Christine S Mun, Bayasgalan Surenkhuu, Yi-Fan Chen, Nour Atassi, Jessica Mun, Christian Kim, Tanya Sheth, Monazzah Akbar Sarwar, Anubhav Pradeep, Sandeep Jain
{"title":"重组脱氧核糖核酸酶 I 滴眼液治疗眼部移植物抗宿主病：随机临床试验结果。","authors":"Christine S Mun, Bayasgalan Surenkhuu, Yi-Fan Chen, Nour Atassi, Jessica Mun, Christian Kim, Tanya Sheth, Monazzah Akbar Sarwar, Anubhav Pradeep, Sandeep Jain","doi":"10.1097/ICL.0000000000001078","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD.</p><p><strong>Methods: </strong>A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.</p><p><strong>Results: </strong>Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).</p><p><strong>Conclusions: </strong>Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.</p>","PeriodicalId":50457,"journal":{"name":"Eye & Contact Lens-Science and Clinical Practice","volume":" ","pages":"233-240"},"PeriodicalIF":2.0000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial.\",\"authors\":\"Christine S Mun, Bayasgalan Surenkhuu, Yi-Fan Chen, Nour Atassi, Jessica Mun, Christian Kim, Tanya Sheth, Monazzah Akbar Sarwar, Anubhav Pradeep, Sandeep Jain\",\"doi\":\"10.1097/ICL.0000000000001078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD.</p><p><strong>Methods: </strong>A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.</p><p><strong>Results: </strong>Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).</p><p><strong>Conclusions: </strong>Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.</p>\",\"PeriodicalId\":50457,\"journal\":{\"name\":\"Eye & Contact Lens-Science and Clinical Practice\",\"volume\":\" \",\"pages\":\"233-240\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Eye & Contact Lens-Science and Clinical Practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/ICL.0000000000001078\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Eye & Contact Lens-Science and Clinical Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/ICL.0000000000001078","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial.
Objective: We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD.
Methods: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.
Results: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).
Conclusions: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.
期刊介绍：
Eye & Contact Lens: Science and Clinical Practice is the official journal of the Contact Lens Association of Ophthalmologists (CLAO), an international educational association for anterior segment research and clinical practice of interest to ophthalmologists, optometrists, and other vision care providers and researchers. Focusing especially on contact lenses, it also covers dry eye disease, MGD, infections, toxicity of drops and contact lens care solutions, topography, cornea surgery and post-operative care, optics, refractive surgery and corneal stability (eg, UV cross-linking). Peer-reviewed and published six times annually, it is a highly respected scientific journal in its field.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
