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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]

Simple Summary: Uveal melanoma is a common eye malignancy and is managed by surgery, brachytherapy or external beam radiation for early-stage disease. Proton therapy is a newer form of radiation therapy and is especially suited to treat large uveal melanoma because of its unique physical characteristics. This review describes the physics, radiobiology, treatment techniques, and clinical outcomes when using proton therapy to treat uveal melanoma, with a focus on choosing between brachytherapy and proton therapy. Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to evaluate the computed tomography (CT) scans of glaucoma patients using prostaglandin analogs (PGA) in one eye, investigate findings associated with prostaglandin-associated periorbitopathy (PAP), and compare these findings with those of the contralateral eyes. Methods: Patients with open-angle glaucoma who had CT images of the orbital region taken for another reason at least one month after starting PGA treatment in one eye were included in the study. Enophthalmos measurements from thin-slice CT images, along with 3D volume measurements of orbital fat tissue, periorbital muscles, and the optic nerve, were performed. Ophthalmological examination findings and treatment information were collected. The values were compared with those of the contralateral eyes of the same patients not using PGA. Intraclass correlation coefficients (ICCs) were computed to evaluate measurement repeatability. Results: Forty patients were included in the study. Among them, 29 (72.5%) used latanoprost, 9 (22.5%) used bimatoprost, and 2 (5%) used travoprost. The mean enophthalmos values on the treated side (15.5 ± 2.0 mm) were lower than on the untreated side (16.1 ± 1.4 mm), but this difference was not statistically significant (p = 0.07). In 29 patients (72.5%), enophthalmos measurements were smaller on the treated side, with 7 patients (17.5%) showing a difference of 2 mm or more. No significant correlation was found between the duration of PGA use and enophthalmos measurements (p = 0.768 r = −0.048). Additionally, no significant differences were found in orbital fat volume, total extraocular muscle volume, and optic nerve volume (p > 0.05). ICC values demonstrated excellent reliability (ICC > 0.75) for all measurements. Conclusions: We did not find significant differences in enophthalmos measurements, orbital fat volume, total muscle volume, and optic nerve volume between the PGA-treated and untreated eyes. [ABSTRACT FROM AUTHOR]

Background: Bleeding within the orbit in the form of a subperiosteal or retrobulbar hematoma is a relatively common complication of trauma and surgery. It affects up to 30% of patients fractures involving the orbital bones. Most cases do not require surgical intervention because they do not cause retinal ischemia or optic nerve neuropathy. The above symptoms occur in only 0.5–1% of patients developing Orbital Compartment Syndrome (OCS). Due to the short period (60–100 min) of time in which the optic nerve and retina can tolerate increased intraocular pressure, it seemed reasonable to evaluate and standardize the surgical management protocol for this rare complication. Objective: The aim of this retrospective study was to retrospectively analyze cases of inframammary haematomas with clinically relevant correlations. Methods: Eighteen patients treated at the Department of Maxillofacial Surgery due to OCS, in Lodz and Poznan, Poland, between 2009 and 2022, were included. APTT, INR, systemic diseases, cause, location and size of hematoma, presence and number of fractures, visual disturbances and pupillary response on the day after surgery and one month after, the type of intervention and time between admission to the hospital and surgery were evaluated. Results: Statistically significant correlations were obtained between the size of the hematoma and the patients' age, the degree of visual disturbance and the weakening of pupillary constriction, severe initial symptoms and poor postoperative outcomes at both postoperative periods studied, immediate and distant poor outcome after decompression surgery and good postoperative outcome persisting one month after. Conclusions: The results obtained in the study and the surgical protocol proposed by the authors are in line with the current state of knowledge regarding orbital hematomas. Some of the correlations described in the literature (such as OCS and anticoagulant treatment) were not demonstrated, but this is probably due to the small study group. Maintaining the 100 min limit as a standard was possible only in early postoperative diagnoses (only 1 of the patients was operated on up to 100 min after the appearance of symptoms). In other cases, the specialized diagnosis took an average of 2785 ± 4020 min or 46 ± 67 h. [ABSTRACT FROM AUTHOR]

Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments—including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation—can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharynx cancer treatment often involves radiation therapy, but choosing the best method can be challenging. This study compares two advanced radiation techniques: one using X-rays and another using protons. Both aim to target the tumor while sparing healthy tissues, but their effectiveness can vary based on the cancer's location and stage. Researchers want to determine which technique works best for different patients, particularly those with cancer close to sensitive brain structures. By analyzing treatment plans for 28 patients, we developed guidelines to help doctors choose the most suitable technique. This research could lead to more personalized and effective treatments, potentially improving outcomes and quality of life for patients with nasopharynx cancer. The findings may also help healthcare providers use resources more efficiently, benefiting both patients and the broader medical community. Background: Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. Methods: HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Results: Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. Conclusions: NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long-term anatomical and functional prognosis of patients with retinal detachment (RD) secondary to acute retinal necrosis (ARN) treated with pars plana vitrectomy (PPV). Methods: This retrospective case series included 21 eyes from 21 patients with RD secondary to ARN. The study analyzed vitreous or aqueous biopsy results, the impact of antiviral therapy, time to retinal detachment, changes in visual acuity (VA), and anatomical and surgical outcomes. All cases underwent 23-gauge PPV with silicone oil tamponade, and an episcleral encircling band was used in 11 cases. All patients received systemic antiviral therapy at diagnosis. Results: Retinal reattachment was achieved in 91% of cases during follow-up, with an average follow-up period of 39.5 ± 36.8 months. The average time from ARN diagnosis to RD onset was 33.3 ± 27.5 days. VZV was detected in 10 eyes through PCR analysis. Significant differences in visual prognosis were found between macula-off and macula-on RD (p = 0.048). Eyes with optic nerve head inflammation had worse final VA (p = 0.010). No significant difference was observed between preoperative VA and VA at the end of follow-up (p = 0.665). Conclusions: VZV was the primary virus associated with ARN-related RD. Early involvement of the macula and optic nerve in retinitis negatively impacted the final visual prognosis. [ABSTRACT FROM AUTHOR]

Background: optic nerve glioblastoma is an uncommon pathology. The optic chiasm, optic tract, or optic nerves are possible places from which the tumor can originate. Most of the neuroimaging findings are nonspecific. To confirm the diagnosis, a biopsy is required. A delay to the treatment plan for optic nerve glioblastoma results in poor patient survival rates. Case report: a 68-year-old woman with an uncomplicated medical history presented with exophthalmos, deteriorating eyesight, and partial loss of vision. Using radiological data together with postoperative histopathological and histochemical analysis, optic nerve glioblastoma, IDH-wildtype, with optic chiasm involvement was diagnosed. Conclusion: optic nerve glioblastoma is a rare and aggressive form of cancer that affects the optic nerve, leading to significant vision impairment and potentially life-threatening complications. Treatment options are restricted and difficult because of the location and nature of the condition; surgery, radiation therapy, and chemotherapy are frequently needed as part of a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

The diameter of the optic nerve sheath is an important indicator for assessing the intracranial pressure in critically ill patients. The methods for measuring the optic nerve sheath diameter are generally divided into invasive and non-invasive methods. Compared to the invasive methods, the non-invasive methods are safer and have thus gained popularity. Among the non-invasive methods, using deep learning to process the ultrasound images of the eyes of critically ill patients and promptly output the diameter of the optic nerve sheath offers significant advantages. This paper proposes a CBC-YOLOv5s optic nerve sheath ultrasound image segmentation method that integrates both local and global features. First, it introduces the CBC-Backbone feature extraction network, which consists of dual-layer C3 Swin-Transformer (C3STR) and dual-layer Bottleneck Transformer (BoT3) modules. The C3STR backbone's multi-layer convolution and residual connections focus on the local features of the optic nerve sheath, while the Window Transformer Attention (WTA) mechanism in the C3STR module and the Multi-Head Self-Attention (MHSA) in the BoT3 module enhance the model's understanding of the global features of the optic nerve sheath. The extracted local and global features are fully integrated in the Spatial Pyramid Pooling Fusion (SPPF) module. Additionally, the CBC-Neck feature pyramid is proposed, which includes a single-layer C3STR module and three-layer CReToNeXt (CRTN) module. During upsampling feature fusion, the C3STR module is used to enhance the local and global awareness of the fused features. During downsampling feature fusion, the CRTN module's multi-level residual design helps the network to better capture the global features of the optic nerve sheath within the fused features. The introduction of these modules achieves the thorough integration of the local and global features, enabling the model to efficiently and accurately identify the optic nerve sheath boundaries, even when the ocular ultrasound images are blurry or the boundaries are unclear. The Z2HOSPITAL-5000 dataset collected from Zhejiang University Second Hospital was used for the experiments. Compared to the widely used YOLOv5s and U-Net algorithms, the proposed method shows improved performance on the blurry test set. Specifically, the proposed method achieves precision, recall, and Intersection over Union (IoU) values that are 4.1%, 2.1%, and 4.5% higher than those of YOLOv5s. When compared to U-Net, the precision, recall, and IoU are improved by 9.2%, 21%, and 19.7%, respectively. [ABSTRACT FROM AUTHOR]

Background: Optic neuropathies represent one of the most frequent causes of vision loss, and they can manifest alone or in conjunction with neurological or systemic symptoms and signs. In recent years, the diagnostic techniques used to detect optic neuropathies have significantly improved, facilitating diagnosis and improving treatment. Among these, ocular ultrasound has assumed a fundamental role, although with conflicting results in the published scientific literature. For this reason, the aim of this review is to analyze the role of ocular ultrasound in the precise and targeted diagnosis of optic neuropathies to better understand the presumed potential of this precious diagnostic tool in the management of these ocular and neurological disorders. Methods: We carried out a search on PubMed and Scopus utilizing terms related to optic neuropathies and ocular ultrasound, including only relevant English full-length research articles, case reports, or case series. Results: Most of the papers published in the scientific literature use only the B-scan ultrasound technique without considering the more precise and objective standardized A-scan technique that allows for performing more accurate diagnostic tests, such as the "30-degree test" and the "optic nerve exercise test". Conclusions: Future clinical trials and research on optic neuropathies should also consider the use of the standardized A-scan technique in order to compare clinical findings not only with B-scan ultrasonography but also with other noninvasive procedures that could be helpful in reaching the correct diagnosis. [ABSTRACT FROM AUTHOR]

Rotenone is a mitochondrial complex I inhibitor that causes retinal degeneration. A study of a rat model of rotenone-induced retinal degeneration suggested that this model is caused by indirect postsynaptic N-methyl-D-aspartate (NMDA) stimulation triggered by oxidative stress-mediated presynaptic intracellular calcium signaling. To elucidate the mechanisms by which rotenone causes axonal degeneration, we investigated morphological changes in optic nerves and the change in retinal ganglion cell (RGC) number in rats. Optic nerves and retinas were collected 3 and 7 days after the intravitreal injection of rotenone. The cross-sections of the optic nerves were subjected to a morphological analysis with axon quantification. The axons and somas of RGCs were analyzed immunohistochemically in retinal flatmounts. In the optic nerve, rotenone induced axonal swelling and degeneration with the incidence of reactive gliosis. Rotenone also significantly reduced axon numbers in the optic nerve. Furthermore, rotenone caused axonal thinning, fragmentation, and beading in RGCs on flatmounts and decreased the number of RGC soma. In conclusion, the intravitreal injection of rotenone in rats induced morphological abnormities with a reduced number of optic nerve axons and RGC axons when the RGC somas were degenerated. These findings help elucidate the pathogenesis of optic neuropathy induced by mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old mother (P1), 12-year-old daughter (P2), and a 2-year-old son (P3). The phenotype included early-onset cataract (P1), optically empty vitreous with avascular membranes (P1, 2), nasal dragging of optic nerve heads associated with foveal hypoplasia (P1, 2), tractional retinoschisis on optical coherence tomography (P2), and peripheral circumferential vitreo-retinal interface abnormality resembling white-without-pressure (P3) progressing to pigmented chorio-retinal atrophy (P1, 2). P2 developed a macula-off retinal detachment, which was treated initially with encircling band + vitrectomy + gas, followed by vitrectomy + heavy silicone oil tamponade for re-detachment from new inferior breaks. Strong vitreo-retinal adhesion was noted intraoperatively, which prevented the separation of posterior hyaloid beyond the equator. Electroretinograms from P1&2 demonstrated attenuated b-waves, a-waves, and flicker responses in light- and dark-adapted conditions, suggestive of generalised retinal dysfunction. Our patients demonstrated the clinical spectrum of Wagner syndrome, highlighting nasal dragging with foveal disruption as a distinguishing feature from other inherited vitreoretinopathies. Surgical outcomes demonstrate significant challenges in managing vitreo-retinal traction and need for further research into strategies to prevent sight loss. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway. [ABSTRACT FROM AUTHOR]

Our goal was to assess the impact of retrobulbar anaesthesia on ocular pressure and perfusion development and to find out if there were systemic or biometric parameters of patients affecting them in order to understand the effect of retrobulbar anaesthesia better. Methods: Changes in intraocular pressure (IOP) and ocular pulse amplitude (OPA) using a dynamic contour tonometer (DCT) were noted before and after retrobulbar anaesthesia (RBA) in combination with five minutes of oculopression at 40 mmHg in 134 patients. Only results with a quality Q 1–3 were considered for further statistical analysis. Systemic and ophthalmic parameters were noted and their impact was tested using linear regression. Results: IOP decreased from 18.9 ± 7.2 mmHg to 15.4 ± 6.3 mmHg (n = 71, p = 0.001) after first RBA. The dosage of midazolam administered during premedication was found to increase IOP significantly after first RBA (B = 3.75; R2 = 0.38). Ocular pulse amplitude decreased significantly from 3.8 ± 1.7 mmHg to 3.0 ± 1.9 mmHg after first RBA (n = 72, p < 0.001). This change was found to be dependent on the presence of diabetes mellitus (n = 68, p = 0.048). Conclusions: IOP and OPA decrease after RBA and oculopression. Caution is needed with midazolam premedication due to potential IOP increase. Patients with diabetes and pre-existing retinal or optic nerve damage should consider alternative anaesthesia methods, such as eye drops or general anaesthesia, due to the observed decrease in OPA after RBA and oculopression. [ABSTRACT FROM AUTHOR]

Background/Objectives: Posterior staphyloma (PS) is a hallmark of pathological myopia, corresponding to a circumscribed outpouching of the eyeball with choroidal thinning and inward scleral deformation at its edges. Its pathogenesis is still unclear, thus constituting a research priority as the prevalence of myopia is increasing worldwide. Recently, it has been suggested that the optic nerve sheaths or oblique muscles are potential promoters of PS through the traction or compression effect that they apply to the eye wall. The inferior oblique muscle (IOM) inserts 1–2 mm from the macula. The projection of its insertion is accessible using Optical Coherence Tomography (OCT). Before launching prospective studies, we sought to detect any choroidal thinning (ChT) in the temporal vicinity of the macula and to measure the distance between it and the fovea (FT-distance). Methods: This retrospective cross-sectional pilot study included 120 eyes. Using Spectralis®-OCT, the area centered by the Bruch's membrane opening–fovea axis was analyzed for ChT and FT-distance. Results: Of the 112 defined eyes, 70% (78 eyes) had ChT. Pachymetry was significantly thinner (p = 0.018) in eyes with than without ChT. The mean FT-distance was 3601.9 ± 93.6 µm. Conclusions: The location of ChT coincided with the insertion distance of the IOM, suggesting a link between them. The association between the presence of ChT and a thinner pachymetry suggests a reduced scleral resistance, as a thinner pachymetry is related to a thinner sclera. Our results suggest a link between ocular deformation and the IOM, which may be relevant for the pathogenesis of PS, warranting further investigation. [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]

Neutrophils, traditionally viewed as first responders to infection or tissue damage, exhibit dynamic and diverse roles in ocular health and disease. This review elaborates on previous findings that showed how neutrophils contribute to ocular diseases. In ocular infections, neutrophils play a pivotal role in host defense by orchestrating inflammatory responses to combat pathogens. Furthermore, in optic nerve neuropathies and retinal degenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR), neutrophils are implicated in neuroinflammation and tissue damage owing to their ability to undergo neutrophil extracellular trap formation (NETosis) and secretion of inflammatory molecules. Targeting neutrophil-dependent processes holds promise as a therapeutic strategy, offering potential avenues for intervention in ocular infections, cancers, and retinal degenerative diseases. Understanding the multifaceted roles of neutrophils in ocular diseases is crucial for developing targeted therapies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGE accumulation is strongly linked to the development of diabetic retinopathy. Type 2 diabetes mellitus is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE–β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with diabetes mellitus and AD. [ABSTRACT FROM AUTHOR]

Glaucoma remains the primary cause of long-term blindness. While diabetes mellitus (DM) and hypertension (HTN) are known to influence glaucoma, other factors such as age and sex may be involved. In this retrospective study, we aimed to investigate the associations between age, sex, DM, HTN, and glaucoma risk. We employed optical coherence tomography (OCT) conducted using a 200 × 200-pixel optic cube (Cirrus HD OCT 6000, version 10.0; Carl Zeiss Meditec, Dublin, CA, USA). Effects obscured by low-test signals were disregarded. Data were amassed from 1337 patients. Among them, 218 and 402 patients had DM and HTN, respectively, with 133 (10%) exhibiting both. A sex-based comparison revealed slightly greater retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL) thickness in females. Patients without DM and HTN were predominantly in their 50 s and 60 s, whereas DM and HTN were most prevalent in those in their 60 s and 70 s. Both RNFL and GCIPL thicknesses decreased with advancing age in most patients. The study revealed that older individuals were more prone to glaucoma than younger individuals, with a higher incidence among patients with DM and HTN and reduced RNFL and GCIPL thicknesses. Furthermore, early detection before advancing age could furnish valuable preventive insights. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) is a relatively uncommon autoantibody demyelinating disorder of the central nervous system (CNS) with heterogeneous clinical manifestations and magnetic resonance imaging (MRI) findings. In recent years, a rare MOGAD subtype characterized by distinct clinical and MRI findings has been described. Seizures and cortical hyperintensities best seen on MRI T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences, associated with headache and cerebral spine fluid (CSF) pleocytosis, are the most important characteristics of this MOGAD entity that is named FLAMES (FLAIR hyperintense cortical lesions in MOG-associated encephalitis with seizures). Because of its rarity and the peculiarities of the brain damage and clinical manifestations, it can be under-recognized and confused with focal viral encephalitis, meningitis, subarachnoid hemorrhage, CNS vasculitis, or mitochondrial cytopathy. We described the case of a 4-year-old previously healthy girl who was admitted for focal-onset, tonic-clonic seizures, fever, and headache, combined with optic neuritis. MRI was characterized by FLAIR imaging showing hyperintense cortical lesions, and a mild leukocytosis in the CSF was detected. Efficacy and rapid response to steroid therapy was observed, and no recurrences of neurological problems or further seizures were reported in the following 12 months. This case report can help in understanding FLAMES characteristics in pediatrics in order to favor early diagnosis and prompt therapy. [ABSTRACT FROM AUTHOR]

The effects of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and visual function were assessed in rat and mouse models of optic nerve (ON) crush. ONs were crushed on Day 1, followed by intravitreal injections of a vehicle or BDNF on Days 1 and 8. The spatial frequency threshold was measured using optokinetic tracking on Days 7 and 14. On Day 15, ganglion cell complex (GCC) thickness was quantified using optical coherence tomography. Furthermore, all eyes were enucleated for immunohistochemical analysis of the surviving RGC somas and axons. BDNF significantly reduced the RGC soma in mice and increased GCC thickness in intact eyes, with apparent axonal swelling in both species. It displayed significantly greater RGC soma survival in eyes with ON injury, with moderately thicker axonal bundles in both species and a thicker GCC in rats. Visual function was significantly reduced in all ON-crushed animals, regardless of BDNF treatment. Thus, we obtained a comprehensive analysis of the structural and functional impact of BDNF in intact and ON-crushed eyes in two rodent models. Our results provide a foundation for further BDNF evaluation and the design of preclinical studies on neuroprotectants using BDNF as a reference positive control. [ABSTRACT FROM AUTHOR]

The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in embryos during the early fetal period, including the second half of the first trimester of pregnancy. Serial sections through the orbit of variously aged embryos allowed us to analyze the nerve in both longitudinal and transverse aspects. A histological assessment and description of the structures surrounding and inside the nerve were performed, highlighting the cellular subtypes involved. By employing immunohistochemical techniques, we could characterize the presence and distribution of astrocytes within the optic nerve. Our findings suggest that by the 8th gestational week (WG) the structures are homologs to all the adult ones but with an early appearance so that maturation processes take place afterward. By this age, the axons forming the nerve are definitive adult axons. The glial cells do not yet exhibit adult phenotype, but their aspect becomes adult toward the 13th week. During its development the optic nerve increases in size then, at 14 weeks, it shrinks considerably, possibly through its neural maturation process. The morphological primordium of the blood–nerve barrier can be first noted at 10 WG and at 13 WG the morphological blood–nerve barrier is definitive. The meningeal primordium can be first noted as a layer of agglomerated fibroblasts, later toward 13 WG splitting in pachymeninx and leptomeninges and leaving space for intrinsic blood vessels. [ABSTRACT FROM AUTHOR]

The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic. [ABSTRACT FROM AUTHOR]

BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective small compound (CPSC) that inhibits BAX-mediated cell death. We examined whether M109S can protect RGC from optic nerve crush (ONC)-induced apoptosis. M109S was administered starting 5 h after ONC for 7 days. M109S was orally administered in two groups (5 mg/kg twice a day or 7.5 mg/kg once a day). The retina was stained with anti-BRN3A and cleaved Caspase-3 (active Caspase-3) that are the markers of RGC and apoptotic cells, respectively. ONC decreased the number of BRN3A-positive RGC and increased the number of active Caspase-3-expressing apoptotic cells. In ONC-treated retina, there were cells that were double stained with anti-BRN3A and ant-cleaved Caspase-3, indicating that apoptosis in BRN3A-positive RGCs occurred. M109S inhibited the decrease of BRN3A-positive cells whereas it inhibited the increase of active Caspase-3-positive cells in the retina of ONC-treated mice, suggesting that M109S inhibited apoptosis in RGCs. M109S did not induce detectable histological damage to the lungs or kidneys in mice, suggesting that M109S did not show toxicities in the lung or kidneys when the therapeutic dose was used. The present study suggests that M109S is effective in rescuing damaged RGCs. Since M109S is an orally bioactive small compound, M109S may become the basis for a portable patient-friendly medicine that can be used to prevent blindness by rescuing damaged optic nerve cells from death. [ABSTRACT FROM AUTHOR]

Background: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. Methods: Spectral-domain optical coherence tomography (SD-OCT) was used to assess nine adult, ADAMTS10-mutant (median age 45.6 months, range 28.8–52.8 months; mean diurnal intraocular pressure (IOP): 29.9 +/− SEM 0.44 mmHg) and three related age-matched control Beagles (mean diurnal IOP: 18.0 +/− SEM 0.53 mmHg). Results: Of all the optic nerve head (ONH) parameters evaluated, the loss of myelin peak height in the horizontal plane was most significant (from 154 +/− SEM 38.4 μm to 9.3 +/− SEM 22.1 μm; p < 0.01). There was a strong significant negative correlation between myelin peak height and IOP (Spearman correlation: −0.78; p < 0.003). There were no significant differences in the thickness of any retinal layers evaluated. Conclusions: SD-OCT is a useful tool to detect early glaucomatous damage to the ONH in dogs before vision loss. Loss in myelin peak height without inner retinal thinning was identified as an early clinical disease marker. This suggests that initial degenerative changes are mostly due to the loss of myelin. [ABSTRACT FROM AUTHOR]

Glaucoma, a leading cause of irreversible blindness, poses a significant global health burden. Early detection is crucial for effective management and prevention of vision loss. This study presents a collection of novel structural biomarkers in glaucoma diagnosis. By employing advanced imaging techniques and data analysis algorithms, we now can recognize indicators of glaucomatous progression. Many research studies have revealed a correlation between the structural changes in the eye or brain, particularly in the optic nerve head and retinal nerve fiber layer, and the progression of glaucoma. These biomarkers demonstrate value in distinguishing glaucomatous eyes from healthy ones, even in the early stages of the disease. By facilitating timely detection and monitoring, they hold the potential to mitigate vision impairment and improve patient outcomes. This study marks an advancement in the field of glaucoma, offering a promising avenue for enhancing the diagnosis and possible management. [ABSTRACT FROM AUTHOR]

Postmortem human eyes were subjected to optic nerve (ON) traction in adduction and elevated intraocular pressure (IOP) to investigate scleral surface deformations. We incrementally adducted 11 eyes (age 74.1 ± 9.3 years, standard deviation) from 26° to 32° under normal IOP, during imaging of the posterior globe, for analysis by three-dimensional digital image correlation (3D-DIC). In the same eyes, we performed uniaxial tensile testing in multiple regions of the sclera, ON, and ON sheath. Based on individual measurements, we analyzed eye-specific finite element models (FEMs) simulating adduction and IOP loading. Analysis of 3D-DIC showed that the nasal sclera up to 1 mm from the sheath border was significantly compressed during adduction. IOP elevation from 15 to 30 mmHg induced strains less than did adduction. Tensile testing demonstrated ON sheath stiffening above 3.4% strain, which was incorporated in FEMs of adduction tethering that was quantitatively consistent with changes in scleral deformation from 3D-DIC. Simulated IOP elevation to 30 mmHg did not induce scleral surface strains outside the ON sheath. ON tethering in incremental adduction from 26° to 32° compressed the nasal and stretched the temporal sclera adjacent to the ON sheath, more so than IOP elevation. The effect of ON tethering is influenced by strain stiffening of the ON sheath. [ABSTRACT FROM AUTHOR]

This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention (p = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease's pathophysiology and warranting further investigation into underlying mechanisms and clinical implications. [ABSTRACT FROM AUTHOR]

Background and Objectives: A magnetic resonance imaging (MRI) scan is part of the diagnostic protocol in pituitary adenoma patients. The goal of the present study is to present and analyse the MRI appearances of the sphenoid sinus (SS) in patients with non-functioning pituitary adenoma (NFPA). Materials and Methods: This is a retrospective case–control study conducted between January 2015 and December 2023 in a tertiary referral hospital. Forty NFPA patients were included in the study group, while the control group consisted of 30 age- and gender-matched cases. Results: The sellar type of SS pneumatization was the most frequently encountered pattern among both groups. The presence of the lateral recess of the SS, mucosal cysts, and sphenoethmoidal cells was similar in both patient groups. The proportion of patients with SS mucosal thickness greater than 3 mm was 42.5% in NFPA group and 3% in the control group, and this difference was statistically significant (p < 0.001). The space between the two optic nerves was significantly larger in the NFPA group as compared to the control group (p < 0.001). Conclusions: Our study was able to establish a statistically significant association between the presence of NFPA and both the thickening of the SS mucosa and increased space between optic nerves. [ABSTRACT FROM AUTHOR]

In recent years, researchers have been interested in neuroprotective therapies as a cutting-edge therapeutic strategy to treat neurodegenerative disorders by shielding the brain system from harmful events. Millions of individuals worldwide suffer from glaucoma, an ocular neurodegenerative disease characterized by gradual excavation of the optic nerve head, retinal axonal damage, and consequent visual loss. The pathology's molecular cause is still mostly unknown, and the current treatments are not able to alter the disease's natural progression. Thus, the modern approach to treating glaucoma consists of prescribing medications with neuroprotective properties, in line with the treatment strategy suggested for other neurodegenerative diseases. For this reason, several naturally derived compounds, including nicotinamide and citicoline, have been studied throughout time to try to improve glaucoma management by exploiting their neuroprotective properties. The purpose of this review is to examine the naturally derived compounds that are currently utilized in clinical practice for neuroprotection in glaucomatous patients based on scientific data, emphasizing these compounds' pivotal mechanism of action as well as their proven therapeutic and neuroprotective benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study is crucial for understanding the rare occurrence of ocular and periocular metastasis in breast cancer. By exploring demographics and clinical aspects, we aim to improve the management of this condition. Our focus is on enhancing treatment strategies, predicting outcomes, and ultimately improving the quality of life for breast cancer patients with ocular metastasis. This study addresses the gaps in knowledge regarding the intricacies of this manifestation, driving progress toward more effective interventions and better patient outcomes. Background: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. Methods: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. Results: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. Conclusions: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis. [ABSTRACT FROM AUTHOR]

Background: The objective of this investigation was to formulate a model for predicting intracranial pressure (ICP) by utilizing optic nerve sheath diameter (ONSD) during endovascular treatment for an aneurysmal subarachnoid hemorrhage (aSAH), incorporating explainable predictive modeling. Methods: ONSD measurements were conducted using a handheld ultrasonography device during the course of endovascular treatment (n = 126, mean age 58.82 ± 14.86 years, and female ratio 67.46%). The optimal ONSD threshold associated with an increased ICP was determined. Additionally, the association between ONSD and ICP was validated through the application of a linear regression machine learning model. The correlation between ICP and various factors was explored through the modeling. Results: With an ICP threshold set at 20 cmH2O, 82 patients manifested an increased ICP, with a corresponding ONSD of 0.545 ± 0.08 cm. Similarly, with an ICP threshold set at 25 cmH2O, 44 patients demonstrated an increased ICP, with a cutoff ONSD of 0.553 cm. Conclusions: We revealed a robust correlation between ICP and ONSD. ONSD exhibited a significant association and demonstrated potential as a predictor of ICP in patients with an ICP ≥ 25 cmH2O. The findings suggest its potential as a valuable index in clinical practice, proposing a reference value of ONSD for increased ICP in the institution. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). Methods: We investigated the expression of PRCP in the optic nerves of experimental autoimmune optic neuritis (EAON)-induced mice. Peripheral blood samples were collected from ON patients (n = 20) and healthy controls (n = 20). ELISA was used to measure the plasma PRCP levels. We performed measurements of visual acuity and the mean thicknesses of the macular ganglion cell layer plus inner plexiform layer (GCL+IPL) at diagnosis and 6 months after diagnosis. Results: The PRCP mRNA expression in EAON-induced mice was markedly higher than that in naïve mice. The mean plasma PRCP level was significantly higher in patients with ON than in controls. Plasma PRCP levels were negatively correlated with logMAR visual acuity at 6 months after diagnosis and differences in macular GCL+IPL thickness during an ON attack. A plasma PRCP level of 49.98 (pg/mL) predicted the recurrence of ON with a 75% sensitivity and 87.5% specificity. Conclusions: Patients with idiopathic acute ON had higher plasma PRCP levels, and this was positively correlated with final visual outcome and well-preserved macular GCL+IPL thickness during an ON attack. The increase in plasma PRCP level may reflect its compensatory secretion to counteract neuroinflammation in ON patients. [ABSTRACT FROM AUTHOR]

Being the primary site of degeneration, the optic nerve has always been the focus of structural glaucoma assessment. The technical advancements, mainly of optical coherence tomography (OCT), now allow for a very precise quantification of the optic nerve head and peripapillary retina morphology. By far the most commonly used structural optic nerve parameter is the thickness of the parapapillary retinal nerve fiber, which has great clinical utility but also suffers from significant limitations, mainly in advanced glaucoma. Emerging novel imaging technologies, such as OCT angiography, polarization-sensitive or visible-light OCT and adaptive optics, offer new biomarkers that have the potential to significantly improve structural glaucoma diagnostics. Another great potential lies in the processing of the data already available. Artificial intelligence does not only help increase the reliability of current biomarkers but can also integrate data from various imaging modalities and other clinical measures to increase diagnostic accuracy. And it can, in a more efficient way, draw information from available datasets, such as an OCT scan, compared to the current concept of biomarkers, which only use a fraction of the whole dataset. [ABSTRACT FROM AUTHOR]

Imaging from optical coherence tomography (OCT) is widely used for detecting retinal diseases, localization of intra-retinal boundaries, etc. It is, however, degraded by speckle noise. Deep learning models can aid with denoising, allowing clinicians to clearly diagnose retinal diseases. Deep learning models can be considered as an end-to-end framework. We selected denoising studies that used deep learning models with retinal OCT imagery. Each study was quality-assessed through image quality metrics (including the peak signal-to-noise ratio—PSNR, contrast-to-noise ratio—CNR, and structural similarity index metric—SSIM). Meta-analysis could not be performed due to heterogeneity in the methods of the studies and measurements of their performance. Multiple databases (including Medline via PubMed, Google Scholar, Scopus, Embase) and a repository (ArXiv) were screened for publications published after 2010, without any limitation on language. From the 95 potential studies identified, a total of 41 were evaluated thoroughly. Fifty-four of these studies were excluded after full text assessment depending on whether deep learning (DL) was utilized or the dataset and results were not effectively explained. Numerous types of OCT images are mentioned in this review consisting of public retinal image datasets utilized purposefully for denoising OCT images (n = 37) and the Optic Nerve Head (ONH) (n = 4). A wide range of image quality metrics was used; PSNR and SNR that ranged between 8 and 156 dB. The minority of studies (n = 8) showed a low risk of bias in all domains. Studies utilizing ONH images produced either a PSNR or SNR value varying from 8.1 to 25.7 dB, and that of public retinal datasets was 26.4 to 158.6 dB. Further analysis on denoising models was not possible due to discrepancies in reporting that did not allow useful pooling. An increasing number of studies have investigated denoising retinal OCT images using deep learning, with a range of architectures being implemented. The reported increase in image quality metrics seems promising, while study and reporting quality are currently low. [ABSTRACT FROM AUTHOR]

In addition to general anesthesia and mechanical ventilation, robotic-assisted laparoscopic radical prostatectomy (RALP) necessitates maintaining a capnoperitoneum and placing the patient in a pronounced downward tilt (Trendelenburg position). While the effects of the resulting fluid shift on the cardiovascular system seem to be modest and well tolerated, the effects on the brain and the blood–brain barrier have not been thoroughly investigated. Previous studies indicated that select patients showed an increase in the optic nerve sheath diameter (ONSD), detected by ultrasound during RALP, which suggests an elevation in intracranial pressure. We hypothesize that the intraoperative fluid shift results in endothelial dysfunction and reduced cerebral clearance, potentially leading to transient neuronal damage. This prospective, monocentric, non-randomized, controlled clinical trial will compare RALP to conventional open radical prostatectomy (control group) in a total of 50 subjects. The primary endpoint will be the perioperative concentration of neurofilament light chain (NfL) in blood using single-molecule array (SiMoA) as a measure for neuronal damage. As secondary endpoints, various other markers for endothelial function, inflammation, and neuronal damage as well as the ONSD will be assessed. Perioperative stress will be evaluated by questionnaires and stress hormone levels in saliva samples. Furthermore, the subjects will participate in functional tests to evaluate neurocognitive function. Each subject will be followed up until discharge. Conclusion: This trial aims to expand current knowledge as well as to develop strategies for improved monitoring and higher safety of patients undergoing RALP. The trial was registered with the German Clinical Trials Register DRKS00031041 on 11 January 2023. [ABSTRACT FROM AUTHOR]

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms. Methods: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed. Results: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss. Conclusion: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF. [ABSTRACT FROM AUTHOR]

Citric acid cycle deficiencies are extremely rare due to their central role in energy metabolism. The ACO2 gene encodes the mitochondrial isoform of aconitase (aconitase 2), the second enzyme of the citric acid cycle. Approximately 100 patients with aconitase 2 deficiency have been reported with a variety of symptoms, including intellectual disability, hypotonia, optic nerve atrophy, cortical atrophy, cerebellar atrophy, and seizures. In this study, a homozygous deletion in the ACO2 gene in two brothers with reduced aconitase 2 activity in fibroblasts has been described with symptoms including truncal hypotonia, optic atrophy, hyperopia, astigmatism, and cerebellar atrophy. In an in vivo trial, triheptanoin was used to bypass the defective aconitase 2 and fill up the citric acid cycle. Motor abilities in both patients improved. [ABSTRACT FROM AUTHOR]

While the typical patient with idiopathic intracranial hypertension (IIH) is an obese female of childbearing age, there are unique patient populations, such as non-obese females, that have not been well studied. Characterizing this subpopulation may increase awareness our of it, which may prevent underdiagnosis and improve our understanding of IIH's underlying pathophysiology. We retrospectively reviewed electronic medical records and compared the clinical and radiological characteristics of non-obese (BMI < 30) and obese (BMI > 30) female patients with IIH. Two hundred and forty-six patients (age 32.3 ± 10) met our inclusion criteria. The non-obese patients (n = 59, 24%) were significantly younger than the obese patients (29.4 ± 9.9 vs. 33.2 ± 10.2, p = 0.004) and had higher rates of severe papilledema (Friesen 4–5; 25.4% vs. 11.8%, p = 0.019), scleral flattening (62.7% vs. 36.9%, p = 0.008), and optic nerve dural ectasia (78.0% vs. 55.6%, p = 0.044). Non-obese patients also had a tendency to have a higher lumbar puncture opening pressure (368 ± 92.7 vs. 344 ± 76.4, p = 0.062). Non-obese patients were three times more likely to present with a combination of scleral flattening and optic nerve dural ectasia (OR = 3.00, CI: 1.57–5.72, χ2 = 11.63, α < 0.001). Overall, non-obese females with IIH were found to have a more fulminant presentation, typified by higher rates of severe papilledema and radiological findings typical for IIH. [ABSTRACT FROM AUTHOR]

This study explores the complication of secondary intraocular pressure (IOP) elevation and consequent glaucoma development in Graves' orbitopathy (GO), an autoimmune disorder associated with hyperthyroidism. Utilizing Octopus 900 visual field testing and optical coherence tomography (OCT), the research established correlations between functional and structural changes in optic nerve regions in patients with GO and patients with GO with elevated IOP (GO IOP) groups. A comparison with primary open-angle glaucoma (POAG) was conducted in a cohort of 182 subjects. The study identifies optic nerve head parameters that effectively differentiate changes in GO and GO IOP groups. In the GO group, the strongest correlation between structural and functional changes was observed in sector 7, while in the GO IOP group, it was in sectors 1 and 7. For POAG, correlation was found in six sectors. Elevated IOP in GO correlates with structural and functional impairments similarly to early glaucoma. Risk factors for GO-related elevated IOP included older age, longer duration of thyroid disease, and higher anti-thyroglobulin values. The study highlights the significance of regular IOP measurements, visual field assessments, and OCT examinations in GO patients. Early antiglaucoma intervention is warranted when characteristic structural and functional changes and/or risk factors are identified. [ABSTRACT FROM AUTHOR]

In this comprehensive review, we delve into the significance of multimodal imaging in diagnosing and managing complications of congenital optic disc anomalies. While the fundus examination is the gold standard tool in the diagnosis of these pathologies, spectral domain (SD) optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) could shed light on the pathogenesis and treatment. Moreover, this review seeks to offer a comprehensive insight into the multimodal approach of these rare congenital pathologies. In conclusion, congenital anomalies of the optic nerve represent a major challenge for ophthalmologists. Further research could be useful to clarify the pathophysiology of these diseases and define a correct and more specific treatment approach. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a relapsing–remitting inflammatory disease characterized by the progression of asymptomatic nodules to deep-seated lesions and fistula formation that leads to suppuration and scarring. Optical coherence tomography angiography (OCTA) is a new non-invasive imaging technique that carefully analyzes retinal microvasculature networks with high-resolution imaging. Recent studies have demonstrated that retinal vessel density and retinal perfusion reflect systemic inflammatory responses. This study's aim was to analyze OCTA-derived retinal microvasculature parameters to understand if patients affected by HS and without any relevant ocular or systemic comorbidities showed impaired retinal vascular function and morphology. Method: We performed a case–control study of HS patients and age- and sex-matched control cohort. A total of 20 eyes from 10 HS patients and 30 eyes from 15 healthy controls were analyzed, and OCTA-derived microvasculature parameters were compared between groups. Results: OCTA images showed that HS patients, compared to healthy controls, were typically characterized by higher values of the foveal avascular zone (FAZ) both in the superficial capillary plexus (SCP) and in the deep capillary plexus (DCP), and by lower values of vessel density (VD)-SCP, VD-DCP, and vessel length density (VLD)-SCP in the foveal region. These findings partially reflect changes that have been demonstrated in diabetic patients that could be induced by a protracted metabolic or systemic inflammatory dysregulation. Conclusions: In conclusion, OCTA enables large-scale, non-invasive visual screening and follow-up of the retinal vasculature features, providing a new strategy for the prevention and monitoring of visual changes in HS patients. [ABSTRACT FROM AUTHOR]

Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species. [ABSTRACT FROM AUTHOR]

Optic neuropathies are characterized by the degeneration of the optic nerves and represent a considerable individual and societal burden. Notably, Leber's hereditary optic neuropathy (LHON) is a devastating vision disease caused by mitochondrial gene mutations that hinder oxidative phosphorylation and increase oxidative stress, leading to the loss of retinal ganglion neurons and axons. Loss of vision is rapid and severe, predominantly in young adults. Penetrance is incomplete, and the time of onset is unpredictable. Recent findings revealed that the incidence of genetic LHON susceptibility is around 1 in 1000, much higher than believed till now. Environmental factors are critical in LHON triggering or severity. Families at risk have a very strong demand for how to prevent the onset or limit the severity of the disease. Here, we review recent knowledge of the extrinsic determinants of LHON expression, including lifestyle, dietary supplements, common chemicals, and drugs. [ABSTRACT FROM AUTHOR]

Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19–related changes in the microvasculature of the optic nerve head. [ABSTRACT FROM AUTHOR]

Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to assess the influence of a single haemodialysis (HD) session on the retinal and optic nerve morphology in end-stage kidney disease (ESKD) patients. Methods: It is a prospective study including only the right eye of 35 chronic kidney disease (CKD) patients subjected to HD. Each patient underwent a full eye examination 30 min before HD (8 a.m.) and 15 min after HD. Optical coherence tomography (OCT) was used to assess the peripapillary retinal nerve fibre layer (pRNFL) thickness, macular nerve fibre layer (mRNFL) thickness, ganglion cell layer with inner plexiform layer thickness (GCL+), GCL++ (mRNFL and GCL+) thickness, total retinal thickness (RT) and total macular volume (TMV). The correlation was tested between such systemic parameters changes as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), body weight, plasma osmolarity and ocular perfusion pressure (OPP) and ultrafiltration volume with total RT and pRNFL thickness changes during HD. Results: In the results of a single HD session, we could observe a statistically significant increase in the total RT thickness (pre-HD 270.4 ± 19.94 μm, post-HD 272.14 ± 20.11 μm; p = 0.0014), TMV (pre-HD 7.48 ± 0.53 mm3, post-HD 7.52 ± 0.55 mm3; p = 0.0006), total pRNFL thickness (pre-HD 97.46 ± 15.71 μm, post-HD 100.23 ± 14.7 μm; p = 0.0039), total GCL+ thickness (pre-HD 70.11 ± 9.24 μm, post-HD 70.6 ± 9.7 μm; p = 0.0044), and GCL++ thickness (pre-HD 97.46 ± 12.56 μm, post-HD 97.9 ± 12.94 μm; p = 0.0081). We observed a significant correlation between the change in total RT and DBP change, as well as between body weight change and the change in total pRNFL thickness. There was also a correlation between total pRNFL thickness change and the presence of diabetes mellitus. Conclusion: Even a single HD session affects the retinal and pRNFL thickness, which should be taken into account when interpreting the OCT results in patients subjected to HD. The impact of changes after a single HD session on selected parameters requires further assessment in subsequent studies, including long-term observation. [ABSTRACT FROM AUTHOR]

We evaluated whether inhibiting sterile alpha and (Toll/interleukin receptor (TIR)) motif-containing 1 (SARM1) activity protects retinal ganglion cells (RGCs) following ischemic axonopathy (rodent nonarteritic anterior ischemic optic neuropathy: rNAION) by itself and combined with ciliary neurotrophic factor (CNTF). Genetically modified SARM1(−) rats were rNAION-induced in one eye and compared against equivalently induced wild-type animals of the same background. Optic nerve (ON) diameters were quantified using optical coherence tomography (SD-OCT). RGCs were quantified 30 d post-induction using retinal stereology for Brn3a(+) nuclei. ON sections were analyzed by TEM and immunohistochemistry. SARM1(−)(−) and WT animals were then bilaterally sequentially rNAION-induced. One eye received intravitreal vehicle injection following induction; the contralateral side received CNTF and was analyzed 30 d post-induction. Inhibiting SARM1 activity suppressed axonal collapse following ischemic axonopathy. SARM1(−) animals significantly reduced RGC loss, compared with WT animals (49.4 ± 6.8% RGC loss in SARM1(−) vs. 63.6 ± 3.2% sem RGC loss in WT; Mann–Whitney one-tailed U-test, (p = 0.049)). IVT-CNTF treatment vs. IVT-vehicle in SARM1(−) animals further reduced RGC loss by 24% at 30 d post-induction, but CNTF did not, by itself, improve long-term RGC survival in WT animals compared with vehicle (Mann–Whitney one-tailed t-test; p = 0.033). While inhibiting SARM1 activity is itself neuroprotective, combining SARM1 inhibition and CNTF treatment generated a long-term, synergistic neuroprotective effect in ischemic neuropathy. Combinatorial treatments for NAION utilizing independent neuroprotective mechanisms may thus provide a greater effect than individual treatment modalities. [ABSTRACT FROM AUTHOR]

A progressive neurological disorder was observed in a male neutered Weimaraner. Clinical signs included fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Neurologic signs were first observed at approximately 4 years, 10 months of age and progressed slowly. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. Humane euthanasia was elected at 6 years, 7 months of age due to increasing severity of the neurological signs. Autofluorescent intracellular granules were observed in the cerebral and cerebellar cortexes, optic nerve, and cardiac muscle of the affected dog. These abnormal inclusions in the cerebral cortex and cardiac muscle immunolabeled with antibodies to mitochondrial ATP synthase subunit c protein, like that observed in the neuronal ceroid lipofuscinosis group of lysosomal storage diseases. Immunolabeling also demonstrated pronounced neuroinflammation in brain tissues. The ultrastructural appearances of the disease-related inclusion bodies in the brain and optic nerve were quite variable. The ultrastructure and locations of many of the inclusions in the nervous tissues suggested that they were derived, at least in part, from the myelin surrounding axons. The storage bodies in the cardiac muscle were located in mitochondria-rich regions and consisted of parallel arrays of membrane-like components interspersed with electron-dense flocculent material. The disease was characterized by pronounced abnormalities in the myelin of the brain and optic nerve consisting of distinctive areas of ballooning between the layers of myelin. The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP, which encodes proteins with CNPase enzyme activity and a structural role in myelin. The mutation predicts a Thr42Met amino acid sequence substitution. Genotyping of archived Weimaraner DNA samples identified an additional G > A variant homozygote with a clinical history and brain lesions similar to those of the proband. Of 304 Weimaraners and over 4000 other dogs of various breeds, the proband and the other Weimaraner that exhibited similar signs were the only two that were homozygous for the CNP missense variant. CNPase immunolabeling was widespread in brain tissues from normal dogs but was undetectable in the same tissues from the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy. Similar disorders have been associated with different CNP variants in Dalmatians and in human subjects. [ABSTRACT FROM AUTHOR]