Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration

Item does not contain fulltextOBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1

Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials.

Item does not contain fulltextOBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD

New appraisals of Kyrieleis plaques: a multimodal imaging study.

PURPOSE: Kyrieleis retinal periarteritis reflects the severe intraocular inflammation experienced by the eye. Its aetiology has not been well established, since only nine cases have been reported and there is no pathological study available in the literature. We determine the pathogenesis of Kyrieleis periarteritis based on interpretation of multimodal imaging findings. METHODS: Charts of patients with Kyrieleis arteritis seen between 2006 and 2014 were retrieved from eight uveitis referral centres throughout the world. Follow-up ranged from 5 to 12\u2005months. RESULTS: Twenty-five eyes with Kyrieleis arteritis from 25 patients were included in the study. Nineteen patients (72%) were male and six (28%) were female. Twenty-three patients were diagnosed with toxoplasmosis retinochoroiditis and two patients had cytomegalovirus retinitis. Fluorescein angiography, fundus autofluorescence and indocyanine green angiography were performed on 25/25 (100%) eyes. In eight eyes (32%), baseline spectral domain optical coherence tomography (SD-OCT) scans were performed along the segmental Kyrieleis arteritis. Fluorescein angiography showed early hypofluorescence and intermediate hyperfluorescence associated with the areas of focal arteritis, whereas indocyanine green angiography of these accumulations showed early hypofluorescence and late hyperfluorescence. Fundus autofluorescence revealed an increased autofluorescence of the vessels corresponding to the Kyrieleis plaques, while SD-OCT scans along the segmental Kyrieleis arteritis showed hyperreflectivity of the vessel wall. CONCLUSIONS: These imaging modalities provide in vivo, quasi-histologic images demonstrating that Kyrieleis plaques are characterised by an inflammatory involvement within the vessels' endothelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing