Ganglion Cell-inner Plexiform Layer Research Articles

Hybrid deep learning and optimal graph search method for optical coherence tomography layer segmentation in diseases affecting the optic nerve.

Accurate segmentation of retinal layers in optical coherence tomography (OCT) images is critical for assessing diseases that affect the optic nerve, but existing automated algorithms often fail when pathology causes irregular layer topology, such as extreme thinning of the ganglion cell-inner plexiform layer (GCIPL). Deep LOGISMOS, a hybrid approach that combines the strengths of deep learning and 3D graph search to overcome their limitations, was developed to improve the accuracy, robustness and generalizability of retinal layer segmentation. The method was trained on 124 OCT volumes from both eyes of 31 non-arteritic anterior ischemic optic neuropathy (NAION) patients and tested on three cross-sectional datasets with available reference tracings: Test-NAION (40 volumes from both eyes of 20 NAION subjects), Test-G (29 volumes from 29 glaucoma subjects/eyes), and Test-JHU (35 volumes from 21 multiple sclerosis and 14 control subjects/eyes) and one longitudinal dataset without reference tracings: Test-G-L (155 volumes from 15 glaucoma patients/eyes). In the three test datasets with reference tracings (Test-NAION, Test-G, and Test-JHU), Deep LOGISMOS achieved very high Dice similarity coefficients (%) on GCIPL: 89.97±3.59, 90.63±2.56, and 94.06±1.76, respectively. In the same context, Deep LOGISMOS outperformed the Iowa reference algorithms by improving the Dice score by 17.5, 5.4, and 7.5, and also surpassed the deep learning framework nnU-Net with improvements of 4.4, 3.7, and 1.0. For the 15 severe glaucoma eyes with marked GCIPL thinning (Test-G-L), it demonstrated reliable regional GCIPL thickness measurement over five years. The proposed Deep LOGISMOS approach has potential to enhance precise quantification of retinal structures, aiding diagnosis and treatment management of optic nerve diseases.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P<0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P<0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P<0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P<0.001). Stronger associations with glaucoma (P interaction=0.001) were noted in participants with a higher glaucoma polygenic risk score. Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal morphological differences in atypical Parkinsonism: A cross-sectional analysis of the AlzEye cohort

ObjectiveAtypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort. MethodsWe conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models. ResultsAmong a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups. ConclusionOur cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature. SignificanceThese findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.

Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Racial-ethnic disparities in concurrent rates of peripapillary & macular OCT parameters among a large glaucomatous clinical population

ObjectivesTo compare rates of change in peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) parameters among different race-ethnicities from a large electronic health record database of subjects with or suspected of glaucoma.MethodsIn this retrospective cohort study, rates of change were obtained using joint longitudinal linear mixed models for eyes with ≥3 visits and ≥1 year of follow-up, adjusting for age, sex, intraocular pressure, central corneal thickness, and baseline pRNFL and mGCIPL thickness. Best linear unbiased predictor estimates of various parameters were stratified by baseline glaucoma severity and analysed by racial-ethnic group.ResultsA total of 21,472 spectral domain optical coherence tomography (OCT) pRNFL scans and 14,431 mGCIPL scans from 2002 eyes were evaluated. A total of 200 (15.6%) and 601 (46.8%) subjects identified as non-Hispanic Black (NHB) and Hispanic, respectively. NHB eyes exhibited faster rates of change in pRNFL among glaucoma suspect (global pRNFL −0.57 ± 0.55 µm/year vs. −0.37 ± 0.62 µm/year among Hispanics, p < 0.001), mild glaucoma (superior pRNFL quadrant −1.20 ± 1.06 µm/year vs. −0.75 ± 1.51 µm/year among non-Hispanic Whites (NHW), p = 0.043), and moderate glaucoma eyes (superior pRNFL quadrant −1.31 ± 1.49 µm/year vs. −0.52 ± 1.26 µm/year among Hispanics, p = 0.003). NHB eyes exhibited faster rates of mGCIPL loss corresponding to pRNFL rates. Global pRNFL and mGCIPL rates were strongly correlated (R2 = 0.70).ConclusionsAdjusted rates of pRNFL and mGCIPL loss significantly differed between racial-ethnic groups when stratified by glaucoma severity, with faster rates among NHB patients. These differences highlight key racial-ethnic disparities in adjusted rates of glaucoma OCT parameters.

Short-Term Morpho-Functional Changes before and after Strabismus Surgery in Children Using Structural Optical Coherence Tomography: A Pilot Study.

To evaluate the immediate alterations in the thickness of the macular ganglion cell-inner plexiform layer (mGCIPL), peripapillary retinal nerve fiber layer (RNFL), inner retinal layer (IRL), and outer retinal layer (ORL) using spectral domain optical coherence tomography (SD-OCT) subsequent to strabismus surgery in pediatric patients diagnosed with horizontal esotropia. Twenty-eight eyes from twenty-one child patients who had undergone uncomplicated horizontal rectus muscle surgery due to strabismus were included. Measurements of RNFL, mGCL-IPL, IRL, and ORL using structural OCT were conducted both before the surgery and one month after the surgical procedure. Importantly, a control group comprising 14 healthy eyes, matched for age and significant refractive error (<3.00 diopters), was included in the current analysis. Our analysis indicated no significant disparity before and after surgery in terms of best-corrected visual acuity (BCVA), RNFL, IRL, and ORL. Conversely, concerning the macular ganglion cell layer-inner plexiform layer analysis, a substantial increase in mGCL-IPL was observed following the surgical intervention. The mean mGCL-IPL measured 60.8 ± 9.2 μm at baseline and 66.1 ± 13.2 μm one month after the surgery (p = 0.026). Notably, comparison between the strabismus group at baseline and the healthy group revealed a significant reduction in mGCL-IPL in the strabismus group (60.8 ± 9.2) compared to the healthy control group (68.3 ± 7.2; p = 0.014). Following strabismus surgery, our observations pointed towards a thickening of the mGCL-IPL layer, which is likely attributable to transient local inflammation. Additionally, we identified a significant differentiation in the mGCL-IPL complex between the pediatric patient group with strabismus and the control group.

Comparison of macular and optic disc vessel density in thyroid orbitopathy: a comparative octa study.

To determine the microvascular and structural changes in the peripapillary and macular areas observed in patients with active thyroid orbitopathy(TO) before and after steroid treatment and compare with inactive TO and the control group by optical coherence tomography angiography (OCTA). This cross-sectional study included 34 eyes of 17 active TO patients, 108 eyes of 54 inactive TO patients, and 60 eyes of 30 healthy controls. Central macular thickness (CMT), ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, central choroidal thickness (CCT), retinal nerve fiber layer (RNFL) thickness, choroidal thickness in the peripapillary region, superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris vessel densities were determined by OCTA in before and after 12-week steroid treatment of active TO cases, inactive TO and control groups. Between the three groups in macula OCTA, a statistically significant difference was observed in the inferior and nasal quadrants in SCP (all p = 0.01) and only in the temporal quadrant choriocapillaris (p = 0.005). In peripapillary OCTA, a statistically significant difference was found only in the central choriocapillaris (p = 0.03). In the comparison of the active group before and after treatment, there was a statistically significant decrease in CMT and CCT; a statistically significant increase was observed in GCL-IPL (all p < 0.01). There was a statistically significant decrease in SCP and DCP only in the central (all p < 0.01). There was a statistically significant increase was found in the lower quadrant macular SCP vessel density and mean macular DCP in post-treatment measurements (p = 0.01 and p = 0.03, respectively). Peripapillary SCP and DCP vessel density was increased after treatment (p < 0.01). Active TO group had lower vessel density than inactive group and after treatment, vessel density was increased. Non-invasive quantitative analysis of retinal and optic disc perfusion using OCTA could be useful in early treatment before complications occur and monitoring patients with TO.

Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON. Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates. 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes (p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC (p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume (p = 0.006), occipital thickness (p = 0.002), and the medial occipital cortex (p = 0.002), but not the lateral occipital lobe. Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Risk factors of internal carotid artery stenosis in patients with proliferative diabetic retinopathy: an analysis using optical coherence tomography and optical coherence tomography angiography

BackgroundThis research investigates the correlation between the severity of internal carotid artery (ICA) stenosis and retinal parameters in patients with proliferative diabetic retinopathy (PDR), aiming to uncover potential risk factors.MethodsA retrospective analysis of 68 patients (136 eyes) diagnosed with bilateral PDR from January 1, 2017, to December 31, 2021, was conducted. Carotid artery stenosis (CAS) was assessed using neck computed tomography angiography (CTA) and carotid duplex ultrasound (CDUS), with stenosis classified into two groups: normal (group 1) and mild or above (group 2), based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Optical coherence tomography (OCT) and OCT angiography (OCTA) measured several retinal parameters, including sub foveal choroidal thickness (SFCT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, vessel density (VD), and foveal avascular zone (FAZ) area. Statistical analyses determined correlations between ICA degrees and retinal parameters.ResultsThis study showed significant differences between groups in total VD, FAZ area, total RNFL thickness, and temporal RNFL thickness, indicating that patients with more severe ICA stenosis had noticeable retinal changes. Other parameters such as hyperlipidemia, total cholesterol levels, and intraocular pressure (IOP) also differed significantly, while no notable differences were observed in SFCT, central VD, average GCIPL, and superior, nasal, and inferior RNFL thickness.ConclusionThe study findings highlight retinal changes, such as an increased FAZ area, decreased total VD, and a total and thinner temporal RNFL, which suggest the need for carotid artery evaluation in patients. These findings have important clinical implications for the need for carotid work up in patients with PDR.

Degradation of Photopic and Mesopic Contrast Sensitivity Function in High Myopes With Partial Posterior Vitreous Detachment.

The purpose of this study was to evaluate the effects of posterior vitreous detachment (PVD) on visual quality in patients with high myopia, as well as investigate the associated factors of photopic and mesopic contrast sensitivity function (CSF) in high myopia. Visual quality was comprehensively assessed in patients with high myopia. Visual acuity, contrast sensitivity (CS) at four spatial frequencies (3, 6, 12, and 18 cycles per degree [c.p.d.]) under photopic and mesopic conditions, as well as the modulation transfer function cutoff value (MTFcutoff), the objective scatter index (OSI), the Strehl ratio (SR), and internal aberrations, were measured in this cross-sectional study. This study included 94 eyes from 47 subjects with bilateral high myopia, including 23 eyes with complete PVD (cPVD), 21 eyes with partial PVD (pPVD), and 50 eyes without PVD (nPVD). There was no significant difference in visual quality between the cPVD group and the nPVD group. Whereas in eyes with pPVD, there was a degradation of overall photopic CSF (versus nPVD, P = 0.048), photopic CS at 3 c.p.d. (versus cPVD, P = 0.009 and versus nPVD, P = 0.032), photopic CS at 18 c.p.d. (versus nPVD, P = 0.033), overall mesopic CSF (versus nPVD, P = 0.033), and secondary astigmatism (versus cPVD, P = 0.044). Under photopic conditions, the factors affecting CSF were pPVD and SR, whereas the factors affecting mesopic CSF were pPVD, OSI, and ganglion cell-inner plexiform layer thickness. The pPVD impaired visual quality in patients with high myopia compared to nPVD or cPVD, and pPVD could be a factor explaining CSF at both photopic and mesopic illumination. Clinicians need to closely monitor patients with high myopia with pPVD due to the potential decline in visual quality and the development of vitreoretinal disorders.

Optical coherence tomography angiography value for detection of early retinal microvascular changes in systemic hypertension

Purpose The aim of this study was to assess the macula and optic disc vessel density (VD) and perfusion and the anatomical alterations at the fovea and optic nerve in chronic treated hypertension (HTN) patients who exhibited no signs of hypertensive retinopathy using optical coherence tomography angiography (OCTA). Patients and methods This is a prospective case–control study that included 37 participants. They were subdivided into two groups: the hypertensive group that included 22 patients (mean age=51.9±5.9 years), with no clinically evident signs of hypertensive retinopathy, and the control group that included 15 individuals (mean age=48.8±3.7 years) with no known history of HTN or other chronic systemic diseases. OCTA scans covering a 6.0×6.0 mm area for the macula and a 4.5×4.5 mm region for the optic nerve head were performed to evaluate the VD, the foveal avascular zone area, macular thickness, and retinal nerve fiber layer (RNFL) thickness. The correlation of the VD measurements with the RNFL thickness was evaluated. Results The hypertensive patients exhibited a significantly lower overall mean macular VD (45.8±6.0) compared to the control group (48.5±2.9, P=0.017). In addition, they exhibited a significantly lower superficial VD in the superior hemifield (46.4±5.3 and 48.6±2.9, respectively, P=0.030). On the other hand, the deep vascular density in the superior hemifield showed no significant difference between the two groups. In addition, the hypertensive patients were found to have a significantly lower average RNFL thickness (103.2±17.8 μm) compared to the control group (117.1±14.1 μm, P=0.001), with specific statistically significant reductions in the superior (P=0.002) and inferior (P=0.004) sectors. Although the central ganglion cell-inner plexiform layer thickness did not reach statistically significant difference between the two groups (HTN: 50.7±12.0 μm vs. control: 55.7±8.8 μm, P=0.055), the hypertensive group exhibited statistically significant reductions in the ganglion cell-inner plexiform layer thickness in the superior (P&lt;0.001), inferior (P=0.002), nasal (P=0.003), and temporal (P=0.001) sectors compared to the controls. There was no statistically significant difference in the size of the foveal avascular zone between the two groups. Conclusion OCTA revealed subclinical alterations in the retinal microvasculature parameters among the hypertensive patients without clinical signs of hypertensive retinopathy, in comparison to normotensive individuals.

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life. This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models. Individuals with persisting amblyopia (n=2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n=18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (-0.23 units (-0.30;-0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL,-2.85 microns (-3.47;-2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (-0.08 units (-0.15;-0.01)) and thinner mGC-IPL (-1.14 microns (-1.74;-0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (-0.17 units (-0.25;-0.08)) and width (-0.13 units (-0.21;-0.04)) compared to control eyes. Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes. Medical Research Council (MR/T000953/1) and the National Institute for Health and Care Research.

Hemifield-based analysis of pattern electroretinography in normal subjects and patients with preperimetric glaucoma

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (β = − 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (β = − 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma.

Combination of serum markers with optical coherence tomography angiography for evaluating neuromyelitis optica spectrum disorders and multiple sclerosis

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), autoimmune inflammatory diseases of the central nervous system, affect the optic nerve and brain. A lumbar puncture to obtain biomarkers is highly invasive. Serum biomarkers and optical coherence tomography angiography (OCTA) are more accessible and less expensive than magnetic resonance imaging and provide reliable, reproducible measures of neuroaxonal damage. This study investigated the association between serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and OCTA metrics. Serum sNfL and sGFAP levels, OCTA values, and clinical characteristics were compared among 91 patients with NMOSD, 81 patients with MS, and 34 healthy controls (HCs) at baseline and 1-year follow-up. ResultssNfL and sGFAP levels were higher while the sGFAP/sNfL quotients were significantly lower in NMOSD and MS patients than those in HCs. At baseline, the average thicknesses of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGC-IPL) were significantly smaller in NMOSD and MS patients than those in HCs (pRNFL: MS 92.0 [80.2; 101] μm, NMOSD 80.0 [59.0; 95.8] μm, vs HC 99.0 [92.0; 104] μm, p < 0.001; mGC-IPL: MS 74.5 [64.2; 81.0] μm, NMOSD 68.0 [56.0; 81.0] μm, vs HC 83.5 [78.0; 88.0] μm, p < 0.001). The vessel density (VD) and perfusion density (PD) were increased in MS patients without optic neuritis compared to HCs (VD: MS 16.7 [15.6; 17.9] HC 15.3 [13.4; 16.9], p = 0.008; PD: MS 0.41 [0.38; 0.43], HC 0.37 [0.32; 0.41], p = 0.017). In NMOSD patients without optic neuritis, sNfL was significantly associated with PD at baseline (r = 0.329, q = 0.041). The baseline and follow-up values of the sNfL level and average pRNFL and mGC-IPL thicknesses in MS patients showed significant differences. NMOSD patients showed significant differences between baseline and follow-up sNfL and sGFAP levels but not OCTA metrics. ConclusionChanges in retinal microvasculature might occur earlier than those in retinal structure and may therefore serve as a promising diagnostic marker for early NMOSD. The combination of serum markers and OCTA metrics could be used to evaluate and differentiate between MS and NMOSD.

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study.

This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR). Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, β-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure. We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854-1.199; P = 0.895) per natural log-transformed β-carotene to 1.052 (95% CI, 0.911-1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801-1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870-1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits. Our study did not support a causal association among six diet-derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells. This study provides valid evidence regarding the use of diet-derived antioxidants for glaucoma patients.

Visual evoked potentials in multiple sclerosis: P100 latency and visual pathway damage including the lateral geniculate nucleus

ObjectiveTo explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS). Methods31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R2 (mR2). ResultsP100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR2 = 0.26), and less strongly with OR-WML (mR2 = 0.17), NAOR-FA (mR2 = 0.13) and pRNFL (mR2 = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR2 = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR2 = −0.56). ConclusionsP100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay. SignificanceOur findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS.

Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort

BackgroundSeveral studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness.MethodsRNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated.ResultsSeveral genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered.ConclusionsOur study does not support the existence of a genetic link between dementia and retinal thickness.