Systemic activation of the complement system in patients with advanced age-related macular degeneration.

PURPOSE: To examine the role of systemic activation of the complement system (assessed by levels of circulating C3a, Ba, and sC5b-9) in patients (n = 122) with advanced age-related macular degeneration, geographic atrophy, and neovascular age-related macular degeneration, compared with cataract controls (n = 27). METHODS: Plasma complement factors were measured using enzyme-linked immunosorbent assays. Statistical analysis included univariate and multivariate logistic regression (p < 0.05). RESULTS: Adjusted for age, the odds ratios of C3a and sC5b-9 for any advanced age-related macular degeneration were 1.78 (95% confidence interval = 1.16-2.73, p < 0.01) and 1.20 (95% confidence interval = 1.04-1.39, p = 0.01), respectively. We found a significantly elevated adjusted odds ratio of C3a (adjusted odds ratio = 1.71, 95% confidence interval = 1.12-2.60, p = 0.01) and sC5b-9 (adjusted odds ratio = 1.22, 95% confidence interval = 1.04-1.43, p = 0.01) for neovascular age-related macular degeneration. Adjusted for age, neither C3a, sC5b-9, nor Ba were associated with geographic atrophy. CONCLUSION: We suggest a role for elevated plasma levels of C3a and sC5b-9 in patients with neovascular age-related macular degeneration. The study's results reinforce the need for more investigation to assess the impact of therapeutic interventions targeted at the complement signaling pathways in age-related macular degeneration.

Therapeutic challenges in the treatment of systemic inflammatory disease in pregnancy.

BACKGROUND: Granulomatosis with polyangiitis and Behçet's disease can occur during pregnancy and may be treated by ophthalmologists, rheumatologists, and obstetricians. We hypothesized that specialty training would affect the way physicians selected therapy. METHODS: Using an online questionnaire, 209 uveitis specialists, 853 rheumatologists, and 2500 obstetricians were surveyed. Respondents were given clinical vignettes containing a female patient who was contemplating pregnancy or in the first trimester and was diagnosed with granulomatosis with polyangiitis or Behçet's disease. RESULTS: In the patient with granulomatosis with polyangiitis, therapy choice between specialties for biologic versus non-biologic systemic immunosuppressive medications was significantly different for both the non-pregnant and pregnant patient (p < 0.00001, p < 0.00003). In the non-pregnant patient diagnosed with Behçet's disease, the therapy choice between biologic versus non-biologic medications was also significantly different (p < 0.0003). CONCLUSIONS: Specialty training affects how physicians manage granulomatosis with polyangiitis and Behçet's disease. Development of inter-specialty guidelines and treatment plans may improve outcomes, communication, and patient care.

Driving and Visual Acuity in Patients with Age-Related Macular Degeneration.

PURPOSE: To assess driving status, habitual visual acuity (VA) in the better-seeing eye, and self-reported driving difficulty among patients diagnosed with age-related macular degeneration (AMD). DESIGN: Cross-sectional cohort study of 553 AMD patients' habitual VA, self-reported driving status, and driving difficulty at time of interview. PARTICIPANTS: Patients diagnosed with AMD and recruited into the University of Colorado registry. METHODS: Measurement of habitual VA by median logarithm of the minimum angle of resolution (logMAR) and Snellen equivalent, as well as 3 categories: 20/40 or better, 20/50 or 20/60, and worse than 20/60. Driving difficulty was self-reported on the 25-item National Eye Institute Visual Function Questionnaire. MAIN OUTCOME MEASURES: Self-reported driving status and driving difficulty. RESULTS: A total of 394 patients (71.2%) reported currently driving at time of study interview. Drivers were significantly younger than nondrivers (mean age, 76.7 years vs. 83.9 years; P < 0.0001) and were more likely to be men (42.6% vs. 25.8%; P = 0.0002). Median habitual VA in the better-seeing eye was better among drivers: 0.097 logMAR (Snellen equivalent, 20/25) versus 0.301 logMAR (Snellen equivalent, 20/40) for nondrivers (P < 0.0001). Among drivers, habitual VA was 20/40 or better for 87.6% of patients, 20/50 to 20/60 for 9.6% of participants, and worse than 20/60 for 2.8% of participants. Driving patients with habitual VA in the better-seeing eye of 20/40 or better reported less difficulty driving compared with patients with 20/50 or worse VA. CONCLUSIONS: In our study, most patients with AMD who were currently driving had at least 20/40 VA in the better-seeing eye. However, 12.4% of patients had VA of 20/50 or worse and reported more difficulties with driving. As the aging population continues to grow with increasing lifespan, the number of patients with AMD will increase, and discussion of driving and VA will become more clinically and legally pertinent.

Proteomic Profiles in Advanced Age-Related Macular Degeneration Using an Aptamer-Based Proteomic Technology.

PURPOSE: To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA. METHODS: We conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome. RESULTS: In this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor-related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling. CONCLUSIONS: We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described. TRANSLATIONAL RELEVANCE: Biomarkers identified in plasma likely reflect systemic alterations in protein expression and may improve our understanding of the mechanisms leading to AMD.

COLORADO AGE-RELATED MACULAR DEGENERATION REGISTRY: Design and Clinical Risk Factors of the Cohort.

PURPOSE: To study new and existing risk factors related to age-related macular degeneration (AMD) phenotypes in a Colorado cohort. METHODS: Age-related macular degeneration was categorized into early, intermediate, or advanced forms. Controls (n = 180) were patients with cataract and no AMD. Demographic and clinical data were gathered by patient interview and verified by chart review. Image data were reviewed by vitreoretinal specialists. Statistical analysis included univariable and multivariate logistic regression analysis (P < 0.05). RESULTS: Among the 456 patients with AMD, 157 (34.4%), 80 (17.6%), and 219 (48.0%) had the early/intermediate, geographic atrophy, and neovascular forms of the disease, respectively. Adjusted for age, African-American race was associated with a reduced risk of early/intermediate (adjusted odds ratio [AOR] = 0.08, confidence interval [CI] = 0.01-0.67) and neovascular AMD (AOR = 0.15, CI = 0.03-0.72). A family history of AMD was a risk factor for early/intermediate (AOR = 4.08, CI = 2.30-7.25), geographic atrophy (AOR = 8.62, CI = 3.77-19.7), and neovascular AMD (AOR = 3.76, CI = 2.16-6.56). A history of asthma was related to the early/intermediate form of AMD (AOR = 2.34, CI = 1.22-4.46). CONCLUSION: Studying AMD in specific populations may reveal novel risk factors such as our finding of a relationship between asthma history and AMD.

Specialty management differences of syphilis and toxoplasmosis surrounding pregnancy: a prospective cross-sectional study.

BACKGROUND: Syphilis and toxoplasmosis are two infectious conditions that can occur during pregnancy. Both these diseases can have ocular manifestations and thus are treated by ophthalmologists and obstetricians. We hypothesized that specialty training would affect the way physicians selected therapy. RESULTS: A total of 209 uveitis specialists and approximately 2500 obstetricians across the USA were surveyed using an online questionnaire distributed via listserv and social media posts. Survey respondents were given a series of clinical vignettes containing case examples of a female patient who was either contemplating pregnancy or in the first trimester and was diagnosed with either syphilis or toxoplasmosis. The questionnaire included a total of four case scenarios with questions relating to the management of these diseases, as well as pregnancy counseling. For the syphilis vignette, a total of 97 physicians responded to the survey questions. Choices of therapy between physician specialty differed significantly (p = 0.0001); however, pregnancy status did not seem to affect therapy choice in syphilis. A total of 96 physicians responded to the survey questions pertaining to the toxoplasmosis vignette. For a non-pregnant patient diagnosed with toxoplasmosis, the differences in therapy choice between specialties were not significant; however, when the patient was pregnant, therapy choice was significantly different between specialties (p = 0.0001). CONCLUSIONS: Differences exist between ophthalmologists and obstetricians concerning the therapy for syphilis and toxoplasmosis during pregnancy. Inter-specialty collaboration is needed to develop consistent criteria to improve the management of these patients.

The role of the maternal and fetal inflammatory response in retinopathy of prematurity.

PROBLEM: There is a paucity of research on the contribution of placental inflammation to severe retinopathy of prematurity (ROP). METHOD OF STUDY: A retrospective cohort study (n = 1217) was conducted of infants screened for ROP (2006-2016). The outcomes of the study were severe ROP (type 1 or type 2 ROP) and low grade ROP. We categorized the placental pathology as the presence of (i) maternal plus fetal inflammatory response, (ii) maternal inflammatory response only, (iii) fetal inflammatory response only and, (iv) no evidence of a maternal or fetal inflammatory response. The data were analyzed using univariate and multivariate logistic regression analyses (P < .05). RESULTS: In this cohort, the number of infants with the maternal plus fetal inflammatory response, the maternal inflammatory response only, the fetal inflammatory response only, and no maternal or fetal inflammatory response was 305 (25%), 82 (7%), 8 (1%), and 822 (67%), respectively. Adjusted for covariates, the maternal plus fetal inflammatory response was a significant risk factor for severe ROP (AOR = 2.6, 95% CI 1.1-5.9, P = .03). None of the categories of placental inflammation were significantly associated with low grade ROP. CONCLUSION: Placental pathology distinguished by the maternal plus fetal inflammatory response was a significant risk factor for severe ROP. Our study supports a link between intrauterine inflammatory events and the subsequent development of severe ROP.

Trends in treatment strategies for suspected bacterial endophthalmitis.

PURPOSE: To describe how vitreoretinal specialists have incorporated the Endophthalmitis Vitrectomy Study (EVS) findings into current practice, to highlight divergences from the EVS recommendations, and address the role of microbial culture in guiding additional treatments. METHODS: This is a cross-sectional survey of vitreoretinal specialists regarding indications used for performing a pars plana vitrectomy (PPV), selection of antibiotics for treatment, utilization of cultures, and treatment strategies for treatment-refractory patients with bacterial endophthalmitis. RESULTS: Of 681 physicians contacted, 149 (21.9%) responded. For patients with visual acuity of light perception or less, 75% of respondents utilized PPV. Intravitreal vancomycin and ceftazidime were used by 100% and 96% of participants respectively. Vitreal cultures were obtained more than 50% of the time by 86.5% of participants, and were used to influence retreatment less than 50% of the time by 77.8% of respondents. For patients with worsening clinical signs 48 hours after initial treatment, 69.8% of participants performed PPV with intravitreal antibiotics. CONCLUSIONS: Although most respondents followed the EVS guidelines, a minority deviated, and the majority generalized their strategy to other forms of endophthalmitis. There is significant variation in retreatment strategies, and while cultures are frequently obtained to help guide these treatments, they are utilized infrequently.