications, also were evaluated. RESULTS: There was no significant difference between IOL groups in Rasch-adjusted QoV scores for frequency (P = 0.95), severity (P = 0.56), and bothersomeness (P = 0.34) of visual symptoms; median (interquartile) scores for these QoV subscales were 29 (15-37), 22 (13-27), and 14 (0-29) for the AT LISA 809M IOL group, respectively, and 32 (15-37), 22 (13-30), and 14 (0-29) for the ReSTOR SN6AD1 IOL group, respectively. Halo was the most prominent dysphotopsia symptom, with 6% in both IOL groups reporting halo symptoms as very bothersome. Complete spectacle independence was achieved in 69 of 84 (82.1%) AT LISA 809M recipients and 66 of 85 (77.6%) ReSTOR SN6AD1 recipients (P = 0.57). Preferred reading distance was slightly nearer for the AT LISA 809M IOL. There were no statistically significant differences in any of the other secondary outcome measures. CONCLUSIONS: Visual symptoms were similar after bilateral implantation of the AT LISA 809M and ReSTOR SN6AD1 IOLs. Both these diffractive bifocal IOLs produce high levels of spectacle independence and patient satisfaction. However, a small but clinically significant minority of patients remained symptomatic and dissatisfied with visual results 4 to 8 months after surgery.

The effect of blur on cortical responses to global form and motion.

Global form and motion sensitivity undergo long development in childhood with motion sensitivity rather than form being impaired in a number of childhood disorders and both impaired in adult clinical populations. This suggests extended development and vulnerability of extrastriate cortical areas associated with global processing. However, in some developmental and clinical populations, it remains unclear to what extent impairments might reflect deficits at earlier stages of visual processing, such as reduced visual acuity and contrast sensitivity. To address this, we investigated the impact of degraded spatial vision on cortical global form and motion processing in healthy adults. Loss of high spatial frequencies was simulated using a diffuser to blur the stimuli. Participants completed behavioral and EEG tests of global form and motion perception under three levels of blur. For the behavioral tests, participants' form and motion coherence thresholds were measured using a two-alternative, forced-choice procedure. Steady-state visual evoked potentials were used to measure cortical responses to changes in the coherence of global form and motion stimuli. Both global form and global motion perception were impaired with increasing blur as measured by elevated behavioral thresholds and reduced cortical responses. However, form thresholds showed greater impairment in both behavioral and EEG measures than motion thresholds at the highest levels of blur. The results suggest that high spatial frequencies play an important role in the perception of both global form and motion but are especially significant for global form. Overall, the results reveal complex interactions between low-level factors and global visual processing, highlighting the importance of taking these factors into account when investigating extrastriate function in low vision populations.

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.

Randomized trial of multifocal intraocular lenses versus monovision after bilateral cataract surgery.

OBJECTIVE: To compare spectacle independence in patients randomized to receive bilateral multifocal intraocular lenses (IOLs) or monofocal IOLs with the powers adjusted to produce monovision. DESIGN: Randomized, multicenter clinical trial. PARTICIPANTS: A total of 212 patients with bilateral, visually significant cataract. METHODS: Before bilateral sequential cataract surgery, patients were randomized (allocation ratio 1:1) to receive bilateral Tecnis ZM900 diffractive multifocal lenses (Abbott Medical Optics, Santa Ana, CA) or Akreos AO monofocal lenses (Bausch & Lomb, Rochester, NY) with the powers adjusted to target -1.25 diopters (D) monovision. Outcomes were assessed 4 months after the second eye underwent operation. MAIN OUTCOME MEASURES: The primary outcome was spectacle independence. Secondary outcomes included questionnaires (VF-11R, dysphotopsia symptoms, and satisfaction) and visual function measures (near, intermediate, and distance logarithm of minimum angle of resolution [logMAR] visual acuity, stereoacuity, contrast sensitivity, and forward light scatter). RESULTS: A total of 212 patients were randomized, and 187 patients (88%) returned for assessment 4 months after surgery. Uniocular distance refractions in the monovision arm showed a mean spherical equivalent of +0.075 D in the distance eye and -0.923 in the near eye. In the multifocal arm, the mean distance spherical equivalents were -0.279 D and -0.174 D in the right and left eyes, respectively. A total of 24 of 93 patients (25.8%) in the monovision arm and 67 of 94 patients (71.3%) in the multifocal arm reported never wearing glasses (P<0.001, Fisher exact test). The adjusted odds ratio of being spectacle free was 7.51 (95% confidence interval, 3.89-14.47). Binocular uncorrected acuities did not differ significantly for distance (0.058 logMAR for monovision vs. 0.076 for multifocal, P = 0.3774) but were significantly worse in the multifocal arm for intermediate acuity (0.149 vs. 0.221, P = 0.0001) and in the monovision arm for near acuity (0.013 vs. -0.025, P = 0.037). In the first postoperative year, 6 patients (5.7%) in the multifocal arm underwent IOL exchange (4 had a bilateral and 2 had a unilateral exchange). No patients in the monovision arm underwent IOL exchange. CONCLUSIONS: Patients randomized to bilateral implantation with the diffractive multifocal Tecnis ZM900 were more likely to report being spectacle independent but also more likely to undergo IOL exchange than those randomized to receive monofocal implants (Akreos AO) with the powers adjusted to give low monovision.

Patient and public preferences for health states associated with AMD.

PURPOSE: Health utility values suitable for calculating quality-adjusted life-years are increasingly used to assess the cost-effectiveness of treatments for age-related macular degeneration (AMD). In the United States, health utilities are usually derived from the patients' own valuation or modeled using visual acuity as a surrogate outcome. In the United Kingdom and throughout Europe, health utilities are derived from public valuations. Our aim was to test if utility values for health states associated with AMD elicited directly from patients were different from those calculated from public tariffs for health-related quality of life (HRQoL) questionnaires. METHODS: Generic preference-based HRQoL questionnaires (EQ-5D and SF-6D) and the time trade-off (TTO) and visual analog scale (VAS) valuation techniques were administered to a sample of UK patients with AMD (N = 60). Health utilities were calculated using standard general population tariffs for the patient EQ-5D and SF-6D health states and directly from patient TTO and VAS scores. RESULTS: Mean utilities derived from the public tariffs were significantly higher than from patients' valuation (mean [±SD], 0.613 (±0.275) for the EQ-5D and 0.628 (±0.114) for the SF-6D compared with 0.481 [±0.411] for the TTO and 56.7 [±21.8] for the VAS score; p < 0.001). The EQ-5D was not significantly different from the SF-6D (p > 0.6). Visual acuity in the better seeing eye was not associated with any utility measure (all r < 0.08; p > 0.2). CONCLUSIONS: Patient and public preferences for health states associated with AMD are different, with patients valuing their health state more severely than the public tariffs of commonly used HRQoL questionnaires. Visual acuity did not predict health utility using any measure, and therefore, care should be taken when using visual acuity as a surrogate measure for utility in health economic analyses.

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.

Text accessibility by people with reduced contrast sensitivity.

PURPOSE: Contrast sensitivity is reduced in people with eye disease, and also in older adults without eye disease. In this article, we compare contrast of text presented in print and digital formats with contrast sensitivity values for a large cohort of subjects in a population-based study of older adults (the Salisbury Eye Evaluation). METHODS: Contrast sensitivity values were recorded for 2520 adults aged 65 to 84 years living in Salisbury, Maryland. The proportion of the sample likely to be unable to read text of different formats (electronic books, newsprint, paperback books, laser print, and LED computer monitors) was calculated using published contrast reserve levels required to perform spot reading, to read with fluency, high fluency, and under optimal conditions. RESULTS: One percent of this sample had contrast sensitivity less than that required to read newsprint fluently. Text presented on an LED computer monitor had the highest contrast. Ninety-eight percent of the sample had contrast sensitivity sufficient for high fluent reading of text (at least 160 words/min) on a monitor. However, 29.6% were still unlikely to be able to read this text with optimal fluency. CONCLUSIONS: Reduced contrast of print limits text accessibility for many people in the developed world. Presenting text in a high-contrast format, such as black laser print on a white page, would increase the number of people able to access such information. Additionally, making text available in a format that can be presented on an LED computer monitor will increase access to written documents.

The effect of low vision rehabilitation in diabetic eye disease: a randomised controlled trial protocol.

PURPOSE: Current research highlights a rising incidence of diabetes and its complications. Diabetic retinopathy is the leading cause of blindness within the working-age population of the United Kingdom. Increasing severity of retinopathy is associated with reduced visual function and participation in daily living. Only 8% of those referred to Moorfields Eye Hospital's low vision clinic have diabetic eye disease, a value less than prevalence figures for diabetes would predict. The lack of evidence for effectiveness of low vision intervention in this patient group could be responsible. Therefore, in line with CONSORT guidance, we present the methodology of the first randomised controlled trial to quantify the effect of low vision rehabilitation on people with diabetic eye disease. METHODS: One hundred participants were recruited into four retinopathy severity groups based on their diagnosis according to the English National Screening Programme Grading Protocol. Participants were randomised to either immediate intervention (1-2 weeks after enrollment) or delayed (control) intervention (3 months after enrollment). Intervention was a standard low vision assessment performed in a hospital clinic. The Activity Inventory (AI), was administered to all participants by telephone within 1 week of enrollment (before any intervention) and repeated at 3 and 6 months. RESULTS: One hundred participants (Type 1: 28, Type 2: 72; male: 62, female 38) have been recruited. Median habitual distance acuity was 0.19 logMAR (6/9, 20/30), with an interquartile range of 0.06-0.30 logMAR (6/7.5-6/12, 20/25-20/40). AI responses were scored by Rasch analysis, providing a measure of visual ability. Median baseline visual ability was 1.64 logits, with an interquartile range of 0.60-3.75 logits. Difference in mean change in visual ability between intervention groups will be assessed 3 months (primary outcome) and 6 months (secondary outcome) after enrollment. CONCLUSIONS: This is the first randomised controlled trial investigating the effectiveness of low vision rehabilitation for people with diabetic eye disease. With recruitment already complete, it is hoped this work will be the first step in guiding referral criteria for those with diabetic eye disease into the low vision service.

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.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].).

Retinal specific measurement of dark-adapted visual function: validation of a modified microperimeter.

BACKGROUND: Scotopic function is an important marker of many retinal diseases and is increasingly used as an outcome measure in clinical trials, such as those investigating gene therapy for Lebers congenital amaurosis. Scotopic visual function has traditionally been measured using an adapted perimetry system such as the Humphrey field analyser (HFA). However this system does not control for fixation errors or poor fixation stability. Here we evaluate the use of an adapted microperimeter to measure visual function at defined retinal regions under scotopic conditions. METHODS: A MP-1 microperimeter (Nidek Technologies, Italy) was modified by adding a 1 log unit Neutral Density filter and a 530 nm shortpass filter within the optical path of the instrument. Stray light was shielded. Fine matrix mapping perimetry was performed on five younger (< 35 years) and five older (> 65 years) subjects with no eye disease and good vision. All subjects were fully dark adapted before testing and pupils were dilated with 1% tropicamide. Tests was performed once on the modified MP-1 microperimeter and once using a modified HFA, in a counterbalanced order. RESULTS: A foveal scotopic scotoma with a sensitivity reduction of >1 log unit was found using each instrument. In addition, the MP-1 system showed the retinal location of the foveal scotoma. Mean test time was 25 minutes for the MP-1 and 32 minutes for the HFA. DISCUSSION: A modified MP-1 microperimeter can be used to measure scotopic retinal function, creating results which are comparable to the modified Humphrey field analyser. Advantages of the MP-1 system include the ability to track the retina through testing, retinal localisation of the scotoma and a faster test time.

Objective visual assessment of antiangiogenic treatment for wet age-related macular degeneration.

PURPOSE: To assess cortical responses in patients undergoing antiangiogenic treatment for wet age-related macular degeneration (AMD) using functional magnetic resonance imaging (fMRI) as an objective, fixation-independent measure of topographic visual function. METHODS: A patient with bilateral neovascular AMD was scanned using fMRI before and at regular intervals while undergoing treatment with intravitreal antiangiogenic injections (ranibizumab). Blood oxygenation level-dependent signals were measured in the brain while the patient viewed a stimulus consisting of a full-field flickering (6 Hz) white light alternating with a uniform gray background (18 s on and 18 s off). Topographic distribution and magnitude of activation in visual cortex were compared longitudinally throughout the treatment period (<1 year) and with control patients not currently undergoing treatment. Clinical behavioral tests were also administered, including visual acuity, microperimetry, and reading skills. RESULTS: The area of visual cortex activated increased significantly after the first treatment to include more posterior cortex that normally receives inputs from lesioned parts of the retina. Subsequent treatments yielded no significant further increase in activation area. Behavioral measures all generally showed an improvement with treatment but did not always parallel one another. The untreated control patient showed a consistent lack of significant response in the cortex representing retinal lesions. CONCLUSIONS: Retinal treatments may not only improve vision but also result in a concomitant improvement in fixation stability. Current clinical behavioral measures (e.g., acuity and perimetry) are largely dependent on fixation stability and therefore cannot separate improvements of visual function from fixation improvements. fMRI, which provides an objective and sensitive measure of visual function independent of fixation, reveals a significant increase in visual cortical responses in patients with wet AMD after treatment with antiangiogenic injections. Despite recent evidence that visual cortex degenerates subsequent to retinal lesions, our results indicate that it can remain responsive as its inputs are restored.

Intrasession repeatability of fixation stability assessment with the Nidek MP-1.

PURPOSE: This study aims to determine the intrasession repeatability and agreement using two methods to analyze fixation stability recorded during microperimetry in patients with macular disease. METHODS: Fifty patients with macular disease were enrolled prospectively to perform two consecutive microperimetry examinations on the Nidek microperimeter-1 (MP-1) using the same 1° red cross for fixation, Humphrey 10 to 2 grid of 68 test loci, 4 to 2 stair-case strategy, and 200 ms duration stimuli of Goldmann III size. Fixational eye movement was recorded during the two microperimetry examinations, and fixation stability was analyzed in two ways: (1) qualitatively through fixation stability grade (unstable, relatively unstable, and stable) and (2) quantitatively by calculating the logarithm of the bivariate contour ellipse area (logBCEA) that encompassed 68% of fixation points. Agreement and repeatability were assessed by unweighted kappa and the coefficient of repeatability. RESULTS: The mean (SD) visual acuity (VA) was 0.34 (0.32) logarithm of minimum angle of resolution. The mean (SD) duration of microperimetry was 13 (4) and 12 (4) min during the first and second measurements, respectively. During the first test, 10, 19, and 21 patients had unstable, relatively unstable, and stable fixation stability grading, respectively. Seventy percent (kappa: 0.53) of the fixation stability grading remained unchanged during repeat measurement. Of the remaining, 14% had a one-step decline and 16% had a one-step improvement in stability grading. The mean logBCEA were 4.28 and 4.24 in first and second tests, respectively (p = 0.43). The coefficient of repeatability for logBCEA was 0.61. CONCLUSIONS: The logBCEA method of analysis for fixation stability assessment is preferable. If logBCEA derived from a microperimetry task is used as part of the core outcome set in a clinical trial, a change of >0.61 may be considered to exceed the limit of test-retest variability.

Quality of life in high myopia before and after implantable Collamer lens implantation.

PURPOSE: To examine changes in vision-related quality of life after implantable Collamer lens (ICL) implantation for the correction of myopia. DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS: We included 34 consecutive patients (68% female; mean age, 37 years [range, 23-49]) with preoperative myopia (mean ± standard deviation [SD] refraction spherical equivalent, -11.0 ± 3.12). INTERVENTION: Bilateral ICL implantation. MAIN OUTCOME MEASURES: Quality of life Impact of Refractive Correction (QIRC) score. RESULTS: The median postoperative interval before questionnaire administration was 4 months (range, 3-7). The QIRC scores were significantly higher postoperatively (preoperative QIRC score [mean ± SD], 40.45 ± 4.83; postoperative QIRC score 53.79 ± 5.60; P < 0.001), with significant improvements (P<0.01) for 14 of 19 items. Nineteen (58%) patients reported a worsening in night vision symptoms (mostly nonspecific glare and halo or arc effects) after surgery, but overall levels of satisfaction were high; 88% were either satisfied or very satisfied with the results of surgery. No patients reported overall dissatisfaction. In free text responses, 11 patients (32%) described ICL implantation as life changing or wished that they had opted for the surgery sooner. CONCLUSIONS: Implantation of an ICL for myopia is associated with significant improvements in quality of life. Any dissatisfaction with the procedure largely relates to night vision symptoms, which are common in the early postoperative period.