Abstract
Background:
Recent evidence has demonstrated the absence of a robust effect of vitamin A on retinitis pigmentosa (RP) patients; however, the actual patients’ knowledge on this topic appears to be limited.
Objectives:
To survey a cohort of Italian patients with a definite diagnosis of RP about their level of knowledge regarding the latest updates on vitamins in RP.
Design:
Survey study administered between January and June 2025 among patients followed up in a specialized Inherited Retinal Dystrophies (IRD) center in Chieti, Italy, Europe.
Methods:
Patients were asked a total of 25 questions regarding their dietary attitude. The questionnaire was manually distributed to patients who could answer individually to the survey. To help with significantly visually impaired patients, all patients were offered to be helped by an assistant for reading issues, in accordance with privacy measures.
Results:
A total of 50 participants were recruited. Of these, 52% of them were taking supplements, 84.6% with vitamin A supplementation, while 7.7% were using multivitamin pills. Participants were surveyed about their knowledge concerning the presence of vitamin A in food, yielding several results: carrots (88%), pumpkin (60%), and kale (60%). Participants referred to exceeding in consuming one of those items in 64% of cases. Specifically, the majority of them overconsumed spinach (62.5%), kale (37.5%), and sweet potatoes (31.3%). While the whole population (100%) was not aware of vitamin impact on certain IRDs, all respondents (100%) manifested their strong interest in gaining knowledge on this topic.
Conclusion:
Our cohort of Italian patients suffering from syndromic and nonsyndromic RP are not fully aware of the impact of vitamins on their condition, and most of them enrich their diet with nutritional supplements. The implementation of projects aimed at improving knowledge on this topic in the affected population is strongly advised to help with the chronic management of this condition.
Introduction
The importance of lifestyle measures is a key point in the management of inherited retinal dystrophies (IRDs), due to the lack of validated approaches for the affected population. Nevertheless, the approval of Voretigene Neparvovec (Luxturna, Novartis Europharm Ltd) for RPE65-related conditions has changed the landscape of IRDs treatments, and today, several targeted and untargeted therapies are being developed, ranging from gene therapy to CRISPR and antisense oligonucleotide.1–3 As a result, halting the disease progression is crucial to preserve the current vision in light of future prospects in potential approaches. IRDs are characterized by high genotypical and phenotypical heterogeneity, and the correct management of these conditions requires a holistic approach, starting from the diagnostic pattern, leading to up-to-date management. Among all, retinitis pigmentosa (RP) is the most common, characterized by a high grade of genotypical and phenotypical heterogeneity, with more than 80 genes known to be implicated in its pathogenesis, leading to progressive photoreceptor dysfunction and cell death. 4
The role of vitamins in ophthalmological disorders has always been highlighted in specific conditions, giving high relevance to the lifestyle attitude. Currently, age-related macular degeneration (AMD) patients are recommended to have a higher antioxidant intake including lutein and zeaxanthin due to their role in halting macular degeneration following the age-related eye disease study 2 (AREDS 2) evidence that conclusively demonstrated the importance of vitamins and mineral supplementation in slowing AMD progression.5,6
Today, most over the counter multivitamin complexes are used by low vision patients despite their underlying condition, and the presence of vitamins is not only limited to pills and food, but it often extends to skincare products and moisturizers. Between 1984 and 1992, a randomized clinical trial suggested that vitamin A supplementation had a positive effect in halting RP progression, underscoring the negative role of vitamin E. 7 In 2023, by sequencing banked DNA samples derived from the trial, Comander et al. 8 were able to identify how different genotypes responded differently to vitamin supplementation. Surprisingly, while confirming the overall deleterious effect of vitamin E, a potential negative effect due to vitamin A supplementation was registered in USH2A and EYS subgroups, and the authors stated the absence of an overall robust positive effect of vitamin A in their whole cohort. As a result, they stopped recommending vitamin A supplementation and kept recommending avoiding high-dose vitamin E supplementation (>30 IU/day) in RP patients. However, little is known about the worldwide patient knowledge of lifestyle impact on RP.
Therefore, the aim of this study is to survey a cohort of Italian patients with a definite diagnosis of RP about their level of knowledge regarding the latest updates on vitamins A and E in RP.
Materials and methods
Our cross-sectional survey study involved patients attending the IRD Unit, Vitreoretinal Department, Surgical Visual Rehabilitation Clinic, of the Gabriele d’Annunzio University, Chieti-Pescara from January 2025 to June 2025. Participants were consecutively enrolled among patients presenting for routine clinical care.
The study was approved by the local IRB of the Gabriele d’Annunzio University, Chieti-Pescara, and followed the STROBE guidelines for reporting observational studies. All patients were asked to participate in the survey, written consent was obtained, and in any case the standard clinical care was affected. Inclusion criteria were >18 years old, clinical and/or molecular diagnosis of isolated or syndromic RP. Patients <18 years old and patients who expressed their willingness not to participate in the survey were excluded.
The vitamin-related survey was developed by a board of three different ophthalmologists expert in IRDs. The questionnaire was written in the Italian language and included a total of 25 questions. The survey was manually distributed to all patients. To help with significantly visually impaired patients, all patients were offered to be helped by an assistant for reading issues. In that cases, oral permission was asked, and the questionnaire was performed by a trained ophthalmologist (C.L.) in accordance with privacy measures. Both questions and the survey are reported in Table 1.
The survey.
The survey questions are here reported. Demographical data, IRD-related data, and dietary records were asked to all participants.
AREDS2, age related eye disease study 2; IRD, inherited retinal dystrophy.
Statistical analysis
Statistical analysis was performed using Excel version 15.0.4433.1508 (Microsoft Office Home and Business 2013, Microsoft Corporation, USA) and R version 3.6.3, R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/. Descriptive analysis was conducted for all variables. Continuous variables were reported as number (n), mean, standard deviation, and median. Categorical variables were summarized as frequencies and percentages.
No sample size calculation was performed, as the study was based on a consecutive convenience sample of all eligible patients accessing the IRD Unit during the predefined recruitment period to ensure inclusion of representative real-world cohort of individuals with isolated or syndromic RP.
Results
Participants
A total of 50 completed questionnaires were collected. All participants answered to all requested items. Among participants, the majority were aged between 18 and 40 years old (48%) and 44% of them were female. Overall, 44% had completed high school, 32% held a university degree, and 24% had a lower level of education.
However, in our analysis no significant association was found between education level and gene knowledge. Participant’s demographical characteristics are reported in Table 2.
Survey participants.
Demographical data including age, sex, and level of education is reported. Additionally, diagnostic data are described.
The majority of enrolled participants were diagnosed for nonsyndromic RP (84%), whereas 16% for Usher syndrome. Interestingly, in only 4% of cases, the diagnosis was defined under the age of 10, while the majority of patients reported to be diagnosed when aged between 18 and 40. Notably, 76% of participants reported knowing the responsible gene for their condition (Table 2).
Dietary
None of the surveyed participants was under dietary regulations. However, when asked about the eventual use of dietary supplements, 52% responded positively. Among these, 84.6% reported using vitamin A supplements, while 7.7% used multivitamin pills. Interestingly, among the subgroup of patients diagnosed with Usher, 4% reported using vitamin A supplementation. Interestingly, in our analysis, the supplement use showed a borderline, nonsignificant trend toward higher gene awareness (p = 0.053).
When asked about the use of specific supplements for their condition, nearly half of enrolled patients (48%) responded affirmatively. Among them, all (100%) had their pills prescribed by the ophthalmologist, and the most common reported composition was rich in Lutein and Vitamin A.
When the question “Do you have additional vitamin A or E in your diet?” was asked, 100% of enrolled patients denied. However, participants were surveyed about their knowledge concerning the presence of vitamin A in food. In this case, multiple answers were allowed. Specifically, the most common answers were carrots (88%), pumpkin (60%), and kale (60%). Furthermore, 64% of participants reported consuming one or more of these foods in greater quantities. Specifically, the majority of them overconsumed spinach (62.5%), kale (37.5%), and sweet potatoes (31.3%; Figure 1). Nevertheless, 100% of respondents did not care about the vitamin concentration in their food, and consistently, the whole population (100%) was not aware about vitamin impact on certain IRDs, despite all respondents (100%) manifested their strong interest in gaining knowledge on this topic. As for AREDS supplementation, 76% of patients were confident they were not taking supplementary pills, while 24% of them were not sure. Likewise, 88% were not aware of using skincare products enriched by retinol or derivatives, despite all participants (100%) reported not checking on their skincare product composition.
Dietary. Participants were asked about their knowledge on vitamin A presence in foods. Therefore, the next question was about any food that was present at a higher quantity in their daily diet. In both cases, multiple answers were applicable.
Discussion
Our analysis first explores the level of knowledge on dietary implications and the impact of vitamins in RP. Despite being overall known, the importance of dietary attitudes in specific genotypes of RP patients has been reevaluated recently with the re-examine performed by Comander et al., 8 who stressed the difference in effect of vitamins A and E on specific RP genotypes. Specifically, the authors reported a negative impact of vitamin A in EYS and USH2A genotypes, and the absence of overall positive effects on the whole cohort, underlying the weight of genotypic differences in RP. Growing evidence has been reported about the importance of vitamins in RP in the last years. Specifically, in 2023, Krašovec et al. 9 proposed vitamin A in its 11-cis-retinal form to play a key role in stabilizing the constitutively active p.G90D rhodopsin in patients carrying p.G90D in RHO, thus proposing its role as potential treatment strategy. However, according to Comander et al., a recent review by the American Academy of Ophthalmology reported the absence of high quality evidences supporting the effectiveness of any form of dietary supplementation for RP.7,10
Today, the level of knowledge on this topic in European patients has not yet been explored, underlining the multitude of measures that one should be aware of when dealing with IRD. Nevertheless, our analysis revealed a low awareness in this topic, with patients not completely prepared when interviewed about their use of vitamin supplements and their attention to the vitamin content in food and products, despite the majority of them still using daily vitamin supplementation. Notably, nearly half of all enrolled patients (48%) and up to 4% of patients diagnosed with Usher syndrome were using vitamin supplements in our series.
Previously, Sofi et al. 11 yet enhanced the role of nutrient intakes in patients with RP and Stargardt disease, suggesting the development of tailored nutritional interventions in the two categories. In fact, in their cohort, Stargardt patients with low vitamin A intake (<600 µg RAE/day) reported better visual outcomes when compared to those with a higher vitamin A intake.
Today, advancements in therapeutics in IRD require the adoption of strict measures to prevent the disease progression, and preserving vision becomes extremely important, with the residual visual function often being a limiting factor in joining clinical trials. In this setting, the dietary regimen, by affecting the disease course, plays a key role in the patient management, being able to modulate the disease. Vitamin A is overall known to have a deleterious effect on Stargardt patients, due to their metabolic defect that makes patients with ABCA4 mutations not able to metabolize vitamin A, thus resulting in the toxic bioproducts that are the main component of lipofuscin. 12 Moreover, the use of deuterated vitamin A in ALK-001 form in the TEASE study has first proposed modified vitamin A as a therapeutic intervention to slower STGD1 progress by acting on the vitamin A dimerization and at the same time, both validating the clinical evidence of the contribute of vitamin A to the pathophysiology of STGD1 and shedding light on possible alternative approaches in this field. 13 Likewise, high doses of vitamin A are known to be cause for multisystemic symptoms with bone and liver toxicity, and severe birth defects that may occur if taken by pregnant women. 14
However, its role in RP patients has often been controversial, with patients often raising their intake to help with vision improvement. The analysis performed by Comander et al. 8 sheds light on the importance of genotyping IRD patients and the relevance of a rigorous update in research. Today, not all patients are still convinced about the value of proceeding with genotyping, and recent analyses have revealed how, despite improvements, a certain amount of patients still does not have access to genetic testing, and there is a significant amount of IRD patients who are not tested, whose genetic testing is inconclusive or who do not receive genetic testing.15,16
Based on the different impacts of vitamins in patients, this analysis underscores both the importance of characterizing patients and the awareness of lifestyle measures that may be impactful in this setting. In fact, in our population, while 84.6% of patients were using vitamin supplements, only 76% of them were aware of the responsible gene for their condition, despite the presence of this knowledge may enable the application of tailored measures that could help in the underlying ophthalmologic condition. Likewise, most patients were not aware of the influence of these nutrients in this setting, despite the whole cohort showing great interest in gaining more knowledge on this topic (100%). This enhances the importance of offering patients the opportunity to dive more into their condition through the presence of peer-to-peer programs, social events, and conferences. The role of nutritional supplements in ophthalmology has been recently ascertained not only with the already consolidated knowledge of the importance of AREDS supplementation in AMD but also in other ophthalmological disorders such as glaucoma, where the neuroprotective role of citicoline and vitamins has been established in the disease management.17–19 However, in our analysis, despite the total of patients showing interest in gaining more knowledge on this topic, the majority of them referred not to focus on the vitamin content in food and products. This was further confirmed by the identification of food rich in vitamin A, a question in our survey that reinforced the lack of knowledge in this topic. Understanding the distribution of vitamin A in daily life is essential, as its presence extends beyond dietary sources to include topical applications such as moisturizers and skincare products. This is attributed to the beneficial dermatological effects of retinol and retinol-related compounds, which play a significant role in skin aging and acne management. 20 Although the majority of patients in our analysis were diagnosed at middle age, RP is typically identified in early life. As a result, the coexistence of RP with other conditions or lifestyle factors requiring the use of vitamin A products or their derivatives may also be observed. In this regard, the impact of the different metabolites in the vitamin A cycle on RP patients should be further investigated and little is known about the topic, with a significant flow in the current literature. Nevertheless, our analysis first investigates the level of knowledge on vitamin impact on RP in an Italian cohort, giving insights into the lack of complete knowledge in this topic and reinforcing the role of tailored, customized approaches in IRD that rely on the presence of a validated underlying genetic analysis.
However, our study has limitations. First, the absence of a sample size estimation that may affect the statistical power. Furthermore, despite we acknowledge the inclusion of only Italian patients as a limitation of this study, not being representative of the multitude of European cultures, this first highlights perceptions on this important theme from a patients perspective. Nevertheless, our results point out the necessity of better knowledge on this important topic, from both clinicians and patients’ point of view.
Being a helpful measure in patients with IRD, we strongly encourage the development of services to support patient empowerment and adherence to evidence-based recommendations, enhancing this knowledge in affected patients and among clinicians, contributing to its potential usefulness in RP management.
