Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial.

PURPOSE: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). PROCEDURES: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. RESULTS: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. CONCLUSION: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients.

Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema.

PURPOSE: To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME). DESIGN: Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial. PARTICIPANTS: Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled. INTERVENTION: Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed. MAIN OUTCOME MEASURES: The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP). RESULTS: The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required. CONCLUSIONS: There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.

OBJECTIVES: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. METHODS: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 µg), half-dose mRNA-1273 (50 µg), mRNA-1273 (100 µg), and MVC-COV1901 (15 µg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. RESULTS: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. CONCLUSIONS: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.

A randomized, controlled comparison of macroscopic conjunctival hyperemia in patients treated with bimatoprost 0.01% or vehicle who were previously controlled on latanoprost.

PURPOSE: To evaluate conjunctival hyperemia associated with bimatoprost 0.01% treatment in patients who replace latanoprost 0.005% with bimatoprost 0.01%. METHODS: Randomized, double-masked, vehicle-controlled, multicenter study of patients with ocular hypertension or glaucoma whose intraocular pressure (IOP) was adequately controlled on latanoprost monotherapy. At baseline, patients discontinued latanoprost and were randomized to treatment with once-daily bimatoprost 0.01% (n = 151) or vehicle (n = 71). The primary endpoint was the peak change in macroscopic hyperemia (conjunctival hyperemia evaluated by gross visual inspection) from baseline to month 1. RESULTS: Bimatoprost 0.01% was noninferior to vehicle in the mean [standard deviation] peak change from baseline macroscopic hyperemia at month 1 (0.18 [0.46] in the bimatoprost 0.01% group vs 0.02 [0.32] in the vehicle group, P = 0.009). The between-group difference was 0.15 (95% confidence interval [CI]: 0.04, 0.26), which was within the predefined margin for noninferiority of 0.5 on a hyperemia grading scale of 0 to +3. There were no statistically significant between-group differences in the percentage of patients with a ≥1-grade increase in macroscopic hyperemia from baseline. Mean IOP was decreased from baseline (-0.7 to -1.3 mm Hg) in the bimatoprost 0.01% group (P ≤ 0.002) and was increased from baseline (+3.3 to +3.6 mm Hg) in the vehicle group (P < 0.001) at month 1. There were no statistically significant between-group differences in adverse events. CONCLUSIONS: Bimatoprost 0.01% was noninferior to vehicle with respect to conjunctival hyperemia in this study population. Replacement of latanoprost with bimatoprost 0.01% in patients with ocular hypertension or glaucoma can result in additional IOP reduction without clinically important hyperemia.

Safety and tolerability of brimonidine purite 0.1% and brimonidine purite 0.15%: a meta-analysis of two phase 3 studies.

OBJECTIVE: To compare the safety and tolerability of two formulations of brimonidine ophthalmic solution, brimonidine Purite (P) 0.1% and brimonidine P 0.15%, for reducing intraocular pressure in patients with glaucoma or ocular hypertension (OHT). STUDY DESIGN AND METHODS: Meta-analysis of safety and tolerability results from two previously reported prospective, randomized, 12-month, double-masked, multicenter, parallel-group clinical studies with similar entry criteria and protocols. In study 1 (two clinical trials), after washout of previous medications, patients with glaucoma or OHT were randomized to thrice-daily treatment with brimonidine P 0.15% (n = 381), brimonidine P 0.2% (n = 383), or brimonidine 0.2% (n = 383). In study 2 (one clinical trial), the treatment arms were thrice-daily brimonidine P 0.1% (n = 215) and brimonidine 0.2% (n = 218). MAIN OUTCOME MEASURE: Treatment-related adverse events (AEs) and discontinuations due to AEs. RESULTS: Treatment-related AEs were significantly reduced with brimonidine P 0.15% compared with brimonidine 0.2% in study 1 (p < 0.001). Treatment-related AEs and discontinuations due to AEs were significantly reduced with brimonidine P 0.1% compared with brimonidine 0.2% in study 2 (p < or = 0.014). In the meta-analysis of study 1 and study 2, the overall incidence of treatment-related AEs was lower with brimonidine P 0.1% than with brimonidine P 0.15% (41.4 vs. 49.7%; p = 0.050). Although the incidence of treatment-related ocular AEs was similar with brimonidine P 0.1% and 0.15% (p = 0.461), treatment-related systemic AEs were less frequent with brimonidine P 0.1% than with brimonidine P 0.15% (4.7 vs. 14.2%; p < 0.001), and there were fewer discontinuations due to systemic AEs with brimonidine P 0.1% than with brimonidine P 0.15% (p = 0.025). CONCLUSIONS: Brimonidine P 0.1% has improved systemic safety and tolerability compared with brimonidine P 0.15%. The ocular safety and tolerability of the formulations are similar. The present meta-analysis is based on only two clinical studies, and additional studies further evaluating the safety and tolerability of these medications are warranted.

Brimonidine-purite 0.1% versus brimonidine-purite 0.15% twice daily in glaucoma or ocular hypertension: a 12-month randomized trial.

OBJECTIVE: To compare the safety and intraocular pressure (IOP)-lowering effects of brimonidine-purite 0.1% with the marketed formulation of brimonidine-purite 0.15% (Alphagan P 0.15%) when used twice daily (BID) by patients with glaucoma or ocular hypertension previously treated with brimonidine-purite 0.15% for at least 6 weeks. METHODS: In a 12-month, randomized, double-masked, multicenter, parallel group, non-inferiority study, patients with glaucoma or ocular hypertension who were treated with brimonidine-purite 0.15% BID were randomly assigned to continue brimonidine-purite 0.15% (n=102) or to administer brimonidine-purite 0.1% (n=105) BID for 12 months. IOP was measured at approximately 8 a.m. (hour 0) and 10 a.m. (hour 2). MAIN OUTCOME MEASURES: Mean change from baseline IOP and adverse events. RESULTS: Demographics and baseline characteristics were similar between treatment groups. Treated-baseline mean IOPs at both timepoints were similar between groups (p > or = 0.606). Brimonidine-purite 0.1% provided IOP-lowering that was non-inferior to brimonidine-purite 0.15% at each of the 12 follow-up timepoints, and there were no statistically significant between-group differences at any timepoint. The most commonly reported adverse event was conjunctival hyperemia (13.5% for brimonidine-purite 0.1%; 10.8% for brimonidine-purite 0.15%). No significant differences in the incidence of adverse events were noted between the two formulations. CONCLUSIONS: Brimonidine-purite 0.1% BID is as effective as brimonidine-purite 0.15% BID in lowering IOP in patients with glaucoma or ocular hypertension who were previously treated with brimonidine-purite 0.15%, and both formulations are well tolerated. Limitations of the study include enrollment of only patients who were already on treatment with brimonidine-purite 0.15%. The 0.1% formulation of brimonidine-purite allows for decreased exposure to brimonidine while providing an IOP-lowering effect comparable to that of the 0.15% formulation. Clinical trial registered at clinicaltrials.gov; identifier: NCT00168363.