Neovascular Age-related Macular Degeneration Research Articles

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Quantification of Choroidal Vascular Hyperpermeability on Ultra-Widefield Indocyanine Green Angiography in Macular Neovascularization.

To obtain a quantitative parameter for the measurement of choroidal vascular hyperpermeability (CVH) on ultra-widefield indocyanine green angiography (UWICGA) using an objective analysis method in macular choroidal neovascularization (CNV). A total of 113 UWICGA images from 113 subjects were obtained, including with 25 neovascular age-related macular degeneration (nAMD), 37 with polypoidal choroidal vasculopathy (PCV) (19 with thin-choroid and 18 with thick-choroid), 33 with pachychoroid neovasculopathy (PNV), and 18 age-matched controls. CVH was quantified on a gray image by the subtraction of 2 synchronized UWICGA images of early and late phases. The measured CVH parameter was compared with human graders and among CNV subtypes and correlated with choroidal vascular density (CVD) and subfoveal choroidal thickness (SFCT). The mean CVH values were 28.58 ± 4.97, 33.36 ± 8.40, 33.61 ± 11.50, 42.19 ± 13.25, and 43.59 ± 7.86 in controls and patients with nAMD, thin-choroid PCV, thick-choroid PCV, and PNV, respectively (p < 0.001). CVH was higher in thick-choroid PCV and PNV compared to the other groups (all p ≤ 0.006). The measured CVH value positively correlated with those reported by human graders (p < 0.001), CVD, and SFCT (p = 0.001 and p < 0.001, respectively). CVH can be measured objectively using quantitative UWICGA analysis. The CVH parameter differs among macular CNV subtypes and correlates with CVD and SFCT.

INTERSESSION REPEATABILITY OF READING PERFORMANCE MEASURES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To assess the intersession repeatability of reading performance measures in patients with previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen). Ninety-one patients (91 eyes) with a diagnosis of previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen) were prospectively enrolled. Reading performance metrics were assessed using Radner charts, and these measurements were repeated after 7 days to obtain the intersession repeatability. To test repeatability, we calculated the intraclass correlation coefficient, the 95% coefficient of repeatability, and the coefficient of variation for each reading parameter: 1) reading acuity (RA-LogRAD); 2) maximal reading speed-words per minute; 3) RA score (RA score-LogRAD); and 4) critical print size-LogRAD. Mean ± standard deviation best-corrected visual acuity was 0.13 ± 0.01 logMAR [range: 0.00-0.30 logMAR]. The intraclass correlation coefficient values indicated a good reliability for all the analyzed metrics (0.901 for RA; 0.859 for max reading speed; 0.906 for RA score; and 0.868 for critical print size). The coefficient of repeatability was 0.2 LogRAD for RA, 63.2 words per minute for max reading speed, 0.2 LogRAD for RA score, and 0.2 LogRAD for critical print size. Coefficient of variation was 5.5% for RA, 8.9% for max reading speed, 5.8% for RA score, and 6.9% for critical print size. Reading performance metrics are characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. Our findings may grant the employment of such measures in trials assessing the visual outcome in these patients.

A pilot image-based analysis of changes in pigment epithelial detachment composition in neovascular age-related macular degeneration

We report changes in pigment epithelial detachment composition indices (PEDCI), derived using an automated algorithm, in six eyes with neovascular age-related macular degeneration (nAMD) through 84 months. Changes in serous, neovascular, and fibrous components (PEDCI-S, N, and F, respectively) were compared. PEDCI-S reduced from 0.60 ± 0.21 (baseline) to 0.17 ± 0.20 (84 months; P = 0.03). PEDCI-N showed a significant increase from 0.30 ± 0.15 to 0.71 ± 0.21 (P = 0.01), whereas PEDCI-F changed minimally (0.10 ± 0.09 to 0.13 ± 0.11; P = 0.69) at 84 months. Overall, PEDCI-S showed a gradual reduction, whereas PEDCI-N increased relative to other constituents through 84 months. PEDCI-F, a surrogate marker of scarring, was not predictive of final visual acuity.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.

To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage." Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed. Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 ± 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.

The Effect of Blue-light Filtering Intraocular Lenses on the Development and Progression of Macular Atrophy in Eyes With Neovascular Age-related Macular Degeneration

PurposeTo assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD). DesignRetrospective clinical cohort study. MethodsnAMD patients with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All OCT scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. Using the Heidelberg software, the area of MA was manually evaluated and calculated (mm2) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event. ResultsIncluded were 373 eyes of 373 patients (mean age 78.6±6.7 years at surgery, 67.4% females). 206 eyes were implanted with BLF IOLs and 167 with non-BLF IOLs with comparable follow-up times (3164±1420 days vs. 3180±1403 days, respectively, P=0.908), and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine pre-existing and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P=0.598 and P=0.399, respectively). Both univariate Kaplan-Meier (P=0.366) and multivariate Cox regression analysis adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (HR 1.236, 95% CI 0.784-1.949, P=0.363). Final MA area at the last visit was 5.14±4.71mm2 for BLF IOLs and 8.56±9.17mm2 for non-BLF IOLs (P=0.028), with the mean annual MA area increase of 0.78±0.84mm2 and 1.26±1.32mm2, respectively (P=0.042). ConclusionsBLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of nAMD patients.

An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen: Age-Related Eye Disease Study Report Number 42

PurposeTo update the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale for risk of late age-related macular degeneration (AMD), including incorporation of reticular pseudodrusen (RPD), and to perform external validation on the AREDS2. DesignPost hoc analysis of two clinical trial cohorts: AREDS and AREDS2. ParticipantsParticipants with no late AMD in either eye at baseline in AREDS (n=2719) and AREDS2 (n=1472). MethodsFive-year rates of progression to late AMD were calculated according to levels 0-4 on the Simplified Severity Scale, following two updates: (i) non-central GA considered part of the outcome rather than a risk feature, and (ii) scale separation according to RPD status (determined by validated deep learning grading of color fundus photographs).Main outcome measures:Five-year rate of progression to late AMD (defined as neovascular AMD or any GA). ResultsIn the AREDS, following the first scale update, the five-year rates of progression to late AMD for levels 0-4 were 0.3%, 4.5%, 12.9%, 32.2%, and 55.6%, respectively. Following both updates, the proportion progressing to late AMD by five years was 8.4% in participants without RPD and 40.6% in those with RPD. As the final Simplified Severity Scale, the five-year progression rates for levels 0-4, respectively, were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, for participants without RPD at baseline, and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, for participants with RPD at baseline. In external validation on the AREDS2, for levels 2-4, the progression rates were similar, at 15.0%, 27.7%, and 45.7% (RPD absent) and 26.2%, 46.0%, and 73.0% (RPD present), respectively. ConclusionsThe AREDS AMD Simplified Severity Scale has been modernized with two important updates. The new scale for individuals without RPD has five-year progression rates of ∼0.5%, 4%, 12%, ∼25%, and 50%, such that the rates on the original scale remain accurate. The new scale for individuals with RPD has five-year progression rates of 3%, 8%, ∼30%, ∼60%, and ∼70%, i.e., approximately double for most levels. This scale fits updated definitions of late AMD, has increased prognostic accuracy, appears generalizable to similar populations, but remains simple for broad risk categorization.

Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration

PurposeTo evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan–vascular endothelial growth factor (VEGF) receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy. DesignPhase 1, multicenter, prospective, open-label, dose-escalation trial. ParticipantsPatients with wAMD and evidence of prior anti-VEGF therapy response. MethodsPatients received a single intravitreal injection of EYP-1901. Main Outcome MeasuresThe primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates. ResultsSeventeen patients enrolled in the 440 μg (3 patients), 1030 μg (1 patient), 2060 μg (8 patients), and 3090 μg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline (CFB) in BCVA was –3.7 letters and –5.4 letters at 6 and 12 months. Mean CFB in CST was +1.7 μm and +2.3 μm at 6 and 12 months. Reduction in treatment burden was 76% and 72% at 6 and 12 months. Of 16 study eyes, 13, 9, and 6 were injection-free up to 3, 6, and 12 months. ConclusionIn the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing Phase 2 and planned Phase 3 trials to assess efficacy and safety.

Psychophysical, electrofunctional, and morphological evaluation in naïve neovascular AMD patients treated with intravitreal anti-VEGF.

The aim of this study was to investigate the retinal morpho-functional characteristics of patients with neovascular wet age-related macular degeneration (nAMD) treated with intravitreal injection (IV) of aflibercept (AFL). The study was conducted on 35 patients previously diagnosed with type 1 nAMD who received a fixed-dosing regimen of aflibercept injections over 12 months. The goal was to assess trends in visual abilities over time by measuring visual acuity (VA), contrast sensitivity (CS), visual evoked potentials (VEPs), and spectral domain-optical coherence tomography (SD-OCT). The same psychophysical, electro-functional, and morphological tests administered at baseline (T0) were repeated 4 to 8 weeks after the last aflibercept injection (Tn), resulting in a total of six examinations. At Tn, all subjects exhibited improved VA for both far and near distances compared to values detected at T0. Similarly, VEP amplitude and latency values at Tn showed a greater P100 improvement than those observed at T0. Additionally, the CS examination at Tn demonstrated improvement, particularly at high spatial stimulation frequencies. The Tn SD-OCT results highlighted a reduction in macular thickness compared to T0 values. This exploratory research indicates that intravitreal injections of AFL, following a fixed-dosing regimen, represent a valuable therapeutic approach for enhancing visual performance. This conclusion is supported by comprehensive statistical analysis of psychophysical, electro-functional, and morphological examinations within the same group of patients with nAMD, as demonstrated for the first time.

Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry

PurposeWe used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the two pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the two monthly treatment arms from the clinical trial. DesignRetrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data SubjectsAll treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for one year from either the CATT or the IRIS Registry MethodsPatients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all non-imaging based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity. ResultsWe identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n= 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n=261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (Exact Matching: 1.9 letters +/- 14.0 vs. IPSW: 2.8 letters +/- 15.0 letters, p=0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (Exact Matching: 2.4 letters +/- 15.4 vs. IPSW: 2.1 letters +/- 16.0 letters, p=0.79). ConclusionsBoth exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared to the clinical trial.

Systemic Arterial Hypertension and Ophthalmohypertension as Independent Risk Factors for Poor Response to Antiangiogenic Therapy with Line 1 Drugs in Neovascular Age-related Macular Degeneration

Purpose: to assess hypertension as a risk factor for a poor response to antiangiogenic therapy.Patients and methods. Systemic blood pressure was studied in 84 patients (92 eyes) with age-related macular degeneration who were treated with intravitreal injections of Eilea in a fixed mode.Results. It was found that significantly more often a poor response to treatment in the form of partial non-resposing or progression of the disease, despite treatment, is associated with elevated diastolic blood pressure (DBP, p = 0.01). An increase in systolic (SBP) blood pressure in patients with arterial hypertension and AMD is accompanied by an increase in eye perfusion pressure (p &lt; 0.01), which apparently worsens the absorption of angiostatics and causes a poor response to treatment. According to the results of the study, the most favorable corridor of SBP values associated with ideal response is in the range of values of 104–140 mm Hg, and DBP is in the range of 68–80 mm Hg st., which should be taken as the recommended parameters of blood pressure in patients with nVMD receiving a course of treatment for Eylea. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to treatment with nVMD with line 1 anti-VEGF therapy drugs. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to nVMD treatment with line 1 anti-VEGF therapy drugs. The biomarker associated with the ideal response was — 12.6 mm Hg, and the corridor of recommended values — 11–21 mm Hg. An increase in ophthalmotonus with the output of personalized values beyond this corridor seems to worsen the outcome of treatment.Conclusion. The identification of modifiable risk factors is extremely important in practical ophthalmology, as it opens up the possibility of increasing the patient’s chances of a better treatment outcome. Modifiable risk factors are valuable and powerful tools that replenish our arsenal. Information about them is important not only in the treatment of AMD, but can also be the patient’s motivation for switching to a healthy lifestyle and reducing the risk of developing the disease.

Obesity as a Risk Factor for the Ineffectiveness of Antiangiogenic Treatment of Neovascular Age-related Macular Degeneration

Purpose: evaluation of obesity as a risk factor for poor outcome (ineffectiveness) of antiangiogenic treatment of patients with neovascular AMD.Patients and methods. Body mass index (BMI) was studied in 84 patients (92 eyes) with neovascular AMD who were treated with intravitreal injections of Eilea in a fixed mode.Results. It was found that a poor treatment outcome in the subgroup with disease progression was associated with obesity of 1–2 degrees; the average BMI in this subgroup (with a deterioration in the morphostructural parameters of the retina) significantly exceeds the indicators of ideal respondents, for comparison: 31.5 ± 0.8 versus 28.6 ± 1.1 (p = 0.04); and the incidence of obese individuals is dominant: 72 %. At the same time, a moderate inverse reliable relationship of BMI with another risk factor — systolic blood pressure (SBP) was found. In this regard, we suggested that obesity indirectly affects the outcome of treatment, since it is “tied” to systolic blood pressure (p = 0.01). An argument in favor of this assumption is a higher correlation coefficient of SAD with the outcome of treatment. The authors hypothesized that obesity contributes to the development of hypertension by increasing the risk of poor outcome of nAMD treatment. The hypothesis explained the association of obesity with the progression of morphostructural changes in the retina in the group of non-responsents with nAMD.Conclusion. Studies have demonstrated a causal relationship between obesity and the outcome of antiangiogenic treatment of patients with nAMD. The data obtained allow us to attribute OBESITY to moderate risk factors for a poor outcome of antiangiogenic treatment of patients with nAMD. Taking into account the fact that OBESITY is a modifiable factor that can be eliminated with certain efforts, opportunities are revealed to reduce the risk of an unfavorable outcome of treatment of patients with nAMD.

인공지능 기반 신생혈관성 나이관련황반변성 진단보조소프트웨어 사용자 인터페이스 개선 연구

With the recent development of Software as a Medical Device (SaMD), the significance of reducing use errors in medical devices is increasing. In this study, we conducted a formative evaluation of Artificial Intelligence (AI)-based software for ophthalmic image detection and diagnosis. The software automatically displays the presence or absence of neovascular age-related macular degeneration using fundus images to assist medical personnel in making diagnostic decisions. We aimed to find ways to reduce the number of use errors in formative evaluations. For this purpose, we conducted usability testing by performing tasks based on use scenarios for usability formative evaluations with intended users in their intended use environments, and then modified the user interface to reduce use errors. The initial formative evaluation revealed errors in utilizing the capture and dragand- drop functions for uploading fundus images, checking analysis results, and perform logout procedures. To reduce use errors, we improved the function by relocating the capture icon, displaying a hand-shaped cursor during dragging, inserting a fundus position guide, and eliminating the drag-and-drop function. We have also enhanced the design to present analytics results in a more intuitive manner and added a separate logout button to reduce the risk of use error. As a result, the number of use errors in the formative evaluation decreased from six to one in the summative evaluation. The development of ophthalmic image detection and diagnosis assistant software that reflects these improvements is expected to enhance user safety, usability, and reduce use errors.

Risk Factor of Neovascular Age­related Macular Degeneration Progression after Cataract Surgery

The prevalence of late AMD, including neovascular AMD or geographic atrophy, and cataract in the same eye after age 80 years is estimated to be 12 and 68 %, respectively. There is currently no consensus on whether cataract surgery is beneficial or harmful for people with dry AMD. Although cataract surgery has been reported to provide better visual outcomes in eyes with AMD 6 months after surgery compared with previously followed eyes, it is unclear whether the timing of surgery relative to the start of AMD treatment influences long-term outcomes. The question of risk factors predisposing to the occurrence of exudation after cataract surgery in people with nAMD remains controversial.

The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported “a little trouble seeing” (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported “a lot of trouble seeing/blindness” (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P &lt; .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study

Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50-89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258. Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. RegenxBio.

The promise of long-term treatment for neovascular age-related macular degeneration

The promise of long-term treatment for neovascular age-related macular degeneration