Search Results (173)

Purpose: The present study aims to evaluate alterations in the peripapillary retinal nerve fiber layer (RNFL) thickness in pediatric patients following surgical resection of childhood-onset craniopharyngioma (CP) and to identify tumor characteristics and other factors influencing these alterations, including changes in the lesion’s location. Design: retrospective clinical cohort study. Methods: A retrospective analysis was conducted on 73 eyes from 38 patients with CP and 64 eyes from 32 age- and sex-matched healthy controls. The mean age of the CP patients was 10.3 ± 4.2 years (range 4–17), while the control group had a mean age of 10.5 ± 3.1 years (range 4–17). Optical coherence tomography (OCT) was used to assess the peripapillary RNFL thickness in the study and control groups. RNFL thickness was analyzed in the superior, inferior, and average sectors, as well as across eight optic nerve sectors. Tumor characteristics were evaluated to determine their correlation with changes in RNFL thickness in individual sectors. Results: Postoperative thickness of peripapillary RNFL in all individual sectors was significantly reduced in the CP group compared to healthy controls. Location, tumor volume, maximum tumor diameter, calcification, ventriculoperitoneal shunt, surgery technique, total resection, presence of Rosenthal fibers, and reoperation due to progression or recurrence correlated with damage to RNFL. Conclusions: CP is associated with significant reductions in RNFL thickness, indicating the tumor’s impact on optic nerve fibers. OCT is a valuable tool for monitoring visual pathway impairment and postoperative outcomes. Correlations between RNFL thickness in individual sectors and clinical parameters may offer valuable insights for diagnosis and monitoring, underlining their potential role in predicting visual outcomes. Regular RNFL evaluation should be integrated into the long-term care of CP patients to optimize visual prognosis and detect progressive or residual damage. Full article

The aim of this paper is to present our experience with the diagnosis and management of nine patients diagnosed with Leber’s hereditay optic neuropathy. Materials and methods: We conducted a prospective, observational study that included nine patients treated with idebenone, followed for a period of 18 months. Results: Our findings suggest that the impact of treatment varies significantly depending on the disease phase. In the acute phase, visual acuity deteriorated from 0.67 logMAR at onset to 0.97 logMAR at 3 months, followed by a slight improvement to 0.88 logMAR at 9 months. In the chronic phase, average values decreased progressively from 1.44 logMAR at onset to 1.26 logMAR at 12 and 18 months. We also observed a consistent treatment benefit over time in eyes harbouring the m.11778 G > A mutation. Although the most powerful predictor of visual outcome remains the mtDNA genotype, young age at onset is correlated with a better prognosis. In the acute phase, more cases of a clinically relevant benefit were observed than expected (33.33% versus 22.22% expected), and fewer clinically relevant worsening cases were observed (0% versus 11.11% expected). Regarding OCT measurement, our study highlighted a significant difference in peripapillary retinal nerve fiber layer thickness between the initial evaluation and the 6-month follow-up (100.83 µm ± 30.2 at baseline versus 96.7 µm ± 24.8 at 6 months). Conclusions: Our paper demonstrates the benefit of idebenone treatment in improving visual acuity in patients with Leber hereditary optic neuropathy. We highlighted the importance of long-term treatment, emphasizing that extended administration is key to achieving favorable outcomes. Full article

Background: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. Methods: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. Results: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. Conclusions: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished. Full article

Dysthyroid optic neuropathy (DON) represents a severe ocular complication in thyroid eye disease (TED) that can lead to vision loss. Although surgical decompression is a well-established treatment modality, the optimal decompression area remains controversial in orbital decompression surgery. Purpose: This study aims to develop and validate a finite element analysis (FEA) model of DON to compare the biomechanical behavior between patients undergoing conventional or augmented orbital decompression surgery, with potential clinical implications for surgical planning. Methods: FEA models were established using magnetic resonance imaging data from patients with myopathic TED. Pre-disease, preoperative, and postoperative FEA models were developed for both the conventional orbital decompression group and the augmented group, in which the posteromedial floor and the orbital process of the palatine bone were additionally removed to analyze the stress distribution and displacement of the optic nerve, eyeball, and orbital wall. A retrospective analysis was performed to validate the biomechanical analysis results. Results: The FEA results reveal that DON patients experience higher stress on the optic nerve, eyeball, and orbital wall than healthy individuals, mainly concentrated at the orbital apex. Postoperatively, the stress on the optic nerve was significantly reduced in both groups. In addition, postoperative stress on the optic nerve was significantly lower in the augmented group than in the conventional group. The clinical results demonstrate that patients in the augmented group experienced significantly faster and more pronounced improvements in visual acuity and visual field. Conclusions: FEA shows that augmented orbital decompression surgery can alleviate stress more effectively, especially for the optic nerve, which was validated by clinical analysis. This developed FEA model of DON may facilitate determining the appropriate surgical procedure for orbital decompression. Full article

Objectives: This review explores the role of swept-source optical coherence tomography (OCT) in diagnosing and monitoring optic nerve neuropathy in Wernicke’s encephalopathy (WE) due to hyperemesis gravidarum, including a case of neuropathy from intractable vomiting in pregnancy. Methods: A literature search was conducted in the PubMed database to select high-quality reviews and original articles on the use of swept-source OCT for assessing optic nerve involvement in WE due to hyperemesis gravidarum. Results: WE is a potentially fatal neuropsychiatric syndrome caused by thiamine deficiency due to various causes, like alcoholism, malnutrition, and prolonged parenteral nutrition. This condition can cause neurological disorders such as imbalance, altered mental status, nystagmus, and ophthalmoplegia. Sometimes, there is also a deterioration of visual acuity with swelling of the optic disc. OCT is a non-invasive imaging tool that can detect optic nerve involvement in WE by assessing peripapillary retinal nerve fiber layer (pRNFL) thickness. In the acute phase, optic disc edema and increased pRNFL thickness may be observed, while chronic-phase changes include optic nerve atrophy and pRNFL thinning. WE may occur in the course of hyperemesis gravidarum in pregnant women. We present a case of a 23-year-old woman at 14 weeks of gestation with WE due to severe hyperemesis gravidarum, manifesting as visual impairment and neurological deficits. MRI confirmed the diagnosis, while OCT revealed transient pRNFL thickening followed by optic nerve atrophy. Conclusions: Early diagnosis and thiamine supplementation are crucial to preventing severe complications. OCT is a valuable tool for detecting and tracking optic nerve changes in WE. Full article

Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders. Full article

Objective: Various orbital conditions (trauma, autoimmune thyroid disease, tumors, infections, congenital malformations) may lead to a consecutive increase in orbital cavity pressure resulting in orbital compartment syndrome (OCS). OCS is associated with acute loss of visual function and a high risk of permanent damage to the optic nerve (compressive optic neuropathy). Orbital decompression surgery (ODS) is a time-critical procedure that reduces pressure on the optic nerve, thereby improving visual function. The surgical management protocol for orbital decompression is not standardized and varies. Surgical techniques differ in orbital fat decompression, lateral canthotomy, and decompression of the medial orbital wall and floor. This retrospective study aims to evaluate surgery procedures and the outcome of visual function after orbital decompression surgery. Methods: In this retrospective study, we evaluated 28 patients (17 male, 11 female) with orbital compartment syndrome from May 2016 to October 2024. All patients underwent orbital decompression surgery as first-line treatment. Visual acuity (VA), diplopia, and ocular motility were analyzed pre- and postoperatively. Recovery was defined as postoperative improvement of vision, diplopia, and ocular motility. Linear and logistic regression analyses were used to assess the associations between clinically relevant risk factors and primary outcomes. Results: Orbital decompression surgery was performed with a median of 8.40 h (Q1: 4.80, Q3: 24.00) upon occurrence of symptoms. The average preoperative measured VA (logMAR) of the affected eye was 1.0. A total of 46% of the patients were preoperatively categorized as ”blind“ according to the WHO visual impairment categories. A total of 96% of the patients showed preoperative ocular motility impairment. Diplopia was preoperatively present in 46% of the patients. After orbital decompression surgery, postoperative visual acuity improved in 36% of the patients. Ocular motility improved by 67% and diplopia by 62% after ODS. The primary surgery technique was two-wall decompression in 68% (19/28) of the cases, followed by one-wall decompression (21%; 6/28), and three-wall decompression (11%; 3/28). Lateral decompression (82%; 23/28) and medial wall decompression (93%; 26/28) were the primary procedures performed. Orbital floor wall decompression was performed in only 14% (4/28) of the cases. Regression analysis revealed a statistically significant effect of preoperative measured vision on postoperative vision, while accounting for age, sex, and time to surgery. Conclusions: Orbital decompression surgery is the time-sensitive first-line treatment of acute visual function loss in OCS. Our data showed a postoperative improvement in visual acuity in 36% of the patients, along with considerable improvement rates in diplopia and ocular motility. The primary surgery technique was a two-wall decompression approach with lateral wall decompression and medial wall decompression. Center-specific timeline optimization of OCS patients is essential. Full article

We recently showed, in a mouse optic nerve crush model, that a sustained cell-based intravitreal administration of ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) synergistically slowed the lesion-induced degeneration of retinal ganglion cells (RGCs), resulting in the presence of approximately 35% viable RGCs eight months after the lesion. However, the combinatorial neuroprotective treatment was initiated shortly after the lesion. To mimic a more clinically relevant situation, we co-administered both factors either three or five days after an intraorbital nerve crush when approximately 35% or 57% of the RGCs were degenerated, respectively. Analyses of the retinas at different time points after the lesion consistently revealed the presence of significantly more surviving RGCs in retinas co-treated with CNTF and GDNF than in retinas treated with either factor alone. For example, when the neurotrophic factors were administered five days after the nerve crush and the animals were analyzed two months after the lesion, retinas co-treated with CNTF and GDNF contained approximately 40% of the RGCs present at the start of treatment. In comparison, monotherapy with either CNTF or GDNF protected only about 15% or 10% of the RGCs present at baseline, respectively. The number of regenerating axons in the distal nerve stumps was similar in CNTF- and CNTF/GDNF-treated animals, despite the significantly higher number of rescued RGCs in the latter group. These findings have potential implications for studies aimed at developing neuroprotective treatments for optic neuropathies such as glaucoma. Full article

Nonsyndromic and syndromic hereditary optic neuropathies (HONs) encompass a variety of genetic illnesses that cause progressive optic nerve damage, resulting in considerable vision impairment. These disorders result from pathogenic variants in mitochondrial or nuclear DNA, impacting essential cellular processes like oxidative phosphorylation, mitochondrial dynamics, and neuroprotection. Advances in next-generation sequencing (NGS) have significantly improved the identification of genetic variations, enabling precise diagnoses and genotype–phenotype correlations. This review consolidates current knowledge regarding the classification, molecular pathogenesis, clinical manifestations, diagnostic methodologies, and emerging therapeutic strategies for HONs. The critical role of mitochondrial dysfunction in optic nerve degeneration highlights the necessity for multimodal therapeutic approaches. Recent clinical trials evaluating gene therapy for Leber hereditary optic neuropathy (LHON) and neuroprotective strategies in dominant optic atrophy (DOA) are discussed. Additionally, individualized therapeutic interventions, as demonstrated by recent case studies involving tailored gene therapies, are evaluated. The integration of molecular and imaging biomarkers in future personalized treatment strategies aims to enhance prognosis and therapeutic outcomes. Full article

Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber’s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA’s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases. Full article

Background/Objectives: Leber hereditary optic neuropathy (LHON) is often misdiagnosed in its early stages as idiopathic single isolated optic neuritis (SION) or multiple-sclerosis-associated optic neuritis (MS-ON) due to the young age of the patients, the subacute vision loss, and the central visual field defect. The aim of this retrospective study was to evaluate changes in the peripapillary RNFL and GCLT over time in patients with early LHON, MS-ON, and SION in order to differentiate Leber hereditary optic neuropathy (LHON) from optic neuritis (ON) in the early stages of the disease. Methods: Patients with LHON and ON (either idiopathic single isolated optic neuritis (SION) or ON as the first symptom of relapsing–remitting multiple sclerosis (MS-ON) were included. Optical coherence tomography (OCT) scans were reviewed. The inclusion criteria were at least one follow-up OCT examination and a definite diagnosis after examination. Changes in the peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell layer thickness (GCLT) in both groups were evaluated over time and compared with normative data. The analysis focused on the early phase (0–45 days) after symptom onset. Results: Nine LHON patients with early OCT scans and twenty patients with ON were included. Quantitative OCT analysis showed greater RNFL swelling in LHON compared to ON during the first 60 days after symptom onset. Between day 61 and day 120, subnormal RNFL values were observed in both groups compared to controls. Thereafter, the RNFL decreased continuously and severely in the LHON group. The RNFL of ON patients did not show a clear progression after day 120. The GCLT in five LHON eyes showed a strong and solid decrease from day 0 to day 45, which was stronger than the moderate atrophy measured in ON eyes. Continuous GCL atrophy was measured until day 121 in LHON, after which a floor effect was reached. The GCLT in the inner nasal and inner inferior sectors was significantly smaller in LHON compared to ON patients on days 0–45. Conclusions: Thinning of the GCLT occurs at an early stage in LHON patients. Thus, GCLT may become a diagnostic tool to differentiate LHON from ON in the early phase of disease. Full article

Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic lesion of the anterior optic nerve (ON), currently untreatable due to the length of time from symptom onset until treatment. We evaluated angiotensin-(1-7) (Ang-(1-7)): the MAS1-receptor ligand, as a possible NAION treatment using the rodent NAION model (rNAION). Long-Evans rats were unilaterally rNAION-induced. One-day post-induction, lesion severity was quantified via optic nerve head (ONH) edema using spectral domain optical coherence tomography. Animals meeting rNAION induction criteria were randomized into (1) Subcutaneous Ang-(1-7) infusion for 28 days and (2) Vehicle. Visual function was assessed using both visual acuity and flash visual evoked potentials (fVEP). Tissues were collected >30d and RGC neurons were quantified by stereology. ONs were histologically examined for inflammation. Ang-(1-7) improved post-rNAION visual function. Ang-(1-7)-treated animals showed improved visual acuity (ANCOVA: p = 0.0084) and improved fVEP amplitudes (ANCOVA: p = 0.0378) vs vehicle controls. The relative degree of improvement correlated with ONH edema severity. Treated animals showed trends towards increased RGC survival, and reduced optic nerve inflammatory cell infiltration. Ang-(1-7) is the first agent effective ≥1 day after rNAION induction. Ang-(1-7) type agonists may be useful in improving long-term function and neuronal survival in clinical NAION and other forms of white matter ischemia. Full article

Thyroid-associated ophthalmopathy (TAO), or Graves’ orbitopathy (GO), is a complex autoimmune disorder affecting orbital tissues, often leading to vision-threatening complications such as dysthyroid optic neuropathy (DON). In this systematic review, conducted following PRISMA guidelines, 22 studies were evaluated to investigate the role of optical coherence tomography (OCT) in assessing retinal and choroidal changes in TAO. Parameters such as the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), ganglion cell layer (GCL), and choroidal thickness were analyzed. RNFL changes varied by disease severity, with significant thinning in DON due to nerve fiber loss and thickening in early DON due to optic disk edema. Subfoveal choroidal thickness (SFCT) was consistently higher in active TAO, correlating positively with the clinical activity score (CAS) and proptosis, suggesting its role as a marker of disease activity. Subgroup analysis revealed that spectral-domain OCT (SD-OCT) was the most sensitive for detecting retinal changes. The findings highlight the effectiveness of OCT in detecting minor retinal and choroidal alterations in TAO. However, the variability of study designs, as well as the lack of longitudinal data, limits the ability to draw broad conclusions. Further standardized, long-term investigations are required to properly understand OCT’s diagnostic and prognostic value in TAO. Full article

Post-acute sequelae of COVID-19 (PASC) syndrome is considered an emergent and diffuse multidisciplinary problem. Compelling evidence suggests that COVID-19 increases symptoms of pre-existent small fiber neuropathy (SFN) and might trigger de novo onset of SFN. In this systematic review, for the first time, we provide a comprehensive overview of the clinical and diagnostic features of PASC-SFN, including the accompanying disorders, disease evolution, and possible treatments, described in the recent literature. Following infection, many patients reported a wide range of symptoms and complications, not self-limiting and independent from previous infection severity. SFN begins more frequently with distal limb burning pain and numbness, which accompany other dysautonomia, cognitive, visual, and osteoarticular disorders involving multiple organ systems. In an initial diagnostic suspicion, some tests might be useful as complementary examinations, such as nerve quantitative sensory testing, electromyography, and optic nerve tomography. Otherwise, definite diagnosis is reached with skin biopsy as the gold standard, along with corneal in vivo microscopy when ocular discomfort is present. Being a long-term condition, multiple and dissimilar symptomatic and disease-modifying drugs were employed for the treatment of this condition with the achievement of partial results, including steroids, pregabalin, gabapentin, duloxetine, vitamins, homotaurine and phosphatidylserine, alpha lipoic acid, immunosuppressants, and intravenous immunoglobulin therapy. PASC-SFN is a complex emerging disease and extremely challenging for physicians. At present, the only feasible management of PASC-SFN is represented by a multidisciplinary tailored approach, with future definitive protocols for diagnosis and treatment deemed essential. Full article

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography (mfERG), pattern electroretinography (PERG), visual evoked potentials (VEP), and electrooculography (EOG) offer insights into retinal and optic nerve function, often detecting abnormalities before clinical symptoms manifest. In hearing loss syndromes like Refsum disease, Usher syndrome (USH), and Wolfram syndrome (WS), electrophysiology facilitates the detection of early retinal changes that precede the onset of visual symptoms. For mitochondrial disorders such as maternally-inherited diabetes and deafness (MIDD), Kearns–Sayre syndrome (KSS), and neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, these tests can be useful in characterizing retinal degeneration and optic neuropathy. In obesity syndromes, including Bardet-Biedl syndrome (BBS), Alström syndrome, and Cohen syndrome, progressive retinal degeneration is a hallmark feature. Electrophysiological techniques aid in pinpointing retinal dysfunction and tracking disease progression. Other syndromes, such as Alagille syndrome (AGS), abetalipoproteinemia (ABL), Cockayne syndrome (CS), Joubert syndrome (JS), mucopolysaccharidosis (MPS), Neuronal ceroid lipofuscinoses (NCLs), and Senior–Løken syndrome (SLS), exhibit significant ocular involvement that can be evaluated using these methods. This review underscores the role of visual electrophysiology in diagnosing and monitoring visual system abnormalities across a range of syndromes, potentially offering valuable insights for early diagnosis, monitoring of progression, and management. Full article