Fig.1. Subretinal bleb stabilized by viscoelastic solution and scleral flap
Fig.2. Рosition off the implant after advancement into the macular region. Guidefoil already removed.
Animal experiments made clear that the stimulation process requires an additional energy. Consequently the concept of an active subretinal implant was developed which feeds the necessary energy for the stimulation process from outside of the eye. A permanent (cable) connection into the subretinal space is mandatory in this concept. Thus a transchoroidal placement of the implant (combined ab externo and ab interno procedure) seems to be the method of choice (Sachs, 2001). With the IMS implant first successful human implantations were carried out but suffered from limited lifetime. This IMS implant strongly met surgical needs. The further developed AMS implant that offers a lifetime of at least 5 years increased in size and has higher rigidity. Surgery tended to be more difficult with this new implant type.
Material and methods
Some 50 legally blind RP patients (no use of residual vision in daily life) were implanted worldwide with an subretinal implant. A design change due to insufficient lifetime led to the development of the AMS chip which was introduced after the implantation of approx. 30 chips. 15 of them were operated by one surgeon who had developed the transchoroidal access. The impact of the change of the design on the result of the surgery was evaluated in this single center to eliminate learning curve effects of different surgeons.
The Implant
The complete subretinal implant is composed of different elements. These parts fulfill the needs of the respective anatomical structure. The requirements of the of the chip in the subretinal space, the extraocular (orbital) path and the sub-dermal path for the cable had to be fulfilled. The implant consists of a polyimide foil strip with the electronic chip for subretinal stimulation mounted on it. The tail of the foil contains the conductive wiring which are connected to a sub dermal silicone cable containing gold wiring. The distal cable ends in receiver coil for the transdermal energy supply in the retroauricular region. The implant change from the IMS to the AMS chip resulted in an increased size of the submacular foil tip and a wider foil tail (compare Fig. 3b and 5) for the energy supply which results in a greater RPE-retina separation area. According the additional material and technical properties a stiffer and more difficult to implant device is the result.
The ocular and subretinal part
Fig.3. Choroidal perforation, limited bleeding which resolved completely (a); choroidal bleeding resolved in the follow up (b); OCT of choroidal perforation. Chip ( high reflective red line). Exact boarder of penetration visible showing choroid and retina on the left side of the chip and retina only on the right side overlying the chip (c)
Fig.4. Aspect of implant beneath RPE and retina (intraoperative) (a); Implant intraoperative beneath retina. RPE after repositioning under the chip. Good visibility of chip (b)
The chip which is square shaped has the 1600 photodiodes with the equal number of TiN electrodes arranged in a rectangular manner. The power supply of the chip is external. This external energy is delivered via the supply lines on the polyimide foil. Light falling onto the chip and the photodiodes drive the device. So the single photo diode worked like a switch pulling energy from outside if activated in the stimulation process.
The foil leaves the eye in the (pre-) equatorial region through the choroid. It is covered for the approx. following 5 mm by a scleral flap. The extra-ocular foil has small polytetraflourethylene patches glued onto it to ease episcleral fixation. This fixation is intended to neutralize the tensile stress. The foil reaches the fornix where it is rather loose to guarantee the mobility of the eye. The path of the subdermal cable starts at the scleral patch and ends at the retro auricular region. In the orbit the cable forms a loop to guarantee eye movement.
The transchoroidal subretinal implantation in humans in detail
One surgical team usually supported by an ENT surgeon is responsible for the extraocular surgery. The stimulation foil and the following silicone cable enter the orbit beneath the upper temporal quadrant of the eye lid. A standard 3-port vitrectomy is carried out and vitreous is removed as far as possible. A critical step is the search for suitable (choroidal) penetration site which should allow the creation of a visible subretinal fluid bleb in the equatorial region. The size of the bleb is crucial. Big blebs create problems during implant advancement. A trapezoid scleral flap with its basis corresponding to the subretinal bleb is created. Care is taken to avoid any choroidal bleeding. The choroid is completely exposed in an area of 1x4 mm and radio-diathermy is applied. Thus the choroid can be punctured. The subretinal space is entered by gaining access into the viscoelastic bleb from outside of the globe. The guide foil allows a safe advancement of this device into the desired subretinal posterior target area. After placement of the stimulation chip the shield can be withdrawn easily. With the implant in its destination the scleral flap is sutured after removing the guide foil. The implant is fixed with patches onto the sclera. Donor scleral or the fascia of the M. temporalis is used to cover the extra-ocular components. In the region of the scleral fixation patch the foil part is followed by a silicon cable with spiral gold wires. 5 cm of the cable is buried in the fornix region without suturing creating a cable loop. This is it to guarantee eye movement. Silicone oil is used as a tamponade medium.
Results and Discussion
The feasibility of a transchoroidal implantation of retina implants was proven in meanwhile 50 patients by 10 surgeons. Three surgeons were contributing to most of this 50 implantations. We evaluate the 15 implantations of one surgeon who was developing the procedure and has experience with both of the implant designs. A stepwise approach of the transchoroidal procedure for both implants is given in Fig. [1, 2].
There are remarkable differences of the tissue of the RP-patient which influence the surgery. The process is described in detail by Sachs (2016).
Choroidal problems in the subgroup of the 15 patient were one perforation in the area of the posterior pole (Fig. 3a, b, c) and two intraoperative misplacements of the implant beneath the choroid and the RPE which was corrected within the same surgery in one patient (Fig. 4a, b). The perforations did not lead to a major bleeding (Fig. 3a, b). In the second patient the chip is partly covered with choroid and a better placement was not to be achieved. Additional problems were not monitored in the follow-up phase. Especially no additional bleedings followed. There was no neovarscular growth in the follow-up. The initial bleeding resolved completely showing a stable situation (Fig. 3b).
The transchoroidal access into the subretinal space in combination with a pars plana vitrectomy is a new developed surgical procedure. It was developed to implant visual prosthetic devices into the subretinal space to restore vision in patients blind from degenerative retinal disease. The severe theoretic possible complications lead to a lot of critics in the period of the development of the surgical procedure especially in the preclinical phase of the animal experiments.
Pigmented areas in RP patients indicate adhesion between RPE and retina. This aspect was unknown before and was never seen in the animal model. To avoid uneventful penetration of the retina during the implantation process a guiding tool was developed and continuously improved. This tiny instrument protects the retina during the implantation of the chip and is of outstanding importance for a successful implantation. An electronic implant like the one which was used for implantation has different rigid zones and is unimplantable without the help of the new developed tool. The ideal performance of the material the rigidity and the flexibility were determined empirically.
With the transition from IMS to AMS these tools may have to be modified to require the new demands of the stiffer implant. A perfect implantation is the key for success of a good electrical stimulation which was a key message from the multi-center study. To what extent the new design influences the long term tolerability is not yet clear. The experienced more unstable position of the implant in the postoperative phase may be a problem but numbers are to low to assess the impact of the problem. The change of the design which led to a better lifetime seemed to be responsible for retinal effects that are currently not understood in the last consequence.
