FormalPara Key Summary Points

Why carry out this study?

Retinitis pigmentosa (RP) is an inherited progressive disease; after glaucoma, RP is the second leading cause of visual impairment in Japan.

Previous studies have shown a correlation between more severe visual impairment and reduced quality of life; however, the economic impacts of RP on Japanese patients have not been studied in detail.

Understanding the quality of life and economic costs of RP is necessary to identify any unmet medical needs of Japanese patients with RP.

What was learned from the study?

The estimated annual and lifetime costs per patient were 218,520 yen (2176 USD) and 18,523,909 yen (184,501 USD), respectively; additional robustness testing increased these estimates to 783,176 yen (7801 USD) and 66,389,827 yen (661,253 USD), respectively.

We found that Japanese patients with RP experience a heavy economic burden and worsened quality of life, with reduced quality of life correlating with increased visual impairment.

Introduction

Retinitis pigmentosa (RP) is one of the inherited retinal dystrophies, which are a heterogeneous group of eye disorders that can result in visual impairment and eventual blindness [1]. The disease is characterized by the loss of rod and cone photoreceptors in the retina, with the loss of rods and the subsequent impairment of low light vision typically occurring first. RP is a progressive disease, whereby affected patients experience a gradual loss of light sensitivity, visual field, and visual acuity, and can lead to complete blindness [2, 3]. Over 1.64 million people in Japan were affected by visual impairment in 2007, equating to a cost of approximately 8785.4 billion yen (72.8 billion USD) in that year alone [4]. Among 99.6% (12,505/12,561) of newly certified visually impaired individuals in the fiscal year of 2015, the most common causative disease was glaucoma (28.6%), followed by RP (14.0%), diabetic retinopathy (12.8%), and macular degeneration (8.0%) [5].

A new gene therapy medication (voretigene neparvovec-rzyl) has recently been approved in both the USA and Europe for patients with retinal pigment epithelium-specific 65 kDa protein-associated Leber congenital amaurosis, or early-onset RP [6]. However, there is currently no available therapy in Japan that can prevent or reverse RP, and management of the disease typically involves supportive care, including services and devices to assist affected patients [1, 7, 8]. Vision loss from RP impacts both the affected patients and their families, resulting in wide-reaching humanistic and socioeconomic implications [9]. It is necessary to understand the current quality of life (QOL) and economic impacts of visual impairment to identify unmet medical needs of Japanese patients with RP. Several previous studies have sought to investigate the link between visual impairment and QOL measures: two Japanese studies have found a correlation between the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) scores and the degree of peripheral visual field loss [10], and between the VFQ-25 scores and visual impairment grade [11]. However, to our knowledge, the economic impacts of RP on Japanese patients have not been studied in detail.

In this study, we investigated the economic costs of visual impairment or blindness incurred by Japanese patients with RP. Furthermore, we investigated the impact on patients’ work productivity and QOL.

Methods

Study Design

This was a non-interventional, cross-sectional study, in which patients with RP were surveyed using quantitative web-based or telephone surveys between September 2021 and November 2021. A web-based survey was chosen to reach patients nationwide, and a telephone interview was provided as an option for patients who had difficulty completing a web-based survey because of their visual impairment, or for other reasons. The questionnaire translated into English is provided as Data S1 in the electronic Supplementary Material; it included assessments of the economic status and out-of-pocket costs for patients, and descriptions of visual acuity and visual field impairment classes, which aligned with the estimated visual ability in the American Medical Association (AMA) Guides [12]. It also included the work productivity measures in the Work Productivity and Activity Impairment Questionnaire (WPAI) [13], and the QOL measures in the Health Utilities Index Mark 3 (HUI3) [14], the VFQ-25 [15], and the 5-level EQ-5D version (EQ-5D-5L) [16]. Appropriate permissions were obtained to reproduce these measures, where necessary. Aids such as audio assistance were available to ensure the survey was appropriate for visually impaired respondents.

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and was compliant with Novartis regulatory standards and all Japanese legal and regulatory requirements. External approval was provided by the Ethics Committee of the Medical Corporation Fujikeikai Kitamachi Clinic (protocol code BGQ08256, 21 July 2021). All patients were informed about the purpose of the study, and informed consent was obtained. Patients under 20 years of age (the legal age of adulthood in Japan, prior to April 2022) were required to complete the survey with their parents/guardians, after obtaining permission from the parents/guardians to participate.

Patients

Patients were recruited via the Japanese Retinitis Pigmentosa Society (JRPS). Patients with a diagnosis of RP who have, or had, a Specific Medical Expenses Recipient Certificate (for Designated Intractable Diseases) for RP, regardless of gene variance status identification, voluntarily participated in this study. The criteria for diagnosis of RP (including subjective symptoms, laboratory test findings, diagnostic judgment, and severity rating) translated into English are provided as Data S2 in the electronic Supplementary Material. The exclusion criteria were as follows: patients with Usher syndrome, Bardet–Biedl syndrome, mucopolysaccharidosis, Kearns–Sayre syndrome, adult Refsum disease, infantile Refsum disease, Alagille syndrome, Bassen–Kornzweig syndrome, Cockayne syndrome, Hallervorden–Spatz syndrome, or Rud syndrome.

Outcomes and Variables

The primary outcome of interest was the direct and indirect economic cost of visual impairment or blindness during the lifetime of patients with RP. The survey questions for this study pertained only to the economic costs incurred by the patient; the amount covered by the healthcare system or insurance was not recorded. Direct economic costs included the patient’s out-of-pocket costs for vision aids (e.g., glasses, magnifiers, guide dogs, and canes), medications and supplements, the cost of healthcare services (e.g., ophthalmologist, orthoptist, walking training instructor, and psychologist visits), and formal care costs. Indirect economic costs included the salary gap between patients with RP and the general population, and the cost of depression/anxiety, including the patient’s out-of-pocket medical costs and the cost of suicide. Secondary outcomes were the specific cost categories (healthcare, vision aids, caregiving), financial aid required by patients, productivity and activity, and the QOL of patients with RP. All outcomes were stratified according to patient demographic factors. The visual impairment of patients was graded according to the physical disability grade [17], the World Health Organization (WHO) definition of distance vision impairment [18], and the visual impairment class (AMA) [12]. The criteria for the visual impairment class (AMA) are provided as Data S3 in the electronic Supplementary Material. All costs were reported in Japanese yen; the costs were converted to USD at a rate of 100.4 yen per 1 USD, unless otherwise noted.

Costs were assessed using 2020 Japanese population data collected by the Ministry of Health, Labour and Welfare [19] and the Statistics Bureau of Japan [20]. As the rate of disease progression can vary widely among patients, the average Japanese life expectancy was used to calculate the lifetime costs. The average Japanese life expectancy was calculated from the reported female and male average life expectancies (87.74 and 81.64 years, respectively, in 2020 [21]), weighted by the female and male population ratio from the 2015 Population Census [22]; thus, lifetime costs for this study were calculated by multiplying the annual cost by 84.77. The average age of onset (11.2 years) was calculated on the basis of a previous report [23].

The salary gap between individuals with RP and the general population was calculated as described in the electronic Supplementary Material (Data S4). The effect of potential confounding factors was minimized by aligning the age and sex groups, and considering the difference in employment rates between the general population and patients with RP. Annual costs associated with depression and anxiety were calculated by multiplying the total annual cost of 138,516 yen [suicide costs: 1115 USD (130,455 yen), out-of-pocket direct medical costs: 689 USD (80,613 yen) × 0.1] by the proportion of patients who were taking medications to manage feelings of depression or anxiety, with reference to the published annual cost of depression [24]. The ratio of patients’ copayment was assumed to be 10%, and workplace costs were not included in this calculation as these costs were addressed in the salary gap calculation. The published USD values of annual costs were converted to yen at 117 yen/1 USD. As there is no available report on the annual cost of anxiety per patient in Japan, the published cost of depression [24] was used to calculate both depression and anxiety costs in this study.

The effect of visual impairment or blindness on productivity and activity in working patients was assessed using the WPAI [13]. Patients were surveyed on their occupations, classified according to the Japan Standard Occupational Classification [25], and patients who identified as students were surveyed on the academic impact of their visual impairment. Additionally, patients were surveyed on the impact of visual impairment on their ability to gain employment. QOL measurements were captured using the HUI3 [14], VFQ-25 [15], and EQ-5D-5L [16].

Statistical Analyses

Parametric or nonparametric tests were used, depending on the distribution of the collected data. For normally distributed data, a t-test or Tukey–Kramer test was used for comparing two groups of patients, or three or more groups of patients, respectively. For non-normally distributed data, a Mann–Whitney U test or Steel–Dwass test was used to compare two groups of patients, or three or more groups of patients, respectively. Polyserial correlation coefficients were calculated to evaluate the correlation between qualitative and quantitative data. Missing data for specific questions were excluded through pairwise deletion from the analysis.

Additional prespecified analyses were performed to ensure the robustness of the primary outcome, excluding patients with apparent inconsistencies in their responses to vision-related questions and outliers to each question. An outlier was defined as a value for which the difference from the mean value exceeded three times the standard deviation. Additionally, the costs were adjusted for the average age of RP onset. The weighted means for each cost were calculated from the age distribution of the patients with RP, which was based on the age categories of individuals with a Specific Medical Expenses Recipient Certificate (for Designated Intractable Diseases). Statistical analyses were conducted using BellCurve Hideyoshi Dplus v 1.10 (Social Survey Research Information Co., Ltd., Tokyo, Japan), Excel (Microsoft Corp., Redmond, WA, USA), or R statistical software v 4.1.2 [26].

Results

Patient Demographic Characteristics

A total of 122 patients with RP were included in the analyses: of these, 55 (45.1%) were men and 67 (54.9%) were women. Most of the survey responses were collected via the web-based survey (n = 101); 21 patients provided information via telephone interviews. The demographics and clinical/disease characteristics of the survey participants are presented in Table 1. The mean age of the patients was 57.4 years (n = 120), with only one patient aged < 18 years; 50/122 (41.0%) patients were employed, and 4/122 (3.3%) were students; 120/122 (98.4%) patients had a physical disability certificate (provided by prefectural governors, designated city mayors, or core city mayors to persons with physical disabilities as specified in the Act on Welfare of Physically Disabled Persons in Japan), with 45/122 (36.9%) classified as grade 1 and 67/122 (54.9%) as grade 2. Overall, 64/122 (52.5%) patients reported visual acuity < 0.05 (3/60), corresponding to “blindness” on the WHO definition of distance vision impairment. The distribution of visual impairment classes ranged from “near-normal vision” [5/122 (4.1%)] to “total blindness” [17/122 (13.9%)], as described by the AMA Guides.

Table 1 Demographics of survey participants
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Primary Outcome: Cost of Visual Impairment to Patients with RP

The economic impacts evaluated in patients with RP included both direct out-of-pocket costs (including vision aids, medications and supplements, formal care including healthcare services, and paid care) and indirect costs from opportunity loss (including salary gaps and the costs of mental health effects), as shown in Table 2. The annual cost per patient was estimated to be 218,520 yen (2176 USD), with a calculated estimated lifetime cost per patient of 18,523,909 yen [184,501 USD; total annual cost × average life expectancy in Japan (84.77 years)]. Out-of-pocket costs stratified by demographic characteristics are reported in Table S1 in the electronic Supplementary Material. The responses to questions regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic indicated that COVID-19 had almost no impact on outcomes in the study.

Table 2 Economic impact of retinitis pigmentosa
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Additional exploratory analyses on the economic impacts on patients with RP, including robustness testing to exclude patients with inconsistent responses to visual impairment questions (n = 4) and outliers, are presented in Table 3. Each of the calculated costs with robustness testing is presented in Table S2 in the electronic Supplementary Material. This subset analysis revealed an increased estimated annual cost per patient and lifetime cost per patient of 783,176 yen (7801 USD) and 66,389,827 yen (661,253 USD), respectively.

Table 3 Exploratory analyses of economic impact on patients with retinitis pigmentosa
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Secondary Economic Outcomes

The use of healthcare services by patients with RP is presented in Table 4. Out of 122 patients, 64 (52.5%) patients reported consulting with ophthalmologists who specialized in RP, and 79 (64.8%) patients reported consulting with general ophthalmologists. The majority of patients (96.7%) reported consulting with ophthalmologists. The use of vision aids by patients with RP is presented in Table 5. Of 122 patients, 97 (79.5%) patients reported using white canes, and 96 (78.7%) patients reported using smartphone apps as vision aids. Most patients [111/122 (91.0%)] reported paying for vision aids in the past, and approximately half [66/122 (54.1%)] reported paying for vision aids within the last year.

Table 4 Healthcare services use and cost by patients with retinitis pigmentosa
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Table 5 Vision aids in daily life
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The care received by patients with RP is presented in Table 6. In total, 64/122 (52.5%) patients reported receiving paid care and 87/122 (71.3%) reported receiving unpaid care. Patients with more severe visual acuity loss, reflected in visual impairment class (AMA), reported receiving significantly more hours of paid care compared with patients with less severe visual acuity loss (Fig. S1, electronic Supplementary Material). Patients with a visual impairment class (AMA) of “total blindness” or “near-blindness” received 322.9 and 274.2 h of paid care per year, respectively, whereas patients with severe low vision received 38.4 h of paid care (“total blindness,” p = 0.004, and “near-blindness,” p = 0.0002).

Table 6 Care received by patients with retinitis pigmentosa
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Financial aid received by patients with RP is presented in Table 7. Overall, 102/122 (83.6%) patients reported receiving a disability pension, whereas 16/122 (13.1%) patients reported receiving no financial aid. The mean total amount of financial support received was 97,830 yen (974 USD) per patient per month. There was a loss of work productivity of 26.2%, which was attributable to presenteeism. The impact on daily activities, other than work, was 31.6% (Table S3, electronic Supplementary Material). The overall employment rate of patients was 41.0% (50/122). Employed patients or working patients (n = 50) included those who were self-employed or employed by companies or corporations. Among patients who were employed by companies or corporations (n = 39, mean age 49.3 years), 56.4% (22/39) of the patients stated that they were in regular employment. The average annual income of working patients was 5,217,078 yen (51,963 USD) (n = 37, mean age 51.7 years). The overall employment rate, the regular employment rate, and the average annual income of working patients in this study [41.0%, 56.4%, and 5,217,078 yen (51,963 USD), respectively] were lower than those in the age-group-matched general Japanese population [82.2%, 68.8%, and 5,916,800 yen (58,932 USD), respectively] [19, 20].

Table 7 Financial aid received by patients with retinitis pigmentosa
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In the robustness analysis, after removing outliers and data from patients with inconsistent responses to visual impairment questions, the average annual income of working patients was reduced to 2,938,625 yen (29,269 USD) (n = 35, mean age 52.1 years). Within the population of employed patients, there was a bias towards professional/technical work [26/50 (52.0%)] and clerical work [14/50 (28.0%)]; there were no sales personnel or manufacturing process workers among the study patients. Furthermore, of the patients employed in professional/technical work, 12/26 (46.2%) were employed in professions such as acupuncture, massage, and moxibustion. Overall, 86/119 (72.3%) patients had either given up on, or were unsuccessful at, securing a job they wanted because of visual impairment, and 15/82 (18.3%) patients who had interviewed for such positions reported having been rejected because of visual impairment. In terms of schooling, the mean number of days of missed classes in the past year was 3.5, of which 57.1% (2.0 days) were due to visual impairment. Students with RP reported that visual impairment had a large influence on both study (62.5%) and other daily activities (82.5%).

Quality of Life Impacts

The VFQ-25, HUI3, and EQ-5D-5L outcomes are presented in Table 8. The overall mean scores of the VFQ-25 and the HUI3 were 42.0 and 0.393, respectively. The overall mean index score of the EQ-5D-5L was 0.833, and the overall mean visual analog scale score was 75.7. In total, 107/122 (87.7%) patients reported experiencing depression and 119/122 (97.5%) patients reported experiencing anxiety. Furthermore, 11/122 (9.0%) patients reported taking medication for either depression or anxiety.

Table 8 Impact of retinitis pigmentosa on quality-of-life measures
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Overall, 48/122 (39.3%) patients reported taking medications, including Adaptinol [a dark-adaptation-improving agent, 32/122 (26.2%)], isopropyl unoprostone [an ion channel opener, 15/122 (12.3%)], kallidinogenase [a circulatory-disorder-improving agent, 8/122 (6.6%)], and mecobalamin [a therapeutic agent for peripheral neuropathy, 8/122 (6.6%)]. In addition, 32/122 (26.2%) patients reported taking supplements, including lutein [23/122 (18.9%)], vitamin A [8/122 (6.6%)], and vitamin C [6/122 (4.9%)]. Nearly half [25/52 [48.1%)] of the patients in this study reported missing work or school every time they visited a medical institution; 78/119 (65.5%) patients reported requiring an accompanying person and 16/52 (30.8%) patients reported that their caregivers also missed work or school every time they attended a medical appointment.

The VFQ-25 and HUI3 data according to the degree of visual impairment are presented in Tables S4 and S5 in the electronic Supplementary Material, respectively. As measured by the VFQ-25, only 8/122 (6.6%) patients were currently driving, of whom 6/8 (75.0%) had either stopped driving at night or were finding it difficult to do so. Poor vision was reported as the main reason for the discontinuation of driving by 64/65 (98.5%) patients. The correlation between vision impairment measures and QOL measures is shown in Fig. 1. Both VFQ-25 scores and HUI3 scores correlated with physical disability grade, distance vision impairment (WHO), and visual impairment class (AMA) (polyserial correlation coefficients 0.628, −0.599, −0.641, and 0.622, −0.578, −0.536, respectively).

Fig. 1
figure 1

Vision impairment and quality of life scores are correlated in patients with retinitis pigmentosa. AMA American Medical Association, EQ-5D-5L the 5-level EQ-5D version, HUI3 Health Utilities Index Mark 3, SD standard deviation, VFQ-25 Visual Function Questionnaire-25, WHO World Health Organization

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Discussion

The results of this non-interventional, cross-sectional study indicate that the burden of RP in Japan, in terms of financial, social, and QOL impacts, is high. The high direct costs borne by those with RP (for healthcare, vision aids, and home assistance) require many affected patients to apply for financial assistance. At the same time, indirect costs (particularly presenteeism and the loss of job opportunities) reduce employment rates and household income considerably compared with average rates and incomes in Japan, resulting in a salary gap. Employed patients or working patients with RP primarily held professional/technical roles (52.0%), which is similar to the proportion previously reported for the visually impaired in Japan (47.8%) [27]. The second most frequently reported occupation was clerical roles at 28.0%, which is higher than reported for visually impaired Japanese (14.8%) [27] and for workers in Japan (20.7%) [28]. Although it is unclear if the results of our survey represent the actual distribution of occupations among patients with RP, the reported occupations may have had an effect on the degree of productivity loss and the salary gap compared with the general population.

We found that gradings of visual impairment based on physical disability grade, distance vision impairment (WHO), and visual impairment class (AMA) correlated with both the VFQ-25 composite score and the HUI3 overall utility score. However, the EQ-5D-5L index score did not correlate with any visual impairment measures, which is consistent with previous reports [11, 29,30,31]. This may be because there are no vision-specific questions in the EQ-5D. Compared with the published age distribution of patients with Recipient Certificates Issued for Specific Disease Treatment [32], the proportion of young patients in this study appears appropriate (one aged < 18 years), but the proportion of elderly patients was lower than expected. In this study, 45/120 (37.5%) patients reported having a grade 1 physical disability, which is higher than previously reported (9.9%) [5]. Conversely, fewer patients reported having a grade 3 or grade 5 physical disability compared with previous studies [5]. We found that 25/116 (21.6%) patients were graded as “normal” using the WHO definition of distance vision impairment, while grading with the AMA Guides suggested fewer patients with “near-normal” vision (5/122, 4.1%). The reason for this may be that, in the WHO definition, vision impairment is determined by visual acuity, rather than visual field loss. Visual field loss occurs before visual acuity loss in patients with RP, with patients retaining normal visual acuity until the later stages of the disease [1]. However, the length of travel time to reach a specialist may discourage patients with RP from visiting specialists; of the 79 patients who reported visiting a general ophthalmologist, 36 indicated that one-way travel time to general ophthalmologists took less than 30 min (45.6%), whereas traveling to an RP specialist required 1 to < 4 h in 39/64 (60.9%) patients and 4 to < 8 h in 4/64 (6.3%) patients. The number of patients who reported receiving paid care (64/122, 52.5%) was lower than the number of patients who reported receiving unpaid care (87/122, 71.3%). One possible reason for this may be the economic burden of RP, which was found to be 170,742 yen (1701 USD) per patient per year. Although economic support is available in Japan for people with disabilities, 16/122 (13.1%) patients reported that they had not been receiving any financial aid. This may be because these patients had less severe visual impairment; this is supported by the finding that patients without financial aid tended to have higher VFQ-25 scores and vision-related HUI3 scores than those who received financial aid.

In this study, we found a high economic cost for patients with RP, reaching an estimated lifetime cost of 661,253 USD/patient (66,389,827 yen/patient). The total annual cost of visual impairment in Japan (including healthcare, financial, and loss of well-being) has been previously estimated to be 44,484 USD/person [4], which is higher than our estimated annual cost of 7801 USD/patient (783,176 yen/patient); however, our study specifically captured costs for patients with RP, whereas the previous study measured costs for all forms of visual impairment. In addition, we have assessed the costs only for patients with RP and have not included costs borne by the wider society, which would have likely increased the estimated cost of RP. High annual costs of inherited retinal diseases have previously been reported in other countries, including the Republic of Ireland and the UK [40,680 USD/person (27,988 pounds sterling/person) and 36,541 USD/person (25,140 pounds sterling/person), respectively; 0.688 pounds sterling was converted to 1 USD to calculate the USD equivalent of each cost] [33]. In the USA, the direct cost of vision loss has been reported to be higher than indirect costs: one study estimated annual costs of 98.7 billion USD and indirect costs of 35.5 billion USD [34], and an earlier study of a population younger than 40 years estimated direct costs of 14.5 billion USD and indirect costs of 13 billion USD [35]. In contrast, a study in the USA and Canada reported higher annual well-being costs (USA: 8432–20,044 million USD, Canada: 859–3514 million USD) of inherited retinal diseases than economic costs (USA: 4982–11,754 million USD, Canada: 455–1849 million USD); 1.247 Canadian dollars was converted to 1 USD to calculate the USD equivalent of each cost [36]. In China, the annual average direct cost per patient with visual impairment was estimated to be 6989 USD [37], which is comparable to the estimated annual cost of 7801 USD/patient (783,176 yen/patient) reported in this study. However, it is important to note that these previous studies included costs borne by the wider society and costs from other causes of visual impairment, while our study has specifically captured the economic impacts on Japanese patients with RP.

As expected, we found that patients with RP have a reduced QOL, and experience challenges relating to work or school, daily activities, driving, and mental health. This is consistent with prior studies [38,39,40], and highlights the need for new treatments and support to improve the lives of affected patients. Although no disease-modifying therapy for RP exists currently, the gradual progression of symptoms may allow patients time to prepare, through vocational or other forms of training, to improve their QOL. Additionally, some patients are diagnosed with RP at an early age, with a reported average age of onset of autosomal recessive and autosomal dominant cases of 8 and 20 years, respectively [23]. Patients who have lived with visual impairment for most of their life may report fewer impacts to their QOL compared with those with a later onset of disease. These conditions, which differ from those in other diseases that cause visual impairment, may affect the attitudes of patients with RP toward visual impairment.

While the patients in our study reported considerable economic and QOL impacts, we consider that these impacts were likely underestimated. Although no data were gathered regarding the ratio of caregivers to patients, we assumed that each patient had no more than one caregiver. If this assumption was incorrect and some patients had more than one caregiver, this would increase the expected cost per patient from caregiver-related costs. Similarly, the cost of paid care may have been underestimated as 27 patients stated that they received paid care but did not provide information regarding the associated expenses. Thus, any costs of paid care for these patients were not included. Costs related to depression included the cost of suicide and direct medical expenses; however, this might not have accounted for the broader impact of poor mental health on the affected patients and their families. In this study, we used the published cost of depression to calculate both depression and anxiety costs. The cost of depression and anxiety may be similar per patient, as the prevalence of anxiety is estimated to be twice as high as that of depression [41], and in Japan, the reported annual cost of anxiety (20.5 billion USD [41]) is approximately twice that of depression (11.0 billion USD [24]). Therefore, we believe that using the reported cost of depression to calculate the depression and anxiety costs, in the absence of a published cost per person of anxiety, is appropriate. Regarding education costs, we only captured the costs for aids related to education, and there may be other education-related expenses borne by patients with RP. For example, attendance at specialized schools may involve additional patient costs. In addition, four patients reported attending classes and only one was below 18 years of age. This small sample size of patients with RP in education suggests that costs related to inadequate education support were not captured.

There are several limitations of this study. As this study relied on each patient’s self-reported economic and QOL impacts, the data may be affected by recall bias. The study may also have a selection bias, as patients were identified via the JRPS and must have presently or previously had a Specific Medical Expenses Recipient Certificate (for Designated Intractable Diseases) and the sample size was limited. Furthermore, although some respondents were interviewed by telephone, the use of a web-based system may have deterred elderly patients from participating, since they are often less technologically adept compared with younger patients. Accordingly, we recommend that the findings from this study be considered in the context of their internal and external validity.

Conclusions

The economic burden per RP patient was estimated to be 218,520 yen (2176 USD) per year and 18,523,909 yen (184,501 USD) over the patient’s lifetime. In an exploratory analysis (robustness testing), the estimated economic burden per RP patient increased to 783,176 yen (7801 USD) per year and 66,389,827 yen (661,253 USD) over the patient’s lifetime. It was demonstrated that the work productivity, activity, and QOL of patients with RP were all reduced by the effects of the disease.