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.

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.

Salary Negotiations: Gender Differences in Attitudes, Priorities, and Behaviors of Ophthalmologists.

PURPOSE: To investigate attitudes, priorities, and behaviors of ophthalmologists in salary negotiations. DESIGN: Cross-sectional study. METHODS: A Qualtrics survey was disseminated to U.S.-based practicing ophthalmologists between November 1, 2021 and March 31, 2022 and assessed attitudes, behaviors, and priorities surrounding salary negotiation during the respondents' first negotiation as a practicing physician and currently. Optional case-based scenarios were also included. RESULTS: Of 424 respondents, 155 (36.5%) identified as male (M) and 269 (63.3%) identified as female (F). Men were more likely to negotiate salary for their first position as an independent ophthalmologist (M 78.3%, F 68.2%; P = .04). Respondents of both genders assessed their success similarly; 85.0% of men and 75.7% of women (P = .07) felt that their negotiation was very successful or somewhat successful. Women were more likely to select "flexibility in clinic/OR schedule for personal commitments" as a priority during salary negation for their first position (M 14.8%, F 23.1%; P = .04). Women ophthalmologists reported feeling more uncomfortable (M 36.1%, F 49.1%; P = .01), intimidated (M 20.0%, F 43.5%; P < .01), and were less likely to feel well-trained (M 24.5%, F 13.0%; P < .01). Most respondents never received formal training in negotiation. CONCLUSIONS: We found significant gender differences among ophthalmologists in attitudes, priorities and behaviors surrounding salary negotiation. There were low reported levels of formal negotiation training, which appears to disadvantage women more than men. These gender disparities suggest that incorporating education about negotiation skills and career development early in training may be impactful.

New Devices in Glaucoma.

Glaucoma remains a leading cause of blindness globally. Minimally invasive treatment techniques are rapidly expanding the availability of therapeutic options for glaucoma. These include devices aimed at enhancing outflow through the subconjunctival space, Schlemm's canal, and suprachoroidal space, sustained-release drug delivery devices, and extraocular devices aiming to reduce glaucomatous progression through other novel means. In this review, we provide an overview of several novel devices either newly available or in development for the medical and surgical management of glaucoma. Further studies are required to determine the long-term efficacy of these devices and how they will integrate into the current landscape of glaucoma management.

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.

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.

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.

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.

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.

Biocompatibility and feasibility of VisiPlate, a novel ultrathin, multichannel glaucoma drainage device.

BACKGROUND: Glaucoma is the leading cause of blindness worldwide. Glaucoma drainage devices and minimally invasive glaucoma surgeries (MIGS) often present with tradeoffs in safety and durability of efficacy. Using a rabbit model, we examined the biocompatibility and feasibility of VisiPlate, a novel, ultrathin, tubeless subconjunctival shunt comprised of a network of microchannels. METHODS: Six naive female New Zealand White rabbits received implants (three only in the right eye with contralateral eye untreated and three in both eyes) composed of a 400-nm-thick aluminum oxide core coated with 2 µm of parylene-C, manufactured with microelectromechanical systems (MEMS) techniques. Tonometry, slit lamp exam, clinical exam, fluorescein patency testing, and histopathology were performed. RESULTS: VisiPlate demonstrated IOP-lowering of 20-40% compared to baseline at each time point over the course of 3 months in the nine implanted eyes. All eyes developed blebs over the implant, and fluorescein testing demonstrated fluid patency at 22 days post-implantation. Slit lamp and clinical observations showed that VisiPlate was well tolerated, with low levels of conjunctival congestion, conjunctival swelling, aqueous flare, hyphema, and iris involvement from surgery that resolved over time. At sacrifice time points of 93 days and 180 days, the only notable observations were mild levels of conjunctival congestion in implanted eyes. Histopathology showed minimal tissue response and no obvious inflammation, fibrosis, or necrosis around the implant. CONCLUSIONS: The results of this in vivo study demonstrate the biocompatibility and IOP-lowering effect of a multichannel, ultrathin subconjunctival shunt in a rabbit model. The data suggest that VisiPlate may safely enhance aqueous outflow and significantly reduce intraocular pressure.

Demographic and Clinical Characteristics Associated with Minimally Invasive Glaucoma Surgery Use: An Intelligent Research in Sight (IRIS®) Registry Retrospective Cohort Analysis.

PURPOSE: Minimally invasive glaucoma surgery (MIGS) is increasingly performed at the time of cataract extraction. Understanding the demographic and clinical characteristics of patients undergoing MIGS procedures may provide insight into patient selection. This study evaluates racial-ethnic and other differences in the use of MIGS in persons with cataract and open-angle glaucoma (OAG). DESIGN: Retrospective cohort study using Intelligent Research in Sight (IRIS) Registry data. PARTICIPANTS: Patients aged ≥ 40 years with a diagnosis of OAG and no history of MIGS or cataract surgery who were undergoing cataract extraction, with or without MIGS, during 2013 to 2017 in the United States. METHODS: Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Variables assessed include age, sex, race-ethnicity, disease severity, insurance type, census region, comorbidity, and cup-to-disc ratio (CDR). RESULTS: The odds of MIGS use was greater among patients who were aged ≥ 60 years (OR, 1.10 [95% CI, 1.05-1.16]); Black (OR, 1.11 [CI, 1.07-1.15]) compared with White; a Medicare recipient (OR, 1.12 [CI, 1.10-1.15]) versus privately insured; or in the Midwest (OR, 1.32 [CI, 1.28-1.36]) or Northeast (OR, 1.26 [CI, 1.22-1.30]) compared with the South. Having moderate rather than mild glaucoma (OR, 1.07 [CI, 1.04-1.11]) and a higher CDR (OR for 0.5 to 0.8 vs. <0.5, 1.24 [CI, 1.21-1.26]; OR for >0.8 to 1.0 vs. <0.5, 1.27 [CI, 1.23-1.32]) were also each associated with increased odds of MIGS use. Use of MIGS was less likely in women (OR, 0.96 [CI, 0.94-0.98]); patients taking 5 to 7 glaucoma medications (OR, 0.94 [CI, 0.90-0.99]) compared with 1 to 2 medications; and patients with severe, compared with mild, glaucoma (OR, 0.64 [CI, 0.61-0.67]). CONCLUSIONS: This analysis highlights the importance of capturing race-ethnicity data and other pertinent patient characteristics in electronic health records to provide insight into practice patterns. Such data can be used to assess the long-term performance of MIGS and other procedures in various patient populations.

Clinical and Economic Burden of Glaucoma by Disease Severity: A United States Claims-Based Analysis.

PURPOSE: To provide updated estimates of the clinical and economic burden in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG) by disease severity in the United States and to estimate incremental costs associated with disease progression. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with 1 or more International Classification of Diseases, 10th Revision, Clinical Modification, diagnoses for OAG or OHT who are 40 years of age or older. METHODS: Patients were identified from IQVIA's PharMetrics Plus database during the index period (October 1, 2015, to August 31, 2017). Patients had continuous health plan enrollment for 12 months or more before and after the index date (first OAG or OHT diagnosis during index period) and were stratified by baseline disease severity based on diagnosis code. Annual eye-related outpatient healthcare use and costs were estimated on a per-user basis. A generalized linear model was used to estimate adjusted mean costs by severity and to evaluate the impact of observed disease worsening on costs. A multivariate logistic regression analysis evaluated the relationship between severity and odds of falls or fractures. MAIN OUTCOME MEASURES: Total eye-related outpatient costs and odds of falls or fractures. RESULTS: One hundred seventy-seven thousand three hundred fifty-two OHT and OAG patients were identified (67.8% with OAG). Open-angle glaucoma patients showed higher eye-related outpatient costs than OHT patients (median, $516 [interquartile range (IQR), $323-$898] vs. $344 [IQR, $197-$617], respectively). Patients with severe OAG showed higher eye-related outpatient costs than moderate and mild OAG patients (median, $639 [IQR, $381-$1264] vs. $546 [IQR, $345-$950] vs. $476 [IQR, $304-$765], respectively; P < 0.0001), as well as higher glaucoma-related pharmacy costs (median, $493 [IQR, $122-$1457] vs. $244 [IQR, $84-$1113] vs. $139 [IQR, $66-$818], respectively; P < 0.0001). In adjusted analyses, disease worsening was associated with at least 2-fold higher annual eye-related outpatient costs (P < 0.0001). Severe OAG patients had significantly higher odds of fall or fracture compared with OHT patients (odds ratio, 1.34; 95% confidence interval, 1.13-1.59). CONCLUSIONS: Updated estimates showed highest eye-related costs for those with severe disease and disease progression among patients with OAG and OHT. Severe OAG was associated with increased risk of falls or fractures compared with patients with OHT. Therapies that delay disease progression may provide clinical and economic benefits.

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.

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.

The association of mitochondrial DNA haplogroups with POAG in African Americans.

Mitochondrial dysfunction has been implicated in the pathogenesis of primary open-angle glaucoma (POAG). However, the potential significance of mitochondrial DNA (mtDNA) haplogroups to POAG has not been evaluated in the overaffected African American population. To investigate the association of mtDNA haplogroups with POAG and its phenotypic characteristics, genotyping data from 4081 African American subjects (1919 cases and 2162 controls) was analyzed using 1293 positions on mtDNA. The overall frequency of mtDNA haplogroups in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort was 37% L3, 29% L2, 21% L1, 4% L0, and 10% non-African haplogroups (non-L). When all haplogroups (L0, L1, L2, and non-L) were compared against theL3 reference group, after adjusting by age and principal component of ancestry, the non-L3 haplogroups showed higher risk of POAG (OR-1.19, p = 0.02), with a particularly strong association among males (OR = 1.41, p = 0.003). More specifically the non-L group was associated with higher POAG risk than the L3 haplogroup (OR = 1.77, p = 0.007, Bonferroni adjusted p = 0.027) and to the L3e (n = 256, OR = 1.92, p = 0.007, Bonferroni adjusted p = 0.029). No significant association was found when genders were analyzed together or in female only analysis. There were no significant differences in various POAG endophenotypes across mtDNA haplogroups. This study expands our knowledge of mitochondrial genetics and mtDNA haplogroup associations in African American POAG. Further work is needed to better understand the functional role of mtDNA polymorphisms and their interactions with nuclear genes that affect POAG.

Non-physician grader reliability in measuring morphological features of the optic nerve head in stereo digital images.

OBJECTIVE: To introduce a new method of grading optic nerve stereo disc photographs and evaluate reproducibility of assessments by non-physician graders in a reading center. METHODS: Three non-physician graders, experienced in grading features of the retina but not the optic nerve head (ONH), were trained by glaucoma specialists to assess digital stereo color images of the ONH. These graders assessed a total of 2554 digital stereo disc images from glaucoma cases and controls participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study by outlining the optic cup and disc. Inter-grader reproducibility of area, height, and width measurements was analyzed. RESULTS: Among all images, the intraclass correlation (95% confidence interval) was 0.90 (0.89, 0.90) for the cup area using only color cues; 0.92 (0.91, 0.92) for the cup area using contour and vascular cues; and 0.99 (0.99, 0.99) for the optic disc area. The intraclass correlation for cup-to-disc ratio (CDR) was 0.61 (0.58, 0.63), as determined by the ratio of optic cup area to optic disc area (using contour and vascular cues). The CDR difference by graders for area was ≤ 0.1 in 65% of images using color/vascular cues and ≤0.1 in 71% of images using color cues. CONCLUSIONS: After adequate training, non-physician graders were able to measure the optic nerve CDR with high inter-grader reliability.

Factors associated with participation by African Americans in a study of the genetics of glaucoma.

Objective: African Americans have been historically underrepresented in research studies. Our aim was to evaluate factors influencing enrollment in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Design: Patients approached to enroll in the POAAGG study were asked to complete a 15-item survey addressing demographic characteristics, knowledge of genetics and glaucoma, and opinions on human research. Survey responses were compared between subjects who enrolled (Enrollers) and did not enroll (Decliners) in the POAAGG study. Results: Enrollers (N = 190) were 3.7 years younger (P = 0.007) and had similar gender, education, and income level to Decliners (N = 117). Knowledge about genetics and glaucoma was similar between groups. Enrollers were more comfortable providing DNA for research studies (93.1% vs 54.1%; P < 0.001) and more likely to have participated in prior studies (P = 0.003) and consider participating in future studies (P < 0.001). Among Decliners, lack of time was the primary reason given for not enrolling. Conclusion: To increase participation of African Americans in genetic research studies, efforts should be made to raise comfort with DNA donation.

Latanoprostene bunod ophthalmic solution 0.024% in the treatment of open-angle glaucoma: design, development, and place in therapy.

Latanoprostene bunod (LBN) 0.024%, a modified prostaglandin analog, was approved on November 2, 2017, for the reduction of IOP in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). LBN works by combining the IOP-lowering effects of the prostaglandin analogs (through the uveoscleral pathway) with nitric oxide-induced relaxation of the trabecular meshwork and Schlemm's canal. Nitric oxide-induced relaxation of the trabecular meshwork and Schlemm's canal leads to increased outflow through the trabecular meshwork and thus lowering of IOP. LBN has now been shown in multiple clinical studies to be effective and safe. In this article, we summarize the clinical trials that led to LBN's approval as well as the comparative studies that have been done to evaluate the efficacy of this drug as compared to other US Food and Drug Administration (FDA)-approved therapies for OAG and OHT. We then review the side effects of treatment that were seen in each of these studies. Finally, we will attempt to discuss the place of this drug in therapy for patients with OAG.