Genistein, a natural tyrosine kinase inhibitor, may act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by its nonlinear pharmacokinetics. We aimed to determine genistein's kinetics and retinal tissue distributions in normal and diabetic rats. We developed an isocratic, reverse-phase C18 HPLC system to measure genistein concentration in blood and retinas of streptozotocin (65 mg/kg IV)-diabetic and non-diabetic rats receiving two types of genistein-rich diet (150 and 300 mg/kg) for ten days. Genistein's decay exhibited a two-compartmental open model. Half-lives of distribution and elimination were 2.09 and 71.79 min, with no difference between groups. Genistein steady-state concentration in blood for 150 and 300 mg/kg diet did not differ between diabetic (0.259 ± 0.07 and 0.26 ± 0.06 μg/ml) and non-diabetic rats (0.192 ± 0.05 and 0.183 ± 0.09 μg/ml). In retina, genistein concentration was significantly higher in diabetic rats (1.05 ± 0.47 and 0.997 ± 0.47 μg/gm wt. vs. 0.087 ± 0.11 and 0.314 ± 0.18 μg/gm wt., p < 0.05). The study determined that increasing genistein dose did not change its bioavailability, perhaps due to the poor aqueous solubility. The retina's increased genistein could be due to increased permeability of blood-retinal barrier that occurs early in diabetes.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. Results: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. Conclusion: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

The attractiveness of a smaller-gauge vitrectomy instrument system is based on the ability to minimize surgically induced trauma from sclerotomy sites, allow self-sealing sclerotomies, improve operative efficiency, and hasten postoperative recovery. Modifications in vitrectomy instrumentation aimed at decreasing the size of instruments must achieve a balance between the ability to achieve smaller incision sizes and maximization of instrument functionality, recognizing that high instrument functionality may not always be compatible with small size. In 1990, de Juan and Hickingbotham19 designed a variety of 25-gauge vitreoretinal instruments for more delicate and precise surgical maneuvers. The infusion rate in a 25-gauge vitrectomy system is lower than that in a routine 20-gauge system, due to the port diameter, which may limit the system's effectiveness. Eyes with pre-existing filtering blebs and other eyes of patients who require vitrectomy may have underlying conditions that put them at risk for difficult-to-control glaucoma.

The subjects repeated the experiment for 3 hours with the audiovisual feedback enabled. Results: With no audiovisual feedback, the percentage of time greater than 10 ° out of position varied from 8.9% to 93.9%. With audiovisual feedback enabled, these percentages ranged from 9.4% to 65%. Three subjects showed significant improvement in their time out of position ( P , 0.01, Fisher’s exact test). Four subjects demonstrated a nonsignificant improvement, and one subject had a significant increase in time out of position with feedback ( P , 0.01). When pooled, all subjects demonstrated a statistically significant decrease in degrees out of position ( P , 0.001, Wilcoxon test) and a statistically significant improvement in total time out of position ( P , 0.001). Conclusion: The novel positioning sensor showed improved positioning compliance in half of the healthy volunteers during our short pilot study. Other subjects derived little benefit from the feedback. The causes for this observation are unclear. However, given the significant improvement as a group, this new technology could be beneficial to patients who struggle with postoperative positioning.

BACKGROUND:A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation.METHODS:Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined.RESULTS:Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical.CONCLUSIONS:Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

This article describes the history of visual prostheses, with emphasis on the development of the Argus II retinal prosthesis system (Second Sight Medical Products, Inc., Sylmar, CA). A brief overview of cortical electrical stimulation in the blind is provided, followed by an account of the design and development of retinal stimulation equipment at the Duke Eye Center in the late 1980s; the first human intraoperative tests there and the subsequent 8 years of tests at the Wilmer Eye Institute; the transfer of the project to the Doheny Eye Institute at the University of Southern California and the founding of Second Sight Medical Products; and the development and clinical trials of the Argus I and Argus II systems. In a series of vignettes, we pay tribute to the many colleagues and patient volunteers without whose help the work would not have been possible. (C) 2016 by the American Academy of Ophthalmology.

PURPOSE:The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN:Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS:Thirty participants in 10 centers in the United States and Europe. METHODS:The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES:The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS:Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS:The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

Over the last 10 years, the success of anti-vascular endothelial growth factor (VEGF) antibodies for the treatment of neovascular age-related macular degeneration (AMD) has made the use of intravitreal injections for the treatment of posterior segment disease commonplace. The application of drugs into vitreous, as either a direct intraocular injection or in the form of sustained-release devices, is currently the focus of many clinical studies to treat a number of retinal and choroidal diseases. The advantages of this approach are that local treatment bypasses the systemic side effects of a drug and enables more direct control over the dose and duration of drug delivery to the target site. Furthermore, as we gain an increased understanding of the pathophysiological processes in diseases such as vitreomacular traction syndrome and diabetic retinopathy, new pharmacologic treatments have arisen that have the potential to obviate the need for surgical intervention or at least facilitate surgery [see chapter VI.A . Pharmacologic vitreolysis]. As technology and our understanding of disease processes evolve, these treatments will undoubtedly become more refined both in the way they are delivered and in the specificity of the pharmacologic target. This chapter reviews the principles of intravitreal drug delivery for both short-term and sustained-release formulations.