Inherited retinal degenerations (IRDs) are a major cause of severe visual impairment worldwide. Promising treatments for these diseases include gene-based, cell-based, and small molecule therapies. A hurdle to initiating clinical trials for IRDs is the lack of prospective natural history studies that have provided quantitative descriptions of changes in retinal structure and function over time. The long-term goal of our research is to develop quantitative methods for describing changes in retinal structure and function in IRDs and to use these methods in future prospective natural history studies and clinical trials for IRDs. Dyschromatopsia is common to all IRDs affecting the central retina. Color vision screening tests are poorly suited to quantitating the severity of dyschromatopsia in IRD. The Cambridge Color Test (CCT) is a commercial computerized system that provides detailed quantitative analysis of color vision. A low vision version of the CCT (LvCCT) was previously used to quantify changes in color vision in low vision patients with dominant optic atrophy (Simunovic M et al Vis Res 1998). Many IRD subjects have reduced visual acuity and central scotoma so we implemented the LvCCT on a ViSaGe System (Cambridge Research Systems Ltd. U.K.) using custom-written software.
The Aims of this protocol were to:
Specific Aim 1 : Examine the sensitivity of the CCT and LvCCT to disease severity in IRD patients by comparing color vision status with changes in retinal structure and function. The LvCCT has proven to be an extremely useful tool to quantitate dyschromatopsia in patients with inherited retinal degeneration including those with extremely poor visual acuity down to 20/800. The test is conceptually simple and we have been able to quantitate color vision in healthy volunteers and IRD patients as young as 5-6 years of age. Quantitative changes in color vision measured with the LvCCT correlate with acuity in RP subjects and cone ERG amplitudes in cone-rod dystrophies. We have now used the LvCCT in a clinical trial with CNGB3 achromatopsia and in a large natural history study of ABCA4 retinopathy. The commercial version of the CCT test has proven to be extremely difficult for IRD patients.
Specific Aim 2 : Examine the effects of eccentric fixation and reduction in visual acuity on the color discrimination thresholds obtained with the CCT and LvCCT. In healthy volunteers, there is a monotonic increase in achromatic area (a measure of dyschromatopsia) with visual acuity. A maximum increase of about 40% in achromatic area occurred when visual acuity was blurred to 20/800. In contrast, for the commercial CCT test, archromatic area paradoxically decreased when acuity was blurred to between 20/200 to 20/400 acuity, and then dramatically increased at 20/800 acuity. These results suggest that the very large increases in achromatic area in IRD patients observed with the LvCCT cannot be explained in terms of reductions in visual acuity. Further, these results suggest presence of spatial artifacts that may provide erroneous cues when measuring color vision in low vision subjects.
Specific Aim 3 : Establish normal ranges for the CCT and LvCCT and determine the inter-session and intra-session variabilities for these two tests. We have established normal ranges for both the CCT and LvCCT from 22 healthy volunteers between 5 and 66 years of age;we found no change in color discrimination over this age range. Intra-session variability of both CCT and LvCCT have been established for healthy volunteers. In the upcoming year we plan to establish intra-session variability for IRD patients and inter-session variabilities for both healthy volunteers and IRD patients
