Comparison of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration with and without subsequent choroidal neovascular membrane development.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of blind registrations in the elderly. Unfortunately, it is difficult to detect the early stage of the disease, when treatment is more likely to be successful. Subjects with very early disease are likely to have abnormal macular function, even in the pre-symptomatic stage. In this study, colour vision was evaluated to establish if subjects at high risk of developing nAMD can be identified, thus allowing earlier diagnosis and possible treatment. METHODS: Colour contrast sensitivity (CCS) was evaluated over time in the fellow unaffected eye of subjects with unilateral nAMD. Participants were divided into Group 1 (182 participants) or Group 2 (15 participants) according to whether nAMD did not or did develop in the study period respectively and the two groups were compared. RESULTS: CCS was increased (i.e. worse colour vision) compared with the age-matched reference range in a high proportion of fellow eyes in both Groups 1 and 2. Global mean CCS values did not show statistically significant differences between the two groups. However, there was a statistically significant difference between mean Group 1 CCS values and the last CCS value prior to nAMD diagnosis from Group 2 subjects. CONCLUSION: This study shows that in patients with unilateral nAMD, colour vision is frequently abnormal in the fellow unaffected eye. Abnormal CCS does not predict the development of nAMD within the 12 month period of the study and therefore it is not a viable screening tool for this pathology.

Colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration.

PURPOSE: To generate the first published reference database of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration and to explore this important feature in quality of vision. BACKGROUND: Quality of vision depends on many factors. Changes in chromatic contrast sensitivity remain largely unexplored in eyes at high risk of neovascular age-related macular degeneration; they may however not only be relevant for quality of life but also an early indicator of the onset of the disease, so it is important to have a means to evaluate any variation in colour contrast sensitivity, especially in view of the likely increase in neovascular age-related macular degeneration as the population ages. METHODS: This prospective longitudinal study evaluated colour contrast sensitivity along the protan and tritan colour axes in 145 eyes at high risk of neovascular age-related macular degeneration. RESULTS: Colour contrast sensitivity showed statistically significant correlations with age and visual acuity, but not gender nor laterality (i.e. whether the right or left eye was being tested). There was significant variability among individuals, especially for the tritan axis, with some subjects well within normal limits for age and others with very poor colour contrast sensitivity. CONCLUSION: This study has generated the first published colour contrast sensitivity reference database for eyes at high risk of neovascular age-related macular degeneration. It has also shown a high inter-individual variability of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration, but the significance of this is unclear. Further work is required to establish if eyes with high colour contrast sensitivity thresholds (i.e. poor colour vision) have a higher risk of developing neovascular age-related macular degeneration over time, and this is the subject of ongoing work.

Transient retinal effects of 5,6-dimethylxanthenone-4-acetic acid (DMXAA, ASA404), an antitumor vascular-disrupting agent in phase I clinical trials.

PURPOSE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), an anticancer vascular-disrupting agent, has induced transient visual symptoms in some patients. Exploratory investigations were undertaken to characterize the visual disturbances in two consecutive phase I trials. METHODS: Assessments were made in 21 patients before and immediately after a 20-minute IV infusion of DMXAA, including visual acuity, funduscopy, color discrimination, pattern electroretinography (PERG), pattern visual-evoked potentials (VEP), and full-field electroretinography (ERG). Evaluation of late effects was undertaken subsequently in 12 patients before and after 6 weeks of IV DMXAA at one dose per week. RESULTS: Frequency and intensity of transient visual disturbance increased with DMXAA dose, occurring in two thirds of patients at 3000 mg x m(-2). Symptoms included blurring, flickering, fragmentation, alteration of colors, and contrast and mild photosensitivity, starting during the infusion and resolving completely, usually within 60 minutes. Visual acuity was unchanged but color discrimination was perturbed. Dose-dependent increases in PERG P50 implicit time by up to 23 ms returned toward baseline values within 90 minutes. Prominent transient changes on ERG included prolonged scotopic rod and 30-Hz flicker implicit times and reduced 30-Hz flicker amplitude. In the second trial, no clinically significant sustained effects were detected, although an increase in bright flash a-wave implicit time (P = 0.022) was seen on whole-group analysis. In vitro studies showed nonspecific phosphodiesterase inhibition by DMXAA. CONCLUSIONS: DMXAA induced acute, transient disturbance of retinal activity consistent with phosphodiesterase inhibition. No clinically significant cumulative effects were noted and most effects occurred at doses higher than those used in ongoing clinical trials (ClinicalTrials.gov numbers, NCT00856336, NCT00863733, and NCT00003697).