Emotional wellbeing of blind patients in a pilot trial with subretinal implants
Participation in first human applications of retinal neuroprosthesis may create psychological stress for blind retinitis pigmentosa patients. The aim of this study was to assess the emotional wellbeing of patients undergoing implantation of a subretinal implant.
Nine blind patients participating in a pilot trial with subretinal implants were enlisted. The Brief Symptom Inventory (BSI), a short self-report scale of nine primary symptoms, was used to assess reaction to the psychological distress related to study participation. The number and the intensity of symptoms were analysed, and global scores for overall psychological distress (tGSI), severity of reported symptoms (tPDSI), and level number of self-reported symptoms (tPST) were calculated. The questionnaire was administered before implantation, 2–3 times during the trial and before explantation.
There were no significant alterations during the trial for the average scores of the nine primary symptoms. One patient, however, showed values higher than the norm, for six subscores before implantation and for eight subscores before explantation. A significant improvement was found in both the overall psychological distress level (tGSI) and the severity of reported symptoms (tPDSI) at the final visit, compared to those at the study start. The number of self-reported symptoms (tPST) was not significantly altered.
In the first ongoing pilot trial with an active, cable-bound subretinal implant, we found that trial participation and the implant procedure and subsequent testing did not have any adverse effects on the participants’ emotional wellbeing. Their distress generally improved during study participation, rather than showing signs of decreased wellbeing.
An active microphotodiode array (aMPDA) has been developed to restore vision in blind patients [1–7]. The cable-bound aMPDA is implanted subretinally, and enables nerve cell stimulation by recoding an electrical signal according to the strength of the brightness of the object to be seen and its surroundings. The psychological effects of participation in the implant project are difficult to predict, as the study involves pioneer work where the outcome is unknown and which may induce severe stress for the patient.
In the planning stage of the very first pilot trial with the subretinal implant, there was neither knowledge nor experience of how blind patients would cope with the workload of novel visual perceptions, the potential stress of study procedures, or the potential disappointment if no perceptions would occur. Patient organizations involved in the preparation phase of the trial raised the issue of a need for psychological support and assessment in this unique trial.
With this background, the major objective of this study was to obtain a measure for the psychological wellbeing of patients participating in the retinal implant project. After consultation with experienced psychologists, the Brief Symptom Inventory (BSI) , an accepted and validated test, was chosen as the most suitable for monitoring the level of distress of the patients during the trial. The BSI is a 53-item, self-report questionnaire which is aimed at supporting clinical decision-making by providing a score for nine psychological symptom parameters and three global indices of distress. Psychological counselling was also offered during study participation.
Materials and methods
Inclusion criteria, patients, and visit schedule
Duration of blindness (years)
Time to explant (weeks)
Measurable visual acuity
Measurable visual acuity
The aMPDA was implanted into one eye. The trial duration was initially planned for 4 weeks, and six patients had it explanted at this time. Because of the positive observations in these first patients, the protocol was amended; in one patient, explantation followed 8 weeks after implantation, and in another patient, explantation was after 20 weeks. One of the patients refused to have the chip explanted.
Psychological counselling was initially scheduled to take part once a week on the patient’s request, and was performed by a consulting specialist from the neighbouring psychiatric hospital, who also administered the BSI. Psychiatrists regularly perform psychological counselling in Germany. Counselling was performed, if possible, by the same psychiatrist for the individual patient. All patients underwent one counselling session at screening, and eight of the nine patients were counselled a further 3 times. One patient felt that he did not require this service. For the six patients who had the device removed after 4 weeks, the counselling was on a weekly basis. For the remaining patients, the three sessions were spread out in the time between implantation and explantation.
Brief symptom inventory
We chose the BSI as an additional questionnaire to accompany the patients in the Retinal Implant Study, because we wished to obtain a measure of the psychological wellbeing (and hence a symptom inventory). This questionnaire provides patient-reported data on 53 items, used to measure nine primary symptom dimensions: Somatization (SOM); Obsessive–Compulsive (O–C); Interpersonal Sensitivity (I-S); Depression (DEP); Anxiety (ANX); Hostility (HOS); Phobic Anxiety (PHOB); Paranoid Ideation (PAR) and Psychoticism (PSY) . The questionnaire provides three major indices representing the overall psychological distress level for the time of testing (total Global Severity Index, tGSI), the severity of reported symptoms (total Positive Symptom Distress Index, tPSDI) and the number of self-reported symptoms (total Positive Symptom Total, tPST). Patients are requested to report only symptoms that have occurred during the previous 7 days, including the day it was completed. Answers are on a 5-point scale, from 0 = “not at all”, to 4 = “extremely”. The questionnaire takes about 10 min to perform. The BSI has been tested for reliability, validity, and utility in more than 400 studies, and provides normative data. The individual values of the participants are therefore reported as standardized values, which we compare to the normative adult non-patient sample of the BSI. A worsening of the condition can be stated only if the value lies above the normal limit of 63. These data are based on the results of 344 males and 341 females (mean age 46 ± 14.7 years), who were a stratified random sample from a large Eastern county of the USA .
The psychological counselling, including BSI testing, was voluntary for the patients. One patient refused to take the opportunity, with the explanation that he felt well, had no problems and had no need to see the psychiatrist; nine patients answered the BSI.
Mean BSI results for the primary symptoms. The number of patients who show values above the normal range (>63) is shown in parentheses
47.67 ± 7.97 (0)
54.44 ± 11.05 (3)
46.22 ± 11.05 (1)
42.78 ± 11.73 (1)
Interpersonal Sensitivity (I-S)
51.22 ± 9.58 (1)
45.44 ± 9.15 (1)
49.44 ± 10.91 (1)
48.11 ± 10.21 (1)
52.89 ± 5.97 (0)
46.67 ± 9.74 (0)
47.89 ± 10.64 (1)
48.11 ± 10.63 (1)
Phobic Anxiety (PHOB)
48.89 ± 6.37 (0)
55.33 ± 10.35 (1)
Paranoid Ideation (PAR)
46.89 ± 11.15 (1)
52.56 ± 10.31 (1)
48.11 ± 11.88 (1)
47.67 ± 11.47 (1)
There are no significant differences in the means of these scores, and none of the means lie outside the normal range. In four of the subscales (Somatization, Phobic Anxiety, Paranoid Ideation and Hostility) there is a small increase in score, (shown in bold in Table 2) and in five symptoms (Obsessive–Compulsive, Interpersonal Sensitivity, Depression, Anxiety and Psychoticism) there is a decrease (shown in italics in Table 2), but alterations are small and around the mean (50). To examine the significance of these findings, we looked at the number of patients who show a significant change (1SD plus measurement errors) over 63. This is shown in parentheses in Table 1. The patient who refused counselling showed scores over or equal to 63 for all but three symptoms (SOM, ANX and PHOB) before implant, and for all parameters except PHOB at the end of the study. Chip explantation was not performed on this patient. Two other patients had increased scores for SOM before implantation.
To obtain an overall view of the psychological state of the subjects, we calculated the total Global Severity Index (tGSI) as shown in Fig. 1 upper panel. Only one subject’s response to BSI led to tGSI value above the normal limit at the beginning of the study (paired t-test: mean difference = 7.22, p = 0.04).
In the central panel of Fig. 1, the total Positive Symptom Distress (tPSDI) is plotted. In this case, three subjects show large scores at the beginning of the study, indicating an emotional burden. The scores at the last visit before explantation were significantly lower than those at the screening visit, i.e., there was less distress at the end of trial participation (paired t-test: mean difference = 16.89; p = 0.02).
In the lower panel of Fig. 1, the total Positive Symptom Total (tPST) scores are plotted. The scores at the last visit are not significantly different to those at screening. One subject shows scores that are consistently above 63, indicating more subscales affected than in normals.
The patient who refused counselling does not show results outside the normal limit. However, the patient who refused to have chip explanted shows results for all tGSI scores, for pre-implant tPSDI scores, and for all tPST scores which are worse than the normal limit.
In Table 1, we also list the outcome of the implant for the subjects. A total of seven patients had visual sensations mediated by the aMPDA (e.g., phosphenes), four of whom had light perception. Two of these four patients had a measurable visual acuity. The patients with a successful outcome showed average scores for these three indices.
The technical and physiological challenges of retina implant trials are enormous, but one must not forget the psychological aspects of such interventions. Psychological stress related to trial participation may raise ethical concerns, and may also influence functional test results. Supported by patient organizations and psychologists, we tried to cope with psychological aspects of the stress which study participation might bring for the pioneer participants. To our knowledge, this is the first time that the emotional wellbeing in patients taking part in retina implant trials has been investigated, although there are several projects worldwide (see, for example, ).
The emotional wellbeing of patients is not a topic that is often covered by common patient-reported outcome measures in ophthalmology. Rather widespread questionnaires, such as the National Eye Institute Visual Functioning Questionnaire — 25 (NEI VFQ25), which is often used to assess visual function and wellbeing, does not measure stress related to the participation in a trial like the one presented here.
At the end of this study, before the retinal implants were extracted, the average results from nine patients showed an increase in score, for four of the nine symptoms measured in the BSI (see Table 1), indicating a small but not significant worsening of emotional wellbeing: The subjects showed an increase in their perception of bodily dysfunction (Somatization), fear in public and open places (Phobic Anxiety), projection of hostility, suspiciousness, fear of loss of autonomy (Paranoid Ideation) and Hostility in thoughts, feelings and actions. All patients appeared to cope well with the situation; they were pleased to have participated in the study, and would happily take part again.
We do not believe that bias or giving answers in a direction supposed to be socially expected have influenced the rating by the patients. Being aware of such effects, the BSI was never performed by someone belonging to the trial team at the eye hospital. It was regarded as important that regular counselling and BSI testing should be carried out by someone independent from the ophthalmological trial team, in case the patient had problems that he did not want to discuss with the study physician. Often the patient developed a mutual trust with the responsible psychiatrist, and kept in touch with him/her for longer than the duration of the trial.
Last but not least, we regard the intensive medical and social care related to trial participation over many weeks contributed to the observed results. Some of the patients had relatively poor social contacts in their normal life, which may have been improved by intensive daily contacts with physicians and the trial team. All patients expressed their satisfaction with the medical and social care provided during the trial, for example that they were accompanied to and from the hospital by a team member, or during their spare time in the hospital if they were without accompanying persons.
Beyond the small sample size — which is typical for pilot trials with novel medical products for rare diseases and demanding intensive trial procedures — there are further limitations of this paper. The baseline or screening values may have been influenced by the closeness of the implantation date. The patients may have been excited or afraid of the long surgery, etc., so the baseline scores may have been artificially increased, facilitating a decrease during the course of the trial. On the other hand, only a few of the baseline values were outside the normal range. It is also possible that persons who volunteer to participate in such trials as this have certain personality traits, which may influence how they respond.
Our study gives important information about the emotional wellbeing of patients involved in participation in retinal implant tests. None of the subjects reported undue stress, and at the start of the trial, average results were within normal population limits and none showed any deterioration during the course of the study.
We thank the following people for their support in this trial: H. Oelman, C. Kuttenkeuler, R. Wilke and T. Zabel. The authors also thank Anne Kurtenbach for her help in preparing this manuscript. The study was supported by the German Federal Ministry of Education and Research (BMBF: 01KP0401) and the Retinal Implant GmBH, Reutlingen, Germany