Xeropthalmia and optic neuropathy secondary to ARFID: a case report.

BACKGROUND: Patients with avoidant/restrictive food intake disorder (ARFID) commonly present with loss of weight or faltering growth in the setting of poor nutrition. However, patients with ARFID can present with micronutrient deficiencies without weight loss. In patients with ARFID, clinicians should be vigilant for micronutrient deficiencies and their presentations. CASE PRESENTATION: We report a unique case of ARFID in a twelve-year-old girl, who developed micronutrient deficiencies and presented with acute visual loss with a preceding history of impaired night vision. Ophthalmic examination revealed xerophthalmia and bilateral optic neuropathy. Investigations showed severe Vitamin A and folate deficiencies which accounted for her clinical findings. In addition, she was also found to have low Vitamin B12, copper, and Vitamin D levels. She had a history of selective eating from a young age with a diet consisting largely of carbohydrates, with no regular intake of meat, dairy, fruit and vegetables. This was not driven by weight or body image concerns. The patient's symptoms improved significantly with appropriate vitamin replacement and continued multidisciplinary care. CONCLUSIONS: This report describes a patient with ARFID presenting with visual complaints. In this case, the selective eating behaviours resulted in xeropthalmia and optic neuropathy. Micronutrient deficiencies are uncommon in developed countries. When these deficiencies are suspected, eating disorders, such as ARFID, should be considered. Similarly, clinicians caring for patients with restrictive eating disorders including ARFID should be familiar with the clinical presentations of various micronutrient deficiencies and consider evaluation and treatment for micronutrient deficiencies when clinically indicated.

Optic nerve decompression through pterional and supraorbital approaches in the treatment of severe traumatic optic neuropathy.

To investigate the effectiveness of optic nerve decompression (OND) in the treatment of severe traumatic optic neuropathy (TON) through pterional and supraorbital approaches, and to identify the prognostic factor for postoperative visual acuity (VA) following OND. Patients with severe TON treated with OND through either pterional or supraorbital approach in our institute from September 2019 to June 2022 were retrospectively reviewed in this study. Demographic information, trauma factors, the interval between trauma and complete blindness, the interval between trauma and surgery, and the associated craniofacial traumas were recorded. Hospitalization days and the postoperative VA of patients in two groups were compared. There were 54 severe TON patients with NLP included in this study; 21 patients underwent OND through the pterional approach, and the other 33 underwent the supraorbital approach. Respectively, in groups of pterional and supraorbital approaches, the average hospitalization days were 9.8 ± 3.2 and 10.7 ± 2.9 days (p = 0.58), the mean durations of follow-up were 18.9 ± 4.3 and 20.8 ± 3.7 months (p = 0.09), and the average circumference of OND were 53.14 ± 15.89 ◦ (range 220 ◦ -278◦) and 181.70 ± 6.56◦ (range 173 ◦ -193◦) (p<0.001). The overall improvement rates of pterional and supraorbital approaches are 57.1% and 45.5% (p = 0.40), respectively. Optic canal fracture (OCF) was revealed to be significantly associated with postoperative VA in the supraorbital approach (Binary: p = 0.014, CI: 1.573-57.087; Ordinal: p = 0.003, CI: 1.517-5.503), but not in the pterional approach. In the group of supraorbital approach, patients with OFC had a higher rate of a better outcome (78.6%) than those without (21.4%). Patients with severe traumatic TON may benefit from OND through either the pterional or supraorbital approach. OCF is a potential prognostic factor for postoperative VA following OND through the supraorbital approach.

Managing intraoperative rupture of internal carotid pseudoaneurysms during endoscopic transnasal optic canal decompression: a case report.

Background: Endoscopic transnasal optic canal decompression is widely used in the treatment of traumatic optic neuropathy (TON) following head and craniofacial trauma. Intraoperative hemorrhage is a catastrophic surgical complication during optic canal decompression. Case description: We present two cases of patients with TON who suffered unexpected intra-operative massive bleeding during endoscopic transnasal optic canal decompression. After intraoperative hemostasis was achieved, emergent cerebral angiograms demonstrated the formation of internal carotid pseudoaneurysms, which were immediately embolized with coils combined with or without Onyx with balloon assistance. One of these cases was also complicated by a postoperative cerebrospinal fluid leak, which failed to be treated with lumbar drainage but was successfully repaired with endoscopic transnasal surgery. Conclusion: The intra-operative rupture of ICA pseudoaneurysm is a rare but catastrophic complication in TON patients. Intraoperative massive bleeding indicates rupture of ICA pseudoaneurysm. Postoperative emergency angiography and endovascular therapy should be arranged to evaluate and repair the cerebral vascular injury. Endoscopic trans-nasal surgery repairing CSF leaks resistant to lumbar drainage could be efficient and safe following pseudoaneurysm embolization.

Prospective assessment of peripapillary microvasculature using optical coherence tomography angiography in para-optic intracranial and sinonasal tumors treated with proton therapy.

PURPOSE: Radiation-induced optic neuropathy (RION) is rare but may lead to blindness. The mechanisms by which this occurs include endothelial and neuronal damage, but RION has been assessed very little in the case of extraocular tumors treated with high-energy proton therapy, the use of which is expanding worldwide. We assessed peripapillary microvascular changes by optical coherence tomography angiography (OCT-A) in patients undergoing high-energy proton therapy for para-optic intracranial or head and neck tumors. MATERIALS AND METHODS: In this prospective institutional review board approved study, patients receiving>40Gy_RBE maximal PBT dose to their optic nerve between 2018 and 2020 underwent quantitative OCT-A analyses. ImageJ software was used to assess changes in the peripapillary superficial vascular complex (SVC) using vascular area density (VAD), vessel length density (VLD) and fractal dimension (FDsk). Uni- and multivariate analyses were performed. RESULTS: Of 47 patients (78 eyes) with 29±6 months of follow-up (range 18-42), 29 patients (61.7%) had previously undergone surgery and 18 (32.1%) had microvascular abnormalities prior to proton therapy. Total radiotherapy dose was the most relevant factor in decreased peripapillary microvasculature. Duration of follow-up was associated with lower VAD (P=0.005) and mean retinal nerve fiber layer (RNFLm) thickness also decreased. There was no significant correlation between OCT-A changes and mean visual defect. CONCLUSION: Peripapillary microvasculature changes may occur from tumor compression or surgery and proton therapy for extraocular tumors. OCT-A may provide quantitative and mechanistic insights into RION before the occurrence of clinical symptoms.

Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

PURPOSE: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. STUDY DESIGN: A descriptive study involving four confirmed LHON patients. METHODS: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. RESULTS: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. CONCLUSION: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation.

Reversal of Sudden Blindness as a Consequence of Isolated Sphenoid Sinus Mucocele: A Case Report and Literature Review.

Mucoceles are locally invasive but benign expansive cystic lesions that can arise within paranasal sinuses. Isolated sphenoid sinus Mucoceles (SSM) are quite rare, comprising less than 1% of all paranasal sinus mucoceles. Due to the critical position and proximity of the sphenoid sinus to vital structures, SSMs can cause a multitude of symptoms and complications. We report a case of a 53-year-old man who presented with sudden vision loss and was found to have an isolated SSM. Following surgical drainage and management of the SSM, the patient had full recovery of visual acuity upon discharge.

Bilateral reversible optic neuropathy as the first sign of Waldenström macroglobulinema.

Objective: To report a case of bilateral reversible optic neuropathy as the first sign of Waldenström macroglobulinemia (WM). Methods: Observational case report. Results: A 52-year-old man had a sudden loss of vision in the left eye. Examinations revealed the presence of a serum monoclonal immunoglobulin (IgM kappa) in the serum. Even after a session of steroid pulse therapy, optic neuropathy became bilateral and then resolved almost completely after 4 months. The condition progressed to WM with multiorgan lesions years later. There was no evidence of optic neuropathy recurrence. The literature revealed two cases of monoclonal gammopathy (MG): a 64-year-old man with multiple myeloma (MM) with IgA lambda and a 51-year-old man with MM with IgG kappa. These cases have similar conditions: 1) visual reduction as an initial symptom of MG, 2) bilateral involvement, 3) no sign of central nervous system (CNS) infiltration shown by normal brain magnetic resonance images, and 4) recovery to a visual acuity of ≥1.0 bilaterally with no reoccurrence. The excessive Igs or B-cell hyperactivity may activate an autoimmune mechanism that reversibly interferes with the bilateral optic nerves. Conclusion: Bilateral optic neuropathy was the initial symptom of WM. There was no evidence of CNS infiltration; it recovered and then did not reoccur. The pathogenesis remained unknown, but two cases of MG were reported in the literature with remarkably similar conditions.

Optic nerve compression associated with visual cortex functional alteration in dysthyroid optic neuropathy: A combined orbital and brain imaging study.

AIMS: To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS: Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS: Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION: The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

Diagnostic criteria for optic neuritis in the acute and subacute phase: clinical uses and limitations.

BACKGROUND: A recent international consensus panel proposed diagnostic criteria for optic neuritis and a new classification. We aimed to investigate the clinical relevance of these diagnostic criteria and classification, in a cohort of patients hospitalized for a suspected diagnosis of optic neuritis. METHODS: We included all patients hospitalized between 2017 and 2022 in our tertiary center for (sub)acute loss of visual acuity suggestive of optic neuritis. Clinical and paraclinical criteria obtained within the first 3 months of symptoms were collected, as well as the final diagnosis which could be optic neuritis or non-optic neuritis. We constructed a contingency table comparing diagnoses based on physician experience to those based on the recently proposed criteria. The subtypes of optic neuritis based on the new classification were compared to subtypes based on the clinician experience. RESULTS: Two hundred fifty-seven patients were included in this study. Prevalence of optic neuritis in our cohort was 88.3%. Sensitivity and specificity of a correct diagnosis using the new criteria were, respectively, 99.5% and 86.7%. The proposed diagnostic criteria overdiagnosed four patients with optic neuritis and missed the diagnosis in one patient. According to the recent classification, idiopathic optic neuritis and clinical isolated syndrome were reclassified mainly as single isolated optic neuritis. CONCLUSION: In our specific cohort of patients hospitalized for acute and subacute optic neuropathy highly suspect of optic neuritis, we found that recently proposed diagnostic criteria and classification of optic neuritis are relevant for our clinical practice. Our interpretation of clinical requirement for definite and possible optic neuritis diagnosis might explain our excellent sensitivity and our high percentage of definite optic neuritis, relative to previous publications. The moderate specificity (86.7%) underlines the importance to include all contextual data in consideration for the diagnosis. The simplification of subgroups is useful, but our study highlights the complexity to find the adequate subgroup for seronegative NMOSD.

Optimised, Broad NGS Panel for Inherited Eye Diseases to Diagnose 1000 Patients in Poland.

Advances in gene therapy and genome editing give hope that new treatments will soon be available for inherited eye diseases that together affect a significant proportion of the adult population. New solutions are needed to make genetic diagnosis fast and affordable. This is the first study of such a large group of patients with inherited retinal dystrophies (IRD) and inherited optic neuropathies (ION) in the Polish population. It is based on four years of diagnostic analysis using a broad, targeted NGS approach. The results include the most common pathogenic variants, as well as 91 novel causative variants, including frameshifts in the cumbersome RPGR ORF15 region. The high frequency of the ABCA4 complex haplotype p.(Leu541Pro;Ala1038Val) was confirmed. Additionally, a deletion of exons 22-24 in USH2A, probably specific to the Polish population, was uncovered as the most frequent copy number variation. The diagnostic yield of the broad NGS panel reached 64.3% and is comparable to the results reported for genetic studies of IRD and ION performed for other populations with more extensive WES or WGS methods. A combined approach to identify genetic causes of all known diseases manifesting in the posterior eye segment appears to be the optimal choice given the currently available treatment options and advanced clinical trials.

Altered functional connectivity of the default mode network in non-arteritic anterior ischaemic optic neuropathy.

The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischaemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischaemic optic neuropathy and 31 healthy controls, matched for age, sex and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis. Compared with healthy controls, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischaemic optic neuropathy.

Vision Loss as a Presenting Symptom of Vitamin B12 Deficiency.

Nutritional optic neuropathy is a rare and often overlooked factor leading to bilateral, symmetrical, and gradual visual impairment. This condition falls within the category of metabolic neuropathies. We documented a case involving bilateral nutritional optic neuropathy attributed to pancytopenia associated with vitamin B12 deficiency. A healthy 65-year-old Indian woman reported a bilateral, progressive, painless decline in vision over the past six months. She had a history of reduced oral intake for the preceding year and denied experiencing any gastrointestinal or constitutional symptoms. Bilateral visual acuity was 1/60. Examination revealed pale optic discs with attenuated vessels in both eyes and a cup-disc ratio of 0.3. The blood analysis showed low indices and a deficiency in serum vitamin B12. Despite undergoing treatment, her vision remained impaired due to the chronic nature of the condition. This case highlights the importance of identifying visual symptoms in an elderly woman experiencing malnutrition caused by inadequate dietary habits, which leads to bilateral nutritional optic neuropathy.

A multifactorial screening model based on the Graves ophthalmopathy quality of life scores in dysthyroid optic neuropathy.

PURPOSE: To validate the Graves ophthalmopathy quality of life (GO-QOL) questionnaire in screening DON and to construct an effective model. METHODS: A total of 194 GO patients were recruited and divided into DON and non-DON (mild and moderate-to-severe) groups. Eye examinations were performed, and quality of life was assessed by the GO-QOL questionnaire. The random forest, decision tree model, receiver operator characteristic (ROC) curve, accuracy and Brier score were determined by R software. RESULTS: In GO-QOL, age, best corrected visual acuity (BCVA), exophthalmos, CAS, severity, and Gorman score were found to be factors related to visual function scores. On the appearance scale, gender, duration of GO, BCVA, exophthalmos, CAS and severity of GO were relevant. Both the visual function scores and appearance scores were significantly lower in DON groups than in non-DON groups (33.18 ± 24.54 versus 81.26 ± 17.39, 60.08 ± 24.82 versus 76.14 ± 27.56). The sensitivity, specificity, and AUC of the visual function scores were 91.1%, 81.7% and 0.939, respectively Visual function scores were used to construct a decision tree model. The sensitivity, specificity, and AUC of the model were 92.9%, 88.0% and 0.941, respectively, with an accuracy of 89.7% and a Brier score of 0.024. CONCLUSIONS: Visual function scores were qualified as a screening method for DON, with a cutoff point of 58. A multifactorial screening model based on visual function scores was constructed.

Maculopapillary Bundle Degeneration in Optic Neuropathies.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. KEY POINTS (BOX): 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.

Permanent Visual Loss as a Complication of Decompressive Surgery for the Treatment of Posterior Fossa Tumours: A Report of Two Cases.

Posterior fossa tumours are one of the most common types of solid neoplasia in paediatric patients. Although impaired vision can occur at presentation, it usually stabilises or improves after decompressive surgery. However, cases of permanent and profound visual loss have been reported following successful tumour resection, despite receiving little attention from the medical community. In this paper, we present two cases of young patients who experienced severe and permanent visual loss following uncomplicated surgery for posterior fossa tumour removal. We discuss the possible mechanism involved in the visual loss and measures to prevent such a dreadful complication.

Characterisation and Visual Outcomes of Fulminant Idiopathic Intracranial Hypertension: A Narrative Review.

Fulminant idiopathic intracranial hypertension (IIH) is a rapid vision-degrading presentation of IIH with limited published studies. This study composed a narrative review of fulminant IIH with the aim of better characterising fulminant IIH presentation and visual outcomes. SCOPUS and PubMed were searched for papers referencing IIH, benign intracranial hypertension, or pseudotumour cerebri. Abstracts were screened for rapid degradation in vision. All studies were required to meet both the modified Dandy and fulminant IIH criteria. Thirty-six studies met the inclusion criteria. Demographics, treatments, and visual outcome data were collected. Case studies made up 69% of the studies and 31% were case series. In total, 72 patients with fulminant IIH were reported, of which 23.6% were paediatric and 96% were female. Surgical intervention occurred in 85% of patients. Anaemia was present in 11% of patients and 85.7% of paediatric patients had a sixth cranial nerve palsy. In conclusion, we propose the following practice guidelines to assist in diagnosing and treating fulminant IIH patients: 1) patients who present with optic disc oedema require urgent visual field testing to evaluate for vision loss; 2) a paediatric patient presenting with a sixth cranial nerve palsy should have a comprehensive eye examination; 3) fulminant IIH can occur in patients with a normal body mass index; and 4) anaemia should be tested for in the setting of fulminant IIH. As little is known about the optimal treatment mechanisms for this presentation, multi-institutional and international collaborations will be a critical step for future research.

Gene therapy for Leber hereditary optic neuropathy.

INTRODUCTION: Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The causative mtDNA variants (the three common are m.11778 G>A/MT-ND4, m.3460 G>A/MT-ND1, and m.14484T>C/MT-ND6) by affecting complex I impair oxidative phosphorylation in retinal ganglion cells, ultimately leading to irreversible cell death and consequent functional loss. The gene therapy based on allotopic expression of a wild-type transgene carried by adeno-associated viral vectors (AVV-based) appears a promising approach in mitochondrial disease and its efficacy has been explored in several large clinical trials. AREAS COVERED: The review work employed basic concepts in mitochondrial diseases, LHON, and gene therapy procedures. Reports from completed trials in LHON (i.e. RESCUE) were reviewed and critically compared. EXPERT OPINION: New challenges, as the improvement of the contralateral untreated eye or the apparently better outcome in patients treated in later stages (6-12 months), were highlighted by the latest gene therapy trials. A better understanding of the pathogenetic mechanisms of the disease together with combined therapy (medical and gene therapy) and optimization in genetic correction approaches could improve the visual outcome of treated eyes.

Bilateral Visual Impairment following Combination Chemotherapy with Carboplatin in Patients with Small Cell Lung Cancer: A Case Report.

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.

A computational study to assess the pathogenicity of single or combinations of missense variants on respiratory complex I.

Variants found in the respiratory complex I (CI) subunit genes encoded by mitochondrial DNA can cause severe genetic diseases. However, it is difficult to establish a priori whether a single or a combination of CI variants may impact oxidative phosphorylation. Here we propose a computational approach based on coarse-grained molecular dynamics simulations aimed at investigating new CI variants. One of the primary CI variants associated with the Leber hereditary optic neuropathy (m.14484T>C/MT-ND6) was used as a test case and was investigated alone or in combination with two additional rare CI variants whose role remains uncertain. We found that the primary variant positioned in the E-channel region, which is fundamental for CI function, stiffens the enzyme dynamics. Moreover, a new mechanism for the transition between π- and α-conformation in the helix carrying the primary variant is proposed. This may have implications for the E-channel opening/closing mechanism. Finally, our findings show that one of the rare variants, located next to the primary one, further worsens the stiffening, while the other rare variant does not affect CI function. This approach may be extended to other variants candidate to exert a pathogenic impact on CI dynamics, or to investigate the interaction of multiple variants.

Orbital intramuscular hydatid cyst causing compressive optic neuropathy: a case report and literature review.

BACKGROUND: Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the orbital region is uncommon, representing less than 1% of all reported hydatid cases. This report details a unique case of an intramuscular hydatid cyst in the orbital region that led to compressive optic neuropathy. CASE PRESENTATION: A 22-year-old male from Kabul, Afghanistan presented with a five-month history of progressive proptosis in his left eye, associated with a gradual decrease in vision over the past three weeks. The left eye exhibited upward globe dystopia, ocular motility limitation, mild conjunctival injection, and chemosis. Diagnosis was achieved through imaging and histopathological examination. Treatment involves surgical removal of the cyst and prolonged albendazole therapy. The postoperative course showed significant improvement in the patient's condition and restoration of his vision. CONCLUSIONS: Despite its rarity, this case underscores the importance of awareness and knowledge of hydatid disease among physicians, especially those working in endemic areas. It emphasizes the importance of including hydatid disease in the differential diagnosis of orbital masses, particularly in endemic regions.