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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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Abstract
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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Phase II/III Clinical Trial of Sub-Tenon Injection of Triamcinolone Acetonide (WP-0508ST) for Diabetic Macular Edema.
Ogura, Y, Shimura, M, Iida, T, Sakamoto, T, Yoshimura, N, Yamada, M, Ishibashi, T
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2019;(3):161-169
Abstract
PURPOSE To assess the efficacy and safety of sub-Tenon injection of triamcinolone acetonide (WP-0508ST) for the patients with diabetic macular edema (DME). METHODS This multicenter, randomized, double-masked, comparative, controlled study was performed in 95 patients with DME. The patients were randomly divided into 20 mg WP-0508ST, 40 mg WP-0508ST, and control groups. RESULTS A significant improvement in central macular thickness (CMT) was observed (p < 0.001) at 12 weeks after a single sub-Tenon injection of 20 mg WP-0508ST. The 40 mg group also demonstrated improvement in CMT, but the difference was not significant. In addition, the best-corrected visual acuity was improved in both the 20 mg and 40 mg groups at 12 weeks. The major side effects were increased intraocular pressure (9.4% in the 20 mg group and 13.3% in the 40 mg group) and lenticular opacity (6.3% in the 20 mg group and 10.0% in the 40 mg group). However, none of the patients with increased intraocular pressure required surgery. CONCLUSION The efficacy and tolerability of WP-0508ST in the treatment of DME were confirmed, and 20 mg was determined to be the optimal dose.
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SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD).
Yeh, S, Kurup, SK, Wang, RC, Foster, CS, Noronha, G, Nguyen, QD, Do, DV, ,
Retina (Philadelphia, Pa.). 2019;(10):1880-1888
Abstract
PURPOSE Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis. METHODS Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography. RESULTS Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure. CONCLUSION A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.
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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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Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic macular edema on randomized paired-eyes.
Doi, N, Sakamoto, T, Sonoda, Y, Yasuda, M, Yonemoto, K, Arimura, N, Uchino, E, Ishibashi, T
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2012;(1):71-8
Abstract
BACKGROUND The present study was performed to compare the effects of pars plana vitrectomy (PPV) and single intravitreaous triamcinolone acetonide (IVTA) on diabetic macular edema (DME) in paired eyes. METHODS Prospective comparative study on randomized paired-eyes was carried out at two hospitals. Forty eyes of 20 patients with bilateral DME were included. One randomly-selected eye was treated with PPV (PPV group), and the other eye was treated with IVTA (4 mg, IVTA group). The central macular thickness (CMT) measured by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) were monitored for 12 months after treatment. Changes from baseline and differences between groups were analyzed using a mixed model. RESULTS At 1 and 3 months, CMT decreased significantly in the IVTA group compared to baseline (p < 0.0001 both), but CMT then increased gradually and no significant difference was found at 12 months (p = 0.90). In the PPV group, CMT decreased continuously and reached a significant level at 12 months (p < 0.0001). CMT of the IVTA group was significantly less than that of the PPV group at 1 month (p = 0.009); however, there was no significant difference at 3 months. Conversely, CMT was significantly less in the PPV group than in the IVTA group at 12 months (p = 0.0003). The changes of BCVA paralleled those of CMT, but no significant difference was detected between baseline BCVA and any time point. CONCLUSIONS Despite the short-term improvement, DME recurred 6 months after IVTA, while it remained resolved after PPV. Although this study did not reveal a significant change of BCVA with either treatment, PPV resolved DME more effectively than IVTA at 1 year.
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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.