Hamilton-Perais Jennifer A, Wright David M, Lim Amelia, Mohite Ajay, Reid Gerard, Hillis Pearse, Sheeran Cora, Lois Noemi
The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
The Centre for Public Health Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
JAMA Ophthalmol. 2025 Oct 30. doi: 10.1001/jamaophthalmol.2025.3980.
Retinal capillary nonperfusion seems crucial in the pathogenesis of sight-threatening diabetic retinopathy (DR); currently, no treatment prevents or reverts it.
To further the understanding of the association between retinal capillary nonperfusion and sensitivity in DR.
DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study was conducted from April 18, 2018, to September 9, 2024, at a single center in the UK. Participants were followed up for up to 2 years; outcome assessors were masked. Adults (aged ≥18 years) with moderate or severe to very severe nonproliferative or proliferative DR with less than high-risk characteristics; at least 1 eye naive to treatment; no other retinal disorders; who were able to provide informed consent; and who were willing undergo retinal imaging were eligible for inclusion. Data analysis was performed from September 2024 to April 2025.
The primary outcome was the association between retinal sensitivity (110° projection perimetry) and retinal perfusion (ultra-widefield angiography) at baseline and changes at 1 and 2 years in the study eye.
Of 66 people approached, 50 were eligible and recruited, and 44 individuals with at least 1 perimetric examination were included. Mean (SD) participant age was 52.1 (12.2) years, and 13 participants (29%) were female. Median hemoglobin A1c was 75.5 mmol/mol (9.1% of total hemoglobin [to convert from percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01]); mean (SD) best-corrected visual acuity letter score was 85.7 (4.7) (Snellen equivalent, 20/20). Mean retinal sensitivity deficit at baseline was associated with perfusion status, with larger deficits in nonperfused areas (n = 354; 11.8 dBs; 95% CI, 10.8-12.8) compared to perfused areas (n = 2092; 6.6 dB; 95% CI, 5.1-8.2; P < .001). Only age correlated positively with sensitivity deficit (estimate, 0.2; 95% CI, 0.1-0.3; P = .006). A deficit of 5 dB or greater occurred in 711 of 2092 (34%) perfused areas; 105 of 354 (30%) nonperfused areas had normal sensitivity. Rates of sensitivity deficit change in perfused and nonperfused areas from baseline to 1 year were -0.20 dB/mo (95% CI, -0.24 to -0.16) and -0.28 dB/mo (95% CI, -0.41 to -0.15) (perfused vs nonperfused, P = .22), respectively (1464 areas); from baseline to 2 years, rates were -0.16 dB/mo (95% CI, -0.20 to -0.12) and -0.34 dB/mo (95% CI, -0.47 to -0.21) (perfused vs nonperfused, P = .007), respectively (542 areas).
In this longitudinal cohort study, although retinal capillary perfusion status was associated with function, sensitivity loss occurred in some perfused areas and normal function in some nonperfused areas; sensitivity deficit decreased over time (approximately 45% in the first year) despite poor glycemic control and high DR grades. These findings should be considered for the management of people with DR and the design of clinical trials.
视网膜毛细血管无灌注在威胁视力的糖尿病视网膜病变（DR）发病机制中似乎至关重要；目前，尚无治疗方法可预防或逆转它。
进一步了解DR中视网膜毛细血管无灌注与敏感度之间的关联。
设计、地点和参与者：这项前瞻性纵向队列研究于2018年4月18日至2024年9月9日在英国的一个中心进行。参与者随访长达2年；结果评估者对情况不知情。患有中度或重度至极重度非增殖性或增殖性DR且无高风险特征的成年人（年龄≥18岁）；至少一只眼未接受过治疗；无其他视网膜疾病；能够提供知情同意；且愿意接受视网膜成像检查的患者符合纳入标准。数据分析于2024年9月至2025年4月进行。
主要结局是研究眼基线时视网膜敏感度（110°投影视野计）与视网膜灌注（超广角血管造影）之间的关联以及1年和2年时的变化。
在66名被邀请者中，50名符合条件并被招募，44名至少进行过一次视野检查的个体被纳入。参与者的平均（标准差）年龄为52.1（12.2）岁，13名参与者（29%）为女性。血红蛋白A1c中位数为75.5 mmol/mol（占总血红蛋白的9.1%[从总血红蛋白百分比转换为总血红蛋白比例，乘以0.01]）；平均（标准差）最佳矫正视力字母评分是85.7（4.7）（Snellen等效值，20/20）。基线时平均视网膜敏感度缺陷与灌注状态相关，与灌注区域（n = 2092；6.6 dB；95%置信区间，5.1 - 8.2）相比，无灌注区域的缺陷更大（n = 354；11.8 dB；95%置信区间，10.8 - 12.8）（P <.001）。只有年龄与敏感度缺陷呈正相关（估计值，0.2；95%置信区间，0.1 - 0.3；P =.006）。2092个（34%）灌注区域中有711个出现5 dB或更大的缺陷；354个（30%）无灌注区域中有105个敏感度正常。从基线到1年，灌注区域和无灌注区域敏感度缺陷变化率分别为-0.20 dB/月（95%置信区间，-0.24至-0.16）和-0.28 dB/月（95%置信区间，-0.41至-0.15）（灌注区域与无灌注区域相比，P =.22）（1464个区域）；从基线到2年，变化率分别为-0.16 dB/月（95%置信区间，-0.20至-0.12）和-0.34 dB/月（95%置信区间，-0.47至-0.21）（灌注区域与无灌注区域相比，P =.007）（542个区域）。
在这项纵向队列研究中，尽管视网膜毛细血管灌注状态与功能相关，但一些灌注区域出现了敏感度丧失，一些无灌注区域功能正常；尽管血糖控制不佳且DR分级较高，但敏感度缺陷随时间下降（第一年约45%）。这些发现应在DR患者的管理和临床试验设计中予以考虑。
