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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.

Highly susceptible fish cell lines are required to isolate and propagate fish nodavirus and the main purpose of the present study is to develop highly susceptible cell lines from Lates calcarifer which is highly vulnerable to viral nervous necrosis. Three permanent cell lines, brain (SBB), eye (SBE) and optic nerve (SBON) were developed from L. calcarifer by explant culture technique and sub-cultured for 97, 128 and 75 respectively, at 28 °C in Leibovitz's L-15 media supplemented with 10% fetal bovine serum (FBS). The plating efficiency of SBB, SBE and SBON cells was determined as 69.09, 63.19 and 48.22%, respectively, and the doubling time was 27, 29 and 38 h, respectively. All these cell lines were stored by cryopreservation at various passage levels, and a recovery rate of 75–95% was observed. Immunostaining of the SBB and SBON cell lines showed that they are of neuronal origin, whereas the SBE cell line is of retinal pigment epithelial origin. Amplification of mitochondrial 16S rRNA gene confirmed that the SBB, SBE and SBON cell lines were of L. calcarifer origin. Three established cell lines showed 15–18% of transfection efficiency. These cell lines were highly susceptible to striped jack nervous necrosis virus (SJNNV) and infection in these cells was confirmed by RT-PCR, immunocytochemistry, Western blot, ELISA and qRT-PCR. The cell lines established from L. calcarifer were continuous, stable and potentially valuable for virological and biomedical studies. [ABSTRACT FROM AUTHOR]

Purpose: To present the outcomes of Ahmed glaucoma valve (AGV) implantation in uveitic glaucoma (UG) in a tertiary eye center in Riyadh, Saudi Arabia. Methods: A retrospective review of all UG patients who underwent AGV implantation at a single, tertiary care eye center from January 2008 to December 2018. The main outcome measures were change in mean intraocular pressure (IOP), number of antiglaucoma medications, overall success rate in different follow-up periods, complete and qualified success from last follow up, and complications. The success of the treatment was defined as patients achieving intraocular pressure (IOP) levels between 6- and 21-mm Hg with or without additional antiglaucoma medications and/or a minimum of 20% reduction from baseline IOP. Results: The study included 74 patients (86 eyes), with a mean follow-up of 4.9 ± 2.9 years. The mean IOP was 32.2 ± 8.5 mmHg at baseline and 16.3 ± 6.6 mmHg at the last follow-up (p < 0.001). The mean number of antiglaucoma medications decreased from 3.5 ± 0.7 preoperatively to 1.3 ± 1.4 at the last follow-up (p < 0.001). Overall survival rates at 1, 3, 5, and 10 years were 96.5%, 92.7%, 91%, and 56.9%, respectively. Complete and qualified success rates were 37.9% and 48.3% at the end of follow up, respectively. The rate of postoperative complications was 56%, of which 18 eyes (20%) required surgical revision. Bivariate Cox proportional hazards regression analysis did not reveal any factors significantly associated with failure. Conclusions: AGV is safe and effective in providing intermediate-term IOP control in UG patients. Complications reported in our cohort were mostly transient and conservatively treated. [ABSTRACT FROM AUTHOR]

Background: The tumor invasion of the skull base structures is very frequent in spheno-orbital meningiomas. The aim of the present study is to evaluate the invasion rate of skull base structures and the best surgical approach and management. Methods: The surgical series of 80 spheno-orbital meningiomas was reviewed. The tumors were classified according to the intraorbital location with respect to the optic nerve axes into three types: I-lateral: II-medial; III-diffuse. The invasion of the orbital apex, optic canal, superior orbital fissure, anterior clinoid, ethmoid-sphenoid sinuses, and infratemporal fossa was evaluated. The rate and extension of involvement of these structures was correlated with the intraorbital location and the surgical approach. The preoperative ophtalmological symptoms and signs and their outcome were also evaluated. Results: Proptosis was found in 79 patients (97%), variable decrease of the visual function in 47 patients (59%), and deficits of the eye movements in 28(35%). The invasion of the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%) was more frequently found, whereas the tumor extension into the ethmoid-sphenoid sinuses (4%) and infratemporal fossa (4%) was rare. Types II and III meningiomas showed significantly higher involvement of the skull base structures than type I ones, which only had 15% invasion of the optic canal. Remission or significant improvement of the visual function occurred postoperatively in 24 among 47 cases (51%), with a higher rate for type I meningiomas vs. other types (p = 0.021, p = 0.019) and worsening in 7 (15%). Conclusions: Spheno-orbital meningiomas growing in the lateral orbital compartment show no involvement of the skull base structures excepting the optic canal as compared to those growing medially or diffusely. The surgical resection of tumor invading the skull base structures should be more extensive as possible, but the risk of optic and oculomotor deficits must be avoided. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to describe the maximum exposure of the infraorbital region via the orbital floor using the transnasal prelacrimal recess approach (PLRA), and to provide an anatomical basis for treating lesions in the infraorbital region. Methods: Ten freshly injected frozen heads were dissected using the PLRA. The orbital floor was removed along the border of the medial infraorbital quadrangle, and the periorbita was opened to expose the infraorbital region. The areas of the medial infraorbital quadrangles were measured and analyzed. The PLRA was applied separately on the left and right sides of each cadaver head, resulting in a total of 20 prelacrimal recess approaches. Results: The PLRA enabled visualization of the optic nerve and the central retinal artery through the orbital floor. By integrating both medial and lateral approaches in relation to the inferior rectus muscle, all crucial anatomical structures within the infraorbital region could be clearly identified. The area of the medial infraorbital quadrangle was 420.65 ± 24.03 mm2. Conclusion: The PLRA provides access through the orbital floor to the maximum boundary of the infraorbital region, including the lateral orbital wall at the outermost level, the superior rectus muscle at the topmost level, and the medial orbital wall at the innermost level. [ABSTRACT FROM AUTHOR]

We characterized the tensile behavior of sclera, optic nerve (ON), and ON sheath in eyes from donors with glaucoma, for comparison with published data without glaucoma. Twelve freshly harvested eyes were obtained from donors with history of glaucoma, of average age 86 ± 7 (standard deviation) years. Rectangular samples were taken from anterior, equatorial, posterior, and peripapillary sclera, and ON sheath, while ON was in native form and measured using calipers. Under physiological temperature and humidity, tissues were preconditioned at 5% strain before loading at 0.1 mm/s. Force–displacement data were converted into engineering stress–strain curves fit by reduced polynomial hyperelastic models and analyzed by tangent moduli at 3% and 7% strain. Data were compared with an age-matched sample of 7 published control eyes. Optic atrophy was supported by significant reduction in ON cross section to 73% of normal in glaucomatous eyes. Glaucomatous was significantly stiffer than control in equatorial and peripapillary regions (P < 0.001). However, glaucomatous ON and sheath were significantly less stiff than control, particularly at low strain (P < 0.001). Hyperelastic models were well fit to stress–strain data (R2 > 0.997). Tangent moduli had variability similar to control in most regions, but was abnormally large in peripapillary sclera. Tensile properties were varied independently among various regions of the same eyes. Glaucomatous sclera is abnormally stiff, but the ON and sheath are abnormally compliant. These abnormalities correspond to properties predicted by finite element analysis to transfer potentially pathologic stress to the vulnerable disk and lamina cribrosa region during adduction eye movement. [ABSTRACT FROM AUTHOR]

To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and to evaluate their usefulness in predicting DR development and progression. Multicenter, multiethnic cohort study. This study included 17 675 participants from the UK Biobank (UKB) who had baseline prediabetes or diabetes, identified in accordance with the 2021 American Diabetes Association guidelines, and were free of baseline DR and an additional 638 participants with type 2 diabetes mellitus from the Guangzhou Diabetic Eye Study (GDES) for external validation. Diabetic retinopathy was determined by ICD-10 codes in the UKB cohort and revised ETDRS grading criteria in the GDES cohort. Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance (NMR) assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort using NMR technology. Model assessments included the concordance (C) statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical usefulness in both cohorts. DR development and progression and retinal microvascular damage. Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C statistic, 0.802 [95% confidence interval (CI), 0.760–0.843] vs. 0.751 [95% CI, 0.706–0.796]; P = 5.56 × 10−4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C statistic, 0.807 [95% CI, 0.711–0.903] vs. 0.617 [95% CI, 0.494–0.740]; P = 1.68 × 10−4) and progression (C statistic, 0.797 [95% CI, 0.712–0.882] vs. 0.665 [95% CI, 0.545–0.784]; P = 0.003) in the external GDES cohort. Improvements in NRIs, IDIs, and clinical usefulness also were evident in both cohorts (all P < 0.05). In addition, lactate and citrate were associated with microvascular damage across macular and optic nerve head regions among Chinese GDES (all P < 0.05). Metabolomic profiling may be effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the optic disc and macula in a large cohort of patients with different severity of optic nerve hypoplasia (ONH) using high‐resolution spectral domain optical coherence tomography (SD‐OCT). Methods: In total, 36 patients (52 ONH eyes and 17 fellow eyes in unilateral cases) and 45 healthy right eyes from 45 controls were evaluated. All patients underwent an examination to confirm the diagnosis. SD‐OCT images of the disc and macula were obtained and analysed both quantitatively and qualitatively. Results: OCT in ONH eyes demonstrated a shorter disc diameter (1061 ± 375 μm vs. 1751 ± 221 μm, p < 0.001), shallower mean cup depth (427 ± 171 μm vs. 551 ± 152 μm, p = 0.01), thinner ganglion cell complex (GCC) perifoveally (47.3 ± 13.0 μm, 60.8 ± 6.0 μm, p < 0.001) and reduced foveal depth (61 ± 36 μm, 119 ± 19 μm, p < 0.001) compared to control eyes. Qualitative analysis showed that 1/3rd of ONH eyes lacked signs of an optic cup, and 2/3rd had reduced or no sign of a foveal pit. Fellow eyes had shorter disc diameter (1446 ± 404 μm vs. 1751 ± 221 μm, p = 0.004) and reduced foveal depth (93 ± 27 μm vs. 119 ± 19 μm, p < 0.001) but similar GCC thickness (60.8 ± 7.1 μm vs. 60.8 ± 6.0 μm, p = 0.738) compared to controls. Disc diameter showed the best correlation with visual acuity in ONH eyes (ρ = 0.517, p < 0.001). Conclusion: ONH eyes have reduced GCC thickness and reduced or no foveal pit. Fellow eyes in presumed unilateral cases have a smaller disc diameter and reduced foveal depth compared to controls, suggesting the possibility of subclinical/mild disease. However, GCC thickness was normal. The correlation between structure and visual function is not always straightforward. [ABSTRACT FROM AUTHOR]

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Objective: There is only one study in the literature in which 3D evaluation of sphenoid sinus volume in patients with cleft lip and palate was used. This shows that this issue has not been adequately evaluated. The present study aimed to compare the volume of the sphenoid sinuses in patients with cleft lip and palate on cone-beam computed tomography images, and to compare them with healthy controls. The high variability of sphenoid sinus volumes poses a risk for iatrogenic lesions during surgical procedures. Because the degree of pneumatization due to increased volume increases the likelihood of exposure of vital neurovascular structures such as the internal carotid artery, maxillary nerves, and optic nerves. Design: Retrospective cohort study. Setting: University Hospital. Patients: A total of 64 patients (32 cleft palate, 32 controls) over 18 years of age who had sphenoid sinuses in the image area were included in our study. Outcomes: Sphenoid Sinus Volume. Results: When the groups were compared in terms of total sinus volume, there was a statistically significant difference between them. Total sinus volume was significantly mean 2.806,87 mm lower in patients with cleft lip and palate compared to the healthy group (P =.015). Conclusion: To be aware this lower volume of the sphenoid sinus in cleft lip and palate patients will be useful for the surgical approach to sphenoid sinus. However, the literature on the subject is insufficient, more comprehensive clinical and radiological studies are needed on a larger sample. [ABSTRACT FROM AUTHOR]

Glaucoma refers to the accumulated loss of retinal cells within the optic nerve or the gradual visual loss caused by optic neuropathy. It is an illness that affects vision in the eye and is considered an irreversible condition that leads to degradation of eyesight. There are often no early warning signs of glaucoma, making it difficult to notice changes in vision due to subtle effects. To date, a large number of Deep Learning (DL) models have been developed for the accurate diagnosis of glaucoma. This work proposes an architecture for deep learning-based glaucoma detection using Convolutional Neural Networks (CNNs). CNNs can distinguish between patterns associated with glaucoma and non-glaucoma conditions, providing a hierarchical structure for classification. Using the proposed method, the disease is detected based on the optic cup-to-disc ratio. The diagnosis is further enhanced by integrating an image data generator for data augmentation. The results demonstrate that the proposed model achieved 98% accuracy, outperforming many existing algorithms. [ABSTRACT FROM AUTHOR]

Background: The resident astrocyte-retinal ganglion cell (RGC) lipoxin circuit is impaired during retinal stress, which includes ocular hypertension-induced neuropathy. Lipoxin B4 produced by homeostatic astrocytes directly acts on RGCs to increase survival and function in ocular hypertension-induced neuropathy. RGC death in the retina and axonal degeneration in the optic nerve are driven by the complex interactions between microglia and macroglia. Whether LXB4 neuroprotective actions include regulation of other cell types in the retina and/or optic nerve is an important knowledge gap. Methods: Cellular targets and signaling of LXB4 in the retina were defined by single-cell RNA sequencing. Retinal neurodegeneration was induced by injecting silicone oil into the anterior chamber of mouse eyes, which induced sustained and stable ocular hypertension. Morphological characterization of microglia populations in the retina and optic nerve was established by MorphOMICs and pseudotime trajectory analyses. The pathways and mechanisms of action of LXB4 in the optic nerve were investigated using bulk RNA sequencing. Transcriptomics data was validated by qPCR and immunohistochemistry. Differences between experimental groups were assessed by Student's t-test and one-way ANOVA. Results: Single-cell transcriptomics identified microglia as a primary target for LXB4 in the healthy retina. LXB4 downregulated genes that drive microglia environmental sensing and reactivity responses. Analysis of microglial function revealed that ocular hypertension induced distinct, temporally defined, and dynamic phenotypes in the retina and, unexpectedly, in the distal myelinated optic nerve. Microglial expression of CD74, a marker of disease-associated microglia in the brain, was only induced in a unique population of optic nerve microglia, but not in the retina. Genetic deletion of lipoxin formation correlated with the presence of a CD74 optic nerve microglia population in normotensive eyes, while LXB4 treatment during ocular hypertension shifted optic nerve microglia toward a homeostatic morphology and non-reactive state and downregulated the expression of CD74. Furthermore, we identified a correlation between CD74 and phospho-phosphoinositide 3-kinases (p-PI3K) expression levels in the optic nerve, which was reduced by LXB4 treatment. Conclusion: We identified early and dynamic changes in the microglia functional phenotype, reactivity, and induction of a unique CD74 microglia population in the distal optic nerve as key features of ocular hypertension-induced neurodegeneration. Our findings establish microglia regulation as a novel LXB4 target in the retina and optic nerve. LXB4 maintenance of a homeostatic optic nerve microglia phenotype and inhibition of a disease-associated phenotype are potential neuroprotective mechanisms for the resident LXB4 pathway. [ABSTRACT FROM AUTHOR]

Background: We assessed the correlation between optic nerve sheath diameter (ONSD) values measured by bedside ultrasound and intracranial pressure (ICP) changes among patients under neurocritical care and evaluated the diagnostic performance of ONSD for increased ICP. Methods: Sixty-seven neurologically critical patients who were hospitalised in the intensive care unit (ICU) of Jining No.1 People's Hospital between September 2023 and March 2024 and underwent lumbar puncture were included. The ONSD was measured and recorded using bedside ultrasound before the lumbar puncture. Patients were divided into normal and increased ICP groups on the basis of the initial lumbar puncture pressure on admission, and both groups were compared. Spearman's correlation analysis was used for evaluating the correlation between ONSD values and ICP. Receiver operating characteristic (ROC) curves were employed for evaluating the diagnostic performance of ONSD for increased ICP. Result: At admission, the Glasgow Coma Scale scores of patients in the increased ICP group were significantly lower than those of patients in the normal ICP group (P < 0.05). The ONSD level of patients in the increased ICP group was significantly higher than that of patients in the normal ICP group (P < 0.05). Spearman's correlation analysis revealed that ONSD positively correlated with ICP among patients with severe neurological diseases (r = 0.777, P < 0.001). The area under the ROC curve when using ONSD for diagnosing lumbar puncture opening pressure ≥ 200 mmH2O was 0.896 (95% confidence interval, 0.817–0.974). When using ONSD ≥ 4.74 mm as the threshold for diagnosing lumbar puncture opening pressure ≥ 200 mmH2O, the sensitivity and specificity were 0.909 and 0.765, respectively. Conclusion: In patients with critical neurological illness, ONSD measured using bedside ultrasound positively correlated with ICP. Increased ICP can be diagnosed for ONSD ≥ 4.74 mm. The ONSD value measured by bedside ultrasound can be used for evaluating ICP among patients with critical neurological illness. [ABSTRACT FROM AUTHOR]

The development of eye pathology is a serious concern for astronauts who spend time in deep space. Microgravity is a major component of the spaceflight environment which could have adverse effects on ocular health. The use of centrifugation to exert forces that partially or fully mimic Earth-level gravity in space is a possible countermeasure to mitigate the effects of microgravity on the eye. Therefore, we subjected mice on the International Space Station (ISS) to microgravity (0 G) or artificial gravity by centrifugation at 0.33 G, 0.67 G, and 1 G, and then performed RNA sequencing (RNA-seq) on optic nerve and retinal tissue after returning them to Earth alive. We find that the microgravity environment induces transcriptomic changes in the optic nerve and retina consistent with an increased oxidative stress load, inflammation, apoptosis, and lipid metabolic stress. We also find that adding artificial gravity on board the ISS attenuates the transcriptomic response to microgravity in a dose-dependent manner. Such attenuation may effectively protect from and mitigate spaceflight-induced detrimental effects on ocular tissue. [ABSTRACT FROM AUTHOR]

Purpose: We describe the clinical findings in a Japanese patient with unilateral traumatic optic neuropathy (TON) who underwent steroid pulse therapy followed by optic canal decompression surgery. The optic nerve function was assessed longitudinally and quantitatively by Goldmann visual fields (GVFs). This was accomplished by measuring the area of each isopter and scotoma, and the findings were compared with the visual acuities recorded during the course of the resolution of the TON. Case Presentation: A 70‐year‐old man suffered from TON in his left eye after falling from a 3 m cliff. On examination at the Saitama Medical University Hospital, his decimal best corrected visual acuity (BCVA) in his left eye was 0.2. Computed tomography revealed a fracture of the lateral wall of the left orbit, but no obvious optic canal fracture was observed. Steroid pulse therapy was started, and optic nerve decompression surgery was performed. After steroid administration, there was a slight improvement in the visual acuity, and a response in the I/3e isopter was present (area 17.76 deg2). However, the V/4e area decreased from 539.35 to 359.36 deg2. Three days after the optic canal decompression surgery, the decimal visual acuity improved to 0.6, and the V/4e area and I/3e area increased to 1122.52 and 46.88 deg2, respectively. Postoperatively, there was a marked improvement in the size of the GVFs that corresponded to the improved visual acuity. The visual acuity of the left eye was 0.8 after 6 months, and the GVF was still not completely normal. Conclusions: Our findings showed the course of recovery of the visual acuity and visual field in an eye with TON. The quantification of GVF was helpful in assessing the course of recovery after the treatments. The new quantitative index of the GVFs may be helpful in evaluating the effectiveness of treatments for optic nerve disorders. [ABSTRACT FROM AUTHOR]

Background: Among young people, multiple sclerosis (MS) accounts for the majority of non-traumatic neurological impairments. Almost all MS patients develop optic neuritis as the illness progresses. In MS, the optic nerve (ON) is vulnerable to demyelinating injury and is considered "eloquent" in comparison with the brain. Thus, it serves as a clinical model for MS. Since the eye is a suitable target for ultrasonography due to its high-water content, non-invasive trans-orbital sonography (TOS) can determine the optic nerve sheath diameter (ONSD). This research aimed to determine the effectiveness of ON ultrasonography as a simple, low-cost method for diagnosing and following up MS patients, facilitating their treatment plan. It correlates the findings of ONSD using TOS and visual-evoked potential (VEP), the number of magnetic resonance imaging (MRI) black holes, and other clinically significant parameters in 30 relapsing–remitting MS (RRMS) patients versus 30 controls. Results: We examined a total of 120 eyes. The ONSD values at 3 mm, 5 mm, and myelination index were significantly lower in the patients (4.7 ± 0.3, 5.5 ± 0.3, and 0.86 ± 0.03, respectively) versus the controls (5.6 ± 0.3, 6.2 ± 0.4, and 0.90 ± 0.03, respectively) (p < 0.001 in each). The mean P 100 latency was significantly delayed in the patients (125.5 ± 6.1 ms) than the controls (100.2 ± 3.3 ms), (p < 0.001). The mean VEP amplitude was significantly lower in the patients (4.9 ± 0.7 μV) than the controls (6.8 ± 0.8 μV) (p < 0.001). There was a highly significant positive correlation between the ONSD and P 100 amplitude, and highly significant negative correlations between the ONSD and disease duration, number of optic neuritis attacks, EDSS, MRI black holes number, and P 100 latency. Conclusions: Trans-orbital sonography is a practical and easily accessible approach for assessing ON atrophy in MS. It can measure axonal loss and brain atrophy indirectly and is a reliable paraclinical diagnostic tool, suggesting that ONSD could be a biomarker of disease activity. [ABSTRACT FROM AUTHOR]

Background: Serum neurofilament light chain (sNfL) is a biomarker of neuroaxonal destruction that correlates with acute inflammation (AI) in multiple sclerosis (MS). However, in the treatment era, progression without AI is the main driver of long-term disability. sNfL may provide added value in detecting ongoing axonal damage and neurological worsening in patients without AI. We conducted a prospective three-year study on patients with a first MS relapse to evaluate the basal cut-off value predicting early increased disability unrelated to relapses. Methods: sNfL levels and AI presence were measured every 6 months during the first year and the Expanded Disability Status Scale (EDSS) was monitored until the third year. Baseline cohorts were stratified by sNfL levels, using a cut-off derived from patients without AI (absence of clinical relapses, new/enlarging T2 lesions, or gadolinium enhancement in magnetic resonance imaging) at year one. Results: Fifty-one patients were included. A sNfL cut-off of 11 pg/mL predicted sustained neurological worsening independent of AI. Patients exceeding this threshold exhibited features of highly active MS (higher proportion of AI, oligoclonal M bands and higher EDSS). Despite AI ablation, sNfL levels persisted elevated and were significantly associated with increased EDSS at baseline and year 3. Patients with low sNfL and concurrent AI (n = 8) experienced relapses in the optic nerve, brainstem, and spinal cord topographies. Conclusion: sNfL elevation may detect patients with increased disability even when AI is controlled. This may reveal mechanisms associated with early axonal degeneration and help identify patients at higher risk of progression. [ABSTRACT FROM AUTHOR]

Background: In cases of optic disc edema or a pale optic disc, distinguishing an episode of optic neuritis (ON) from that of non-arteritic anterior ischemic optic neuropathy (NAION) during a clinical examination is challenging. Optical coherence tomography angiography (OCTA) can reveal differences in peripapillary vascular network structures and provide biomarkers for differential diagnosis. Methods: A total of 23 eyes with NAION, 22 eyes with demyelinating ON (DON), and 27 eyes from healthy participants were imaged using OCTA to observe the radial peripapillary capillaries (RPCs). Optical coherence tomography was used to measure peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (mGCC). Data for all patients were recorded at 2–3 weeks and more than 3 months after the symptom onset. Results: A total of 23 affected eyes from 23 patients with NAION (average age 52.17 ± 7.92 years), 22 eyes from 22 patients with demyelinating optic neuritis (DON) (average age 47.88 ± 19.24 years), and 27 eyes from 27 healthy individuals (average age 46.43 ± 14.08 years) were included in the study. There were no significant differences in sex, age, and eye laterality between any two groups (F = 0.968, 0.475, 0.870; p > 0.05). Throughout the course of NAION and DON, the superior RPC, superior mGCC, and peripapillary RNFL decreased with time (p < 0.05). In contrast, the inferotemporal RPC and inferior mGCC did not decrease from the acute to chronic stage in NAION (t = 1.639, 0.834, p = 0.117, 0.413). Compared with the normal group, patients with NAION and DON exhibited a sharp reduction in the average RPC, RNFL, and GCC from the acute to the chronic stage (p < 0.05). Patients with DON exhibited a significant decrease in the inferotemporal RPC and inferior mGCC compared with the patients with NAION (p < 0.05). In contrast, there were no significant differences in the inferior mGCC at the chronic stage between the patients with NAION and those with ON (t = 2.547, p = 0.093). Conclusion: Various structural and microvascular changes were observed in patients with NAION and ON, indicating distinct features of the optic nerve during the different stages of NAION and ON. Peripapillary vascular density, measured using spectral domain OCT (SD-OCT), may be a biomarker to distinguish NAION from ON. [ABSTRACT FROM AUTHOR]

Traumatic optic neuropathy (TON) consists of damage to the optic nerve following head injury and affects about 0.5–5% of patients with closed head injuries. It is characterized by a sudden decrease in visual acuity and/or visual field loss. Surgical treatment is usually warranted when ongoing compression occurs at the level of the optic canal. We describe the technical nuances of endoscopic endonasal approach for compressive TON and add evidence supporting this approach as a valid option to treat this condition. [ABSTRACT FROM AUTHOR]

Optic nerve (ON) injury causes blindness in adult mammals as their retinal ganglion cells (RGCs) cannot regenerate axons. However, amphibian RGC axons do not experience the same regenerative failure. Studying the regeneration process of the ON in amphibians holds profound implications for regenerative medicine and human health. Using transgenic tadpoles and laser micro-optics, we developed a reproducible ON transection and regeneration model. Through microscopy of axon dynamics, functional testing to assess visual pathway recovery, TUNEL cell death and EdU cell proliferation assays, and RNA-seq of the retina and optic nerve, we characterized the optic nerve injury response and subsequent recovery. Our model suggests no chemoattractant gradient exists early in regeneration, with defasciculated axons sprouting in random directions from the globe-proximal cut end. Once individual axons reach the appropriate targets in the brain, their tract is reinforced by other regenerating axons, restoring normal ON morphology. Thus, guidance cues or scaffolding from brain-innervating axons likely support later stages of regeneration. After 14 days, the regenerated ON is morphologically indistinguishable from the naïve ON, and visual function is restored. We found no evidence of RGC death or new RGC formation in the model, suggesting that ON regeneration involves remodeling of injured axons of pre-existing RGCs. [ABSTRACT FROM AUTHOR]

Impaired visual function is a prevalent feature of optic neuritis (ON) in multiple sclerosis (MS). Abnormal visual evoked potential (VEP) findings of increased latencies, reduced amplitudes and abnormal waveforms as well as decreased retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT) are hallmarks of ON-induced visual dysfunction. Here we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to investigate the functional and pathological progression during early (before any clinical symptoms), peak (initial maximal clinical symptoms), and late (chronic disease for > 3 weeks) disease stages. Demyelination and initial stages of axon damage were observed in early EAE. Significant demyelination, inflammation, increased axon damage and impaired P1/N2 amplitudes and latencies by VEP were seen in middle and late EAE groups. A decrease in RNFL thickness by OCT was observed only during late EAE. NanoString analysis of optic nerves from late EAE indicated elevated inflammation-related genes, reduced myelin-related genes, and changes in axon degeneration-related genes. Early inflammatory demyelination and functional deficits of the visual pathway, if untreated, may lead to severe irrecoverable axon damage in EAE. These studies potentially help explain the progression of visual dysfunction during MS. [ABSTRACT FROM AUTHOR]

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Neuromyelitis optica spectrum disorder (NMOSD) affects the optic nerves and spinal cord but can also cause focal brain inflammation. Subcortical pathology may contribute to the etiology of cognitive deficits in NMOSD. Using myelin water imaging, we investigated cerebral normal‐appearing white matter (NAWM) and thalamic metrics and their association with cognition in NMOSD participants compared to healthy controls (HC).Seventeen NMOSD participants and 21 HC were scanned on a 3.0‐Tesla MRI scanner using a multicomponent driven‐equilibrium single‐pulse observation of T1 and T2 protocol. Tissue compartment and thalamic volumes (normalized to intracranial volume), T1 relaxation time, and myelin water fraction (MWF) were reported. Eleven NMOSD participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive evaluation. Group comparisons were performed using Student's t‐test. The association between thalamic metrics and SDMT score was assessed using multiple regression analysis with age as a covariate.Compared to HC, NMOSD participants had reduced white matter volume (−14.2%, p < .0001), increased T1 relaxation time (+2.29%, p = .022), and lower MWF (−3.64%, p = .024) in NAWM. NMOSD group had a trend for smaller thalamic volumes than HC (−5.52%, p = .082) and no differences in thalamic MWF (p = .258) or T1 (p = .714). Thalamic T1 predicted SDMT score (adjusted R2 = .51, p = .04) when controlling for age.NAWM in NMOSD demonstrates diffuse abnormalities with increased water content and demyelination, suggesting a diffuse disease process overlooked by focal inflammation measures. Increased water content, as a biomarker for diffuse thalamic pathology, may partially explain cognitive impairment in NMOSD. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities—specifically whether they originate in the inner or outer retina—remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease. [ABSTRACT FROM AUTHOR]

Detecting and monitoring elevated intracranial pressure (ICP) is crucial in managing various neurologic and neuro-ophthalmic conditions, where early detection is essential to prevent complications such as seizures and stroke. Although traditional methods such as lumbar puncture, intraparenchymal and intraventricular cannulation, and external ventricular drainage are effective, they are invasive and carry risks of infection and brain hemorrhage. This has prompted the development of non-invasive techniques. Given that direct, non-invasive access to the brain is limited, a significant portion of research has focused on utilizing the eyes, which uniquely provide direct access to their internal structure and offer a cost-effective tool for non-invasive ICP assessment. This review explores the existing non-invasive ocular techniques for assessing chronically elevated ICP. Additionally, to provide a comprehensive perspective on the current landscape, invasive techniques are also examined. The discussion extends to the limitations inherent to each technique and the prospective pathways for future advancements in the field. [ABSTRACT FROM AUTHOR]

Background: Endoscopic Endonasal Decompression for Traumatic Optic Nerve Injury has become an established endoscopic technique. However, Poor sphenoid sinus pneumatization often obscures landmarks, elevating the risk to vital neurovascular structures. Method: By decompressing the orbital apex region and determining the contour of the optic nerve, sequential decompression of the medial wall, superomedial wall, and inferomedial wall of the optic canal. Conclusion: This surgical technique can gradually reveal the contour of the optic canal when the anatomical landmarks on the lateral wall of the sphenoid sinus are unclear, ensuring the surgery can be completed safely and effectively. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions To evaluate the safety of repeated low‐level red‐light (RLRL) therapy in children, and the dynamic evolution of choroidal and retinal blood flow.This is a single‐centre, randomised, single‐blind, parallel‐group clinical trial. Seventy myopic children were randomly assigned to either the intervention group [receiving RLRL therapy plus single‐vision spectacle (SVS)] or the control group (wearing SVS). Participants underwent comprehensive ophthalmic examinations following their first irradiation, 9 months continuous RLRL therapy and stop of treatment. Quantitative analyses of choroidal and retinal microcirculation were analysed via optical coherence tomography angiography.Over 9 months of treatment, while the RLRL treatment demonstrated significantly less increases in refractive error and axial length compared with the SVS treatment (ps < 0.05), no abnormalities in fundus structure or visual function (mfERG, VEP and microperimetry) were detected (ps > 0.05). A single red‐light exposure did not exert a significant influence on choroidal thickness (ps > 0.05). Upon continuous treatment, the RLRL group achieved peak values in these circulations at 9 months (ps < 0.05). Following cessation of exposure, all circulations exhibited a declining trend, reaching similar levels in both groups (ps > 0.05). As the frequency of red‐light exposures intensified, there was a consistent surge in these circulations (ps < 0.05).Nine months of continuous RLRL exposure does not cause toxic side effects on retinal or optic nerve functions, and there is a time‐dependent cumulative response in choroidal and retinal circulation. [ABSTRACT FROM AUTHOR]

Pathogenic heterozygous variants in CACNA1A are associated with familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6, and more recently, neurodevelopmental disorders. We describe a severe, early-onset phenotype including severe muscular hypotonia, early-onset epileptic seizures, apnoea, optic atrophy and dysphagia in three siblings carrying compound heterozygous frameshift variants in CACNA1A. Two male patients died at the age of 5 or 14 months of suspected SIDS or severe developmental epileptic encephalopathy (DEE) with refractory seizures and apnoea. A male child (index patient) developed severe early-onset DEE including seizures and ictal apnoea at the age of 4 weeks. Another male child developed generalized epilepsy and mild intellectual impairment in late infancy, and his mother and his maternal uncle were identified as carriers of a known CACNA1A pathogenic variant [c.2602delG heterozygous, p. (Ala868Profs*24)] with a diagnosis of episodic ataxia type 2. This maternal pathogenic variant c.2602delG was detected in the index patient and child 2. Trio-Exome sequencing identified an additional heterozygous pathogenic variant in the CACNA1A gene, c.5476delC, p.(His1826Thrfs*30) in the index patient and child 2, which was inherited from the asymptomatic father. In conclusion, the novel compound heterozygosity for two frameshift pathogenic variants, maternally [c.2602delG, p.(Ala868Profs*24)] and paternally [c.5476delC, p.(His1826Thrfs*3)] is associated with a severe phenotype of early-onset DEE. This observation highlights the necessity of additional analyses to clarify unusual phenotypes even if a pathogenic variant has already been identified, and expands the clinical spectrum of CACNA1A -related disorders. [ABSTRACT FROM AUTHOR]

To objectively correlate distortions of optic apparatus morphology in patients with pituitary adenomas undergoing trans-sphenoidal surgery. In this retrospective analysis, visual acuity (VA), visual field (VF), and total visual (TV) function were objectively scored in patients selected from an institutional cohort of pituitary adenomas. The following imaging measures of optico-chiasmatic morphology were recorded preoperatively, and at 3 months after surgery: chiasm area, mid-chiasm height (CH), optic nerve-canal bending angle (BA), and optic nerve kinking angle (ONKA). Receiver operator characteristic analysis was performed to establish optimal thresholds for achieving a "normal" TV score of 200 at 1-year follow-up. Seventy-one eyes were individually studied. VA, VF, and TV scores significantly improved after surgery, both at the 3-month and at the 1-year follow-up visits (P < 0.001). Cranio-caudal tumor dimension was significantly associated with VA, VF, and TV scores, both preoperatively and postoperatively. There were significant changes in CH (P < 0.001), BA (P < 0.001), and ONKA (P < 0.001) at 3 months after surgery, but not in chiasm area (P = 0.061). Baseline VA, VF, and TV scores were positively correlated with preoperative CH and ONKA, while VF and TV scores also demonstrated significant negative correlations with preoperative BA. VF scores at 1-year follow-up were significantly correlated with preoperative and change in BA values, as well as with preoperative and change in ONKA values. Receiver operator characteristic analysis revealed that only the preoperative ONKA was found to have acceptable discrimination (area under the curve >0.7) for predicting "normal" TV score. Chiasm sag was noted in 45.8% of patients at 1-year follow-up, but was not associated with delayed visual deterioration in any case. Anatomic realignment of the optic apparatus 3 months following trans-sphenoidal surgery predicts VF scores, but not VA or TV scores at 1-year follow-up. Patients with preoperative ONKA values of more than 139.3° have a 76% chance of achieving normal TV scores 1 year after surgery. Postoperative chiasm sag appears to be clinically irrelevant at short-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma is a leading cause of irreversible blindness. Glaucomatous intraocular pressure (IOP) triggers deleterious effects, including gliosis, optic nerve (ON) axonal retraction, neurotrophic factor deprivation, inflammation, and other pathological events, leading to retinal ganglion cell (RGC) loss. Trophic factor impairment enhances RGC apoptosis susceptibility. Neuritin 1 (NRN1), a neurotrophic protein downstream of various neurotrophins, exhibited RGC protection and regeneration in axotomy models. We evaluated human recombinant NRN1's impact on human RGCs cultured in pressurized conditions within the ex vivo translaminar autonomous system to simulate glaucoma pathogenesis. Methods: Human glaucomatous and non-glaucomatous donor eyes were obtained from eye banks according to the Declaration of Helsinki. Initially, we evaluated NRN1and RGC marker expression in glaucoma and non-glaucomatous retina to determine the NRN1 level and its association with RGC loss. Further, we evaluated NRN1's therapeutic potential by treating pressurized human eyes at normal and high IOP for seven days. Retina, ON, and conditioned medium were analyzed for RGC survival (THY1, RBPMS), gliosis (GFAP), apoptosis (CASP3, CASP7), and extracellular matrix deposition (COLIV, FN) by qRT-PCR and western blotting. Paraphenylenediamine staining assessed ON axonal degeneration, whereas ex vivo electroretinogram assessed retinal activity. Results: Glaucomatous retinas exhibited significant reductions in both NRN1 (*p = 0.007, n = 5) and RGC marker expression (*p = 0.04, n = 5). NRN1 treatment reduced gliosis, extracellular matrix deposition, ON degeneration, and increased retinal activity in pressure-perfused eyes. Conclusions: Our study confirms that NRN1 enhances human RGC survival and improves retinal function in degenerative conditions, substantiating it as a promising candidate for rescuing human RGCs from degeneration. [ABSTRACT FROM AUTHOR]

Corneal hysteresis (CH) is associated with glaucomatous structural changes. We retrospectively investigated the association between CH and the regional circumpapillary retinal nerve fibre layer thickness (cpRNFLT) in 419 eyes of 419 patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). CH was used as the explanatory variable, and cpRNFLT (total and quadrant) was used as the dependent variable. Standardized β coefficients were compared both overall and between the NTG and POAG groups. Multiple regression analysis with CH as the explanatory variable and cpRNFLT parameters as the dependent variables suggested that even after adjusting for age, sex, intraocular pressure (IOP), axial length, and central corneal thickness, all areas of the cpRNFLT were significantly associated with CH, except for the nasal quadrant. In the stratified analysis by glaucoma type, a positive relationship between CH and regional cpRNFLT tended to be maintained in the NTG group but not in the POAG group (P = 0.060 for interaction). Additionally, in the NTG group, the CH-inferior cpRNFLT relationship was particularly strong in the less-IOP fluctuation group. These results suggest that CH may be a potential predictor of anatomical vulnerability around the optic nerve, particularly enhancing the inferior regions of NTG. [ABSTRACT FROM AUTHOR]

Glaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context. In this study, we evaluated mitochondrial genome variation and heteroplasmy using massively parallel sequencing of mtDNA in a cohort of patients with POAG, and in a subset assess the role of somatic mitochondrial genome mutations in disease pathogenesis using paired samples of peripheral blood leukocytes and ocular tissue (Tenon's ocular fibroblasts). An enrichment of potentially pathogenic nonsynonymous mtDNA variants was identified in Tenon's ocular fibroblasts from participants with POAG. The absence of oxidative DNA damage and predominance of transition variants support the concept that errors in mtDNA replication represent the predominant mutation mechanism in Tenon's ocular fibroblasts from patients with POAG. Pathogenic somatic mitochondrial genome mutations were observed in people with POAG. This supports the role of somatic mitochondrial genome variants in the etiology of glaucoma. [ABSTRACT FROM AUTHOR]

We report two patients who displayed evidence of localized ocular inflammation after CAR T-cell infusion. To manage the resulting severe visual impairment, systemic corticosteroids were administered to both patients. This treatment led to a reduction in local inflammation and restored vision in one of the patients. [ABSTRACT FROM AUTHOR]

Objective: To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons. Methods: A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists. Results: Studies reporting ocular abnormalities during the prenatal (n = 5) and postnatal (n = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed. Conclusion: This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized. Protocol registration: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188. [ABSTRACT FROM AUTHOR]

Objective: 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. Design, Patients and Measurements: 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. Results: 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. Conclusion: 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]

[Display omitted] • The RXR agonist 9CDHRA was utilised to determine its neuroprotective abilities. • Signs of transsynaptic degeneration were reduced in mice administered 9CDHRA. • Injured mice had restored VEP visual assessments with 9CDHRA treatment. • This supports previous research defining RXR agonist's remyelinating properties. Neurodegenerative and demyelinating disease, such as multiple sclerosis (MS) are at the forefront of medical research and the discovery of new drugs and therapeutics. One phenomenon of degeneration seen in these diseases is transsynaptic degeneration (TSD), where damage from one axon spreads to the other axons that are connected to it synaptically. It has previously been found that demyelination occurs prior to neuronal loss in an experimental form of induced TSD. Retinoid-x receptor (RXR) agonists have been shown to promote remyelination. Therefore, this study aimed to reveal the effects of a novel endogenous RXR-γ agonist, 9- cis -13,14-dihydroretinoic acid (9CDHRA), on preventing or restoring the effects of TSD. 9CDHRA was administered to mice following optic nerve crush (ONC) procedures, and electrophysiology (visual evoked potential, VEP) and histological (immunofluorescent) assessments were performed. It was found that 9CDHRA treatment effectively delayed glial activation and reduced the presence of apoptosis at the site of injury and further anterogradely in the visual system, including the lateral geniculate nucleus (LGN) and primary visual cortex (V1). Most notably, 9CDHRA was able to maintain myelin levels following ONC, and effectively protected from demyelination. This was corroborated by VEP recordings with improved P1 latency. The promising findings regarding the injury attenuating and myelin protecting properties of 9CDHRA necessitates further investigations into the potential therapeutic uses of this compound. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to describe the temporal changes in causes and prevalence of childhood visual impairment in Denmark based on the National Danish Registry of Children with Visual Impairment (NDRCVI). Methods: Annual reports on the NDRCVI since its establishment in 1979 were reviewed and data on the number of registered children and the causes for registration with a visual impairment were evaluated. Results: The average annual incidence of childhood visual impairment in Denmark is 2.8 per 1000 live‐born children and the prevalence of childhood visual impairment is 1.6 per 1000 children <18 years. Today, fewer children are severely visually impaired (visual acuity ≤6/60) at the time of registration (31.6% since 2010 vs. 51.1% in the 1980s). Cerebral visual impairment and optic nerve atrophy have remained common causes of childhood visual impairment whereas sequelae to retinopathy of prematurity have been almost eliminated as a cause. Systemic comorbidities are more common now in children with visual impairment (seen in 63.9% in the last decades vs. 44.6%in the 1980‐ties). Conclusion: Whereas the prevalence of visual impairment has remained relatively stable over the years, the severity of visual impairment has improved, suggesting that more children will be able to live an active life supported by aids compensating vision loss. However, more children have systemic comorbidities in combination with their visual impairment suggesting that children with visual impairment face a life not only limited by the obstacles of poor vision. This calls for multidisciplinary management and support of affected children and families. [ABSTRACT FROM AUTHOR]

A 71-year-old woman developed sudden, painful, decreased vision in the left eye accompanied by progressive instability. Initial examination revealed left optic disc edema, and macular optical coherence tomography confirmed the presence of intraretinal and subretinal fluid, as well as hyperreflective material under the retinal pigment epithelium. Subsequent investigations, including brain magnetic resonance imaging and a comprehensive serological analysis, ruled out infectious and autoimmune causes, further complicating the diagnostic picture. The patient's vision in both eyes continued to deteriorate, prompting empirical corticosteroid treatment. While the vision improved, the case took an unexpected turn with worsening neurological symptoms. Ultimately a brain biopsy was consistent with diffuse large B-cell lymphoma. [ABSTRACT FROM AUTHOR]

The optic nerve canal (ONC) is a fine skeletal structure that contains the optic nerve. However, it has not been thoroughly examined. This necessitates establishing a baseline knowledge of the geometrical and volumetric parameters of the ONC. The data of twenty patients who received a cone beam computed tomography examination were prepared using a voxel-based segmentation. The measurement was performed separately by two examiners on virtual skull models in stereolithography format in Geomagic Wrap®. The results showed that the volume of the ONC varied between 92.48 mm3 and 162.7 mm3 (M = 123.46 mm3, SD = 26.61 mm3). Sex-specific statistically significant differences in volume were detected only for the right side. The angle of the ONC to the skull base was independent of the diameter of the canal. Both the intrarater and interrater comparisons of the measurements showed high values of reproducibility of the results. This study showed that a virtual anatomical model provides a feasible and reliable method to investigate the ONC. The examination technique could have a wider range of application in anthropology and application in clinical medicine. Advances in the automation of radiological diagnostics and the digital analysis of X-ray images could help to reduce examination times. [ABSTRACT FROM AUTHOR]

Purpose: To compare children's stereometric optic disc parameters and inner retinal thickness measured by optical coherence tomography (OCT) in two different moments in life in the same children and to establish a correlation between the optic nerve head (ONH) area and the difference of these parameters in the two observations. Methods: In this observational cohort, children were evaluated on two occasions: at 6.7 ± 1.6 and 13.2 ± 0.7 years of age. Cup volume, neuroretinal rim (NRR) area, average cup-to-disc ratio, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell inner plexiform layer (GCIPL) were measured by the Cirrus HD-OCT (Carl Zeiss Meditec AG). Results: A total of 175 children were included, 89 boys (50.9%) and 86 girls (49.1%). There was a significant decrease of the NRR area (P <.001) and increase of the cup volume (P <.001) on the second observation. The pRNFL thickness and GCIPL thickness also decreased (P <.001 and P =.002, respectively). There was a positive correlation between the ONH area and the difference of the cup volume (P =.047; r = 0.102) and a negative correlation with the difference of the NRR area (P <.001; r = 0.237). Conclusions: During childhood, there is an increase of the cup volume, a decrease of the NRR area, and a decrease of inner retinal layer thickness (more significant in the superior and inferior quadrants) measured by OCT. This study demonstrates that in children with large discs the enlargement of the cup and decrease of the NRR is more evident. Considering these changes, the physiological enlargement of the cup in a child with a large disc can be misinterpreted as the development of a glaucomatous lesion. [J Pediatr Ophthalmol Strabismus. 2024;61(6):410–415.] [ABSTRACT FROM AUTHOR]

This article presents two miniaturized antennas designed for retinal prosthesis devices, aimed at enhancing vision for blind individuals with functional optic nerves. The implantable antenna is 2.2 mm wide, 2.15 mm tall, and 0.78 mm thick. It works in the ISM bands but is small because it uses slot incorporation and high-permittivity substrates. High-frequency structure simulator (HFSS) electromagnetic simulations show great performance, with a 16.66% impedance bandwidth at 2.4 GHz and a 10.34% bandwidth at 5.8 GHz. The peak gain values are -27.76 dB at 2.4 GHz and -16.40 dB at 5.8 GHz. We have also developed an extraocular antenna for telemetry and energy transfer, with dimensions of 36x36x1.6 mm³. Validation through CST calculation software confirms the efficacy of both antenna designs. Implantable antennas hold significant promise in biomedical antenna research, demonstrating capabilities conducive to retinal implantation and offering potential advancements in vision restoration technology. [ABSTRACT FROM AUTHOR]

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is down- regulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration. [ABSTRACT FROM AUTHOR]

Introduction: Caffeine, the most widely consumed psychoactive drug globally, has been associated with vascular changes in various organs, including the retina. Researchers have reported vascular constriction in the retina in response to caffeine, although data on its effects remain limited and somewhat contradictory. Further research is needed to clarify the specific impact of caffeine on retinal blood vessels and its potential implications for ocular health. Purpose: To investigate the effects of 200 mg of caffeine on systolic and diastolic blood pressure (SBP and DBP) and retinal vessel density (VD) assessed by optical coherence tomography angiography (OCTA). Methods: Prospective randomized, double‐blind placebo‐controlled, IRB‐approved study in 59 healthy low caffeine users (< 136 mg of caffeine daily). Baseline 3 × 3 and 6 × 6 mm OCTA scans centered on the fovea as well as a 6 × 6 mm scans centered on the optic nerve head (ONH) were obtained. Participants were randomly assigned into caffeine group (CG, n = 42) receiving 200 mg caffeine pill or placebo group (PG, n = 17). OCTA scans were repeated at 60 and 120 min after intervention. VD was measured with Advanced Retina Imaging (ARI) network software (Carl Zeiss Meditec, Dublin, CA) for superficial capillary plexus (SCP) and deep capillary plexus (DCP). SBP/DBP readings were recorded before each imaging session. Ordinary one‐way analysis of variance (ANOVA) of each group was performed using GraphPad Prism Version 9.3.0. Results: Both groups had comparable demographics and OCTA parameters at baseline. Two hours after intervention, the CG had a significantly higher SBP (123 ± 7 mmHg) and DBP (81 ± 5 mmHg) compared to the control group (118 ± 7 mmHg, 77 ± 6 mmHg) (p value = 0.012, 0.023). Regarding the OCTA VD metrics, there were no significant differences in VD between the caffeine and placebo groups, regardless of whether the scans were centered on the macula or ONH. Additionally, the comparison across different OCTA scan modalities, specifically the 3 × 3 mm and 6 × 6 mm scans, showed no discernible differences among groups. Conclusion: In conclusion, 200 mg of caffeine elevated blood pressure after 2 h but did not impact the retinal VD. This underscores the intricate relationship between caffeine, blood pressure, and retinal vascular dynamics, prompting further exploration of their implications for ocular health, especially in subjects with vascular disease. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo describe an upper eyelid swinging approach (U-Swing) that is suitable for the surgical excision of a large benign encapsulated lesions located in the intraconal space superolateral to the optic nerve.This is a retrospective case series. The study included a review of five patients’ records who had large encapsulated intraconal masses, superolateral to the optic nerve, and who underwent surgical excision with the U-Swing approach in the authors’ institute over the last 10 years. This approach entailed a planned upper temporal fornix-based conjunctival flap and a lateral canthotomy. Preoperative radiological investigations, pre- and post-operative vision testing, and photographs were presented with at least 6 months follow-up.All patients within the 1st postoperative month had minimal postoperative edema, minimal conjunctival redness, no visible conjunctival or skin scar, normal pupil size and pupil reaction, full extra ocular motility, recovered upper eyelid position and excursion.The U-Swing approach provides a horizontally expandable surgical window that allows safe removal of a large, encapsulated intraconal mass, superolateral to the optic nerve with low morbidity and rapid recovery. [ABSTRACT FROM AUTHOR]

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy. [ABSTRACT FROM AUTHOR]

Key points Spontaneous cerebrospinal fluid rhinorrhea (sCSFR) is often accompanied by an increase in intracranial pressure (ICP). The widening of optic nerve sheath diameter (ONSD) is an indicator of increased ICP. Using CT to measure ONSD is a simple and noninvasive auxiliary method for determining high ICP in sCSFR patients. Spontaneous cerebrospinal fluid rhinorrhea (sCSFR) is often accompanied by an increase in intracranial pressure (ICP).The widening of optic nerve sheath diameter (ONSD) is an indicator of increased ICP.Using CT to measure ONSD is a simple and noninvasive auxiliary method for determining high ICP in sCSFR patients. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions The purpose of this study is to describe modification of the lateral enucleation technique without ligation or clamping of the optic nerve, document the incidence of complications, estimate intraoperative blood loss and identify possible risk factors for the developments of complications.Medical records of dogs, cats, and rabbits undergoing lateral enucleation without clamping of the optic nerve were identified and retrospectively reviewed for post‐operative complications (2000–2022). The significance of possible risk factors for the development of complications, including species, sex, age, eye, surgeon, presumed ocular surface infection, cultures, follow‐up, antibiotics, NSAIDs, complications and diabetes mellitus was examined in a subset of these patients (2019–2022). As a prospective study, intraoperative blood loss was estimated by gravimetric analysis in an additional subset.Records of 1296 enucleations were retrospectively reviewed and detailed evaluation regarding potential risk factors was performed in 446 enucleations. The overall complication rate and surgical site infection rate was 2.31% and 2.08% respectively. Only Pseudomonas spp. bacterial culture was associated with development of complications. Estimated relative intraoperative blood loss was 2.2% and 4.1% in 43 dogs and 29 cats respectively.The modified lateral enucleation technique is a safe and fast procedure with minimal risk of postoperative complications in dogs, cats, and rabbits. Based on the anatomy of the orbital vasculature ligation or clamping of the optic nerve and surrounding tissue is contraindicated. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models. The results show that impaired mitophagy exists in RGCs of our experimental glaucomatous model. In vivo, PR-619 increased RGCs survival in glaucomatous rats. In vitro, it protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression. Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ratios, and elevated LAMP1 levels, indicating enhanced mitophagy in vivo and in vitro. Moreover, numbers of mitophagosomes were increased in optic nerves of PR-619-treated ocular hypertensive rats in vivo. Furthermore, parkin knockdown negated the salutary effects of PR-619 and attenuated expression of parkin-dependent mitophagy effectors in RGCs subjected to glutamate excitotoxicity in vitro. Collectively, these findings implicate augmented parkin-mediated mitophagy as the mechanistic substrate underscoring the neuroprotective capacity of PR-619 in experimental glaucoma. These revelations engender the prospect that pharmacological agents or biotherapeutics augmenting parkin-mediated mitophagy may proffer viable therapeutic modalities for glaucomatous neurodegeneration characterized by impaired mitophagy. [ABSTRACT FROM AUTHOR]