Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

PURPOSE: To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). METHODS: This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. RESULTS: A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1 mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. CONCLUSION: Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. KEY MESSAGES: What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

PURPOSE: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care. DESIGN: Observational study. PARTICIPANTS: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years. METHODS: This study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye. MAIN OUTCOME MEASURES: Prevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes). RESULTS: Based on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively. CONCLUSIONS: This study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Detecting Progression in Advanced Glaucoma: Are Optical Coherence Tomography Global Metrics Viable Measures?

SIGNIFICANCE: Optical coherence tomography (OCT) summary measures have been suggested as a way to detect progression in eyes with advanced glaucoma. Here, we show that these measures have serious flaws largely due to segmentation errors. However, inspection of the images and thickness maps can be clinically useful. PURPOSE: This study aimed to test the hypothesis that recently suggested global OCT measures for detecting progression in eyes with advanced progression are seriously affected by segmentation mistakes and other errors that limit their clinical utility. METHODS: Forty-five eyes of 38 patients with a 24-2 mean deviation worse than -12 dB had at least two spectral domain OCT sessions (0.8 to 4.4 years apart) with 3.5-mm circle scans of the disc and cube scans centered on the fovea. Average (global) circumpapillary retinal nerve fiber layer thickness, GcRNFL, and ganglion cell plus inner plexiform layer thickness, GGCLP, were obtained from the circle and cube scan, respectively. To evaluate progression, ΔGcRNFL was calculated for each eye as the GcRNFL value at time 2 minus the value at time 1, and ΔGGCLP was calculated in a similar manner. The b-scans of the six eyes with the highest and lowest ΔGcRNFL and ΔGGCLP values were examined for progression as well as segmentation, alignment, and centering errors. RESULTS: Progression was a major factor in only 7 of the 12 eyes with the most negative values of either ΔGcRNFL or ΔGGCLP, whereas segmentation played a role in 8 eyes and was the major factor in all 12 eyes with the largest positive values. In addition, alignment (one eye) and other (three eyes) errors played a secondary role in four of the six eyes with the most negative ΔGcRNFL values. CONCLUSIONS: For detecting the progression of advanced glaucoma, common summary metrics have serious flaws largely due to segmentation errors, which limit their utility in clinical and research settings.

Artificial Intelligence Classification of Central Visual Field Patterns in Glaucoma.

PURPOSE: To quantify the central visual field (VF) loss patterns in glaucoma using artificial intelligence. DESIGN: Retrospective study. PARTICIPANTS: VFs of 8712 patients with 13 951 Humphrey 10-2 test results from 13 951 eyes for cross-sectional analyses, and 824 patients with at least 5 reliable 10-2 test results at 6-month intervals or more from 1191 eyes for longitudinal analyses. METHODS: Total deviation values were used to determine the central VF patterns using the most recent 10-2 test results. A 24-2 VF within a 3-month window of the 10-2 tests was used to stage eyes into mild, moderate, or severe functional loss using the Hodapp-Anderson-Parrish scale at baseline. Archetypal analysis was applied to determine the central VF patterns. Cross-validation was performed to determine the optimal number of patterns. Stepwise regression was applied to select the optimal feature combination of global indices, average baseline decomposition coefficients from central VFs archetypes, and other factors to predict central VF mean deviation (MD) slope based on the Bayesian information criterion (BIC). MAIN OUTCOME MEASURES: The central VF patterns stratified by severity stage based on 24-2 test results and a model to predict the central VF MD change over time using baseline test results. RESULTS: From cross-sectional analysis, 17 distinct central VF patterns were determined for the 13 951 eyes across the spectrum of disease severity. These central VF patterns could be divided into isolated superior loss, isolated inferior loss, diffuse loss, and other loss patterns. Notably, 4 of the 5 patterns of diffuse VF loss preserved the less vulnerable inferotemporal zone, whereas they lost most of the remaining more vulnerable zone described by the Hood model. Inclusion of coefficients from central VF archetypical patterns strongly improved the prediction of central VF MD slope (BIC decrease, 35; BIC decrease of >6 indicating strong prediction improvement) than using only the global indices of 2 baseline VF results. Eyes with baseline VF results with more superonasal and inferonasal loss were more likely to show worsening MD over time. CONCLUSIONS: We quantified central VF patterns in glaucoma, which were used to improve the prediction of central VF worsening compared with using only global indices.

An Ultraflexible and Stretchable Aptameric Graphene Nanosensor for Biomarker Detection and Monitoring.

An ultraflexible and stretchable field-effect transistor nanosensor is presented that uses aptamer-functionalized monolayer graphene as the conducting channel. Specific binding of the aptamer with the target biomarker induces a change in the carrier concentration of the graphene, which is measured to determine the biomarker concentration. Based on a Mylar substrate that is only 2.5-µm thick, the nanosensor is capable of conforming to underlying surfaces (e.g., those of human tissue or skin) that undergo large bending, twisting, and stretching deformations. In experimental testing, the device is rolled on cylindrical surfaces with radii down to 40 µm, twisted by angles ranging from -180° to 180°, or stretched by extensions up to 125%. With these large deformations applied either cyclically or non-recurrently, the device is shown to incur no visible mechanical damage, maintain consistent electrical properties, and allow detection of TNF-α, an inflammatory cytokine biomarker, with consistently high selectivity and low limit of detection (down to 5 × 10-12M). The nanosensor can thus potentially enable consistent and reliable detection of liquid-borne biomarkers on human skin or tissue surfaces that undergo large mechanical deformations.

Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms.

PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.

Spatial correlation between localized decreases in exploratory visual search performance and areas of glaucomatous visual field loss.

BACKGROUND: Visual search is a critical skill for several daily tasks and may be compromised in patients with impaired vision. The objective of this study was to study the relationships between exploratory visual search performance (EVSP) visual field (VF) sensitivity in patients with glaucoma. METHODS: Primary open-angle glaucoma patients (POAG; n = 29) and healthy (Control; n = 28) individuals with best corrected visual acuity better than 0.2 logMAR underwent a comprehensive ophthalmological examination, including Humphrey VF tests (24-2 SITA-Standard), and a monocular exploratory visual search digit-based task performed using a software that quantifies the time spent to find a targert on a random array of digits distributed on nine sequential screens. The screens were divided into five areas to topographically match with five VF sectors. RESULTS: As expected, POAG eyes had worse VF mean deviation (MD) sensitivity and EVSP than Controls (MD - 8.02 ± 7.88 dB vs - 1.43 ± 1.50 dB, p < 0.0001; and total EVSP time 106.42 ± 59.64 s vs 52.75 ± 19.07 s, p < 0.0001). MD sensitivity of both groups significantly correlated with total EVSP time (POAG r = - 0.45, p = 0.01; and Control r = 0.37, p = 0.049). A significant relationship was observed between EVSP (individual time) and both visual acuity (p = 0.006) and glaucoma diagnosis (p = 0.005). The mean sensitivity of the peripheral VF areas of the POAG group showed significant correlation with the individual search time in the corresponding spatial areas, except in the peripheral superior temporal area (r = - 0.35, p = 0.06). CONCLUSION: These data indicate that POAG patients' EVSP is impaired in topographically-correspondent VF areas with sensitivity loss. Visual search may be considered as a measure of impairment of daily activities in glaucoma patients, if further similar tests using binocular conditions corroborate our findings.

Effect of Topical Periocular Steroid Use on Intraocular Pressure: A Retrospective Analysis.

PURPOSE: To study the effect of periocular steroid use on intraocular pressure (IOP). METHODS: Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. RESULTS: Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1-83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of <1 mm Hg. One patient had a clinically significant intermediate steroid response of 7 mm Hg. CONCLUSIONS: Periocular steroid treatment causes a statistically significant rise in IOP in eyes with higher baseline IOP measurements, the risk of which increases with follow up. While this change is not always correlated with a clinically significant rise in IOP, clinicians should monitor more closely patients at greatest risk of steroid response.

Reversal of Glaucoma Hemifield Test Results and Visual Field Features in Glaucoma.

PURPOSE: To develop a visual field (VF) feature model to predict the reversal of glaucoma hemifield test (GHT) results to within normal limits (WNL) after 2 consecutive outside normal limits (ONL) results. DESIGN: Retrospective cohort study. PARTICIPANTS: Visual fields of 44 503 eyes from 26 130 participants. METHODS: Eyes with 3 or more consecutive reliable VFs measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm standard 24-2) were included. Eyes with ONL GHT results for the 2 baseline VFs were selected. We extracted 3 categories of VF features from the baseline tests: (1) VF global indices (mean deviation [MD] and pattern standard deviation), (2) mismatch between baseline VFs, and (3) VF loss patterns (archetypes). Logistic regression was applied to predict the GHT results reversal. Cross-validation was applied to evaluate the model on testing data by the area under the receiver operating characteristic curve (AUC). We ascertained clinical glaucoma status on a patient subset (n = 97) to determine the usefulness of our model. MAIN OUTCOME MEASURES: Predictive models for GHT results reversal using VF features. RESULTS: For the 16 604 eyes with 2 initial ONL results, the prevalence of a subsequent WNL result increased from 0.1% for MD < -12 dB to 13.8% for MD ≥-3 dB. Compared with models with VF global indices, the AUC of predictive models increased from 0.669 (MD ≥-3 dB) and 0.697 (-6 dB ≤ MD < -3 dB) to 0.770 and 0.820, respectively, by adding VF mismatch features and computationally derived VF archetypes (P < 0.001 for both). The GHT results reversal was associated with a large mismatch between baseline VFs. Moreover, the GHT results reversal was associated more with VF archetypes of nonglaucomatous loss, severe widespread loss, and lens rim artifacts. For a subset of 97 eyes, using our model to predict absence of glaucoma based on clinical evidence after 2 ONL results yielded significantly better prediction accuracy (87.7%; P < 0.001) than predicting GHT results reversal (68.8%) with a prescribed specificity 67.7%. CONCLUSIONS: Using VF features may predict the GHT results reversal to WNL after 2 consecutive ONL results.

Visual Field Change and 24-Hour IOP-Related Profile with a Contact Lens Sensor in Treated Glaucoma Patients.

PURPOSE: To test the hypothesis that a 24-hour recording of intraocular pressure (IOP)-related measurements derived from a contact lens sensor (CLS) correlates to the rate of visual field progression in treated glaucomatous eyes. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Forty treated glaucomatous patients with 8 or more 24-2 visual field tests. METHODS: Twenty-four-hour recording with a CLS that provides IOP-related measurements. MAIN OUTCOME MEASURES: Rates of visual field mean deviation (MD) change before and at the time of CLS recording and CLS parameters, namely number of large peaks, mean peak ratio, wake-to-sleep slope, amplitude and area under the cosine curve, and variability from the mean. RESULTS: When comparing the rate of MD change before and at the time of CLS recording of all patients, the average slope was -0.05 dB/year faster in the beginning compared with the end (P = 0.087), suggesting a deceleration of progression by the time of CLS recording. The number of long peaks and the mean peak ratio when patients were awake were the best predictors of faster progression. The combination of CLS parameters provided better measures of goodness of fit than Goldmann IOP parameters (mean, peak, and fluctuation) in the same period. CONCLUSIONS: Intraocular pressure-related parameters obtained with 24-hour recording with a CLS were associated with the rate of visual field progression in treated glaucomatous eyes. This technology may be useful in detecting eyes at higher risk of glaucoma progression while receiving treatment.

African Descent and Glaucoma Evaluation Study (ADAGES): Racial Differences in Optic Disc Hemorrhage and Beta-Zone Parapapillary Atrophy.

PURPOSE: To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (ßPPA) between individuals of African descent (AD) and European descent (ED). DESIGN: Prospective, multicenter, observational cohort. PARTICIPANTS: A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS: Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and ßPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with ßPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. MAIN OUTCOME MEASURES: Differences in frequency of DH and prevalence of ßPPA. RESULTS: A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas ßPPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have ßPPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P = 0.008). CONCLUSIONS: Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of ßPPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of ßPPA affect the likelihood of glaucomatous progression.

A new index to monitor central visual field progression in glaucoma.

PURPOSE: The visual field index (VFI) summarizes global visual field (VF) data and was developed to monitor glaucoma progression using 24-2 and 30-2 strategies. We applied similar principles and statistical procedures to develop a new parameter, the central field index (CFI), to monitor 10-2 VF progression. DESIGN: Retrospective cohort. PARTICIPANTS: Glaucoma patients with paracentral defects seen on 24-2 perimetry and followed up with at least 5 10-2 VF tests. METHODS: The CFI was developed by calculating age-corrected defect depth at test points obtained during 10-2 examinations. The sensitivities at these points were scored as percentages similar to the method described for the VFI: 100-[(|total deviation|/age-corrected normal threshold) × 100]. A weighting procedure was applied based on published estimates of the occipital cortical spatial magnification. For validation, we performed mixed linear model testing for the association between CFI rates of change (%/year) and known risk factors for glaucoma progression in a population with established glaucoma and at least 5 10-2 VF tests. To determine whether the CFI was affected by cataract, as is known to occur with mean deviation (MD), we conducted a pilot evaluation comparing rates of CFI change in 3 groups: (1) eyes with cataract, (2) pseudophakic eyes, and (3) eyes in which cataract surgery was performed in the middle of the series. MAIN OUTCOME MEASURES: Rates of CFI and MD change. RESULTS: Central field index values were calculated for 176 eyes of 142 patients. The mean rate of CFI change of the entire sample was -1.10%/year (95% confidence interval, -1.03 to -1.16%/year). Elevated intraocular pressure (P<0.001) was associated significantly with faster CFI change, whereas lens status did not influence CFI rates of change (P>0.100) CONCLUSIONS: We developed and validated a new index to monitor central field progression that is minimally affected by the presence or removal of cataract and that correlates significantly with an important risk factor for glaucoma progression. This new index may become useful for glaucoma management, especially when combined with conventional static perimetry strategies.

Defining 10-2 visual field progression criteria: exploratory and confirmatory factor analysis using pointwise linear regression.

PURPOSE: To test different visual field progression criteria using trend analysis in a glaucoma population followed with long sequences of 10-2 tests as a first attempt to understand and document rates of progression in the central field. DESIGN: Retrospective cohort study. PARTICIPANTS: We included 146 eyes of 146 patients with established glaucoma. METHODS: Pointwise linear regression analysis using the methods of ordinary least squares was performed on the 68 test locations of the 10-2 visual field sequences. Threshold sensitivities at each test location were plotted as the dependent variable against follow-up time as the independent variable. Statistically significant progression or improvement of a visual field test point was defined if its regression slope measured ≤-1.0 dB/year or ≥+1.0 dB/year, respectively, at P<0.01. We explored sets of criteria to define visual field progression, generating a hypothetical sensitivity (progression), specificity (improvement), and progression-to-improvement ratio (PIR) for each criterion. The criterion with the highest PIR was deemed the one with best performance. Latent class analysis (LCA) was used to determine visual field sectors with highest inter-correlation. MAIN OUTCOME MEASURES: The performance of different visual field progression criteria to detect fast rates of mean deviation (MD) change. RESULTS: Median baseline 10-2 MD value was -12.0 dB (interquartile range [IQR], -6.7 to -17.8 dB), and the median rate of 10-2 MD change over time was -0.38 dB/year (IQR, -0.07 to -0.77 dB/year). The highest PIR was obtained with the progression criterion requiring at least 3 test points located in the same LCA-derived 10-2 visual field sector progressing faster than -1.0 dB/year at P<0.01. This criterion was further validated for content and convergence. CONCLUSIONS: This is the first study to investigate progression criteria for 10-2 visual fields using rates of change and to test their performance and validity. These findings may be useful to improve the monitoring of patients with glaucoma at different levels of functional loss and to develop new perimetric algorithms that scrutinize specific visual field locations for a more accurate detection of progression.

Retinal blood vessel positional shifts and glaucoma progression.

PURPOSE: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with ≥8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<-0.02 decibels [dB]/year), moderate (-0.02 to -0.65 dB/year), or fast (≥-0.65 dB/year) progression. To determine whether graders' assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. METHODS: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). MAIN OUTCOME MEASURES: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. RESULTS: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P = 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P< 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs. -0.29 dB/year; 95% confidence interval [CI], 0.03-0.48); P = 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P = 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1-4.5; P = 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7-83.6; P< 0.001) and DH (OR, 4.6; 95% CI, 1.5-15.5; P< 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. CONCLUSIONS: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.

Effect of focal lamina cribrosa defect on glaucomatous visual field progression.

OBJECTIVE: To evaluate the association between focal, structural defects of the lamina cribrosa (LC) and glaucomatous visual field (VF) progression. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 169 patients with glaucoma (169 eyes) with a range of glaucomatous damage. METHODS: Serial horizontal and vertical enhanced-depth imaging optical coherence tomography (EDI OCT) B-scans of the optic nerve head were obtained from patients with glaucoma with 5 or more prior Humphrey 24-2 VFs (Carl Zeiss Meditec, Inc, Dublin, CA). The EDI OCT scans were reviewed for the presence of focal LC defects (laminar holes or disinsertions with a diameter >100 µm). The VF progression was defined as having ≥ 2 significantly progressing test points (with a slope calculated using pointwise linear regression [PLR], worse than -1.0 dB/year at P<0.01). Age, intraocular pressure (IOP), baseline VF mean deviation (MD), disc hemorrhage, and central corneal thickness (CCT) were recorded. MAIN OUTCOME MEASURES: The relationship between focal LC defects and the rate and risk of VF progression. RESULTS: Mean age and VF MD at the time of EDI OCT were 69 ± 12 years and -11.49 ± 6.87 dB, respectively. Sixty eyes (36%) progressed according to PLR criteria. Progression was more common in eyes with, rather than without, focal LC defects (38/81 eyes [47%] vs. 22/88 eyes [25%], P = 0.003). Among the evaluated parameters, the presence of focal LC defects, disc hemorrhage, higher mean follow-up IOP, greater number of VFs, and longer follow-up period were significantly associated with VF progression in the multivariable analyses (odds ratios, 2.90, 4.66, 1.22, 1.25, and 1.27, respectively; P = 0.010, P = 0.002, P = 0.002, P<0.001, and P<0.001, respectively). The mean global progression rate was significantly faster in the group with focal LC defect than in the group with no focal LC defect (-0.54 ± 0.99 dB/year vs. -0.28 ± 0.52 dB/year; P = 0.031). Among the 60 progressing eyes, despite no significant difference in the mean number of progressing VF points per eye (6.7 ± 7.0 vs. 6.5 ± 4.4; P = 0.899), the mean localized progression rate was significantly faster in the eyes with focal LC defects than in the eyes with no focal LC defects (-2.85 ± 1.85 dB/year vs. -1.75 ± 0.56 dB/year; P = 0.009). CONCLUSIONS: Focal LC defects are strongly associated with glaucomatous VF progression, and eyes with focal LC defects tend to progress faster than those without.

Nocturnal systemic hypotension increases the risk of glaucoma progression.

OBJECTIVE: The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility. METHODS: The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months. MAIN OUTCOME MEASURES: The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year). RESULTS: Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression (P<0.02). CONCLUSIONS: Cumulative nocturnal hypotension predicted VF loss in this cohort. Our data suggest that the duration and magnitude of decrease in nocturnal blood pressure below the daytime MAP, especially pressures that are 10 mmHg lower than daytime MAP, predict progression of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a result of medications, may lead to worsening of VF defects.

Identifying Rapid Glaucoma Progression Using Hemifield Rates of Progression.

PRCIS: Hemifield rates of progression are more sensitive to focal progression (or faster progression) than global rates. This can aid in tailoring management and treatment decisions. PURPOSE: To determine if the rate of progression (ROP) of each hemifield of the 24-2 visual field (VF) aids in the detection of rapidly progressing eyes. METHODS: In this retrospective longitudinal study, we evaluated 1658 eyes of 1658 consecutive glaucoma patients with global mean deviation (MD) VF loss between -3 and -15 dB at baseline and ≥8 reliable VF tests (Swedish Interactive Thresholding Algorithm 24-2) with over ≥3 years of follow-up. The ROP (dB/year) based on global MD, superior hemifield MD, and inferior hemifield MD was calculated. The worst hemifield ROP (ROPworst) and hemifield ROP absolute difference (ROPdiff) were determined for each eye. Eyes were categorized based on the ROP from each metric as slow (-0.5 dB/year or better), rapid (worse than -0.5 dB/year), very rapid (worse than -1.0 dB/year), and catastrophic (worse than -2.0 dB/year) progression. The rate of significant asymmetric hemifield progression rate (ROPdiff ≥0.5 dB/year) was also evaluated. RESULTS: On average, ROPworst was faster than ROPglobal by 0.25±0.3 dB/year ( P <0.001). Based on ROPworst, 422 eyes (25%) were classified as progressing more rapidly than the ROPglobal classification. Over 40% (153/339) of the eyes classified as rapid progressors by ROPglobal were classified as very rapid or catastrophic progressors based on ROPworst. Eyes that progressed more rapidly based on ROPworst also had a higher rate of asymmetric progression. CONCLUSION: Hemifield ROPs are more sensitive to focal progression (or faster progression) than global rates and can aid in tailoring management and treatment decisions.

Glaucoma Detection Using Optical Coherence Tomography: Reviewing the Pitfalls of Comparison to Normative Data.

PRCIS: Optical coherence tomography is essential in managing glaucoma. This review describes various artifacts that originate from using a normative database to compare the individual's scans. This is a review paper regarding artifacts in optical coherence tomography imaging for glaucoma arising from using a normative database as a reference for healthy retinal nerve fiber layer and ganglion cell layer.