Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations.

Purpose: The purpose of this study was to investigate structure-function correlations in multiple evanescent white dot syndrome (MEWDS) using microperimetry (MP) and spectral-domain optical coherence tomography (SD-OCT). Methods: Single-center prospective observational study including 14 eyes from 13 patients with MEWDS monitored over a median of 49.5 days (interquartile range = 29-92 days). Investigations focused on best-corrected visual acuity (BCVA), foveal granularity, and the Photoreceptor Reflectivity Ratio (PRR) as a measure of photoreceptor integrity. MP assessed average retinal threshold sensitivity (RTS) and bivariate contour ellipse area (BCEA) for fixation stability. A linear mixed model was used to test associations and interactions among RTS, time, and clinical variables. A hierarchical linear mixed model was used to analyze structure-function relationships, addressing both individual and location-specific variations. Results: Overall, 2340 MP locations were tested. PRR revealed a transient decrease within 30 days post-presentation, indicative of early photoreceptor disruption, followed by a progressive increase, signaling recovery. Significantly lower foveal sensitivity (RTS = 14.8 ± 7.4 vs. 22.5 ± 4.4 decibel [dB], P = 0.04) and increased fixation spread (63% BCEA = 1.26 ± 0.97 vs. 0.48 ± 0.35 deg2, P = 0.06) were noted in eyes with foveal granularity compared to those without. A significant increase in RTS was demonstrated over time (0.066 dB/day, P < 0.001), with a central-to-peripheral gradient of improvement. The interaction between follow-up time and baseline BCVA (P < 0.001) indicated more rapid improvement in eyes with worse initial vision. There was a robust, nonlinear association between PRR and RTS across all tested locations (P < 0.001), becoming asymptotic for sensitivity losses exceeding 20 dB. Conclusions: Photoreceptor reflectivity accurately aligned with visual function in MEWDS on longitudinal examinations. The central-to-peripheral gradient of improvement may suggest specific vulnerabilities underlying the area around the disc.

Estimating the Distribution of True Rates of Visual Field Progression in Glaucoma.

Purpose: The purpose of this study was to estimate the distribution of the true rates of progression (RoP) of visual field (VF) loss. Methods: We analyzed the progression of mean deviation over time in series of ≥ 10 tests from 3352 eyes (one per patient) from 5 glaucoma clinics, using a novel Bayesian hierarchical Linear Mixed Model (LMM); this modeled the random-effect distribution of RoPs as the sum of 2 independent processes following, respectively, a negative exponential distribution (the "true" distribution of RoPs) and a Gaussian distribution (the "noise"), resulting in a skewed exGaussian distribution. The exGaussian-LMM was compared to a standard Gaussian-LMM using the Watanabe-Akaike Information Criterion (WAIC). The random-effect distributions were compared to the empirical cumulative distribution function (eCDF) of linear regression RoPs using a Kolmogorov-Smirnov test. Results: The WAIC indicated a better fit with the exGaussian-LMM (estimate [standard error]: 192174.4 [721.2]) than with the Gaussian-LMM (192595 [697.4], with a difference of 157.2 [22.6]). There was a significant difference between the eCDF and the Gaussian-LMM distribution (P < 0.0001), but not with the exGaussian-LMM distribution (P = 0.108). The estimated mean (95% credible intervals, CIs) "true" RoP (-0.377, 95% CI = -0.396 to -0.359 dB/year) was more negative than the observed mean RoP (-0.283, 95% CI = -0.299 to -0.268 dB/year), indicating a bias likely due to learning in standard LMMs. Conclusions: The distribution of "true" RoPs can be estimated with an exGaussian-LMM, improving model accuracy. Translational Relevance: We used these results to develop a fast and accurate analytical approximation for sample-size calculations in clinical trials using standard LMMs, which was integrated in a freely available web application.

Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage.

Purpose: The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco's area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. Methods: One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H1: change in RA) or vertically (H2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. Results: The RMSE was 2.09 (95% CI = 1.92-2.26) under H1 and 2.49 (95% CI = 2.24-2.72) under H2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. Conclusions: Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.

Improving the Accuracy and Speed of Visual Field Testing in Glaucoma With Structural Information and Deep Learning.

Purpose: To assess the performance of a perimetric strategy using structure-function predictions from a deep learning (DL) model. Methods: Visual field test-retest data from 146 eyes (75 patients) with glaucoma with (median [5th-95th percentile]) 10 [7, 10] tests per eye were used. Structure-function predictions were generated with a previously described DL model using cicumpapillary optical coherence tomography (OCT) scans. Structurally informed prior distributions were built grouping the observed measured sensitivities for each predicted value and recalculated for each subject with a leave-one-out approach. A zippy estimation by sequential testing (ZEST) strategy was used for the simulations (1000 per eye). Ground-truth sensitivities for each eye were the medians of the test-retest values. Two variations of ZEST were compared in terms of speed (average total number of presentations [NP] per eye) and accuracy (average mean absolute error [MAE] per eye), using either a combination of normal and abnormal thresholds (ZEST) or the calculated structural distributions (S-ZEST) as prior information. Two additional versions of these strategies employing spatial correlations were tested. Results: S-ZEST was significantly faster, with a mean average NP of 213.87 (SD = 28.18), than ZEST, with a mean average NP of 255.65 (SD = 50.27) (P < 0.001). The average MAE was smaller for S-ZEST (1.98; SD = 2.37) than ZEST (2.43; SD = 2.69) (P < 0.001). Spatial correlations further improved both strategies (P < 0.001), but the differences between ZEST and S-ZEST remained significant (P < 0.001). Conclusions: DL structure-function predictions can significantly improve perimetric tests. Translational Relevance: DL structure-function predictions from clinically available OCT scans can improve perimetry in glaucoma patients.

Validating Trend-Based End Points for Neuroprotection Trials in Glaucoma.

Purpose: The purpose of this study was to evaluate the power of trend-based visual field (VF) progression end points against long-term development of event-based end points accepted by the US Food and Drug Administration (FDA). Methods: One eye from 3352 patients with ≥10 24-2 VFs (median = 11 years) follow-up were analyzed. Two FDA-compatible criteria were applied to these series to label "true-progressed" eyes: ≥5 locations changing from baseline by more than 7 dB (FDA-7) or by more than the expected test-retest variability (GPA-like) in 2 consecutive tests. Observed rates of progression (RoP) were used to simulate trial-like series (2 years) randomly assigned (1000 times) to a "placebo" or a "treatment" arm. We simulated neuroprotective "treatment" effects by changing the proportion of "true progressed" eyes in the two arms. Two trend-based methods for mean deviation (MD) were assessed: (1) linear mixed model (LMM), testing average difference in RoP between the two arms, and (2) time-to-progression (TTP), calculated by linear regression as time needed for MD to decline by predefined cutoffs from baseline. Power curves with 95% confidence intervals were calculated for trend and event-based methods on the simulated series. Results: The FDA-7 and GPA-like progression was achieved by 45% and 55% of the eyes in the clinical database. LMM and TTP had similar power, significantly superior to the event-based methods, none of which reached 80% power. All methods had a 5% false-positive rate. Conclusions: The trend-based methods can efficiently detect treatment effects defined by long-term FDA-compatible progression. Translational Relevance: The assessment of the power of trend-based methods to detect clinically relevant progression end points.

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

Spatiotemporal summation of perimetric stimuli in healthy observers.

Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatiotemporal interaction has important implications for modeling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration, and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modeling disease, especially glaucoma.

Five-Year Visual Field Outcomes of the HORIZON Trial.

PURPOSE: To compare visual field (VF) progression between glaucoma patients receiving cataract surgery alone (CS) or with a Hydrus microstent (CS-HMS). DESIGN: Post hoc analysis of VF data from the HORIZON multicenter randomized controlled trial. METHODS: A total of 556 patients with glaucoma and cataract were randomized 2:1 to either CS-HMS (369) or CS (187) and followed up for 5 years. VF was performed at 6 months and then every year after surgery. We analyzed data for all participants with at least 3 reliable VFs (false positives < 15%). Average between-group difference in rate of progression (RoP) was tested using a Bayesian mixed model and a 2-sided Bayesian P value <.05 (main outcome). A multivariable model measured the effect of intraocular pressure (IOP). A survival analysis compared the probability of global VF sensitivity dropping by predefined cutoffs (2.5, 3.5, 4.5, and 5.5 dB) from baseline. RESULTS: Data from 352 eyes in the CS-HMS arm and 165 in the CS arm were analyzed (2966 VFs). The mean RoP was -0.26 dB/y (95% credible interval -0.36, -0.16) for CS-HMS and -0.49 dB/y (95% credible interval -0.63, -0.34) for CS. This difference was significant (P = .0138). The difference in IOP only explained 17% of the effect (P < .0001). Five-year survival analysis showed an increased probability of VF worsening by 5.5 dB (P = .0170), indicating a greater proportion of fast progressors in the CS arm. CONCLUSIONS: CS-HMS has a significant effect on VF preservation in glaucoma patients compared with CS alone, reducing the proportion of fast progressors.

Objective Quantification of Posterior Segment Inflammation: Measuring Vitreous Cells and Haze Using Optical Coherence Tomography.

PURPOSE: To objectively grade posterior segment inflammation by measuring vitreous cells and haze on optical coherence tomography (OCT) scans and to compare OCT-based results with clinical grading. DESIGN: Evaluation of a diagnostic test. METHODS: OCT scans of patients with uveitis were collected at 3 timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the vitreous haze (National Eye Institute [NEI] scale) were assessed. The density of vitreous cells was calculated on each OCT scan manually and automatically through a bespoke algorithm. Vitreous haze was indirectly measured on OCT scans by calculating the vitreous/retinal pigmented epithelium (VIT/RPE)-relative intensity manually and automatically. The variation of OCT-derived measurements over time was assessed. OCT-derived measurements were compared with clinical grading. RESULTS: A total of 222 scans from 74 eyes were analyzed. Both vitreous cell density and VIT/RPE-relative intensity significantly decreased over time. Cell density correlated with the clinical grading with a significant increase at each grade of the NEI scale. By contrast, the VIT/RPE-relative intensity was positively correlated with the clinical grade overall but there was no significant difference when comparing contiguous grades of the NEI scale. Infectious uveitis had a higher cell density. The intraclass correlation coefficient between manual and automatic assessment was 0.83 for cell density and 0.423 for the VIT/RPE-relative intensity. CONCLUSIONS: Posterior segment inflammation could be objectively graded through OCT scans. Vitreous cell density was assessed manually and automatically with good agreement and correlated better with NEI clinical grading compared with VIT/RPE-relative intensity.

Two-Year Visual Field Outcomes of the Treatment of Advanced Glaucoma Study (TAGS).

PURPOSE: to compare visual field (VF) progression between the 2 arms of the Treatment of Advanced Glaucoma Study (TAGS). DESIGN: Post hoc analysis of VF data from a 2-arm, multicenter, randomized controlled clinical trial. METHODS: A total of 453 patients with newly diagnosed advanced open-angle glaucoma in at least 1 eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (n = 227) or medication in their index eye (n = 226) and followed-up for 2 years with 2 24-2 VF tests at baseline, 4, 12, and 24 months. Data were analyzed for participants with a reliable VF (false positive rate < 15%) at baseline and at least 2 other time points. Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5, and 2 dB) was compared using survival analysis. RESULTS: This study analyzed 211 eyes in the trabeculectomy first arm and 203 eyes in the medication first arm. The average RoP (estimate [95% credible intervals]) was -0.59 [-0.88, -0.31] dB/year in the medication first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy first arm. The difference was not significant (Bayesian P-value = .353). More eyes progressed in the medication first arm, but this difference was not significant. CONCLUSIONS: There was no significant difference in the average RoP at 2 years.

Exploring Vitreous Haze as a Potential Biomarker for Accelerated Glymphatic Outflow and Neurodegeneration in Multiple Sclerosis: A Cross-Sectional Study.

BACKGROUND: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space. Here, we tested whether vitreous haze (VH) can provide novel insights into the relationship between neurodegeneration and the ocular glymphatic system in MS. METHODS: This cross-sectional study comprised 315 persons with MS and 87 healthy controls (HCs). VH was quantified from optical coherence tomography (OCT) volume scans. Neurodegeneration was determined on three-dimensional T1 (3DT1) MRI, lesion detection on fluid-attenuated inversion (FLAIR), and layer thickness on OCT. Generalized estimating equations, corrected for age, were used to analyze associations between VH and metrics for neurodegeneration, demographics, and clinical scales. Group differences were determined between mild, moderate, and severe disability. RESULTS: On the group level, VH scores were comparable between MS and control (p = 0.629). In MS, VH scores declined with disease duration (ß = -0.009, p = 0.004) and age (ß = -0.007, p = 0.001). There was no relation between VH scores and higher age in HCs. In MS patients, VH was related to normalized gray (NGMV, ß = 0.001, p = 0.011) and white matter volume (NWMV, ß = 0.001, p = 0.003), macular ganglion cell-inner plexiform layer thickness (mGCIPL, ß = 0.006, p < 0.001), and peripapillary retinal nerve fiber layer thickness (pRNFL, ß = 0.004, p = 0.008). VH was significantly lower in severe compared to mild disability (mean difference -28.86%, p = 0.058). CONCLUSIONS: There is a correlation between VH on OCT and disease duration, more severe disability and lower brain volumes in MS. Biologically, these relationships suggest accelerated glymphatic clearance with disease-related atrophy.

OCT Assisted Quantification of Vitreous Inflammation in Uveitis.

Purpose: Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH. Methods: In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed. Results: One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03). Conclusions: OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities. Translational Relevance: OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.

Hierarchical Censored Bayesian Analysis of Visual Field Progression.

Purpose: To develop a Bayesian model (BM) for visual field (VF) progression accounting for the hierarchical, censored and heteroskedastic nature of the data. Methods: Three versions of a hierarchical BM were developed: a simple linear (Hi-linear); censored at 0 dB (Hi-censored); heteroskedastic censored (Hi-HSK). For the latter, we modeled the test variability according to VF sensitivity using a large test-retest cohort (1396 VFs, 146 eyes with glaucoma). We analyzed a large cohort of 44,371 VF tests from 3352 eyes from five glaucoma clinics. We quantified the bias in the estimated rate-of-progression, the detection of progression (Hit-rate [HR]), the median time-to-progression and the prediction error of future observations (mean absolute error [MAE]). HR and time-to-progression were compared at matched false-positive-rate (FPR), quantified using permutations of a separate test-retest cohort (360 tests, 30 eyes with glaucoma). BMs were compared to simple linear regression and Permutation-Analyses-of Pointwise-Linear-Regression. Differences in time-to-progression were tested using survival analysis. Results: Censored models showed the smallest bias in the rate-of-progression. The three BMs performed very similarly in terms of HR and time-to-progression and always better than the other methods. The average reduction in time-to-progression was 37% with the BMs (P < 0.001) at 5% FPR. MAE for prediction was very similar among methods. Conclusions: Bayesian hierarchical models improved the detection of VF progression. Accounting for censoring improves the precision of the estimates, but minimal effect is provided by accounting for heteroskedasticity. Translational Relevance: These results are relevant for quantification of VF progression in practice and for clinical trials.

Structural Endpoints and Outcome Measures in Uveitis.

Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.

Evidence for Structural and Functional Damage of the Inner Retina in Diabetes With No Diabetic Retinopathy.

Purpose: To provide structural and functional evidence of inner retinal loss in diabetes prior to vascular changes and interpret the structure-function relationship in the context of an established neural model. Methods: Data from one eye of 505 participants (134 with diabetes and no clinically evident vascular alterations of the retina) were included in this analysis. The data were collected as part of a large population-based study. Functional tests included best-corrected visual acuity, Pelli-Robson contrast sensitivity, mesopic microperimetry, and frequency doubling technology perimetry (FDT). Macular optical coherence tomography volume scans were collected for all participants. To interpret the structure-function relationship in the context of a neural model, ganglion cell layer (GCL) thickness was converted to local ganglion cell (GC) counts. Results: The GCL and inner plexiform layer were significantly thinner in participants with diabetes (P < 0.05), with no significant differences in the macular retinal nerve fiber layer or the outer retina. All functional tests except microperimetry showed a significant loss in diabetic patients (P < 0.05). Both FDT and microperimetry showed a significant relationship with the GC count (P < 0.05), consistent with predictions from a neural model for partial summation conditions. However, the FDT captured additional significant damage (P = 0.03) unexplained by the structural loss. Conclusions: Functional and structural measurements support early neuronal loss in diabetes. The structure-function relationship follows the predictions from an established neural model. Functional tests could be improved to operate in total summation conditions in the macula, becoming more sensitive to early loss.

A novel quantitative analysis method for idiopathic epiretinal membrane.

PURPOSE: To introduce a novel method to quantitively analyse in three dimensions traction forces in a vast area of the ocular posterior pole. METHODS: Retrospective analysis of 14 eyes who underwent peeling surgery for idiopathic, symptomatic and progressive epiretinal membrane. The technique measures the shift in position of vascular crossings after surgery from a fixed point, which is the retinal pigmented epithelium. This shift is defined as the relaxation index (RI) and represents a measure of the postoperative movement of the retina due to released traction after surgery. RESULTS: Best-corrected visual acuity was significantly better than baseline at all follow ups while the RI had its maximum value at baseline. Moreover, we found a significant correlation between best-corrected visual acuity at 6 months and RI at baseline. CONCLUSION: While all previous published methods focused on bi-dimensional changes observed in a small region, this study introduces a three-dimensional assessment of tractional forces. Future integration of RI into built-in processing software will allow systematic three-dimensional measurement of intraretinal traction.

Automated quantification of posterior vitreous inflammation: optical coherence tomography scan number requirements.

Quantifying intraocular inflammation is crucial in managing uveitis patients. We assessed the minimum B-scan density for reliable automated vitreous intensity (VI) assessment, using a novel approach based on optical coherence tomography (OCT). OCT volume scans centered on the macula were retrospectively collected in patients with uveitis. Nine B-scans per volume scan at fixed locations were automatically analyzed. The following B-scan selections were compared against the average score of 9 B-scans per volume scan as a reference standard: 1/3/5/7 central scans (1c/3c/5c/7c), 3 widely distributed scans (3w). Image data of 49 patients (31 females) were included. The median VI was 0.029 (IQR: 0.032). The intra-class-correlation coefficient of the VI across the 9 B-scans was 0.923. The median difference from the reference standard ranged between 0.001 (7c) and 0.006 (1c). It was significantly lower for scan selection 3w than 5c, p(adjusted) = 0.022, and lower for selection 7c than 3w, p(adjusted) = 0.003. The scan selections 7c and 3w showed the two highest areas under the receiver operating curve (0.985 and 0.965, respectively). Three widely distributed B-scans are sufficient to quantify VI reliably. Highest reliability was achieved using 7 central B-scans. Automated quantification of VI in uveitis is reliable and requires only few OCT B-scans.

Revisiting the Drasdo Model: Implications for Structure-Function Analysis of the Macular Region.

Purpose: To provide a consistent implementation of a retinal ganglion cell (RGC) displacement model proposed by Drasdo et al. for macular structure-function analysis, customizable by axial length (AL). Methods: The effect of axial length on the shape of the inner retina was measured on 235 optical coherence tomography (OCT) scans from healthy eyes, to provide evidence for geometric scaling of structures with eye size. Following this assumption, we applied the Drasdo model to map perimetric stimuli on the radially displaced RGCs using two different methods: Method 1 only displaced the center of the stimuli; Method 2 applied the displacement to every point on the edge of the stimuli. We compared the accuracy of the two methods by calculating, for each stimulus, the number of expected RGC receptive fields and the number RGCs calculated from the histology map, expected to be equivalent. The same calculation was repeated on RGC density maps derived from 28 OCT scans from 28 young healthy subjects (age < 40 years) to confirm our results on clinically available measurements. Results: The size of the retinal structures significantly increased with AL (P < 0.001) and was well predicted by geometric scaling. Method 1 systematically underestimated the RGC counts by as much as 60%. No bias was observed with Method 2. Conclusions: The Drasdo model can effectively account for AL assuming geometric scaling. Method 2 should be used for structure-function analyses. Translational Relevance: We developed a free web App in Shiny R to make our results available for researchers.

Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.

Purpose: To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images. Methods: Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study. Results: The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84. Conclusions: The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset. Translational Relevance: Merged information from multimodal images improves segmentation performance of chorioretinal lesions.