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A prospective randomized clinical trial comparing nepafenac, intravitreal triamcinolone and no adjuvant therapy for epiretinal membrane.
Mandelcorn, ED, Al-Falah, M, Zhao, LD, Kertes, P, Devenyi, R, Lam, WC
Acta ophthalmologica. 2022;(1):e297-e303
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Abstract
PURPOSE To compare the efficacy of topical nepafenac 0.1% versus intravitreal triamcinolone acetonide (IVTA) at the conclusion of vitrectomy surgery versus no adjuvant therapy (NAT) in improving macular morphology post-operatively in patients undergoing vitrectomy for epiretinal membrane (ERM), as measured by optical coherence tomography (OCT) imaging and best-corrected visual acuity (BCVA). METHODS Design: Prospective randomized clinical trial Setting: Multi-centre 80 patients scheduled to undergo vitrectomy surgery for idiopathic ERM were randomized to receive either IVTA (4 mg/0.1 cc) at the end of surgery, topical nepafenac sodium 0.1% TID for 1 month post-operation or no adjuvant treatment (NAT). Optical coherence tomography (OCT) imaging, best-corrected visual acuity and intraocular pressure (IOP) were measured before surgery, and 1 and 2 months post-operation. RESULTS Although all three groups showed reduction in macular thickness post-operation, the NAT group showed the most improvement, with a reduction of 136.18 ± 29.84 μm at two months. There was no statistically significant difference in macular thickness between the groups at each time point, p = 0.158. The NAT group also had the best recovery in BCVA with an improvement of 0.207 logMAR (10.35 letters) at two months post-operation. There was no statistically significant difference in BCVA between the groups, p = 0.606. There was statistically significant difference in the IOP between the three groups, p = 0.04 only at 1-month visit. The IVTA group had the highest rise in average IOP at both 1 and 2 months post-operation (2.72 and 1.58 mmHg, respectively). CONCLUSION Our study data suggest there was no advantage in the use of topical nepafenac or IVTA for post-vitrectomy ERM surgery.
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Liraglutide Treatment Does Not Induce Changes in the Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Diabetic Retinopathy.
Arendt Nielsen, T, Sega, R, Uggerhøj Andersen, C, Vorum, H, Drewes, AM, Jakobsen, PE, Brock, B, Brock, C
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2022;(1):114-121
Abstract
Purpose: Liraglutide treatment has shown promising anti-inflammatory and nerve regenerative results in preclinical and clinical trials. We sought to assess if liraglutide treatment would induce nerve regeneration through its anti-inflammatory and neurotrophic mechanisms by increasing peripapillary retinal nerve fiber layer (RNFL) thickness in individuals with long-term type 1 diabetes. Methods: Secondary analyses were performed on a prospective, double-blinded, randomized, placebo-controlled trial on adults with type 1 diabetes, distal symmetric polyneuropathy (DSPN), and confirmed diabetic retinopathy, who were randomized 1:1 to either 26 weeks placebo or liraglutide treatment. The primary endpoint was a change in peripapillary RNFL thickness between treatments, assessed by optical coherence tomography. Results: Thirty-seven participants were included in the secondary analysis. No differences in mean peripapillary RNFL thickness (overall ΔMean RNFL thickness; liraglutide -1 (±8) μm (-1%) vs. placebo -1 (±5) μm (-1%), P = 0.78, n = 37) or any of the quadrants. Peripapillary RNFL thicknesses were shown between treatments in either nonproliferative (ΔMean RNFL thickness; liraglutide -1 (±5) μm (-1%) vs. placebo 0 (±4) μm (0%), P = 0.80, N = 26) or proliferative diabetic retinopathy subgroup (ΔMean RNFL thickness; liraglutide -2 (±14) μm (-3%) vs. placebo -1 (±6) μm (-2%), P = 0.88, N = 11). Conclusions: In this study, 26 weeks of liraglutide treatment did not induce measurable changes in the assessed optic nerve thickness. Thus, this methodology does not support the induction of substantial nerve regeneration in this cohort with established retinopathy and DSPN. The trial was approved by the Danish Health and Medicines Authority. Informed consent was obtained from all participants. TODINELI study: EUDRA CT 2013-004375-12, Ethics Ref: N-20130077 Clinical trial registration number: clinicaltrials.gov NCT02138045.
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The Utility of Routine Fundus Photography Screening for Posterior Segment Disease: A Stepped-wedge, Cluster-randomized Trial in South India.
Shekhawat, NS, Niziol, LM, Sharma, SS, Joseph, S, Robin, AL, Gillespie, BW, Musch, DC, Woodward, MA, Venkatesh, R
Ophthalmology. 2021;(7):1060-1069
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Abstract
PURPOSE To assess whether routine fundus photography (RFP) to screen for posterior segment disease at community eye clinics (vision centers [VCs]) in India increases referral to centralized ophthalmolic care. DESIGN Stepped-wedge, cluster-randomized trial. PARTICIPANTS Patients aged 40 to 75 years and those aged 20 to 40 years with a known history of hypertension or diabetes mellitus presenting to 4 technician-run VCs associated with the Aravind Eye Care System in India. METHODS VCs (clusters) were randomized to standard care or RFP across five 2-week study periods (steps). Patients in each cluster received standard care initially. At the start of each subsequent step, a randomly chosen cluster crossed over to providing RFP to eligible patients. All clusters took part in RFP during the last step. Standard care involved technician eye exams, optional fundus photography, and teleconsultation with an ophthalmologist. RFP involved eye exams, dilation and 40-degree fundus photography, and teleconsultation with an ophthalmologist. MAIN OUTCOME MEASURES Standard care and RFP clusters were compared by the proportion of patients referred for in-person evaluation by an ophthalmologist because of fundus photography findings and urgency of referral (urgently in ≤ 2 weeks vs. nonurgently in > 2 weeks). Generalized linear mixed models adjusting for cluster and step were used to estimate the odds of referral due to fundus photography findings compared with standard care. RESULTS A total of 1447 patients were enrolled across the VCs, including 737 in the standard care group and 710 in the RFP group. Compared with standard care, the RFP group had a higher proportion of referrals due to fundus photography findings (11.3% vs. 4.4%), nonurgent referrals due to fundus photography (9.3% vs. 3.3%), and urgent referrals due to fundus photography (1.8% vs. 1.1%). The RFP intervention was associated with a 2-fold increased odds of being referred because of photography findings compared with standard care (odds ratio, 2.07; 95% confidence interval, 0.98-4.40; P = 0.058). CONCLUSIONS Adding RFP to community eye clinics was associated with an increased odds of referral compared with standard care. This increase in referral was mostly due to nonurgent posterior segment disease.
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Dapagliflozin increases retinal thickness in type 2 diabetic patients as compared with glibenclamide: A randomized controlled trial.
Fernandes, VHR, Chaves, FRP, Soares, AAS, Breder, I, Kimura-Medorima, ST, Munhoz, DB, Cintra, RMR, Breder, JC, Barreto, J, Nadruz, W, et al
Diabetes & metabolism. 2021;(6):101280
Abstract
AIM: In patients with type 2 diabetes mellitus (T2DM) a progressive thinning in the central retinal thickness (CRT) is mainly related to neuroretinal degeneration and occurs before the decline in visual acuity or capillary density. We investigated the change in CRT by optical coherence tomography (OCT) in T2DM patients after 12 weeks of treatment with dapagliflozin or glibenclamide. METHODS Ninety-seven patients (57 ± 7 years) with T2DM and clinical or subclinical atherosclerosis were randomized 1:1 to dapagliflozin (10 mg/day) or glibenclamide (5 mg/day) on top of metformin XR 1.5 g/day. OCT was obtained in all patients enrolled in the study, both at the time of randomization and at the end of the study. RESULTS Baseline and post-treatment values of fasting glucose and glycated hemoglobin were equivalent in the two arms. There was no difference in change in diabetic retinopathy status after therapy. The center subfield thickness changed by +2(6)μm in the dapagliflozin group and by -1(7) μm in the glibenclamide group (P = 0.001). CONCLUSION A short-term treatment with dapagliflozin may increase CRT as compared with equivalent glycemic control with glibenclamide.
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Effect of Aflibercept on Diabetic Retinopathy Severity and Visual Function in the RECOVERY Study for Proliferative Diabetic Retinopathy.
Alagorie, AR, Velaga, S, Nittala, MG, Yu, HJ, Wykoff, CC, Sadda, SR
Ophthalmology. Retina. 2021;(5):409-419
Abstract
PURPOSE To evaluate the effect of intravitreal aflibercept on diabetic retinopathy (DR) severity and visual function in patients with proliferative DR (PDR) without diabetic macular edema (DME). DESIGN Prospective, longitudinal, multicenter clinical trial. PARTICIPANTS Forty eyes of 40 patients with PDR and no DME were enrolled in this study. Patients were randomized into monthly and quarterly 2-mg aflibercept injection cohorts and were treated over a period of 12 months. METHODS All patients underwent ultra-widefield fundus imaging including pseudocolor and fluorescein angiography using an Optos 200Tx device. MAIN OUTCOME MEASURES Severity of DR at baseline, month 6, and month 12 was evaluated using the DR severity scale (DRSS). The DRSS scores were correlated with the 25-item Visual Function Questionnaire (VFQ-25) and 39-item Visual Function Questionnaire (VFQ-39) scores at baseline and month 12. RESULTS Mean age of the patients was 48.2 years (range, 25-75 years), mean duration of diabetes mellitus was 16.1 years (range, 2-36 years), and median glycated hemoglobin level was 8.8% (IQR, 7.4%-10%). Both monthly and quarterly groups demonstrated a statistically significant regression in DRSS from baseline to month 12 (P < 0.001). The monthly group demonstrated a statistically significant greater regression of DRSS score at the month 6 visit compared with the quarterly group (P = 0.019). However, the difference between the two groups became statistically insignificant at month 12 visit (P = 0.309). Also no difference was found in mean VFQ-25 and VFQ-39 composite scores between the monthly and quarterly groups at month 12 (P = 0.947 and P = 0.921, respectively). The improvement in mean VFQ-25 and VFQ-39 composite scores at month 12 was correlated significantly with improvement in DRSS score (r = 0.384 and P = 0.039, and r = 0.361 and P = 0.046, respectively). CONCLUSIONS In this study of eyes with PDR without DME, both monthly and quarterly aflibercept injection groups showed significant improvement in DR severity at month 12 compared with baseline. The improvement in DRSS score was associated with an improvement in VFQ-25 and VFQ-39 composite score.
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Spectral-Domain OCT Predictors of Visual Outcomes after Ranibizumab Treatment for Macular Edema Resulting from Retinal Vein Occlusion.
Yiu, G, Welch, RJ, Wang, Y, Wang, Z, Wang, PW, Haskova, Z
Ophthalmology. Retina. 2020;(1):67-76
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PURPOSE To evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE). DESIGN Post hoc analysis of prospective clinical trial data. PARTICIPANTS Two hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema. METHODS Baseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections. MAIN OUTCOME MEASURES Association of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections. RESULTS Before therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001). CONCLUSIONS Although SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.
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COMPARISON OF INTRAVITREAL DEXAMETHASONE IMPLANT AND AFLIBERCEPT IN PATIENTS WITH TREATMENT-NAIVE DIABETIC MACULAR EDEMA WITH SEROUS RETINAL DETACHMENT.
Ozsaygili, C, Duru, N
Retina (Philadelphia, Pa.). 2020;(6):1044-1052
Abstract
PURPOSE To compare the efficacy and safety of intravitreal dexamethasone (DEX) implant versus aflibercept in patients with treatment-naive diabetic macular edema with inflammatory biomarkers. METHODS Ninety-eight eyes of 62 treatment-naive patients with diabetic macular edema with serous retinal detachment and hyperreflective foci were enrolled. Each patient was randomized to receive either aflibercept or DEX implant treatment. The treatment protocol included 3 monthly injections of 2 mg of aflibercept as a loading phase in the anti-vascular endothelial growth factor group and 0.7 mg of DEX implant in the DEX group and then pro re nata treatment. Primary outcome measures were mean changes in visual acuity and central retinal thickness at the end of the 12-month follow-up. RESULTS Forty-eight eyes of 29 patients were received DEX implant, and 50 eyes of 33 patients received the aflibercept injection. Mean central retinal thickness decreased from 615.2 µm at baseline to 297.7 µm at 12 months in the DEX group (P < 0.001) and from 576.5 µm to 367.4 µm in the aflibercept group (P < 0.001). Except for the first month, mean central retinal thickness reduction was significantly higher in the DEX group (P < 0.05, Mann-Whitney U Test). Visual acuity improved significantly at the end of the follow-ups (46.3-52.7 Early Treatment Diabetic Retinopathy Study letters in the DEX group and 47.5-56.8 Early Treatment Diabetic Retinopathy Study letters in the aflibercept group at 12 months, P < 0.001, paired-sample t-test). Adjusting by baseline values, the increase in mean visual acuity during the 12-month follow-ups favored the aflibercept group (P < 0.01), 25% of the DEX-treated eyes and 42% of the aflibercept treated eyes experienced 10 or more Early Treatment Diabetic Retinopathy Study letters visual gain (P: 0.058). The DEX group received significantly fewer (2.6 vs. 7.2) injections (P: 0.001). CONCLUSION It was observed that the both of DEX implant and aflibercept were effective and safe in treatment-naive diabetic macular edema patients with inflammatory phenotype. Anatomical results were found to be better in the DEX group, and functional results were found to be better in the aflibercept group. In pseudophakic eyes, the functional superiority of aflibercept ceased to exist, and the low number of injections in the DEX implant group was seen as an advantage.
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Associations of Variation in Retinal Thickness With Visual Acuity and Anatomic Outcomes in Eyes With Neovascular Age-Related Macular Degeneration Lesions Treated With Anti-Vascular Endothelial Growth Factor Agents.
Evans, RN, Reeves, BC, Maguire, MG, Martin, DF, Muldrew, A, Peto, T, Rogers, C, Chakravarthy, U
JAMA ophthalmology. 2020;(10):1043-1051
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IMPORTANCE When initiating anti-vascular endothelial growth factor (VEGF) treatment for patients with neovascular age-related macular degeneration (nAMD), knowledge of prognostic factors is important for advising patients and guiding treatment. We hypothesized that eyes with greater fluctuation in retinal thickness over time have worse outcomes than eyes with less variation. OBJECTIVE To investigate whether visual and anatomic outcomes in eyes with nAMD initiating anti-VEGF treatment are associated with fluctuations in retinal thickness. DESIGN, SETTING, AND PARTICIPANTS In this study using data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and the Inhibition of VEGF in Age-Related Choroidal Neovascularization (IVAN) randomized clinical trial, people with previously untreated nAMD were included. Data were collected from February 2008 to November 2012, and data were analyzed from April 2017 to April 2020. MAIN OUTCOMES AND MEASURES Foveal center point thicknesses (FCPTs) were extracted from 1165 study eyes from CATT and 566 study eyes from the IVAN trial, excluding those with 3 measurements or less. For each eye, the SD of FCPT was calculated. Eyes were grouped by FCPT SD quartile. Associations of FCPT SD quartile with outcomes were quantified at month 24 or the last available visit by linear or logistic regression, adjusting for baseline best-corrected visual acuity (BCVA) and randomized allocations to drug and treatment regimen, for BCVA, development of fibrosis, and development of macular atrophy. RESULTS Of the 1731 included patients, 1058 (61.1%) were female, and the mean (SD) age was 78.6 (7.4) years. The median (interquartile range) FCPT SD was 40.2 (27.1-61.2) in the IVAN cohort and 59.0 (38.3-89.4) in the CATT cohort. After adjustment for baseline BCVA and trial allocations, BCVA worsened significantly across the quartiles of FCPT SD; the difference between the first and fourth quartiles was -6.27 Early Treatment Diabetic Retinopathy Study letters (95% CI, -8.45 to -4.09). The risk of developing fibrosis and macular atrophy also increased across FCPT SD quartiles. Odds ratios ranged from 1.40 (95% CI, 1.03 to 1.91) for quartile 2 to 1.95 (95% CI, 1.42 to 2.68) for quartile 4 for fibrosis and from 1.32 (95% CI, 0.90 to 1.92) for quartile 2 to 2.10 (95% CI, 1.45 to 3.05) for quartile 4 for macular atrophy. CONCLUSIONS AND RELEVANCE Greater variation in retinal thickness in eyes with nAMD during treatment with anti-VEGF was associated with worse BCVA and development of fibrosis and macular atrophy in these post hoc analyses, despite protocol-directed treatment frequency. Practitioners may want to consider variation in retinal thickness when advising patients about their prognosis.
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CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA.
Fischer, MD, Ochakovski, GA, Beier, B, Seitz, IP, Vaheb, Y, Kortuem, C, Reichel, FFL, Kuehlewein, L, Kahle, NA, Peters, T, et al
Retina (Philadelphia, Pa.). 2020;(1):160-168
Abstract
PURPOSE Choroideremia (CHM) is a rare inherited retinal degeneration resulting from mutation of the CHM gene, which results in absence of functional Rab escort protein 1 (REP1). We evaluated retinal gene therapy with an adeno-associated virus vector that used to deliver a functional version of the CHM gene (AAV2-REP1). METHODS THOR (NCT02671539) is a Phase 2, open-label, single-center, randomized study. Six male patients (51-60 years) with CHM received AAV2-REP1, by a single 0.1-mL subretinal injection of 10 genome particles during vitrectomy. Twelve-month data are reported. RESULTS In study eyes, 4 patients experienced minor changes in best-corrected visual acuity (-4 to +1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); one gained 17 letters and another lost 14 letters. Control eyes had changes of -2 to +4 letters. In 5/6 patients, improvements in mean (95% confidence intervals) retinal sensitivity (2.3 [4.0] dB), peak retinal sensitivity (2.8 [3.5] dB), and gaze fixation area (-36.1 [66.9] deg) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure. CONCLUSION Gene therapy with AAV2-REP1 can maintain, and in some cases, improve, visual acuity in CHM. Longer term follow-up is required to establish whether these benefits are maintained.
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Outcomes in Patients with Diabetic Macular Edema Requiring Cataract Surgery in VISTA and VIVID Studies.
Moshfeghi, AA, Thompson, D, Berliner, AJ, Saroj, N
Ophthalmology. Retina. 2020;(5):481-485
Abstract
PURPOSE To evaluate the impact of cataract surgery on visual and anatomic outcomes in patients with diabetic macular edema treated with intravitreal aflibercept injection (IAI) or laser control and who did not require rescue therapy. DESIGN Post hoc analysis of 2 phase 3 trials, Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID). PARTICIPANTS Fifty-four patients (laser treatment, n = 11; IAI, n = 43) who underwent cataract surgery during the study period. METHODS In VISTA and VIVID, patients received IAI 2 mg every 4 weeks, IAI 2 mg every 8 weeks after 5 monthly doses, or laser control through week 100. Starting at week 24, if rescue treatment criteria were met, IAI patients received laser therapy, and laser therapy patients received IAI 2 mg every 8 weeks (after 5 monthly doses). Patients who received rescue treatment before cataract surgery were excluded. MAIN OUTCOME MEASURES Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in the laser control and pooled IAI groups before and after cataract surgery. RESULTS The cumulative incidence of cataract surgery did not depend on treatment group assignment (rate ratio, = 1.517; 95% confidence interval, 0.782-2.944; P = 0.2174). At the last study visit before surgery, BCVA was 62.2 and 56.9 letters and CRT was 342 μm and 301 μm in the laser control and IAI groups, respectively. At the first study visit after cataract surgery, BCVA was improved significantly in both the laser control and IAI groups to 73.5 letters (P = 0.010 compared with last visit before surgery) and 67.2 letters (P < 0.001 compared with last visit before surgery), respectively. Corresponding change in CRT was a modest increase to 364 μm (P > 0.05 compared with last visit before surgery) and 359 μm (P = 0.013 compared with last visit before surgery), respectively. CONCLUSIONS Incidence of cataract surgery was similar in both treatment groups. Despite a modest worsening in CRT after cataract surgery, BCVA was improved in both treatment groups.