TRANSPLANTATION OF SUBRETINAL STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM FOR STARGARDT DISEASE: A Phase I Clinical Trial.

PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.

Comparison of clinical effects of two latanoprost 0.005% solutions (Xalatan® and Arulatan®) in primary open-angle glaucoma or ocular hypertensive patients: a randomized clinical trial.

Purpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan® [ALT] versus the reference drug Xalatan® [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P<0.05. Computerized analysis was performed using the R software, version 3.4.4. Results: A total of 45 patients were randomized to the two treatment groups: ALT (22) and XLT (23). A statistically significant reduction in IOP from baseline was observed in both treatment groups at all timepoints, while no statistically significant difference between groups was detected. By week 12, observed IOP reduction was -7.95 and -7.89 mmHg in the ALT and in the XLT groups, respectively (P=0.60). Treatment difference between the ALT and the XLT groups was -0.06 mm Hg (95% CI: -0.97, 0.85) and fell within the interval set for therapeutic non-inferiority. There was no statistically significant difference between the two groups in terms of safety profiles. The most commonly reported side effect was mild conjunctival/palpebral hyperemia. Conclusion: ALT was considered non-inferior to XLT in achieving a statistically significant reduction in IOP at 12 weeks in POAG and OH patients. No significant difference in the occurrence of side effects was found between both groups.

EFFECTS OF A MODIFIED VITRECTOMY PROBE IN SMALL-GAUGE VITRECTOMY: An Experimental Study on the Flow and on the Traction Exerted on the Retina.

PURPOSE: Thorough this experimental study, the physic features of a modified 23-gauge vitrectomy probe were evaluated in vitro. METHODS: A modified vitrectomy probe to increase vitreous outflow rate with a small-diameter probe, that also minimized tractional forces on the retina, was created and tested. The "new" probe was created by drilling an opening into the inner duct of a traditional 23-gauge probe with electrochemical or electrodischarge micromachining. Both vitreous outflow and tractional forces on the retina were examined using experimental models of vitreous surgery. RESULTS: The additional opening allowed the modified probe to have a cutting rate of 5,000 cuts per minute, while sustaining an outflow approximately 45% higher than in conventional 23-gauge probes. The modified probe performed two cutting actions per cycle, not one, as in standard probes. Because tractional force is influenced by cutting rate, retinal forces were 2.2 times lower than those observed with traditional cutters. CONCLUSION: The modified probe could be useful in vitreoretinal surgery. It allows for faster vitreous removal while minimizing tractional forces on the retina. Moreover, any available probe can be modified by creating a hole in the inner duct.

An Innovative Surgical Technique for Subretinal Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium in Yucatan Mini Pigs: Preliminary Results.

BACKGROUND AND OBJECTIVE: To develop a safe and efficient surgical procedure for subretinal implantation into porcine eyes of a human embryonic stem cell-derived retinal pigmented epithelium (hESC-RPE) monolayer seeded onto a Parylene-C scaffold. This implant is referred to as CPCB-RPE1. MATERIALS AND METHODS: Ultrathin Parylene-C scaffolds were seeded with hESC-RPE and surgically implanted into the subretinal space of Yucatan mini pigs (n = 8). The surgery consisted of pars plana vitrectomy, induction of a limited retinal detachment, and peripheral retinotomy for insertion of the monolayer using a novel tissue injector, followed by silicone oil tamponade injection, laser photocoagulation around the retinotomy site, and inferior iridectomy. Oral cyclosporine was administered from day 1 and during the entire follow-up period. Three months later, the animals were euthanized and the eyes and major organs were submitted for histological analysis. Adjacent sections underwent immunohistochemical analysis to detect human cells using anti-TRA-1-85 (human blood group antigen) antibody and DAPI antibodies. RESULTS: The cell monolayer was immunopositive for TRA-1-85 3 months after implantation and migration from the Parylene-C scaffold was not detected. One eye had a mild inflammatory reaction around the implant that was negative for human biomarkers. No intraocular or systemic tumors were detected. CONCLUSION: The hESC-RPE cells survived for 3 months in this animal model. The surgical procedure for subretinal implantation of CPCB-RPE1 is feasible and safe, without cell migration off the scaffold or development of ocular or systemic tumors.

Fluidics comparison between dual pneumatic and spring return high-speed vitrectomy systems.

BACKGROUND AND OBJECTIVE: To compare the water and vitreous flow rates and duty cycle (DC) between two ultrahigh-speed vitrectomy systems: pneumatic with spring return (SR) and dual pneumatic (DP) probes. MATERIALS AND METHODS: The flow rate was calculated using a high-sampling precision balance that measured the mass of water and vitreous removed from a vial by a vitreous cutter. Frame-by-frame analysis of a high-speed video of the cutter was used to determine the DC. Three cutters of each gauge (20, 23, and 25 G) were tested with an SR and a DP system using the standard DC setting (biased open) at 0 (water only), 1,000, 2,000, 3,000, 4,000, and 5,000 cuts per minute (CPM) with aspiration levels of 100, 200, 300, 400, 500, and 600 mm Hg. RESULTS: The DC was slightly higher with the SR system using most parameters and gauges although without statistical significance. The water flow rate was somewhat higher with the SR system, except for 25 G with 4,000 and 5,000 CPM. The vitreous flow rate was similar using most parameters, with the SR system showing higher flows at lower cut rates (1,000-3,000 CPM). CONCLUSIONS: SR and DP systems produced similar water and vitreous flow rates. Additional studies in human eyes are necessary to confirm these findings.