Retinitis pigmentosa (RP) is an incurable set of inherited retinal degenerative disorders characterized by photoreceptor loss and night blindness.¹ The Argus II retinal prosthesis system (Second Sight Medical Products) is a recently developed and FDA-approved epiretinal prosthesis used to induce vision through electrical stimulation of the retina in patients with advanced-stage RP.² The Argus II prosthesis system consists of an external eyeglass video camera with a video processing unit (VPU) that transmits electrical stimuli to an internal epiretinal implant that stimulates the surviving retinal cells.

Five-year clinical trial results of the Argus II were promising, with the majority of patients demonstrating sustained improvement on both visual function and functional vision tests with the device turned on.² However, the percentage of subjects performing better on visual function assessments with the system turned on decreases annually.^2,3 It is critical to understand why visual function efficacy decreases with time after implantation of the device to maximize sustainable patient outcomes. Optimization of retinal prosthesis technology, surgical implantation, and rehabilitation plans are active areas under investigation to maintain visual improvement.

One aspect of the rehabilitation process that has not been thoroughly investigated is the effect of device usage time on visual outcomes over time. In this study, the authors sought to explore the relationship between device usage time and visual function outcomes.

METHODS

This study was IRB approved and informed consent was obtained. All procedures were reviewed and in accordance with the tenets of the Declaration of Helsinki. The data presented in this study are not identifiable to individual patients.

We conducted a retrospective review of 5 patients implanted with the Argus II retinal prosthesis system by a single vitreoretinal surgeon at Stony Brook Hospital between January 2018 and February 2020. Follow-up visits were performed by Second Sight rehabilitation specialists at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after implantation. Visual function at these visits was measured by 2 assessments: direction of motion and square localization. Results from the visual function assessments were reported in terms of the mean error. Additionally, a phone questionnaire was used to estimate the average daily usage of the Argus device at the 5 follow-up visits.

Statistical analyses were performed with Microsoft Excel and Graphpad Prism (Graphpad Software). An unpaired 2-tailed t test was used to determine whether the percentage change in mean error was statistically different when the device was on compared to off between follow-up visits.

RESULTS

Mean time of device use was greater than 3 hours a day for 3 subjects and less than 1 hour a day for 2 subjects. For analysis, patients were grouped into high users (greater than 3 hours a day) and low users (less than 3 hours a day). The mean percentage change between on and off was calculated for each patient at each follow-up visit. The high-user group demonstrated an average improvement of 14% for the square localization when the device was on compared to off at the 24-month visit, whereas the low-user group demonstrated a 100% decrease in visual function with the device on compared to off. On the direction of motion test, both the higher and lower user groups demonstrated decreases in performance of 6% and 59% when the device was on compared to off, respectively. Compared to 3 months, there were no significant differences at each subsequent follow-up in the high user group. The trend in percentage change in mean error for square localization is shown in Figure 1, and the trend in percentage change in mean error direction of motion tests is shown in Figure 2.

DISCUSSION

With many retinal prosthesis devices under development, optimized rehabilitation guidelines are critical to sustained visual efficacy. A multidisciplinary team of investigators, surgeons, rehabilitation specialists, and engineers presented their recommendations on optimizing visual outcomes.⁴ Rehabilitation focuses on supplementing the patient’s remaining useful vision with the new visual percepts. These percepts grow dimmer with extended device use, creating difficulty in integrating them into users’ compensatory visual skills.^4,5 Although authors mention periods of device use that may be less helpful, there is no discussion on the effect of extended device use on long-term visual outcomes.

In the study described here, no appreciated difference was found in the effect of device usage time on visual outcomes. Participants who use the device more often perform comparably to subjects that use the device for a limited time. Device usage time does not appear to be a barrier to sustained efficacy. Rehabilitation is not uniform across sites, but all patients in this study underwent the same rehabilitation program. Device programmers have noted decreasing sensitivity of the device with continuous stimulation.⁴ This may be a product of increased perceptual thresholds following implantation.⁶ Increasing thresholds may be contributing to the gradual decrease in visual function, but baseline perceptual thresholds were not found to correlate with visual function outcomes.⁴

Individual variability in device usage time may be explained by patient expectations. Motivation to continue using the device may decrease when artificial vision does not meet preimplantation expectations. Patient engagement and average daily use increased in participants using a computer-assisted rehabilitation program.⁷ These participants demonstrated improvements on functional, but not visual measures of performance.⁷

Rehabilitation is one aspect of retinal prosthesis outcomes. Given the progressive nature of RP, long-term visual outcomes may be gradually declining despite use of the prosthesis. Specific genotype, remaining useful vision, and age at time of intervention are 2 other variables that may influence outcomes.

Limitations to the study include a small sample size of 5 patients. Recall bias is an additional potential limitation, because participants were asked to recollect their usage time at different time intervals over the past 2 years. Longer follow-up in a larger cohort of patients is necessary to delineate variables leading to reduced visual outcomes over time. Functional vision data, an important outcome measure, was not available for analysis in this cohort of patients. Studies have demonstrated a weak correlation between visual function and functional vision performance.⁸ Participants using the device more may be focusing on improving real-world daily tasks. Future studies should investigate the link between device usage time and functional vision performance. With only a small number of participants implanted with this prosthesis worldwide, continued refinement and standardization of visual function and functional vision tests that correlate well with each other is necessary to accurately assess therapeutic benefit.

CONCLUSION

The findings of this study indicate that time of Argus II use does not have a significant effect on visual outcomes. These findings will help guide the design of future rehabilitation protocols for retinal implants. RP

REFERENCES

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