Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy

Sarega Gurudas; Karen Frudd; Jayapal Jeya Maheshwari; Yeddula Rebecca Revathy; Sobha Sivaprasad; Shruthi Mahalakshmi Ramanathan; Vignesh Pooleeswaran; A. Toby Prevost; Eleni Karatsai; Sandra Halim; Shruti Chandra; Paul Nderitu; Dolores Conroy; Subramanian Krishnakumar; Sowmya Parameswaran; Kuppamuthu Dharmalingam; Kim Ramasamy; Rajiv Raman; Colin Jones; Haralabos Eleftheriadis; John Greenwood; Patric Turowski

doi:10.1001/jamaophthalmol.2022.1175

Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy

Sarega Gurudas, Karen Frudd, Jayapal Jeya Maheshwari, Yeddula Rebecca Revathy, Sobha Sivaprasad^*, Shruthi Mahalakshmi Ramanathan, Vignesh Pooleeswaran, A. Toby Prevost, Eleni Karatsai, Sandra Halim, Shruti Chandra, Paul Nderitu, Dolores Conroy, Subramanian Krishnakumar, Sowmya Parameswaran, Kuppamuthu Dharmalingam, Kim Ramasamy, Rajiv Raman, Colin Jones, Haralabos EleftheriadisJohn Greenwood, Patric Turowski

^*Corresponding author for this work

Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.

Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.

Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A_1c.

Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A_1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data).

Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

Funding Information:

reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. Dr Sivaprasad reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund and personal fees from Bayer, Novartis, Oxurion, Apellis, Allergan, Roche, and Boehringer Ingelheim outside the submitted work. Dr Prevost reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund through the medical research council during the conduct of the study and personal fees from Roche for being the statistical member of an independent data monitoring committee outside the submitted work. Dr Eleftheriadis reported receiving grants from Bayer and Novartis to attend ophthalmology conferences outside the submitted work. Dr Turowski reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. No other disclosures were reported.

Publisher Copyright:

Original language	English
Pages (from-to)	587-597
Number of pages	11
Journal	JAMA Ophthalmology
Volume	140
Issue number	6
Early online date	22 Mar 2022
DOIs	https://doi.org/10.1001/jamaophthalmol.2022.1175
Publication status	Published - Jun 2022

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Gurudas, S., Frudd, K., Maheshwari, J. J., Revathy, Y. R., Sivaprasad, S., Ramanathan, S. M., Pooleeswaran, V., Prevost, A. T., Karatsai, E., Halim, S., Chandra, S., Nderitu, P., Conroy, D., Krishnakumar, S., Parameswaran, S., Dharmalingam, K., Ramasamy, K., Raman, R., Jones, C., ... Turowski, P. (2022). Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy. JAMA Ophthalmology, 140(6), 587-597. https://doi.org/10.1001/jamaophthalmol.2022.1175

@article{c20c44c23898488a9fef9367a95dae8c,

title = "Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy",

abstract = "Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c.Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.Funding Information:reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. Dr Sivaprasad reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund and personal fees from Bayer, Novartis, Oxurion, Apellis, Allergan, Roche, and Boehringer Ingelheim outside the submitted work. Dr Prevost reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund through the medical research council during the conduct of the study and personal fees from Roche for being the statistical member of an independent data monitoring committee outside the submitted work. Dr Eleftheriadis reported receiving grants from Bayer and Novartis to attend ophthalmology conferences outside the submitted work. Dr Turowski reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. No other disclosures were reported.Publisher Copyright:{\textcopyright} 2022 American Medical Association. All rights reserved.",

author = "Sarega Gurudas and Karen Frudd and Maheshwari, {Jayapal Jeya} and Revathy, {Yeddula Rebecca} and Sobha Sivaprasad and Ramanathan, {Shruthi Mahalakshmi} and Vignesh Pooleeswaran and Prevost, {A. Toby} and Eleni Karatsai and Sandra Halim and Shruti Chandra and Paul Nderitu and Dolores Conroy and Subramanian Krishnakumar and Sowmya Parameswaran and Kuppamuthu Dharmalingam and Kim Ramasamy and Rajiv Raman and Colin Jones and Haralabos Eleftheriadis and John Greenwood and Patric Turowski",

note = "The article was accepted on 15th March 2022 - From: [email protected] Date: 16 March 2022 at 04:10:23 GMT+5:30 To: [email protected] Subject: OPH21-2867R Decision Letter Reply-To: [email protected] March 15, 2022 Prof Sobha Sivaprasad NIHR Moorfields Biomedical Research Centre Morfields Eye Hospital London United Kingdom RE: Manuscript #OPH21-2867R, Multicenter validation of diagnostic circulating biomarkers to detect sight threatening diabetic retinopathy Dear Prof Sivaprasad: We are pleased to accept your manuscript for publication in JAMA Ophthalmology pending receipt of all authorship forms. Thank you for the prompt and thoughtful revision. Your manuscript is accepted with the understanding that it represents new information, it is not under simultaneous consideration by another publication, and its message has not been published previously in any language. Please remember that you should not disclose the fact that your manuscript has been accepted to anyone, except coauthors and contributors and as noted below, without permission of the editor. Any information you may receive about the proposed publication date of your article is tentative and should be kept confidential. Shortly before publication, the publication date can be confirmed by contacting the manuscript editor or the journal office. Prepublication distribution of the accepted manuscript in hard copy or electronic format without permission is prohibited. Do not use social media to post information or {"}tweet{"} about your article before publication. Many authors work with their institution{\textquoteright}s media relations department to send out press releases about their publications. However, please note that the news media should not release any information about your article until 10 AM Central Time on the day of its publication. There is a strict embargo until then. If you or your media relations department needs help in coordinating press conferences or releases, please contact the JAMA Network Media Relations Department at [email protected] or 312-464-JAMA (312-464-5262). First and last authors (ie, those listed first and last in the article byline) may claim 10 CME credits (AMA PRA Category 1 Credit) after publication of articles in JAMA Network Journals. First and last authors will receive a subsequent email from the CME provider after the article is published with instructions about claiming CME credits. An edited version of your manuscript will be sent to you for final approval. It is likely that you will also receive questions about the text, tables, or figures. Your manuscript is accepted, therefore, with the understanding that it may later be necessary to consider some changes in text or ancillary material. NOTE: Please verify and confirm that all conflict of interest disclosure information for you and all coauthors is accurate, complete, and up-to-date and is reported in the Disclosures section at the end of the manuscript in a manner consistent with that reported in each author's completed Authorship Form. JAMA Ophthalmology's policy requires that all authors disclose any potential conflicts of interest involving the work under consideration for publication (during the time involving the work, from initial conception and planning to present); any relevant financial activities outside the submitted work (during the 3 years prior to submission); and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what is written in the submitted work (based on all relationships that were present during the 3 years prior to submission). Potential conflicts of interest include but are not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers' bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. For example, authors of a manuscript about hypertension should report all financial relationships they have with all manufacturers of products used in the management of hypertension, not only those relationships with companies whose specific products are mentioned in the manuscript. Authors without potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations, should indicate no such interests. Please contact me immediately if you have any questions about this policy. The JAMA Ophthalmology ranks among the top clinical ophthalmology journals for impact factor. Your article will reach close to 14,000 subscribers around the globe. As you know, considerable time and effort went into the review of your manuscript. We hope you will in turn be willing to assist us as a peer reviewer for other manuscripts submitted to the JAMA Ophthalmology in the future. Thank you for selecting the JAMA Ophthalmology to publish your work. We look forward to reviewing your future submissions. Sincerely, Neil M. Bressler, MD Editor in Chief JAMA Ophthalmology Confidentiality Note: This communication, including any attachments, is solely for the use of the addressee, may contain privileged, confidential or proprietary information, and may not be redistributed in any way without the sender's consent. Thank you. ",

year = "2022",

month = jun,

doi = "10.1001/jamaophthalmol.2022.1175",

language = "English",

volume = "140",

pages = "587--597",

journal = "JAMA Ophthalmology",

issn = "2168-6165",

number = "6",

}

Gurudas, S, Frudd, K, Maheshwari, JJ, Revathy, YR, Sivaprasad, S, Ramanathan, SM, Pooleeswaran, V, Prevost, AT, Karatsai, E, Halim, S, Chandra, S, Nderitu, P, Conroy, D, Krishnakumar, S, Parameswaran, S, Dharmalingam, K, Ramasamy, K, Raman, R, Jones, C, Eleftheriadis, H, Greenwood, J & Turowski, P 2022, 'Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy', JAMA Ophthalmology, vol. 140, no. 6, pp. 587-597. https://doi.org/10.1001/jamaophthalmol.2022.1175

TY - JOUR

T1 - Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy

AU - Gurudas, Sarega

AU - Frudd, Karen

AU - Maheshwari, Jayapal Jeya

AU - Revathy, Yeddula Rebecca

AU - Sivaprasad, Sobha

AU - Ramanathan, Shruthi Mahalakshmi

AU - Pooleeswaran, Vignesh

AU - Prevost, A. Toby

AU - Karatsai, Eleni

AU - Halim, Sandra

AU - Chandra, Shruti

AU - Nderitu, Paul

AU - Conroy, Dolores

AU - Krishnakumar, Subramanian

AU - Parameswaran, Sowmya

AU - Dharmalingam, Kuppamuthu

AU - Ramasamy, Kim

AU - Raman, Rajiv

AU - Jones, Colin

AU - Eleftheriadis, Haralabos

AU - Greenwood, John

AU - Turowski, Patric

N1 - The article was accepted on 15th March 2022 - From: [email protected] Date: 16 March 2022 at 04:10:23 GMT+5:30 To: [email protected] Subject: OPH21-2867R Decision Letter Reply-To: [email protected] March 15, 2022 Prof Sobha Sivaprasad NIHR Moorfields Biomedical Research Centre Morfields Eye Hospital London United Kingdom RE: Manuscript #OPH21-2867R, Multicenter validation of diagnostic circulating biomarkers to detect sight threatening diabetic retinopathy Dear Prof Sivaprasad: We are pleased to accept your manuscript for publication in JAMA Ophthalmology pending receipt of all authorship forms. Thank you for the prompt and thoughtful revision. Your manuscript is accepted with the understanding that it represents new information, it is not under simultaneous consideration by another publication, and its message has not been published previously in any language. Please remember that you should not disclose the fact that your manuscript has been accepted to anyone, except coauthors and contributors and as noted below, without permission of the editor. Any information you may receive about the proposed publication date of your article is tentative and should be kept confidential. Shortly before publication, the publication date can be confirmed by contacting the manuscript editor or the journal office. Prepublication distribution of the accepted manuscript in hard copy or electronic format without permission is prohibited. Do not use social media to post information or "tweet" about your article before publication. Many authors work with their institution’s media relations department to send out press releases about their publications. However, please note that the news media should not release any information about your article until 10 AM Central Time on the day of its publication. There is a strict embargo until then. If you or your media relations department needs help in coordinating press conferences or releases, please contact the JAMA Network Media Relations Department at [email protected] or 312-464-JAMA (312-464-5262). First and last authors (ie, those listed first and last in the article byline) may claim 10 CME credits (AMA PRA Category 1 Credit) after publication of articles in JAMA Network Journals. First and last authors will receive a subsequent email from the CME provider after the article is published with instructions about claiming CME credits. An edited version of your manuscript will be sent to you for final approval. It is likely that you will also receive questions about the text, tables, or figures. Your manuscript is accepted, therefore, with the understanding that it may later be necessary to consider some changes in text or ancillary material. NOTE: Please verify and confirm that all conflict of interest disclosure information for you and all coauthors is accurate, complete, and up-to-date and is reported in the Disclosures section at the end of the manuscript in a manner consistent with that reported in each author's completed Authorship Form. JAMA Ophthalmology's policy requires that all authors disclose any potential conflicts of interest involving the work under consideration for publication (during the time involving the work, from initial conception and planning to present); any relevant financial activities outside the submitted work (during the 3 years prior to submission); and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what is written in the submitted work (based on all relationships that were present during the 3 years prior to submission). Potential conflicts of interest include but are not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers' bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. For example, authors of a manuscript about hypertension should report all financial relationships they have with all manufacturers of products used in the management of hypertension, not only those relationships with companies whose specific products are mentioned in the manuscript. Authors without potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations, should indicate no such interests. Please contact me immediately if you have any questions about this policy. The JAMA Ophthalmology ranks among the top clinical ophthalmology journals for impact factor. Your article will reach close to 14,000 subscribers around the globe. As you know, considerable time and effort went into the review of your manuscript. We hope you will in turn be willing to assist us as a peer reviewer for other manuscripts submitted to the JAMA Ophthalmology in the future. Thank you for selecting the JAMA Ophthalmology to publish your work. We look forward to reviewing your future submissions. Sincerely, Neil M. Bressler, MD Editor in Chief JAMA Ophthalmology Confidentiality Note: This communication, including any attachments, is solely for the use of the addressee, may contain privileged, confidential or proprietary information, and may not be redistributed in any way without the sender's consent. Thank you.

PY - 2022/6

Y1 - 2022/6

N2 - Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c.Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.Funding Information:reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. Dr Sivaprasad reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund and personal fees from Bayer, Novartis, Oxurion, Apellis, Allergan, Roche, and Boehringer Ingelheim outside the submitted work. Dr Prevost reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund through the medical research council during the conduct of the study and personal fees from Roche for being the statistical member of an independent data monitoring committee outside the submitted work. Dr Eleftheriadis reported receiving grants from Bayer and Novartis to attend ophthalmology conferences outside the submitted work. Dr Turowski reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. No other disclosures were reported.Publisher Copyright:© 2022 American Medical Association. All rights reserved.

AB - Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c.Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.Funding Information:reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. Dr Sivaprasad reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund and personal fees from Bayer, Novartis, Oxurion, Apellis, Allergan, Roche, and Boehringer Ingelheim outside the submitted work. Dr Prevost reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund through the medical research council during the conduct of the study and personal fees from Roche for being the statistical member of an independent data monitoring committee outside the submitted work. Dr Eleftheriadis reported receiving grants from Bayer and Novartis to attend ophthalmology conferences outside the submitted work. Dr Turowski reported receiving grants from the UK Research and Innovation and Global Challenge Research Fund during the conduct of the study. No other disclosures were reported.Publisher Copyright:© 2022 American Medical Association. All rights reserved.

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DO - 10.1001/jamaophthalmol.2022.1175

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Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy

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