Faculty Bibliography

PURPOSE/OBJECTIVE:To compare the long-term safety and efficacy of amniotic membrane-umbilical cord (AM-UC) and pericardium patch grafts in reducing glaucoma shunt tube exposure. DESIGN/METHODS:Multicenter, prospective, randomized clinical trial. PARTICIPANTS/METHODS:Adults with uncontrolled glaucoma undergoing glaucoma drainage device (GDD) implantation. METHODS:Patients were randomized to receive GDD with either AM-UC or pericardium patch grafts to cover GDD tubes. Patients were followed up clinically with anterior segment (AS) OCT to assess patch graft stability and host-tissue integration prospectively. MAIN OUTCOME MEASURES/METHODS:Tube exposure, graft thinning, and graft-related complications. RESULTS:A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67±13 years underwent GGD implantation using Baerveldt (n = 72) or Ahmed valve (n = 9). Tubes were inserted in the anterior chamber (n = 71), sulcus (n = 6), or pars plana (n = 4). Tube ligation was performed with Baerveldt GDD along with fenestration (n = 51) or orphan trabeculectomy (n = 21). Tubes were covered with AM-UC (n = 41) or pericardium (n = 40). The mean follow-up time was 29±8 months (range, 13-40 months). Tube exposure occurred in 1 eye (2%) in the AM-UC group at 3 months and in 2 eyes (5%) in the pericardium group at 2 and 6 months (P = 0.54). Sequential AS OCT showed better host-tissue integration and significantly less graft thinning in the AM-UC group. Early graft thinning (≤3 months) occurred in 5 eyes (12%) in the AM-UC group and in 17 eyes (43%) in the pericardium group (P = 0.002). Late thinning occurred in 2 eyes (5%) and 11 eyes (28%) in the AM-UC and pericardium groups, respectively (P = 0.007). Graft translucency and cosmetic appearance of the AM-UC graft were superior to those of the pericardium graft. No evidence of graft rejection or infection was associated with the patch grafts in either group. CONCLUSIONS:Amniotic membrane-umbilical cord grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. Its high-tensile strength, low immunogenicity, and excellent host-tissue integration significantly reduced graft thinning.

Importance/UNASSIGNED:Although almost equal numbers of male and female medical students enter into ophthalmology residency programs, whether they have similar surgical experiences during training is unclear. Objective/UNASSIGNED:To determine differences for cataract surgery and total procedural volume between male and female residents during ophthalmology residency. Design, Setting, Participants/UNASSIGNED:This retrospective, longitudinal analysis of resident case logs from 24 US ophthalmology residency programs spanned July 2005 to June 2017. A total of 1271 residents were included. Data were analyzed from August 12, 2017, through April 4, 2018. Main Outcomes and Measures/UNASSIGNED:Variables analyzed included mean volumes of cataract surgery and total procedures, resident gender, and maternity or paternity leave status. Results/UNASSIGNED:Among the 1271 residents included in the analysis (815 men [64.1%]), being female was associated with performing fewer cataract operations and total procedures. Male residents performed a mean (SD) of 176.7 (66.2) cataract operations, and female residents performed a mean (SD) of 161.7 (56.2) (mean difference, -15.0 [95% CI, -22.2 to -7.8]; P < .001); men performed a mean (SD) of 509.4 (208.6) total procedures and women performed a mean (SD) of 451.3 (158.8) (mean difference, -58.1 [95% CI, -80.2 to -36.0]; P < .001). Eighty-five of 815 male residents (10.4%) and 71 of 456 female residents (15.6%) took parental leave. Male residents who took paternity leave performed a mean of 27.5 (95% CI, 13.3 to 41.6; P < .001) more cataract operations compared with men who did not take leave, but female residents who took maternity leave performed similar numbers of operations as women who did not take leave (mean difference, -2.0 [95% CI, -18.0 to 14.0]; P = .81). From 2005 to 2017, each additional year was associated with a 5.5 (95% CI, 4.4 to 6.7; P < .001) increase in cataract volume and 24.4 (95% CI, 20.9 to 27.8; P < .001) increase in total procedural volume. This increase was not different between genders for cataract procedure volume (β = -1.6 [95% CI, -3.7 to 0.4]; P = .11) but was different for total procedural volume such that the increase in total procedural volume over time for men was greater than that for women (β = -8.0 [95% CI, -14.0 to -2.1]; P = .008). Conclusions and Relevance/UNASSIGNED:Female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, a finding that warrants further exploration to ensure that residents have equivalent surgical training experiences during residency regardless of gender. However, this study included a limited number of programs (24 of 119 [20.2%]). Future research including all ophthalmology residency programs may minimize the selection bias issues present in this study.

Purpose/UNASSIGNED:Besides glia-driven neuroinflammation, growing evidence from analysis of human blood samples, isolated autoantibodies, and postmortem tissues also support systemic immune responses during neurodegeneration in glaucoma patients. To explore the T-cell-mediated component of systemic immunity, this study analyzed T lymphocytes in patients' blood. Methods/UNASSIGNED:Blood samples were collected from 32 patients with glaucoma and 21 nonglaucomatous controls, and mononuclear cells were isolated by Histopaque density gradient centrifugation. T-cell subset distribution was analyzed by multicolor flow cytometry after helper (Th) and cytotoxic fractions, and Th subpopulations, were stained with antibodies to CD4, CD8, or distinctive markers, such as IFN-γ (for Th1), IL-4 (for Th2), IL-17A (for Th17), and CD25/FoxP3 (for T regulatory cells [Tregs]). In addition, proliferative activity and cytokine secretion of T cells were analyzed after in vitro stimulation. Results/UNASSIGNED:Analysis of T-cell subset distribution detected a glaucoma-related shift. Despite similar frequencies of CD4+ or CD8+ T cells, or Th1, Th2, or Th17 subsets in glaucoma and control groups, glaucomatous samples exhibited a trend toward decreased frequency of CD4+ (or CD8+)/CD25+/FoxP3+ Tregs within the entire CD4+ (or CD8+) population (P < 0.001). Furthermore, CD4+ T cells in glaucomatous samples presented a greater stimulation response (∼3-fold) as characterized by increased proliferation and proinflammatory cytokine secretion (P < 0.05). Conclusions/UNASSIGNED:These findings suggest that the immunity activated in glaucoma may not be counterbalanced by an efficient immune suppression. More work is encouraged to determine whether shifted T-cell homeostasis may contribute to neurodegeneration in glaucoma, and/or whether T-cell subset imbalance may serve as a biomarker of autoimmune susceptibility.

This review article aimed to highlight the application and use of artificial intelligence (AI) in optical coherence tomography (OCT) imaging in ophthalmology. Artificial intelligence programs seek to simulate intelligent human behavior in computers. With an abundance of patient data, especially with the advent and growing use of imaging modalities such as OCT, AI programs provide us with the unique opportunity to analyze this plethora of information and assist in making clinical decisions in the field of ophthalmology. Groups around the world have developed and evaluated AI programs that gather data from diagnostic modalities, such as OCT, that assist in the diagnosis and management of ophthalmological diseases with a high accuracy. Artificial intelligence programs using OCT have the potential to play a significant role in the diagnosis and management of ophthalmological disease in the near future. Incorporation of AI in medicine, however, is not without its pitfalls. Some limitations of AI in ophthalmology are also discussed in this review. These include the deskilling of physicians due to increase in reliance on automation, inability of AI programs to take a holistic approach to clinical encounters with patients, requirement of pre-existing strong datasets to train AI programs, and the inability of AI programs to incorporate the ambiguity and variability that is intrinsic to the nature of clinical medicine.

Artificial intelligence (AI) is a branch of computer science that deals with the development of algorithms that seek to simulate human intelligence. We provide an overview of the basic principles in AI that are essential to the understanding of AI and its application in health care. We also present a descriptive analysis of the current state of AI in various fields of medicine, especially ophthalmology. Finally, we review the potential limitations and challenges that come along with the development and implementation of this new technology that will likely play a major role in clinical medicine in the near future.

PURPOSE/OBJECTIVE:To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS:Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS:Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES/METHODS:Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS:The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS:With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

OBJECTIVE:Find genetic contributions to glaucoma in African Americans. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS:1875 POAG cases and 1709 controls, self-identified as African Descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGESIII) and Wake Forest School of Medicine. METHODS:MegaChip genotypes were imputed to Thousand Genomes data. Association of SNPs with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by Receiver Operator Characteristics (ROC-AUC). MAIN OUTCOME/RESULTS:POAG defined by visual field loss without other non-ocular conditions (N=1875). Advanced POAG was defined by age-based mean deviation of visual field (N=946). RESULTS:) was observed, not in LD with the previously reported ED SNP. Additional previously identified loci associated with POAG in AD were: 8q22, AFAP1, TMCO1. An AUC of 0.62 was observed with an unweighted genetic risk score composed of 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC=0.74 and AUC=0.94, respectively. CONCLUSIONS:A novel association with advanced POAG in the ENO4 locus was putatively identified in subjects of African descent. In addition to this finding, this GWAS in AD POAG subjects contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine-mapping of regions due to shorter average linkage disequilibrium (FNDC3B). While not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.