Chong Yu Jeat, Teo Kelvin Yi Chong, Wong Wendy, Tan Anna C S, Su Xinyi, Gilead Noa, Chan Hiok Hong, Ibrahim Farah, Fenner Beau, Ong Charles, Sun Christopher, Sim Shaun, Chee Caroline, Chakravarthy Usha, Cheung Chui Ming Gemmy
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Department of Medical Retina, Singapore National Eye Centre, Singapore.
JAMA Ophthalmol. 2025 May 1;143(5):393-399. doi: 10.1001/jamaophthalmol.2025.0250.
The potential benefit of adding photodynamic therapy (PDT) to intravitreal aflibercept injection (IAI) in eyes with polypoidal choroidal vasculopathy (PCV) remains unclear.
To compare the functional and anatomical benefit of combination therapy using reduced-fluence PDT (RF-PDT) plus IAI vs IAI monotherapy in participants with PCV.
DESIGN, SETTING, AND PARTICIPANTS: This double-masked, sham-controlled, randomized clinical trial was conducted at 2 centers in Singapore from January 2021 to June 2024 for participants aged 50 years or older with symptomatic macular PCV confirmed on indocyanine green angiography. Data were analyzed from January 2021 to June 2024.
Randomization 1:1 to RF-PDT plus 2 mg of IAI or sham-PDT plus 2 mg of IAI at week 0. Follow-up was at 4 weeks and retreatment with IAI, per protocol pro re nata regimen.
The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Secondary outcomes, not adjusted for multiple analyses, included proportion of eyes with polypoidal lesion (PL) closure at week 12 per indocyanine green angiography .
Only 60 (43 male [71.6%] and 17 female [28.4%]; mean [SD] age, 71.3 [5.7] years) of the planned 160 participants were enrolled between January 2021 and June 2023. Among these, 30 of 30 (100%) and 30 of 30 participants (100%) in combination and monotherapy groups, respectively, returned for the 52-week follow-up. Baseline BCVA letter score (approximate Snellen equivalent [SD]) was 62.0 (20/63 [10.6]) and 62.0 (20/63 [10.7]) in the combination and monotherapy arms, respectively. At week 52, mean gain in BCVA was 12.7 (combination) vs 11.9 (monotherapy) (difference = 0.8 letters; 95% CI, -3.0 to 6.0 letters; P = .82). At week 12, the PL closure rate occurred in 20 of 30 eyes (66.7%) vs 10 of 30 eyes (33.3%) in the combination and monotherapy arms, respectively (difference = 33.4%; 95% CI, 9.5%-57.2%; P = .02).
With less than half of the planned sample size enrolled, no superiority in BCVA outcomes for either arm was detected and the combination arm could not be shown to be not worse (not noninferior) to the monotherapy arm. While PL closure at week 12 was greater in the combination arm, secondary outcome results, which were not adjusted for multiple analyses, should be considered hypothesis generating and not associated with a clinically relevant functional outcome in this trial.
ClinicalTrials.gov Identifier: NCT03941587.
在患有息肉状脉络膜血管病变（PCV）的眼睛中，在玻璃体内注射阿柏西普（IAI）基础上加用光动力疗法（PDT）的潜在益处仍不明确。
比较在PCV患者中，低剂量光动力疗法（RF-PDT）联合IAI与IAI单药治疗的功能和解剖学益处。
设计、地点和参与者：这项双盲、假对照、随机临床试验于2021年1月至2024年6月在新加坡的2个中心进行，纳入年龄在50岁及以上、经吲哚菁绿血管造影确诊为有症状性黄斑PCV的参与者。数据于2021年1月至2024年6月进行分析。
在第0周按1:1随机分组接受RF-PDT联合2mg IAI或假PDT联合2mg IAI。随访在4周时进行，并根据方案按需进行IAI再治疗。
主要结局是从基线到第52周最佳矫正视力（BCVA）的平均变化。次要结局（未针对多重分析进行调整）包括根据吲哚菁绿血管造影在第12周时息肉样病变（PL）闭合的眼比例。
在2021年1月至2023年6月期间，计划纳入的160名参与者中仅60名（43名男性[71.6%]和17名女性[28.4%]；平均[标准差]年龄，71.3[5.7]岁）被纳入。其中，联合治疗组和单药治疗组分别有30名参与者中的30名（100%）和30名参与者中的30名（100%）返回进行52周随访。联合治疗组和单药治疗组的基线BCVA字母评分（近似Snellen等效值[标准差]）分别为62.0（20/63[10.6]）和62.0（20/63[10.7]）。在第52周时，BCVA的平均增益联合治疗组为12.7，单药治疗组为11.9（差值 = 0.8个字母；95%置信区间，-3.0至6.0个字母；P = 0.82）。在第12周时，联合治疗组30只眼中有20只（66.7%）PL闭合，单药治疗组30只眼中有10只（33.3%）PL闭合（差值 = 33.4%；95%置信区间，9.5%-57.2%；P = 0.02）。
由于纳入的样本量不到计划样本量的一半，未检测到任何一组在BCVA结局上有优越性，且无法证明联合治疗组不比单药治疗组差（并非非劣效）。虽然联合治疗组在第12周时PL闭合情况更好，但未针对多重分析进行调整的次要结局结果应被视为产生假设，且在本试验中与临床相关的功能结局无关。
ClinicalTrials.gov标识符：NCT03941587。
