Faculty Bibliography

PURPOSE: Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. METHODS: Retrospective review of children /= 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. CONCLUSION: In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

PURPOSE/OBJECTIVE:To report an unusual case of postcataract endophthalmitis secondary to Bosea thiooxidans. METHODS:Case report. RESULTS:An 86-year-old man presented with postoperative endophthalmitis 3 weeks after uncomplicated cataract surgery. He complained of a headache and blurry vision but denied having eye pain. Slit-lamp examination demonstrated leukocytes with a fibrinous membrane in the anterior segment and vitritis. A diagnosis of acute postoperative endophthalmitis was made, and the patient was treated with intravitreal antibiotics. Culture of vitreous tap revealed Bosea thiooxidans, a gram-negative rod found in soil and water systems. CONCLUSION/CONCLUSIONS:To our knowledge, this report is the first to describe Bosea thiooxidans endophthalmitis and one of a few reports of human infection with this microbial agent.

PURPOSE: To summarize key concepts, as well as early safety and efficacy signals from clinical trials, for stem/progenitor cell-based interventions for retinal disease. DESIGN: Interpretive essay. METHODS: Review and synthesis of selected recent reports of stem/progenitor cell-based approaches for retinal disease, with interpretation and perspective. RESULTS: Stem/progenitor cell-based interventions represent a novel class of potential therapies for retinal diseases, such as age-related macular degeneration and inherited retinal dystrophies, aoong others. Sources include pluripotent stem cells and fetal and postnatal tissues. Two mechanisms of "rescue" have been proposed: regenerative or trophic. Although pluripotent and fetal sourced-cell types have been tested in preclinical animal models of retinal disease, many postnatal stem/progenitor cell populations currently in trial do not have preclinical safety or efficacy data. Some early-phase trials of cell therapies suggest acceptable safety profiles. Other reports, involving some types of autologous, nonocular cell sources, have been linked to severe, blinding complications. Larger trials will be needed to determine short-term and long-term safety and efficacy of these cell-based interventions. CONCLUSIONS: Stem/progenitor cell-based interventions have the potential to address blinding retinal diseases that affect hundreds of millions worldwide. Yet no Food and Drug Administration-approved stem cell therapies for retinal disease exist. Although some early-phase trial data are promising, reports of blinding complications from cell interventions remain troubling. It is paramount to apply a strong level of scientific rigor toward a well-planned, step-wise sequence of preclinical and clinical studies, to determine whether this class of potential therapies will be safe and effective for individuals with retinal diseases.

PURPOSE: The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. METHODS: Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. RESULTS: An adequate volume of vitreous fluid (100-200 muL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42-926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. CONCLUSIONS: Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.

PURPOSE OF REVIEW: The purpose of review is to summarize the literature addressing nonocular adverse events in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. RECENT FINDINGS: The incidence of overall nonocular serious adverse events varied from 0 to 39.3% and nonocular adverse events ranged from 0 to 86.9%. Few studies have reported a significant association between use of intravitreal anti-VEGF agents and overall incidence of adverse events, stroke, myocardial infarction, nonocular hemorrhage and death, with overall greater concern in patients treated with bevacizumab. Additionally, history of stroke or other arterial thromboembolic event may be a risk factor for future stroke in patients treated with intravitreal anti-VEGF agents. Theories explaining the mechanisms of increased risk of nonocular adverse events secondary to anti-VEGF agent use surround the necessity of VEGF for the normal functioning of the endothelium and the damage incurred with use of anti-VEGF agents. SUMMARY: Current data are insufficient to definitively conclude that intravitreal anti-VEGF agents are safe, although there is a trend toward an overall favorable systemic safety profile. Caution should be exerted in patients with a history of cardiovascular disease, as these patients may be at greater risk for nonocular serious adverse events.