ImportancePrevention of diabetic retinopathy is important to keep vision and quality of life.ObjectiveTo examine the effects of an intensive multifactorial intervention and hypoglycemia on retinopathy in people with type 2 diabetes.Design, Setting, and ParticipantsJ-DOIT3 (Japan Diabetes Optimal Integrated Treatment Study for 3 Major Risk Factors of Cardiovascular Diseases) is a multicenter, open-label, parallel-group randomized clinical trial that examined the efficacy of an intensified multifactorial intervention on cardiovascular outcomes and mortality in people with type 2 diabetes aged 45 to 69 years with hypertension and/or dyslipidemia. The study was conducted at 81 sites in Japan from June 2006 to March 2009, and data analysis was performed from September 2018 to August 2025.InterventionsParticipants were randomly assigned to intensive therapy for glucose, blood pressure, and lipids or conventional therapy and were followed up for a median duration of 8.5 years.Main Outcomes and MeasuresThis study is a secondary analysis of retinopathy events of the secondary outcomes, composed of onset of retinopathy, progression of retinopathy, and loss of vision likely due to retinopathy.ResultsAmong 2540 total participants (5080 eyes) randomly assigned to intensive therapy or conventional therapy, mean (SD) age was 59.0 (6.3) years, and 965 participants (38.0%) were female. Intensive therapy was associated with a risk reduction in onset of retinopathy (hazard ratio [HR], 0.83; 95% CI, 0.70-0.98; P = .03) but not with progression of retinopathy (HR, 1.02; 95% CI, 0.70-1.49; P = .93). Hemoglobin A1c (HbA1c) at 1 year after randomization was associated with onset (HR, 1.31; 95% CI, 1.13-1.51; P < .001), even after adjustment for baseline risk factors (ie, lower body mass index, longer duration of diabetes, higher fasting plasma glucose, higher blood pressure, and comorbid nephropathy), with no clear HbA1c threshold observed. Moreover, compared with those without a hypoglycemic episode during the intervention, the risk of onset was higher in those with 0.5 hypoglycemic episodes per year or fewer (HR, 1.25; 95% CI, 1.02-1.53) and even higher in those with more than 1 hypoglycemic episode per year (HR, 1.85; 95% CI, 1.39-2.47).Conclusions and RelevanceThis secondary analysis of the J-DOIT3 randomized clinical trial shows that in a randomized clinical trial setting, higher HbA1c and nonsevere hypoglycemia are associated with higher risk of onset of retinopathy in people with type 2 diabetes, even when good glycemic management, with a very low incidence of severe hypoglycemia, is achieved, suggesting the importance of strict glycemic management without any hypoglycemia.Trial RegistrationClinicalTrials.gov Identifier: NCT00300976.
{"title":"Effect of a Multifactorial Intervention on Retinopathy in People With Type 2 Diabetes: A Secondary Analysis of the J-DOIT3 Randomized Clinical Trial.","authors":"Takayoshi Sasako,Kohjiro Ueki,Kengo Miyoshi,Kana Miyake,Tomohisa Aoyama,Yukiko Okazaki,Naoki Ishizuka,Toshimasa Yamauchi,Mitsuhiko Noda,Takashi Kadowaki, ","doi":"10.1001/jamaophthalmol.2025.3819","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3819","url":null,"abstract":"ImportancePrevention of diabetic retinopathy is important to keep vision and quality of life.ObjectiveTo examine the effects of an intensive multifactorial intervention and hypoglycemia on retinopathy in people with type 2 diabetes.Design, Setting, and ParticipantsJ-DOIT3 (Japan Diabetes Optimal Integrated Treatment Study for 3 Major Risk Factors of Cardiovascular Diseases) is a multicenter, open-label, parallel-group randomized clinical trial that examined the efficacy of an intensified multifactorial intervention on cardiovascular outcomes and mortality in people with type 2 diabetes aged 45 to 69 years with hypertension and/or dyslipidemia. The study was conducted at 81 sites in Japan from June 2006 to March 2009, and data analysis was performed from September 2018 to August 2025.InterventionsParticipants were randomly assigned to intensive therapy for glucose, blood pressure, and lipids or conventional therapy and were followed up for a median duration of 8.5 years.Main Outcomes and MeasuresThis study is a secondary analysis of retinopathy events of the secondary outcomes, composed of onset of retinopathy, progression of retinopathy, and loss of vision likely due to retinopathy.ResultsAmong 2540 total participants (5080 eyes) randomly assigned to intensive therapy or conventional therapy, mean (SD) age was 59.0 (6.3) years, and 965 participants (38.0%) were female. Intensive therapy was associated with a risk reduction in onset of retinopathy (hazard ratio [HR], 0.83; 95% CI, 0.70-0.98; P = .03) but not with progression of retinopathy (HR, 1.02; 95% CI, 0.70-1.49; P = .93). Hemoglobin A1c (HbA1c) at 1 year after randomization was associated with onset (HR, 1.31; 95% CI, 1.13-1.51; P < .001), even after adjustment for baseline risk factors (ie, lower body mass index, longer duration of diabetes, higher fasting plasma glucose, higher blood pressure, and comorbid nephropathy), with no clear HbA1c threshold observed. Moreover, compared with those without a hypoglycemic episode during the intervention, the risk of onset was higher in those with 0.5 hypoglycemic episodes per year or fewer (HR, 1.25; 95% CI, 1.02-1.53) and even higher in those with more than 1 hypoglycemic episode per year (HR, 1.85; 95% CI, 1.39-2.47).Conclusions and RelevanceThis secondary analysis of the J-DOIT3 randomized clinical trial shows that in a randomized clinical trial setting, higher HbA1c and nonsevere hypoglycemia are associated with higher risk of onset of retinopathy in people with type 2 diabetes, even when good glycemic management, with a very low incidence of severe hypoglycemia, is achieved, suggesting the importance of strict glycemic management without any hypoglycemia.Trial RegistrationClinicalTrials.gov Identifier: NCT00300976.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"200 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaophthalmol.2025.3612
Jiyeong Kim, Seong Joon Ahn, Jiyeon Park, Emily W. Gower, Jee-Eun Chung
Importance Systemic medications may have unrecognized macular toxic effects; early identification might be important for vision preservation. Objectives To identify systemic drugs potentially associated with maculopathy via pharmacovigilance reporting and to evaluate their macular adverse effects in a nationwide encounter database. Design, Setting, and Participants This 2-part study included (1) disproportionality analysis for candidate identification, using 15 748 maculopathy-related individual case safety reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) between July 2014 and December 2023, and (2) a population-based cohort study for association evaluation, using the South Korean Health Insurance Review and Assessment Service (HIRA) database among users of the candidate drugs, covering approximately 50 million individuals. Data were analyzed from January 1, 2015, to December 31, 2023. Exposure Use of systemic drugs identified as candidate signals in FAERS. Main Outcomes and Measures Reporting odds ratios for signal detection in FAERS and incidence rate ratios, hazard ratios, and cumulative incidence of maculopathy in HIRA. Results Five systemic drugs with underrecognized macular toxic effects—fingolimod, apixaban, paclitaxel, ibrutinib, and sildenafil—were identified among the top 30 maculopathy signals in FAERS. In HIRA, the incidence rate ratios for maculopathy following exposure (vs preexposure) were 1.92 (95% CI, 0.62-5.96) for fingolimod, 3.08 (95% CI, 2.68-3.54) for apixaban, 2.85 (95% CI, 1.62-5.02) for paclitaxel, 3.71 (95% CI, 2.58-5.34) for ibrutinib, and 2.75 (95% CI, 2.17-3.48) for sildenafil. The cumulative incidence rates ranged from 4.4% (fingolimod) to 15.7% (apixaban). Dose-response relationships were observed for paclitaxel (hazard ratio, 2.01 [95% CI, 1.77-2.29] for third vs first quartile) and ibrutinib (hazard ratio, 4.82 [95% CI, 1.39-16.81] for fourth vs first quartile). Conclusions and Relevance These findings suggest that the integration of pharmacovigilance signal detection and nationwide health claims analysis identified associations of maculopathy with apixaban, paclitaxel, ibrutinib, and sildenafil. This combined approach offers a potentially cost-effective, robust method for identifying systemic drugs with possibly underrecognized macular adverse effects.
{"title":"Systemic Drugs Associated With Maculopathy","authors":"Jiyeong Kim, Seong Joon Ahn, Jiyeon Park, Emily W. Gower, Jee-Eun Chung","doi":"10.1001/jamaophthalmol.2025.3612","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3612","url":null,"abstract":"Importance Systemic medications may have unrecognized macular toxic effects; early identification might be important for vision preservation. Objectives To identify systemic drugs potentially associated with maculopathy via pharmacovigilance reporting and to evaluate their macular adverse effects in a nationwide encounter database. Design, Setting, and Participants This 2-part study included (1) disproportionality analysis for candidate identification, using 15 748 maculopathy-related individual case safety reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) between July 2014 and December 2023, and (2) a population-based cohort study for association evaluation, using the South Korean Health Insurance Review and Assessment Service (HIRA) database among users of the candidate drugs, covering approximately 50 million individuals. Data were analyzed from January 1, 2015, to December 31, 2023. Exposure Use of systemic drugs identified as candidate signals in FAERS. Main Outcomes and Measures Reporting odds ratios for signal detection in FAERS and incidence rate ratios, hazard ratios, and cumulative incidence of maculopathy in HIRA. Results Five systemic drugs with underrecognized macular toxic effects—fingolimod, apixaban, paclitaxel, ibrutinib, and sildenafil—were identified among the top 30 maculopathy signals in FAERS. In HIRA, the incidence rate ratios for maculopathy following exposure (vs preexposure) were 1.92 (95% CI, 0.62-5.96) for fingolimod, 3.08 (95% CI, 2.68-3.54) for apixaban, 2.85 (95% CI, 1.62-5.02) for paclitaxel, 3.71 (95% CI, 2.58-5.34) for ibrutinib, and 2.75 (95% CI, 2.17-3.48) for sildenafil. The cumulative incidence rates ranged from 4.4% (fingolimod) to 15.7% (apixaban). Dose-response relationships were observed for paclitaxel (hazard ratio, 2.01 [95% CI, 1.77-2.29] for third vs first quartile) and ibrutinib (hazard ratio, 4.82 [95% CI, 1.39-16.81] for fourth vs first quartile). Conclusions and Relevance These findings suggest that the integration of pharmacovigilance signal detection and nationwide health claims analysis identified associations of maculopathy with apixaban, paclitaxel, ibrutinib, and sildenafil. This combined approach offers a potentially cost-effective, robust method for identifying systemic drugs with possibly underrecognized macular adverse effects.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"12 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaophthalmol.2025.3821
Abhimanyu S Ahuja,Alfredo A Paredes,Benjamin K Young
ImportanceGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown.ObjectiveTo evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs).Design, Setting, and ParticipantsThis retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025.ExposuresPatients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.Main Outcomes and MeasuresThe primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching.ResultsA total of 91 408 patients were included. After propensity score matching for the primary analysis, 45 704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35 753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35 732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P < .001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P < .001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P < .001). No differences were observed in progression to exudative AMD.Conclusions and RelevanceIn this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.
{"title":"Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration.","authors":"Abhimanyu S Ahuja,Alfredo A Paredes,Benjamin K Young","doi":"10.1001/jamaophthalmol.2025.3821","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3821","url":null,"abstract":"ImportanceGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown.ObjectiveTo evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs).Design, Setting, and ParticipantsThis retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025.ExposuresPatients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.Main Outcomes and MeasuresThe primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching.ResultsA total of 91 408 patients were included. After propensity score matching for the primary analysis, 45 704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35 753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35 732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P < .001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P < .001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P < .001). No differences were observed in progression to exudative AMD.Conclusions and RelevanceIn this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"108 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaophthalmol.2025.3829
Teng Liu,Benjamin J Wendel,Jennifer Huey,Palash Bharadwaj,Russell N Van Gelder,Brian Chou,Ramkumar Sabesan
{"title":"Optoretinography and Adaptive Optics Microperimetry in a Patient With AZOOR.","authors":"Teng Liu,Benjamin J Wendel,Jennifer Huey,Palash Bharadwaj,Russell N Van Gelder,Brian Chou,Ramkumar Sabesan","doi":"10.1001/jamaophthalmol.2025.3829","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.3829","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"21 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1001/jamaophthalmol.2025.4254
Kathryn A Colby,Andrea L Blitzer
{"title":"Impact of the Diabetes Endothelial Keratoplasty Study.","authors":"Kathryn A Colby,Andrea L Blitzer","doi":"10.1001/jamaophthalmol.2025.4254","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4254","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"33 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1001/jamaophthalmol.2025.4253
Francis W Price,Loretta B Szczotka-Flynn,Marianne O Price,Colleen E Bauza,Zachariah W Reed,Baha M Arafah,Mark A Greiner,Paula J Johnson,Devon B Keeler,Shahzad I Mian,Sanjay V Patel,Sudeep Pramanik,Mark C Soper,Mark A Terry,Michael S Titus,David D Verdier,Craig Kollman,Roy W Beck,Jonathan H Lass,
ImportanceIf the success of Descemet membrane endothelial keratoplasty (DMEK) is not affected by whether the donor has diabetes, then the donor pool should expand.ObjectiveTo determine whether the 1-year DMEK success rate is affected by the presence of diabetes in the donor.Design, Setting, and ParticipantsThis was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2025 at 28 clinical sites (46 surgeons), with donor corneas provided by 13 eye banks in the US. Included in the study were individuals undergoing low to moderate risk DMEK (95% for Fuchs endothelial corneal dystrophy). Study data were analyzed from April to September 2025.InterventionDMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure (comparable with randomization) to achieve an approximate 2:1 distribution, respectively.Main Outcomes and MeasuresGraft success at 1 year.ResultsA total of 1097 individuals (1421 study eyes; median [IQR] age, 71 [66-76] years; 631 female [57.5%]) were included in the study. The 1-year cumulative probability of graft success was 96.3% (95% CI, 95.0%-97.5%) among 912 study eyes (64.2%) receiving tissue from donors without diabetes and 97.1% (95% CI, 95.5%-98.4%) among 509 study eyes (35.8%) receiving tissue from donors with diabetes (difference between groups = 0.7 percentage points; 95% CI, -1.2 to 2.6; P = .63). The 1-year cumulative probability of graft success was 96.5% (95% CI, 93.6%-98.9%) in the mild donor diabetes severity subgroup (n = 173) and 97.3% (95% CI, 95.4%-98.8%) in the moderate to severe donor diabetes severity subgroup (n = 336), using a diabetes severity rating scale based on medical history. The rates of primary donor failure, early failure related to surgical complications, and subsequent failure were as follows: 2.5% (23 of 912), 0.7% (6 of 912), and 0.3% (3 of 912), respectively, in recipients of tissue from a donor without diabetes, and 2.6% (13 of 509), 0.4% (2 of 509), and 0%, respectively, among recipients of tissue from a donor with diabetes. There were no failures due to graft rejection.Conclusions and RelevanceThe 1-year success rate in eyes undergoing DMEK with successfully prepared tissue was very high regardless of donor diabetes status. These results, supported by the separately reported finding that endothelial cell loss and cornea morphometry after 1 year were not affected by donor diabetes status, provide strong support for having no restrictions on the use of tissue from donors with diabetes for DMEK.Trial RegistrationClinicalTrials.gov Identifier: NCT05134480.
{"title":"Donor Diabetes and 1-Year Descemet Membrane Endothelial Keratoplasty Success Rate: A Randomized Clinical Trial.","authors":"Francis W Price,Loretta B Szczotka-Flynn,Marianne O Price,Colleen E Bauza,Zachariah W Reed,Baha M Arafah,Mark A Greiner,Paula J Johnson,Devon B Keeler,Shahzad I Mian,Sanjay V Patel,Sudeep Pramanik,Mark C Soper,Mark A Terry,Michael S Titus,David D Verdier,Craig Kollman,Roy W Beck,Jonathan H Lass, ","doi":"10.1001/jamaophthalmol.2025.4253","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4253","url":null,"abstract":"ImportanceIf the success of Descemet membrane endothelial keratoplasty (DMEK) is not affected by whether the donor has diabetes, then the donor pool should expand.ObjectiveTo determine whether the 1-year DMEK success rate is affected by the presence of diabetes in the donor.Design, Setting, and ParticipantsThis was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2025 at 28 clinical sites (46 surgeons), with donor corneas provided by 13 eye banks in the US. Included in the study were individuals undergoing low to moderate risk DMEK (95% for Fuchs endothelial corneal dystrophy). Study data were analyzed from April to September 2025.InterventionDMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure (comparable with randomization) to achieve an approximate 2:1 distribution, respectively.Main Outcomes and MeasuresGraft success at 1 year.ResultsA total of 1097 individuals (1421 study eyes; median [IQR] age, 71 [66-76] years; 631 female [57.5%]) were included in the study. The 1-year cumulative probability of graft success was 96.3% (95% CI, 95.0%-97.5%) among 912 study eyes (64.2%) receiving tissue from donors without diabetes and 97.1% (95% CI, 95.5%-98.4%) among 509 study eyes (35.8%) receiving tissue from donors with diabetes (difference between groups = 0.7 percentage points; 95% CI, -1.2 to 2.6; P = .63). The 1-year cumulative probability of graft success was 96.5% (95% CI, 93.6%-98.9%) in the mild donor diabetes severity subgroup (n = 173) and 97.3% (95% CI, 95.4%-98.8%) in the moderate to severe donor diabetes severity subgroup (n = 336), using a diabetes severity rating scale based on medical history. The rates of primary donor failure, early failure related to surgical complications, and subsequent failure were as follows: 2.5% (23 of 912), 0.7% (6 of 912), and 0.3% (3 of 912), respectively, in recipients of tissue from a donor without diabetes, and 2.6% (13 of 509), 0.4% (2 of 509), and 0%, respectively, among recipients of tissue from a donor with diabetes. There were no failures due to graft rejection.Conclusions and RelevanceThe 1-year success rate in eyes undergoing DMEK with successfully prepared tissue was very high regardless of donor diabetes status. These results, supported by the separately reported finding that endothelial cell loss and cornea morphometry after 1 year were not affected by donor diabetes status, provide strong support for having no restrictions on the use of tissue from donors with diabetes for DMEK.Trial RegistrationClinicalTrials.gov Identifier: NCT05134480.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"12 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1001/jamaophthalmol.2025.4261
Jonathan H Lass,Beth Ann Benetz,David D Verdier,Loretta B Szczotka-Flynn,Colleen E Bauza,Zachariah W Reed,Mark A Greiner,Shahzad I Mian,Sanjay V Patel,Sudeep Pramanik,Francis W Price,Mark C Soper,Mark A Terry,Michael S Titus,Craig Kollman,Roy W Beck,Marianne O Price,
ImportanceThe effect of cornea donor diabetes on endothelial cell density (ECD) and morphometry after Descemet membrane endothelial keratoplasty (DMEK) is not known.ObjectiveTo determine whether endothelial cell loss (ECL) and morphometric changes 1 year after successful DMEK are related to cornea donor's diabetes status.Design, Setting, and ParticipantsThis was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2024 at 28 US clinical sites (46 surgeons) and 13 eye banks. Included in the trial were the eyes of recipients (some of whom received tissue from donors without diabetes and others who received tissue from donors with diabetes) who underwent successful DMEK, primarily for Fuchs endothelial corneal dystrophy, and had at least 1 analyzable postoperative endothelial image.InterventionDMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure to achieve an approximate 2:1 distribution.Main Outcomes and MeasuresECD, ECL, coefficient of variation in cell area (CV), and percentage of hexagonal cells (HEX) at 1 year from eye bank and postoperative specular central endothelial images.ResultsA total 1274 eyes of 982 recipients (mean [SD] age, 70 [8] years; 569 female [57.9%]; 816 [64.1%] with tissue from donors without diabetes and 458 [35.9%] with tissue from donors with diabetes) were included in the study. Preoperatively, mean (SD) central ECD in tissue from donors without diabetes and with diabetes were 2676 (290) cells/mm2 and 2671 (286) cells/mm2, respectively. At 1 year, mean (SD) ECL was 28.3% (16.1%) and 28.0% (17.0%), in the donor groups without and with diabetes, respectively (adjusted mean difference = -0.4%; 95% CI, -2.3% to 1.4%), resulting in a mean (SD) 1-year ECD of 1927 (498) cells/mm2 and 1920 (496) cells/mm2, respectively (adjusted mean difference = 10 cells/mm2; 95% CI, -36 to 56; P = .95). No difference in ECD at 1 year associated with diabetes severity was noted (P = .97). Mean (SD) CV did not differ at 1 year between the 2 groups of eyes (31.5% [4.1%] vs 31.4% [4.1%]; adjusted mean difference = -0.4%; 95% CI, -0.9% to 0.1%; P = .51), and mean (SD) HEX did not differ at 1 year between the 2 groups of eyes (57.7% [5.8%] vs 57.2% [5.8%]; adjusted mean difference = 0.1%, 95% CI, -0.8% to 0.9%; P = .33).Conclusions and RelevanceThis randomized clinical trial found that ECL and morphometry 1 year after DMEK were not affected by cornea donor diabetes status. With comparable 1-year graft success with tissue from donors with and without diabetes demonstrated in this trial, these findings support the use of corneas from donors with diabetes for endothelial keratoplasty procedures.Trial RegistrationClinicalTrials.gov Identifier: NCT05134480.
{"title":"Endothelial Cell Loss 1 Year After Successful DMEK in the Diabetes Endothelial Keratoplasty Study: A Randomized Clinical Trial.","authors":"Jonathan H Lass,Beth Ann Benetz,David D Verdier,Loretta B Szczotka-Flynn,Colleen E Bauza,Zachariah W Reed,Mark A Greiner,Shahzad I Mian,Sanjay V Patel,Sudeep Pramanik,Francis W Price,Mark C Soper,Mark A Terry,Michael S Titus,Craig Kollman,Roy W Beck,Marianne O Price, ","doi":"10.1001/jamaophthalmol.2025.4261","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2025.4261","url":null,"abstract":"ImportanceThe effect of cornea donor diabetes on endothelial cell density (ECD) and morphometry after Descemet membrane endothelial keratoplasty (DMEK) is not known.ObjectiveTo determine whether endothelial cell loss (ECL) and morphometric changes 1 year after successful DMEK are related to cornea donor's diabetes status.Design, Setting, and ParticipantsThis was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2024 at 28 US clinical sites (46 surgeons) and 13 eye banks. Included in the trial were the eyes of recipients (some of whom received tissue from donors without diabetes and others who received tissue from donors with diabetes) who underwent successful DMEK, primarily for Fuchs endothelial corneal dystrophy, and had at least 1 analyzable postoperative endothelial image.InterventionDMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure to achieve an approximate 2:1 distribution.Main Outcomes and MeasuresECD, ECL, coefficient of variation in cell area (CV), and percentage of hexagonal cells (HEX) at 1 year from eye bank and postoperative specular central endothelial images.ResultsA total 1274 eyes of 982 recipients (mean [SD] age, 70 [8] years; 569 female [57.9%]; 816 [64.1%] with tissue from donors without diabetes and 458 [35.9%] with tissue from donors with diabetes) were included in the study. Preoperatively, mean (SD) central ECD in tissue from donors without diabetes and with diabetes were 2676 (290) cells/mm2 and 2671 (286) cells/mm2, respectively. At 1 year, mean (SD) ECL was 28.3% (16.1%) and 28.0% (17.0%), in the donor groups without and with diabetes, respectively (adjusted mean difference = -0.4%; 95% CI, -2.3% to 1.4%), resulting in a mean (SD) 1-year ECD of 1927 (498) cells/mm2 and 1920 (496) cells/mm2, respectively (adjusted mean difference = 10 cells/mm2; 95% CI, -36 to 56; P = .95). No difference in ECD at 1 year associated with diabetes severity was noted (P = .97). Mean (SD) CV did not differ at 1 year between the 2 groups of eyes (31.5% [4.1%] vs 31.4% [4.1%]; adjusted mean difference = -0.4%; 95% CI, -0.9% to 0.1%; P = .51), and mean (SD) HEX did not differ at 1 year between the 2 groups of eyes (57.7% [5.8%] vs 57.2% [5.8%]; adjusted mean difference = 0.1%, 95% CI, -0.8% to 0.9%; P = .33).Conclusions and RelevanceThis randomized clinical trial found that ECL and morphometry 1 year after DMEK were not affected by cornea donor diabetes status. With comparable 1-year graft success with tissue from donors with and without diabetes demonstrated in this trial, these findings support the use of corneas from donors with diabetes for endothelial keratoplasty procedures.Trial RegistrationClinicalTrials.gov Identifier: NCT05134480.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"356 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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