Primary Optic Atrophy Research Articles

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+.

BILATERAL PRIMARY OPTIC ATROPHY IN A PATIENT WITH HYDROCEPHALUS – A RARE CASE

Objective – To report the rare ophthalmological ndings in a patient diagnosed with hydrocephalus Material And Methods – We report the case of a 2yr old female child who presented with hydrocephalus. CT Brain was done which was suggestive of gross dilatation of both the lateral ventricles and fourth ventricle and thinning of the cortex was seen. A detailed ophthalmological evaluation was done which showed reduced ocular motility, lagophthalmos and right esotropia. Fundus examination showed bilateral primary optic atrophy with blurred margins of the optic disc. The Results – clinical history, detailed ophthalmological examination and investigations suggest that hydrocephalus and thinning of the cortex led to retrograde optic atrophy in this patient. Hydrocephalus and thinning of the cort Conclusion – ex led to retrograde optic atrophy. Due to high degree of thinning of the occipital lobe caused by hydrocephalus, we do not expect the patient's visual functions to develop in future. Awareness regarding consequences of untreated cases of hydrocephalus and screening for ophthalmological signs is important. Timely intervention can prevent progression of the disease and lead to improved quality of life in such patients.

Cephalic Disorders with Neuro-Ophthalmic Manifestations

Purpose: To report three different cases of cephalic disorders with neuro-ophthalmic manifestations. Method: Descriptive case report. Case Summary Case 1: 14 years female came with Primary optic atrophy (POA) of both eyes associated with poor intelligence. MRI brain showed disproportionate dilatation of both occipital horn of lateral ventricle suggestive of Colpocephaly. Case 2: 16 years male presented with POA of eyes, horizontal jerky nystagmus and left sided hemiparesis with contracture of left hand since birth. MRI brain suggestive of Open lip Schizencephaly. Case 3: 12 years boy came with alternate exodeviation, left sided hemiparesis since birth. MRI brain suggestive of right sided Procencephalic cyst. Conclusion: Cephalic disorders caused by disturbance in development of fetal nervous system. For most cephalic disorder’s treatment is only symptomatic and supportive. Early diagnosis may ensure patient’s quality of living.

ADRENOLEUKODYTROPHY IN MOROCCAN CHILD: CASE REPORT

A boy of 10 years was admitted in our hospital for recurrent generalized seizures, spastic tetraparesis.A gradual impairment of vision and abnormal behaviors noticed for last 3 years. His family history find an uncle (motherÂ’s brother) deceaded at the age of 6 years without a stated diagnosis, examination finding revealed generalized hyperpimentation more marked on lips and finger nails.Neurogical examination find spastic tetraparesis, deep tendon reflexes were brisk and pupils were roud and reacting to light.Fundoscopic examination note bilateral primary optic atrophy, his cardiovascular, respiratory and abdominal systems were clinically normal. All routine investigations revealed normal finding exception biochemical features (very high ACTH level, Low basal cortisol), of primary adrenal failure. MRI of the head showed bilateral white matter abnormalities in parieto-occipital regions. The diagnosis of adrenoleukodystrophy was strongly suggested from the medical history, biochemical and radiological findings of brain. The purpose of our report case is to highlight this rare disease to all, because its progress can be delayed with early diagnosis and itÂ’s incidence can be reduced by genetic counseling.

Predictors of early visual outcome after endoscopic trans sphenoidal excision of pituitary adenomas

BACKGROUND: Endoscopic transsphenoidal excision has revolutionized the surgical management of pituitary macroadenoma. There had been several retrospective studies on the factors determining the visual outcome after surgical excision of pituitary adenoma, but very few prospective studies were published in this context. This is a prospective study of the factors predicting visual outcome following endoscopic transsphenoidal excision of pituitary adenoma. Various factors like age, duration of visual symptoms, the volume of the tumour, suprasellar extension, parasellar extension, type of adenoma, pituitary apoplexy, completion of excision, fundoscopic changes, and preoperative visual deficits were studied. METHODS: Single centre prospective observational study done between November 2016 to December 2018. Thirty patients with pituitary macroadenoma who underwent trans nasal endoscopic excision were studied with preoperative and postoperative visual impairment score (VIS) and the visual outcome was categorized as a good outcome if there was more than 5% improvement in VIS and as worse otherwise. Various predictors that may influence the outcome were statistically compared. RESULTS: 83.3% of patients (n=25) showed improvement in their vision at 6months follow-up. Overall visual outcome (considering both parameters visual acuity and visual field together) was dependent on suprasellar extension (P=0.01), completion of excision (P=0.004), and primary optic atrophy (P=0.018). On subgroup analysis recovery in visual acuity was significantly determined by the preoperative tumour volume(P=0.041), suprasellar extension (P=0.006), completion of excision(P=0.003), and primary optic atrophy (P=0.013). The improvement in the field of vision depended on the severity of preoperative field defects (P=0.04) and completion of excision (P=0.01). CONCLUSIONS: The factors predicting the early visual outcome were the suprasellar extension, completion of excision, preoperative field deficits, and primary optic atrophy. This study highlights the importance of early and proper intervention in pituitary adenomas managed surgically to procure the desired result.

Neuro-ophthalmic manifestations of central nervous system tuberculosis: Compilation of three diverse unique presentations

Tubercular meningitis is the most devastating form of tuberculosis. Neuro-ophthalmic involvement can manifest as cranial nerve palsies, pupil abnormalities, disc changes, like papillitis, papilloedema, or optic atrophy and choroidal tubercles. The rate and extent of recovery are strongly. Related to early diagnosis and treatment. Herein, we describe a constellation of three cases of central nervous system tuberculosis with aberrant regeneration of oculomotor nerve, optochiasmatic arachnoiditis presenting as bilateral primary optic atrophy and the last case of parietal lobe tuberculoma presenting as homonymous hemianopia, each one with its own characteristic ocular findings.

Новые возможности нейропротекторной терапии при дегенеративных и ишемических поражениях сетчатки и зрительного нерва

The presented literature review highlights the significance of the ischemia as a reason of reducing visual acuity in case of having such diseases as rhegmatogenous retinal detachment, primary open-angle glaucoma, AION and optic nerve atrophy. The expediency of prescribing “Cytoflavin” in the background of ischemia in case of neurodegenerative eye diseases is justified. The evidence of the effectiveness of this medicine in ophthalmological practice is provided.

A Case of Invasive Aspergillosis Involing Orbital Apex and Optic Nerve Sheath.

Spread of fungal infection neurally is a rare phenomenon. Hereby we report a case of fifty year old diabetic female with primary optic atrophy and aspergillosis of orbital apex and optic nerve sheath. In this case fungal debris was found in sphenoid sinus, orbital apex and optic nerve sheath. This patient had mild proptosis on left eye. This is a rare condition of fungal growth in the optic nerve sheath. Radiological investigation revealed bony erosion in posterior wall of sphenoid sinus. Functional endoscopic sinus surgery was done and sample sent for KOH mount, fungal culture and histopathological examination revealing aspergillus fumigatus and post op follow up with antifungal therapy.

Optic Chiasmatic Hypothalamic Glioma Presented as with Panhypopituitarism with Bilateral Primary Optic Atrophy

Optic chiasmatic hypothalamic gliomas are among common primary neoplasm of the optic nerve. It presents with decreased vision as well as features of hypopituitarism due to infiltration of the hypothalamus. In this case report, a young man presented with loss of libido, increased thirst, gradual loss of vision, bilateral optic atrophy and visual field defect. The MRI of sellar and paraseller region showed optic chiasmaticglioma with hypothalamic extension and biochemical parameter showed panhypopituitarism. We diagnosed this patient as a case of Optic chiasmatic hypothalamic gliomas (OCHGS) with panhypopituitarism with partial cranial diabetes insipidus with bilateral primary optic atrophy.The patient underwent surgery after adequate hormonal treatment but died due to post-operative complications
 Bangladesh Med J. 2020 Sept; 49(3) : 49-52

LGG-10. AN UNUSUAL PRESENTATION OF BILATERAL OPTIC NERVE GLIOMA IN CROUZON SYNDROME

Optic pathway gliomas (OPGs) are low grade gliomas intrinsic to the visual pathway, frequently associated with Neurofibromatosis Type 1 (NF-1). Bilateral OPGs without chiasmatic involvement are almost pathognomonic for NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month old male patient with craniosynostosis and Crouzon Syndrome, an autosomal dominant disorder caused by activating FGFR2 mutations associated with craniosynostosis and optic atrophy. The patient’s c.1032 G>A pathogenic variant in FGFR2 is a variant known to affect splicing and results in a protein that lacks part of an important domain involved in ligand binding. Although FGFR1 mutations have been implicated in low-grade glioma through MAPK activation, FGFR2 mutations have not yet been described in OPGs, although they have been described in epileptogenic low-grade gliomas and mixed neuronal-glial tumors. Our patient presented with worsening vision in the setting of known Crouzon Syndrome. An eye examination revealed bilateral primary optic atrophy. Brain and orbital MRIs demonstrated fusiform dilation and STIR hyperintensity of the intraorbital segments of the optic nerves bilaterally with normal pre-chiasmatic optic segments. There were no other radiographic or physical stigmata suggestive of NF-1. Next generation sequencing and copy number analysis from peripheral blood were negative for variants in NF1. RNA based studies for NF1 aberrations are pending. Although follow up MRI scans demonstrated stable size of his OPGs, the risk of further visual deficit was considered significant due to his pre-existing optic atrophy and poor baseline visual acuity. Therefore, he was started on vincristine and carboplatin chemotherapy according to A9952, and induction therapy has been well tolerated. To our knowledge, this is the first patient with Crouzon Syndrome who has developed bilateral optic pathway gliomas. Orbital MRIs should be considered for these patients with worsening visual acuity not explained by other causes.

A Case Report of Bilateral Primary Optic Atrophy in Children: Osteopetrosis - An Uncommon Cause

A Case Report of Bilateral Primary Optic Atrophy in Children: Osteopetrosis - An Uncommon Cause

Effectiveness of Low Vision Aids in patients with low vision attending a medical college hospital

Introduction: Low vision is defined as visual impairment despite treatment, surgery, or standard refractive correction, but with the potential to use the residual vision. The aim of the study was to explore the clinical profile of patients requiring Low Vision Aids (LVA) and assess the effectiveness, of LVA among patients with low vision. Material and Methods: Fifty patients fulfilling the criteria of low vision were recruited after obtaining informed written consent and detailed ocular evaluation was done to detect the cause of low vision. A trial of LVAs was done for near using hand-held magnifiers (+6D, +14D, +20D), stand magnifiers (+8D, +14D, +20D) and spectacle magnifiers (+6D, +10D, +14D, +20D) and visual improvement was noted. Similarly, LVAs were tried for distance using telescope 2.5X and clip-on telescope 3X. Results: The majority of the participants (72%) belonged to the upper lower class. The most common causes of low vision were heritable conditions like retinitis pigmentosa (24%), bilateral primary optic atrophy (18%), and macular dystrophies (16%). The most effective low vision aids were handheld and stand magnifiers which improved vision by one to four lines. The magnifiers were most effective in eyes with macular dystrophy, retinitis pigmentosa, and age-related macular degeneration. Conclusion: Low vision aids are potential methods of improving the residual vision in low vision patients. In the background of the high and increasing prevalence of low vision and poor awareness about low vision aids among them, efforts are necessary to rehabilitate them with affordable and accessible low vision services.

Ранні ознаки розвитку компресійної атрофії зорового нерва при базальних новоутвореннях головного мозку за даними оптичної когерентної томографії

Ранні ознаки розвитку компресійної атрофії зорового нерва при базальних новоутвореннях головного мозку за даними оптичної когерентної томографії

Pott’s Spine with Tubercular Meningitis and Primary Optic Atrophy: An Enigma with a Rare Cautionary Tale

AbstractTuberculosis of spine, known as Pott’s spine, is a significant health risk. Misdiagnosis or delayed diagnosis with lack of timely interventions lead to serious neurological complications and is associated with morbidity and mortality. We present a case of Pott’s spine who developed tubercular meningitis with decreased vision due to primary optic atrophy, to highlight the significance of thorough clinical and neuroradiological workup with instillation of prompt antitubercular therapy in patients of central nervous system tuberculosis (CNS TB). This association of Pott’s spine with decreased vision secondary to primary optic atrophy due to tubercular involvement of the second cranial nerve is very rare. Here, associated risk factors, varied clinical presentations, complications, and treatment of CNS TB are reviewed.

Photoreceptors in a mouse model of Leigh syndrome are capable of normal light-evoked signaling

Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation's severity. Primary optic nerve atrophy resulting from death of retinal ganglion cells is the most prominent ocular manifestation of mitochondrial disease. However, dysfunction of other retinal cell types has also been described, sometimes leading to a loss of photoreceptors and retinal pigment epithelium that manifests clinically as pigmentary retinopathy. A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy. It has also been reported that ndufs4-/- mice display diminished light responses at the level of photoreceptors or bipolar cells. By conducting electroretinography (ERG) recordings in live ndufs4-/- mice, we now demonstrate that this defect occurs at the level of retinal photoreceptors. We found that this deficit does not arise from retinal developmental anomalies, photoreceptor degeneration, or impaired regeneration of visual pigment. Strikingly, the impairment of ndufs4-/- photoreceptor function was not observed in ex vivo ERG recordings from isolated retinas, indicating that photoreceptors with complex I deficiency are intrinsically capable of normal signaling. The difference in electrophysiological phenotypes in vivo and ex vivo suggests that the energy deprivation associated with severe mitochondrial impairment in the outer retina renders ndufs4-/- photoreceptors unable to maintain the homeostatic conditions required to operate at their normal capacity.

PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.

ObjectiveTo identify disease‐causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy.MethodsWe performed genome‐wide sequencing, homozygosity mapping, and segregation analysis for novel disease‐causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient‐derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification.ResultsWe identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair‐bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP‐binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′‐phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization.InterpretationWe show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240

EPIDEMIOLOGY AND CAUSES OF OPTIC ATROPHY IN GENERAL OUTPATIENT DEPARTMENT OF LUMBINI EYE INSTITUTE

INTRODUCTION: Optic atrophy is usually applied to the condition of the disc following degeneration of the optic nerve. The present study was done to explore the epidemiology and causes of optic atrophy. MATERIAL AND METHODS: A cross-sectional study of 100 cases of optic atrophy patients with convenience sampling was conducted from 1 July 2012 to 23 September 2012. Clinical history was taken including demography. Visual acuity was taken, pupillary reaction tested and posterior segment examined. Optic atrophy was diagnosed by optic disc examination with slit lamp bio-microscopy with aid of 90D lens. Disc pallor with diminution of vision was used as parameter to diagnose optic atrophy. RESULTS: Out of 100 patients, male were 54%. It was bilateral in 26%. The mean age was 53.6 years (+/-18.11 yrs SD). The highest occurrence was seen in 61-70 yrs age range. Glaucoma was the most common cause of optic atrophy involving 58%. Out of 42% non-glaucomatous optic atrophy, 55% manifested primary optic atrophy, 38% secondary optic atrophy and 7% consecutive optic atrophy. The non-glaucomatous causes were trauma, optic neuritis, central retinal vein occlusion, intracranial space occupying lesions, papilloedema and in nine cases cause was unknown. Socially blind patients comprised of 37%. CONCLUSION: Optic atrophy was nearly equal in occurrence in both male and female and common above 4th decade of life. Glaucoma was commonest cause. Non-glaucomatous optic atrophy was also not uncommon and several causal factors should be considered.Journal of Universal College of Medical Sciences (2015) Vol.03 No.02 Issue 10 Page: 26-29

Primary Optic Atrophy in Osteopetrosis

Osteopetrosis is a rare disorder of defective osteoclastic resorption of bone, resulting in abnormally dense bones. Two main forms are milder adult onset autosomal dominant form and severe infantile malignant autosomal recessive form. Both types of mutations lead to disturbances of acidification needed for normal osteoclast function. We report a rare ocular finding in a rare case of malignant variety of osteopetrosis. A five month old girl child diagnosed as malignant variety of osteopetrosis with failure to thrive on fundus examination revealed chalky white optic discs with sharply demarcated borders bilaterally. Cranial neuropathies are caused due to improper bone remodeling leading to narrowing of cranial nerve foramina and compression of nerves in skull foramina. Allogeneic hematopoietic stem cell transplantation is the only treatment known to significantly alter the course of disease. *Chintan Dedhia, Nilesh Parekh, Neepa Gohil, Hetal Patel, Yogesh Parmar

Crouzon syndrome with primary optic nerve atrophy and normal brain functions: A case report

BackgroundThis report and review of literature aimed to assess an unusual case of Crouzon syndrome characterized by distinctive disfigurement of craniofacial skeletal and soft tissue structures with primary optic nerve atropy. MethodsWe present a case of a 12-year-old girl with Crouzon syndrome displaying classic facial abnormalities with reduced vision and hearing loss. ConclusionCrouzon syndrome should be managed as early as possible as it results in airway obstruction, decreased vision, mental retardation and poor cosmetic appearance.

Paraganglioma of Right Cervical Plexus–A Case Report

Head and neck paragangliomas (HNPs) and pheochromocytomas are rare tumors. Catecholamine secreting tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic ganglia are referred to as pheochromocytomas and extra adrenal catecholamine secreting paragangliomas (extra adrenal pheochromocytomas) respectively. The distinction between pheochromocytoma and paraganglioma is an important one because of implications for associated neoplasms, risk for malignancy, and genetic testing. Paragangliomas are rare tumors of the head and neck and are of diagnostic challenge. We report a case of 55year old male who had a neck swelling, cough with expectoration, which on extensive evaluation revealed to be Paraganglioma with primary optic atrophy.