Faculty Bibliography

PURPOSE/OBJECTIVE:To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. DESIGN/METHODS:Observational cross-sectional study. PARTICIPANTS/METHODS:A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. METHODS:Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. MAIN OUTCOME MEASURES/METHODS:Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. RESULTS:The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). CONCLUSIONS:In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted.

PURPOSE/OBJECTIVE:The purpose of this study was to compare the required supplemental anesthesia and postoperative patient pain score in individuals undergoing glaucoma surgery under topical anesthesia (TA) versus retrobulbar anesthesia (RB). MATERIALS AND METHODS/METHODS:A retrospective, interventional, comparative cohort study of 261 eyes of 225 patients undergoing glaucoma and combined glaucoma with cataract surgery were included in the study. The main outcome measures were the amount of supplemental, systemic intraoperative anesthesia used and the postoperative pain scale between patients undergoing TA versus RB anesthesia. A secondary analysis was performed between combined glaucoma and cataract surgery versus glaucoma surgery alone. RESULTS:About 6.2% patients complained of pain after glaucoma surgery (8.1% among TA group and 3.1% among RB group; P=0.049). Overall, pain tended to be mild with a mean score of 0.32 of 10 for TA and 0.08 of 10 for RB (P=0.027). The amount of IV anesthetics used intraoperatively was lower in the RB anesthesia compared with the TA group (midazolam, P=0.042; fentanyl, P<0.001; propofol, P<0.001). In addition, patients undergoing RB anesthesia were less likely to use postoperative pain medication (P<0.001). There was no difference in pain score (P=0.707) or in the amount of IV anesthetics (all P>0.350) between eyes undergoing combined versus glaucoma surgery alone. CONCLUSIONS:Although supplemental anesthesia and pain scores were statistically increased in the topical group, the prevalence and the severity of pain was low. Therefore, TA is feasible and a reasonable option for glaucoma surgery. Furthermore, this conclusion applies when glaucoma surgery is performed alone or in combination with the other eye surgery.

Purpose/UNASSIGNED:This pilot cross-sectional study aimed to determine age-related changes of the retinal nerve fiber layer (RNFL) thickness in retinal periphery by swept-source optical coherence tomography-based analysis. Methods/UNASSIGNED:Forty eyes of 40 healthy subjects were studied in three age groups, group 1 (20-40 years, n=15), group 2 (41-60 years, n=14), and group 3 (≥61 years, n=11). Wide-angle swept-source optical coherence tomography scans, including the optic disc and macula, were montaged with the nasal peripheral optical coherence tomography images acquired with a contralateral gaze. The peripapillary and peripheral RNFL thickness values were obtained for nasal and temporal sides. The ratio of peripheral-to-peripapillary RNFL thickness was also calculated for these sectors. Results/UNASSIGNED:<0.02 for nasal and temporal sides, respectively) was also detected. Conclusion/UNASSIGNED:The age-related decline should be taken into consideration when determining the glaucoma-related alterations in peripheral RNFL thickness. Continued analysis in patients with ocular hypertension and glaucoma should help determine whether RNFL in the periphery with lower nerve tissue reserve might be more susceptible to injury, whether injury to the peripheral RNFL might be easier to detect, and/or whether analysis of the peripheral RNFL thickness could improve clinical diagnosis and follow-up of glaucoma.

Purpose:Glaucoma-related molecular biomarkers can improve clinical testing to diagnose the disease early, predict its prognosis, and monitor treatment responses. Based on the evidence of increased oxidative stress in glaucomatous tissues, this study analyzed oxidative stress-related biomarker candidates in blood and aqueous humor samples with or without glaucoma. Methods:The blood and aqueous humor samples collected from carefully selected groups of 96 patients with glaucoma and 64 healthy subjects without glaucoma were included in the study. The samples were analyzed for protein carbonyls and advanced glycation end products (AGEs) through ELISA-based quantification assays. To allow proper comparisons, the Goldmann-Witmer coefficient that reflects the ratio of aqueous humor to blood values corrected to total protein concentration in individual samples was calculated. Results:Blood and aqueous humor levels of protein carbonyls and AGEs were found significantly higher in glaucomatous samples compared with age-matched nonglaucomatous controls (P < 0.001). The glaucoma-related increase in protein carbonyls and AGEs was more prominent in aqueous humor samples than blood samples (2.6-fold versus 1.9-fold for protein carbonyls, and 3.1-fold versus 1.9-fold for AGEs; P < 0.001). Comparison of the Goldmann-Witmer coefficients indicated greater values for protein carbonyls (1.37 ± 0.3 vs. 3.07 ± 0.8) and AGEs (1.2 ± 0.3 vs. 3.2 ± 1.1) in the glaucoma group (P < 0.001). Conclusions:Findings of this study encourage further validation studies of oxidative stress-related biomarkers in glaucoma. Analysis of protein carbonyls and AGEs in longitudinal studies of larger and heterogeneous patient cohorts should better assess the value of these promising candidates as molecular biomarkers of glaucoma for clinical predictions.

Importance/UNASSIGNED:Recent evidence supports the presence of macular damage (within 8° of the central field) to retinal ganglion cells and associated central visual field (VF) defects in glaucoma, even in early stages. Despite this, to our knowledge, the association of 10-2 VF damage with vision-related quality of life (QOL) has not been well studied. Objective/UNASSIGNED:To determine the association between QOL and visual function as measured by 24-2 and 10-2 VFs in patients with primary open-angle glaucoma and to test the hypothesis that patients with vision-related QOL disproportionate to their 24-2 VF status may exhibit 10-2 damage overlooked by the 24-2 test. Design, Setting, and Participants/UNASSIGNED:In this cross-sectional analysis of observational cohort study data taken from a tertiary care specialty practice, 113 patients with glaucoma with the entire range of 24-2 VF damage completed the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Data were collected from May 2014 to January 2015 and were analyzed from March 2016 to May 2016. Interventions/UNASSIGNED:Standardized binocular 24-2 and 10-2 VF sensitivities were calculated for each patient. Main Outcomes and Measures/UNASSIGNED:Association of binocular 24-2 and 10-2 VF sensitivity with Rasch-calibrated NEI VFQ-25 scores. Detection of outliers was based on Cook distance of the regression of binocular 24-2 and NEI VFQ-25 score. Outlier association with QOL was then assessed using a linear regression model, with binocular 10-2 VF sensitivity as the independent variable. Results/UNASSIGNED:Of the 113 patients, the mean (SD) age was 70.1 (10.9) years, and 51 (45.1%) were male and 71 (62.8%) were white. The composite NEI VFQ-25 score was associated with both binocular 24-2 (β = 1.95; 95% CI, 0.47-3.43; P = .01) and 10-2 (β = 2.57; 95% CI, 1.12-4.01; P = .001) sensitivities, but the 10-2 VF univariable model showed an almost 2-fold better fit to the data (R2 = 9.2% vs 4.9%). However, the binocular 10-2 sensitivities of 24-2 outliers had the strongest association with the composite NEI VFQ-25 scores (β = 2.78; 95% CI, 0.84-4.72; P = .006.) and the best fit to the data (R2 = 18.2%.). Conclusions and Relevance/UNASSIGNED:The 10-2 VF model showed a stronger association with NEI VFQ-25 score than the 24-2 VF model. Patients with disproportionately low quality of vision relative to patients with 24-2 VF damage may have damage on the central field missed by the 24-2 grid. Future prospective testing, including additional dimensions of quality of life, is indicated.

Importance/UNASSIGNED:Little is known about the association between structural macular damage and self-reported visual function of people with glaucoma. Objective/UNASSIGNED:To determine the association between vision-related quality of life among patients with primary open-angle glaucoma with structural macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) loss identified by spectral-domain optical coherence tomography (SD-OCT) machine-generated deviation maps and thickness measurements. Design, Setting, and Participants/UNASSIGNED:This cross-sectional prospective study was conducted from March 1, 2014, to March 30, 2015, at the Department of Ophthalmology at Columbia University Medical Center. The participants were 107 patients who were enrolled in the study and represented the entire range of glaucomatous damage. All 214 eyes of the 107 participants underwent 10-2 visual field tests and SD-OCT scans, and all participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). They also received ophthalmologic examination, including medical history review, best-corrected visual acuity, slitlamp biomicroscopy, intraocular pressure measurement, gonioscopy, dilated ophthalmoscopy, and standard automated perimetry. Macular RGC+IPL loss was determined by diffuse or focal patterns on SD-OCT-generated deviation maps (probability map that compared patients with aged-matched normative database) and thickness measurements. Main Outcomes and Measures/UNASSIGNED:Regression analyses to assess the association of NEI VFQ-25 scores (score range: 41.9-99.5; higher scores indicate better functioning) with patterns of RGC+IPL loss and with RGC+IPL thickness measurements. Results/UNASSIGNED:Of the 107 patients, 48 (45%) were men and the mean (SD) age was 65 (11) years. The self-reported race/ethnicity of participants consisted of 45 (46%) black, 47 (48%) white, and 6 (6%) "other" individuals. In the univariable analyses, patients with diffuse macular RGC+IPL loss had mean composite Rasch-calibrated NEI VFQ-25 scores that were 6.15 points lower than the scores of patients with focal damage (β = -6.15; 95% CI, -11.7 to -0.59; P = .03). The effect remained significant even after controlling for mean RGC+IPL thickness (β = -7.64; 95% CI, -14.2 to -1.03; P = .02). Conclusions and Relevance/UNASSIGNED:Characteristic patterns of glaucoma-related macular RGC+IPL loss appeared to be more important predictors of vision-related quality of life than thickness measures, with diffuse RGC+IPL loss as an indicator for diminished vision-related quality of life.

Importance/UNASSIGNED:β-zone parapapillary atrophy (βPPA) has been reported as a risk factor for glaucoma onset and progression. Previous studies have shown that the prevalence of βPPA differs between individuals of African descent (AD) and European descent (ED). Objective/UNASSIGNED:To test whether the association between the presence and progression of βPPA vs visual field progression of glaucoma differs between these 2 ancestry groups. Design, Setting, and Participants/UNASSIGNED:In a prospective, multicenter, longitudinal cohort study, 634 individuals (1090 eyes) enrolled in the African Descent and Evaluation Study (ADAGES) with a diagnosis of glaucomatous optic neuropathy (GON) or ocular hypertension (OHT) and at least 2 disc stereophotographs were included. Two graders masked to clinical and ancestry data reviewed and graded the baseline and last disc stereophotographs for the presence of βPPA at baseline and βPPA progression (development or enlargement). Mixed-effects linear models were tested with visual field mean deviation as a dependent variable and time (alone and with interaction terms) as independent variables. ADAGES enrollment began in January 2003 and ended in July 2006; follow-up ended in 2016. Exposures/UNASSIGNED:Disc stereophotographs. Main Outcomes and Measures/UNASSIGNED:Progression of βPPA in AD and ED individuals. Results/UNASSIGNED:In 634 patients, a total of 814 eyes of AD (395 eyes) and ED (419) patients with GON and 276 eyes of AD (106) and ED (170) patients with OHT who were enrolled in ADAGES were analyzed. There were 336 (53.0%) women in the study; mean (SD) age was 61.9 (12.7) years. In the OHT group, the association between βPPA at baseline and visual field progression was not significantly different between AD and ED eyes (β = 0.071; 95% CI, -0.016 to 0.158; P = .11), nor was the association between βPPA progression and visual field progression (β = 0.020; 95% CI, -0.465 to 0.506; P = .93). In the GON group, ED eyes with baseline βPPA progressed faster than did AD eyes with baseline βPPA (β = -0.124; 95% CI, -0.241 to -0.007; P = .04), although the association between βPPA progression and visual field progression did not differ significantly between race groups (β = -0.101; 95% CI, -0.323 to 0.119; P = .37). Conclusions and Relevance/UNASSIGNED:Race had a significant effect on the association between baseline βPPA and rates of visual field progression in eyes with GON. Progression of βPPA was not associated with faster visual field progression in either racial group.