Dataset Information

Relationship between retinal fluid characteristics and vision in neovascular age-related macular degeneration: HARBOR post hoc analysis.

ABSTRACT:

Purpose

To evaluate the relationship between retinal fluid location, amount/severity, and vision with ranibizumab-treated neovascular age-related macular degeneration (nAMD).

Methods

In the phase 3 HARBOR trial (NCT00891735), treatment-naive patients with nAMD received ranibizumab 0.5 or 2.0 mg through month 24. This post hoc analysis included eyes with subretinal fluid (SRF) and/or intraretinal fluid (IRF) at screening, baseline, or week 1, and optical coherence tomography data at months 12 and 24 (n = 917). Outcomes were best-corrected visual acuity (BCVA) change from baseline and proportion of eyes with 20/40 or better vision at months 12 and 24. Eyes were stratified by the location, amount, and/or severity of fluid.

Results

At baseline, 86% and 63% of eyes had SRF and IRF, respectively. Among eyes with residual SRF, mean BCVA gains at each time point were greater in eyes with central versus noncentral SRF; location did not affect the odds of having 20/40 or better vision over 24 months. Eyes with 20/40 or better BCVA at month 12 had significantly lower SRF thickness versus eyes with worse vision; however, no difference was apparent at month 24. Vision was comparatively worse in eyes with residual IRF at months 12 and 24; location and severity did not appear to affect this outcome.

Conclusion

Residual IRF was associated with worse vision outcomes, regardless of location/severity, whereas, despite continued treatment, residual SRF was not associated with worse vision outcome at 24 months, regardless of location/thickness. These data suggest complex relationships between residual fluid, severity, and vision.

SUBMITTER: Sadda S

PROVIDER: S-EPMC9666309 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationship between retinal fluid characteristics and vision in neovascular age-related macular degeneration: HARBOR post hoc analysis.

Sadda SriniVas S Holekamp Nancy M NM Sarraf David D Ebraheem Adel A Fan Wenying W Hill Lauren L Blotner Steve S Spicer Galin G Gune Shamika S

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 20220610 12

<h4>Purpose</h4>To evaluate the relationship between retinal fluid location, amount/severity, and vision with ranibizumab-treated neovascular age-related macular degeneration (nAMD).<h4>Methods</h4>In the phase 3 HARBOR trial (NCT00891735), treatment-naive patients with nAMD received ranibizumab 0.5 or 2.0 mg through month 24. This post hoc analysis included eyes with subretinal fluid (SRF) and/or intraretinal fluid (IRF) at screening, baseline, or week 1, and optical coherence tomography data a ...[more]

PMID: 35687173

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Project description:PurposeTo evaluate retinal fluid volume data extracted from optical coherence tomography (OCT) scans by artificial intelligence algorithms in the treatment of neovascular age-related macular degeneration (NV-AMD).DesignPerspective.MethodsA review was performed of retinal image repository datasets from diverse clinical settings.SettingsClinical trial (HARBOR) and trial follow-on (Age-Related Eye Disease Study 2 10-year Follow-On); real-world (Belfast and Tel-Aviv tertiary centers).Patients24,362 scans of 1,095 eyes (HARBOR); 4,673 of 880 (Belfast); 1,470 of 132 (Tel-Aviv); 511 of 511 (Age-Related Eye Disease Study 2 10-year Follow-On). ObservationProcedures: Vienna Fluid Monitor or Notal OCT Analyzer applied to macular cube scans. OutcomeMeasures: Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) volumes.ResultsThe fluid volumes measured in neovascular AMD were expressed efficiently in nanoliters. Large ranges that differed by population were observed at the treatment-naïve stage: 0-3,435 nL (IRF), 0-5,018 nL (SRF), and 0-10,022 nL (PED). Mean volumes decreased rapidly and consistently with anti-vascular endothelial growth factor therapy. During maintenance therapy, mean IRF volumes were highest in Tel-Aviv (100 nL), lower in Belfast and HARBOR-Pro Re Nata, and lowest in HARBOR-monthly (21 nL). Mean SRF volumes were low in all: 30 nL (HARBOR-monthly) and 48-49 nL (others).ConclusionsQuantitative measures of IRF, SRF, and PED are important biomarkers in NV-AMD. Accurate volumes can be extracted efficiently from OCT scans by artificial intelligence algorithms to guide the treatment of exudative macular diseases. Automated fluid monitoring identifies fluid characteristics in different NV-AMD populations at baseline and during follow-up. For consistency between studies, we propose the nanoliter as a convenient unit. We explore the advantages of using these quantitative metrics in clinical practice and research.

Project description:IntroductionThe aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment.MethodsARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive.ResultsOf 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16-100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non-injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs. + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non-injection-intensive patients (central retinal thickness change from baseline to Week 104: - 160 [154] vs. - 167 [136] µm).ConclusionsIn ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination.Clinicaltrialsgov Identifier: NCT02581891.

Project description:ImportanceMost neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity.ObjectiveTo evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase.Design, setting, and participantsThis was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up. The 3 home-monitoring tests evaluated included the following: (1) the KeepSight Journal (KSJ [International Macular and Retinal Foundation]), which contains paper-based near-vision tests presented as word puzzles, (2) the MyVisionTrack (mVT [Genentech]) vision-monitoring mobile app, viewed on an Apple mobile operating system-based device, and (3) the MultiBit (MBT [Visumetrics]) app, viewed on an Apple mobile operating system-based device. Participants were asked to test weekly; mVT and MBT scores were transmitted automatically, and KSJ scores were returned to the research office every 6 months. Raw scores between hospital follow-ups were summarized as averages. Patients were recruited from 6 UK hospital eye clinics and were 50 years and older with at least 1 eye first treated for active nAMD for at least 6 months or longer to a maximum of 42 months before approach. Participants were stratified by time since starting treatment. Study data were analyzed from May to September 2021.ExposuresThe KSJ, mVT, and MBT were compared with the reference standard (in-hospital ophthalmologist examination).Main outcomes and measuresEstimated area under receiver operating characteristic curve (AUROC). The study had 90% power to detect a difference of 0.06, or 80% power to detect a difference of 0.05, if the AUROC for 2 tests was 0.75.ResultsA total of 297 patients (mean [SD] age, 74.9 [6.6] years; 174 female [58.6%]) were included in the study. At least 1 hospital follow-up was available for 312 study eyes in 259 participants (1549 complete visits). Median (IQR) home-monitoring testing frequency was 3 (1-4) times per month. Estimated AUROC was less than 0.6 for all home-monitoring tests, and only the KSJ summary score was associated with lesion activity (odds ratio, 3.48; 95% CI, 1.09-11.13; P = .04).Conclusions and relevanceResults suggest that no home-monitoring vision test evaluated provided satisfactory diagnostic accuracy to identify active nAMD diagnosed in hospital eye service follow-up clinics. Implementing any of these evaluated tests, with ophthalmologists only reviewing test positives, would mean most active lesions were missed, risking unnecessary sight loss.

Project description:IntroductionSwitching to an alternative anti-vascular endothelial growth factor (anti-VEGF) agent has been suggested for patients with neovascular age-related macular degeneration (nAMD) who have a suboptimal response to initial therapy. However, post hoc analyses of some studies have shown that continuation of initial anti-VEGF therapy is, in many cases, associated with stable visual outcomes or gradual gains.MethodsThis ARIES (ClinicalTrials.gov Identifier: NCT02581891) post hoc analysis describes outcomes in patients with treatment-naïve nAMD receiving treat-and-extend intravitreal aflibercept (IVT-AFL) for 104 weeks, who were identified as meeting criteria for an early hypothetical switch. Patients were categorized retrospectively according to six criteria (presence of central intraretinal and/or subretinal fluid at week 8 or 24, with/without a next planned treatment interval ≤ 8 weeks, and with/without gains in best-corrected visual acuity [BCVA] ≤ 5 letters [with absolute BCVA < 70 letters]).ResultsHypothetical switch criteria were largely met due to the presence of central subretinal fluid rather than intraretinal fluid. Depending on the criterion, 8-46% of patients were considered to be hypothetical switchers. BCVA outcomes were not worse in the hypothetical switchers, irrespective of criteria. Using criteria of intraretinal/subretinal fluid at week 24 and a next planned treatment interval ≤ 8 weeks, mean changes in BCVA (letters) from baseline in hypothetical switchers and non-switchers were: + 6.1 (95% confidence interval [CI] 3.4, 8.8) and + 6.6 (95% CI 4.7, 8.6), respectively, at week 24; + 8.2 (95% CI 5.0, 11.3) and + 7.5 (95% CI 5.3, 9.7), respectively, at week 52; and + 5.7 (95% CI 1.3, 10.1) and + 3.4 (95% CI 0.1, 6.7), respectively, at week 104.ConclusionsIn newly diagnosed nAMD, there appears little rationale for early switching from IVT-AFL since, with continuous proactive treatment, comparable visual gains can be achieved by patients meeting hypothetical switch criteria compared with those who initially respond well on a treat-and-extend regimen. However, further prospective studies are needed.Trial registrationClinicalTrials.gov Identifier: NCT02581891. Video summary of the ARIES Post Hoc Analysis "Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration" (MP4 54283 KB).

Project description:PurposeFluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity.MethodsTwo eyes of a White woman in her 90s with anti-vascular endothelial growth factor treated bilateral type 3 neovascularization secondary to age-related macular degeneration were osmicated, prepared for submicrometer epoxy resin sections, and correlated to eye-tracked spectral domain OCT. Examples of intraretinal tissue fluid were sought among similarly prepared donor eyes with fibrovascular scars, in a web-based age-related macular degeneration histopathology resource. Fluid stain intensity was quantified in reference to Bruch's membrane and the empty glass slide.ResultsExudative fluid by OCT was slightly reflective and dynamically responded to anti-vascular endothelial growth factor. On histology, this fluid stained moderately, possessed a smooth and homogenous texture, and contained blood cells and fibrin. Nonexudative fluid in degenerative cysts and in outer retinal tubulation was minimally reflective on OCT and did not respond to anti-vascular endothelial growth factor. By histology, this fluid stained lightly, possessed a finely granular texture, and contained mainly tissue debris. Quantification supported the qualitative impressions of fluid stain density. Cells containing retinal pigment epithelium organelles localized to both fluid types.ConclusionsHigh-resolution histology of osmicated tissue can distinguish between exudative and nonexudative fluid, some of which is transudative.Translational relevanceOCT and histological features of different fluid types can inform clinical decision-making and assist in the interpretation of newly available automated fluid detection algorithms.

Dataset Information

Relationship between retinal fluid characteristics and vision in neovascular age-related macular degeneration: HARBOR post hoc analysis.

Purpose

Methods

Results

Conclusion

Publications

Relationship between retinal fluid characteristics and vision in neovascular age-related macular degeneration: HARBOR post hoc analysis.

Similar Datasets

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