Dataset Information

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials.

ABSTRACT:

Background

Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

Methods

Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models.

Results

Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference -6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference -75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference -41.9 um; p=0.001) and year 2 (difference -43.3 um; p=0.001).

Conclusions

In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones.

Trial registration number

ClinicalTrials.gov NCT00593450.

SUBMITTER: Core JQ

PROVIDER: S-EPMC10245276 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials.

Core Jason Q JQ Hua Peiying P Daniel Ebenezer E Grunwald Juan E JE Jaffe Glenn G Maguire Maureen G MG Ying Gui-Shuang GS

The British journal of ophthalmology 20220415 7

<h4>Background</h4>Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patie ...[more]

PMID: 35428655

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Project description:ObjectiveTo describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).DesignProspective cohort study within a randomized clinical trial.ParticipantsPatients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).MethodsEyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation.Main outcome measuresScar formation.ResultsScar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4-3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1-1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7-3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7-3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1-2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3-2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5-0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars.ConclusionsApproximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.

Project description:PurposeTo describe morphologic and visual outcomes in eyes with angiographic cystoid macular edema (CME) treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (nAMD).DesignProspective cohort study within a randomized clinical trial.ParticipantsA total of 1185 CATT study subjects.MethodsBaseline fluorescein angiography (FA) images of all CATT study eyes were evaluated for CME. Grading of other characteristics on optical coherence tomography (OCT) and photographic images at baseline and during 2-year follow-up was completed by readers at the CATT Reading Centers. Three groups were created on the basis of baseline CME and intraretinal fluid (IRF) status: (1) CME, (2) IRF without CME, (3) neither CME nor IRF.Main outcome measuresVisual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2.ResultsAmong 1131 participants with images of sufficient quality for determining CME and IRF at baseline, 92 (8.1%) had CME, 766 (67.7%) had IRF without CME, and 273 (24.1%) had neither. At baseline, eyes with CME had worse mean VA (letters) than eyes with IRF without CME and eyes with neither CME nor IRF (52 vs. 60 vs. 66 letters, P < 0.001); higher mean total CRT (μm) on OCT (514 vs. 472 vs. 404, P < 0.001); and greater hemorrhage, retinal angiomatous proliferation (RAP) lesions, and classic choroidal neovascularization (CNV). All groups showed improvement in VA at follow-up; however, the CME group started and ended with the worst VA among the 3 groups. Central retinal thickness, although higher at baseline for the CME group, was similar at 1 and 2 years follow-up for all groups. More eyes with CME (65.3%) developed scarring during 2 years of follow-up compared with eyes with IRF without CME (43.8%) and eyes with neither CME nor IRF (32.5%; P < 0.001).ConclusionsIn CATT, eyes with CME had worse baseline and follow-up VA, although all groups showed similar rates of improvement in VA during 2 years of follow-up. Cystoid macular edema seems to be a marker for poorer visual outcomes in nAMD because of underlying baseline retinal dysfunction and subsequent scarring.

Project description:PurposeTo evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD).DesignCohort study within the Comparison of AMD Treatments Trials (CATT).ParticipantsPatients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline.MethodsPresence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection.Main outcome measuresIncident nAMD and GA.ResultsAmong 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%).ConclusionsIn fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

Dataset Information

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials.

Background

Methods

Results

Conclusions

Trial registration number

Publications

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials.

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