Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis

Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis Abhishek Naidu, Nimra Ghani, Mohammad Saad Yazdanie, Khurram Chaudhary This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-32698/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Sep, 2020 Read the published version in BMC Ophthalmology → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background: Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis. Methods: 5 patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session. Results: 3 patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold. Conclusion: Our results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes. Ophthalmology Argus II Argus II Retinal Prosthesis Direction of Motion Electrode array-retina gap distance Gap distance Low vision Optical Coherence Tomography (OCT) Retinitis Pigmentosa Square Localization Visual Function Figures Figure 1 Figure 2 Background Retinitis Pigmentosa (RP) is an inherited degenerative disorder resulting in the loss of photoreceptor cells of the outer retina. Over 1 million patients worldwide suffer from RP, which leads to progressive vision loss that can pose significant challenges in many facets of their lives. More than 190 genes have been implicated in the pathogenesis of RP and all mutations inevitably result in degeneration of the photoreceptor layer 1 . However, the inner retinal cells are largely preserved in RP, serving as a target for direct electrical stimulation in order to generate phosphenes that may be perceivable by the patient 2 . Producing and manipulating these phosphenes to accurately reflect the surrounding visual environment is the common objective for electric stimulation-based visual prostheses. The Argus II Retinal Prosthesis System (Second Sight Medical Products Inc., Sylmar, California, USA) was developed for the purpose of providing artificial vision in patients with outer retinal degenerative diseases such as RP. It became commercially available after receiving FDA approval as a humanitarian device in 2013. Roughly, the Argus II consists of an implantable epiretinal 60-channel electrode array connected wirelessly to a portable computer (Visual Processing Unit, VPU). The VPU receives real-time images from a video camera mounted onto glasses worn by the patient. Wireless connection between the electrode array and the VPU occurs via an external coil (side arm of the glasses) and an internal coil (housed in the internal unit) that utilize radiofrequency telemetry. An application-specific-integrated-circuit (ASIC) within the internal unit generates electrical impulses in accordance with the VPU output. These impulses are relayed to the electrode array, ultimately stimulating the inner retina in order to produce an artificial image 1,2 . Surgical techniques for implantation of the Argus II retinal prosthesis may vary depending on patient factors, globe anatomy, and surgeon preferences. Array positioning over the macular region is a requisite for optimal visual outcomes 3 . Normally, a spring-tensioned titanium retinal tack is used to affix the electrode at the posterior pole in order to ensure close apposition of the electrode to the retinal surface. However, even with the concavity of the electrode, complete apposition of the electrode array against the retina may not occur. Ahuja et al. 3 demonstrated that complete or near complete apposition results in a lower perceptual threshold. However, the effect of the electrode array-retina gap distance on objective visual function outcomes has not been elucidated. This study aims to determine how the electrode array-retina gap distance influences postoperative visual outcomes in patients with RP implanted with the Argus II retinal prosthesis, with the hypothesis that smaller gap distances correlate with more significant visual improvement. Methods Patient Eligibility and Demographics Patients enrolled in the Argus II Post-Approval Study (PAS) were invited to join this study. Eligibility criteria included a diagnosis of outer retinal dystrophy, some residual light perception, ability to undergo surgery under anesthesia, and ability and willingness to comply with post-operative follow-up and testing. Exclusion criteria included co-morbid ocular conditions (e.g. advanced glaucoma, optic glioma) that could compromise the functional optic nerves and tracts. Pretesting at the baseline visit included visual function testing, general slit lamp examination, Optical Coherence Tomography imaging (Cirrus HD-OCT Machine, Carl Zeiss Meditec, Dublin, Calif.) and fundus photography. A total of 5 patients with implantation of the Argus II device were enrolled in the study (Table 1 ). All patient recruitment, study investigations and surgeries were conducted at Stony Brook University Hospital and its affiliated sites. Surgeries were performed by one vitreoretinal surgeon under general anesthesia at the Stony Brook University Hospital. Table 1 Demographics of patients included in the study at baseline. Patient # Gender Age Range Diagnosis Years since Diagnosis Visual Acuity at Presentation 01 F 60–70 Leber’s Congenital Amaurosis Unknown Bare Light Perception (BLP) 02 F 50–60 Retinitis Pigmentosa 19 Bare Light Perception (BLP) 03 M 70–80 Retinitis Pigmentosa 28 Bare Light Perception (BLP) 04 M 70–80 Retinitis Pigmentosa 48 Bare Light Perception (BLP) 05 M 60–70 Retinitis Pigmentosa 33 Light Perception (LP) Data Collection Data was collected from patient visits at baseline prior to implantation, post-operative month 1 (M1), month 3 (M3), month 6 (M6), and year 1 (Y1). At M1, activation and programming of the device took place and visual function testing was deferred. Visual function testing was performed at M3, M6 and Y1. Sensitivity detection thresholds (to be defined later) were collected when possible at M1, M3, M6 and Y1. Gap distances were measured from Optical Coherence Tomography (OCT) images at M1, M3, M6, and Y1. All data was collected by two authors, cross-checked for accuracy and thoroughness, and independently reviewed by two other authors. Microsoft Excel was utilized for data collection. Visual Function The visual function of patients with the Argus II retinal implant were assessed using Square Localization (SL) and Direction of Motion (DOM) measures which were developed by Second Sight. SL involves locating and touching a white square set against a black background on a touchscreen monitor with the device ON and OFF. The distance (measured in number of pixels) between the true center of the square and the location at which the patient touches the monitor where they perceive the center of the square to be is measured, with smaller pixel distances indicating higher accuracy 2 . DOM testing utilizes a white bar that moves across a black screen in a particular direction, and the patient attempts to determine the direction of motion of the white bar. The angle between the true direction of motion and the patient’s perceived direction of motion is measured, with smaller angles indicating higher accuracy 2 All testing was performed under controlled conditions and overseen by trained personnel. Visual function data was extracted retrospectively from the Argus II Post-Approval Study. Sensitivity Detection Threshold The Argus II device is programmed at M1 for initial programming prior to turning on the camera in order to find stimulation levels that are suitable for the patient to be set on their Video Processing Unit (VPU) 4 , 5 . During the first session, the electrodes whose resistances are too high are disabled and the electrodes that are functional and usable are determined. A quick scan of the array is done using various stimulation amplitudes to determine which electrodes are able to produce a percept or phosphene. The minimum current that is needed for the patient to see a phosphene fifty percent of the time is defined for each electrode 1 , 4 . The video signal from the camera is mapped to the electrical signal for individual or groups of electrodes, determining which electrodes are being stimulated and at what respective frequency. These values are set to the patients VPU to be used in different conditions 1 . Programming for this study included use of the “Programming Assistant” software that is designed to streamline the programming process to measure general sensitivity 1 , 4 . Through use of this software, the camera alignment process is simplified and comfort is determined under more real-world stimulation conditions 1 . Depending on the patient experience, the device can be reprogrammed on a regular basis for a readjustment in response to changes to the array or the patient’s responses to the electrode stimulation 5 , 6 . The brightness of perception and the number of electrodes that give the patient a perception may decrease over time. Patients may need several reprogramming sessions in order to fully optimize the use of the device 5 . The sensitivity detection from each programming session for each patient was provided by from the programming technician from Second Sight where the values for sensitivity (µA) of each electrode for each session and the maximum current (µA) of each electrode per stimulation were collected and analyzed. Electrode Array-Retina Apposition Distance (Gap Distance) A Cirrus HD-OCT Machine was utilized by the PAS study to capture images during each patient visit. Parameters for capture at each visit included a 6 mm x 6 mm macular cube image (acquiring 512 nasotemporal scans x 128 superoinferior scans) which were utilized for study purposes. Images were located using unique patient identifiers and analyzed using Zeiss OCT analytical software. Eligible scans included a majority of the 60 electrodes and a surrounding portion of retina, the ability to visualize or estimate the precise location of each electrode, and a signal strength of at least 5 out of 10 (determined by the Zeiss software). While in the macular cube view of the software, the perpendicular nasotemporal and superoinferior raster lines were placed directly over the center of each visualized electrodes (Fig. 1 ). On the associated horizontal and vertical tomograms, the built-in caliper measurement tool was used to measure the vertical distance (in µm) between the electrode array and retina (Fig. 2 ). These measurements were taken for each patient at M3, M6 and Y1. The electrodes were designated a label (A-F, 1–10) to ensure consistency of measurements at each visit. Out of 1200 electrodes, 1124 (93.7%) were able to be measured. Statistical Analysis At each visit for SL testing, the difference in pixel distance with the device OFF and ON (OFF – ON) was calculated, with positive values indicating an improvement with the device ON. Similarly, at each visit for DOM testing, the difference in degrees with the device OFF and ON (OFF – ON) was measured, with positive values indicating an improvement with the device ON. For patients that demonstrated an average improvement in SL and DOM testing, a two-tailed paired t-test was performed. To correlate visual function with gap distance, Regression analysis between the average OFF – ON measurements and gap distances (with R = -1 indicating an overall improvement in visual function with smaller gap distances) was performed. Regression analysis was also used to determine the correlation between sensitivity detection threshold and change in visual function (average OFF – ON measurements). Statistical analyses were performed on Microsoft Excel. Results Correlation of electrode-retina gap with sensitivity detection threshold The mean sensitivity threshold detection from all programming and reprogramming sessions (Table 2 ) were analyzed in relation to the average electrode array-retina gap distance from all 5 patients. No significant correlation with sensitivity detection threshold and the electrode array-retina gap distance was found (p > 0.05, 0.98). Table 2 Sensitivity Detection Thresholds measured at four sessions. Sensitivity (µA) Patient # Session 1 Session 2 Session 3 Session 4 Average 01 120.41 --- --- --- 120.41 02 66.13 136.8 156.2 --- 119.71 03 141.05 --- ---- ---- 141.05 04 143.35 --- --- --- 143.35 05 130.96 190.73 218.62 197.89 184.55 Visual Function Outcomes In SL testing, 3 out of 5 patients demonstrated an improvement in visual function at M3, M6 and Y1 with the device ON (Table 3 , Fig. 3 ). 1 out of these 3 patients had a statistically significant average improvement in visual function (p < 0.05) using a two-tailed paired t-test. 1 patient demonstrated a marginal improvement at M3 (0.90 pixels), but this improvement was not seen at M6 or Y1. In DOM testing, 2 patients demonstrated an improvement in visual function when averaged over the three visits, with 1 patient having an improvement at M3, M6, and Y1 (Table 3 , Fig. 4 ). 1 patient showed an improvement at M6, but this improvement was not seen at other visits. None of the improvements in DOM testing were found to be statistically significant (p > 0.05). Table 3 Results of Square Localization (SL) and Direction of Motion (DOM) Testing at month 3 (M3), month 6 (M6), and year 1 (Y1) measured as a change in pixels (SL) or degrees (DOM) between testing with the device OFF and ON. A positive number indicates an improvement with the device ON. Square Localization Testing Direction of Motion Testing Device OFF – ON (pixels) Device OFF – ON (degrees) Patient # M3 M6 Y1 Average M3 M6 Y1 Average 01 18.67 81.47 71.14 57.09 2.39 14.74 14.20 10.45 02 0.90 -37.71 -81.36 -39.39 -15.58 -13.87 -43.74 -24.39 03 -52.20 -71.52 -52.72 -58.81 -10.03 -19.02 -8.94 -12.66 04 111.50 113.72 100.17 108.46 -2.10 0.63 -21.80 -7.76 05 27.96 18.35 108.99 51.76 1.32 8.54 -3.21 2.22 Correlation of Visual Function with Gap Distance The mean change in visual function with the device OFF and ON over the 3 testing visits was analyzed in relation to the average electrode array-retina gap distance from all 5 patients (Fig. 5 ). No significant correlation was found between SL measures and electrode array-retina gap distance (r = 0.20, p = 0.74). No significant correlation was found between DOM measures and electrode array-retina gap distance (r = -0.18, p = 0.77). Discussion The Argus II retinal prosthesis is a relatively novel medical device that can marginally restore some functional vision in patients suffering from retinal dystrophies. Numerous studies have demonstrated that a statistically significant improvement in visual function can occur in some patients, and it can no doubt impact their lives tremendously 7 , 8 , 9 , 10 . Our study’s analysis of SL results in patients with the device further demonstrates that a significant improvement in visual function is possible, with 1 patients performing better with the device ON. An exploration of the factors that influence these positive or negative outcomes is crucial to our understanding of how to further improve visual prosthetic technology. Ahuja et al 3 determined that the electrode array-retina gap distance strongly affects electrical threshold in patients implanted with the Argus II retinal prosthesis, with complete apposition correlating with lower perceptual thresholds. Our study aimed to determine how the gap distance correlates with functional measures of visual acuity such as Square Localization and Direction of Motion testing. As our results demonstrate, there does not seem to be a correlation between the electrode-array retina gap distance and visual outcome as determined by SL and DOM testing. The patient with the largest average gap distance (patient 04, Avg = 399.37 µm) had the greatest average improvement in SL testing (108.46 pixels). Conversely, the patient with complete apposition of the electrode (patient 02, Avg = 0 µm) at all visits demonstrated decreased visual functions in both SL and DOM testing. While there may not be a correlation between gap distance and visual function, this leads us to hypothesize that complete apposition of the electrode array on the retina may not be necessary for optimal visual outcomes in all patients. This becomes a crucial element in determining patient eligibility for patients with anatomical defects that could affect apposition. Rizzo et al 2 and Delyfer et al 11 have demonstrated that complete apposition of the electrode array on the retina may not be possible in patients with a posterior staphyloma. However, our results demonstrate that patients with staphylomas may not necessarily be precluded from implantation of the Argus II retinal prosthesis, as visual improvement may still occur in the presence of an electrode array-retina gap. An improvement in visual function in patients with a posterior pole staphyloma implanted with the Argus II retinal prosthesis has been demonstrated by Seider et al. 12 . It is possible that other staphyloma factors such as size, shape, and location may affect visual function outcomes rather than its presence alone. One patient with almost complete apposition of the electrode array on the retina (average gap distance 0.38 µm, 0.27 µm, 8.70 µm at M3, M6, Y1, respectively) developed clinically significant retinoschisis. It is possible that complete apposition of the array may increase the risk of adverse postoperative outcomes due to traction, overstimulation of the retina, and inflammatory changes resulting in remodeling of the inner retinal layers. SL and DOM testing are inherently arduous and time consuming, requiring patients to remain focused and motivated in order to perform optimally. Testing results may be influenced by frustration and avolition, although all attempts were made to ensure that patients completed testing in a comfortable environment. One patient (03) was on an SSRI antidepressant during all testing visits and seemed more motivated to perform well. SL and DOM testing although requires some degree of hand-eye coordination, a skill which may have slightly regressed in these patients due to a long-standing history of blindness. Testing methods that are less time consuming and easier for low-vision patients to perform would allow for a more accurate determination of post-operative visual function. Subjective measures that allow for a better assessment of what patient goals for the device may be and how they hope the device could be used to achieve them would also provide more crucial information for the device’s potential for patient benefit. Furthermore, optimal utilization of the Argus II retinal prosthesis requires visual rehabilitation and self-learning by the patient during their day-to-day life. Depending on the quality and quantity of visual rehabilitation, and the amount of time a patient spends with the device turned ON, their ability to interpret the generated phosphenes would be affected. It is also possible that overuse of the device could negatively impact visual function through constant electrical stimulation. These factors could ultimately influence performance on SL and DOM testing. Lastly, we noted that gap distances changed over time, with three patients having changes of over 50 µm between testing visits. This may be due to the positioning tack coming into contact with extraocular muscles at the scleral interface, or anatomical changes post-operatively. Our study is also limited by a small sample size (n = 5). Future studies with a larger data set may provide any opportunity to further explore the relationship between electrode-retina gap distance and visual outcomes. Conclusion Our study demonstrates that the post-operative electrode array-retina gap distance may not affect objective visual function outcomes in all patients implanted with the Argus II retinal prosthesis. This finding is an important consideration in patient selection criteria and surgical method as complete apposition of the electrode array on the retina is likely not necessary in all patients for optimal post-operative visual outcomes. In fact, complete apposition could possibly lead to adverse effects due to traction placed on the retina or overstimulation of the inner retinal cell layers. Positioning of the electrode array in relation to the macula may be a more crucial factor in providing benefit to patients implanted with the Argus II retinal prosthesis. Abbreviations SL Square Localization DOM Direction of Motion HD-OCT High Definition-Optical Coherence Tomography RP Retinitis Pigmentosa VPU Video Processing Unit OCT Optical Coherence Tomography M1 Month 1 M3 Month 3 M6 Month 6 Y1 Year 1 Declarations Ethics approval and consent to participate Approval from the Institutional Review Board (IRB) of Stony Brook University was obtained prior to initiation of the study. Written informed consent was obtained from all participants prior to their inclusion in the study. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on request. Competing interests The authors declare that they have no competing interests. Funding No funding was received for this study. Authors' contributions AN and NG extracted and analyzed visual function data, electrode array-retina gap distances and sensitivity detection thresholds. Data analysis was independently reviewed by MY and KC. All authors prepared, read and approved the final manuscript. Acknowledgements Not applicable. References Ghodasra DH, Chen A, Arevalo JF, et al. Worldwide Argus II implantation: recommendations to optimize patient outcomes. BMC Ophthalmol. 2016;16:52. 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):1282–90. Ahuja AK, Yeoh J, Dorn JD, et al. Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects. Trans Vis Sci Tech. 2013;2(4):1. Farvardin M, Afarid M, Attarzadeh A, et al. The Argus-II Retinal Prosthesis Implantation; From the Global to Local Successful Experience. Frontiers in Neuroscience. 2018;12:584. Sight S. Argus. II Retinal Prosthesis System Fitting Manual 2013; 090002–004. Gregori N, Callaway N, Hoeppner C, et al. Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients After Argus II Implantation: An International Study. Am J Ophthalmol. 2018;193:87–99. 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(5):632–6. Kotecha A, Zhong J, Stewart D, da Cruz L. The Argus II prosthesis facilitates reaching and grasping tasks: a case series. BMC Ophthalmol. 2014;14(71):1–8. Humayun MS, Dorn JD, Da Cruz L, et al. Interim results from the international trial of second sight’s visual prosthesis. Ophthalmology. 2012;119(4):779–88. Ahuja AK, Dorn JD, Caspi A, et al. Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br J Ophthalmol. 2011;95(4):539–43. Delyfer MN, Gaucher D, Govare M, et al. Adapted Surgical Procedure for Argus II Retinal Implantation: Feasibility, Safety, Efficiency, and Postoperative Anatomic Findings. Ophthalmology Retina. 2018;2(4):276–87. Seider MI, Hahn P. Argus II retinal prosthesis malrotation and repositioning with intraoperative optical coherence tomography in a posterior staphyloma. Clinical ophthalmology. 2015;9:2213–6. Cite Share Download PDF Status: Published Journal Publication published 17 Sep, 2020 Read the published version in BMC Ophthalmology → Version 3 posted Submission checks completed at journal 30 Aug, 2020 Editorial decision: Accept 27 Aug, 2020 Editor assigned by journal 25 Aug, 2020 Editor invited by journal 25 Aug, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-32698","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":1840607,"identity":"17affdec-1252-4d10-9d19-ce5a5267584a","order_by":0,"name":"Abhishek Naidu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABZ0lEQVRIie2SQWvCMBiGIx31EvEayXB/oRIoDov9Kw2FeimbY7CTDEGol4q3Iej2Gwa77DBYQsBTqVdHPczLTg7cReZpa7upnQ6242B9IMlH8j58CQSAlJS/CIKAZZpAiWoGgRZvSvFJNIx4AZ/zt4oF4G8UsFLCuNhS1rGNke93OF/eagTg1pQ9OyNdz3aG+OROKxYuBB8/NspHeSDxAG6aTHxD5DxLBftDhV86AXWhb+Hek0UwtsyyMUSnhaZsVjYKGNuKyDhCC6+tiJwTGBDZKoZM0Ctsq4g2Eb1mMNxZGwehwpfOW6jU5qHi6wnleBEr9yy/SChKqLCcw1SA7KgLy7grpY9t+aMLgHJCKU28KGkSGdl1PvBN6noeqfSYRQp9i0RvoT0hk8PBWikGLnlZOtVSF9Vu5rOzqp5tu6WgzrQiCszpw2vjnHbbrel4tvsL5ES9h76eSbvxbaT5z5mUlJSUf8Q7o8WEq81MVEUAAAAASUVORK5CYII=","orcid":"","institution":"Stony Brook University Renaissance School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Abhishek","middleName":"","lastName":"Naidu","suffix":""},{"id":1840608,"identity":"711e61b6-4107-4f9d-acdb-2da6b500614a","order_by":1,"name":"Nimra Ghani","email":"","orcid":"","institution":"Stony Brook University Renaissance School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nimra","middleName":"","lastName":"Ghani","suffix":""},{"id":1840609,"identity":"def0eaaf-ce73-477e-b4ed-454dc669ff48","order_by":2,"name":"Mohammad Saad Yazdanie","email":"","orcid":"","institution":"Stony Brook University Renaissance School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Saad","lastName":"Yazdanie","suffix":""},{"id":1840610,"identity":"a30bab49-2ad0-4d29-ad09-a08602223085","order_by":3,"name":"Khurram Chaudhary","email":"","orcid":"","institution":"Stony Brook University Renaissance School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Khurram","middleName":"","lastName":"Chaudhary","suffix":""}],"badges":[],"createdAt":"2020-05-30 22:36:32","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.3.rs-32698/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-32698/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-020-01631-6","type":"published","date":"2020-09-17T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2209646,"identity":"82c2b015-d254-47be-8dc8-12476222df89","added_by":"auto","created_at":"2020-09-02 20:51:01","extension":"tif","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":233548,"visible":true,"origin":"","legend":" OCT macular cube fundus view depicting electrode array positioned over macula. The macular cube scan in the Zeiss OCT software was used to measure the electrode array-retina gap distance at each individual electrode. 60 electrodes per array in a 6x10 grid were labeled as A-F and 1-10. Perpendicular nasotemporal and superoinferior raster lines were positioned to intersect at the center of the desired electrode using the fundus view.","description":"","filename":"Figure1400DPI.tif","url":"https://assets-eu.researchsquare.com/files/rs-32698/v3/Figure1400DPI.tif"},{"id":2209647,"identity":"28c690e7-66f2-4e19-83d6-5759b9d899cf","added_by":"auto","created_at":"2020-09-02 20:51:01","extension":"tif","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":154628,"visible":true,"origin":"","legend":" OCT macular cube horizontal and vertical tomograms. After targeting a specific electrode with the raster lines, the software’s caliper measurement tool was used to measure the distance along the raster lines between the electrode array and the surface of the retina on the associated horizontal and vertical tomograms. ","description":"","filename":"Figure2400DPI.tif","url":"https://assets-eu.researchsquare.com/files/rs-32698/v3/Figure2400DPI.tif"},{"id":13587912,"identity":"126a9e87-f222-4abb-a22a-6a7ce5253262","added_by":"auto","created_at":"2021-09-17 04:53:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":926460,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-32698/v3/7123df3e-8c72-411f-a1fb-eb83a2c3c3b3.pdf"}],"financialInterests":"","formattedTitle":"Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis","fulltext":[{"header":"Background","content":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003c/strong\u003eRetinitis Pigmentosa (RP) is an inherited degenerative disorder resulting in the loss of photoreceptor cells of the outer retina. Over 1 million patients worldwide suffer from RP, which leads to progressive vision loss that can pose significant challenges in many facets of their lives. More than 190 genes have been implicated in the pathogenesis of RP and all mutations inevitably result in degeneration of the photoreceptor layer\u003csup\u003e1\u003c/sup\u003e. However, the inner retinal cells are largely preserved in RP, serving as a target for direct electrical stimulation in order to generate phosphenes that may be perceivable by the patient\u003csup\u003e2\u003c/sup\u003e. Producing and manipulating these phosphenes to accurately reflect the surrounding visual environment is the common objective for electric stimulation-based visual prostheses.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Argus II Retinal Prosthesis System (Second Sight Medical Products Inc., Sylmar, California, USA) was developed for the purpose of providing artificial vision in patients with outer retinal degenerative diseases such as RP. It became commercially available after receiving FDA approval as a humanitarian device in 2013. Roughly, the Argus II consists of an implantable epiretinal 60-channel electrode array connected wirelessly to a portable computer (Visual Processing Unit, VPU). The VPU receives real-time images from a video camera mounted onto glasses worn by the patient. Wireless connection between the electrode array and the VPU occurs via an external coil (side arm of the glasses) and an internal coil (housed in the internal unit) that utilize radiofrequency telemetry. An application-specific-integrated-circuit (ASIC) within the internal unit generates electrical impulses in accordance with the VPU output. \u0026nbsp;These impulses are relayed to the electrode array, ultimately stimulating the inner retina in order to produce an artificial image\u003csup\u003e1,2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSurgical techniques for implantation of the Argus II retinal prosthesis may vary depending on patient factors, globe anatomy, and surgeon preferences. Array positioning over the macular region is a requisite for optimal visual outcomes\u003csup\u003e3\u003c/sup\u003e. Normally, a spring-tensioned titanium retinal tack is used to affix the electrode at the posterior pole in order to ensure close apposition of the electrode to the retinal surface. However, even with the concavity of the electrode, complete apposition of the electrode array against the retina may not occur. Ahuja \u003cem\u003eet \u003c/em\u003e\u003cem\u003eal.\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003e demonstrated that complete or near complete apposition results in a lower perceptual threshold. However, the effect of the electrode array-retina gap distance on objective visual function outcomes has not been elucidated. This study aims to determine how the electrode array-retina gap distance influences postoperative visual outcomes in patients with RP implanted with the Argus II retinal prosthesis, with the hypothesis that smaller gap distances correlate with more significant visual improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Eligibility and Demographics\u003c/h2\u003e \u003cp\u003ePatients enrolled in the Argus II Post-Approval Study (PAS) were invited to join this study. Eligibility criteria included a diagnosis of outer retinal dystrophy, some residual light perception, ability to undergo surgery under anesthesia, and ability and willingness to comply with post-operative follow-up and testing. Exclusion criteria included co-morbid ocular conditions (e.g. advanced glaucoma, optic glioma) that could compromise the functional optic nerves and tracts. Pretesting at the baseline visit included visual function testing, general slit lamp examination, Optical Coherence Tomography imaging (Cirrus HD-OCT Machine, Carl Zeiss Meditec, Dublin, Calif.) and fundus photography. A total of 5 patients with implantation of the Argus II device were enrolled in the study (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All patient recruitment, study investigations and surgeries were conducted at Stony Brook University Hospital and its affiliated sites. Surgeries were performed by one vitreoretinal surgeon under general anesthesia at the Stony Brook University Hospital.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics of patients included in the study at baseline.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient #\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge Range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYears since Diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVisual Acuity at Presentation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026ndash;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeber\u0026rsquo;s Congenital Amaurosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBare Light Perception (BLP)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRetinitis Pigmentosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBare Light Perception (BLP)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRetinitis Pigmentosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBare Light Perception (BLP)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRetinitis Pigmentosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBare Light Perception (BLP)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026ndash;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRetinitis Pigmentosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLight Perception (LP)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eData was collected from patient visits at baseline prior to implantation, post-operative month 1 (M1), month 3 (M3), month 6 (M6), and year 1 (Y1). At M1, activation and programming of the device took place and visual function testing was deferred. Visual function testing was performed at M3, M6 and Y1. Sensitivity detection thresholds (to be defined later) were collected when possible at M1, M3, M6 and Y1. Gap distances were measured from Optical Coherence Tomography (OCT) images at M1, M3, M6, and Y1. All data was collected by two authors, cross-checked for accuracy and thoroughness, and independently reviewed by two other authors. Microsoft Excel was utilized for data collection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eVisual Function\u003c/h2\u003e \u003cp\u003eThe visual function of patients with the Argus II retinal implant were assessed using Square Localization (SL) and Direction of Motion (DOM) measures which were developed by Second Sight. SL involves locating and touching a white square set against a black background on a touchscreen monitor with the device ON and OFF. The distance (measured in number of pixels) between the true center of the square and the location at which the patient touches the monitor where they perceive the center of the square to be is measured, with smaller pixel distances indicating higher accuracy\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. DOM testing utilizes a white bar that moves across a black screen in a particular direction, and the patient attempts to determine the direction of motion of the white bar. The angle between the true direction of motion and the patient\u0026rsquo;s perceived direction of motion is measured, with smaller angles indicating higher accuracy\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e All testing was performed under controlled conditions and overseen by trained personnel. Visual function data was extracted retrospectively from the Argus II Post-Approval Study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity Detection Threshold\u003c/h2\u003e \u003cp\u003eThe Argus II device is programmed at M1 for initial programming prior to turning on the camera in order to find stimulation levels that are suitable for the patient to be set on their Video Processing Unit (VPU)\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. During the first session, the electrodes whose resistances are too high are disabled and the electrodes that are functional and usable are determined. A quick scan of the array is done using various stimulation amplitudes to determine which electrodes are able to produce a percept or phosphene. The minimum current that is needed for the patient to see a phosphene fifty percent of the time is defined for each electrode\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. The video signal from the camera is mapped to the electrical signal for individual or groups of electrodes, determining which electrodes are being stimulated and at what respective frequency. These values are set to the patients VPU to be used in different conditions\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Programming for this study included use of the \u0026ldquo;Programming Assistant\u0026rdquo; software that is designed to streamline the programming process to measure general sensitivity\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Through use of this software, the camera alignment process is simplified and comfort is determined under more real-world stimulation conditions\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Depending on the patient experience, the device can be reprogrammed on a regular basis for a readjustment in response to changes to the array or the patient\u0026rsquo;s responses to the electrode stimulation\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The brightness of perception and the number of electrodes that give the patient a perception may decrease over time. Patients may need several reprogramming sessions in order to fully optimize the use of the device\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The sensitivity detection from each programming session for each patient was provided by from the programming technician from Second Sight where the values for sensitivity (\u0026micro;A) of each electrode for each session and the maximum current (\u0026micro;A) of each electrode per stimulation were collected and analyzed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eElectrode Array-Retina Apposition Distance (Gap Distance)\u003c/h2\u003e \u003cp\u003eA Cirrus HD-OCT Machine was utilized by the PAS study to capture images during each patient visit. Parameters for capture at each visit included a 6\u0026nbsp;mm x 6\u0026nbsp;mm macular cube image (acquiring 512 nasotemporal scans x 128 superoinferior scans) which were utilized for study purposes. Images were located using unique patient identifiers and analyzed using Zeiss OCT analytical software. Eligible scans included a majority of the 60 electrodes and a surrounding portion of retina, the ability to visualize or estimate the precise location of each electrode, and a signal strength of at least 5 out of 10 (determined by the Zeiss software). While in the macular cube view of the software, the perpendicular nasotemporal and superoinferior raster lines were placed directly over the center of each visualized electrodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). On the associated horizontal and vertical tomograms, the built-in caliper measurement tool was used to measure the vertical distance (in \u0026micro;m) between the electrode array and retina (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These measurements were taken for each patient at M3, M6 and Y1. The electrodes were designated a label (A-F, 1\u0026ndash;10) to ensure consistency of measurements at each visit. Out of 1200 electrodes, 1124 (93.7%) were able to be measured.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAt each visit for SL testing, the difference in pixel distance with the device OFF and ON (OFF \u0026ndash; ON) was calculated, with positive values indicating an improvement with the device ON. Similarly, at each visit for DOM testing, the difference in degrees with the device OFF and ON (OFF \u0026ndash; ON) was measured, with positive values indicating an improvement with the device ON. For patients that demonstrated an average improvement in SL and DOM testing, a two-tailed paired t-test was performed. To correlate visual function with gap distance, Regression analysis between the average OFF \u0026ndash; ON measurements and gap distances (with R = -1 indicating an overall improvement in visual function with smaller gap distances) was performed. Regression analysis was also used to determine the correlation between sensitivity detection threshold and change in visual function (average OFF \u0026ndash; ON measurements). Statistical analyses were performed on Microsoft Excel.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation of electrode-retina gap with sensitivity detection threshold\u003c/h2\u003e \u003cp\u003eThe mean sensitivity threshold detection from all programming and reprogramming sessions (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were analyzed in relation to the average electrode array-retina gap distance from all 5 patients. No significant correlation with sensitivity detection threshold and the electrode array-retina gap distance was found (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, 0.98).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSensitivity Detection Thresholds measured at four sessions.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eSensitivity (\u0026micro;A)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatient #\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSession 1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSession 2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eSession 3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eSession 4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e120.41\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e156.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e119.71\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e----\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e----\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e141.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e143.35\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e190.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e218.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e197.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e184.55\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eVisual Function Outcomes\u003c/h2\u003e \u003cp\u003eIn SL testing, 3 out of 5 patients demonstrated an improvement in visual function at M3, M6 and Y1 with the device ON (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). 1 out of these 3 patients had a statistically significant average improvement in visual function (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using a two-tailed paired t-test. 1 patient demonstrated a marginal improvement at M3 (0.90 pixels), but this improvement was not seen at M6 or Y1. In DOM testing, 2 patients demonstrated an improvement in visual function when averaged over the three visits, with 1 patient having an improvement at M3, M6, and Y1 (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). 1 patient showed an improvement at M6, but this improvement was not seen at other visits. None of the improvements in DOM testing were found to be statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of Square Localization (SL) and Direction of Motion (DOM) Testing at month 3 (M3), month 6 (M6), and year 1 (Y1) measured as a change in pixels (SL) or degrees (DOM) between testing with the device OFF and ON. A positive number indicates an improvement with the device ON.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eSquare Localization Testing\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eDirection of Motion Testing\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eDevice OFF \u0026ndash; ON (pixels)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eDevice OFF \u0026ndash; ON (degrees)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatient #\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eM3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eY1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eM3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eM6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eY1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e57.09\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e10.45\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-37.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-81.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-39.39\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-15.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-13.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-43.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e-24.39\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-52.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-71.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-52.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-58.81\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-10.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-19.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-8.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e-12.66\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e108.46\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-21.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e-7.76\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e51.76\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-3.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e2.22\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation of Visual Function with Gap Distance\u003c/h2\u003e \u003cp\u003eThe mean change in visual function with the device OFF and ON over the 3 testing visits was analyzed in relation to the average electrode array-retina gap distance from all 5 patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). No significant correlation was found between SL measures and electrode array-retina gap distance (r\u0026thinsp;=\u0026thinsp;0.20, p\u0026thinsp;=\u0026thinsp;0.74). No significant correlation was found between DOM measures and electrode array-retina gap distance (r = -0.18, p\u0026thinsp;=\u0026thinsp;0.77).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cp\u003eThe Argus II retinal prosthesis is a relatively novel medical device that can marginally restore some functional vision in patients suffering from retinal dystrophies. Numerous studies have demonstrated that a statistically significant improvement in visual function can occur in some patients, and it can no doubt impact their lives tremendously\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Our study\u0026rsquo;s analysis of SL results in patients with the device further demonstrates that a significant improvement in visual function is possible, with 1 patients performing better with the device ON. An exploration of the factors that influence these positive or negative outcomes is crucial to our understanding of how to further improve visual prosthetic technology. Ahuja et al\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e determined that the electrode array-retina gap distance strongly affects electrical threshold in patients implanted with the Argus II retinal prosthesis, with complete apposition correlating with lower perceptual thresholds. Our study aimed to determine how the gap distance correlates with functional measures of visual acuity such as Square Localization and Direction of Motion testing.\u003c/p\u003e \u003cp\u003eAs our results demonstrate, there does not seem to be a correlation between the electrode-array retina gap distance and visual outcome as determined by SL and DOM testing. The patient with the largest average gap distance (patient 04, Avg\u0026thinsp;=\u0026thinsp;399.37\u0026nbsp;\u0026micro;m) had the greatest average improvement in SL testing (108.46 pixels). Conversely, the patient with complete apposition of the electrode (patient 02, Avg\u0026thinsp;=\u0026thinsp;0\u0026nbsp;\u0026micro;m) at all visits demonstrated decreased visual functions in both SL and DOM testing. While there may not be a correlation between gap distance and visual function, this leads us to hypothesize that complete apposition of the electrode array on the retina may not be necessary for optimal visual outcomes in all patients. This becomes a crucial element in determining patient eligibility for patients with anatomical defects that could affect apposition. Rizzo et al\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and Delyfer et al\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e have demonstrated that complete apposition of the electrode array on the retina may not be possible in patients with a posterior staphyloma. However, our results demonstrate that patients with staphylomas may not necessarily be precluded from implantation of the Argus II retinal prosthesis, as visual improvement may still occur in the presence of an electrode array-retina gap. An improvement in visual function in patients with a posterior pole staphyloma implanted with the Argus II retinal prosthesis has been demonstrated by Seider et al.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. It is possible that other staphyloma factors such as size, shape, and location may affect visual function outcomes rather than its presence alone.\u003c/p\u003e \u003cp\u003eOne patient with almost complete apposition of the electrode array on the retina (average gap distance 0.38\u0026nbsp;\u0026micro;m, 0.27\u0026nbsp;\u0026micro;m, 8.70\u0026nbsp;\u0026micro;m at M3, M6, Y1, respectively) developed clinically significant retinoschisis. It is possible that complete apposition of the array may increase the risk of adverse postoperative outcomes due to traction, overstimulation of the retina, and inflammatory changes resulting in remodeling of the inner retinal layers.\u003c/p\u003e \u003cp\u003eSL and DOM testing are inherently arduous and time consuming, requiring patients to remain focused and motivated in order to perform optimally. Testing results may be influenced by frustration and avolition, although all attempts were made to ensure that patients completed testing in a comfortable environment. One patient (03) was on an SSRI antidepressant during all testing visits and seemed more motivated to perform well. SL and DOM testing although requires some degree of hand-eye coordination, a skill which may have slightly regressed in these patients due to a long-standing history of blindness. Testing methods that are less time consuming and easier for low-vision patients to perform would allow for a more accurate determination of post-operative visual function. Subjective measures that allow for a better assessment of what patient goals for the device may be and how they hope the device could be used to achieve them would also provide more crucial information for the device\u0026rsquo;s potential for patient benefit. Furthermore, optimal utilization of the Argus II retinal prosthesis requires visual rehabilitation and self-learning by the patient during their day-to-day life. Depending on the quality and quantity of visual rehabilitation, and the amount of time a patient spends with the device turned ON, their ability to interpret the generated phosphenes would be affected. It is also possible that overuse of the device could negatively impact visual function through constant electrical stimulation. These factors could ultimately influence performance on SL and DOM testing. Lastly, we noted that gap distances changed over time, with three patients having changes of over 50\u0026nbsp;\u0026micro;m between testing visits. This may be due to the positioning tack coming into contact with extraocular muscles at the scleral interface, or anatomical changes post-operatively. Our study is also limited by a small sample size (n\u0026thinsp;=\u0026thinsp;5). Future studies with a larger data set may provide any opportunity to further explore the relationship between electrode-retina gap distance and visual outcomes.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eOur study demonstrates that the post-operative electrode array-retina gap distance may not affect objective visual function outcomes in all patients implanted with the Argus II retinal prosthesis. This finding is an important consideration in patient selection criteria and surgical method as complete apposition of the electrode array on the retina is likely not necessary in all patients for optimal post-operative visual outcomes. In fact, complete apposition could possibly lead to adverse effects due to traction placed on the retina or overstimulation of the inner retinal cell layers. Positioning of the electrode array in relation to the macula may be a more crucial factor in providing benefit to patients implanted with the Argus II retinal prosthesis.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSquare Localization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDOM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDirection of Motion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHD-OCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh Definition-Optical Coherence Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRetinitis Pigmentosa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVPU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVideo Processing Unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOptical Coherence Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eM1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMonth 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eM3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMonth 3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eM6\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMonth 6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eY1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eYear 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval from the Institutional Review Board (IRB) of Stony Brook University was obtained prior to initiation of the study. Written informed consent was obtained from all participants prior to their inclusion in the study. All procedures performed in this study were in\u0026nbsp;accordance with the ethical standards of the institutional and/or national research committee and\u0026nbsp;with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAN and NG extracted and analyzed visual function data, electrode array-retina gap distances and sensitivity detection thresholds. Data analysis was independently reviewed by MY and KC. All authors prepared, read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e \u003cspan\u003eGhodasra DH, Chen A, Arevalo JF, et al. Worldwide Argus II implantation: recommendations to optimize patient outcomes. BMC Ophthalmol. 2016;16:52.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eRizzo 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\u0026ndash;90.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAhuja AK, Yeoh J, Dorn JD, et al. Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects. Trans Vis Sci Tech. 2013;2(4):1.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eFarvardin M, Afarid M, Attarzadeh A, et al. The Argus-II Retinal Prosthesis Implantation; From the Global to Local Successful Experience. Frontiers in Neuroscience. 2018;12:584.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSight S. Argus. II Retinal Prosthesis System Fitting Manual 2013; 090002\u0026ndash;004.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGregori N, Callaway N, Hoeppner C, et al. Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients After Argus II Implantation: An International Study. Am J Ophthalmol. 2018;193:87\u0026ndash;99.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eda 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(5):632\u0026ndash;6.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eKotecha A, Zhong J, Stewart D, da Cruz L. The Argus II prosthesis facilitates reaching and grasping tasks: a case series. BMC Ophthalmol. 2014;14(71):1\u0026ndash;8.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eHumayun MS, Dorn JD, Da Cruz L, et al. Interim results from the international trial of second sight\u0026rsquo;s visual prosthesis. Ophthalmology. 2012;119(4):779\u0026ndash;88.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAhuja AK, Dorn JD, Caspi A, et al. Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br J Ophthalmol. 2011;95(4):539\u0026ndash;43.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eDelyfer MN, Gaucher D, Govare M, et al. Adapted Surgical Procedure for Argus II Retinal Implantation: Feasibility, Safety, Efficiency, and Postoperative Anatomic Findings. Ophthalmology Retina. 2018;2(4):276\u0026ndash;87.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSeider MI, Hahn P. Argus II retinal prosthesis malrotation and repositioning with intraoperative optical coherence tomography in a posterior staphyloma. Clinical ophthalmology. 2015;9:2213\u0026ndash;6.\u003c/span\u003e \u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Argus II, Argus II Retinal Prosthesis, Direction of Motion, Electrode array-retina gap, distance, Gap distance, Low vision, Optical Coherence Tomography (OCT), Retinitis, Pigmentosa, Square Localization, Visual Function","lastPublishedDoi":"10.21203/rs.3.rs-32698/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-32698/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePost-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e 5 patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit.\u0026nbsp;Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 3 patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes. \u003c/p\u003e","manuscriptTitle":"Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-09-02 20:51:00","doi":"10.21203/rs.3.rs-32698/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-08-30T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-08-27T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-26T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-25T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-08-22 21:31:53","doi":"10.21203/rs.3.rs-32698/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2020-08-20T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-19T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-19T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-06-13 03:45:12","doi":"10.21203/rs.3.rs-32698/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-07-05T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-06-27T12:00:00+00:00","index":4,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"reviewerAgreed","content":"","date":"2020-06-22T12:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-06-21T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-06-16T12:00:00+00:00","index":2,"fulltext":"Recommendation: Reject\nForm responses:\n---\n\nComments to Author:\n---\nThe authors presented a study in which they investigate the correlation of the average electrode array-retina gap distance and the objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis. Overall, the study is underpowered with only 5 five patients included. The negative results were likely to be due to the small sample size and insufficient statistical power. The authors may need to fix this problem before they draw the conclusion that the average electrode array-retina gap distance is not correlated to the visual outcomes.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-06-16T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThe authors present an interesting study regarding an advanced therapy for rod-cone retinal dystrophies, as is the Argus II retinal implant. Their results are interesting and deserve dissemination. The data collection methodology is correct. However, the statistical analysis will need to be clompetely redone because, as I will explain, the statistical methods used are very prone to bias for several reasons.\n1- The authors should specify which is the unit of analysis for each of the study objectives: patients or electrodes. If the unit of analysis is the patient (which I assume is more clinically significant), the sample is small, and non-parametric statistical tests should be preferred.\n2- On the other hand, when the unit of analysis is the electrode, we will have new potential source of bias, which we could call inter-electrode correlation. This is the fact that electrodes in the same eye will behave more similarly between themselves than with electrodes in different eyes. This also applies for sequential measurements in the same eye. In order to overcome this source of bias, generalized estimating equations should be used in order to analyse the dataset.\n3- Lastly, the inability to detect a statistically significant correlation with such a small sample size (statistically speaking, as I am aware of the difficulty of recruiting 5 such patients) does not imply that the correlation does not exist. The authors should state that a statistically significant correlation could not be found, instead of that there is no correlation between the variables. The discussion should be rewritten taken this into account.\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-06-14T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-06-13T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-06-13T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-06-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-06-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-06-11T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"74f4a21c-cb10-43a9-b132-dd4040758b86","owner":[],"postedDate":"September 2nd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":344967,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2020-09-20T15:02:00+00:00","versionOfRecord":{"articleIdentity":"rs-32698","link":"https://doi.org/10.1186/s12886-020-01631-6","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2020-09-17 12:00:00","publishedOnDateReadable":"September 17th, 2020"},"versionCreatedAt":"2020-09-02 20:51:00","video":"","vorDoi":"10.1186/s12886-020-01631-6","vorDoiUrl":"https://doi.org/10.1186/s12886-020-01631-6","workflowStages":[]},"version":"v3","identity":"rs-32698","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-32698","identity":"rs-32698","version":["v3"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}