Importance of Patient Selection and Screening

The Argus II is currently the only FDA-approved retinal prosthesis device in North America, while the Alpha AMS holds CE approval, with ongoing evaluation of its efficacy. Proper patient selection and screening are crucial for successful outcomes with these devices.

For the Argus II, the indications for implantation include being 25 years or older, having a prior history of useful vision, experiencing profound visual loss due to the loss of photoreceptors (e.g., retinitis pigmentosa), having limited visual acuity (e.g., hand motion, bare light, or no light perception in both eyes), demonstrating retinal responsiveness to electrical stimulation through tests like dark-adapted flash and visual evoked potential (VEP), requiring pseudophakic, aphakic, or cataract surgery prior to implantation, and being able to attend post-implant follow-up and rehabilitation^[1].

Contraindications include having better vision than counting fingers in one eye, ocular conditions that hinder visualization or affect device functionality, systemic conditions contraindicating general anesthesia, presence of incompatible implants or metallic devices, significant hearing impairments interfering with device interaction, and inability to comply with follow-up and rehabilitation due to cognitive decline or conditions like dementia^[2].

Similarly, the indications for Alpha AMS implantation are comparable to the Argus II, with the exception that age specification is not mentioned. However, the retina must have a thickness of >100 μm to require functionality for Alpha AMS implants. Indications include light perception without projection or no light perception in hereditary retinal diseases, end-stage primary rod cone or cone rod dystrophies, a prior history of normal visual function for >12 years, pseudophakic or aphakic status prior to implantation, fluorescein angiography showing retinal vascular perfusion, evidence of inner retinal function observed through phosphene threshold elicitation, and the ability to provide informed consent and attend follow-up and rehabilitation^[3]. Contraindications involve ophthalmic conditions affecting visual function, retina thickness of <100 μm or absence of inner retinal layering, scar tissue, occipital stroke, congenital blindness, severe amblyopia, substantial corneal opacity, active inflammation (uveitis), systemic conditions posing risks during general anesthesia, life expectancy <1 year, and inability to comply with follow-up and rehabilitation due to psychiatric/neurological diseases^[2][4]. 

Pre-Operative Assessment, Examination, and Imaging

A comprehensive pre-operative assessment is essential in identifying appropriate candidates for retinal prostheses. This assessment involves a clinical examination, including a thorough ophthalmic examination with anterior segment evaluation and dilated fundus examination. These examinations assess the patient's ocular health and identify any contraindications to device placement. Additionally, ancillary tests such as optical coherence tomography (OCT), ultrasonography, and optical biometry are conducted to evaluate retinal health and ocular anatomy, ensuring favorable conditions for optimal device functionality^[5][6].

Post-Operative Rehabilitation

Post-operative rehabilitation is pivotal in maximizing the benefits of retinal prostheses, helping patients adapt to the unique artificial vision they provide. Rehabilitation aims to teach patients how to effectively utilize the device's limited vision in conjunction with their existing auditory and tactile skills. The involvement of family members and a supportive social network is crucial in facilitating the rehabilitation process by providing encouragement and motivation^[7][8].

When considering any surgical procedure, it is important to assess the balance between benefits and risks. The following section provides a comprehensive risk-to-benefit analysis of retinal prostheses by examining their clinical outcomes.

Safety and Adverse Events

Epiretinal Prostheses

In a study conducted by Shaffrath et al. (2019) on the Argus II prosthesis system, 47 adults were followed for 12 months, revealing a total of 13 serious adverse events. Of these, 9 were related to the implant, and 4 were related to the procedure. Adverse events included conjunctival erosions (n = 4), hypotony (n = 2), explantation (n = 2), ocular inflammation (n = 1), tractional retinal detachment (n = 1), and rhegmatogenous retinal detachment (n = 1). While most adverse events resolved, two cases persisted (hypotony for eight months and permanent rhegmatogenous retinal detachment). Another study by Stanga et al. reported three cases of retinal detachment in five patients, all successfully treated. In a recent study by Delyfer et al. (2021), two serious adverse events were reported among 17 subjects with Argus II implants, including vitreous hemorrhage and endophthalmitis. Other adverse events included macular edema, choroidal detachment, conjunctival cyst, keratitis, bilateral phlebitis, and ptosis. All adverse events resolved, except for ptosis^[9][10][11].

For the IRIS 2 epiretinal device, clinical trials reported a total of 17 adverse events. Among these, 11 were non-serious adverse events, including phlebitis and tack detachment requiring refixation, all of which resolved. The remaining six events were categorized as serious and involved hypotony secondary to fluid leak from the sclerotomy site, vitreoretinal preretinal traction, and persistent pain^[12].

The implantation of epiretinal devices, similar to routine vitreoretinal surgery, is a relatively straightforward procedure, resulting in a well-controlled rate of complications^[13].

Subretinal Prostheses

Subretinal implants pose technical challenges due to adhesions between the retina and retinal pigment epithelium, as well as limited surgical familiarity^[14].

Older studies on Alpha IMS subretinal implants reported adverse events such as transient increased intraocular pressure and resolved retinal detachment with explantation, accompanied by retinal fibrotic changes^[15]. A study on the newer Alpha AMS edition revealed cases of surgical dehiscence (n = 4), implant displacement (n = 2), partial loss of silicone oil tamponade (n = 1), and pain (n = 1), all of which were self-limiting or well-managed^[4].

The PRIMA device, a subretinal retinal prosthesis, showed adverse events related to procedural complications, including choroidal hemorrhage due to inadvertent choroidal insertion caused by patient movement, focal subretinal hemorrhage, and device displacement due to non-adherence to post-operative movement limitations. Increased intraocular pressure resulting from post-operative medication non-adherence was successfully treated in one patient^[16].

Suprachoroidal Prostheses

Suprachoroidal implants are considered less technically and surgically challenging compared to other types, and they minimize the need for retinal incisions^[17]. Clinical trials following patients for 56 weeks post-implantation reported expected non-serious adverse events such as pain, swelling, tenderness, conjunctival injection, ocular pressure sensation, and local inflammation^[18]. One case of increased ocular pressure associated with topical steroid use for eyelid edema was resolved by tapering the medication and appropriate treatment^[18], aligning with earlier studies on suprachoroidal devices^[17].

Overall, these findings are consistent with older reports of limited adverse events in retinal prostheses, where complications were either minimal or well-managed^[19]. The frequency and type of complications corresponded to the invasiveness of the implant procedure, with suprachoroidal retinal prostheses showing the least adverse outcomes. Nevertheless, retinal prostheses remain safe and effective tools for restoring visual function in individuals with macular degeneration.

Visual Function and Outcomes

Epiretinal Prostheses

Recent studies have provided interesting insights into visual function. An analysis of the Argus II prosthesis revealed varying outcomes. Localization squares generated at random showed that 45% experienced benefits, while 55% saw no difference or benefit when the device was off. Regarding the direction of motion, the results were split with 35% benefiting and 65% not experiencing a difference^[10].

Functional outcomes of the device are often assessed using the functional low-vision observer-rated assessment (FLORA) questionnaire. Researchers studying epiretinal retinal prosthetic use in individuals with age-related macular degeneration found mixed benefits on screen-based tasks, but improvements were noted on all tasks evaluated by the FLORA when the device was on^[9].

In the evaluation of the IRIS 2, improvements were observed in square localization and direction of motion detection at the 3-month and 6-month intervals. The study also reported enlarged visual fields and enhanced picture recognition when the device was on^[12].

Subretinal Prostheses

The Alpha IMS showed improved light source perception in 86% of participants, which decreased to 59% for localization and only 21% for motion detection, with one participant crediting their success to chance^[15].

Daily living activities, such as identifying items on a dining table, telling the time, and reading letters, were also assessed. Among the participants, 45% found the device useful, 27% found little benefit, and 28% saw no benefit in completing these tasks^[15].

In the study by Edwards et al. on the Alpha AMS, tabletop object identification and grayscale contrast detection showed improvement. However, participants still faced difficulties in telling the time, regardless of whether the device was on or off. Regarding screen-based tasks, light localization and perception had better outcomes with the device on, while no benefit was observed for motion detection compared to the device off^[16].

Analysis of the PRIMA subretinal device demonstrated improvements in eccentric natural acuity and accurate identification of bar orientation^[17].

Suprachorodial Prostheses

A study on suprachoroidal retinal implants in patients with late-stage retinitis pigmentosa found varying levels of improvement in daily activities. Tasks relying on vision, such as washing dishes, organizing laundry, and identifying doorways and people in non-crowded spaces, showed the greatest benefits between 17 and 44 weeks post-implantation^[20]. However, identifying food on a plate remained challenging due to limited visual information and quality^[20]. Walking around the home and using stairs showed no difference with or without the device^[20]. Laboratory-based tasks demonstrated higher scores in square localization and improved motion discrimination with the device on^[18].

Post-implantation, individuals with prosthetic vision exhibited oculomotor behavior in motion discrimination tasks, including smooth pursuit and altered opto-kinetic reflex with upbeat nystagmus regardless of stimulus motion^[21]. These "naturalistic oculomotor responses" suggest possibilities for device development and complexity augmentation^[21].

Overall, studies on retinal prostheses (epiretinal, subretinal, and suprachoroidal) showed mixed results in improving visual function and facilitating daily activities in individuals with macular degeneration. While some tasks like square localization and motion detection may improve with the device, others may not show a significant difference when the device is off. Self-report questionnaires like FLORA indicated benefits with the device on, but the specific tasks and type of prosthesis influenced the outcomes. Further research is needed to optimize retinal prostheses and fully understand their potential benefits and limitations in clinical practice. Daily activities such as washing dishes and identifying doorways and people in non-crowded spaces can be facilitated, but identifying food on a plate remains challenging.

Rehabilitative Programs

Rehabilitative programs are crucial for optimizing patient outcomes in the clinical implementation of retinal prostheses. Users face a steep learning curve and often find the visualized phosphenes stressful and cognitively fatiguing^[22]. Lack of rehabilitation can lead to discontinuation of device use due to reasons such as familiarity with home environment, general disappointment, or inconvenience^[22][23]. Participants may be unprepared for the significant differences between prosthetic vision and natural vision, but some adjust conditions to reduce intensity or use the device for visual entertainment^[22].

Obstacles that interfere with vision, such as phosphenes persisting after stimulation or fading in certain areas of the retina, require correction through head movements. These factors should be considered during patient rehabilitation to optimize prosthesis efficacy^[24]. Rehabilitation strategies, including auditory cueing and head movements, have shown promise in improving visual search, perception, and refreshing the visual field viewed by the camera^[25][26].

A pilot study explored the feasibility of the Computer Assisted Rehabilitation Environment System (CAREN), incorporating visual exercises and dual-task training. After four weeks of biweekly sessions, CAREN was found to be safe, feasible, and effective in improving functional outcomes^[27]. Case studies also emphasize the importance of a multidisciplinary approach in managing patient expectations^[23].