Correlation of Color Fundus Photograph Grading with Risks of Early Age-related Macular Degeneration by using Automated OCT-derived Drusen Measurements

We evaluated automated OCT-derived drusen volume measures in a population-based study (n = 4,512) aged ≥40 years, and its correlation with conventional color fundus photographs (CFP)-derived early AMD features. Participants had protocol-based assessment to capture medical and ocular history, genotyping for SNPs in CFH, ARMS2, and CETP, CFP-based AMD grading and automated drusen volume based on SD-OCT using built-in software (Cirrus OCT advanced RPE analysis software). Significantly fewer eyes with early AMD features (drusen, hyperpigmentation, soft or reticular drusen) had drusen volume = 0 mm3 (p < 0.001). In eyes with drusen volume > 0 mm3, increasing AMD severity was associated with increase in drusen volume (correlation coefficient 0.17, p < 0.001). However 220 (59.14%) of 372 participants with AMD based on CFP grading had drusen volume = 0 mm3. Factors associated with drusen volume included age (OR 1.42 per 5 years, 95% confidence interval [CI] 2.76, 4.48), systolic blood pressure (OR1.00, 95% CI 1.00, 1.01), ethnic Malay (OR 1.54, 95% CI 1.29, 1.83) and Chinese (OR 1.66, 95% CI 1.37, 2.01) compared to Indian. The ARMS2 rs10490924 T allele was associated with increased drusen volume in subjects with AMD (multivariable adjusted OR1.54, 95% CI 1.08, 2.19). Automated OCT-derived drusen volume is correlated with CFP-based AMD grading in many, but not all subjects. However the agreement is not good. These two modalities provide complementary information and should be incorporated into future studies.

[1]  T. Wong,et al.  Singapore Indian Eye Study‐2: methodology and impact of migration on systemic and eye outcomes , 2017, Clinical & experimental ophthalmology.

[2]  C. Cheung,et al.  Clinical Relevance and Application of the Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration. , 2016, JAMA ophthalmology.

[3]  R. Klein,et al.  Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. , 2014, The Lancet. Global health.

[4]  Sina Farsiu,et al.  Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration. , 2016, Ophthalmology.

[5]  M. Daly,et al.  Association of variants in the LIPC and ABCA1 genes with intermediate and large drusen and advanced age-related macular degeneration. , 2011, Investigative ophthalmology & visual science.

[6]  Jost B Jonas,et al.  Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations. , 2012, Human molecular genetics.

[7]  S Claiborne Johnston,et al.  Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling , 2009, The Lancet Neurology.

[8]  E. Agrón,et al.  Evaluating the Validity of the Age-Related Eye Disease Study Grading Scale for Age-Related Macular Degeneration: AREDS2 Report 10. , 2016, JAMA ophthalmology.

[9]  Srinivas R Sadda,et al.  Accuracy and reproducibility of automated drusen segmentation in eyes with non-neovascular age-related macular degeneration. , 2012, Investigative ophthalmology & visual science.

[10]  Justine R. Smith,et al.  Retinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye , 2017, Translational vision science & technology.

[11]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[12]  R. Klein,et al.  The Wisconsin age-related maculopathy grading system. , 1991, Ophthalmology.

[13]  Alan Agresti,et al.  Tutorial in Biostatistics A review of tests for detecting a monotone dose–response relationship with ordinal response data , 1997 .

[14]  W. Cumberland,et al.  A Wilcoxon-type test for trend. , 1995, Statistics in medicine.

[15]  Jiayan Huang,et al.  Association of OCT-Derived Drusen Measurements with AMD-Associated Genotypic SNPs in the Amish Population , 2015, Journal of clinical medicine.

[16]  Sina Farsiu,et al.  Quantitative comparison of drusen segmented on SD-OCT versus drusen delineated on color fundus photographs. , 2010, Investigative ophthalmology & visual science.

[17]  M. Szklo,et al.  The Multi-Ethnic Study of Atherosclerosis (MESA) , 2012 .

[18]  P. Armitage Tests for Linear Trends in Proportions and Frequencies , 1955 .

[19]  Paul Mitchell,et al.  Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study. , 2002, Ophthalmology.

[20]  Jennifer I. Lim,et al.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. , 2001, Archives of ophthalmology.

[21]  R. Klein,et al.  Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis. , 2016, Ophthalmology.

[22]  J. J. Wang,et al.  Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. , 1995, Ophthalmology.

[23]  Dean P. Jones,et al.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. , 2001, Archives of ophthalmology.

[24]  Grading Diabetic Retinopathy from Stereoscopic Color Fundus Photographs - An Extension of the Modified Airlie House Classification: ETDRS Report Number 10. , 2020, Ophthalmology.

[25]  J. Brody,et al.  FACTORS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AN ANALYSIS OF DATA FROM THE FI1R8T NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY , 1988 .

[26]  B. Lujan,et al.  Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration. , 2011, Ophthalmology.

[27]  A Agresti,et al.  A review of tests for detecting a monotone dose-response relationship with ordinal response data. , 1997, Statistics in medicine.

[28]  Sina Farsiu,et al.  Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images. , 2012, Investigative ophthalmology & visual science.

[29]  P. Mitchell,et al.  Singapore Malay Eye Study: rationale and methodology of 6‐year follow‐up study (SiMES‐2) , 2012, Clinical & experimental ophthalmology.

[30]  Y. Teo,et al.  Aggregate Effects of Intraocular Pressure and Cup-to-Disc Ratio Genetic Variants on Glaucoma in a Multiethnic Asian Population. , 2015, Ophthalmology.

[31]  P. Mitchell,et al.  Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians. , 2014, Investigative ophthalmology & visual science.

[32]  P. Mitchell,et al.  Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The Singapore Malay Eye Study. , 2017, Ophthalmology.

[33]  U. Schmidt-Erfurth,et al.  A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration , 2017, Eye.

[34]  Qiang Chen,et al.  Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images , 2017, Translational vision science & technology.

[35]  D. Rodger,et al.  Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population , 2015, Eye.

[36]  P. Mitchell,et al.  Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays. , 2014, Ophthalmology.

[37]  Qiang Chen,et al.  Automated drusen segmentation and quantification in SD-OCT images , 2013, Medical Image Anal..

[38]  W. Freeman,et al.  OPTICAL COHERENCE TOMOGRAPHY-RASTER SCANNING AND MANUAL SEGMENTATION IN DETERMINING DRUSEN VOLUME IN AGE-RELATED MACULAR DEGENERATION , 2010, Retina.

[39]  William J Feuer,et al.  Comparison of drusen area detected by spectral domain optical coherence tomography and color fundus imaging. , 2013, Investigative ophthalmology & visual science.

[40]  P. Mitchell,et al.  Validating the AREDS Simplified Severity Scale of Age-Related Macular Degeneration with 5- and 10-Year Incident Data in a Population-Based Sample. , 2016, Ophthalmology.