Retinal Ganglion Cell-inner Plexiform Layer Research Articles

Peripapillary Versus Macular Thinning to Detect Progression According to Initial Visual Field Loss Location in Normal-Tension Glaucoma

PurposeTo investigate the predictive capabilities of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thinning to detect visual field (VF) progression in normal-tension glaucoma patients with an initial parafoveal scotoma (IPFS) or nasal step (INS). DesignRetrospective cohort study. Methods185 early-stage glaucoma eyes, followed for 10 years, were retrospectively stratified into IPFS and INS groups. Progressive pRNFL and mGCIPL thinning were assessed using spectral-domain optical coherence tomography and VF progression using both event- or trend-based analysis. Kaplan-Meier survival analysis compared VF survival in each VF phenotype with or without progressive pRNFL and mGCIPL thinning. Cox proportional regression analysis identified VF progression factors. ResultsVF progression was detected in 42 IPFS (n=86) and 47 INS (n=99) eyes. Among VF progressors, pRNFL thinning was significantly faster in INS group compared to IPFS group (P < 0.01), while mGCIPL thinning was similar (P = 0.16). At five years, eyes with progressive mGCIPL thinning showed significantly lower VF survival in both VF phenotypes (all P < 0.05). Progressive pRNFL thinning showed significantly lower VF survival only in INS eyes (P = 0.015). Cox multivariate regression revealed that mGCIPL thinning predicted subsequent VF progression in IPFS eyes, while mGCIPL and pRNFL thinning had significant associations with VF progression in INS eyes. ConclusionsmGCIPL outperforms pRNFL at early follow-up in detecting VF progression in IPFS eyes but not INS eyes. Appropriate selection of structural parameters (mGCIPL vs pRNFL) maximizes early VF progression detection according to initial VF defect location.

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

To 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. In 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. A 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). Adjusted 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.

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.

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.

Optical Coherence Tomography Parameters and Optimal Cut-off Values for Predicting Visual Prognosis in Ethambutol-Induced Optic Neuropathy.

The objective of this study was to evaluate the prognostic value of optical coherence tomography (OCT) parameters in patients with ethambutol-induced optic neuropathy (EON) and establish their optimal cut-off values for predicting visual acuity outcomes. A retrospective cross-sectional study was conducted on 64 eyes of 32 patients with EON who underwent OCT. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were measured using Cirrus high-definition OCT (HD-OCT) within 3 months after EON diagnosis. Visual acuity of patients was recorded and analyzed at the first visit, the 1-year visit, and the latest visit. Prognostic capacities of OCT parameters for visual prognosis were evaluated and their optimal cut-off values for predicting final visual acuity were established. Increased pRNFL thickness was significantly associated with better visual acuity at 1 year postdiagnosis and the latest visit. A significant association was established between increased pRNFL thickness and a higher rate of recovery to visual acuity >20/25 at 1 year postdiagnosis. Receiver-operating characteristic curves identified ideal cut-off values for OCT parameters as follows: pRNFL thickness of 83 μm (sensitivity 100%, specificity 48.3%) and mGCIPL thickness of 74 μm (sensitivity 100%, specificity 83.3%) for visual acuity >20/25 at 1 year, mGCIPL thickness of 61 μm (sensitivity 85.7%, specificity 71.4%) for visual acuity >20/40 at 1 year, with corresponding AUCs exceeding 0.7. Both pRNFL and mGCIPL thickness possess potential values for predicting visual outcomes in patients with EON. Future research should continue to explore the utility of OCT parameters in EON prognosis.

SARS-CoV-2 neurovascular invasion supported by Mendelian randomization

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to affect vessels and nerves and can be easily visualized in the retina. However, the effect of SARS-CoV-2 on retinal morphology remains controversial. In the present research, we applied Mendelian randomization (MR) analysis to estimate the association between SARS-CoV-2 and changes in the thickness of the inner retina.MethodsTwo-sample MR analysis was conducted using summary-level data from 3 open genome-wide association study databases concerning COVID-19 infection (2,942,817 participants) and COVID-19 hospitalization (2,401,372 participants); moreover, the dataset of inner retina thickness, including the macular retinal nerve fiber layer (mRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL), included 31,434 optical coherence tomography (OCT) images derived from healthy UK Biobank participants. All the participants were of European ancestry. The inverse variance weighted (IVW) meta-analysis was used as our primary method. Various complementary MR approaches were established to provide robust causal estimates under different assumptions.ResultsAccording to our MR analysis, genetically predicted COVID-19 infection was associated with an increased risk of mRNFL and mGCIPL thickness (OR = 1.74, 95% CI 1.20–2.52, P = 3.58 × 10–3; OR = 2.43, 95% CI 1.49–3.96, P = 3.6 × 10–4). The other MR methods produced consistent results. However, genetically predicted COVID-19 hospitalization did not affect the thickness of the inner retina (OR = 1.11, 95% CI 0.90–1.37, P = 0.32; OR = 1.28, 95% CI 0.88–1.85, P = 0.19).ConclusionThis work provides the first genetically predictive causal evidence between COVID-19 infection and inner retinal thickness in a European population. These findings will contribute to further understanding of the pathogenesis of COVID-19 and stimulate improvements in treatment modalities.

Optical coherence tomography angiography analysis in patients with intracranial hypertension.

Evidence on peripapillary microvasculature in intracranial hypertension (IH) after the regression of papilledema is still scarce. The aim of this preliminary study was to determine the association between structural changes in the optic nerve and the retina and peripapillary microvasculature in patients with IIH. We conducted a retrospective study. The study included 39 eyes of 21 patients with IIH. Treatment for IIH and history of obesity were registered from each patient. Moreover, OCT analysis including retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness, and OCTA analysis including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus were performed. Correlation analysis revealed a high correlation between GCIPL thickness and peripapillary PD and FI (p < 0,05, r > 0,7), whereas the degree of correlation between RNFL thickness and peripapillary microvascular parameters was low (p < 0,05, r < 0,7). Patients with regressed papilledema had significantly lower GCIPL thickness and peripapillary PD than control subjects (p < 0,05). Peripapillary microvascular measurements are highly correlated with GCIPL thickness in patients with IIH. Moreover, GCIPL thickness and peripapillary PD are significantly inferior in patients with regressed papilledema compared to control group. Thus, we suggested that peripapillary microvascular parameters may be an early indicator of optic nerve atrophy in patients with IIH.

Retinal neurodegeneration in diabetic retinopathy with systemic hypertension.

To identify the impact of hypertension (HTN) on inner retinal layer thickness in patients with diabetic retinopathy (DR). In this retrospective cross-sectional study, participants were divided into three groups: type 2 diabetes patients without DR (DM group), patients with DR (DR group), and patients with both DR and HTN (DR+HTN group). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, measured using optical coherence tomography, were compared among the groups. A total of 470 eyes were enrolled: 224 eyes in the DM group, 131 eyes in the DR group, and 115 eyes in the DR+HTN group. The mean RNFL thicknesses were 95.0 ± 7.7, 92.5 ± 10.1, and 89.2 ± 11.2μm, and the mean GC-IPL thicknesses were 84.0 ± 5.7, 82.0 ± 7.6, and 79.2 ± 8.1μm in each group, respectively (all P < 0.001). In the DR+HTN group, the DR stage showed a significant association with pRNFL (B = - 5.38, P = 0.014) and GC-IPL (B = - 5.18, P = 0.001) thicknesses in multivariate analyses. Subgroup analyses revealed that pRNFL (P = 0.007) and GC-IPL (P = 0.005) thicknesses decreased significantly as DR progressed only in the DR+HTN group. Patients with both DR and HTN exhibited much thinner pRNFL and GC-IPL, compared with patients with DR only. These results may have been related to the amplified diabetic retinal neurodegeneration and synergistic impact of ischemia in DR patients with concurrent HTN. Additionally, the progression of DR resulted in more severe inner retinal damage when combined with HTN.

Comparison of Patterns of Structural Progression in Primary Open Angle Glaucoma and Pseudoexfoliation Glaucoma.

Primary open angle glaucoma and pseudoexfoliation glaucoma showed different progression patterns of the retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning in OCT-guided progression analysis. To compare the patterns of progression of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning by guided progression analysis (GPA) of optical coherence tomography (OCT) in primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). The progression of RNFL and GCIPL thinning was assessed by the GPA of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). By overlaying the acquired images of the RNFL and GCIPL thickness-change maps, the topographic patterns of progressive RNFL and GCIPL thinning were evaluated. The rates of progression of RNFL and GCIPL thinning were analyzed and compared between patients with POAG and those with PXG. Of the 248 eyes of 248 patients with POAG (175 eyes of 175 patients) or PXG (73 eyes of 73 patients) enrolled, 156 POAG eyes and 48 PXG eyes were included. Progressive RNFL thinning was significantly more common in PXG than in POAG ( P =0.005). According to the RNFL progression-frequency maps, progression appeared mainly in the superotemporal and inferotemporal areas in POAG, whereas it had invaded more into the temporal area in PXG. According to the GCIPL maps, progression was most common in the inferotemporal area in both POAG and PXG. The average progression rate of GCIPL thinning was faster in PXG than in POAG ( P =0.013), and when analyzed in 2 halves (superior/inferior), the progression rate of the inferior half was faster in PXG than in POAG ( P =0.011). OCT GPA showed progression patterns of RNFL and GCIPL thinning in POAG and PXG. Understanding the specific patterns of progressive RNFL and GCIPL thinning according to glaucoma type may prove helpful to glaucoma-patient treatment and monitoring.

Evaluation of ganglion cell-inner plexiform layer thickness in the diagnosis of pre-perimetric glaucoma and comparison to retinal nerve fiber layers.

Evaluation of ganglion cell-inner plexiform layer thickness in the diagnosis of pre-perimetric glaucoma (PPG) and comparison to retinal nerve fiber layers. This study was a prospective hospital-based study. A total of 30 PPG and control patients were studied for retinal nerve fiber layer thickness (RNFL) and ganglion cell-inner plexiform layer complex (GC-IPL) by spectral-domain optical coherence tomography. PPG was defined as eyes with a normal visual field and one or more localized RNFL defects that were associated with a typical glaucomatous disc appearance. Diagnostic abilities of GC-IPL, optic nerve head (ONH), and RNFL parameters were computed using area under receiver-operating curve (AUROC), sensitivity, and specificity. GC-IPL parameters showed significant changes in PPG cases as compared to normal subjects in each region ( P value < 0.001). RNFL parameters also differed significantly from normal subjects in all quadrants ( P value 0.003 to < 0.001). Within GC-IPL parameters, the superotemporal region had the maximum area under the curve (AUC), followed by inferior, superior, and inferotemporal regions. Within RNFL parameters, the inferior quadrant had the maximum AUC, followed by superior and nasal quadrants. the GC-IPL parameters in PPG showed that the AUC of the GC-IPL parameters was much higher than those of the ONH and RNFL values. Although both the parameters RNFL and GC-IPL showed significant changes in PPG patients compared to healthy subjects, a higher AUC of GC-IPL points toward the higher sensitivity of GC-IPL than RNFL for detecting glaucoma in early stages.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (μm) were measured on the OCT tool. Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.

Retinal nerve fiber layer and ganglion cell complex thickness in diabetic smokers without diabetic retinopathy

Purpose To compare the thickness of the retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL) in smoker and nonsmoker diabetics without diabetic retinopathy. Materials and Methods Patients with diabetes were divided into two groups according to their smoking status: Group 1 consisted of 38 smoker diabetics who had chronically smoked more than 20 cigarettes per day for more than five years; Group 2 consisted of 38 nonsmoker diabetics. After a detailed ophthalmologic examination, the mean and regional (superior, supratemporal, inferior, inferotemporal, temporal, nasal, superonasal, and inferonasal) RNFL and GC-IPL thicknesses were measured with spectral-domain optic coherence tomography (SD-OCT) and compared between groups. Results The mean age was 54.7 ± 10.5 and 51.2 ± 9.7 years in the smoker and nonsmoker groups, respectively (p = 0.14). Gender, duration of diabetes, and the mean axial length were similar between groups (p:0.43, p:0.54, p: 0.52, respectively). Mean RNFL thickness was 89.1 ± 8.0 µm in the smoker group and 93.4 ± 7.0 µm in the nonsmoker group, and it was significantly thinner in the smoker group (p = 0.01). The temporal RNFL thickness in the smoker group was thinner than in the nonsmoker group (p = 0.02). There was no difference in superior, inferior, and nasal RNFL thicknesses between the groups (p = 0.31, p = 0.12, p = 0.39, respectively). The mean macular GC-IPL thickness of the smoker and nonsmoker groups was 78.53 ± 15.74 µm and 83.08 ± 5.85 µm, respectively (p = 0.09). Superior, superonasal, inferonasal, inferior, inferotemporal, and superotemporal quadrant GC-IPL thicknesses were similar between the groups (p = 0.07, p = 0.60, p = 0.55, p = 0.77, p = 0.71, p = 0.08, respectively). The groups showed no difference in minimum GC-IPL thickness (p = 0.43). There was a significant negative correlation between smoking exposure and mean, inferior quadrant RNFL thicknesses in the smoker group (p = 0.04, r= −0.32, and p = 0.01, r= −0.39, respectively). Conclusion Mean RNFL thickness was significantly thinner in smoker diabetics. Although not statistically significant, especially mean, superior, and superotemporal GC-IPL was thinner in smoker diabetics. The results suggest a potential association between the coexistence of diabetes and smoking with alterations in RNFL and GC-IPL thickness.

Cardiovascular disease and thinning of retinal nerve fiber layer in a multi-ethnic Asian population: the Singapore epidemiology of eye diseases study.

Our study aimed to examine the relationship between cardiovascular diseases (CVD) with peripapillary retinal fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles in a large multi-ethnic Asian population study. 6,024 Asian subjects were analyzed in this study. All participants underwent standardized examinations, including spectral domain OCT imaging (Cirrus HD-OCT; Carl Zeiss Meditec). In total, 9,188 eyes were included for peripapillary RNFL analysis (2,417 Malays; 3,240 Indians; 3,531 Chinese), and 9,270 eyes (2,449 Malays, 3,271 Indians, 3,550 Chinese) for GCIPL analysis. History of CVD was defined as a self-reported clinical history of stroke, myocardial infarction, or angina. Multivariable linear regression models with generalized estimating equations were performed, adjusting for age, gender, ethnicity, diabetes, hypertension, hyperlipidaemia, chronic kidney disease, body mass index, current smoking status, and intraocular pressure. We observed a significant association between CVD history and thinner average RNFL (β = -1.63; 95% CI, -2.70 to -0.56; p = 0.003). This association was consistent for superior (β = -1.79, 95% CI, -3.48 to -0.10; p = 0.038) and inferior RNFL quadrant (β = -2.14, 95% CI, -3.96 to -0.32; p = 0.021). Of the CVD types, myocardial infarction particularly showed significant association with average (β = -1.75, 95% CI, -3.08 to -0.42; p = 0.010), superior (β = -2.22, 95% CI, -4.36 to -0.09; p = 0.041) and inferior (β = -2.42, 95% CI, -4.64 to -0.20; p = 0.033) RNFL thinning. Among ethnic groups, the association between CVD and average RNFL was particularly prominent in Indian eyes (β = -1.92, 95% CI, -3.52 to -0.33; p = 0.018). CVD was not significantly associated with average GCIPL thickness, albeit a consistent negative direction of association was observed (β = -0.22, 95% CI, -1.15 to 0.71; p = 0.641). In this large multi-ethnic Asian population study, we observed significant association between CVD history and RNFL thinning. This finding further validates the impact of impaired systemic circulation on RNFL thickness.

Vertical asymmetry analysis of the macular microvasculature in epiretinal membrane patients with open-angle glaucoma

To identify the usefulness of vertical asymmetry analysis of the retinal microvasculature in epiretinal membrane (ERM) patients accompanied by open-angle glaucoma (OAG). Subjects were divided into three groups: normal controls (group 1), patients with ERM (group 2), and patients with both ERM and OAG (group 3). Retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, vessel density (VD), and the absolute vertical difference of pRNFL (vdRNFL), GC-IPL (vdGC-IPL), and VD (vdVD) were compared among groups. Logistic regression analysis was performed to determine the factors associated with OAG. Diagnostic accuracy based on the area under the curve (AUC) was conducted. The VD of the full area was 20.9 ± 1.2, 20.0 ± 1.9, and 18.8 ± 2.2 mm−1 (P < 0.001) for groups 1, 2, and 3, respectively. The vdVD differed significantly between group 2 and group 3 (P < 0.001), whereas vdRNFL (P = 0.531) and vdGC-IPL (P = 0.818) did not show a significant difference. Multivariate logistic analyses showed that average pRNFL thickness (OR 0.924, P = 0.001) and vdVD (OR 5.673, P < 0.001) were significant factors associated with OAG in ERM patients. The AUC of the vdVD was 0.81 (95% CI 0.72–0.89), and the combination of average pRNFL thickness and vdVD had the highest AUC (0.87; 95% CI 0.78–0.95; P < 0.001). ERM patients with OAG had a significantly thinner pRNFL thickness, lower macular VD, and higher vdVD than those without OAG. Average pRNFL thickness and vdVD were significant factors associated with OAG in patients with ERM. Additionally, the combination of average pRNFL thickness and vdVD showed good diagnostic performance for OAG in patients with ERM.

The relationship between retinal neurodegenerative changes and overactive bladder syndrome in multiple sclerosis

IntroductionThis study aimed to compare the neuroaxonal damage of the optic nerve and retina in multiple sclerosis (MS) patients with and without overactive bladder (OAB). Patients and MethodsWe included patients with MS, divided into two groups, based on the severity of OAB symptoms, as evaluated by the OAB-V8 questionnaire. The groups were compared in terms of each dial of the Expanded Disability Status Scale (EDSS), best-corrected visual acuity, intraocular pressure, peripapillary retinal nerve fiber layer (pRNFL) thickness, macular thickness, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness. ResultsThe study involved a total of 120 eyes, 78 eyes from 43 female patients, and 42 from 22 male patients. There were 86 eyes (Group 1) with OAB-V8 score under 8 and there were 34 eyes (Group 2) with OAB-V8 score of 8 or over. EDSS median value was 1 (0–2) for Group 1 and 2 (0.8–3.3) for Group 2 (p = 0.004). A comparison of pRNFL thicknesses showed statistically significant lower average, superior, and inferior median values in Group 2. A comparison of mGCIPL thicknesses showed statistically significant lower values in Group 2 for superior, superonasal, inferotemporal, and superotemporal quadrants ConclusionThis study revealed, for MS patients without optic neuritis attacks, there was a higher incidence of OAB when the EDSS score was higher. There was a statistically significant relationship between the existence of OAB and thinning in both mGCIPL and pRNFL. The most relevant factor for OAB was found to be pRFNL inferior quadrant thinning.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial.

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells, affecting vision. The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation. However, although the macular thickness can be normalized with each of these two therapies used alone, the vision does not improve in many patients. This might result from the incomplete recovery of retinal ganglion cell injury. Therefore, a prospective, non-randomized, controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery. In this trial, 150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods, followed by treatment with anti-vascular endothelial growth factor drugs, laser photocoagulation therapy, and their combination. All patients will be followed up for 12 months. The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment. The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1, 3, 6, and 9 months after treatment, retinal nerve fiber layer thickness, best-corrected visual acuity, macular area thickness, and choroidal thickness before and 1, 3, 6, 9, and 12 months after treatment. Safety measure is the incidence of adverse events at 1, 3, 6, 9, and 12 months after treatment. The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period. The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity. The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No. (2023)(26) on April 25, 2023, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2300072478, June 14, 2023, protocol version: 2.0).

The influence of smoking on retinal ganglion cell-inner plexiform layer complex in male diabetes

Purpose This study aims to evaluate the influence of smoking on ganglion cell-inner plexiform layer complex (GC-IPL) thickness and central macular thickness (CMT) measured by spectral domain optical coherence tomography (OCT) in male diabetes. Methods 90 smoking and 90 never-smoking male subjects were included in this study. They were divided into six groups based on the diagnostic criteria for diabetes and the Early Treatment Diabetic Retinopathy Study (ETDRS) classification: smoking healthy subjects (SH, n = 20), non-smoking healthy subjects (NSH, n = 20), smoking diabetic patients without diabetic retinopathy (SNDR, n = 40), non-smoking diabetic patients without diabetic retinopathy (NSNDR, n = 40), smoking diabetic patients with diabetic retinopathy (SDR, n = 30), and non-smoking diabetic patients with diabetic retinopathy (NSDR, n = 30). After a full ophthalmologic examination, GC-IPL thickness and central macular thickness (CMT) were measured by OCT. Statistical analysis was performed to compare GC-IPL thickness and CMT between groups. Multiple linear regression equations were constructed to explore the potential risk factors of mean GC-IPL thickness. Results There were no significant differences in GC-IPL thickness and CMT between SH and NSH (all p > 0.05). Mean, superonasal, superior, superotemporal, inferonasal, inferior GC-IPL (p＜0.001, p＜0.001, p＜0.001, p = 0.003, p = 0.001, and p = 0.005, respectively) were thinner in the SNDR than NSNDR except for inferotemporal GC-IPL thickness and CMT (p = 0.066, p = 0.605, respectively). Mean, superonasal, superior, and inferonasal GC-IPL were thinner in the SDR than NSDR (p = 0.019, p = 0.045, p = 0.037, and p = 0.049, respectively). Multiple regression analysis demonstrated that age (β [SE], −0.141 [0.060]; p = 0.020) and smoking (β [SE], −4.470 [1.015]; p＜0.001) were the most important determinants for mean GC-IPL thickness. Conclusion Smoking is associated with reduced retinal GC-IPL thickness in male diabetes. Smoking behavior and age are important determinants of mean GC-IPL thickness.

Short-term changes detected by corneal topography and optical coherence tomography after prophylactic laser iridotomy in primary angle closure suspect.

To evaluate early changes in anterior segment parameters by Scheimpflug-Placido disc topography system and changes in retinal layers by optical coherence tomography in primary angle-closure suspects after laser peripheral iridotomy. One eye of 26 patients with primary angle closure suspect and of 20 healthy subjects were included in this retrospective cross-sectional study. Anterior chamber depth/volume, iridocorneal angle and central corneal thickness were obtained by Scheimpflug-Placido disc topography system. Retinal thickness, retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness were acquired by optical coherence tomography. All the tests were repeated 1week and 1month after laser peripheral iridotomy. The mean ages of the patients and healthy controls were 64.8 ± 10.7years and 64.5 ± 3.9years, respectively (p = 0.990). Anterior chamber depth/volume and iridocorneal angle value were lower in the PACS group (p < 0.001, for all). Anterior chamber volume and iridocorneal angle increased significantly after laser peripheral iridotomy (p = 0.004, for both). While foveal thickness decreased significantly after laser peripheral iridotomy (p = 0.027), retinal nerve fiber layer thickness increased in superior and temporal quadrants (p = 0.038 and p = 0.016, respectively). Our results suggest that LPI in patients with PACS provides improved retinal thickness and RNFL thickness, as well as anterior chamber parameters.

Associations between Chronic Kidney Disease and Thinning of Neuroretinal Layers in Multiethnic Asian and White Populations

To evaluate the relationships between chronic kidney disease (CKD) with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness profiles of eyes in Asian and White populations. Cross-sectional analysis. A total of 5066 Asian participants (1367 Malays, 1772 Indians, and 1927 Chinese) from the Singapore Epidemiology of Eye Diseases Study (SEED) were included, consisting of 9594 eyes for peripapillary RNFL analysis and 8661 eyes for GCIPL analysis. Additionally, 45 064 White participants (87 649 eyes) from the United Kingdom Biobank (UKBB) were included for both macular RNFL analysis and GCIPL analysis. Nonglaucoma participants aged ≥ 40 years with complete data for estimated glomerular filtration rate (eGFR) were included from both SEED and UKBB. In SEED, peripapillary RNFL and GCIPL thickness were measured by Cirrus HD-OCT 4000. In UKBB, macular RNFL and GCIPL were measured by Topcon 3D-OCT 1000 Mark II. Chronic kidney disease was defined as eGFR < 60 ml/min/1.73 m2 in both data sets. To evaluate the associations between kidney function status with RNFL and GCIPL thickness profiles, multivariable linear regression with generalized estimating equation models were performed in SEED and UKBB data sets separately. Average peripapillary and macular RNFL thickness and macular GCIPL thickness. In SEED, after adjusting for age, gender, ethnicity, systolic blood pressure, antihypertensive medication, diabetes, hyperlipidemia, body mass index, smoking status, and intraocular pressure, presence of CKD (β=-1.31; 95% confidence interval [CI],-2.37 to-0.26; P= 0.015) and reduced eGFR (per10ml/min/1.73 m2; β=-0.32; 95% CI,-0.50 to-0.13; P= 0.001) were associated with thinner average peripapillary RNFL. Presence of CKD (β=-1.63; 95% CI,-2.42 to-0.84) and reduced eGFR (per10 ml/min/1.73 m2; β=-0.30; 95% CI,-0.44 to-0.16) were consistently associated with thinner GCIPL in SEED (all P < 0.001). In UKBB, after adjusting for the above-mentioned covariates (except ethnicity), reduced eGFR (per 10 ml/min/1.73 m2; β=-0.06; 95% CI,-0.10 to-0.01; P= 0.008) was associated with thinner macular RNFL and CKD (β=-0.62; 95% CI,-1.16 to-0.08; P= 0.024) was associated with thinner average GCIPL. We consistently observed associations between CKD and thinning of RNFL and GCIPL across Asian and White populations' eyes. These findings further suggest that compromised kidney function is associated with RNFL and GCIPL thinning. The author(s) have no proprietary or commercial interest in any materials discussed in this article.