OBJECTIVE: 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.
CONCLUSIONS: 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.

BACKGROUND: Papilledema is the optic disc swelling caused by increased intracranial pressure (ICP) that can damage the optic nerve and cause subsequent vision loss. Pseudopapilledema refers to optic disc elevation without peripapillary fluid that can arise from several optic disc disorders, with optic disc drusen (ODD) being the most frequent cause. Occasionally, pseudopapilledema patients are mistakenly diagnosed as papilledema, leading to the possibility of unneeded procedures. We aim to thoroughly examine the most current evidence on papilledema and pseudopapilledema causes and several methods for distinguishing between both conditions.
METHODS: An extensive literature search was conducted on electronic databases including PubMed and google scholar using keywords that were relevant to the assessed pathologies. Data were collected and then summarized in comprehensive form.
RESULTS: Various techniques are employed to distinguish between papilledema and pseudopapilledema. These techniques include Fundus fluorescein angiography, optical coherence tomography, ultrasonography, and magnetic resonance imaging. Lumbar puncture and other invasive procedures may be needed if results are suspicious.
CONCLUSIONS: Papilledema is a sight-threatening condition that may lead to visual affection. Many disc conditions may mimic papilledema. Accordingly, differentiation between papilledema and pseudopailledema is crucial and can be conducted through many modalities.

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.
METHODS: 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.

BACKGROUND: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better understanding and identifying PHOMS are important for monitoring the condition of optic nerve.
METHODS: A young female presented to the ophthalmic clinic with blurred vision of both eyes. Protrusions resembling \"C-shaped donut\" were found circling the optic discs bilaterally. These lesions were homogenous hyperreflective on OCT, while they were also hypoautofluorescent and hypoechogenic. Meanwhile, cystoid macular edema (CME) was also identified in both eyes. The patient was then diagnosed as PHOMS with CME. A short-term glucocorticoids therapy was prescribed systemically. The logMAR best-corrected visual acuity (BCVA) of both eyes reached 0.0 in 4 months with recovery of CME, while the PHOMS remained.
CONCLUSIONS: There is currently no report on PHOMS with CME. More attentions should be paid to PHOMS, for they are potential biomarkers for axoplasmic stasis involved in different diseases of the optic nerve.

OBJECTIVE: 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.
RESULTS: 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.
UNASSIGNED: 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.

UNASSIGNED: Deep learning architectures can automatically learn complex features and patterns associated with glaucomatous optic neuropathy (GON). However, developing robust algorithms requires a large number of data sets. We sought to train an adversarial model for generating high-quality optic disc images from a large, diverse data set and then assessed the performance of models on generated synthetic images for detecting GON.
UNASSIGNED: A total of 17,060 (6874 glaucomatous and 10,186 healthy) fundus images were used to train deep convolutional generative adversarial networks (DCGANs) for synthesizing disc images for both classes. We then trained two models to detect GON, one solely on these synthetic images and another on a mixed data set (synthetic and real clinical images). Both the models were externally validated on a data set not used for training. The multiple classification metrics were evaluated with 95% confidence intervals. Models\' decision-making processes were assessed using gradient-weighted class activation mapping (Grad-CAM) techniques.
UNASSIGNED: Following receiver operating characteristic curve analysis, an optimal cup-to-disc ratio threshold for detecting GON from the training data was found to be 0.619. DCGANs generated high-quality synthetic disc images for healthy and glaucomatous eyes. When trained on a mixed data set, the model\'s area under the receiver operating characteristic curve attained 99.85% on internal validation and 86.45% on external validation. Grad-CAM saliency maps were primarily centered on the optic nerve head, indicating a more precise and clinically relevant attention area of the fundus image.
UNASSIGNED: Although our model performed well on synthetic data, training on a mixed data set demonstrated better performance and generalization. Integrating synthetic and real clinical images can optimize the performance of a deep learning model in glaucoma detection.
UNASSIGNED: Optimizing deep learning models for glaucoma detection through integrating DCGAN-generated synthetic and real-world clinical data can be improved and generalized in clinical practice.

Optical coherence tomography (OCT) displays the retinal nerve fiber layer (RNFL) or macular ganglion cell and inner plexiform layer (GCIPL) thickness below 1st percentile in red color. This finding generally indicates severe inner-retinal structural changes and suggests poor visual function. Nevertheless, some individuals show preserved visual function despite these circumstances. This study aimed to identify the correlation between best-corrected visual acuity (BCVA) and inner-retinal thickness based on OCT parameters in various optic neuropathy patients with extremely low RNFL/GCIPL thickness, and determine the limitation of OCT for predicting visual function in these patients. 131 patients were included in the study. The mean BCVA in logMAR was 0.55 ± 0.70 with a broad range from - 0.18 to 3.00. Among the OCT parameters, temporal GCIPL (r = - 0.412) and average GCIPL (r = - 0.366) exhibited the higher correlations with BCVA. Etiological comparisons of optic neuropathies revealed significantly lower BCVA in LHON (all p < 0.05). Idiopathic optic neuritis (ON) and MOGAD exhibited better and narrower BCVA distributions compared to the other optic neuropathies. OCT had limited utility in reflecting BCVA, notwithstanding significant inner-retinal thinning after optic nerve injuries. Caution is needed in interpreting OCT findings, especially as they relate to the etiology of optic neuropathy.

BACKGROUND: The pathophysiology of toxico-nutritional optic neuropathies remains debated, with no clear understanding of the respective roles played by the direct alcohol toxicity, smoking and the often associated vitamin deficiencies, which are risk factors for optic neuropathy. Our aim was to investigate genetic susceptibility in patients with bilateral infraclinical optic neuropathy associated with chronic alcohol use disorder.
METHODS: This retrospective cohort study included 102 visually asymptomatic patients with documented alcohol use disorder from a French reference center. Optic neuropathy was identified with optical coherence tomography (OCT), after which genetic susceptibility in the group of affected patients was investigated. Genetic testing was performed using panel sequencing of 87 nuclear genes and complete mitochondrial DNA sequencing.
RESULTS: Optic neuropathy was detected in 36% (37/102) of the included patients. Genetic testing of affected patients disclosed two patients (2/30, 6.7%) with optic neuropathy associated with pathogenic variants affecting the SPG7 gene and five patients (5/30, 16.7%) who harbored variants of uncertain significance close to probable pathogenicity in the genes WFS1, LOXL1, MMP19, NR2F1 and PMPCA. No pathogenic mitochondrial DNA variants were found in this group.
CONCLUSIONS: OCT can detect presence of asymptomatic optic neuropathy in patients with chronic alcohol use disorder. Furthermore, genetic susceptibility to optic neuropathy in this setting is found in almost a quarter of affected patients. Further studies may clarify the role of preventative measures in patients who might be predisposed to avoidable visual loss and blindness.

Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with a clinical diagnosis of ION, the underlying genetic variants remain unknown. In this case study, we describe a potentially new disease-associated gene, NSUN3, for IONs. The proband was a young woman with consanguineous parents. She presented with bilateral optic atrophy and nystagmus at the age of seven years. Genetic testing revealed the homozygous variant c.349_352dup p.(Ala118Glufs*45) in NSUN3, with a segregation in the family compatible with autosomal recessive inheritance. Additional functional analysis showed decreased NSUN3 mRNA levels, slightly diminished mitochondrial complex IV levels, and decreased cell respiration rates in patient fibroblasts compared to healthy controls. In conclusion, pathogenic variants in NSUN3 can cause optic neuropathy. Trio whole-exome sequencing should be considered as a diagnostic strategy in ION cases where standard diagnostic analysis does not reveal disease-causing variants.

BACKGROUND: Middle fossa arachnoid cysts (MFACs) are rare, congenital lesions that may rupture and cause symptoms of elevated intracranial pressure. We sought to describe the presence of and factors associated with optic nerve edema in MFACs, focusing on the utility of ophthalmologic evaluations for guiding cyst management.
METHODS: We reviewed clinical and radiographic information for all patients with MFACs with ophthalmologic evaluations at our institution. Headache, cranial nerve palsy, emesis, altered mental status, fatigue, and seizures were considered MFAC-related symptoms. Univariate and multivariable analyses evaluated factors associated with optic edema.
RESULTS: Fifty-one patients between 2003 and 2022 were included. Cysts were a median volume of 169.9 cm3 (interquartile range: 70.5, 647.7). Evidence of rupture with subdural hematoma/hygroma occurred in 19 (37.3%) patients. Eighteen (35.3%) patients underwent surgery for their cyst and/or rupture-associated intracranial bleed. Eleven (21.6%) patients had optic edema; all were symptomatic and experienced cyst rupture. Ten of these patients received surgery. Postoperatively, optic edema resolved in 80% of cases. Cyst volume and symptoms were not associated with optic edema; however, patients with ruptured cysts, particularly those with traumatic rupture, were more likely to have optic edema and receive surgery (P < 0.001).
CONCLUSIONS: We found optic edema in 21.6% of evaluated MFACs, and this comprised of 57.9% of ruptured cases. Optic edema was not found in unruptured cysts. Cyst fenestration improved optic edema and patient symptoms. In conjunction with clinical history and neuroimaging, optic edema may help guide MFAC management, particularly in patients with cyst rupture.