Color Vision in Inherited Retinal Degenerations

遗传性视网膜变性中的色觉

• 批准号: 8938363
• 负责人: Brett Jeffrey
• 金额: $ 24.25万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938363
• 关键词: 6 year old; Affect; Age; Age-Years; Area; Autosomal Dominant Optic Atrophy; Cells; Central Scotomas; Clinical Trials; Color; Color Visions; Computer software; Cone; Cues; Custom; Discrimination; Disease; Future; Genes; Goals; Measures; Methods; Morphologic artifacts; Natural History; Normal Range; Patients; Photoreceptors; Protocols documentation; Research; Retina; Retinal; Retinal Diseases; Retinitis Pigmentosa; Severities; Severity of illness; Structure; System; Testing; Time; Vision Screening; Visual Acuity; Visual impairment; Writing; achromatopsia; base; computerized; dyschromatopsia; healthy volunteer; inherited retinal degeneration; prospective; sample fixation; small molecule; systems research; tool

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

遗传性视网膜变性（IRD）是世界范围内严重视力损害的主要原因。这些疾病的有希望的治疗方法包括基于基因的，基于细胞的和小分子疗法。启动IRD临床试验的一个障碍是缺乏前瞻性自然史研究，这些研究提供了视网膜结构和功能随时间变化的定量描述。我们研究的长期目标是开发定量方法来描述IRD视网膜结构和功能的变化，并将这些方法用于未来的前瞻性自然史研究和IRD临床试验。 色觉障碍常见于所有影响中央视网膜的IRD。 色觉筛查测试不适合量化IRD色觉障碍的严重程度。剑桥颜色测试（CCT）是一种商业计算机化系统，可提供色觉的详细定量分析。低视力版本的CCT（LvCCT）先前用于量化显性视神经萎缩低视力患者的色觉变化（Simunovic M等人维斯研究，1998年）。 许多IRD受试者具有降低的视敏度和中心暗点，因此我们在ViSaGe系统（剑桥研究系统有限公司，英国）上实施LvCCT。使用定制的软件。 本方案的目的是： 具体目标1：通过比较色觉状态与视网膜结构和功能的变化，检查CCT和LvCCT对IRD患者疾病严重程度的敏感性。 LvCCT已被证明是一种非常有用的工具，用于定量遗传性视网膜变性患者（包括视力极差至20/800的患者）的色觉障碍。 该测试在概念上很简单，我们已经能够量化健康志愿者和5-6岁的IRD患者的色觉。 用LvCCT测量的色觉定量变化与RP受试者的敏锐度和视锥-视杆细胞营养不良的视锥ERG振幅相关。 我们现在已经在CNGB 3色盲的临床试验和ABCA 4视网膜病变的大型自然史研究中使用了LvCCT。 商业版本的CCT测试已被证明是非常困难的IRD患者。 具体目标二：检查偏心固视和视力下降对CCT和LvCCT获得的辨色阈值的影响。 在健康志愿者中，随着视力的增加，无色区（色觉障碍的量度）单调增加。 当视力模糊到20/800时，无色区最大增加约40%。 相比之下，对于商业CCT测试，当视力模糊到20/200到20/400之间时，消色差区域矛盾地减少，然后在20/800视力时急剧增加。 这些结果表明，LvCCT观察到的IRD患者的非彩色区域非常大的增加不能用视力下降来解释。 此外，这些结果表明存在的空间伪影，可能会提供错误的线索时，测量低视力受试者的色觉。 具体目标3：确定CCT和LvCCT的正常范围，并确定这两项测试的会话间和会话内变异性。 我们已经建立了正常范围的CCT和LvCCT从22名健康志愿者之间的5和66岁，我们发现在这个年龄范围内的颜色辨别没有变化。已确定健康志愿者CCT和LvCCT的疗程内变异性。 在接下来的一年里，我们计划建立IRD患者的会话内变异性和健康志愿者和IRD患者的会话间变异性