Pub Date : 2024-11-14DOI: 10.1001/jamaophthalmol.2024.4784
Jennifer M Chang-Wolf, Tyler G Kinzy, Sjoerd J Driessen, Lauren A Cruz, Sudha K Iyengar, Neal S Peachey, Tin Aung, Chiea Chuen Khor, Susan E Williams, Michele Ramsay, Olusola Olawoye, Adeyinka Ashaye, Caroline C W Klaver, Michael A Hauser, Alberta A H J Thiadens, Jessica N Cooke Bailey, Pieter W M Bonnemaijer
<p><strong>Importance: </strong>Primary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.</p><p><strong>Objective: </strong>To evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.</p><p><strong>Design, setting, and participants: </strong>This was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023.</p><p><strong>Exposures: </strong>Three PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS).</p><p><strong>Main outcomes and measures: </strong>Odds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components.</p><p><strong>Results: </strong>A total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs.</p><p><strong>Conclusions and relevance: </strong>In this cross-sectional study, despite some improvements in OR-based risk stratification using the Ghara
{"title":"Performance of Polygenic Risk Scores for Primary Open-Angle Glaucoma in Populations of African Descent.","authors":"Jennifer M Chang-Wolf, Tyler G Kinzy, Sjoerd J Driessen, Lauren A Cruz, Sudha K Iyengar, Neal S Peachey, Tin Aung, Chiea Chuen Khor, Susan E Williams, Michele Ramsay, Olusola Olawoye, Adeyinka Ashaye, Caroline C W Klaver, Michael A Hauser, Alberta A H J Thiadens, Jessica N Cooke Bailey, Pieter W M Bonnemaijer","doi":"10.1001/jamaophthalmol.2024.4784","DOIUrl":"10.1001/jamaophthalmol.2024.4784","url":null,"abstract":"<p><strong>Importance: </strong>Primary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.</p><p><strong>Objective: </strong>To evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.</p><p><strong>Design, setting, and participants: </strong>This was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023.</p><p><strong>Exposures: </strong>Three PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS).</p><p><strong>Main outcomes and measures: </strong>Odds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components.</p><p><strong>Results: </strong>A total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs.</p><p><strong>Conclusions and relevance: </strong>In this cross-sectional study, despite some improvements in OR-based risk stratification using the Ghara","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1001/jamaophthalmol.2024.4877
Yuxuan Guan, Xingrong Ma, Peizeng Yang
A 20-year-old Chinese woman was experiencing fever, malaise, headache, nausea, vomiting, and neck stiffness for 2 weeks. Further examination revealed inflammation, vitritis and cystoid macular edema, tortuous dilatation of retinal venous vessels with fluorescence leakage, and hyperfluorescence in the optic disc. What would you do next?
{"title":"Viral Meningoencephalitis and Bilateral Blurry Vision","authors":"Yuxuan Guan, Xingrong Ma, Peizeng Yang","doi":"10.1001/jamaophthalmol.2024.4877","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4877","url":null,"abstract":"A 20-year-old Chinese woman was experiencing fever, malaise, headache, nausea, vomiting, and neck stiffness for 2 weeks. Further examination revealed inflammation, vitritis and cystoid macular edema, tortuous dilatation of retinal venous vessels with fluorescence leakage, and hyperfluorescence in the optic disc. What would you do next?","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"6 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610343","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 : 2024-11-14DOI: 10.1001/jamaophthalmol.2024.4868
Vincent Q. Pham, Takashi Nishida, Sasan Moghimi, Christopher A. Girkin, Massimo A. Fazio, Jeffrey M. Liebmann, Linda M. Zangwill, Robert N. Weinreb
ImportanceLong-term variability of blood pressure may be associated with visual field (VF) progression in patients with glaucoma.ObjectivesTo investigate the association between blood pressure parameters and VF progression over time in patients with glaucoma.Design, Setting, and ParticipantsThis retrospective cohort study of longitudinal data included patients with suspected or confirmed glaucoma who were selected from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Patients underwent blood pressure and VF testing from November 2000 to December 2022, and data were analyzed in October 2023.ExposureSuspected or confirmed glaucoma.Main Outcomes and MeasuresMean and SD values of blood pressure variables were calculated for systolic and diastolic arterial pressures. These parameters were incorporated into multivariable mixed-effect models to investigate the association between blood pressure parameters and mean intraocular pressure with rates of VF mean deviation loss. Interaction terms between blood pressure parameters and mean intraocular pressure were also included in the models.ResultsA total of 1674 eyes from 985 patients were assessed (mean [SD] age, 61.2 [0.4] years; 563 female [57.2%]). The mean rate of VF mean deviation change was −0.13 (95% CI, −0.16 to −0.10) dB/y over a mean follow-up of 8.0 (95% CI, 7.7-8.2) years. The interaction terms of higher mean blood pressure and higher SD of blood pressure were associated with faster annual mean deviation changes for both mean arterial pressure (0.02 [95% CI, 0.01-0.04] dB/y per 1-mm Hg higher; P = .001) and diastolic arterial pressure (0.02 [95% CI, 0.01-0.03] dB/y per 1-mm Hg higher; P &lt; .001). The interaction term of higher SD of blood pressure and higher mean intraocular pressure was associated with faster annual mean deviation changes for both mean arterial pressure (0.01 [95% CI, 0.00-0.02] μm per 1-mm Hg higher; P = .003) and diastolic arterial pressure (0.01 [95% CI, 0.00-0.01] μm per 1-mm Hg higher; P = .001).Conclusions and RelevanceIn this cohort study, higher mean blood pressure and higher SD of blood pressure were associated with faster VF progression. These findings suggest that long-term variability of blood pressure may be a modifier of the association between intraocular pressure and VF progression in glaucoma.
{"title":"Long-Term Blood Pressure Variability and Visual Field Progression in Glaucoma","authors":"Vincent Q. Pham, Takashi Nishida, Sasan Moghimi, Christopher A. Girkin, Massimo A. Fazio, Jeffrey M. Liebmann, Linda M. Zangwill, Robert N. Weinreb","doi":"10.1001/jamaophthalmol.2024.4868","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4868","url":null,"abstract":"ImportanceLong-term variability of blood pressure may be associated with visual field (VF) progression in patients with glaucoma.ObjectivesTo investigate the association between blood pressure parameters and VF progression over time in patients with glaucoma.Design, Setting, and ParticipantsThis retrospective cohort study of longitudinal data included patients with suspected or confirmed glaucoma who were selected from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Patients underwent blood pressure and VF testing from November 2000 to December 2022, and data were analyzed in October 2023.ExposureSuspected or confirmed glaucoma.Main Outcomes and MeasuresMean and SD values of blood pressure variables were calculated for systolic and diastolic arterial pressures. These parameters were incorporated into multivariable mixed-effect models to investigate the association between blood pressure parameters and mean intraocular pressure with rates of VF mean deviation loss. Interaction terms between blood pressure parameters and mean intraocular pressure were also included in the models.ResultsA total of 1674 eyes from 985 patients were assessed (mean [SD] age, 61.2 [0.4] years; 563 female [57.2%]). The mean rate of VF mean deviation change was −0.13 (95% CI, −0.16 to −0.10) dB/y over a mean follow-up of 8.0 (95% CI, 7.7-8.2) years. The interaction terms of higher mean blood pressure and higher SD of blood pressure were associated with faster annual mean deviation changes for both mean arterial pressure (0.02 [95% CI, 0.01-0.04] dB/y per 1-mm Hg higher; <jats:italic>P</jats:italic> = .001) and diastolic arterial pressure (0.02 [95% CI, 0.01-0.03] dB/y per 1-mm Hg higher; <jats:italic>P</jats:italic> &amp;lt; .001). The interaction term of higher SD of blood pressure and higher mean intraocular pressure was associated with faster annual mean deviation changes for both mean arterial pressure (0.01 [95% CI, 0.00-0.02] μm per 1-mm Hg higher; <jats:italic>P</jats:italic> = .003) and diastolic arterial pressure (0.01 [95% CI, 0.00-0.01] μm per 1-mm Hg higher; <jats:italic>P</jats:italic> = .001).Conclusions and RelevanceIn this cohort study, higher mean blood pressure and higher SD of blood pressure were associated with faster VF progression. These findings suggest that long-term variability of blood pressure may be a modifier of the association between intraocular pressure and VF progression in glaucoma.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"1 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610342","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 : 2024-11-14DOI: 10.1001/jamaophthalmol.2024.4783
Loka Thangamathesvaran, Aaron Z. Priluck, Bryn M. Burkholder, Mark P. Breazzano, Sophie Cai
This case report describes an HIV-positive patient with bilateral syphilitic panuveitis, for whom diagnosis was initially delayed by negative treponemal testing.
本病例报告描述了一名患有双侧梅毒性泛葡萄膜炎的 HIV 阳性患者，起初由于特雷波纳试验阴性而延误了诊断。
{"title":"Negative Treponemal Serologies in Syphilitic Panuveitis","authors":"Loka Thangamathesvaran, Aaron Z. Priluck, Bryn M. Burkholder, Mark P. Breazzano, Sophie Cai","doi":"10.1001/jamaophthalmol.2024.4783","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4783","url":null,"abstract":"This case report describes an HIV-positive patient with bilateral syphilitic panuveitis, for whom diagnosis was initially delayed by negative treponemal testing.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"12 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610344","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 : 2024-11-14DOI: 10.1001/jamaophthalmol.2024.4867
Todd P Margolis, Anat Galor, Gary D Novack
{"title":"Implications of Diagnostic Error in Ocular Surface Disease: The Role of Anchoring and Ambiguous Diagnostic Terminology.","authors":"Todd P Margolis, Anat Galor, Gary D Novack","doi":"10.1001/jamaophthalmol.2024.4867","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4867","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620651","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 : 2024-11-07DOI: 10.1001/jamaophthalmol.2024.4696
Rebhi O. Abuzaitoun, Kari H. Branham, Gabrielle D. Lacy, Robert B. Hufnagel, Meenakshi M. Kumar, Juha W. Koskenvuo, Sari Tuupanen, Todd Durham, Peter Y. Zhao, Maria Fernanda Abalem, Chris A. Andrews, Dana Schlegel, Naheed W. Khan, Abigail T. Fahim, John R. Heckenlively, David C. Musch, K. Thiran Jayasundera
ImportanceThe association of race and detection of pathogenic variants using wide-panel genetic testing for inherited retinal diseases (IRD), to our knowledge, has not been studied previously.ObjectiveTo investigate the genetic detection rates of wide-panel testing in Black and non-Hispanic White patients with IRDs.Design, Setting, ParticipantsThis 2-group comparison used retrospective patient data that were collected at the University of Michigan (UM) and Blueprint Genetics (BG). At UM, inclusion criteria included having a clinical IRD diagnosis, wide-panel genetic testing, and both parents and the patient self-identifying as the same race (Black or non-Hispanic White). Logistic regression analysis was used; the dependent variable was genetic test result (positive or negative/inconclusive) and the independent variables were race, age, sex, phenotype, and number of genes tested. In the BG database, patients with wide-panel testing and self-reported race were included; detection rate comparison analysis based on race was performed using χ2 test of independence. These data were analyzed from October 30, 2013, through October 26, 2022.Main Outcome and MeasureGenetic test result was considered positive if pathogenic/likely pathogenic variants were detected.ResultsA total of 572 patients were included in UM, 295 were males (51.6%). Mean age was 45 years. There were 54 Black patients (9.4%) and 518 White patients (90.6%). Black race (odds ratio [OR], 0.25; 95% CI, 0.14-0.46; P &lt; .001) and age (OR per 10 years, 0.84; 95% CI, 0.76-0.92; P &lt; .001) were independently associated with decreased odds of a positive test. In the BG database, 142 of 320 of Black patients (44.4%) had a positive/likely positive test result, a proportion lower than White patients (1691 of 2931 [57.7%]) (χ2 = 18.65; df = 1; P &lt; .001).Conclusions and RelevanceResults from this study highlight a lower genetic detection rate for Black patients than for White patients with IRDs. This supports a concern that the current development of IRD therapeutics is highly dependent on the ability to identify the genetic cause of disease. Patients with no known genetic diagnosis may be disadvantaged in terms of prognostication, inheritance counseling, reproductive decision-making, and eligibility for potential therapeutic options, including clinical trials. As future treatments become available, these findings suggest the need to examine the genetic detection rates across majority and minority subgroups alike.
{"title":"Racial Disparities in Genetic Detection Rates for Inherited Retinal Diseases","authors":"Rebhi O. Abuzaitoun, Kari H. Branham, Gabrielle D. Lacy, Robert B. Hufnagel, Meenakshi M. Kumar, Juha W. Koskenvuo, Sari Tuupanen, Todd Durham, Peter Y. Zhao, Maria Fernanda Abalem, Chris A. Andrews, Dana Schlegel, Naheed W. Khan, Abigail T. Fahim, John R. Heckenlively, David C. Musch, K. Thiran Jayasundera","doi":"10.1001/jamaophthalmol.2024.4696","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4696","url":null,"abstract":"ImportanceThe association of race and detection of pathogenic variants using wide-panel genetic testing for inherited retinal diseases (IRD), to our knowledge, has not been studied previously.ObjectiveTo investigate the genetic detection rates of wide-panel testing in Black and non-Hispanic White patients with IRDs.Design, Setting, ParticipantsThis 2-group comparison used retrospective patient data that were collected at the University of Michigan (UM) and Blueprint Genetics (BG). At UM, inclusion criteria included having a clinical IRD diagnosis, wide-panel genetic testing, and both parents and the patient self-identifying as the same race (Black or non-Hispanic White). Logistic regression analysis was used; the dependent variable was genetic test result (positive or negative/inconclusive) and the independent variables were race, age, sex, phenotype, and number of genes tested. In the BG database, patients with wide-panel testing and self-reported race were included; detection rate comparison analysis based on race was performed using χ<jats:sup>2</jats:sup> test of independence. These data were analyzed from October 30, 2013, through October 26, 2022.Main Outcome and MeasureGenetic test result was considered positive if pathogenic/likely pathogenic variants were detected.ResultsA total of 572 patients were included in UM, 295 were males (51.6%). Mean age was 45 years. There were 54 Black patients (9.4%) and 518 White patients (90.6%). Black race (odds ratio [OR], 0.25; 95% CI, 0.14-0.46; <jats:italic>P</jats:italic> &amp;lt; .001) and age (OR per 10 years, 0.84; 95% CI, 0.76-0.92; <jats:italic>P</jats:italic> &amp;lt; .001) were independently associated with decreased odds of a positive test. In the BG database, 142 of 320 of Black patients (44.4%) had a positive/likely positive test result, a proportion lower than White patients (1691 of 2931 [57.7%]) (χ<jats:sup>2</jats:sup> = 18.65; <jats:italic>df</jats:italic> = 1; <jats:italic>P</jats:italic> &amp;lt; .001).Conclusions and RelevanceResults from this study highlight a lower genetic detection rate for Black patients than for White patients with IRDs. This supports a concern that the current development of IRD therapeutics is highly dependent on the ability to identify the genetic cause of disease. Patients with no known genetic diagnosis may be disadvantaged in terms of prognostication, inheritance counseling, reproductive decision-making, and eligibility for potential therapeutic options, including clinical trials. As future treatments become available, these findings suggest the need to examine the genetic detection rates across majority and minority subgroups alike.","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"9 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597017","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 : 2024-11-07DOI: 10.1001/jamaophthalmol.2024.4376
Sayuri Sekimitsu, Nabil Ghazal, Kanza Aziz, Yan Zhao, Rishabh K. Singh, John H. Fingert, Mae O. Gordon, Michael A. Kass, Todd Scheetz, Ayellet V. Segrè, Louis R. Pasquale, Janey L. Wiggs, James D. Brandt, Nazlee Zebardast
ImportancePrimary open-angle glaucoma (POAG) is a heritable disease. A polygenic risk score (PRS) threshold may be used to identify individuals at low risk of disease onset.ObjectiveTo assess the utility of a POAG PRS to identify ocular hypertensive individuals at low risk of disease onset.Design, Setting, and ParticipantsThis is a post hoc analysis of the Ocular Hypertension Treatment Study (OHTS), a multicenter randomized clinical trial across 22 centers in the US conducted among 1636 participants with ocular hypertension from February 1994 to April 2019 with available genetic data. Of the 1636 original participants, 1077 had available genetic data; after excluding 67 for missing data, data quality concerns, or ancestry other than European or African, 1010 were included in the present analysis. Data for this report were analyzed from November 2023 to June 2024.ExposureFrom 1994-2002, participants were randomized to receive topical intraocular pressure (IOP)–lowering medications. From 2002 onwards, all participants were given topical IOP-lowering medications.Main Outcome and MeasureTwenty-year conversion rates by POAG PRS threshold, baseline randomization status, and OHTS clinical risk tertile.ResultsAmong the 1010 participants in this study, 563 (65.8%) were female, and the mean (SD) age was 55.9 (9.4) years. In a mixed-effects logistic regression model adjusted for OHTS risk factors for conversion to POAG and randomization status, a PRS under the 48th percentile was associated with a 1.49 times higher likelihood of disease-free status after 20 years of follow-up (95% CI, 1.04-2.15; <jats:italic>P</jats:italic> = .03; unadjusted hazard ratio [HR], 1.64; 95% CI, 1.13-2.38; <jats:italic>P</jats:italic> = .009), compared with high polygenic risk. When we stratified the trial cohort into nongenetic OHTS clinical risk tertiles, the largest differences in survival probability at 20 years based on PRS threshold was observed in eyes in the highest tertile, initial observation group (20-year conversion rate: 61.1% in the high polygenic risk group vs 23.8% in the low polygenic risk group; 95% CI, −63.0 to −11.6; <jats:italic>P</jats:italic> = .01), with randomization to early treatment partially mitigating the effect of high genetic risk (20-year conversion rate: 37.3% in the high polygenic risk group vs 24.1% in the low polygenic risk group; 95% CI, −35.6 to 9.3%; <jats:italic>P</jats:italic> = .32).Conclusions and RelevanceThese findings support considering use of a POAG PRS threshold to identify individuals at low risk of disease onset, with those below the PRS threshold more likely to have lower conversion rates over 20 years. Among those considered at highest risk based on the OHTS clinical risk model, early treatment may partially offset the association with high genetic risk but provide limited benefit for those with low genetic risk.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link
{"title":"Primary Open-Angle Glaucoma Polygenic Risk Score and Risk of Disease Onset","authors":"Sayuri Sekimitsu, Nabil Ghazal, Kanza Aziz, Yan Zhao, Rishabh K. Singh, John H. Fingert, Mae O. Gordon, Michael A. Kass, Todd Scheetz, Ayellet V. Segrè, Louis R. Pasquale, Janey L. Wiggs, James D. Brandt, Nazlee Zebardast","doi":"10.1001/jamaophthalmol.2024.4376","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4376","url":null,"abstract":"ImportancePrimary open-angle glaucoma (POAG) is a heritable disease. A polygenic risk score (PRS) threshold may be used to identify individuals at low risk of disease onset.ObjectiveTo assess the utility of a POAG PRS to identify ocular hypertensive individuals at low risk of disease onset.Design, Setting, and ParticipantsThis is a post hoc analysis of the Ocular Hypertension Treatment Study (OHTS), a multicenter randomized clinical trial across 22 centers in the US conducted among 1636 participants with ocular hypertension from February 1994 to April 2019 with available genetic data. Of the 1636 original participants, 1077 had available genetic data; after excluding 67 for missing data, data quality concerns, or ancestry other than European or African, 1010 were included in the present analysis. Data for this report were analyzed from November 2023 to June 2024.ExposureFrom 1994-2002, participants were randomized to receive topical intraocular pressure (IOP)–lowering medications. From 2002 onwards, all participants were given topical IOP-lowering medications.Main Outcome and MeasureTwenty-year conversion rates by POAG PRS threshold, baseline randomization status, and OHTS clinical risk tertile.ResultsAmong the 1010 participants in this study, 563 (65.8%) were female, and the mean (SD) age was 55.9 (9.4) years. In a mixed-effects logistic regression model adjusted for OHTS risk factors for conversion to POAG and randomization status, a PRS under the 48th percentile was associated with a 1.49 times higher likelihood of disease-free status after 20 years of follow-up (95% CI, 1.04-2.15; <jats:italic>P</jats:italic> = .03; unadjusted hazard ratio [HR], 1.64; 95% CI, 1.13-2.38; <jats:italic>P</jats:italic> = .009), compared with high polygenic risk. When we stratified the trial cohort into nongenetic OHTS clinical risk tertiles, the largest differences in survival probability at 20 years based on PRS threshold was observed in eyes in the highest tertile, initial observation group (20-year conversion rate: 61.1% in the high polygenic risk group vs 23.8% in the low polygenic risk group; 95% CI, −63.0 to −11.6; <jats:italic>P</jats:italic> = .01), with randomization to early treatment partially mitigating the effect of high genetic risk (20-year conversion rate: 37.3% in the high polygenic risk group vs 24.1% in the low polygenic risk group; 95% CI, −35.6 to 9.3%; <jats:italic>P</jats:italic> = .32).Conclusions and RelevanceThese findings support considering use of a POAG PRS threshold to identify individuals at low risk of disease onset, with those below the PRS threshold more likely to have lower conversion rates over 20 years. Among those considered at highest risk based on the OHTS clinical risk model, early treatment may partially offset the association with high genetic risk but provide limited benefit for those with low genetic risk.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"295 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596977","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 : 2024-11-07DOI: 10.1001/jamaophthalmol.2024.4652
Reeda Bou Said, Andrew J. Barkmeier
A 46-year-old woman is referred for a second opinion with recent onset of suspected seizures and imbalance. Fundus examination revealed bilateral discrete perifoveal circular areas of atrophy. What would you do next?
{"title":"Bilateral Perifoveal Atrophy in a 46-Year-Old Woman","authors":"Reeda Bou Said, Andrew J. Barkmeier","doi":"10.1001/jamaophthalmol.2024.4652","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4652","url":null,"abstract":"A 46-year-old woman is referred for a second opinion with recent onset of suspected seizures and imbalance. Fundus examination revealed bilateral discrete perifoveal circular areas of atrophy. What would you do next?","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"24 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596984","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 : 2024-10-31DOI: 10.1001/jamaophthalmol.2024.4515
Jay B Lusk, Brian Mac Grory, Fan Li
{"title":"Considerations Regarding Association of Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Jay B Lusk, Brian Mac Grory, Fan Li","doi":"10.1001/jamaophthalmol.2024.4515","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4515","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545443","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 : 2024-10-31DOI: 10.1001/jamaophthalmol.2024.4530
Mahyar Etminan, Mohammad A Mansournia
{"title":"Considerations Regarding Association of Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Mahyar Etminan, Mohammad A Mansournia","doi":"10.1001/jamaophthalmol.2024.4530","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.4530","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545448","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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