Pub Date : 2025-01-09DOI: 10.1001/jamaophthalmol.2024.5703
James Loughman, Gareth Lingham, Ernest Kyei Nkansah, Emmanuel Kobia-Acquah, Daniel Ian Flitcroft
ImportanceAdditional data are required regarding atropine treatment regimens for control of myopia progression.ObjectiveTo investigate the efficacy and safety of different atropine regimens for myopia in children.Design, Setting, and ParticipantsThis was a secondary analysis of the 3-year results of the 24-Month Myopia Outcome Study of Atropine in Children (MOSAIC) trial, called the MOSAIC2 trial. The MOSAIC trial was an investigator-led, double-masked, randomized clinical trial of different atropine concentrations and regimens. The MOSAIC2 study took place at the Centre for Eye Research Ireland, in Dublin, Ireland, and included children and adolescents with myopia from the MOSAIC trial. Data analysis was conducted from November 2023 to February 2024.InterventionsParticipants were randomly assigned to the following cohorts: group 1, nightly placebo for 2 years then 0.05% atropine eye drops for 1 year and group 2, nightly 0.01% atropine eye drops for 2 years then rerandomization to placebo nightly, tapering placebo, or tapering of 0.01% atropine eye drops for 1 year.Main Outcomes and MeasuresObserved changes in cycloplegic spherical equivalent refraction and axial length from month 24, or baseline, to month 36.ResultsA total of 199 children with myopia (mean [SD] age, 13.9 [2.4] years; 121 female [60.8%]) of the 250 children and adolescents from the MOSAIC trial were included in the MOSAIC2 trial analysis. Of 83 participants assigned to group 1, 66 (79.5%) reconsented to year 3, and 61 (73.5%) completed the trial. Of 167 participants assigned to group 2, 133 (79.6%) continued to year 3, and 121 (72.5%) completed the trial (0.01% atropine, then nightly placebo: n = 31 and n = 29 [93.5%]; 0.01% atropine, then tapering placebo: n = 29 and n = 25 [86.2%]; 0.01% atropine then tapering 0.01% atropine: n = 73 and n = 67 [91.8%], respectively). Compared with the group taking placebo then 0.05% atropine, the combined atropine then placebo groups had more spherical equivalent progression (adjusted difference, −0.13 diopters [D]; 95% CI, −0.22 to −0.04 D; <jats:italic>P</jats:italic> = .01) and axial elongation (adjusted difference, 0.06 mm; 95% CI, 0.02-0.09 mm; <jats:italic>P</jats:italic> = .008), and the group taking 0.01% atropine then tapering 0.01% atropine had more axial elongation (adjusted difference, 0.04 mm; 95% CI, 0.009-0.07 mm; <jats:italic>P</jats:italic> = .04). In the group taking placebo then 0.05% atropine, 15% (n = 10) and 8% (n = 5) reported blurred near vision and photophobia, respectively, during year 3, compared with 3% (n = 2) and 0%, respectively, in the group taking 0.01% atropine then tapering 0.01% atropine, and no reports in both placebo groups.Conclusions and RelevanceDespite more adverse events, participants using 0.05% atropine during year 3 had no differences in treatment completion rates and exhibited 0.13-D less myopia progression and 0.06-mm less axial elongation, compared with participants using placebo, supporting cons
{"title":"Efficacy and Safety of Different Atropine Regimens for the Treatment of Myopia in Children","authors":"James Loughman, Gareth Lingham, Ernest Kyei Nkansah, Emmanuel Kobia-Acquah, Daniel Ian Flitcroft","doi":"10.1001/jamaophthalmol.2024.5703","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.5703","url":null,"abstract":"ImportanceAdditional data are required regarding atropine treatment regimens for control of myopia progression.ObjectiveTo investigate the efficacy and safety of different atropine regimens for myopia in children.Design, Setting, and ParticipantsThis was a secondary analysis of the 3-year results of the 24-Month Myopia Outcome Study of Atropine in Children (MOSAIC) trial, called the MOSAIC2 trial. The MOSAIC trial was an investigator-led, double-masked, randomized clinical trial of different atropine concentrations and regimens. The MOSAIC2 study took place at the Centre for Eye Research Ireland, in Dublin, Ireland, and included children and adolescents with myopia from the MOSAIC trial. Data analysis was conducted from November 2023 to February 2024.InterventionsParticipants were randomly assigned to the following cohorts: group 1, nightly placebo for 2 years then 0.05% atropine eye drops for 1 year and group 2, nightly 0.01% atropine eye drops for 2 years then rerandomization to placebo nightly, tapering placebo, or tapering of 0.01% atropine eye drops for 1 year.Main Outcomes and MeasuresObserved changes in cycloplegic spherical equivalent refraction and axial length from month 24, or baseline, to month 36.ResultsA total of 199 children with myopia (mean [SD] age, 13.9 [2.4] years; 121 female [60.8%]) of the 250 children and adolescents from the MOSAIC trial were included in the MOSAIC2 trial analysis. Of 83 participants assigned to group 1, 66 (79.5%) reconsented to year 3, and 61 (73.5%) completed the trial. Of 167 participants assigned to group 2, 133 (79.6%) continued to year 3, and 121 (72.5%) completed the trial (0.01% atropine, then nightly placebo: n = 31 and n = 29 [93.5%]; 0.01% atropine, then tapering placebo: n = 29 and n = 25 [86.2%]; 0.01% atropine then tapering 0.01% atropine: n = 73 and n = 67 [91.8%], respectively). Compared with the group taking placebo then 0.05% atropine, the combined atropine then placebo groups had more spherical equivalent progression (adjusted difference, −0.13 diopters [D]; 95% CI, −0.22 to −0.04 D; <jats:italic>P</jats:italic> = .01) and axial elongation (adjusted difference, 0.06 mm; 95% CI, 0.02-0.09 mm; <jats:italic>P</jats:italic> = .008), and the group taking 0.01% atropine then tapering 0.01% atropine had more axial elongation (adjusted difference, 0.04 mm; 95% CI, 0.009-0.07 mm; <jats:italic>P</jats:italic> = .04). In the group taking placebo then 0.05% atropine, 15% (n = 10) and 8% (n = 5) reported blurred near vision and photophobia, respectively, during year 3, compared with 3% (n = 2) and 0%, respectively, in the group taking 0.01% atropine then tapering 0.01% atropine, and no reports in both placebo groups.Conclusions and RelevanceDespite more adverse events, participants using 0.05% atropine during year 3 had no differences in treatment completion rates and exhibited 0.13-D less myopia progression and 0.06-mm less axial elongation, compared with participants using placebo, supporting cons","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"15 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939872","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 : 2025-01-09DOI: 10.1001/jamaophthalmol.2024.5619
Xiuju Chen, Xiao Liu, Shihe Cui, Gang Wang, Yiting Liu, Guang Qu, Lixin Jiang, Yong Liu, Xiaoxin Li
ImportanceBietti crystalline dystrophy (BCD) is a severe genetic retinopathy caused by variants in the CYP4V2 gene. Currently, there is no approved treatment for BCD.ObjectiveTo evaluate safety and vision outcomes following gene therapy with adeno-associated virus (AAV) encoding CYP4V2 (rAAV-hCYP4V2, NGGT001 [Next Generation Gene Therapeutics]).Design, Setting, and ParticipantsThis open-label, dose-escalation nonrandomized clinical trial was conducted from February 2023 to May 2024 at 2 study sites in China. Patients with genetically confirmed biallelic disease-linked CYP4V2 variants received subretinal injections of rAAV2-hCYP4V2 at 1 of 2 dosage levels and were followed up for 12 months.InterventionA single unilateral injection of 1.5 × 1011 or 3.0 × 1011 total vector genomes of recombinant AAV-hCYP4V2 in the worse eye, based on visual acuity letter score.Main Outcomes and MeasuresThe primary outcome was safety, assessed by clinical examination of ocular inflammation and evaluated by routine clinical chemistry and immunogenicity testing. Secondary outcomes were changes in visual function from baseline in best-corrected visual acuity (BCVA), microperimetry, and contrast sensitivity 12 months after treatment.ResultsAmong 12 patients with BCD (6 patients per dose group), mean (SD) patient age was 40.5 (7.1) years, and 5 patients (42%) were female. No severe adverse events related to the treatment were observed. However, mild intraocular inflammation was noted in 1 participant. The median (IQR) baseline BCVA letter score for the study eye was 34 (10-53), equivalent to 20/200 Snellen, while the nonstudy eye had a median (IQR) BCVA of 60 (40-67), equivalent to approximately 20/63 Snellen. At 12 months, the study eye improved by a mean (SD) letter score of 13.9 (13.1) compared with 6.3 (7.4) in the nonstudy eye. The 12-month median (IQR) BCVA for the study eye was 53 (37-64) (equivalent to approximately 20/80 Snellen) and 62 (42-70) (approximately 20/50 Snellen) for the nonstudy eye.Conclusions and RelevanceThis open-label, exploratory nonrandomized clinical trial identified no serious safety concerns related to gene therapy over 12 months’ follow-up among patients with BCD. While improvement in BCVA was noted, the magnitude was within test-retest values typically noted in eyes with very low levels of visual acuity, and BCVA improvement in both the study and nonstudy eyes could be related to a learning effect, with greater improvement in the study eye possibly related to study eyes’ being the worse-seeing eye.Trial RegistrationClinicalTrials.gov Identifier: NCT06302608
{"title":"Safety and Vision Outcomes Following Gene Therapy for Bietti Crystalline Dystrophy","authors":"Xiuju Chen, Xiao Liu, Shihe Cui, Gang Wang, Yiting Liu, Guang Qu, Lixin Jiang, Yong Liu, Xiaoxin Li","doi":"10.1001/jamaophthalmol.2024.5619","DOIUrl":"https://doi.org/10.1001/jamaophthalmol.2024.5619","url":null,"abstract":"ImportanceBietti crystalline dystrophy (BCD) is a severe genetic retinopathy caused by variants in the <jats:italic>CYP4V2</jats:italic> gene. Currently, there is no approved treatment for BCD.ObjectiveTo evaluate safety and vision outcomes following gene therapy with adeno-associated virus (AAV) encoding CYP4V2 (rAAV-hCYP4V2, NGGT001 [Next Generation Gene Therapeutics]).Design, Setting, and ParticipantsThis open-label, dose-escalation nonrandomized clinical trial was conducted from February 2023 to May 2024 at 2 study sites in China. Patients with genetically confirmed biallelic disease-linked <jats:italic>CYP4V2</jats:italic> variants received subretinal injections of rAAV2-hCYP4V2 at 1 of 2 dosage levels and were followed up for 12 months.InterventionA single unilateral injection of 1.5 × 10<jats:sup>11</jats:sup> or 3.0 × 10<jats:sup>11</jats:sup> total vector genomes of recombinant AAV-hCYP4V2 in the worse eye, based on visual acuity letter score.Main Outcomes and MeasuresThe primary outcome was safety, assessed by clinical examination of ocular inflammation and evaluated by routine clinical chemistry and immunogenicity testing. Secondary outcomes were changes in visual function from baseline in best-corrected visual acuity (BCVA), microperimetry, and contrast sensitivity 12 months after treatment.ResultsAmong 12 patients with BCD (6 patients per dose group), mean (SD) patient age was 40.5 (7.1) years, and 5 patients (42%) were female. No severe adverse events related to the treatment were observed. However, mild intraocular inflammation was noted in 1 participant. The median (IQR) baseline BCVA letter score for the study eye was 34 (10-53), equivalent to 20/200 Snellen, while the nonstudy eye had a median (IQR) BCVA of 60 (40-67), equivalent to approximately 20/63 Snellen. At 12 months, the study eye improved by a mean (SD) letter score of 13.9 (13.1) compared with 6.3 (7.4) in the nonstudy eye. The 12-month median (IQR) BCVA for the study eye was 53 (37-64) (equivalent to approximately 20/80 Snellen) and 62 (42-70) (approximately 20/50 Snellen) for the nonstudy eye.Conclusions and RelevanceThis open-label, exploratory nonrandomized clinical trial identified no serious safety concerns related to gene therapy over 12 months’ follow-up among patients with BCD. While improvement in BCVA was noted, the magnitude was within test-retest values typically noted in eyes with very low levels of visual acuity, and BCVA improvement in both the study and nonstudy eyes could be related to a learning effect, with greater improvement in the study eye possibly related to study eyes’ being the worse-seeing eye.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.clinicaltrials.gov/study/NCT06302608?cond=NCT06302608&amp;amp;rank=1\">NCT06302608</jats:ext-link>","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":"20 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939873","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 : 2025-01-01DOI: 10.1001/jamaophthalmol.2024.4856
Weixiong He, Samantha Sze-Yee Lee, Santiago Diaz Torres, Xikun Han, Puya Gharahkhani, Michael Hunter, Chandrakumar Balartnasingam, Jamie E Craig, Alex W Hewitt, David A Mackey, Stuart MacGregor
Importance: Early detection of glaucoma is essential to timely monitoring and treatment, and primary open-angle glaucoma risk can be assessed by measuring intraocular pressure (IOP) or optic nerve head vertical cup-disc ratio (VCDR). Polygenic risk scores (PRSs) could provide a link between genetic effects estimated from genome-wide association studies (GWASs) and clinical applications to provide estimates of an individual's genetic risk by combining many identified variants into a score.
Objective: To construct IOP and VCDR PRSs with clinically relevant predictive power.
Design, setting, and participants: This genetic association study evaluated the PRSs for 6959 of 51 338 individuals in the Canadian Longitudinal Study on Aging (CLSA; 2010 to 2015 with data from 11 centers in Canada) and 4960 of 5107 individuals the community-based Busselton Healthy Aging Study (BHAS; 2010 to 2015 in Busselton, Western Australia) with an artificial intelligence grading approach used to obtain precise VCDR estimates for the CLSA dataset. Data for approximately 500 000 individuals in UK Biobank from 2006 to 2010 were used to validate the power of the PRS. Data were analyzed from June to November 2023.
Main outcomes and measures: IOP and VCDR PRSs and phenotypic variance (R2) explained by each PRS.
Results: Participants in CLSA were aged 45 to 85 years; those in BHAS, 46 to 64 years; and those in UK Biobank, 40 to 69 years. The VCDR PRS explained 22.0% (95% CI, 20.1-23.9) and 19.7% (95% CI, 16.3-23.3) of the phenotypic variance in VCDR in CLSA and BHAS, respectively, while the IOP PRS explained 12.9% (95% CI, 11.3-14.6) and 9.6% (95% CI, 8.1-11.2) of phenotypic variance in CLSA and BHAS IOP measurements. The VCDR PRS variance explained 5.2% (95% CI, 3.6-7.1), 12.1% (95% CI, 7.5-17.5), and 14.3% (95% CI, 9.3-19.9), and the IOP PRS variance explained 2.3% (95% CI, 1.5-3.3), 3.2% (95% CI, 1.3-5.8), and 7.5% (95% CI, 6.2-8.9) (P < .001) across African, East Asian, and South Asian populations, respectively.
Conclusions and relevance: VCDR and IOP PRSs derived using a large recently published multitrait GWAS exhibited validity across independent cohorts. The findings suggest that an IOP PRS has the potential to identify individuals who may benefit from more intensive IOP-lowering treatments, which could be crucial in managing glaucoma risk more effectively. Individuals with a high VCDR PRS may be at risk of developing glaucoma even if their IOP measures fall within the normal range, suggesting that these PRSs could help in early detection and intervention, particularly among those who might otherwise be considered at low risk based on IOP alone.
{"title":"Predictive Power of Polygenic Risk Scores for Intraocular Pressure or Vertical Cup-Disc Ratio.","authors":"Weixiong He, Samantha Sze-Yee Lee, Santiago Diaz Torres, Xikun Han, Puya Gharahkhani, Michael Hunter, Chandrakumar Balartnasingam, Jamie E Craig, Alex W Hewitt, David A Mackey, Stuart MacGregor","doi":"10.1001/jamaophthalmol.2024.4856","DOIUrl":"10.1001/jamaophthalmol.2024.4856","url":null,"abstract":"<p><strong>Importance: </strong>Early detection of glaucoma is essential to timely monitoring and treatment, and primary open-angle glaucoma risk can be assessed by measuring intraocular pressure (IOP) or optic nerve head vertical cup-disc ratio (VCDR). Polygenic risk scores (PRSs) could provide a link between genetic effects estimated from genome-wide association studies (GWASs) and clinical applications to provide estimates of an individual's genetic risk by combining many identified variants into a score.</p><p><strong>Objective: </strong>To construct IOP and VCDR PRSs with clinically relevant predictive power.</p><p><strong>Design, setting, and participants: </strong>This genetic association study evaluated the PRSs for 6959 of 51 338 individuals in the Canadian Longitudinal Study on Aging (CLSA; 2010 to 2015 with data from 11 centers in Canada) and 4960 of 5107 individuals the community-based Busselton Healthy Aging Study (BHAS; 2010 to 2015 in Busselton, Western Australia) with an artificial intelligence grading approach used to obtain precise VCDR estimates for the CLSA dataset. Data for approximately 500 000 individuals in UK Biobank from 2006 to 2010 were used to validate the power of the PRS. Data were analyzed from June to November 2023.</p><p><strong>Main outcomes and measures: </strong>IOP and VCDR PRSs and phenotypic variance (R2) explained by each PRS.</p><p><strong>Results: </strong>Participants in CLSA were aged 45 to 85 years; those in BHAS, 46 to 64 years; and those in UK Biobank, 40 to 69 years. The VCDR PRS explained 22.0% (95% CI, 20.1-23.9) and 19.7% (95% CI, 16.3-23.3) of the phenotypic variance in VCDR in CLSA and BHAS, respectively, while the IOP PRS explained 12.9% (95% CI, 11.3-14.6) and 9.6% (95% CI, 8.1-11.2) of phenotypic variance in CLSA and BHAS IOP measurements. The VCDR PRS variance explained 5.2% (95% CI, 3.6-7.1), 12.1% (95% CI, 7.5-17.5), and 14.3% (95% CI, 9.3-19.9), and the IOP PRS variance explained 2.3% (95% CI, 1.5-3.3), 3.2% (95% CI, 1.3-5.8), and 7.5% (95% CI, 6.2-8.9) (P < .001) across African, East Asian, and South Asian populations, respectively.</p><p><strong>Conclusions and relevance: </strong>VCDR and IOP PRSs derived using a large recently published multitrait GWAS exhibited validity across independent cohorts. The findings suggest that an IOP PRS has the potential to identify individuals who may benefit from more intensive IOP-lowering treatments, which could be crucial in managing glaucoma risk more effectively. Individuals with a high VCDR PRS may be at risk of developing glaucoma even if their IOP measures fall within the normal range, suggesting that these PRSs could help in early detection and intervention, particularly among those who might otherwise be considered at low risk based on IOP alone.</p>","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":"15-22"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681565","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 : 2025-01-01DOI: 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":"7-14"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","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 : 2025-01-01DOI: 10.1001/jamaophthalmol.2024.5491
Jacob S Heng, Yannis M Paulus
{"title":"Novel In-Office Procedure for Retinal Detachment.","authors":"Jacob S Heng, Yannis M Paulus","doi":"10.1001/jamaophthalmol.2024.5491","DOIUrl":"10.1001/jamaophthalmol.2024.5491","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":"60-61"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812978","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 : 2025-01-01DOI: 10.1001/jamaophthalmol.2024.5364
Jonathan E Shaw, Alicia J Jenkins
{"title":"Diabetic Retinopathy-Another Possible Target for SGLT2 Inhibitors?","authors":"Jonathan E Shaw, Alicia J Jenkins","doi":"10.1001/jamaophthalmol.2024.5364","DOIUrl":"10.1001/jamaophthalmol.2024.5364","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":"71-72"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785433","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 : 2025-01-01DOI: 10.1001/jamaophthalmol.2024.5121
Madeleine K Nowak, Francesca C Fortenbaugh, David H Salat
{"title":"Visual Deficits in Patients With Mild Traumatic Brain Injury.","authors":"Madeleine K Nowak, Francesca C Fortenbaugh, David H Salat","doi":"10.1001/jamaophthalmol.2024.5121","DOIUrl":"10.1001/jamaophthalmol.2024.5121","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":"43-44"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728682","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 : 2025-01-01DOI: 10.1001/jamaophthalmol.2024.5104
Madelynn Corda, Jonathan Shepherd, Alan D Proia
{"title":"Strongyloides stercoralis Choroiditis.","authors":"Madelynn Corda, Jonathan Shepherd, Alan D Proia","doi":"10.1001/jamaophthalmol.2024.5104","DOIUrl":"10.1001/jamaophthalmol.2024.5104","url":null,"abstract":"","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":"83-85"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728676","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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