No optical coherence tomography changes in premanifest Huntington's disease mutation carriers far from disease onset

Abstract

Background: Spectral-domain optical coherence tomography (OCT) may detect retinal changes as a biomarker in neurodegenerative diseases like manifest Huntington's disease (HD). We investigate macular retinal layer thicknesses in a premanifest HD (pre-HD) cohort and healthy controls (HC).Methods: Pre-HD mutation carriers underwent standardized ratings and a preset macular OCT scan. Thickness values were determined for each sector of all macular retinal layers, the mean of all sectors and the mean of the inner ring (IR, 3 mm) after segmentation (Heyex segmentation batch). HC were retrospectively included from an existing database. The IR thickness of the ganglion cell layer (GCL), retinal nerve fiber layer (RNFL), GCL + inner plexiform layer (GCIPL), and total retina were included in the exploratory correlation analyses with paraclinical ratings and compared to HC. Results:The analyses comprised n = 24 pre-HD participants (n = 10 male, n = 14 female) and n = 38 HC (n = 14 male, n = 24 female). Retinal layer parameters did not correlate with paraclinical ratings. Expected correlations between established HD biomarkers were robust. The IR thicknesses of the GCL, GCIPL, and total retina did not differ between pre-HD and HC. The IR thickness of the RNFL was significantly higher in pre-HD participants (pre-HD: 23.22 µm (standard deviation 2.91), HC: 21.26 µm (1.90), p = .002).Discussion: In this cross-sectional cohort of genetically determined pre-HD participants, neurodegenerative features were not detected with retinal layer segmentation.Since our pre-HD collective was more than 16 years before disease onset, OCT may not be sensitive enough to detect early changes.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington’s Disease compared to healthy controls: A cross-sectional prospective study

“…The attenuated GCIPL thickness found in our study confirms prior work that identified thinning in both the ganglion cell layer and the inner plexiform layer in individuals with [41,42]. In contrast, our study focused on individuals who were genetically positive and in the prodromal or motor manifest disease stage, and therefore had a more advanced form of HD than the 2 prior which could account for the differences seen in GCIPL thickness.…”

“…HD[40]. Interestingly, GCIPL attenuation was not found by Mazur-Michałek et al and Schmid et al[41,42]. Both papers had slightly different cohorts than our study, with Mazur-Michałek et al studying asymptomatic individuals who were genetically positive for HD and Schmid et al studying both individuals who were genetically positive and in the asymptomatic or the prodromal disease stage…”

“…The attenuated GCIPL thickness found in our study confirms prior work that identified thinning in both the ganglion cell layer and the inner plexiform layer in individuals with symptomatic HD [ 40 ]. Interestingly, GCIPL attenuation was not found by Mazur- Michałek et al and Schmid et al [ 41 , 42 ]. Both papers had slightly different cohorts than our study, with Mazur-Michałek et al studying asymptomatic individuals who were genetically positive for HD and Schmid et al studying both individuals who were genetically positive and in the asymptomatic or the prodromal disease stage [ 41 , 42 ].…”

“…Interestingly, GCIPL attenuation was not found by Mazur- Michałek et al and Schmid et al [ 41 , 42 ]. Both papers had slightly different cohorts than our study, with Mazur-Michałek et al studying asymptomatic individuals who were genetically positive for HD and Schmid et al studying both individuals who were genetically positive and in the asymptomatic or the prodromal disease stage [ 41 , 42 ]. In contrast, our study focused on individuals who were genetically positive and in the prodromal or motor manifest disease stage, and therefore had a more advanced form of HD than the 2 prior which could account for the differences seen in GCIPL thickness.…”