Multifocal pupillographic objective perimetry in age-related maculopathy

Abstract

Age-related macular degeneration (AMD) is a multifactorial disease caused by the interaction of environmental and genetic factors (Rattner & Nathans, 2006). Prevalence data has identified AMD as the leading cause of visual impairment and blindness in the western world (Hawkins et al., 1999; Klein et al., 2007). Recent advances in retinal imaging have improved the detection of pathology, allowing for timely diagnosis, identification of prognostic factors and the monitoring of therapy to be made. However, the newer imaging modalities fail to provide information on retinal function leaving clinicians to rely on diagnostically poor examination techniques to determine a patient's change in visual function (Ivers et al., 2001). The purpose of this thesis was to investigate the effects of various stages of AMD on the pupillary response with the secondary aim of determining the diagnostic potential of multifocal pupillographic objective perimetry (mfPOP) in AMD.

Our investigation began with the determination of the optimal features for centrally directed stimuli in multifocal pupillography. To overcome the effects of saturation and achieve high signal to noise ratios from stimuli presented in the central visual field, we conducted a series of 3 experiments testing on normal subjects a range of stimulus presentation intervals, spatial densities, visual angles and luminances. We determined that longer stimulus presentation intervals with low resolution (24-region) non-overlapping layouts at a luminance of approximately 250 cd/m{u00B2} achieved the largest contraction amplitudes and shortest times to peak response. We utilized the optimal stimulus features determined from our initial investigation to conduct a series of clinical experiments on subjects with early and advanced stages AMD. We also wished to assess the ability of mfPOP to monitor the effect of treatment for exudative AMD over time.

Contrary to our preliminary study results in normals, our investigation of the effects of exudative AMD on retinal function measured by mfPOP identified higher resolution stimuli (44 region) with shorter presentation intervals to elicit the largest changes in pupillary responses. In addition, receiver operator characteristic (ROC) analysis confirmed this stimulus to be the most diagnostic. The results suggest that signal convergence elicited from large slow stimulus presentations reduces the effects of localized severe defects. A subsequent study examining retinal dysfunction following 3 months of ranibizumab therapy confirmed our previous results. What was striking was the revelation that prior to treatment, the delay of pupillary responses to multifocal stimuli were the most vulnerable in AMD, and demonstrated the largest improvement following the typical course of therapy. There was also evidence that peripheral hypersensitivity was predicative of good treatment outcomes as expressed by reductions in retinal thickness.

Our final experiment investigated the potential of mfPOP to identify subjects with early clinical signs of AMD with the aim of offering prognostic factors identifying patients at risk of rapid progression. Implementing a novel stimulus presentation technique we demonstrated temporal response impairment biased to the superior hemifield in early AMD subjects. Our results suggested that mfPOP may identify retinal dysfunction in eyes with preserved visual acuity and in the absence of clinically visible signs. Show more