Sectoral Retinal Nerve Fiber Layer Research Articles

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell Complex Rates of Change in Patients With Moderate to Advanced Glaucoma

PurposeTo compare ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) rates of change (RoC) in eyes with central or moderate to advanced glaucoma. DesignProspective cohort study. Participants918 matched macular and RNFL OCT scan pairs from 109 eyes (109 patients) enrolled in the Advanced Glaucoma Progression Study with ≥2 years of follow-up and ≥4 OCT scans. MethodsWe exported GCC and RNFL thickness measurements in 49 central macular superpixels and 12 RNFL clock-hour sectors, respectively. We applied our latest Bayesian hierarchical longitudinal model to estimate population and subject-specific baseline thickness (intercepts) and rates of change (RoC) in macular superpixels and RNFL sectors. Global RNFL and GCC RoC were analyzed in a single bivariate longitudinal model to properly compare them accounting for the correlation between their RoC. Main Outcome MeasuresProportion of significant negative (deteriorating) and positive (improving) RoC expressed in μm/year. Standardized RoC were calculated by dividing RoC by the corresponding population SD. Analyses were repeated in eyes with visual field mean deviation (MD) ≤–6 and >–6 dB. ResultsAverage (SD) 24-2 visual field MD and follow-up length were –8.6 (6.3) dB and 4.2 (0.5) years, respectively. Global RNFL RoC (–0.70 µm/year) were faster than GCC (–0.44 µm/year) (p<.001); corresponding normalized RoC were not significantly different (p=0.052). In bivariate analysis, patients with a significant negative global RNFL RoC (n=63, 57%) or GCC (n=56, 51%) frequently did so for both outcomes (n=49, 45%). The average proportion of significantly decreasing RNFL sectors within an eye was 30.7% in eyes with MD >–6 dB compared to 20.5% in those with MD ≤–6 dB (p=0.014); the proportions for GCC superpixels were 21.1% vs. 18.7%, respectively (p=0.63). ConclusionsBoth GCC and RNFL measures can detect structural progression in glaucoma patients with central damage or moderate to advanced glaucoma. The clinical utility of RNFL imaging decreases with worsening severity of glaucoma.

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype–Phenotype Characterization Compared to OPA1 Patients

PurposeHeterozygous mutations in AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated to isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DesignCross-sectional study. MethodsThe following neuro-ophthalmological parameters were collected: Log MAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness at optic coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and gender-matched group of OPA1 patients with 1:2 ratio. All eyes were analysed using Clustered Wilcoxon rank sum test using Rosner-Glynn-Lee method. Results44 eyes from 23 ACO2 and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (p=0.029, p=0.023), average (p=0.012, p=0.0007) and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. ConclusionsClinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems associated to an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and resulted virtually indistinguishable from classic OPA1-DOA.

Retinal nerve fiber layer thickness and peripapillary vasculature of post-COVID-19 patients with and without olfactory/gustatory dysfunction symptoms.

We aimed to compare retinal nerve fiber layer (RNFL) thickness and peripapillary vessel density values between COVID-19 patients with or without olfactory/gustatory dysfunction symptoms and healthy controls. We evaluated RNFL and radial peripapillary capillary vessel density (RPC-VD) values of 41 patients who had COVID-19 history and age- and gender-matched control group including 31 healthy individuals with optical coherence tomography angiography. First, post-COVID-19 group's and control group's RNFL and RPC-VD values were compared, then post-COVID-19 patients were divided into subgroups according to the presence (subgroup-A) and absence (subgroup-B) of olfactory/gustatory dysfunction symptoms, and same parameters were analyzed for subgroups. Forty-one eyes of 41 post-COVID-19 patients and 31 eyes of 31 age- and gender-matched healthy controls were included in this cross-sectional study. In RNFL analysis, inferior sector thickness was found significantly lower in post-COVID-19 patients by comparison with control group (P = 0.041). In subgroup analyses, COVID-19 patients who first presented with olfactory/gustatory dysfunction symptoms had higher peripapillary and whole image optic disc capillary density (P = 0.011 and P = 0.002) compared to those who had not had these symptoms. Lower RPC-VD and RNFL thickness were detected in COVID-19 patients compared to healthy controls. Higher Disc-VD values were found in COVID-19 patients with chemosensorial dysfunction (CSD) symptoms compared to those who had not had these symptoms probably due to milder disease course in COVID-19 with CSD. Sectorial RNFL attenuation in COVID-19 might have occurred secondary to peripapillary capillary circulation defect.

Global and sectoral retinal nerve fiber layer thickness in glaucoma suspects and primary open-angle glaucoma patients attending a tertiary care center in South India

ABSTRACT Background: Spectral-domain optical coherence tomography (OCT) can identify the presence of localized glaucomatous structural damage. The peripapillary retinal nerve fiber layer (RNFL) thickness is a popular OCT parameter used for glaucoma diagnosis and monitoring progression. Aim: To measure the peripapillary RNFL thickness, the pattern of RNFL defect, and association of RNFL with the severity of glaucoma using Spectralis Spectral Domain – OCT in patients with primary open-angle glaucoma (POAG) at a glaucoma clinic in a tertiary care teaching hospital in south India. Methods: Cross-sectional study design. Peripapillary RNFL thickness of 109 glaucomatous eyes of 56 patients aged 40–75 years having POAG, ocular hypertension, or suspected to have glaucoma but without visual field (VF) defects were included in the study. The cross-sectional thickness of RNFL using a 3.46 mm circle centered around the disc in 6 segments were measured and defects in the RNFL were identified by comparing measurements from each patient with the normative database. Results: The study included 109 eyes with 51 (46.79%) preperimetric eyes and 58 (53.21%) POAG eyes (with field defects). The average global thickness in the study population was 91.31 ± 12.81 µm for preperimetric eyes and 67.76 ± 17.33 µm for eyes with glaucoma. There was significant thinning in all segments between eyes with POAG and normal eyes with the mean difference highest in the inferotemporal segment (mean difference of 73.05) and the superotemporal segment (mean difference of 55.85). The global RNFL thickness had a coefficient of − 0.015 (standard error [SE] 0.003, 95% confidence interval [CI]: 0.02–0.009, R2 = 0.29) for mild glaucoma, −0.010 (SE 0.004, 95% CI: 0.02–0.003, R2 = 0.12) for moderate and − 0.18 (SE: 0.001, 95% CI: 0.022–0.014, R2 = 0.60) for severe glaucoma compared to preperimetric eyes in a linear regression model that adjusted for age and gender. Global and sector-wise RNFL thickness also had a significant area under Receiver Operator Characteristic (0.84, 95% CI: 0.78. 0.91) that showed the ability to discriminate between preperimetric and glaucomatous eyes. Possible “floor effect” of RNFL thickness was shown by 7 eyes with advanced glaucoma cases. Conclusion: RNFL thinning can be used as a parameter to assess glaucomatous structural loss that can aid in early diagnosis and monitoring of disease progression, to grade the severity of the disease in primary open-angle glaucoma, and when VFs cannot be done.

Analysis of Vessel Density Using OCTA in Nonarteritic Anterior Ischemic Optic Neuropathy

Purpose: To investigate the intraocular vessel density in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA).Methods: Medical records of patients with NAION were retrospectively analyzed. Their age, sex, best corrected visual acuity, color vision results, mean deviation of visual field test were analyzed. Using results of OCT and OCTA that was performed at first visit within 3 weeks of symptom onset, vessel densities in eyes with NAION were evaluated by comparing contralateral unaffected eyes. Furthermore, in only affected eyes, the correlation between visual acuity at the time of diagnosis and anatomical factors such as mean vessel density and retinal nerve fiber layer (RNFL) thickness was investigated.Results: Twenty-five patients (11 males and 14 females) were enrolled in this study and the mean age was 65.92 ± 9.37 years. Whole RNFL thickness in affected eye was significantly lower than that in unaffected eye (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). The average peripapillary vessel density was also significantly lower in affected eyes, 45.63% ± 7.60% compared to that in the contralateral eyes, 51.44% ± 3.40% (&lt;i&gt;p&lt;/i&gt; = 0.004). In analysis of only 25 affected eyes, there was no significant correlation between each sectoral peripapillary RNFL thickness and vessel density. There was also no significant correlation between the visual acuity and the vessel density and retinal nerve fiber layer thickness in the ischemic peripapillary hemisphere. However, there was a significant negative correlation between the visual acuity and the un-ischemic peripapillary hemisphere with a coefficient of -0.608 (&lt;i&gt;p&lt;/i&gt; = 0.001).Conclusions: The higher vessel density of nonaffected sector, the better visual acuity at the time of diagnosis in patients with NAION. Patency of blood supply in the preserved peripapillary intraretinal vessel density sector may affect the visual function.

Optical coherence angiography of optic disc in eyes with primary open‐angle glaucoma and normal tension glaucoma with equal levels of structural damage

AbstractPurpose: To compare visual field (VF), nerve fibre and ganglion cell loss and changes in peripapillary vasculature in age matched patients with normal‐tension (NTG) and high tension glaucoma (HTG) at an equal level of glaucomatous structural damage of the optic nerve head (ONH).Methods: For the present study a retrospective analysis of patients with NTG and HTG was performed. One eye of each patient was randomly assigned for further analysis. To provide a reliable case by case match of HTG and NTG eyes, an equal optic disk size as measured by available spectral‐domain OCT system (RTVue XR OCT Avanti System; Optovue Inc., Fremont, CA) and an equal estimated excavation of the optic disk were chosen. Optic nerve head parameters, retinal nerve fibre layer (RNFL) ganglion cell (GCC) thickness and vessel densities (VD) in the peripapillary area were measured automatically by OCT with a respective software. Forty eyes with NTG, were matched according to the same glaucomatous ONH damage based on cup to disc ratio rim area and disc size with 40 eyes with HTG.Results: Mean age of patients was 68.5 ± 12 (27–84) years. The visual field index, RNFL, GCC thickness and peripapillary VDs in the HTG eyes were similar to those in the NTG eyes (mean VFI 79.6 vs. 78.8 p = 0.84, mean RNFL thickness 71.5 vs. 72.05 μm p = 0.87, mean GCC thickness 76.2 vs. 74.5 μm p = 0.62, mean peripapillary VD 43.6 vs. 43.8% p = 0.87). There was no difference in sectoral RNFL thickness and peripapillary VDs between HTG and NTG. In both groups, univariate regression analysis using the Pearson correlation coefficient showed VFI significantly correlated with RNFL thickness (NTG r = 0.423 p = 0.006 HTG r = 0.514 p = 0.002), and peripapillary VD (NTG r = 0.793 p &lt; 0.001 HTG p = 0.534 p = 0.001) in both groups but with GCC thickness (NTG r = 0.585 p &lt; 0.001) only in eyes with NTG.Conclusions: At an equal level of glaucomatous structural damage of the ONH indicated by cup to disk ratio and RNFL thickness, NTG patients seem to have same losses of peripapillary vasculature. Visual field index correlated with RNFL thickness and peripapillary vessel density in both groups.

Influence of Patient Age and Presence of Optic Disc Drusen on Fluctuations in Retinal Nerve Fiber Layer Thickness.

It is generally believed that optic disc drusen (ODD) change only over long periods of time. Because, in our experience, this does not apply to younger patients, we investigated the natural course of changes of the peripapillary retinal nerve fiber layer (RNFL) in patients with ODD. In this retrospective study, 40 eyes with and 40 eyes without ODD were examined, both cohorts were equally subdivided into younger subjects (20 years or younger) and older subjects (21 years or older). Three optical coherence tomography (OCT) scans of the peripapillary RNFL that had an interval of at least 1 month were required for each patient to be included in this study. The largest difference in total RNFL thickness (delta RNFL-t) and in RNFL thickness of the most differing sector (delta RNFL max) measured by OCT was compared. The differences in total RNFL thickness and in the most differing RNFL sector in the group of patients with ODD younger than 21 years were significantly larger than in each of the other 3 groups ( P = 0.0001). The other 3 groups did not differ significantly. Patients with ODD younger than 21 years have distinct variations in peripapillary RNFL thickness without evidence of increased intracranial pressure. In the absence of further pathological findings or neurological symptoms, an observational approach seems adequate in these patients.

Retinal nerve fiber layer decrease and choroidal layer increase after four weeks of buprenorphine/naloxone maintenance treatment in opioid use disorder

Background and ObjectivesSpectral-domain optical coherence tomography (SD-OCT) findings in substance use disorders have been investigated in recent years. In this study, we compared the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), and the choroid thickness (CT) of OUD and control groups before and after buprenorphine/naloxone maintenance treatment (BN-MT). MethodsThe OUD group consisted of 46 male subjects and the control group consisted of 49 male subjects. Patients with chronic opioid use and opioid positivity in their urine during the initial SD-OCT application were included in the study. At the end of the fourth week of BN-MT, SD-OCT was repeated and BN positivity was detected in the urine of the patients at this time. ResultsThere was a significant difference between OUD and control groups in terms of nasal superior and CT values of both eyes (p<0.05) before BN use. The values of RNFL sectors and CT of both eyes before and after BN-MT differed significantly (p<0.05); CT increased and RNFL sectors decreased. After BN-MT, psychometric scales differed significantly in favor of the patients (p<0.05). The SD-OCT values of the OUD group after BN-MT were compared with the control group: the right IPL (p=0.003), the left IPL (p=0.023), the right N (p=0.001) and the left N (p<0.001) values were significantly lower in the OUD group. ConclusionThis is the first study to show the SD-OCT findings of patients with OUD before and after BN-MT. The findings of this study may indicate possible effects of chronic opioid use in patients and/or possible effects of exogenous opioid or BN present in the body during SD-OCT applications. However, based on our findings, it is not possible to distinguish between the two possible outcomes. The fact that the use of BN acting through opioid receptors has different effects from exogenous opioids may be due to different receptor profiles.

The "Topography" of Glaucomatous Defect Using OCT and Visual Field Examination.

AimTo describe the modifications in the superior and inferior retinal nerve fiber layer (RNFL) thickness regarding the distribution of the VF defects for the horizontal meridians in glaucomatous patients and the differences in the RNFL thickness topography between glaucomatous and healthy subjects.MethodsOne hundred twenty eyes of 91 patients affected by glaucoma and 94 eyes of 51 normal patients were retrospectively reviewed. Computerized 30°VF (Octopus G1 Dynamic strategy) and optical coherence tomography (OCT) ONH and 3D disk analysis were performed in all cases. The RNFL thickness measures analyzed in both groups were superior-nasal (SN), superior-temporal (ST), inferior-nasal (IN), and inferior temporal (IT) sectors. The VFs were classified according to the distribution of the VF defect as for the horizontal meridian in the pattern deviation plot as superior, inferior, predominantly superior, or predominantly inferior.ResultIn the glaucomatous group, 78 eyes (65%) showed a predominantly superior VF defect, while 38 eyes (32%) showed a predominantly inferior VF defect. Fifty-six eyes (46.7%) presented an exclusively superior, and 27/120 eyes (22.5%) presented an exclusively inferior VF defect. In the control group, the thickest RNFL sector was IT. The ST sector showed the thickest RNFL in presence of an exclusive superior VF defect. In case of an exclusive inferior VF defect, the thickest RNFL was the IT sector. VF showing superior defect presented a more altered MD than the VF with an inferior defect.ConclusionGlaucomatous damage affects both the superior and inferior neural rim almost simultaneously. However, the neural rim loss seems to be asymmetric, involving the inferior or superior rim depending on the predominant involvement of the superior or inferior hemifield at the VF test. Particularly, the IT sector appears to be the most compromised in glaucomatous eyes. Therefore, the asymmetry between superior and inferior RNFL could support the diagnosis of glaucoma.How to cite this articlede Paula A, Perdicchi A, Pocobelli A, et al. The “Topography” of Glaucomatous Defect Using OCT and Visual Field Examination. J Curr Glaucoma Pract 2022;16(1):31-35.

Change of peripapillary retinal nerve fiber layer and choroidal thickness during 4-year myopic progress: Boramae Myopia Cohort Study Report 4

AimsTo investigate the longitudinal changes of peripapillary retinal nerve fibre layer (RNFL) and choroidal thickness during myopic axial elongation.MethodsPeripapillary RNFL and choroidal thickness were prospectively evaluated by spectral-domain optical coherence...

Evaluating associations of RNFL thickness and multifocal VEP with cognitive assessment and brain MRI volumes in older adults: Optic nerve decline and cognitive change (ONDCC) initiative.

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.0)) years were recruited in the Optic Nerve Decline and Cognitive Change (ONDCC) study in this observational clinical investigation. OCT was conducted for retinal nerve fibre layer (RNFL) and mfVEP for amplitude and latency measurements. Participants undertook neuropsychological tests for cognitive performance and MRI for volumetric evaluation of various brain regions. Generalised estimating equation models were used for association analysis (p < 0.05). The brain volumetric measures including total grey matter (GM), cortex, thalamus, hippocampal and fourth ventricular volumes were significantly associated with global and sectoral RNFL. RNFL thickness correlated with delayed recalls of California verbal learning test (CVLT) and Rey complex figure test (RCFT). The mfVEP amplitudes associated with cerebral white matter (WM) and cingulate GM volumes in MRI and CVLT, RCFT and trail making test outcomes. A significant association of mfVEP latency with logical memory delayed recall and thalamus volume was also observed. Our results suggested significant association of specific RNFL and mfVEP measures with distinctive brain region volumes and cognitive tests reflecting performance in memory, visuospatial and executive functional domains. These findings indicate that the mfVEP and RNFL measurements may parallel brain structural and neuropsychological measures in the older population.

Correlation of retinal nerve fiber layer thickness with perimetric staging in primary open-angle glaucoma – A cross-sectional study

BACKGROUND:Glaucoma is a progressive optic neuropathy, characterized by structural optic nerve damage with corresponding field defects. Primary open-angle glaucoma (POAG) is the most common. Although perimetry is the gold standard, retinal nerve fiber layer (RNFL) thickness by spectral-domain optical coherence tomography (SD-OCT) has proved reliable in the detection of pre-perimetric glaucoma. There is preferential involvement of various sectors of the peripapillary RNFL in the different stages of POAG.PURPOSE:The purpose of this study is to assess RNFL thickness and determine preferential involvement of different sectors of peripapillary RNFL in the various stages of POAG using SD-OCT.MATERIALS AND METHODS:Forty-nine patients with POAG underwent complete ophthalmic examination including visual field testing and RNFL thickness measurement. Perimetric findings were used to categorize them into mild, moderate, and severe stages of glaucoma. The RNFL thickness values were analyzed and compared with perimetric results.RESULTS:The average RNFL loss in mild, moderate, and severe POAG was 25.44%, 29.67%, and 44.15%, respectively. A statistically significant correlation (P < 0.05) between RNFL loss and severity of glaucoma was found in all except the superior and temporal sectors. A statistically significant (P < 0.05) negative correlation was noted between visual field index and RNFL loss in all sectors except the nasal-superior in moderate POAG and all sectors in severe POAG. Mean deviation and RNFL loss showed a significant positive correlation in temporal-inferior (TI) sector in mild POAG and all sectors in the severe group.CONCLUSION:RNFL thickness decreases with increase in glaucoma severity and is a reliable parameter to differentiate mild from severe POAG. The TI followed by nasal-inferior RNFL sector is the most sensitive to glaucomatous damage in all three stages.

Correlations between cognitive assessment and RNFL changes in OCT in healthy aging subjects

AbstractBackgroundThe retinal nerve fibre layer (RNFL) comprises retinal ganglion cell axons and link the outer neuroretina to the higher visual cortex. The retina is the only part of the central nervous system that can be visualised directly and non‐invasively by optical coherence tomography (OCT). The study aimed to examine whether changes in the visual pathway are correlated with various domains of cognitive function assessment. We evaluated correlation between retinal structural (OCT) and neuropsychological (trail making test, TMT; Boston naming test, BNT) measures in healthy aging subjects.MethodIn the present cross‐sectional clinical study, 74 healthy aging subjects were recruited from the Optic Nerve Decline and Cognitive Changes (ONDCC) study. All participants underwent OCT peripapillary ring scan protocol for RNFL analysis, TMT testing for attention and executive function and BNT neuropsychological examination for the detection of word‐retrieval or naming difficulties. Averaged RNFL thickness measures were used to analyse the relationship with TMT and BNT. Correlations between TMT, BNT and OCT parameters were analysed using partial correlation and controlled for age and gender (P &lt; 0.05).ResultThe mean (SD) age of the current cohort is 67.5 (± 9.0 years). At baseline, significant correlation was observed between TMT‐test A and nasal RNFL thickness (r = ‐0.33, P = 0.009). The BNT also demonstrated mild but significant positive correlations with global (r = 0.32, P = 0.01), nasal (r = 0.27, P = 0.03) and nasal inferior (r = 0.33, P = 0.01) sectoral RNFL thicknesses respectively.ConclusionThe results indicated a significant correlation between RNFL thickness and executive function domain of cognitive assessment. Sectoral RNFL was also significantly correlated with naming ability (BNT) across the cohort of healthy elderly. These findings suggest that the RNFL measures may parallel cognitive decline in the aging population. Further studies are planned in confirmed cognitively impaired subjects.

Structural abnormalities associated with glaucoma using swept-source optical coherence tomography in patients with systemic sclerosis.

Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

Reading cognition from the eyes: association of retinal nerve fibre layer thickness with cognitive performance in a population-based study.

With the eye as a window to the brain, non-invasive fast screening of retinal nerve fibre layer thickness poses the opportunity for early detection of cognitive decline leading to dementia. Our objective is to determine whether performance in various neurocognitive tests has an association with itemized retinal nerve fibre layer thickness. Detailed investigation of associations factored in sex and eye-side. The large population-based LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was conducted at Leipzig University, Germany from 2011 to 2014. Randomly selected participants (N = 10 000) were drawn from population registry in an age- and gender-stratified manner, focusing on 40–80 years. Cognitive function was examined with the CERAD-NP Plus test-battery (Consortium to Establish a Registry for Alzheimer’s Disease), Stroop-Test, Reading the Mind in the Eyes-Test and Multiple-Choice Vocabulary Intelligence Test. Circumpapillary retinal nerve fibre layer thickness was measured with Optical Coherence Tomography. Subjects with reliable measurements (≥50 B-scan repetitions, signal-to-noise-ratio ≥20 dB, ≤5% missing A-scans) and without clinical eye pathology (sample A) and additional exclusion due to conditions of the central nervous system (sample B) were evaluated. The relationship between cognitive function and retinal nerve fibre layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior and nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to the corresponding brain hemisphere. We analysed 11 124 eyes of 6471 subjects [55.5 years of age (19.1–79.8 years), 46.9% male]. Low cognitive performance was predominantly associated with thinner retinal nerve fibre layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex and scan radius) presented individual results for each test, differentiating between sex and eye-side. For instance, verbal fluency tests and Trail Making Test-B show stronger association in females; Trail Making Test-A shows right-eye dominance. Findings in Trail-Making-Test-A projected to left brain hemisphere, and the ratio incongruent to neutral in the Stroop test projected to right brain-hemisphere. Separate assessment for sex and eye-side is presented for the first time in a population-based study. Location-specific sectorial retinal nerve fibre layer thickness was found to be an indicator for cognitive performance, giving an option for early detection of cognitive decline and the potential of early treatment. The eye as a window to the brain was studied with optical coherence tomography and connected to cognition. Girbardt et al. report that thinner retinal nerve fibre layer thickness was found to be a meaningful index for poorer cognitive performance which presents the potential for prediction of future cognitive decline.

Estimating the Severity of Visual Field Damage From Retinal Nerve Fiber Layer Thickness Measurements With Artificial Intelligence.

PurposeThe purpose of this study was to assess the accuracy of artificial neural networks (ANN) in estimating the severity of mean deviation (MD) from peripapillary retinal nerve fiber layer (RNFL) thickness measurements derived from optical coherence tomography (OCT).MethodsModels were trained using 1796 pairs of visual field and OCT measurements from 1796 eyes to estimate visual field MD from RNFL data. Multivariable linear regression, random forest regressor, support vector regressor, and 1D convolutional neural network (CNN) models with sectoral RNFL thickness measurements were examined. Three independent subsets consisting of 698, 256, and 691 pairs of visual field and OCT measurements were used to validate the models. Estimation errors were visualized to assess model performance subjectively. Mean absolute error (MAE), root mean square error (RMSE), median absolute error, Pearson correlation, and R-squared metrics were used to assess model performance objectively.ResultsThe MAE and RMSE of the ANN model based on the testing dataset were 4.0 dB (95% confidence interval = 3.8–4.2) and 5.2 dB (95% confidence interval = 5.1–5.4), respectively. The ranges of MAE and RMSE of the ANN model on independent datasets were 3.3–5.9 dB and 4.4–8.4 dB, respectively.ConclusionsThe proposed ANN model estimated MD from RNFL measurements better than multivariable linear regression model, random forest, support vector regressor, and 1-D CNN models. The model was generalizable to independent data from different centers and varying races.Translational RelevanceSuccessful development of ANN models may assist clinicians in assessing visual function in glaucoma based on objective OCT measures with less dependence on subjective visual field tests.

Optical coherence tomography-measured retinal nerve fiber layer thickness values compensated with a multivariate model and discrimination between stable and progressing glaucoma suspects

PurposeOur previously introduced multivariate model, compensating for intersubject variability, was applied to circumpapillary retinal nerve fiber layer (RNFL) values measured with optical coherence tomography in glaucoma suspects with or without prior progressive optic disc (OD) change in a series of confocal scanning laser tomography (CSLT, HRT III) measurements.MethodsIn this prospective study, OD change during CSLT follow-up was determined with strict, moderate, and liberal criteria of the topographic change analysis (TCA). Model compensation (MC) as well as age compensation (AC) was applied to RNFL sectors (RNFLMC vs. RNFLAC). Diagnostic performance of RNFLMC vs. RNFLAC was tested with an area under the receiver operating characteristic (AUROC) and was compared between methods.ResultsForty-two glaucoma suspects were included. Patients without prior progressive OD change during the CSLT follow-up (= stable) had thicker RNFL thickness values in most areas and for all progression criteria. RNFLMC AUROC for the global RNFL (0.719) and the inferior quadrant (0.711) performed significantly better compared with RNFLAC AUROC (0.594 and 0.631) to discriminate between stable and progressive glaucoma suspects as defined by the moderate criteria of CSLT progression analysis (p = 0.028; p = 0.024).ConclusionMC showed a slight but significant improvement in detection of subjects with prior progressive OD change among a group of glaucoma suspects, when compared to AC, which is the compensation method commonly used during OCT data evaluation in daily routine. Further studies are warranted to validate the present results.

The influence of axial myopia on optic disc characteristics of glaucoma eyes

This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

PurposeTo study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT).MethodsIn this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC).ResultsOut of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group.ConclusionsWe identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

Prediction of Visual Field Progression from OCT Structural Measures in Moderate to Advanced Glaucoma

To test the hypothesis that visual field (VF) progression can be predicted from baseline and longitudinal optical coherence tomography (OCT) structural measurements. Prospective cohort study. A total of 104 eyes (104 patients) with ≥3 years of follow-up and ≥5 VF examinations were enrolled. We defined VF progression based on pointwise linear regression on 24-2 VF (≥3 locations with slope less than or equal to -1.0 dB/year and P < .01). We used elastic net logistic regression (ENR) and machine learning to predict VF progression with demographics, baseline circumpapillary retinal nerve fiber layer (RNFL), macular ganglion cell/inner plexiform layer (GCIPL) thickness, and RNFL and GCIPL change rates at central 24 superpixels and 3 eccentricities, 3.4°, 5.5°, and 6.8°, from fovea and hemimaculas. Areas-under-ROC curves (AUC) were used to compare models. Average ± SD follow-up and VF examinations were 4.5 ± 0.9 years and 8.7 ± 1.6, respectively. VF progression was detected in 23 eyes (22%). ENR selected rates of change of superotemporal RNFL sector and GCIPL change rates in 5 central superpixels and at 3.4°and 5.6° eccentricities as the best predictor subset (AUC=0.79 ± 0.12). Best machine learning predictors consisted of baseline superior hemimacular GCIPL thickness and GCIPL change rates at 3.4° eccentricity and 3 central superpixels (AUC=0.81 ± 0.10). Models using GCIPL-only structural variables performed better than RNFL-only models. VF progression can be predicted with clinically relevant accuracy from baseline and longitudinal structural data. Further refinement of proposed models would assist clinicians with timely prediction of functional glaucoma progression and clinical decision making.