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The aim of this study was to determine the short-term compliance with regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). Home-based outcomes were compared with in-clinic outcomes determined using (1) the same tablet device under supervision, and (2) the Macular Integrity Assessment (MaIA) microperimeter.Single-center longitudinal compliance and reliability study.A total of 73 participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields-macular (MRF-m) iPad application. Volunteers were asked to return 6 weekly tests from home, guided by audio instructions. We determined compliance with weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and RS were compared to in-clinic assays (MaIA). Data are given as mean ± SD or as median [quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits.A total of 59 participants submitted 6 home examinations with a median intertest interval of 8.0 [7.0-17] days. Compliance with weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was information technology (IT) logistic reasons. Of 694 home examinations submitted, 96% were reliable (false-positive results25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, P.05) compared to the MaIA.Home monitoring produces reliable results that differ from in-clinic tests because of test design. This should not affect self-monitoring once an at-home baseline is established, but these differences will affect comparisons with in-clinic outcomes. Reasonable compliance with weekly testing was achieved. Improved IT support might lead to better compliance.

The effect of sub-threshold nano-second laser (SNL) treatment on retinal function remains unknown.SNL treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the longitudinal effect of SNL treatment on retinal function.This was a sub-study of the LEAD trial; a 36-month, multi-centre, randomized and sham-controlled trial.Subjects with iAMD.Eligible participants were assigned randomly to receive SNL or sham treatment to the study eye at 6-monthly visits. Multi-focal electro-retinography (mfERG) was performed at each study visit from a study site. The mfERG responses were grouped into three regions (central, middle and outer rings) and compared between the SNL and sham group.mfERG P1 response amplitude and implicit time.Data were collected from 50 subjects (26 in the SNL group, 24 in the sham group). At baseline, the P1 amplitudes of both the study eyes and the fellow eyes were similar between the groups at all rings. In the sham group, the P1 amplitude gradually decreased over time (P .05). In the SNL group, there was an improvement in P1 amplitude which became statistically significant at the 36-month visit, detected in both the treated and fellow eyes at the central (P = .005) and middle ring (P = .007) but not at the outer ring (P = .070). No difference in P1 implicit time detected between the groups (P .05).SNL treatment improved electro-physiological function. mfERG could be useful for monitoring AMD progression and evaluating the efficacy of SNL treatment.

PURPOSE: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. RESULTS: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P = 0.628). CONCLUSIONS: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

Purpose To report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation. Methods Four subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals. Results All four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects' daily lives was confirmed by an orientation and mobility assessor and subject self-report. Conclusions These interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life. Translational Relevance A suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.

Purpose There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. Design The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial. Participants Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. Methods Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT®; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals. Main Outcome Measures The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. Results Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33–1.14; P = 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09–0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80–8.18; P = 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant. Conclusions In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT® laser, but they should not be extrapolated to other short-pulse lasers.

IMPORTANCE: Improved vision self-monitoring tools are required for people at risk of neovascular complications from age related macular degeneration (AMD). BACKGROUND: to report the self-monitoring habits of participants with intermediate AMD using the Amsler grid chart, and the use of personal electronic devices and gameplay in this over 50 year old cohort. DESIGN: single-centre descriptive study carried out at the Centre for Eye Research (CERA), Melbourne, Australia. PARTICIPANTS: 140 participants over 50 years of age, with a diagnosis of intermediate AMD and best-corrected visual acuity (BCVA) of ≥6/12 in each eye. METHODS: structured questionnaire survey of participants who were enrolled in natural history of AMD studies at CERA. MAIN OUTCOME MEASURES: frequency of vision self-monitoring using the Amsler grid chart, and frequency of general use of personal electronic devices and gameplay. RESULTS: Of 140 participants with mean age of 70.5 years, 83.6% used an Amsler grid chart, but only 39.3% used it once per week. Most participants (91.4%) used one or more personal electronic devices. Of these, over half (54.7%) played games on them, among whom 39% played games once a day. Of participants aged 50-69 years, 92% (95%CI 85.1-98.9) were willing to play a game to monitor their vision, compared to 78% (95%CI 69.0-87.0) of those aged 70 years and older (P

Purpose: In a clinical trial (NCT03406416) of a second-generation (44-channel) suprachoroidal retinal prosthesis implanted in subjects with late-stage retinitis pigmentosa (RP), we assessed performance in real-world functional visual tasks and emotional well-being. Methods: The Functional Low-Vision Observer Rated Assessment (FLORA) and Impact of Vision Impairment-Very Low Vision (IVI-VLV) instruments were administered to four subjects before implantation and after device fitting. The FLORA contains 13 self-reported and 35 observer-reported items ranked for ease of conducting task (impossible-easy, central tendency given as mode). The IVI-VLV instrument quantified the impact of low vision on daily activities and emotional well-being. Results: Three subjects completed the FLORA for two years after device fitting; the fourth subject ceased participation in the FLORA after fitting for reasons unrelated to the device. For all subjects at each post-fitting visit, the mode ease of task with device ON was better or equal to device OFF. Ease of task improved over the first six months with device ON, then remained stable. Subjects reported improvements in mobility, functional vision, and quality of life with device ON. The IVI-VLV suggested self-assessed vision-related quality of life was not impacted by device implantation or usage. Conclusions: Subjects demonstrated sustained improved ease of task scores with device ON compared to OFF, indicating the device has a positive impact in the real-world setting. Translational Relevance: Our suprachoroidal retinal prosthesis shows potential utility in everyday life, by enabling an increased environmental awareness and improving access to sensory information for people with end-stage RP.

Purpose We determine the feasibility of using a home-based tablet device to monitor retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD), the benefits of weekly reminders, and the comparison with clinic-based results. Methods A customized test for tablets was designed to measure RS (within central 2°) in individuals with iAMD at weekly intervals in their home, with remote data collection. Half of the participants were randomized to receive weekly test reminders. Clinic-based microperimetric macular sensitivity results were compared to tablet results. Participation rates were analyzed at 2 months. Results Of 38 participants (mean age, 70.3 years) with iAMD enrolled in the study, 21 (55%) were using the tablet-based test at 2 months. Common reasons for inactivity were noncompatible devices (41.1%) or other technology access issues (35.3%). Participants with weekly reminders completed tests more regularly (6.6 ± 3.9 vs. 8.7 ± 4.1 days, P = 0.01), but weekly reminders showed no effect on participation rates (P = 0.69). Mean RS from the tablet device (25.03 ± 2.41 dB) was not significantly different from the clinic-based microperimetry performance (25.21 ± 2.20 dB; P = 0.58). Conclusions Regular monitoring of retinal function on a tablet device in a home setting in individuals with iAMD is feasible with results comparable to those of clinic-based microperimetry. Weekly reminders resulted in more frequent testing. Seamless ability to access technology will be important for higher participation rates. Translational relevance The use of home-monitoring on a tablet-device is promising, but adequate support for an older cohort to take up technology is required if such a tool is to be useful for long-term home monitoring.

Purpose To determine the natural history of asymptomatic, subretinal fluid (SRF) in intermediate age-related macular degeneration (iAMD) and highlight the entity of nonexudative detachment of the neurosensory retina (NEDNR). Design Prospective, observational case series. Participants Cases of iAMD with bilateral drusen >125 μm who were participating in a longitudinal study, in whom spectral-domain (SD)-OCT imaging detected asymptomatic SRF. Methods Participants underwent clinical examinations every 6 months with multimodal imaging that included infrared reflectance, fundus autofluorescence, and SD-OCT. The grading center identified eyes with SRF. Eyes with SRF ≤30 μm were monitored more regularly, whereas eyes with SRF >30 μm underwent fluorescein angiography (FA) and indocyanine green angiography (ICGA). Subretinal fluid without evidence of neovascularization or polyp was termed “NEDNR”. All cases of SRF underwent swept-source OCT angiography (SS-OCTA) to determine if choroidal neovascularization (CNV) was present and were then followed prospectively. Main Outcome Measures Natural history of iAMD eyes with SRF that had no evidence of neovascularization during the monitoring period of 30 to 54 months. Results Sixteen eyes of 12 patients with iAMD developed asymptomatic SRF over a follow-up period of 30 to 54 months. Four eyes developed occult CNV on FA and were no longer followed in this study. Four eyes developed SRF ≤30 μm, and 8 eyes developed SRF >30 μm, with 11 of the 12 eyes developing subretinal hyperreflective material (SHRM). None of these 12 eyes showed any evidence of neovascularization at the initial detection of SRF and were termed “NEDNR”. During the follow-up period of 12 to 36 months after the onset of SRF, only 1 eye developed exudative CNV. The remaining 11 eyes failed to demonstrate any abnormal choroidal vasculature on SS-OCTA, including 4 eyes with cuticular drusen in which SHRM developed into a large subfoveal vitelliform-like deposit. Conclusions Multimodal imaging is helpful for the interpretation and management of asymptomatic SRF in iAMD. In some eyes, all imaging, including SS-OCTA, failed to demonstrate subclinical neovascularization, and we use the acronym NEDNR to describe these cases. This phenotype within iAMD needs to be recognized and monitored to determine if and when treatment might be needed.