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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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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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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.
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Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial.
Yeh, S, Khurana, RN, Shah, M, Henry, CR, Wang, RC, Kissner, JM, Ciulla, TA, Noronha, G, ,
Ophthalmology. 2020;(7):948-955
Abstract
PURPOSE Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). DESIGN Phase 3 masked, randomized trial. PARTICIPANTS One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. METHODS Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12. MAIN OUTCOME MEASURES The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24. RESULTS In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively). CONCLUSIONS Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.
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Effect of intravitreal triamcinolone acetonide injection at the end of vitrectomy for vitreous haemorrhage related to proliferative diabetic retinopathy.
Takamura, Y, Shimura, M, Katome, T, Someya, H, Sugimoto, M, Hirano, T, Sakamoto, T, Gozawa, M, Matsumura, T, Inatani, M, et al
The British journal of ophthalmology. 2018;(10):1351-1357
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BACKGROUND/AIMS: To investigate whether intravitreal injection of triamcinolone acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR). METHODS This prospective, multicentre, randomised study conducted at seven sites in Japan enrolled patients diagnosed as having VH following PDR. Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA at the end of the surgery. Anterior flare intensity (AFI), central retinal thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery and compared. RESULTS Number of patients who completed 6 months of follow-up was 40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week (P=0.019) and 1 month (P=0.037). There were no significant differences in CRT, BCVA and IOP between the groups through the observational periods. In the cases with macular oedema >350 µm of CRT at 3 days, CRT was significantly lower in the IVTA+VIT group than in the VIT group at 1 month (P=0.041). CONCLUSIONS IVTA combined with vitrectomy and cataract surgery contributed to inhibit the postoperative inflammation in patients with VH due to PDR. The effect of IVTA in the reduction of diabetic macular oedema may be limited to the early stage after surgery. TRIAL REGISTRATION NUMBER UMIN000020376, Post-results.
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Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema.
Bressler, SB, Glassman, AR, Almukhtar, T, Bressler, NM, Ferris, FL, Googe, JM, Gupta, SK, Jampol, LM, Melia, M, Wells, JA, et al
American journal of ophthalmology. 2016;:57-68
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PURPOSE To compare long-term vision and anatomic effects of ranibizumab with prompt or deferred laser vs laser or triamcinolone + laser with very deferred ranibizumab in diabetic macular edema (DME). DESIGN Randomized clinical trial. METHODS Eight hundred and twenty-eight study eyes (558 [67%] completed the 5-year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + prompt laser. The latter 2 groups could initiate ranibizumab as early as 74 weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. RESULTS At 5 years mean (± standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the ranibizumab + deferred laser (N = 111), ranibizumab + prompt laser (N = 124), laser/very deferred ranibizumab (N = 198), and triamcinolone + laser/very deferred ranibizumab (N = 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The difference (95% confidence interval) in mean change between ranibizumab + deferred laser and laser/very deferred ranibizumab and triamcinolone + laser/very deferred ranibizumab was 4.4 (1.2-7.6, P = .001) and 2.8 (-0.9 to 6.5, P = .067), respectively, at 5 years. CONCLUSIONS Recognizing limitations of follow-up available at 5 years, eyes receiving initial ranibizumab therapy for center-involving DME likely have better long-term vision improvements than eyes managed with laser or triamcinolone + laser followed by very deferred ranibizumab for persistent thickening and vision impairment.
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Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network.
Bressler, SB, Almukhtar, T, Aiello, LP, Bressler, NM, Ferris, FL, Glassman, AR, Greven, CM, ,
Retina (Philadelphia, Pa.). 2013;(10):2080-8
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PURPOSE Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. METHODS Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. RESULTS In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. CONCLUSION A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.
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Evaluation of masking study participants to intravitreal injections in a randomized clinical trial.
Glassman, AR, Stockdale, CR, Beck, RW, Baker, C, Bressler, NM, ,
Archives of ophthalmology (Chicago, Ill. : 1960). 2012;(2):190-4
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OBJECTIVE To evaluate the success of masking study participants to treatment allocation using sham intravitreal injections. METHODS Eyes were randomized to receive sham injections plus prompt laser, intravitreal ranibizumab injections plus prompt laser, intravitreal ranibizumab injections plus deferred laser, or intravitreal triamcinolone acetonide injections plus prompt laser up to every 16 weeks with sham injections intermittently. All eyes could receive treatment or sham as often as every 4 weeks. Participants with 2 study eyes had 1 eye randomized to sham plus prompt laser and 1 eye randomized to a real injection group. Sham injections were performed by pressing the syringe hub against the conjunctiva to mimic a real injection. Laser treatment was not masked. At the 1-year visit, participants were asked if they believed that the injections received during the study were real, sham, or sometimes real and sometimes sham. RESULTS Among 423 participants with 1 study eye, the correct assignment was stated by 9.9% of the sham plus prompt laser group, 88.0% of the ranibizumab plus prompt laser group, 89.6% of the unmasked ranibizumab plus deferred laser group, and 44.0% of the triamcinolone plus prompt laser group. Among 112 participants with 2 study eyes, the correct assignment was stated for 24.1% of the sham plus prompt laser eyes. CONCLUSIONS Successful masking of an intravitreal injection can be accomplished when a sham injection procedure carefully mimics a real injection procedure. Masking seems less successful when one eye is receiving a real injection and the other eye is receiving a sham injection or when an individual eye receives both real and sham injections.
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Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation.
, , Googe, J, Brucker, AJ, Bressler, NM, Qin, H, Aiello, LP, Antoszyk, A, Beck, RW, Bressler, SB, Ferris, FL, et al
Retina (Philadelphia, Pa.). 2011;(6):1009-27
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PURPOSE To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation. METHODS Three hundred and forty-five eyes with a visual acuity of 20/320 or better, center-involved diabetic macular edema receiving focal/grid laser, and diabetic retinopathy receiving prompt panretinal photocoagulation were randomly assigned to sham (n = 123), 0.5-mg ranibizumab (n = 113) at baseline and 4 weeks, and 4-mg triamcinolone at baseline and sham at 4 weeks (n = 109). Treatment was at investigator discretion from 14 weeks to 56 weeks. RESULTS Mean changes (±SD) in visual acuity letter score from baseline were significantly better in the ranibizumab (+1 ± 11; P < 0.001) and triamcinolone (+2 ± 11; P < 0.001) groups compared with those in the sham group (-4 ± 14) at the 14-week visit, mirroring retinal thickening results. These differences were not maintained when study participants were followed for 56 weeks for safety outcomes. One eye (0.9%; 95% confidence interval, 0.02%-4.7%) developed endophthalmitis after receiving ranibizumab. Cerebrovascular/cardiovascular events occurred in 4%, 7%, and 3% of the sham, ranibizumab, and triamcinolone groups, respectively. CONCLUSION The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.
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Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.
Elman, MJ, Bressler, NM, Qin, H, Beck, RW, Ferris, FL, Friedman, SM, Glassman, AR, Scott, IU, Stockdale, CR, Sun, JK, et al
Ophthalmology. 2011;(4):609-14
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OBJECTIVE To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). DESIGN Multicenter, randomized clinical trial. PARTICIPANTS A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. METHODS Continuation of procedures previously reported for the randomized trial. MAIN OUTCOME MEASURES Best-corrected visual acuity and safety at the 2-year visit. RESULTS At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. CONCLUSIONS The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.
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Baseline predictors of visual acuity and retinal thickness outcomes in patients with retinal vein occlusion: Standard Care Versus COrticosteroid for REtinal Vein Occlusion Study report 10.
Scott, IU, VanVeldhuisen, PC, Oden, NL, Ip, MS, Blodi, BA, Hartnett, ME, Cohen, G, ,
Ophthalmology. 2011;(2):345-52
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OBJECTIVE To investigate baseline factors associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study. DESIGN Two multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and one evaluating participants with branch retinal vein occlusion (BRVO). PARTICIPANTS Participants with follow-up data of 1 year or more, including 238 with CRVO and 367 with BRVO. METHODS Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method, and central retinal thickness was measured by optical coherence tomography (OCT). Regression analysis related these outcomes to 20 baseline measures. Multiple P values were adjusted to control the false discovery rate. MAIN OUTCOME MEASURES Outcome measures of visual acuity letter score included absolute change from baseline, a gain of ≥ 15 from baseline, and a loss of ≥ 15 from baseline. Outcome measures of center point thickness included absolute change from baseline, a measurement of ≤ 250 μm, and a measurement of ≥ 500 μm. Outcomes were assessed at 1 and 2 years. RESULTS For CRVO and BRVO, younger age was associated with improved visual acuity and central retinal thickness outcomes. For CRVO, triamcinolone treatment and less severe anatomic abnormalities of the retina (center point thickness and areas of retinal hemorrhage, thickening, and fluorescein leakage) were predictive of better visual acuity outcomes. For BRVO, no history of coronary artery disease was predictive of improved visual acuity outcomes. For center point thickness outcomes, shorter duration of macular edema was associated with improvement in both disease entities. For CRVO, higher baseline visual acuity letter score was predictive of favorable OCT outcomes. For BRVO, lower baseline visual acuity letter score, presence of dense macular hemorrhage, and no prior grid photocoagulation were predictive of favorable OCT outcomes. CONCLUSIONS Several factors were predictive of better visual acuity outcomes and more favorable OCT outcomes, including younger age and shorter duration of macular edema, respectively. These factors may assist clinicians in predicting disease course for patients with CRVO and BRVO.