Mitochondrial DNA A3243G variant-associated retinopathy: a meta-analysis of the clinical course of visual acuity and correlation with systemic manifestations

The mitochondrial DNA A3243G (m.3243A&gt;G) variant causes a wide spectrum of phenotypes, with pigmentary retinopathy as the most common ocular finding. We undertook this meta-analysis to investigate the clinical course of visual acuity (VA) in patients with m.3243A&gt;G variant and provide key clinical correlations with systemic manifestations. A PubMed literature search was performed and studies were selected after satisfying pre-set inclusion criteria. Demographic and clinical data, including retinal findings and systemic manifestations were recorded. Cross-sectional and linear regression analyses were used to investigate the relationship between VA and age, as well as between the age at diagnosis of retinopathy and the mean ages at diagnosis of sensorineural hearing loss or diabetes. The age and prevalence of systemic manifestations among patients with and without retinopathy were studied using <i>t-</i>tests and Mann–Whitney U-tests (performed on binarized data). Likelihood ratios were computed. The mean VA (average of both eyes) of 90 patients (72.2% female; 65/90) were collected from 18 studies published between 1990 and 2018. The baseline mean age was 45.2 years (range 17 to 92). The mean logMAR VA was 0.10 (- 0.12 to 1.39). There was a statistically significant linear correlation between the logMAR VA and age (<i>p = </i>.008). The VA of patients less than or equal to 50 years of age was significantly better than that of patients older than 50 years (0.06 vs.0.18 logMAR, <i>p</i> = .002). 67 patients (74.4%) showed a characteristic pigmentary retinopathy with a mean age at diagnosis of 47.9 years (17 to 92) and VA of 0.14 logMAR (- 0.12 to 1.24). Age at diagnosis of retinopathy was linearly correlated with age at diagnosis of hearing loss or diabetes (<i>p .001). Patients with retinopathy were more likely to have hearing loss (83.6% vs. 56.5%, <i>p = </i>.03) or diabetes (56.7% vs. 17.4%, <i>p = </i>.001) than those without retinopathy. Those with both hearing loss and diabetes had an earlier onset of retinopathy than those without (46.4 vs. 60.4 years, <i>p</i> = .01). Patients without both hearing loss and diabetes were 5.3–fold less likely to develop a retinopathy.</i> Patients with m.3243A&gt;G variant pigmentary retinopathy maintain highly functional VA until around the fifth decade of life, after which significant visual decline ensues. Patients without hearing loss and diabetes have a lower likelihood of exhibiting a retinopathy, which tends to appear about one decade after hearing loss and diabetes are diagnosed.

线粒体DNA（mitochondrial DNA）A3243G（m.3243A>G）变异可引发广泛表型谱，其中色素性视网膜病变是最常见的眼部表现。我们开展此项荟萃分析，旨在探究携带m.3243A>G变异患者的视力（visual acuity, VA）临床转归，并明确其与全身表现的关键临床关联。
通过PubMed数据库进行文献检索，筛选符合预设纳入标准的相关研究。研究人员记录了受试者的人口学特征与临床数据，包括视网膜表现及全身表现。采用横断面分析与线性回归分析，分别探究视力与年龄、视网膜病变诊断年龄与感音神经性听力损失（sensorineural hearing loss）或糖尿病的平均诊断年龄之间的关联。
针对二分类数据，采用t检验与Mann-Whitney U检验，对比伴或不伴视网膜病变患者的全身表现出现年龄与患病率，并计算似然比（likelihood ratios）。
从1990年至2018年发表的18项研究中，共收集到90例患者的平均双眼视力数据，其中女性占比72.2%（65/90）。受试者基线平均年龄为45.2岁（年龄范围17~92岁），平均对数最小分辨角（logMAR）视力为0.10（取值范围-0.12~1.39）。logMAR视力与年龄存在显著统计学线性相关（p=0.008）。≤50岁患者的视力显著优于50岁以上患者（0.06 vs 0.18 logMAR，p=0.002）。
67例患者（74.4%）出现特征性色素性视网膜病变，该类患者的视网膜病变诊断平均年龄为47.9岁（年龄范围17~92岁），平均logMAR视力为0.14（取值范围-0.12~1.24）。视网膜病变诊断年龄与听力损失或糖尿病的诊断年龄呈线性相关（p=0.001）。伴视网膜病变患者较无视网膜病变患者更易合并听力损失（83.6% vs 56.5%，p=0.03）或糖尿病（56.7% vs 17.4%，p=0.001）。同时合并听力损失与糖尿病的患者，其视网膜病变发病年龄早于未合并二者的患者（46.4岁 vs 60.4岁，p=0.01）。无听力损失与糖尿病的患者发生视网膜病变的概率仅为合并二者患者的1/5.3（即低5.3倍）。
携带m.3243A>G变异的色素性视网膜病变患者，在50岁左右仍可维持良好的视功能，此后将出现显著的视力下降。无听力损失与糖尿病的患者出现视网膜病变的概率更低，且视网膜病变通常在听力损失与糖尿病确诊约10年后出现。