Rodrigo A. Brant Fernandes

Artificial vision through neuronal stimulation

INTRODUCTION The term visual prosthesis refers to any device capable of eliciting visual percepts in an individual through electrical stimulation of any part of the visual system. BACKGROUND Blindness can be due to eye pathology or due to damage of the lateral geniculate or visual cortex. Eye pathology other than diseases that affect the cornea and lens are numerous and some of the leading causes are diabetic retinopathy, age-related macular degeneration, retinal detachment, glaucoma, and retinal vascular occlusions. The visual prosthesis can be divided into non-retinal and retinal approaches. Non-retinal approaches include cortical and optic nerve prosthesis. Retinal approaches are aimed at eye pathologies in which at least part of the optic nerve remains intact whereas when the optic nerve is nearly completely damaged and/or the eye itself is disfigured or degenerated then a non-retinal approach is warranted. The retinal prosthesis can be placed on the surface of the retina, in the subretinal space or in the suprachoroidal space. RESULTS Several independent groups related variable degrees of success in promoting visual sensations through electrical stimulation of the visual system. Every technique, equipment and anatomical target has its advantages and disadvantages, and the biological/electrical-mechanical interface is still the aspect of the research towards a chronic, long term, reliable biomimetic implant. CONCLUSIONS The visual prostheses have achieved significant developments in recent years. We see continued improvement in visual acuity with increasing number and density of electrodes. Even though the visual acuity is still poor relative to normal vision, these subjects can read letters using their implants. Perhaps more importantly, blind patients can use these devices for mobility and orientation.

Performance analysis of ultrahigh-speed vitreous cutter system.

Purpose: To evaluate flow rates and duty cycle for different sizes of ultra–high-speed pneumatic vitreous cutters. Methods: A precision balance measured the mass of water and vitreous removed from a vial. Porcine vitreous was obtained within 12 hours of killed at a local slaughterhouse and kept at 4°C. Twenty-, 23- and 25-gauge (n = 3 of each gauge) pneumatic cutters were tested at 0 (water), 1,000, 2,000, 3,000, 4,000, and 5,000 cuts per minute with aspiration levels of 100, 200, 300, 400, 500, and 600 mmHg. Frame-by-frame analysis of high-speed video was used to determine the duty cycle. Results: Larger gauge cutters associated with higher aspiration levels produced greater vitreous and water flow rates (P < 0.05). As the cut rate increased, the vitreous flow rate increased (maximum flow at 5,000 cuts per minute) and the water flow rate decreased (P < 0.05). The duty cycle of the new-generation cutters decreased as cut speeds increased, using all 3 gauges (P < 0.001). Vitreous flow rates averaged 10 times less than water flow rates using the same cutter at the same settings. Conclusion: Ultra–high-speed vitreous cutters produce consistent vitreous and water flow rates across the tested range of cuts per minute and aspiration levels.

Fluidics in a dual pneumatic ultra high-speed vitreous cutter system.

Background: Dual pneumatic systems use two separate air line tubes to open and close the cutter and can achieve high cut rates. The purpose of this study is to evaluate the influence of gauge size, cut rate and aspiration on the flow rate performance of ultra high-speed cutters operated with a commercially available dual pneumatic vitrectomy system. Methods: Analysis of a high-speed video was used to determine duty cycle. Flow rates from 20-, 23- and 25-gauge cutters were calculated in predetermined conditions of aspiration levels and cut rates; water and fresh porcine vitreous samples were studied. Results: For all three gauges of cutters, the duty cycle and water flow showed an inverse correlation with increasing cut rates and a direct correlation with increasing aspiration levels (p < 0.05). Vitreous flow rates from all gauges increased with increasing aspiration and cut rates (p < 0.05). Conclusion: Larger gauges of the cutters as well as higher aspiration and cut rate levels resulted in improvement of the vitreous flow rates. A good understanding of the different flow rate settings is essential for the surgeon and optimizes the safety of surgical procedures.

Analysis of a 23-gauge ultra high-speed cutter with duty cycle control.

Purpose: The purpose of the study was to determine the performance of dual pneumatic ultra high–speed 23-gauge cutters operated with variable duty cycle (DC) settings. Methods: Frame-by-frame analysis of high-speed video was used to determine the DC in core, 50–50, and shave modes. Using three cutters at various cycles per minute and aspiration levels, mass of water or vitreous removed from a vial was measured within a specified time period. Average flow rates were calculated for each aspiration level and cut rate with the different DC options. Results: The DC increased with increasing cut rate in the shave mode was relatively stable in the 50–50 mode and decreased for the core mode. The DC converged at 5,000 cycles per minute for the 3 different modes. Water flow curves followed the DC variation. Vitreous flow rates for all the DC modes increased with increasing cut rates and peaked at 5,000 cycles per minute (P < 0.05). The results of the 50–50 mode, which had isolated the DC influence, showed that increasing aspiration and/or cut rate independently increased the vitreous flow rate. Conclusion: Progressive values of aspiration and/or cut rate increase the vitreous flow rate, independently of the DC. The DC control also has an important effect on the vitreous flow, but this effect was reduced at high cut rates because of convergence of the DC modes.

In vivo detection of hESC-RPE cells via confocal near-infrared fundus reflectance.

BACKGROUND AND OBJECTIVE To investigate whether the confocal near-infrared reflectance (NIR) imaging modality could detect the in vivo presence of retinal pigment epithelium cells derived from embryonic human stem cells (hESC-RPE) implanted into the subretinal space of the Royal College of Surgeons (RCS) rat. MATERIALS AND METHODS Monthly NIR images were obtained from RCS rats implanted with either hESC-RPE seeded on a parylene membrane (n = 14) or parylene membrane without cells (n = 14). Two independent, masked investigators graded the images. Histology and immunohistochemistry were performed at different time points (150, 210, and 270 postnatal days of age). RESULTS NIR images revealed that an average of 20.53% of the parylene membrane area was covered by hESC-RPE. RPE-65 and TRA-1-85 confirmed the presence of human-specific RPE cells in those animals. No areas corresponding to cells were found in the group implanted with membrane only. Intergrader agreement was high (r = 0.89-0.92). CONCLUSION The NIR mode was suitable to detect the presence of hESC-RPE seeded on a membrane and implanted into the subretinal space of the RCS rat.

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.

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.