Graefe's Archive for Clinical and Experimental Ophthalmology

, Volume 251, Issue 6, pp 1489–1493

Emotional wellbeing of blind patients in a pilot trial with subretinal implants

Authors

    • STZ eyetrial at the Centre for OphthalmologyUniversity Eye Hospital
  • Stefan Klingberg
    • Department of Psychiatry and PsychotherapyUniversity of Tübingen
  • Eberhart Zrenner
    • Institute of Ophthalmic ResearchUniversity Eye Hospital
  • Barbara Wilhelm
    • STZ eyetrial at the Centre for OphthalmologyUniversity Eye Hospital
Retinal Disorders

DOI: 10.1007/s00417-012-2210-6

Cite this article as:
Peters, T., Klingberg, S., Zrenner, E. et al. Graefes Arch Clin Exp Ophthalmol (2013) 251: 1489. doi:10.1007/s00417-012-2210-6

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Emotional wellbeingRetinaImplant

Introduction

An active microphotodiode array (aMPDA) has been developed to restore vision in blind patients [17]. 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) [8], 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

Participants were blind patients whose main diagnosis was retinitis pigmentosa with no other serious eye or general diseases. They had been included in a pilot trial of subretinal implants, in the Centre for Ophthalmology, Tübingen, Germany. In Table 1 we list details of the patients. They were between 26 and 56 years old (mean 45 years), and all were males who had been blind for an average of 7.6 years (range 2–20 years). They had had no useful vision for up to 20 years, and a visual acuity of >20/200 earlier in life. Bright light stimulation mediated some limited light perception without any recognition of shapes. Twelve patients participated in the pilot trial; one withdrew consent on the evening before the implantation due to concerns about the implantation and sudden fear. Nine of the patients took part in this study: eight completed the study according to the protocol, one patient disagreed about the explantation, which was planned at the end of the trial. The study was approved by the Ethics Committee of the Medical Faculty, University of Tübingen, and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All patients gave their informed consent prior to their inclusion in the study.
Table 1

Patient overview

Subject number

Age

Duration of blindness (years)

Time to explant (weeks)

Outcome

1

44

2.0

not explanted

Visual sensations

2

48

6.0

4

Visual sensations

3

53

12.0

4

No sensations

4

51

10.0

4

No sensations

5

56

5.0

4

Light perception

6

26

3.5

4

Light perception

7

51

20.0

4

Visual sensations

8

35

5.0

8

Measurable visual acuity

9

41

5.0

20

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.

The time-points of the examinations for each subject can be seen in Fig. 1. Twenty-five visits were planned, irrespective of the duration of implant. Explantation was performed after the last examination. The data points show visits where the BSI was administered to assess emotional wellbeing. Overall, most subjects were measured 4 or 5 times. The arrows show the time of aMPDA implantation and explantation.
https://static-content.springer.com/image/art%3A10.1007%2Fs00417-012-2210-6/MediaObjects/417_2012_2210_Fig1_HTML.gif
Fig. 1

Results of each patient for each BSI test. The x axis indicates the visit number of the ophthalmological examination. Data points show the time points of BSI administration. The results of each subject are shown with a different symbol. Horizontal lines indicate the normal range. Upper panel tGSI scores; centre panel tPSDI scores; lower panel tPST scores. A paired t-test shows significant decrease in tGSI and tPSD values at the end of the trial

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) [8]. 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 [8].

Results

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.

In Table 2, we show the results of the BSI for the nine primary subscales. For every patient, a standardized score for each subscale has been computed, which is based on the normative data for adults provided in the test manual. The standardized scores have been transformed into t-values, which have by definition a mean of 50 and a standard deviation of 10.
Table 2

Mean BSI results for the primary symptoms. The number of patients who show values above the normal range (>63) is shown in parentheses

Symptom dimensions

Pre-implant

Pre-explant

Somatization (SOM)

47.67 ± 7.97 (0)

54.44 ± 11.05 (3)

Obsessive–Compulsive (O–C)

46.22  ± 11.05 (1)

42.78 ± 11.73 (1)

Interpersonal Sensitivity (I-S)

51.22 ± 9.58 (1)

45.44 ± 9.15 (1)

Depression (DEP)

49.44 ± 10.91 (1)

48.11 ± 10.21 (1)

Anxiety (ANX)

52.89 ± 5.97 (0)

46.67 ± 9.74 (0)

Hostility (HOS)

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)

Psychoticism (PSY)

48.11 ± 11.88 (1)

47.67 ±  11.47 (1)

bold type indicates an increase in score, italic type indicates a decrease in score

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.

Discussion

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, [9]).

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.

Limitations

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.

Conclusions

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.

Acknowledgments

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

Copyright information

© Springer-Verlag Berlin Heidelberg 2012