Eren Mustafa, Kucukevcilioglu Murat, Durukan Ali Hakan
a Department of Ophthalmology , Marmaris Public Hospital , Mugla , Turkey.
b Department of Ophthalmology , Gulhane Training and Research Hospital , Ankara , Turkey.
Cutan Ocul Toxicol. 2018 Sep;37(3):275-280. doi: 10.1080/15569527.2018.1446976. Epub 2018 Mar 20.
To examine retinal sensitivity in patients on hydroxychloroquine (HCQ) with no evidence of retinopathy.
Seventy patients on HCQ and 30 healthy control subjects were included prospectively. All subjects underwent complete ophthalmic examination including best corrected visual acuity, tonometry, colour vision testing, biomicroscopy of anterior segment, dilated fundoscopy, 10-2 visual field testing, and spectral domain optical coherence tomography. The patients and control subjects who met the inclusion criteria and had normal tests underwent microperimetry (MP) testing. First, all patients were compared with the control group. Secondly, patients were divided into three sets of groups based on (1) duration of use ≤5 years (DOU≤5) and >5 years (DOU>5), (2) daily dose ≤5 mg/kg/day (DD≤ 5) and >5 mg/kg/day (DD>5), and (3) a cumulative dose ≤1000 gr (CD≤ 1000) and >1000 gr (CD>1000), and these groups were compared to each other and to the control group. A correlation analysis was also performed between MP sensitivity and DOU, DD, and CD.
Seven patients on HCQ showing visual field abnormality were excluded which yielded 63 patients and 30 control subjects for the final analysis. We observed significant differences only in the central region but not in the paracentral or peripheral regions on MP in HCQ users. The median MP sensitivities in the central region were significantly lower in all the patients [84 (63-100) dB], and in subgroups of DOU >5 [84 (63-99) dB], DD >5 [82 (63-97) dB] and CD >1000 [82 (63-92) dB] when compared to controls [89.7 (83-98) dB]. A statistically significant correlation was found only between DD and MP sensitivity in the central region (r = -0.263; p = 0.02).
MP sensitivities in the central macula were significantly lower in patients taking HCQ for more than 5 years, at a daily dose more than 5 mg per day, and with a cumulative dose over 1000 gr. Further research investigating long-term follow-up changes in MP sensitivities is needed to determine cutoff values for early retinal toxicity.
检查服用羟氯喹（HCQ）但无视网膜病变证据的患者的视网膜敏感性。
前瞻性纳入70例服用HCQ的患者和30名健康对照者。所有受试者均接受了全面的眼科检查，包括最佳矫正视力、眼压测量、色觉测试、眼前节生物显微镜检查、散瞳眼底检查、10-2视野测试和光谱域光学相干断层扫描。符合纳入标准且检查结果正常的患者和对照者接受了微视野计（MP）测试。首先，将所有患者与对照组进行比较。其次，根据（1）使用时间≤5年（DOU≤5）和>5年（DOU>5），（2）每日剂量≤5mg/kg/天（DD≤5）和>5mg/kg/天（DD>5），以及（3）累积剂量≤1000克（CD≤1000）和>1000克（CD>1000）将患者分为三组，这些组相互之间以及与对照组进行比较。还对MP敏感性与DOU、DD和CD之间进行了相关性分析。
7例显示视野异常的服用HCQ患者被排除，最终纳入分析的有63例患者和30名对照者。我们观察到，HCQ使用者在MP检查中仅在中央区域存在显著差异，而在旁中央或周边区域无显著差异。与对照组[89.7（83-98）dB]相比，所有患者[84（63-100）dB]以及DOU>5[84（63-99）dB]、DD>5[82（63-97）dB]和CD>1000[82（63-92）dB]亚组的中央区域MP敏感性中位数显著降低。仅在中央区域发现DD与MP敏感性之间存在统计学显著相关性（r = -0.263；p = 0.02）。
服用HCQ超过5年、每日剂量超过5mg且累积剂量超过1000克的患者，其黄斑中央区域的MP敏感性显著降低。需要进一步研究MP敏感性的长期随访变化，以确定早期视网膜毒性的临界值。
