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AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

PurposeMutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFβ) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFβ signaling ameliorated ASD, supporting a role for the TGFβ pathway in disease pathogenesis. Here, we tested whether altered TGFβ signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice.MethodsTo test the role of TGFβ signaling in glaucoma-relevant phenotypes, we genetically reduced TGFβ signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFβ ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry.ResultsCol4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFβ receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice.ConclusionsOur results suggest that elevated TGFβ signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice.

Glaucoma leads to vision loss due to retinal ganglion cell death. Astrocyte reactivity contributes to neurodegeneration. Our recent study found that lipoxin B4 (LXB4), produced by retinal astrocytes, has direct neuroprotective actions on retinal ganglion cells. In this study, we aimed to investigate how the autacoid LXB4 influences astrocyte reactivity in the retina under inflammatory cytokine-induced activation and during ocular hypertension. The protective activity of LXB4 was investigated in vivo using the mouse silicone-oil model of chronic ocular hypertension. By employing a range of analytical techniques, including bulk RNA-seq, RNAscope in-situ hybridization, qPCR, and lipidomic analyses, we discovered the formation of lipoxins and expression of the lipoxin pathway in rodents (including the retina and optic nerve), primates (optic nerve), and human brain astrocytes, indicating the presence of this neuroprotective pathway across various species. Findings in the mouse retina identified significant dysregulation of the lipoxin pathway in response to chronic ocular hypertension, leading to an increase in 5-lipoxygenase (5-LOX) activity and a decrease in 15-LOX activity. This dysregulation was coincident with a marked upregulation of astrocyte reactivity. Reactive human brain astrocytes also showed a significant increase in 5-LOX. Treatment with LXB4 amplified the lipoxin biosynthetic pathway by restoring and amplifying the generation of another member of the lipoxin family, LXA4, and mitigated astrocyte reactivity in mouse retinas and human brain astrocytes. In conclusion, the lipoxin pathway is functionally expressed in rodents, primates, and human astrocytes, and is a resident neuroprotective pathway that is downregulated in reactive astrocytes. Novel cellular targets for LXB4s neuroprotective action are inhibition of astrocyte reactivity and restoration of lipoxin generation. Amplifying the lipoxin pathway is a potential target to disrupt or prevent astrocyte reactivity in neurodegenerative diseases, including retinal ganglion cell death in glaucoma.

Glaucoma is an eye disease that damages the optic nerve (or retina) and impairs vision. This disease can be prevented with regular checkups, but this increases the workload for professionals and the time it takes to get results. So an automated method using deep learning would be helpful for detection of disease. In order to shorten the diagnosis time for glaucoma, this paper proposed a deep learning based method for automatic glaucoma detection. The experiments are conducted on glaucoma datasets available on Kaggle. This paper used transfer learning based pretrained models namely DenseNet169, MobileNet, InceptionV3, Xception, ReseNet152V2,and VGG19. Among all models DenseNet169 gives best result with accuracy 0.993590 and precision and recall of 0.993671 and 0.9935895 respectively. A comparison of the best model results with existing work shows that the proposed model provides better results. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, glaucoma is the second biggest cause of blindness globally, with roughly 60 million cases documented worldwide in 2010. Glaucoma is a disease that, if left untreated, may cause irreparable damage to the optic nerve, ultimately resulting in blindness. Examining the optic nerve head, which includes the assessment of the cup-to-disc ratio, is regarded as one of the most important ways of structural diagnosis of the illness in its early stages. Optic Disc (OD) segmentation is a critical stage in analyzing the colour fundus image. In this work, the DRISHTI-GS and LAG images are resized and normalized as part of the preprocessing process. The optic disc is segmented using the trained UNET. Cropping is done to the optic disc following segmentation. Take segmented images and extract the statistical and edge characteristics. The optic image is then classified as normal or glaucoma using the trained KNN classifier. This work achieves an accuracy of 0.997, a sensitivity of 0.986, a specificity of 0.982 for the Drishti-GS, an accuracy of 0.987, and a sensitivity of 0.972 and a specificity of 0.992 for the LAG databases, respectively. [ABSTRACT FROM AUTHOR]

Background: During gynecological laparoscopic surgery, pneumoperitoneum and the Trendelenburg position (TP) can lead to increased intracranial pressure (ICP). However, it remains unclear whether perioperative fluid therapy impacts ICP. The purpose of this research was to evaluate the impact of restrictive fluid (RF) therapy versus conventional fluid (CF) therapy on ICP in gynecological laparoscopic surgery patients by measuring the ratio of the optic nerve sheath diameter (ONSD) to the eyeball transverse diameter (ETD) using ultrasound. Methods: Sixty-four patients who were scheduled for laparoscopic gynecological surgery were randomly assigned to the CF group or the RF group. The main outcomes were differences in the ONSD/ETD ratios between the groups at predetermined time points. The secondary outcomes were intraoperative circulatory parameters (including mean arterial pressure, heart rate, and urine volume changes) and postoperative recovery indicators (including extubation time, length of post-anaesthesia care unit stay, postoperative complications, and length of hospital stay). Results: There were no statistically significant differences in the ONSD/ETD ratio and the ONSD over time between the two groups (all p > 0.05). From T2 to T4, the ONSD/ETD ratio and the ONSD in both groups were higher than T1 (all p < 0.001). From T1 to T2, the ONSD/ETD ratio in both groups increased by 14.3%. However, the extubation time in the RF group was shorter than in the CF group [median difference (95% CI) -11(-21 to -2) min, p = 0.027]. There were no differences in the other secondary outcomes. Conclusion: In patients undergoing laparoscopic gynecological surgery, RF did not significantly lower the ONSD/ETD ratio but did shorten the tracheal extubation time, when compared to CF. Trial registration: ChiCTR2300079284. Registered on December 29, 2023. [ABSTRACT FROM AUTHOR]

Background: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by increased intracranial pressure. Whilst lumbar puncture (LP) is necessary for the diagnosis of IIH, its therapeutic effect remains unclear. Our aim was to evaluate the therapeutic effect of a single LP in people with IIH (pwIIH). Methods: In this prospective observational study, we analysed short-term neurological and ophthalmological outcomes in pwIIH before, one (D1) and seven days (D7) after the LP. The primary outcome was the change in papilledema degree from baseline. Secondary outcomes included visual outcomes, morphological changes in optical coherence tomography (peripapillary retinal nerve fibre layer [pRNFL] thickness and ganglion cell layer [GCL] volume) and transbulbar sonography (arachnoid optic nerve sheath diameter [AONSD]), and headache outcomes (peak and median headache severity and burden related to headache). Results: We included 30 pwIIH (mean age 32.8 years [SD 8.4], 93.3% female, median cerebrospinal fluid [CSF] opening pressure 33.0 cmCSF [IQR 26.9–35.3], median body mass index (BMI) 34.8 kg/m2 [IQR 30.9–40.9]). The median papilledema grading at baseline was 2 (Friedman DI (1999) Pseudotumor cerebri. Neurosurg Clin N Am 10(4):609–621 viii); (Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ (2019) The expanding burden of idiopathic intracranial hypertension. Eye Lond Engl 33(3):478–485); (Ab D, Gt L, Nj V, Sl G, Ml M, Nj N et al. (2007) Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol [Internet]. Apr [cited 2024 Jun 2];143(4). https://pubmed.ncbi.nlm.nih.gov/17386271/) and was significantly reduced at D7 (2 [1–2], p = 0.011). Median pRNFL thickness had decreased significantly at D7 (-9 μm [-62.5, -1.3], p = 0.035), with pRNFL thickness at baseline being associated with the pRNFL change (F(1,11) = 18.79, p = 0.001). Mean AONSD had decreased significantly at both D1 (-0.74 mm [0.14], p < 0.001) and D7 (-0.65 mm [0.17], p = 0.01), with AONSD at baseline being associated with the change in AONSD at both time points (D1: β= -0.89, 95% CI -1.37, -0.42, p = 0.002; D7: β= -0.85, 95% CI -1.42, -0.28, p = 0.007). Peak headache severity was slightly lower at D7 (-1/10 [-3, 0], p = 0.026), whereas median headache severity and headache burden remained unchanged. Conclusions: This short-term follow-up study in pwIIH undergoing a single LP suggests a moderate effect on ophthalmological but not headache outcomes. The usefulness of LP as a therapeutic measure in IIH remains controversial and should likely be reserved for patients with limited treatment options, e.g., in pregnancy or intolerability to medication. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of neurodegenerative diseases that can lead to irreversible blindness. Yet, the progression can be slowed down if diagnosed and treated early enough. Optical coherence tomography angiography (OCTA) can non-invasively provide valuable information about the retinal microcirculation that has shown to be correlated with the onset of the disease. The vessel density (VD) is the most commonly used biomarker to quantify this vascular information. However, different studies showed that there is a great impact of the acquisition area on the performance of the VD to distinguish between glaucoma patients and a healthy control group. It also seems that the separate capillary plexuses are differently affected by the disease and therefore also influence the results. So in this study we investigate the impact of the acquisition area (3 × 3 mm macular scan, 6.44 × 6.4 mm macular scan, 6 × 6 mm optic nerve head (ONH) scan) and the different plexuses on the machine-learning-based distinction between glaucoma patients and healthy controls. The results yielded that the 6 × 6 mm ONH show the best performance over all plexuses. Moreover the deep learning-based approach outperforms the VD as a biomarker on every acquisition area and plexus. In addition to that, it also performs better than traditional biomarkers obtained from the OCT scans that are used in the clinical routine for diagnosis and progression tracking of glaucoma. Consequently, OCTA scans of the ONH might be a useful addition to OCT when studying glaucoma. [ABSTRACT FROM AUTHOR]

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage, and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and nonnervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising noninvasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. Methods Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. Results We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: β = −1.91; P  = 0.029; EDV: β = −0.57; P  = 0.032) and significantly elevated OND (β = 0.79; P  = 0.003) compared with controls. RI did not significantly differ from controls (β = −0.06, P  = 0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (P  = 0.048) and EDV (P  = 0.040). No association was found with RI (P  = 0.249), while a positive significant association was noted with OND (P  < 0.001). Conclusions This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA. [ABSTRACT FROM AUTHOR]

Background: The clinical spectrum and diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has evolved in the setting of an optimized anti-MOG-IgG cell-based assay and expert consensus. The McDonald criteria for MS have been revised multiple times to improve the accuracy and specificity of diagnosis on a framework based on clinical presentation, MRI findings, and CSF results. While the uses of MS and MOGAD diagnostic criteria are helpful for typical cases, such utility for patients with overlapping clinical, laboratorial, and imaging features is unknown, posing diagnostic and management uncertainties. Objectives: To report a multicenter cohort of patients with overlapping phenotypic features of MOGAD and MS and evaluate the application of new MOGAD diagnostic criteria. Methods: A collaborative retrospective cohort study was performed to identify patients with both positive serum anti-MOG-IgG and fulfillment of the MS revised 2017 McDonald criteria. Clinical and radiographic features of patients fulfilling inclusion criteria were reviewed longitudinally, including relapses, repeated MRI, and MOG-IgG testing in detail to allow the panel of expert opinion to assign to each case. The International MOGAD Panel proposed criteria were applied at onset and last follow-up to each case and compared to the expert author diagnosis assignment based on presentation, clinical and imaging features, and response to treatment. Results: Ten of 225 (4%) MOG-IgG seropositive cases met study inclusion criteria [seven of 10 were female; age at initial event: eight adults (mean age 26.8 years), two adolescents (mean age 14.5 years)]. AQP4-IgG was negative for all. Apart from serum titers of MOG-IgG, distinguishing clinical and radiographic features [i.e., clinical severity of the initial demyelinating event, radiographic features (optic nerve/spine/brain), and presence/absence of lesion normalization on serial scans] led to consensus of three separate classifications differing by degrees of shared features of MOGAD and MS. Patients were classified by expert panel into (1) Classic MOGAD even with MS-like, well-defined brain lesions, when severe events and most T2 lesions normalized (n = 5; MOG-IgG titers 1:100, 1:20, 1:160, 1:40, 1:200); (2) Classic RRMS included cases thought to have likely false positive or clinically irrelevant MOG-IgG, due to mild clinical events and no radiographic normalization of well-defined MS-like lesions (n = 3; MOG titers 1:20, 1:100, 1:40); (3) MOGAD and MS overlapping phenotype was defined by those with a combination of mild and severe clinical events, partial T2 lesion normalization, both well- and ill-defined lesions (n = 2; MOG titers 1:20, 1:100). The application of the International MOGAD Panel criteria categorized five patients (50%) in agreement with expert assignment. One additional patient was classified in agreement to assignment when MOGAD criteria were applied after serial MOG-IgG titers testing. Discussion: While the International MOGAD Panel diagnostic criteria have helped with accuracy for the diagnosis of this condition, in a group of patients seropositive for MOG-IgG with overlapping clinical and imaging features of RRMS criteria review may lead to increased accuracy. Serial serologies, repeated imaging, close attention to clinical course, and response to therapy are possible variables to consider for further refinement of MOGAD diagnostic criteria. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is a network disorder that can cause alterations in retinal morphology due to microstructural changes in the brain. The aim of our study was to use spectral optical coherence tomography (OCT) to assess the possible effects of neuronal degeneration on the intraretinal layers and macular structures of people with epilepsy and epilepsy subgroups. Methods: We enrolled 52 consecutive people with epilepsy (37 females, 15 males; mean age 29.8±9.9 years; range, 17-48 years) and 40 healthy volunteers (27 females, 13 males; mean age 33.3±10.2 years; range, 19-49 years) in this study. Both eyes of all participants were assessed by using spectral-domain OCT. Optical coherence tomography was used to assess the thickness of the peripapillary retinal nerve fiber layer (RNFL), ganglion cell layer-inner plexiform layer (GCC-IPL), central macula, and central macular volume. Results: In comparison to healthy controls, people with epilepsy showed a thinner GCC-IPL in the superior and superior-nasal quadrants, as well as reduced macular thickness and macular volume (p<0.05). The thickness of the GCC-IPL layer in the superior and inferior subquadrants was negatively affected by frequent seizures (>5 seizures/year), polytherapy, and long-duration of epilepsy (≥10 years) (p<0.05). However, we did not find any other statistically significant associations between OCT measurements, age, sex, and epilepsy type (focal and generalized onset epilepsy). Conclusion: Individuals with epilepsy exhibited microstructural alterations in the retinal layers, primarily in the superior and inferior quadrants. Frequent seizures, polytherapy, and long-duration of epilepsy may result in neuronal damage in the afferent visual system. [ABSTRACT FROM AUTHOR]

Diffusion‐based tractography in the optic nerve requires sampling strategies assisted by anatomical landmark information (regions of interest [ROIs]). We aimed to investigate the feasibility of expert‐placed, high‐resolution T1‐weighted ROI‐data transfer onto lower spatial resolution diffusion‐weighted images. Slab volumes from 20 volunteers were acquired and preprocessed including distortion bias correction and artifact reduction. Constrained spherical deconvolution was used to generate a directional diffusion information grid (fibre orientation distribution‐model [FOD]). Three neuroradiologists marked landmarks on both diffusion imaging variants and structural datasets. Structural ROI information (volumetric interpolated breath‐hold sequence [VIBE]) was respectively registered (linear with 6/12 degrees of freedom [DOF]) onto single‐shot EPI (ss‐EPI) and readout‐segmented EPI (rs‐EPI) volumes, respectively. All eight ROI/FOD‐combinations were compared in a targeted tractography task of the optic nerve pathway. Inter‐rater reliability for placed ROIs among experts was highest in VIBE images (lower confidence interval 0.84 to 0.97, mean 0.91) and lower in both ss‐EPI (0.61 to 0.95, mean 0.79) and rs‐EPI (0.59 to 0.86, mean 0.70). Tractography success rate based on streamline selection performance was highest in VIBE‐drawn ROIs registered (6‐DOF) onto rs‐EPI FOD (70.0% over 5%‐threshold, capped to failed ratio 39/16) followed by both 12‐DOF‐registered (67.5%; 41/16) and nonregistered VIBE (67.5%; 40/23). On ss‐EPI FOD, VIBE‐ROI‐datasets obtained fewer streamlines overall with each at 55.0% above 5%‐threshold and with lower capped to failed ratio (6‐DOF: 35/36; 12‐DOF: 34/34, nonregistered 33/36). The combination of VIBE‐placed ROIs (highest inter‐rater reliability) with 6‐DOF registration onto rs‐EPI targets (best streamline selection performance) is most suitable for white matter template generation required in group studies. [ABSTRACT FROM AUTHOR]

Treatment of primary open-angle glaucoma has centered on the lowering of intraocular pressure that damages the optic nerve; however, this strategy is not uniformly successful, especially in normal tension glaucoma, and there is interest in antioxidant, anti-inflammatory, and other neuroprotective strategies. Vegetarian diets are known to be rich in antioxidant and anti-inflammatory components and have a number of established health benefits. Thus, it would be reasonable to assume that vegetarian diets would be beneficial in glaucoma, but this approach has not been well studied. We examine the possible role of vegetarian diets and their components in the incidence and progression of glaucoma. [ABSTRACT FROM AUTHOR]

A 60-year-old man presented to an outside ophthalmology clinic with 1 month of progressive vision loss in the right eye (OD). Right optic disc edema was noted. Brain and orbit magnetic resonance imaging revealed right optic nerve and left occipital lobe enhancement. He was seen initially by neurology and neurosurgery and subsequently referred to neuro-ophthalmology for consideration of optic nerve biopsy. He was seen 3 months after his initial symptom onset where vision was light perception OD and a relative afferent pupillary defect with optic nerve edema. OS was unremarkable. A lumbar puncture with flow cytometry was negative for multiple sclerosis and lymphoma. At his oculoplastic evaluation for optic nerve biopsy, his vision was noted to be no light perception OD. Optic nerve biopsy demonstrated non-caseating granulomatous inflammation consistent with neurosarcoidosis. The patient was started on high-dose oral steroids with improvement of disc edema, as well as significant improvement in optic nerve and intracranial parenchymal enhancement, although his vision never improved. [ABSTRACT FROM AUTHOR]

Purpose: To assess the associations between physiology and demographics, non‐ocular pathology and pharmaceutical drug use against peri‐papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. Methods: A retrospective, cross‐sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer‐inner plexiform layer (GCL‐IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non‐ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). Results: A multitude of non‐ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to −29.3 [−49.88, −8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and −10.18 [−16.62, −3.74] μm macular GCL‐IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, −0.31 [−0.53, −0.09] vertical CDR, −0.06 [−0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL‐IPL T; all p < 0.05). Conclusion: There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health. [ABSTRACT FROM AUTHOR]

Introduction: Congenital enophthalmos is a rare condition characterized by posterior displacement of the globe, often associated with bony orbital anomalies or whole globe development defects. The purpose of this report is to present two unrelated cases of congenital enophthalmos secondary to anomalous accessory orbital bands and to describe characteristics of orbital imaging that differentiate this condition from the other causes. Methods: The case records of two patients who presented with congenital enophthalmos and were discovered to have anomalous accessory orbital extraocular muscle bands were reviewed. The clinical features, initial diagnosis, high resolution magnetic resonance imaging (MRI) findings, and surgical outcomes were noted. A 3-dimensional reconstruction model was used to understand the approach and surgical management in one of the cases. Results: Both patients presented with unilateral severe enophthalmos, globe retraction, and restricted ocular motility in all directions since birth. High-resolution MRI of the orbits revealed a short anomalous band, isointense to the muscle, arising from a rectus muscle belly and attaching to the posteroinferior part of the globe adjacent to the optic nerve. The caliber of the extraocular muscles and ocular motor nerves was normal. In one patient, surgery was not pursued due to the extreme posterior location of the band with proximity to the optic nerve. In the other patient, the deviation did not improve, despite successfully severing the accessory band, due to extensive scarring. Conclusion: Anomalous accessory orbital extraocular muscle bands are a rare and often overlooked cause of congenital enophthalmos when associated with limited ocular motility. Imaging the orbit can aid in diagnosis and help differentiate it from other causes. Safe surgical approaches to address the problem are limited, and available approaches may not be effective. These two cases highlight that the management of accessory extraocular muscle bands causing enophthalmos can be extremely challenging and difficult to improve even with intensive surgical intervention. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. Methods: This is a prospective case–control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new‐onset, treatment‐naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) ‐matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non‐targeted mass spectrometry. Results: Serum sphingosine 1‐phosphate (S1P), adenosine, and glutamate were 0.46‐fold (q < 0.0001), 0.25‐fold (q = 0.0048), and 0.44‐fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl‐lysophosphatidylcholine (LysoPC‐18) and 2‐palmitoyl‐lysophosphatidylcholine (LysoPC‐16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) ‐fold lower. LysoPC‐18 was higher in patients with moderate–severe versus mild papilledema (p = 0.022). LysoPC‐18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = −0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC‐16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new‐onset IIH. Interpretation: We identify perturbed metabolism in new‐onset IIH. S1P and LysoPC‐16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595–607 [ABSTRACT FROM AUTHOR]

Visual evoked potential (VEP) is an established modality that allows safe brain tumor resection and preservation of optical function. We herein present a case of a pediatric craniopharyngioma with significant improvement in the VEP amplitude detected during endoscopic transsphenoidal surgery (ETS) and obvious postoperative improvement in visual acuity. A 13-year-old boy presented with visual acuity disturbance in his right eye and was followed up for 5 months by an ophthalmologist. His visual acuity rapidly worsened, and a suprasellar lesion with calcification was found on brain computed tomography. The patient underwent tumor resection during ETS with intraoperative transcranial VEP monitoring. Gross total tumor resection was achieved without injury to the perforators, including the superior hypophyseal arteries. The VEP amplitude was unstable, and significant waves were not detectable before tumor resection; however, a positive wave was detected after removing most of the tumor and exposing the bilateral optic nerves and optic chiasm. Subsequently, negative and positive VEP waves were continuously detected. Visual acuity improved remarkably on postoperative day 10. This case demonstrated both a significant increase in the intraoperative VEP amplitude and rapid postoperative improvement in visual acuity. We surmised that the preoperative rapid worsening of visual dysfunction, intraoperative increase in the VEP amplitude, and significant postoperative improvement in visual acuity were associated with the compression of the optic nerves by the internal carotid artery, anterior cerebral artery, and tumor. [ABSTRACT FROM AUTHOR]

Introduction: This study was designed to analyze clinical and radiographic features of adult patients coexisting with NMDAR-IgG and MOG-IgG. Methods: Eleven adult patients coexisting with NMDAR-IgG and MOG-IgG were collected from Xiangya Hospital, Central South University, between June 2017 and December 2021. Fifty-five patients with anti-NMDAR encephalitis and 49 with MOG-AD were served as controls. Results: Onset age was 27 (IQR 20–34) years old. Seizures and psychotic symptoms were prominent symptoms. Ten of eleven patients presented abnormal T2/FLAIR hyperintensity, mainly involving the cortex, brainstem, and optic nerve. Compared with the NMDAR IgG (+)/MOG IgG (−) group, the NMDAR IgG (+)/MOG IgG (+) group showed more ataxia symptoms (27.3% vs. 3.6%, P = 0.037), while more T2/FLAIR hyperintensity lesions were found in the brainstem (54.5% vs. 7.3%, P < 0.001) and optic nerve (27.3% vs. 1.8%, P = 0.011) with more abnormal MRI patterns (90.9% vs. 41.8%, P = 0.003). In comparison with the NMDAR IgG (−)/MOG IgG (+) group, the NMDAR IgG (+)/MOG IgG (+) group had more seizures (72.7% vs. 24.5%, P = 0.007) and mental symptoms (45.5% vs. 0, P < 0.001). The NMDAR IgG (+)/MOG IgG (+) group tended to be treated with corticosteroids alone (63.6% vs. 20.0%, P = 0.009), more prone to recur (36.5% vs. 7.3%, P = 0.028) and lower mRS score (P = 0.036) at the last follow-up than pure anti-NMDAR encephalitis. Conclusion: The symptoms of the NMDAR IgG (+)/MOG IgG (+) group were more similar to anti-NMDAR encephalitis, while MRI patterns overlapped more with MOG-AD. Detecting both NMDAR-IgG and MOG-IgG maybe warranted in patients with atypical encephalitis symptoms and demyelinating lesions in infratentorial regions. [ABSTRACT FROM AUTHOR]

Purpose: We report a case of bilateral intraocular infiltration of DLBCL after CAR-T therapy. Methods: Retrospective case report. Results: A 62-year-old Caucasian male with medical history of high-grade DLBCL presented with papillitis and vitritis upon completion of CAR-T therapy. Thorough infectious and diagnostic work-ups were performed. Diagnostic vitreous tap revealed intraocular lymphoma. The patient received external beam radiotherapy to both orbits with dramatic improvement in disc edema and vitritis. However, subsequent MRI showed development of intracranial metastatic disease, and the patient died within the same month. Conclusion: Atypical intraocular metastasis of DLBCL may occur following CAR-T therapy and may indicate secondary changes in immunosurveillance within immune-privileged sites such as the eye. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose Methods Results Conclusions Perspectives To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser‐induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO.A reliable and reproducible model of laser‐induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX‐4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age‐matched control retinas were analyzed using qRT‐PCR.Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL‐positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT‐PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia.This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia‐related neuronal cell damage.Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO. [ABSTRACT FROM AUTHOR]

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS. [ABSTRACT FROM AUTHOR]

Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies. [ABSTRACT FROM AUTHOR]

A compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss. However, little is known about dendritic structural preservation in pathologic environments and remodelling in mature neurons. Retinal ganglion cell dendritic atrophy is an early pathological feature in animal models of the disease and has been demonstrated in port-mortem human glaucoma samples. Here we report that a nicotinamide (a precursor to NAD through the NAD salvage pathway) enriched diet provides robust retinal ganglion cell dendritic protection and preserves dendritic structure in a rat model of experimental glaucoma. Metabolomic analysis of optic nerve samples from the same animals demonstrates that nicotinamide provides robust metabolic neuroprotection in glaucoma. Advances in our understanding of retinal ganglion cell metabolic profiles shed light on the energetic shift that triggers early neuronal changes in neurodegenerative diseases. As nicotinamide can improve visual function short term in existing glaucoma patients, we hypothesize that a portion of this visual recovery may be due to dendritic preservation in stressed, but not yet fully degenerated, retinal ganglion cells. [ABSTRACT FROM AUTHOR]

Glaucoma is an eye disease that often has no symptoms until it is advanced. According to the World Health Organization (WHO), after cataracts, glaucoma is the second-leading cause of permanent blindness globally and is expected to affect 111.8 million patients by 2040. Early detection of glaucoma is important to reduce the risk of permanent blindness. Detection is achieved by structural measurement of early thinning of the retinal nerve fiber layer (RNFL). The RNFL is the portion of the retina located outside the optic nerve head (ONH) and can be observed in fundus images of the retina. Analysis of retinal fundus images can be performed with computer assistance using machine learning, especially deep learning. This study proposes a deep learning-based model, a convolutional neural network (CNN) using the EfficientNet architecture combined with long short-term memory (LSTM), for laucoma detection. Using ACRIMA, DRISHTI-GS, and RIM-ONE DL datasets with k-fold cross-validation, the model achieved high performance on the ACRIMA dataset: accuracy 0.9799, loss 0.0596, precision 0.9802, sensitivity 0.9799, specificity 0.9771, and F1score 0.9799. This EfficientNet and LSTM combination (e-LSTM) outperformed previous studies, offering a promising alternative for evaluating retinal fundus images in glaucoma detection. [ABSTRACT FROM AUTHOR]

Background: Posterior globe flattening (PGF) is a specific neuroimaging sign in patients with idiopathic intracranial hypertension (IIH), but its detection is based on subjective qualitative neuroradiological assessment. This study sought to evaluate the utility of transorbital ultrasound to detect and quantify PGF in IIH patients using the Posterior Globe Angle (PGA). Methods: Consecutive IIH patients and healthy controls were enrolled in a prospective case-control study. Transorbital ultrasound was performed to assess the presence of PGF. For quantification of PGF, an angular measurement (PGA) was performed with the vertex centering the optic nerve at a predefined distance from the lamina cribrosa and angle legs tangentially aligned to the borders of the vitreous body. PGA measurements were compared between IIH patients and healthy controls. Additionally, the diagnostic accuracy of PGA measurements in detecting PGF was evaluated using ROC analysis. Results: Thirty-one IIH patients (37.3 ± 12.3 years, 29 female) and 28 controls (33.3 ± 11.8 years, 21 female) were compared. PGF was present in 39% of IIH patients and absent in the control group. PGA3mm measurements significantly differed between IIH and controls (116.5° ± 5.5 vs. 111.7° ± 2.9; p < 0.001). A PGA3mm cutoff of ≥ 118.5° distinguished IIH patients from controls with 100% specificity, while retaining a sensitivity of 37.5%. Conclusions: Transorbital ultrasound may be applied to detect and quantify PGF in IIH patients. Prospective, multicenter studies with extended cohorts and blinded design are needed to validate these preliminary findings and confirm the diagnostic utility of transorbital ultrasound for the assessment of PGF in IIH. [ABSTRACT FROM AUTHOR]

Myelin is a vital structure that is key to rapid saltatory conduction in the central and peripheral nervous systems. Much work has been done over the decades examining the biochemical composition and morphology of myelin at the light and electron microscopic levels. Here we report a method to study myelin based on the fluorescent probe Nile Red. This lipophilic dye readily partitions into live and chemicallyfixed myelin producing bright, well‐resolved images of the sheath. Using spectral confocal microscopy, a complete emission spectrum of Nile Red fluorescence can be acquired for each pixel in an image. The solvatochromic properties of Nile Red cause its emission spectrum to change depending on the polarity of its local environment. Therefore, measuring spectral shifts can report subtle changes in the physicochemical properties of myelin. We show differences in myelin polarity in central versus peripheral nervous system and in different regions of central nervous system white matter of the mouse brain, together with developmental and sex variations. This technique is also well suited for measuring subtle changes in myelin properties in live ex vivo white matter specimens. We also demonstrate how light deprivation induces a myelin polarity change in adult mouse optic nerve underscoring a continuing myelin plasticity in response to axonal activity well into adulthood. The Nile Red spectroscopic method allows measurement of subtle physicochemical changes in myelin that can importantly influence its electrical properties and by extension, conduction velocities in axons. [ABSTRACT FROM AUTHOR]

Fish retinal ganglion cells (RGCs) can regenerate after optic nerve lesions (ONLs). We previously reported that heat shock factor 1 (HSF1) and Yamanaka factors increased in the zebrafish retina 0.5–24 h after ONLs, and they led to cell survival and the transformation of neuro-stem cells. We also showed that retinoic acid (RA) signaling and transglutaminase 2 (TG2) were activated in the fish retina, performing neurite outgrowth 5–30 days after ONLs. In this study, we found that RA signaling and TG2 increased within 0.5 h in the zebrafish retina after ONLs. We examined their interaction with the TG2-specific morpholino and inhibitor due to the significantly close initiation time of TG2 and HSF1. The inhibition of TG2 led to the complete suppression of HSF1 expression. Furthermore, the results of a ChIP assay with an anti-TG2 antibody evidenced significant anti-TG2 immunoprecipitation of HSF1 genome DNA after ONLs. The inhibition of TG2 also suppressed Yamanaka factors' gene expression. This rapid increase in TG2 expression occurred 30 min after the ONLs, and RA signaling occurred 15 min before this change. The present study demonstrates that TG2 regulates Yamanaka factors via HSF1 signals in the acute phase of fish optic nerve regeneration. [ABSTRACT FROM AUTHOR]

The optic nerve sheath diameter (ONSD) can predict intracranial pressure and outcomes in neurological disease, but it remains unclear whether a small ONSD can be accurately measured on routine CT images with a slice thickness of approximately 4–5 mm. We measured the ONSD and ONSD/eyeball transverse diameter (ETD) ratio on routine-slice (4 mm) and thin-slice (0.6–0.75 mm) brain CT images from initial scans of acute ischemic stroke (AIS) patients. ONSD-related variables, National Institutes of Health Stroke Scale (NIHSS) scores, and age were compared between good (modified Rankin Scale [mRS] ≤ 2) and poor (mRS > 2) outcomes at discharge. Among 155 patients, 38 had poor outcomes. The thin-slice ONSD was different between outcome groups (p = 0.047), while the routine-slice ONSD showed no difference. The area under the curve (AUC) values for the ONSD and ONSD/ETD were 0.58 (95% CI, 0.49–0.66) and 0.58 (95% CI, 0.50–0.66) on the routine-slice CT, and 0.60 (95% CI, 0.52–0.68) and 0.62 (95% CI, 0.54–0.69) on the thin-slice CT. The thin-slice ONSD/ETD ratio correlated with initial NIHSS scores (r = 0.225, p = 0.005). After adjusting for NIHSS scores and age, ONSD-related variables were not associated with outcomes, and adding them to a model with NIHSS scores and age did not improve performance (all p-values > 0.05). Although ONSD measurements were not an independent outcome predictor, they correlated with stroke severity, and the thin-slice ONSD provided a slightly better prognostic performance than the routine-slice ONSD. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To compare blood flow (BF) impairment patterns in different optic neuropathies using laser speckle flowgraphy (LSFG).This retrospective study enrolled 24 eyes of 24 patients with non‐arteritic anterior ischemic optic neuropathy (NAAION), 59 eyes of 59 patients with optic neuritis (ON), 677 eyes of 677 patients with open‐angle glaucoma (OAG), and 110 eyes of 110 controls. The patient backgrounds of all groups were compared. Ophthalmologic findings were evaluated, adjusting for age, sex, blood pressure, pulse rate, and underlying systemic diseases with 1:1 optimal propensity score matching. We used LSFG to obtain optic nerve head (ONH) vessel‐area mean blur rate (MBR; ONH‐MV), ONH tissue‐area MBR (ONH‐MT), and choroidal MBR. The NAAION and ON groups were compared with the control and OAG groups.Best‐corrected visual acuity was worse in the NAAION, ON, and OAG groups than in controls (p < 0.001). Circumpapillary retinal nerve fibre layer thickness was higher in the NAAION and ON groups and lower in the OAG group than in controls (p < 0.001). Compared to controls, the NAAION and OAG groups had significantly lower ONH‐MV, ONH‐MT, and choroidal MBR (p < 0.05). Additionally, the NAAION group had lower ONH‐MV and choroidal MBR than the OAG group (p = 0.003 and p < 0.001, respectively) but no difference in ONH‐MT (p = 0.857). The ON group had significantly lower ONH‐MV and choroidal MBR compared to the controls (p < 0.001 and p = 0.022, respectively) but no difference in ONH‐MT (p = 0.773).Optic neuropathies showed different patterns of ocular BF impairment. Therefore, LSFG can be a useful tool for differentiating optic neuropathies. [ABSTRACT FROM AUTHOR]

Glaucoma is a multifactorial optic neuropathy that primarily affecting retinal ganglion cells (RGC). Brimonidine is an intraocular pressure-lowering drug with reported neuroprotective properties. This study aimed to compare the neuroprotective effects of topical and intraperitoneal (IP) brimonidine on RGCs from different retinal segments in a murine optic nerve crush (ONC) model. Methods: forty-one Balb/c mice underwent unilateral ONC and were divided into three study groups: fifteen animals received saline drops twice per day and two additional IP injections of saline; fourteen mice received brimonidine drops twice per day; and 12 mice received brimonidine eye drops twice per day and two additional IP brimonidine injections. Animals were sacrificed seven days post-ONC, and immunohistochemical staining of retinal whole mounts was performed using neuronal NeuN and GFAP staining. Microscopic pictures of the central, middle, and peripheral regions of the retina were taken. The density of the retinal cells was assessed. Results: The total RGC density after ONC and RGC densities in all retinal eccentricities were significantly higher in the brimonidine eye drop and IP combination treatment group than in the saline drop + saline IP, and brimonidine drop treatment groups. Conclusions: brimonidine eye drops supplemented with IP brimonidine injections improved RGC survival in a preclinical model of ONC. [ABSTRACT FROM AUTHOR]

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder that principally targets the central nervous system, specifically the spinal cord and optic nerves. NMOSD is often associated with thyroid pathologies such as Graves’ disease or Hashimoto’s thyroiditis. Thyroid eye disease (TED) is an autoimmune condition characterized by inflammation and hypertrophy of the extraocular muscles. Dysthyroid optic neuropathy (DON), a critical complication of TED, may lead to irreversible visual loss. We report a case of DON complicated by NMOSD. Case Presentation: We report a case of an autoimmune disease presenting as DON in a 44-year-old Japanese woman with a history of Graves’ disease, who experienced reduced visual acuity and orbital pain. Brain magnetic resonance imaging disclosed hypertrophy of the rectus muscles, compressing the optic nerve bilaterally. Consequently, she was diagnosed with DON and underwent three courses of steroid semi-pulse therapy and left orbital decompression surgery, alleviating optic nerve compression. Nevertheless, the visual prognosis remained poor. A subsequent serological test showed positive for aquaporin-4 antibody. Treatment with satralizumab, an interleukin-6 receptor monoclonal antibody, was initiated in conjunction with steroids to suppress the autoimmune response and reduce NMOSD relapse risk. Following this treatment, no NMOSD recurrences were reported. Conclusion: This case highlights the necessity of considering the possible coexistence of DON and NMOSD in patients with autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introduction: Primary vitreoretinal lymphoma (PVRL) is a rare malignant tumor that typically involves the retina, vitreous, or optic nerve head. PVRL often occurs concurrently with central nervous system lymphoma. Here, we present the first report of a patient with biopsy-confirmed PVRL presenting solely with asymptomatic peripheral drusenoid lesions. Case Presentation: A woman in her 70s presented with new elevated amelanotic yellow lesions with overlying pigment in both of her eyes not previously seen prior to cataract surgery. Over the next 4 months, there was waxing and waning of lesions which resolved and first appeared in the right eye and then the left. A diagnostic vitrectomy of the left eye revealed B-cell lymphoma. The patient elected for initial treatment with radiation therapy of both orbits. A new lesion was identified in her right eye nearly 18 months after starting maintenance therapy with ibrutinib, following which systemic chemotherapy with methotrexate was initiated. Conclusion: Elevated clinical suspicion for a malignant process is needed for patients with progressive new retinal lesions in older age. Local radiation therapy to the orbits alone may not be sufficient to prevent progression despite initial presentation showing confinement of disease to the intraocular space. [ABSTRACT FROM AUTHOR]

Objective Design, Patients and Measurements Results Conclusion Optic nerve hypoplasia (ONH), the congenital underdevelopment of the optic nerve, is an increasing cause of visual impairment and is associated with pituitary dysfunction. Past studies have focused on the relationship between ONH, pituitary deficiencies, and brain imaging. However, recent studies have demonstrated the true risk for hypopituitarism lies with the presence or absence of ONH, irrespective of midline brain findings. This study reviewed the relationship between the health of the optic nerve (visual acuity) and pituitary gland (number and age of development of pituitary deficiencies) as a way to stratify risk, regardless of imaging findings.Retrospective chart review of 197 patients seen at a single center from 2013 to 2022. Visual assessment was defined by distance acuity, and the presence of nystagmus or afferent pupillary defect. Pituitary deficiencies were diagnosed per Endocrine Society guidelines.In children with bilateral ONH (bONH), profound visual impairment was associated with more pituitary deficiencies between 0 and 15 years of age. The odds of having any pituitary deficiency were 4.9 times higher (95% confidence interval [95% CI]: 2.4–10.1) for patients with bONH versus unilateral ONH (uONH). Central hypothyroidism was the most common first presenting pituitary deficiency followed by growth hormone across all patients.This study shows a significant association between severity of visual impairment and increased probability of pituitary deficiencies in children with bONH versus uONH. Children with ONH require urgent endocrine evaluation due to risk of pituitary deficiencies, but risk stratification may also be based on severity of visual impairment. [ABSTRACT FROM AUTHOR]

Bilateral edematous optic disc swelling from papilledema is caused by elevated intracranial pressure (ICP). Idiopathic intracranial hypertension (IIH), a clinical syndrome with elevated ICP of unclear etiology, is a frequent cause of this condition. IIH typically affects obese middle-aged females. Papilledema usually has a fairly symmetrical bilateral pattern. Unilateral papilledema is a rare disorder that must be detected early to avoid optic nerve damage. However, the etiology of unilateral papilledema remains unclear. Based on bilateral optic nerve sheath diameter measurements, we aimed to find an explanation for the unilaterality in this rare case. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive lysosomal storage disease associated with high mortality and morbidity rates. The most distinctive ocular manifestations of cystinosis are photophobia, tearing, and blurred vision. Herein, we assessed the ocular involvement of four patients from two families diagnosed with infantile nephropathic cystinosis using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). Anterior segment OCT demonstrated multiple hyperreflective punctate deposits, and IVCM revealed needle-shaped bright crystal deposits in the corneal stroma in all patients. Three patients also had crystal deposits in the epithelium, where epithelial cell disruption was observed. Crystal deposits around the subepithelial nerve plexus were noted in some sections. In one patient, round and needle-shaped bright deposits along with inflammatory cells were observed in the limbal region of the conjunctiva. Infrared fundus images of two female siblings revealed hyperreflective crystal-like deposits around the optic disc, macula, and peripheral retina, and enhanced depth imaging OCT showed accumulation of crystals in all layers of the retina. [ABSTRACT FROM AUTHOR]

Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently – restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries. [ABSTRACT FROM AUTHOR]

Objectives Midline suprasellar meningiomas include planum sphenoidale, tuberculum sellae, and diaphragma sellae meningiomas. Multiple classifications have been previously documented; however, they come with controversies and limitations, including those with surgical implications. The aim of this study was to classify suprasellar meningiomas based on their behavior toward the underlying bone and neurovascular structures. Methods Patients with newly diagnosed suprasellar meningiomas that underwent extended endoscopic transnasal approach between 2015 and 2021 were included in this study. The following parameters were evaluated: chiasmatic sulcus length, location of the optic chiasm and nerves, optic canal involvement, and vascular displacement. Results We identified 40 cases of midline suprasellar meningiomas, 1 diaphragma sellae meningioma (type A), 10 tuberculum sellae meningiomas (type B), 9 chiasmatic sulcus meningiomas (type C), and 10 planum sphenoidale meningiomas (type D). Asymmetrical visual complaints were most common in chiasmatic sulcus meningiomas, followed by tuberculum sellae meningiomas (66 and 50%, respectively). Chiasmatic sulcus meningiomas showed increased separation between the optic chiasm and the A1/A2 complex (8.9 mm) compared with tuberculum sellae (2.7 mm) and planum sphenoidale (1.9 mm) meningiomas. Compared with other types, increased chiasmatic sulcus length was observed in chiasmatic sulcus meningiomas. Conclusion Preoperative evaluation of bone involvement and tumor relation to neurovascular structures can be used to classify suprasellar meningiomas. Chiasmatic sulcus meningioma is a distinct subtype of suprasellar meningiomas. Its unique behavior toward nearby neurovascular structures could be of surgical value during tumor resection. [ABSTRACT FROM AUTHOR]

This study aimed to examine the existing literature that investigated the effectiveness of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) as a biomarker for idiopathic intracranial hypertension (IIH). Our search was conducted on January 17th, 2024, and included the databases, Medline, Scopus, Embase, Cochrane, Latin American and Caribbean Health Sciences Literature (LILACS), International Standard Randomized Controlled Trial Number (ISRCTN) registry, and the International Clinical Trials Registry Platform (ICTRP). Our final review included 84 articles. In 74 studies, OCT was utilized as the primary ocular imaging method, while OCT-A was employed in two studies including eight studies that utilized both modalities. Overall, the results indicated that IIH patients exhibited significant increases in retinal nerve fiber layer (RNFL) thickness, total retinal and macular thickness, optic nerve head volume, and height, optic disc diameter and area, rim area, and thickness compared to controls. A significant correlation was observed between cerebrospinal fluid (CSF) pressure and OCT parameters including RNFL thickness, total retinal thickness, macular thickness, optic nerve head volume, and optic nerve head height. Interventions aimed at lowering CSF pressure were associated with a substantial improvement in these parameters. Nevertheless, studies comparing peripapillary vessel density using OCT-A between IIH patients and controls yielded conflicting results. Our systematic review supports OCT as a powerful tool to accurately monitor retinal axonal and optic nerve head changes in patients with IIH. Future research is required to determine the utility of OCT-A in IIH. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Prompt diagnosis of tuberculous meningitis (TBM) is crucial to prevent severe complications like cranial nerve involvement and irreversible visual impairment. Early suspicion and intervention are essential, especially in tuberculosis‐endemic regions. Rapid initiation of anti‐tuberculosis therapy and vigilant monitoring for complications, such as hydrocephalus, improve patient outcomes and prevent long‐term disabilities. This case study provides a comprehensive overview of the difficulties associated with predicting and managing tuberculous meningitis (TBM). The predictive aspect is hindered by the subacute nature of TBM, featuring a prodromal phase lasting 7–10 days, followed by manifestations like severe headaches, altered mental status, stroke, hydrocephalus, and cranial neuropathies. Additionally, vision loss is a disabling complication. All components of the visual pathway, especially the optic nerve and optic chiasma, are frequently and dominantly affected. While antibiotics can promptly resolve meningitis in most cases, approximately 10% of infections progress to chronic meningitis, with tuberculosis meningitis being the most common form. Our patient initially presented with nonspecific symptoms, which later evolved into symptoms that indicate viral meningitis and was started on empirical therapy. Subsequently, due to clinical suspicion of tuberculosis meningitis and persistent symptoms despite treatment, she was placed in anti‐tuberculosis therapy (ATT) but unfortunately developed complications such as hydrocephalus and blindness. To address the hydrocephalus, a Ventriculo‐Peritoneal shunt was implanted. Despite delayed treatment and diagnosis, most of her symptoms resolved except for blindness, for which there was only partial recovery. [ABSTRACT FROM AUTHOR]

Purpose To compare the quality of optic nerve photographs from three different handheld fundus cameras and to assess the reproducibility and agreement of vertical cup-to-disk ratio (VCDR) measurements from each camera. Methods Adult patients from a comprehensive ophthalmology clinic and an intravitreous injection clinic in northern Thailand were recruited for this cross-sectional study. Each participant had optic nerve photography performed with each of 3 handheld cameras: the Volk iNview, Volk Pictor Plus, and Peek Retina. Images were graded for VCDR in a masked fashion by two photo-graders and images with > 0.2 discrepancy in VCDR were assessed by a third photo-grader. Results A total of 355 eyes underwent imaging with three different handheld fundus cameras. Optic nerve images were judged ungradable in 130 (37%) eyes imaged with Peek Retina, compared to 36 (10%) and 55 (15%) eyes imaged with the iNview and Pictor Plus, respectively. For 193 eyes with gradable images from all 3 cameras, inter-rater reliability for VCDR measurements was poor or moderate for each of the cameras, with intraclass correlation coefficients ranging from 0.41 to 0.52. A VCDR ≥ 0.6 was found in 6 eyes on iNview images, 9 eyes on Pictor Plus images, and 3 eyes on Peek images, with poor agreement between cameras (e.g., no eyes graded as VCDR ≥ 0.6 on images from both the iNview and Pictor Plus). Conclusions Inter-rater reliability of VCDR grades from 3 handheld cameras was poor. Cameras did not agree on which eyes had large VCDRs. [ABSTRACT FROM AUTHOR]

As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair. [ABSTRACT FROM AUTHOR]

Purpose: The optic nerve sheath meningioma (ONSM) is one of the most challenging tumors in orbital surgery. From the perspective of mental health and patient needs, we analyzed the necessity and importance of the endoscopic transnasal approach (ETA) combined with optic nerve transection (ONT) in gross-total resection (GTR) in ONSM patients with residual vision and aim to broaden the use of ONT for specific people. Methods: The authors included patients with ONSMs who were treated between 2014 and 2022. We divided those cases into two groups named ETA group and lateral orbitotomy approach (LOA) group. We present the application of ETA and analyze the preoperative indication of the ONT and compared the advantages and disadvantages between ETA and LOA. The degree of tumor resection was based on imaging and surgical evaluation. Results: A total of 23 patients with ONSM were included. Sixteen patients underwent ETA, and seven underwent LOA. Among ETA cases, GTR was achieved in 14 patients with ONT and most patients maintained normal eye movement function (75%) and morphology (93.75%). In the ETA group, 14 patients experienced vision loss, while two other patients saw improvements in vision. And proptosis was alleviated (5.20 ± 2.34 vs 0.27 ± 0.46, p < 0.0001). Six patients with blindness and proptosis of the LOA group resulted in GTR with ONT and ophthalmectomy. Although intracranial extension and recurrence included no cases in the two groups, a significant psychological gap was presented due to cosmetic problems. Conclusions: Under the premise of reducing damage and improving aesthetics, the selection of ETA combined with ONT to gross-total resect ONSMs successfully provides a minimally invasive access with acceptable complications. As an important adjunct to GTR in the surgical treatment of ONSM, the scope of ONT application should be expanded to relieve the patient's psychological burden. [ABSTRACT FROM AUTHOR]

Background: During neurogenesis, growing axons must navigate through the complex extracellular environment and make correct synaptic connections for the proper functioning of neural circuits. The mechanisms underlying the formation of functional neural networks are still only partially understood. Results: Here we analyzed the role of a novel gene si:ch73‐364h19.1/drish in the neural and vascular development of zebrafish embryos. We show that drish mRNA is expressed broadly and dynamically in multiple cell types including neural, glial, retinal progenitor and vascular endothelial cells throughout the early stages of embryonic development. To study Drish function during embryogenesis, we generated drish genetic mutant using CRISPR/Cas9 genome editing. drish loss‐of‐function mutant larvae displayed defects in early retinal ganglion cell, optic nerve and the retinal inner nuclear layer formation, as well as ectopic motor axon branching. In addition, drish mutant adults exhibited deficient retinal outer nuclear layer and showed defective light response and locomotory behavior. However, vascular patterning and blood circulation were not significantly affected. Conclusions: Together, these data demonstrate important roles of zebrafish drish in the retinal ganglion cell, optic nerve and interneuron development and in spinal motor axon branching. Key Findings: si:ch73‐364h19.1 / drish gene encodes a putative transmembrane protein, which is expressed in neural, glial and vascular endothelial cells in zebrafish embryos.Drish zebrafish mutants show defects in retinal ganglion cell differentiation.Drish mutants exhibit defective branching of motor axons.Drish mutant larvae and adults display reduced swimming activity, a defective light response and deficient prey capture. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential causal association between COVID-19 exposure and optic nerve and visual pathway disorders through a two-sample bidirectional Mendelian randomization (MR) analysis, and to provide empirical support for the lung-brain axis. Methods: This MR analysis utilized publicly accessible summary-level data from genome-wide association studies on COVID-19 (n=158,783) and optic nerve and visual pathway diseases (n=412,181), primarily involving individuals of European descent. The random-effect inverse-variance weighted estimation was applied as the main analytical approach, complemented by MR-Egger, weighted median, and weighted mode methods. The heterogeneity and pleiotropy of the instrumental variables were assessed using Cochran's Q test, leave-one-out sensitivity analysis, MR-Egger intercept test, MR-PRESSO, and funnel plot evaluations. Results: In the forward analysis, the inverse-variance weighted method identified a significant causal effect of COVID-19 on optic nerve and visual pathway disorders (odds ratio = 1.697, 95% confidence interval: 1.086-2.652, p = 0.020). Directionally consistent results were also observed with MR-Egger regression, weighted median, and weighted mode approaches. Conversely, the reverse analysis revealed no causal effects of optic nerve and visual pathway disorders on COVID-19 susceptibility. Conclusion: Our findings suggest that COVID-19 exposure may increase the risk of developing optic nerve and visual pathway disorders, supporting the lungbrain axis hypothesis. These results underscore the importance of vigilant monitoring of the visual system in patients recovering from COVID-19 and suggest potential avenues for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation We investigated the effects of adding regions to current dissemination in space (DIS) criteria for multiple sclerosis (MS).Participants underwent brain, optic nerve, and spinal cord MRI. Baseline DIS was assessed by 2017 McDonald criteria and versions including optic nerve, temporal lobe, or corpus callosum as a fifth region (requiring 2/5), a version with all regions (requiring 3/7) and optic nerve variations requiring 3/5 and 4/5 regions. Performance was evaluated against MS diagnosis (2017 McDonald criteria) during follow‐up.Eighty‐four participants were recruited (53F, 32.8 ± 7.1 years). 2017 McDonald DIS criteria were 87% sensitive (95% CI: 76–94), 73% specific (50–89), and 83% accurate (74–91) in identifying MS. Modified criteria with optic nerve improved sensitivity to 98% (91–100), with specificity 33% (13–59) and accuracy 84% (74–91). Criteria including temporal lobe showed sensitivity 94% (84–98), specificity 50% (28–72), and accuracy 82% (72–90); criteria including corpus callosum showed sensitivity 90% (80–96), specificity 68% (45–86), and accuracy 85% (75–91). Criteria adding all three regions (3/7 required) had sensitivity 95% (87–99), specificity 55% (32–76), and accuracy 85% (75–91). When requiring 3/5 regions (optic nerve as the fifth), sensitivity was 82% (70–91), specificity 77% (55–92), and accuracy 81% (71–89); with 4/5 regions, sensitivity was 56% (43–69), specificity 95% (77–100), and accuracy 67% (56–77).Optic nerve inclusion increased sensitivity while lowering specificity. Increasing required regions in optic nerve criteria increased specificity and decreased sensitivity. Results suggest considering the optic nerve for DIS. An option of 3/5 or 4/5 regions preserved specificity, and criteria adding all three regions had highest accuracy. [ABSTRACT FROM AUTHOR]

Neurons, exhibiting unique polarized structures, rely primarily on the mitochondrial production of ATP to maintain their hypermetabolic energy requirements. To maintain a normal energy supply, mitochondria are transported to the distal end of the axon. When mitochondria within the axon are critically damaged beyond their compensatory capacity, they are cleared via autophagosomal phagocytosis, and the degradation products are recycled to replenish energy. When the mitochondria are dysfunctional or their transport processes are blocked, axons become susceptible to degeneration triggered by energy depletion, resulting in neurodegenerative diseases. As the final checkpoint for mitochondrial quality control, axonal mitophagy is vital for neuronal growth, development, injury, and regeneration. Furthermore, abnormal axonal mitophagy is crucial in the pathogenesis of optic nerve-related diseases such as glaucoma. We review recent studies on axonal mitophagy and summarize the progress of research on axonal mitophagy in optic nerve-related diseases to provide insights into diseases associated with axonal damage in optic ganglion cells. [ABSTRACT FROM AUTHOR]

Background: Implantable electroencephalography (EEG) recording devices have been used for ultra-long-term epilepsy monitoring both in clinical and home settings in people. Objective and accurate seizure detection and recording at home could be of great benefit in diagnosis, management and research in canine idiopathic epilepsy (IE). Continuous EEG monitoring would allow accurate detection of seizure patterns, seizure cycles, and seizure frequency. An EEG acquisition system usable in an "out of clinic" setting could improve owner and veterinary compliance for EEG diagnostics and seizure management. Objectives: Whether a subcutaneous ultra-long term EEG monitoring device designed for humans could be implanted in dogs. Animals: Cadaver study with 8 medium to large breed dogs. Methods: Comparatively using a subcutaneous and submuscular approach to implant the UNEEG SubQ-Implant in each dog. Positioning was controlled via CT post implantation and cranial measurements were taken. Results: In four of the eight dogs a submuscular implantation without any complications was possible. Complications were close contact to the optic nerve in the first approaches, before the implantation angle was changed and in the smallest dog contact of the implant with the orbital fat body. Cranial measurements of less than 95 mm length proved to be too small for reliable implantation via this approach. The subcutaneous approach showed severe limitations and the implant was prone to dislocation. Conclusion: The UNEEQ SubQ-Implant can be implanted in dogs, via submuscular approach. CT imaging and cranial measurements should be taken prior to implantation. [ABSTRACT FROM AUTHOR]