Emory University School of Medicine, Atlanta, Georgia.
Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina.
JAMA Ophthalmol. 2023 Mar 1;141(3):260-266. doi: 10.1001/jamaophthalmol.2022.6093.
Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan polysulfate (PPS).
To evaluate the 2-year evolution of maculopathy associated with PPS use after drug cessation.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively evaluated the natural history of patients with maculopathy associated with PPS use. Participants seen at the Emory Eye Center were enrolled between December 1, 2018, and December 1, 2019, and data were collected through November 30, 2021.
The main outcomes were changes in visual function and structure. Visual function was assessed annually with refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), mesopic microperimetry, and dark adaptometry. Structural outcomes included presence and extent of complete retinal pigment epithelium and outer retinal atrophy (cRORA), macular central subfield thickness (CST), and subfoveal choroidal thickness (SFCT).
Of the 12 participants (23 eyes), 11 (91.7%) were female (1 [8.3%] male), 11 (91.7%) were White (1 [8.3%] Black), and median (IQR) age at enrollment was 58 (47-64) years. Median (IQR) time from PPS discontinuation to initial visit was 0.6 (0.4-1.9) years. Median baseline ETDRS BCVA letter score was 83 (Snellen equivalent, 20/20) (IQR, 80-86.5 [20/25-20/20]), with a median 2-year change of -3 (IQR, -6 to -0.5; P = .08). Four eyes (17.4%) had a letter score decline of 15 or more, all associated with progressive cRORA. Median change in microperimetry average threshold was -3.5 dB (IQR, -4.1 to -2.5 dB; P = .001), and percent reduced threshold was 32.5% (IQR, 20.3%-52.8%; P = .004). Nine eyes (39%) had macular cRORA at baseline, with a median linearized growth rate of 0.23 mm/y (IQR, 0.22-0.25 mm/y). Two eyes (8.7%) without atrophy at baseline developed new-onset cRORA. Median baseline CST was 284 μm (IQR, 253-291 μm), with a median 2-year change of -5 μm (IQR, -13 to 0.5 μm; P = .0497). Median 2-year change in SFCT was 1 μm (IQR, -18 to 16 μm; P = .91).
The findings of this cohort study suggest that functional and structural deficits continue to progress in PPS-associated maculopathy even after drug cessation. Additional study is needed to determine whether these findings can be generalized to other patients with PPS-associated maculopathy and whether longer follow-up could determine subsequent disease course.
先前的回顾性研究为停止使用戊聚糖多硫酸酯（PPS）治疗后与 PPS 相关的黄斑病变患者的疾病进展提供了有限的证据。
评估停止使用 PPS 后与 PPS 相关的黄斑病变的 2 年演变情况。
设计、地点和参与者：这项队列研究前瞻性评估了与 PPS 相关的黄斑病变患者的自然病史。2018 年 12 月 1 日至 2019 年 12 月 1 日期间，在埃默里眼中心就诊的患者被招募，并于 2021 年 11 月 30 日收集数据。
主要结果是视觉功能和结构的变化。每年通过屈光度和早期糖尿病视网膜病变研究（ETDRS）最佳矫正视力（BCVA）、中视微视力和暗适应测量来评估视觉功能。结构结果包括完全视网膜色素上皮和外层视网膜萎缩（cRORA）、黄斑中央小视野厚度（CST）和中心凹下脉络膜厚度（SFCT）的存在和程度。
在 12 名参与者（23 只眼）中，11 名（91.7%）为女性（1 名[8.3%]为男性），11 名（91.7%）为白人（1 名[8.3%]为黑人），入组时的中位（IQR）年龄为 58（47-64）岁。从 PPS 停药到首次就诊的中位（IQR）时间为 0.6（0.4-1.9）年。中位基线 ETDRS BCVA 字母评分 83（Snellen 等效值，20/20）（IQR，80-86.5 [20/25-20/20]），中位 2 年变化为-3（IQR，-6 至-0.5；P=0.08）。有 4 只眼（17.4%）的字母评分下降了 15 分或更多，所有这些都与进行性 cRORA 有关。微视力平均阈值的中位变化为-3.5 dB（IQR，-4.1 至-2.5 dB；P=0.001），阈值降低百分比为 32.5%（IQR，20.3%-52.8%；P=0.004）。基线时有 9 只眼（39%）存在黄斑 cRORA，其线性生长率的中位值为 0.23 mm/y（IQR，0.22-0.25 mm/y）。基线时没有萎缩的 2 只眼（8.7%）新出现 cRORA。中位基线 CST 为 284 μm（IQR，253-291 μm），中位 2 年变化为-5 μm（IQR，-13 至 0.5 μm；P=0.0497）。SFCT 的中位 2 年变化为 1 μm（IQR，-18 至 16 μm；P=0.91）。
这项队列研究的结果表明，即使在停止使用 PPS 后，与 PPS 相关的黄斑病变的功能和结构缺陷仍在继续进展。需要进一步的研究来确定这些发现是否可以推广到其他与 PPS 相关的黄斑病变患者，以及更长时间的随访是否可以确定随后的疾病进程。
