Luke J. Saunders

Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes

Purpose The purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients. Methods Two hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy. Results Age-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65). Conclusions Optical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG.

Ophthalmic statistics note 5: diagnostic tests—sensitivity and specificity

This is the fifth statistics note produced by the Ophthalmic Statistics Group (OSG) which is designed to be a simple guide to ophthalmic researchers on a statistical issue with an applied ophthalmic example. The OSG is a collaborative group of statisticians who have come together with a desire to raise the statistical standards of ophthalmic researcher by increasing statistical awareness of common issues.

Detecting Changes in Retinal Function: Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement (ANSWERS)

Visual fields measured with standard automated perimetry are a benchmark test for determining retinal function in ocular pathologies such as glaucoma. Their monitoring over time is crucial in detecting change in disease course and, therefore, in prompting clinical intervention and defining endpoints in clinical trials of new therapies. However, conventional change detection methods do not take into account non-stationary measurement variability or spatial correlation present in these measures. An inferential statistical model, denoted ‘Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement’ (ANSWERS), was proposed. In contrast to commonly used ordinary linear regression models, which assume normally distributed errors, ANSWERS incorporates non-stationary variability modelled as a mixture of Weibull distributions. Spatial correlation of measurements was also included into the model using a Bayesian framework. It was evaluated using a large dataset of visual field measurements acquired from electronic health records, and was compared with other widely used methods for detecting deterioration in retinal function. ANSWERS was able to detect deterioration significantly earlier than conventional methods, at matched false positive rates. Statistical sensitivity in detecting deterioration was also significantly better, especially in short time series. Furthermore, the spatial correlation utilised in ANSWERS was shown to improve the ability to detect deterioration, compared to equivalent models without spatial correlation, especially in short follow-up series. ANSWERS is a new efficient method for detecting changes in retinal function. It allows for better detection of change, more efficient endpoints and can potentially shorten the time in clinical trials for new therapies.

Practical landmarks for visual field disability in glaucoma

Background/Aims To assess whether mean deviation (MD) from automated perimetry is related to the visual field (VF) component for legal fitness to drive (LFTD) in glaucoma patients. Methods Monocular 24-2 VFs of 2604 patients with bilateral VF damage were retrospectively investigated. Integrated visual fields were calculated and used as a surrogate to assess LFTD according to current UK driving licence criteria. The better eye MD (BEMD), worse eye MD (WEMD) and a measure utilising MD of both eyes were compared, to assess respective diagnostic capabilities to predict LFTD (using the integrated visual field surrogate test as the gold standard) and a ‘Probability of Failure’ (PoF) for various defect levels was calculated. Results BEMD appears to be a good predictor of the VF component for a patients LFTD (receiver operating characteristic area under the curve: 96.2%); MDs from both eyes offered no significant extra diagnostic power (area under the curve: 96.4%). PoF for BEMD thresholds of ≤−10 dB and ≤−14 dB were 70 (95% CI 66% to 74%) and 92% (87% to 95%), respectively. Conclusion There is a strong relationship between BEMD and a patients LFTD. PoF values for LFTD associated with readily available MD values provide practical landmarks for VF disability in glaucoma.

Measurement Precision in a Series of Visual Fields Acquired by the Standard and Fast Versions of the Swedish Interactive Thresholding Algorithm: Analysis of Large-Scale Data From Clinics

IMPORTANCE Swedish Interactive Thresholding Algorithm (SITA) testing strategies for the Humphrey Field Analyzer have become a clinical standard. Measurements from SITA Fast are thought to be more variable than SITA Standard, yet some clinics routinely use SITA Fast because it is quicker. OBJECTIVE To examine the measurement precision of the 2 SITA strategies across a range of sensitivities using a large number of visual field (VF) series from 4 glaucoma clinics in England. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at Moorfields Eye Hospital in London, England; Gloucestershire Eye Unit at Cheltenham General Hospital; Queen Alexandra Hospital in Portsmouth, England; and the Calderdale and Huddersfield National Health Service Foundation Trust that included 66,974 Humphrey 24-2 SITA Standard VFs (10,124 eyes) and 19,819 Humphrey 24-2 SITA Fast VFs (3654 eyes) recorded between May 20, 1997, and September 20, 2012. Pointwise ordinary least squares linear regression of measured sensitivity over time was conducted using VF series of 1 random eye from each patient. Residuals from the regression were pooled according to fitted sensitivities. For each sensitivity (decibel) level, the standard deviation of the residuals was used to estimate measurement precision and were compared for SITA Standard and SITA Fast. Simulations of progression from different VF baselines were used to evaluate how different levels of precision would affect time to detect VF progression. MAIN OUTCOME AND MEASURE Median years required to detect progression. RESULTS Median (interquartile range) patient age, follow-up, and series lengths for SITA Standard were 64 (53-72) years, 6.0 (4.0-8.5) years, and 6 (4-8) VFs, respectively; for SITA Fast, medians (interquartile range) were 70 (61-78) years, 5.1 (3.2-7.3) years, and 5 (4-6) VFs. Measurement precision worsened as sensitivity decreased for both test strategies. In the 20 to 5 dB range, SITA Fast was less precise than SITA Standard; this difference was largest between 15 to 10 dB, where variability in both methods peaked. Translated to median time to detection, differences in measurement precision were negligible, suggesting minimal effects on time to detect progression. CONCLUSIONS AND RELEVANCE Although SITA Standard is a more precise testing algorithm than SITA Fast at lower VF sensitivities, it is unlikely to make a sizeable difference to improving the time to detect VF progression.

REPRODUCIBILITY OF VESSEL DENSITY MEASUREMENT WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EYES WITH AND WITHOUT RETINOPATHY.

Purpose: To determine the intravisit and intervisit reproducibility of optical coherence tomography angiography measurements of macular vessel density in eyes with and without retinal diseases. Methods: Fifteen healthy volunteers and 22 patients with retinal diseases underwent repeated optical coherence tomography angiography (Angiovue Imaging System, Optovue Inc) scans after pupil dilation on 2 separate visit days. For each visit day, the eyes were scanned twice. Vessel density defined as the proportion of vessel area with flowing blood over the total measurement area was calculated using Angiovue software. Intravisit and intervisit reproducibility were summarized as coefficient of variations and intraclass correlation coefficients were calculated from variance component models. Results: The coefficient of variations representing the intravisit reproducibility of the superficial macular vessel density measurements for different quadrants on 3 mm × 3-mm scans varied from 2.1% to 4.9% and 3.4% to 6.8% for healthy and diseased eyes, respectively, and for the intervisit it was 2.9% to 5.1% and 4.0% to 6.8%, respectively. The coefficient of variations were lower in healthy eyes than in diseased eyes, lower for intravisit than for intervisit, lower on 3 mm × 3-mm scans than on 6 mm × 6-mm scans, and lower for paracentral subfields than for central subfield. Conclusion: The evidence presented here demonstrates good reproducibility of optical coherence tomography angiography for measurement of superficial macula vessel density in both healthy eyes and eyes with diabetic retinopathy without diabetic macular edema.

Reproducibility of Optical Coherence Tomography Angiography Macular and Optic Nerve Head Vascular Density in Glaucoma and Healthy Eyes

Purpose: Optical coherence tomography angiography (OCT-A) is a noninvasive technology that allows visualization of retinal blood vessels. It is important to determine reproducibility of measurements as low precision can impair its diagnostic capabilities. The purpose of this study is to determine intravisit and intervisit reproducibility of optic nerve head (ONH) and macular vessel density measurements with OCT-A. Patients and Methods: Fifteen healthy volunteers and 14 glaucoma patients completed 2 OCT-A (AngioVue; Optovue Inc.) scanning sessions on each of 2 separate days to assess intravisit and intervisit reproducibility. A series of ONH and macula scans were acquired at each session. Vessel density (%), the proportion of vessel area over the total measurement area was calculated. Reproducibility was summarized using coefficients of variation (CV) and intraclass correlation coefficients calculated from variance component models. Results: In healthy eyes, the CV of intravisit and intervisit global vessel density measures ranged from 1.8% to 3.2% in ONH scans and 2.5% to 9.0% in macular scans. In glaucoma eyes, the CV of intravisit and intervisit global vessel density measures ranged from 2.3% to 4.1% in ONH scans and 3.2% to 7.9% in macular scans. CVs were lower for global than sectorial measures. Global OCT-A ONH intraclass correlation measurements for the retinal nerve fiber layer in healthy eyes were lower (range: 0.65 to 0.85) than in glaucoma eyes (range: 0.89 to 0.94). Scan size did not make large differences in measurement CVs. Conclusions: Reproducibility of OCT-A ONH and macula vessel density measurements is good. Moreover, glaucoma patients have sparser vessel density with poorer reproducibility than healthy subjects.

What rates of glaucoma progression are clinically significant

ABSTRACT Introduction: Clinically important rates of glaucoma progression (worsening) are ones that put a patient at risk of future functional impairment or reduction of vision-related quality of life (VRQoL). Most treated eyes do not progress at rates that will lead to future visual impairment, but there are a significant proportion (3–17%) of eyes, that are at risk of impairment even under clinical care. While very fast rates of progression (e.g. MD progression of –1.5 dB/year) are generally problematic, much slower rates also may be deleterious for young patients, particularly those diagnosed with late disease. Areas covered: This review provides an overview of what we know about rates of glaucomatous visual field and structural loss. It also summarizes the literature on what stage of vision loss affects vision related quality of life, and the value of predicting functional impairment based on life expectancy and severity of the disease. Expert commentary: It is important to consider life expectancy, disease severity and vision-related quality of life based treatment targets to estimate future prognosis when evaluating whether a rate of glaucoma progression can be clinically relevant.

Are rates of vision loss in patients in English glaucoma clinics slowing down over time? Trends from a decade of data.

PurposeTo examine changes in rates of visual field (VF) progression in patients attending a sample of glaucoma clinics in England between 1999 and 2012.MethodsAn archive of 473 252 Humphrey VFs recorded across the UK was retrospectively examined. Distribution of rates recorded in the first half of the decade was compared with the second. The relationship between age and severity of MD loss at baseline with rates of loss and frequency of testing was examined.ResultsVF series from 18 926 eyes were analysed. Median rate of MD loss for the period before and after 2003 was −0.11 and −0.06 dB/year, respectively, but the proportion of eyes with medium or fast rates of MD loss remained constant. Median rate of MD loss in older (>70 years) eyes was faster than that observed in younger (<60 years) eyes (−0.21 compared with −0.01 dB/year). Median rate of loss did not vary with severity of MD loss at baseline. Frequency of testing, typically carried out annually, did not vary by age, rate of loss or disease severity.ConclusionsVFs of eyes treated in the first half of the decade deteriorated more rapidly than those in the second half. Several factors might explain these differences but average effects were small and there was no reduction in the proportion of rapidly progressing eyes over the decade. Older age and, to a lesser extent, worse VF damage at diagnosis are indicators for faster VF loss in clinics, but frequency of VF testing was similar for all patients.

Patterns of Binocular Visual Field Loss Derived from Large-Scale Patient Data from Glaucoma Clinics

PURPOSE To estimate prevalence of visual field (VF) loss in superior and inferior hemifields in binocular VFs in a large sample of patients with bilateral glaucoma. DESIGN Retrospective cohort study. PARTICIPANTS Glaucoma patients and suspects attending 4 regionally different secondary-care eye clinics in the United Kingdom. METHODS Binocular integrated visual fields (IVFs) using a best location method were constructed for 16 642 patients with bilateral VF loss. A significant VF defect was defined as 3 or more VF locations less than a certain sensitivity threshold, such as 20 dB. Patients were classified as having a VF defect in the inferior hemifield, superior hemifield, both hemifields, or neither hemifield. The criteria for number of locations and sensitivity threshold (in decibels) were varied across a large range of values. In addition, factor analysis was applied to the sensitivity values (in decibels) of the IVFs to determine common defect patterns in an automated fashion. MAIN OUTCOME MEASURES Ratio of patients with binocular VF defects in the superior compared with the inferior areas of the IVF. RESULTS Estimates of the ratio of patients having binocular VF defects in the superior compared with the inferior region of the IVF ranged from 2.1 (95% confidence interval, 2.1-2.4) to as high as 5.1 (95% confidence interval, 4.7-5.5), depending on the defect criteria used. Fewer than 10% of those patients exhibiting relatively early binocular VF loss had a defect confined to the inferior region only. Common patterns of binocular VF loss were dominated chiefly by superior hemifield defects. CONCLUSIONS In a clinical population of patients with measurable VF loss in both eyes, superior-only binocular VF loss is more common than inferior-only loss. These estimates, derived from large collections of electronic medical records, are useful for interpreting findings about location of binocular VF loss impacting everyday activities and examining visual disability in glaucoma.