The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) ...for the management of primary RRD.
Prospective, randomized controlled trial.
Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o'clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina.
Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively.
The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success.
One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P < 0.001).
Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.
To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone ...acetonide.
Retrospective, comparative case series.
Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records.
The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given.
The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis.
Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis compared with those without postinjection antibiotics. The risk of endophthalmitis after intravitreal injection varied among agents that were used. Among the 9 cases of clinically suspected endophthalmitis, regardless of prophylactic strategies used, the incidence of endophthalmitis per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in 5386 for bevacizumab.
The overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics.
We reviewed the literature on the efficacy and safety of pars plana vitrectomy (PPV), scleral buckle (SB), and pneumatic retinopexy (PR) for the management of rhegmatogenous retinal detachments ...(RRDs). A systematic search was performed on three databases from inception to September 2020. Randomized controlled trials (RCTs) comparing RRD management options were included. Meta-analysis was performed using a random effects model. Eighteen RCTs and 2,751 eyes were included. For PPV versus SB, early postoperative corrected distance visual acuity (CDVA) favored SB (weighted mean <1 month postoperatively: ~counting fingers for PPV versus ~20/260 for SB, P = 0.02), but differences were nonsignificant at other time points. There was no difference for primary reattachment (P = 0.08). PPV had a lower incidence of choroidal detachment (P = 0.004), hypotony (P = 0.01), and strabismus/diplopia (P = 0.04) but a higher incidence of iatrogenic breaks (P = 0.003) and cataract development/progression (P = 0.05) relative to SB. Combination management was nonsignificantly different relative to PPV alone for CDVA, complications and reattachment rate.
In closing, PPV is associated with a slower visual recovery, but similar final visual acuity and primary reattachment rate relative to SB. Combination procedures did not improve primary reattachment rates or vision relative to standalone PPV. Heterogeneity was seen across the included trials, and further randomized trials are needed to reduce the uncertainty of these estimates.
Refractory diabetic macular edema (DME) to monthly intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy has a prevalence of approximately 40% in landmark clinical trials. Options ...for these patients include use of intravitreal steroids, focal laser, or switching to an alternative anti-VEGF agent. We summarize the key conclusions from studies analyzing the efficacy of switching anti-VEGF agents for refractory DME. Twenty-four studies were included in analysis. The most common definitions of refractory in the included studies were a central retinal thickness (CRT) greater than 300μm or a reduction in CRT less than 10% after at least 3-6 prior anti-VEGF injections. Switching to intravitreal aflibercept (IVA) from either intravitreal ranibizumab (IVR) or bevacizumab (IVB) is associated with moderate to significant improvement in central subfield thickness and may be an appropriate choice for patients with refractory DME. The improvement in retinal thickness and edema is typically seen after the first 3 injections of IVA post-switch. Switching to IVR has also demonstrated improvement in CRT at 3–6 months post switch in large sample population studies. Future studies are required to elucidate the ideal time point for a switch in anti-VEGF agent or which patients would benefit from this change.
IMPORTANCE: Although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) reported herein and the Treat and Extend study ...provided data to show noninferiority of treat-and-extend (T&E) at 12 months, to date there are few data on 24-month T&E trials compared with monthly dosing. OBJECTIVE: To compare the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD) after 24 months. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, multicenter, noninferiority intention-to-treat trial with a margin of −5 letters in best-corrected visual acuity (BCVA) from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 patients with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to August 28, 2018, and data analysis was performed between August 29 and September 12, 2018. INTERVENTIONS: Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab, 0.5 mg, in either a T&E or monthly dosing regimen. MAIN OUTCOMES AND MEASURES: Mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24. RESULTS: Of the 580 randomized patients, 350 were women (60.3%) and 547 were white (94.3%). Mean (SD) age was 78.8 (7.8) years. By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001). The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, −1.6 to 3.3; P = .21). There was a gain of 15 or more letters in 25.5% of the T&E group and 23.1% of the monthly treatment group (difference, 2.4%; 95% CI, −6.8% to 11.6%; P = .59) and a loss of 15 or more letters in 6.5% of the T&E group and 5.8% of the monthly treatment group (difference, −0.7%; 95% CI, −9.9% to 8.5%; P = .85). CONCLUSIONS AND RELEVANCE: These findings suggest that change in vision from baseline is not worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02103738
To compare the efficacy of ranibizumab using a treat-and-extend (T&E) regimen with monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD).
Prospective, ...randomized, open-label, multicenter, noninferiority, postauthorization study.
Treatment-naive patients with choroidal neovascularization secondary to AMD.
Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab at a dose of 0.5 mg in either a T&E or monthly dosing regimen. The noninferiority of T&E compared with the monthly dosing regimen was to be shown using a margin of 5 letters in best-corrected visual acuity (BCVA) improvement.
Mean change in BCVA in Early Treatment Diabetic Retinopathy Study letters from baseline to month 12.
Baseline and 12-month visual acuity data are available for 526 patients (T&E, n = 268; monthly, n = 258). At baseline, mean age was 78.8 years (standard deviation SD, 7.8 years), 60.3% were women, and 94.3% were white. No significant between-group baseline differences were observed. The primary outcome of noninferiority regarding visual acuity was met with mean BCVA improvement of 8.4 letters (SD, 11.9 letters) and 6.0 letters (SD, 11.9 letters; P = 0.017) in the T&E and monthly regimens, respectively, with a between-group mean difference of 2.38 letters (95% confidence interval, 0.32-4.45 letters). Per protocol, a secondary analysis was performed to test for superiority of number of injections received up to month 12. This analysis demonstrated significantly fewer injections with T&E versus monthly dosing (9.4 and 11.8 injections, respectively), with a mean difference of -2.46 injections (95% confidence interval, -2.68 to -2.23 injections).
The 12-month results of this 2-year study demonstrated that regarding visual outcomes, the T&E regimen was noninferior to a monthly dosing regimen. Similar visual outcomes in the T&E group as in the monthly dosing group were achieved with significantly fewer injections.
IMPORTANCE: Variability in response to anti–vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help ...anticipate responses to anti-VEGF therapy. OBJECTIVES: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. DESIGN, SETTING, AND PARTICIPANTS: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. INTERVENTIONS: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. MAIN OUTCOMES AND MEASURES: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. RESULTS: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, −190.88; interquartile range IQR, −634.20 to −26.54; P < .001), VEGF (median change, −639.45; IQR, −1040.61 to −502.61; P < .001), placental growth factor (median change, −1.31; IQR, −5.99 to −0.01; P < .001), IL-6 (median change, −38.61; IQR, −166.72 to −2.80; P < .001), and monocyte chemoattractant protein 1 (median change, −90.13; IQR, −382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). CONCLUSIONS AND RELEVANCE: Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.
Introduction: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&E) relative to monthly ...administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Methods: Treatment-naïve patients with nAMD were randomized to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics. Results: A total of 285 participants undergoing T&E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was −79.2 ± 95.0, −143.9 ± 128.9, −97.7 ± 101.1, −120.9 ± 105.3, and −133.2 ± 108.8 μm in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. Conclusion: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8–10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&E in nAMD.
To describe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the characteristics of retinal detachments (RD) at a tertiary centre.
Retrospective consecutive case series.
One hundred ...and ninety eyes of 188 patients with primary, rhegmatogenous RD.
Patients with RD who presented over a 1-year period (September 14, 2019 to September 13, 2020). The relationship between demographic, anatomic, and visual acuity parameters were compared before and after onset of the pandemic using generalized estimating equations.
Macular status and corrected distance visual acuity on presentation.
One hundred and eighty-seven eyes, divided into 2 cohorts: pre-COVID (n = 100 September 14, 2019 to March 13, 2020) and post-COVID (n = 87, March 14, 2020 to September 13, 2020). Of the eyes, 63.2% (n = 87) presented with macular detachment in the post-COVID group compared with 45% (n = 100) in the pre-COVID group (odds ration OR, 2.14; 95% confidence interval CI,1.19–3.86; p = 0.011). As well, eyes in the pre-pandemic cohort had significantly fewer detached quadrants on initial examination (OR, 0.53; 95% CI, 0.30–0.93; p = 0.026). Patients in the post-COVID group had a significantly worse corrected distance visual acuity at baseline (mean difference MD = –0.35 logMAR, 95% CI, –0.60 to –0.09; p = 0.008), but not at 1 month or at final follow-up. No differences were seen between groups with respect to demographics, lens status, treatment, time to presentation, or chronicity. Pneumatic retinopexy was the most commonly performed procedure in both cohorts, with a 71.5% success rate.
Closures after the COVID-19 pandemic affected the characteristics of RDs at presentation with respect to macular detachment, extent of RD, and presenting visual acuity. At final follow-up, final visual acuity and anatomic outcomes were similar between the 2 groups. These data are helpful for future patient education, triaging, and treatment decision making.
Décrire l'effet de la pandémie de COVID-19 sur les caractéristiques des décollements de la rétine (DR) dans un centre de soins tertiaires.
Étude rétrospective portant sur une série de cas consécutifs.
190 yeux de 188 patients présentant un DR rhegmatogène primitif.
On a comparé, chez des patients qui ont consulté en raison d'un DR sur une période de 1 an (du 14 septembre 2019 au 13 septembre 2020), le lien entre les paramètres démographiques, les caractéristiques anatomiques et l'acuité visuelle avant et après le début de la pandémie au moyen d’équations d'estimation généralisées.
État maculaire et acuité visuelle corrigée de loin au moment de l'examen initial.
187 yeux ont été répartis en 2 cohortes: 100 yeux qui ont été examinés avant la pandémie de COVID-19 (du 14 septembre 2019 au 13 mars 2020 – période pré-COVID) et 87 qui ont été examinés après le début de la pandémie (du 14 mars 2020 au 13 septembre 2020 – période post-COVID). On a observé un décollement maculaire dans 63,2 % des cas (n = 87 yeux) dans le groupe post-COVID, comparativement à 45,0 % des cas (n = 100 yeux) dans le groupe pré-COVID (rapport de cotes RC = 2,14; intervalle de confiance IC à 95 % = 1,19 à 3,86; p = 0,011). De même, les yeux de la cohorte pré-COVID présentaient significativement moins de quadrants décollés lors de l'examen initial (RC = 0,53; IC à 95 % = 0,30 à 0,93; p = 0,026). L'acuité visuelle corrigée de loin des patients du groupe post-COVID était significativement moindre au départ (DM = -0,35 logMAR; IC à 95 % = -0,60 à -0,09; p = 0,008), mais ce n’était plus le cas lors du suivi à 1 mois ou du suivi final. Aucune différence n'a été observée entre les groupes quant aux paramètres démographiques, à l’état du cristallin, au traitement, au moment de l'examen initial et au caractère chronique. Le traitement le plus fréquent dans les 2 cohortes a été la rétinopexie pneumatique, et le taux de réussite s'est élevé à 71,5 %.
La fermeture des services médicaux dans le contexte de la pandémie de COVID-19 a eu des répercussions sur les caractéristiques des DR observées au moment de l'examen initial quant au décollement maculaire, à l'ampleur du DR et à l'acuité visuelle. Au moment de la visite finale, l'acuité visuelle et les résultats anatomiques étaient semblables dans les 2 groupes. Ces données seront utiles pour ce qui est de la sensibilisation des patients, du processus de triage et des décisions thérapeutiques.
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