Abstract
Purpose:
To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2.
Methods:
Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69–78, 78–83, and 83–101 years) and AMD outcomes.
Results:
Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity.
Conclusions:
In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity.
Translational Relevance:
The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.
Macular thickness and volume measurements of the central circle (1 mm diameter), inner ring (3 mm diameter), and outer ring (6 mm diameter) were expressed as means ± standard deviation (SD) or least squares mean ± standard error (SE). Age was categorized into tertiles, and a P value for continuous trend over years was computed. AMD outcomes were expressed as a categorical variable, including no AMD, early AMD, intermediate AMD, and late AMD. We investigated the association between mean macular thickness and age tertile, as well as mean macular thickness and AMD outcomes, adjusted for age. Generalized estimating equations were used, which enabled the use of scans from both study eyes of each participant. Empirical standard error estimates were used for generalized estimating equations parameter estimation considering within person correlation. A two-tailed P value < 0.05 was considered significant. We also examined the age-adjusted associations between BCVA and individual layer thickness in the central circle, including sensitivity analyses, excluding participants with cataract and late AMD. Statistical analysis was performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA).
We provide normative macular thickness data for a unique and well-characterized cohort of women, mostly white, aged 69 to 101 years in the CAREDS2 study, an ancillary study of the WHI-OS. The peripheral macula thinned with increasing age, particularly in the GCL, IPL, and ONL of the inner retina. Retinal thickness did not differ between eyes with AMD compared to without AMD in the neural retina (retina without the RPE layer). Greater thickness in the ONL may confer advantages for visual acuity, independent of age and AMD. Additional studies of retinal thickness in relation to vision function could enhance our understanding of the value in retinal thickness measurements in clinical practice.
With the population aging in the United States and a likely increase in the prevalence of age-related diseases, including AMD, our study will help to better understand AMD among older women. In addition, the results of the current analysis can be used in future epidemiological and clinical studies evaluating the associations between the macular thickness and age-related diseases.
The authors are grateful for the time and energy that the CAREDS2 participants devoted to collecting the data which informed this work. The authors also thank Elizabeth Showers, at the University of Wisconsin Photographic Reading Center, for her assistance with project management.
*The Second Carotenoids in Age-Related Eye Disease Study Research Group:
University of Wisconsin – Madison: Julie Mares, Barbara Blodi, Yao Liu, Amitha Domalpally, Corinne Engelman, Ronald Gangnon, Gloria Sarto; Oregon Health Sciences University: Steven Bailey, Erin LeBlanc (Kaiser-Permanente); University of Iowa: Karen Gehrs, Robert Wallace, Jennifer Robinson; Women's Health Initiative: Lesley Tinker; University of Texas: D. Max Snodderly; University of Georgia: Randy Hammond; University at Buffalo: Amy Millen; Tufts University: Elizabeth Johnson; CAREDS 2 Examiners and Clinical Coordinators: Portland, OR: Jennifer Maykoski, Ann Lundquist; Madison, WI: Chris Smith, Kim Wood, Jennie Perry-Raymond; Iowa City, IA: Heather Stockman, Jean Walshire, and Christine Sinkey.
CAREDS2 Coordinating Center Staff at the University of Wisconsin – Madison. Thomas Lawler, Courtney Blomme, Kim Wood, Kristen Hall, Diane Pauk, Esther Mezhibovsky; Scientists: Krista Christensen, and Marine Nalbandyan.
Short list of WHI investigators: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MD) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller.
Clinical Coordinating Center: Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg.
Investigators and Academic Centers: (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.
Supported by National Eye Institute grants EY013018, EY016886 and EY025292, and a supplement to EY025292-01S1 from the Office of Dietary Supplements. This work was also supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. to the UW Madison Department of Ophthalmology and Visual Sciences, and in part by a National Eye Institute Vision Research Core grant (P30 EY016665) to the UW Madison Department of Ophthalmology and Visual Sciences. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 2107-26, 42129-32, and 44221. The project described was supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR002373. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.
Disclosure: T. Etheridge, None; Z. Liu, None; M. Nalbandyan, None; S. Cleland, None; B.A. Blodi, None; J.A. Mares, None; S. Bailey, None; R. Wallace, None; K. Gehrs, None; L.F. Tinker, None; R. Gangnon, None; A. Domalpally, None