ENDOSCOPE- ASSISTED AND CONTROLLED ARGUS II EPIRETINAL PROSTHESIS IMPLANTATION IN CASESES WITH LATE-STAGE RETINITIS PIGMENTOSA: A Two-Case Report

Emin ÖZMERT(x), Sibel DEMİREL(x)

 ABSTRACT:

Several different approaches to restoring sight to those blind from outer retinal degeneration are currently under investigation, including stem cell therapy, gene therapy, and visual prostheses. Although many approaches of different visual prostheses showed promise, to date, Argus II Epiretinal Prosthesis System  developed over 10 years in the clinic, it is the world’s first and only FDA and CE-Mark approved retinal prosthesis for people blinded by outer retinal degenerations. The incidence of serious adverse events decreased overtime after minor changes were made on the implant design, and improvements in the surgical steps.  In order to further decrease the scleral incision-related complications and  enhance the assessment of the tack position and the contact between the array and inner macular surface, we have used the ophthalmic endoscope during the ragular course of Argus II implantation surgery in two patients with late-stage retinitis pigmentosa in an attemp to improve the anatomical and functional outcomes.

Key words: Argus II, retinal prosthesis, artificial vision, retinal  tack, array, endoscope

 ——————————————————————————

(x): Ankara University Faculty of Medicine Department  of Ophthalmology,

Cebeci Hastanesi Mamak Yolu Dikimevi, 06340 Ankara, TURKEY

 BACKGROUND

Outer retinal degenerative diseases such as retinitis pigmentosa (RP) and dry age-related macular degeneration destroy photoreceptors but leave a significant percentage of inner retinal cells (ganglion and bipolar cells) intact and functional (1,2,3). Several different approaches to restoring sight to those blind from outer retinal degeneration are currently under investigation, including stem cell therapy, gene therapy, and visual prostheses. On this basis, vision-restoring implants have been developing to interface with various parts of the visual pathway, particularly the retina (4). One such device is the epiretinal implant, which targets retinal ganglion cells by having the electrodes contacting the inner surface of the retina (3).  Although many approaches of different visual prostheses showed promise, to date, Argus II Epiretinal Prosthesis System ( Second Sight Medical Products, Sylmar, California, USA) developed over 10 years in the clinic, and it is currently the world’s first and only FDA and CE-Mark approved retinal prosthesis for people blinded by outer retinal degenerations. The Argus II Retinal Prosthesis System consists of a camera worn on a pair of glasses that transmits electrical signals to an array of 60 electrodes implanted on a patient’s macula. The array bypasses the photoreceptor layer and directly stimulate these remaining inner retinal cells with the signal transmitted via  the normal visual pathway to the visual cortex (3,5,6).

Electrical stimulation to the remaining cells of the retina by  the Argus II device produces spots of light, called phosphenes, that are visible to users of the device. Users learn to interpret these visual percepts, thereby regaining some  limited sense of sight to patients who have been blind due to late-stage RP (2,3,5,7). The Functional Low-Vision Observer Rated Assessment (FLORA)  was developed  to evaluate functional visual ability and well-being in a population of subjects whose ultra-low vision has been restored by Argus II Retinal Prosthesis System. Polling of the more than 100 RP patients implanted with the Argus II indicates that navigation and orientation are among the major benefits of the Argus II. It has also proven to be safe and stable during chronic implantation (8,9). The recent report of Second Sight Company published  on December 2015 states that, Argus II can reliably withstand long-term implant (> 8 years) in a significant number of subjects with an acceptible safety profile. Using the system, blind subjects showed improved performance on visual tasks, and results are sustained out to 5 years (10).

A transscleral cable connection is a weak point of all system, because it theoretically allows microorganisms to enter causing endophthalmitis.  Leakage through the pars plana incision site may also cause serious postoperative hypotony. The incidence of serious adverse events (SAEs) decreased overtime after minor changes were made on the implant design, and improvements in the surgical steps (4,11). In the recent publication these       low-rate but significant SAEs are  infective endophthalmitis 0.0%, hypotony 3.4%, re-tack 0.0%, retinal detachment 3.4%, retinal break 0.0%, sclerotomy leak 1.1%, explant 1.1%  in all commercial-implanted patients (10).

In an attempt to manage all these scleral incision-related complications, to control the positions of retinal tack and the contact between the array and the inner surface of macula, as a first time in the literature, we have used the ophthalmic microendoscope during the regular course of Argus II implantation surgery  which proposed by Second Sight’s Surgeon Manual in two late-stage RP patients (12).

 

SURGICAL METHOD

The Argus II device consists of an extraocular part and an intraocular part without any extra-orbital components. The surgical approach therefore is a complex of combined extra / intraocular procedure. The manifacturer calculates and prescribes the distances from limbus for scleral incision and tabs sutures based on the biometric data obtained with ultrasound examination of the axial lenght prior to the surgery. Surgical approach of epiretinal Argus II implantation  is adopted using standard vitreoretinal techniques without routine use of silicone oil.  Since aphakic  or pseudophakic  situation of the eye is preferable,  lens removal   2 weeks before the implantation surgery  or pars plana lensectomy during the surgery is performed. Vitrectomy ports are prepared at 3-9 o’clock positions, infusion line is inserted at infero-temporal quadran and 25-G chandelier  light is introduced at 6 o’clock position which provides sufficient illumination during bimanual work.

After the placement of the extrascleral part which consist of receiving coil and electronics case, a full vitrectomy following complete posterior vitreous detachment is performed with the assistance of triamcinolone acetoide ( 4 ml / 0.1 ml) to ensure whether all vitreous remnants are removed from the vitreous base and the retinal surface.                   A perpendicular 5.2 mm scleral incision through the pars plana has to be made to insert the cable with the epiretinal stimulator array of 60 microelectrodes at its tip.  Just before creating the scleral incision, the prescribed setback distance from the limbus, which depends on the patient’s axial lenght, is measured along the cable axis and marked  the center of the sclerotomy site (Figure 1) . A 30-G fine is inserted from the prepared central mark through the pars plana(Figure 2). With endoscope, we decide to check the prescribed scleral incision site internally  in order to confirm the proper location (fine needle test). The 23-G nasal scleral incision which prepared for regular vitrectom surgery is used to insert the 23-G fiberoptic-type endoscope probe with 120 degree visual field (Endo Optiks Inc, Model E2 MicroProbe, Laser and Endoscopy System, OME 2000, NJ-USA). With direct endoscopic viewing, we control the pars plana, trace of the fine needle, and ora serrata (Figure 3), which are impossible with antero-posterior view of operating microscope without doing scleral indentation.  If the scleral incision site which was controlled internally by endoscope seems to be appropriate, a 5.2 mm-with scleral incision is created to insert the array according to surgeon  manual of the manifacturer (Figure 4). If  the scleral incision site  looks unsuitable the measurement to the limbus prescribed and provided by the manifacturer is revised. After making scleral incision and insertion of the electronics array, we have to check the retroiridal space  with endoscope for having complications such as ciliary body, choroidal detachment and retinal tear (Figure 5).  If there is no any scleral incision-related issues, then we can proceed to the further surgical steps.

If everything was planned and performed according to the measurements and to the recommendations, the electrode array should land without any force at the macular area and should ideally not cover the optik disc. Positioning of the device over the central macula with minimal space between the array and the retinal surface is essential. If the stimulator is not centered in the macula the narrowing  sutures at the incision site need to be modified. If everything looks appropriate, the implant is fixated using a retinal tack. The application of the retinal  tack, its insertion, the release of the handle, and ensuring  a good contact of the array with the macular surface are the most critical parts of  the procedure. We can check the position of the tack  and the contact between the macular surface and the array  with the excellent  side-viewing capability  of the curved-probe of the endoscope, in contrast to the antero-posterior viewing of the operating microscope (Figure 6).  Nonperpendicular or shallow tacking causes the device to move away from the retina. At the end of the surgery, we have to control the peripheral retina and vitreous base without scleral indentation since electronics were secured to the sclera at the begining of the surgery. All these steps were  accomplised by ophthalmic microendoscope easily with no endoscope-related complications without any need of scleral indentation.

CASES

Case 1:

46-year-old man (U.A.) who had late-stage RP for last 10 years with barely light perception and projection in both eyes. After the routine ocular examination including      SD-OCT and fundus autofluorescence, and discussion on the surgery, fitting / rehabilitation procedures, and possiple benefits and complications of the method, the subject received the Argus II Retinal Prosthesis System on left eye, typically the worse-seeing eye,  on 28 December 2015.  Endoscope-assisted and controlled regular surgical procedure for Argus II epiretinal implantation were performed without any complication. Lens was removed just before the vitrectomy phase by pars plana lensectomy.  He is currently on the forth rehabilitation session, and can detect the white plates and glassess on the dark table, and some square and lines on the screen.

Case 2:

31-year-old man (U.Y.) who had late-stage RP for last 8 years with barely light perception and projection in both eyes. After the routine ocular examination including SD-OCT and fundus autofluorescence, and discussion on the surgery, fitting / procedures, and possiple benefits and complications of the method, the patient received the Argus II Retinal Prosthesis System on left eye, typically the worse-seeing eye on 27 June 2016.  Two weeks before the implantation surgery phacoemulsification without intraocular lens implantation was done. Endoscope-assisted and controlled regular surgical procedure were performed without any complication. He is currently on the first rehabilitation session, and can follow the light on the floor.

In both cases, during the fitting procedure, we had complete active electrodes with proper impedance measurement, and perfect placement of the arrays. So far, there was  no any complication such as retinal tear, hypotony ar ciliary body detachment, and  tacking issues.

DISCUSSION:

During the regular course of Argus II  implantation surgery, we have decided to use the 23-G fiber-fused type ophthalmic microendoscope  to have its some potantial benefits and advantages. Endoscope probe consists of illumination, viewing and laser fibers, and is inserted through the nasal pars plana sclerotomy created for the vitrectomy (13).

The insertion of the array requires complete removal of anterior vitreous in this area to minimize the pulling effect of the residual vitreus remnants; otherwise the risk of the development of ciliary body detachment and / or retinal tear will increase.  The perence of the residual vitreous tissue can be seen with endoscope completly because of the normal anatomical contour of the retroiridal tissues and real relationship  of the traction forces since scleral indentation was not perform. This would be advantage because the electronic case and receiving coil have already been sutured on the sclera around the globe.

The creation of scleral incision for insertion of the array is one of the most important step of the surgery. Its distance from the limbus is calculated based on the biometric data obtained from axial lenght measurement made by ultrasound examination. But this approach may not be suitable in every case because of developmental variations of ora serrata such as meridional folds, meridional complexes and oral buys are common and occur in 47%  of 204 normal eyes. In moderate or high myopia, the ora serrata is often located posterior to the rectus muscle insertions. Pars plana zone is 3 mm wide in the nasal quadrants  and  5 mm wide in the temporal quadrants. Fiberoptic transillumination through the pupil can be used to demonstrate ora serrata when choosing location for pars plana incision(14).  In these eyes  having this type of variations in the normal pattern of the pars plana,  if scleral incision is created only according to the axial lenght measurement we may face with scleral incision-related complications. In order to minimize these risks fine needle test may be a useful approach.

We have controlled the location of the 5.2 mm pars plana incision internally by the endoscope just before creating the full thicknes incision in order to see the wheather or not the incision site is proper. Just after ceration of the scleral and choroidal incisions and insertion of the array and cable, it would be helpful to see the retroiridal space to detect if some serious complications such as retinal tear, ciliary body damage and / or detachment are developed.

An important aspect of all epiretinal devices is the distance between the retina’s inner surface and electrodes. To achieve a significant membrane potential change in retina, the stimulating electrodes have to be applied as close to the target cells as possible. Care has to be taken intraoperatively to achieve a tight contact between the implant and the retina (15). Under operating macroscopic wieving, it is hard to assess the contact  because of its antero-posterior wieving. By the side vieving capability of the endoscope, surgeon can assess the conformity of the contact between the array and inner surface of macula, and the degree of the retinal tack compression. In the presence of improper situations retacking can be considered.

As a general rule, at the end of the vitreoretinal surgery, it is so important to check the retroiridal area with scleral indentation to detect the serious complications such as ciliary body / choroidal detachment and retinal tear(s).  Scleral indentation may be limited and harmful since the precence of electronic case and coil sutured to the sclera. This aim  can be accomplished  by the endoscope easily, quickly and completely without any damage to the electronic devices. If retinal tear is detected, it can be treated  by endoscopic endolaser application at the same time, and if necessary appropriate intraocular tamponade is chosen. The position of the cable, passing through  the pars plana incision, can also be assessed  whether there is any tilt or bent that causes the leak and postoperative severe hypotony.In this case, it  is necessary to change the sutures to correct the tilting or benting of the cable.

CONCLUSION:

Although the SAEs and complications occur less frequently due to improvement in device design and surgical steps of Argus II implantation surgery, there  are still some sclerotomy incision-related complications such as retinal damage, infringe upon the ciliary body, inadequate placement of the electrode array over the fovea and tacking issues. Intraoperative assistance of ophthalmic microendoscope may further decreases the rate of devastating severe complications that their treatment might be difficult or unsuccessful. Learning and using the endoscope is easier in the implantation surgery because the natural lens has been already removed. It is fact that endoscope is an additional cost to the surgery; however it is worthwhile to have it, because it prevents difficult additional surgeries and expenses. It also further improves the surgical and functional outcome because of more controlled surgery.

 

 

REFERENCES:

1. Chuang AT, Margo CE, Greenberg PB. Retinal implants: a systematic review. Br J Ophthalmol 2014; 98:852-856.
2. Dorn JD, Ahuja AK, Caspi A, et al. The detection of motion by blind subjects with the epiretinal 60-electrode ( Argus II) retinal prosthesis. JAMA Ophthalmol 2013; 131(2):183-189.
3. 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; 1-8.
4. Kasi H, Hasenkamp W, Cosendai G, et al. Simulation of epiretinal prostheses – evaluation of geometrical factors affecting stimulation. J Neuroengineering and Rehabilitation 2011; 8(44):1-10.
5. Ho AC, Humayun MS, Dorn JD, et al. Long-term results from an Epiretinal prosthesis to restore sight to the blind. Ophthalmology 2015; 1-8.
6. Da Cruz L, Coley BF, Dorn J, et al. The Argus II Epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br J Ophthalmol 2013; 97:632-636.
7. Barry MP, Dagnelie G. Use of the Argus II retinal prosthesis to improve visual guidance of fine hand movements. Invest Ophthalmol Vis Sci 2012; 53:5095-5101.
8. FLORA: Phase I development of a functional vision assassment for prosthetic vision users. Clin Exp Optometry 2015; DOI:10.1111/cxo.12242:1-6.
9. Hahn P. The next generation of artificial vision. Retina Today 2015; 10 (2): 61-66.
10. Clinical Update 1 December 2015, Second Sight Medical Products, Inc. Sylmar, CA 91342 USA.
11. Retina Implant Care-Basics, Procedures and Follow-up. Ed: Walter P. International Medical Publishers, London Boston, 2014.
12. Argus II Retinal Prosthesis system, Surgeon Manual. Second Sight Medical Products, Inc. Sylmar, CA 91342 USA.
13. Uram M: Endoscopic Surgery in Ophthalmology. Lippincott Williams&Wilkins, Philadelphia, Baltimore, New York, 2003.
14. Anatomy and Physiology. Retinal Detachment.Eds: Michelson RG, Wilkinson CP, Rice TA. St Louis, Baltimore, The CV Mosby Company, 1990.
15. Tsai D, Chen S, Protti DA. Et al. Responses of retinal ganglion cells to extracellular electrical stimulation, from single cell to population: model-based analysis. PLoS ONE. 2012; 7(12):e53357.

 

 

FIGURES

 

Figure 1: Prescribed setback distance from the limbus is measured and the center of

the sclerotomy site is marked for scleral incision

Figure 2: A 30-G fine needle is inserted through the prepared central mark on

pars plana. The tip of the needle is seen at the border between ciliary body and

pars plana by endoscope

Figure 3: Pars plana, ora serrata and trace of the needle ( large white dot) is controlled by

the direct viewing of the endoscope. Needle trace is located perfectly on the pars

plana, indicating the suitable scleral incision site

Figure 4: If surgeon is convinced that  scleral incision site looks appropriate ,  a  5.2 mm

scleral and choroidal incisions are created  under endoscopic viewing

Figure 5 : After insertion of the cable and array, retroiridal space is controlled for the

incision and / or vitreous -related  complications, whether there is tilt or bent in

the electronic cable and improper wound closure, which leads to postoperative

severe hypotony, by the endoscope clearly without any need of scleral indentation

Figure 6: With the side viewing capability of the curved endoscope probe, the compression

degree of  the tack ( left), position of the array in relation to the optic disc,  and the

contact between the array and the  inner surface of macula can be assessed and

assured clearly  before ending the surgery