The Future of Imaging in Detecting Glaucoma Progression.
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ABSTRACT:
SUBMITTER: Lavinsky F
PROVIDER: S-EPMC5777232 | biostudies-other | 2017 Dec
REPOSITORIES: biostudies-other
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The Future of Imaging in Detecting Glaucoma Progression.
Lavinsky Fabio F Wollstein Gadi G Tauber Jenna J Schuman Joel S JS
Ophthalmology 20171201 12S
Ocular imaging has been heavily incorporated into glaucoma management and provides important information that aids in the detection of disease progression. Longitudinal studies have shown that the circumpapillary retinal nerve fiber layer is an important parameter for glaucoma progression detection, whereas other studies have demonstrated that macular parameters, such as the ganglion cell inner plexiform layer and optic nerve head parameters, also are useful for progression detection. The introd ...[more]
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Project description:PURPOSE:To evaluate whether loss of 5 ?m or more in global retinal nerve fiber layer (RNFL) thickness on spectral-domain (SD) between 2 consecutive visits is specific for glaucoma progression. DESIGN:Prospective cohort. PARTICIPANTS:Ninety-two eyes of 49 control participants and 300 eyes of 210 glaucoma patients. METHODS:Patients completed at least 5 standard automated perimetry and SD OCT examinations at 6-month intervals over at least 2 years. Eyes were categorized as progressing from glaucoma if the average RNFL declined by 5 ?m or more between 2 consecutive visits. The false-positive proportion was estimated by 2 methods: (1) 5-?m or more loss in control participants and (2) 5-?m or more gain in glaucoma. The false-positive proportion was subtracted from the cumulative proportion of eyes categorized with glaucoma progression to estimate the true progression prevalence. MAIN OUTCOME MEASURES:False-positive and true progression prevalence of patients with glaucoma detected as progressing on SD OCT. RESULTS:After 5 years of semiannual testing, the cumulative proportion of false-positive results based on 5-?m or more RNFL losses between visits was 24.8% in the control participants. Although 40.6% of glaucoma eyes were diagnosed with progression at 5 years, only 15.8% would have been considered to show true progression based on the expected false-positive ratio from the control participants (i.e., 40.6%-24.8%). The cumulative proportion of an intervisit gain of 5 ?m or more at 5 years was 27.4% in glaucoma eyes, suggesting that only 13.2% of eyes with glaucoma truly had progressed (i.e., 40.6%-27.4%). CONCLUSIONS:Loss of 5 ?m or more in average RNFL thickness between consecutive SD OCT tests is not specific for glaucoma progression. Application of this intervisit rule of 5 can result in a high cumulative proportion of false-positive results over time, which could lead to unnecessary interventions in patients whose disease is stable. More specific diagnostic criteria are needed to help clinicians determine whether patients with glaucoma are progressing so that therapy escalation is both timely and appropriate.
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Project description:PurposeThe rule of 5 is a simple rule for detecting retinal nerve fiber layer (RNFL) change on spectral-domain OCT (SD-OCT), in which a loss of 5 μm of global RNFL on a follow-up test is considered evidence of significant change when compared with the baseline. The rule is based on short-term test-retest variability of SD-OCT and is often used in clinical practice. The purpose of this study was to compare the rule of 5 with trend-based analysis of global RNFL thickness over time for detecting glaucomatous progression.DesignProspective cohort.ParticipantsA total of 300 eyes of 210 glaucoma subjects followed for an average of 5.4±1.5 years with a median of 11 (interquartile range, 7-14) visits.MethodsTrend-based analysis was performed by ordinary least-squares (OLS) linear regression of global RNFL thickness over time. For estimation of specificity, false-positives were obtained by assessing for progression on series of randomly permutated follow-up visits for each eye, which removes any systematic trend over time. The specificity of trend-based analysis was matched to that of the rule of 5 to allow meaningful comparison of the "hit rate," or the proportion of glaucoma eyes categorized as progressing at each time point, using the original sequence of visits.Main outcome measuresComparison between hit rates of trend-analysis versus rule of 5 at matched specificity.ResultsAfter 5 years, the simple rule of 5 identified 37.5% of eyes as progressing at a specificity of 81.1%. At the same specificity, the hit rate for trend-based analysis was significantly greater than that of the rule of 5 (62.9% vs. 37.5%; P < 0.001). If the rule of 5 was required to be repeatable on a consecutive test, specificity improved to 93.4%, but hit rate decreased to 21.0%. At this higher specificity, trend-based analysis still had a significantly greater hit rate than the rule of 5 (47.4% vs. 21.0%, respectively; P < 0.001).ConclusionsTrend-based analysis was superior to the simple rule of 5 for identifying progression in glaucoma eyes and should be preferred as a method for longitudinal assessment of global SD-OCT RNFL change over time.
| S-EPMC7704802 | biostudies-literature
Project description:ObjectiveTo evaluate the ability of a binocular automated pupillograph to discriminate healthy subjects from those with glaucoma.DesignCross-sectional observational study.ParticipantsBoth eyes of 116 subjects, including 66 patients with glaucoma in at least 1 eye and 50 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Eyes were classified as glaucomatous by repeatable abnormal standard automated perimetry (SAP) or progressive glaucomatous changes on stereophotographs.MethodsAll subjects underwent automated pupillography using the RAPDx pupillograph (Konan Medical USA, Inc., Irvine, CA).Main outcome measuresReceiver operating characteristic (ROC) curves were constructed to assess the diagnostic ability of pupil response parameters to white, red, green, yellow, and blue full-field and regional stimuli. A ROC regression model was used to investigate the influence of disease severity and asymmetry on diagnostic ability.ResultsThe largest area under the ROC curve (AUC) for any single parameter was 0.75. Disease asymmetry (P <0.001), but not disease severity (P = 0.058), had a significant effect on diagnostic ability. At the sample mean age (60.9 years), AUCs for arbitrary values of intereye difference in SAP mean deviation (MD) of 0, 5, 10, and 15 dB were 0.58, 0.71, 0.82, and 0.90, respectively. The mean intereye difference in MD was 2.2±3.1 dB. The best combination of parameters had an AUC of 0.85; however, the cross-validated bias-corrected AUC for these parameters was only 0.74.ConclusionsAlthough the pupillograph had a good ability to detect glaucoma in the presence of asymmetric disease, it performed poorly in those with symmetric disease.
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Project description:Purpose: To determine if ultrasonography is necessary to detect progression of choroidal melanocytic tumors undergoing sequential multi-modal imaging with color photography, autofluorescence (AF) and optical coherence tomography (OCT). Methods: All patients with choroidal melanoma undergoing treatment at Moorfields Eye Hospital between January 2016 and March 2020 were reviewed to identify those with treatment deferred by ?2 months. Tumors that showed progression prior to treatment, defined as an increase in (a) basal dimensions (b) thickness (c) orange pigment and/or (d) sub-retinal fluid, were included. Mushroom shape, Orange pigment, Large size, Enlargement and Sub-retinal fluid (MOLES) scores were assigned to all tumors at earliest date and date of treatment. Results: A total of 99 patients with a mean age of 66 years (range: 26-90) were included. The initial MOLES score was 1 in 2 cases, 2 in 23 cases, and ?3 in 74 cases. Progression was detected with sequential color photography alone in 100% of MOLES 1/2 and 97% of lesions with a MOLES score of ?3. When findings on AF and OCT were included, sensitivity for detecting subtle change without ultrasonography improved to 100% for MOLES 3 and 97% for MOLES 4/5. Only one patient included in this study had an isolated increase in thickness that may have been missed had sequential ultrasonography not been performed. Overall, the sensitivity for detecting progression with color photographs alone was 97% (95% CI 93-100%) and increased to 99% (95% CI 97-100%) by including autofluorescence and OCT. Conclusions: Monitoring of choroidal nevi, particularly those classified as MOLES 1 or 2 (i.e., low-risk or high-risk naevi), can be accomplished safely without the need for ultrasonography. The findings of this study may remove barriers to the implementation of tele-oncology clinics for the monitoring of choroidal melanocytic tumors.
| S-EPMC7408899 | biostudies-literature
Project description:In this manuscript we develop a deep learning algorithm to improve estimation of rates of progression and prediction of future patterns of visual field loss in glaucoma. A generalized variational auto-encoder (VAE) was trained to learn a low-dimensional representation of standard automated perimetry (SAP) visual fields using 29,161 fields from 3,832 patients. The VAE was trained on a 90% sample of the data, with randomization at the patient level. Using the remaining 10%, rates of progression and predictions were generated, with comparisons to SAP mean deviation (MD) rates and point-wise (PW) regression predictions, respectively. The longitudinal rate of change through the VAE latent space (e.g., with eight dimensions) detected a significantly higher proportion of progression than MD at two (25% vs. 9%) and four (35% vs 15%) years from baseline. Early on, VAE improved prediction over PW, with significantly smaller mean absolute error in predicting the 4th, 6th and 8th visits from the first three (e.g., visit eight: VAE8: 5.14?dB vs. PW: 8.07?dB; P?<?0.001). A deep VAE can be used for assessing both rates and trajectories of progression in glaucoma, with the additional benefit of being a generative technique capable of predicting future patterns of visual field damage.
| S-EPMC6888896 | biostudies-literature
Project description:Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO-VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP-lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.
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Project description:We evaluated three new pixelwise rates of retinal height changes (PixR) strategies to reduce false-positive errors while detecting glaucomatous progression.Diagnostic accuracy of nonparametric PixR-NP cluster test (CT), PixR-NP single threshold test (STT), and parametric PixR-P STT were compared to statistic image mapping (SIM) using the Heidelberg Retina Tomograph. We included 36 progressing eyes, 210 nonprogressing patient eyes, and 21 longitudinal normal eyes from the University of California, San Diego (UCSD) Diagnostic Innovations in Glaucoma Study. Multiple comparison problem due to simultaneous testing of retinal locations was addressed in PixR-NP CT by controlling family-wise error rate (FWER) and in STT methods by Lehmann-Romano's k-FWER. For STT methods, progression was defined as an observed progression rate (ratio of number of pixels with significant rate of decrease; i.e., red-pixels, to disk size) > 2.5%. Progression criterion for CT and SIM methods was presence of one or more significant (P < 1%) red-pixel clusters within disk.Specificity in normals: CT = 81% (90%), PixR-NP STT = 90%, PixR-P STT = 90%, SIM = 90%. Sensitivity in progressing eyes: CT = 86% (86%), PixR-NP STT = 75%, PixR-P STT = 81%, SIM = 39%. Specificity in nonprogressing patient eyes: CT = 49% (55%), PixR-NP STT = 56%, PixR-P STT = 50%, SIM = 79%. Progression detected by PixR in nonprogressing patient eyes was associated with early signs of visual field change that did not yet meet our definition of glaucomatous progression.The PixR provided higher sensitivity in progressing eyes and similar specificity in normals than SIM, suggesting that PixR strategies can improve our ability to detect glaucomatous progression. Longer follow-up is necessary to determine whether nonprogressing eyes identified as progressing by these methods will develop glaucomatous progression. (ClinicalTrials.gov number, NCT00221897).
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Project description:PurposeVarious global indices are available to summarize results from standard automated perimetry. This study asks which index can detect significant deterioration earliest, for a fixed specificity.DesignComparison of prognostic indices.MethodsTwo cohorts were tested. A test-retest cohort contained 5 reliable visual fields, within a short interval, from 45 eyes of 23 participants with glaucoma and/or likelihood of developing glaucoma. A separate longitudinal cohort contained 508 eyes from 330 participants, tested on average 13 times. Three global indices were extracted: mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). For each index we defined a critical P value CritIndex, such that 5% of test-retest series showed significant deterioration with P < CritIndex, using artificial "test dates" in random order. Therefore these criteria have 95% specificity over series of 5 tests. The times to detect significant deterioration in the longitudinal cohort were compared using a survival analysis model.ResultsThe median time to detect significant deterioration with MD was 7.3 years (95% confidence interval [CI] 6.8-7.9 years). For VFI, the median was 8.5 years (95% CI 7.9-9.0 years); this comparison had P = .088. For PSD, the median was 10.5 years (95% CI 9.3-11.7 years), slower than MD with P < .001. Within the first 5 years of a series, MD detected significant deterioration in 138 eyes, vs 104 for VFI (P = .0013) and 107 for PSD (P = .029).ConclusionsMD detected significant deterioration sooner than VFI or PSD. In particular, MD detected more eyes in the first 5 years of their follow-up, which were presumably undergoing more rapid progression.
| S-EPMC5376527 | biostudies-literature
Project description:PurposeTo investigate predictive factors associated with the rate of visual field (VF) loss in open-angle glaucoma.DesignProspective multicenter cohort study.MethodsPerimetric glaucoma patients of the Advanced Imaging for Glaucoma study were selected for analysis if they had 9 completed visits. Confirmed rapid significant progression (CRSP) of VF was defined as a significant (P < 0.05) negative VF index (VFI) slope of -1%/year or a mean deviation slope of -0.5 dB/year, confirmed at 2 consecutive follow-up visits. Slow progression was defined as VFI slope greater than -0.5%/year or a mean deviation slope of -0.25 dB/year. Fourier-domain optical coherence tomography (FD-OCT) measured optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thicknesses. Logistic regression was used to identify baseline predictors for CRSP and slow progression. Linear regression was used to identify baseline predictors for the VFI and mean deviation slope.ResultsEyes (n = 150) of 103 participants were included. Slow progression was observed in 80 eyes (53.3%) and CRSP in 23 eyes (15.3%). Larger NFL and GCC baseline focal loss volume (FLV), thinner central corneal thickness, and lower VFI were significant (P < 0.05) baseline predictors of more rapid progression on univariate analysis. The predictor with the highest odds ratio (OR) was NFL-FLV, which was also the most significant non-VF predictor in the multivariate analysis. Eyes with NFL-FLV >8.5% had an OR of 2.67 for CRSP and 0.42 for slow progression. Disc hemorrhage during the follow-up was also important, with an OR of 2.61 for CRSP and 0.23 for slow progression for each occurrence.ConclusionsFocal loss measured by FD-OCT or VF along with CCT are strong baseline predictors for the rate of glaucoma progression.
| S-EPMC6548618 | biostudies-literature
Project description:ImportanceAutomated deep learning (DL) analyses of fundus photographs potentially can reduce the cost and improve the efficiency of reading center assessment of end points in clinical trials.ObjectiveTo investigate the diagnostic accuracy of DL algorithms trained on fundus photographs from the Ocular Hypertension Treatment Study (OHTS) to detect primary open-angle glaucoma (POAG).Design, setting, and participantsIn this diagnostic study, 1636 OHTS participants from 22 sites with a mean (range) follow-up of 10.7 (0-14.3) years. A total of 66 715 photographs from 3272 eyes were used to train and test a ResNet-50 model to detect the OHTS Endpoint Committee POAG determination based on optic disc (287 eyes, 3502 photographs) and/or visual field (198 eyes, 2300 visual fields) changes. Three independent test sets were used to evaluate the generalizability of the model.Main outcomes and measuresAreas under the receiver operating characteristic curve (AUROC) and sensitivities at fixed specificities were calculated to compare model performance. Evaluation of false-positive rates was used to determine whether the DL model detected POAG before the OHTS Endpoint Committee POAG determination.ResultsA total of 1147 participants were included in the training set (661 [57.6%] female; mean age, 57.2 years; 95% CI, 56.6-57.8), 167 in the validation set (97 [58.1%] female; mean age, 57.1 years; 95% CI, 55.6-58.7), and 322 in the test set (173 [53.7%] female; mean age, 57.2 years; 95% CI, 56.1-58.2). The DL model achieved an AUROC of 0.88 (95% CI, 0.82-0.92) for the OHTS Endpoint Committee determination of optic disc or VF changes. For the OHTS end points based on optic disc changes or visual field changes, AUROCs were 0.91 (95% CI, 0.88-0.94) and 0.86 (95% CI, 0.76-0.93), respectively. False-positive rates (at 90% specificity) were higher in photographs of eyes that later developed POAG by disc or visual field (27.5% [56 of 204]) compared with eyes that did not develop POAG (11.4% [50 of 440]) during follow-up. The diagnostic accuracy of the DL model developed on the optic disc end point applied to 3 independent data sets was lower, with AUROCs ranging from 0.74 (95% CI, 0.70-0.77) to 0.79 (95% CI, 0.78-0.81).Conclusions and relevanceThe model's high diagnostic accuracy using OHTS photographs suggests that DL has the potential to standardize and automate POAG determination for clinical trials and management. In addition, the higher false-positive rate in early photographs of eyes that later developed POAG suggests that DL models detected POAG in some eyes earlier than the OHTS Endpoint Committee, reflecting the OHTS design that emphasized a high specificity for POAG determination by requiring a clinically significant change from baseline.
| S-EPMC8931672 | biostudies-literature