Optical coherence tomography angiography in the diagnosis of ocular disease.

Clinical imaging provided by optical coherence tomography (OCT) and its variant, OCT-angiography (OCT-A), has revolutionised eyecare practice. The imaging techniques allow for the identification and quantification of ocular structures, supporting the diagnosis and prognosis of eye disease. In this review, an overview of the usefulness of OCT-A imaging in the diagnosis and management of a range of ocular conditions is provided when used in isolation or in combination with other imaging modalities and measures of visual function (visual field results). OCT-A imaging has the capacity to identify and quantify ocular vasculature non-invasively, thereby assisting the clinician in the diagnosis or to determine the efficacy of intervention in ocular conditions impacting retinal vasculature. Thus, additional clinically useful information can be obtained in eye diseases involving conditions such as those impacting retinal vessel occlusion, in diabetic retinopathy, inherited retinal dystrophy, age-related macular degeneration, choroidal neovascularisation and optic nerve disorders. Through a clinical case series, various ocular conditions are reviewed, and the impact of OCT-A imaging is discussed. Although OCT-A imaging has great promise and is already used in clinical management, there is a lack of set standards to characterise altered vascular features in disease and consequently for prognostication, primarily due to a lack of large-scale clinical trials and variability in OCT-A algorithms when generating quantitative parameters.

Characterisation of the normal human ganglion cell-inner plexiform layer using widefield optical coherence tomography.

PURPOSE: To describe variations in ganglion cell-inner plexiform layer (GCIPL) thickness in a healthy cohort from widefield optical coherence tomography (OCT) scans. METHODS: Widefield OCT scans spanning 55° × 45° were acquired from 470 healthy eyes. The GCIPL was automatically segmented using deep learning methods. Thickness measurements were extracted after correction for warpage and retinal tilt. Multiple linear regression analysis was applied to discern trends between global GCIPL thickness and age, axial length and sex. To further characterise age-related change, hierarchical and two-step cluster algorithms were applied to identify locations sharing similar ageing properties, and rates of change were quantified using regression analyses with data pooled by cluster analysis outcomes. RESULTS: Declines in widefield GCIPL thickness with age, increasing axial length and female sex were observed (parameter estimates -0.053, -0.436 and -0.464, p-values <0.001, <0.001 and 0.02, respectively). Cluster analyses revealed concentric, slightly nasally displaced, horseshoe patterns of age-related change in the GCIPL, with up to four statistically distinct clusters outside the macula. Linear regression analyses revealed significant ageing decline in GCIPL thickness across all clusters, with faster rates of change observed at central locations when expressed as absolute (slope = -0.19 centrally vs. -0.04 to -0.12 peripherally) and percentage rates of change (slope = -0.001 centrally vs. -0.0005 peripherally). CONCLUSIONS: Normative variations in GCIPL thickness from widefield OCT with age, axial length and sex were noted, highlighting factors worth considering in further developments. Widefield OCT has promising potential to facilitate quantitative detection of abnormal GCIPL outside standard fields of view.

Derivation of human retinal cell densities using high-density, spatially localized optical coherence tomography data from the human retina.

This study sought to identify demographic variations in retinal thickness measurements from optical coherence tomography (OCT), to enable the calculation of cell density parameters across the neural layers of the healthy human macula. From macular OCTs (n = 247), ganglion cell (GCL), inner nuclear (INL), and inner segment-outer segment (ISOS) layer measurements were extracted using a customized high-density grid. Variations with age, sex, ethnicity, and refractive error were assessed with multiple linear regression analyses, with age-related distributions further assessed using hierarchical cluster analysis and regression models. Models were tested on a naïve healthy cohort (n = 40) with Mann-Whitney tests to determine generalizability. Quantitative cell density data were calculated from histological data from previous human studies. Eccentricity-dependent variations in OCT retinal thickness closely resemble topographic cell density maps from human histological studies. Age was consistently identified as significantly impacting retinal thickness (p = .0006, .0007, and .003 for GCL, INL and ISOS), with gender affecting ISOS only (p < .0001). Regression models demonstrated that age-related changes in the GCL and INL begin in the 30th decade and were linear for the ISOS. Model testing revealed significant differences in INL and ISOS thickness (p = .0008 and .0001; however, differences fell within the OCT's axial resolution. Qualitative comparisons show close alignment between OCT and histological cell densities when using unique, high-resolution OCT data, and correction for demographics-related variability. Overall, this study describes a process to calculate in vivo cell density from OCT for all neural layers of the human retina, providing a framework for basic science and clinical investigations.

High sampling resolution optical coherence tomography reveals potential concurrent reductions in ganglion cell-inner plexiform and inner nuclear layer thickness but not in outer retinal thickness in glaucoma.

PURPOSE: To analyse optical coherence tomography (OCT)-derived inner nuclear layer (INL) and outer retinal complex (ORC) measurements relative to ganglion cell-inner plexiform layer (GCIPL) measurements in glaucoma. METHODS: Glaucoma participants (n = 271) were categorised by 10-2 visual field defect type. Differences in GCIPL, INL and ORC thickness were calculated between glaucoma and matched healthy eyes (n = 548). Hierarchical cluster algorithms were applied to generate topographic patterns of retinal thickness change, with agreement between layers assessed using Cohen's kappa (κ). Differences in GCIPL, INL and ORC thickness within and outside GCIPL regions showing the greatest reductions and Spearman's correlations between layer pairs were compared with 10-2 mean deviation (MD) and pattern standard deviation (PSD) to determine trends with glaucoma severity. RESULTS: Glaucoma participants with inferior and superior defects presented with concordant GCIPL and INL defects demonstrating mostly fair-to-moderate agreement (κ = 0.145-0.540), which was not observed in eyes with no or ring defects (κ = -0.067-0.230). Correlations (r) with MD and PSD were moderate and weak in GCIPL and INL thickness differences, respectively (GCIPL vs. MD r = 0.479, GCIPL vs. PSD r = -0.583, INL vs. MD r = 0.259, INL vs. PSD r = -0.187, p = <0.0001-0.002), and weak in GCIPL-INL correlations (MD r = 0.175, p = 0.004 and PSD r = 0.154, p = 0.01). No consistent patterns in ORC thickness or correlations were observed. CONCLUSIONS: In glaucoma, concordant reductions in macular INL and GCIPL thickness can be observed, but reductions in ORC thickness appear unlikely. These findings suggest that trans-synaptic retrograde degeneration may occur in glaucoma and could indicate the usefulness of INL thickness in evaluating glaucomatous damage.

A comparison of deep learning U-Net architectures for posterior segment OCT retinal layer segmentation.

Deep learning methods have enabled a fast, accurate and automated approach for retinal layer segmentation in posterior segment OCT images. Due to the success of semantic segmentation methods adopting the U-Net, a wide range of variants and improvements have been developed and applied to OCT segmentation. Unfortunately, the relative performance of these methods is difficult to ascertain for OCT retinal layer segmentation due to a lack of comprehensive comparative studies, and a lack of proper matching between networks in previous comparisons, as well as the use of different OCT datasets between studies. In this paper, a detailed and unbiased comparison is performed between eight U-Net architecture variants across four different OCT datasets from a range of different populations, ocular pathologies, acquisition parameters, instruments and segmentation tasks. The U-Net architecture variants evaluated include some which have not been previously explored for OCT segmentation. Using the Dice coefficient to evaluate segmentation performance, minimal differences were noted between most of the tested architectures across the four datasets. Using an extra convolutional layer per pooling block gave a small improvement in segmentation performance for all architectures across all four datasets. This finding highlights the importance of careful architecture comparison (e.g. ensuring networks are matched using an equivalent number of layers) to obtain a true and unbiased performance assessment of fully semantic models. Overall, this study demonstrates that the vanilla U-Net is sufficient for OCT retinal layer segmentation and that state-of-the-art methods and other architectural changes are potentially unnecessary for this particular task, especially given the associated increased complexity and slower speed for the marginal performance gains observed. Given the U-Net model and its variants represent one of the most commonly applied image segmentation methods, the consistent findings across several datasets here are likely to translate to many other OCT datasets and studies. This will provide significant value by saving time and cost in experimentation and model development as well as reduced inference time in practice by selecting simpler models.

Prediction of visual field defects from macular optical coherence tomography in glaucoma using cluster analysis.

PURPOSE: To assess the accuracy of cluster analysis-based models in predicting visual field (VF) defects from macular ganglion cell-inner plexiform layer (GCIPL) measurements in glaucomatous and healthy cohorts. METHODS: GCIPL measurements were extracted from posterior pole optical coherence tomography (OCT), from locations corresponding to central VF test grids. Models incorporating cluster analysis methods and corrections for age and fovea to optic disc tilt were developed from 493 healthy participants, and 5th and 1st percentile limits of GCIPL thickness were derived. These limits were compared with pointwise 5th and 1st percentile limits by calculating sensitivities and specificities in an additional 40 normal and 37 glaucomatous participants, as well as applying receiver operating characteristic (ROC) curve analyses to assess the accuracy of predicting VF results from co-localised GCIPL measurements. RESULTS: Clustered models demonstrated globally low sensitivity, but high specificity in the glaucoma cohort (0.28-0.53 and 0.77-0.91, respectively), and high specificity in the healthy cohort (0.91-0.98). Clustered models showed similar sensitivities and superior specificities compared with pointwise methods (0.41-0.65 and 0.71-0.98, respectively). There were significant differences in accuracy between clusters, with relatively poor accuracy at peripheral macular locations (p < 0.0001 for all comparisons). CONCLUSIONS: Cluster analysis-based models incorporating age correction and holistic consideration of fovea to optic disc tilt demonstrated superior performance in predicting VF results to pointwise methods in both glaucomatous and healthy eyes. However, relatively low sensitivity and poorer performance at the peripheral macula indicate that OCT in isolation may be insufficient to predict visual function across the macula accurately. With modifications to criteria for abnormality, the concepts suggested by the described normative models may guide prioritisation of VF assessment requirements, with the potential to limit excessive VF testing.

Prediction of Retinal Ganglion Cell Counts Considering Various Displacement Methods From OCT-Derived Ganglion Cell-Inner Plexiform Layer Thickness.

Purpose: To compare various displacement models using midget retinal ganglion cell to cone (mRGC:C) ratios and to determine viability of estimating RGC counts from optical coherence tomography (OCT)-derived ganglion cell-inner plexiform layer (GCIPL) measurements. Methods: Four Drasdo model variations were applied to macular visual field (VF) stimulus locations: (1) using meridian-specific Henle fiber length along the stimulus circumference; (2) using meridian-specific differences in RGC receptive field and counts along the stimulus circumference; (3) per method (2), averaged across principal meridians; and (4) per method (3), with the stimulus center displaced only. The Sjöstrand model was applied (5) along the stimulus circumference and (6) to the stimulus center only. Eccentricity-dependent mRGC:C ratios were computed over displaced areas, with comparisons to previous models using sum of squares of the residuals (SSR) and root mean square error (RMSE). RGC counts estimated from OCT-derived ganglion cell layer (GCL) and GCIPL measurements, from 143 healthy participants, were compared using Bland-Altman analyses. Results: Methods 1, 2, and 5 produced mRGC:C ratios most consistent with previous models (SSR 3.82, 4.07, and 3.02; RMSE 0.22, 0.23, and 0.20), while central mRGC:C ratios were overestimated by method 3 and underestimated by methods 4 and 6. RGC counts predicted from GCIPL measurements were within 16% of GCL-based counts, with no notable bias with increasing RGC counts. Conclusions: Sjöstrand displacement and meridian-specific Drasdo displacement applied to VF stimulus circumferences produce mRGC:C ratios consistent with previous models. RGC counts can be estimated from OCT-derived GCIPL measurements. Translational Relevance: Implementing appropriate displacement methods and deriving RGC estimates from relevant OCT parameters enables calculation of the number of RGCs responding to VF stimuli from commercial instrumentation.

Clinical Evaluations of Macular Structure-Function Concordance With and Without Drasdo Displacement.

Purpose: The purpose of this study was to compare concordance between ganglion cell-inner plexiform layer (GCIPL) data from the Cirrus optical coherence tomographer (OCT) Ganglion Cell Analysis (GCA) and visual fields (VFs), with and without Drasdo displacement. Methods: From 296 open-angle glaucoma participants, GCIPL deviation and raw thickness data were extracted over locations per the 10-2 VF test grid, with and without application of Drasdo displacement, with global and eccentricity-dependent sensitivities and specificities calculated for both. With OCT and VF data classified as within or outside normative limits, pattern deviation values were compared using paired t-tests and Spearman correlations. Regression models were applied to pattern deviation values as a function of GCIPL thickness, and differences in model performance with and without displacement were compared using extra sums-of-squares F tests. Results: There were small but significant improvements in global specificity without displacement (0.58-0.59 with displacement and 0.61 without displacement), without notable differences in sensitivity (0.77-0.78 with displacement and 0.76-0.78 without displacement). At abnormal VF locations and without displacement, a higher proportion of correct OCT classifications (P = 0.0008) and significant correlation with worsening pattern deviation values were observed (r = 0.50, P = 0.002). Regression models indicated significantly steeper slopes with Drasdo displacement centrally (P = 0.002-0.04). Conclusions: With GCA deviation maps, small improvements in structure-function concordance were observed without displacement, which are unlikely to be clinically meaningful. Using GCIPL thickness data, significantly better structure-function concordance was observed centrally with Drasdo displacement. Translational Relevance: Applying Drasdo displacement on probability-based reports is unlikely to alter clinical impressions of structure-function concordance, but applying displacement with GCIPL thickness data may improve detection of structure-function concordance.

Ganglion cell-inner plexiform layer measurements derived from widefield compared to montaged 9-field optical coherence tomography.

CLINICAL RELEVANCE: With equivalent inner retinal thickness measurements compared to a more conventional composite optical coherence tomography (OCT) protocol, Widefield optical coherence tomography (WF-OCT) is a clinically viable, time-saving option facilitating detection of ocular pathologies within the central 55° of the retina. PURPOSE: To compare ganglion cell-inner plexiform layer (GCIPL) thicknesses obtained using a single WF-OCT scan and standard composite OCT scans acquired in 9 fields of gaze (9F-OCT). METHODS: Thirteen healthy participants underwent WF-OCT and 9F-OCT using the Spectralis OCT. The GCIPL was automatically segmented with a manual review for 9F-OCT and was manually segmented for WF-OCT. After registration, differences in GCIPL thicknesses were compared using 95% confidence intervals computed from one-sample t-tests and Bland-Altman analyses. Location-specific differences in B-scan tilt were analysed using Spearman correlations and linear regression models. To determine whether B-scan tilt influences GCIPL measurements, regression models of tilt versus differences between perpendicular and axial GCIPL thickness were applied. RESULTS: While scattered locations demonstrated significant GCIPL thickness differences between WF-OCT and 9F-OCT, most differences did not exceed the axial pixel resolution of the instrument of 3.87 µm. Bland-Altman analyses indicated no notable bias using WF-OCT. Moderate correlations indicating significant location-specific differences in B-scan tilt were observed for temporal, central and inferior B-scans (r = -0.62 to 0.72), with linear regression models predicting a maximum difference in the tilt of 4.65°. The quadratic regression model indicated that at tilts greater than 27.3°, perpendicular GCIPL measurements become increasingly thin relative to axial measurements. CONCLUSIONS: GCIPL thicknesses and B-scan tilts from WF-OCT are comparable to 9F-OCT, indicating that WF-OCT can be applied clinically to obtain valid inner retinal OCT measurements over 55° of the central retina with relative ease. However, for peripheral locations, B-scan tilt may need to be considered when measuring GCIPL thicknesses.

Intra-session repeatability of anterior chamber depth across the chamber width using Pentacam Scheimpflug imaging in healthy subjects.

PURPOSE: Despite the importance of anterior chamber depth (ACD) measurements in disease and ageing, the repeatability and their threshold for change is not known. Our purpose was to determine the intra-session repeatability of Pentacam Scheimpflug photography for measuring the ACD across the chamber width in healthy subjects and thus inform expected limits of normality. METHODS: Pentacam Scheimpflug photography was used to obtain ACD measurements at 57 points across the central 8mm of the chamber width from one randomly selected eye of 130 healthy (normal vision and no ocular diseases, except age-normal cataracts) subjects (median age 58.0 years, interquartile range 46.3-63.0 years; 48 males, 82 females). Intra-session ACD measurements were compared. Univariate and multivariate linear regression was performed to identify categorical and continuous variables demonstrating a significant relationship with ACD and its repeatability. RESULTS: Bland-Altman analyses showed no directional or depth-dependent bias in the difference between the first and second tests (mean bias -0.003 mm, 95% limits of agreement -0.115 to +0.109 mm). Multivariate analysis found gender to be a significant factor (p < 0.0001), but not age (p = 0.69) nor ethnicity (p = 0.65), although the model fit was poor (R2  = 0.004). There were no regional differences in repeatability measures found in males, but six locations in the superior aspect in females were found to be significantly different in their repeatability characteristics. Tolerance limits used to calculate the number of step sizes between <20 and >60-year-old age groups found 8.1-11.5 steps for females, and 7.5-9.2 steps for males. CONCLUSIONS: Scheimpflug imaging using the Pentacam has excellent intra-session repeatability. Only gender appeared to affect repeatability characteristics, manifesting with a greater number of meaningful steps of change between two extremes of age range in females compared to males, which provides guidance for identifying clinically significant and measurable change between tests.

Clinical Trial: Diurnal IOP Fluctuations in Glaucoma Using Latanoprost and Timolol with Self-Tonometry.

SIGNIFICANCE: Assessment of treatment efficacy via comparison with a target IOP is fundamental in monitoring patients with open-angle glaucoma and ocular hypertension. This article highlights that diurnal IOP fluctuations obtained using self-tonometry may more accurately reflect IOP responses to therapy. PURPOSE: This study aimed to investigate fluctuations in diurnal IOP measurements in patients with open-angle glaucoma and ocular hypertension treated with latanoprost 0.005% and timolol 0.25%. METHODS: In this crossover treatment trial, 14 participants performed self-tonometry with iCare HOME 4 times daily for (1) 1 week using latanoprost, (2) 4 weeks using no medications, and (3) 2 weeks using timolol. Daily peak IOPs, IOP fluctuations, and mean IOPs from different treatments were compared on an individual basis. Treatment efficacy between medications was assessed by comparing mean percentage IOP reductions with latanoprost and timolol across participants. In addition, effects of age, years since commencing latanoprost, sex, and diagnosis were investigated, and peak IOP times were compared with assess impacts on diurnal profiles. RESULTS: Between individuals, IOP responses ranged from reductions in peak IOPs, IOP fluctuations, and mean IOPs on both medications to no change in any parameter and medication. IOP fluctuations showed greater mean percentage reductions than did peak and mean IOPs (χ2 = 16.51, P = .002). There were significant associations between years since commencing latanoprost and peak and mean IOP responses on timolol (r = 0.69, P = .007), and sex and relative reductions in IOP fluctuations on both medications (P = .03). There were no differences in peak IOP times between treatment conditions. CONCLUSIONS: Despite variability in IOP responses to latanoprost and timolol, IOP fluctuation with self-tonometry was more consistent in evaluating target IOP, reflecting its importance in ascertaining true IOP response to topical therapies. These findings may impact clinical decision making based on target IOP criteria in patients on topical therapy.

Topical Review: Assessment of Binocular Sensory Processes in Low Vision.

SIGNIFICANCE: This article summarizes the evidence for a higher prevalence of binocular vision dysfunctions in individuals with vision impairment. Assessment for and identification of binocular vision dysfunctions can detect individuals experiencing difficulties in activities including reading, object placement tasks, and mobility.Comprehensive vision assessment in low vision populations is necessary to identify the extent of remaining vision and to enable directed rehabilitation efforts. In patients with vision impairment, little attention is typically paid to assessments of binocular vision, including ocular vergence, stereopsis, and binocular summation characteristics. In addition, binocular measurements of threshold automated visual fields are not routinely performed in clinical practice, leading to an incomplete understanding of individuals' binocular visual field and may affect rehabilitation outcomes.First, this review summarizes the prevalence of dysfunctions in ocular vergence, stereopsis, and binocular summation characteristics across a variety of ocular pathologies causing vision impairment. Second, this review examines the links between clinical measurements of binocular visual functions and outcome measures including quality of life and performance in functional tasks. There is an increased prevalence of dysfunctions in ocular alignment, stereopsis, and binocular summation across low vision cohorts compared with those with normal vision. The identification of binocular vision dysfunctions during routine low vision assessments is especially important in patients experiencing difficulties in activities of daily living, including but not limited to reading, object placement tasks, and mobility. However, further research is required to determine whether addressing the identified deficits in binocular vision in low vision rehabilitative efforts directly impacts patient outcomes.

Custom extraction of macular ganglion cell-inner plexiform layer thickness more precisely co-localizes structural measurements with visual fields test grids.

We aimed to evaluate methods of extracting optical coherence tomography (OCT)-derived macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements over retinal locations corresponding to standard visual field (VF) test grids. A custom algorithm was developed to automatically extract GCIPL thickness measurements from locations corresponding to Humphrey Field Analyser 10-2 and 30-2 test grids over Goldmann II, III and V stimulus sizes from a healthy cohort of 478 participants. Differences between GCIPL thickness measurements based on VF test grids (VF-based paradigms) and the 8 × 8 grid, as per instrument review software, were analyzed, as were impacts of fovea to optic disc tilt and areas over which GCIPL thickness measurements were extracted. Significant differences between the VF-based paradigms and the 8 × 8 grid were observed at up to 55% of locations across the macula, with the greatest deviations at the fovea (median 25.5 µm, 95% CI 25.24-25.72 µm, P < .0001). While significant correlations with fovea to optic disc tilt were noted at up to 33% of locations distributed 6°-8° from the foveal center, there were no marked differences in GCIPL thickness measurements between VF-based paradigms using different stimulus sizes. As such, standard high-density OCT measurement paradigms do not adequately reflect GCIPL measurements at retinal locations tested with standard VF patterns, with the central macular region contributing most to the observed differences and with further correction required for fovea to optic disc tilt. Spatial direction of GCIPL thickness measurements will improve future comparisons of structure and function, thereby improving methods designed to detect pathology affecting the inner retina.

Cluster analysis reveals patterns of age-related change in anterior chamber depth for gender and ethnicity: clinical implications.

PURPOSE: To identify patterns of age-, gender- and refractive- related changes in Scheimpflug-based anterior chamber depth across the central 8 mm of chamber width, to derive normative models, potentially useful for angle closure disease diagnosis. METHODS: This was a retrospective, cross-sectional study. Scheimpflug photography was used to obtain anterior chamber depth measurements at 57 points across the central 8 mm of the chamber width from one eye of each healthy subject (male Caucasians (n = 189), female Caucasians (n = 186), male Asians (n = 165) and female Asians (n = 181)). Sliding window and nonlinear regression analysis was used to identify the age-related changes in chamber depth. Hierarchical cluster analysis was used to identify test locations with statistically identical age-related shifts, which were used to perform age-correction for all subjects, resulting in normative distributions of chamber depth across the chamber width. The model was examined with and without the contribution of spherical equivalent refractive error. RESULTS: Distinct clusters, demonstrating statistically indistinguishable age-related changes of chamber depth over time, were identified. These age-related changes followed a nonlinear regression (fifth or sixth order polynomial). Females tended to have a greater rate of chamber depth shallowing. Incorporating refractive error into the model produced minimal changes to the fit relative to the ground truth. Comparisons with cut-offs for angle closure from the literature showed that ageing alone was insufficient for identifying angle closure disease. CONCLUSIONS: Age-, ethnicity- and gender-related differences need to be acknowledged in order to utilise anterior chamber depth data for angle closure disease diagnosis correctly. Ageing alone does not adequately account for the angle closure disease process.

Normal aging changes in the choroidal angioarchitecture of the macula.

The choroidal vascularity index (CVI) has been shown to be sensitive in detecting changes in choroidal angioarchitecture in a range of ocular diseases. However, changes in CVI in association with normal physiological aging and spatial distribution remains to be determined. This is significant as a range of ocular conditions with choroidal degeneration are associated with aging. In this study, we assessed CVI for 106 healthy eyes from 106 individuals (range 21-78 years old, ~ 20 individuals/decade) at 15 eccentricities across the macula (0, 230 µm, 460 µm, 690 µm, 1,150 µm, 1,380 µm and 2,760 µm from the fovea in the superior and inferior direction). Total choroidal area, luminal area and stromal area were all significantly decreased with age (p < 0.001 for all parameters). CVI was also significantly decreased with age (p < 0.01) and eccentricity. Fitting of quadratic regression curves to CVI as a function of age yielded a good fit for all eccentricities (r2 = 0.55-0.80) and suggested a decrease in CVI from the ages of 33-43 years at a rate of 0.7-2.7% per decade. CVI was lower in the inferior versus superior retina at matching eccentricities and a significant difference in age-related decline of CVI with eccentricity only occurred in inferior locations. These findings suggest choroidal angioarchitecture declines from the 4th decade of life with potential eccentricity differences in the inferior and superior retina. Considering the number of age-related diseases with choroidal dysfunction, these results provide foundational knowledge to understand choroidal involvement in these diseases.

Macula Ganglion Cell Thickness Changes Display Location-Specific Variation Patterns in Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to examine changes in the ganglion cell layer (GCL) of individuals with intermediate age-related macular degeneration (AMD) using grid-wise analysis for macular optical coherence tomography (OCT) volume scans. We also aim to validate the use of age-correction functions for GCL thickness in diseased eyes. Methods: OCT macular cube scans covering 30° × 25° were acquired using Spectralis spectral-domain OCT for 87 eyes with intermediate AMD, 77 age-matched normal eyes, and 254 non-age-matched normal eyes. The thickness of the ganglion cell layer (GCL) was defined after segmentation at 60 locations across an 8 × 8 grid centered on the fovea, where each grid location covered 0.74 mm2 (approximately 3° × 3°) within the macula. Each GCL location of normal eyes (n = 77) were assigned to a specific iso-ganglion cell density cluster in the macula, based on patterns of age-related GCL thickness loss. Analyses were then performed comparing AMD GCL grid-wise data against corresponding spatial clusters, and significant AMD GCL thickness changes were denoted as values outside the 95% distribution limits. Results: Analysis of GCL thickness changes revealed significant differences between spatial clusters, with thinning toward the fovea, and thickening toward the peripheral macula. The direction of GCL thickness changes in AMD were associated more so with thickening than thinning in all analyses. Results were corroborated by the application of GCL thickness age-correction functions. Conclusions: GCL thickness changed significantly and nonuniformly within the macula of intermediate AMD eyes. Further characterization of these changes is critical to improve diagnoses and monitoring of GCL-altering pathologies.

Modeling Changes in Corneal Parameters With Age: Implications for Corneal Disease Detection.

PURPOSE: To apply computational methods to model normal age-related changes in corneal parameters and to establish their association with demographic factors, thereby providing a framework for improved detection of subclinical corneal ectasia (SCE). DESIGN: Cross-sectional study. METHODS: One hundred seventeen healthy participants were enrolled from Centre for Eye Health (Sydney, Australia). Corneal thickness (CT), front surface sagittal curvature (FSSC), and back surface sagittal curvature (BSSC) measurements were extracted from 57 corneal locations from 1 eye per participant using the Pentacam HR. Cluster analyses were performed to identify locations demonstrating similar variations with age. Age-related changes were modeled using polynomial regression with sliding window methods, and model accuracy was verified with Bland-Altman comparisons. Pearson correlations were applied to examine the impacts of demographic factors. RESULTS: Concentric cluster patterns were observed for CT and FSSC but not for BSSC. Sliding window analyses were best fit with quartic and cubic regression models for CT and FSSC/BSSC, respectively. CT and FSSC sliding window models had narrower 95% limits of agreement compared with decade-based models (0.015 mm vs 0.017 mm and 0.14 mm vs 0.27 mm, respectively), but were wider for BSSC than decade-based models (0.73 mm vs 0.54 mm). Significant correlations were observed between CT and astigmatism (P = .02-.049) and FSSC and BSSC and gender (P = <.001-.049). CONCLUSIONS: The developed models robustly described aging variations in CT and FSSC; however, other mechanisms appear to contribute to variations in BSSC. These findings and the identified correlations provide a framework that can be applied to future model development and establishment of normal databases to facilitate SCE detection.

Development of a Spatial Model of Age-Related Change in the Macular Ganglion Cell Layer to Predict Function From Structural Changes.

PURPOSE: To develop location-specific models of normal, age-related changes in the macular ganglion cell layer (GCL) from optical coherence tomography (OCT). Using these OCT-derived models, we predicted visual field (VF) sensitivities and compared these results to actual VF sensitivities. DESIGN: Retrospective cohort study. METHODS: Single eyes of 254 normal participants were retrospectively enrolled from the Centre for Eye Health (Sydney, Australia). Macular GCL measurements were obtained using Spectralis OCT. Cluster algorithms were performed to identify spatial patterns demonstrating similar age-related change. Quadratic and linear regression models were subsequently used to characterize age-related GCL decline. Forty participants underwent additional testing with Humphrey VFs, and 95% prediction intervals were calculated to measure the predictive ability of structure-function models incorporating cluster-based pooling, age correction, and consideration of spatial summation. RESULTS: Quadratic GCL regression models provided a superior fit (P value <.0001-.0066), establishing that GCL decline commences in the late 30s across the macula. The equivalent linear rates of GCL decline showed eccentricity-dependent variation (0.13 µm/yr centrally vs 0.06 µm/yr peripherally); however, average, normalized GCL loss per year was consistent across the 64 macular measurement locations at 0.26%. The 95% prediction intervals describing predicted VF sensitivities were significantly narrower across all cluster-based structure-function models (3.79-4.99 dB) compared with models without clustering applied (5.66-6.73 dB, P < .0001). CONCLUSIONS: Combining spatial clustering with age-correction based on regression models allowed the development of robust models describing GCL changes with age. The resultant superior predictive ability of VF sensitivity from ganglion cell measurements may be applied to future models of disease development to improve detection of early macular GCL pathology.