UCL Institute of Ophthalmology, London, EC1V 9EL, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, EC1V 2PD, UK.
Eye (Lond). 2024 Apr;38(5):853-862. doi: 10.1038/s41433-023-02791-7. Epub 2023 Oct 28.
Bietti Crystalline Dystrophy (BCD) is an autosomal recessive progressive retinal disease caused by mutations in CYP4V2. We have characterised the natural history including structural and functional measures to identify potential outcome metrics for future clinical trials.
Molecularly-confirmed BCD patients with biallelic variants in CYP4V2 were retrospectively identified from Moorfields Eye Hospital (UK). Clinical details including results of molecular genetic testing, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (OCT) scans were extracted. From OCT scans, ellipsoid zone (EZ) measures, foveal thickness of the whole retina, outer retina and choroid were measured. Age-related changes of clinical parameters were assessed with linear mixed models.
Twenty-eight BCD patients were identified, with median age at baseline of 37 years (interquartile range [IQR]: 30-49.5). Median follow-up was 7.7 years (IQR: 3.4-14.5). Most patients (41.7%) showed chorioretinal atrophy at baseline. All OCT parameters showed significant age-related loss (p < 0.05), with EZ measures and choroidal thickness displaying the most rapid degeneration (2.3-3.3% per year vs 0.6-1.5% per year). Median BCVA was 0.2 LogMAR (IQR: 0-0.5) at baseline and showed small age-related loss ( + 0.016 LogMAR per year, p = 0.0019). Patients exhibited substantial phenotypic variability.
BCD presents between age 25 and 40, and slowly progresses to an advanced chorioretinal atrophy and vision loss by age 60. BCVA may be preserved until late, and is seemingly poorly representative of disease progression. OCT parameters capturing EZ and choroid changes may afford more suitable trial outcome measures.
Bietti 结晶状营养不良（BCD）是一种常染色体隐性进行性视网膜疾病，由 CYP4V2 中的突变引起。我们已经对其自然病史进行了描述，包括结构和功能测量，以确定未来临床试验的潜在结局指标。
从 Moorfields Eye Hospital（英国）回顾性确定了 CYP4V2 中存在双等位基因突变的分子确诊 BCD 患者。提取了临床详细信息，包括分子遗传学检测结果、最佳矫正视力（BCVA）和光谱域光学相干断层扫描（OCT）扫描结果。从 OCT 扫描中，测量了椭圆体带（EZ）测量值、整个视网膜、外视网膜和脉络膜的中心凹厚度。使用线性混合模型评估临床参数的年龄相关性变化。
确定了 28 名 BCD 患者，基线时的中位年龄为 37 岁（四分位距 [IQR]：30-49.5）。中位随访时间为 7.7 年（IQR：3.4-14.5）。大多数患者（41.7%）在基线时有脉络膜视网膜萎缩。所有 OCT 参数均显示出显著的年龄相关性损失（p<0.05），EZ 测量值和脉络膜厚度显示出最快的退化速度（每年 2.3-3.3% vs 每年 0.6-1.5%）。基线时的中位 BCVA 为 0.2 LogMAR（IQR：0-0.5），且年龄相关性损失较小（每年增加 0.016 LogMAR，p=0.0019）。患者表现出明显的表型变异性。
BCD 在 25 至 40 岁之间发病，并在 60 岁时缓慢进展为晚期脉络膜视网膜萎缩和视力丧失。BCVA 可能会保留到很晚，并且似乎与疾病进展相关性较差。OCT 参数可捕获 EZ 和脉络膜变化，可能提供更适合的试验结局指标。
