The Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, CA) is a surgically implantable device designed to provide artificial vision to patients with outer retinal degenerative diseases, especially retinitis pigmentosa (RP). The system was first assessed in 30 blind subjects, 28 of whom had end-stage RP, in an international clinical trial.1 The patients were evaluated by color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT) during the follow-up, and the long-term safety results were found acceptable. After U.S. Food and Drug Administration approval and becoming commercially available, the system has been widely used all over the world including our institution.
In this case report, our aim is to present the fundus autofluorescence (FAF), spectral-domain OCT (SD-OCT) imaging characteristics, and OCT angiography (OCTA) features in a patient with end-stage RP who had received Argus II retinal prosthesis implantation 1 year ago.
The Argus II retinal prosthesis system was implanted to the more visually impaired right eye with only light perception in a 58-year-old patient with end-stage RP using the method described previously.1 Simultaneous cataract extraction was performed. Preoperative evaluation revealed the characteristic retinal findings as well as severe loss of FAF compatible with outer retinal atrophy (Figure 1). There were no extraocular or intraocular complications experienced perioperatively or postoperatively. During the 23-gauge vitrectomy, the posterior hyaloid could not be detached as a whole, but the macular area was cleansed of any hyaloid remnants using a diamond-dusted scraper and microforceps. The first fitting session was after 2 weeks, and rehabilitation began at 1 month. The patient used the system actively for 2.5 hours to 3 hours daily, attended follow-up visits monthly, and attended the rehabilitation sessions biweekly. He experienced an improvement in his self-estimated visual perceptions as well as square localization and motion discrimination tests1 when the system was active. All 60 electrodes were functional. Funduscopy showed no proliferation over or near the array or the tack and no retinal edema or hemorrhage (Figure 2). SD-OCT cross-sectional images revealed consistently good contact between the array and the retina except for the irregular retinal surface areas, especially the atrophic fovea. Some cystic changes in the retinal layers and tiny strands between the atrophic fovea and the undersurface of the electrode array were detected on the 9-month visit, which persisted without change through the first year. OCTA (AngioVue; Optovue, Fremont, CA) was used to obtain split-spectrum amplitude-decorrelation angiography.2 The scanning area was captured in 3 mm × 3 mm and 6 mm × 6 mm sections centered on the fovea. We ignored the superficial capillary plexus (SCP) because the auto-segmentation software accepted the inferior surface of the array as the inner boundary instead of the retinal surface (Figure 3). The foveal avascular zone (FAZ) was larger and irregular on the implanted eye. Deep capillary plexus (DCP) flow area was estimated to be 0.603 mm2 in the implanted eye and 0.746 mm2 in the fellow eye in a selected area with a radius of 1 mm from the fovea. Blood vessels and capillaries could be visualized on the DCP (beneath the inner plexiform) and choriocapillaris levels bilaterally.
Preoperative color fundus photography, fundus autofluorescence, and fluorescein angiography images of the right (bottom row) and the left eyes (top row) of the patient with end-stage retinitis pigmentosa using optical coherence tomography.
Color fundus photography, fundus autofluorescence, and enhanced high-definition 12.00 mm scan length optical coherence tomography (OCT) images of the electrode array-implanted eye 1 year after the surgery using OCT angiography.
Retina OverVue 6 mm × 6 mm scan-size image. Optical coherence tomography angiography (OCTA) segmentation at the deep, outer retina, and choriocapillaris levels of the right electrode-array implanted eye (top row) and the left fellow eye (bottom row). Vessels could be demonstrated in the deep capillary plexus and the choriocapillaris levels. The colored deep capillary plexus OCTA images at the right column demonstrates grid-based vessel flow density (%).
In a preclinical epiretinal prosthesis study, chronic electrical stimulation of canine retina with an electrode array containing 16 electrodes did not adversely affect the retina.3 Rod-cone dysplasia type 1 blind dogs and a visually unimpaired dog were stimulated for 120 days for 8 hours to 10 hours per day and 4 days to 5 days per week, and fundus examination, fluorescein angiographical findings, and histopathological examination did not reveal any adverse features attributable to the electrical stimulation.
Postmortem morphometric analysis of the retina from a 79-year-old patient with end-stage RP who was the first to be implanted with a 16 electrode-containing Argus I active epiretinal array was reported.4 Except for the tack site shown to be replaced by fibrosis, there was no significant difference when comparing the retina underlying the array and the corresponding perimacular regions with those of two patients with RP. The authors concluded that long-term implantation for 5 years and 3 months and electrical stimulation did not result in damage that could be appreciated in a morphometric analysis of the optic nerve and retina.
Twelve-month outcomes of five patients from a single center demonstrated good biocompatibility.5 There were no signs of chronic intraocular inflammation, proliferative vitreoretinopathy, or epiretinal membrane formation. Clinical examination and OCT revealed good positioning of the arrays on the retina except for one patient with posterior staphyloma. In another case series, three Argus II retinal prosthesis-implanted eyes, two of which had RP, were evaluated by OCT.6 Proximity of the array to the retinal surface indicated a correlation between electrode-retina distance and perceptual threshold in two of three eyes. The electrode array retina interface and placement of the array on the macula was also found to be paramount in another clinical study.7 Macular placement of the array is preferred because fovea is the center of both high-acuity vision and cortical-based attention in the normally sighted, and ganglion cell density is highest in the macula.
Evaluation of a blind 55-year-old patient with RP 10 years after implantation with the Argus I showed a slight increase in the electrode-retina distance for some electrodes.8 There was a fibrotic tissue development around the tack realized at the third post-implantation year, which was compatible with a change in the impedance and the perceptual threshold. There was no leakage or staining related to the array on angiography, but due to the contact with the array, some retinal areas were found to be reshaped on OCT. The natural degenerative course of the disease may have had a contribution, as well.
Recently, the use of intraoperative OCT imaging by portable or microscope-integrated system was found to be feasible during implantation of Argus II before and after tacking.9 Also the surface area that the implant will be placed can be checked for any remaining epiretinal membrane or hyaloid remnants.
OCTA is a new, noninvasive, dyeless method of retinal microvascular imaging, allowing the detection of vascular abnormalities in the retina and the choriocapillaris.2 Thirty-two eyes of 16 patients with RP with an average age of 53 years and BCVA of 0.5 logMAR ± 0.3 logMAR were evaluated by swept-source OCTA 3 × 3.10 Vessel density analysis in the SCP and DCP showed statistically significant lower results in the patient group when compared with the control group. Similar findings in addition to lower choriocapillaris plexus density were also reported in a recent study using OCTA.11 Patients with RP showed a bigger FAZ at the DCP, and most of vascular impairment in RP patients localized in the DCP. In patients with advanced RP, there is a functional dysregulation of both retinal and choroidal vasculature that causes occlusion of vessel lumen and reduction of blood flow in accordance with the degeneration of the outer retina and the retinal pigment epithelium. Although OCTA cannot visualize blood flow if it is lower than the minimum detectable threshold, in our case, the larger FAZ in the implanted eye compared with the fellow eye is attributable to the severe disappearance of DCP due to more extensive macular atrophy.
In this report, after 1 year, the array showed stable and good contact with the retina. We did not encounter any retinal disorganization at the tack site, except for some cystic changes and strands attributable either to remaining hyaloid or a limited proliferative process parafoveally. We could visualize the DCP and choriocapillaris using OCTA in an Argus II epiretinal prosthesis-implanted eye for the first time, to our knowledge. In addition to visualization of the DCP layer, a tack insertion may induce iatrogenic choroidal neovascular membrane formation, visualization of the choriocapillaris using OCTA may be logical in detecting any membrane before doing a more invasive fluorescein angiography.8 Comparison of the same eye data before and after the implantation may have been more helpful than comparison with the non-operated, fellow eye. Due to the shadow artifacts of the electrodes, electrical wires, and the thick handle of the electrode-array, the color-coded grid flow density map was modified making its interpretation difficult, but still DCP flow area and vessel density calculations could be made. Therefore, we think that early postoperative OCTA evaluation and comparison of the findings thereafter during the follow-up period may be more logical. OCTA is a new imaging technique and its capability and efficacy for use in retinal prosthesis implanted eyes needs to be further determined.
- Humayun MS, Dorn JD, da Cruz L, et al. Argus II Study Group. Interim results from the international trial of Second Sight's visual prosthesis. Ophthalmology. 2012;119(4):779–788. doi:10.1016/j.ophtha.2011.09.028 [CrossRef]
- Spaide RF, Klancnik JM Jr., Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45–50. doi:10.1001/jamaophthalmol.2014.3616 [CrossRef]
- Güven D, Weiland JD, Fujii G, et al. Long-term stimulation by active epiretinal implants in normal and RCD1 dogs. J Neural Eng. 2005;2(1):S65–73. doi:10.1088/1741-2560/2/1/009 [CrossRef]
- Eng JG, Agrawal RN, Tozer KR, et al. Morphometric analysis of optic nerves and retina from an end-stage retinitis pigmentosa patient with an implanted active epiretinal array. Invest Ophthalmol Vis Sci. 2011;52(7):4610–4616. doi:10.1167/iovs.09-4936 [CrossRef]
- Rizzo S, Belting C, Cinelli L, et al. The Argus II Retinal Prosthesis: 12-month outcomes from a single-study center. Am J Ophthalmol. 2014;157(6):1282–1290. doi:10.1016/j.ajo.2014.02.039 [CrossRef]
- Parmeggiani F, De Nadai K, Piovan A, Binotto A, Zamengo S, Chizzolini M. Optical coherence tomography imaging in the management of the Argus II retinal prosthesis system. Eur J Ophthalmol. 2017;27(1):e16–e21. doi:10.5301/ejo.5000852 [CrossRef]
- Ahuja AK, Yeoh J, Dorn JD, et al. Factors affecting perceptual threshold in Argus II retinal prosthesis subjects. Transl Vis Sci Technol. 2013;2(4):1. doi:10.1167/tvst.2.4.1 [CrossRef]
- Yue L, Falabella P, Christopher P, et al. Ten-year follow-up of a blind patient chronically implanted with epiretinal prosthesis Argus I. Ophthalmology. 2015;122(12):2545–2552.e1. doi:10.1016/j.ophtha.2015.08.008 [CrossRef]
- Rachitskaya AV, Yuan A, Marino MJ, Reese J, Ehlers JP. Intraoperative OCT imaging of the Argus II Retinal Prosthesis System. Ophthalmic Surg Lasers Imaging Retina. 2016;47(11):999–1003. doi:10.3928/23258160-20161031-03 [CrossRef]
- Battaglia Parodi M, Cicinelli MV, Rabiolo A, et al. Vessel density analysis in patients with retinitis pigmentosa by means of optical coherence tomography angiography. Br J Ophthalmol. 2017;101(4):428–432. doi:10.1136/bjophthalmol-2016-308925 [CrossRef]
- Toto L, Borrelli E, Mastropasqua R, et al. Macular features in retinitis pigmentosa: Correlations among ganglion cell complex thickness, capillary density, and macular function. Invest Ophthalmol Vis Sci. 2016;57(14):6360–6366. doi:10.1167/iovs.16-20544 [CrossRef]