Retinal Layer Thickness Measurements Research Articles

Diagnostic Performance for Detection of Glaucomatous Structural Damage Using Pixelwise Analysis of Retinal Thickness Measurements.

To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis. For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations. Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356). Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Longitudinal evaluation of circumpapillary structure-function and vasculature-function relationships in acute and sub-acute nonarteritic anterior ischemic optic neuropathy

PurposeTo investigate the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) using circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements, circumpapillary vessel density (cpVD) and the corresponding/final visual outcomes at different stages of nonarteritic anterior ischemic optic neuropathy (NAION). MethodsThirty eyes of 30 patients with acute NAION were included. LogMAR best-corrected visual acuity(BCVA), mean deviation (MD) and visual field index (VFI), cpRNFL thickness and cpVD across different retinal layers were examined at baseline, 2 weeks and 1 month after diagnosis. Potential correlations between the Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters and visual outcomes were investigated in both acute and sub-acute NAION. ResultsSignificant global and regional correlations in S-F relationship were identified exclusively in sub-acute stage (p < 0.05). However, among the OCTA parameters for the acute NAION, the temporal cpVD in superficial vessel complex (SVC) and inner retinal layer (IRL) exhibited positive correlations with corresponding and final visual acuity and visual field outcomes. In the sub-acute stage of NAION, the cpVD of global or temporal section in radial peripapillary capillary (RPC), SVC and IRL were positively correlated with visual outcomes. ConclusionSignificant longitudinal V-F relationships exist both globally and regionally, in acute and sub-acute NAION. The cpVD parameters of the SVC and IRL are potentially valuable for evaluating corresponding and final visual outcomes and highlights the importance of monitoring cpVD over cpRNFL thickness in acute NAION.

Correlation between optical coherence tomography angiography measured vessel density and retinal nerve fiber layer thickness in moderate primary open angle glaucoma cases and normal controls

: Aim of this study was to establish a correlation between findings obtained from Optical Coherence Tomography Angiography (OCT-A) and Retinal Nerve Fiber Layer (RNFL) thickness measurements in a series of moderate Primary Open Angle Glaucoma (POAG) cases and normal controls. In this observational cross-sectional study a total of 100 eyes were included, comprising 50 eyes with glaucoma and 50 control eyes without glaucoma. All participants underwent comprehensive anterior and posterior segment evaluations, intraocular pressure (IOP) measurement using Goldmann applanation tonometer, gonioscopy, visual field testing, and OCT imaging, which included OCT-A. The OCT-A imaging was performed using the RTvue XR Avanti by Optovue. Two types of analysis were conducted: a comparative analysis between the normal and glaucomatous groups using an unpaired t-test to assess differences in RNFL thickness and vessel density values, and a correlation analysis within each group to examine the strength of correlation between RNFL loss and reduction in vascular density. The results showed a significant reduction in vessel density index in all quadrants of glaucomatous eyes compared to normal eyes. Moreover, this reduced vessel density was found to be significantly correlated with the reduction in RNFL thickness in glaucoma patients. Specifically, the uperior and inferior quadrants exhibited the strongest correlation with each other. The severity of vascular compromise demonstrated a significant correlation with the extent of retinal nerve fiber loss in patients with glaucoma. OCT-A can serve as a valuable adjunct in the diagnosis of glaucoma and monitoring its progression.

Peripapillary and subfoveal choroidal vascular index in patients with tension-type headache and migraine.

This study aimed to evaluate the choroidal vascular characteristics of patients followed up with different headache diagnoses. Prospective comparative study. This study included 21 patients with migraine with visual aura (MwA), 20 with migraine without aura, 29 patients experiencing episodic tension-type headache, and 30 healthy participants. The participants was performed refraction values, axial length, and intraocular pressure were examined. Choroidal thickness was determined in all participants with HD-line optical coherence tomography (OCT) in the subfoveal, nasal, and temporal quadrants 500 μm from the fovea. Using special image processing software, luminal area (LA), stromal area, total choroidal area, and choroidal vascular index (CVI) values were calculated in both macular and peripapillary regions. OCT was also used to perform peripapillary retinal nerve fiber layer (pRNFL) thickness and optic disc head measurements. Spherical refraction, axial length, and intraocular pressure values did not significantly differ among the four groups with similar gender and age distributions (P > 0.05). The LA values in both macular and peripapillary regions were found to be statistically significantly lower in the MwA group (P = 0.007 and P = 0.005, respectively). There was no statistically significant difference among the groups in terms of the remaining choroidal area parameters or CVI values (P > 0.05). The groups also did not show any significant difference in the pRNFL or optic disc head measurements performed in different quadrants (P > 0.05). While LA, one of the choroidal vascular parameters, was found to be lower in the MwA group in both the macular and peripapillary regions, there were no statistically significant differences between the groups in terms of the peripapillary or macular CVI values.

Linking physiology and demographics, non-ocular pathology and pharmaceutical drug use to standard OCT measures of the inner retina: The PPP project.

To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05). There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.

Enhancing the structure–function relationship in glaucoma using anatomical compensation of retinal nerve fibre layer

Background/aimsTo investigate whether compensating retinal nerve fibre layer (RNFL) thickness measurements for demographic and anatomical ocular factors can strengthen the structure–function relationship in patients with glaucoma.Methods600 eyes from 412 patients...

Anatomical Features can Affect OCT Measures Used for Clinical Decisions and Clinical Trial Endpoints.

To understand the association between anatomical parameters of healthy eyes and optical coherence tomography (OCT) circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. OCT cpRNFL thickness was obtained from 396 healthy eyes in a commercial reference database (RDB). The temporal quadrant (TQ), superior quadrant (SQ), inferior quadrant (IQ), and global (G) cpRNFL thicknesses were analyzed. The commercial OCT devices code these values based on percentiles (red, <1%; yellow, ≥1% and <5%), after taking age and disc area into consideration. Four anatomical parameters were assessed: fovea-to-disc distance, an estimate of axial length, and the locations of the superior and the inferior peaks of the cpRNFL thickness curve. Pearson correlation values were obtained for the parameters and the thickness measures of each of the four cpRNFL regions, and t-tests were performed between the cpRNFL thicknesses coded as abnormal (red or yellow, <5%) versus normal (≥5%). For each of the four anatomical parameters, the correlation with the thickness of one or more of the TQ, SQ, IQ, and G regions exceeded the correlation with age or disc area. All four parameters were significantly (P < 0.001) associated with the abnormal cpRNFL values. The significant parameters were not the same for the different regions; for example, a parameter could be negatively correlated for the TQ but positively correlated with the SQ or IQ. In addition to age and disc area, which are used for inferences in normative databases, four anatomical parameters are associated with cpRNFL thickness. Taking these additional anatomical parameters into consideration should aid diagnostic accuracy.

Comparison of the Circumpapillary Structure-Function and Vasculature-Function Relationships at Different Glaucoma Stages Using Longitudinal Data.

This study investigated the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) data using circumpapillary retinal nerve fiber layer thickness (cpRNFLT) measurements from optical coherence tomography (OCT), circumpapillary vessel density (cpVD) from OCT angiography (OCTA), and the corresponding visual field mean sensitivities at different glaucoma stages. A total of 107 eyes from 107 glaucoma patients with progressive visual field (VF) changes followed up for an average of 3.33 ± 1.39years were enrolled, including early-to-moderate (51 eyes) and advanced (56 eyes) stages. The rates of longitudinal change in the VF mean deviation (MD), cpRNFLT, and cpVD were evaluated using linear mixed-effects models and compared between different glaucoma stages. Longitudinal global and regional S-F and V-F relationships were assessed by repeated measures correlation analysis by glaucoma stage. No significant differences were found in the rates of VF MD and cpVD changes (P > 0.05) between the two glaucoma stage groups. CpRNFLT decreased more rapidly in the early-to-moderate stage group (P < 0.001) in which significant longitudinal global and regional correlations were found in both S-F and V-F relationships (all P < 0.05), except for the nasal sector. Significant global and regional correlations were only found in V-F relationship in advanced stage cases (all P < 0.05). Significant longitudinal V-F relationships exist globally and regionally regardless of glaucoma stage but no longitudinal S-F relationship is present in advanced glaucoma. Longitudinal follow-up of cpVD parameters may be useful for monitoring glaucomatous VF progression at all disease stages.

Assessment of linear regression of peripapillary optical coherence tomography retinal nerve fiber layer measurements to forecast glacuoma trajectory.

Linear regression of optical coherence tomography measurements of peripapillary retinal nerve fiber layer thickness is often used to detect glaucoma progression and forecast future disease course. However, current measurement frequencies suggest that clinicians often apply linear regression to a relatively small number of measurements (e.g., less than a handful). In this study, we estimate the accuracy of linear regression in predicting the next reliable measurement of average retinal nerve fiber layer thickness using Zeiss Cirrus optical coherence tomography measurements of average retinal nerve fiber layer thickness from a sample of 6,471 eyes with glaucoma or glaucoma-suspect status. Linear regression is compared to two null models: no glaucoma worsening, and worsening due to aging. Linear regression on the first M ≥ 2 measurements was significantly worse at predicting a reliable M+1st measurement for 2 ≤ M ≤ 6. This range was reduced to 2 ≤ M ≤ 5 when retinal nerve fiber layer thickness measurements were first "corrected" for scan quality. Simulations based on measurement frequencies in our sample-on average 393 ± 190 days between consecutive measurements-show that linear regression outperforms both null models when M ≥ 5 and the goal is to forecast moderate (75th percentile) worsening, and when M ≥ 3 for rapid (90th percentile) worsening. If linear regression is used to assess disease trajectory with a small number of measurements over short time periods (e.g., 1-2 years), as is often the case in clinical practice, the number of optical coherence tomography examinations needs to be increased.

Association of WDR36 polymorphisms with primary open-angle glaucoma

Background: Various genes contribute to the pathophysiology of primary open-angle glaucoma (POAG). The WD repeat domain 36 (WDR36) gene may participate in T cell activation and, hence, in the pathogenesis of POAG. We investigated the association of two WDR36 gene single nucleotide polymorphisms (SNPs) with POAG.&#x0D; Methods: This cross-sectional study recruited patients aged &gt;40 years with POAG and investigated the rs10038177 and rs1971050 SNPs of WDR36 using polymerase chain reaction and direct DNA sequencing. All participants underwent comprehensive ocular examination, visual field assessment using the Swedish Interactive Threshold Algorithm standard 24-2 threshold test, and measurement of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography.&#x0D; Results: We enrolled 105 patients with a mean (standard deviation) age of 55.41 (8.56) years and a male-to-female ratio of 56 (53.3%) to 49 (46.7%), most of whom had a diagnosis of POAG for 2 to 5 years (60.0%). Most participants had diabetes (90.5%) but not hypertension (88.6%). There was a significant association of rs10038177 (P&lt;0.05), but not rs1971050 (P&gt;0.05), with family history of glaucoma. The association between rs10038177 and intraocular pressure was significant (P&lt;0.05), but that between rs1971050 and intraocular pressure was not (P&gt;0.05). No significant association was observed between mean cup-to-disc ratio and either SNP (both P&gt;0.05). For rs10038177, a significant association was found only with the RNFLT of the superior quadrant (P&lt;0.05), whereas for rs1971050, a significant association was found with the RNFLT of all four quadrants and average RNFLT (all P&lt;0.05). However, pairwise comparisons revealed no significant differences between genotypes (P&gt;0.05 for all pairwise comparisons). The association of rs10038177 with glaucoma severity was insignificant (P&gt;0.05), and most patients with the TC genotype (71.7%) had moderate severity. There was no significant association between rs1971050 and glaucoma severity (P&gt;0.05).&#x0D; Conclusions: We observed genetic links between some, but not all, characteristics of POAG and the rs10038177 and rs1971050 SNPs of WDR36. Follow-up studies on these and other WDR36 SNPs in populations with different genetic backgrounds are necessary to confirm this genetic association.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes...

How Radioactive Iodine Treatment Affects the Retina.

Objective The aim of this study was to quantitatively assess the macular and retinal nerve fiber layer thicknesses in patients with hyperthyroidism and thyroid cancer undergoing radioactive iodine (RAI) therapy. Study Design This prospective study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Bagcilar Training and Research Hospital Clinical Research Ethics Committee. Written informed consent was obtained from the patients following a detailed explanation of the study objectives and protocol. Patient selection was randomized. Patients scheduled for RAI treatment in the Nuclear Medicine Clinic were referred to the ophthalmology clinic, respectively. Patients without additional ocular pathology were included in the study. Methods All patients had received RAI therapy using Iodine-131 for hyperthyroidism or thyroid cancer. A complete ophthalmological examination and measurement of macular and retinal nerve fiber layer thickness using optical coherence tomography were performed on all patients before and at the first and sixth months and in first year after RAI treatment. The results were prospectively evaluated. Results The study included 80 eyes of 40 patients. The hyperthyroid group was group 1, and the thyroid cancer group was group 2. There were 25 patients in group 1 and 15 patients in group 2. The mean age was 43.76 ± 11.85 years (range: 22-65 years) in group 1 and 39.87 ± 9.13 years (range: 30-58 years) in group 2. There was no significant difference between the two groups regarding age and sex ( p > 0.05). In both groups, no significant difference was found in the macular thickness and retinal nerve fiber layer thicknesses values obtained in both eyes before and after the RAI treatment. Conclusion As a result of our study, we observed that RAI intake did not harm the retinal layer.

Normative optical coherence tomography reference ranges of the optic nerve head, nerve fiber layer, and macula in healthy Saudi children.

To use the Cirrus high-definition (HD)-OCT to establish normative data for the macula and optic disc in healthy Saudi children and to examine the effect of age and gender on these parameters. This retrospective study was carried out at King Abdulaziz University Hospital (KAUH), Saudi Arabia from November 2022 to April 2023. The study involved 135 full-term and healthy Saudi children aged 4-18 years who were evaluated at the KAUH ophthalmology clinic. Detailed demographic and ocular disease history data were obtained from the patients' medical records. The main outcome measures of the study included measurements of retinal nerve fiber layer (RNFL) thickness, macular thickness, and optic nerve head (ONH). The mean macular volume was 9.9mm3, the mean macular thickness was 275.9 μm, and the mean central subfield thickness was 240.6 μm. There was no significant association between age and the macular values, except for the superior inner macula. Boys had significantly thicker central macula than girls, while the RNFL quadrants were not different between age groups and genders. The mean values for RNFL thickness, disc area, rim area, and cup volume were 93.9 μm, 2mm2, 1.6mm2, and 0.3mm3, respectively. The vertical ratio of cup to disc was 0.4. Normative values for macular and optic nerve measures among Saudi children were established using the Cirrus HD-OCT device to serve as a reference.

Effect of Repeated Intravitreal Injections in Glaucoma Spectrum Diseases.

To evaluate whether repeated intravitreal injections (IVI) with an anti-vascular endothelial growth factor (anti-VEGF) agent are associated with glaucomatous progression in eyes with glaucoma spectrum diseases (GSD). Single-center, retrospective, longitudinal study of patients with bilateral and similar GSD who: (1) received ≥8 IVI in only one eye during the study period; (2) had ≥2 retinal nerve fiber layer thickness (RNFL) measurements obtained by spectral-domain optical coherence tomography (SD-OCT) at least 12 months apart. The primary outcome was the absolute RNFL thickness change, comparing injected and fellow uninjected eyes. Linear mixed effects models were constructed, including a multivariable model. Sixty-eight eyes from 34 patients were included, 34 injected and 34 fellow uninjected eyes. Average baseline age was 67.68±21.77 years with a follow-up of 3.66±1.89 years and 25.12±14.49 IVI. RNFL thickness decreased significantly from 80.92±15.78 to 77.20±17.35 μm (p<0.001; -1.18±1.93 μm/year) in injected eyes and from 79.95±17.91 to 76.61±17.97 μm (p<0.001; -1.07±0.98 μm/year) in uninjected eyes. In a multivariable linear mixed model of injected eyes, only higher baseline RNFL thickness (p < 0.001) significantly predicted higher absolute RNFL thickness loss. Neither absolute RNFL thickness variation (p=0.716) nor RNFL rate (p=0.779) was significantly different between paired injected and uninjected eyes. Absolute IOP variation was not significantly different between groups (16.62±4.77 to 15.09±4.34 mmHg in injected eyes and 17.68±5.01 to 14.50±3.39 mmHg in fellow uninjected eyes; p=0.248). The proportion of eyes receiving glaucoma medical treatment increased significantly in both groups (55.9% to 76.5% in injected eyes; p=0.039; 58.8% to 76.5% in uninjected eyes; p = 0.031). The number of glaucoma medications also increased significantly in both groups (1.03±1.11 to 1.59±1.18 glaucoma medications in injected eyes; p=0.003; 1.09±1.11 to 1.56±1.19 glaucoma medications in uninjected eyes; p=0.003). Repeated IVI do not seem to accelerate glaucomatous progression. Future studies with a longer follow-up are needed.

Interactions of optic radiation lesions with retinal and brain atrophy in early multiple sclerosis.

Retrograde trans-synaptic neuroaxonal degeneration is considered a key pathological factor of subclinical retinal neuroaxonal damage in multiple sclerosis (MS). We aim to evaluate the longitudinal association of optic radiation (OR) lesion activity with retinal neuroaxonal damage and its role in correlations between retinal and brain atrophy in people with clinically isolated syndrome and early MS (pweMS). Eighty-five pweMS were retrospectively screened from a prospective cohort (Berlin CIS cohort). Participants underwent 3T magnetic resonance imaging (MRI) for OR lesion volume and brain atrophy measurements and optical coherence tomography (OCT) for retinal layer thickness measurements. All pweMS were followed with serial OCT and MRI over a median follow-up of 2.9 (interquartile range: 2.6-3.4) years. Eyes with a history of optic neuritis prior to study enrollment were excluded. Linear mixed models were used to analyze the association of retinal layer thinning with changes in OR lesion volume and brain atrophy. Macular ganglion cell-inner plexiform layer (GCIPL) thinning was more pronounced in pweMS with OR lesion volume increase during follow-up compared to those without (Difference: -0.82 μm [95% CI:-1.49 to -0.15], p = 0.018). Furthermore, GCIPL thinning correlated with both OR lesion volume increase (β [95% CI] = -0.27 [-0.50 to -0.03], p = 0.028) and brain atrophy (β [95% CI] = 0.47 [0.25 to 0.70], p < 0.001). Correlations of GCIPL changes with brain atrophy did not differ between pweMS with or without OR lesion increase ( = 5.92e-7 , p = 0.762). Faster GCIPL thinning rate is associated with increased OR lesion load. Our results support the value of GCIPL as a sensitive biomarker reflecting both posterior visual pathway pathology and global brain neurodegeneration.

The diagnostic accuracy of photopic negative responses evoked by broadband and chromatic stimuli in a clinically heterogeneous population

PurposeTo compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort.MethodsAdults referred for electrophysiological investigations were recruited consecutively for this single-centre, prospective, paired diagnostic accuracy study. PhNRs were recorded to red flashes (1.5 cd·s·m−2) on a blue background (10 cd·m−2) and to white flashes on a white background (the latter being the ISCEV standard LA 3 stimulus). PhNR results were compared with a reference test battery assessing RGC/optic nerve structure and function including optical coherence tomography (OCT) retinal nerve fibre layer thickness and mean RGC volume measurements, fundus photography, pattern electroretinography and visual evoked potentials. Primary outcome measures were differences in sensitivity and specificity of the two PhNR methods.ResultsTwo hundred and forty-three participants were initially enrolled, with 200 (median age 54; range 18–95; female 65%) meeting inclusion criteria. Sensitivity was 53% (95% confidence intervals [CI] 39% to 68%) and 62% (95% CI 48% to 76%), for WW and RB PhNRs, respectively. Specificity was 80% (95% CI 74% to 86%) and 78% (95% CI 72% to 85%), respectively. There was a statistically significant difference between sensitivities (p = 0.046) but not specificities (p = 0.08) of the two methods. Receiver operator characteristic (ROC) area under the curve (AUC) values were 0.73 for WW and 0.74 for RB PhNRs.ConclusionPhNRs to red flashes on a blue background may be more sensitive than white-on-white stimuli, but there is no significant difference between specificities. This study highlights the value and potential convenience of using white-on-white stimuli, already used widely for routine ERG assessment.

Normative Percentiles of Retinal Nerve Fiber Layer Thickness and Glaucomatous Visual Field Loss.

Circumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT. A longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test. There were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models. Our results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms. Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

Relationship Between Retinal Layer Thickness and Genetic Susceptibility to Age-Related Macular Degeneration in Asian Populations

For OCT retinal thickness measurements to be used as a prodromal age-related macular degeneration (AMD) risk marker, the 3-dimensional (3D) topographic variation of the relationship between genetic susceptibility to AMD and retinal thickness needs to be assessed. We aimed to evaluate individual retinal layer thickness changes and topography at the macula that are associated with AMD genetic susceptibility. Genetic association study. A total of 1579 healthy participants (782 Chinese, 353 Malays, and 444 Indians) from the multiethnic Singapore Epidemiology of Eye Diseases study were included. Spectral-domain OCT and automatic segmentation of individual retinal layers were performed to produce 10 retinal layer thickness measurements at each ETDRS subfield, producing 3D topographic information. Age-related macular degeneration genetic susceptibility was represented via single nucleotide polymorphisms (SNPs) and aggregated via whole genome (overall) and pathway-specific age-related macular degeneration polygenic risk score (PRSAMD). Associations of individual SNPs, overall PRSAMD, and pathway-specific PRSAMD with retinal thickness were analyzed by individual retinal layer and ETDRS subfield. CFH rs10922109, ARMS2-HTRA1 rs3750846, and LIPC rs2043085 were the top AMD susceptibility SNPs associated with retinal thickness of individual layers (P<1.67×10-3), all at the central subfield. The overall PRSAMD was most associated with thinner L9 (outer segment photoreceptor/retinal pigment epithelium complex) thickness at the central subfield (β=-0.63 μm; P=5.45×10-9). Pathway-specific PRSAMD for the complement cascade (β=-0.53 μm; P=9.42×10-7) and lipoprotein metabolism (β=-0.05 μm; P=0.0061) were associated with thinner photoreceptor layers (L9 and L7 [photoreceptor inner/outer segments], respectively) at the central subfield. The mean PRSAMD score was larger among Indians compared with that of the Chinese and had the thinnest thickness at the L9 central subfield (β=-1.00 μm; P=2.91×10-7; R2=5.5%). Associations at other retinal layers and ETDRS regions were more heterogeneous. Overall genetic susceptibility to AMD and the aggregate effects of the complement cascade and lipoprotein metabolism pathway are associated most significantly with L7 and L9 photoreceptor thinning at the central macula in healthy individuals. Photoreceptor thinning has potential to be a prodromal AMD risk marker, and topographic variation should be considered. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of retinal thickness measured by optical coherence tomography in patients with generalized anxiety disorder

PurposeTo compare the peripapillary retinal nerve fiber layer thickness, macular thickness, ganglion cell layer thickness, and inner plexiform layer thickness determined by Optic Coherence Tomography in the patient group diagnosed with a generalized anxiety disorder who did not receive any psychiatric medication with the healthy control group. MethodsForty newly diagnosed, drug-free Generalized Anxiety Disorder patients and 43 healthy age- and gender-matched control subjects were included in the study. Macular thickness, ganglion cell layer thickness, inner plexiform layer thickness, and peripapillary retinal nerve fiber layer thickness were measured using optical coherence tomography. Structured Clinical Interviews and a State-Trait Anxiety Scale were applied to both groups. ResultsGender distributions (P = 0.965) and mean ages were similar between the groups (P = 0.340). Retinal nerve fiber layer thickness measurements were not significantly different between the groups. We observed statistically significant thinning in the inner superior, inner nasal, inner temporal, inner inferior, and outer inferior quadrants of the macula in the patient group compared to the control group (P = 0.046, P = 0.046, P = 0.020, P = 0.007, P = 0.014). We found thinning at the Ganglion cell layer in the inner inferior and outer temporal quadrants (Respectively P = 0.018, P = 0.049), inner plexiform layer in the inner nasal, inner temporal, and inner inferior quadrants (Respectively P = 0.046, P = 0.044, P = 0.011) compared to the control group. ConclusionsThis is the first study to reveal thinning in the macula, ganglion cell layer, and inner plexiform layer in newly diagnosed, drug-free Generalized Anxiety Disorder patients compared to the control group.