-
1.
Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy: The EMERALD Study.
Lois, N, Cook, JA, Wang, A, Aldington, S, Mistry, H, Maredza, M, McAuley, D, Aslam, T, Bailey, C, Chong, V, et al
Ophthalmology. 2021;(4):561-573
Abstract
PURPOSE The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. DESIGN Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. PARTICIPANTS Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. METHODS A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). MAIN OUTCOME MEASURES Primary outcome: sensitivity of the new pathway. SECONDARY OUTCOMES specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. RESULTS The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. CONCLUSIONS The new pathway has acceptable sensitivity and would release resources. Users' suggestions should guide implementation.
-
2.
A Randomized, Double-Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Patients with Visual Impairment due to Diabetic Macular Edema (KITE).
Garweg, JG
Klinische Monatsblatter fur Augenheilkunde. 2020;(4):450-453
Abstract
BACKGROUND Brolucizumab is a single-chain variable antibody fragment (scVF) that specifically binds to VEGF-A. The results of two large phase III, multicentre, randomized clinical trials comparing intravitreal treatment with Brolucizumab and Aflibercept in neovascular age-related degeneration demonstrated its potency in the treatment of neovascular age-related macular degeneration (nAMD). METHODS The currently tested injected dose of 6 mg Brolucizumab results in a 11.2 - 13.3 times higher equivalent molar dose compared to Aflibercept 2 mg. Thus, it is conceivable that the effect of Brolucizumab in DME exceeds that of other currently used anti-VEGF agents with regards to effect durability; this was confirmed for nAMD in a phase I/II study. RESULTS Approved anti-VEGF drugs have shown unprecedented success compared to laser treatment with regards to restoration of visual acuity and improvement of diabetic retinopathy severity scores for up to 5 years. The visual gains were sustained after the loading phase and a reduced number of injections were required after the first year independent of the treatment strategy. Compared to pan-retinal laser photocoagulation, the time to progression of DRP was markedly extended and was proven by better preservation of the visual field, prevention of severe vision loss, hemorrhagic complications, and the need for intraocular surgery. CONCLUSIONS The ongoing prospective, randomized, phase III clinical studies in DME, KITE, and KESTREL aim to confirm the non-inferiority of Brolucizumab 6 mg compared to Aflibercept 2 mg on a functional and morphological level as well as durability effect over 2 years.
-
3.
Complete Posterior Vitreous Detachment Reduces the Need for Treatment of Diabetic Macular Edema.
Anderson, W, Piggott, K, Bao, YK, Pham, H, Kavali, S, Rajagopal, R
Ophthalmic surgery, lasers & imaging retina. 2019;(11):e266-e273
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVE To evaluate the vitreomacular interface and its relation to treatment burden for diabetic macular edema (DME) in patients without overt vitreomacular traction (VMT). PATIENTS AND METHODS A retrospective cohort study of 494 eyes from 274 patients who had macular spectral-domain optical coherence tomography (SD-OCT) and did not have proliferative diabetic retinopathy, DME, or VMT at the initial visit. Posterior vitreous detachment (PVD) was categorized at the initial visit into five stages (0-4) using SD-OCT parameters alone. RESULTS Two of 34 eyes (6.9%) presenting with a complete PVD required DME treatment during follow-up, whereas 144 of 460 eyes (31.3%) without a complete PVD at baseline required treatment (P = .001, Chi-squared). After adjusting for age, ethnicity, gender, and HbA1c, complete PVD at baseline was associated with a significant reduction in risk of DME therapy (hazard ratio: 0.18; 95% confidence interval, 0.05-0.73; P = .02). CONCLUSION Complete PVD is independently associated with a reduced need for DME treatment. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e266-e273.].
-
4.
Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.
Wielders, LHP, Schouten, JSAG, Winkens, B, van den Biggelaar, FJHM, Veldhuizen, CA, Murta, JCN, Goslings, WRO, Kohnen, T, Tassignon, MJ, Joosse, MV, et al
Journal of cataract and refractive surgery. 2018;(7):836-847
Abstract
PURPOSE To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING Twelve European study centers. DESIGN Randomized clinical trial. METHODS Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 μm and 9.7 μm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.
-
5.
A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema.
Gale, JD, Berger, B, Gilbert, S, Popa, S, Sultan, MB, Schachar, RA, Girgenti, D, Perros-Huguet, C
Investigative ophthalmology & visual science. 2018;(6):2659-2669
Abstract
PURPOSE Ligands for the proinflammatory C-C chemokine receptor types 2 and 5 (CCR2 and CCR5) are elevated in the eyes of patients with diabetic macular edema (DME). We evaluated the efficacy and safety of PF-04634817, an oral CCR2/5 dual antagonist, versus intravitreal ranibizumab, in adult subjects with DME. METHODS In this phase II, randomized, placebo-controlled, double-masked study, eligible subjects (≥18 years of age) had type 1 or 2 diabetes and DME with best-corrected visual acuity (BCVA) of 20/32 or worse (letter score ≤ 78), and up to 20/320 or better (≥24 letter score), in the study eye. Subjects were assigned randomly 1:1 to once-daily (QD) oral PF-04634817 200 mg plus masked sham therapy as placebo or monthly intravitreal ranibizumab 0.3/0.5 mg plus QD oral placebo. The primary objective was to evaluate the efficacy of PF-04634817 compared with ranibizumab in change from baseline in BCVA after 12 weeks in a noninferiority design. Noninferiority was based on BCVA 80% confidence interval (CI): there had to be a less than three letter loss in the PF-04634817 arm compared with the ranibizumab arm. RESULTS A total of 199 subjects were randomized. Least squares mean difference in change in BCVA from baseline to week 12 in the study eye for the PF-04634817 arm was -2.41 letters (80% CI: -3.91, -0.91; P = 0.04) compared with ranibizumab. PF-04634817 was well tolerated. CONCLUSIONS Treatment with oral CCR2/5 receptor dual antagonist PF-04634817 was associated with a modest improvement in BCVA, but did not meet the predefined noninferiority criteria compared with intravitreal ranibizumab.
-
6.
Evaluation of Efficacy and Safety of Dexamethasone Intravitreal Implants of Vitrectomized and Nonvitrectomized Eyes in a Real-World Study.
Rezkallah, A, Malclès, A, Dot, C, Voirin, N, Agard, É, Vié, AL, Denis, P, Mathis, T, Kodjikian, L
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2018;(8):596-602
Abstract
PURPOSE To compare the efficacy and safety of the dexamethasone (DEX) intravitreal implant of vitrectomized and nonvitrectomized eyes in real-world conditions. METHODS This was a retrospective, multicenter, observational study. All consecutive patients presenting with at least one 0.7-mg intravitreal injection of DEX implant were included in this study. A total of 186 eyes in 170 patients were analyzed. Fifty-nine eyes were vitrectomized at baseline and 127 eyes had no vitrectomy at the last visit. Among the baseline-vitrectomized eyes analyzed, 72.9% were treatment naive eyes, and 44.1% of nonvitrectomized eyes had no prior treatment. RESULTS There was no statistically significant difference in the variation in best-corrected visual acuity (BCVA) between the 2 groups (P = 0.343). Variations of BCVA and central macular thickness were not significantly different between nonvitrectomized eyes and baseline-vitrectomized eyes. The intraocular pressure profile was the same in both nonvitrectomized eyes and baseline-vitrectomized eyes. The mean interval between injections was 6.9 months (2; 27.7) for nonvitrectomized eyes and 5.2 months (4; 22.1) for baseline-vitrectomized eyes (P = 0.001). The mean number of IVIs was 2 (1; 6) for nonvitrectomized eyes and 2.3 (1; 10) for baseline-vitrectomized eyes (P = 0.188) during the total follow-up period. CONCLUSION This large cohort shows that vitrectomy does not seem to influence the efficacy and safety profile of dexamethasone intravitreal implant for DME.
-
7.
Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study.
Singer, MA, Dugel, PU, Fine, HF, Capone, A, Maltman, J
Ophthalmic surgery, lasers & imaging retina. 2018;(6):425-435
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVE Dexamethasone intravitreal implant (DEX) (Ozurdex; Allergan plc, Dublin, Ireland) is approved for the treatment of diabetic macular edema (DME). This study assessed the real-world effectiveness, safety, and reinjection interval of DEX in adult patients with DME. PATIENTS AND METHODS This was a phase 4, prospective, multicenter (18 U.S. sites), observational study. RESULTS The study population comprised 177 patients (180 eyes; 93.8% previously treated). Baseline mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were 54.4 letters and 424.6 μm, respectively. DEX was administered as monotherapy or with other DME therapy (55%/45%). The mean reinjection interval was 5.0 months. Mean maximum BCVA change from baseline after the first three DEX injections was +9.1 letters, +7.7 letters, and +7.0 letters, respectively (P < .001); 36.0% of eyes achieved 15-letter or greater BCVA improvement. Mean maximum CRT change from baseline was -137.7 μm (P < .001). CONCLUSION DEX used alone or with other DME therapy improved visual and anatomic outcomes in DME patients in clinical practice, with no new safety concerns. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:425-435.].
-
8.
Continuous positive airway pressure effect on visual acuity in patients with type 2 diabetes and obstructive sleep apnoea: a multicentre randomised controlled trial.
West, SD, Prudon, B, Hughes, J, Gupta, R, Mohammed, SB, Gerry, S, Stradling, JR, ,
The European respiratory journal. 2018;(4)
Abstract
We sought to establish whether continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) in people with type 2 diabetes and diabetic macular oedema (DMO) improved visual acuity.We randomly assigned 131 eligible patients aged 30-85 years from 23 UK centres with significant DMO causing visual impairment (LogMAR letters identified ≥39 and ≤78, score 0.92-0.14) plus severe OSA on screening to either usual ophthalmology care (n=67) or usual ophthalmology care plus CPAP (n=64) for 12 months.Mean age of participants was 64 years, 73% male, mean body mass index 35.0 kg·m- 2 Mean 4% oxygen desaturation index was 36 events·h-1 There was no significant difference in the visual acuity at 12 months between the CPAP group and the control group (mean LogMAR 0.33 (95% CI 0.29-0.37) versus 0.31 (95% CI 0.27-0.35); p=0.39), and no significant correlation between change in LogMAR and average CPAP use. The median±sd (range) daily CPAP use was 3.33±2.25 (0-7.93) h at 3 months, 3.19±2.54 (0-8.07) h at 6 months and 3.21±2.70 (0-7.98) h at 12 months.CPAP therapy for OSA did not improve visual acuity in people with type 2 diabetes and DMO compared with usual care alone over 12 months.
-
9.
Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Factors Associated with Vision and Edema Outcomes.
Bressler, SB, Beaulieu, WT, Glassman, AR, Gross, JG, Melia, M, Chen, E, Pavlica, MR, Jampol, LM, ,
Ophthalmology. 2018;(11):1776-1783
-
-
Free full text
-
Abstract
PURPOSE To identify baseline factors associated with change in visual acuity or development of vision-impairing central-involved diabetic macular edema (DME) over 2 years when treating proliferative diabetic retinopathy (PDR) with ranibizumab or panretinal photocoagulation (PRP). DESIGN Post hoc analyses of randomized, multicenter clinical trial data. PARTICIPANTS Eyes completing the 2-year visit (n = 328) or without vision-impairing central-involved DME at baseline (n = 302) in Diabetic Retinopathy Clinical Research Network Protocol S. METHODS Intravitreous ranibizumab (0.5 mg/0.05 ml) or PRP. MAIN OUTCOME MEASURES Change in visual acuity (area under the curve) and development of vision-impairing (20/32 or worse) central-involved DME over 2 years. RESULTS After multivariable model selection with adjustment for baseline visual acuity and central subfield thickness, no factors were identified as associated with change in visual acuity or development of vision-impairing central-involved DME within the ranibizumab group. In the PRP group, worse change in visual acuity was more likely with higher hemoglobin A1c level (-0.6 letters per 1% increase; 95% confidence interval [CI], -1.2 to -0.1 letters; continuous P = 0.03), more severe diabetic retinopathy (difference between high-risk PDR or worse vs. moderate PDR or better, -2.8 letters [95% CI, -5.5 to -0.2 letters]; continuous P = 0.003), and higher mean arterial pressure (difference between ≥100 mmHg vs. <100 mmHg, -2.0 letters [95% CI, -4.6 to 0.5 letters]; continuous P = 0.009). Development of vision-impairing central-involved DME was more likely with higher hemoglobin A1c level (hazard ratio [HR] per 1% increase, 1.31 [95% CI, 1.13-1.52]; continuous P < 0.001), more severe diabetic retinopathy (HR for high-risk PDR or worse vs. moderate PDR or better, 1.46 [95% CI, 0.73-2.92]; continuous P = 0.03), and the presence of cystoid abnormalities within 500 μm of the macula center (HR, 2.90 [95% CI, 1.35-6.24]; P = 0.006). CONCLUSIONS For eyes managed with PRP, higher hemoglobin A1c level and more severe diabetic retinopathy were associated with less vision improvement and an increased risk of vision-impairing central-involved DME developing. When managing PDR with ranibizumab, eyes gained vision, on average, with no baseline characteristics identified as associated with visual acuity or central-involved DME outcomes.
-
10.
Effectiveness and safety of dexamethasone implants for postsurgical macular oedema including Irvine-Gass syndrome: the EPISODIC-2 study.
Bellocq, D, Pierre-Kahn, V, Matonti, F, Burillon, C, Voirin, N, Dot, C, Akesbi, J, Milazzo, S, Baillif, S, Soler, V, et al
The British journal of ophthalmology. 2017;(3):333-341
Abstract
AIM: To assess the effectiveness of intravitreal dexamethasone implants for treating postsurgical macular oedema (PSMO) including Irvine-Gass syndrome and determining the predictive factors of treatment response. METHODS Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. One hundred patients were included between April 2011 and June 2014, with a minimum of 1-year follow-up. Patients received dexamethasone implant 0.7 mg at baseline. Clinical characteristics, best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and intraocular pressure were measured at each visit. The main outcome measure was the change in BCVA (Early Treatment of Diabetic Retinopathy Study (ETDRS) letters: L). An analysis of predictive factors of treatment response is also provided. RESULTS Mean improvement in BCVA was 9.6 (±10.6) L at month 6 and 10.3 (±10.7) L at month 12 (p<0.001). The proportion of eyes with gains in BCVA of 15 or more letters was 32.5% and 37.5% at months 6 and 12, respectively. The mean reduction in CSMT was 135.2 and 160.9 µm at months 6 and 12, respectively (p<0.001). Thirty-seven per cent of patients did not need a second injection after the first injection during follow-up. The presence of at least one PSMO risk factor decreases the probability of a gain in visual acuity (VA) ≥10 L (p=0.006). Initial VA ≤50 L at baseline and non-naïve status decrease the probability of having only one injection during follow-up (p=0.044). CONCLUSIONS The significant gain in BCVA from baseline achieved at month 6 was maintained at month 12 after intravitreal injection of dexamethasone implant. Naïve status seems to be a good predictive factor of treatment response.