Abstract：
OBJECTIVE: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT).
METHODS: Post hoc subgroup analysis of a prospective study.
METHODS: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch\'s membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit.
RESULTS: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001).
CONCLUSIONS: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.
METHODS: Post hoc subgroup analysis of a prospective study.
METHODS: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch\'s membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit.
RESULTS: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001).
CONCLUSIONS: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.
摘要：
目的：使用扫频源光学相干断层扫描（SS-OCT）研究了中度AMD（iAMD）眼中高反射病灶（HRF）的总黄斑负荷与持续性脉络膜超透射缺损（hyperTD）发病之间的关系。
方法：一项前瞻性研究的事后亚组分析。
方法：对纳入前瞻性SS-OCT研究的受试者的iAMD眼进行回顾性回顾。在基线和随访时，所有眼睛均接受6×6mmSS-OCT血管造影（SS-OCTA）成像。使用面部视网膜下色素上皮（subRPE）平板，其分割边界位于布鲁赫膜（BM）下方64-400µm处，以识别持续性脉络膜高TDs。在基线时，没有一只眼睛有持续性的高TDs。基于相应的B扫描，使用相同的subRPE平板识别可归因于直接内（iHRF）或沿RPE（rpeHRF）定位的HRF的脉络膜低透射缺陷（hypoTD）。两个独立的分级者使用半自动算法来验证和完善HRF轮廓。每次访视时测量5mm中央凹圆内的HRF面积和玻璃疣体积。
结果：纳入本研究的121例患者的171只眼的中位随访时间为59.1个月（95CI：52.0-67.8个月）。其中,149只眼睛（87%）患有HRF，82例(48%)在随访期间出现至少一种持续性的高热TD。尽管单变量Cox回归分析显示玻璃疣体积和总HRF面积均与第一次持续性高TD的发作有关。多变量分析表明，总HRF面积是高血压发作的唯一重要预测因素（P<0.001）。ROC分析确定HRF面积≥0.07mm²，以预测一年内持续性hyperTDs的发作，曲线下面积（AUC）为0.661（0.570-0.753），对应的敏感性为55%，特异性为74%（P<0.001）。
结论：HRF的总黄斑负荷，其中包括沿RPE和视网膜内的HRF，是从iAMD到持续性hyperTDs发作的疾病进展的重要预测因子，应作为一个关键的OCT生物标志物，在未来的临床试验中选择具有疾病进展高风险的iAMD患者。
方法：一项前瞻性研究的事后亚组分析。
方法：对纳入前瞻性SS-OCT研究的受试者的iAMD眼进行回顾性回顾。在基线和随访时，所有眼睛均接受6×6mmSS-OCT血管造影（SS-OCTA）成像。使用面部视网膜下色素上皮（subRPE）平板，其分割边界位于布鲁赫膜（BM）下方64-400µm处，以识别持续性脉络膜高TDs。在基线时，没有一只眼睛有持续性的高TDs。基于相应的B扫描，使用相同的subRPE平板识别可归因于直接内（iHRF）或沿RPE（rpeHRF）定位的HRF的脉络膜低透射缺陷（hypoTD）。两个独立的分级者使用半自动算法来验证和完善HRF轮廓。每次访视时测量5mm中央凹圆内的HRF面积和玻璃疣体积。
结果：纳入本研究的121例患者的171只眼的中位随访时间为59.1个月（95CI：52.0-67.8个月）。其中,149只眼睛（87%）患有HRF，82例(48%)在随访期间出现至少一种持续性的高热TD。尽管单变量Cox回归分析显示玻璃疣体积和总HRF面积均与第一次持续性高TD的发作有关。多变量分析表明，总HRF面积是高血压发作的唯一重要预测因素（P<0.001）。ROC分析确定HRF面积≥0.07mm²，以预测一年内持续性hyperTDs的发作，曲线下面积（AUC）为0.661（0.570-0.753），对应的敏感性为55%，特异性为74%（P<0.001）。
结论：HRF的总黄斑负荷，其中包括沿RPE和视网膜内的HRF，是从iAMD到持续性hyperTDs发作的疾病进展的重要预测因子，应作为一个关键的OCT生物标志物，在未来的临床试验中选择具有疾病进展高风险的iAMD患者。
