Purpose

To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD).

Methods

Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant.

Results

Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes.

Conclusion

This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age.

中文翻译：

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日本第二个患有Malattia Leventinese/Doyne蜂窝状视网膜营养不良的家庭

目的

描述第二个日本家族 Malattia Leventinese/Doyne 蜂窝状视网膜营养不良 (ML/DHRD) 患者的临床和遗传发现。

方法

两名患者（一名 41 岁男性先证者和他的第三个儿子）接受了全面的眼科检查，包括全视野和多焦视网膜电图 (ERG)。进行 Sanger 测序以检测EFEMP1基因变异 (p.Arg345Trp)，该变异被确定为唯一的致病性变异。

结果

基因分析显示，两名患者都携带杂合变异，但其他未受影响的家庭成员没有。尽管先证者在初次就诊时在后极表现出无数呈放射状分布的玻璃疣和良好的视力，但在 15 年的随访期间出现了双侧脉络膜新生血管 (CNV)。先证者在左眼 (LE) 中接受了 15 次玻璃体内抗血管内皮生长因子 (VEGF) 注射，在右眼 (RE) 中接受了两次注射。在 56 岁时，他的十进制最佳矫正视力在 LE 和 RE 中分别为 0.1 和 1.2。全场 ERG 显示，虽然杆和组合响应在正常幅度内，但锥体和 30-Hz 闪烁响应的幅度略有下降。多焦 ERG 显示 LE 的中枢反应减弱，RE 的时间反应减弱。在 20 岁的儿子中，多焦 ERG 显示双眼正常反应。

结论

这是首例发生双侧 CNV 且双眼均接受抗 VEGF 治疗的患者发生 ML/DHRD 的报告。虽然多灶性 ERG 表现出黄斑功能恶化，但广义光感受器功能一直保留到中年。