Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

Using Natural Language Processing to Identify Different Lens Pathology in Electronic Health Records.

PURPOSE: Nearly all published ophthalmology-related Big Data studies rely exclusively on International Classification of Diseases (ICD) billing codes to identify patients with particular ocular conditions. However, inaccurate or nonspecific codes may be used. We assessed whether natural language processing (NLP), as an alternative approach, could more accurately identify lens pathology. DESIGN: Database study comparing the accuracy of NLP versus ICD billing codes to properly identify lens pathology. METHODS: We developed an NLP algorithm capable of searching free-text lens exam data in the electronic health record (EHR) to identify the type(s) of cataract present, cataract density, presence of intraocular lenses, and other lens pathology. We applied our algorithm to 17.5 million lens exam records in the Sight Outcomes Research Collaborative (SOURCE) repository. We selected 4314 unique lens-exam entries and asked 11 clinicians to assess whether all pathology present in the entries had been correctly identified in the NLP algorithm output. The algorithm's sensitivity at accurately identifying lens pathology was compared with that of the ICD codes. RESULTS: The NLP algorithm correctly identified all lens pathology present in 4104 of the 4314 lens-exam entries (95.1%). For less common lens pathology, algorithm findings were corroborated by reviewing clinicians for 100% of mentions of pseudoexfoliation material and 99.7% for phimosis, subluxation, and synechia. Sensitivity at identifying lens pathology was better for NLP (0.98 [0.96-0.99] than for billing codes (0.49 [0.46-0.53]). CONCLUSIONS: Our NLP algorithm identifies and classifies lens abnormalities routinely documented by eye-care professionals with high accuracy. Such algorithms will help researchers to properly identify and classify ocular pathology, broadening the scope of feasible research using real-world data.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Factors Associated with Large Cup-to-Disc Ratio and Blindness in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study.

BACKGROUND/AIMS: Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry. In these patients' eyes, a large cup-to-disc ratio (LCDR > 0.90) suggests greater retinal ganglion cell loss, though these patients often display varied visual ability. This study investigated the prevalence and risk factors associated with LCDR in African ancestry individuals with POAG and explored the differences between blind (>20/200) and not blind (≤20/200) LCDR eyes. METHODS: A case-control methodology was used to investigate the demographic, optic disc, and genetic risk factors of subjects in the Primary Open-Angle African American Glaucoma Genetics Study. Risk factors were analyzed using univariable and multivariable logistic regression models with inter-eye correlation adjusted using generalized estimating equations. RESULTS: Out of 5605 eyes with POAG, 1440 eyes (25.7%) had LCDR. In the multivariable analysis, LCDR was associated with previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.04), decreased mean deviation (OR = 1.08), increased pattern standard deviation (OR = 1.06), thinner retinal nerve fiber layer (OR = 1.05), nasalization of vessels (OR = 2.67), bayonetting of vessels (OR = 1.98), visible pores in the lamina cribrosa (OR = 1.68), and a bean-shaped cup (OR = 2.11). Of LCDR eyes, 30.1% were classified as blind (≤20/200). In the multivariable analysis, the statistically significant risk factors of blindness in LCDR eyes were previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.05), decreased mean deviation (OR = 1.04), and decreased pattern standard deviation (OR = 0.90). CONCLUSIONS: These findings underscore the importance of close monitoring of intraocular pressure and visual function in African ancestry POAG patients, particularly those with LCDR, to preserve visual function.

Prevalence and factors associated with optic disc grey crescent in the Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

AIM: To investigate the prevalence and factors associated with optic disc grey crescent (GC) in African Americans with glaucoma. METHODS: Stereo optic disc image features from subjects with glaucoma in the Primary Open-Angle African Ancestry Glaucoma Genetics Study were evaluated independently by non-physician graders and discrepancies adjudicated by an ophthalmologist. Risk factors for GC were evaluated by logistic regression models with intereye correlation accounted for by generalised estimating equations. Adjusted ORs (aORs) were generated. RESULTS: GC was present in 227 (15%) of 1491 glaucoma cases, with 57 (3.82%) bilateral and 170 (11.4%) unilateral. In multivariable analysis, factors associated with GC were younger age (aOR 1.27, 95% CI 1.11 to 1.43 for every decade younger in age, p=0.001), diabetes (aOR 1.46, 95% CI 1.09 to 1.96, p=0.01), optic disc tilt (aOR 1.84, 95% CI 1.36 to 2.48, p<0.0001), a sloping retinal region adjacent to the outer disc margin (aOR 2.37, 95% CI 1.74 to 3.32, p<0.0001) and beta peripapillary atrophy (aOR 2.32, 95% CI 1.60 to 3.37, p<0.0001). Subjects with GC had a lower mean (SD) value of the ancestral component q0 than those without GC (0.22 (0.15) vs 0.27 (0.20), p=0.001), consistent with higher degrees of African ancestry. CONCLUSIONS: More than 1 in 10 glaucoma cases with African ancestry have GC, occurring more frequently in younger subjects, higher degrees of African ancestry and diabetes. GC was associated with several ocular features, including optic disc tilt and beta peripapillary atrophy. These associations should be considered when evaluating black patients with primary open-angle glaucoma.

Risk factors for structural and functional progression of primary open-angle glaucoma in an African ancestry cohort.

BACKGROUND/AIMS: To investigate the rates of structural and functional progression of primary open-angle glaucoma in an African ancestry cohort and identify risk factors for progression. METHODS: This retrospective study included 1424 eyes from glaucoma cases in the Primary Open-Angle African American Glaucoma Genetics cohort, with ≥2 visits for retinal nerve fibre layer (RNFL) thickness and mean deviation (MD) measurements over ≥6-month follow-up. The rates of structural progression (change in RNFL thickness/year) and functional progression (change in MD/year) were calculated from linear mixed effects models, accounting for intereye correlation and longitudinal correlation. Eyes were categorised as slow, moderate or fast progressors. Risk factors for progression rates were assessed using univariable and multivariable regression models. RESULTS: The median (interquartile) rates of progression were -1.60 (-2.05 to -1.15) µm/year for RNFL thickness and -0.40 (-0.44 to -0.34) decibels/year for MD. Eyes were categorised as slow (structural: 19%, functional: 88%), moderate (structural: 54%, functional: 11%) and fast (structural: 27%, functional: 1%) progressors. In multivariable analysis, faster RNFL progression was independently associated with thicker baseline RNFL (p<0.0001), lower baseline MD (p=0.003) and beta peripapillary atrophy (p=0.03). Faster MD progression was independently associated with higher baseline MD (p<0.0001), larger cup-to-disc ratios (p=0.02) and lower body mass index (p=0.0004). CONCLUSION: The median rates of structural and functional progression in this African ancestry cohort were faster than the rates reported from previously published studies in other ethnic groups. Higher baseline RNFL thickness and MD values were associated with faster progression rates. Results highlight the importance of monitoring structural and functional glaucoma progression to provide timely treatment in early disease.

Elevated IOP following a bladder filling protocol: A case report.

Purpose: We describe a patient with elevated intraocular pressure (IOP) secondary to an oral water bolus and examine the utility of the water-drinking test. Observations: A 66-year-old male with a history of hypertension presented with headache, bilateral retro-orbital ache, and blurry vision. Symptoms began shortly after his radiation treatment for prostate cancer, for which he consumed a water bolus to fill his bladder 30 minutes prior to treatment initiation. On exam, he had bilateral elevated IOP that responded to topical IOP-lowering medications. Gonioscopy demonstrated open angles and fundus exam showed non-glaucomatous optic nerves with pronounced retinal venous tortuosity. The water-drinking test showed a peak intraocular pressure of 20 mmHg in the right eye (5 mmHg increase from baseline) and 23 mmHg in the left eye (8 mmHg increase from baseline), suggesting impairment of the outflow system in the left compared to the right eye. He was started on topical IOP-lowering therapy and followed in our clinic as a glaucoma suspect. Conclusions: Consumption of a water bolus can be associated with IOP elevation and may be a risk factor in patients with otherwise normal IOPs at risk for glaucoma. The water-drinking test was historically used as provocative testing for open-angle glaucoma and may have an updated role in evaluating at-risk patients without ocular hypertension.

Differential regulation of nucleus accumbens glutamate and GABA in obesity-prone and obesity-resistant rats.

Obesity is one of the leading health concerns in the United States. Studies from human and rodent models suggest that inherent differences in the function of brain motivation centers, including the nucleus accumbens (NAc), contribute to overeating and thus obesity. For example, there are basal enhancements in the excitability of NAc GABAergic medium spiny neurons (MSN) and reductions in basal expression of AMPA-type glutamate receptors in obesity-prone vs obesity-resistant rats. However, very little is known about the regulation of extracellular glutamate and GABA within the NAc of these models. Here we gave obesity-prone and obesity-resistant rats stable isotope-labeled glucose (13 C6 -glucose) and used liquid chromatography mass spectrometry (LC-MS) analysis of NAc dialysate to examine the real-time incorporation of 13 C6 -glucose into glutamate, glutamine, and GABA. This novel approach allowed us to identify differences in glucose utilization for neurotransmitter production between these selectively bred lines. We found that voluntarily ingested or gastrically infused 13 C6 -glucose rapidly enters the NAc and is incorporated into 13 C2 -glutamine, 13 C2 -glutamate, and 13 C2 -GABA in both groups within minutes. However, the magnitude of increases in NAc 13 C2 -glutamine and 13 C2 -GABA were lower in obesity-prone than in obesity-resistant rats, while basal levels of glutamate were elevated. This suggested that there may be differences in the astrocytic regulation of these analytes. Thus, we next examined NAc glutamine synthetase, GAD67, and GLT-1 protein expression. Consistent with reduced 13 C2 -glutamine and 13 C2 -GABA, NAc glutamine synthetase and GLT-1 protein expression were reduced in obesity-prone vs obesity-resistant groups. Taken together, these data show that NAc glucose utilization differs dramatically between obesity-prone and obesity-resistant rats, favoring glutamate over GABA production in obesity-prone rats and that reductions in NAc astrocytic recycling of glutamate contribute to these differences. These data are discussed in light of established differences in NAc function between these models and the role of the NAc in feeding behavior.

Self-identified Black Race as a Risk Factor for Intraocular Pressure Elevation and Iritis Following Prophylactic Laser Peripheral Iridotomy.

PRCIS: In primary angle closure suspects (PACS), self-identified Black race was a risk factor for intraocular pressure (IOP) elevation and iritis following laser peripheral iridotomy (LPI). Laser type was not associated with either immediate post-LPI IOP elevation or iritis in multivariate analysis. PURPOSE: The aim was to determine the impact of laser type and patient characteristics on the incidence of IOP elevation and iritis after LPI in PACS. MATERIALS AND METHODS: The electronic medical records of 1485 PACS (2407 eyes) who underwent either neodymium-doped yttrium-aluminum-garnet or sequential argon and neodymium-doped yttrium-aluminum-garnet LPI at the University of Pennsylvania between 2010 and 2018 were retrospectively reviewed. Average IOP within 30 days before LPI (baseline IOP), post-LPI IOP within 1 hour, laser type, laser energy, and the incidence of new iritis within 30 days following the procedure were collected. Multivariate logistic regression accounting for intereye correlation was used to assess factors associated with incidence of post-LPI IOP elevation and iritis, adjusted by age, sex, surgeon, and histories of autoimmune disease, diabetes, and hypertension. RESULTS: The incidence of post-LPI IOP elevation and iritis were 9.3% (95% confidence interval: 8.1%-10.5%) and 2.6% (95% CI: 1.9%-3.2%), respectively. In multivariate analysis, self-identified Black race was a risk factor for both IOP elevation [odds ratio (OR): 2.08 compared with White; P=0.002] and iritis (OR: 5.07; P<0.001). Higher baseline IOP was associated with increased risk for post-LPI IOP elevation (OR: 1.19; P<0.001). Laser type and energy were not associated with either post-LPI IOP elevation or iritis (P>0.11 for all). CONCLUSIONS: The incidence of immediate IOP elevation and iritis following prophylactic LPI was higher in Black patients independent of laser type and energy. Heightened vigilance and increased medication management before and after the procedure are suggested to help mitigate these risks.

Prevalence and Factors Associated with Optic Disc Tilt in the Primary Open-Angle African American Glaucoma Genetics Study.

PURPOSE: To investigate the prevalence and factors associated with optic disc tilt in the eyes of Black Americans with glaucoma. DESIGN: Cross-sectional. PARTICIPANTS: Subjects with glaucoma participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. METHODS: Stereo pairs of optic disc images were assessed independently by POAAGG-certified nonphysician graders for quantitative features including maximum and minimum linear disc diameters, and qualitative features including gradeability of images, shape of the cup, rim plane position, ß-peripapillary atrophy, sloping region adjacent to the outer disc margin, and rim pallor. Discrepancies were adjudicated by an ophthalmologist. Descriptive statistics and P values were generated for associations of tilt with demographic and ocular characteristics. Stepwise multivariable analysis was performed with logistic regression using Generalized Estimating Equations (GEEs) to account for inter-eye correlation within subjects. MAIN OUTCOME MEASURES: Tilt Ovality Index (TOI) of >1.30 and Stereoscopically Identified optic disc Tilt (SIT). RESULTS: Among 1251 subjects with data on both eyes, 104 (8.3%) had TOI. Subjects with TOI were less likely to be male (adjusted odds ratio [aOR], 0.46, 95% confidence interval [CI], 0.29-0.74, P < 0.001). Eyes with TOI were less likely to have large cup disc ratios (aOR, 0.18, 95% CI, 0.06-0.53, P < 0.001) and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.31, 95% CI, 0.19-0.49, P < 0.001). Among 1007 subjects with data on both eyes, 254 (25.2%) had SIT. Subjects with SIT were younger (aOR, 0.95, 95% CI, 0.93-0.96, P < 0.001), and eyes with SIT were more likely to have oval-shaped discs compared with round discs (aOR, 1.82, 95% CI, 1.32-2.52, P < 0.001), more likely to have a sloping region adjacent to the outer disc margin instead of being flat (aOR, 3.26, 95% CI, 2.32-4.59, P < 0.001), and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.59, 95% CI, 0.41-0.85, P < 0.001). Both TOI and SIT were not associated with myopia. CONCLUSIONS: There are substantial numbers of tilted optic discs in glaucoma patients with African ancestry. They occur more frequently in female subjects and younger subjects and are associated with several ocular features but not with myopia.

Assessing the efficacy of 3D-printed ear protectors on mask adherence at an academic ophthalmology center.

PURPOSE: In the ophthalmology setting, given the close proximity required for the clinical exam, appropriate mask usage and fit is essential. This study aims to assess how a simple, cost-effective 3D-printed face mask ear protectors (EP) attachment may decrease discomfort, increase compliance, and improve fit in an academic institution's Ophthalmology department. METHODS: Face mask EPs were distributed to patients and providers in the Ophthalmology department. A validated questionnaire was administered before and 2 weeks after EP usage. The survey included questions on demographics and frequency of mask usage during a spectrum of activities. Descriptive statistics were performed with Fischer's t test. RESULTS: Post-EP responses demonstrated an increased likelihood of mask usage across all activities, although not statistically significant. The greatest change was during outdoor activities, with a 14.3% increase in highest utilization. Post-EP, all subjects were very likely to wear masks while shopping and 91.7% while in the workplace. EP usage decreased the number of noncompliant individuals while spending time with friends and family by 93.3%. Almost no subjects reported mask removal of >15 times per hour post-EP. The increase in mask compliance was greatest for low mask utilizers. 91.9% reported improved comfort, 91.9% reported improved fit, and 81.6% reported increased mask usage. CONCLUSION: Our results suggest that simple cost-effective 3D-printed ear protectors may improve fit, comfort, and overall mask compliance. The results of this study should drive broader public health efforts to further investigate whether mask attachments can improve overall mask compliance through better comfort and fit.

Learning from Black/African American Participants: Applying the Integrated Behavioral Model to Assess Recruitment Strategies for a Glaucoma Genetic Study.

The underrepresentation of African American (AA) participants in medical research perpetuates racial health disparities in the United States. Open-ended phone interviews were conducted with 50 AA adults from Philadelphia who had previously participated in a genetic study of glaucoma that included complimentary ophthalmic screenings. Recruitment for the genetic study was done in partnership with a Black-owned radio station. Thematic analysis of interview transcripts, guided by the integrated behavior model (IBM), identified self-reported motivations for participating in this care-focused and community-promoted research program. Findings revealed that decisions to enroll were influenced by strong instrumental attitudes regarding learning more about personal health and contributing to future care options for others. Notable normative influences that factored into participants' decisions to enroll in the study included hearing about the study from a respected community media outlet, friends, and family. About one-third of respondents discussed past and current racial discrimination in medical research as an important sociocultural frame within which they thought about participation, suggesting that experiential attitudes play a continuing role in AA's decisions to enroll in medical research studies. Medical researchers seeking to recruit AA participants should collaborate with community partners, combine enrollment opportunities with access to health services, and emphasize the potential for new research to mitigate racial inequalities.

Evaluation of the Cirrus High-Definition OCT Normative Database Probability Codes in a Black American Population.

PURPOSE: Race-adjusted interpretation of data from Cirrus high-definition OCT (HD-OCT) devices is not standard practice. The aim of this study is to evaluate differences in peripapillary retinal nerve fiber layer (RNFL) thickness between healthy Black Americans and the Cirrus HD-OCT normative database. DESIGN: This is a cross-sectional observational study using control patients recruited from the greater Philadelphia, Pennsylvania, area. PARTICIPANTS: A total of 466 eyes were included in this study. Subjects were retrospectively identified from the control cohort of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. METHODS: Using an age-stratified or linear regression method, we reclassified white-green-yellow-red color probability codes for RNFL thicknesses by quadrant. MAIN OUTCOME MEASURES: The distribution of reclassified color codes was compared with the expected 5%-90%-4%-1% percentiles and to the original color codes by the Cirrus machine. RESULTS: Average RNFL thickness in the POAAGG control cohort was thinner than in the Cirrus normative database in all except the nasal quadrant. The original color codes of the POAAGG cohort did not fall into the expected distributions, with more RNFL measurements assigned as white and red codes than expected (9.5% and 1.7%) and fewer measurements assigned as green and yellow codes than expected (85.3% and 3.5%) (P < 0.001). Compared with the original Cirrus machine, reclassification using linear regression produced color codes closest to the expected distributions (P = 0.09). The proportion of abnormal results shifted closer to the expected 5% in the nasal (1.3%, P < 0.001 vs. 3.0%, P = 0.048) and temporal (8.2%, P = 0.002 vs. 3.6%, P = 0.18) quadrants. CONCLUSIONS: Results further establish the presence of structural differences in the RNFL of Black American patients. Color code reclassification suggests that the existing Cirrus database may not be accurately evaluating glaucomatous nerves in patients of African descent. This study addresses an unmet need to assess Cirrus HD-OCT color probability codes in a Black American population.

Recruitment strategies and lessons learned from a large genetic study of African Americans.

Genetic studies must enroll large numbers of participants to obtain adequate statistical power. Data are needed on how researchers can best use limited financial and practical resources to achieve these targets, especially in under-represented populations. This paper provides a retrospective analysis of the recruitment strategies for a large glaucoma genetics study in African Americans. The Primary Open-Angle African American Glaucoma Genetics study enrolled 10,192 African American subjects from the Philadelphia region. Major recruitment approaches included clinic enrollment from University of Pennsylvania (UPenn) sites, clinic enrollment from external sites, sampling of Penn Medicine Biobank (PMBB), and community outreach. We calculated the enrollment yield, cost per subject, and seasonal trends of these approaches. The majority (65%) of subject were enrolled from UPenn sites with an average cost of $133/subject. Over time, monthly case enrollment declined as the pool of eligible subjects was depleted. Expanding to external sites boosted case numbers ($129/subject) and the biobank provided additional controls at low cost ($5/subject), in large part due to the generosity of PMBB providing samples free of cost. Community outreach was costly with low return on enrollment ($978/subject for 220 subjects). Summer months (Jun-Aug) produced the highest recruitment yields (p<0.001). Genetic studies will benefit from a multi-pronged and culturally sensitive recruitment approach. In our experience, the biobank was most cost-effective for control enrollment, while recruitment from clinics (including expansion to new sites) was necessary to recruit fully phenotyped cases.

A Precise Method to Evaluate 360 Degree Measures of Optic Cup and Disc Morphology in an African American Cohort and Its Genetic Applications.

(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76-0.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.

Netarsudil-associated epithelial keratopathy.

PURPOSE: To report 2 cases with a novel finding of bullous epithelial keratopathy associated with netarsudil use. OBSERVATIONS: A 72-year-old man with history of primary open angle glaucoma was started on netarsudil daily in both eyes for uncontrolled intraocular pressures despite treatment with latanoprost, brimonidine, and dorzolamide-timolol. One month later he presented with bilateral conjunctival hyperemia, predominantly inferior corneal epithelial bullae, and keratic precipitates without hypopyon. Netarsudil was discontinued, and the patient was started on topical steroids. One week later, the hyperemia and corneal edema had resolved while many small keratic precipitates persisted.A 29-year-old man with history of rubella-associated glaucoma and chronic postoperative inflammation on prednisolone was started on netarsudil in his left eye only for elevated intraocular pressures despite latanoprost, brimonidine, and dorzolamide-timolol. Two months later, he complained of eye pain and decreased vision since starting netarsudil. Examination revealed mild hyperemia and inferior corneal epithelial bullae without keratic precipitates. Netarsudil was discontinued, and two weeks later, conjunctival injection resolved and cornea cleared. CONCLUSIONS AND IMPORTANCE: Netarsudil ophthalmic solution 0.02% (Rhopressa) is a rho-kinase inhibitor recently approved for lowering intraocular pressure in open-angle glaucoma or ocular hypertension. As netarsudil continues to be increasingly used, physicians and patients need to be aware of this new possible adverse effect.

Cytomegalovirus retinitis in an immunocompetent host after complicated cataract surgery.

PURPOSE: To report a case of an immunocompetent patient who developed cytomegalovirus (CMV) retinitis after complicated cataract surgery resulting in aphakia. OBSERVATIONS: A 67-year-old man with type 2 diabetes developed retinitis six months after cataract surgery that resulted in aphakia. Anterior chamber DNA testing was positive for CMV. Comprehensive systemic work-up revealed no immune insufficiency. The retinitis was successfully treated with intravitreal foscarnet and extended oral valgancyclovir treatment, however, he subsequently developed rhegmatogenous retinal detachment. CONCLUSION AND IMPORTANCE: CMV retinitis may occur in immunocompetent patients in the setting of aphakia and prolonged topical steroid use.

Evaluation of a multimedia marketing campaign to engage African American patients in glaucoma screening.

Our objective was to determine which messaging approaches from a marketing campaign were most effective in recruiting African American individuals to a glaucoma screening and research study. We conducted a multimedia marketing campaign in Philadelphia from 01/31/2018 to 06/30/2018. Messaging approaches included radio advertisements and interviews (conducted in partnership with a local radio station with a large African American listener base), print materials, event tables, and online postings. Participants received free glaucoma screenings and the opportunity to enroll in our glaucoma genetics study. These screenings allowed individuals with glaucoma to receive a full examination and treatment plan with a glaucoma specialist, as well as to contribute to future efforts to identify genetic variants underlying this disease. We compared inquiry, enrollment, and cost yield for each messaging approach. Our campaign resulted in 154 unique inquiries, with 98 patients receiving glaucoma screenings (64%) and 60 patients enrolling in our study (39%). Commercials on WURD radio yielded the highest number of inquiries (62%) and enrollments (62%), but at relatively high cost ($814/enrolled patient). The most inexpensive approach that yielded more than five enrollments was postcards ($429/enrolled patient). Our campaign suggests that high-frequency commercials and postcards distributed at targeted healthcare locations are particularly effective and affordable options for connecting with the African American community. Our findings can help to inform recruitment efforts for other understudied diseases in minority populations.

A rhlI 5' UTR-Derived sRNA Regulates RhlR-Dependent Quorum Sensing in Pseudomonas aeruginosa.

N-Acyl homoserine lactone (AHL) quorum sensing (QS) controls expression of over 200 genes in Pseudomonas aeruginosa. There are two AHL regulatory systems: the LasR-LasI circuit and the RhlR-RhlI system. We mapped transcription termination sites affected by AHL QS in P. aeruginosa, and in doing so we identified AHL-regulated small RNAs (sRNAs). Of interest, we noted that one particular sRNA was located within the rhlI locus. We found that rhlI, which encodes the enzyme that produces the AHL N-butanoyl-homoserine lactone (C4-HSL), is controlled by a 5' untranslated region (UTR)-derived sRNA we name RhlS. We also identified an antisense RNA encoded opposite the beginning of the rhlI open reading frame, which we name asRhlS. RhlS accumulates as wild-type cells enter stationary phase and is required for the production of normal levels of C4-HSL through activation of rhlI translation. RhlS also directly posttranscriptionally regulates at least one other unlinked gene, fpvA. The asRhlS appears to be expressed at maximal levels during logarithmic growth, and we suggest RhlS may act antagonistically to the asRhlS to regulate rhlI translation. The rhlI-encoded sRNAs represent a novel aspect of RNA-mediated tuning of P. aeruginosa QS.IMPORTANCE The opportunistic human pathogen Pseudomonas aeruginosa possesses multiple quorum sensing systems that regulate and coordinate production of virulence factors and adaptation to different environments. Despite extensive research, the regulatory elements that play a role in this complex network are still not fully understood. By using several RNA sequencing techniques, we were able to identify a small regulatory RNA we named RhlS. RhlS increases translation of RhlI, a key enzyme in the quorum sensing pathway, and represses the fpvA mRNA encoding one of the siderophore pyoverdine receptors. Our results highlight a new regulatory layer of P. aeruginosa quorum sensing and contribute to the growing understanding of the role regulatory RNAs play in bacterial physiology.

Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study: gender and risk of POAG in African Americans.

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects' mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44-1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences.