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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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The effects and safety of intravitreal triamcinolone injections in the treatment of diabetic macular edema.
Zając-Pytrus, HM, Kaczmarek, R, Strońska-Lipowicz, D, Pomorska, M, Misiuk-Hojło, M
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2017;(1):45-49
Abstract
BACKGROUND Diabetic macular edema (DME) is responsible for three-quarters of vision-loss cases in diabetic eye disease. In most cases, early treatment by laser photocoagulation can only stabilize vision. Glucocorticoids have been used as a local pharmacological treatment in DME when the inflammation seems to have a pathological background. OBJECTIVES The aim of the study was to establish the effectiveness and safety of intravitreal triamcinolone injections in the treatment of DME. MATERIAL AND METHODS Twenty mg intravitreal injections of triamcinole acetonide (IVTA) were applied to 110 DME patients after ineffective laserphotocoagulation or as an initial treatment. Best corrected visual acuity (BCVA) for distant and near vision, central retinal thickness and intraocular pressure (IOP) were analyzed before and after the treatment at intervals of 1 week, 1 month, 3 months and 6 months. The measurements were continued in cases of repeated IVTA. RESULTS Statistically significant improvements were observed in BCVA in near and distant vision, as well as a decrease in central retinal thickness after all time-intervals following IVTA. BCVA in distant vision was not significantly improved after repeated IVTA. IOP increases were observed 1 week, 1 and 3 months after IVTA, but not at 6 months after IVTA. No sight-threatening side effects of IVTA were observed. CONCLUSIONS IVTA is useful in stabilizing DME progression, although its therapeutic effect may be timelimited.
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A prospective clinical trial on the influence of a triamcinolone/demeclocycline and a calcium hydroxide based temporary cement on pain perception.
Willershausen, B, Willershausen, I, Ehlers, V, Azaripour, A, Briseño, B
Head & face medicine. 2012;:9
Abstract
INTRODUCTION The aim of this clinical trial was to compare the degree of short term post-operative irritation after application of a triamcinolone/demeclocycyline based or a calcium hydroxide based provisional cement. METHODS A total of 109 patients (55 female and 54 male; mean age: 51 ± 14 years) with primary or secondary dentinal caries were randomly assigned to the two treatment groups of this biomedical clinical trial (phase III). Selection criteria were good systemic health and treated teeth, which were vital and showed no symptoms of pulpitis. Up to three teeth were prepared for indirect metallic restorations, and the provisional restorations were cemented with a triamcinolone/demeclocycyline (Ledermix) or a calcium hydroxide (Provicol) based material. The intensity of post-operative pain experienced was documented according to the VAS (4, 12, 20, 24, and 82 h) and compared to VAS baseline. RESULTS A total of 159 teeth were treated (Ledermix: 83 teeth, Provicol: 76 teeth). The minor irritation of the teeth, experienced prior to treatment, was similar in both groups; however, 4 h after treatment this value was significantly higher in the Provicol group than in the Ledermix group (p < 0.005, t-test). After 12 h, the difference was no longer significant. The number of patients taking analgesics for post-treatment pain was higher in the Provicol group (n = 11/53) than in the Ledermix group (n = 3/56). CONCLUSIONS The patients had no long term post-operative pain experience in both groups. However, within the first hours after cementation the sensation of pain was considerably higher in the Provicol group than in the Ledermix group.
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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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SCORE Study report 1: baseline associations between central retinal thickness and visual acuity in patients with retinal vein occlusion.
Scott, IU, VanVeldhuisen, PC, Oden, NL, Ip, MS, Blodi, BA, Jumper, JM, Figueroa, M, ,
Ophthalmology. 2009;(3):504-12
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OBJECTIVE To investigate the relationship between baseline center point retinal thickness measured by optical coherence tomography (OCT) and best-corrected visual acuity in eyes with macular edema associated with retinal vein occlusion and to investigate other factors associated with baseline visual acuity letter score. DESIGN The Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study includes 2 multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and the other evaluating participants with branch retinal vein occlusion (BRVO). PARTICIPANTS After omitting 17 participants with missing or unreliable OCT measurements, analyses proceeded with 665 enrolled SCORE Study participants (665 eyes), including 262 with CRVO and 403 with BRVO. METHODS At baseline, center point thickness was measured by OCT (Stratus OCT 3 [n=663] and OCT2 [n=2]; Carl Zeiss Meditech, Dublin, CA), and visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) methodology. MAIN OUTCOME MEASURES Center point thickness and best-corrected E-ETDRS visual acuity letter score. RESULTS The correlation coefficient for the association between baseline OCT-measured center point thickness and best-corrected E-ETDRS visual acuity letter score is -0.27 (95% confidence limit: -0.38 to -0.16) for participants in the CRVO trial and -0.28 (95% confidence limit: -0.37 to -0.19) in the BRVO trial. Regression modeling estimated the following decrease in baseline visual acuity letter score for every 100-microm increase in OCT-measured center point thickness: 1.7 letters (P=0.0007) for CRVO and 1.9 letters (P<0.0001) for BRVO. On the basis of multivariate regression models, baseline factors significantly associated (P<0.05, after adjusting for multiple testing) with baseline visual acuity letter score include age and duration of macular edema for CRVO participants and center point thickness and presence of cystoid spaces for BRVO participants. CONCLUSIONS The correlation between OCT-measured center point thickness and visual acuity letter score is modest. OCT-measured center point thickness represents a useful tool for the detection and monitoring of macular edema in retinal vein occlusion, but it cannot reliably substitute for visual acuity measurements.
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Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis.
Singh, S, Pal, V, Dhull, CS
Indian journal of ophthalmology. 2001;(4):241-5
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PURPOSE To study and compare the efficacy of supratarsal injection of dexamethasone sodium phosphate, triamcinolone acetonide and hydrocortisone sodium succinate in treating refractory vernal keratoconjunctivitis (VKC). METHODS Prospective randomized, double-masked, case control trial, including 90 eyes of 45 patients with refractory VKC. Both eyes of each patient were randomly assigned to receive supratarsal injection of one of three compounds under study: dexamethasone sodium phosphate (2 mg), triamcinolone acetonide (10.5 mg), and hydrocortisone sodium succinate (50 mg). RESULTS All the three drugs were equally effective with no statistically significant difference in the time of resolution of cobblestone papillae, lid oedema, conjunctival discharge and chemosis, Tranta's dots and shield ulcers. There was no statistically significant difference in the severity and rate of recurrence of disease following supratarsal injection of all the three drugs. But recurrence of disease to same severity was seen within 6 months of injection in all cases irrespective of compounds used. CONCLUSION Supratarsal injection of corticosteroids is very effective for temporary suppression of severe inflammation associated with VKC.