Pregnancy outcomes in the medical management of glaucoma: An international multicenter descriptive survey.

PURPOSE: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications. METHODS: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications. RESULTS: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate (p = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant. CONCLUSIONS: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay.

Validating the Generalizability of Ophthalmic Artificial Intelligence Models on Real-World Clinical Data.

Purpose: This study aims to investigate generalizability of deep learning (DL) models trained on commonly used public fundus images to an instance of real-world data (RWD) for glaucoma diagnosis. Methods: We used Illinois Eye and Ear Infirmary fundus data set as an instance of RWD in addition to six publicly available fundus data sets. We compared the performance of DL-trained models on public data and RWD for glaucoma classification and optic disc (OD) segmentation tasks. For each task, we created models trained on each data set, respectively, and each model was tested on both data sets. We further examined each model's decision-making process and learned embeddings for the glaucoma classification task. Results: Using public data for the test set, public-trained models outperformed RWD-trained models in OD segmentation and glaucoma classification with a mean intersection over union of 96.3% and mean area under the receiver operating characteristic curve of 95.0%, respectively. Using the RWD test set, the performance of public models decreased by 8.0% and 18.4% to 85.6% and 76.6% for OD segmentation and glaucoma classification tasks, respectively. RWD models outperformed public models on RWD test sets by 2.0% and 9.5%, respectively, in OD segmentation and glaucoma classification tasks. Conclusions: DL models trained on commonly used public data have limited ability to generalize to RWD for classifying glaucoma. They perform similarly to RWD models for OD segmentation. Translational Relevance: RWD is a potential solution for improving generalizability of DL models and enabling clinical translations in the care of prevalent blinding ophthalmic conditions, such as glaucoma.

Topical netarsudil for treatment of glaucoma with elevated episcleral venous pressure: A pilot investigation in sturge-weber syndrome.

PURPOSE: Topical netarsudil 0.02% may reduce intraocular pressure (IOP) by decreasing episcleral venous pressure (EVP), which carries theoretical utility for glaucoma associated with elevated EVP. A role for netarsudil in patients with elevated EVP is evaluated in a pilot investigation using a cohort of individuals with Sturge-Weber syndrome (SWS). METHODS: Retrospective study of patients with SWS and glaucoma who were treated with netarsudil. Five patients (six eyes) were identified. Data collected included demographics, visual acuity, IOP, glaucoma medical and surgical treatments, and adverse effects of netarsudil. RESULTS: Mean age was 13.6 ± 8.5 years. EVP elevation was presumed based on clinical stigmata and/or historical features. Mean number of baseline glaucoma medications was 3.3 ± 1.2. There was a significant reduction in the IOP at netarsudil initiation (mean 26.2 ± 4.5 mmHg) to 1 month of netarsudil therapy (mean 20.2 ± 3.8 mmHg, p = 0.0283) and latest IOP on netarsudil (mean 17.6 ± 1.4 mmHg, p = 0.0034). Mean duration of netarsudil therapy was 18.7 ± 11.8 months. Three patients required additional glaucoma procedures; one patient required an additional glaucoma medication. Three eyes (50%) developed conjunctival hyperemia. One patient discontinued netarsudil at 29 months, to reduce drop burden. CONCLUSIONS: Netarsudil can effectively reduce IOP in patients with SWS, even when used as a fourth or fifth glaucoma medication. A possible role for netarsudil in the management of patients with elevated EVP is suggested pending further future investigations.

An Association Between Large Optic Cupping and Total and Regional Brain Volume: The Women's Health Initiative.

PURPOSE: To investigate the relationships between optic nerve cupping and total and regional brain volumes. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: Women 65 to 79 years of age without glaucoma with cup-to-disc ratio (CDR) measurements from the Women's Health Initiative (WHI) Sight Examination study and magnetic resonance imaging (MRI)-based total and regional brain volumes from the WHI Memory Study MRI-1 were included. Large CDR was defined as 0.6 or greater in either eye. Generalized estimating equation models were used to account for intra-brain correlations between the right and left sides. The final analysis was adjusted for demographic and clinical characteristics and for total brain volume (for regional analyses). RESULTS: Final analyses included 471 women, with the mean age ± SD was 69.2 ± 3.6 years; 92.8% of the subjects were white. Of 471 women, 34 (7.2%) had large CDR. Controlling for total brain volume and for demographic and clinical characteristics, lateral ventricle volume was 3.01 cc larger for subjects with large CDR compared to those without large CDR (95% CI = 0.02 to 5.99; P = .048). Furthermore, frontal lobe volume was 4.78 cc lower for subjects with large CDR compared to those without (95% CI = -8.71, -0.84; P = 0.02), and occipital lobe volume was 1.86 cc lower for those with large CDR compared to those without (95% CI = -3.39, -0.3; P =.02). CONCLUSIONS: Our analysis suggests that in women aged 65 years or more, large CDR is associated with lower relative total brain volume and absolute regional volume in the frontal and occipital lobes. Enlarged CDR in individuals without glaucoma may represent a sign of optic nerve and brain aging, although more longitudinal data are needed.

Effect of Low-Fat Dietary Modification on Incident Open-Angle Glaucoma.

PURPOSE: We tested whether dietary modification (DM) altered the risk for incident primary open-angle glaucoma (POAG). DESIGN: Secondary analysis of a randomized intervention trial. PARTICIPANTS: We linked Medicare claims data to 45 203 women in the Women's Health Initiative Dietary Modification Trial, of which 23 776 participants were enrolled in fee-for-service Medicare Part B and had physician claims. METHODS: Women were randomized to follow either DM (a low-fat diet, with increased vegetable, fruit, and grain intake) or their usual diet without modification. Nine thousand three hundred forty women were randomized to the DM intervention, whereas 13 877 women were randomized to the control group. Our analyses were based on an intention-to-treat design, with a follow-up to the end of continuous Medicare coverage, death, or the last claims date (12/31/2018), whichever occurred first. Primary open-angle glaucoma was defined as the first claim with the International Classification of Diseases, Ninth or Tenth Revision, codes. Dietary data were assessed using a food frequency questionnaire. MAIN OUTCOME MEASURES: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of POAG. Subgroup analyses were performed with P values for interaction. RESULTS: After exclusion of women with Medicare-derived glaucoma before randomization, the final analysis included 23 217 women (mean age, 64.4 ± 5.8 years). Baseline characteristics were balanced between the intervention and control groups. Primary open-angle glaucoma incidence was 11.1 per 1000 woman-years (mean follow-up, 11.6 ± 7.4 years; mean DM duration, 5.2 ± 3.2 years). We found no overall benefit of DM in reducing incident POAG (HR, 1.04; 95% CI, 0.96-1.12). Race and participant age did not modify this relation (P = 0.08 and P = 0.24 for interaction, respectively). In further analysis of baseline nutrient and food intake stratified by quartile groups, risk of open-angle glaucoma (OAG) in DM participants in the lowest quartile group for percentage calories (kilocalories) from total fat (33.8 or lower) was increased (HR, 1.22; 95% CI, 1.05-1.41; P = 0.007 for interaction). CONCLUSIONS: Analysis suggests that DM in participants in the lowest quartile group for percentage calories from total fat at baseline increased the risk of incident OAG among women regardless of age or race. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score.

PURPOSE: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. DESIGN: This was a retrospective study using data from the Women's Health Initiative. METHODS: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. RESULTS: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). CONCLUSIONS: Independent of the CDR GRS, women with large CDR had a lower cognitive function.

Perioperative Care of the Patient with Eye Pathologies Undergoing Nonocular Surgery.

The authors reviewed perioperative ocular complications and implications of ocular diseases during nonocular surgeries. Exposure keratopathy, the most common perioperative eye injury, is preventable. Ischemic optic neuropathy, the leading cause of perioperative blindness, has well-defined risk factors. The incidence of ischemic optic neuropathy after spine fusion, but not cardiac surgery, has been decreasing. Central retinal artery occlusion during spine fusion surgery can be prevented by protecting eyes from compression. Perioperative acute angle closure glaucoma is a vision-threatening emergency that can be successfully treated by rapid reduction of elevated intraocular pressure. Differential diagnoses of visual dysfunction in the perioperative period and treatments are detailed. Although glaucoma is increasingly prevalent and often questions arise concerning perioperative anesthetic management, evidence-based recommendations to guide safe anesthesia care in patients with glaucoma are currently lacking. Patients with low vision present challenges to the anesthesia provider that are becoming more common as the population ages.

Refractive Outcomes for Combined Phacoemulsification and Glaucoma Drainage Procedure.

INTRODUCTION: To evaluate the refractive outcome of combined cataract extraction and glaucoma drainage device (GDD) surgery. METHODS: Patients who had undergone combined phacoemulsification with GDD surgery [Baerveldt, Abbott Medical, Abbott Park (IL) or Ahmed valve, New World Medical, Rancho Cucamonga (CA)] between June 2009 and August 2017 were included in the study. The main outcome measure evaluated was whether or not spherical equivalent (SE) between ± 1D from target refraction was achieved at 3-6 months postoperatively. RESULTS: The final analysis included 42 eyes of 38 patients who underwent combined phacoemulsification and GDD surgery. A refractive outcome of spherical equivalent (SE) between ± 1D of the target refraction was achieved in 30 of 42 eyes (71.43%) at 3-6 months after surgery. Mean preoperative axial length (AL) of eyes with postoperative SE outside ± 1D from target (SD = 0.98, p = 0.003) was noted to be 25.37 ± 0.98 mm (longer mean AL) and that of eyes with SE between ± 1D (SD = 0.89, p = 0.000) was found to be 23.34 ± 0.89 mm (average mean AL). Twelve (29%) eyes were noted to have a mean 0.52D (SD = 0.49; range 0.02-1.49) of corneal astigmatism induced by combined surgery. Age, central corneal thickness, preoperative anterior chamber depth, and pre- and postoperative intraocular pressure did not significantly affect refractive outcomes. CONCLUSION: Refractive outcomes within 1.00D of the target refraction were achieved in most patients undergoing a combined surgical approach. Longer AL was a risk factor among patients with refractive change > 1.00D from target.

Experience with netarsudil 0.02% and latanoprostene bunod 0.024% as adjunctive therapy for glaucoma.

PURPOSE: To assess the effectiveness and safety of adjunctive topical netarsudil 0.02% and latanoprostene bunod 0.024% in patients with glaucoma. METHODS: A retrospective, multi-center, cohort study of patients with glaucoma treated with netarsudil 0.02% or latanoprostene bunod from five tertiary care centers. Inclusion criteria included patients with glaucoma treated with either medication as adjunctive therapy. Outcomes included mean absolute intraocular pressure (IOP) reduction and relative IOP reduction from baseline. Adverse reactions and reasons for discontinuation were reported. One-way analysis of variance, Kruskal-Wallis rank sum test, and Mann Whitney U test compared the outcomes. RESULTS: A total of 95 eyes (95 patients) on netarsudil and 41 eyes (41 patients) on latanoprostene bunod were analyzed. Mean duration of use was 54.3 ± 28 days for netarsudil and 82.9 ± 51.2 days for latanoprostene bunod. At the final visit, mean IOP reduction was 3.9 ± 4.6 mmHg (17.5 ± 6.0%) (p < 0.0001) with netarsudil and 2.9 ± 3.7 mmHg (13.6 ± 16.3%) (p < 0.0001) with latanoprostene bunod. IOP lowering did not depend on baseline number of IOP-lowering medications. The most common reason for discontinuation was non-effectiveness in both groups. CONCLUSION: Similar to monotherapy, netarsudil and latanoprostene bunod demonstrated efficacy in lowering IOP when used as adjunctive therapy.

Assessment of a novel ophthalmology tele-triage system during the COVID-19 pandemic.

BACKGROUND: In response to the COVID-19 pandemic, a web-based tele-triage system was created to prioritize in-person clinic visits and ensure safety at the University of Illinois at Chicago Department of Ophthalmology and Visual Sciences during a statewide shelter-in-place order. The aim of this study is to evaluate the impact of the tele-triage system on urgent visit volume and explore the characteristics of acute visit requests at a tertiary referral eye center. METHODS: This retrospective study analyzed acute visit requests between April 6, 2020 and June 6, 2020. Descriptive statistics, chi-square tests, ANOVA, and bivariate logistic regression were used to compare variables with a p-value of 0.05. RESULTS: Three hundred fifty-eight surveys were completed. Mean age was 49.7 ± 18.8 years (range 2-91). The majority of requests were determined as urgent (63.0%) or emergent (0.8%). Forty-nine patients had recent eye trauma (13.7%), and the most common reported symptoms were new onset eye pain (25.7%) and photophobia (22.9%). Most patients were self-referred (63.7%), though provider referral was more common in patients with symptoms of new onset lid swelling (p < 0.01), diplopia (p < 0.01), flashing lights (p = 0.02), or droopy eyelid (p < 0.01). Patients presenting with symptom onset within 48 h tended to be younger (45.8 years) versus those with symptom duration of 48 h to 1 week (49.6 years), or more than 1 week (52.6 years; p < 0.01). CONCLUSION: This novel tele-triage system screened out one-third of acute visit requests as non-urgent, which limited in-person visits during the initial shelter-in-place period of the pandemic. Tele-triage systems should be implemented in eye care practices for future emergency preparedness.

Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma.

Primary open-angle glaucoma (POAG) is an age-dependent, intraocular pressure (IOP)-related degeneration of the retinal ganglion cells (RGC). At present, IOP is the only modifiable factor that has been identified to prevent glaucomatous vision loss. Though the pathogenesis of glaucomatous optic neuropathy is still not well understood, increasing evidence suggests oxidative stress may contribute to the induction and progression of glaucoma. Furthermore, antioxidant use may be protective against glaucoma through various mechanisms, including reducing IOP, preserving vascular health, and preventing ganglion cell loss. This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

An Association Between Large Optic Nerve Cupping and Cognitive Function.

PURPOSE: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. METHODS: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. RESULTS: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). CONCLUSIONS: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial.

PURPOSE: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. DESIGN: Secondary analysis of randomized controlled trial data. METHODS: We linked Medicare claims data to 25 535 women in the Women's Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625 mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625 mg/day + MPA 2.5 mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval. RESULTS: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age = 68.5 ± 4.8 years). The OAG incidence was 7.6% (mean follow-up = 11.5 ± 5.2 years; mean HT duration = 4.4 ± 2.3 years). Increased age (P trend = .01) and African-American race (HR = 2.69, 95% CI = 2.13-3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR = 1.01, 95% CI = 0.79-1.29 in the CEE trial, and HR = 1.05, 95% CI = 0.85-1.29 in the CEE + MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction = .01), and risk was reduced in African-American women treated with CEE (HR = 0.49, 95% CI = 0.27-0.88), compared to placebo. Race did not modify the relation between CEE + MPA use and OAG risk (P interaction = .68). CONCLUSIONS: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed.