3D RNFL Structure and High-Resolution Perimetry For Assessing Glaucomatous Damage (NIH R01 EY024542). Indiana University School of Optometry, Bloomington, Indiana, USA. Principal Investigator: Prof William H Swanson.

Glaucoma is one of the leading causes of preventable blindness, and currently available treatments are not sufficient to halt progression in many patients. While much has been learned about the biology of glaucoma, development of new forms of treatment has been stymied by three barriers: high between-subject variability in ganglion cell number in normal eyes, high within-subject variability for perimetry in patients with glaucoma, and the slow rate of progression of the disease. The proposed research integrates neural modeling and clinical research to develop improved methods for diagnosing glaucoma and for assessing progression towards blindness. The results are intended to improve measures for both clinical trials and ongoing patient care, while at the same time improving basic science understanding of the pathophysiology of glaucoma and providing guidance for biological studies of the disease process. Innovative uses of clinical devices will guide testing with custom systems, and statistical analyses will utilize the synergy between structural and functional measures of glaucomatous damage. High-resolution retinal imaging of retinal nerve fiber layer (RNFL) will be performed on patients with glaucoma using a custom advanced adaptive optics scanning laser ophthalmoscope (AOSLO) as well as custom use of spectral domain optical coherence tomography (SD-OCT). High-resolution perimetry will be performed in corresponding regions of the visual field, using custom stimuli that are resistant to optical artifacts that affect conventional perimetry.

 

Early detection of glaucoma progression using a novel individualized approach (NIH R01 EY025756). University of Alabama at Birmingham, Birmingham, AL, USA. Principal Investigator: Prof Lyne Racette.

 

The long-term goal is to reduce the time needed to detect glaucoma progression. With an individualized model to detect progression that uses structural and functional data jointly, the specific aims are (1) to determine whether individualized approaches to identify glaucoma progression leads to earlier detection of progression compared to methods based on population statistics, (2) to determine which combination of structural and functional parameters identifies glaucoma progression at the earliest point in time, and (3) to determine the shortest period of time needed for our individualized approach to detect glaucoma progression.

 

The Open Perimetry Initiative for the new generation of portable perimeters.

The advent of new technologies and the development of cross-platform software are paving the way for a new wave of portable devices for visual field testing. The transition from traditional projection perimetry to display-based perimetry requires analysis and adaption of conventional perimetry methods and provides an opportunity to revise and improve. The Open Perimetry Initiative aims to expand perimetry knowledge base and make it freely accessible to anybody interested. Expansion of knowledge base is essential to equip clinicians and researchers with the necessary tools to objectively assess different products and solutions for the new generation of portable perimeters.

 

Testing of the far peripheral visual field —obtaining the full view (Veterans Administration, I01 RX-001821-01A1). University of Iowa Health Care, Iowa City, IA, USA. Principal Investigator: Prof Michael Wall.

The goal is to develop precise, accurate, and efficient threshold estimation of the full visual field. We have used the Open Perimetry Initiative to develop custom perimetry tests which are available from github. The specific aims of this proposal are (1) to characterize the location of far peripheral visual field defects of optic neuropathies to static stimuli, (2) to develop a Bayesian strategy to test the full visual field in less than 10 minutes per eye, (3) to validate the full visual field testing with the new Bayesian strategy perimetry test, and (4) to determine whether the correlation between retinal nerve fiber layer structure from Optical Coherence Tomography and perimetric results with the full visual field is greater than using only the central visual field.

 

Signals for accommodative responses in humans (ERC StG 309416). Universitat de València, Valencia, Spain. Principal Investigator: Prof Robert Montés-Micó.

The long-term objectives were to identify optical signals that control accommodation and emmetropization of the eye, and to identify the mechanisms that mediate the optical signals. We found that accommodation does not respond differently to different wavefront aberration characteristics. However, there is more to accommodation of the eye than simply minimizing retinal blur. Optical vergence with and without feedback was found to be an important cue for accommodation.

 

Application of psychophysical models to visual disorders (NIH R01 EY007716). Indiana University, Bloomington, IN, USA. Principal Investigator: Prof William H Swanson.

The long-term function of this research program was to relate visual deficits to the underlying cellular pathophysiology of disease processes, with the current focus exclusively on glaucoma. The research applies a quantitative cortical neural pooling model to analysis of perimetric damage produced by glaucoma, with the goals of reducing perimetric variability and improving relations between clinical measures of glaucomatous damage. The R package visualFields was originally developed as part of this project.

 

Measuring aberrations of accommodated myopic eyes over a wide field of view and developing peripheral image quality metrics. Indiana University, Bloomington, IN, USA. Principal Investigator: Prof Larry N Thibos.

As part of the ongoing project, routine statistical analyses were developed, along with exploratory analyses of image quality metrics of the accommodating eye for emmetropes and myopes.

 

Non-parametric stimulus-response functions for psychophysics (EPSRC EP/C003470/1). The University of Manchester, Manchester, UK. Principal Investigator: Prof David H Foster.

This applications-oriented project aimed to provide a simple, flexible procedure for estimating psychometric functions and deriving thresholds from them, with minimum assumptions. The approach was based on locally weighted polynomial regression. The deliverable of the project was a package called modelfree.

 

Mechanisms underlying visual coding of surface color in natural scenes (EPSRC EP/B000257/1) with David H Foster. The University of Manchester, Manchester, UK. Principal Investigator: Prof David H Foster.

The aims of the project were to determine the limits on how absolute and relative information about surface color is coded, how that information is affected by memory, and how current theories of surface-color coding need to be modified to account for actual human performance. We developed a MatLab package to compute the offset Kozachenko-Leonenko estimators of Shannon's differential entropy and of continuous mutual information.

 

Information-theoretic estimates of surface-color coding in natural scenes (EP/E056512/1) with David H Foster. The University of Manchester, Manchester, UK. Principal Investigator: Prof David H Foster.

The aims were to quantify how much information (in Shannon's sense) is carried by achromatic and chromatic pathways in viewing natural scenes under different illuminations and the effects of the different spatial resolutions of these two pathways on information-carrying capacity.

 

An individualized model to monitor glaucoma progression (BrightFocus Foundation). University of Alabama at Birmingham, Birmingham, AL, USA. Principal Investigator: Prof Lyne Racette.

We validated the structure-function model in an independent cohort (the Ocular Hypertension Treatment Study) and estimate the sensitivity and specificity of the structure-function model for predicting which patients will progress.

 

Early detection of glaucoma progression using functional and structural data jointly (Glaucoma Research Foundation Shaffer grant). Indiana University, Indianapolis, IN, USA. Principal Investigator: Prof Lyne Racette.

We continued the development of the structure-function model and compared it against conventional models of glaucoma progression to see which model detected progression earlier.

 

A novel individualized structure-function model to monitor glaucoma progression (IUPUI DRIVE). Indiana University, Indianapolis, IN, USA. Principal Investigator: Prof Lyne Racette.

We developed a model to improve the detection and monitoring of glaucoma progression. This model combined structural and functional data and was individualized to each patient. The model summarized the dynamics of structure-function change as the diseases progresses. It estimates the state of the disease (position and velocity) vectors.