Specific Aim 1: To examine the sensitivity of the low vision CCT (LvCCT) to the severity of retinal disease in inherited retinal degeneration(IRD) by comparing color vision status with changes in photoreceptor structure and function. We have recruited 55 subjects with IRDs. Changes in color vision differ between participants with retinitis pigmentosa (RP) and those with cone-rod degenerations (CRD). In RP, all participants with visual acuity from 20/25 to 20/40 had tritan changes in color vision (i.e. confusion along the blue-yellow axis). With worsening visual acuity, the level of dyschromatopsia progressed in RP but the type of color defect were non-specific ( i.e. did not align with classical lines of red-green or blue-yellow color confusion). Our measure of dyschromatopsia, achromatic area (AA) correlated with logMAR acuity (p<0.001), central retinal thickness (p<0.001) and log cycle x cycle ERG amplitude (p<0.004) in RP. In participants with CRD and Stargardt Disease, the relationship between changes in color vision and structural and other functional measures was more complex than for RP. As for RP, achromatic area was inversely correlated with logMAR (P<0.0001; R2 = 0.3). However, there was wide variation in achromatic area for a given visual acuity. For example, CRD participants with 20/125 visual acuity ranged from normal color vision to those who were functionally achromatic (i.e. unable to discriminate any color). Conversely, normal color vision was associated with visual acuities ranging from 20/16 to 20/160. Ten of thirteen subjects with visual acuity of 20/320 or worse had measureable color vision highlighting the utility of the LvCCT in the low vision population. Islands of retinal preservation at or near the fovea were associated with better color vision even in the presence of widespread geographic atrophy. In CRD participants, scotopic, photopic and 30 Hz ERG amplitudes were inversely correlated (P=0.010; P<0.0001; P=0.003) with achromatic area. Similarly scotopic, photopic and 30 Hz ERG implicit times were positively correlated with logAA (P=0.021; P<0.007; P<0.007). In summary, our experience with the LvCCT in patients with retinal degenerations has shown the utility of this test in low vision patients. Many patients with advanced RP may have good visual acuity but narrow visual fields and subsequently no measurable ERG response. Conversely, CRD patients often have reduced acuity in addition to poor and eccentric fixation which, makes classical field testing difficult. We have found color vision is altered in most participants with retinal degeneration and that the LvCCT can be used to measure color vision in most patients with advanced retinal disease. We propose that the test would be good as an outcome measure in clinical trials for retinal degenerations.
Specific Aim 2 : Examine the effects of eccentric fixation and reduction in visual acuity on the color discrimination thresholds obtained with the LvCCT. Two subjects have completed the experiment examining the effect of eccentric fixation on color discrimination thresholds. Color thresholds were measured from the fovea and 5, 10 and 15 deg superior to the fovea. Achromatic area increased by 64% at 10 deg eccentricity but was still within the normal range described for healthy volunteers fixing at the fovea. Color discrimination worsened at 15 deg eccentricity, with achromatic area more than double (AA = 75) that obtained with foveal fixation (AA=33). However participants with CRD with fixation >10 deg from the fovea had achromatic areas ranging from 200 to 2472. These results indicate that eccentric fixation alone in CRD participants cannot account for changes in color results. The poorer color discrimination in these participants results from changes in retinal function and structure. Five subjects have completed the experiments examining the effects of reduction in visual acuity on color discrimination thresholds. Experiments with the commercial version of CCT indicate the presence of edge and/or luminance cues that allow participants to achieve substantially better color discrimination thresholds when acuity was reduced down to 20/200- 20/400 using optical blur compared with thresholds at 20/20 acuity. In contrast, with the low vision version of the CCT (LvCCT) that we implemented on a ViSaGe system using custom written software, showed a small 20% increase in color thresholds when acuity was blurred to 20/200-20/400. Further optical blur of visual acuity to 20/800 resulted in a total 40% increase in color thresholds compared with 20/20 acuity. These experiments provide strong evidence that color discrimination can be measured down to 20/800 acuity with the LvCCT and further that absolute thresholds are not greatly affected by the loss of acuity alone.
Specific Aim 3 : Establish normal ranges for the CCT and LvCCT and determine the inter-session and intra-session variabilities for these two tests.
Aim 3 a: Normal range: Color discrimination thresholds have been measured from 24 participants aged 5.9 to 60.6 years (median = 25.2 years). Mean ( S.D.) achromatic area for normal subjects was 1.19 0.27 log UV (linear units: mean = 15.6 UV, range of 4.9 54.3 UV). Achromatic area was not correlated with age.
Aim 3 bi: Intra-session variability: Color discrimination thresholds have been measured in 10 participants twice from the dominant eye in on session. Intra-session variability was 0.165 log UV (linear units = 1.5) which equated to a coefficient of variability of 10%.
