Motivations and expectations of parents seeking genetic testing for their children with ocular genetic disease

ABSTRACT Background To date, almost 600 genes have been associated with ocular genetic diseases. As these discoveries are made, clinical genetic testing continues to grow and become a more common element in the diagnostic workup of children with blindness and reduced vision. However, few studies have explored the motivations of parents of pediatric patients for pursuing genetic testing or the topics they would like to discuss during their visit. This study explored these gaps in the existing knowledge of clinical care for children with vision loss. Materials and Methods We distributed a REDCap survey to parents of pediatric patients in the Indiana University Ocular Genetics Clinic and through the Foundation Fighting Blindness MyRetinaTracker database to examine factors that motivate families to undergo genetic testing, topics they are interested in discussing, and satisfaction with their current care. Results Parents were primarily motivated by the opportunity to learn about their child’s prognosis, formal diagnosis, and possible treatment options. Parents were most interested in discussing prognosis, adaptations for vision loss, and testing logistics. Parents reported satisfaction with the care received; however, less than half were very satisfied with their understanding of prognosis and the support resources provided. Conclusions Parents seem to be generally satisfied by the care from their ocular genetics team. However, families’ desires are not being fully met, especially with information about prognosis and support resources. As the field of ocular genetics continues to grow, it is important we improve these offerings and optimize care for this patient population.


Introduction
Ocular genetic diseases, such as retinitis pigmentosa, optic atrophy, and congenital glaucoma, account for approximately 50% of all cases of blindness and reduced vision in children (1). Some of these conditions can be more difficult to clinically diagnose than others due to the non-specificity of symptoms (2). According to a study by Branham and Yashar (3), this already difficult patient experience can be further complicated by a lack of information communicated to them throughout the diagnostic process, limited emotional support from providers, and fear for the future. These are gaps in the care that is regularly provided to families of children with an ocular genetic disease. Therefore, it is important to identify what factors influence patient experience and satisfaction in clinic so that medical providers can improve care for this patient population.
The number of genes and variants associated with ocular genetic disease is constantly growing, and to date scientists have discovered almost 600 genes related to ocular disorders (4). These discoveries have allowed for increased ability to find genetic diagnoses for affected families, enabling ophthalmologists and ophthalmological care teams to provide a specific prognosis, as well as offer potential treatments and clinical trial opportunities (2,5). However, these individual treatment options can only be provided after genetic testing has occurred (1).
Multiple studies examining the expectations of adults with ocular genetic conditions have found that, in addition to information about treatment options and recurrence risk, patients are looking for practical information regarding financial support and adaptations for their new lifestyle (6)(7)(8)(9). Two studies conducted in China found that many factors including education, monthly income, disease severity, previous experience with the disease, and potential psychological stress were associated with parental attitudes towards diagnostic genetic testing for children with an ocular genetic disease (10,11). No studies to date have evaluated expectations of parents with children of ocular disorders in the United States.
Early intervention is critical for optimal treatment of ocular genetic conditions, yet not all parents agree to genetic testing for their children (1,11). It is imperative to understand what motivates parents to obtain genetic testing for their children, and to be informed regarding parents' expectations of the testing and the ophthalmology visit in general. This study explores these factors in order to better inform clinicians on how to improve care in this patient community.

Materials and methods
This study was determined to be exempt by the Indiana University institutional review board. All methods were conducted in accordance with the tenets of the Declaration of Helsinki.

Study participants
Parents of patients seen in the Indiana University Ocular Genetics Clinic from 13 December 2018 (when it opened) to 31 October 2021 were invited to participate in the study survey via a phone call and/or email. Patients were contacted three times via phone and/or email over a 3-month period from August 2021 to October 2021. Individuals belonging to two additional support groups, the Center for the Visually Impaired, which is based in Atlanta, GA and the Foundation Fighting Blindness, a national organization based in Maryland, were also invited to participate via an email blast from the support group network. A flyer with information about the study and links to the survey was distributed to all participants. Inclusion criteria included parents of pediatric patients (aged 0-17 at the time of genetic evaluation and/or testing) who were English-speaking and had received genetic counseling and/or genetic testing for an ocular genetic disease.

Instrumentation
The online survey was designed using REDCap, a HIPAA compliant data collection tool (12,13). The opening paragraphs contained information about participation in the survey. Choosing to continue past this section of the survey indicated consent to participate. In addition to demographic information, respondents were asked about their history of and interest in genetic counseling and genetic testing for their children. They were then asked to rank the level of influence (little to no influence, some influence, a lot of influence) that each of the following factors had on their decision to undergo genetic testing or not: prognosis, possible treatment options, family planning, impact on family members' health, family history of genetic eye disease, research participation, doctor recommendation, insurance coverage, out-of-pocket cost, age of the child, and limitations of genetic testing. They were also asked to rate their level of interest (little to no interest, some interest, a lot of interest) in discussing the following topics during their ocular genetics visit: recurrence risk, prognosis, test logistics, pros and cons of genetic testing, future financial support options for child's care, adaptations for vision loss, support in making decisions about genetic testing, emotional support groups, and information about how to discuss a child's diagnosis with him or her.
Parents were then asked how satisfied (not satisfied, somewhat satisfied, very satisfied) they were with the ocular genetics team regarding validation of their concerns, support received during their decision-making process, educational resources provided, understanding of the diagnosis following the visit, and the amount of information provided about their child's diagnosis. The survey ended by implementing the Genetic Counseling Satisfaction Scale (GCSS) originally created by Tercyak et al. (14). The GCSS is a validated instrument consisting of six questions about general patient satisfaction measured using a five-point Likert scale (1 = strongly disagree, 2 = somewhat disagree, 3 = uncertain, 4 = somewhat agree, 5 = strongly agree). The Likert responses to the GCSS were summed to calculate an overall GCSS that could range between 6 (low satisfaction) and 30 (high satisfaction). The entire survey is available in Supplemental Material.
After completing the study survey, respondents were invited to enter their email into a second survey to enter a drawing to win one of five $50 Amazon gift cards. This second survey was separate from the study survey, which allowed participant responses to remain anonymous. The funding for the gift cards was provided by the Indiana University Department of Medical and Molecular Genetics.

Data analysis
A Fisher's exact test was utilized to examine association between categorical variables. Due to the skewed distribution of the GCSS scores (Supplemental Figure S1), individual variables were examined for association with GCSS using a nonparametric Kruskal-Wallis test for each variable alone. Variables tested included satisfaction regarding: support received while making a decision about undergoing testing and validation of concerns by healthcare provider. For these factors we compared somewhat satisfied and very satisfied. We excluded the not satisfied category for statistical analyses of these two factors since only one individual was not satisfied. The remaining variables: support resources provided, understanding of child's ocular genetic disease after the visit, understanding of the prognosis after the visit, and amount of information about child's condition provided were compared for three satisfaction levels (not satisfied, somewhat satisfied, very satisfied). Variables predicting GCSS (p < .10) were then entered simultaneously into one analysis of variance (ANOVA) in order to evaluate the contribution of each variable after adjusting for all variables in the model. Only variables with p < .10 were included in the final model. Means and standard error of GCSS for these variables are adjusted to account for variables included in the final model.

Demographics
Approximately 370 individuals were invited to participate. Data was analyzed from the responses of 59 participants who completed at least 50% of the survey, giving us a response rate of 15.9%. The majority of participants were Caucasian (84.6%, n = 44), and female (82.7%, n = 43). Ages ranged from 23 to 67 years old, with a mean of 38.8 years (standard deviation (SD) = 9.5). The majority were married or cohabitating at the time of their child's ocular genetics evaluation (78.8%, n = 41). Education levels of the participants were spread relatively evenly between some college (27.5%), Associate's degree (17.6%), Bachelor's degree (23.5%), and graduate or professional degree (21.6%). However, there were also some individuals who reported their education level as having some high school experience or having a high school diploma. A majority (57.7%) of individuals reported that they had private insurance at the time of the ocular genetics visit, while 42.3% reported having Medicaid insurance. Out-of-pocket costs for genetic testing ranged from $0 to +$2,500. All demographic information is summarized in Table 1.
The children of the participants were 66.7% male and 31.4% female, and ages of symptom-onset and diagnosis ranged from birth to 18-years-old. The most common diagnoses reported were retinal dystrophies. All diagnoses are summarized in Table 2. Approximately 28.8% of these individuals reported having a family history of an ocular genetic disease.

Uptake of genetic testing
Most children (89.8%; n = 53) underwent genetic testing, and 10.2% (n = 6) did not undergo genetic testing. As shown in Figure 1, most children were tested either at the time of their diagnosis (34.0%) or a few months after their diagnosis (41.5%). Most parents believed that these were the most ideal times for children to undergo genetic testing, with 67.8% believing that testing at the time of diagnosis is best and 22.0% believing that testing a few months after diagnosis is best. All responses are depicted in Figure 1.
Parents were also asked about the factors that influenced their decision to pursue genetic testing for their children. As depicted in Figure 2, the three factors most often reported as having "a lot of influence" were the ability to understand their child's prognosis (93.2%, n = 55), the ability to learn about possible treatment options (87.9%, n = 51), and the ability to establish a formal diagnosis (79.3%, n = 46). These factors were also the top responses chosen when participants were asked to rank the three factors that most influenced their decision. The factors least often reported as having "a lot of influence" were the age of their child (19.0%, n = 11), the possible limitations of genetic testing (25.4%, n = 15), and family planning information (25.4%, n = 15). Responses to all factors are provided in Supplemental Table S1.
Parents who underwent genetic counseling were more likely to pursue genetic testing for their children (Fisher's exact p = .048). Of the individuals who saw a genetic counselor for either pre-and/or post-test counseling (n = 55), 92.7% pursued genetic testing, while 7.3% did not. However, of those individuals who did not receive genetic counseling (n = 4), 50% pursued genetic testing and 50% did not.

Expectations for the ocular genetics visit
Parents were also asked how interested they were in discussing various topics with their ocular genetics care team. As shown in Figure 3, parents most often reported having "a lot of interest" in discussing the prognosis for their child's ocular genetic condition (94.5%, n = 52), practical adaptations for vision loss (61.8%, n = 34), and details and logistics of the genetic testing process (56.4%, n = 31). Some parents also expressed "a lot of interest" in discussing pros and cons of genetic testing (51.8%, n = 29), support in decision making about genetic testing (44.6%, n = 25), information about how to talk to their child about their ocular genetic condition (42.9%, n = 24), recurrence risk (41.1%, n = 23), and financial support options (40.0%, n = 22). Few parents had "a lot of interest" in discussing referrals to emotional support groups (21.4%, n = 12). Responses for all topics are provided in Supplemental Table 2.
When asked which format(s) parents would prefer to receive take-home information, 80.0% (n = 44) reported written information such as letters summarizing the visit, pamphlets, etc. Internet resources such as links to websites or online support groups were desired by 63.6% (n = 35) of individuals. Only 9.1% (n = 5) of individuals were interested in taking home audio information such as recordings or CDs.

Satisfaction
The mean GCSS, measuring level of satisfaction with parents' ocular genetics evaluation, was 26.3 out of 30 possible points (SD = 4.2), meaning that a majority of participants were very satisfied with their experience with the ocular genetics care team. ANOVA revealed that of the various methods of support, the most significant predictor of GCSS was satisfaction with the support resources provided (F(2,44) = 11.3, p < .0001; Kruskal-Wallis p = .0039), in that parents who were "very satisfied" with support resources had higher GCSS scores (mean = 25.1, SE = 1.10) compared to those who were not satisfied with support resources (mean = 19.5, SE = 1.27). Parents who were "very satisfied" with the validation of their concerns by the healthcare provider also had higher scores (mean = 25.1, SE = 0.72) compared to those who were somewhat satisfied (mean = 21.6, SE = 1.57; F(1,44) = 3.8, p = .059; Kruskal-Wallis p = .07). Satisfaction with support received while making a decision about undergoing genetic testing was similarly associated with GCSS scores in that those who were very satisfied had higher scores (mean = 24.6, SE = 1.01) than those who were somewhat satisfied individuals (n = 34) felt very satisfied with their understanding of their child's diagnosis following their visit; however, only 47.3% (n = 26) felt very satisfied with their understanding of their child's prognosis. In fact, 10.9% (n = 6) of parents were not satisfied with their understanding of the prognosis. Parents were less satisfied with the resources provided to them during or after a visit with the ocular genetics care team: 57.4% of parents (n = 31) were very satisfied with the educational resources and 45.5% (n = 25) were very satisfied with the support resources. Approximately 18.0% of parents (n = 10) were not satisfied with the support resources provided to their family.

Comfort talking to their children
When asked about their level of comfort with talking to their children about their ocular genetic condition, 80.0% of parents reported feeling very comfortable having this discussion, 13.3% were somewhat comfortable, and 6.7% were not at all comfortable. The timing of genetic counseling was significantly associated with these comfort levels in parents (Fisher's exact p = .02). Of the people who were very comfortable talking to their children, 55.0% had genetic counseling before and after genetic testing was initiated, compared to 32.6% who only had genetic counseling before and 11.6%  who only had genetic counseling after testing returned. There was no association of comfort with family history of an ocular genetic disorder (Fisher's exact p = .44).

Discussion
This is one of the first studies to elucidate factors that influence parents' decisions to pursue genetic testing, the topics they were most interested in discussing, and their level of satisfaction with their experiences thus far. Almost all parents reported that they were most interested in discussing their child's prognosis and specific diagnosis; these factors were also consistently ranked as having the most influence on the decision to undergo genetic testing. This is consistent with previous studies analyzing the expectations of adults with ocular genetic disease, which revealed that adult patients desired and expected to receive detailed information about the future course of their condition (6,7). However, despite this strong desire, less than half of the participants in our survey reported that they were very satisfied with their understanding of their child's prognosis following their visit. This reveals a significant gap between the information these individuals want to receive and what they are actually receiving. Unfortunately, this study was unable to discern the source of these parents' dissatisfaction. It is possible that this lack of satisfaction stems from the uncertainty of prognosis that can be seen with many ocular genetic diseases due to the fact that the rate and nature of the progression of vision loss can vary based on environmental and genetic factors (15). It is also possible that this dissatisfaction may be related to uninformative genetic testing results. In cases where a molecular diagnosis was not achieved, families may be inherently dissatisfied because they did not receive the answers for their child that they desired. Whatever the source of this dissatisfaction, it is important that we identify and address it to improve parent satisfaction with the information received. In addition to wanting to learn more about prognosis, parents also showed interest in discussing details about the genetic testing process and adaptations for vision loss. A study by McKibbin et al. (8) reported that their participants, adults with inherited retinal disease, were interested in testing logistics as well. They reported interest in knowing exactly what the test would be looking for, how long it would take, how the result would be delivered, and who would deliver that result (8). The interest in discussing adaptive resources was also echoed in previous studies of adult preferences for the ocular genetics visit (7). Beyond the specifics of their diagnosis, patients were also interested in learning about practical information and lifestyle adjustments they will have to make as their vision loss progresses (7). This practical information might include information about learning braille, using a white cane, or adaptations in school and employment for those with reduced vision. Adaptive resources such as these can make a positive impact in the lives of individuals with vision loss, allowing them to maintain their independence and engage in the activities they enjoy (16).
The majority of parents whose children underwent genetic testing indicated they were motivated to pursue testing in order to learn about possible treatment options. This desire to use genetic information to seek out treatment plans was also observed in studies of parental motivations for genetic testing in China (11). Although treatments for ocular genetic conditions are not yet readily available, many gene therapies are currently in clinical trial stages, and one gene therapy product for Leber congenital amaurosis, Luxturna, has been approved for clinical use (17). These exciting developments should be included in the discussion about treatment options for patients with ocular genetic disease.
A rather unexpected result of our study was learning that recurrence risk information for the purposes of family planning was a primary motivator for fewer than a quarter of parents who chose to undergo testing. In fact, over one-third of parents had little to no interest in discussing this risk during their ocular genetics visit. This is in direct contrast with multiple studies about the motivations and preferences of both adults and parents of children with ocular genetic disease in China which noted that having information about inheritance and recurrence risk was important for making informed decisions about reproductive options (7)(8)(9)11). In fact, one study even posited that reproductive age may be an ideal time to pursue genetic testing, a sentiment that was not supported by our data (9). This discrepant outcome could be due to cultural differences. Some of the studies cited above were conducted in China, whereas this study was primarily performed in a large hospital-based clinic in the Midwest. The difference in sentiment could also be due to the fact that some of the above studies focused on adult patients with ocular genetic diseases, who may be concerned about passing the condition on to future children, whereas the parents in the current study were primarily focused on the child who already had the condition.
Another motivator that was surprisingly only endorsed by about one-third of the parents was the impact on the health of other family members, including siblings of the affected child. This largely contrasts the primary motivations of individuals seeking genetic testing in the cancer specialty where patients described a feeling of obligation to undergo testing to provide information for their family members (18). It is possible that the difference between the ocular genetics families and cancer families lies in the fact that genetic testing for a hereditary cancer syndrome often allows for preventative screenings and procedures whereas ocular genetic testing often does not. Nevertheless, it is important for future studies to further analyze the impact of ocular genetic testing on close family members who may also be at risk.
Overall, according to the genetic counseling satisfaction scores, participants reported being satisfied with their experience in the ocular genetics clinic. Almost all participants reported that they were very satisfied with the validation of their feelings by the ocular genetics team, which is a key component of a patient's overall satisfaction with their healthcare experience (16). It is vitally important that healthcare providers continue to validate patient concerns and support them through their time in clinic. It is encouraging to see that almost all parents in our sample were very satisfied by the validation they received thus far.
Despite this overall satisfaction, our participants did not have high levels of satisfaction in all individual aspects of their care. In addition to the lack of satisfaction with their understanding of the prognosis following the visit, participants also had lower levels of satisfaction with the support resources provided to them. Higher satisfaction with support resources was associated with higher GCSS scores; therefore, it is important that we learn where this lack of satisfaction stems from so that we can improve the support resources provided to patients, thereby improving their satisfaction with their experience in the ocular genetics clinic.
While there were many strengths of this study, including representation of a wide range of ocular genetic diseases and ages of symptom onset, there were also some limitations that affect the generalizability of the data. One of the more significant limitations was the fact that the majority of our participants underwent genetic testing. This uneven split between those who pursued testing and those who chose not to pursue testing did not allow us to adequately compare the differing opinions between these groups. The motivations and expectations of those who did not undergo genetic testing cannot be generalized from the data of six individuals. Second, our sample was not especially diverse. The majority of our participants were Caucasian females between the ages of 30 and 39. Finally, this study had a low response rate, and seven individuals did not fully complete the survey. Despite the limitations, these findings are a valuable starting point to gaining a greater understanding of the motivations and expectations of parents of pediatric ocular genetics patients. We hope that this research will lead to larger, more generalizable studies to further the knowledge in this field. Finally, we were unable to differentiate between patients seen in the Indiana Ocular Genetics Clinic and those seen in other clinics who were recruited through support groups; therefore, it was impossible to compare baseline clinical or demographic characteristics between these two recruitment strategies.
Genetic testing for ocular genetic disease is a crucial part of the diagnostic work-up for many patients. The opportunity to pursue genetic testing affords families the ability to empower themselves with information about their family's health and health risks. According to our study, the most important factors motivating families to pursue genetic testing were prognosis, establishing a specific diagnosis, and possible treatment options. Furthermore, during their ocular genetics appointment, families were most interested in discussing prognosis, adaptations to vision loss, and testing logistics. Families were less interested in discussing support groups and recurrence risk. It is vitally important that clinicians consider this information so that they can best meet the needs of the families of pediatric ocular genetics patients. Facilitating discussions with families about the information that they desire will result in more specialized care and foster a supportive and beneficial experience.