Barboni Piero, Savini Giacomo, Feuer William J, Budenz Donald L, Carbonelli Michele, Chicani Filipe, Ramos Carolina Do V F, Salomao Solange R, Negri Annamaria De, Parisi Vincenzo, Carelli Valerio, Sadun Alfredo A
2 Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna - Italy.
Eur J Ophthalmol. 2012 Nov-Dec;22(6):985-91. doi: 10.5301/ejo.5000154. Epub 2012 May 4.
Recent investigations suggested that unaffected carriers of Leber hereditary optic neuropathy (LHON) may show subclinical visual alterations. Structural changes have also been detected by optical coherence tomography (OCT), which revealed a temporal thickening of the retinal nerve fiber layer (RNFL). These changes may reflect compensatory effects such as mitochondria accumulation within the RNFL axons. This study aimed to investigate whether the RNFL of LHON carriers shows greater than expected thickness variations, which may reflect transient subclinical changes, over the course of years.
Using Stratus OCT, the RNFL thickness was measured yearly from 2005 to 2008 in 24 Brazilian LHON carriers, all with homoplasmic 11778/ND4 mtDNA mutation. An Italian sample of 20 healthy subjects served as a control. Data were compared also to a previously published sample (n=59) of glaucomatous eyes.
The LHON carriers showed test-retest standard deviations that were larger than normal controls in the temporal (p=0.004), superior (p<0.0001), and inferior quadrants (p=0.019). Compared to the glaucoma cases, no statistical differences were observed.
The RNFL thickness in LHON carriers, when measured at different time points, has higher variability than in normal subjects. Transitory RNFL swelling may be caused either by compensatory mechanisms (increased mitochondrial biogenesis) or by axonal stasis preceding decompensation of retinal ganglion cells. In both situations, these changes may represent the origin of the visual alterations previously detected in LHON carriers. Alternatively, increased variability of RNFL thickness may be influenced by the LHON microangiopathy, as retinal blood vessels contribute to the OCT RNFL thickness measurements.
近期研究表明，Leber遗传性视神经病变（LHON）的未患病携带者可能存在亚临床视觉改变。光学相干断层扫描（OCT）也检测到了结构变化，显示视网膜神经纤维层（RNFL）颞侧增厚。这些变化可能反映了诸如RNFL轴突内线粒体积累等代偿效应。本研究旨在调查LHON携带者的RNFL在数年过程中是否显示出大于预期的厚度变化，这可能反映短暂的亚临床变化。
使用Stratus OCT，在2005年至2008年期间每年对24名巴西LHON携带者的RNFL厚度进行测量，所有携带者均为纯合子11778/ND4线粒体DNA突变。选取20名意大利健康受试者作为对照。数据还与之前发表的青光眼患者样本（n = 59）进行了比较。
LHON携带者在颞侧（p = 0.004）、上方（p < 0.0001）和下方象限（p = 0.019）的重测标准差大于正常对照组。与青光眼病例相比，未观察到统计学差异。
在不同时间点测量时，LHON携带者的RNFL厚度变异性高于正常受试者。短暂的RNFL肿胀可能是由代偿机制（线粒体生物合成增加）或视网膜神经节细胞失代偿前的轴突停滞引起的。在这两种情况下，这些变化可能代表了之前在LHON携带者中检测到的视觉改变的起源。或者，RNFL厚度变异性增加可能受LHON微血管病变影响，因为视网膜血管会影响OCT对RNFL厚度的测量。
