Perspectives of optic nerve prostheses.

http://informahealthcare.com/idt ISSN 1748-3107 print/ISSN 1748-3115 online Disabil Rehabil Assist Technol, Early Online: 1–9 ! 2014 Informa UK Ltd. DOI: 10.3109/17483107.2014.961178

RESEARCH PAPER

Perspectives of optic nerve prostheses

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Frank John Lane1, Kristian Nitsch2, Margaret Huyck2, Philip Troyk3, and Ken Schug4 1

Department of Rehabilitation Psychology, 2Department of Psychology, 3Department of Biomedical Engineering, and 4Department of Chemistry, Illinois Institute of Technology, Chicago, IL, USA Abstract

Keywords

A number of projects exist that are investigating the ability to restore visual percepts for individuals who are blind through a visual prosthesis. While many projects have reported the results from a technical basis, very little exists in the professional literature on the human experience of visual implant technology. The current study uses an ethnographic methodological approach to document the experiences of the research participants and study personnel of a optic nerve vision prosthesis project in Brussels, Belgium. The findings have implications for motivation for participating in clinical trials, ethical safeguards of participants and the role of the participant in a research study.

Ethics, ethnography, human experience, vision prostheses History Received 22 April 2014 Revised 20 August 2014 Accepted 30 August 2014 Published online 26 November 2014

ä Implications for Rehabilitation

Rehabilitation practitioners are often solicited by prospective participants to assist in evaluating a clinical trial before making a decision about participation. Rehabilitation professionals should be aware that: The decision to participate in a clinical trial is ultimately up to the individual participant. However, participants should be aware that family members might experience stress from of a lack of knowledge about the research study. The more opportunities a participant has to share thoughts and feelings about the research study with investigators will likely result in a positive overall experience. Ethical safeguards put in place to protect the interests of an individual participant may have the opposite effect and create stress. Rehabilitation professionals can play an important role as participant advocates from recruitment through termination of the research study. Participant hope is an important component of participation in a research study. Information provided to participants by investigators during the consent process should be balanced carefully with potential benefits, so it does not destroy a participant’s hope.

Introduction Vision prostheses have been implanted in human participants for almost 59 years [1]. Currently, projects focusing on the optic nerve, retina and visual cortex, are at various stages of implantation in both animal models and human trials. In preparation for the human implantation of the Illinois Institute of Technology cortical visual prosthesis, the authors began looking for information in the literature that would guide the development of recruitment, screening and participant consent procedures. While vision prosthesis projects advance worldwide, it is interesting that there is no known discussion in the literature about the human experience of being implanted with a vision prosthesis. As a preliminary step, we conducted focus group interviews with prospective vision prosthesis recipients. While the results provided some insight into the information that might be Address for correspondence: Dr Frank John Lane, PhD, Department of Rehabilitation Psychology, Illinois Institute of Technology, 3105 S. Dearborn St., Chicago, IL 60616, USA. E-mail: [email protected]

important to participants in future studies, we believed the information provided only limited perspective. We concluded that it was necessary to interview individuals who had previously been implanted with a vision prosthesis to understand and document the depth of insight and knowledge that can only result from personal experience and reflection. We began interviewing individuals that were previously implanted with a cortical prosthesis by William Dobelle. Dobelle did not publish the results of his studies, presumably due to his death and the abrupt termination of the project in 2005. The Dobelle interviews represent the first attempt at understanding and documenting the experiences of individuals who had previously been implanted with vision prostheses. We were also presented with an opportunity to interview individuals who had been implanted with optic nerve prostheses in Brussels, Belgium. After close evaluation, we believed that there were unique aspects of the project, particularly with regards to the role the participants played and the ethical safeguards established to protect participants, which would require a level of data collection and observation beyond a traditional qualitative interview.

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This article is a report of an ethnographic study of the Microsystems based Visual Prosthesis (MIVIP) project and its follow-up, the Optimization of a Visual Implantable Prosthesis (OPTIVIP) project, carried out at the Universite Catholique De Louvain located in Brussels, Belgium between 1996 and 2003 [2]. The study of the MIVIP and OPTIVIP projects was designed to answer basic questions about human experiences in clinical trials. The authors believe that the reported results should become a required component of all future discussions within Institutional Reviews Boards; specifically with regards to procedures and participant safeguards such as recruitment, screening, consent and design of future vision implant studies.


Prior research on visual prosthetic devices Overview Visual prosthetic devices have been implanted into human participants who are blind since the 1960s. The first implants were designed for the visual cortex and investigators have continued to work on their development [1,3–7]. In addition to cortical implant devices, investigators have developed vision implants for the optic nerve [2,8] and the retina [9–12]. At the Eye and the Chip World Congress on Artificial Human Vision in September 2012, 22 presenters reported on developments regarding implants for the retina, visual cortex and the optic nerve (Eye and the Chip, September, 2012). Some investigators have reported restoration of visual perception, however at this time, full restoration of vision is still not possible (The 2012 Eye and the Chip). Cortical implant projects The concept of a cortical visual prosthesis for individuals who are blind is based on studies that demonstrated that localized electrical stimulation of the human visual cortex can produce phosphenes, which are perceptions of small dots of light in the visual field [13]. Brindley & Lewin were the first to implant an electrode assembly into the visual cortex of a 52-year-old female nurse blinded in an automobile accident. A total of 80 electrodes were laid across the participant’s visual cortex and penetrated the pericranium [1]. The results of the Brindley and Lewin [1] study demonstrated that a permanent cortical visual prosthesis was possible. Dobelle project The Dobelle project continued the work of Brindley and experimented with the implantation and stimulation of surface electrodes in the visual cortex. The Dobelle studies continued over a period of almost 30 years between the mid-1970s and 2005, resulting in the implantation of 19 (known) blind recipients [14–18]. The latter Dobelle studies used an image processing system that converted images captured by a camera into phosphene patterns [14]. Dobelle initially implanted 64 electrodes into the first participant. The remaining 16 participants were implanted in two stages, with eight recipients in each stage. The number of electrodes implanted ranged from 140 to 512. While the Dobelle institute was located on Long Island, the implant procedures were performed in Lisbon, Portugal due to the lack of FDA approval for the clinical trials. Subsequent device testing, however, was conducted at the facility in Long Island, NY. Participants were charged between $54 000 and $200 000 USD for the procedure, which included the device, medical procedures and, in some cases, transportation. The first eight individuals implanted had contact with one another and, in some cases, met at the Dobelle Institute on Long Island; however, the second group of individuals shared no contact.

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NIH project The National Institute of Health (NIH) experimented with intracortical microstimulation by implanting floating microelectrodes into the visual cortex [13]. Thirty-eight mircoelectrodes were implanted into the right visual cortex, near the occipital pole, of a 42-year-old woman who had been totally blind for a period of 22 years due to glaucoma. The stimulation of the microelectrodes continued for a period of 4 months. The participant reported perceiving phosphenes, which were produced by 34 of the 38 implanted electrodes. The conclusion that can be drawn from these experiments is that point-sized visual percepts can be obtained by stimulating surface and intracortical electrodes. These percepts sometimes remain stable over weeks or months and some alteration of their shape, size, intensity, and location can be achieved by varying the electrical stimulation parameters. However, the integration of these discrete phosphenes into a perceived image was not achieved [19,20]. Chicago focus group project In an initial attempt to understand what would motivate an individual who is blind to pursue a vision implant, how potential benefits and risks would be understood, and what decision making processes would be used, Lane, Huyck, Troyk & Schug [21] conducted a series of focus groups with prospective volunteers. The focus groups were designed to capture what information is important to a person who is blind to feel comfortable consenting to a clinical trial to implant a vision prosthesis. A total of 30 individuals who were blind were recruited from the Chicago Lighthouse for the Blind as well as the Blind Services Agency in Chicago, Illinois. All participants attended an informational session that described how the Illinois Institute of Technology intracortical implant device was theorized to work and how participants may see phosphenes in their visual field. They were then interviewed in a focus group format. While participants indicated that restoration of vision was a strong motivator, they emphasized that what would be considered vision for a sighted individual is very different than for someone who is blind. Just the restoration of minimal light perception, for example, can, in many cases, increase safety and independence with regards to ambulation, and could be considered a significant improvement in visual perception. Participants also indicated that altruism was a strong motivator in considering whether or not to participate in a clinical trial and in some cases, a desire to explore and experience ‘‘cutting edge’’ research was also expressed. Remarkably, interest in exploring new research was a stronger overall motivator among the individuals in the sample than restoration of vision itself [21]. Decision-making is unique across individuals and varies as a function of perceived risks and benefits. Participants expressed a strong desire to assess the research team’s commitment to their well-being as part of their decision-making process. Making provisions for their medical care due to complications related to the procedure was a particular concern of potential participants and a strong factor in their decision-making process. Whom they would involve in their decision-making process also varied by individual but often included spouses, children, other family members, clergy, primary care physicians and other people who are blind. Furthermore, it became clear that individuals would have to be totally blind to consider being implanted with such a device, as the potential benefits were not considered worth the loss of even mere light perception. The results of the Chicago Focus Group study captured the perspectives of individuals who are blind and potential

Optic nerve project ethnography

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participants in a vision prosthesis trial. However, we questioned whether these perspectives would reflect those of an actual volunteer in a vision prosthesis study, or if the results were artifacts of self-report bias. Furthermore, understanding the perspective of individuals who have already participated in an experimental procedure may have the added benefit of helping us understand dimensions of the human experience that have not been considered.


The Belgian optic nerve implant research projects Our focus in this report is on two projects that involved the implantation of optic nerve vision prostheses in human participants. The Microsystems based Visual Prosthesis (MIVIP; December 1996–November 1999) and its follow-up Optimization of a Visual Implantable Prosthesis (OPTIVIP; January 2001–December 2003) were designed to implant a cuff electrode on the optic nerve. The electrode was implanted intracranially in the first project (MIVIP) and intraorbitally in the second project (OPTIVIP). The participants recruited for the study were individuals who had lost their vision due to retinitis pigmentosa. The research team included a clinical psychologist, Geraldine, who was tasked with participant recruitment. She sent flyers to agencies serving the blind in Belgium, further requesting that a representative from each agency in turn, send out the flyers to their constituents. A total of 42 individuals responded to the initial mailing of recruitment flyers. Individuals were screened using criteria explained in greater detail in the results section. Out of 42 respondents, one participant was chosen for the first study. The participant for the second phase of the project was recruited in the same manner, although the research team reported the number of respondents was much smaller because they were ‘‘fishing in the same pond’’. The initial phase (MIVIP) of the project included animal studies, which subsequently led to the first generation implant in a human volunteer (‘‘participant Alpha’’) in 1998. The second phase (OPTIVIP) began with the recruitment of volunteers in November of 2002 and resulted in a cuff electrode being implanted in a second volunteer (‘‘participant Beta’’). Regular testing of the two volunteers continued formally until the end of 2003; informal, less frequent testing was continuing at the time the visit to the project December 2009.

Methods Ethnographic methodology is widely used by anthropologists to describe the context of a phenomenon or set of phenomena from the perspective of an insider [22]. In order to achieve an inside perspective, researchers typically embed themselves within a community and utilize various methods of data and artifact collection. Participant observations, interviews and the collection of reports, publications and other written records are among the most commonly used methods by trained observers. When we were offered the opportunity to learn about the optic nerve prosthesis project, we believed that an ethnographic approach was appropriate to answer research questions about the project because: (1) the small number of individuals implanted, (2) the distinctive research culture found in the European union at the time and (3) the importance of documenting the experiences of the project participants. Our initial research questions were: (1) how was the project understood by the members of the research team and then communicated to the recipients of the prosthesis? (2) how did the recipients of the optic nerve vision prosthesis perceive the risks and benefits of the procedure and understand their role in the project?

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Participants We worked directly with the co-investigator of the MIVIP/ OPTIVIP projects, Jean, who contacted Alpha and Beta to see if they were willing to meet with us. In addition, we met with some of the family members of each recipient, which included a son, daughter-in-law and a spouse; the clinical psychologist on the project; a co-investigator/researcher who is a trained biomedical engineer and neurologist; and the projects computer engineer (Table 1). The Institutional Review Board (IRB) at the Illinois Institute of Technology in Chicago, Illinois, approved the research study prior to making the trip. The participants were not provided with any compensation for their involvement in this study. Data collection Interviews Preliminary interview guides were developed for the recipients, family members and research team members. The items were designed to be general, open-ended questions that provided the interviewees an opportunity to share their experiences and leave ample time for the investigators to explore participant responses. The interview guide is shown in Table 2. An informed consent document describing the purpose of the interview/research project was read to each participant. Participants were afforded an opportunity to ask questions and once they agreed to consent, each participant signed a consent form, which included permission to audio and video record the interviews. Because Alpha and her family did not speak English, Geraldine served as a translator for those interviews. Beta and his wife interacted comfortably in English. Observations We observed Alpha and Beta interacting with individuals involved in the research project. We documented our observations in the form of field notes throughout the duration of the visit, and compared notes at the end of each day. Our field notes were included in the final analysis. Documentation All MIVIP/OPTIVIP project materials including proposals, reports and notes from the vision testing conducted with participants were made available to us. A list of the documents by title is provided in Table 3. It is noteworthy that because of the proprietary nature of vision prosthesis projects, much of the work remains unpublished. Therefore, the wealth of information contained in the reports of the project listed in Table 2 was invaluable to understanding the MIVIP and OPTIVIP projects.

Table 1. List of participants including role in the project and length of interview in hours. Participants Jean Geraldine Alpha Alpha’s Son Alpha’s Daughter-in-law Beta Beta’s spouse Engineer Total interview hours

Role Researcher Psychologist Implantee Family Family Implantee Family Engineer

Time (h) 9.00 2.25 1.50 1.50 0.00 1.50 1.00 1.00 17.75

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Table 2. Project documentation reviewed by investigators. 1. OPTIVIP Project: Final report of Empirica GmbH, Bonn for GREN Brussels Survey of User needs and expectations (WP6/T 2.2) Dr. Rainald von Gizycki, 11 February 2004 (42 pages). 2. OPTIVIP Deliverable D-WP6-3 Final report on the ethical rules and principles applicable to prosthetic device research. Jean Delbeke, 31 March 2005 (IST 2000 25145-GREN) (12 pages) [28]. 3. The declaration of Helsinki, The World Medical Association (6 pages). 4. International Ethical Guidelines for Biomedical Research Involving Human Subjects. The Council for International Organizations of Medical Sciences (CIOMS) (67 pages) [27]. 5. Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine. Council of Europe (13 pages). 6. Additional protocol to the convention on human rights and biomedicine, concerning biomedical research. Council on Europe (16 pages). 7. Ethical Aspects of ICT Implants in the Human Body. Opinion of the European Group on Ethics in Science and New Technologies to the European Commission (36 pages) [26]. 8. World Medical Association International Code of Medical Ethics. The World Medical Association (WMA; 3 pages). 9. IEEE Code of Ethics. Institute of Electrical and Electronics Engineers. Inc. (2 pages). 10. International Digest of Health Legislation: Belgian Law. The World Health Organization (WHO; 5 pages). 11. Acceptance of visual prostheses by potential patient users. The OPTIVIP consortium, EMPIRICA and GREN (9 pages). Total number of pages of documentation: 211

Table 3. Qualitative interview questions for participants. What were your reactions upon learning about the project? What was appealing about participating in this project? What were your concerns? Who did you consult about participating? What motivated you to participate in the project? What kind of information was important to you while you were making a decision? What was your understanding of the risks of the project? What was your understanding of the benefits of the project? What, if any, expectations did you have about the procedures and the outcome before you had the surgery? How did you go about deciding to participate in the project? Looking back on your experience now, is there anything you would like to have known before deciding to participate? What should we as a research team do to make this a good experience for the volunteers for a new intracortical visual device?

Data analysis A systematic analysis appropriate for the qualitative data collected was used [23,24]. The videotape and audiotape files of the seven participants were professionally transcribed verbatim and a digital file was created. After the transcriptions were complete, a second interpreter who was fluent in both French and English checked the translations and made minor suggestions to improve their accuracy. We reviewed the transcripts for accuracy, which established the official record for analysis. The two investigators independently reviewed the transcripts and ‘‘open-coded’’ the narrative. We compared the results and reached agreement on a coding scheme to be used for axial coding [23,24]. The narrative was then re-analyzed and coded so that each portion of the text was coded on at least one axis. Once axial coding was completed, we reviewed each theme to determine whether it was justified or could be captured under a different theme. After the axes were agreed upon, we met with a


third member of the research who reviewed the data and assisted in the organization and interpretation of the results. This process was used to develop broader themes [23,24]; a hierarchical structure emerged from the themes that were agreed upon by all investigators.

Results The context: sensitivity to experiments with humans The MIVIP and OPTIVIP projects were conducted in Belgium during a time (1996–2003) when several other research teams were developing methods of restoring vision in people with blindness. Many of these projects focused on modifications to the eye itself, while the MIVIP and OPTIVIP teams emphasized direct stimulation of the optic nerve using a cuff electrode device. This project represented a unique approach to assistive implant technology designed to restore vision, but it was regarded, by some, as very experimental and unlikely to ‘‘succeed’’. While the European Commission funded the project, concerns about the ethical implications of conducting experimental research on human subjects prompted the European Commission to require additional safeguards of participants in the form of an Ethical Reflection Group (ERG). Every research project involving human participants is subject to specific procedures and safeguards designed to protect volunteers from practices that could potentially result in harm. Typically, an Institutional Review Board makes an assessment of whether the proposed procedures could potentially cause harm to a participant, and to establish that any potential harm would be balanced by potential benefits, resulting in equipoise. However, the efficacy of the procedures for the MIVIP and OPTIVIP projects had not yet been demonstrated and clear protocols for ensuring informed consent had not been established, prompting additional safeguards for the volunteers involved [25]. To address the need for additional safeguards, the investigators created internal Ethical Reflection Groups (ERG) as a required component of the MIVIP and OPTIVIP projects. Each volunteer that participated in the project was assigned an individual ERG. Each ERG unit was designed to include three members of the research team including (1) the researcher, (2) the research team psychologist and (3) one additional research member. In addition, external delegates not part of the research team, including an official representative of the ‘‘Commission d’Ethique Biomedicale Hospitalo-Facultaire’’ of the Universite de Catholique Louvain, and one personal representative of each volunteer was selected for each ERG. Participant Alpha’s physician, and participant Beta’s spouse filled the role of ‘‘personal representative’’ respectively. The ‘‘representatives’’ of each volunteer were expected to represent the personal and safety interests of the volunteer while remaining distinct from the research group. The internal ERGs were mandated to internally monitor compliance of the biomedical tasks with ethical rules and principles. In particular, the volunteer selection procedure, the informed consent agreement, the experimental procedures, surgery and any departure from the initial planning were to be explicitly handled during a meeting. Each independent ERG was expected to meet quarterly throughout the duration of the research projects. The psychologist on the research team believed that the ERGs helped maintain the focus on the human dimensions of the project, which, in her view, was not easy when working primarily with medical and engineering professionals. The focus of the meetings emphasized the participant’s feeling rather than the technical and engineering components of project. For instance, when Alpha experienced a death in the family, the ERG suspended testing for a month until the Alpha expressed a desire to return.



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While the additional safeguards by the Ethical Reflection Groups provided monitoring of the recruitment, screening and experimental procedures, including surgery and post-implant testing, these controls did not necessarily translate into a better experience for the participant. Alpha, for example, reported that the ERG did not result in the participant feeling as if the interests raised were being represented. Following the first review of the project, one of the reviewers expressed disbelief that Alpha’s level of vision had been adequately assessed, and that the participant really understood what was being consenting to. He thus decreed that Alpha should see a vision specialist not associated with the project, and have an assessment with a judge to determine individual understanding. Alpha (and the investigators) felt that the additional testing was unnecessary. Alpha described the meeting with the judge as frightening, even traumatic; and could not understand why he was challenging the participant’s willingness to participate, and Alpha did not want to be drawn into the legal system. (It turned out that the recommendations came from one of the ERG panel members who was involved in a competitor project and later found to have a conflict of interest.) Jean (one of the project directors) and the project psychologist felt that the ethical regulations governing clinical trials in the European Union at the time of the project were sufficient for the protection of the participants in the project. It appears that the additional safeguards were not perceived as helpful from the perspective of at least one of the participants. While some might argue that a funding source has the authority to establish a panel of experts to ensure that the rights of the participants are protected, the researchers felt the invasive approach used by the funders to monitor the participants did not allow for the typical collaboration expected between a funder and group of investigators to maintain the necessary autonomy to facilitate the proposed project. Recruiting and screening volunteers Participant recruitment consisted of distributing announcements to blind service agencies and requesting them to provide information regarding the research projects to their members. Preliminary interviews, which included a description of the project, were conducted with individuals who expressed initial interest in participating. If the prospective participant expressed continued interest, a physiological test with surface electrodes over the optic nerve determined where participants were able to perceive phosphenes. Each individual participated in a psychological screening interview. An ophthalmologist screened each prospective participant to verify they were totally blind (no light perception), due only to retinitis pigmentosa. For the first trial, approximately 1000 flyers were disseminated, 42 inquiries were received and 10 individuals were interviewed, resulting in one volunteer. Recruitment procedures were similar for the second phase of the research project. The criteria for inclusion included: (1) being well adjusted to vision loss; (2) absence of guilt as a motivator for participating; (3) absence of depression; (4) absence of unreasonable expectations; (5) ability to perceive phosphenes; and (6) totally blind with no light perception. Guilt and a desire for reparation as motivations to participate were both believed to be indicators of poor psychological adjustment to blindness. Specifically, researchers noted that individuals often expressed motivations to participate related to wanting to atone for passing on the disease (retinitis pigmentosa) to their children genetically. The researchers described these markers of psychological maladjustment to blindness as concerns that they were unprepared to manage throughout the project, stating ‘‘they should not come here to be punished’’.

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Motivations to volunteer Each participant spoke about their motivations for participating in the MIVIP and OPTIVIP projects. Three motivational factors emerged consistently, including (1) beneficence, (2) curiosity and (3) the hope of restoration of visual percepts. Alpha indicated that the primary motivation was to contribute to the understanding of RP so that (several) family members with the same condition may benefit. Furthermore, they indicated that they were ‘‘curious and wanted to know more about the project’’. Their family members not only concurred, but also emphasized that Alpha hoped (still) to have some personal benefit from the device. Beta was initially motivated by the hope that the device would be of personal benefit. As the project progressed, they both became discouraged that it did not result in vision restoration but Alpha noted that ‘‘you always hope for something’’. Beta also emphasized the importance of ‘‘making a contribution’’, along with a curiosity in the process of ‘‘how it all works’’. In addition, participant Beta described having had time as the participant was no longer employed; the trips to the testing lab replaced his prior trips to his part-time job. Decision-making processes The decision to participate in the research project involved different processes for each individual. Alpha indicated that the final decision to participate was made independently, and the family was informed. In fact, the members of her family we interviewed described not feeling ‘‘consulted’’. They were very worried at first that if something would go wrong she would become more dependent on them. Beta consulted with the family, the participant’s spouse and adult children; however, the final decision was reserved as independent. Beta’s spouse, was initially concerned about the medical safety of the project, but did not object to the individual’s involvement after conducting an inquiry and determining that the medical risks involved were minimal. Geraldine emphasized the importance of discussing any doubts about the procedures with family members to foster support and understanding. However, she also believed strongly that the final decision must be left to the volunteer. What makes a good participant? We asked all the team members (researchers and volunteers) to describe the qualities they believed would make for a desirable candidate in experimental human implant projects such as MIVIP, OPTIVIP, and the proposed ICVP study. The results, grouped by themes are summarized below. Medical and technical dimensions Jean and the engineer emphasized their decision to only include individual who had no options for restoring vision by augmenting the eye itself. The implant devices designed in the MIVIP and OPTIVIP projects relied on a functioning optic nerve; thus, they were looking for volunteers who had no light perception, but who could identify light phosphenes when direct electrical stimulation was applied to the optic nerve directly behind the eye. While for the purposes of these projects only totally blind individuals were deemed viable candidates for participation, they recognized the potential value of including volunteers with residual vision, to investigate whether stimulation lowers response thresholds, and thus might be regarded as a treatment for retinitis pigmentosa. Alpha and Beta suggested that individuals, who had lost their vision recently, so they could recall visual schemas, would be ideal – as long as they have successfully made the initial adjustment to blindness and were not expecting total vision

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restoration. Everyone we interviewed mentioned that prospective volunteers should be in good enough health to endure surgery and subsequent clinical testing.


Psychological qualities Psychological screenings conducted by Geraldine and Jean during the recruitment process assessed for indicators of guilt, an apparent desire for punishment or atonement, psychological maladjustment to disability, and the presence of depression, all of which were regarded as exclusionary criteria for the project. As both projects progressed, they were able to identify psychological participant characteristics embodied by both volunteers, believed to be important for satisfactory volunteer experiences, including patience, perseverance, optimism/hopefulness, cooperativeness and realistic expectations regarding project outcomes. Jean and Geraldine emphasized the importance of patience as a participant characteristic, stating, ‘‘They must be very patient as well’’ and ‘‘it is also a quality of a good volunteer being part of the research’’. Patience was identified as an essential quality of the MIVIP and OPTIVIP projects volunteers because of the time consuming nature of the procedures. Participants were involved in testing sessions typically lasting 3–4 h, and were expected to attend approximately two sessions per week. Furthermore, each session consisted of repetitive stimulation of the electrodes and the mapping of phosphenes, which required the participants to continuously describe their visual percepts. In addition, they saw a link between patience and expectations noting ‘‘if they expect a quick solution to their problem, obviously they will not be patient, so it obviously is linked to their expectations’’. While the initial testing and mapping period to establish thresholds lasted for 1 year, the entire project took investigators nearly 10 years to complete from initiation to cessation. Alpha said: ‘‘When I commit to do something I will see it through’’. Beta observed: ‘‘Scientists must be patient, and they were. I was more impatient. I wanted results more quickly, but I wouldn’t give up’’. Optimism and hopefulness played a unique role in the perceptions, motivations and expectations for each of the participants. Alpha noted the tendency to ‘‘focus on the benefits of anything’’, indicating an inclination towards being optimistic and positive in the individual’s perspective. In a similar vein, Alpha’s son emphasized the individual’s desire for the project’s success, independent of personal benefit in the form of vision restoration. Beta said that ‘‘we should not expect anything for ourselves’’ however, ‘‘you cannot avoid having a little hope’’. This balanced view conveys the sense that the volunteers believed the project worth doing, whether or not they personally benefited. This theme of hope tempered with realistic expectations was evident for both participants and the research team. Jean emphasized the necessity of accurately conveying realistic expectations. As he said, ‘‘all rational explanations that were given were do not expect anything from this’’ while not ‘‘actively fighting any hope’’. He and Geraldine both discussed the challenges of maintaining a sense of hope while providing realistic and honest expectations. Geraldine noted the importance of cooperation and the ability of the volunteers to work as members of a multidisciplinary research team. Cooperation and working as an integrated research team, which allowed for open communication and effective feedback, engendered a sense of inclusive membership for the volunteers, and fostered respectful interactions between participants and researchers. Furthermore, participant cooperation and inclusion were important to ensure that volunteers felt that they were able to contribute and feel part of the project at large. In addition, at the time of the projects, the scrutiny by the European Union resulted in significant media attention by the press. The


elevated level of attention directed towards human subjects research at the time, necessitated discretion about the project to avoid misinterpretation. This discretion was required from all individuals involved in the MIVIP and OPTIVIP projects, extending beyond the research team members to the participants as well. Roles within the research team Participant The roles of the participants in the OPTIVIP and MIVIP projects were largely unique within human subjects’ research; as Jean said, the volunteers were treated as ‘‘members of the research team’’. Alpha and Beta were invited to participate in weekly research meetings to assist the research team with interpreting data, and to help the team understand their experiences of participating in the project. The participant’s involvement in multiple facets of the project stemmed from two sources; (1) some of the researchers directly encouraged their active engagement and (2) the mandated ethical safeguard committee, the ERG, provided a forum for the volunteers to express feedback and empowered them to voice their thoughts and concerns. The participants’ involvement as active members of the research team engendered a sense of inclusion and commitment that continued to have apparent effects at the time of this study. While the MIVIP and OPTIVIP projects ended 3 years prior to the current study, participants were still willing to travel (taking 1–2 h) to the university to participate in the interviews, stating, ‘‘we are like a family’’. Roles of family members The role that family members assumed was different for each participant. Alpha indicated that the decision was made independently, and informed family members about the procedures involved in the project. Alpha’s son and his wife expressed distress about what they perceived to be a lack of information throughout the duration of the project. Specifically, they expressed concerns related to Alpha’s independence in the event that ‘‘something happened’’. Various members of Alpha’s family fulfilled several different roles. One of Alpha’s sons acted as the primary source of transportation to and from the research clinic, while other family members were initially uninvolved in the research project. It is unclear if Alpha’s other family member elected to not be involved or if Alpha chose to not include them at the onset of the project. During the project Alpha’s son who had been the primary source of transportation and general support passed away, which resulted in suspending testing due to Alpha’s distress. After a brief interval, Alpha returned to the project, and for several years relied on transportation programs for people with disabilities to commute to and from the research clinic. In the later years, several of Alpha’s other family members became more involved in the project, transporting Alpha to the clinic. These family members felt inadequately acknowledged and included during the project, and expressed frustration that after initially promising results, that Alpha had not made more progress. They described wondering why Alpha had not been provided with a device to take home to practice with, were unaware that each of the volunteers were working with different versions of the implant device, and that neither had been effective in restoring visual perception. While these family members expressed a desire to have been included as members of the extended research team, they indicated no awareness that their perceived unavailability during the early phases of the research was related to the lack of efforts to reach out to them.


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Beta’s family members appeared to have limited involvement. While Beta consulted with spouse and children at the onset of the project, once the procedure was identified as having minimum risks, Beta participated relatively independent of his family members, relying on public transportation to and from the research clinic.


Psychologist and patient advocate The role of the research team psychologist within the project was distinctive. The psychologist began the project as a doctoral graduate student, and became involved in part due to her experiences as a person with visual impairment. Her training as a psychologist and personal experience with visual impairment made her a unique asset to the research team. While her initial responsibilities included the recruitment and psychological screening of all prospective research participants, her role evolved and expanded throughout the duration of the research project. After Alpha had been selected, Geraldine began to function as a patient advocate, attending all meetings and ensuring that the volunteer understood all of the information presented to the participant, particularly throughout the informed consent process. Due to Alpha’s unfamiliarity with the academic and research communities, the psychologist, acting as a ‘‘patient advocate’’ served as lingual interpreter and cultural liaison. The bond established between Alpha and Geraldine was evident throughout our visit. In contrast, the relationship between the psychologist and Beta was not as active. While she was available to Beta as an advocate, the participant expressed no interest or need of a patient advocate. What makes for a good volunteer experience? For both volunteers, the sense of being appreciated as a respected member of the research team came through as a crucial element in engendering positive evaluations of their participation. Alpha noted that the ‘‘team acted normally with me’’, and was pleased that the research team had advocated on the participant’s behalf. In addition, for Alpha, remaining anonymous was very important; as the participant said, ‘‘I don’t want people coming to visit me’’. Beta and spouse agreed that feeling included as appreciated research partners was very important to them. Furthermore, it was emphasized that during ‘‘retirement’’ it was important to feel needed, worthwhile and recognized. Jean’s reflections on the project What did the Belgian team learn about vision? A theme that emerged clearly was that the MIVIP/OPTIVIP team learned a lot about the visual system and the processes of visual perceptions. One of the researchers believed that a great deal of basic research is required before a functioning visual prosthesis can be designed. As Jean said: We must do the basic sciences. We have learned a lot from our experiments, even though they were not successful in some ways. We should be aware that the basic model is wrong. At the neural level we think if we stimulate one cell we get one pixel, but we do not know what we will get if we stimulate a second pixel; it may not be additive. You cannot construct an image from the nerves stimulated in the optic nerve; within the brain, the image will be even more complex. We just do not have the projections of the external world. . .we don’t know anything about the logic. All we know is that it is not what we commonly accept. We have to search for new explanations for how it works.

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Jean went on to say: We know almost nothing about the visual codes in the optic nerve – or in the brain or higher levels. We only know that what we know is not logical. Neurology students have first to understand that the perceptual system is not a mirror of what we see. If you try to make a visual prosthesis you will learn about the visual cortex. With monkeys you can only learn about what you already know about perceptions; you will not discover, or find out something you did not expect. Jean said he believes the project was a success in that they learned more about how vision works, but it was unsuccessful in terms of developing functioning optic nerve prostheses. He reported that they found many things that were unexpected. For example, stimulating part of the optic nerve did not yield the expected retinotopically related phosphene but a small patch that is located more centrally (in the person’s visual field) with stronger stimuli. He reported that when they stimulated a large part of the optic nerve section all they found was a small phosphene in the center of the subject’s visual field. The team found that phosphene perceptions resulted from broad spatiotemporal interactions between the activities in different optic nerve fibers. Now they know that it is related to a code in the optic nerve but they still do not know what the code is. In terms of color, they never had control of that characteristic of the phosphenes, as the colors were not constant. There seemed to be a pattern by date; some days the phosphenes would appear to the individual as green and other days they would appear as red. They documented almost all possible colors, including black phosphenes. Interestingly, many individuals who are blind do not see black. Some see grey, others shadows and some a kaleidoscope of colors yet the shades of black were perceptible for one of the participants. Jean reported that an individual’s eye movements had to be integrated in a practical visual prosthesis so that objects could be referred to in their real location and not the retinotopically activated position. Also, the long evolution of retinitis pigmentosa before total blindness creates a dilemma; Jean’s assessment is that it seems the visual system tends to lose much of its functionality before a visual implant can be justified. Facilitating a multidisciplinary research team Jean described his role with the research team in the following way; ‘‘I was the cement – though I don’t mean I was the only cement’’. This statement reflects his experiences fulfilling the role of facilitator between the various disciplines involved in the project, which included research volunteers, an ophthalmologist, psychologists, engineers, physicians, technicians and ethical representatives. He acknowledged the unique contributions that each team member was able to provide; however, he did not appear to ascribe superior importance to any particular discipline, rather lauding a ‘‘whole chemistry’’ between team members. He emphasized the importance of open communication when there are multiple opinions, stating, ‘‘In a project like that there’s continuously disagreement but you must keep working together. That is the right equilibrium. You must have that’’. This perspective underlines the essential nature of working within a multidisciplinary teamwork structure.

Discussion Limitations There are inherent limitations to the ethnographic methodology used in this investigation, and therefore, the conclusions drawn

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from this study may not be generalizable First, the conclusions drawn are dependent on the observations and interpretations of us, as investigators; we bring our own biases to this effort, no matter how objective we try to be. Second, observer bias is difficult to control for in the setting because establishing an acceptable interrater reliability is difficult in a field setting without operational definitions. Third, it is difficult to generalize the results of the study due to selection bias. We recognize we had access to the perceptions of a small portion of the original scientific investigator team, since the project was no longer active. Finally, ethnographic research also requires time to build the necessary trust needed to elicit substantive responses. There was insufficient time for the investigators to establish such a relationship prior to conducting the interviews because of the geographical distance between the investigators and the project. Implications for rehabilitation practice The findings from the ethnographic study of the MIVIP–OPTIVIP project in Belgium have been organized into areas that are likely of concern to rehabilitation personnel. The findings of the study can be utilized by rehabilitation personnel to assist potential participants evaluate information and make a decision about participating. The list of recommended discussion topics are appropriate for any individual considering participating in a clinical trial involving basic sensory processes. The recommendations and discussion topics include: screening, informed consent, decision-making, participant autonomy, role of the participant and conflict of interest. (1) Screening. The screening process for potential participants in a clinical trial should include an assessment by a psychologist for adjustment to blindness, motivation for participating in the study, emotional state with particular emphasis on feelings of guilt and/or depression, expectations of the device, and the participant’s degree of light perception. The ideal participant would be well adjusted to blindness and present with a level of guilt and/or depression that is not clinically relevant to the study. Participants should have reasonable motivations and expectations for the device and have residual light perception that is not only appropriate for the scientific goals of the study, but also considers the potential impact of the residual perception loss. (2) Informed consent. The informed consent document should contain the potential risks associated with an invasive medical procedure. It should also contain less known psychological consequences such as the potential for a participant to develop a bond with researchers and participant involvement in the study may provide meaning in the individual’s life. Investigations looking at psychological effects of participating in a clinical trial for a vision prosthesis are relatively new so investigators should stay current on research results and incorporate them into the informed consent process. (3) Decision-making. Each participant has the right to determine how s/he makes the decision to participate, including whether, or how to place themselves at risk. Including family members and significant others within the decision process must be at the will of the participant, but it is important to be aware that support configurations can change over time. For example, an individual not consulted by the participant at the beginning of the study may later be included by the participant, making it important to ask participants at each decision point whom they want to involve. For participants who choose to make independent decisions and not consult with family members, participants should be made aware that the lack of information can


potentially create fear and become frustrating for family members. (4) Autonomy. The ability to balance the clients need for autonomy with the needs of an Institutional Review Board to minimize risk and protect the participant is a challenging task. Individual differences play a large part in determining how much ‘‘protection’’ a participant needs and this was evident in the current study. The use of a participant advocate was one example of how to minimize risk by ensuring the participant understood what was being communicated. However, the need for the advocate varied based on individual need for such protection. The function of the ethical reflection groups are an example of how participant protection may create harm. Support provided to volunteers appears to be best tailored to the individual. Some volunteers may benefit from substantial mentoring and support while others may regard it as intrusive. (5) Role. Once volunteers have been vetted through appropriate medical, psychological and social screenings, there are benefits to being accepted as full members of the research team. They may be able to contribute important data to the investigators that may not otherwise be available if there is not a mechanism in place to receive participant feedback. Participation as a valued research team member also appears to be rewarding for at least a few volunteers who were motivated to participate in clinical trial research – while the role of the patient advocate varies between participants, there was a clear benefit of having a professional work either directly or indirectly with the participant(s) to ensure information was disseminated in a manner they could understand and to monitor participant experience. (6) Conflict of interest. A large number of groups around the globe are working on various implants designed to restore visual perception. While the number of investigations is sizeable, the overall community is small and the potential for conflicts of interest are of genuine concern. Groups designed to advise, provide oversight and otherwise monitor progress should be screened for potential conflicts of interest. While this may not appear to be the purview of a potential participant, this study shows an example of how such a conflict of interest can potentially have negative impact on the participants. To this end, it is important for such safeguards to be in place by investigators.

Conclusion The ethnographic study of the MIVIP and OPTIVIP project was conducted to gather in-depth qualitative data on the experiences of individuals who had received vision prosthesis and to understand the context in which the project occurred and the protocols used to recruit, screen and inform participants in the study. The aspects of the MIVIP and OPTIVIP project that stood out were (1) the ethical protocols in place to safeguard the participants, (2) the focus on the participant as a member of the research team, (3) the impact that lack of knowledge can have on family members and (4) the advocacy role that psychologists can play in a clinical trial. The protocols put in place to safeguard the participants appeared to strengthen the ethics of the project from the perspective of the funding source, however, appeared to be viewed as interference and had a negative impact on one participant. While such safeguards might be necessary, it may also be important to weigh the benefits of ethical controls against the potential for a negative participant experience. In circumstances where extreme controls are necessary, it would be important to ask the participants to share their view and have it taken into consideration.


DOI: 10.3109/17483107.2014.961178

The involvement of participants as a member of the research team appeared to have an empowering affect. The participants voiced that their involvement in the project left them feeling as if they were part of a family. This sentiment resonated through the meeting, which felt much like a family reunion. While some may view such a strong bond as problematic in a clinical trial, the benefit to the research team was participants who were committed for the duration of the project and attended scheduled appointments without attrition. Participants also felt comfortable sharing unsolicited information with the research team about their experiences, which may not have occurred if their input was not regarded as important. In this regard, Institutional Review Boards may need to modify the evaluation processes that they typically apply to large multi-participant trials, such as those for pharmaceutical studies, when assessing the structure and value of singleparticipant medical device trials. The degree of family involvement in decision-making varied between the two participants. For the participant who exercised independence by keeping information about the project away from family members, the lack of information had a negative effect. It is the right of the participant to choose what information to share with family members and what to keep private. However, participants should be aware that withholding information from family members can result in them drawing inaccurate conclusions based on a lack of information. Lack of information may also result in family members feeling helpless and marginalized during an important event in a loved one’s life. The psychologist was utilized for recruitment and screening, which was consistent with her clinical training. For example, the presence of guilt, an apparent desire for punishment or atonement, psychological maladjustment to disability and the presence of depression were regarded as exclusionary criteria for the project. Qualities such as patience, perseverance, optimism, hopefulness and clear expectations were qualities determined appropriate for inclusion in the project. In addition to the typical role the psychologist would play, it was unusual to take on the role of advocate for the project. While only one of the two participants utilized the psychologist in this role, it appeared to function well for that participant. The psychologist was utilized to ensure that the participant understood complex information and to aid in processing information during decision-making. Future projects should consider utilizing a psychologist in the various roles outlined here, perhaps employing more than one practitioner, particularly when the nature of information regarding vision prostheses, the types of vision the participant can expect is complex.

Declaration of interest This work was funded by the Brain Research Foundation, the Pritzker-Galvin Challenge Fun, and private donations. The author’s are grateful to Jean Delbeke, the participants and staff at the Universite Catholique De Louvain, Brussels, Belgium for their openness and willingness to be interviewed and allow us to immerse ourselves in their project over a one-week period.

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Increased optic nerve radiosensitivity following optic neuritis.

Primary optic nerve meningioma.

Optic nerve aplasia.

Optic nerve sheath meningiomas.

[Optic nerve evulsion].

[Optic nerve drusen].

Optic nerve monitoring.

Optic nerve aspergillosis.

Optic nerve infarction.

Hypoplasia of the optic nerve.

Spectrum of optic nerve hypoplasia.

Electron microscopy of the mouse optic nerve: a quantitative study of the total optic nerve fibers.

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia.

Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults.

Prostaglandin E2 changes in the retina and optic nerve of an eye with injured optic nerve.

Optical coherence tomography imaging of the optic nerve head pre optic and post optic nerve sheath fenestration.

Pediatric optic nerve sheath meningioma.

Retinal and optic nerve ischemia.

Iodochlorhydroxyquin and optic nerve damage.

Optic nerve glioma: an update.

Retinal and optic nerve diseases.

Morphological and functional changes of the optic nerve following traumatic optic nerve injuries in rabbits.

Optic nerve decompression. Presumed postoperative development of medullated nerve fibers.