Pub Date : 2024-05-27DOI: 10.1101/2024.05.27.24306765
Zeynep Sahin, Sara Pisani, Paul Nderitu, Ashwin V Venkataraman, Ta-Wei Guu, Dag Aarsland, Timothy Jackson, Dominic ffytche
Introduction Retinal neurodegeneration has recently been shown to occur in tandem with neurodegenerative disease. In the expectation that disease modifying treatments for Alzheimer’s Disease and Parkinson’s Disease will soon become available, it will be important to have clinically useful biomarkers for neurodegenerative disease subtyping to guide early diagnosis, inform on prognosis and stratify subgroups for treatment. Understanding differences in detectable retina changes in individuals with different neurodegenerative disease subtypes is therefore fundamental. The emerging field of oculomics posits that systemic and neurodegenerative disease can be characterised using detectable ocular biomarkers within retinal diagnostics. The aim of this review is to compare the performance of common retinal imaging modalities in neurodegenerative disease detection and subtyping.
{"title":"Using Retinal diagnostics as a Biomarker for Neurodegenerative Diseases: Protocol for a systematic review","authors":"Zeynep Sahin, Sara Pisani, Paul Nderitu, Ashwin V Venkataraman, Ta-Wei Guu, Dag Aarsland, Timothy Jackson, Dominic ffytche","doi":"10.1101/2024.05.27.24306765","DOIUrl":"https://doi.org/10.1101/2024.05.27.24306765","url":null,"abstract":"<strong>Introduction</strong> Retinal neurodegeneration has recently been shown to occur in tandem with neurodegenerative disease. In the expectation that disease modifying treatments for Alzheimer’s Disease and Parkinson’s Disease will soon become available, it will be important to have clinically useful biomarkers for neurodegenerative disease subtyping to guide early diagnosis, inform on prognosis and stratify subgroups for treatment. Understanding differences in detectable retina changes in individuals with different neurodegenerative disease subtypes is therefore fundamental. The emerging field of oculomics posits that systemic and neurodegenerative disease can be characterised using detectable ocular biomarkers within retinal diagnostics. The aim of this review is to compare the performance of common retinal imaging modalities in neurodegenerative disease detection and subtyping.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141172004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1101/2024.05.06.24306943
Shahin Hallaj, William Halfpenny, Benton G. Chuter, Robert N. Weinreb, Sally L. Baxter, Qi N. Cui
Objective This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP).
目的 本研究旨在提供有关胰高血糖素样肽 1 受体（GLP-1R）激动剂对眼压（IOP）影响的数据。
{"title":"Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change","authors":"Shahin Hallaj, William Halfpenny, Benton G. Chuter, Robert N. Weinreb, Sally L. Baxter, Qi N. Cui","doi":"10.1101/2024.05.06.24306943","DOIUrl":"https://doi.org/10.1101/2024.05.06.24306943","url":null,"abstract":"<strong>Objective</strong> This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP).","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140938627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1101/2024.04.30.24306626
S. Sladek, N. Unger-Manhart, C. Siegl, H. Dellago, P. Zieglmayer, P. Lemell, M. Savli, R. Zieglmayer, W. Geitzenauer, M. Laengauer, E. Prieschl-Grassauer
Purpose This randomized, placebo-controlled, crossover, double-blind, single site trial was aimed to evaluate efficacy and safety of Tacrosolv, a novel eye drop solution containing solubilized tacrolimus, in adult participants with grass pollen induced allergic conjunctivitis.
{"title":"Alleviation of allergic rhinoconjunctivitis symptoms in participants treated with a 0.005% tacrolimus eye drop solution","authors":"S. Sladek, N. Unger-Manhart, C. Siegl, H. Dellago, P. Zieglmayer, P. Lemell, M. Savli, R. Zieglmayer, W. Geitzenauer, M. Laengauer, E. Prieschl-Grassauer","doi":"10.1101/2024.04.30.24306626","DOIUrl":"https://doi.org/10.1101/2024.04.30.24306626","url":null,"abstract":"<strong>Purpose</strong> This randomized, placebo-controlled, crossover, double-blind, single site trial was aimed to evaluate efficacy and safety of Tacrosolv, a novel eye drop solution containing solubilized tacrolimus, in adult participants with grass pollen induced allergic conjunctivitis.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140887605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1101/2024.04.27.24306443
Ishita Garg, Benjamin I. Meyer, Ryan A. Gallo, Sara T. Wester, Daniel Pelaez
Context Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R).
{"title":"A Novel Association Between Human Papillomavirus and Thyroid Eye Disease","authors":"Ishita Garg, Benjamin I. Meyer, Ryan A. Gallo, Sara T. Wester, Daniel Pelaez","doi":"10.1101/2024.04.27.24306443","DOIUrl":"https://doi.org/10.1101/2024.04.27.24306443","url":null,"abstract":"<strong>Context</strong> Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R).","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140838317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1101/2024.04.06.24305169
Ameenat L Solebo, Salomey Kellett, Jugnoo Rahi, Andrew D Dick, Jane Ashworth, Gisella Cooper, Eibhlin McLoone, Kirithika Muthusamy, Rachel Pilling, Harry Petrushkin, Valerija Tadic
We aimed to develop and assess age-appropriate child and young person, self and proxy report tools to capture and characterise eye symptoms in childhood ocular inflammatory disease.
{"title":"Childhood Ocular Inflammation Sensations and Symptoms Reporting Questionnaire (ChOIR-Q): Development and assessment of a paediatric self-report tool","authors":"Ameenat L Solebo, Salomey Kellett, Jugnoo Rahi, Andrew D Dick, Jane Ashworth, Gisella Cooper, Eibhlin McLoone, Kirithika Muthusamy, Rachel Pilling, Harry Petrushkin, Valerija Tadic","doi":"10.1101/2024.04.06.24305169","DOIUrl":"https://doi.org/10.1101/2024.04.06.24305169","url":null,"abstract":"We aimed to develop and assess age-appropriate child and young person, self and proxy report tools to capture and characterise eye symptoms in childhood ocular inflammatory disease.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-06DOI: 10.1101/2024.04.04.24305351
Suzo Ambindwile Malakibungu, Andrew Makupa, William Makupa
Background Despite the advance of cataract surgery astigmatism still occur after cataract surgery due to several reasons these include the preparation and closure of the surgical wound, the choice of suture material, and both intraoperative and postoperative manipulations in Phacoemulsification and Extracapsular cataract Etraction.
{"title":"Evaluation of Cataract Surgery as a Cause of Astigmatism among Patients Undergoing Phacoemulsification and Extracapsular Cataract Extraction at KCMC Hospital","authors":"Suzo Ambindwile Malakibungu, Andrew Makupa, William Makupa","doi":"10.1101/2024.04.04.24305351","DOIUrl":"https://doi.org/10.1101/2024.04.04.24305351","url":null,"abstract":"<strong>Background</strong> Despite the advance of cataract surgery astigmatism still occur after cataract surgery due to several reasons these include the preparation and closure of the surgical wound, the choice of suture material, and both intraoperative and postoperative manipulations in Phacoemulsification and Extracapsular cataract Etraction.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1101/2024.03.24.24304809
William Woof, Thales A.C. de Guimaraes, Saoud Al-Khuzaei, Malena Daich Varela, Sagnik Sen, Pallavi Bagga, Bernardo Souza Mendes, Mital Shah, Paula Burke, David G. Parry, Siying Lin, Gunjan Naik, Alan Sousa da Silva, Biraja Ghoshal, Bart Liefers, Dun Jack Fu, Michalis Georgiou, Yichen Liu, Quang Nguyen, Yu Fujinami-Yokokawa, Nathaniel Kabiri, Dayyanah Sumodhee, Jennifer Furman, Praveen J. Patel, Ismail Moghul, Juliana Sallum, Samantha R. De Silva, Birgit Lorenz, Frank G. Holz, Kaoru Fujinami, Andrew R Webster, Omar A. Mahroo, Susan M. Downes, Savita Madhusudhan, Konstantinos Balaskas, Michel Michaelides, Nikolas Pontikos
Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients. Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset. Main Outcome Measures: Quantitative FAF imaging features including area in mm2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM, ABCC6, ABCA4, RDH12, and RPE65, with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm2. The five genes with the largest hyper-AF areas were BEST1, CDH23, RDH12, MYO7A, and NR2E3, with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm2 respectively. The five genes with largest ring areas were CDH23, NR2E3, CRX, EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm2. Vessel density was found to be highest in EFEMP1, BEST1, TIMP3, RS1, and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes (RPGR, USH2A, RHO, EYS) found EYS to be the fastest progressor at -0.18 mm2/year. Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.
{"title":"Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3000 Inherited Retinal Disease Patients from the United Kingdom","authors":"William Woof, Thales A.C. de Guimaraes, Saoud Al-Khuzaei, Malena Daich Varela, Sagnik Sen, Pallavi Bagga, Bernardo Souza Mendes, Mital Shah, Paula Burke, David G. Parry, Siying Lin, Gunjan Naik, Alan Sousa da Silva, Biraja Ghoshal, Bart Liefers, Dun Jack Fu, Michalis Georgiou, Yichen Liu, Quang Nguyen, Yu Fujinami-Yokokawa, Nathaniel Kabiri, Dayyanah Sumodhee, Jennifer Furman, Praveen J. Patel, Ismail Moghul, Juliana Sallum, Samantha R. De Silva, Birgit Lorenz, Frank G. Holz, Kaoru Fujinami, Andrew R Webster, Omar A. Mahroo, Susan M. Downes, Savita Madhusudhan, Konstantinos Balaskas, Michel Michaelides, Nikolas Pontikos","doi":"10.1101/2024.03.24.24304809","DOIUrl":"https://doi.org/10.1101/2024.03.24.24304809","url":null,"abstract":"Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients.\u0000Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients.\u0000Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019.\u0000Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset.\u0000Main Outcome Measures: Quantitative FAF imaging features including area in mm2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM, ABCC6, ABCA4, RDH12, and RPE65, with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm2. The five genes with the largest hyper-AF areas were BEST1, CDH23, RDH12, MYO7A, and NR2E3, with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm2 respectively. The five genes with largest ring areas were CDH23, NR2E3, CRX, EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm2. Vessel density was found to be highest in EFEMP1, BEST1, TIMP3, RS1, and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes (RPGR, USH2A, RHO, EYS) found EYS to be the fastest progressor at -0.18 mm2/year.\u0000Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140323168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1101/2024.03.27.24304979
Maria Constanza Tripolone, Luis Alberto Issolio, Daniel Perez, Pablo Alejandro Barrionuevo
Purpose To assess contrast sensitivity (CS) for detecting visual changes in suspected POAG patients. Methods CS was measured foveally at photopic conditions and peripherally at mesopic conditions using sinusoidal gratings of 4 cycles/degree. In experiment 1, foveal and peripheral CS were assessed in suspected POAG patients and age-matched healthy control subjects. In experiment 2, foveal CS was assessed in early POAG patients age-matched with suspected POAG group. Analysis was done considering two age ranges (Under and Over 50 years of age). Correlations between CS and clinical parameters were evaluated. Results Peripheral CS was decreased only for older POAG suspect patients from the control group (Over 50: p = 0.008. Under 50: p = 0.566). Foveal CS was reduced in POAG suspect participants for both age ranges (Over 50: p = 0.028. Under 50: p < 0.001) and in early POAG patients (Under 50: p = 0.001; Over 50: p < 0.001), both compared to the control group. Foveal CS was lower in early POAG compared to POAG suspect for older patients (Over 50: p = 0.019. Under 50: p = 0.824). Foveal CS was correlated with cup-disc ratio in early POAG patients (Early: p < 0.001. Suspect: p = 0.766) and with age in both patient groups (Early: p = 0.001. Suspect: p = 0.002). Conclusion CS is affected in patients with a high risk of developing POAG and recently diagnosed. Our results suggest that CS could serve as a screening tool, detecting early damage even before structural changes occur.
{"title":"CONTRAST SENSITIVITY IS IMPAIRED IN SUSPECTED PRIMARY OPEN-ANGLE GLAUCOMA PATIENTS","authors":"Maria Constanza Tripolone, Luis Alberto Issolio, Daniel Perez, Pablo Alejandro Barrionuevo","doi":"10.1101/2024.03.27.24304979","DOIUrl":"https://doi.org/10.1101/2024.03.27.24304979","url":null,"abstract":"Purpose\u0000To assess contrast sensitivity (CS) for detecting visual changes in suspected POAG patients.\u0000Methods\u0000CS was measured foveally at photopic conditions and peripherally at mesopic conditions using sinusoidal gratings of 4 cycles/degree. In experiment 1, foveal and peripheral CS were assessed in suspected POAG patients and age-matched healthy control subjects. In experiment 2, foveal CS was assessed in early POAG patients age-matched with suspected POAG group. Analysis was done considering two age ranges (Under and Over 50 years of age). Correlations between CS and clinical parameters were evaluated. Results\u0000Peripheral CS was decreased only for older POAG suspect patients from the control group (Over 50: p = 0.008. Under 50: p = 0.566). Foveal CS was reduced in POAG suspect participants for both age ranges (Over 50: p = 0.028. Under 50: p < 0.001) and in early POAG patients (Under 50: p = 0.001; Over 50: p < 0.001), both compared to the control group. Foveal CS was lower in early POAG compared to POAG suspect for older patients (Over 50: p = 0.019. Under 50: p = 0.824). Foveal CS was correlated with cup-disc ratio in early POAG patients (Early: p < 0.001. Suspect: p = 0.766) and with age in both patient groups (Early: p = 0.001. Suspect: p = 0.002).\u0000Conclusion\u0000CS is affected in patients with a high risk of developing POAG and recently diagnosed. Our results suggest that CS could serve as a screening tool, detecting early damage even before structural changes occur.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140323165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-27DOI: 10.1101/2024.03.25.24304828
Li Yen Goh, Oscar Hou In Chou, Sharen Lee, Teddy Tai Loy Lee, Jeremy Man To Hui, Hugo Pui Hok Him, Wing Tak Wong, Carlin Chang, Bernard M.Y. Cheung, Gary Tse, Jiandong Zhou
Background/Aims: Type 2 diabetes mellitus (T2DM) is an extremely prevalent disease with multisystem complications. We aim to compare the effects of two common glucose lowering medications; sodium glucose co-transporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I), on the incidence of diabetic retinopathy and cataracts in T2DM patients in Hong Kong. Methods: Retrospective population-based cohort study of T2DM patients treated with SGLT2I or DPP4I between 1st January 2015 and 31st December 2020. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed on demographics, past co-morbidities, number of prior hospitalizations, duration from T2DM diagnosis to intial drug exposure, non-SGLT2I/DPP4I medications (including other anti-diabetes drugs), abbreviated modification of diet in renal disease, HbA1c, fasting glucose, and their time-weighted means. Sensitivity analysis using a one-year lag time and competing risk analyses using cause-specific and sub-distribution hazard models were conducted. Results: This study cohort included 26 165 SGLT2I and 42 796 DPP4I users (total: N=68 961 patients; 56.43% males, median age: 62.0 years old (standard deviation (SD): 12.8)). Over a median follow-up of 5.56 years (IQR: 5.24-5.80) and after propensity score matching (SGLT2I: N=26 165; DPP4I: N=26 165), SGLT2I users had lower incidences of cataract (4.54% vs. 6.64%%, standardised mean difference [SMD]=0.09) and diabetic retinopathy (3.65 vs. 6.19, SMD=0.12) compared to DPP4I users. SGLT2I use was associated with lower risks of new onset cataract (HR: 0.67, 95% CI: [0.62-0.72] P<0.0001) and diabetic retinopathy (hazard ratio [HR]: 0.57, 95% confidence interval [CI]: [0.53-0.62], P<0.0001). These associations remained significant on multivariable Cox regression ;cataract: HR: 0.69, 95% CI: 0.64-0.75 (P<0.0001); diabetic retinopathy: HR: 0.68, 95% CI: 0.63-0.75 (P<0.0001). Conclusions: Amongst T2DM patients in Hong Kong, SGLT2I use was associated with lower risks of new onset cataract or diabetic retinopathy compared to DPP4I use.
{"title":"Lower Risk of Incident Cataracts and Diabetic Retinopathy amongst Individuals Treated with Sodium Glucose Cotransporter-2 Inhibitor Compared to Dipeptidyl Peptidase-4 Inhibitor in Type 2 Diabetes Mellitus","authors":"Li Yen Goh, Oscar Hou In Chou, Sharen Lee, Teddy Tai Loy Lee, Jeremy Man To Hui, Hugo Pui Hok Him, Wing Tak Wong, Carlin Chang, Bernard M.Y. Cheung, Gary Tse, Jiandong Zhou","doi":"10.1101/2024.03.25.24304828","DOIUrl":"https://doi.org/10.1101/2024.03.25.24304828","url":null,"abstract":"Background/Aims: Type 2 diabetes mellitus (T2DM) is an extremely prevalent disease with multisystem complications. We aim to compare the effects of two common glucose lowering medications; sodium glucose co-transporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I), on the incidence of diabetic retinopathy and cataracts in T2DM patients in Hong Kong.\u0000Methods: Retrospective population-based cohort study of T2DM patients treated with SGLT2I or DPP4I between 1st January 2015 and 31st December 2020. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed on demographics, past co-morbidities, number of prior hospitalizations, duration from T2DM diagnosis to intial drug exposure, non-SGLT2I/DPP4I medications (including other anti-diabetes drugs), abbreviated modification of diet in renal disease, HbA1c, fasting glucose, and their time-weighted means. Sensitivity analysis using a one-year lag time and competing risk analyses using cause-specific and sub-distribution hazard models were conducted.\u0000Results: This study cohort included 26 165 SGLT2I and 42 796 DPP4I users (total: N=68 961 patients; 56.43% males, median age: 62.0 years old (standard deviation (SD): 12.8)). Over a median follow-up of 5.56 years (IQR: 5.24-5.80) and after propensity score matching (SGLT2I: N=26 165; DPP4I: N=26 165), SGLT2I users had lower incidences of cataract (4.54% vs. 6.64%%, standardised mean difference [SMD]=0.09) and diabetic retinopathy (3.65 vs. 6.19, SMD=0.12) compared to DPP4I users. SGLT2I use was associated with lower risks of new onset cataract (HR: 0.67, 95% CI: [0.62-0.72] P<0.0001) and diabetic retinopathy (hazard ratio [HR]: 0.57, 95% confidence interval [CI]: [0.53-0.62], P<0.0001). These associations remained significant on multivariable Cox regression ;cataract: HR: 0.69, 95% CI: 0.64-0.75 (P<0.0001); diabetic retinopathy: HR: 0.68, 95% CI: 0.63-0.75 (P<0.0001).\u0000Conclusions: Amongst T2DM patients in Hong Kong, SGLT2I use was associated with lower risks of new onset cataract or diabetic retinopathy compared to DPP4I use.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140315346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26DOI: 10.1101/2024.03.22.24304594
Julie A. Jurgens, Brenda J. Barry, Wai-Man Chan, Sarah MacKinnon, Mary C. Whitman, Paola M. Matos Ruiz, Brandon M. Pratt, Eleina M. England, Lynn Pais, Gabrielle Lemire, Emily Groopman, Carmen Glaze, Kathryn A. Russell, Moriel Singer-Berk, Silvio Alessandro Di Gioia, Arthur S. Lee, Caroline Andrews, Sherin Shaaban, Megan M. Wirth, Sarah Bekele, Melissa Toffoloni, Victoria R. Bradford, Emma E. Foster, Lindsay Berube, Cristina Rivera-Quiles, Fiona M. Mensching, Alba Sanchis-Juan, Jack M. Fu, Isaac Wong, Xuefang Zhao, Michael W. Wilson, Ben Weisburd, Monkol Lek, Ocular CCDD Phenotyping Consortium, Harrison Brand, Michael E. Talkowski, Daniel G. MacArthur, Anne O'Donnell-Luria, Caroline D. Robson, David G. Hunter, Elizabeth C. Engle
Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). Methods: We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations. Results: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses. Conclusion: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.
{"title":"Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders","authors":"Julie A. Jurgens, Brenda J. Barry, Wai-Man Chan, Sarah MacKinnon, Mary C. Whitman, Paola M. Matos Ruiz, Brandon M. Pratt, Eleina M. England, Lynn Pais, Gabrielle Lemire, Emily Groopman, Carmen Glaze, Kathryn A. Russell, Moriel Singer-Berk, Silvio Alessandro Di Gioia, Arthur S. Lee, Caroline Andrews, Sherin Shaaban, Megan M. Wirth, Sarah Bekele, Melissa Toffoloni, Victoria R. Bradford, Emma E. Foster, Lindsay Berube, Cristina Rivera-Quiles, Fiona M. Mensching, Alba Sanchis-Juan, Jack M. Fu, Isaac Wong, Xuefang Zhao, Michael W. Wilson, Ben Weisburd, Monkol Lek, Ocular CCDD Phenotyping Consortium, Harrison Brand, Michael E. Talkowski, Daniel G. MacArthur, Anne O'Donnell-Luria, Caroline D. Robson, David G. Hunter, Elizabeth C. Engle","doi":"10.1101/2024.03.22.24304594","DOIUrl":"https://doi.org/10.1101/2024.03.22.24304594","url":null,"abstract":"<strong>Purpose:</strong> To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). <strong>Methods:</strong> We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations.\u0000<strong>Results:</strong>\u0000Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., <em>MYH10</em>, <em>KIF21B</em>, <em>TGFBR2</em>, <em>TUBB6</em>), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., <em>CDK13</em>, <em>TGFB2</em>), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., <em>TUBA4A</em>, <em>KIF5C</em>, <em>CTNNA1</em>, <em>KLB</em>, <em>FGF21</em>), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses.\u0000<strong>Conclusion:</strong> This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.","PeriodicalId":501390,"journal":{"name":"medRxiv - Ophthalmology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140303102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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