Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

Macular vessel density in central retinal artery occlusion with retinal arterial cannulation.

To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm-1 vs. 7.89 ± 1.02 mm-1, P = 0.0001), while there wasn't significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm-1 vs. 2.89 ± 0.22 mm-1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

Development of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration.

PURPOSE OF REVIEW: This review provides background on the remaining unmet needs with antivascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (nAMD). We also discuss the developmental story of the Port Delivery System with ranibizumab (PDS; SUSVIMO, Genentech, Inc., South San Francisco, CA, USA). RECENT FINDINGS: Real-world studies have shown that undertreatment is a major reason for continued vision loss in the anti-VEGF era. As a result, there is a need for long-acting anti-VEGF treatment options for patients with nAMD, diabetic macular edema, and other retinal diseases. The PDS is a solid state, refillable, intraocular long-acting drug delivery system that continuously delivers a customized formulation of ranibizumab into the vitreous for 6 months. In a phase 3 trial, the PDS showed equivalent visual acuity improvements with monthly ranibizumab injections in patients with nAMD and adverse events associated with the PDS were well understood and manageable. SUMMARY: The PDS is the first US Food and Drug Administration-approved treatment for nAMD that provides continuous delivery of an anti-VEGF molecule. The PDS offers a unique drug delivery system that has the potential to serve as a platform to be used with other molecules in the future.

Endovascular surgery in the field of ophthalmology.

In this article, we provide an overview of the current perspectives on endovascular surgery in ophthalmology, including a description of the various approaches, recent clinical results and future prospects. Experimental studies of endovascular surgery in ophthalmology started in the 1980s; since then, a considerable amount of research has been done to develop the procedure for clinical use. During the past two decades endovascular surgery has been performed on eyes with retinal vascular disorders, including central retinal vein occlusion and central retinal artery occlusion. The first endovascular surgery on human eyes was performed in 1998 on a patient with central retinal vein occlusion (CRVO). The most recent techniques used in retinal endovascular surgery involve manual injection of liquid agents such as tissue plasminogen activator into major retinal vessels using a 47 or 48-gauge micro-needle. New technology using a bimanual procedure and digitally assisted vitrectomy systems enables surgeons to perform this delicate procedure more effectively. Recent results reported from a number of researchers corroborate the effectiveness of the procedure. Endovascular surgery is one of the latest techniques in the field of ophthalmology and has garnered significant interest from vitreoretinal surgeons. However, it is also at the limit of what surgeons are able to accomplish with manual precision. There is still much to learn and improve to maximize the potential of this approach. The combination of skills as a surgeon, sound science, objective clinical evidence and cutting edge technology will lead to improvements in this field.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

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.

Novel positioning sensor with real-time feedback for improved postoperative positioning: pilot study in control subjects.

INTRODUCTION: Repair of retinal detachment frequently requires use of intraocular gas. Patients are instructed to position themselves postoperatively to appose the intraocular bubble to the retinal break(s). We developed a novel wearable wireless positioning sensor, which provides real-time audiovisual feedback on the accuracy of positioning. METHODS: Eight healthy volunteers wore the wireless sensor for 3 hours while instructed to maintain their head tilted toward the 2 o'clock meridian with no audiovisual feedback. Positioning accuracy was recorded. 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.

The Bionic Eye: A Quarter Century of Retinal Prosthesis Research and Development.

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.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

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.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

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.

Same-Day Versus Next-Day Repair of Fovea-Threatening Primary Rhegmatogenous Retinal Detachments.

PURPOSE: To evaluate the outcomes of same-day versus next-day repair of fovea-threatening rhegmatogenous retinal detachments (FT RRD). DESIGN: Retrospective, multi-surgeon observational case series. METHODS: Operative reports and medical records were reviewed to evaluate a number of visual and anatomic outcomes, including presenting features, intraoperative complications, and postoperative results in the repair of primary FT RRD undergoing same-day versus next-day repair with scleral buckling, pars plana vitrectomy, or both procedures. PARTICIPANTS: A total of 96 consecutive patients (43 same-day, 45 next-day, and eight two days later) were compared. RESULTS: There was no statistically significant difference in visual outcomes between same-day and next-day repair at postoperative months 3 and 6 and at last follow-up (month 3 mean BCVA 20/30 same day; 20/32 next day; p = 0.82). Preoperative vision was strongly correlated with postoperative acuity. Effect of differences in length or type of visual symptoms, location of RRD, gender, or lens status on postoperative month 3 best-corrected visual acuity (BCVA) was not statistically significant. Overall, 85% of patients had a BCVA of 20/40 or better at postoperative month 3. Reoperation rate and intraoperative complications were not statistically different between the two groups. Re-attachment was achieved in all but one patient in both groups. Time in the operating room was longer for same-day surgery (2.98 ± 0.46 hours) compared to next-day surgery (2.54 ± 0.38 hours) (p < 0.001), which was statistically significant even when factoring in the type of surgery performed. However, one case did progress to a macula-off detachment in a superior RRD with breaks found in lattice degeneration. CONCLUSION: Next-day surgery provided equivalent visual outcomes. Emergent, same-day surgery has logistical and resource implications as it may be more expensive, may necessitate rescheduling of previously booked cases, and may limit preoperative examination by the surgeon and perioperative team.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.

PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects 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. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Extraction of retinal tacks from subjects implanted with an epiretinal visual prosthesis.

BACKGROUND: Retinal tacks, first developed for the treatment of complex retinal detachments, have more recently been used for the fixation of epiretinal electrode arrays as part of implanted visual prostheses. Here, we report on the clinical experience of extracting four such tacks after chronic implantation. The ability to safely extract retinal tacks ensures that epiretinal devices can be repositioned or removed if necessary. METHODS: Custom-built, titanium alloy retinal tacks were mechanically removed from the posterior coats after prolonged implantation (up to 19 months). The resulting wound was characterized by clinical evaluation, fundus photography, and fluorescein angiography while being monitored for stability over time. The wounds were also compared to earlier published reports of the healing response around retinal tacks in human subjects. RESULTS: Tack extraction was accomplished successfully, without complication, in all four subjects. The wound site was readily identified by pale scar tissue. No change in the wound size or appearance was noted over many months of post-operative observation (up to 22 months after explant). No adverse effects on overall ocular health were detected. CONCLUSION: Extraction of retinal tacks from subjects implanted with epiretinal prostheses can be performed without significant complication. The long-term healing response appears to be stable and localized in eyes afflicted with retinitis pigmentosa or choroideremia. There was also minimal, if any, impact on the local circulatory system. These cases suggest that the use of retinal tacks for anchoring epiretinal visual prostheses does not preclude safe repositioning or removal of the device more than a year after implant.

Effect of intravitreal bevacizumab on intraocular pressure in a case of severe chronic hypotony.

PURPOSE: Chronic severe hypotony is associated with many serious ocular consequences, including phthisis. This case illustrates a possible new therapy for chronic hypotony. METHODS: This study is a case report of a 75-year-old man who had undergone trabeculectomy followed by multiple retinal surgeries and developed chronic hypotony in the left eye for more than 1 year. RESULTS: Treatment with intravitreal bevacizumab led to an elevation of intraocular pressure to 8 mmHg 1 week later. Hypotony returned within 2 weeks (2 mmHg) and variably remained for 2 months (0-10 mmHg) until a repeat injection of intravitreal bevacizumab resulted in another elevation in intraocular pressure, which was sustained (5-8 mmHg over 2 months). We postulate that antivascular endothelial growth factor therapy may influence aqueous production through restoration of tight junctions in the nonpigmented ciliary epithelium. Vascular endothelial growth factor and antivascular endothelial growth factor therapies have been demonstrated to modulate tight junctions in many other tissues in the body, including retinal pigment epithelium, ovarian tissue, vascular endothelium, liver, and brain vasculature. CONCLUSION: We postulate that antivascular endothelial growth factor therapy may play a role in treating hypotony by enhancing the function of tight junctions in the ciliary body and restoring aqueous production. Further studies are necessary to better clarify the influence of antivascular endothelial growth factor on intraocular pressure and aqueous production.

Subretinal delivery of immunoglobulin G with gold nanoparticles in the rabbit eye.

PURPOSE: To examine the feasibility of subretinal delivery of immunoglobulin G (IgG) adsorbed onto gold nanoparticles (GNPs) and its histologic distribution in the rabbit retina after the injection. METHODS: Goat IgG was adsorbed onto GNPs electrostatically. Goat IgG-adsorbed GNPs or buffer with goat IgG was injected into the subretinal space of rabbit eyes and followed up for 3 months by examination of fundus photographs, immunohistochemistry against goat IgG, and transmission electron microscopy (TEM). Human retinal pigment epithelial cells (ARPE-19 cells) were cultured, and cell proliferation with or without GNPs was assayed. RESULTS: At 1 week after the subretinal injection of goat IgG-adsorbed GNPs, retinal degeneration was observed in the outer retina, and goat IgG was immunolabeled in the retinal pigment epithelium (RPE) and the photoreceptor cells. TEM showed GNPs located in the outer segments and in the lysosomes in the RPE at 1 month and no apparent cytotoxicity of the RPE. There were no inhibitory effects of GNPs on proliferation of ARPE-19 cells. CONCLUSIONS: Goat IgG was successfully delivered into photoreceptor cells and RPE using GNPs, though retinal degeneration in the outer retina occurred in this model. This might be an alternative drug delivery method to photoreceptors and RPE.

Helical intravitreal triamcinolone acetonide implant: a 6-month surgical feasibility study in rabbits.

BACKGROUND AND OBJECTIVE: To investigate the surgical feasibility and safety of a long-term intravitreal triamcinolone acetonide (TA) sustained delivery system. MATERIALS AND METHODS: Pigmented rabbits were implanted with sustained-release formulations containing 925 microg of TA within a non-biodegradable polymer coating: Dose A (n = 15) with a slow delivery rate of 1 to 2 microg/day and Dose B (n = 15) releasing 3 to 5 microg/day. Additionally, a control group (n = 10) using a device coated with polymer only was implanted. The devices were surgically implanted through a 30-gauge sclerotomy into the vitreous cavity. The animals were clinically observed for up to 6 months after the surgery with complete ophthalmologic examinations. Histologic evaluation of a subset of eyes was performed at the conclusion of the study. RESULTS: Implants were successfully implanted in all 40 eyes. Ocular examinations revealed excellent implant tolerability. In all eyes, there was no significant postoperative inflammation at 1 week of follow-up. There was no increase in intraocular pressure during the follow-up period and histologic evaluation demonstrated no significant abnormalities. Minimal and localized vitreous hemorrhage was observed in 22.5% of implanted eyes and mostly cleared at 1 month after surgery. During the 6 months of follow up, localized lens opacities associated with physical implant contact developed in 66.6% of eyes. CONCLUSION: The surgical procedure using the intravitreal TA sustained delivery device is feasible. Surgical complications were generally mild, with lens opacities attributable to unique anatomical features of the rabbit eye. Long-term follow-up and histology revealed excellent implant tolerability.

A novel method to oxygenate intraocular irrigation fluids with an in-line oxygenator.

PURPOSE: We describe a novel method to oxygenate intraocular irrigation solutions involving an in-line oxygenator. METHODS: Either lactated Ringer (LR) solution or balanced salt solution (BSS) was oxygenated with the FE390 Stainless In-line Oxygenation Assembly (Beer, Beer, and More Beer, Concord, CA). After running a 100-mL of solution through the in-line oxygenator, oxygen saturation was measured with a dissolved oxygen meter. A control experiment involving the oxygenator without oxygen perfusion was performed. Paired t-tests were used to compare oxygen saturation changes before and after oxygenation. RESULTS: In comparison with the original BSS, there was an increase in oxygen saturation of 162 +/- 47% (n = 40; P < 0.05). Without oxygenation perfusion, there was only a 24 +/- 14% (n = 40) increase in oxygen levels in BSS, which was significantly lower than that in treated BSS (P < 0.05). In comparison with the original LR solution, there was an increase in oxygen saturation of 208 +/- 21% (n = 40; P < 0.05). Without oxygenation perfusion, there was only a 21 +/- 9% (n = 40) gain in oxygen saturation in the control LR solution, which was statistically lower as well (P < 0.05). CONCLUSION: The in-line oxygenator is an efficient tool for oxygenating BSS and LR solution. It represents a potential efficient and convenient method to oxygenate irrigating solutions for vitreoretinal surgeries.

Effect of oxygenated intraocular irrigation solutions on the electroretinogram after vitrectomy.

PURPOSE: To investigate the effect of oxygenated intraocular irrigating solutions on electroretinograms (ERGs) for postvitrectomy rabbits. METHODS: Eight groups of five rabbits each underwent pars plana vitrectomy on the right eye; the left eye of each rabbit served as control. The intraocular irrigating solutions were balanced salt solution (BSS), BSS-plus, BSS + oxygen (BSS + O2), BSS-plus + O2, and combinations of each with the addition of endoillumination (L). All animals were evaluated by single-flash scotopic electroretinography on the operated and nonoperated eyes before surgery and at 1 hour, 1 day, 1 week, and 1 month after surgery by an unmasked observer. The main outcome measures were dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios. The results for the different groups were compared by analysis of variance. RESULTS: Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS-plus and BSS-plus + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.01 +/- 0.09, 0.50 +/- 0.11, 0.95 +/- 0.11, 0.97 +/- 0.11, and 0.99 +/- 0.08 and 0.98 +/- 0.08, 0.59 +/- 0.10, 0.92 +/- 0.06, 0.97 +/- 0.08, and 0.97 +/- 0.10, respectively. At both 1 hour and 1 day after surgery, rabbits treated with BSS-plus + O2 had an earlier b-wave return to baseline findings, but the differences were not statistically significant (P > 0.05). Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS and BSS + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.02 +/- 0.10, 0.47 +/- 0.09, 0.77 +/- 0.07, 0.89 +/- 0.07, and 0.89 +/- 0.07 and 1.02 +/- 0.06, 0.62 +/- 0.16, 0.94 +/- 0.09, 0.97 +/- 0.08, and 0.96 +/- 0.06, respectively. One hour and 1 day after surgery, ERG readings for rabbits treated with BSS + O2 exhibited a statistically significantly earlier return of ERG voltage to baseline values compared with both BSS and BSS + L (P = 0.05 and P = 0.02, respectively). One day after surgery, rabbits treated with BSS alone had the lowest ERG ratios. One week and 1 month after surgery, for all solutions tested other than BSS, ERG values were within normal limits. CONCLUSION: The use of oxygenated solutions appears to affect ERG readings after pars plana vitrectomy. Further studies to evaluate the role of oxygenated solutions in different vitreoretinal surgical procedures are warranted.

Application of a new subretinal injection device in the dog.

The use of a new subretinal injection device (RetinaJect Subretinal Cannula, SurModics, Inc., Eden Prairie, MN) to access the subretinal space in the canine model was evaluated. Subretinal injections were performed in 33 mongrel dogs between 2 and 52 months of age (median = 9 months). In 5 normal dogs the injection of 150 microl saline or India ink occurred by using a conventional subretinal injection device (CSID) with a 30-gauge anterior chamber irrigating cannula. The sclera had to be surgically exposed and penetrated before the subretinal injection with the CSID could occur. After removing the CSID, the conjunctiva over the sclerotomy site had to be closed. In a second group of 28 dogs [16 normals, 10 RPE65 mutants, and 2 with progressive rod cone degeneration (prcd)], the 25-gauge needle of the RetinaJect was used to penetrate the conjunctiva and the sclera. Once the tip of the needle was close to the retinal surface, a 39-gauge polyimide cannula was extended and brought into apposition with the retina for the subsequent subretinal injection of 150 microl saline, India ink, or adeno-associated virus (AAV). No closure of the conjunctiva was required. The animals were clinically monitored between 1 and 59 weeks after surgery. From this second group 25 eyes were harvested for routine histological analysis either immediately after surgery or after a clinical observation time of between 1 and 40 weeks. Both devices provided equally successful access to the subretinal space. The main advantage of the RetinaJect was that no surgical dissection was required; this led to a shorter procedure time and milder postoperative conjunctival swelling. In summary, the use of the RetinaJect can be recommended as an alternative to the CSID for subretinal injections in dogs.

A new model of experimental subretinal neovascularization in the rabbit.

Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 microl of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 microl of Matrigel only; three rabbits used as controls received subretinal injections of 20 microl phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.