ObjectiveTo report the incidence of endophthalmitis, in addition to its clinical and microbiological aspects, after intravitreal injection of vascular-targeting agents.MethodsA retrospective review of a consecutive series of 10,142 intravitreal injections of vascular targeting agents (bevacizumab, ranibizumab, triamcinolone acetonide, and preservative-free triamcinolone acetonide) between June 1, 2007 and January 31, 2010, performed by a single service (TGM) at the Bascom Palmer Eye Institute.ResultsOne case of clinically-suspected endophthalmitis was identified out of a total of 10,142 injections (0.009%), presenting within three days of injection of bevacizumab. The case was culture-positive for Staphylococcus epidermidis. Final visual acuity was 20/40 after pars plana vitrectomy surgery.ConclusionsIn this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.

Purpose. To measure the chemotherapeutic effects of focal melphalan (intravitreal and subconjunctival) on tumor burden, hypoxia, and vasculature in LHBETATAG murine retinoblastoma model. Methods. LHBETATAG transgenic mice were treated with a single 1 mcg intravitreal injection of melphalan, 100 mcg subconjunctival injection, or semiweekly 10 mcg subconjunctival injections for 3 weeks. At 1 or 3 weeks, eyes were enucleated, serially sectioned, and processed with haematoxylin and eosin (H&E) for tumor burden measurements and probed with immunofluorescence to analyze tumor hypoxia and vasculature. Results. Focal melphalan significantly reduced retinal tumor size (P < 0.02) when given intravitreally or subconjunctivally. Eyes treated with a one-time intravitreal injection of 1 mcg melphalan had significantly smaller tumors at both 1 week (P = 0.017) and at 3 weeks after injection (P = 0.005). Intratumoral hypoxia showed a significant decline in hypoxia at 1 week following intravitreal injection and after maximum dosage of subconjunctival melphalan. Total vasculature was not significantly affected following intravitreal administration. Conclusion. Focal delivery of melphalan via intravitreal or subconjunctival injection has a significant effect on reducing tumor burden, hypoxia, and vasculature, in the treatment of murine retinoblastoma tumors.

Purpose:The purpose of this study is to analyze the dose response of the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, on tumor burden and hypoxia, and study the treatment effect on vasculature in LHBETATAG retinal tumors.Methods:This study was approved by the Institutional Animal Care and Use Committee and follows Association for Research in Vision and Ophthalmology guidelines. Eighteen-week-old LHBETATAG retinal tumor eyes (n = 30) were evaluated. Mice were divided into five groups and received periocular injections once weekly for two consecutive weeks of: a) 80% DMSO (dimethyl sulfoxide, vehicle control), b) 0.00333 mg/kg, c) 0.167 mg/kg, d) 3.33 mg/kg, and e) 6.67 mg/kg of rapamycin. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature with immunohistochemistry techniques.Results:Reduction in tumor burden and hypoxia was significantly different between rapamycin doses and control (P < 0.002). Eyes treated with rapamycin at 0.167, 3.33, and 6.67 mg/kg showed a significant decrease in tumor burden in comparison with the vehicle control group (P = 0.019, P = 0.001, P = 0.009, respectively) and the 0.00333 mg/kg dose response (P = 0.023, P = 0.001, P = 0.010, respectively). Eyes treated with rapamycin at 3.33 mg/kg showed a significant reduction in the amount of hypoxia in comparison with the lower concentration groups (0.00333 and 0.167 mg/kg) of rapamycin (P = 0.024 and P = 0.052, respectively). The number of mature vessels was significantly lower in the 3.33 mg/kg treated versus vehicle control (P = 0.015; equal variances assumed, t-test for equality of means). The number of neovessels was not significantly different between both groups (P = 0.092).Conclusion:Inhibition of mTOR was shown to reduce tumor burden, hypoxia, and vasculature in the LHBETATAG retinoblastoma tumor model. Rapamycin may have a role in combination with chemotherapy or other adjuvant therapies to enhance retinoblastoma tumor control.

ObjectiveBecause the American College of Rheumatology (ACR) practice guidelines affect the United States' and international treatment practice, we used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to characterize the quality of the guidelines and to identify potential areas for improvement.MethodsUsing the six quality domains in the AGREE II online tool, four reviewers assessed the practice guidelines available at the ACR website and the immediately previous version to summarize the domain scores for each guideline and examine trends over time.ResultsAs of April 2016, the ACR website listed nine guidelines, four with immediate previous versions. Based on AGREE II, the minimum and maximum for each domain (with higher being better) of the current guidelines were 78‐99 for Scope and Purpose, 57‐99 for Stakeholder Involvement, 87‐ 96 for Rigor of the Methodology, 83‐99 for Clarity of Presentation, 49‐78 for Applicability, 69‐85 for Editorial Independence, and 71‐96 overall. Over time, although the average domain quality of the guidelines improved for all, the Applicability and Editorial Independence domains had the least amount of improvement. For the four guidelines with previous versions, the mean (SD) absolute improvements for each domain were 18 (±11) for Scope and Purpose, 13 (±8) for Stakeholder Involvement, 38 (±22) for Rigor of the Methodology, 25 (±15) for Clarity of Presentation, 22 (±12) for Applicability, 24 (±17) for Editorial Independence, and 31 (±5) overall.ConclusionBased on the AGREE II instrument, the ACR guidelines have achieved high quality over the past 16 years. The Applicability and Editorial Independence domains have the greatest potential for future improvement.

PurposeTo analyze functional and anatomical outcomes following 23/25+ gauge microincisional pars plana vitrectomy surgery (MIVS) in patients with radiation-related retinal detachment after successful 125-iodine (I-125) brachytherapy treatment for malignant uveal melanoma.Patients and methodsRetrospective case series of 102 consecutive eyes of 102 patients with history of uveal melanoma treated with I-125 brachytherapy that underwent MIVS at the Bascom Palmer Eye Institute. All cases were evaluated for surgical complications and local tumor control. Extended follow-up included Snellen’s best-corrected visual acuity, intraocular pressure evaluation, quantitative echography, indirect ophthalmoscopy, and fundus imaging with optical coherence tomography/wide-field photography.ResultsAll patients had radiation-related complications, including retinal detachment (102 eyes), vasculopathy (91 eyes), optic neuropathy (32 eyes), and/or vitreous hemorrhage (8 eyes). Sixty-seven patients had vitreoretinal traction. Average follow-up after MIVS was 19.5 months, and from plaque removal was 57.7 months. Interval from plaque to MIVS was 38.1 months. Initial visual acuity was 20/258, which improved to 20/101 at 1 month, 20/110 at 3 months, 20/116 at 6 months, and 20/113 at 12 months (P < 0.05). No eyes required enucleation. Melanoma-related mortality was 0.9% (1/102). There was no intra- or extraocular tumor dissemination, and no tumor recurrence.ConclusionMIVS was effective in improving visual function and anatomy in patients with radiation-related retinal detachment. Tumors decreased in size and there was no evidence of recurrence or tumor dissemination. This combined procedure addresses the modifiable causes of visual loss in patients with previously treated malignant uveal melanoma and has the potential to enhance their visual function.