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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 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.

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.

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. 0.8 to 1.0 vs. 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.

To report 5-year treatment outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study.Multicenter randomized clinical trial.A total of 242 eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 patients in the tube group and 117 patients in the trabeculectomy group.Patients were enrolled at 16 clinical centers and randomly assigned to treatment with a tube shunt (350-mmThe primary outcome measure was the rate of surgical failure, defined as intraocular pressure (IOP)21 mmHg or reduced20% from baseline, IOP ≤ 5 mmHg, reoperation for glaucoma, or loss of light perception. Secondary outcome measures included IOP, glaucoma medical therapy, and visual acuity.The cumulative probability of failure after 5 years of follow-up was 42% in the tube group and 35% in the trabeculectomy group (P = 0.21; hazard ratio = 1.31; 95% confidence interval = 0.86-2.01). At 5 years, IOP (mean ± standard deviation) was 13.4 ± 3.5 mmHg in the tube group and 13.0 ± 5.2 mmHg in the trabeculectomy group (P = 0.52), and the number of glaucoma medications (mean ± standard deviation) was 2.2 ± 1.3 in the tube group and 1.3 ± 1.4 in the trabeculectomy group (P0.001).Trabeculectomy with MMC and tube shunt surgery produced similar IOPs after 5 years of follow-up in the PTVT Study, but fewer glaucoma medications were required after trabeculectomy. No significant difference in the rate of surgical failure was observed between the 2 surgical procedures at 5 years.

To describe postoperative complications encountered in the Primary Tube Versus Trabeculectomy (PTVT) Study during 5 years of follow-up.Multicenter randomized clinical trial.A total of 242 eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 patients in the tube group and 117 patients in the trabeculectomy group.Patients were enrolled at 16 clinical centers and randomly assigned to treatment with a tube shunt (350-mmSurgical complications, reoperations for complications, visual acuity, and cataract progression.Early postoperative complications occurred in 24 patients (19%) in the tube group and 40 patients (34%) in the trabeculectomy group (P = 0.013). Late postoperative complications developed in 27 patients (22%) in the tube group and 32 patients (27%) in the trabeculectomy group (P = 0.37). Serious complications producing vision loss and/or requiring a reoperation were observed in 3 patients (2%) in the tube group and 9 patients (8%) in the trabeculectomy group (P = 0.11). Cataract progression was seen in 65 patients (52%) in the tube group and 52 patients (44%) in the trabeculectomy group (P = 0.30). Surgical complications were not associated with a higher rate of treatment failure (P = 0.61), vision loss (P = 1.00), or cataract progression (P = 0.77) CONCLUSIONS: A large number of surgical complications were observed in the PTVT Study, but most were transient and self-limited. The incidence of early postoperative complications was higher following trabeculectomy with MMC than with tube shunt surgery. The rates of late postoperative complications, serious complications, and cataract progression were similar with both surgical procedures after 5 years of follow-up. Surgical complications did not increase the risk of treatment failure, vision loss, or cataract progression.

Loss of the ability to drive is highly associated with depressive symptoms in older persons. There are many reasons why an individual may give up driving, poor vision being an important one. Given the high prevalence of glaucoma in this population and the critical role that vision plays in the ability to drive, it is therefore important to consider how glaucomatous vision loss plays into the ability to drive safely. In this review article, we will summarize the literature on the topic of glaucoma and driving and the studies that have been done to evaluate this topic. Studies of both the self-perceived impact of glaucomatous visual field loss on driving as well as studies that include on-road and simulated driving experiments will be reviewed. We will discuss how patients with glaucoma may be assessed for their driving safety and review how we treat and evaluate these patients in our own practices.

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.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.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.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; P0.001). Higher baseline IOP was associated with increased risk for post-LPI IOP elevation (OR: 1.19; P0.001). Laser type and energy were not associated with either post-LPI IOP elevation or iritis (P0.11 for all).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.

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.

PRECIS This retrospective study characterized the efficacy and safety of three different microinvasive glaucoma surgery (MIGS) procedures in a predominantly African-American population at the Philadelphia Veterans Affairs Hospital (Hydrus, Kahook, iStent), demonstrating no significant difference in IOP and medication reduction between the three at long term follow up. PURPOSE To compare the efficacy and safety of three different microinvasive glaucoma surgery (MIGS) procedures in a predominantly African-American population. METHODS Retrospective cohort study of patients undergoing cataract extraction combined with one of three MIGS procedures (Hydrus, iStent, Kahook) at the Philadelphia Veterans Affairs Medical Center between 1/1/2015 and 11/1/2020. Analysis of variance and regression models were used to compare reduction in intraocular pressure (IOP) and medication use among three MIGS types. RESULTS 123 eyes of 112 patients were included, including 56 (45.5%) eyes for Hydrus, 40 (32.5%) eyes for iStent , and 27 (22.0%) eyes for Kahook. Adjusted mean IOP reduction was greater for Hydrus at postoperative day 1 (-4.49 vs. -1.76 for iStent and -1.69 for Kahook, P=0.05 and greater for Kahook at postoperative week 1 (-2.53 vs. +0.70 for iStent vs. -1.41 for Hydrus, P=0.02), but did not differ significantly between MIGS types at subsequent postoperative visits (all P>0.05). In multivariable analysis, MIGS type was not significantly associated with reduction in IOP or medication use at 9-12 months postoperatively. There were no significant differences in complication rates across MIGS types. CONCLUSION In this study, the difference in IOP lowering and medication reduction postoperatively between the Hydrus, iStent, and Kahook was not statistically significant after postoperative day 1. More studies are needed to evaluate outcomes of MIGS surgeries in glaucoma populations of different disease severity.

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.

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.Retrospective cohort study.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.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.Total eye-related outpatient costs and odds of falls or fractures.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; P0.0001), as well as higher glaucoma-related pharmacy costs (median, $493 [IQR, $122-$1457] vs. $244 [IQR, $84-$1113] vs. $139 [IQR, $66-$818], respectively; P0.0001). In adjusted analyses, disease worsening was associated with at least 2-fold higher annual eye-related outpatient costs (P0.0001). 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).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.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects African Americans. Large-scale POAG genetic studies have focused on individuals of European and Asian ancestry, limiting our understanding of disease biology. Here we report genetic analysis of the largest-ever deeply phenotyped African American population (n=5950), identifying a novel POAG-associated SNP on chromosome 11 near the TRIM66 gene (rs112369934). POAG trait association also implicated SNPs in genes involved in trabecular meshwork homeostasis and retinal ganglion cell maintenance. These new loci deepen our understanding of the pathophysiology of POAG in African Americans.

Purpose To report 1-year treatment outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. Design Multicenter, randomized clinical trial. Participants Two hundred forty-two eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 in the tube group and 117 in the trabeculectomy group. Methods Patients were enrolled at 16 clinical centers and assigned randomly to treatment with a tube shunt (350-mm 2 Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC; 0.4 mg/ml for 2 minutes). Main Outcome Measures Intraocular pressure (IOP), glaucoma medical therapy, visual acuity, visual fields, surgical complications, and failure (IOP of more than 21 mmHg or reduced by less than 20% from baseline, IOP of 5 mmHg or less, reoperation for glaucoma, or loss of light perception vision). Results The cumulative probability of failure during the first year of follow-up was 17.3% in the tube group and 7.9% in the trabeculectomy group ( P = 0.01; hazard ratio, 2.59; 95% confidence interval, 1.20–5.60). Mean ± standard deviation IOP was 13.8±4.1 mmHg in the tube group and 12.4±4.4 mmHg in the trabeculectomy group at 1 year ( P = 0.01), and the number of glaucoma medications was 2.1±1.4 in the tube group and 0.9±1.4 in the trabeculectomy group ( P P = 0.06). Serious complications requiring reoperation or producing a loss of 2 Snellen lines or more occurred in 1 patient (1%) in the tube group and 8 patients (7%) in the trabeculectomy group ( P = 0.03). Conclusions Trabeculectomy with MMC had a higher surgical success rate than tube shunt implantation after 1 year in the PTVT Study. Lower IOP with use of fewer glaucoma medications was achieved after trabeculectomy with MMC compared with tube shunt surgery during the first year of follow-up. The frequency of serious complications producing vision loss or requiring reoperation was lower after tube shunt surgery relative to trabeculectomy with MMC.

Background: It is currently unclear whether primary open-angle glaucoma (POAG) affects neurological functions outside of vision, such as cognition. Objective: This study examined the association between POAG and cognitive impairment in African Americans. Methods: Masked interviewers administered the Montreal Cognitive Assessment (MoCA) to patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study at the Scheie Eye Institute. Cases were further assessed for retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss. Univariate and multivariate linear regression analyses were performed to compare mean MoCA score between cases and controls and to assess the association between POAG severity and MoCA score. Results: A total of 137 patients completed the MoCA, including 70 cases and 67 controls. The mean age ± SD was 68.7 ± 11.2 years for cases and 65.7 ± 10.4 years for controls (p = 0.11). The mean MoCA total score (out of 30 points) was 20.3 among POAG cases and 21.3 among controls (mean difference = –1.03, 95% confidence interval, CI = –2.54 to 0.48, p = 0.18). After adjusting for age, gender, education level, diabetes, hypertension, and smoking status, the mean difference in the MoCA total score between cases and controls was –0.64 (95% CI = –1.72 to 0.45, p = 0.25). Among cases, more VF loss was associated with lower total MoCA score for mean deviation (adjusted linear trend p = 0.02) and VF index (adjusted linear trend p = 0.03). There was no significant association between average RNFL thickness and total MoCA score. Conclusions: POAG cases and controls had similar neurocognitive function as measured by the MoCA. Among POAG cases, worse VF loss was associated with lower MoCA. Future studies are needed to further elucidate the clinical effect of neuropathy in POAG.

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

The crystalline lens plays an important role in the pathophysiology of primary angle closure and primary angle-closure glaucoma. The aging process is associated with a progressive enlargement of the lens, resulting in greater iridolenticular and iridotrabecular contact, which exacerbates both pupillary block and appositional angle closure, irrespective of the cataract status of the lens. Cataract surgery has been shown to widen the angle and reduce intraocular pressure in eyes with primary angle closure or primary angle-closure glaucoma. Recently, clear lens phacoemulsification has been suggested as a treatment modality in such eyes. We review the literature on clear lens extraction in eyes with angle closure and discuss its efficacy, safety, and indications. Although it is evident that clear lens extraction is beneficial in eyes with primary angle closure and primary angle-closure glaucoma, it is technically challenging and should be performed by experienced surgeons who not only master the procedure but are also able to deal with potential complications. Since the follow-up of the reviewed studies is relatively short, long-term follow-up (>10 years) of patients who undergo this procedure is needed to evaluate the safety and confirm the early benefits reported.

Background/aims ONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan. Methods Adults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days. Results Day 29 mean diurnal IOP was −7.2 mm Hg for ONO-9054 vs −6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤−25%, ≤−30% and ≤−35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p

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.

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.

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

Underrepresented in medicine individuals have historically been discouraged to consider surgical subspecialties and instead encouraged toward primary care fields thus representing less than 2% of the workforce in these areas. In the last 15 years, the Rabb-Venable Excellence in Research program has worked with medical students, residents, and fellows in preparing them to become ophthalmologists, medical researchers, academicians, or private practice. While the Rabb-Venable program centers on expanding the number of ophthalmologists, pipeline programs exist to enhance the representation of URM individuals in other medical specialties to decrease health disparities. This chapter discusses the Rabb-Venable program, funded by the National Institutes of Health and the sponsorship of the National Medical Association (NMA), has combined a research competition at the annual meeting of the NMA. The Rabb-Venable program is geared toward increasing the number of (URM) in the field of ophthalmology and increasing the number of URM participants in academic medicine. The program has a twofold mission of supporting the development of the clinical specialty of ophthalmology and creating physician researchers through leadership, academic excellence, professionalism, service, and mentorship. Exploration of the different types of eye diseases that disproportionally affect minority groups are identified. In addition the medical students who have been part of the program and are eligible to apply have had an 84% rate of matching in ophthalmology.

To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort.FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities.Positive FH was associated with increased risk of POAG (age-adjusted odds ratio and 95% confidence interval 3.4 [2.8, 4.1]). In age-adjusted analysis among POAG cases, positive FH was associated with younger age (P.001), female sex (P.001), hypertension (P = .006), use of hypertension medication (P = .03), and prior glaucoma surgery (P = .02). Cases with positive FH also had thicker retinal nerve fiber layers (P = .03).The risk conferred by positive FH suggests strong genetic underpinnings for some patients with this disease, which will be investigated by genome-wide association studies and whole exome sequencing. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Purpose To describe the baseline characteristics of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort, the largest African American population with primary open-angle glaucoma (POAG) recruited at a single institution (University of Pennsylvania [UPenn], Department of Ophthalmology, Scheie Eye Institute) to date. Design Population-based, cross-sectional, case-control study. Participants A total of 2520 African American subjects aged 35 years or more who were recruited from the greater Philadelphia, Pennsylvania area. Methods Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current ZIP codes surrounding UPenn were recorded and US census data were queried to infer socioeconomic status. The eye examination included measurement of visual acuity (VA) and intraocular pressure, and a detailed anterior and posterior segment examination, including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography, and measurement of central corneal thickness. Main Outcome Measures The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco use, ocular conditions (including blindness, cataract, nonproliferative diabetic retinopathy, and age-related macular degeneration), and use of ocular medication and surgery were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort. Results Of the 2520 African Americans recruited to the POAAGG study to date, 2067 (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria and completed the detailed clinical ocular examination. Cases were more likely to have a lower BMI ( P P P P = 0.02), and be female ( P Conclusions The POAAGG study has currently recruited more than 2000 African Americans eligible for a POAG genetics study. Blindness and low BMI were significantly associated with POAG. This population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level.

Background African Americans have been historically under-represented in genetic studies. More research is needed on effective recruitment strategies for this population, especially on approaches that supplement traditional clinic enrollment. This study evaluates the cost and efficacy of four supplemental recruitment methods employed by the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Methods After enrolling 2304 patients from University of Pennsylvania ophthalmology clinics, the POAAGG study implemented four new recruitment methods to supplement clinic enrollment. These methods included: 1) outreach in the local community, 2) in-house screening of community members (“in-reach”), 3) expansion to two external sites, and 4) sampling of the Penn Medicine Biobank. The cost per subject was calculated for each method and enrollment among cases, controls, and suspects was reported. Results The biobank offered the lowest cost ($5/subject) and highest enrollment yield (n = 2073) of the four methods, but provided very few glaucoma cases (n = 31). External sites provided 88% of cases recruited from the four methods (n = 388; $85/subject), but case enrollment at these sites declined over the next 9 months as the pool of eligible subjects was depleted. Outreach and in-reach screenings of community members were very high cost for low return on enrollment ($569/subject for 102 subjects and $606/subject for 45 subjects, respectively). Conclusions The biobank offered the most cost-effective method for control enrollment, while expansion to external sites was necessary to recruit richly phenotyped cases. These recruitment methods helped the POAAGG study to exceed enrollment of the discovery cohort (n = 5500) 6 months in advance of the predicated deadline and could be adopted by other large genetic studies seeking to supplement clinic enrollment.

Objective: No method of grading visual field (VF) defects has been widely accepted throughout the glaucoma community. The SCHEIE (Systematic Classification of Humphrey visual fields-Easy Interpretation and Evaluation) grading system for glaucomatous visual fields was created to convey qualitative and quantitative information regarding visual field defects in an objective, reproducible, and easily applicable manner for research purposes.Methods: The SCHEIE grading system is composed of a qualitative and quantitative score. The qualitative score consists of designation in one or more of the following categories: normal, central scotoma, paracentral scotoma, paracentral crescent, temporal quadrant, nasal quadrant, peripheral arcuate defect, expansive arcuate, or altitudinal defect. The quantitative component incorporates the Humphrey visual field index (VFI), location of visual defects for superior and inferior hemifields, and blind spot involvement. Accuracy and speed at grading using the qualitative and quantitative components was calculated for non-physician graders.Results: Graders had a median accuracy of 96.67% for their qualitative scores and a median accuracy of 98.75% for their quantitative scores. Graders took a mean of 56 seconds per visual field to assign a qualitative score and 20 seconds per visual field to assign a quantitative score.Conclusion: The SCHEIE grading system is a reproducible tool that combines qualitative and quantitative measurements to grade glaucomatous visual field defects. The system aims to standardize clinical staging and to make specific visual field defects more easily identifiable. Specific patterns of visual field loss may also be associated with genetic variants in future genetic analysis.

Background The question of whether DNA obtained from saliva is an acceptable alternative to DNA from blood is a topic of considerable interest for large genetics studies. We compared the yields, quality and performance of DNAs from saliva and blood from a mostly elderly study population. Methods Two thousand nine hundred ten DNAs from primarily elderly subjects (mean age ± standard deviation (SD): 65 ± 12 years), collected for the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study, were evaluated by fluorometry and/or spectroscopy. These included 566 DNAs from blood and 2344 from saliva. Subsets of these were evaluated by Sanger sequencing (n = 1555), and by microarray SNP genotyping (n = 94) on an Illumina OmniExpress bead chip platform. Results The mean age of subjects was 65, and 68 % were female in both the blood and saliva groups. The mean ± SD of DNA yield per ml of requested specimen was significantly higher for saliva (17.6 ± 17.8 μg/ml) than blood (13.2 ± 8.5 μg/ml), but the mean ± SD of total DNA yield obtained per saliva specimen (35 ± 36 μg from 2 ml maximum specimen volume) was approximately three-fold lower than from blood (106 ± 68 μg from 8 ml maximum specimen volume). The average genotyping call rates were >99 % for 43 of 44 saliva DNAs and >99 % for 50 of 50 for blood DNAs. For 22 of 23 paired blood and saliva samples from the same individuals, the average genotyping concordance rate was 99.996 %. High quality PCR Sanger sequencing was obtained from ≥ 98 % of blood (n = 297) and saliva (n = 1258) DNAs. DNA concentrations ≥10 ng/μl, corresponding to total yields ≥ 2 μg, were obtained for 94 % of the saliva specimens (n = 2344). Conclusions In spite of inferior purity, the performance of saliva DNAs for microarray genotyping was excellent. Our results agree with other studies concluding that saliva collection is a viable alternative to blood. The potential to boost study enrollments and reduce subject discomfort is not necessarily offset by a reduction in genotyping efficiency. Saliva DNAs performed comparably to blood DNAs for PCR Sanger sequencing. Electronic supplementary material The online version of this article (doi:10.1186/s12920-016-0172-y) contains supplementary material, which is available to authorized users.

Objective To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., monocular trial) is a better assessment of medication response than testing each eye independently. Design Analysis of data from a prospective, randomized, clinical trial. Participants Two hundred six participants with ocular hypertension randomized to the observation group and later started on a topical prostaglandin analog (PGA). Methods Participants were started on a topical PGA in 1 eye and returned in approximately 1 month to determine medication response. The IOP response of the trial eye was determined by the IOP change between baseline and 1 month in the trial eye alone (unadjusted method) and by adjusting for the IOP change in the fellow eye between the same visits (adjusted method). Our "gold standard" for medication response was the IOP change in the trial eye between up to 3 pre- and 3 posttreatment visits on the same medication. Pearson correlation was used to compare the gold standard with the unadjusted and adjusted methods. In addition, symmetry of IOP response between trial and fellow eyes to the same medication was determined by correlating the trial eye IOP change between up to 3 pre- and 3 posttreatment visits to the fellow eye IOP change between the same visits. Main Outcome Measures Correlations of IOP change of the trial eye using the gold standard to the IOP change of the trial eye using the unadjusted and adjusted methods. Results The correlations of IOP change using the gold standard to the IOP change using the unadjusted and adjusted methods were r = 0.40 and r = 0.41, respectively. The correlation of IOP change of both eyes between the same pre- and posttreatment visits was r = 0.81. Conclusions The monocular trial (i.e., adjusted method) appears equivalent to testing each eye independently (i.e., unadjusted method); however, neither method is adequate to determine medication response to topical PGAs. Both eyes have a similar IOP response to the same PGA. Further studies to understand IOP fluctuation are necessary to improve current methods of assessing medication response. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose We investigate the function of the V83I polymorphism (m.6150G>A, rs879053914) in the mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) gene and its role in African American (AA) primary open-angle glaucoma (POAG). Methods This study used Sanger sequencing (1339 cases, 850 controls), phenotypic characterization of Primary Open-Angle African American Glaucoma Genetics study (POAAGG) cases, a masked chart review of CO1 missense cases (V83I plus M117T, n = 29) versus wild type cases (n = 29), a yeast 2-hybrid (Y2H) cDNA library screen, and quantification of protein–protein interactions by Y2H and ELISA. Results The association of V83I with POAG in AA was highly significant for men (odds ratio [OR] 6.5; 95% confidence interval [CI] 2.0–21.3, P = 0.0001), but not for women (OR 1.1; 95% CI, 0.62–2.00, P = 0.78). POAG cases having CO1 double missense mutation (V83I + M117T, L1c2 haplogroup) had a higher cup-to-disc ratio (0.77 vs. 0.71, P = 0.04) and significantly worse visual function (average pattern standard deviation, 6.5 vs. 4.3, P = 0.009; average mean deviation −10.4 vs. −4.5, P = 0.006) when compared to matched wild type cases (L1b haplogroup). Interaction of the V83I region of CO1 with amyloid beta peptide (Aβ) was confirmed by ELISA assay, and this interaction was abrogated by V83I. A Y2H screen of an adult human brain cDNA library with the V83 region of CO1 as bait retrieved the UBQLN1 gene. Conclusions The V83I polymorphism was associated strongly with POAG in AA men and disrupts Aβ-binding to CO1. This region also interacts with a neuroprotective protein, UBQLN1.

Ophthalmology departments can play a unique role in providing care for at-risk patients. This study analyzed the age, gender,and socioeconomic measures for 267,286 unique African American patients seen at University of Pennsylvania Health System (UPHS). Patients seen by the Ophthalmology Department (n=33,801) were older and more likely to be from impoverished zipcodes than those seen by other UPHS specialists. These results hint at several inherent advantages of ophthalmology departmentsin recruiting older, disadvantaged patients to their clinics. We found that supplementing this advantage with strong patient relationships, involvement of community leaders, and customized outreach efforts was key to overcoming access-to-care issues and to reaching these patients. This provides ophthalmologists with a unique opportunity to capture and refer systemic conditions with ocular manifestations and to possibly reduce disparities such as post-hospitalization readmission and mortality observed disproportionately in impoverished populations.

Subject gender, age, DNA characteristics and genotyping results corresponding to the samples used for genotyping. (“B” sample IDs indicate DNA from blood and “S” sample IDs are DNA from saliva). (DOCX 31 kb)

Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools (“Pool-seq”), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1 lineages, associated with Leber hereditary optic neuropathy (LHON) severity, was confirmed to be common (>5%) but was not significantly enriched in the POAG cases. Two variants linked to the composition of the gut microbiome, m.15784T>C (rs527236194, haplogroup L2a1) and m.16390G>A (rs41378955, L2 haplogroups), were also enriched in the case DNA pools. Conclusions These results implicate African mtDNA haplogroups L1c2, L1c2b, and L2 as risk factors for POAG. Approximately one in four African Americans have these mitochondrial ancestries, which may contribute to their elevated glaucoma risk. These haplogroups are defined in part by ancestral variants in the MT-RNR2 and/or MT-CO1 genes, several of which have prior disease associations, such as MT-CO1 missense variants that have been implicated in prostate cancer.

Objective: To identify the major risk factors for primary open-angle glaucoma (POAG) in individuals of African descent. Methods: We searched PubMed for relevant articles, with results spanning April 1947 to present. All abstracts were reviewed and, where relevant to POAG and race, articles were catalogued and analyzed. Additional sources were identified through citations in articles returned by our search. Results: Numerous potential POAG risk factors were identified and organized into categories by demographics (age, sex, and skin color), lifestyle choices (smoking, alcohol), comorbidities (hypertension, diabetes, and obesity), ophthalmic findings (eye structure, central corneal thickness, corneal hysteresis, elevated intraocular pressure, myopia, cataract, and vascular abnormalities), family history, socioeconomic status, and adherence. Older age, male sex, lower central corneal thickness, decreased corneal hysteresis, elevated intraocular pressure, myopia, vascular abnormalities, and positive family history were definitively associated with increased risk of POAG. Conclusions: Individuals at greatest risk for POAG should be screened by an ophthalmologist to allow earlier detection and to slow disease progression. Further studies on the genetics of the disease will provide more insight into underlying pathologic mechanisms and could lead to improved therapeutic interventions. Continued research in urban areas with large populations of blacks is especially needed.

Our objective is to investigate which factors and patient characteristics are associated with success in Trabectome surgery. A total of 658 phakic cases with at least of 12 months follow-up were included in the analysis. Baseline demographics and medical data were collected. The main outcome measure was intraocular pressure (IOP), glaucoma medication (Rx), and secondary glaucoma surgery if any. Success was defined as IOP reduction of 20% or more from preoperative IOP and IOP < 21 mm Hg with no secondary surgery throughout the follow-up period. Risk factors for failure were determined by using univariate and multivariate cox regression. At baseline, the average IOP was 23.6 ± 7.8 mm Hg and the average number of medications was 2.6 ± 1.3 for all cases. At 12 months, the average IOP was 16.0 ± 3.6 mm Hg (P

To describe the baseline characteristics of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort, the largest African American population with primary open-angle glaucoma (POAG) recruited at a single institution (University of Pennsylvania [UPenn], Department of Ophthalmology, Scheie Eye Institute) to date.Population-based, cross-sectional, case-control study.A total of 2520 African American subjects aged 35 years or more who were recruited from the greater Philadelphia, Pennsylvania area.Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current ZIP codes surrounding UPenn were recorded and US census data were queried to infer socioeconomic status. The eye examination included measurement of visual acuity (VA) and intraocular pressure, and a detailed anterior and posterior segment examination, including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography, and measurement of central corneal thickness.The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco use, ocular conditions (including blindness, cataract, nonproliferative diabetic retinopathy, and age-related macular degeneration), and use of ocular medication and surgery were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort.Of the 2520 African Americans recruited to the POAAGG study to date, 2067 (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria and completed the detailed clinical ocular examination. Cases were more likely to have a lower BMI (P0.01) and report a history of blindness (VA of ≤20/200; P0.001), whereas controls were more likely to have diabetes (P0.001), have nonproliferative diabetic retinopathy (P = 0.02), and be female (P0.001). Study participants were drawn largely from predominantly African American neighborhoods of low income, high unemployment, and lower education surrounding UPenn.The POAAGG study has currently recruited more than 2000 African Americans eligible for a POAG genetics study. Blindness and low BMI were significantly associated with POAG. This population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level.

Primary open-angle glaucoma (POAG) is a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. In the United States, POAG is most prevalent in African-Americans. Mitochondrial genetics and dysfunction have been implicated in POAG, and potentially pathogenic sequence variations, in particular novel transversional base substitutions, are reportedly common in mitochondrial genomes (mtDNA) from POAG patient blood. The purpose of this study was to ascertain the spectrum of sequence variation in mtDNA from African-American POAG patients and determine whether novel nonsynonymous, transversional or other potentially pathogenic sequence variations are observed more commonly in POAG cases than controls. mtDNA from African-American POAG cases (n = 22) and age-matched controls (n = 22) was analyzed by deep sequencing of a single 16,487 base pair PCR amplicon by Ion Torrent, and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The ratio of novel variants to POAG cases was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 cases, novel nonsynonymous changes in 1 of 22 cases and novel transversions in 0 of 22 cases; these proportions are significantly lower (p

To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., monocular trial) is a better assessment of medication response than testing each eye independently.Analysis of data from a prospective, randomized, clinical trial.Two hundred six participants with ocular hypertension randomized to the observation group and later started on a topical prostaglandin analog (PGA).Participants were started on a topical PGA in 1 eye and returned in approximately 1 month to determine medication response. The IOP response of the trial eye was determined by the IOP change between baseline and 1 month in the trial eye alone (unadjusted method) and by adjusting for the IOP change in the fellow eye between the same visits (adjusted method). Our "gold standard" for medication response was the IOP change in the trial eye between up to 3 pre- and 3 posttreatment visits on the same medication. Pearson correlation was used to compare the gold standard with the unadjusted and adjusted methods. In addition, symmetry of IOP response between trial and fellow eyes to the same medication was determined by correlating the trial eye IOP change between up to 3 pre- and 3 posttreatment visits to the fellow eye IOP change between the same visits.Correlations of IOP change of the trial eye using the gold standard to the IOP change of the trial eye using the unadjusted and adjusted methods.The correlations of IOP change using the gold standard to the IOP change using the unadjusted and adjusted methods were r = 0.40 and r = 0.41, respectively. The correlation of IOP change of both eyes between the same pre- and posttreatment visits was r = 0.81.The monocular trial (i.e., adjusted method) appears equivalent to testing each eye independently (i.e., unadjusted method); however, neither method is adequate to determine medication response to topical PGAs. Both eyes have a similar IOP response to the same PGA. Further studies to understand IOP fluctuation are necessary to improve current methods of assessing medication response.Proprietary or commercial disclosure may be found after the references.

Glaucoma diagnosis, management, and research require complex assessments of the optic disc. Over many decades, the gold standard of optic disc evaluation in glaucoma has been the qualitative evaluation of stereo photographic images of the optic disc, most typically as 35-mm slides or other film-based media. More recently, automated optic disc analyzers have been introduced that use either laser technologies or polarized light to image the optic disc and/or the retinal nerve fiber layer. Studies with these instruments infrequently compare them directly to stereo photographs, and available reports generally find their diagnostic precision comparable to stereo photographs.1–5 So far, the qualitative evaluation of stereo optic disc images by experienced observers remains the reference standard for optic disc evaluation in glaucoma6–8 despite the subjectivity and variability inherent in this conventional approach.9,10 As examples, contemporary clinical glaucoma trials, such as the Ocular Hypertension Treatment Study (OHTS),11,12 the Low-Pressure Glaucoma Treatment Study (LoGTS)13 and the European Glaucoma Prevention Study (EGPS),14,15 used human observers to grade conventional stereo photos to evaluate the optic disc. We are adapting modern computer vision methods to optic disc diagnosis in glaucoma but were concerned with the limited number of published comparisons of digital and film imaging formats for optic disc photographs, as ophthalmic photography has migrated from film-based to digital images. The few published reports mostly have assessed the utility of digital optic nerve images for quantitative parameters long used in glaucoma evaluation, such as the cup-to-disc ratio.16–21 In contrast, in a considerably more extensive body of literature, the utility of digital images has been compared to that of film images in retinal diseases such as diabetic retinopathy22–26 or macular degeneration.27–29 To address the suitability of digital stereo optic disc images as a platform for developing novel computerized approaches for glaucoma diagnosis, we assessed the quality and definition of optic disc features by directly comparing optic disc images obtained from individual subjects and displayed in different formats. We sought to avoid the well-known inaccuracies in trying to assign quantitative estimates such as the cup-to-disc ratio.9,10 Specifically, we obtained stereo color optic disc images contemporaneously in both digital and 35-mm slide film formats in subjects with a range of optic disc cup sizes and included both scanned and grayscale images in the analysis.

To evaluate whether baseline visual field data and asymmetries between eyes predict the onset of primary open-angle glaucoma (POAG) in Ocular Hypertension Treatment Study (OHTS) participants.A new index, mean prognosis (MP), was designed for optimal combination of visual field thresholds, to discriminate between eyes that developed POAG from eyes that did not. Baseline intraocular pressure (IOP) in fellow eyes was used to construct measures of IOP asymmetry. Age-adjusted baseline thresholds were used to develop indicators of visual field asymmetry and summary measures of visual field defects. Marginal multivariate failure time models were constructed that relate the new index MP, IOP asymmetry, and visual field asymmetry to POAG onset for OHTS participants.The marginal multivariate failure time analysis showed that the MP index is significantly related to POAG onset (P0.0001) and appears to be a more highly significant predictor of POAG onset than either mean deviation (MD; P = 0.17) or pattern standard deviation (PSD; P = 0.046). A 1-mm Hg increase in IOP asymmetry between fellow eyes is associated with a 17% increase in risk for development of POAG. When threshold asymmetry between eyes existed, the eye with lower thresholds was at a 37% greater risk of development of POAG, and this feature was more predictive of POAG onset than the visual field index MD, though not as strong a predictor as PSD.The MP index, IOP asymmetry, and binocular test point asymmetry can assist in clinical evaluation of eyes at risk of development of POAG.

Objectives To create a fully automated, combined perimetry program consisting of a static examination and a kinetic examination, and to compare the results of this test with standard static and kinetic visual fields (VFs). Methods Fifty-six patients (74 eyes) undergoing neuro-ophthalmic or glaucoma evaluation who had standard static or kinetic perimetry examinations underwent the combined perimetry test. This automated, combined test, performed on the Octopus 101 perimeter, consisted of a static tendency-oriented perimetry examination and a preprogrammed kinetic examination. Three masked physician reviewers independently classified all of the VFs. The VF pairs were considered a match if the consensus descriptions of the standard and combined VFs matched. Results Thirty-seven eyes underwent evaluation for neuro-ophthalmic disease (comparison standard test, 20 static and 17 kinetic) and 37 for glaucoma (comparison standard test, 17 static and 20 kinetic). The VP pairs matched in 32 eyes (86%) in the neuro-ophthalmic group and 28 (76%) in the glaucoma group. On inspection by a fourth reviewer, many of the nonmatching VF pairs were those for which a consensus was not reached, but still conveyed similar information. Two glaucomatous eyes demonstrated central scotomata not delineated by the combined examination findings. Two subtle nasal steps were detected solely by the combined examination. The combined test ranged in time from 6 to 12 minutes per eye. Conclusions The Octopus 101 perimeter can be used to create an automated test that combines the advantages of static and kinetic perimetry and produces equivalent results while not requiring examiner expertise.