Is retina affected in Huntington’s disease? Is optical coherence tomography a good biomarker?

Aim of the study Comparative cross-sectional study of retinal parameters in Huntington’s disease and their evaluation as marker of disease progression. Clinical rationale for the study Huntington’s disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. Materials and methods This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington’s disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. Results HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. Conclusions The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington’s disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington’s disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. Clinical implications Current retinal parameters are not appropriate for monitoring HD disease progression

Změny sítnice se nepodílí na vzniku vizuálních halucinací u Parkinsonovy choroby

Parkinson’s disease (PD) is characterized by motor and nonmotor symptoms. Nonmotor symptoms include primarily visual hallucinations (VH). The aim of our study was to establish whether patients with PD and visual hallucinations (PDH+) have structural changes of retina detected by an optical coherence tomography (OCT) in comparison with PD patients without visual hallucinations (PDH−). We examined 52 PD patients (18 with VH, 34 without VH) and 15 age and sex matched healthy controls. Retinal nerve fiber layer (RNFL) thickness and macular thickness and volume were assessed by OCT. Functional impairment of retina was assessed using 2.5% contrast sensitivity test. For OCT outcomes we analyzed 15 PDH+ and 15 PDH− subjects matched for age, gender, and PD duration. For contrast sensitivity we analyzed 8 pairs of patients matched for age, gender, and visual acuity. There was no significant difference in RNFL thickness and macular thickness and macular volume between 15 PDH+ and 15 PDH− subjects, and also between a group of 44 PD patients (both PDH+ and PDH−) and 15 age and gender matched healthy controls. No significant difference was found for 2.5% contrast sensitivity test values between PDH+ and PDH− subjects. Therefore we conclude that functional and structural changes in retina play no role in genesis of VH in PD.Parkinsonova nemoc (PD) je charakterizována motorickými a nemotorickými příznaky. Mezi nemotorické příznaky patří především zrakové halucinace (VH). Cílem naší studie bylo zjistit, zda pacienti s PD a vizuálními halucinacemi (PDH +) mají strukturální změny sítnice detekované optickou koherentní tomografií (OCT), ve srovnání s pacienty s Parkinsonovou nemocí bez vizuální halucinace (PDH-). Vyšetřili jsme 52 PD pacientů (18 s VH, 34 bez VH) a 15 pacientů kontrolní skupiny. Vrstva nervových vláken (RNFL), tloušťka, makulární tloušťka a objem byly hodnoceny pomocí OCT. Funkční poškození sítnice bylo hodnocena za použití 2,5% testu citlivosti kontrastu. Výsledky jsme analyzovali pro 15 PDH + a 15 PDH- odpovídajících věkem, pohlavím a trváním PD. Pro kontrastní citlivost jsme analyzovali 8 párů pacientů odpovídajících věkem, pohlavím a zrakovou ostrostí. Nebyl žádný významný rozdíl v tloušťce RNFL a makulární tloušťce a makulárním objemu mezi 15 PDH + a 15 PDH-, jakož i mezi skupinou 44 pacientů s PD (jak PDH + a PDH-) a 15 zdravých osob. Žádný významný rozdíl byl nalezen ani pro 2,5% hodnoty kontrastní citlivosti testů mezi PDH + a PDH-. Proto jsme došli k závěru, že funkční a strukturální změny v sítnici nehrají žádnou roli při vzniku VH u PD

Is retina affected in Huntington's disease? Is optical coherence tomography a good biomarker?

Aim of the studyComparative cross-sectional study of retinal parameters in Huntington's disease and their evaluation as marker of disease progression.Clinical rationale for the studyHuntington's disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted.Materials and methodsThis is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington's disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure.ResultsHD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology.ConclusionsThe results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington's disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington's disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test.Clinical implicationsCurrent retinal parameters are not appropriate for monitoring HD disease progression

NovelOPA1missense mutation in a family with optic atrophy and severe widespread neurological disorder

Purpose:  To identify the underlying molecular genetic cause in a Czech family with optic atrophy, deafness, ptosis, ophthalmoplegia, polyneuropathy and ataxia transmitted as an autosomal dominant trait. Methods:  Ophthalmological and neurological examination followed by molecular genetic analyses. Results:  Seven family members were clinically affected. There was a variable but progressive visual, hearing and neurological disability across the family as a whole. The majority of subjects presented with impairment of visual function and a variable degree of ptosis and/or ophthalmoplegia from the first to the third decade of life. Deafness, neuropathy and ataxia appeared later, in the third and fourth decade. Migraine, tachycardia, intention tremor, nystagmus and cervical dystonia were observed in isolated individuals. A significant overall feature was the high level of neurological disability leading to 3 of 4 members being unable to walk or stand unaided before the age of 60 years. A novel missense mutation c.1345A>C (p.Thr449Pro) in OPA1 segregating with the disease phenotype over three generations was detected. In silico analysis supported pathogenicity of the identified sequence variant. Conclusion:  Our work expands the spectrum of mutation in OPA1, which may lead to severe multisystem neurological disorder. The molecular genetic cause of dominant optic atrophy in the Czech population is reported for the first time. We propose that regular cardiac follow-up in patients diagnosed with dominant optic atrophy and widespread neurological disease should be considered