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.

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.

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.

Family History in the Primary Open-Angle African American Glaucoma Genetics Study Cohort.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association between Primary Open-Angle Glaucoma and Cognitive Impairment as Measured by the Montreal Cognitive Assessment.

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.

Trabectome success factors.

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 ±â€Š7.8 mm Hg and the average number of medications was 2.6 ±â€Š1.3 for all cases. At 12 months, the average IOP was 16.0 ±â€Š3.6 mm Hg (P < .01) and the average number of medications was 1.8 ±â€Š1.3 (P < .01). Based on the result of multivariate cox regression model, we found that the Trabectome + Phaco (TP) and Trabectome alone (TA) group had a 94% and 79% survival rate at 12 months, respectively. TP cases had 78% lower risk of failure than TA (95% confidence interval [CI]: 54-89), diagnosis of pseudoexfoliation glaucoma had a 54% lower risk of failure than primary open angle glaucoma patients (95% CI: 1-78). Hispanics had an estimated hazard ratio that is 60% lower than Caucasians (95% CI: 18-80); 20% of TA cases and 3% of TP cases were required to undergo additional secondary surgery (P < .01).Trabectome surgery, whether in combination with phacoemulsification cataract removal or stand alone, is associated with a significant reduction of IOP and glaucoma medication. Patients having a higher baseline IOP are expected to have a higher IOP reduction after Trabectome. Pseudoexfoliation glaucoma, combination with phacoemulsification cataract surgery and Hispanic race are factors associated with enhanced Trabectome survival.

Association of primary open-angle glaucoma with mitochondrial variants and haplogroups common in African Americans.

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.

Primary Open-Angle Glaucoma in Individuals of African Descent: A Review of Risk Factors.

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.

The primary open-angle african american glaucoma genetics study: baseline demographics.

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 < 0.01) and report a history of blindness (VA of ≤20/200; P < 0.001), whereas controls were more likely to have diabetes (P < 0.001), have nonproliferative diabetic retinopathy (P = 0.02), and be female (P < 0.001). Study participants were drawn largely from predominantly African American neighborhoods of low income, high unemployment, and lower education surrounding UPenn. 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.