Dominant Optic Atrophy Research Articles

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or ‘wolframinopathies’, exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the ‘plus’ phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells.

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy most frequently associated with OPA1 mutations. Most variants result in haploinsufficiency, and patient cells express roughly half of the normal levels of OPA1 protein. OPA1 is a mitochondrial GTPase that is essential for normal mitochondrial function. We identified and characterized STK-002, an antisense oligonucleotide (ASO) designed to prevent the incorporation of a naturally occurring alternatively spliced nonproductive exon in OPA1. STK-002 dose dependently reduced the inclusion of this exon, and increased OPA1 protein in human cells, including ADOA patient-derived fibroblasts. ADOA patient cells manifest reduced mitochondrial respiration, and treatment with STK-002 improved the parameters of mitochondrial respiratory function in these cells. Since STK-002 increases OPA1 through the wild-type allele, we assessed retinal OPA1 in wild-type cynomolgus monkeys and rabbits after intravitreal administration of STK-002 or a rabbit-specific surrogate. Increased OPA1 protein was produced in retinal tissue in both species at 4 weeks after ASO injection and persisted in monkeys at 8 weeks. STK-002 and enhanced OPA1 immunofluorescence were visualized in retinal ganglion cells of cynomolgus monkeys treated with the ASO. Cumulatively, these data support the progression of STK-002 toward the clinic as the first potential disease-modifying treatment for ADOA.

Hereditary Optic Neuropathies

Hereditary optic neuropathies are a rare disease group, and Leber's Hereditary Optic Neuropathy (LHON), Dominant Optic Atrophy (DOA) and Recessive Optic Atrophies are included in this disease group. These diseases may be isolated or accompanied by other systemic disorders. Leber's Hereditary Optic Neuropathy is the most common hereditary mitochondrial disease. Leber's Hereditary Optic neuropathy presents with acute-subacute, painless vision loss in the 2nd-3rd decade of life, and the other eye is usually affected within 6-8 weeks. Dominant Optic Atrophy is the most common hereditary optic neuropathy and causes slowly progressive, bilateral, symmetric vision loss in the first decade. Recessive optic atrophy begins at an earlier age than DOA, and nystagmus and severe vision loss are observed in these patients. Although there is no definitive treatment for hereditary optic neuropathies today, idebenone treatment and gene therapy for 11778 gene mutation are performed for LHON.

Identification of biomarkers reflecting OPA1-related Dominant Optic Atrophy severity to infer patient cohorts eligible to clinical trials

Identification of biomarkers reflecting OPA1-related Dominant Optic Atrophy severity to infer patient cohorts eligible to clinical trials

MicroRNA-181a/b modulation as possible therapeutic strategy for Autosomal Dominant Optic Atrophy

MicroRNA-181a/b modulation as possible therapeutic strategy for Autosomal Dominant Optic Atrophy

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies.

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy

From Mild Cases to Critical Cases of COVID-19: The Role of Genes in Inflammasome and Mitochondrial Dynamics

The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment. The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC). The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-κB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold). CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway.

Metabolic Deficits in the Retina of a Familial Dysautonomia Mouse Model.

Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber's hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients' serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson's, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30-P90, and dopamine levels were 25-35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.

Family Planning in Genetic Optic Atrophies in Israel, a Case Series and a Discussion of Ethical Considerations.

Patients with genetic optic atrophies must navigate all stages of life with their visual impairment, including the important milestone of family planning. Advances in genetic testing now allows physicians and affected families to consider medical help with the aim of preventing blindness through preconception, preimplantation, and perinatal methods. This case series presents 4 patients with different genetic optic atrophies (Leber hereditary optic neuropathy [LHON], autosomal dominant optic atrophy, Wolfram syndrome, and papillorenal syndrome) who were followed by the Neuro-Ophthalmology Unit at a tertiary medical center between 2010 and 2023 and were of child-bearing age. The aim of this study was to increase understanding in family planning options for patients with optic atrophies, raise awareness of the solutions available, and provide guidance for clinicians to support their patients. Advances in medicine, genetics, and medical technology allow multidisciplinary teams to assist patients in fulfilling their desire for a genetically healthy offspring. Customized solutions can be designed to meet the specific challenges posed by each type of genetic optic atrophy. The solutions proposed in this series are based on genetic testing done in the parents, which then allows to plan medical and genetic intervention individually. The solutions opted for in this series range from the decision to not have another child until PGD (Preimplantation genetic diagnosis). We describe how genetic advancements have made it possible for patients with the 4 most common hereditary optic atrophies to fulfill their wish to have children without visually threatening genetic mutations. We also review the recent literature on the penetrance of optic atrophy in OA-mutation carriers and raise 2 significant ethical considerations: the reduction of a future life to a non-life-threatening impairment and that of public expenditure for non-life-threatening conditions.

Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.

Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C>T (p.Gln621Ter) in the OPA1 Gene.

Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.

Targeting DRP1 with Mdivi-1 to correct mitochondrial abnormalities in ADOA+ syndrome.

Autosomal dominant optic atrophy plus (ADOA+) is characterized by primary optic nerve atrophy accompanied by a spectrum of degenerative neurological symptoms. Despite ongoing research, no effective treatments are currently available for this condition. Our study provided evidence for the pathogenicity of an unreported c.1780T>C variant in the OPA1 gene through patient-derived skin fibroblasts and an engineered HEK293T cell line with OPA1 downregulation. We demonstrate that OPA1 insufficiency promoted mitochondrial fragmentation and increased DRP1 expression, disrupting mitochondrial dynamics. Consequently, this disruption enhanced mitophagy and caused mitochondrial dysfunction, contributing to the ADOA+ phenotype. Notably, the Drp1 inhibitor, mitochondrial division inhibitor-1 (Mdivi-1), effectively mitigated the adverse effects of OPA1 impairment. These effects included reduced Drp1 phosphorylation, decreased mitochondrial fragmentation, and balanced mitophagy. Thus, we propose that intervening in DRP1 with Mdivi-1 could correct mitochondrial abnormalities, offering a promising therapeutic approach for managing ADOA+.

Ellipsoid Zone Reflectivity: Exploring its Potential as a Novel Non-Invasive Biomarker for Assessing Mitochondrial Function

ABSTRACT The ellipsoid zone (EZ) on macular optical coherence tomography (OCT) scans exhibits high intensity due to a high density of light-scattering mitochondria, making its reflectivity a potential marker for mitochondrial function. Here, we developed a reliable analysis tool for extracting relative EZ reflectivity and explore its potential as a biomarker in various diseases. We analysed OCT scans of patients with optic neuritis (ON), primary progressive optic neuropathy (PPON), chronic progressive external ophthalmoplegia (CPEO), dominant optic atrophy (DOA), and healthy controls. EZ reflectivity (normalised to the retina pigment epithelium (RPE) and outer nuclear layer (ONL)) was evaluated. Reliability was assessed using intraclass correlation coefficients (ICC), and group differences were analysed through multivariable linear regression, adjusting for relevant confounders. In total, 12 controls, 23 ON patients, 7 CPEO patients, 13 DOA patients, and 13 PPON patients were included. EZ/RPE20% and EZ/ONL ratios demonstrated good test–retest reliability with ICCs of 0.76 (p < .001) and 0.63 (p = .013), respectively. Multivariable regression analysis revealed that median EZ/RPE20% and EZ/ONL ratios were lower in CPEO (r = -0.12, p = .036, and r = -0.59, p = .011), DOA (r = -0.16, p = .049, and r = -0.55, p = .082), PPON (r = -0.17, p = .014, and r = -0.57, p = .037), and ON (r = -0.11, p = .013, and r = -0.42, p = .006) compared to controls, respectively. These data show that EZ reflectivity can be reliably determined from OCT scans and appears to be reduced in neuroinflammatory and mitochondrial disorders. Further validation in larger prospective cohorts is warranted, but our findings suggest that EZ reflectivity might serve as a non-invasive in-vivo biomarker for mitochondrial health.

Maculopapillary Bundle Degeneration in Optic Neuropathies.

Degeneration of the maculopapillary bundle (MPB) is a prominent feature in a spectrum of optic neuropathies. MPB-selective degeneration is seen in specific conditions, such as nutritional and toxic optic neuropathies, Leber hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA). Despite their distinct etiologies and clinical presentations, which encompass variations in age of incidence and monocular or binocular onset, these disorders share a core molecular mechanism: compromised mitochondrial homeostasis. This disruption is characterized by dysfunctions in mitochondrial metabolism, biogenesis, and protein synthesis. This article provides a comprehensive understanding of the MPB's role in optic neuropathies, emphasizing the importance of mitochondrial mechanisms in the pathogenesis of these conditions. Optical coherence tomography studies have characterized the retinal nerve fiber layer changes accompanying mitochondrial-affiliated optic neuropathies. Selective thinning of the temporal optic nerve head is preceded by thickening in early stages of these disorders which correlates with reductions in macular ganglion cell layer thinning and vascular atrophy. A recently proposed mechanism underpinning the selective atrophy of the MPB involves the positive feedback of reactive oxygen species generation as a common consequence of mitochondrial dysfunction. Additionally, new research has revealed that the MPB can undergo degeneration in the early stages of glaucoma, challenging the historically held belief that this area was not involved in this common optic neuropathy. A variety of anatomical risk factors influence the propensity of glaucomatous MPB degeneration, and cases present distinct patterns of ganglion cell degeneration that are distinct from those observed in mitochondria-associated diseases. This review synthesizes clinical and molecular research on primary MPB disorders, highlighting the commonalities and differences in their pathogenesis. 1.Temporal degeneration of optic nerve fibers accompanied by cecocentral scotoma is a hallmark of maculopapillary bundle (MPB) degeneration. 2.Mechanisms of MPB degeneration commonly implicate mitochondrial dysfunction. 3.Recent research challenges the traditional belief that the MPB is uninvolved in glaucoma by showing degeneration in the early stages of this common optic neuropathy, yet with features distinct from other MPB-selective neuropathies. 4.Reactive oxygen species generation is a mechanism linking mitochondrial mechanisms of MPB-selective optic neuropathies, but in-vivo and in-vitro studies are needed to validate this hypothesis.

Two Different Nuclear Mitochondrial DNA Mutations Associated with Retinal Abnormalities

Purpose: To report the posterior pole imaging characteristics of two patients with pathogenic nuclear mitochondrial mutations. Methods: Case reports Results: The first case, a 61-year-old patient, initially diagnosed with age-related macular degeneration, exhibited focal hyperpigmentation and increased autofluorescence in the parafoveal macula, along with geographic atrophy and mild optic nerve pallor. Optical coherence tomography (OCT) showed ellipsoid zone (EZ) attenuation, hyperreflective foci colocalizing to the hyperpigmentation, subretinal deposits, and hypertransmission defects. He was found to have a pathogenic mutation of MFN2, a gene defect associated with Charcot-Marie-Tooth disease. The second case, a 65-year-old patient presented with loss of central vision with pallor of the optic nerve. OCT imaging showed widespread loss of the interdigitation zone and EZ attenuation peripheral to the foveal region. There was thinning of the ganglion cell and nerve fiber layers. A pathogenic OPA1 mutation, the leading cause of autosomal dominant optic atrophy, was found. Both MFN2 and OPA1 produce proteins integral in mitochondrial fusion. Conclusions: The findings of these cases suggest ocular examinations may be helpful in evaluating patients with nuclear mitochondrial mutations using the near microscopic resolution of OCT. Retinal imaging may highlight structural abnormalities related to mitochondrial problems and allows direct imaging of the EZ, a layer dominated by mitochondria and a place where direct imaging of mitochondria is possible, in vivo.

Genetic underpinnings explored: OPA1 deletion and complex phenotypes on chromosome 3q29

BackgroundCopy number variations (CNVs) have emerged as significant contributors to the elusive genetic causality of inherited eye diseases. In this study, we describe a case with optic atrophy and a brain aneurysm, in which a de novo CNV 3q29 deletion was identified.Case presentationA 40-year-old female patient was referred to our department after undergoing aneurysm transcatheter arterial embolization for a brain aneurysm. She had no history of systemic diseases, except for unsatisfactory best-corrected visual acuity (BCVA) since elementary school. Electrophysiological tests confirmed the findings in retinal images, indicating optic nerve atrophy. Chromosomal microarray analysis revealed a de novo deletion spanning 960 kb on chromosome 3q29, encompassing OPA1 and six neighboring genes. Unlike previously reported deletions in this region associated with optic atrophy, neuropsychiatric disorders, and obesity, this patient displayed a unique combination of optic atrophy and a brain aneurysm. However, there is no causal relationship between the brain aneurysm and the CNV.ConclusionIn conclusion, the optic atrophy is conclusively attributed to the OPA1 deletion, and the aneurysm could be a coincidental association. The report emphasizes the likelihood of underestimating OPA1 deletions due to sequencing technology limitations. Recognizing these constraints, healthcare professionals must acknowledge these limitations and consistently search for OPA1 variants/deletions in Autosomal Dominant Optic Atrophy (ADOA) patients with negative sequencing results. This strategic approach ensures a more comprehensive exploration of copy-number variations, ultimately enhancing diagnostic precision in the field of genetic disorders.

The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.

Mitochondrial single-stranded DNA-binding protein (mtSSB) is essential for mitochondrial DNA (mtDNA) replication. Recently, several mtSSB variants have been associated with autosomal dominant mitochondrial optic atrophy and retinal dystrophy. Here, we have studied at the molecular level the functional consequences of one of the most severe mtSSB variants, R107Q. We first studied the oligomeric state of this variant and observed that the mtSSBR107Q mutant forms stable tetramers in vitro. On the other hand, we showed, using complementary single-molecule approaches, that mtSSBR107Q displays a lower intramolecular ssDNA compaction ability and a higher ssDNA dissociation rate than the WT protein. Real-time competition experiments for ssDNA-binding showed a marked advantage of mtSSBWT over mtSSBR107Q. Combined, these results show that the R107Q mutation significantly impaired the ssDNA-binding and compacting ability of mtSSB, likely by weakening mtSSB ssDNA wrapping efficiency. These features are in line with our molecular modeling of ssDNA on mtSSB showing that the R107Q mutation may destabilize local interactions and results in an electronegative spot that interrupts an ssDNA-interacting-electropositive patch, thus reducing the potential mtSSB-ssDNA interaction sites.

Short Wavelength Automated Perimetry, Standard Automated Perimetry, and Optical Coherence Tomography in Dominant Optic Atrophy.

Background: Blue-yellow axis dyschromatopsia is well-known in Autosomal Dominant Optic Atrophy (ADOA) patients, but there were no data on the correlation between retinal structure and short-wavelength automated perimetry (SWAP) values in this pathology. Methods: In this cross-sectional case-control study, we assessed the correlation between best corrected visual acuity (BCVA), standard automated perimetry (SAP), SWAP, and optical coherence tomography (OCT) parameters of 9 ADOA patients compared with healthy controls. Correlation analysis was performed between BCVA, mean deviation, pattern standard deviation (PSD), and fovea sensitivity (FS) values and the OCT thickness of each retinal layer and the peripapillary retinal nerve fiber layer (pRNFL). Results: The following significant and strong correlations were found: between BCVA and ganglion cell layer (GCL) and the global (G) pRNFL thicknesses; between SAP FS and GCL and the G-pRNFL thicknesses; between SWAP PSD and total retina, GCL, inner plexiform layer, inner nuclear layer, inner retinal layer and the temporal pRNFL thicknesses. We found a constant shorter duration of the SITA-SWAP compared with the SITA-STANDARD strategy. Conclusions: SWAP, SAP, and BCVA values provided relevant clinical information about retinal involvement in our ADOA patients. The perimetric functional parameters that seemed to correlate better with structure involvement were FS on SAP and PSD on SWAP.

Chinese expert consensus on the clinical diagnosis and treatment of autosomal dominant optic atrophy (2024)

Autosomal dominant optic atrophy (ADOA) primarily affects retinal ganglion cells and their axons, resulting in varying degrees of central vision loss from childhood. Due to the rarity of ADOA in clinical practice, Chinese ophthalmologists currently lack sufficient understanding of the disease and experience non-standardized diagnostic procedures and high clinical and genetic misdiagnosis rates. To address these issues, the Ophthalmology Group of China Alliance for Rare Diseases/Beijing Society of Rare Disease Clinical Care and Accessibility and the Neuro-ophthalmology Group of Ophthalmology Branch of Chinese Medical Association have established an expert panel to form consensus opinions based on extensive discussions. This consensus would enhance the knowledge and diagnostic capabilities of Chinese clinicians regarding ADOA and promote awareness of related treatment principles and genetic counseling.