Nerve Fibers Research Articles

DAMPs Drive Fibroinflammatory Changes in the Glaucomatous ONH.

The optic nerve head (ONH) is well known to be the initial site of glaucomatous damage; however, the molecular mechanisms initiating this pathology are not fully understood. To further understand the initiating factors in glaucomatous damage we utilized a novel mouse model of glaucoma, B6.EDA+/+ mice, which constitutively express fibronectin containing the extra domain A (FN+EDA). FN+EDA is a known damage-associated molecular pattern (DAMP) that activates Toll-like receptor 4 and elicits a fibro-inflammatory response. Eyes from B6.EDA+/+ and C57BL/6J mice were evaluated for retinal ganglion cell (RGC) death, retinal nerve fiber layer (RNFL) thickness, and optic nerve (ON) damage at 12 months and 22 months of age. ONH sections were isolated using laser capture microdissection for subsequent RNA-sequencing and Gene Set Enrichment Analysis (GSEA). GSEA results were confirmed using immunohistochemical (IHC) staining. B6.EDA+/+ mice exhibit significantly higher intraocular pressure, loss of RGCs, thinning of the RNFL, and progressive levels of ON damage at 12 months and 22 months of age compared to C57BL/6J controls. Protein expression of DAMPs FN+EDA and biglycan was significantly increased in B6.EDA+/+ mice compared to C57BL/6J controls. GSEA analysis identified significantly up- and downregulated gene groupings at both 12 months and 22 months of age, and IHC staining at 12 and 18 months of age demonstrated significant increases of IFNα, IFNβ, and pSTAT1 expression in B6.EDA+/+ mice compared to C57BL/6J controls. Our study characterizes glaucomatous changes to the retina, ON, and ONH over the course of 2 years and identifies novel molecular pathways associated with these pathophysiological changes. These data illustrate the effects of FN+EDA on the fibro-inflammatory response in the aging ONH in a novel mouse model of glaucoma.

Diagnostic Performance for Detection of Glaucomatous Structural Damage Using Pixelwise Analysis of Retinal Thickness Measurements.

To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis. For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations. Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356). Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Histological assessment of potential inferior alveolar nerve injury following osteotomy of the mandibular buccal cortex using a piezoelectric saw.

The present study aimed to evaluate the effect of Piezosurgery on histopathologic features of the inferior alveolar nerve (IAN) damage after osteotomy of the buccal cortex of the mandible using piezoelectric devices in Hamdani sheep.A total of ten healthy mature female sheep were included. Each side of the mandible underwent two different experiments: the first experiment operated directly on the mental nerve by touching and activating the piezo tip on the nerve for ten seconds for the left side and thirty seconds for the right side. In the second experiment, the inferior alveolar nerve was touched by an activated piezo tip inside the mandibular canal for ten seconds on the left side and thirty seconds on the right side. All the nerve samples underwent histopathological evaluation, and the scoring system was performed to assess the nerve structures. Mental nerves exposed to piezo tip for 10 seconds showed mild abnormality including disruption of the perineurium with the endoneurium remaining intact. Mental nerves exposed for 30 seconds showed moderate injury with destruction of the perineurium and moderate degeneration of nerve fibers, nevertheless, the endoneurium remained continuous with normal node of Ranvier. Severe damage of the inferior alveolar nerve was seen after exposure to piezo tip for 10 seconds, which showed sloughing of the perineurium and severe vacuolar degeneration of nerve fibers, partial disruption of the endoneurium; however, the axons were still intact. Inferior alveolar nerves exposed for 30 seconds revealed destruction of the perineurium, marked vacuolar degeneration of nerve fibers, focal damage of axon and loss of endoneurium (axonotmesis).Piezosurgery devices have the potential to cause severe nerve damage during surgery and should be used very carefully.

Optic Nerve Sheath Fenestration: A Retrospective Review of Its Safety, Efficacy, and Impact on Optical Coherence Tomography.

This study aimed to evaluate the safety and efficacy of optic nerve sheath fenestration using visual acuity, perimetry, and optical coherence tomography. A retrospective review of patients who underwent an optic nerve sheath fenestration at an academic center between 2016 and 2021 was performed with institutional review board approval. Outcome measures included visual acuity, perimetric mean deviation, optic disc edema grade, improvement in symptoms, and intraoperative and postoperative complications. Optical coherence tomography data collected included macular ganglion cell volume and thickness, as well as retinal nerve fiber layer thickness. Preoperative baseline data and 1-, 6-, and 12-month postoperative data were collected. Repeated measures with a mixed-effects model were used for continuous data, and linear regression analyses were performed. A total of 55 patients (86 eyes) underwent optic nerve sheath fenestration, via a medial transconjunctival approach by the same orbital surgeon. After 12-month follow-up, visual acuity (P < 0.05), perimetric mean deviation (P < 0.05), and optic disc edema (P < 0.001) improved in the operative eye. Retinal nerve fiber layer thickness decreased from a mean of 165 to 92 µm (P < 0.001). Macular ganglion cell volume was found to have a small decrease from baseline and correlated well with visual acuity, contrast sensitivity testing, and perimetric mean deviation (P < 0.001). Optic nerve sheath fenestration performed via a medial transconjunctival approach is a safe and effective method to preserve vision in patients with papilledema, particularly in cases of fulminant or progressive idiopathic intracranial hypertension. Quantitative measurements of the macular ganglion cell layer can serve as a useful adjunct to other diagnostic testing.

Ocular effects of synthetic cannabinoids: a case-control study.

To evaluate the ocular effects of "Bonzai", a synthetic cannabinoid (SC), in seropositive and seronegative users. Sixty eyes of 60 consecutive male patients with a history of "Bonzai" use and 30 eyes of 30 age-matched male healthy controls were enrolled in this case-control study. Patients with past "Bonzai" use were grouped as seropositive (n:30) and seronegative (n:30) according to urine toxicology tests. All groups were compared for blood pressures, intraocular pressure, foveal and parafoveal retinal thicknesses, subfoveal and parafoveal choroidal thicknesses, measurements of the peripapillary retinal nerve fibre layer (RNFL), and macular ganglion cell complex (GCC), subfoveal total choroidal, luminal and stromal areas, and choroidal vascularity index (CVI). No differences were noted in blood pressures between the groups (p > 0.05). The mean intraocular pressure was significantly lower in the seropositive group than in the other groups (p < 0.001). Foveal and retinal thicknesses, RNFL, and GCC measurements did not differ between the groups (p > 0.05). Subfoveal and parafoveal choroidal thicknesses and areas were lower in the seropositive group than in the other groups (p < 0.001, for all). CVI increased in both groups with "Bonzai" use compared to the control group (p < 0.001, for all). This study indicates that intraocular pressure may decrease, and choroidal changes may be observed in SC users. Further clinical studies with a larger sample size, especially using purified SC for therapeutic purposes, are needed to confirm the present findings, and further histopathologic studies are required to clarify the changes in the choroid despite SC seronegativity. NCT06235346.

Evaluation of the early effects of the first-dose administration of the Sinovac vaccine on the retina, choroid, and optic disc using optical coherence tomography (OCT) and OCT-angiography

Aim To determine the effects of the first-dose administration of the Sinovac vaccine on the retina, choroid, and optic disc in healthy participants. Methods This prospective design study was conducted with 27 healthy healthcare workers who received the first dose of Sinovac vaccine and 25 healthy controls who were not vaccinated. In the vaccinated group, ophthalmological examinations and measurements were performed before vaccination and one week and one month after vaccination. Subfoveal, nasal, and temporal choroidal thicknesses (CTs), retinal nerve fiber layer (RNFL) thickness, and macular thickness (MT) were determined using spectral domain-optical coherence tomography at all visits. Superficial, deep, and peripapillary radial capillary plexus (superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary, respectively), choriocapillaris vascular density, and foveal avascular zone parameters were measured on optical coherence tomography-angiography (OCT-A). Results No significant difference was detected between the two groups in terms of the parameters measured by OCT and OCT-A (p > 0.05 for all). The CT values measured in all quadrants were significantly higher at the first week after vaccination (p < 0.05 for all), and they returned to their pre-vaccination values at the first month post-vaccination measurement (p > 0.05 for all). Concerning the RNFL and MT values, there was no significant difference between the pre-vaccination and post-vaccination first-week measurements (p > 0.05 for all), but a statistically significant increase was detected in the post-vaccination first-month MT and RNFL measurements (p < 0.05 for all). Only the decreases in the foveal DCP and choriocapillaris vascular density values were significant at the first week after vaccination (p < 0.05 for all). Conclusion The early changes detected after vaccination in this study suggest the possibility that autoimmune, vascular, and inflammatory diseases may simultaneously emerge in the early post-vaccination period or may be triggered after vaccination, or that the vaccine may unmask these diseases.

Five-year changes in retinal nerve fibre layer thickness in the adult population: a population-based cohort study.

Distinguishing between the pathological thinning of the retinal nerve fibre layer (RNFL) and age-related reduction requires a comprehensive understanding of the longitudinal changes in RNFL thickness within a healthy population. To determine five-year changes in RNFL thickness and associated factors in people aged 45-69 years. This report pertains to the second and third phases of the Shahroud Eye Cohort Study. Participants were recruited by a multi-stage cluster sampling in Shahroud, Iran. Data on demographic details, visual acuity, non-cycloplegic refraction, and slit-lamp biomicroscopy were collected. High-definition optical coherence tomography was employed for retinal imaging. A total of 1,524 eyes from 908 participants were examined. The average RNFL thickness was 92.2 ± 8.5 (95% CI: 91.6 to 92.8) and 93.1 ± 8.7 μm (95% CI: 92.5 to 93.7) in the first and second phases with a five-year mean change of 0.95 ± 4.15 μm (95% CI: 0.70 to 1.20). The RNFL thickness mean changes in the superior, inferior, nasal, and temporal quadrants were 2.51 ± 7.86 (95% CI: 2.01 to 3.02), 2.93 ± 7.39 (95% CI: 2.56 to 3.29), -0.53 ± 6.15 (95% CI: -0.84 to -0.21), and -1.01 ± 4.67 μm (95% CI: -1.27 to -0.75), respectively. The five-year changes in average RNFL thickness were inversely correlated with axial length (β = -0.69, p < 0.001), mean keratometry (β = -0.37, p = 0.017), and baseline RNFL thickness (β = -0.617, p < 0.001). In hyperopic individuals, the increase in average RNFL thickness (β = 0.65, p = 0.012) was significantly greater than in those with emmetropia. Macular volume (β = 1.65, p < 0.001) showed a direct association with five-year changes in average RNFL thickness. Over 5 years, RNFL thickness changes were clinically insignificant in the normal population. The mean RNFL thickness seems to remain stable unless there is ocular disease. However, increased axial length and steeper keratometric readings were linked to RNFL thinning. Those with thicker RNFL measurements were at higher risk of thinning over time.

Effects of Stress and Strain on the Optic Nerve Head on the Progression of Glaucoma.

In primary open-angle glaucoma, the rate of retinal nerve fiber layer thickness decrease was negatively correlated with lamina cribrosa strain, which was associated with intraocular pressure and optic nerve head geometric factors. We hypothesized that the biomechanical deformation of the optic nerve head (ONH) contributes to the progression of primary open-angle glaucoma (POAG). This study investigated the biomechanical stress and strain on the ONH in patients with POAG using computer simulations based on finite element analysis (FEA) and analyzed its association with disease progression. We conducted a retrospective analysis that included patients diagnosed with early-to-moderate stage POAG. The strains and stresses on the retinal nerve fiber layer (RNFL) surface, prelaminar region, and lamina cribrosa (LC) were calculated using computer simulations based on FEA. The correlations between the rate of RNFL thickness decrease and biomechanical stress and strain were investigated in both the progression and non-progression groups. The study included 71 and 47 patients in the progression and non-progression groups, respectively. In the progression group, the factors exhibiting negative correlations with the RNFL thickness decrease rate included the maximum and mean strain on the LC. In multivariate analysis, the mean strain on the LC was associated with optic disc radius, optic cup deepening, axial length, and mean intraocular pressure (IOP), whereas the maximum strain was only associated with mean IOP. In early-to-moderate stage POAG, the rate of RNFL thickness decrease was influenced by both the mean and maximum strain on the LC. Strains on the LC were associated with mean IOP, optic disc radius, axial length, and optic cup deepening. These results suggest that not only IOP but also ONH geometric factors are important in the progression of glaucoma.

Is there a relationship between the keratoconus and the peripapillary choroidal vasculature?

To evaluate the peripapillary/parapapillary choroidal vascular parameters in the keratoconus (KC) and to determine the relationship between topography parameters and the peripapillary/parapapillary choroidal vascular parameters. Ninety eyes of ninety patients with different stages of KC and 29 eyes of twenty-nine patients without KC were enrolled in the study. Patients with KC were divided into three groups according to the Amsler-Krumeich classification scale. The choroidal vasculature was assessed by choroidal vascular parameters [such as parapapillary choroidal microvascular density (pCMVd) and peripapillary choroidal vascularity index (pCVI)]. These parameters were also evaluated for correlation with other parameters. The retinal nerve fibre layer thickness (RNFLT) of the superior-temporal area and the pCVI were decreased in group 3 compared to the control group (superiror-temporal RNFLT: 122.27 ± 21.43 vs 139.90 ± 21.7, p = 0.01 and pCVI: 67.04 ± 4.14 vs 69.99 ± 4.38, p = 0.04). The superior-temporal RNFLT was decreased in group 3 compared to group 2 (122.27 ± 21.43 vs 141.83 ± 25.58, p = 0.006). There was a negative correlation between pCVI and average simulated keratometry (mean sim K), but this association was weak (r = -0.29 p = 0.001). This study demonstrated that there may be changes in pCVI in patients with grade 3 KC and that there may be an association between pCVI and mean sim K. As KC grade increases, pCVI may decrease. Furthermore, pCVI may have a negative correlation with mean sim K.

Progressive maculopathy in a child resulting from vitreopapillary traction on a congenitally anomalous nerve.

To present a case of worsening maculopathy and vision loss due to vitreopapillary traction associated with an anomalous optic nerve head in a pediatric patient successfully managed with pars plana vitrectomy. Retrospective case report. A 13-year-old boy presented with unilateral maculopathy that slowly progressed over a four-year period. As his visual acuity declined, he became increasingly symptomatic. The macular pathology occurred in the setting of vitreopapillary traction overlying multiple congenital optic nerve abnormalities, including a myelinated nerve fiber layer and a Bergmeister papilla. Following pars plana vitrectomy to alleviate the traction, the patient's macular appearance improved, and his vision slowly recovered to baseline. There are limited reports of congenital optic nerve anomalies associated with vitreopapillary traction and maculopathy among any age group. This report illustrates a pediatric case in which removal of traction on the nerve head by pars plana vitrectomy was the key therapeutic intervention to alleviate the maculopathy.

Optical Coherence Tomography Image Analysis for Detection of Alzheimer’s Disease: A Comprehensive Structured Review

Optical Coherence Tomography (OCT) has emerged as a promising non-invasive imaging modality for the early detection of Alzheimer’s Disease (AD). This systematic literature review aims to consolidate current research on OCT image analysis for AD detection, addressing the growing need for early and accurate diagnostic tools. Despite the advances in neuroimaging, early diagnosis of AD remains challenging due to its asymptomatic nature in initial stages and the invasiveness of traditional methods. To achieve this, we conducted an extensive search of related articles from reputable databases (Scopus and Web of Science), focusing on studies published between 2022-2024. The flow of study was based on PRISMA framework. The database found (n = 29) final primary data. This review was divided into three themes, (1) retinal and ocular biomarkers for AD, (2) optical coherence tomography angiography (OCTA) and imaging techniques, and (3) machine learning and computational approaches for Alzheimer’s disease diagnosis. Key findings include the enlargement of the periarteriole capillary-free zone and changes in retinal nerve fibre layer thickness as potential AD biomarkers. Based on the review, the implementation of image analysis for OCT images have shown substantial potential for AD detection. By evaluating the past studies, gaps for the current research were discovered including the need for larger, more diverse cohorts and longitudinal studies to validate these biomarkers. In summary, detection of AD is possible through thorough OCT image analysis, but further research could be suggested to enhance its clinical applicability and reliability.

Applicability of ISNT rule to retinal nerve fiber layer thickness by SD-OCT in normal subjects.

The usefulness of the Inferior>Superior>Nasal>Temporal (ISNT) rule for the neuroretinal rim (NRR) has been widely used in differentiating normal eyes from glaucoma, but only a few studies have assessed whether this classical ISNT rule applies to the retinal nerve fibre layer (RNFL). This study aimed to determine the applicability of the ISNT rule for the peripapillary RNFL thickness in normal eyes using Spectral Domain Optical Coherence Tomography (SD-OCT) and assess if variants of the ISNT rule apply. A cross-sectional study was conducted on 120 eyes of 62 healthy subjects who fulfilled the study criteria. Peripapillary RNFL thickness was measured by OCT scan and each eye's global, superior, temporal, nasal, and inferior quadrant thickness was noted. The values obtained were analyzed to determine the percentage of eyes obeying the ISNT rule and its variants. The ISNT rule for RNFL thickness was applicable for normal subjects in only 53.33% of cases. Removing the nasal quadrant from analysis increased the number of eyes obeying the IST rule to 71.66%. Further exclusion of the temporal quadrant showed almost the same results (75%) for the IS rule. The ISNT rule for RNFL thickness could be validated in only 53.33% of normal individuals. Though documented as useful for NRR during ophthalmoscopy in glaucoma diagnosis, the ISNT rule did not apply to the quadrant values on RNFL on SD-OCT examination.

Glaucoma in Pathological Myopia, Diagnosis and Treatment Approaches

The rising global prevalence of myopia is contributing to an increase in pathological myopia (PM). Myopia has been extensively documented as a risk factor for primary open-angle glaucoma. However, glaucomatous changes in eyes with PM typically occur at normal intraocular pressures. Moreover, the unique anatomical alterations observed in PM result in distinctive differences in the clinical appearance of the optic nerve head and peripapillary region. Consequently, the evaluation of optic nerve cupping is more challenging in these cases than in those of normal eyes. Therefore, the diagnosis and treatment of glaucoma in this patient group is challenging. Furthermore, these patients may present with established visual field defects that can mimic glaucoma. On the other hand, optical coherence tomography is less useful for the detection and monitoring of disease due to the lack of normative data for these anatomically unique eyes. The most crucial factor in detecting early glaucomatous changes is the monitoring of the progression of retinal nerve fiber layer thinning over time. Consequently, the most effective method of monitoring glaucoma patients with PM is through longitudinal follow-up. Finally, the medical and surgical management of glaucoma in patients with pathologic myopic glaucoma presents its own unique challenges.

Optic Disc Features in Pathological Myopia And Myopic Optic Neuropathy

Pathological myopia is defined as excessive axial elongation accompanied by various structural changes in the fundus and optic disc, leading to a decrease in best-corrected visual acuity. Today, with the widespread use of optical coherence tomography (OCT) in ophthalmology, optic disc pathologies have been identified in addition to fundus findings. Due to axial elongation, large optic disc, tilted optic disc, retinal nerve fiber changes, peripapillary atrophy, intachoroidal cavitation and peripapillary-prelaminar schisis are observed. Optic neuropathy occurs in some cases secondary to all these changes occurring in the optic disc. Myopic optic neuropathy can be examined under two headings: glaucomatous/glaucoma-like and nonglaucomatous. In this review, optic disc changes and myopic optic neuropathy, which are important causes of vision loss, are discussed.

Optical Coherence Tomography and Optical Coherence Tomography Angiography in Optic Nerve Disorders

Optic nerve disorders encompass a wide range of diseases. While it may be an isolated disease, such as optic disc drusen, it may also occur as a symptom of pathology in the central nervous system, such as multiple sclerosis. Optical coherence tomography (OCT) is an important auxiliary test used in optic nerve disorders as it allows cross-sectional imaging of the retina and optic nerve head at high resolution. OCT is used in the diagnosis of optic nerve disorders, evaluation of response to treatment, and prediction of visual prognosis by measuring retinal layers such as the ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL).

7219 Ocular Findings in Jansen Metaphyseal Chondrodysplasia

Abstract Disclosure: F. Obiezu: None. K. Pan: None. A. Ninan: None. K.L. Roszko: None. L.S. Weinstein: None. C.R. Ferreira: None. R.I. Gafni: None. T. Magone De Quadros Costa: None. M.T. Collins: None. S. Jha: None. Jansen Metaphyseal Chondrodysplasia (JMC) is an ultra-rare disorder, with only 30 patients estimated to have the disease globally. It is caused by heterozygous pathogenic variants in PTHR1 that result in constitutive activation of parathyroid hormone type 1 receptor (PTHR1) signaling. A detailed description of craniofacial manifestations of the disease is lacking. Here we characterize the ophthalmological manifestations in patients with JMC. Six patients (4 males, 67%) with genetically confirmed JMC underwent a detailed ophthalmological evaluation, spectral-domain optical coherence tomography (OCT), craniofacial CT and 18F-NaF PET/CT scans. Median age at the time of the visit was 27.5 [IQR: 29] years. On physical examination, all patients were noted to have widely spaced eyes; 5 of the 6 had down slanted palpebral fissures, proptosis, or ptosis. Two patients had incomplete or defective closure of the eyelids (lagophthalmos), of which one had a history of progressive right facial nerve palsy with profuse epiphora. The second patient had central visual field defects, bilateral moderate optic disc pallor and bilateral retinal nerve fiber layer (RNFL) atrophy on OCT exam with bilateral optic canal narrowing on CT. Notably, comparison of these findings with a prior scan performed 5 years earlier showed progressive decrease in RNFL bilaterally. This patient had a history of prolonged intravenous bisphosphonate therapy, initiated in infancy for hypercalcemia and continued for over a decade. A third patient had normal vision, subtle temporal pallor of the optic nerve heads on dilated fundus exam, normal average RNFL, but decreased retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4 of the 6 patients compared to age-matched reference range indicating a chronic optic nerve atrophic process. These data represent the first comprehensive report of the ophthalmologic findings in a cohort of patients with JMC. They demonstrate that patients with JMC have significant eye findings that appear to be more prevalent and pronounced with age. This suggests age-related, progressive optic neuropathy, which can be assessed by demonstrating OCT retinal GCA and RNFL loss and, may be a feature of JMC. The benefit and effect of long-term bisphosphonate therapy in patients with JMC remains unclear. Patients with JMC should undergo regular ophthalmologic examination including optic nerve OCT, visual field testing, and craniofacial imaging. Presentation: 6/1/2024

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or ‘wolframinopathies’, exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the ‘plus’ phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Longitudinal Assessment of Ocular Biomarkers in Individuals With Gulf War Illness Symptoms.

Gulf War illness (GWI) is characterized by a constellation of symptoms, including, but not limited to, diarrhea, fatigue, and memory problems that affect Gulf War veterans. Currently, there are no objective biomarkers for GWI. Previous studies have identified differences in optical coherence tomography (OCT) metrics between individuals with GWI symptoms and those without. However, there are limited data on how these metrics change over time. Therefore, in this current study, we conducted a prospective case-control investigation to determine if OCT metrics show longitudinal changes in those affected by GWI. We conducted a prospective study with 100 Gulf War-era veterans at the Miami Veterans Affairs Hospital from November 2018 to February 2022. Inclusion criteria required service during 1990-1991, with both deployed and nondeployed veterans included. Exclusions were based on factors like active infection, unmanaged psychotic disorders, significant head injuries, severe neurological disorders, and eye pathologies affecting OCT imaging. All participants provided informed consent, and the study was institutional review board-approved and conducted per the Declaration of Helsinki and Health Insurance Portability and Accountability Act guidelines. GWI symptoms were assessed using the modified Kansas questionnaire, categorizing veterans into groups based on GWI symptoms presence and deployment status. Data on demographics, comorbidities, medications, and medical and ocular diagnoses were collected. Participants underwent OCT imaging at 2 time points, 1 year apart, with macular, retinal nerve fiber layer, and ganglion cell layer-inner plexiform layer (GCL-IPL) thicknesses measured. Additionally, blood samples were collected and cytokine levels measured at baseline. Data analysis involved descriptive statistics, t-tests, and multivariable regression models. Statistical analyses were performed using SPSS 28.0. Logistic regression demonstrated that post-traumatic stress disorder (odds ratio [OR]: 8.18, 95% confidence interval [CI]: 2.327-28.851, P = .001) and a lower baseline macular thickness in the outer nasal segment (OR: 0.959, 95% CI: 0.924-0.994, P = .023) remained significantly associated with GWI symptoms. The model also found that individuals with GWI symptoms were more likely to have an increase in inner temporal GCL-IPL layer thickness over a 1-year period (OR: 1.187, 95% CI: 0.974-1.447, P = .089). When analysis was conducted only among those deployed, only baseline interleukin (IL) 1a (OR = 1.24, CI = 1.019-1.52, P = .03) and interleukin-10 (OR = 0.95, CI = 0.91-0.99, P = .02) levels remained significantly associated with GWI symptoms. Baseline OCT measures, especially a thinner outer nasal macula, were associated with GWI symptoms. Longitudinally, individuals with GWI symptoms had greater thickening of their inferotemporal GCL compared to those without symptoms. When the model was re-examined in deployed veterans, OCT measures (at baseline and longitudinally) no longer remained significantly related with GWI symptoms and instead baseline levels of plasma inflammatory cytokine markers, IL1a and IL10, were most closely related to symptoms. Our longitudinal study builds on our previous retrospective and cross-sectional work on identifying ocular biomarkers in GWI. Across the studies, macular thinning at baseline and inferotemporal GCL-IPL thickening have been noted between cases and controls. Some of these findings share correlates with OCT biomarkers identified in conditions such as Alzheimer's, Parkinson's and Multiple Sclerosis. This is significant as it may help contextualize future research and help us develop better models of GWI.

Discogenic Low Back Pain: Anatomic and Pathophysiologic Characterization, Clinical Evaluation, Biomarkers, AI, and Treatment Options.

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes.

Local Sustained Dinutuximab Delivery and Release From Methacrylated Chondroitin Sulfate.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. High-risk NB is a subset of the disease that has poor prognosis and requires multimodal treatment regimens, with a 50% rate of recurrence despite intervention. There is a need for improved treatment strategies to reduce high-risk patient mortality. Dinutuximab is an anti-GD2 antibody ideal for targeting GD2 expressing NB cells, but binding of the antibody to peripheral nerve fibers leads to severe pain during systemic administration. Intratumoral delivery of the anti-GD2 antibody would allow for increased local antibody concentration, without increasing systemic toxicity. Chondroitin Sulfate (CS) is a biocompatible glycosaminoglycan that can be methacrylated to form CSMA, a photocrosslinkable hydrogel that can be loaded with therapeutic agents. The methacrylation reaction time can be varied to achieve different degrees of substitution, resulting in different release and degradation profiles. In this work, 4 and 24 h reacted CSMA was used to create hydrogels at 10% and 20% CSMA. Sustained in vitro release of dinutuximab from these formulations was observed over a 24-day period, and 4 h reacted 10% CSMA hydrogels had the highest overall dinutuximab release over time. An orthotropic mouse model was used to evaluate in vivo response to dinutuximab loaded 4 h methacrylated 10% CSMA hydrogels as compared to bolus tail vein injections. Tumor growth was monitored, and there was a statistically significant increase in the days to reach specific tumor size for tumors treated with intratumoral dinutuximab-loaded hydrogel compared to those treated with dinutuximab solution through tail vein injection. This supports the concept that locally delivering dinutuximab within the hydrogel formulation slowed tumor growth. The CSMA hydrogel-only treatment slowed tumor growth as well, an interesting effect that may indicate interactions between the CSMA and cell adhesion molecules in the tumor microenvironment. These findings demonstrate a potential avenue for local sustained delivery of dinutuximab for improved anti-tumoral response in high-risk NB.