BETA-PERIPAPILLARY ATROPHY AND GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS.
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ABSTRACT: Purpose
To determine associations between beta-peripapillary atrophy (B-PPA) and incidence and growth of geographic atrophy (GA) in eyes treated with anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Methods
We included 245 cases with incident GA and 245 controls matched by baseline demographics and characteristics associated with development of GA in the CATT. Baseline color images were graded for the type of B-PPA, defined as presence of hypopigmentation with visible choroidal vessels and sclera that is adjacent to the optic disk. Beta-peripapillary atrophy was further classified as scleral ring, sclera, sclera/choroidal blood vessels, or combination. Areas of each type of B-PPA and the circumferential extent of B-PPA were measured.Results
Beta-peripapillary atrophy was present in 58% of eyes developing GA and in 52% without GA (P = 0.17). The greater circumferential extent of sclera/choroidal blood vessels B-PPA in relation to the optic disk was associated with incident GA (P = 0.02) and the GA size at first observation (P = 0.047). Beta-peripapillary atrophy was not associated with GA growth rates (P>0.05). Patients without B-PPA had a higher number of GA-associated risk alleles of ARMS2 (P = 0.0003) and HTRA1 (P = 0.001).Conclusion
The extent of sclera/choroidal blood vessel B-PPA was associated with the GA incidence and size but not with the growth rate in eyes treated for neovascular age-related macular degeneration. Beta-peripapillary atrophy and GA may share some common pathophysiologic pathways unrelated to the GA-associated risk alleles evaluated.
SUBMITTER: Kolomeyer AM
PROVIDER: S-EPMC7641972 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).DesignCohort within a randomized clinical trial.ParticipantsWe analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment.MethodsEyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs).Main outcome measuresDevelopment of GA.ResultsBy 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3.ConclusionsApproximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.
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Project description:PurposeTo determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials.MethodsParticipants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models.ResultsIn multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios ≤1.86, P ≥ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P = 0.02).ConclusionNone of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.
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Project description:ImportanceRetinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated.ObjectiveTo determine the incidence and progression of non-GA (NGA) and associated risk factors.Design, setting, and participantsThis study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019.InterventionsParticipants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Participants were treated according to best medical judgement thereafter.Main outcomes and measuresIncidence of nAMD-associated NGA (hypopigmentation and hyperpigmentation in color images) and progression; adjusted risk ratios (aRR) for baseline characteristics.ResultsAmong 1107 participants, risk of NGA was 35% (391 eyes), 59% (246 eyes), and 81% (122 eyes) at 1, 2, and 5 years, respectively. Risk factors for NGA included worse visual acuity (20/200-20/320: aRR, 1.74 [95% CI, 1.24-2.43], compared with ≤20/40; P = .006), larger neovascularization area (>4 disc areas: aRR, 1.31 [95% CI, 1.01-1.71], compared with ≤1 disc areas; P = .007), switched drug regimen (aRR, 1.28 [95% CI, 1.06-1.54], compared with as-needed injections; P = .02), and single-nucleotide variants Age-Related Maculopathy Susceptibility 2 (ARMS2) (TT variant: relative risk [RR], 1.53 [95% CI, 1.22-1.93]; P = .001) and HtrA Serine Peptidase 1 (HTRA1) (AG variant: RR, 1.23 [95% CI, 1.01-1.48]; AA variant: RR, 1.51 [95% CI, 1.20-1.91]; P = .002). Sub-retinal pigment epithelium thickness was protective (>275 μm: aRR, 0.59 [95% CI, 0.46-0.75], compared with ≤75 μm; P < .001). Among 389 eyes with NGA by 2 years and subsequent color images, risk of progression to GA was 29%, 43%, and 50% at 1, 3, and 4 years, respectively. Risk factors for progression to GA included worse visual acuity (20/200-20/320: aRR, 2.75 [95% CI, 1.54-4.93], compared with ≤20/40; P < .001), worse fellow-eye visual acuity (<20/40: aRR, 1.77 [95% CI, 1.12-2.79], compared with ≥20/40; P = .01), fellow-eye GA (aRR, 1.71 [95% CI, 1.06-2.75]; P = .03), and pseudodrusen in either eye (aRR, 1.65 [95% CI, 1.17-2.34]; P = .005). Subretinal fluid was associated with a decreased risk of progression (aRR, 0.42 [95% CI, 0.28-0.63]; P < .001).Conclusions and relevanceIn this study, after 2 years of protocol-guided anti-vascular endothelial growth factor treatment for nAMD, more than half of the eyes in the study developed NGA in the location of nAMD. After 3 additional years of regular care, half of them progressed to GA.Trial registrationClinicalTrials.gov Identifier: NCT00593450.
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Project description:Geographic atrophy (GA) is a progressive, advanced form of age-related macular degeneration leading to visual function impairment and irreversible vision loss. Standard clinical tests to evaluate visual function in patients with GA provide poor anatomic-functional correlation, whereas fundus imaging does not assess the visual function deficit. Microperimetry is a psychophysical visual function test that spatially maps retinal sensitivity and allows for identification of correlation of anatomic features with visual function. In this review, we present an overview of mesopic microperimetry for GA, including commercially available microperimetry devices, strategies to capture a mesopic microperimetry test, and strategies to assess and interpret microperimetry data in patients with GA. We demonstrate the importance of microperimetry data for assessing GA progression and for evaluating visual function loss through anatomic-functional correlations. Although valuable, current microperimetry tests require an extensive time commitment from the patient and examiner, and the development of faster, more reproducible and accessible methods is important to enable broader use of microperimetry in both clinical and research settings.
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Project description:ObjectiveTo describe the incidence and outcomes of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to assess the effect of prophylactic topical antimicrobials on incidence.DesignCohort study within a randomized clinical trial.ParticipantsPatients enrolled in CATT.MethodsPatients with neovascular age-related macular degeneration received intravitreal injections of ranibizumab or bevacizumab under 1 of 3 dosing regimens. The study protocol specified preinjection preparation to include use of a sterile lid speculum and povidone iodine (5%). Use of preinjection and postinjection antibiotics was at the discretion of the treating ophthalmologist. Patients were followed up monthly for 2 years.Main outcome measuresDevelopment of endophthalmitis and visual acuity.ResultsEndophthalmitis developed after 11 of 18 509 injections (1 per 1700 [0.06%]; 95% confidence interval, 0.03%-0.11%), and in 11 of 1185 patients (0.93%; 95% confidence interval, 0.52-1.66). Incidence of endophthalmitis was 0.15% among injections with no antibiotic use, 0.08% among injections with preinjection antibiotics only, 0.06% among injections with postinjection antibiotics only, and 0.04% among injections with preinjection and postinjection antibiotics (P = 0.20). All eyes were treated with intravitreal antibiotics and 4 underwent vitrectomy. Among the 11 affected eyes, the final study visual acuity was 20/40 or better in 4 eyes (36%), 20/50 to 20/80 in 2 eyes (18%), 20/100 to 20/160 in 3 eyes (27%), and worse than 20/800 in 2 eyes (18%). The final visual acuity was within 2 lines of the visual acuity before endophthalmitis in 5 eyes (45%).ConclusionsRates of endophthalmitis were low and similar to those in other large-scale studies. Use of topical antibiotics either before or after injection does not seem to reduce the risk for endophthalmitis.
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