Search Results (19)

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs. Full article

Introduction. Leber hereditary optic neuropathy (LHON) is a condition characterized by bilateral acute or subacute vision loss in seemingly healthy individuals. Depending on the disease stage and initial presentation, it is often diagnosed as optic neuritis. Elevated levels of endogenous and exogenous glucocorticoids have been associated with the onset of central serous chorioretinopathy (CSCR). In our patient, CSCR developed after only three days of pulse corticosteroid therapy, prescribed due to initial presentation as bilateral optic neuritis (papillitis). Objective. Through our case report, we aimed to highlight that CSCR can develop after the initiation of pulse corticosteroid therapy in a patient with LHON and to propose choroidal thickness as a potential contributing factor for this complication. Case Presentation. A 27-year-old male patient presented with painless subacute vision loss in both eyes. The decline in vision developed gradually over 20 days, prior to the patient’s referral to the UKCS Eye Disease Clinic for further examination and treatment, and was not accompanied by pain during eye movements. Initial investigations upon admission to the clinic established the diagnosis of optic neuritis. Consequently, pulse corticosteroid therapy was administered. Three days after the initiation of intravenous methylprednisolone, the patient developed bilateral central serous chorioretinopathy. After cessation of therapy, there was a rapid resolution of choroidopathy, but no improvement in visual acuity, prompting genetic testing. Subsequent laboratory results revealed a positive test for the LHON mutation m.3460 G>A (MT-ND1). Conclusions. LHON is often misdiagnosed as optic neuritis, as upon initial presentation the optic nerve disk often does not exhibit the apparent characteristics of LHON. Numerous studies have documented the development of central serous chorioretinopathy following corticosteroid treatment, though none have reported the onset of CSCR after only three days of pulse corticosteroid therapy. Increased choroidal thickness is a characteristic of the acute phase of LHON and may be associated with the development of CSCR in our patient. Full article

Background: Central and branch retinal artery occlusion (CRAO and BRAO) are critical causes of acute vision loss, predominantly affecting older adults with systemic vascular pathology. These occlusions typically result from embolic events, leading to partial or complete retinal ischemia. Methods: This retrospective case series report details of our 10-year experience using the 1064 nm Nd:YAG laser for Transluminal Nd:YAG Embolysis (TYE) in order to lyse visible emboli within the retinal arteries. Results: We conducted a retrospective case series involving 18 patients treated by TYE for different retinal arteries occlusions between 2014 and 2024. TYE effectively restored blood flow in the occluded arteries, with variable but generally favorable visual outcomes. Our article highlights significant clinical and interventional aspects of three treated patients: a BRAO case with multiple transluminal emboli, a case of double BRAO and a CRAO case. We also report the successful use of TYE for intraluminal lysing of an embolus located outside the optic disc. The procedures were well-tolerated, with minor complications such as preretinal or vitreous hemorrhages resolving spontaneously. Conclusions: TYE is a minimally invasive therapeutic option for retinal artery occlusion with visible emboli, particularly when intervention occurs shortly after the onset of symptoms. Compared to observation, TYE can improve visual outcomes and reduce the risk of permanent vision loss, presenting a significant advancement in the management of this ophthalmic emergency. The worldwide experience with TYE is continuously increasing. Further research with larger cohorts is recommended to validate these results and refine the treatment protocol. Full article

Glaucoma is one of the world’s leading causes of irreversible vision loss. It is often asymptomatic until it reaches an advanced stage, which can have a significant impact on patients’ daily lives. This paper describes the case of a 50-year-old female patient who presented with acute onset of ocular pain, photophobia, and loss of visual acuity in her right eye (RE). The patient’s medical history includes congenital cataracts, surgical aphakia, nystagmus, strabismus, amblyopia, and secondary glaucoma. Ophthalmological examination showed BCVA RE-hand movement, left eye (LE)—0.08 with an intraocular pressure (IOP) of 30 mmHg in RE and 16 mmHg in LE. Biomicroscopic examination of RE showed corneal graft, epithelial and endothelial edema, endothelial precipitates, corneal neovascularization, aphakia, and Ahmed valve superotemporally. Despite maximal topical and systemic treatment, Ahmed valve, and trabeculectomy, secondary glaucoma in the right eye remained refractory. Reimplantation of an Ahmed valve was performed. This resulted in a favorable outcome with increased visual acuity and controlled intraocular pressure. The combination of aphakia, penetrating keratoplasty, and secondary glaucoma is a challenge for any surgeon. It is important that both the perioperative risks and the possible complications are carefully assessed in each patient, especially if associated pathology is present. Full article

Background and Objectives: This study aims to investigate the potential association between the COVID-19 pandemic and a new presentation of central serous chorioretinopathy (CSCR). Materials and Methods: A retrospective analysis was conducted, comparing the incidence of new-onset CSCR cases among ophthalmology patients in a regional medical facility in southern Israel between two distinct periods: the COVID-19 pandemic era in Israel, which occurred from 27 February 2020 to 20 December 2020, and the non-pandemic period from calendar years 2018 to 2021, excluding the specific epidemic phase mentioned. Disease severity was evaluated based on recovery time, visual acuity loss, and central macular thickness via OCT. Results: Over the four-year period, 35 new cases of CSCR were recorded. During the COVID-19 pandemic, 17 new cases (0.005% per population) were identified, compared with 18 new cases (0.002% per population) in the preceding three years. The odds ratio for acute CSCR during the pandemic was 2.83 (95% CI, 1.46–5.50) with a p-value of 0.02. CSCR cases during the pandemic seemed to exhibit worse clinical characteristics, though not statistically significant. Additionally, 22.2% of the COVID-19 pandemic group had confirmed COVID-19 cases, which was statistically significantly higher than the general population’s reported cases (6%). Conclusion: The study revealed a statistically significant increase of over 2.5 times in acute CSCR incidence during the COVID-19 pandemic compared with non-pandemic periods. The findings suggest that the pandemic’s stressful changes may have unintended consequences on the occurrence of CSCR, highlighting the importance of mental health support and psychoeducation for affected patients. Full article

Acute optic neuritis (AON) is a common cause of sudden visual loss in young patients. Because of the risk of demyelinating disease, patients affected by unilateral or bilateral optic neuritis should be evaluated and treated accordingly. Despite advancements in imaging of the brain and retina, misdiagnosis of AON is not uncommon. Indeed, some acute disorders of the retina have the potential to mimic AON and their prompt diagnosis may avoid unnecessary neurologic investigation, psychological stress to the patient, and delays in treatment. This review describes uncommon retinal disorders presenting with sudden-onset visual loss and absent or subtle funduscopic manifestation that can mimic AON. Multimodal retinal imaging is essential in detecting these conditions and in their differential diagnosis. It behooves neurologists and general ophthalmologists to be aware of these entities and be familiar with multimodal imaging of the retina. Full article

This paper presents a literature review and a case of an 83-year-old otherwise healthy female patient with a history of recent syncope, a sudden-onset right-sided temporal headache, diplopia, and vision loss. An exam revealed right-sided upper eyelid ptosis, myosis, vision loss, ophthalmoplegia, and a positive relative afferent pupillary defect on the right eye. CT showed sphenoid sinus opacification, eroded lateral sinus wall, Vidian canal, disease extension to the posterior ethmoid air cells, orbital apex, medial orbital wall, and pterygopalatine fossa. An orbital apex syndrome (Jacod’s syndrome), Horner syndrome, and pterygopalatine fossa infection were diagnosed due to the acute invasive fungal sinusitis developed from a sphenoid sinus fungal ball. The patient was treated with antimicrobial therapy and transnasal endoscopic surgery twice to decompress the orbital apex, drain the abscess and obtain specimens for analysis. The right-sided ptosis, visual loss, ophthalmoplegia, and headache resolved entirely. No immune or comorbid diseases were identified, microbiological and histopathological analyses were negative, and MRI could not be performed on the presented patient. For that reason, the diagnostic procedure was non-standard. Nevertheless, the treatment outcome of this vision and life-threatening disease was satisfactory. Treating the fungal ball in an older or immunocompromised patient is essential to prevent invasive fungal rhinosinusitis and fatal complications. Full article

Moraxella species are Gram-negative coccobacilli that typically colonize the flora of the human upper respiratory tract and have low pathogenic potential. There are limited case reports implicating the organisms as the cause of endocarditis, bacteremia, septic arthritis, ocular infection, and meningitis. In cases of keratitis and conjunctivitis, Moraxella nonliquefaciens is not commonly isolated from the ocular surface. We present a case of a diabetic patient who developed late-onset bleb-related endophthalmitis caused by M. nonliquefaciens 4 years after glaucoma filtering surgery. Within one day, the patient presented with an acutely fulminant course with sudden visual loss, redness, and ocular pain. Appropriate antibiotic treatment and early vitrectomy resulted in a favorable final visual acuity of 20/100, which was his vision prior to infection. The use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass spectrometry (MALDI-TOF MS) enabled the rapid identification of the organism. Endophthalmitis caused by M. nonliquefaciens should be considered in patients who underwent glaucoma filtering surgery with antifibrotic agents. Full article

Background: Neuro-ophthalmic manifestations after vaccines are rare, with optic neuritis (ON) being the most common presentation. Patients with vaccine-related ON are similar to those with idiopathic ON. The temporal relationship between vaccination against and the occurrence of ON is vital. Here, we report a case of bilateral ON after the administration of the ChAdOx1-S nCoV-19 SARS-CoV-2 vaccine. Case: A 49-year-old healthy Asian female presented with sudden onset of bilateral blurred vision within 2 days. She complained of photophobia and extraocular pain upon movement over 3 days. Upon examination, her best corrected visual acuity (BCVA) was 20/30 in the right eye and 20/200 in the left eye. Anterior segment findings were unremarkable, with normal intraocular pressure. Fundoscopic examination revealed bilateral disc edema with vessel engorgement. Visual field examination revealed profound visual field defect in both eyes. She denied any trauma, use of new medication or medical history. She had received the ChAdOx1 nCoV-19 SARS-CoV-2 vaccine 14 days prior. Under suspicion of vaccine-related optic neuritis, she was given intravenous methylprednisolone 1 gm/day for 3 days, shifting to oral prednisolone under gradual tapering for 2 weeks. Conclusions: Typically presenting with sudden-onset visual decline and extraocular pain during movement, acute ON is generally idiopathic. Bilateral ON is rare, but quick identification is important because it can potentially lead to permanent loss of vision if left untreated. Vaccination-induced ON is even rarer but not difficult to treat. However, such patients require further evaluation and long-term follow-up because they may be prone to other neurological disorders in the future. Full article

Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation. It is characterized by acute and subacute visual loss predominantly affecting young men. The mtDNA mutation is transmitted to all maternal lineages. However, only approximately 50% of men and 10% of women harboring a pathogenic mtDNA mutation develop optic neuropathy, reflecting both the incomplete penetrance and its unexplained male prevalence, where over 80% of patients are male. Nuclear modifier genes have been presumed to affect the penetrance of LHON. With conventional genetic methods, prior studies have failed to solve the underlying pathogenesis. Whole exome sequencing (WES) is a new molecular technique for sequencing the protein-coding region of all genes in a whole genome. We performed WES from five families with 17 members. These samples were divided into the proband group (probands with acute onset of LHON, n = 7) and control group (carriers including mother and relative carriers with mtDNSA 11778 mutation, without clinical manifestation of LHON, n = 10). Through whole exome analysis, we found that many mitochondria related (MT-related) nuclear genes have high percentage of variants in either the proband group or control group. The MT genes with a difference over 0.3 of mutation percentage between the proband and control groups include AK4, NSUN4, RDH13, COQ3, and FAHD1. In addition, the pathway analysis revealed that these genes were associated with cofactor metabolism pathways. Family-based analysis showed that several candidate MT genes including METAP1D (c.41G > T), ACACB (c.1029del), ME3 (c.972G > C), NIPSNAP3B (c.280G > C, c.476C > G), and NSUN4 (c.4A > G) were involved in the penetrance of LHON. A GWAS (genome wide association study) was performed, which found that ADGRG5 (Chr16:575620A:G), POLE4 (Chr2:7495872T:G), ERMAP (Chr1:4283044A:G), PIGR (Chr1:2069357C:T;2069358G:A), CDC42BPB (Chr14:102949A:G), PROK1 (Chr1:1104562A:G), BCAN (Chr 1:1566582C:T), and NES (Chr1:1566698A:G,1566705T:C, 1566707T:C) may be involved. The incomplete penetrance and male prevalence are still the major unexplained issues in LHON. Through whole exome analysis, we found several MT genes with a high percentage of variants were involved in a family-based analysis. Pathway analysis suggested a difference in the mutation burden of MT genes underlining the biosynthesis and metabolism pathways. In addition, the GWAS analysis also revealed several candidate nuclear modifier genes. The new technology of WES contributes to provide a highly efficient candidate gene screening function in molecular genetics. Full article

Acute idiopathic blind spot enlargement syndrome (AIBSES) is characterized by unilateral visual field loss in the blind spot area, acute onset photopsia, and funduscopically few or no optic disc changes. AIBSES predominantly affects young adults and is often misdiagnosed as optic neuritis because of low awareness. Optical coherence tomography (OCT) has become the gold standard in diagnosing AIBSES as a disease of the outer retina. In our case series, we present three consecutive patients with AIBSES followed prospectively with and without steroid therapy. The patients, aged 25 to 27 years, presented in our neuroophthalmology department between 2020 and 2021. We report their disease course and management and discuss therapeutic options, as no well-established procedures exist. Common pitfalls and diagnostic errors are analysed. Two women and one man showed unilateral acute-onset photopsia and blind spot enlargement on perimetry without visual acuity reduction. Spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany) revealed marked peripapillary changes in the ellipsoid zone and autofluorescence in all patients, corresponding to faint blurring of the optic disc margin. Characteristically, there was no P100 latency delay in the visual evoked potential in any of the patients. Two patients received weight-adapted oral prednisolone, which was gradually tapered over six to eight weeks. Two patients showed full recovery of their symptoms at six and seven months after onset, while mild defect healing was seen in one treated patient after 12 months. Follow-up OCT showed restoration of the outer retinal layers 6–12 months after disease onset. Careful history taking and an unprejudiced ophthalmological workup helps in diagnosing AIBSES in young adults with unilateral acute visual field defects. While its etiology is still unclear, accurate diagnosis of AIBSES can be made with peripapillary OCT. In our cases, the disease course of AIBSES was much better than its reputation. Early corticosteroid treatment may support outer retinal reorganisation, which can be followed with OCT in accordance with visual field restoration. This should be addressed in a prospective study. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or impaired consciousness. Depending upon the patient’s age at the onset of COVID-19 and other factors, up to ~35% of all elderly COVID-19 patients develop a mild-to-severe encephalopathy due to complications arising from a SARS-CoV-2-induced cytokine storm and a surge in cytokine-mediated pro-inflammatory and immune signaling. In fact, this cytokine storm syndrome: (i) appears to predispose aged COVID-19 patients to the development of other neurological complications, especially those who have experienced a more serious grade of COVID-19 infection; (ii) lies along highly interactive and pathological pathways involving SARS-CoV-2 infection that promotes the parallel development and/or intensification of progressive and often lethal neurological conditions, and (iii) is strongly associated with the symptomology, onset, and development of human prion disease (PrD) and other insidious and incurable neurological syndromes. This commentary paper will evaluate some recent peer-reviewed studies in this intriguing area of human SARS-CoV-2-associated neuropathology and will assess how chronic, viral-mediated changes to the brain and CNS contribute to cognitive decline in PrD and other progressive, age-related neurodegenerative disorders. Full article

Background: Treatment of non-arteritic central retinal artery occlusion is still inconsistent. Therefore, the current study aimed to evaluate the efficacy of intravenous thrombolysis (IVT) and describe the prevalence of co-occurring ischemic brain lesions in patients with acute visual loss due to ischemia. Methods: We analysed 38 consecutive patients with acute visual loss between January 2015 and June 2020. Patients presenting within 4.5 h of symptom onset without any contraindication were treated with IVT. Patients underwent neurologic and ophthalmologic examination and diagnostic workup for the underlying aetiology. Follow-up was performed after 3 and 12 months. Results: Patients treated with IVT had a significantly better functional outcome at discharge compared to patients treated conservatively. No additional ischemic brain lesions were detected (0 of 38). Three patients had extracranial carotid artery stenosis ≥50%. Atrial fibrillation was present in four patients, three of whom already received oral anticoagulation. In the remaining 31 patients no embolic source was detected. However, the number of plaques were rated mild to moderate. Within three months, one patient developed transient visual loss while another suffered a contralateral transient ischemic attack. Conclusions: IVT may represent a safe and effective treatment option in patients with isolated visual loss due to ischemia. The aetiology was atherosclerotic burden rather than embolism caused by carotid stenosis or atrial fibrillation, bringing the current diagnostic procedure and therapy into question. Randomized trials are necessary to evaluate the efficacy and safety of IV thrombolysis and clarify the aetiology of isolated visual loss due to ischemia. Full article

Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease. Full article

(1) Introduction: A subset of individuals experiencing long COVID symptoms are affected by ‘brain fog’, a lay term that often refers to general cognitive dysfunction but one that is still poorly characterised. In this study, a comprehensive clinical characterisation of self-reported brain fog was conducted vis-à-vis other long COVID symptoms and parameters of mental, cognitive, and physical health. (2) Methodology: Adult participants reporting long COVID symptoms were recruited from hospital clinics and as self-referrals. Participants completed a battery of questionnaires and clinical assessments, including COVID-19 history, symptomatology, self-reported scales (Chalder Fatigue Scale [CFQ], Center for Epidemiological Studies Depression Scale, and Impact of Events Scale–Revised), computer-based cognitive assessments (simple response time and choice reaction time tasks), physical performance tests (gait velocity and muscle strength assessments), and an orthostatic active stand test. A systematic comparison between participants with and without self-reported brain fog was conducted, and a backwards binary logistic regression model was computed to identify the strongest independent associations with brain fog. This was complemented by an automatic cluster analysis to rank the importance of associations. Finally, a structural equation model was postulated with a causal model of key symptomatic indicators and functional consequences of brain fog as a latent variable. (3) Results: Of 108 participants assessed, brain fog was a self-reported symptom in 71 (65.7%) participants. Those with brain fog were at a longer point in time since COVID-19 onset and reported longer duration of low activity during the acute illness. When assessed, those with brain fog had higher frequencies of subjective memory impairment, word-finding difficulties, dizziness, myalgia, arthralgia, hyperhidrosis, cough, voice weakness, throat pain, visual and hearing problems, dysosmia, paraesthesia, chest pain, skin rashes, and hair loss; mean scores in fatigue, depression, and post-traumatic stress scales were higher; performance in both computer-based cognitive tasks was poorer; and measured gait speed and grip strength were lower. The logistic regression suggested that the best independent associations with brain fog were memory impairment, CFQ, and myalgia. The cluster analysis suggested that the most important associations with brain fog were CFQ, dizziness, myalgia, reduced gait speed, word-finding difficulties, reduced grip strength, and memory impairment. The SEM was consistent with key indicators of brain fog being CFQ, dizziness, myalgia, word-finding difficulties, and memory impairment; and reduced grip strength, gait speed, and cognitive response times its functional consequences. (4) Conclusions: The findings indicate that self-reported brain fog in long COVID is a recognisable symptom cluster primarily characterised by fatigue, dizziness, myalgia, word-finding difficulties, and memory impairment and has adverse psychological and psychomotor correlates. In long COVID, brain fog should be regarded as a wide-ranging symptom and addressed holistically with medical, psychological, and rehabilitative supports as guided by individual needs. Full article