Foveal reflection analysis in a clinical setting

Abstract

The primary aim of this thesis was to investigate the clinical-diagnostic value of the Foveal Reflection Analyzer (FRA). This was achieved by studying cone-photoreceptor involvement in several ophthalmic diseases. A secondary aim was to investigate the putative protective role of macular pigment and melanin on the incidence and progression of aging macula disorder (AMD). In the course of the study, we also performed a study with the Macular Pigment Reflectometer to investigate the possibility to separately measure the optical densities of lutein and zeaxanthin, the constituents of the macular pigment, in vivo. This had not been achieved before. The FRA measures the spectral and directional properties of light reflected from the fovea. Together with a model fit procedure it provides, in a fast and patient friendly way, a series of parameters that stand for properties of reflectors and absorbers in the eye. In particular, it provides Rd, a parameter for the reflection from cone outer segments, an indication for the integrity of the foveal cones. By using Rd, the FRA can be used as a sensitive device for the objective determination of foveal cone abnormalities. We have shown that in diabetes patients without retinopathy (chapter 4), and in primary open-angle glaucoma patients with severe central visual field defects (chapter 5), the integrity of the foveal cone outer segments was compromised. Optical Coherence Tomography (OCT) did not reveal any foveal abnormalities. In a case of central serous chorioretinopathy (chapter 2)and one of multiple evanescent white dot syndrome (chapter 3), the FRA was able to detect and follow-up the foveal cone integrity status in a quantitative way. This was also possible with OCT, but only in a qualitative way, by observing the foveal photoreceptor inner/outer segment junction. A difference in melanin or macular pigment optical density larger than respectively 32% or 34% measured with the FRA between the two eyes of one person might point to pathology in either eye (chapter 8). As additional information the FRA provides the optical densities of retinal macular pigment and (sub)retinal melanin. Both pigments are thought to protect against AMD. However, using both a cross-sectional (chapter 6) and a longitudinal study (chapter 7), we found no significant evidence that macular pigment or melanin played a protective role against early AMD. The FRA is also able to measure the constituents of the macular pigment, zeaxanthin and lutein, separately in vivo. In chapter 9 this was outlined for the Macular Pigment Analyzer, a simplified version of the FRA and might help to further untangle the interesting question whether MP or one of its constituents protects against AMD. We have proven that fundus reflectometry together with a model fit procedure can be used for the follow-up of temporal changes in the optical density of macular pigment or its constituents after supplementation with zeaxanthin. Knowledge on foveal cone integrity and optical lens density in different stages of several ophthalmic diseases might also contribute to a better understanding of the pathology of these diseases.