The assessment of structural and functional test results for early detection of hydroxychloroquine macular toxicity.

PURPOSE: To assess structural (optical coherence tomography, fundus autofluorescence) and functional (contrast sensitivity and visual field) test results which were used for detecting early retinal changes in patients using oral hydroxychloroquine. METHODS: Patients using oral hydroxychloroquine for at least one year were divided into two groups according to the duration of drug use. Groups 1 and 2 consisted of patients with drug use for more than 5 years and 1-5 years, respectively. The drug-using groups were compared with the control group. The mean retinal nerve fiber layer (RNFL), central macular thickness (CMT), ganglion cell-inner plexiform layer (GC-IPL), static 10-2 visual field, fundus autofluorescence (FAF) imaging, and contrast sensitivity tests were performed and statistically compared between groups. RESULTS: Median and temporal quadrant RNFL thicknesses were found to be statistically significantly lower in the drug groups. In the drug groups, the GC-IPL sectoral and mean thicknesses were found to be statistically lower in all quadrants. Central macular thickness was also found to be similar in all three groups. There was no significant difference between the groups in visual field parameters. Macular FAF images were significantly higher in the drug users, but there was no significant difference between the three groups in foveal FAF images. Contrast sensitivity measurements were significantly lower in the drug groups than in the control group at all spatial frequencies except 6 and 18 cycles/degree. CONCLUSIONS: The combined use of structural and functional tests in patients using hydroxychloroquine provides useful information in detecting early retinal changes.

Inner retinal layer thickness alterations in adult and pediatric patients with neurofibromatosis 1.

This study compared the thickness of each intraretinal layer in patients with neurofibromatosis 1 (NF1) and controls to analyze the association between intraretinal layer thickness and visual function. The macular spectral-domain optical coherence tomography volumetric dataset obtained from 68 eyes (25 adult eyes, 43 pediatric eyes) with NF1 without optic glioma and 143 control eyes (100 adult eyes, 43 pediatric eyes) was used for image auto-segmentation. The intraretinal layers segmented from the volumetric data included the macular retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer. Cases and controls were compared after adjusting for age, sex, refractive error, and binocular use. The association between retinal layer thickness and visual acuity was also analyzed. The GCIPL was significantly thinner in both adult and pediatric patients with NF1 compared with healthy controls. Average RNFL and GCIPL thicknesses were associated with visual acuity in adult patients with NF1. In pediatric patients, average GCIPL thickness was associated with visual acuity. These results suggest that changes in the inner retinal layer could be a biomarker of the structural and functional status of patients with NF1.

A Novel Artificial Intelligence-Based Classification of Highly Myopic Eyes Based on Visual Function and Fundus Features.

Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features. Methods: We enrolled 616 highly myopic eyes of 616 patients. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering. Results: With 83.35% total variance explained, highly myopic eyes were classified into four AI categories. The percentages of AI categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. Contrast acuity of the eyes in AI category 1 was the highest, which decreased by half in AI category 2. For AI categories 2 to 4, every increase in category led to a decrease of 0.23 logarithm of the minimum angle of resolution in contrast acuity. Compared with those in AI category 1, eyes in AI category 2 presented a higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in AI categories 3 and 4 presented significantly higher percentage of MMD ≥ 3, thinner nasal macular thickness and p-RNFL (P < 0.05). Multivariate regression showed AI category 4 had higher MMD grades and thinner macular compared with AI category 3. Conclusions: We proposed an AI-based classification of highly myopic eyes with clear relevance to visual function and fundus features. Translational Relevance: This classification helps to discover the early hidden visual deficits of highly myopic patients, becoming a useful tool to evaluate the disease comprehensively.

Using Multi-Layer Perceptron Driven Diagnosis to Compare Biomarkers for Primary Open Angle Glaucoma.

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG). Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA). Results: MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model. Conclusions: Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.

Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.

Characterisation and distribution of human coronary artery innervation.

BACKGROUND: A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches. AIMS: This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries. METHODS: Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres. RESULTS: A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 µm [31-73], middle 38 µm [26-58], distal 31 µm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 µm [31-81]), followed by the LAD (42 µm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005). CONCLUSIONS: Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.

Association of Retinal Nerve Fiber Layer Thinning With Elevated High Density Lipoprotein Cholesterol in UK Biobank.

Purpose: The purpose of this study was to investigate the association between retinal nerve fiber layer (RNFL) thickness and high-density lipoprotein cholesterol (HDL-C) in a healthy population. Methods: This cross-sectional study included 31,738 UK Biobank participants with high quality optical coherence tomography (OCT) images, excluding those with neurological or ocular diseases. The locally estimated scatterplot smoothing (LOESS) curve and multivariable piecewise linear regression models were applied to assess the association between HDL-C and RNFL thickness, and HDL-C subclasses were further analyzed using nuclear magnetic resonance (NMR) spectroscopy. Results: Multivariate piecewise linear regression revealed that high HDL-C levels (>1.7 mmol/L in women or > 1.5 mmol/L in men) were associated with thinner RNFL thickness (women: ß = -0.13, 95% confidence interval [CI] = -0.23 to -0.02, P = 0.017; male: ß = -0.23, 95% CI = -0.37 to -0.10, P = 0.001). Conversely, a significant positive association between HDL-C and RNFL thickness was observed when HDL-C was between 1.4 and 1.7 mmol/L for female participants (ß = 0.13, 95% CI = 0.02 to 0.24, P = 0.025). NMR analysis showed that these associations are potentially driven by distinct HDL-C subclasses. Conclusions: This study revealed an association between HDL-C levels and retinal markers of neurodegenerative diseases, suggesting that elevated HDL-C may serve as a new risk factor for neurodegenerative conditions. These findings may contribute to the implementation of preventive interventions and improved patient outcomes.

Evaluation of choroidal thickness and optic disc parameters in patients with chronic phase gout.

PURPOSE: This study aims to assess the disparities in choroidal thickness and optic disc parameters between individuals diagnosed with chronic gout and an age- and gender-matched control cohort. METHODS: This cross-sectional study involved 30 gout patients receiving treatment at the Rheumatology clinic, alongside 30 healthy control individuals matched for age and gender. A comprehensive ophthalmological assessment, encompassing visual acuity measurement, intraocular pressure evaluation, slit-lamp biomicroscopy, and dilated fundus examination, was conducted for all participants. Peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and subfoveal choroidal thickness (SFCT) were quantified utilizing Spectral Domain Optical Coherence Tomography. RESULTS: The mean age within the study group was 54.53 ± 9.43 years, while the control group's mean age was 53.20 ± 10.36 years. In both the gout and control cohorts, there were 28 men and 2 women. No significant differences were observed in age and gender between the groups. Gout patients manifested thinner RNFL and GCC across all quadrants; however, statistically significant thinning was only evident in the nasal and inferior quadrants for RNFL. Despite a thinner SFCT observed in gout patients compared to controls, this discrepancy did not attain statistical significance. CONCLUSION: Chronic phase gout patients may display alterations in optic disc and macular parameters, alongside potential variations in choroidal thickness. Nevertheless, more controlled studies encompassing a larger participant pool are imperative to substantiate our findings.

Detecting Visual Field Worsening From Optic Nerve Head and Macular Optical Coherence Tomography Thickness Measurements.

Purpose: Compare the use of optic disc and macular optical coherence tomography measurements to predict glaucomatous visual field (VF) worsening. Methods: Machine learning and statistical models were trained on 924 eyes (924 patients) with circumpapillary retinal nerve fiber layer (cp-RNFL) or ganglion cell inner plexiform layer (GC-IPL) thickness measurements. The probability of 24-2 VF worsening was predicted using both trend-based and event-based progression definitions of VF worsening. Additionally, the cp-RNFL and GC-IPL predictions were combined to produce a combined prediction. A held-out test set of 617 eyes was used to calculate the area under the curve (AUC) to compare cp-RNFL, GC-IPL, and combined predictions. Results: The AUCs for cp-RNFL, GC-IPL, and combined predictions with the statistical and machine learning models were 0.72, 0.69, 0.73, and 0.78, 0.75, 0.81, respectively, when using trend-based analysis as ground truth. The differences in performance between the cp-RNFL, GC-IPL, and combined predictions were not statistically significant. AUCs were highest in glaucoma suspects using cp-RNFL predictions and highest in moderate/advanced glaucoma using GC-IPL predictions. The AUCs for the statistical and machine learning models were 0.63, 0.68, 0.69, and 0.72, 0.69, 0.73, respectively, when using event-based analysis. AUCs decreased with increasing disease severity for all predictions. Conclusions: cp-RNFL and GC-IPL similarly predicted VF worsening overall, but cp-RNFL performed best in early glaucoma stages and GC-IPL in later stages. Combining both did not enhance detection significantly. Translational Relevance: cp-RNFL best predicted trend-based 24-2 VF progression in early-stage disease, while GC-IPL best predicted progression in late-stage disease. Combining both features led to minimal improvement in predicting progression.

Keeping track of time: An interaction of mossy fibers and climbing fibers.

Precisely tracking time over second-long timescales is important for accurate anticipation and consequential actions, yet the neurobiological underpinnings remain unknown. In this issue of Neuron, Garcia-Garcia and colleagues1 show that computations in the cerebellum resulting from interactions between the mossy fiber and climbing fiber pathways contribute to long-interval learning during operant conditioning.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Can the diameter of nerve fibers be effectively utilized to enhance the accuracy of determining the length of the aganglionic segment compared to intraoperative biopsy in patients with Hirschsprung's disease?

OBJECTIVE: The aim of this study is to investigate the accuracy of utilizing neural fiber trunk diameter in accurately diagnosing the length of the aganglionic segment in patients definitively diagnosed with Hirschsprung's disease. RESULTS: In this study, 40 patients (19 males, 21 females; mean age 2.5 ± 2.2646 years) were assessed for Hirschsprung's disease. Constipation was the main symptom (75%), followed by abdominal issues. All underwent contrast enema and rectal suction biopsy for diagnosis, followed by surgery (predominantly Soave and Swensen techniques). Majority (85%) had rectosigmoid involvement. Neural fiber diameter was measured, with 52.5% ≤40 µm and 47.5% >40 µm. Statistical analysis showed 40% sensitivity(CI:95%) and 47% specificity(CI:95%) with a cutoff of 40.5 µm. Cohen's kappa index for aganglionic segment size was 0.7.

Peripapillary retinal nerve fibre layer thinning in patients with X-linked retinoschisis.

AIMS: To assess peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with X-linked retinoschisis (XLRS), as pRNFL thinning may limit functional improvements in gene therapy trials. METHODS: This retrospective multicentre study included 49 eyes from 25 patients diagnosed with XLRS. Data collected with multimodal imaging at baseline and last follow-up (when available) included age, best-recorded visual acuity (BRVA), central retinal thickness, macular volume (MV), presence and location of peripheral retinoschisis and pRNFL thickness in the global (G), superotemporal (TS), superonasal (NS), inferotemporal (TI), inferonasal (NI), nasal (N) and temporal (T) sectors. Retinal sensitivity, assessed by microperimetry, was also recorded for seven patients at baseline. RESULTS: pRNFL was thinner (below the fifth percentile) in at least one sector in 72% of right eyes and 79% of left eyes, with thinning across three or more sectors in 20% of right and 17% of left eyes. In 44% of cases, thinning occurred in the temporal sectors of both eyes, with no nasal sectoral thinning. Number of peripheral retinoschisis quadrants matched thinned pRNFL sectors. A strong positive correlation was found between MV and temporal pRNFL thickness (r=0.71, p<0.01), while weak negative correlation trends were noted with age (p=0.05) and BRVA (logMAR; p=0.12) related to temporal thickness of pRNFL sectors. CONCLUSION: pRNFL thinning, predominantly sectoral and linked to macular or peripheral retinoschisis, occurs in about three-quarters of patients with XLRS, while diffuse thinning occurs in one-fifth. Temporal pRNFL thinning might occur only after the collapse of intraretinal cystoid cavities in the macula.

Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study.

AIMS: To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. METHODS: Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability. RESULTS: The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at -0.00005 established non-inferiority against a margin of -0.4 (p = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9-1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9-0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. INTERPRETATION: Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.

LONGITUDINAL CHANGE OF RETINAL LAYER THICKNESS IN COGNITIVELY NORMAL ELDERLY SUBJECTS: Population-Based Cohort Study.

PURPOSE: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people. METHODS: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured. RESULTS: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer. CONCLUSION: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals.

Retinal ganglion cell complex thickness in subjects with diabetes mellitus and uncontrolled hypertension in China.

PURPOSE: To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. METHODS: Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. RESULTS: Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (ß = 3.868, p = 0.011). GCC thickness would decrease 0.255 µm per year as the age increased (ß=-0.255, p < 0.001). In a subgroup of 574 subjects with uncontrolled hypertension, DM was associated with an increased average of GCC thickness (ß = 1.929, p = 0.022). CONCLUSIONS: The present results revealed a significant interactive relationship between blood pressure status and DM. The average GCC thickness increased in individuals with DM combined with uncontrolled hypertension, which should be considered in the measurement of GCC. Further studies are warranted to explore ganglion cells changes as a non-invasive method to detect neuron alterations in individuals with DM and uncontrolled hypertension. TRAIL REGISTRATION: The registration number of the present trial in the Chinese Clinical Trial Registry is ChiCTR2000037944.

Effect of magnification error and axial length on circumpapillary capillary density and retinal nerve fiber layer thickness.

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9-28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT.

Optic Nerve Head Morphology and Macula Ganglion Cell Inner Plexiform Layer Thickness in Axially Anisometropic Rhesus Monkeys.

Purpose: The purpose of this study was to determine the effects of axial elongation on optic nerve head morphology and macula inner retinal thickness in young rhesus monkeys. Methods: Both eyes of 26 anisometropic, 1-year-old rhesus monkeys were imaged using optical coherence tomography (OCT). Before imaging, the animals were sedated, their eyes were dilated, and axial length was measured using an optical biometer. OCT imaging included a 20 degrees, 24-line radial scan centered on the optic nerve head (ONH) and two 20 degrees × 20 degrees raster scans, one centered on the ONH and the other on the macula. Radial scans were analyzed using programs written in MATLAB to quantify the Bruch's membrane opening (BMO) area and position, minimum rim width (MRW), anterior lamina cribrosa surface (ALCS) position, size of any scleral crescent, circumpapillary retinal nerve fiber layer (RNFL), and choroid thickness (pCh). Macula total retinal thickness (mTRT) and ganglion cell inner plexiform layer (GCIPL) thicknesses were quantified from macula scans. Linear least square regression was determined for OCT measures and axial length of the right eye, and for inter-eye differences. Results: Animals were 341 ± 18 days old at the time of imaging. BMO area (R2 = 0.38), ALCS position (R2 = 0.45), scleral crescent area (R2 = 0.35), pCh thickness (R2 = 0.21), mTRT (R2 = 0.24), and GCIPL thickness (R2 = 0.16) were correlated with the axial length (all P < 0.05). For each of these parameters, the right-eye regression slope did not differ from the slope of the interocular difference (P > 0.57). Conclusions: There are posterior segment morphological differences in anisometropic rhesus monkeys related to axial length. Whether these differences increase the risk of pathology remains to be investigated.

Highly efficient modeling and optimization of neural fiber responses to electrical stimulation.

Peripheral neuromodulation has emerged as a powerful modality for controlling physiological functions and treating a variety of medical conditions including chronic pain and organ dysfunction. The underlying complexity of the nonlinear responses to electrical stimulation make it challenging to design precise and effective neuromodulation protocols. Computational models have thus become indispensable in advancing our understanding and control of neural responses to electrical stimulation. However, existing approaches suffer from computational bottlenecks, rendering them unsuitable for real-time applications, large-scale parameter sweeps, or sophisticated optimization. In this work, we introduce an approach for massively parallel estimation and optimization of neural fiber responses to electrical stimulation using machine learning techniques. By leveraging advances in high-performance computing and parallel programming, we present a surrogate fiber model that generates spatiotemporal responses to a wide variety of cuff-based electrical peripheral nerve stimulation protocols. We used our surrogate fiber model to design stimulation parameters for selective stimulation of pig and human vagus nerves. Our approach yields a several-orders-of-magnitude improvement in computational efficiency while retaining generality and high predictive accuracy, demonstrating its robustness and potential to enhance the design and optimization of peripheral neuromodulation therapies.