Nerve Fibers Research Articles

Demyelination and neurodegeneration early in experimental autoimmune encephalomyelitis contribute to functional deficits in the anterior visual pathway

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

Vitrectomy in Small idiopathic MAcuLar hoLe (SMALL) study: Internal limiting membrane peeling versus no peeling.

To compare vitrectomy with and without internal limiting membrane (ILM) peeling in small idiopathic macular holes. Retrospective multicentre study including consecutive eyes with ≤250 μm idiopathic macular hole treated with vitrectomy. The primary outcome was hole closure rate. Best-corrected visual acuity (BCVA) change, closure patterns on optical coherence tomography, rates of external limiting membrane (ELM) and ellipsoid zone (EZ) recovery, and rate of complications were also investigated. In total, 693 eyes were included. Hole closure rate was 98% in the peeling and 85% in the no-peeling group (p < 0.001). At 12 months, mean BCVA change was 0.38 ± 0.22 logMAR in the peeling and 0.45 ± 0.21 logMAR in the no-peeling group (p = 0.02); 66% versus 80% of eyes had a U-shaped morphology, respectively; EZ recovery rate was 75% and 93%, respectively (p = 0.02). In the no-peeling group, eyes with a vitreomacular traction (VMT) showed a 96% closure rate, comparable to the peeling group (p = 0.40). The incidence of adverse events was similar except for dissociated optic nerve fibre layer (55% in the peeling vs. 9% in the no-peeling group, p < 0.001). In small idiopathic macular holes, ILM peeling provides a higher closure rate compared to no-peeling; however, if a VMT is present closure rates are comparable. In closed macular holes, the no-peeling technique provides advantages in terms of visual outcome and anatomical recovery.

Accelerated Epigenetic Aging is Associated with Faster Glaucoma Progression: A DNA Methylation Study.

To investigate the association between epigenetic age acceleration and glaucoma progression. Retrospective cohort study. 100 primary open-angle glaucoma (POAG) patients with fast progression and 100 POAG patients with slow progression. Subjects were classified as fast or slow progressors based on rates of change in standard automated perimetry (SAP) mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Epigenetic age was calculated using the Horvath, Hannum, PhenoAge, and GrimAge clocks from DNA methylation profiles obtained from blood samples. Age acceleration (AgeAccel) was defined as the residual from a linear regression of epigenetic age on chronologic age, with positive values suggesting faster biological aging. Multivariable logistic regression models estimated the association between AgeAccel and likelihood of fast progression, adjusting for confounders. Difference in epigenetic age acceleration between fast and slow glaucoma progressors. The mean rate of SAP MD change in the fastest progressing eye was -1.06 dB/year (95% CI: -1.28 to -0.85) for fast progressors compared to -0.10 dB/year (95% CI: -0.16 to -0.04) for slow progressors (P<0.001). For RNFL thickness, corresponding values were -1.60 μm/year (95% CI: -1.97 to -1.23) and -0.76 μm/year (95% CI: -1.04 to -0.48), respectively (P<0.001). Fast progressors demonstrated significantly greater age acceleration compared to slow progressors for the Horvath clock (mean difference = 2.93 years, 95% CI: 1.48 to 4.39, P<0.001) and Hannum clock (mean difference = 1.24 years, 95% CI: 0.03 to 2.46, P=0.045). In multivariable models, each year of Horvath AgeAccel was associated with 15% higher odds of fast progression (OR 1.15, 95% CI 1.07-1.23, P<0.001), after adjusting for sex, race, intraocular pressure, central corneal thickness, baseline disease severity, smoking status and follow-up time. Hannum and GrimAge clocks also showed significant associations with fast progression. The association between AgeAccel and fast progression was stronger in subjects with relatively low IOP during follow-up. Accelerated epigenetic aging was associated with faster glaucoma progression. These findings suggest that faster biological age, as reflected in DNA methylation, may increase optic nerve susceptibility to damage, highlighting epigenetic age as a potential prognostic biomarker.

Clinical correlation of optic nerve head analysis performed by SD-OCT in children with pseudopapilledema and papilledema

PurposeTo investigate some diagnostic indicators in optic nerve head (ONH) analysis of children with ‘Pseudopapilledema’ and ‘Papilledema’ by Spectral Domain Optical Coherence Tomography (SD-OCT). MethodsMedical records of 52 children with optic disc swelling, who were followed up by the departments of pediatric neurology and ophthalmology between May 2018 and May 2019 were reviewed retrospectively. Cases were classified as group 1 (Papilledema secondary to Idiopathic Intracranial Hypertension) including 54 eyes of 27 cases, group 2 (Pseudopapilledema secondary to bilateral optic disc drusen) including 50 eyes of 25 cases and control group. Three-dimensional imaging of ONH, peripapillary retinal nerve fiber layer (RNLF) thickness, Bruch's membrane opening height in the nasal respectively temporal quadrant (BMHN, BMH-T) levels were measured by SD-OCT and B-mode ocular ultrasonography data of all cases were evaluated. ResultsWhen RNFL levels were compared between groups, nasal RNFL levels were found to be significantly higher in group 1 cases compared to group 2 (p < 0.001). In 3D imaging of the ONH among group 1 patients, the mean height of the apex in disc swelling was significantly higher than that of group 2 (p = 0,024). The apex in disc swelling was mostly observed to be localized at the middle and had a diffuse swelling pattern in group 1; whereas, in group 2, the it was localized mostly at the nasal quadrant. This variation was statistically significant (p < 0.001). When, Bruch's membrane opening height in the nasal respectively temporal quadrant (BMHN, BMH-T) levels were compared, the measurements obtained were found to be significantly higher in group 1 (p = 0,050 and p = 0,003 respectively). ConclusionNasal RNFL values of SD-OCT, Bruch's membrane opening height in the nasal respectively temporal quadrant (BMHN, BMH-T) levels, the location of the apex in disc swelling obtained by 3D analysis of the ONH are found to be potential diagnostic parameters when combined with clinical findings. It is important that the nasal quadrant elevation, where the highest peak in 3D imaging was measured, was higher in the papilledema group. The elevation of the optic disc peak in 3D imaging can be used as a parameter to help clinicians distinguish between optic disc drusen (ODD) and papilledema.

PreserFlo MicroShunt versus trabeculectomy: an updated meta-analysis and systematic review.

This meta-analysis compares PreserFlo (PF) and trabeculectomy (TB) in moderate-to-advanced glaucoma (defined by visual fields with a mean deviation (MD) worse than -6dB). Key outcomes include success rates (qualified success is defined as a target IOP of less than 21mm Hg or a 20% reduction from baseline at the endpoint, with or without medications. Complete success is achieving these targets without any medications), intraocular pressure (IOP), complications, reinterventions, needling, glaucoma medication reduction, retinal nerve fibre layer (RNFL), and visual field progression. We searched PubMed, Scopus, and Cochrane Central up to 13/01/24, including randomized and non-randomized studies with at least 2months follow-up. Bias risk was assessed using ROB-2 for RCTs and ROBIN-I for non-RCTs. Publication bias was evaluated via funnel plots and Egger's regression. Ten studies (n = 1833 eyes; 57.4% PF) were analyzed. Preoperative IOP was 22.1mmHg; 56.1% had moderate-to-severe glaucoma. No significant differences were found in qualified (QSR) and complete success rates (CSR) between PF and TB. Trabeculectomy achieved better IOP outcomes (mean difference, MD 1.59mmHg; p = 0.0004) and greater IOP reduction (MD -2.52mmHg; p = 0.0003), but PF showed less visual field progression (MD -1.21; p = 0.03) and lower hypotony maculopathy risk (OR 0.30; p = 0.03). PF had a higher reintervention rate, particularly in patients without prior glaucoma surgery (OR 1.74; p = 0.02) or with primary open-angle glaucoma (OR 1.84; p = 0.04). Trabeculectomy is more effective for uncontrolled glaucoma up to 2years, while PF presents a lower risk of hypotony-related events and may benefit patients sensitive to visual field progression. Study strengths include detailed subgroup analyses and mid-term follow-up, with limitations noted in the number of RCTs. What is known PreserFlo MicroShunt has been shown to provide an efficient surgical solution for intraocular pressure (IOP) control with a favourable safety profile. Compared to trabeculectomy thereis still contentious regarding the best surgical approach. What is new Trabeculectomy is more effective in uncontrolled glaucoma patients up to 2 years, particularly if lower target IOPs are considered. PreserFlo had lower hypotony-related events risk and may be preferred for patients sensitive to visual field loss. PreserFlo showed a higher risk of reintervention, especially without prior glaucoma surgery or primary open-angle glaucoma diagnosis.

Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy.

Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN). Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression. We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m2 [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68-0.89) and SFN (0.85, 0.75-0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48-0.69, SFN: AUC: 0.59, 0.46-0.73) and CCM metrics (DSP: AUC range: 0.55-0.60, SFN: AUC range: 0.45-0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68-0.85, SFN: AUC: 0.81, 0.73-0.88). More participants (52%) preferred skin biopsies to CCM. Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting. clinicaltrials.gov: NCT03617185.

Association of tear osmolarity and corneal nerves structure in dry eye disease: an in vivo study.

To evaluate the structural changes in corneal sub-basal nerves of dry eye disease (DED) patients with tear hyperosmolarity versus normosmolar tears. A prospective evaluation of the tear film (keratograph 5M), tear osmolarity, and sub-basal corneal nerves (laser scanning in-vivo confocal microscopy) was performed in a cohort of 53 DED patients (106 eyes) diagnosed as per DEWS II criteria. Patients with tear hyperosmolarity (Group 1, n = 48 eyes) were compared with DED patients without tear hyperosmolarity (Group 2, n = 58 eyes). Of 53 patients (27 females), 28 had Sjogren's syndrome, and the rest had meibomian gland dysfunction. There were more SS patients (21 vs 7) and females in Group 1. The two groups were similar in age, TMH, NIBUT, meibomian gland loss, bulbar redness, and corneal staining, except for Schirmer I (p < 0.001), and tear osmolarity (p < 0.001; worse in group 1). The groups did not differ in dendritic cell density, whether immature (53.8 vs. 38) or mature (2.7 vs. 0). The significantly different corneal nerve parameters were nerve fiber length (p = 0.005), density (p = 0.01), and branching density (p = 0.04), with lower values observed in group 1. Only tear osmolarity had a weak negative correlation with corneal nerve fiber length (r, -0.38), density (r, -0.32), and branching (r, -0.28). SS patients with hyperosmolar tears had reduced nerve fiber length and branching compared to SS patients with normosmolar tears. Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length despite similar levels of conjunctival congestion, tear film stability, and meibomian gland loss in DED patients. What is known • Corneal nerves are reduced in density and length in dry eye disease patients. • Laboratory studies have shown fragmentation of corneal nerves on exposure to hyperosmolar solutions. What is new • Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length in dry eyes compared to normosmolar tears. • The effect is independent of dendritic cell density.

The Hidden Hand in White Matter: Pericytes and the Puzzle of Demyelination.

Disruption of myelin, the fatty sheath-insulating nerve fibers in the white matter, blocks or slows the rapid transmission of electrical signals along nerve cells and contributes to several neurodegenerative diseases such as multiple sclerosis. Traditionally, research has focused on neuronal dysfunction as the primary factor, including autoimmunity, infections, inflammation, and genetic disorders causing demyelination. However, recent insights emphasize the critical role of pericytes, non-neuronal cells that regulate blood flow and maintain the health of blood vessels within white matter. This Perspective explores the principal mechanisms through which pericyte dysfunction contributes to damage and demyelination, including impaired communication with neurons (neurovascular uncoupling), excessive formation of scar tissue (fibrosis), and the infiltration of detrimental substances from the bloodstream. Understanding these mechanisms of pericyte-driven demyelination may lead to the creation of new therapeutic strategies for tackling a range of neurodegenerative conditions.

Is Our Limited Understanding of the Effects of Nerve Stimulation Resulting in Poor Outcomes and the Need for Better "Rescue Programming" in SNM and PTNS, and Lost Opportunities for New Sites of Stimulation? ICI-RS 2024.

Sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) are strongly recommended by international guidelines bodies for complex lower urinary tract dysfunctions. However, treatment failure and the need for rescue programming still represent a significant need for long-term follow-up. This review aimed to describe current strategies and future directions in patients undergoing such therapies. This is a consensus report of a Think Tank discussed at the Annual Meeting of the International Consultation on Incontinence - Research Society (ICI-RS), June 6-8, 2024 (Bristol, UK): "Is our limited understanding of the effects of nerve stimulation resulting in poor outcomes and the need for better 'rescue programming' in SNM and PTNS, and lost opportunities for new sites of stimulation?" Rescue programming is important from two different perspectives: to improve patient outcomes and to enhance device longevity (for implantable devices). Standard SNM parameters have remained unchanged since its inception for the treatment of OAB, nonobstructive urinary retention, and voiding dysfunction. SNM rescue programming includes intermittent stimulation (cycling on), increased frequency and changes in pulse width (PW). The effect of PW setting on SNM outcomes remains unclear. Monopolar configurations stimulate more motor nerve fibers at lower stimulation voltage; hence, this could be an option in patients who failed bipolar stimulation in the long term. Unfortunately, there is little evidence for rescue programming for PTNS. However, the development of implantable devices for intermittent stimulation of the tibial nerve may increase long-term adherence to therapy and increase interest in alternative programming. There has been recent promising neurostimulation targeting the pudendal nerve (PNS), especially in BPS/IC. More recently, preliminary data addressed the benefits of high-frequency bilateral pudendal nerve block for DESD and adaptive PNS on both urgency and stress UI in women. The exploration of rescue programming and new stimulation sites remains underutilized, and there are opportunities that could potentially expand the therapeutic applications of nerve stimulation. By broadening the range of target sites, clinicians may be able to tailor treatments according to individual patient needs and underlying conditions, thereby improving overall outcomes. However, further studies are still needed to increase the level of evidence, potentially allowing for an individualized treatment both in patients who are candidates for electrostimulation and in those who have already received surgical implants but seek a better outcome.

The concept of the Schwann cell by Louis Ranvier and his school: The ‘interannular segment’ as a cell unit

ABSTRACT The hundredth anniversary of the death of French histologist Louis Ranvier (1835‒1922) is an opportunity to reexamine his elaboration of the first concept of the Schwann cell. A loyal supporter of Theodor Schwann and his discoveries, and an attentive reader of the work of Albert von Kölliker, Ranvier studied the anatomic details of the myelinated nerve fiber with picrocarminate staining. The diffusion of the dye into the nerve fiber at the cut ends and at the sites of the annular constrictions (Ranvier’s nodes) set him on the path to defining a new cellular entity surrounding the axon, the “interannular segment,” comprising a Schwann nucleus, myelin, and cytoplasm. Ramón y Cajal recognized in 1913 that this concept of the Schwann cell according to Ranvier and his pupil William Vignal had been a brilliant intuition, but it was widely rejected until it was rediscovered using electron microscopy in the 1950s. The article reconstructs the steps of Ranvier and Vignal in building this Schwann cell concept, as well as establishing bridges with the discoveries of the 1950s.

The possibilities of using adaptive optics in modern ophthalmology

Until recently, the assessment of individual retinal cells was possible only with the help of histological examination, since such retinal imaging methods as scanning laser ophthalmoscopy and optical coherence tomography had low resolution to obtain images of structures at the cellular level, which was mainly due to aberrations caused by the optics of the eye. Adaptive optics technology has improved the performance of optical systems by correcting optical wavefront aberrations. Adaptive optics allows noninvasively visualizing the retina at the microscopic level in vivo, providing the opportunity to analyze individual structures such as photoreceptors, blood vessels, nerve fibers, ganglion cells and a lattice plate. Adaptive optics imaging in patients with diabetic retinopathy makes it possible to accurately determine the spatial distribution of cones, a decrease in which is associated with the presence of diabetic retinopathy and an increase in the severity of the disease. The detection of differences in cone distribution density between the control group and patients with diabetes mellitus without clinical signs of diabetic retinopathy may contribute to its early diagnosis, as well as a deeper understanding of the consequences of changes in the photoreceptor apparatus. Adaptive optics imaging methods are able to identify disorders of photoreceptor cells and assess the degree of progression of age-related macular degeneration, which definitely expands diagnostic capabilities at the early stages of its detection. Assessment of the condition of nerve fiber bundles through the use of Adaptive optics helps to identify changes associated with glaucoma, and also provides the ability to visualize details that cannot be evaluated using optical coherence tomography. Adaptive optics imaging allows you to directly measure the wall of retinal vessels and the diameter of their lumen. The ratio of wall thickness to vessel lumen and the cross-sectional area of the vessel wall directly reflect the remodeling process and can be used for the purpose of early diagnosis and monitoring of hypertension.

Longitudinal evaluation of retinal neuroaxonal loss in epilepsy using optical coherence tomography.

People with epilepsy (PwE) suffer from progressive brain atrophy, which is reflected as neuroaxonal loss on the retinal level. This study aims to provide initial insight into the longitudinal dynamics of the retinal neuroaxonal loss and possible driving factors. PwE and healthy controls (HC; 18-55 years of age) underwent spectral domain optical coherence tomography at baseline and 7.0 ± 1.5 and 6.7 ± 1.0 months later, respectively. The change in retinal thickness/volume and annualized percentage change (APC) were calculated for the peripapillary retinal nerve fiber layer (pRNFL), the macular RNFL (mRNFL), the ganglion cell inner plexiform layer (GCIP), the inner nuclear layer, and the total macular volume (TMV). Group comparisons and multiple linear models with stepwise backward selection were performed to evaluate associations with demographic and clinical parameters. PwE (n = 44, 21 females, mean age = 35.6 ± 10.9 years) revealed a significant decrease in the pRNFL, mRNFL, GCIP, and TMV thickness or volume in the study interval. When compared to HC (n = 56, 37 females, mean age = 32.7 ± 8.3 years), the APC of the pRNFL (-.98 ± 3.13%/year) and the GCIP (-1.24 ± 2.56%/year) were significantly more pronounced in PwE (p = .01 and p = .046, respectively). Of note, atrophy of the mRNFL was significantly influenced by the number of antiseizure medications (ASMs; p = .047) and increasing age of PwE (p = .03). Contradictory results, however, were revealed for the impact of seizures. In epilepsy, progression of retinal neuroaxonal loss was already detectable at short-term follow-up. PwE who receive a high number of ASMs seem to be at risk for accelerated neuroaxonal loss, stressing the importance of well-considered and effective antiseizure therapy.

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.