Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements

Abstract

PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.

Morphological and Functional Inner and Outer Retinal Layer Abnormalities in Eyes with Permanent Temporal Hemianopia from Chiasmal Compression

“…In such studies, retinal microcysts were more prominent in the parafoveal area, corresponding to the area with the largest concentration of both Müller and ganglion cells ( 61 ). Researchers ( 20 , 62 ) have suggested that vitreous traction could be associated with the occurrence of INL microcysts, but we find it an unlikely pathogenic factor, since in a previous study, the microcysts were restricted to the nasal hemiretina of eyes with temporal hemianopia and BA of the optic nerve ( 22 ), making it unlikely that the vitreous would draw only the hemiretina with severe GCL loss. In view of the importance of Müller cells for the maintenance of the retinal framework, we believe that RGC atrophy may have a tractional effect on Müller cells, resulting in increased thickness in areas with RGC damage.…”

A neurodegenerative perspective on mitochondrial optic neuropathies

“…As for LHON, macular GC-IPL thickness measurements could prove a more useful structural biomarker that correlates better with visual acuity loss compared with peripapillary RNFL values [18]. Another observation made possible by high-resolution OCT imaging is the documentation of microcystic macular changes in the inner nuclear layer of patients with LHON and DOA [17, 29]. These retinal abnormalities are not associated with leakage on fluorescein angiography and they have been attributed to focal retinal schisis induced by vitreous traction on the background of severe RNFL atrophy.…”

Pulling and Tugging on the Retina: Mechanical Impact of Glaucoma Beyond the Optic Nerve Head

“…[14][15][16] Several mechanisms have been proposed to explain the development of INL pseudo-cysts, including retinal inflammation, breakdown of the blood-retinal barrier, trans-synaptic degeneration of neurons within the INL and/or traction by the vitreous. 14,[16][17][18][19][20] However, none of these have been established, nor have any been able to account for the complete spectrum of findings observed in these cases (discussed below). 13 ).…”

“…As mentioned above, several potential mechanisms have been proposed to explain the development of microcystic macular edema. 14,[16][17][18][19][20] However, none are completely satisfactory in the context of the following considerations. First, cystoid lacunae develop within the INL only where the more proximal retinal layers (RNFL, GCL, and IPL) are thickest in healthy retina, but have undergone rapid degeneration due to loss of retinal ganglion cells and their axons.…”