PURPOSE:To assess anatomic and visual function data from 3 randomized, sham-controlled clinical trials of revakinagene taroretcel-lwey in participants with macular telangiectasia type 2 (MacTel). DESIGN:This study pooled data from 1 phase II (NTMT-02) clinical trial and 2 identically designed phase III (NTMT-03-A and NTMT-03-B) clinical trials of revakinagene taroretcel-lwey in MacTel. PARTICIPANTS:In total, 67 participants (99 eyes) from NTMT-02, 115 participants (115 eyes) from NTMT-03-A, and 113 participants (113 eyes) from NTMT-03-B were included in the study. The pooled population included 327 eyes from 295 participants (165 participants who received revakinagene taroretcel-lwey and 162 who underwent sham surgical procedure). METHODS:Assessments were conducted on data from the individual trials as well as on a single pooled population from all 3 trials. MAIN OUTCOME MEASURES:The rate of ellipsoid zone (EZ) area loss over 24 months and changes from baseline in monocular reading speed loss, aggregate retinal sensitivity loss measured by microperimetry, and best-corrected visual acuity (BCVA) were assessed. RESULTS:In the pooled analysis, a 36.2% reduction in the rate of EZ area loss over 24 months was observed with revakinagene taroretcel-lwey (0.118 mm2/24 months; 95% confidence interval [CI], 0.087-0.149) versus sham (0.185 mm2/24 months; 95% CI, 0.154-0.217) (nominal P = 0.003). A 68.2% reduction in monocular reading speed loss at 24 months from baseline was observed with revakinagene taroretcel-lwey (-4.65 words per minute [WPM]; 95% CI, -9.58 to -0.27) versus sham (-14.60 WPM; 95% CI, -20.41 to -8.79) (nominal P = 0.01). Across the 3 trials, a 36.6% reduction in aggregate retinal sensitivity loss was reported over 24 months with revakinagene taroretcel-lwey (28.47 dB; 95% CI, 6.62-50.31) compared with sham (44.85 dB; 95% CI, 36.99-52.72) (nominal P < 0.001). Both treatment groups experienced minimal changes in BCVA over 24 months. CONCLUSIONS:In this pooled analysis, revakinagene taroretcel-lwey reduced the rate of MacTel disease progression and preserved visual function over 24 months, as shown by reductions in the rate of EZ area loss, reading speed loss, and aggregate retinal sensitivity loss. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PURPOSE : To report the efficacy of early versus delayed pegcetacoplan treatment in eyes with geographic atrophy (GA) secondary to age-related macular degeneration as well as the 48-month safety profile of pegcetacoplan. DESIGN : Efficacy and safety data from the phase 3 GALE open-label extension (OLE) of the phase 3 OAKS and DERBY studies, representing up to 48 months of continuous pegcetacoplan treatment, were analyzed. PARTICIPANTS : Eyes with nonsubfoveal or subfoveal GA receiving pegcetacoplan in OAKS and DERBY continued receiving pegcetacoplan at the same dosing regimen in GALE, and sham-observed eyes with nonsubfoveal or subfoveal GA in OAKS and DERBY crossed over to active treatment in GALE at the same dosing interval in those studies. METHODS : The overall population included eyes with nonsubfoveal GA and eyes with subfoveal GA. Subgroup analyses were performed on data from eyes with nonsubfoveal GA and eyes with subfoveal GA. The early treatment group comprised eyes receiving pegcetacoplan for 48 months across the OAKS, DERBY, and GALE studies. The delayed treatment group included sham-observed eyes from OAKS and DERBY which crossed over at 24 months to receive pegcetacoplan treatment for 24 months in the GALE OLE. MAIN OUTCOME MEASURES : GA area growth rate, amount of retinal tissue preserved, risk of progression to absolute scotoma, and safety. RESULTS : In the overall population, 48 continuous months of pegcetacoplan treatment reduced GA area growth rate by up to 24% compared with projected sham, translating to 1.88 mm2 of retinal tissue. Approximately three times more retinal tissue (up to 3.16 mm2 with monthly treatment) was preserved in eyes with nonsubfoveal GA in the early treatment group compared with eyes in the nonsubfoveal GA delayed treatment group (1.11 mm2). Reduced risk of progression to absolute scotoma of all central 4 and 16 loci (32% and 43%, respectively) was observed in the overall population. GALE safety data were consistent with the findings of the OAKS and DERBY studies. CONCLUSIONS : Pegcetacoplan demonstrated effectiveness in slowing GA progression and consistent safety over 48 months. Long-term anatomic and functional outcomes support the importance of early treatment to maximize the preservation of retinal tissue and function.
BACKGROUND: The aim of this study was to evaluate the efficacy of femoral outflow during endovascular treatment for all types of aortoiliac occlusive disease (AIOD) and to identify risk factors associated with restenosis, limb salvage, and patency. METHODS: This retrospective cohort study of prospectively collected data included consecutive patients with AIOD who underwent aortoiliac angioplasty. Three groups were analyzed: 1) patients with patency of the profunda femoris artery (PFA) and occlusion of the superficial femoral artery (SFA); 2) patients with both PFA and SFA patent; and 3) patients with PFA patency and SFA stenosis. RESULTS: A total of 102 patients underwent aortoiliac angioplasty with an initial technical success rate of 100%. The groups comprised 31 (30.4%) with isolated PFA patency, 62 (60.8%) with both PFA and SFA patent, and 9 (8.8%) with PFA patency and SFA stenosis. Primary patency rates at 1000 days were 70.0% (PFA group), 82.6% (PFA/SFA group), and 83.3% (SFA group), P=0.07. Secondary patency rates at 720 days were 88.5% (PFA group), 100%, (PFA/SFA group) and 100% (PFA/SFA group), (P=0.46). Limb salvage rates at 1000 days were 96.4%, 94.4%, and 100% (P=0.46), respectively. Cox regression analysis showed that primary patency was significantly worse among patients treated with bare metal stents (HR 12.41; 95% CI 1.48.103.57; P=0.020), while concomitant common femoral endarterectomy (CFE) was protective (HR 0.152; 95% CI 0.027-0.870; P=0.034). Chronic kidney disease was independently associated with reduced survival (HR 2.61; 95% CI 1.01-6.81; P<0.001). CONCLUSIONS: The PFA alone can provide adequate femoral outflow for sustained long-term outcomes following endovascular treatment of AIOD. Covered stents achieve superior patency and freedom from reintervention compared with bare metal stents, and concomitant CFE further improves results. These findings support a tailored approach to AIOD management that prioritizes robust inflow and a healthy PFA outflow, without necessitating routine SFA revascularization in all patients.
Abstract Purpose To evaluate the safety and exploratory outcomes of a single intravitreal injection of OGX110, a peptide agonist of CXCR3, in eyes with persistent fluid secondary to neovascular age-related macular degeneration (nAMD) despite ongoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods This prospective, open-label, sequential dose-escalation phase I study ( NCT05904691 ) enrolled subjects receiving standard-of-care intravitreal anti-VEGF therapy. Subjects received a single intravitreal injection of OGX110 at 0.5 mg, 1.0 mg, or 2.0 mg (n=3 per cohort), 7 to 14 days after the anti-VEGF injection. Results All nine enrolled subjects completed follow-up through day 56. Two subjects (22%) experienced at least 1 adverse event (AE); all were mild and unrelated to study treatment. Exploratory analyses showed a BCVA change of +1.4 letters following anti-VEGF injection and +4.4 letters from OGX110 baseline to 4 weeks (P < 0.05). Six of 9 subjects gained at least 3 ETDRS letters after OGX110. Anatomic responses were heterogeneous. Four eyes showed a reduction in CRT after anti-VEGF injection that was maintained after OGX110 administration. One additional eye demonstrated a substantial reduction in CRT after OGX110 despite minimal response to anti-VEGF treatment. Conclusions A single intravitreal injection of OGX110 was well tolerated. Exploratory functional and anatomic findings suggest biologic activity; interpretation is limited by small sample size, open-label design, absence of a concurrent control group, and inter-subject heterogeneity. These results support further study in a controlled trial. Translational Relevance OGX110 represents a mechanistically distinct investigational approach for nAMD that may warrant further evaluation in eyes with persistent.
Macular telangiectasia type 2 (MacTel), a bilateral, neurodegenerative disease associated with photoreceptor loss, often leads to progressive scotomas, metamorphopsia, and impaired reading function. Revakinagene taroretcel-lwey, a Food and Drug Administration (FDA)–approved encapsulated cell-based therapy for adults with MacTel, is surgically inserted into the vitreous cavity and provides sustained intraocular delivery of recombinant human ciliary neurotrophic factor (CNTF). Results from two phase 3 randomized clinical trials support the efficacy and safety of revakinagene taroretcel-lwey; explant analyses have demonstrated bioactive CNTF release up to 14.5 years. This report summarizes the surgical procedure and techniques for revakinagene taroretcel-lwey implantation, including implant preparation, insertion, wound closure, and postoperative procedures, and highlights scenarios where expert guidance may help to prevent intraoperative errors and minimize the potential for postsurgical adverse events. Standardizing surgical steps and incorporating expert guidance into surgical technique may reduce adverse events, including migration and extrusion, wound leaks, and infections, supporting safe long-term CNTF delivery for treatment of MacTel.
