Progressive Bilateral Visual Loss Research Articles

Clinical Insights into Bardet-biedl Syndrome and Retinitis Pigmentosa: A Case Report

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by learning impairments, obesity, post-axial polydactyly, retinal dystrophy, and hypogonadism. Numerous related minor characteristics are crucial for the clinical management of BBS and can aid in the diagnosing process. In 80% of patients, sequencing known disease-causing genes can confirm the diagnosis, which is based on clinical symptoms. BBS genes encode proteins involved in cilia biogenesis and function that localize to the basal body and cilia. Defective cilia resulting from mutations partially explain the pleiotropic effects seen in BBS. We report the case of a 23-year-old patient referred to the nephrology department for progressive bilateral visual acuity loss.

Successful Treatment of Clinically Diagnosed Cancer-Associated Retinopathy with Intravitreal Dexamethasone Implant Followed by 0.18 mg Fluocinolone Implant without Systemic Immunosuppression.

To report a case of clinically diagnosed cancer-associated retinopathy (CAR) successfully treated with intravitreal corticosteroid implants without systemic immunosuppression. Case report with multimodal imaging. An 80-year-old man without known systemic malignancy presented with debilitating shimmering, hemeralopia and rapidly progressive bilateral vision loss following uncomplicated cataract surgery. Mild vitritis, extensive photoreceptor loss, mottling of retinal pigmentary epithelium (RPE), and mild vascular attenuation were found in both eyes. Full field electroretinogram (ffERG) showed severe bilateral rod-cone dysfunction. Infectious etiologies and vitreoretinal lymphoma were ruled out. During cancer workup, intravitreal corticosteroid treatment was offered. Significant anatomical improvement with reconstitution of ellipsoid zone, improved RPE irregularities and functional improvement, were observed 3 weeks after bilateral intravitreal dexamethasone implants (Ozurdex). 2 months later, patient received bilateral intravitreal 0.18mg fluocinolone acetonide implants (YUTIQ). Later, a colonic adenocarcinoma was found (pathologic stage pT3 pN0). Patient recovered well from surgery and no chemotherapy was needed. 9 months since bilateral intravitreal fluocinolone acetonide implants (11 months since bilateral intravitreal dexamethasone implants), best corrected vision maintained at 20/25-2 OD, 20/20 OS without ongoing treatments. Bilateral reconstitution of ellipsoid zones and nearly resolution of RPE irregularities remained stable. Repeat ffERG demonstrated improved cone response OS and stable diminished rod response OU. Patient reports resolution of ocular symptoms. The sustained improvements with intravitreal corticosteroid monotherapy suggest potential advantages using local therapy over systemic treatment. Long term follow-up is warranted. Further research is needed to evaluate the efficacy of using 0.18mg fluocinolone implant (YUTIQ) to treat CAR.

Optic Neuropathy Secondary to Linezolid for Multidrug-resistant Mycobacterial Tuberculosis

Abstract
 Introduction : Toxic optic neuropathy is well known side effect of medications, including linezolid in patients with MDR-TB. We present 2 cases of patients with linezolid associated ON.
 Case Illustration : A 28 year pld man (case 1) and a 50 year old woman complained bilateral progressive visual loss after long term use of linezolid (both 8 months). On initial visit, case 1 presented with 0.1 visual acuity and case 2 presented with counting finger visual acuity. Both have hyperemic optic disc. OCT showed optic disc edema. Both patients showed generalized visual field defect on the Humphrey test. We immediately stopped the linezolid treatment.
 Discussion : The exact mechanism of linezolid induced ON is still unclear. It may be caused by impaired mitochondrial function for adenosine triphosphate (ATP) synthesis within retinal nerve fiber layer. Duration of linezolid therapy affects the prognosis for linezolid ON.
 Conclusion : Both Ophthalmologist and Physicians must be aware that visual function monitoring and early recognition of toxicity linezolid. Immediate cessation of linezolid has favorable visual recovery

PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders

An 18-year-old man presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cognitive decline since early adolescence. A neurological examination disclosed spastic dysarthria, left eye divergent strabismus, bilateral ophthalmoparesis, impaired smooth pursuit, severe spastic paraparesis of the lower limbs with global brisk tendon reflexes, bilateral extensor plantar responses, and bilateral ankle clonus reflex. Bilateral dysdiadochokinesia of the upper limbs, Stewart-Holmes rebound phenomenon, bilateral dysmetria, and a bilateral abnormal finger-to-nose test were observed. Markedly reduced bilateral visual acuity (right side 20/150, left side 20/400) and moderate to severe optic atrophy were detected. Neuroimaging studies showed cerebellar atrophy and bilateral optic nerves and optic tract atrophy as the main findings. As a complicated Hereditary Spastic Paraplegia, autosomal dominant Spinocerebellar Ataxia, or inherited neurometabolic disorders were suspected, a large next-generation sequencing-based gene panel testing disclosed the heterozygous pathogenic variant c.162-1G>A in intron 1 of the PNPT1 gene. A diagnosis of PNPT1-related spastic ataxia was established. Clinicians must be aware of the possibility of PNPT1 pathogenic variants in cases of spastic ataxia and spastic paraplegias that are associated with optic atrophy and marked cognitive decline, regardless of the established family history of neurological compromise.

VIRAL RETINITISOCCURING IN IMMUNOCOMPETENTINDIVIDUAL

Retinal damage due to HSV is severe, with an extensive inflammatory reaction producing yellowish-white exudates and retinal necrosis. We report the case of a 30-year-old patient who presented with a rapidly progressive bilateral visual acuity loss Treatment with intravenous acyclovir halts the progression of retinitis in most cases. Otherwise, foscarnet and other systemic antiviral agents may be indicated.

A 48-year-old female with chronic, progressive bilateral vision loss and dyspnea.

To describe a unique case of isolated, bilateral serous retinal detachments associated with primary pulmonary arterial hypertension. Case report. A 48-year-old woman with primary pulmonary arterial hypertension presented with bilateral vision loss. She was found to have bilateral serous retinal detachments in the macula with accumulation of the fibrinous material. Optical coherence tomography demonstrated intraretinal and subretinal fluid, hyperreflective material in the subretinal space, and choroidal engorgement. Fluorescein angiography demonstrated pooling in the maculas, an area of blockage corresponding with the area of subretinal exudative material, and a petalloid pattern of leakage in the maculas without evidence of retinal vascular leakage. Her ocular symptoms improved with aggressive medical management of her pulmonary arterial hypertension with the addition of eplerenone. Primary pulmonary arterial hypertension results in chronically elevated systemic venous pressure, leading to both systemic and ocular symptoms. It is important to consider this systemic condition in the differential diagnosis of serous retinal detachments to provide adequate multidisciplinary management.

Unilateral Exophthalmia Revealing Postpartum Thrombophlebitis

Introduction: Cerebral thrombophlebitis of the peripartum is a rare entity but its occurrence is serious and can compromise the vital prognosis. The clinical picture is variable, which makes early diagnosis difficult. Patients and Methods: We report the case of a 28-year-old patient, on oral contraception for 3 years, with no previous history; who presented rapidly progressive bilateral visual acuity loss associated with headaches. The examination revealed a painless exophamia of the left eye without motor deficit, a slight chemosis with subconjunctival venous vasodilatation, associated with a bilateral papillary edema confirmed by OCT. CT scan showing a cerebral thrombophlebitis of the superior longitudinal sinus extended to the jugular vein with slight cerebral edema. The patient was immediately admitted to the intensive care unit and put on heparin therapy and additional immunological tests. Discussion: Pregnancy and postpartum increases the risk of thrombotic events. The most common cause in women of childbearing age is hypercoagulability, associated with the postpartum period, pregnancy, or oral contraceptives which is the case of our patient. Clinical symptoms are very polymorphic. The main thing is to think about it in order to make an early diagnosis. The positive diagnosis is neuroradiological. Improved diagnostic methods and consequent earlier treatment have markedly improved the prognosis of CVT in recent year. Conclusion: Postpartum cerebral venous thrombosis is a rare but serious pathology. The clinical diagnosis is not easy because of the clinical polymorphism, it is necessary to know how to think about it even in front of purely ophthalmological signs and to ask for neuro-radiological examinations to confirm it. The prognosis remains good if the diagnosis is made in time and if the treatment is started early.

Optic neuritis in lung adenocarcinoma: A challenging diagnosis

Optic neuritis with CRMP-5 IgG is a paraneoplastic inflammation of the optic nerve associated with lung cancer, mostly small-cell lung cancer. We present the case of a patient with lung adenocarcinoma who developed progressive bilateral visual loss a few months after immune-chemotherapy with pembrolizumab and after Covid-19 vaccination. Positive CRMP-5 IgG were detected in blood sample and complete work-up – including brain MRI - did not show any progression. High dose systemic corticoids were administered with transient improving, followed by intravenous immunoglobulins, methotrexate and rituximab but despite negativization of CRMP-5 IgG, the patient had a progressive visual loss.

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.

Dominant Optic Atrophy Caused by the c.1334G>A Mutation of the OPA1 Gene

Purpose: Dominant optic atrophy is one of the most common hereditary optic neuropathies, causing progressive bilateral vision loss that begins early in life. Optic atrophy 1 (OPA1) gene mutation brings about mitochondrial dysfunction, which results in clinical manifestations of dominant optic atrophy. Here, we report a case of dominant optic atrophy caused by the c.1334G>A mutation of the OPA1 gene, the first known case in Korea to our knowledge.Case summary: A 12-year-old female patient with no specific medical history or systemic symptoms visited our clinic complaining of a progressive decrease in vision in either eye. Slit-lamp microscopy, intraocular pressure, ocular motility, and pupil reflex were normal. However, her best-corrected visual acuity in both eyes was 20/100, and her color vision was reduced to 8/12 in Ishihara’s test. Fundus examination showed temporal pallor of the optic nerve head in both eyes, and a corresponding cecocentral scotoma was observed on Goldmann visual field examination. Optical coherence tomography revealed significant thinning of the peripapillary retinal fiber layer and macular ganglion cell layer in both eyes. Genetic examination confirmed the c.1334G>A mutation of the OPA1 gene.Conclusions: We report a case of dominant optic nerve atrophy caused by c.1334G>A mutation of the OPA1 gene and its clinical manifestations.

Multimodal imaging of bilateral immunogammopathy maculopathy associated to Waldenström's macroglobulinemia.

Our aim is to report a case with bilateral Waldenström's macroglobulinemia (WM) associated maculopathy, assessed with multimodal imaging including swept source optical coherence tomography (SS-OCT) and OCT-Angiography (OCT-A). Observational case report. A 61-year-old diabetic woman with history of treated WM currently in remission, presented with progressive bilateral visual loss. Best-corrected visual acuity was 20/100 in the right eye (RE) and 20/200 in the left eye (LE). Fundus examination showed bilateral microaneurysms and retinal punctuate hemorrhages and a large macular serous detachment in the LE. There was no retinal ischemia on FA nor macular dye leakage. SS-OCT showed a significant schisis-like intraretinal fluid accumulation in the RE and a large prominent macular detachment with significant subretinal fluid accumulation in the LE. Retinal and choriocapillaris vascular densities were normal on OCT-A. Our case illustrated characteristic multimodal imaging findings in WM associated maculopathy such as schisis-like intraretinal fluid accumulation and angiographically silent serous macular detachment. OCT-A could non-invasively analyze macular vascular densities layer-by-layer, without noticing any vascular anomaly.

Multimodal Retinal Imaging in Spinocerebellar Ataxia Type 1 Maculopathy

Objectives: The objective of the study was to investigate and report the multimodal ocular imaging findings associated with spinocerebellar ataxia type 1 (SCA 1) associated maculopathy. Methods: A full ophthalmologic assessment was completed in a 70-year-old male with confirmed SCA1 and noted progressive bilateral vision loss. Investigations included dilated fundus examination, full-field electroretinography, and swept-source optical coherence tomography (OCT). Results: On neurologic and ophthalmologic examination, he was found to have hypermetric saccades, horizontal nystagmus, and reduced color vision bilaterally. His best-corrected visual acuity was confirmed to be 20/80 OD and 20/100 OS at the time of consultation. Initial fundus photography was most notable for bilateral hypopigmentation of the fovea. Corresponding OCT imaging demonstrated an attenuation of the ellipsoid zone, in keeping with photoreceptor loss. Conclusion: The ocular imaging results suggest that the vision loss in the presented case occurred in the context of pigmentary macular dystrophy secondary to photoreceptor dysfunction and retinal pigment epithelial degeneration. This association offers an explanation with respect to the progressive vision loss, but further analyses would be required to determine the temporal correlation of clinical symptoms with imaging abnormalities. These findings suggest that SCA1 be considered as a potential cause for vision impairment, with possible benefits of visual assessment at the time of diagnosis.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases

BackgroundIgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentationTwo ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave’s disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.ConclusionsA high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

Bilaminar Chitosan Scaffold for Sellar Floor Repair in Transsphenoidal Surgery.

BackgroundEndoscopic endonasal transsphenoidal surgery (EETS) is a standard technique used to approach sellar tumors. It is relatively safe, minimally invasive and carries a low risk of complications. However, one of the common complications reported with this technique is CSF leakage which causes morbidity, an increase in recovery time and hospital costs. This complication usually occurs from violation of the diaphragma sellae and a defect in the structures of the sellar floor or incomplete repair. In this article we report the first case with the use of a novel bilaminar chitosan scaffold which can be potentially used in the repair of the sellar floor, primarily aiming to the bony part of this structure.Case PresentationAfter a personalized design employing a tissue engineering strategy, we reconstructed the sellar floor in a 65-year-old woman who had undergone EETS for a pituitary adenoma with progressive bilateral visual loss. To repair the bony defect of the sellar floor, we used a novel bilaminar chitosan scaffold. The patient had an unremarkable postoperative course with no evidence of CSF leak. The polymer was well tolerated without toxicity, infection or complications. After 2 years of follow up the patient remains neurologically intact, and in good endocrinological status.ConclusionThis is the first report of the use of this biomaterial and its biocompatibility in a clinical setting for the repair of the sellar floor during EETS. Our experience with chitosan bilaminar scaffold and in several preclinical studies in the literature have demonstrated good biocompatibility and effective bioengineered bone regeneration due to its excellent osteoconductive properties, this study pretends to be one landmark for further clinical research and larger case series with the use of this personalized tissue engineering materials in order to see they real efficacy to increase the surgeon armamentarium.

Potential Risk in Combined Use of Capsule Retractors and Capsular Tension Rings

The aim of this study, present a complication associated with capsular tension ring (CTR) implantation after placement of capsule retractors. A 66-year-old man presented with progressive bilateral vision loss. He had no history of ocular trauma, and previous eye surgery. In ophthalmological examination bilateral large zonular deficiency had been noted in both eyes. The remaining ocular and medical history was unremarkable. Cataract extraction with IOL placement was performed in the right eye by the help of capsule retractors and CTR. On attempted removal one of the capsule retractor, it was discovered that the CTR had passed through the retractor's distal loop. Additional gently manipulation and rotation of the CTR through the retractor’s distal loop was ended with atraumatic removal of the capsule retractor. Though capsule retractors improve challenge of weak zonules during cataract surgery, the instrument itself may cause complications and unwanted problems when combined use with CTRs.

Bilateral phacoemulsification and toric extended depth of focus intraocular lens implantation in Alport's syndromes

Alport syndrome is a hereditary disorder characterized by sensorineural deafness, renal disease, and ocular abnormalities, including anterior lenticonus with high refractive errors. We report a case of Alport's syndrome with bilateral anterior lenticonus that was submitted to phacoemulsification and toric extended depth of focus (EDOF) intraocular lens (IOL) implantation. A 49-year-old male patient presented with progressive bilateral visual loss for 10 years. His past medical history included a diagnosis of Alport's syndrome, with renal transplantation 20 years ago. The best-corrected visual acuity was 20/80 in the right eye and 20/63 in the left eye. Examination showed anterior lenticonus and anterior subcapsular opacities. Phacoemulsification and toric EDOF-IOL implantation were performed in both eyes. Capsulorhexis was challenging because of a highly elastic anterior capsule, which was aided by the use of a viscoadaptive ophthalmic viscosurgical device. The postoperative period was uneventful, with good refractive and visual outcomes.

The ying and yang of idebenone: Not too little, not too much – cell death in NQO1 deficient cells and the mouse retina

Idebenone has recently been investigated as a drug therapy for Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. Although several studies have shown that idebenone can promote vision recovery in patients with LHON, the evidence for the efficacy of idebenone is still limited. Idebenone failed to demonstrate superiority over placebo in the primary end-points of the only published randomised, double-blind, placebo-controlled trial. There appears to be a patient-specific response to idebenone with high variability in therapeutic outcomes. A recent study suggested that the cytosolic enzyme NAD(P)H: quinone acceptor oxidoreductase (NQO1) is the major enzyme involved in the activation of idebenone, and the beneficial effects of idebenone are dependent on the expression of NQO1. Here, we confirm the NQO1-dependent activity of idebenone, but we also show, for the first time, that the cytotoxicity of idebenone is linked to cellular expression of NQO1. Upon idebenone administration, cells deficient in NQO1 show a marked decrease in viability in comparison to NQO1 expressing cells, with idebenone causing ROS production and deleterious effects on ATP levels and cell viability. In addition, our data highlights that only cells expressing NQO1 can significantly activate idebenone, indicating that other proposed metabolic activation pathways, such as complex II and glycerol-3-phosphate dehydrogenase, do not play a significant role in idebenone activation. Furthermore, we provide evidence of idebenone-induced toxicity in the retina ex-vivo, which can be explained by the variation of NQO1 expression between different cell types in the mouse retina. Idebenone mediated cell rescue in the rotenone ex vivo model also indicated that this drug has a narrow therapeutic window. These findings will help to guide the development of future therapies and drug delivery strategies including intra-ocular administration. The specific dependence of idebenone activity on NQO1 may also explain the variation in patient outcomes in clinical trials.

Autoimmune retinopathy with positive anti-recoverin antibodies not associated with neoplasms: Case report

Abstract The case is presented of a non-paraneoplastic autoimmune retinopathy (AIR) with positive anti-recoverin autoantibodies. A 28-year-old woman presented with a rapidly progressive bilateral visual loss of 8 months onset. Funduscopic examination revealed diffuse fine mottled atrophic changes in both eyes. Fluorescein angiographic studies showed a pattern of mottled areas of early hyperfluorescence without leakage of dye. In the ocular coherence tomography it was observed that was a loss of external layers. The electroretinogram showed absence of rod and cone responses in the right eye, and diminished cone response associated to absence of rod response in the left eye. AIR was suspected, and empirical corticosteroid treatment was started while waiting for Western blot results, which was finally positive for recoverin, GAPDH, anti-alpha-enolase, and aldolase. The patient was able to be treated, and her visual acuity remained stable, but as soon as it was suspended, vision was completely lost in the right eye and reduced to hand movement in the left eye.

Retinopatía autoinmune con anticuerpos antirecoverina no asociado a neoplasia: a propósito de un caso

The case is presented of a non-paraneoplastic autoimmune retinopathy (AIR) with positive anti-recoverin autoantibodies.A 28-year-old woman presented with a rapidly progressive bilateral visual loss of 8 months onset. Funduscopic examination revealed diffuse fine mottled atrophic changes in both eyes. Fluorescein angiographic studies showed a pattern of mottled areas of early hyperfluorescence without leakage of dye. In the ocular coherence tomography it was observed that was a loss of external layers. The electroretinogram showed absence of rod and cone responses in the right eye, and diminished cone response associated to absence of rod response in the left eye. AIR was suspected, and empirical corticosteroid treatment was started while waiting for Western-blot results, which was finally positive for recoverin, GAPDH, anti-alpha-enolase, and aldolase. The patient was able to be treated, and her visual acuity remained stable, but as soon as it was suspended, vision was completely lost in the right eye and reduced to hand movement in the left eye.

Leber\u2019s hereditary optic neuropathy, intellectual disability and epilepsy presenting with variable penetrance associated to the m.3460G\u2009>A mutation and a heteroplasmic expansion of the microsatellite in MTRNR1 gene \u2013 case report

BackgroundLeber’s hereditary optic neuropathy (LHON) associated with mutations in mitochondrial DNA (mtDNA) typically manifests only optic nerve involvement but in some patients may develop additional neurological complications. The cause of this association is not clear.Case presentationWe present a case of a 24-year-old male with a history of subacute, painless, and rapidly progressive bilateral vision loss. We performed ophthalmological, neurological and neuropsychological investigations in the proband and his LHON family. The proband showed optic neuropathy, epilepsy, migraine, and intellectual disability; all the maternal relatives did not manifest optic neuropathy but a moderate to severe intellectual disability. Genetic screening revealed a novel association of the LHON m.3460G > A primary mutation with the m.T961delT + C(n)ins within the mitochondrial encoded 12S RNA (MTRNR1) gene which segregates with the intellectual disability through the maternal branch of the family. We also found a significant increase of mtDNA content in all the unaffected homo/heteroplasmic mutation carriers with respect to either affected or control subjects.ConclusionThis is the first case reporting the co-segregation of a mutation in MTRNR1 gene with a LHON primary mutation, which may be a risk factor of the extraocular signs complicating LHON phenotype. In addition, the data herein reported, confirmed that the key factor modulating the penetrance of optic atrophy in the family is the amount of mtDNA.