Volume 18, Number 5
THE LATEST PUBLISHED RESEARCH
Welcome to Review of Ophthalmology's Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.
INSIDE THIS ISSUE:
Progression of Atrophy Between Neovascular & Non-Neovascular AMD
Researchers compared enlargement rates over five years of follow-up in geographic atrophy vs. macular atrophy associated with macular neovascularization, as part of a retrospective, longitudinal comparative case series.
Participants included a consecutive series of age-related macular degeneration patients with GA or MA with MNV.
Atrophic regions on serial registered fundus autofluorescence (FAF) images were semi-automatically delineated, and area measurements were recorded every 6 ±3 months for the first two years of follow-up and at yearly intervals up to five years.
Main outcome measures were annual raw and square root transformed atrophy growth rates.
A total of 117 eyes of 95 patients were included (61 in the GA and 56 in the MA cohorts); 100 percent and 38.5 percent of eyes completed two and five years of follow-up, respectively. Here are some of the findings:
Researchers determined that presence of MNV was associated with a slower rate of expansion resulting in overall smaller areas of atrophy over time. They added that these findings support the hypothesis that MNV may protect against the progression of atrophy.
SOURCE: Airaldi M, Corvi F, Cozzi M, et al. Differences in long-term progression of atrophy between neovascular and non-neovascular age-related macular degeneration. Ophthalmol Retina 2022; Apr 20. [Epub ahead of print].
Macular Atrophy in Eyes with nAMD in the Ladder Trial
Genentech researchers evaluated whether macular atrophy rates differed in eyes with neovascular age-related macular degeneration treated continuously with the company’s Port Delivery System with ranibizumab (PDS; now approved with the brand name Susvimo) vs. ranibizumab given as a bolus intravitreal injection.
The preplanned exploratory analysis was based on a Phase II, multicenter, randomized, active treatment-controlled, dose-ranging study.
Participants included patients diagnosed with nAMD within nine months of screening who had received at least two previous intravitreal anti-vascular endothelial growth factor injections of any agent and were responsive to treatment.
Eyes were randomized (3:3:3:2) to treatment with the PDS (filled with a customized formulation of ranibizumab 10 mg/ml, 40 mg/ml, or 100 mg/ml and refilled pro re nata) or monthly intravitreal ranibizumab 0.5 mg injections.
Main outcome measures included macular atrophy prevalence, incidence and progression.
The analysis population consisted of 220 eyes (58, 62, 59 and 41 eyes in the PDS 10 mg/ml, 40 mg/ml, 100 mg/ml and monthly intravitreal ranibizumab 0.5 mg injection arms, respectively). Here are some of the findings:
Researchers wrote that, in the Phase II Ladder trial, no evidence of worse MA with the PDS relative to monthly intravitreal ranibizumab 0.5 mg injections was found. They advised that larger trials focusing on MA are needed to confirm this finding.
SOURCE: Jaffe GJ, Cameron B, Kardatzke D, et al. Prevalence and progression of macular atrophy in eyes with neovascular age-related macular degeneration in the Phase 2 Ladder trial of the port delivery system with ranibizumab. Ophthalmol Retina 2022; Apr 12. [Epub ahead of print].
Predicting Treatment Frequency of Ranibizumab Injections in DME
Investigators evaluated the predictors of annual treatment frequency in the second year of pro re nata intravitreal ranibizumab injections for diabetic macular edema, as part of a retrospective study.
They reviewed 65 eyes of 60 patients with center-involved DME that received PRN injections after three monthly loading doses. The central subfield thickness and qualitative findings were assessed on spectral-domain optical coherence tomography images. Investigators then sought to determine whether parameters at baseline or at the 12-month visit were associated with treatment frequency in the second year.
Here are some of the findings:
Investigators found that cumulative doses of ranibizumab injections, central subfield thickness and hyperreflective walls in the foveal cystoid spaces at 12-month visits were predictors of the frequency of ranibizumab injections during the second year of treatment for DME.
SOURCE: Nishikawa K, Murakami T, Ishihara K, et al. Factors predicting the treatment frequency of ranibizumab injections during the second year in diabetic macular edema. Jpn J Ophthalmol 2022; Apr 19. [Epub ahead of print].
Six-year Incidence of AMD and Correlation to OCT-derived Drusen Volume Measurements in a Chinese Population
Investigators reported the six-year incidence of optical coherence tomography-derived age-related changes in drusen volume and related systemic and ocular associations.
Chinese adults ages 40 years and older were assessed at baseline and six years with color fundus photography (CFP) and spectral-domain OCT. CFPs were graded for age-related macular degeneration features, and drusen volume was generated using commercially available automated software.
A total of 4,172 eyes of 2,580 participants (mean age 58.12 ±9.03 years; 51.12 percent women) had baseline and six-year follow-up CFP for grading; of them, 2,130 eyes of 1,305 participants had gradable SD-OCT images, available for analysis. Here are some of the findings:
Scientists found that AMD incidence detected at six years on CFP and correlated OCT-derived drusen volume measurement change was low. They added that older age and some systemic risk factors were associated with drusen volume change, and that their findings offer new insights into relationships between systemic risk factors and outer retinal morphology in Asian eyes.
SOURCE: Tan AC, Chee ML, Fenner BJ, et al. Six-year incidence of age-related macular degeneration and correlation to OCT-derived drusen volume measurements in a Chinese population. Br J Ophthalmol 2021; Oct 4. [Epub ahead of print].
Visual Outcomes of ForeseeHome Remote Telemonitoring: The ALOFT Study
Researchers evaluated long-term visual acuity and performance of a monitoring strategy with a self-operated artificial intelligence enabled home monitoring system in conjunction with standard care for early detection of neovascular age related macular degeneration. The retrospective review was sponsored and funded by Notal Vision.
The study included patients with dry AMD from five referral clinics. Researchers reviewed clinical data of patients monitored with the ForeseeHome (FSH) device from August 2010 to July 2020.
Main outcome measures included:
A total of 3,334 eyes of 2,123 patients were reviewed (mean age: 74 ±8 years) were monitored for a mean duration of 3.1 ±2.4 years, with a total of 1,706,433 tests in 10,474 eye-monitoring years. Here are some of the findings:
Researchers concluded that patients in the FSH monitoring program showed excellent long-term VA years after conversion to nAMD.
SOURCE: Mathai M, Reddy S, Elman MJ, et al. Analysis of the Long-term visual Outcomes of ForeseeHome Remote Telemonitoring - The ALOFT study. Ophthalmol Retina 2022; April 25. [Epub ahead of print].
Predominantly Persistent Intraretinal Fluid in CATT
Investigators described predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity, along with retinal anatomic findings at long-term follow-up in eyes treated with pro re nata ranibizumab or bevacizumab for neovascular age-related macular degeneration.
The study involved a cohort within the Participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment.
Investigators assessed IRF presence on optical coherence tomography scans at baseline and monthly follow-up visits by the Duke OCT Reading Center. PP-IRF through week 12, year 1 and year 2 were defined as IRF presence at baseline and ≥80 percent of follow-up visits. Among eyes with baseline IRF, mean VA scores (letters) and change from baseline were compared between eyes with and without PP-IRF. Adjusted mean VA scores and change from baseline were also calculated using linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Outcomes were also adjusted by concomitant predominantly persistent subretinal fluid.
Primary outcome measures included:
Here are some of the findings:
Investigators wrote that approximately one-quarter of eyes had PP-IRF through year two. PP-IRF through year one was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA, although PP-IRF through year two was independently associated with worse long-term VA and scar development, investigators added.
SOURCE: Core JQ, Pistilli M, Hua P, et al; Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group. Predominantly persistent intraretinal fluid in the comparison of age-related macular degeneration treatments trials (CATT). Ophthalmol Retina 2022; Apr 8. [Epub ahead of print].
Thiazolidinedione Use & Retinal Fluid in CATT
Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular edema and increased vascular endothelial cell permeability. Macular neovascularization in age-related macular degeneration and associated fluid leakage may be influenced by thiazolidinediones. This study aimed to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity in patients treated with bevacizumab or ranibizumab for neovascular AMD.
The secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials included participant self-reported diabetes status and thiazolidinedione usage at baseline. Visual acuity; intraretinal, subretinal and subretinal pigment epithelium fluid; and foveal thickness of retinal layers were evaluated at baseline and during two-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularization lesion type in multivariable regression models.
Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference -6.2 letters; p=0.02), increased intraretinal fluid at year two (75 vs. 50 percent, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year one (difference -75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year one (difference -41.9 um; p=0.001) and year two (difference -43.3 um; p=0.001).
In this exploratory analysis, diabetic patients taking thiazolidinediones who were treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and increased IRF compared to patients not taking thiazolidinediones.
SOURCE: Core JQ, Hua P, Daniel E, et al; Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group. Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials. Br J Ophthalmol 2022; Apr 15. [Epub ahead of print].
Macular Choroidal Thickness and Risk of Referable DR in Type 2 Diabetes
Researchers looked at the associations between choroidal thickness and two-year incidence of referable diabetic retinopathy, as part of a prospective cohort study.
Patients with type 2 diabetes in Guangzhou, China, ages 30 to 80 years, underwent comprehensive exams, including standard 7-field fundus photography. Macular CT was measured using a commercial swept-source optical coherence tomography device (DRI OCT Triton, Topcon). The relative risk (RR) with 95% confidence intervals helped quantify the association between CT and new-onset RDR. The prognostic value of CT was assessed using the area under the ROC curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
Here are some of the findings:
Researchers determined that CT thinning, measured by SS-OCT, was an early imaging biomarker for the development of RDR, suggesting that alterations in CT play an essential role in DR occurrence.
SOURCE: Wang W, Li L, Wang J, et al. Macular choroidal thickness and the risk of referable diabetic retinopathy in type 2 diabetes: A 2-year longitudinal study. Invest Ophthalmol Vis Sci 2022; Apr 1;63(4):9.
Anti-VEGF Therapy for ME Secondary to HRVO vs. CRVO: SCORE2 Report 18
Intravitreal anti-vascular endothelial growth factor injections are commonly used to treat eyes with macular edema secondary to hemiretinal vein occlusion or central retinal vein occlusion. Information on whether differences exist in outcomes after anti-VEGF therapy can help guide treatment for the different disease types.
Investigators compared baseline characteristics, treatment burden and outcomes of macular edema treatment in participants with HRVO with those of participants with CRVO.
This post hoc outcome analysis from the Study of Comparative Treatments for Retinal Vein Occlusion 2 randomized clinical trial included 362 participants with macular edema caused by HRVO or CRVO, treated at 66 U.S. sites. Randomization began in September 2014, and the last month 24 follow-up visit occurred in February 2018. Data were analyzed from April 2020 to May 2021.
Eyes were initially randomized to six monthly intravitreal injections of aflibercept or bevacizumab, and were treated according to protocol between months six and 12 depending on six-month outcome. After month 12, patients were treated per investigator discretion and observed through month 60.
The main outcome was mean visual acuity letter score (VALS).
Of 362 included patients, 157 (43.4 percent) were female, and the mean age was 68.9 ±12 years. Outcome data were analyzed up to month 24 owing to substantial missing data at later visits. Here are some of the findings:
Investigators found Black race was more prevalent among participants with HRVO than CRVO and that no differences were observed in the frequency of treatments for macular edema between eyes with CRVO and HRVO, although eyes with CRVO presented with worse visual acuity and more macular edema on average than eyes with HRVO. The magnitude of VALS improvement, central retinal thickness in response to anti-VEGF therapy and treatment burden were similar between the groups, investigators added.
SOURCE: Scott IU, Oden NL, VanVeldhuisen PC, et al.; SCORE2 Study Investigator Group. Baseline characteristics and outcomes after anti-vascular endothelial growth factor therapy for macular edema in participants with hemiretinal vein occlusion compared with participants with central retinal vein occlusion: Study of comparative treatments for retinal vein occlusion 2 (SCORE2) Report 18. JAMA Ophthalmol 2022; Mar 24. [Epub ahead of print].
Efficacy of Tocilizumab for Non-infectious Uveitis in STOP-Uveitis Study
Researchers used a composite endpoint scoring system to assess efficacy of two doses of the intravenous arthritis drug tocilizumab (TCZ) in eyes with non-infectious uveitis. They used data from the STOP-Uveitis Study (a Phase II multicenter, randomized interventional clinical trial), in which monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month six were administered.
Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiography; and (5) steroid taper. Each component of the grading system was graded as: (+1) improvement; (−1) worsening; or (0) no change, based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups.
Thirty-seven patients were analyzed. Here are some of the findings:
Researchers found that both doses of intravenous TCZ were effective in improving or maintaining stability in patients using the composite endpoint scoring system. They found that such a composite scoring system may be a better measure to assess efficacy outcomes vs. only vitreous haze or other single outcome measures.
SOURCE: Hassan M, Sadiq MA, Ormaechea MS, et al. Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study. Br J Ophthalmol 2022; Apr 4. [Epub ahead of print].
The following companies presented these findings at the Association for Research in Vision and Ophthalmology annual meeting, May 1-4, in Denver and virtually.
Iveric Bio Presents Post Hoc Analysis from GATHER1
Iveric Bio announced a post hoc analysis evaluating the reduction in geographic atrophy lesion growth observed in patients receiving Zimura (avacincaptad pegol) compared to patients receiving sham in the completed GATHER1 clinical trial would be presented at the Retinal World Congress in Fort Lauderdale, Fla. The study analyzes the reduction in GA lesion growth, in a subset of GATHER1 patients, based on the distance of a patient’s GA lesion from the foveal center at baseline. In line with the overall results of GATHER1, a reduction of GA lesion growth in patients receiving Zimura as compared to patients receiving sham was consistently observed across all baseline distances from the foveal center, the company says. Read more.
Stealth Drug Fails to Meet Primary Endpoints in ReCLAIM-2 Trial
Stealth BioTherapeutics announced that data from its Phase II ReCLAIM-2 trial evaluating elamipretide in patients with geographic atrophy secondary to dry age-related macular degeneration reveal the trial didn’t meet its primary endpoints (mean changes in low-luminance visual acuity and GA). However, it added that a secondary endpoint showed that elamipretide improved visual function for GA patients. Read more.
Researchers Discover Cellular Events Preceding Eye Disease
Molecular and cellular changes in rod photoreceptors are detectable in a mouse model of retinal degeneration several days prior to observable morphological changes, according to National Eye Institute researchers. The findings, published in Human Molecular Genetics, could point to new therapeutic targets for retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. The results provide a temporal framework for understanding the role of mitochondria-related, metabolic, and calcium signaling pathways in early stages preceding the onset of retinal neurodegeneration. Read more.
UCI Study Suggests Base Editing Can Help Treat LCA
SOURCE: National Eye Institute, April 2022
Lineage Announces a Fifth Cell Therapy Program
Annexon Completes Enrollment for ARCHER Phase II Trial
Annexon completed enrollment for the Phase II ARCHER trial evaluating its anti-C1q candidate, ANX007, in patients with geographic atrophy. Annexon says it plans to report topline data on the primary endpoint in the first half of 2023 following 12 months of treatment, with full data expected after the six-month off-treatment period. Read more.
Adverum Proceeds with IND Amendment for ADVM-022 Phase II Trial
Per its request, Adverum Biotechnologies received FDA feedback related to its planned Phase II trial of ADVM-022 in wet age-related macular degeneration. Adverum requested the FDA’s input to ensure a complete filing of its Investigational New Drug amendment for the trial, designed to evaluate the 2 X 1011 vg/eye dose and a new lower 6 X 1010 vg/eye dose of ADVM-022, along with new enhanced prophylactic steroid regimens, including local steroids and a combination of local and systemic steroids. Read more.
SOURCE: Adverum Biotechnologies, April 2022
RetinAI Discovery Gets FDA Nod
RetinAI Medical announced FDA 510(k) clearance of RetinAI Discovery, the company’s image and data management platform. Read more.
Source: RetinAI Medical, May 2022
Phospholine Iodide Gets Orphan Drug Designation
Fera pharmaceuticals' drug Phospholine Iodide (echothiophate iodide for ophthalmic solution) was just granted Orphan Drug Designation by the FDA for the treatment of Stargardt disease. Read more.
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