There is compelling evidence that glaucomatous damage to the macula occurs even in early stages of the disease. The macula comprises about 30% of all retinal ganglion cells and its information corresponds to over 50% of the visual cortex. However, glaucomatous damage to the macula is often missed in clinical practice. Some of the reasons are: 1) traditional glaucoma knowledge supports that glaucoma is fundamentally a peripheral disease; 2) inherent limitations of conventional clinical tests to detect damage to the macula; and 3) the paucity of large, prospective studies that describe the nature of glaucomatous damage to the macula. Our group has published numerous papers in the past two years showing that macular damage is prevalent among patients with early glaucoma if one employs the appropriate tools to assess it, namely 10-2 visual fields and high-resolution optical coherence tomography (OCT). This information comes from a unique prospective cross- sectional database and techniques we developed to produce objective metrics of structure and function. Now that we understand the cross-sectional nature of macular damage, this proposal aims to: 1) develop a longitudinal database including patients with early glaucoma and healthy controls, 2) to test models that explain progression of macular damage, and 3) to apply new statistical methods combining structural and functional tests which could improve the accuracy to detect progression and shorten the length of clinical trials. Our main hypothesis is that incorporating 10-2 visual field testing and high-resolution OCT scans of the macula to the conventional repertoire of technologies used in clinical practice, in addition to translating recently described statistical methods into softwares that can be used in daily practice, enhances the performance and confidence to detect glaucoma progression.
In Aim 1 we plan to follow healthy subjects and glaucoma patients at regular intervals with 10-2, 24-2 visual fields, and swept source (ss) OCT tests and define metrics of short- and long-term test variability that are needed to differentiate true progression from 'noise'. To date, there is no such database combining these technologies.
In Aim 2 we plan to combine metrics of structure and function from this longitudinal database using two methods: a spatial approach, which will ultimately produce a joint structure-function index using 10-2 and ssOCT data; and a temporal approach, which will employ Bayesian statistics to measure rates of progression using trend analysis. By the end of the study, our contributions to the field should be: 1) to make available a unique and pristine longitudinal database that could be used for other hypotheses testing, 2) to translate techniques recently described in the literature into objective tools to be readily useful in clinicl practice, and 3) to mitigate the burdens of progressive loss of central vision in glaucoma.

Public Health Relevance

Structural and Functional Progression of Glaucomatous Damage to the Macula Glaucomatous damage to the macula is very prevalent and is often missed using conventional clinical tests. Given the high density of retinal ganglion cells in the macula and their overwhelming representation in the visual cortex, damage to the macula substantially affects health-related quality of life. While there has been a lot of research on glaucoma progression, relatively little is known about progression of early glaucoma damage. This project investigates the nature of progressive damage to the macula and proposes new methods to improve accuracy to detect clinically significant progression.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY025253-01
Application #
8859854
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Chin, Hemin R
Project Start
2015-05-01
Project End
2018-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Liebmann, Kevin; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M (2017) Measuring Rates of Visual Field Progression in Linear Versus Nonlinear Scales: Implications for Understanding the Relationship Between Baseline Damage and Target Rates of Glaucoma Progression. J Glaucoma 26:721-725
De Moraes, C Gustavo; Hood, Donald C; Thenappan, Abinaya et al. (2017) 24-2 Visual Fields Miss Central Defects Shown on 10-2 Tests in Glaucoma Suspects, Ocular Hypertensives, and Early Glaucoma. Ophthalmology 124:1449-1456
Alhadeff, Paula A; De Moraes, Carlos G; Chen, Monica et al. (2017) The Association Between Clinical Features Seen on Fundus Photographs and Glaucomatous Damage Detected on Visual Fields and Optical Coherence Tomography Scans. J Glaucoma 26:498-504
De Moraes, C Gustavo; Liebmann, Jeffrey M; Levin, Leonard A (2017) Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma. Prog Retin Eye Res 56:107-147
Thenappan, Abinaya; De Moraes, Carlos Gustavo; Wang, Diane L et al. (2017) Optical Coherence Tomography and Glaucoma Progression: A Comparison of a Region of Interest Approach to Average Retinal Nerve Fiber Layer Thickness. J Glaucoma 26:473-477
Hood, Donald C; De Cuir, Nicole; Blumberg, Dana M et al. (2016) A Single Wide-Field OCT Protocol Can Provide Compelling Information for the Diagnosis of Early Glaucoma. Transl Vis Sci Technol 5:4