Randomized Trial of Biosimilar XSB-001 versus Reference Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To evaluate the efficacy, safety, and immunogenicity of a ranibizumab biosimilar candidate (XSB-001) versus reference product (Lucentis) for neovascular age-related macular degeneration (nAMD). DESIGN: Phase III, multicenter, randomized, double-masked, parallel-group study. PARTICIPANTS: Patients with nAMD. METHODS: Eligible patients were randomized (1:1) to receive intravitreal injections of XSB-001 or reference ranibizumab (0.5 mg [0.05 ml]) in the study eye once every 4 weeks for 52 weeks. Efficacy and safety assessments continued through 52 weeks of treatment. MAIN OUTCOME MEASURES: Primary end point was change from baseline in best-corrected visual acuity (BCVA) by ETDRS letters at week 8. Biosimilarity was concluded if the 2-sided 90% confidence interval (CI) (United States) or 95% CI (rest of world) for the difference in least-squares (LS) mean change in BCVA at week 8 between treatment groups was within the predefined equivalence margin of ± 3.5 letters. RESULTS: In total, 582 patients (n = 292 XSB-001, n = 290 reference ranibizumab) were randomized. Mean age was 74.1 years, most patients (85.2%) were White, and 55.8% were women. Mean BCVA score at baseline was 61.7 and 61.5 ETDRS letters in the XSB-001 and reference ranibizumab groups, respectively. At week 8, the LS mean (standard error [SE]) change in BCVA from baseline was 4.6 (0.5) ETDRS letters in the XSB-001 group and 6.4 (0.5) letters in the reference ranibizumab group (LS mean [SE] treatment difference: -1.8 [0.7] ETDRS letters; 90% CI, -2.9 to -0.7; 95% CI, -3.1 to -0.5). The 90% CI and 95% CI for LS mean difference in change from baseline were within the predefined equivalence margin. At week 52, LS mean (SE) change in BCVA was 6.4 (0.8) and 7.8 (0.8) letters, respectively (LS mean [SE] treatment difference, -1.5 [1.1] ETDRS letters; 90% CI, -3.3 to 0.4; 95% CI, -3.6 to 0.7). There were no clinically meaningful differences between treatments in anatomical, safety, or immunogenicity end points through week 52. CONCLUSIONS: XSB-001 demonstrated biosimilarity to reference ranibizumab in patients with nAMD. Treatment with XSB-001 for 52 weeks was generally safe and well tolerated, with a safety profile similar to the reference product. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[Comparison of results of photorefractive keratectomy and laser in situ keratomileusis in the treatment of hyperopia using a flying spot eximer laser]. / A repülópont technikával végzett fotorefraktív keratectomia és a lézer in situ keratomileusis módszerek összehasonlítása a hypermetropia kezelésében.

PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) and Laser in situ keratomieusis (LASIK) in eyes treated with hyperopia. PATIENTS AND METHODS: group 1 consisted of PRK-operated eyes, group 2 consisted of LASIK-operated eyes. In each group 20 eyes of 20 patients were listed. The average age in Group 1 was 33.4 +/- 8.4 year, while in group 2 it was 34.2 +/- 7.9 year. Refractive treatments were carried out with the Asclepion Meditec MEL 70 G-Scan flying spot excimer laser, LASIK flaps were created by the Moria CB manual microkeratome. RESULTS: In group 1, pre-operative refraction was +4.2 +/- 1.1 D (SE = spherical equivalent), in group 2 it was +4.8 +/- 1.21 D. Six months following surgery refraction was +0.35 +/- 0.12 D (SE) in group 1, while +0.38 +/- 0.14 D (SE) in group 2. The uncorrected visual acuity was 0.92 +/- 0.04 in group 1 and 0.91 +/- 0.01 in group 2.85% of eyes in group 1 and 95% of eyes in group 2 had a 1.0 uncorrected visual acuity. In group 1, 95% of the eyes were within +/- 1.0 D of targeted refraction, while in group 2, 100% achieved this. Best spectacle corrected visual acuity (BSCVA) did not change in 90% of group 1, while in 5% it increased by 1 and in the remaining 5% decreased by 1 Snellen line. In group 2. BSCVA remained unchanged in 85% of eyes, while in 10% it increased and in 5% decreased by 1 Snellen line. In group 1, glare was reported in 4 eyes, while in group 2.5 eyes reported postoperative glare, mainly during night driving. CONCLUSION: Effectivity, predictability and safety was good in both treatment groups. Results of hyperopic eyes below +6.0 D of preoperative refraction were not dependent on the type of operation (PRK or LASIK).

C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before and after penetrating keratoplasty.

PURPOSE: The aim of this pilot study was to determine the presence of complement activation products in tears from pre- and postkeratoplasty eyes and the fellow eyes in order to investigate the activation of the classical and alternative pathways of the complement system in the early postkeratoplasty period. METHODS: Tear samples from both eyes of 19 prekeratoplasty patients were tested. From 10 patients, samples were taken before operation, one week and 3 weeks after penetrating keratoplasty. Only baseline and 1 weak samples, and baseline and 3 week samples were available from 5 and 2 patients, respectively, while only baseline tear samples were collected from 2 patients. Tear concentration of two complement activation products, C1rs-C1inh and C3bBbP were determined by enzyme-linked immunosorbent assay. RESULTS: There was no difference (p = 0.339) between baseline samples of the eyes waiting for operation (0.93 +/- 0.51 AU/ml, mean +/- SEM) and the fellow eyes (0.33 +/- 0.33 AU/ml) in respect of mean C1rs-C1inh complex concentration. The one-week samples of the operated eyes revealed significantly (p = 0.006) elevated levels of C1rs-C1inh complexes (18.8. +/- 6.37 AU/ml), compared to their baseline samples (1.18 +/- 0.64 AU/ml), whereas the one-week values of the fellow eyes did not differ from the baseline values. Compared to the increased one-week values, the three-week values decreased to the baseline values in the operated eyes. C3bBbP could be detected in 3/68 tear samples. CONCLUSIONS: In our study we demonstrated the increased concentration of C1rs-C1inh complex in several tear samples taken early after human penetrating keratoplasty. These findings provide direct evidence that the classical pathway of complement may be activated in the early postoperative period after penetrating keratoplasty.

[Experience with laser in situ keratomileusis]. / A lézer in situ keratomileusis mútétek során szerzett tapasztalataink.

AIM OF THE STUDY: To evaluate the results of laser in situ keratomileusis (LASIK) in groups with different refractive errors. PATIENTS AND METHODS: 68 LASIK procedure have been performed in the following patient groups: Group 1 (-3.0 D to -6.0 D) n = 14; Group 2 (-6.25 D to -9.0 D) n = 29; Group 3 (-9.25 D to -14.0 D) n = 13; Group 4 (eyes with hyperopic refractive error between +1.75 D and +7.5 D) n = 12. A Moria CB manual mikrokeratom was used, flap thickness was 130 microns. Excimer laser treatment was carried out with Asclepion-Meditec MEL 70 G-Scan flying spot excimer laser. Follow-up time is 6 months. RESULTS: The preoperative correction decreased in Group 1. from -4.45 D +/- 0.93 D (SE = spherical equivalent) to -0.04 D +/- 0.13 D, in Group 2. from -7.81 D +/- 0.98 D (SE) to -0.56 D +/- 0.9 D, in Group 3. from -11.33 D +/- 1.97 D (SE) to -1.88 D +/- 1.64 D, and in Group 4. from +4.67 D +/- 1.67 D (SE) to +0.24 D +/- 0.50 D 6 months following LASIK. The best spectacle corrected visual acuity (BSCVA) decreased by 2 or more Snellen lines in 4 eyes in Group 2, in 2 eyes in Group 3, and there was no change in Group 1 and Group 4. BSCVA improved by 2 or more Snellen lines in one eye in Group 2, in 2 eyes in Group 3 and there was no change in Group 1 and in Group 4. CONCLUSIONS: The preoperative correction decreased significantly following LASIK procedure in each patient group. The method was found to be effective, safe and durable during the 6 months follow-up. Application is recommended especially in eyes with a refractive error higher than -6.0 D due to possible intra- and early postoperative complications.