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To compare the outcomes of rAAV2-ND4 injection in treated versus fellow eyes with Leber's hereditary optic neuropathy (LHON). The protocol was pre-registered on PROSPERO (CRD42023441669). PubMed, Ovid MEDLINE, Cochrane CENTRAL, Google Scholar, Embase, CrossRef, OpenAlex, and Web of Science were reviewed from 1990–2023. Our analysis included 358 eyes of 307 patients. Of them, 256 (83%) patients received unilateral injections while 51 (17%) received bilateral injections. The mean age was 32 years. Baseline visual acuity (VA) of unilaterally injected eyes was 1.62. At 1 year, it was 1.6 compared to 1.4 (p = 0.002) in noninjected eyes. Baseline VA of bilaterally injected eyes was 1.6 and postoperatively at 1.5 years, it became 1.3 (p = 0.003). rAAV2/2-ND4 intravitreal injections showed no major differences in terms of improving visual acuity between treated and untreated eyes of the same patient. However, larger prospective RCTs, especially concerning OCT parameters, and visual field, are recommended to provide a better understanding and comparison. [ABSTRACT FROM AUTHOR]

We report the case of a 24-year-old previously healthy man who presented with an unusual combination of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) and Leber’s hereditary optic neuropathy (LHON). Initially experiencing two episodes of painless visual acuity reduction, the patient responded well to glucocorticoid therapy, coinciding with an MOG antibody titre of 1:32. However, a subsequent third episode of painless vision loss did not improve with continued glucocorticoid treatment. Further diagnostic workup revealed a mitochondrial DNA mutation (11778 G>A), confirming the diagnosis of LHON. This unique presentation highlights the necessity of considering multiple aetiologies in cases of optic neuropathy where the cause is not immediately apparent, especially when the response to standard treatments is inconsistent. Our findings suggest that dual pathologies may coexist and should be considered in unexplained cases of optic neuropathy to facilitate appropriate clinical management. [ABSTRACT FROM AUTHOR]

Leber’s hereditary optic neuropathy (LHON) causes subacute visual loss, and, in the acute phase, the optic disc shows hyperemia, peripapillary telangiectasia, and swelling of the retinal nerve fiber layer (RNFL). Rarely, retinal hemorrhage may be present. In this study, we investigated LHON cases with retinal hemorrhage in the acute phase. Among 82 cases (164 eyes) of LHON who visited the Inoue Eye Hospital, retinal hemorrhage was observed in 5 cases (5 eyes). The age at onset was 36 (27–46) years, with 4 male cases. Mitochondrial DNA analysis revealed the presence of the m.11778G > A variant in four patients and the m.14484T > C variant in one patient. There was no medical history and no excessive smoking or alcohol consumption in any of the cases. In all cases, retinal hemorrhages were observed in the RNFL, accompanying the characteristic optic disc findings of LHON. Fluorescein angiography performed in three cases showed no leakage from the optic disc or blood vessels. While rare, the presence of retinal hemorrhage along the RNFL during the acute phase of LHON should be recognized, as it may warrant consideration of alternative diagnoses. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is one of the hereditary optic neuropathies and is principally caused by three frequent mitochondria deoxyribonucleic acid (DNA) pathogenic variants (m.11778 G>A, m.3460 G>A, and m.14484T>C). These pathogenic variants account for 90% of LHON cases, with rare pathogenic variants accounting for the remaining cases. We report the first Japanese case of LHON with the m.13051 G>A pathogenic variant, which is a rare primary pathogenic variant of LHON. A 24-year-old woman developed subacute visual loss in both eyes over several months. The best corrected visual acuity (BCVA) was 6/120 in her right eye (OD) and 6/7.5 in her left eye (OS). A relative afferent pupillary defect was not detected. Humphrey visual field testing revealed a central scotoma OD and a temporal paracentral scotoma OS. Fundus examination showed the presence of a pale optic disc OD and optic disc swelling with peripapillary microangiopathy OS. Orbital magnetic resonance imaging showed no abnormal findings. As the mitochondrial DNA gene testing demonstrated the m.13051 G>A pathogenic variant, the patient was diagnosed with LHON. Subsequently, her BCVA worsened to 6/600 in each eye, followed by a nearly plateau-like progression thereafter. This mutation has been primarily reported in Europe but has not yet been confirmed in the Asian region. This case also indicates the importance of examining the whole mitochondrial DNA gene for pathogenic variants in cases where one of the three major pathogenic variants has not been not detected. [ABSTRACT FROM AUTHOR]

A 29-year-old female with no family history presented with bilateral progressive blurred vision. Her symptoms appeared at 12-years-old and her visual acuity had since deteriorated from 0.6 to 0.2 bilaterally with decreased critical flicker frequency and bilateral central scotomas. She did not have a relative afferent pupillary defect. Fundoscopy revealed no distinct disc hyperaemia, atrophy, or peripapillary telangiectatic vessels. The retinal nerve fibre layer appeared normal on optical coherence tomography in each eye; however, loss of the interdigitation zone and the disruption of the ellipsoid zone at the fovea were observed in both eyes. Multifocal electroretinography revealed decreased amplitudes at both macula regions. Mitochondrial deoxyribonucleic acid analysis identified an m.14502T>C mutation, one of the primary mutations causing Leber's hereditary optic neuropathy (LHON). Despite the presence of a marked LHON mutation, however, she was clinically diagnosed as having an occult macular dystrophy. There have only been five previous case reports, all of which were sporadic, which detail the clinical characteristics of the m.14502T>C mutation. The m.14502T>C phenotype is somewhat consistent with that of the other major mutations, including young onset, bilateral progressive visual impairment, and a typical LHON fundus. Nevertheless, m.14502T>C alone has an extremely low penetrance and its phenotype may be minimal or subclinical, as seen in our case. Since little is known about the clinical course of the m.14502T>C mutation it may be possible that the LHON phenotype may appear in later stages of life. Moreover, m.14502T>C may function as a modifier gene, which alters the phenotype of other coexisting major LHON mutations, including penetrance and the severity of the disease, through synergistic effects. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA) genes encoding subunits of complex I in the mitochondrial respiratory chain. The most common mutations causing LHON are G11778A, G3460A and T14484C, but there are also several less common mutations. LHON presents as acute or subacute bilateral visual loss, usually affecting young males. The aim of this study was to assess the clinical symptomatology and genetic analysis of Bulgarian patients with LHON. Twenty-two patients were diagnosed with LHON based on clinical evaluation and genetic examination (17 males and 5 females); 12 of them were previously reported, while 8 males and 2 females are newly diagnosed. A full neuroophthalmologic and genetic examination was performed. Eight patients had a family history of LHON, while 14 were isolated cases. The age at onset ranged from 3 to 43 years, and visual acuity ranged from counting fingers to 0.9. Genetic testing revealed various mutations, including a rare mutation G3635A in MT-ND1 in five affected members of one pedigree and digenic inheritance of G11778A and T14484C in three individuals from a different family. A variant m.15988A > G in the mitochondrial gene MT-TP with a high level of heteroplasmy was found in one patient. In addition to the most common mutations causing LHON, our patients also had rare mutations. These results suggest that genetic analysis of the entire mtDNA sequence is recommended in cases with strong clinical suspicion of LHON, since new rare mtDNA pathogenic variants are being identified. [ABSTRACT FROM AUTHOR]

We report a case of late-onset Leber's hereditary optic neuropathy (LHON) with concurrent retinal detachment, mild retinal pigment epithelial changes, cataract and hyperintensity on fluid-attenuated inversion recovery magnetic resonance imaging affecting the entire retrobulbar visual pathway. We also documented that progression of the visual field defect correlated with retinal nerve fibre layer and ganglion cell layer-inner plexiform layer changes on optical coherence tomography. Our case provides further understanding of LHON as a disorder of the entire pre-geniculate pathways and also highlights that detailed history taking in addition to recognition of typical sequential optic disc appearance and visual field characteristics at different stages of LHON remain critical even in this era of modern imaging, autoimmune biomarkers and genetic testing. [ABSTRACT FROM AUTHOR]

In this study we have assessed the clinical and genetic characteristics of an Irish Leber's hereditary optic neuropathy (LHON) cohort and assessed for useful biomarkers of visual prognosis. We carried out a retrospective review of clinical data of patients with genetically confirmed LHON presenting to an Irish tertiary referral ophthalmic hospital. LHON diagnosis was made on classic clinical signs with genetic confirmation. Alternate diagnoses were excluded with serological investigations and neuro-imaging. Serial logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was stratified into 'on-chart' for logMAR 1.0 or better and 'off-chart' if worse than logMAR 1.0. Serial optical coherence tomography scans of the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) monitored structure. Idebenone-treated and untreated patients were contrasted. Statistical analyses were performed to assess correlations of presenting characteristics with final VA. Forty-four patients from 34 pedigrees were recruited, of which 87% were male and 75% harboured the 11778 mutation. Legal blindness status was reached in 56.8% of patients by final review (mean 74 months). Preservation of initial nasal RNFL was the best predictor of on-chart final VA. Females had worse final VA than males and patients presenting at < 20 years of age had superior final VA. Idebenone therapy (50% of cohort) yielded no statistically significant benefit to final VA, although study design precludes definitive comment on efficacy. The reported cases represent the calculated majority of LHON pedigrees in Ireland. Visual outcomes were universally poor; however, VA may not be the most appropriate outcome measure and certain patient-reported outcome measures may be of more use when assessing future LHON interventions. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurological inflammatory disorder known to attack the heavily myelinated regions of the nervous system including the optic nerves, cerebellum, brainstem and spinal cord. This review will discuss the clinical manifestations and investigations for MS and other similar neurological inflammatory disorders affecting vision, as well as the effects of MS treatments on vision. Assessment of visual pathways is critical, considering MS can involve multiple components of the visual pathway, including optic nerves, uvea, retina and occipital cortex. Optical coherence tomography is increasingly being recognised as a highly sensitive tool in detecting subclinical optic nerve changes. Magnetic resonance imaging (MRI) is critical in MS diagnosis and in predicting long-term disability. Optic neuritis in MS involves unilateral vision loss, with characteristic pain on eye movement. The visual loss in neuromyelitis optica spectrum disorder tends to be more severe with preferential altitudinal field loss, chiasmal and tract lesions are also more common. Other differential diagnoses include chronic relapsing inflammatory optic neuropathy and giant cell arteritis. Leber's hereditary optic neuropathy affects young males and visual loss tends to be painless and subacute, typically involving both optic nerves. MS lesions in the vestibulocerebellum, brainstem, thalamus and basal ganglia may lead to abnormalities of gaze, saccades, pursuit and nystagmus which can be identified on eye examination. Medial longitudinal fasciculus lesions can cause another frequent presentation of MS, internuclear ophthalmoplegia, with failure of ipsilateral eye adduction and contralateral eye abduction nystagmus. Treatments for MS include high-dose corticosteroids for acute relapses and disease-modifying medications for relapse prevention. These therapies may also have adverse effects on vision, including central serous retinopathy with corticosteroid therapy and macular oedema with fingolimod. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that leads to acute or subacute, painless, bilateral loss of vision, caused by degeneration of retinal ganglion cells that most affects men in their second or third decade of life. We describe a woman with compressive optic neuropathy with a concurrent LHON-associated mitochondrial mutation. Temporal hemifield defect connected to central scotoma and concurrent abduction limitation are diagnostic clues in identifying chiasmal compression with craniopharyngioma. This case emphasizes an awareness of the possible coexistence of compressive and hereditary optic neuropathy. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial optic neuropathies such as Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA) have been shown to produce an optic neuropathy secondary to retinal ganglion cell loss with thinning of the retinal ganglion cell complex (RGCC). Methods: We performed a retrospective analysis assessing the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL) along with the macular retinal ganglion cell-inner plexiform layer (RGC-IPL) using optical coherence tomography (OCT). We compared these changes among acute and chronic LHON, DOA, and normal healthy control patients. Results: Patients with chronic LHON exhibited statistically significant thinning of the RNFL in the superior, nasal, and inferior quadrants of the retina. In acute LHON, the RNFL was relatively thicker in all but the temporal quadrant when compared with respective quadrants in normal eyes; however, statistical significance was not achieved. In DOA, the RNFL was thinnest in the superior and inferior quadrants of the retina, measuring between acute and chronic LHON thickness values. In chronic LHON and DOA, both the pRNFL and RGC-IPL were significantly thinner in all four retinal quadrants relative to controls. Conclusions: This article represents the first comparative study of the RGCC between LHON and DOA. Our findings demonstrated significant thickness reductions in pRNFL and macular RGC-IPL in patients with LHON and DOA, with different specific patterns consistent with the general patterns of thinning classically observed. This study suggests the usefulness of the RGCC as a potential in vivo biomarker for assessing disease in patients with LHON and DOA. [ABSTRACT FROM AUTHOR]

Ethambutol is utilised in the treatment ofMycobacterium aviumandMycobacterium tuberculosisinfection. The authors report two siblings who developed the adverse effect of ethambutol-induced optic chiasmopathy, with recovery following cessation of ethambutol. Discussion explores potential genetic predisposition to development of this condition and its resolution. Ethambutol optic neuropathy (EON), Leber’s hereditary optic neuropathy (LHON), and other optic neuropathies of mitochondrial origin share a common pathophysiology. Consequently, the authors postulate treatments utilised in LHON, including vitamin B supplementation and idebenone, may have benefit in EON. This article presents concepts for further research, suggesting a potential genetic susceptibility to EON and its treatment. [ABSTRACT FROM PUBLISHER]

Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders. We report here the clinical, genetic and molecular analysis of mitochondrial DNA (mtDNA) in eight Han Chinese families carrying the known mitochondrial 11778G > A(MT-ND4) mutation. Thirty-seven (26 males/11 females) of 77 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. The penetrances were from 25% to 75%, with the average of 42%, and the age-at-onset for visual impairment varied from 10 to 25 years, with the average of 17 in these Chinese pedigrees. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroupD4j. Except the known m.11778G > A mutation, the m.11696G > A(MT-ND4) mutation caused the substitution of an isoleucine for valineat amino acid position 313, located in a predicted transmembrane region of ND4. And, it is reported that the m.11696G > A mutation was associated with LHON, and appeared to contribute to higher penetrance in these nine Chinese families than other Chinese families carrying only the m.11778G > A mutation. Therefore, the mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary LHON-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families. [ABSTRACT FROM PUBLISHER]

Optic nerve disorders lead to visual loss and can result: from multiple etiologies, including optic neuritis, anterior ischemic optic neuropathy, glaucoma, Leber's hereditary optic neuropathy and dominant optic atrophy. The recent advances in imaging technologies often supplement the history and clinical examination for identification of optic neuropathies. Correlation between the structural and functional changes in eye is important to validate these diagnostic techniques. Advancement in the understanding of disease process has led to the development of new potential therapeutic targets that may enable apt management of these conditions. Animal models play a crucial role in understanding the pathophysiology of these disorders, identifying therapeutic targets and testing prospective drugs, which are vital for providing better patient care. In this review, the authors aim to provide a clinical update to the readers about these optic neuropathies in addition to the essential role played by animal research in progressing their current state of knowledge. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to describe the clinical features and molecular findings of a unique case of Leber''s hereditary optic neuropathy (LHON)/mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) overlap syndrome presenting as nonischemic central retinal vein occlusion (CRVO). Methods: An 11-year-old Chinese girl presented with sudden onset of bilateral blurred vision. The clinical history, imaging studies, and molecular analysis results were reviewed. The PubMed and OVID databases were used for literature review. Results: Nonischemic CRVO in the subject''s right eye and tortuosity of small and medium-sized retinal arterioles in the left eye were found at initial presentation. Bilateral optic disc pallor was then noted with recovery of CRVO. Severe headache and several stroke-like episodes occurred subsequently, with elevated lactate levels in serum and cerebrospinal fluid. LHON/MELAS overlap syndrome was diagnosed, and mitochondrial DNA sequencing revealed G13513A heteroplasmic mutation. Vision was 20/30 in the right eye and 20/800 in the left eye at the last visit. Conclusions: Mitochondrial DNA G13513A mutation can cause LHON/MELAS overlap syndrome. Nonischemic CRVO is a rare manifestation of LHON/MELAS. Atypical findings in cases of LHON should raise the suspicion of overlap syndrome or other mitochondrial diseases. [ABSTRACT FROM AUTHOR]

Leber''s hereditary optic neuropathy (LHON) is an inherited condition leading to bilateral centrocaecal scotoma. Phosphodiesterase type-5 (PDE5) inhibitors such as tadalafil are widely used for male erectile dysfunction. We present a case of a middle-aged male whose LHON presented acutely following tadalafil use. It is postulated that this is due to alteration in the optic nerve head perfusion. [ABSTRACT FROM AUTHOR]

Metabolic optic neuropathies present in a very similar fashion but yet show some distinct variations. Investigations have revealed that the common pathologic basis of these optic neuropathies is a dysfunction of oxidative phosphorylation in mitochondria leading to retinal ganglion cell degeneration. This impairment can be genetic or acquired. Leber's hereditary optic neuropathy and dominant optic atrophy are the two primary inherited optic neuropathies, whereas acquired metabolic optic neuropathies can be due to toxins or nutritional deficiencies. Mitochondria are remarkable cytoplasmic organelles carrying their own DNA and are also influenced by nuclear DNA. The genetic background is pivotal in understanding the molecular mechanisms and the wide spectrum of clinical phenotypes of these disorders. Understanding the genetic, environmental and epigenetic interplays will be important for the development of therapeutic strategies aimed to protect against retinal ganglion cell death. [ABSTRACT FROM AUTHOR]

We report a case of Leber's hereditary optic neuropathy ( LHON) masquerading as optic neuritis with late visual recovery. A 28-year-old man had gradual visual loss in both eyes for two weeks. Visual acuity was 0.4 in the right eye and 0.7 in the left. Fundus examination revealed hyperaemic discs in each eye. Fluorescein angiography revealed dye leakage at both optic discs in the late phase. Static perimetry ( Humphrey 30-2) revealed bilateral relative central scotomata. Magnetic resonance imaging of the optic nerves was normal and his lumbar puncture showed normal opening pressure. He received steroid pulse therapy for three days. Nevertheless, vision in his right eye deteriorated to 0.1 one month later and left vision worsened to 0.05 six months later. Fifteen months after onset, his vision began to improve. At 21 months, his vision recovered to 0.9 R and 1.0 L. Peripheral blood DNA sequencing revealed 14484 mutation of mitochondrial DNA ( mtDNA). Visual recovery can occur in patients with Leber's hereditary optic neuropathy with mtDNA 14484 mutation. LHON could be misdiagnosed as optic neuritis in some cases. Molecular examination of mtDNA mutation can confirm the diagnosis of LHON in clinically controversial patients. We should keep in mind the diagnosis of LHON when optic neuritis shows poor response to pulse therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe clinical features and search for primary mitochondrial DNA (mtDNA) mutations in 13 unrelated Brazilian patients with Leber’s hereditary optic neuropathy (LHON). Methods: Analysis of the G11778A, G3460A, and T14484C mutations was done by polymerase chain reaction and restriction fragment length polymorphism, and mutations were confirmed by direct sequencing. Mean age of onset was 24.5 years and all cases were bilateral. Results: Sex ratio (12M:1F) and frequency of simultaneous involvement (9/13) were higher than in other studies. In nine cases there was familial recurrence: 24 male and two female relatives. Ten patients had a mutation: G11778A in six, T14484C in three and one G3460A. The frequency of patients bearing a primary mutation was lower than that described in multicentric studies but similar to that observed among Asians. A higher frequency of the T14484C mutation was detected. Conclusions: The contribution of Amerindians and Africans to the Brazilian mtDNA pool may account for differences in the type and frequency of primary LHON mutations. [ABSTRACT FROM AUTHOR]

A 14-year-old girl who was diagnosed as having Leber's hereditary optic neuropathy with the 11778 mutation in the mitochondrial DNA was followed up by investigating the visual field alteration periodically over a three-year period. She was first seen with a sudden decrease of visual acuity in the right eye. Goldmann's perimetry showed a large central scotoma in the right eye and small relative scotomas in the upper part of the left eye which was still asymptomatic. Visual acuity in the left eye, however, decreased two months later. At that time, a large absolute central scotoma was detected. The absolute central scotomas in both eyes gradually shrank to change to a relative one in one and a half years after the onset, sequentially leading to an increase of visual acuity which was finally 0.15 OD and 1.0 OS. The long-term evaluation in our case indicated that the development of visual field changes was almost identical in both eyes and that slow recovery of visual acuity was a result of the gradual shrinkage to breakthrough of central scotoma. [ABSTRACT FROM AUTHOR]