Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
Centre for Eye Research Australia, Royal Victorian Eye & Ear Hospital, Melbourne, Australia; and Ophthalmology, University of Melbourne, Department of Surgery, Melbourne, Australia.
Ophthalmology. 2017 Mar;124(3):303-309. doi: 10.1016/j.ophtha.2016.11.011. Epub 2016 Dec 16.
To assess the difference in severity of disease in primary open-angle glaucoma (POAG) patients with a Myocilin (MYOC) disease-causing variant who presented through normal clinical pathways (Clinical cases) versus those who were examined following genetic testing (Genetic cases).
Retrospective clinical and molecular study.
Seventy-three MYOC mutation carriers identified through the Australian and New Zealand Registry of Advanced Glaucoma.
Individuals were classified based on how they first presented to an ophthalmologist: Clinical cases were referred by their general practitioner or optometrist, and Genetic cases were referred following positive results from genetic testing for the previously identified familial MYOC variant (cascade genetic testing). All cases were then sub-classified into 4 groups (unaffected, glaucoma suspect, glaucoma, advanced glaucoma) according to the severity of disease at the time of their first examination by an ophthalmologist.
Glaucoma clinical parameters and age at presentation.
At their first examination, 83% of Genetic cases were unaffected and 17% were glaucoma suspect, whereas among Clinical cases 44% were glaucoma suspect, 28% had glaucoma, and 28% had advanced glaucoma. Genetic cases were significantly younger at presentation than Clinical cases (40.6±12.5 vs. 47.5±16.7 years; P = 0.018). The mean highest intraocular pressure (32.2±9.7 vs. 17.6±3.6 mmHg; P < 0.001), cup-to-disc ratio (0.65±0.27 vs. 0.48±0.13; P = 0.006), and mean deviation on visual field testing (-10.0±10.3 vs. -1.2±1.2; P < 0.001) were all significantly worse in Clinical cases compared with Genetic cases. Individuals with common MYOC p.Gln368Ter variant were further analyzed separately to account for the phenotypic variability of different disease-causing variants. All findings remained significant after adjusting for the common MYOC p.Gln368Ter variant.
Our findings demonstrated that MYOC cascade genetic testing for POAG allows identification of at-risk individuals at an early stage or even before signs of glaucoma are present. To our knowledge, this is the first study to demonstrate the clinical utility of predictive genetic testing for MYOC glaucoma.
评估通过常规临床途径就诊的原发性开角型青光眼（POAG）携带有致病性 Myocilin（MYOC）突变的患者（临床病例）与通过遗传检测就诊的患者（遗传病例）之间疾病严重程度的差异。
回顾性临床和分子研究。
通过澳大利亚和新西兰高级青光眼登记处确定的 73 名 MYOC 突变携带者。
根据他们首次就诊于眼科医生的方式对个体进行分类：临床病例由他们的全科医生或验光师转诊，遗传病例在先前确定的家族性 MYOC 变体（级联遗传检测）的遗传检测结果阳性后转诊。所有病例随后根据眼科医生首次检查时的疾病严重程度进一步细分为 4 组（无影响、青光眼疑似、青光眼、晚期青光眼）。
青光眼临床参数和就诊年龄。
在首次检查时，83%的遗传病例无影响，17%为青光眼疑似，而在临床病例中，44%为青光眼疑似，28%为青光眼，28%为晚期青光眼。遗传病例的就诊年龄明显小于临床病例（40.6±12.5 岁比 47.5±16.7 岁；P=0.018）。遗传病例的最高眼内压（32.2±9.7mmHg 比 17.6±3.6mmHg；P<0.001）、杯盘比（0.65±0.27 比 0.48±0.13；P=0.006）和视野检测的平均偏差值（-10.0±10.3dB 比-1.2±1.2dB；P<0.001）均明显差于临床病例。对常见的 MYOC p.Gln368Ter 变体进一步进行了单独分析，以解释不同致病变体的表型变异性。调整常见的 MYOC p.Gln368Ter 变体后，所有发现仍然具有统计学意义。
我们的研究结果表明，针对 POAG 的 MYOC 级联遗传检测可在早期甚至在出现青光眼迹象之前识别出高危个体。据我们所知，这是第一项证明 MYOC 青光眼预测性遗传检测临床实用性的研究。
