Effects of radiofrequency energy on human articular cartilage: an analysis of 5 systems.

BACKGROUND: Previous radiofrequency work has not rigidly controlled energy application to the articular cartilage, giving uncertain results published to date. HYPOTHESIS: At minimal settings, radiofrequency probes cause cell death in measurable areas when applied to human articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Simulating operating room conditions, 5 commercially available radiofrequency probes were attached to a customized jig to standardize a minimal contact pressure of each probe tip to 2.0 g. Keeping all variables the same, probes were placed on specific points of fresh grade II human cartilage with treatment times of 1 and 3 seconds at the manufacturer's recommended settings. Grade III cartilage was also tested with a treatment time of 3 seconds, and grade II cartilage was studied with the probe held 1 mm off the cartilage surface. Cartilage was blindly analyzed by confocal microscopy using a live/dead cell viability assay to determine the extent of cell death. RESULTS: Radiofrequency probes produced significant cellular death in the form of a half-circle into the cartilage to variable depths. For treatment times of 1 and 3 seconds, cell death measurements ranged from 404 to 539 mum and 1034 to 1283 mum, respectively. One probe failed to show any effect, with minimal evidence of cell death or cartilage smoothing. When probes were kept a 1.0-mm distance above the cartilage, no cell death or cartilage smoothing was noted. Radiofrequency treatment of grade III cartilage penetrated to the subchondral bone. There was no statistically significant difference between the damage caused by monopolar and bipolar probes when tested under these rigidly controlled conditions. CONCLUSION: These results showed significant cellular death at these minimal conditions to the underlying chondrocytes with radiofrequency probes. Surgeons using this technology need to be aware of the power and dangerous potential these probes can have on articular cartilage.

The value of preoperative tests in the selection of blind patients for a permanent microelectronic implant.

PURPOSE: To determine the best candidates (ie, those requiring lowest current levels delivered to the retina to elicit visual perceptions) for long-term implantation of a microelectronic retinal implant through a series of preoperative visual, psychophysical, and electrophysiological tests. METHODS: This study protocol was granted an investigational device exemption by the Food and Drug Administration and was approved by the institutional review board at the University of Southern California. After informed consent was obtained, all subjects underwent the following preoperative tests: dark-adapted bright flash and 30-Hz flicker electroretinograms, electrical evoked responses (EERs) using a Burian-Allen corneal electrode to stimulate the globe, and psychophysical tests to evaluate the light and electrically elicited visual perceptions. Intraocular stimulation (IOS) of the retina was performed by an array of electrodes positioned on the internal limiting lamina. RESULTS: Lower vision correlated with less sensitive psychophysical responses (P<.0001). Lower vision and less sensitive psychophysical tests correlated with higher EER values for stimulus pulse widths of 2 ms (P<.0008) and 4 ms (P<.0002). Lower IOS currents correlated with more sensitive psychophysical responses (P<.02) and lower EER values at 4 ms (P<.04). CONCLUSIONS: Preoperative testing, especially psychophysical and electrophysiological tests to assess light and electrically driven visual responses, can help in evaluating patients for suitability for receiving a permanent microelectronic retinal implant. Further study is warranted.

Implantable MicroPump for Drug Delivery in Patients with Diabetic Macular Edema.

PURPOSE: To demonstrate the safety and surgical feasibility of the first-in-man ocular implant of a novel Posterior MicroPump Drug Delivery System (PMP) in patients with diabetic macular edema (DME) and to report on the device capabilities for delivering a programmable microdose. METHODS: This was a single center, single arm, open-label, prospective study. Eleven patients with DME and visual acuity equal to or worse than 20/40 were included. The PMP prefilled with ranibizumab was implanted into the subconjunctival space. After implantation, the PMP was wirelessly controlled to deliver a programmed microdose. Comprehensive ophthalmic exams and optical coherence tomography were performed biweekly for 90 days. At the end of the study, the PMP was explanted and the subjects thereafter received standard of care for DME (i.e., laser or intravitreal injections). RESULTS: All 11 surgical implantations were without complications and within the skill sets of a retinal surgeon. No serious adverse events occurred during the follow-up period. At no point were visual acuity and central foveal thickness worse than baseline in the implanted eye. The PMP delivered the programmed ranibizumab dosage in seven subjects. The remaining four patients received a lower than target dose, and the treatment was complemented with standard intravitreal injection. CONCLUSIONS: This study demonstrates the first-in-man safety of the Replenish MicroPump implant for a period of 90 days and its capability to deliver a microdose into the vitreous cavity. Further studies to enable longer-term safety and to demonstrate the feasibility of multiple programmable drug delivery are necessary.

One-Year Feasibility Study of Replenish MicroPump for Intravitreal Drug Delivery: A Pilot Study.

PURPOSE: To determine the feasibility of the surgical procedure and to collect some safety data regarding the bioelectronics of a novel micro drug pump for intravitreal drug delivery in a Beagle dog model for up to 1 year. METHODS: Thirteen Beagle dogs were assigned to two groups. The experimental group (n = 11) underwent pars plana implantation of MicroPump; the body of which was sutured episclerally, while its catheter was secured at a pars plana sclerotomy. The control group (n = 2) underwent sham surgeries in the form of a temporary suturing of the MicroPump, including placement of the pars plana tube. Baseline and follow-up exams included ophthalmic examination and imaging. The experimental animals were euthanized and explanted at predetermined time points after surgery (1, 3, and 12 months), while the control animals were euthanized at 3 months. All operated eyes were submitted for histopathology. RESULTS: Eyes were scored according to a modified McDonald-Shadduck system and ophthalmic imaging. Neither the implanted eyes nor the control eyes showed clinically significant pathological changes beyond the expected surgical changes. The operated eyes showed neither significant inflammatory reaction nor tissue ingrowth through the sclerotomy site compared with the fellow eyes. CONCLUSION: This study shows that the Replenish Posterior MicroPump could be successfully implanted with good safety profile in this animal model. TRANSLATIONAL RELEVANCE: The results of this study in a Beagle dog model are supportive of the biocompatibility of Replenish MicroPump and pave the way to the use of these devices for ocular automated drug delivery after further testing in larger animal models.

Advances in the development of visual prostheses.

Visual prostheses are based on neuronal electrical stimulation at different locations along the visual pathway (ie, cortical, optic nerve, epiretinal, subretinal). In terms of retinal prostheses, advances in microtechnology have allowed for the development of sophisticated, high-density integrated circuit devices that may be implanted either in the subretinal or epiretinal space. Analogous to the cochlear implants for some forms of deafness, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that would excite the remaining spared inner retinal neurons in patients with diseases such as retinitis pigmentosa and age-related macular degeneration. The different types of implants and recent results are discussed, but special emphasis is given to retinal implants.

Angiographic characteristics in patients undergoing macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To review in a standardized fashion pre- and postoperative fluorescein angiographic characteristics in patients undergoing limited macular translocation (LMT) with scleral imbrication to treat subfoveal choroidal neovascularization (SFCNV) secondary to age-related macular degeneration (AMD). The current study was undertaken to assess any potential effects of the translocation procedure on altering the angiographic characteristics of SFCNV before laser photocoagulation. METHODS: A consecutive series of patients undergoing LMT for AMD was identified retrospectively. The pre- and postoperative fluorescein angiograms were reviewed in a masked fashion. Angiographic characteristics evaluated included pre- and postoperative lesion components, stability of lesion, and the amount of retinal translocation obtained. RESULTS: Eighty-eight patients (90 eyes) had angiograms of adequate quality to permit evaluation. Time between the preoperative and the prelaser angiogram ranged from 2 to 84 days (median 7.5 days). Neovascular complexes remained unchanged or decreased in size in 79% of patients. There was no statistically significant difference in lesion size between the pre- and postoperative periods (P = 0.34). Retinal movement ranged from 160 microm to 3,320 microm (median 960 microm), with 61% of cases undergoing effective translocation (i.e., the fovea was moved away from the neovascular complex). None of the lesion components or demographic factors evaluated affected the amount of translocation obtained. Larger lesions were more likely to remain subfoveal following translocation (P = 0.004). CONCLUSION: The size and lesion characteristics appear relatively stable following translocation. Amount of retinal movement is not associated with angiographic lesion characteristics. Only size was associated with achievement of desired translocation in the final model, with large lesions being less likely to achieve desired translocation. In our study group, the amount of retinal translocation was variable with 61% of cases undergoing effective translocation.