Introduction
The use of Stem Cell Therapy (SCT) in ocular diseases such as age-related macular degeneration (AMD) is currently being investigated in U.S. Food and Drug Administration (FDA)-approved trials.1 However, many clinics in the U.S. have adopted this therapy without an appropriate Investigational New Drug Application (IND) from the FDA by using adipose-based stem cells, which are easy to obtain and therefore easy to use in a non-approved, clinical setting.1 The dangers of non-approved SCT were presented in a case study of three patients who received adipose-based SCT from stem cell clinics and later presented with devastating vision loss.1
In August 2017, the FDA increased its regulation over stem cell clinics due to the prevalence of clinics offering non-FDA approved SCT.2 These businesses marketed their treatment via online websites and used advanced, scientific language to present vague information regarding FDA approval and therapy safety.3,4 Given the complex nature of SCT, a majority of patients are not fully educated in the nuances of these unapproved therapies and are potentially susceptible to harmful treatments.3,4
In this prospective study, we investigated retina clinic intravitreal injection patient knowledge and experiences regarding SCT for retinal diseases.
Methods
This study was approved by the University of Miami Institutional Review Board, adhered to the tenets of the Declaration of Helsinki, and was performed in accordance with the Health Insurance Portability and Accountability Act of 1996. A survey was completed by patients presenting to retina clinic for intravitreal injection therapy from February 2020 to March 2021. Of note, survey collection was temporarily halted due to restrictions instituted as a result of the COVID-19 pandemic. The surveys were provided in English and Spanish and patient consent was recorded. The survey administered evaluated patient knowledge about SCTs for retinal disease. Demographics and clinical diagnoses were also recorded. Pearson chi-square tests for independence were used for gender and ethnicity comparisons. All statistical analyses were conducted using SAS University Edition. A p-value <0.05 was considered statistically significant.
Results
A total of 87 participants responded to the survey study, with the most common diagnosis being exudative age-related macular degeneration (26, 29.9%, Table 1). Out of 87 patients, 2 did not respond to questions regarding ethnicity, 1 patient did not respond to questions regarding race, and 11 patients did not respond to questions regarding diagnosis.
Table 1:
Summary Table of Patient Demographics in SCT Survey Respondents
| Number of Respondents, N (Percentage of Total N= 87,%) | |
|---|---|
| Total Surveys Administered | 87 (100%) |
| Age (years) | |
| 21–30 | 1 (1.1%) |
| 31–40 | 1 (1.1%) |
| 41–50 | 4 (4.6%) |
| 51–60 | 15 (17.2%) |
| 61–70 | 29 (33.3%) |
| 71–80 | 21 (24.1%) |
| 81–90 | 15 (17.2%) |
| 91–100 | 1 (1.1%) |
| Gender | |
| Female | 48 (55.2%) |
| Male | 39 (44.8%) |
| Ethnicity * | |
| Hispanic | 49 (56.3%) |
| Non-Hispanic | 36 (41.4%) |
| Did not respond | 2 (2.3%) |
| Race * | |
| Black | 11 (12.6%) |
| White | 71 (81.6%) |
| Asian | 4 (4.6%) |
| Did not respond | 1 (1.1%) |
| Diagnosis | |
| AMD (dry, wet, non-specified) | 26 (29.9%) |
| Macular Edema† | 19 (21.8%) |
| CRVO | 11 (12.6%) |
| Retinopathy§ | 18 (20.7%) |
| Neovascular Glaucoma | 1 (1.1%) |
| Other ¶ | 1 (1.1%) |
| Did not respond | 11 (12.6%) |
AMD: age-related macular degeneration; CRVO: central retinal vein occlusion
Includes self-reported data.
Includes diabetic and radiation retinopathy diagnoses.
Includes diabetic and cystoid macular edema.
Inflammatory status-post cataract extraction with intraocular lens implant
Survey results disclosed that 57/87 (65.5%) respondents believed that all clinical trials found online are regulated by the FDA. Of 55 respondents who answered “true” to believing all clinical trials found online are regulated by the FDA, 36/55 (65.5%) were Hispanic and 19/55 (34.5%) were non-Hispanic (p=.049). In total, 47/86 (54.7%) respondents believed there were current FDA-approved and commercially available SCTs for retinal disease and 35/86 (40.7%) respondents stated that they would consider SCT for their retinal disease even if it was not approved by the FDA.
Few patients were aware of the risks related to unapproved SCT therapies, with 9/86 (10.5%) respondents answering “yes” they were aware of risks associated with the use of non-FDA approved stem cells for retinal disease. All nine respondents aware of risks associated with SCT were male. When participants were asked whether a medical professional had ever spoken with them about the benefits or risks of SCT for retinal disease, 0/87 (0%) reported “risks only”, 4/87 (4.6%) reported “benefits only”, 5/87 (5.7%) reported “both risks and benefits”, and 78/87 (89.7%) answered “neither risks nor benefits”. Only 2/87 (2.3%) respondents in our study had been contacted by a stem cell clinic offering therapy for retinal disease, and only 9/87 (10.3%) patients reported that they had seen advertising for stem cell clinics offering therapy for retinal disease.
Discussion
The results of our study demonstrated a high prevalence of patient misinformation regarding SCT for retinal diseases. Many of the patients who completed the survey falsely believed that all clinical trials found online are regulated by the U.S. FDA. This finding is problematic, considering stem cell clinics preferentially use online advertisements to harness patient interest.4 For instance, many stem cell clinics advertise their research on the website https://clinicaltrials.gov/ without stating their IND status with the FDA.1 As a result, patients may choose to undergo therapy that utilizes unregulated stem cell products after they visit this website under the false pretense of engaging in legitimized research.
Additionally, the majority of patients surveyed were unaware of any risks associated with the use of non-FDA approved SCT for retinal disease. Considering the severity of the risks associated with unproven SCTs, including retinal detachment and permanent blindness, it is crucial to address this current knowledge gap.1 While patient education regarding the risks of these unproven therapies is crucial, it is also important for ophthalmologists to be aware of the prevalence of these dangerous SCT clinics. One 2017 report found that 76 clinic websites were offering unregulated SCTs for ophthalmic disease.4 Although the FDA works to regulate clinics providing dangerous therapies, there is no way to completely remove online advertisements associated with them, and therefore patients are still at risk of encountering false information.
This study is limited by the survey group of 87 patients from an individual retina clinic in a single geographic location and the limited self-reported data analyzed. The time frame for the study was stretchd due to unforeseen clinical shut-downs related to the COVID-19 pandemic. Additionally, our study only assessed patients receiving intravitreal injection therapy. Despite these limitations, this study provides important insights.
In conclusion, this study demonstrates a lack of patient knowledge regarding the poor regulation of SCT use for retinal disease. This study, in combination with previous studies which depict the potential deleterious effects of non-FDA approved SCT, indicates a continued unmet need in improved patient education to proactively prevent patients from being harmed by predatory deregulated clinics.
Financial Support:
Bascom Palmer Eye Institute received funding from the NIH Core Grant P30EY014801, Department of Defense Grant #W81XWH-13-1-0048, and a Research to Prevent Blindness Unrestricted Grant. The sponsors or funding organizations had no role in the design or conduct of this research.
Footnotes
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Conflict of Interest: NAY (Advisor: Alimera Sciences, Alcon, Novartis, Genentech), AEK (Consultant/Advisor (Alimera Sciences, Allergan, Bausch + Lomb, Genentech, Novartis, Recens Medical, Regeneron, Spark Therapeutics; Speaker: Optos, Spark Therapeutics; Grant Funding: Genentech, Spark Therapeutics), JS (Consultant: Alcon, Allergan, Dorc, Genentech, Regeneron),
Meeting Presentation: Presented at The Association for Research in Vision and Ophthalmology (ARVO), 2021
References
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