mGCIPL Thickness Research Articles

The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank

To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR). Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n= 94 206 and n= 27 777, respectively), macular inner retinal OCT measurements (n=36 274 and n= 9991, respectively), and glaucoma status (n= 86 803 and n= 23 556, respectively). We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma. Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status. In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by+0.57 μm (P < 0.001) and+0.42 μm (P= 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of+0.08 mmHg (P= 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome. Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk of diabetic retinopathy and retinal neurodegeneration in individuals with type 2 diabetes: Beichen Eye Study.

Our aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL). This cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automatically via optical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness. Among the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted β = -0.19 [95% CI, -0.25 to -0.13] μm; P < 0.001), cardiovascular events (adjusted β = -0.95 [95% CI, -1.78 to -0.12] μm; P = 0.03), and axial length (adjusted β = -0.82 [95% CI, -1.29 to -0.35] μm; P = 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR. Multiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.

PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Multiple sclerosis optic neuritis and trans-synaptic pathology on cortical thinning in people with multiple sclerosis.

The multi-order visual system represents an excellent testing site regarding the process of trans-synaptic degeneration. The presence and extent of global versus trans-synaptic neurodegeneration in people with multiple sclerosis(pwMS) is not clear. To explore cross-sectional and longitudinal relationships between retinal, thalamic and cortical changes in pwMS with and without MS-related optic neuritis (pwMSON and pwoMSON) using MRI and optical coherence tomography (OCT). 162 pwMS and 47 healthy controls (HCs) underwent OCT and brain MRI at baseline and 5.5-years follow-up. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) thicknesses were determined. Global volume measures of brain parenchymal volume (BPV)/percent brain volume change (PBVC), thalamic volume and T2-lesion volume (LV) were derived using standard analysis protocols. Regional cortical thickness was determined using FreeSurfer. Cross-sectional and longitudinal relationship between the retinal measures, thalamic volume and cortical thickness were assessed using age, BPV/PBVC and T2-LV adjusted correlations and regressions. After age, BPV and T2-LV adjustment, the thalamic volume explained additional variance in the thickness of pericalcarine (R2 increase of 0.066, standardized β = 0.299, p = 0.039) and lateral occipital (R2 increase of 0.024, standardized β = 0.299, p = 0.039) gyrii in pwMSON. In pwoMSON, the thalamic volume was a significant predictor only of control (frontal) regions of pars opercularis. There was no relationship between thalamic atrophy and cortical thinning over the follow-up in both pwMS with and without MSON. While numerically lower in the pwMSON group, the inter-eye difference was not able to predict the presence of MSON. MSON can induce a measurable amount of trans-synaptic pathology on second-order cortical regions.

Association Between Retinal Features From Multimodal Imaging and Schizophrenia

The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts. To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population. This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022. Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers. A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 μm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 μm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 μm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes. In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.

Topographic Differences in Superficial Macular Vessel Density in Eyes with Early Primary Open-Angle Glaucoma and Normal Tension Glaucoma

Introduction: The aim of the study was to compare macular vascular microcirculation in early primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and normal subjects. Methods: 99 patients with early glaucoma (99 eyes: 60 POAG and 39 NTG) and 78 normal subjects were included. All subjects underwent optical coherence tomography angiography scan at 6 × 6 mm macular area. Macular vessel density (VD) and perfusion density (PD) and 9 sectors were compared between the controls, POAG, and NTG groups. Linear regression analysis was used to investigate the relationship between VD and other variables including macular PD, signal strength (SS), and mean macular ganglion cell-inner plexiform layer (mGCIPL) thickness. Results: Significant losses in total area of VD and PD were detected in POAG and NTG groups compared to the controls (all p < 0.01). There were no significant differences in all inner sectors of macular VD and PD between POAG and controls (all p > 0.05). Except for outer-nasal sector, all other outer sectors of macular VD and PD were significantly lower in POAG than in the controls (all p < 0.01). The inferior-inner sector and all outer sectors of VD and PD were significantly lower in NTG than in the controls (all p < 0.01). Macular VD was significantly correlated with macular PD (r = 0.99, p < 0.001), SS (r = 0.60, p < 0.001), and mGCIPL thickness (r = 0.51, p < 0.001). Conclusions: Macular microcirculation declined significantly in early POAG and NTG patients. Macular microcirculation loss in the NTG group was more central and nasal compared with that in the POAG group. A decrease in macular VD was correlated with lower macular PD, lower SS, and thinner mGCIPL thickness.

Evaluation of Macular Ganglion Cell-Inner Plexiform Layer in Children with Deprivational Amblyopia Who Underwent Unilateral Cataract Surgery.

Background and Objectives: The aim of the study is to assess macular ganglion cell and inner plexiform layer (mGCIPL) thickness in deprivational amblyopic eyes (AE), fellow non-amblyopic eyes (FE) and normal eyes (NE) using spectral. domain optical coherence tomography (SD-OCT). Materials and Methods: Twenty two children (64% boys) who underwent surgical removal of unilateral congenital or developmental cataracts and exhibited visual impairment despite postoperative visual rehabilitation were included in the study. Cataract surgery was performed in patients aged 55.82 ± 35.85 months (range 6 to 114 months). The mean age of the study group was 9.73 ± 2.85 years (range 5 to 15 years). The comparison group consisted of 22 healthy age- and gender-matched children. The best corrected visual acuity (BCVA) after surgery was: 0.75 ± 0.27 (range 0.3 to 1.3) in AE, 0.1 ± 0.13 (range 0 to 0.5) in FE and 0.04 ± 0.07 (range 0 to 0.2) in NE. OCT scans were performed in all patients and subsequently corrected for axial length related magnification errors. Results: The average thickness of mGCIPL was 70.6 ± 11.28 μm in AE; 77.50 ± 6.72 μm in FE and 81.73 ± 5.18 μm in NE. We found that mGCIPL was statistically significantly thinner in deprivation AE compared to FE (p = 0.038) and NE (p = 0.0005). The minimum thickness of mGCIPL was respectively: 62.68 ± 13.2 μm, 70.3 ± 7.61 μm, and 74.5 ± 5.47, and also differed between AE and FE (p = 0.023) and AE and NE (p = 0.0004). Also, measurements in the inferior, inferotemporal, and superotemporal sectors showed thinning of mGCIPL in AE compared to NE. Conclusions: This analysis may suggest that deprivational amblyopia caused by unilateral congenital or developmental cataract in children may be associated with mGCIPL thinning.

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank

To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. UK Biobank participants with data on intraocular pressure (IOP) (n=109097), OCT-derived macular inner retinal layer thickness measures (n=46236) and glaucoma status (n=173407). Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P<0.001) and thinner mGCIPL (-0.17 μm; P= 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P= 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P<0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Proprietary or commercial disclosure may be found after the references.

Effects of Cataract on Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness on Swept Source Optical Coherence Tomography.

To evaluate the changes in peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell-inner plexiform layer (mGC-IPL) thickness measured by swept source optical coherence tomography (SS-OCT) following cataract surgery in patients with glaucoma. We included 42 glaucoma eyes and 42 case-matched normal eyes that underwent cataract surgery without complications. One matching set included one glaucoma eye and one case-matched normal eye. The age, sex, and cataract subtype scores were similar for each group. Before and within 3 months of surgery, we measured the pRNFL thickness and mGCIPL thickness by SS-OCT. Following cataract surgery, the image quality (IQ) of SS-OCT improved in both groups. The thickness of the pRNFL and mGC-IPL increased in the mean values and all areas, except for pRNFL from 1 to 4 o'clock in the glaucoma group and at 1 o'clock in the normal group. Posterior subcapsular cataract was related to the change in IQ following surgery. The glaucoma and normal group showed greater pRNFL thickness change due to lesser preoperative pRNFL thickness. Furthermore, the mGC-IPL thickness change was greater in the glaucoma group because of lesser preoperative mGC-IPL thickness. By contrast, the normal group demonstrated greater mGC-IPL thickness change due to higher cortical cataract scores. Cataracts caused the deterioration of the IQ in SS-OCT, thereby resulting in an undermeasurement of the pRNFL and mGC-IPL thickness. Preoperative pRNFL and mGC-IPL were negatively associated with postoperative pRNFL and mGCIPL thickness change in the glaucoma and normal groups. Therefore, ophthalmologists should particularly consider the effect of cataract while diagnosing glaucoma using SS-OCT.

Prognostic Factors for Visual Outcomes in Acute Anterior Optic Neuritis Using Optical Coherence Tomography

Purpose: To identify the clinical characteristics and predictors of visual outcomes in acute anterior optic neuritis patients treated with high-dose steroid pulse therapy using spectral domain optical coherence tomography (SD-OCT).Methods: In this study, the medical records of 34 acute anterior optic neuritis patients treated with intravenous high-dose steroid pulse therapy and followed-up for at least 3 months were retrospectively reviewed. The patients were divided into two groups based on the final best-corrected visual acuity (BCVA); group 1 (n = 23) had a final BCVA ≥20/32, while group 2 (n = 11) had a final BCVA &lt;20/32. Clinical characteristics and optical parameters obtained using SD-OCT were evaluated to identify factors influencing the final visual outcome.Results: There were no statistically significant differences in clinical or demographic data between the two groups. Peripapillary retinal nerve fiber layer (pRNFL) swelling at initial presentation was less common (p = 0.015), and the time to pRNFL thickness stabilization was longer (p = 0.016), in group 1. Multivariate logistic regression demonstrated better final visual acuity for patients in whom pRNFL thickness stabilization took longer, as well as in those with a smaller reduction in macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and those without recurrence (p = 0.002, 0.016, and 0.035, respectively).Conclusions: Intravenous high-dose steroid pulse therapy much improved long-term visual outcomes in acute anterior optic neuritis patients with delayed pRNFL thickness stabilization, a smaller mGCIPL thickness reduction, and no recurrence. This suggests that inner retinal layer thickness and recurrence after stabilization may serve as biomarkers for final visual acuity after intravenous steroid treatment in acute anterior optic neuritis.

Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis.

Macular involvement in optic neuritis (ON) is well-recognised but poorly understood and may be of clinical relevance. This study explores macular structure-function correlates in acute ON. This cross-sectional cohort study recruited ON patients within 14days of symptom onset. Subjectsunderwent pattern electroretinography (PERG), pattern visual evoked potentials (PVEP) and optical coherence tomography (OCT) imaging. PERG P50 and N95 components were correlated with OCT data. Twenty-six individuals with ON were recruited, comprising eleven multiple sclerosis (MS-ON), six myelin oligodendrocyte glycoprotein associated (MOG-ON) and nine with isolated ON. These were compared with 28 healthy controls. PVEPs were undetectable in 11 (42%) of individuals with ON. When detectable, PVEP P100 was delayed (median 136ms range 110-173ms) and amplitude reduced (median 6μV, range 3-14μV) in ON compared with controls (both p < 0.001). PERG P50 component amplitudes, largely reflecting macular function, were reduced in affected eyes (median 2.3μV; range 0.8-5.0μV) compared with controls (3.3μV; range 2.8-5.7μV) and compared with fellow eyes (p < 0.001). The N95:P50 ratio was below the reference range in the affected eyes of five patients. Eight cases (32%) had subnormal P50 amplitudes (< 2.0μV), and these patients had poorer visual acuity (p = 0.020). P50 amplitudes were positively correlated with an increase in inner nuclear layer thickness (rs = 0.36; p = 0.009) and macular ganglion cell and inner plexiform layer (mGCIPL) thickness (rs = 0.44, p = 0.022). PERG P50 component reduction reveals dysfunction of inner macular layers in acute ON and correlates with structural alterations on OCT. These early macular pathologic processes are likely to contribute to the visual loss.

Ganglion cell inner plexiform layer thickness measured by optical coherence tomography to predict visual outcome in chiasmal compression

We evaluated the prognostic value of the preoperative macular ganglion cell inner plexiform layer (mGCIPL) thickness along with peripapillary retinal nerve fiber layer (pRNFL) thickness measured by optical coherence tomography (OCT) and estimated an optimal cut-off value to predict postoperative visual field (VF) recovery in adult patients with chiasmal compression after decompression surgery. Two hundred forty eyes of 240 patients aged 20 years or older for which preoperative high-definition Cirrus OCT parameters and pre- and postoperative visual function data were available. The prognostic power of pRNFL and mGCIPL thicknesses for complete postoperative VF recovery or significant VF improvement (improvement ≥ 2 dB in the mean deviation) were assessed. The cut-off values for OCT parameters for VF recovery were estimated. The study found that the higher the preoperative pRNFL and mGCIPL thicknesses, the higher the probability of complete postoperative VF recovery (p = 0.0378 and p = 0.0051, respectively) or significant VF improvement (p = 0.0436 and p = 0.0177, respectively). The area under the receiver operating characteristic analysis of preoperative OCT parameters demonstrated that the mGCIPL thickness showed an area under the curve (AUC) of more than 0.7 for complete VF recovery after decompression surgery (AUC = 0.725, 95% CI: 0.655, 0.795), and the optimal mGCIPL thickness cut-off value for complete VF recovery was 77.25 µm (sensitivity 69% and specificity 69%). Preoperative mGCIPL thickness was a powerful predictor of visual functional outcome after decompression surgery for chiasmal compression.

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness Values Using Spectral-Domain and Swept-Source OCT.

PurposeTo compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell–inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC).MethodsCross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves.ResultsBoth SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities.ConclusionsThickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects.Translational RelevanceOCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients.

Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank.

PurposeThe purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.MethodsIn a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.ResultsStatin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = −0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = −0.15 microns, 95% CI = −0.28 to −0.01, P = 0.03) but not with mGCIPL thickness (difference = −0.12 microns, 95% CI = −0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction ≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).ConclusionsWe found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.

Association of Central Retinal Arteriolar and Venular Equivalents with Brain-aging and Macular Ganglion Cell-inner Plexiform Layer Thickness

ABSTRACT Introduction Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration. Methods Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005–2008) age 21–84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010–2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015–2017, were also investigated. Results Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively. Discussion The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

Effect of oral citicoline therapy on retinal nerve fiber layer and ganglion cell-inner plexiform layer in patients with primary open angle glaucoma

To evaluate the short-term effects of oral citicoline therapy on the retinal nerve fiber layer (RNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) in patients with primary open angle glaucoma (POAG). Fifty-four eyes of 54 patients with POAG glaucoma included in the study. In addition to a topical hypotensive, 250-mg oral citicoline was administered to 27 patients, while 27 patients were assigned as the control group. RNFL and mGCIPL values were measured using optical coherence tomography (OCT) at 1d before treatment and 3mo after the initiation of treatment. At the third month visit, citicoline treatment was discontinued and drug-free control (wash-out) measurements were obtained at the fourth month in citicoline group. The average RNFL thickness was significantly higher at month 3 than the baseline (P=0.038) in citicoline group. However, this improvement partially regressed after a 1-month wash-out period. No statistically significant changes in RNFL were observed in the superior, nasal, temporal and inferior quadrants at months 3 and 4 (P>0.05). The change in the average and inferior quadrant RNFL thickness in the citicoline group at 3mo was significantly greater than the control group (P=0.006 and P=0.014, respectively). There were no significant differences between the groups according to the change in mGCIPL thickness and the superior, nasal and temporal quadrant RNFL thickness (P>0.05). With oral citicoline treatment, the loss in the average RNFL is prevented in POAG patients in the short-term. Study data show that citicoline may have a significant impact on slowing glaucoma progression, which could have a potential neuroprotective effect.

Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom

Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling. To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness. This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021. Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index. Multiple sclerosis case status and mGCIPL thickness. A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted β = -3.09 [95% CI, -5.70 to -0.48] μm; P = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (β = -0.93 [95% CI, -1.07 to -0.79] μm; P < .001), but there was no statistically significant association in individuals with MS (β = -2.27 [95% CI, -4.76 to 0.22] μm; P = .07). Smoking was not associated with mGCIPL thickness in MS. However, smoking was associated with greater mGCIPL thickness in control individuals (β = 0.89 [95% CI, 0.74-1.05 μm]; P < .001). These findings suggest that high alcohol intake was associated with retinal features indicative of more severe neurodegeneration, whereas smoking was associated with higher odds of being diagnosed with MS.

Optical Coherence Tomography Angiography Compared With Optical Coherence Tomography for Detection of Early Glaucoma With High Myopia.

Purpose: To investigate the diagnostic abilities of the perfusion density (PD) and structural thickness parameters in the peripapillary and macular regions measured by optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) and to test if their diagnostic abilities of early glaucoma are different between highly myopic (HM) and non-highly myopic (NHM) patients.Methods: A total of 75 glaucoma patients and 65 controls were included in the analyses. The glaucoma detection abilities of macular PD and peripapillary PD, along with macular ganglion cell-inner plexiform layer (mGCIPL) thickness and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared between the HM and NHM group. Diagnostic ability was assessed by area under the receiver operating characteristics (AUC) curves, adjusted by age, axial length, and signal strength.Results: The diagnostic ability of macular PD and mGCIPL thickness had no significant difference in both HM and NHM groups. However, the diagnostic ability of peripapillary PD except in the temporal section was significantly lower in the HM group than in the NHM group (all p < 0.05). The diagnostic ability of the superior, nasal, and average pRNFL thickness was also significantly lower in the HM group than in the NHM group (all p < 0.05).Conclusion: This study demonstrated that although peripapillary PD and macular PD were both significantly reduced in patients with highly myopia, the diagnostic ability of peripapillary PD in HM patients was significantly lower than that in NHM patients, while macular PD was not. Macular OCTA along with OCT imaging should be included in the imaging algorithm in early glaucoma diagnosis in highly myopic patients.

DISCRIMINATION OF EYES WITH PRIMARY OPEN-ANGLE GLAUCOMA FROM NORMAL USING MACULAR GC-IPL THICKNESS

Objective: Primary open-angle glaucoma (POAG), a neuro-ophthalmological disease, is a condition of slowly progressive loss of retinal ganglion cells which are evident as characteristic optic nerve head vicissitudes and visual field defects, only after death of more than 40% of cells. This huge loss when witnessed is started to treat only if the patient approaches an ophthalmologist with a significant complaint, leading to optic nerve head examination, which means being an asymptomatic disease, it is usually left undiagnosed until advanced. An additional system of diagnosis of the disease earlier in the stage can aid reduce the burden of the blindness of POAG. Methods: Among a total of 62 eyes of 31 subjects, 40 eyes of 20 POAG subjects, and 22 eyes of 11 age-matched healthy subjects were recruited. All of them underwent Spectral Domain Optical Coherence Tomography macular and optic disk scans to note macular ganglion cell–inner plexiform layer (mGCIPL) and retinal nerve fiber layer (RNFL) thicknesses. Statistical analysis was did using an unpaired t-test and calculating a two-tailed p value, in which the significance was indicated by p&lt;0.05. Results: Similar to peripapillary RNFL thickness, the mGCIPL parameters, that is, minimum GCIPL thickness and GCIPL thickness in all sectors decreased significantly in POAG eyes to be able to discriminate them from normal. mGCIPL and RNFL thickness decreased as the severity of glaucoma increased. Conclusion: The minimum GCIPL thickness and that in all sectors can discriminate POAG eyes from healthy eyes significantly and has comparable performance to that of peripapillary RNFL thickness.

Combining Structural and Vascular Parameters to Discriminate Among Glaucoma Patients, Glaucoma Suspects, and Healthy Subjects.

PurposeCompare the ability of peripapillary and macular structural parameters, vascular parameters, and their integration to discriminate among glaucoma, suspected glaucoma (GS), and healthy controls (HCs).MethodsIn this study, 196 eyes of 119 patients with glaucoma (n = 81), patients with GS (n = 48), and HCs (n = 67) underwent optical coherence tomography (OCT) and OCT angiography to measure peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) thicknesses, radial peripapillary capillary perfusion density (RPC-PD), and macular GCIPL perfusion density (GCIPL-PD). Parameters were integrated regionally with logistic regression and globally with machine learning algorithms. Diagnostic performances were evaluated with area under the receiver operating characteristic (AUROC) curves.ResultsPatients with glaucoma had mild to moderate damage (median, −3.3 dB; interquartile range, −6.5 to −1.4). In discriminating between patients with glaucoma and the HCs, pRNFL thickness had higher AUROC curve values than RPC-PD for average (0.87 vs. 0.62; P < 0.001), superior (0.86 vs. 0.54; P < 0.001), inferior (0.90 vs. 0.71; P < 0.001), and temporal (0.65 vs. 0.51; P = 0.02) quadrants. mGCIPL thickness had higher AUROC curve values than GCIPL-PD for average (0.84 vs. 0.68; P < 0.001), superotemporal (0.76 vs. 0.65; P = 0.016), superior (0.72 vs. 0.57; P = 0.004), superonasal (0.70 vs. 0.56; P = 0.01), inferotemporal (0.90 vs. 0.72; P < 0.001), inferior (0.87 vs. 0.69; P < 0.001), and inferonasal (0.78 vs. 0.65, P = 0.012) sectors. All structural multisector indices had higher diagnostic ability than vascular ones (P < 0.001). Combined structural–vascular indices did not outperform structural indices. Similar results were found to discriminate glaucoma from GS.ConclusionsCombining structural and vascular parameters in a structural–vascular index does not improve diagnostic ability over structural parameters alone.Translational RelevanceOCT angiography does not add additional benefit to structural OCT in early to moderate glaucoma diagnosis.