Echols Benjamin S, Clark Mark E, Swain Thomas A, Chen Ling, Kar Deepayan, Zhang Yuhua, Sloan Kenneth R, McGwin Gerald, Singireddy Ramya, Mays Christian, Kilpatrick David, Crosson Jason N, Owsley Cynthia, Curcio Christine A
Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
Ophthalmol Retina. 2020 Nov;4(11):1059-1068. doi: 10.1016/j.oret.2020.05.001. Epub 2020 May 7.
Hyperreflective foci (HRF) are OCT biomarkers for the progression of nonneovascular age-related macular degeneration (AMD) attributed to anteriorly migrated retinal pigment epithelial cells. We examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS); we identified a histologic candidate for HRS.
Cross-sectional study and histologic survey.
Patients with healthy maculae (n = 34), early AMD (n = 26), and intermediate AMD (n = 41).
AMD severity was determined by color fundus photography. In OCT scans, HRF and HRS were counted manually. Vision tests probed cones (best-corrected visual acuity [VA], contrast sensitivity), mixed cones and rods (low-luminance VA, low-luminance deficit, mesopic light sensitivity), or rods (scotopic light sensitivity, rod-mediated dark adaptation [RMDA]). An online AMD histopathologic resource was reviewed.
Vision in eyes assessed for HRF and HRS; histologic candidate for HRS.
In 101 eyes of 101 patients, HRF and HRS were identified in 25 and 95 eyes, respectively, with good reliability. Hyperreflective foci were present but sparse in healthy eyes, infrequent in early AMD eyes, and frequent but highly variable among intermediate AMD eyes (mean±standard deviation [SD] number per eye, 0.1 ± 0.2, 0.2 ± 0.5, and 1.9 ± 3.4 for healthy, early AMD, and intermediate AMD eyes, respectively). Hyperreflective specks outnumbered HRF in all groups (mean±SD, 4.5 ± 3.2, 6.3 ± 5.8, and 19.4 ± 22.4, respectively). Delayed RMDA was associated strongly with more HRF and HRS (P < 0.0001). Hyperreflective foci also were associated with worse low-luminance VA (P = 0.0117). Hyperreflective specks were associated with worse contrast sensitivity (P = 0.0278), low-luminance VA (P = 0.0010), low-luminance deficit (P = 0.0031), and mesopic (P = 0.0018) and scotopic (P < 0.0001) sensitivity. By histologic analysis, cone lipofuscin was found in outer retinal layers of 25% of healthy aged eyes.
Hyperreflective foci and HRS are markers of cellular activity associated with visual dysfunction, especially delayed RMDA, an AMD risk indicator assessing efficiency of retinoid resupply. Hyperreflective specks may represent lipofuscin translocating inwardly within cones. HRF and HRS may serve as structural end points in clinical trials targeting AMD stages earlier than atrophy expansion. These results should be confirmed in a larger sample.
高反射灶（HRF）是由于视网膜色素上皮细胞向前迁移所致的非新生血管性年龄相关性黄斑变性（AMD）进展的光学相干断层扫描（OCT）生物标志物。我们研究了视杆和视锥介导的视力与HRF以及较小的高反射斑点（HRS）之间的关联；我们确定了HRS的一个组织学候选物。
横断面研究和组织学调查。
健康黄斑患者（n = 34）、早期AMD患者（n = 26）和中期AMD患者（n = 41）。
通过彩色眼底照相确定AMD严重程度。在OCT扫描中，手动计数HRF和HRS。视力测试检测视锥（最佳矫正视力[VA]、对比敏感度）、视锥和视杆混合功能（低亮度VA、低亮度缺陷、中间视觉光敏感度）或视杆功能（暗视光敏感度、视杆介导的暗适应[RMDA]）。查阅了一个在线AMD组织病理学资源。
评估HRF和HRS的眼中的视力；HRS的组织学候选物。
在101例患者的101只眼中，分别在25只和95只眼中发现了HRF和HRS，可靠性良好。高反射灶在健康眼中存在但稀疏，在早期AMD眼中不常见，在中期AMD眼中常见但差异很大（每只眼的平均数±标准差[SD]，健康眼、早期AMD眼和中期AMD眼分别为0.1±0.2、0.2±0.5和1.9±3.4）。在所有组中，高反射斑点的数量均超过HRF（平均数±SD分别为4.5±3.2、6.3±5.8和19.4±22.4）。延迟的RMDA与更多的HRF和HRS密切相关（P < 0.0001）。高反射灶还与较差的低亮度VA相关（P = 0.0117）。高反射斑点与较差的对比敏感度（P = 0.0278）、低亮度VA（P = 0.0010）、低亮度缺陷（P = 0.0031）以及中间视觉（P = 0.0018）和暗视（P < 0.0001）敏感度相关。通过组织学分析，在25%的健康老年眼中的视网膜外层发现了视锥脂褐质。
高反射灶和HRS是与视觉功能障碍相关的细胞活动标志物，尤其是延迟的RMDA，RMDA是一种评估视黄醛再供应效率的AMD风险指标。高反射斑点可能代表视锥内脂褐质向内移位。HRF和HRS可能作为比萎缩扩大更早的AMD阶段的临床试验中的结构终点。这些结果应在更大样本中得到证实。
