Gorin Michael B, Weeks Daniel E, Baron Robert V, Conley Yvette P, Ortube Maria C, Nusinowitz Steven
Department of Ophthalmology, David Geffen School of Medicine-UCLA, Stein Eye Institute, Los Angeles, CA 90095, USA.
Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Clin Med. 2014 Nov 28;3(4):1335-56. doi: 10.3390/jcm3041335.
The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.
减轻与年龄相关性黄斑变性（AMD）相关视力丧失的个人和社会负担的关键在于，能够在将个人风险和成本降至最低的同时，启动能在产生最大益处的阶段减缓或阻止疾病进展的治疗方法。迫切需要找到临床标志物，这些标志物与基因检测的特异性相结合，能够识别出处于AMD最早阶段且能从预防性治疗中获益的个体。这些临床标志物是AMD的内表型，存在于可能患AMD的个体以及有AMD临床证据的个体中。如果与AMD相关的临床特征能够在疾病发生前或最早阶段被检测到，那么它们也可能是潜在的内表型，但我们和其他人已经表明，情况并非总是如此。多项研究表明，视紫红质再生的动态变化（暗适应动力学和/或临界闪烁融合频率）可能是AMD相关早期视网膜功能障碍更微妙的指标。人们可以使用基于已知遗传风险变异的遗传风险概况来测试这些指标的相关性。这些功能指标可能会提高AMD预测模型的敏感性和特异性，也可能有助于区分在预后和治疗方面可能存在差异的AMD临床亚型。
