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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.
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NONCONFOCAL ULTRA-WIDEFIELD SCANNING LASER OPHTHALMOSCOPY: Polarization Artifacts and Diabetic Macular Edema.
Ajlan, RS, Barnard, LR, Mainster, MA
Retina (Philadelphia, Pa.). 2020;(7):1374-1378
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PURPOSE Bowtie-shaped polarization artifacts are often present in nonconfocal ultra-widefield scanning laser ophthalmoscope (SLO) images. We studied these artifacts and evaluated their potential value as clinical biomarkers in screening for center-involving diabetic macular edema (DME). METHODS We performed a retrospective, observational, cohort study on 78 diabetic adult patients (143 eyes) who had spectral domain optical coherence tomography and nonmydriatic nonconfocal ultra-widefield SLO testing on the same day. Scanning laser ophthalmoscope green-only (532 nm), red-only (635 nm), and composite pseudocolor (532 plus 635 nm) images were examined for the presence of a foveal bowtie polarization artifact. RESULTS Polarization artifacts were absent in all but one eye with center-involving DME (32 of 33 eyes). Polarization artifacts were also absent in many eyes without center-involving DME (49 of 110 eyes in pseudocolor images). As clinical biomarkers of center-involving DME, artifact absence has high specificity (99, 100, and 98% for green, red, and pseudocolor images, respectively) but poor sensitivity (49, 31, and 40% for green, red, and pseudocolor images, respectively). CONCLUSION Foveal bowtie-shaped polarization artifacts occur routinely in nonconfocal ultra-widefield SLO images. Their presence indicates preserved foveal Henle fiber layer structure. Contemporary nonconfocal ultra-widefield SLO images lack the sensitivity for their bowtie artifacts to serve as reliable biomarkers in screening for center-involving DME.
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Intravitreal aflibercept for submacular hemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
Kim, JH, Kim, CG, Lee, DW, Yoo, SJ, Lew, YJ, Cho, HJ, Kim, JY, Lee, SH, Kim, JW
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2020;(1):107-116
Abstract
PURPOSE To evaluate the efficacy of intravitreal aflibercept monotherapy for submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS This prospective, phase 4 clinical trial included 29 patients diagnosed with fovea-involving submacular hemorrhage secondary to neovascular AMD (7 patients) or PCV (22 patients). Patients were initially administered 3 monthly aflibercept injections, followed by 1 injection every 2 months. The primary outcome measure was changes in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) during the 56-week study period. Other key outcome measures were the proportion of patients who exhibited changes in BCVA of ≥ 15 ETDRS letters from baseline and changes in central retinal thickness (CRT). RESULTS The mean size of hemorrhage was 6.2 ± 4.8-disc-diameter area. The mean BCVA significantly improved from 52.9 ± 17.8 ETDRS letters at week 0 (baseline) to 71.8 ± 16.1 letters at week 56 (P < 0.001). At week 56, improvement in BCVA of ≥ 15 letters was noted in 16 patients (55.2%), whereas none of the patients experienced a loss of ≥ 15 letters. The mean CRT significantly decreased from 498.9 ± 194.2 μm at week 0 to 248.3 ± 45.0 μm at week 56 (P < 0.001). During the study period, retinal break developed in one patient. CONCLUSIONS Intravitreal aflibercept administered every 2 months after the 3 initial monthly doses was found to be an effective and safe treatment method for submacular hemorrhage secondary to neovascular AMD.
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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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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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Early visual field changes in patients with type 1 diabetes mellitus.
Ozates, S, Simsek, M, Elgin, U, Keskin, M, Aycan, Z
European journal of ophthalmology. 2020;(6):1467-1472
Abstract
PURPOSE To assess the visual field sensitivity changes and investigate the association between visual field sensitivity and retinal nerve fiber layer thickness in patients with type 1 diabetes mellitus. MATERIALS AND METHODS In this cross-sectional and observational study, 46 patients (22 males, 24 females) with type 1 diabetes mellitus and no diabetic retinopathy formed the diabetes mellitus group and 50 age-matched healthy subjects (32 males, 18 females) formed the control group. Retinal nerve fiber layer thickness, full-threshold standard automated perimetry, and short-wavelength automated perimetry were performed. Main outcomes were retinal nerve fiber layer thickness, mean deviation, pattern standard deviation, and short fluctuation. RESULTS Average retinal nerve fiber layer thickness was significantly thinner in the diabetes mellitus group (p < 0.001). The mean values of mean deviation and pattern standard deviation of the full-threshold standard automated perimetry did not differ between the groups (p = 0.179, p = 0.139, respectively). Mean short fluctuation was significantly greater in the diabetes mellitus group (p < 0.001). Both mean deviation and pattern standard deviation of the short-wavelength automated perimetry were significantly greater in the diabetes mellitus group (p < 0.001, p < 0.001, respectively). Pattern standard deviation of short-wavelength automated perimetry equal or higher than 1.57 dB had 91% sensitivity and 90% specificity (area under the curve = 0.969, p < 0.001) and short fluctuations of full-threshold standard automated perimetry equal or higher than 0.80 dB had 80% sensitivity and 76% specificity over detecting early retinal nerve fiber layer loss in patients with type 1 diabetes mellitus (area under the curve = 0.855, p < 0.001). CONCLUSION This study showed that thinner retinal nerve fiber layer in patients with type 1 diabetes mellitus may be associated with abnormal retinal sensitivity to short-wavelength stimulations in short-wavelength automated perimetry; however, retinal sensitivity to white stimulus was similar to that in healthy subjects in full-threshold standard automated perimetry.
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ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND RISK OF TRACTION RETINAL DETACHMENT IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY: Pooled Analysis of Five DRCR Retina Network Randomized Clinical Trials.
Bressler, NM, Beaulieu, WT, Bressler, SB, Glassman, AR, Melia, BM, Jampol, LM, Jhaveri, CD, Salehi-Had, H, Velez, G, Sun, JK, et al
Retina (Philadelphia, Pa.). 2020;(6):1021-1028
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PURPOSE To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.
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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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Diabetic retinopathy and ultrawide field imaging.
Ashraf, M, Shokrollahi, S, Salongcay, RP, Aiello, LP, Silva, PS
Seminars in ophthalmology. 2020;(1):56-65
Abstract
The introduction of ultrawide field imaging has allowed the visualization of approximately 82% of the total retinal area compared to only 30% using 7-standard field Early Treatment Diabetic Retinopathy (ETDRS) photography. This substantially wider field of view, while useful in many retinal vascular diseases, is particularly important in diabetic retinopathy where eyes with predominantly peripheral lesions or PPL have been shown to have significantly greater progression rates compared to eyes without PPL. In telemedicine settings, ultrawide field imaging has substantially reduced image ungradable rates and increased rate of disease identification allowing care to be delivered more effectively. Furthermore, the use of ultrawide field fluorescein angiography allows the visualization of significantly more diabetic retinal lesions and allows more accurate quantification of total retinal nonperfusion, with potential implications in the management of diabetic retinopathy and diabetic macular edema. The focus of this paper is to review the current role of ultrawide field imaging in diabetic retinopathy and its possible future role in innovations for retinal image analysis such as artificial intelligence and vessel caliber measurements.
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Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.
Antoszyk, AN, Glassman, AR, Beaulieu, WT, Jampol, LM, Jhaveri, CD, Punjabi, OS, Salehi-Had, H, Wells, JA, Maguire, MG, Stockdale, CR, et al
JAMA. 2020;(23):2383-2395
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IMPORTANCE Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. OBJECTIVE To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. INTERVENTIONS Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. RESULTS Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept. CONCLUSIONS AND RELEVANCE Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02858076.