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Bascom Palmer Eye Institute

Delia Cabrera DeBuc, Ph.D.

General Information

Delia Cabrera DeBuc, Ph.D.

Research Subject

Quantitative Ophthalmic Imaging

Vision Science Focus

Diabetic Retinopathay, Multiple Sclerosis, Retinitis Pigmentosa, Age-Related Macular Degeneration

Published Articles

Roles

Research Associate Professor of Ophthalmology

Summary

Dr. Cabrera DeBuc is a member of the research program in ophthalmic imaging at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. As a faculty member, she works with scientists on basic science projects and collaboratively with ophthalmologists on applications of her findings to clinical practice. Specifically, her research focuses on physical and mathematical modeling of retinal and corneal morphology as visualized by optical imaging in order to quantify pathological features and treatment-induced changes in patients with ocular diseases. She is a physicist who has worked for the past 10 years on methods to improve ocular imaging and image analysis for clinical use. Her research group has been supported by grants from the Juvenile Diabetes Research Foundation and the National Eye Institute. Dr. Cabrera DeBuc major research undertaking not only includes novel experimental approaches and imaging technologies but also encompasses a more complete study design to better characterize the pathogenesis of diabetic retinopathy. Particularly, her research will make it possible to provide clinicians with a powerful method for screening, follow-up, and considering early prophylactic treatment of the diabetic retinal tissue.

Current Research

Quantitative assessment of early changes of diabetic retinal pathology

Diabetic retinopathy (DR) is a sight-threatening microvascular complication leading to vision loss in millions of patients in industrialized and developed countries. The pathogenesis of DR is complex and still remains incompletely understood. The prevalence of DR increases with diabetes duration. Therefore, an objective test for the early diagnosis and evaluation of DR treatment is certainly needed in order to identify the individuals at great risk for vision-threatening problems. Our goal is to improve the early diagnosis and treatment of diabetic retinopathy.
Optical coherence tomography (OCT) is a sophisticated non-invasive technique based on optical interferometry that provides the best available spatial and temporal resolution to quantify and detect local abnormalities in the human retina (see Fig. 1).

Figure 1
Figure 1. Normal Macular Histology vs. OCT (Adapted from Drexler et al., 2001, Nature Medicine, Vol. 7, No.4, 502-507)

Although DR has been traditionally viewed as a disorder of retinal vasculature, retinal neurodegeneration may be a primary pathology that gives rise to microvascular changes. However, studies describing the role of altered overall retinal structure in the diabetic eye appear contradictory and some controversy remains. In this project, we are developing novel diagnostic parameters to discriminate diabetic eyes with early retinopathy from healthy and diabetic eyes without retinopathy. As this project is revealing, the preceding step of manifest DR may be a neurodegeneration of the retina which seems to be detectable in vivo by OCT mapping of the local retinal abnormalities and corresponds to previous experimental results. This aspect of diabetic retinal changes is not yet a part of the common thinking about diabetes, but future studies using OCT image segmentation techniques, elaborating histological and functional changes of the macula in diabetic patients may shed light on this very first step possibly leading to the further sequelae of DR.

This project is under development as part of a collaboration with the Department of Ophthalmology at the Semmelweis University in Budapest, Hungary.

Advanced imaging for diabetic retinopathy (AIDR study)

Advances in preventing vision loss in diabetic patients are hindered by limited understanding of mechanisms underlying DR and the altered relationships between the retinal neural tissue and retinal vasculature. Therefore, an objective test for the early diagnosis and evaluation of DR treatment is certainly needed in order to identify the individuals at great risk for vision-threatening problems. Studies have shown that, in DR, retinal neurodegeneration may be a primary pathology that gives rise to microvascular changes. Our goal is to prevent visual loss in diabetic patients with advanced optical imaging devices, such as Fourier Domain Optical Coherence Tomography systems (FD-OCT) and the Retinal Function Imager (RFI). These devices can facilitate a better understanding of the underlying sight-threatening complications of DR and the altered relationships between the neural retina and blood vessels. Our objective is to test the hypothesis that retinal structure alteration precedes disturbances in retinal hemodynamics and visual function deficit in DR. Our hypothesis predicts that retinal structure alteration precedes disturbance of retinal hemodynamics, and at each stage of progressive DR the magnitude of structure deterioration will be larger than the magnitude of hemodynamic disturbance and visual function deficit. Our results will provide quantitative information about retinal blood flow in diabetic patients with and without retinopathy, and will improve the early diagnosis and treatment of DR. Our impact will influence clinical practice by providing a means of identifying better clinical endpoints for DR clinical trials that are more sensitive to early disease progression than visual acuity and define the exact role of the blood circulation abnormalities in the DR progression.

Improving the quantitative assessment of intraretinal features by determining both structural and optical properties of the retinal tissue in diabetic patients with OCT

OCT is usually employed for the measurement of retinal thickness. However, coherent reflected light carries more information characterizing the optical properties of tissue. In addition, texture measures may provide additional information to characterize abnormalities at the early stage of retinopathy. Therefore, changes in tissue optical properties and texture descriptors may provide further information regarding cellular layers and early damage in diabetic ocular disease. While only few studies using OCT have demonstrated macular thinning along with selective thinning of intraretinal layers in patients with early DR, there have been no previous studies evaluating in detail the retinal optical properties in diabetic patients with and without retinopathy. In this project, we are developing methods to measure optical parameters and thickness of the various cellular layers of the retina. In addition, we are investigating the relationship between these quantities in order to develop quantitative measures to detect both early DR and eventual DR progression. Our main objectives are: 1) to develop an objective methodology encompassing novel optical-structural measures based on image processing of OCT data; and 2) to test the hypothesis that these optical-structural measures extracted from OCT images can be used to discriminate between healthy and pathological eyes. Our outcome will make it possible to provide clinicians with a powerful method for screening, follow-up, and considering early prophylactic treatment of the diabetic retinal tissue.

Fractal analysis for classification of diabetes-induced retinal damage in optical coherence tomography

Fractal analysis has been shown in the past decade to be able to characterize many complex structures in nature. Particularly, biological systems often exhibit self-similar or fractal scaling characteristics. We are analyzing the fractal dimensionality of retinal morphology in healthy subjects and diabetic patients with and without early retinopathy to ascertain if diabetes affects retinal structure fractality. The use of fractal analysis for classification of diabetes-induced retinal damage in OCT clinical data could potentially provide additional diagnostic information for early detection and progression of DR.

In vivo evaluation of retinal neurodegeneration in patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disorder that affects the central nervous system. The disease is characterized by demyelination that leads to axonal dysfunction and neuronal loss. Unmyelinated neuronal cells offer a good possibility to examine axonal loss as the thickness of the myelin sheath does not affect the nerve thickness results. The innermost layer of the retina is the retinal nerve fiber layer (RNFL) being comprised of the axons of the retinal ganglion cells which get myelin sheath only after leaving the eye through the lamina cribrosa. Therefore, the thickness measurement of the RNFL might be a good marker of the axonal damage in MS patients. The purpose of this project is to assess macular morphology in patients with MS with or without optic neuritis in medical history and also to determine which OCT parameter has the greatest ability to detect neuronal damage in patients with MS. Our early results show that mainly the ganglion cells are affected in MS and changes can be already present in eyes without previous history of optic neuritis which could be the result of axonal degeneration due to the disease process of MS. This could facilitate the cost-effective follow-up of neurodegeneration due to MS (see Fig. 2). By the use of OCT image segmentation, we could also show in vivo that neurodegeneration affects the ganglion cells and not the outer retina, while episodes of optic neuritis are resulting in a further pronounced loss of the retinal ganglion cells.

Figure 2
Figure 2. Top: OCT image of a healthy macula after processing with OCTRIMA. Bottom: Column graph showing the differences in the thickness of the intraretinal layers between the groups (ON-: not affected eye; ON+: affected eye). Abbreviations: GCC, ganglion cell complex; GCL+IPL, ganglion cell layer and inner plexiform layer complex; INL, inner nuclear layer; ONL, outer nuclear layer; OPL, outer plexiform layer; RNFL, retinal nerve fiber layer; RPE, retinal pigmentepithelial layer.

This project is under development as part of collaboration with the Department of Ophthalmology at the Semmelweis University in Budapest, Hungary.

The structure and function of the macula in patients with advanced retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy with a world-wide prevalence of approximately 1:4000. Quantitative data about the intraretinal structures can be observed with the use of OCT image processing softwares. Several authors have reported OCT thinning of the photoreceptor layer in RP patients. However, there is little consistency emerging from studies of inner retinal structure. We are exploring the correlation between retinal structure and function in patients with RP using multifocal electroretinography and optical coherence tomography. Our early results are consistent with degeneration of the outer retina preceding inner retinal changes in RP (see Fig. 3)

Figure 3
Figure 3. Schematic drawing of the observed pathological changes in the macula of patients with RP. Top: normal structure of a healthy macula. Middle: schematic drawing of a macula in the DRF (decreased retinal function on mfERG) group. Bottom: image of a macula in the NCRF (no central retinal function on mfERG) group. Blue color denotes thinning, while red color is for thickening. Note that RNFL thickening occurs early in the peripheral region, while the pericentral ganglion cell layer (GCL+IPL) is only affected in the NCRF group despite the thinning of the pericentral ONL already in the DRF group.

Currently, there is no effective treatment for RP. The use of retinal implants is a possible avenue for the restoration of vision to the blind. However, the efficacy of such implants depends upon the cells of the inner nuclear layer and the ganglion cell layer being functionally intact. The quantitative structural data provided by OCT image segmentation could be a valuable tool in effective selection of patients where the integrity of the ganglion cell layer is a pre-requisite for potential use of retinal prostheses, and could act as a useful outcome measure in therapeutic interventions.

This project is under development as part of a collaboration with the Department of Ophthalmology at the Semmelweis University in Budapest, Hungary.