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COMPARISON OF THE INTERNAL LIMITING MEMBRANE INSERTION TECHNIQUE AND THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE WITH VITRECTOMY TO TREAT MACULAR HOLE-ASSOCIATED RETINAL DETACHMENT.
Zhu, K, Lei, B, Wong, W, Zhang, J, Guo, Y, Chen, H, Song, F, Chang, Q, Xu, G, Zhang, Y
Retina (Philadelphia, Pa.). 2021;(1):37-44
Abstract
PURPOSE To compare the anatomical and functional outcomes of macular hole (MH)-associated retinal detachment after vitrectomy with the internal limiting membrane (ILM) insertion technique or the inverted ILM flap technique. METHODS In this retrospective observational study, we reviewed the medical records of 49 eyes with MH-associated retinal detachment that underwent vitrectomy with the ILM insertion (26 eyes) or ILM flap (23 eyes) technique. RESULTS The MH closure rate at 12 months was greater in the ILM flap group versus the ILM insertion group (95% vs. 73%, respectively, P = 0.059). The postoperative best-corrected visual acuity (BCVA) at 12 months was significantly better in the ILM flap group (P = 0.014). All eyes (100%) showed an improvement in the BCVA of ≥0.3 logarithm of the minimum angle of resolution (15 Early Treatment Diabetic Retinopathy Study letters) in the ILM flap group versus 20 eyes (77%) in the ILM insertion group (P = 0.026). The preoperative BCVA and the ILM flap technique were significantly correlated with the postoperative BCVA (P = 0.028 and 0.027, respectively) and BCVA improvement (≥0.3 logarithm of the minimum angle of resolution [15 Early Treatment Diabetic Retinopathy Study letters]; P = 0.003 and 0.026, respectively). CONCLUSION The inverted ILM flap technique was more effective in improving the postoperative BCVA in patients with MH-associated retinal detachment when compared with the ILM insertion technique. The preoperative BCVA and the ILM flap technique were independent prognostic factors for visual outcomes in patients with MH-associated retinal detachment.
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Diabetic vascular hyperpermeability: optical coherence tomography angiography and functional loss assessments of relationships among retinal vasculature changes.
Arima, M, Nakao, S, Kaizu, Y, Wada, I, Yamaguchi, M, Fujiwara, K, Akiyama, M, Stitt, AW, Sonoda, KH
Scientific reports. 2021;(1):4185
Abstract
Our study assessed the influence of vascular permeability on vascular flow density (FD)-correlated retinal sensitivity (RS) in DR. In this cross-sectional, prospective, consecutive study, RS in the extrafoveal macula of DR patient was measured by microperimetry. FD was measured in the total, superficial, and deep capillary plexus layers (TCP, SCP, and DCP) by optical coherence tomography angiography. All measurement points were classified into four categories according to intensity of fluorescein leakage and FD, and the RS reduction was compared. A stratified analysis by retinal thickness (RT) was also performed. Fourteen eyes (14 patients) were enrolled. FDs at 207 RS measurement points were analyzable. For TCP, SCP and DCP, the leakage did not decrease RS at points where FD was maintained. The greater the leakage, the smaller the RS reduction at points with low FD in TCP (P = .020). Points with high leakage showed a significant smaller RS reduction than points with low leakage (P = .001 for TCP, P = .040 for SCP, and P = .046 for DCP) only in areas with low RT and low FD. Our results suggested that vascular hyperpermeability may inhibit the RS reduction in the non-edematous ischemic diabetic retina.
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Outcomes by Baseline Choroidal Neovascularization Features in Age-Related Macular Degeneration: A Post Hoc Analysis of the VIEW Studies.
Steinle, NC, Du, W, Gibson, A, Saroj, N
Ophthalmology. Retina. 2021;(2):141-150
Abstract
PURPOSE To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti-vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). DESIGN Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. PARTICIPANTS One thousand eight hundred four patients with nAMD. METHODS Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. MAIN OUTCOMES MEASURES Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. RESULTS Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P < 0.01). Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both P < 0.01). With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of 15 letters or more decreased. CONCLUSIONS This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.
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Two-year interim safety results of the 0.2 µg/day fluocinolone acetonide intravitreal implant for the treatment of diabetic macular oedema: the observational PALADIN study.
Mansour, SE, Kiernan, DF, Roth, DB, Eichenbaum, D, Holekamp, NM, Kaba, S, Werts, E
The British journal of ophthalmology. 2021;(3):414-419
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Abstract
BACKGROUND The 0.2 µg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, 'real-world' safety results for the FAc implant in DMO. METHODS This 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 µg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured. RESULTS Data were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1-3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (p<0.001) and the percentage of patients with CST ≤300 µm was significantly increased (p=0.041). CONCLUSION Few IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit-risk profile in the management of DMO, especially when administered after a prior steroid challenge. TRIAL REGISTRATION NUMBER NCT02424019.
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Relationship of Topographic Distribution of Geographic Atrophy to Visual Acuity in Nonexudative Age-Related Macular Degeneration.
Shen, LL, Sun, M, Ahluwalia, A, Young, BK, Park, MM, Toth, CA, Lad, EM, Del Priore, LV
Ophthalmology. Retina. 2021;(8):761-774
Abstract
PURPOSE To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. DESIGN Retrospective analysis of a multicenter, prospective, randomized controlled trial. PARTICIPANTS The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. METHODS We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. MAIN OUTCOME MEASURES Geographic atrophy area in macular subfields and VA. RESULTS The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P < 0.001). Total GA area correlated poorly with VA (r2 = 0.07). Among GA areas in 9 subfields, only GA area in the central zone was associated independently with VA (P < 0.001). We determined 1 mm as the optimal diameter for the central zone in which GA area correlated best with VA (r2 = 0.45). On average, full GA coverage of the central 1-mm diameter zone corresponded to 34.8 letters' decline in VA. The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm diameter zone (2.7 letters/year vs. 2.8 letters/year; P = 0.94). CONCLUSIONS The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.
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INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR DIABETIC VITREOUS HEMORRHAGE: A Randomized Clinical Trial.
Rush, RB, Del Valle Penella, A, Reinauer, RM, Rush, SW, Bastar, PG
Retina (Philadelphia, Pa.). 2021;(5):1118-1126
Abstract
PURPOSE To evaluate the benefits of internal limiting membrane peeling in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for the treatment of vitreous hemorrhage. METHODS Two hundred and fifty-eight proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage were enrolled into the trial. Patients were randomized into one of two cohorts: Group A patients underwent internal limiting membrane peeling, whereas Group B patients did not undergo internal limiting membrane peeling. The main outcome was best-corrected visual acuity at 6 months. Secondary outcomes were optical coherence tomography central macular thickness at 6 months, incidence of diabetic macular edema treatment during the postoperative trial period, and incidence of epiretinal membrane at 6 months. RESULTS Two hundred and seven patients were randomized and completed 6 months follow-up. Group A had better best-corrected visual acuity at 6 months than Group B (P < 0.01). Group A had a lower incidence of diabetic macular edema treatment during the postoperative trial period and a lower incidence of epiretinal membrane at 6 months than Group B (P = 0.02 and P < 0.001, respectively). There was a trend toward lower central macular thickness on optical coherence tomography in Group A than Group B (P = 0.09). There were no significant differences in baseline details or complications intraoperatively or postoperatively between cohorts. CONCLUSION This trial demonstrated better vision, fewer postoperative diabetic macular edema treatments, and a lower incidence of epiretinal membrane at 6 months when internal limiting membrane peeling was performed. Internal limiting membrane peeling may be considered a vital maneuver to perform in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage.
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Visual Acuity in Retinal Vein Occlusion, Diabetic, and Uveitic Macular Edema: Central Subfield Thickness and Ellipsoid Zone Analysis.
Ciulla, TA, Kapik, B, Grewal, DS, Ip, MS
Ophthalmology. Retina. 2021;(7):633-647
Abstract
PURPOSE This study assessed relationships between best-corrected visual acuity (BCVA), central subfield thickness (CST), and ellipsoid zone (EZ) integrity in macular edema (ME) patients. DESIGN Post hoc analysis of 6 clinical trials, which included verified diagnoses, protocol refractions, and reading center assessment of OCT images. PARTICIPANTS Participants (n = 1063) were diagnosed with ME from retinal vein occlusion (RVO), diabetic retinopathy (DR; diabetic macular edema, DME), or noninfectious uveitis (NIU). METHODS For CST, 2 clinical trials for each disorder were analyzed. For EZ, 3 studies across 2 disorders were analyzed. MAIN OUTCOME MEASURES Primary outcomes were correlations between BCVA and CST, and between BCVA and 4 central subfield EZ grades. RESULTS For baseline BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.56 (774 eyes; 95% confidence interval [CI], -0.61 to -0.51; P < 0.001); DME, -0.50 (91 eyes; 95% CI, -0.64 to -0.33; P < 0.001); and ME from NIU, -0.38 (198 eyes; 95% CI, -0.49 to -0.26; P < 0.001). Regarding change from baseline to 24 weeks for both BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.35 (95% CI, -0.43 to -0.27; P < 0.001); DME, -0.30 (95% CI, -0.48 to -0.09; P = 0.006); and ME from NIU, -0.42 (95% CI, -0.53 to -0.29; P < 0.001). Acute and chronic ME showed similar baseline and 24-week change linear correlations. With lower baseline CST, a trend of decreased baseline and 24-week change correlations was found. For central subfield EZ at baseline, mean BCVA progressively worsened with each of 4 EZ grades in 185 eyes with gradable EZ (DME, 41 eyes; NIU, 144 eyes; P ≤ 0.050 for all pairwise comparisons except between normal and questionably abnormal EZ grades). Eyes with normal baseline central subfield EZ showed greater 24-week change in BCVA than those with abnormal baseline EZ (15.00 letters vs. 8.16 letters; P = 0.0005, with baseline BCVA, CST, and age as covariates). CONCLUSIONS Despite these correlations, CST and EZ integrity, as graded herein, account for the minority of BCVA variation in patients with ME resulting from RVO, DR, and NIU.
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Longitudinal Assessment of Retinal Thinning in Adults With and Without Sickle Cell Retinopathy Using Spectral-Domain Optical Coherence Tomography.
Lim, JI, Niec, M, Sun, J, Cao, D
JAMA ophthalmology. 2021;(3):330-337
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IMPORTANCE Determination of retinal thinning rates may help to identify patients who are at risk of progression of sickle cell retinopathy. OBJECTIVE To assess the rates of macular thinning in adults with and without sickle cell retinopathy using spectral-domain optical coherence tomography (OCT) and to identify ocular and systemic risk factors associated with retinal thinning. DESIGN, SETTING, AND PARTICIPANTS This longitudinal prospective case-control study enrolled adult participants from a university-based retina subspecialty clinic between February 11, 2009, and July 3, 2019. The study was designed in autumn 2008 and conducted from February 2, 2009, to July 3, 2020. Participants with sickle cell retinopathy (sickle cell group) were matched by age and race with participants without sickle cell retinopathy (control group). Participants received annual spectral-domain OCT and clinical examinations. Those with at least 1 year of follow-up by July 3, 2020, were included in the analysis. Data were analyzed from February 2, 2009, to July 3, 2020. MAIN OUTCOMES AND MEASURES The primary outcome was comparison of spectral-domain OCT measurements from early-treatment diabetic retinopathy study subfield rates of retinal thinning between eyes with and without sickle cell retinopathy and between different sickle cell hemoglobin subtypes. The secondary outcome was identification of ocular and systemic risk factors associated with rates of retinal thinning. RESULTS Among 370 adults (711 eyes) enrolled in the study, 310 participants (606 eyes) had sickle cell retinopathy, and 60 participants (105 eyes) did not. Of those, 175 of 310 participants (56.5%; 344 of 606 eyes [56.8%]; mean [SD] age, 37.8 [12.8] years; 126 women [72.0%]) in the sickle cell group and 31 of 60 participants (51.7%; 46 of 105 eyes [43.8%]; mean [SD] age, 59 [15.4] years; 22 women [71.0%]) in the control group had at least 1 year of clinical and spectral-domain OCT follow-up data from baseline. The mean (SD) follow-up was 53.7 (32.6) months for the sickle cell group and 54.6 (34.9) months for the control group. Rates of macular thinning in the sickle cell group were significantly higher than those in the control group for the inner nasal (difference, -1.18 μm per year; 95% CI, -1.71 to -0.65 μm per year), inner superior (difference, -1.03 μm per year; 95% CI, -1.78 to -0.29 μm per year), inner temporal (difference, -0.61 μm per year; 95% CI, -1.16 to -0.07 μm per year), and outer nasal (difference, -0.41 μm per year; 95% CI, -0.80 to -0.03 μm per year) quadrants. Patients with sickle cell hemoglobin SC and sickle cell hemoglobin β-thalassemia subtypes had higher rates of retinal thinning than those with the sickle cell hemoglobin SS subtype. Risk factors associated with greater rates of retinal thinning included participant age, stage of retinopathy, previous stroke, and presence of hypertension, acute chest syndrome, or diabetes. Hydroxyurea therapy was associated with decreased rates of retinal thinning and may be a protective factor. CONCLUSIONS AND RELEVANCE In this study, rates of retinal thinning were higher among participants with sickle cell retinopathy compared with those without sickle cell retinopathy, and thinning rates increased with participant age and stage of retinopathy. These findings suggest that identifying anatomic worsening of sickle cell maculopathy through spectral-domain OCT may be a useful parameter to evaluate the progression of sickle cell retinopathy.
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Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration.
Khurana, RN, Kunimoto, D, Yoon, YH, Wykoff, CC, Chang, A, Maturi, RK, Agostini, H, Souied, E, Chow, DR, Lotery, AJ, et al
Ophthalmology. 2021;(7):1027-1038
Abstract
PURPOSE To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. PARTICIPANTS The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. METHODS At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). MAIN OUTCOME MEASURES Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). RESULTS For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. CONCLUSIONS Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.
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Suprachoroidal CLS-TA plus Intravitreal Aflibercept for Diabetic Macular Edema: A Randomized, Double-Masked, Parallel-Design, Controlled Study.
Barakat, MR, Wykoff, CC, Gonzalez, V, Hu, A, Marcus, D, Zavaleta, E, Ciulla, TA
Ophthalmology. Retina. 2021;(1):60-70
Abstract
PURPOSE This study evaluated the potential safety, efficacy, and durability advantages of investigational triamcinolone acetonide suspension (CLS-TA; Clearside Biomedical, Alpharetta, GA) administered suprachoroidally in conjunction with intravitreal aflibercept compared with aflibercept monotherapy for treatment of diabetic macular edema (DME). DESIGN TYBEE was a prospective, controlled, double-masked study. Patients were randomized 1:1 to CLS-TA and aflibercept (active) or aflibercept monotherapy (control), and assessed over 24 weeks. PARTICIPANTS Treatment-naive DME patients with best-corrected visual acuity (BCVA) of 20 to 70 letters and central subfield retinal thickness (CST) of more than 300 μm. METHODS Patients in the active group (n = 36) received CLS-TA and aflibercept at baseline and week 12. Patients in the control group (n = 35) received aflibercept at baseline, week 4, week 8, and week 12. To mask both groups, sham suprachoroidal and intravitreal injections were utilized. All patients were eligible to receive aflibercept as needed at weeks 4, 8, 16, and 20 per prespecified criteria. MAIN OUTCOME MEASURE Mean change in BCVA from baseline. Treatment differences were assessed with a 2-sided significance level of 0.10. RESULTS Mean BCVA changes from baseline to week 24 were not statistically different in the active and control groups (intention-to-treat [ITT] population: +11.4 letters and +13.8 letters [P = 0.288]; per protocol [PP] population: +12.3 letters and +13.5 letters [P = 0.664]; respectively). Greater improvement in CST was seen in the active versus control group (ITT population: -212.1 μm and -178.6 μm [P = 0.089]; PP population: -226.5 μm and -176.1 μm [P = 0.035]; respectively). Compared with the control group, eyes in the active group received fewer treatments (scheduled plus as-needed treatments averaging 4.6 versus 2.6, respectively). No treatment-related serious adverse events were observed. Ocular adverse events were low for both arms. Cataract events, all assessed as unrelated to treatment, and events of elevated intraocular pressure trended higher in the active group. CONCLUSIONS CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept for treatment of DME provides simliar visual benefit at 24 weeks' follow-up compared with aflibercept monotherapy, is well tolerated and shows modest anatomic benefit with potential to reduce treatment burden.