Evaluation of non-exudative microcystoid macular abnormalities secondary to retinal vein occlusion.

PURPOSE: We aimed to investigate non-exudative microcystoid macular abnormalities for visual and anatomical outcome in patients with retinal vein occlusion (RVO) with and without glaucomatous optic neuropathy (GON). METHODS: Medical records of 124 eyes (105 patients) with RVO were reviewed and analyzed. Eyes demonstrating microcystoid macular abnormalities were divided into 2 groups, those with evidence of glaucoma (group A) and those without glaucoma (group B). Best-corrected visual acuity (BCVA), the prevalence and number of microcystoid macular abnormalities, and number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were compared at baseline and follow-up. RESULTS: Seventy-one out of 105 eyes (67.6%) with RVO displayed microcystoid macular abnormalities. Thirty-eight out of 71 eyes (53.5%) presented with concomitant glaucoma (group A), while the remaining 33 eyes (42.6%) had no history of glaucoma (group B). At the end of the follow-up period, mean BCVA was worse in group A versus group B (20/80 versus 20/40, respectively; p = .003). The mean number of anti-VEGF injections was 10.1 ± 9.2 in group A versus 5.9 ± 6.9 in group B (p = .03). CONCLUSION: Eyes with RVO and concomitant glaucoma exhibited a significantly higher number of microcystoid macular abnormalities and worse BCVA versus eyes with RVO without glaucoma.

Longitudinal Macular Structure-Function Relationships in Glaucoma.

PURPOSE: To investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. METHODS: OCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity. MAIN OUTCOME MEASURES: Magnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time. RESULTS: The median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding. CONCLUSIONS: Correlations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

Predictors of Long-Term Visual Field Fluctuation in Glaucoma Patients.

PURPOSE: To identify predictive factors for visual field (VF) fluctuation in glaucoma patients. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 1392 eyes (816 patients) with 6 or more VFs and 3 years or more of follow-up. METHODS: For each eye, the VF mean deviation (MD) and the pointwise sensitivities were regressed against time to model the series trend, and the root mean square error (RMSE) was estimated as a measure of variability. Potential predictors were selected with least absolute shrinkage and selection operator regression and included eye laterality, ethnicity, glaucoma type, intraocular pressure (IOP) fluctuation, baseline best corrected-visual acuity, intervening cataract or glaucoma surgery, length of follow-up, frequency of testing, baseline MD, rates of VF progression, and median false positive (FP) and false negative (FN) responses. MAIN OUTCOME MEASURES: Predictors of global and pointwise VF long-term fluctuation. RESULTS: In the global model, left eye (0.063 dB; P = 0.022), Asian descent (0.265 dB; P = 0.006), larger IOP fluctuation (0.051 dB; P < 0.001), intervening cataract surgery (0.090 dB; P = 0.023), longer follow-up (0.130 dB; P < 0.001), worse baseline MD (-0.145 dB; P < 0.001), faster VF decay rate (-0.090 dB; P < 0.001), and higher FP rate (0.145 dB; P < 0.001) and FN rate (0.220 dB; P < 0.001) were predictors of VF fluctuation. In the pointwise model, larger IOP fluctuation (0.039 dB; P = 0.022), longer follow-up (0.340 dB; P < 0.001), higher VF frequency (0.238 dB; P = 0.002), intervening glaucoma surgery (0.190 dB; P = 0.01), worse baseline MD (-0.535 dB; P < 0.001), faster VF decay rate (-0.340 dB; P < 0.001), and higher FP rate (0.255 dB; P < 0.001) and FN rate (0.395 dB; P < 0.001) were associated with increased fluctuation. The multivariable model explained 57% and 28% of the pointwise and global variances, respectively. CONCLUSIONS: This study identified novel predictors of VF fluctuation, and explains nearly 60% of the pointwise variance. In the presence of factors predictive of high fluctuation, increased frequency of testing and better analytics will help to identify VF progression more accurately.

Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. METHODS: A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. RESULTS: Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. CONCLUSIONS: Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.

The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. METHODS: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation. RESULTS: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. CONCLUSIONS: Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.

Laser Peripheral Iridotomy in Primary Angle Closure: A Report by the American Academy of Ophthalmology.

PURPOSE: To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). METHODS: Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. RESULTS: Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2% to 57% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0%-8% of PAC suspect (PACS), 42% to 67% of PAC, 21% to 47% of acute PAC (APAC), and 83%-100% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0% to 0.3% per year in PACS and 0% to 4% per year in PAC. Complications after LPI included IOP spike (8-17 mmHg increase from baseline in 6%-10%), dysphotopsia (2%-11%), anterior chamber bleeding (30%-41%), and cataract progression (23%-39%). CONCLUSIONS: Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.

Spectral-Domain OCT: Helping the Clinician Diagnose Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current published literature on the use of spectral domain (SD) OCT to help detect changes associated with the diagnosis of glaucoma. METHODS: Searches of the peer-reviewed literature were conducted on June 11, 2014, November 7, 2016, August 8, 2017, and April 19, 2018, in the PubMed and Cochrane Library databases and included only articles published since the last glaucoma imaging Ophthalmic Technology Assessment, which included articles up until February 2006. The abstracts of these 708 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 74 articles were selected, and the panel methodologist (K.N.-M.) assigned ratings to them according to the level of evidence. Two articles were rated level I, 57 articles were rated level II, and the 15 level III articles were excluded. RESULTS: Spectral-domain OCT is capable of detecting damage to the retinal nerve fiber layer (RNFL), macula, and optic nerve in patients with preperimetric and perimetric glaucoma (level I and II evidence). The most commonly studied single parameter was RNFL thickness. Of note, RNFL thickness measurements are not interchangeable between instruments. Various commercially available SD OCT instruments have similar abilities to distinguish patients with known glaucoma from normal subjects. Despite different software protocols, all SD OCT instruments are able to detect the same typical pattern of glaucomatous RNFL loss that affects primarily the inferior, inferior temporal, superior, and superior temporal regions of the optic nerve (level II evidence). Across many SD OCT instruments, macular imaging also can detect a preferential inferior, inferior temporal, and superior temporal thinning in patients with glaucoma compared with controls. Best disc parameters for detecting glaucomatous nerve damage are global rim area, inferior rim area, and vertical cup-to-disc ratio. Studies suggest that newer reference-plane independent optic nerve parameters may have the same or better detection capability when compared with older reference-plane dependent disc parameters (level II evidence). CONCLUSIONS: Structural glaucomatous damage can be detected by SD OCT. Optic nerve, RNFL, and macular parameters can help the clinician distinguish the anatomic changes that are associated with patients with glaucoma when compared with normal subjects.

Disinfection of Tonometers: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.

Trabeculectomy Can Improve Long-Term Visual Function in Glaucoma.

PURPOSE: To measure the magnitude and direction of visual field (VF) rates of change in glaucoma patients after intraocular pressure (IOP) reduction with trabeculectomy. DESIGN: Retrospective, comparative, longitudinal cohort study. PARTICIPANTS: Patients with open-angle glaucoma. METHODS: Patients who underwent trabeculectomy (Trab) with mitomycin-C (74 eyes of 64 patients) with ≥4 reliable VF measurements before and after trabeculectomy and at least 4 years of follow-up before and after surgery were included. Decay or improvement exponential models were used to calculate pointwise rates of perimetric change before and after surgery. A separate comparison (Comp) group with unoperated glaucoma (71 eyes of 65 patients) with similar baseline damage, number of VF tests, and follow-up was used to address possible regression to the mean. Proportions of VF locations decaying or improving before and after surgery in the Trab group, and during the first and second halves of follow-up in the Comp group, were calculated. A multivariate analysis was used to explore variables associated with VF improvement. MAIN OUTCOME MEASURES: The rate of pointwise VF change before and after surgery in the Trab group and Comp group. RESULTS: Patients in the Trab group were followed for 5.1±2.1 years (mean ± standard deviation) before and 5.4±2.3 years after surgery, with 8.9±4.7 VF tests before and 9.0±4.4 VF tests after surgery. The mean rate of change for all VF locations slowed from -2.5±9.3%/year before surgery to -0.10±13.1%/year after surgery (P < 0.001). In the Trab group, 70% of locations decayed and 30% improved preoperatively; postoperatively, 56% decayed and 44% improved. The differences between the Trab and Comp groups were significant (P < 0.0001, chi-square test). The magnitude of IOP reduction correlated with the excess number of VF locations that exhibited long-term improvement postoperatively (P = 0.009). In the Trab group, 57% of eyes had ≥10 improving VF locations postoperatively. CONCLUSIONS: The results show that trabeculectomy slows the rate of perimetric decay and provide evidence of sustained, long-term improvement of visual function in glaucoma. These findings suggest the possibility of reversal of glaucomatous dysfunction of retinal ganglion cells and their central projections.

Detecting Fast Progressors: Comparing a Bayesian Longitudinal Model to Linear Regression for Detecting Structural Changes in Glaucoma.

PURPOSE: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model identifies macular superpixels with rapidly deteriorating ganglion cell complex (GCC) thickness more efficiently than simple linear regression (SLR). DESIGN: Prospective cohort study. SETTING: Tertiary Glaucoma Center. SUBJECTS: One hundred eleven eyes (111 patients) with moderate to severe glaucoma at baseline and ≥4 macular optical coherence tomography scans and ≥2 years of follow-up. OBSERVATION PROCEDURE: Superpixel-patient-specific GCC slopes and their posterior variances in 49 superpixels were derived from our latest Bayesian HSL model and Bayesian SLR. A simulation cohort was created with known intercepts, slopes, and residual variances in individual superpixels. MAIN OUTCOME MEASURES: We compared HSL and SLR in the fastest progressing deciles on (1) proportion of superpixels identified as significantly progressing in the simulation study and compared to SLR slopes in cohort data; (2) root mean square error (RMSE), and SLR/HSL RMSE ratios. RESULTS: Cohort- In the fastest decile of slopes per SLR, 77% and 80% of superpixels progressed significantly according to SLR and HSL, respectively. The SLR/HSL posterior SD ratio had a median of 1.83, with 90% of ratios favoring HSL. Simulation- HSL identified 89% significant negative slopes in the fastest progressing decile vs 64% for SLR. SLR/HSL RMSE ratio was 1.36 for the fastest decile of slopes, with 83% of RMSE ratios favoring HSL. CONCLUSION: The Bayesian HSL model improves the estimation efficiency of local GCC rates of change regardless of underlying true rates of change, particularly in fast progressors.

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell Complex Rates of Change in Patients with Moderate to Advanced Glaucoma.

PURPOSE: To compare ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) rates of change (RoC) in eyes with central or moderate to advanced glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: 918 matched macular and RNFL OCT scan pairs from 109 eyes (109 patients) enrolled in the Advanced Glaucoma Progression Study with ≥2 years of follow-up and ≥4 OCT scans. METHODS: We exported GCC and RNFL thickness measurements in 49 central macular superpixels and 12 RNFL clock-hour sectors, respectively. We applied our latest Bayesian hierarchical longitudinal model to estimate population and subject-specific baseline thickness (intercepts) and rates of change (RoC) in macular superpixels and RNFL sectors. Global RNFL and GCC RoC were analyzed in a single bivariate longitudinal model to properly compare them accounting for the correlation between their RoC. MAIN OUTCOME MEASURES: Proportion of significant negative (deteriorating) and positive (improving) RoC expressed in µm/year. Standardized RoC were calculated by dividing RoC by the corresponding population SD. Analyses were repeated in eyes with visual field mean deviation (MD) ≤-6 and >-6 dB. RESULTS: Average (SD) 24-2 visual field MD and follow-up length were -8.6 (6.3) dB and 4.2 (0.5) years, respectively. Global RNFL RoC (-0.70 µm/year) were faster than GCC (-0.44 µm/year) (p<.001); corresponding normalized RoC were not significantly different (p=0.052). In bivariate analysis, patients with a significant negative global RNFL RoC (n=63, 57%) or GCC (n=56, 51%) frequently did so for both outcomes (n=49, 45%). The average proportion of significantly decreasing RNFL sectors within an eye was 30.7% in eyes with MD >-6 dB compared to 20.5% in those with MD ≤-6 dB (p=0.014); the proportions for GCC superpixels were 21.1% vs. 18.7%, respectively (p=0.63). CONCLUSIONS: Both GCC and RNFL measures can detect structural progression in glaucoma patients with central damage or moderate to advanced glaucoma. The clinical utility of RNFL imaging decreases with worsening severity of glaucoma.

Efficacy of Smoothing Algorithms to Enhance Detection of Visual Field Progression in Glaucoma.

Purpose: To evaluate and compare the effectiveness of nearest neighbor (NN)- and variational autoencoder (VAE)-smoothing algorithms to reduce variability and enhance the performance of glaucoma visual field (VF) progression models. Design: Longitudinal cohort study. Subjects: 7150 eyes (4232 patients), with ≥ 5 years of follow-up and ≥ 6 visits. Methods: Vsual field thresholds were smoothed with the NN and VAE algorithms. The mean total deviation (mTD) and VF index rates, pointwise linear regression (PLR), permutation of PLR (PoPLR), and the glaucoma rate index were applied to the unsmoothed and smoothed data. Main Outcome Measures: The proportion of progressing eyes and the conversion to progression were compared between the smoothed and unsmoothed data. A simulation series of noiseless VFs with various patterns of glaucoma damage was used to evaluate the specificity of the smoothing models. Results: The mean values of age and follow-up time were 62.8 (standard deviation: 12.6) years and 10.4 (standard deviation: 4.7) years, respectively. The proportion of progression was significantly higher for the NN and VAE smoothed data compared with the unsmoothed data. VF progression occurred significantly earlier with both smoothed data compared with unsmoothed data based on mTD rates, PLR, and PoPLR methods. The ability to detect the progressing eyes was similar for the unsmoothed and smoothed data in the simulation data. Conclusions: Smoothing VF data with NN and VAE algorithms improves the signal-to-noise ratio for detection of change, results in earlier detection of VF progression, and could help monitor glaucoma progression more effectively in the clinical setting. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An Artificial Intelligence Enabled System for Retinal Nerve Fiber Layer Thickness Damage Severity Staging.

Purpose: To develop an objective glaucoma damage severity classification system based on OCT-derived retinal nerve fiber layer (RNFL) thickness measurements. Design: Algorithm development for RNFL damage severity classification based on multicenter OCT data. Subjects and Participants: A total of 6561 circumpapillary RNFL profiles from 2269 eyes of 1171 subjects to develop models, and 2505 RNFL profiles from 1099 eyes of 900 subjects to validate models. Methods: We developed an unsupervised k-means model to identify clusters of eyes with similar RNFL thickness profiles. We annotated the clusters based on their respective global RNFL thickness. We computed the optimal global RNFL thickness thresholds that discriminated different severity levels based on Bayes' minimum error principle. We validated the proposed pipeline based on an independent validation dataset with 2505 RNFL profiles from 1099 eyes of 900 subjects. Main Outcome Measures: Accuracy, area under the receiver operating characteristic curve, and confusion matrix. Results: The k-means clustering discovered 4 clusters with 1382, 1613, 1727, and 1839 samples with mean (standard deviation) global RNFL thickness of 58.3 (8.9) µm, 78.9 (6.7) µm, 87.7 (8.2) µm, and 101.5 (7.9) µm. The Bayes' minimum error classifier identified optimal global RNFL values of > 95 µm, 86 to 95 µm, 70 to 85 µm, and < 70 µm for discriminating normal eyes and eyes at the early, moderate, and advanced stages of RNFL thickness loss, respectively. About 4% of normal eyes and 98% of eyes with advanced RNFL loss had either global, or ≥ 1 quadrant, RNFL thickness outside of normal limits provided by the OCT instrument. Conclusions: Unsupervised machine learning discovered that the optimal RNFL thresholds for separating normal eyes and eyes with early, moderate, and advanced RNFL loss were 95 µm, 85 µm, and 70 µm, respectively. This RNFL loss classification system is unbiased as there was no preassumption or human expert intervention in the development process. Additionally, it is objective, easy to use, and consistent, which may augment glaucoma research and day-to-day clinical practice. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Bayesian Hierarchical Spatial Longitudinal Model Improves Estimation of Local Macular Rates of Change in Glaucomatous Eyes.

Purpose: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model improves estimation of local macular ganglion cell complex (GCC) rates of change compared to simple linear regression (SLR) and a conditional autoregressive (CAR) model. Methods: We analyzed GCC thickness measurements within 49 macular superpixels in 111 eyes (111 patients) with four or more macular optical coherence tomography scans and two or more years of follow-up. We compared superpixel-patient-specific estimates and their posterior variances derived from the latest version of a recently developed Bayesian HSL model, CAR, and SLR. We performed a simulation study to compare the accuracy of intercept and slope estimates in individual superpixels. Results: HSL identified a significantly higher proportion of significant negative slopes in 13/49 superpixels and a significantly lower proportion of significant positive slopes in 21/49 superpixels than SLR. In the simulation study, the median (tenth, ninetieth percentile) ratio of mean squared error of SLR [CAR] over HSL for intercepts and slopes were 1.91 (1.23, 2.75) [1.51 (1.05, 2.20)] and 3.25 (1.40, 10.14) [2.36 (1.17, 5.56)], respectively. Conclusions: A novel Bayesian HSL model improves estimation accuracy of patient-specific local GCC rates of change. The proposed model is more than twice as efficient as SLR for estimating superpixel-patient slopes and identifies a higher proportion of deteriorating superpixels than SLR while minimizing false-positive detection rates. Translational Relevance: The proposed HSL model can be used to model macular structural measurements to detect individual glaucoma progression earlier and more efficiently in clinical and research settings.

Prediction of Visual Field Progression with Baseline and Longitudinal Structural Measurements Using Deep Learning.

PURPOSE: Identifying glaucoma patients at high risk of progression based on widely available structural data is an unmet task in clinical practice. We test the hypothesis that baseline or serial structural measures can predict visual field (VF) progression with deep learning (DL). DESIGN: Development of a DL algorithm to predict VF progression. METHODS: 3,079 eyes (1,765 patients) with various types of glaucoma and ≥5 VFs, and ≥3 years of follow-up from a tertiary academic center were included. Serial VF mean deviation (MD) rates of change were estimated with linear-regression. VF progression was defined as negative MD slope with p<0.05. A Siamese Neural Network with ResNet-152 backbone pre-trained on ImageNet was designed to predict VF progression using serial optic-disc photographs (ODP), and baseline retinal nerve fiber layer (RNFL) thickness. We tested the model on a separate dataset (427 eyes) with RNFL data from different OCT. The Main Outcome Measure was Area under ROC curve (AUC). RESULTS: Baseline average (SD) MD was 3.4 (4.9)dB. VF progression was detected in 900 eyes (29%). AUC (95% CI) for model incorporating baseline ODP and RNFL thickness was 0.813 (0.757-0.869). After adding the second and third ODPs, AUC increased to 0.860 and 0.894, respectively (p<0.027). This model also had highest AUC (0.911) for predicting fast progression (MD rate <1.0 dB/year). Model's performance was similar when applied to second dataset using RNFL data from another OCT device (AUC=0.893; 0.837-0.948). CONCLUSIONS: DL model predicted VF progression with clinically relevant accuracy using baseline RNFL thickness and serial ODPs and can be implemented as a clinical tool after further validation.

National Eye Institute Visual Function Questionnaire: usefulness in glaucoma.

The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) is the most commonly used patient-reported outcome measure to assess vision-related quality of life in patients with glaucoma. Glaucoma negatively affects the composite and several NEI-VFQ subscale scores; this effect is correlated with the severity of glaucomatous visual field loss. Contrast sensitivity, glare, and dark adaptation are potential items that could be added to the NEI-VFQ to make it more responsive to changes in vision-related quality of life in patients with glaucoma.

Combined phacoviscocanalostomy versus phacoemulsification alone in patients with coexisting cataract and mild-to-moderate open-angle glaucoma; a randomized-controlled trial.

BACKGROUND/OBJECTIVE: Management of concomitant cataract and glaucoma depends on the stage of glaucoma and the patient's situation. There are different surgical options for handling visually significant cataract and mild-to-moderate open-angle glaucoma (OAG). We aimed to compare the one-year results of phacoemulsification alone versus phacoviscocanalostomy in these patients. SUBJECTS/METHODS: This was a parallel-arm, single-masked, randomized-controlled trial, conducted at Farabi Eye Hospital, Tehran, Iran between January 2016 and January 2018. We enrolled 89 eyes from 89 patients with mild-to-moderate primary OAG or pseudoexfoliative glaucoma (PEXG) with visually significant age-related cataract. They randomly underwent phacoemulsification alone (n = 44) or combined phaco-viscocanalostomy (n = 45). All patients had a 12-month follow-up period, and the mean intraocular pressure (IOP), the number of antiglaucoma medications, and complete and qualified success rates were compared. RESULTS: After the 1st and 3rd months, the mean IOP showed significantly decreased in the phaco-visco group compared to the phaco group (P < 0001 and P = 0.004, respectively), but it was not statistically significant at 6th and 12th months (P = 0.540 and P = 0.530). The need for antiglaucoma medication and the complete and qualified success rates were significantly in favour of the phaco-visco group in all postoperative visits (P < 0.05). CONCLUSIONS: Although both phacoemulsification alone and phacoviscocanalostomy procedures can be considered for patients with mild-to-moderate OAG, we found better success rates using phacoviscocanalostomy. Therefore, if the surgeon is an expert in performing this technique, this non-penetrating procedure can be applied in patients with visually significant cataract and earlier stages of OAG, especially in patients with PEXG.