Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population

IMPORTANCE Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). OBJECTIVE To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs. DESIGN, SETTING, AND PARTICIPANTS This case-control studywas conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014. MAIN OUTCOMES AND MEASURES Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes. RESULTS Of 74 patients included in the analysis, 32 (43%) were malemean (SD) age was 36.01 [15.42] years. HLA-A*66: 01 (odds ratio [OR], 24.095% CI, 2.79-206.0P < 001), HLA-B*44: 03 (OR, 2.7195% CI, 1.11-6.65P = 04), and HLA-C*12: 03 (OR, 5.695% CI, 1.67-18.80P = 006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11: 01 (OR, 0.07495% CI, 0.004-1.26P = 008), HLA-B*08: 01 (OR, 0.1595% CI, 0.02-1.15P = 048), and HLA-B*51: 01 (OR, 0.2395% CI, 0.05-1.03P = 045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry14 males and 25 femalesage, 35.2 [14.4] yearsand 133 controls: 66 Pardo and 61 European ancestry55 males and 78 femalesage, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66: 01 and HLA-C*12: 03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66: 01 was associated with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 12.295% CI, 1.19-125.0P = 03and European: OR, 21.295% CI, 0.97-465.0P = 04). An association was observed only in the European cohort for HLA-B*44: 03 (OR, 5.5095% CI, 1.47-20.50P = 01) and HLA-C*12: 03 (OR, 8.7995% CI, 1.83-42.20P = 008). CONCLUSIONS AND RELEVANCE This study suggests that HLA-A*66: 01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44: 03 and HLA-C*12: 03 might be markers only in those of European ancestry. Moreover, HLA-A*11: 01 might be a marker of resistance to CM-SJS/TEN with SOCs.Ministry of Education, Culture, Sports, Science and Technology of the Japanese governmentJapan Society for the Promotion of Science Core-to-Core Program Advanced Research NetworksJapanese Ministry of Health, Labor and WelfareKyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of MedicineMinistry of Education, Brazil-JapanFundacao de Amparo a Pesquisa do Estado de Sao PauloUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilPrefectural Univ Med, Dept Frontier Med Sci & Technol Ophthalmol, Kyoto, JapanUniv Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, JapanOsaka Univ, Dept Stat Genet, Osaka, JapanRIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, JapanKyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, JapanUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilWeb of Scienc

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial

Purpose: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.Design: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.Participants: Patients aged &gt; 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants &gt;= 2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.Methods: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.Main Outcome Measure: The 52-week endothelial immune rejection rate.Results: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis.Conclusions: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection. (C) 2022 by the American Academy of Ophthalmolog

Bevacizumab in High-Risk Corneal Transplantation

To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.The 52-week endothelial immune rejection rate.Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03–0.65, P = 0.01) in a post hoc Cox regression analysis.In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection