Characteristics of a Large Database of Healthy Eyes From Optometry Practices: Implications for a Real-World Reference Database.

Purpose: To compare an optical coherence tomography (OCT) real-world reference database (RW-RDB) of "healthy" eyes obtained from optometry practices to a commercial reference database (RDB). Methods: OCT scans from 6804 individuals 18 years and older were sampled from a larger database tested at 10 optometry practices involved in refractive and screening services. Employing a reading center method, OCT scans from both eyes of 4932 (4.9K) individuals were judged to be of acceptable quality with an absence of pathology. The 4.9K RW-RDB was compared to a commercial RDB with 398 eyes (398 RDB). Results: The means and distributions of global circumpapillary retinal nerve fiber layer (G-cpRNFL) and global ganglion cell layer (G-GCL) thickness, as well as five key anatomical parameters affecting cpRNFL thickness, were not significantly different for all but one parameter (fovea-to-disc distance) and one thickness metric (G-cpRNFL). In both cases, the difference amounted to less than 1.5%. By design, the number of 4.9K RW-RDB eyes 70 years and older (724, 14.7%) was greater than for the 398 RDB (40, 10.1%). The error bands on the 5% and 1% quantile regression lines (QRLs) were substantially narrower for the 4.9K RW-RDB. Conclusions: The 398 RDB and 4.9K RW-RDB have similar characteristics and appear to come from a similar population. However, the large size of the 4.9K RW-RDB leads to narrower error bands of the QRLs, which has the potential to increase accuracy. Translational Relevance: The larger RW-RDB offers the opportunity to better characterize healthy eyes for clinical diagnosis and clinical trials by furthering our understanding of the patterns of artifacts, exploring covariates, developing separate RW-RDBs, and/or improving AI models.

Normative Profile of Retinal Nerve Fiber Layer Thickness and Lamina Cribrosa-Related Parameters in a Healthy Non-Glaucoma Cynomolgus Monkey Colony.

Purpose: The purpose of this study was to investigate the normal range of ophthalmic parameters and the correlations between systematic and ocular parameters and retinal nerve fiber layer (RNFL) thickness among a healthy non-glaucoma cynomolgus monkey colony. Methods: All included monkeys were given detailed ophthalmic examinations, including anterior and posterior segments. Furthermore, univariate and multivariate linear regression models were conducted to estimate the relationship between systemic and ophthalmic parameters and global RNFL thickness. Results: A total of 349 non-glaucoma monkeys (18.69 ± 2.88 years old) were collected. The global RNFL thickness was 94.61 ± 10.13 µm, and sex-specific differences existed in all sectors. The decreasing trend of RNFL is as follows: inferotemporal, superotemporal, inferonasal, superonasal, temporal, and nasal. For lamina cribrosa (LC)-related parameters, cup depth (P < 0.01), LC thickness (P = 0.014), and Bruch's membrane opening (BMO) - minimum rim width 2 (P = 0.002) were greater in the male group. However, LC depth (P = 0.02), anterior laminar insertion depth-1 (P = 0.009), and mean anterior laminar insertion depth (P = 0.029) of female monkeys were greater than those of male monkeys. In multivariate linear regression, only older age was significantly related to reduced global RNFL thickness (P < 0.001). Conclusions: Our findings suggest the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkeys and humans. Therefore, the impact of this difference on outcomes should be fully considered in laboratory animal studies. Our findings are also significant in terms of developing a normative optical coherence tomography (OCT) database in nonhuman primates (NHPs). Translational Relevance: We found that the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkey colonies and humans should be thoroughly taken into account in laboratory animal studies.

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.

Evaluation of lamina cribrosa parameters, nerve fiber thickness, and macular thickness in primary open-angle glaucoma and pseudoexfoliation glaucoma using optical coherence tomography.

PURPOSE: To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT). METHODS: A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups. RESULTS: In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05). CONCLUSION: The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG.

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.

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.

Differential protection by nicotinamide in a mouse model of glaucoma DBA/2J revealed by second-harmonic generation microscopy.

Glaucoma is a blinding disease where the retinal ganglion cells and their axons degenerate. Degradation of axonal microtubules is thought to play a critical role in the pathogenesis, but the mechanism is unknown. Here we investigate whether microtubule disruption in glaucoma can be alleviated by metabolic rescue. The integrity of axonal microtubules and the morphology of the retinal nerve fibers were evaluated by second-harmonic generation microscopy in a mouse model of glaucoma, DBA/2J, which received a dietary supplement of nicotinamide (NAM) for reducing metabolic stress. It was compared with control DBA/2J, which did not receive NAM, and non-glaucomatous DBA/2J-Gpnmb+. We found that the morphology of the retinal nerve fibers, but not axonal microtubules, are significantly protected by NAM. The decoupling is analogous to microtubule deficit, a glaucoma pathology in which axonal microtubules exhibit rapid degradation compared to the morphology of the retinal nerve fibers. Understanding microtubule deficit could provide insights into the divergent responses to NAM. From co-registered images of second-harmonic generation and immunofluorescence, it was determined that microtubule deficit was not due to a shortage of tubulins. Furthermore, microtubule deficit colocalized with the sectors in which the retinal ganglion cells were disconnected from the brain, suggesting that microtubule disruption is associated with axonal transport deficit in glaucoma. Together, our data suggests significant role axonal microtubules play in glaucomatous degeneration, offering a new opportunity for neuroprotection.

Association between retinal nerve fiber layer thickness and psychiatric disorders: a mendelian randomization study.

BACKGROUND: Retinal nerve fiber layer thickness, as a new visual indicator that may help diagnose mental disorders, is gaining attention from researchers. However, the causal relationship between retinal nerve fiber layer thickness and mental disorders is still to be effectively proved. METHODS: A bidirectional Two-sample Mendelian randomization analysis was utilized to analyse aggregated data from large-scale genome-wide association studies, we selected genetic loci for retinal nerve fiber layer thickness in independent retinal abnormalities and three prevalent psychiatric disorders (schizophrenia, depression, bipolar disorder) as instrumental variables. The Two-sample Mendelian randomization analysis was mainly performed by inverse variance weighting and weighted median method. The Cochran Q test and leave-one-out sensitivity were used to ensure the robustness of the results. The Mendelian random polymorphism residuals and outliers were used to detect single nucleotide polymorphism outliers, and MR-Egger intercept test was used to test single nucleotide polymorphism horizontal pleiotropy. RESULTS: IVW showed that retinal nerve fiber layer thickness was positively associated with schizophrenia (OR = 1.057, 95%CI: 1.000-1.117, P < 0.05), in the study of bipolar disorder, MR analysis also suggested a positive causal relationship between retinal nerve fiber layer thickness and bipolar disorder (OR = 1.025, 95%CI: 1.005-1.046, P < 0.05), which indicated possible causal relationships between retinal nerve fiber layer thickness and these two diseases. Depression (OR = 1.000143, 95%CI: 0.9992631-1.001024, P = 0.74) indicated no significant causal association. No reverse causal effects of psychiatric disorders on retinal nerve fiber layer thickness were found. CONCLUSIONS: A statistically significant causal relationship between retinal nerve fiber layer thickness and schizophrenia and bipolar disorder has been supported by genetic means, indicating RNFL has potential to aid in the diagnosis of schizophrenia and bipolar disorder.

Preoperative OCT-Derived Nasal Perifoveal Retinal Nerve Fiber Layer Thickness Predictively Correlates Long-Term Visual Acuity Post Oil Removal Surgery.

Purpose: With the widespread application of silicone oil in vitreoretinal surgery, the purpose of this study was to determine the risk factors of long-term vision loss 12 months post oil removal in retina-detached eyes treated with vitrectomy and silicone oil tamponade. Methods: Of the 592 patients approached, eligible eyes completed the investigation up to 12 months post-oil-removal. Eligible eyes underwent pars-plana vitrectomy following oil tamponade. Oil removal was performed after 3 to 28 months in different individuals, under the condition that the retina has reattached as well as the hemorrhage and inflammation has dissolved. Postoperative best-corrected visual acuity (BCVA), age, sex, and interval between tamponade and removal were recorded, and retinal thickness was determined using optical coherence tomography (OCT). Results: Fifty eyes of 50 participants aged 31 to 83 years were enrolled. BCVA (LogMAR) 12 months post-oil-removal improved in 25 of 40 (62.5%) patients, varying from 0.05 (20/22) to 1.0 (20/200) (mean ± SD = 0.55 ± 0.32). Pre-oil-removal nasal perifoveal retinal nerve fiber layer thickness varied from 16 to 83 µm (38.40 ± 18.50), and was significantly linked with post-oil-removal BCVA (0.5%, 95% confidence interval 0.0%-1.0%; P = 0.046). Conclusions: This study demonstrates the risk factors and prognosis of visual function after long-term regeneration post vitrectomy, oil tamponade, and oil removal, thereby underscoring the need for a complete, dynamic examination of retinal structure via OCT measurement. Related studies should be conducted on a larger scale to facilitate the stratification of late-period vision damage in retina-detached eyes. Translational Relevance: This study developed OCT-based clinical markers for the postoperative visual prognosis of eyes affected by retinal detachment.

Characterizing Presumed Displaced Retinal Ganglion Cells in the Living Human Retina of Healthy and Glaucomatous Eyes.

Purpose: The purpose of this study was to investigate the large somas presumed to be displaced retinal ganglion cells (dRGCs) located in the inner nuclear layer (INL) of the living human retina. Whereas dRGCs have previously been studied in mammals and human donor tissue, they have never been investigated in the living human retina. Methods: Five young, healthy subjects and three subjects with varying types of glaucoma were imaged at multiple locations in the macula using adaptive optics optical coherence tomography. In the acquired volumes, bright large somas at the INL border with the inner plexiform layer were identified, and the morphometric biomarkers of soma density, en face diameter, and spatial distribution were measured at up to 13 degrees retinal eccentricity. Susceptibility to glaucoma was assessed. Results: In the young, healthy individuals, mean density of the bright, large somas was greatest foveally (550 and 543 cells/mm2 at 2 degrees temporal and nasal, respectively) and decreased with increasing retinal eccentricity (38 cells/mm2 at 13 degrees temporal, the farthest we measured). Soma size distribution showed the opposite trend with diameters and size variation increasing with retinal eccentricity, from 12.7 ± 1.8 µm at 2 degrees to 15.7 ± 3.5 µm at 13 degrees temporal, and showed evidence of a bimodal distribution in more peripheral locations. Within and adjacent to the arcuate defects of the subjects with glaucoma, density of the bright large somas was significantly lower than found in the young, healthy individuals. Conclusions: Our results suggest that the bright, large somas at the INL border are likely comprised of dRGCs but amacrine cells may contribute too. These somas appear highly susceptible to glaucomatous damage.

Macular exudate in idiopathic intracranial hypertension affects outer retina and visual acuity.

BACKGROUND: Optical coherence tomography (OCT) is suggested as a potential tool for retinal biomarkers in idiopathic intracranial hypertension (IIH). We explored how macular exudate (ME) affects retinal structure in IIH and investigated its relationship with their clinical features. METHODS: Patients diagnosed with IIH and matched controls were enrolled. ME detection was done on fundus photography; swept-source OCT was used to image and measure the retinal sublayer thicknesses, including the retinal nerve fibre layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer retinal layer (ORL). IIH patients underwent lumbar puncture where intracranial pressure (ICP) was assessed. RESULTS: 195 eyes from 98 IIH patients (42 eyes had ME) and 224 eyes from 112 controls were included. IIH patients had thicker INL and ORL compared with controls (both p<0.001) while IIH eyes with ME had thicker INL and ORL thicknesses compared with eyes without ME (both p<0.05). In IIH patients, the retinal sublayer thicknesses correlated with their ICP levels, and GCIPL thickness correlated with visual acuity (VA). Furthermore, ME was associated with higher ICP, worse papilledema and lower VA (all p<0.001). CONCLUSION: ME affects retinal thickness in IIH patients and is associated with more severe clinical features in IIH. OCT may provide biomarkers informative of clinical changes in IIH. Further longitudinal studies are needed to explore the evolution of ME and its relationship to VA and retinal structure.

Comparison of ganglion cell layer thickness and pattern electroretinography among glaucoma suspects and healthy controls.

PURPOSE: To evaluate the difference in ganglion cell layer (GCL) thickness on optical coherence tomography (OCT) and waveform on pattern electroretinography (PERG) among glaucoma suspects and healthy controls. METHODS: An analytical, cross-sectional study was done on 100 eyes of 50 subjects, equally divided in the glaucoma suspect and control group. Subjects with an asymmetrically increased vertical cup-to-disc ratio and without any perimetric change were taken as suspects, and subjects with normal findings were taken as controls. GCL thickness was evaluated on spectral domain OCT at 3 mm, 3.45 mm, and 6 mm centering the foveola, and P50, N95 wave forms were recorded according to the standard PERG protocol. RESULTS: In this study, we observed that the average GCL thickness is significantly less in glaucoma suspects at 3.45 mm (p = 0.045) and at 6 mm (p < 0.001) circle zone. On PERG, P50 amplitude was significantly low in glaucoma suspects in comparison to controls (p = 0.007). There was significantly increased implicit time for both P50 and N95 in glaucoma suspects (p < 0.001). For N95 amplitude, a non-significant (p = 0.127) difference was observed among the two groups. At 3.45 mm, average GCL thickness showed a weak negative correlation with N95 implicit time (r = - 0.286, p = 0.044), a weak positive correlation with P50 amplitude (r = 0.349, p = 0.013), and at 6 mm, a weak positive correlation with P50 amplitude (r = 0.311, p = 0.028) in glaucoma suspects. CONCLUSIONS: Analysing GCL thickness can help in the structural assessment of preperimetric glaucoma. PERG can be used as a valuable tool for the detection of ganglion cell dysfunction, even before cell loss.

Delayed Surgical Reversal of Optic Nerve Compression Leads to Exponential Degeneration of Optic Nerve Fibers and Selective Sparing of the Small Fibers.

Purpose: To evaluate the effectiveness of surgical reversal of experimental optic nerve compression in treating persistent compressive optic neuropathy and to explore the relationship between surgical outcomes and the timing of the procedure. Methods: Surgical reversal procedures (decompression surgery) were conducted at five time intervals: 1, 3, and 7 days and 2 and 3 weeks following optic nerve compression in a rabbit model. The groups were labeled as DC-1d, DC-3d, DC-7d, DC-2w, and DC-3w, respectively. The study investigated changes in ganglion cell complex (GCC) thickness using spectral-domain optical coherence tomography and the percentage of surviving retinal ganglion cells (RGCs) through immunofluorescence staining and optic nerve axons stained with p-phenylenediamine at 4 weeks after decompression. Additionally, the area distribution of surviving axons was analyzed. Results: The decline in GCC thickness was halted following decompression. The remaining thickness of the GCC in group DC-1d was found to be statistically significantly higher at 2, 3, and 4 weeks postonset compared to the no-decompression group. Similarly, GCC thickness in group DC-3d was significantly higher at 3 and 4 weeks postonset. The percentage of surviving RGCs and axons at 4 weeks postonset exhibited an exponential correlation with the onset time of decompression, with R2 values of 0.72 and 0.78, respectively. The surviving axon area declined following delayed decompression. Conclusions: Persistent substantial compression on the optic nerve leads to exponential degeneration of the optic nerve, initially affecting larger optic nerve fibers. Early intervention aimed at relieving the compression on the optic nerve may offer potential benefits in mitigating the degenerative effects and conserving visual function.

Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy.

OBJECTIVES: Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification. METHODS: All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features. RESULTS: Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001). CONCLUSION: We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods.

Optical coherence tomography angiography analysis of the fellow eye in unilateral pseudoexfoliation syndrome.

PURPOSE: To compare the macular and optic disc vascular parameters in the unaffected fellow eyes of subjects with unilateral pseudoexfoliation syndrome (PXS) and controls using optical coherence tomography angiography (OCTA). METHODS: The medical records of 61 eyes of 61 patients were analyzed in a retrospective study. Of these, 30 eyes were unaffected fellow eyes and 31 eyes were control eyes. The vessel density (VD), perfusion density (PD) and foveal avascular zone (FAZ)-related parameters of the superficial capillary plexus (SCP) in the circumpapillary and macular area and the VD and PD of the deep capillary plexus (DCP) in the macular area were measured using OCTA after dilatation and were compared between two groups after adjustment for age, sex and axial length. RESULTS: There were no statistically significant differences in sex ratio or mean age, central corneal thickness measurements, refractive errors, intraocular pressures and axial length between both groups (all P > 0.05). In the circumpapillary area, inferior VD and PD in the inner zone, as well as average, temporal, inferior, and nasal VD and PD in the outer zone were significantly reduced in the unaffected fellow eyes with unilateral PXS, while the circumpapillary retinal nerve fiber layer (RNFL) thicknesses were similar between groups. In the macular SCP, VDs were significantly lower in all sectors in the inner area and in the outer zones (p < 0.05 for all), PDs were significantly lower in all sectors (p < 0.05 for all) except the nasal sector of the outer zone (p = 0.003 for average, p = 0.029 for superior sector, p = 0.004 for temporal sector, p < 0.001 for inferior sector), and the FAZ circularity (p = 0.037) were significantly lower in the unaffected fellow eyes with unilateral PXS, whereas macular ganglion cell inner plexiform layer (GCIPL) thickness was similar between the two groups. CONCLUSIONS: Although circumpapillary RNFL and GCIPL thicknesses were similar between the two groups, VDs and PDs in the circumpapillary and macular SCP and FAZ circularity were significantly lower in the fellow eye of subjects with unilateral PXS.

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.

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.

Evaluation of insomnia effect on ganglion cell complex, middle retina, and choroid.

PURPOSE: Insomnia is a common psychiatric disorder that has oxidative and degenerative effects on the brain. It is thought that the brain's processes affect the retina through their synaptic connections. However, the effects of sleep disorders on the retina and choroid are not fully understood. We aimed to investigate the impact of insomnia on retinal nerve fiber layer (RNFL), central foveal thickness, retinal layers, and choroidal thickness. METHODS: The right eye of 16 healthy controls and 15 patients with insomnia complaints for 3 months, no history of psychiatric drug use, and an Insomnia Severity Index (ISI) score of 15 or higher were included in the study. The retinal layers and RNFL analyses were performed using optical coherence tomography (OCT), and choroidal layers were analyzed using enhanced depth imaging OCT. RESULTS: Nasal and temporal ganglion cell complex thicknesses were significantly lower in patients with insomnia compared to the controls (97 µm vs. 111 µm P = 0.004; 94 µm vs. 105 µm P = 0.012, respectively). A significant negative correlation was detected between the ISI score and global RNFL thickness (rho, P = 0.03) Additionally, pachychoroid-like vascular structures were observed in choroidal images. CONCLUSION: These changes in the retina and the choroid layers due to insomnia may be precursors to retinal degenerative conditions, such as age-related macular degeneration that may occur in the future. Multicenter studies including more patients are needed to demonstrate the importance of quality sleep for eye health.