Bilateral Loss Of Central Vision Research Articles

What OPA1 models teach us about potential therapy

Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, affecting approximately 1 in 25 000 people. DOA has an insidious onset in early childhood. It presents typically with bilateral central painless vision loss, dyschromatopsia, and optic disc pallor due to gradual retinal ganglion cell (RGC) loss and optic nerve degeneration. 60%–70% of genetically confirmed DOA cases are associated with variants in OPA1. OPA1 is an ubiquitously expressed GTPase that regulates mitochondrial homeostasis through coordination of inner membrane fusion, maintenance of cristae structure, and maintenance of bioenergetic output. Over 250 known pathogenic variants in OPA1 have been reported, with missense variants within the GTPase domain associated with an increased susceptibility to developing DOA plus (DOA+), a multisystemic syndromic form of the disease with extraocular features, including sensorineural hearing loss and ataxia. Current therapeutic options to treat DOA are limited. Idebenone has been shown to protect against visual loss in Leber's hereditary optic neuropathy (LHON). In DOA off ‐label retrospective series show some promise in some patients.Animal models for OPA1 DOA, have been reported, including Drosophila, C elegans, Danio rerio and mouse models. They have cast light on some potential therapeutic modalities. Despite limitations, murine models of DOA are currently indispensable for understanding pathophysiology of disease, drug testing and development. They replicate many symptoms and signs of human disease. However, there are caveats. Chemically induced Complex I deficits are very toxic. Genetic models of mitochondrial mutation affect protein integrity and function and can cause severe pathologies. This is made more problematic if there is a need for aging the mouse to bring out the full phenotype. We shall review the mouse models and describe some features that aid or our understanding of pathophysiological mechanisms. Our research has characterized the earliest morphological changes as a progressive loss of synapses, dendrite retraction and RGC remodelling and loss of connectivity. In the DOA mouse Opa1+/− mouse (B6;C3‐Opa1Q285STOP), heterozygous Opa1+/− mice develop visual defects, on psychophysics (optokinetic response) and electrophysiology (VEP, PhNR), consistent with RGC dysfunction. There is depressed mitochondrial Complex I and IV activity. Visible structural changes and disrupted axon morphology in the optic nerve are seen. We have carried out a randomized, placebo‐controlled trial of the benzoquinone idebenone in our ADOA mouse, which revealed a limited therapeutic effect on RGC dendropathy and visual function.It is apparent that there are large differences between the rodent and primate visual system. The fovea of the retina, a critical component for central vision is one of the only primate‐specific components of the mammalian nervous system and is thus, not found in rodent. For these reasons, there is a strong case to use human cells. We shall review data on induced human pluripotent stem cell (hiPSC) with OPA1 mutation, with or without differentiation to RGCs, as models, and on CRISPRCas9 correction of patient‐derived OPA1 iPSC lines.

Generation of an iPSC line (RMCGENi020-A) from a patient with Stargardt disease harboring the recurrent intronic ABCA4 variant c.4253+43G>A

Pathogenic variants in ABCA4 are associated with Stargardt disease (STGD1), an autosomal recessive macular dystrophy characterized by bilateral central vision loss due to a progressive degeneration of retinal cells. An induced pluripotent stem cell (iPSC) line was generated from late-onset STGD1 patient-derived fibroblasts harboring bi-allelic ABCA4 variants by lentivirus-induced reprogramming. The obtained iPSC line (RMCGENi020-A) showed pluripotent features after the reprogramming process. The generation of this iPSC line facilitates its use to differentiate it into relevant retinal-like cell models, with the aim to adequately evaluate the effects of the ABCA4 variants.

Leber Optic Neuropathy and Low Vision Rehabilitation: A Case Report

Leber’s Hereditary Optic Neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction; which leads to a bilateral and painless loss of central vision. Unfortunately at this time, there is no proven treatment to prevent or reverse this optic neuropathy. Therefore, individualized low vision rehabilitation services and assistive devices are essential to help people with LHON regain their independence and quality of life. We highlight through a case study the importance of psychic support as well as the impact of low vision rehabilitation on a young man with LHON.

A Rare Case of Ocular Syphilis With Bilateral Central Visual Loss in a Young Man Who Was Negative for HIV

A Rare Case of Ocular Syphilis With Bilateral Central Visual Loss in a Young Man Who Was Negative for HIV

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber's Hereditary Opic Neuropathy.

Leber's Hereditary Optic Neuropathy (LHON) is the most common primary mitochondrial DNA disorder. It is characterized by bilateral severe central subacute vision loss due to specific loss of Retinal Ganglion Cells and their axons. Historically, treatment options have been quite limited, but ongoing clinical trials show promise, with significant advances being made in the testing of free radical scavengers and gene therapy. In this review, we summarize management strategies and rational of treatment based on current insights from molecular research. This includes preventative recommendations for unaffected genetic carriers, current medical and supportive treatments for those affected, and emerging evidence for future potential therapeutics.

Oculomotor changes following learned use of an eccentric retinal locus

People with bilateral central vision loss sometimes develop a new point of oculomotor reference called a preferred retinal locus (PRL) that is used for fixating and planning saccadic eye movements. How individuals develop and learn to effectively use a PRL is still debated; in particular, the time course of learning to plan saccades using a PRL and learning to stabilize peripheral fixation at the desired location. Here we address knowledge limitations through research describing how eye movements change as a person learns to adopt an eccentric retinal locus. Using a gaze-contingent, eye tracking-guided paradigm to simulate central vision loss, 40 participants developed a PRL by engaging in an oculomotor and visual recognition task. After 12 training sessions, significant improvements were observed in six eye movement metrics addressing different aspects involved in learning to use a PRL: first saccade landing dispersion, saccadic re-referencing, saccadic precision, saccadic latency, percentage of useful trials, and fixation stability. Importantly, our analyses allowed separate examination of the stability of target fixation separately from the dispersion and precision of the landing location of saccades. These measures explained 50% of the across-subject variance in accuracy. Fixation stability and saccadic precision showed a strong, positive correlation. Although there was no statistically significant difference in rate of learning, individuals did tend to learn saccadic precision faster than fixation stability. Saccadic precision was also more associated with accuracy than fixation stability for the behavioral task. This suggests effective intervention strategies in low vision should address both fixation stability and saccadic precision.

Activation of lesion projection zone in primary visual cortex is dependent on bilateral central vision loss in patients with end-stage glaucoma.

To investigate activation of the lesion projection zone (LPZ) in the primary visual cortex during end-stage glaucoma using functional magnetic resonance imaging (fMRI), as well as the relationship between fMRI responses and clinical data. Twelve subjects with bilateral end-stage glaucoma (group A), 12 with unilateral end-stage glaucoma (group B) and 12 healthy controls (group C) were enrolled. fMRI was performed under two testing stimuli conditions: passive viewing of a full-field flickering checkerboard and active viewing of a one-back task with scene images. In fMRI analysis, the primary visual cortex was divided into six regions of interest (ROIs). The beta values of the six ROIs were compared across the three groups using one-way analysis of variance under two viewing conditions. Associations between the fMRI beta value and clinical data including multifocal electroretinogram (mfERG), microperimeter-1 and optical coherence tomography were analysed by Spearman correlation. The beta values for ROIs 1-3 representing the LPZ were significantly different between the three groups under active viewing conditions, whereas no significant changes were detected under passive viewing. In group A, there were significant differences between all six ROIs for the two viewing conditions, while no significant differences were found in groups B and C. In group A, the P-wave amplitudes of the mfERG was significantly correlated with the beta values of ROIs 1 and 2 under active viewing. In addition, the P-wave latencies of the mfERG were significantly correlated with the beta values for ROIs 2-5. No associations were found between fMRI beta values and clinical data in groups B and C. Activation of the LPZ in the primary visual cortex was observed in patients with bilateral end-stage glaucoma under active viewing conditions. These changes were correlated with residual retinal function.

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study

BackgroundLeber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center.MethodsFrom the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201–339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine.ResultsWe analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5–82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5–7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05).ConclusionsThe high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON.

Stargardt Disease

Stargardt disease is a slowly progressing macular dystrophy with an onset of disease most commonly in children and young adults. Numerous genes have been found to be associated with this disease, with variants in the retina specific ATP- binding cassette transporter (ABCA4) gene being most common. Each variant may have distinct clinical features, however, patients generally experience bilateral central vision loss and poor visual acuity ranging from 20/70 to 20/200. Diagnosis is often made through clinical presentation and may be assisted by fluorescein angiography (FA), spectral domain optical coherence tomography (OCT), fundus autofluorescence (FAF) or electrophysiological assessment. Currently, there are multiple classification systems of Stargardt disease that include Fishman STGD classification system, groupings due to electroretinography (ERG) findings, and types based on FAF imaging. Though there are currently no clinically proven treatments for Stargardt disease, physicians often recommend patients avoid direct sunlight, smoking cigarettes, and excessive intake of vitamin A. Potential treatments currently under investigation include strategies using gene replacement therapy, stem cell therapy, and pharmacologic agents. The purpose of this paper is to review the current knowledge of the genetics, classifications, and treatments of Stargardt disease, while underscoring the need for further research in potential treatment routes.

Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells.

Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterized by the preferential loss of retinal ganglion cells (RGCs), resulting in optic nerve degeneration and progressive bilateral central vision loss. More than 60% of genetically confirmed patients with DOA carry variants in the nuclear OPA1 gene, which encodes for a ubiquitously expressed, mitochondrial GTPase protein. OPA1 has diverse functions within the mitochondrial network, facilitating inner membrane fusion and cristae modelling, regulating mitochondrial DNA maintenance and coordinating mitochondrial bioenergetics. There are currently no licensed disease-modifying therapies for DOA and the disease mechanisms driving RGC degeneration are poorly understood. Here, we describe the generation of isogenic, heterozygous OPA1 null induced pluripotent stem cell (iPSC) (OPA1+/−) through clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing of a control cell line, in conjunction with the generation of DOA patient-derived iPSC carrying OPA1 variants, namely, the c.2708_2711delTTAG variant (DOA iPSC), and previously reported missense variant iPSC line (c.1334G>A, DOA plus [DOA]+ iPSC) and CRISPR/Cas9 corrected controls. A two-dimensional (2D) differentiation protocol was used to study the effect of OPA1 variants on iPSC-RGC differentiation and mitochondrial function. OPA1+/−, DOA and DOA+ iPSC showed no differentiation deficit compared to control iPSC lines, exhibiting comparable expression of all relevant markers at each stage of differentiation. OPA1+/− and OPA1 variant iPSC-RGCs exhibited impaired mitochondrial homeostasis, with reduced bioenergetic output and compromised mitochondrial DNA maintenance. These data highlight mitochondrial deficits associated with OPA1 dysfunction in human iPSC-RGCs, and establish a platform to study disease mechanisms that contribute to RGC loss in DOA, as well as potential therapeutic interventions.

A Case of Bilateral Pseudo Papilledema Revealing a Leber’s Hereditary Optic Neuropathy

Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disease caused by mutations in mitochondrial DNA affecting the respiratory complex I and leading to the death of retinal ganglion cells (RGCs) [1]. It is characterized by sudden onset and usually severe bilateral loss of central vision, predominantly in young men [2]. The risk of vision loss is 50% among men and 10% among women who carry LHON primary mutations in the mitochondrial DNA [3]. We report an atypic case of LHON in a young 11 years old girl.

Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease

To describe the longitudinal progression and phenotypic association of bilateral foveomacular vitelliform lesions in the setting of ABCA4 disease. Case report and cross-sectional cohort study. Nineteen patients with confirmed ABCA4 disease exhibiting an optical gap phenotype. Multimodal retinal imaging across multiple visits included autofluorescence imaging, spectral-domain OCT (SD-OCT), and OCT angiography. Electro-oculogram (EOG) and full-field electroretinogram testing results were analyzed. Exome sequencing was performed for diagnostic confirmation and the verification of other variations. Light-peak-to-dark-trough ratio (Arden ratio) on EOG; thickness and en face maps of various retinal layers on SD-OCT; area measurements on 488- and 787-nm autofluorescence images; and the presence of variation in vitelliform-associated genes identified using exome sequencing. A 25-year-old White man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid. The result of EOG testing was inconsistent with bestrophinopathy (Arden ratio= 1.62), and no generalized rod or cone dysfunction was detected on full-field electroretinogram. Exome sequencing identified the pathogenic variants c.5882G>A (p.(Gly1961Glu)) and c.4139C>T (p.(Pro1380Leu)) in ABCA4 and no other vitelliform-associated genes. Significant thinning and abnormal reflectivity of photoreceptor-attributable layers as well as near-infrared autofluorescence abnormalities were found in lesion-adjacent areas. Complete resorption of the vitelliform fluid occurred after 30 months, after which the optical gap lesions exhibited an enlarged and "cavitated" appearance. Phenotypic screening for additional cases from a large ABCA4 disease database (n= 602) identified 18 additional patients at various stages of optical gap lesion formation, most of whom harbored the c.5882G>A (p.(Gly1961Glu)) variant (P < 0.001), although none had apparent vitelliform fluid. At least 5 of the 18 (31.6%) patients exhibited optical gap lesions with the distinct "cavitated" appearance, whereas the lesions remained unperturbed in the other patients over the course of examination. Foveomacular vitelliform deposition is a mechanistically congruent but rare manifestation of ABCA4 disease. Specifically, this disease phenotype may be clinically associated with the c.5882G>A (p.(Gly1961Glu)) allele and optical gap lesions.

Retinal Circular RNA hsa_circ_0087207 Expression Promotes Apoptotic Cell Death in Induced Pluripotent Stem Cell-Derived Leber's Hereditary Optic Neuropathy-like Models.

Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.

Teaching NeuroImage: Rapid Identification of Infectious Optic Neuritis by Next-Generation Sequencing.

A 52-year-old, HIV-negative woman presented with one year of bilateral painless central vision loss that worsened over 3 months. A medical examination revealed Argyll Robertson pupil (i.e., accommodates but does not react to light). Single-read next-generation sequencing (NGS) of the CSF identified 89 sequence reads corresponding to Treponema, elevated CSF protein, pleocytosis, negative antiaquaporin-4, antimyelin oligodendrocyte glycoprotein antibody levels, retinal nerve fiber layer thinning, and bilateral nerve sheath enhancement (Figures 1–2). The patient received penicillin and oral prednisolone, which improved her vision. Infectious causes of optic neuritis are complex (Table).1,2 NGS is an emerging method with the potential to rapidly identify atypical optic neuritis.

NI-19 A case of Leber’s hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri

BACKGROUND: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The cranial magnetic resonance imaging (MRI) of LHON patients varies from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. CASE REPORT: We report a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2’-deoxyguanosine positivity, suggesting the presence of oxidative stress. CONCLUSION: LHON is extremely difficult to diagnose unless we suspect or know the disease. The present case brings attention not only to LHON but other mtDNA mutated diseases that need to be considered with diffuse white matter changes or GC.

Exploration of dynamic text presentations in bilateral central vision loss.

Dynamic text presentation methods may improve reading ability in patients with central vision loss (CVL) by eliminating the need for accurate eye movements. We compared rapid serial visual presentation (RSVP) and horizontal scrolling text presentation (scrolling) on reading rate and reading acuity in CVL observers and normally-sighted controls with simulated CVL (simCVL). CVL observers' (n=11) central scotomas and preferred retinal loci (PRL) for each eye were determined with MAIA microperimetry and fixation analysis. SimCVL controls (n=16) used 4° inferior eccentric viewing, enforced with an Eyelink eye-tracker. Observers read aloud 4-word phrases randomly drawn from the MNREAD sentences. Six font sizes (0.50-1.30logMAR) were tested with the better near acuity eye and both eyes of CVL observers. Three font sizes (0.50-1.00logMAR) were tested binocularly in simCVL controls. Text presentation duration of each word for RSVP or drift speed for scrolling was varied to determine reading rate, defined as 50% of words read correctly. In a subset of CVL observers (n=7), relationships between PRL eccentricity, reading threshold and rate were explored. SimCVL controls demonstrated significantly faster reading rates for RSVP than scrolling text (p<0.0001), and there was a significant main effect of font size (p<0.0001). CVL patients demonstrated no significant differences in binocular reading rate between font sizes (p=0.12) and text presentation (p=0.25). Similar results were seen under monocular conditions. Readingacuity for RSVP and scrolling worsened with increasing PRL eccentricity (μ=4.5°, p=0.07). RSVP reading rate decreased significantly with increasing eccentricity (p=0.02). Consistent with previous work, reading acuity worsened with increasing PRL eccentricity. RSVP and scrolling text presentations significantly affected reading rate in simCVL, but not in CVL observers, suggesting that simCVL results may not generalise to pathological CVL.

Impact of living with a bilateral central vision loss due to geographic atrophy—qualitative study

ObjectiveGeographic atrophy (GA), a type of dry age-related macular degeneration, affects vision as central vision loss (CVL). The challenges faced due to bilateral CVL in activities of daily living and...

Stargardt disease: Multimodal imaging: A review.

Stargardt disease (STGD1) is an autosomal recessive retinal dystrophy, characterised by bilateral progressive central vision loss and subretinal deposition of lipofuscin‐like substances. Recent advances in molecular diagnosis and therapeutic options are complemented by the increasing recognition of new multimodal imaging biomarkers that may predict genotype and disease progression. Unique non‐invasive imaging features of STDG1 are useful for gene variant interpretation and may even provide insight into the underlying molecular pathophysiology. In addition, pathognomonic imaging features of STGD1 have been used to train neural networks to improve time efficiency in lesion segmentation and disease progression measurements. This review will discuss the role of key imaging modalities, correlate imaging signs across varied STGD1 presentations and illustrate the use of multimodal imaging as an outcome measure in determining the efficacy of emerging STGD1 specific therapies.

Decreased Volume of Lateral and Medial Geniculate Nuclei in Patients with LHON Disease-7 Tesla MRI Study.

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder leading to severe and bilateral loss of central vision, with a young male predilection. In recent years, multiple studies examined structural abnormalities in visual white matter tracts such as the optic tract and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect grey matter parts of the visual pathway. This study aimed at improving our understanding of morphometric changes in the lateral (LGN) and medial (MGN) geniculate nuclei and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. A quantitative analysis of the LGN and MGN volume was performed for all individuals. Additionally, morphometric results of LGN and MGN were correlated with variables covering selected aspects of the clinical picture of LHON. In comparison with healthy controls (HC), LHON participants showed a significantly decreased volume of the right LGN and the right MGN. Nevertheless, the volume of the right LGN was strongly correlated with the averaged thickness value of the right retinal nerve fiber layer (RNFL). The abnormalities in the volume of the LHON patients’ thalamic nuclei indicate that the disease can cause changes not only in the white matter areas constituting visual tracts but also in the grey matter structures. Furthermore, the correlation between the changes in the LGN volume and the RNFL, as well as the right optic nerve surface area located proximally to the eyeball, suggest some associations between the atrophy of these structures. However, to fully confirm this observation, longitudinal studies should be conducted.