Amblyopia—A novel virtual round table to explore the caregiver perspective

A survey aimed to capture the caregiver's perspective on the impact of amblyopia and its treatment on the child and family, as well as caregivers' views on the design and feasibility of clinical trials investigating dichoptic binocular therapies for amblyopia.


INTRODUC TION
][3][4][5] Unilateral amblyopia, the most common cause of monocular visual loss in children, is defined as an interocular difference of two or more lines of VA, with the best-corrected VA in the worse eye ≤0.20 logMAR (equivalent to Snellen VA worse than 6/9.5). 6,77][28][29][30][31] Disease in the non-amblyopic eye can also have a significant impact on earnings and economic stability, 32 with amblyopic patients reported to express feelings of fear and concern regarding the safety of their better eye. 27hile there is limited research on the effect of anisometropic amblyopia on QoL, noticeable ocular misalignment in strabismic amblyopia is associated with negative social interactions and school performance, and an increased susceptibility to psychiatric diseases and depression. 33,34arents of children with strabismus have also reported difficulties in establishing a relationship with their child, and have an increased susceptibility to depression or anxiety. 33Parents of children with both strabismic and anisometropic amblyopia have also expressed feelings of worry that their child may feel different from other children. 35n a recent study, adults with anisometropic amblyopia had received little or no information from their eye care providers about their condition or regarding available treatment options. 27Patients felt there were limited treatment options available to them in adulthood, and expressed uncertainty about the real-life benefit of treatments. 27][44][45] Furthermore, novel and emerging dichoptic therapies for amblyopia embed binocular stimulation in engaging movies and video game play at home, 46,47 and have shown larger improvements after shorter treatment durations (as little as 2 weeks) compared with patching. 47This may serve to circumvent the challenge of non-adherence to occlusion therapy, which can be poor due to the social and psychological effects of having to wear a patch, alongside the impaired vision experienced by the child upon occlusion of their better-seeing eye, which can affect daily activities and social interactions. 26,48,49n view of the QoL impact associated with traditional mainstay amblyopia therapy, patient and caregiver perspectives should be considered when designing and implementing clinical trials for emerging amblyopia treatments.1][52] The EMA's Management Board endorsed an updated patient engagement framework in 2022, which outlined the basis for involving patients and consumers in Agency activities, 51

Key points
• Parents recognised the lifelong benefit of effective amblyopia treatment; however, they highlighted that there is often a lack of a defined treatment plan for managing amblyopia and felt there was inadequate information on the condition provided by eye care professionals or available online or from patient organisations.• Parents communicated that it is difficult for children to understand that wearing glasses and an eye patch should help them in the future, and emphasised that amblyopia treatment poses more of a burden on the child and family than the condition itself.Treatment burden is exacerbated with unsuccessful treatment outcomes.• Parents reported that a new treatment for amblyopia should be safe, non-invasive and more comfortable (skin-friendly) than an adhesive eye patch.Treating at home, potentially for a shorter duration, and with a game that entertained their child were the main reasons parents would join a clinical study for an emerging dichoptic binocular therapy.
while the FDA's patient-focused drug development (PFDD) initiative aims to ensure that the patient experience of disease and treatment becomes an integral component of regulatory filing, drug development and regulatory review. 506][57] Parents can also develop ongoing and genuine interactions with study teams, providing an opportunity to elicit valuable insights into factors that influence parental decisions to participate in clinical research 57 and the parents' comprehension of the trial, which may differ from that intended by the practitioners responsible for recruitment. 58A number of methods are employed for assessing the patient or caregiver experience for various eye conditions, including amblyopia.These include qualitative interviews, 59,60 quantitative questionnaires 29,61,62 and social media listening studies. 63,64n addition, virtual global advisory boards have been recently utilised to successfully capture insights of patients living with presbyopia and dry eye disease. 65,66In a similar manner, this caregiver survey used a virtual advisory-board platform to conduct interactive, moderated, structured discussions between caregivers of amblyopic children, patient advocates and healthcare professionals (HCPs) to better understand the patient and caregiver journey in amblyopia, as well as the impact of amblyopia treatment on the child and family.The caregiver survey further aimed to capture the caregiver's perspective on the design of clinical trials investigating dichoptic binocular therapies for amblyopia, which would provide valuable insights for the development of future clinical trials.

Participants and discussion platform
Parents of children with amblyopia, patient advocacy group representatives and HCPs were invited and included in the caregiver survey.Parents were recruited through their HCPs and from eye health-focused patient advocacy groups, with the goal of including caregivers of children who had received or are currently receiving treatment for a formal diagnosis of amblyopia.HCPs were identified based on internationally recognised expertise in the field of amblyopia and peer-reviewed publications on the subject, with the aim of participating HCPs representing the perspectives of ophthalmologists and optometrists.All participants were informed of the objectives of the project and future use of the results, and provided written, informed consent to take part in the round-table discussion.Participants were remunerated according to local fair market value guidelines. 67rior to the discussion, all participants joined an initial 30-min call to explain the purpose of the caregiver survey, introduce the virtual advisory-board platform (Within3, withi n3.com) and demonstrate how to navigate the platform.Parents were furthermore provided with information and presentations on amblyopia (background on the condition including cause, patient population, available therapies and impact on QoL), a description of dichoptic stimulation and summary of different binocular dichoptic treatments for amblyopia, an overview of the clinical research process and stages of clinical trials and potential designs of planned Novartis clinical trials in this area (including study objectives, eligibility criteria, study design and a description of what typical study visits and tests would entail).
The structured discussion took place on Within3's online discussion platform over 14 days in September 2021.The session moderator, an independent patient engagement consultant, posted initial questions but did not take part in the subsequent discussions.The moderator had access to patient responses and could provide clarification, probe for additional information or suggest that parents seek feedback from their children where appropriate.HCPs did not participate in answering the structured questions but answered questions from parents as guided by the moderator and provided expert clinical knowledge when necessary.The platform was available 24/7 during the 2-week period, thus ensuring convenience for participants.Automatic translation allowed all respondents to post and read other posts in their native language, enabling richer conversations and diverse representation.

Discussion topics and analysis
Key topics explored in the round-table discussions included the patient and caregiver lived experience of amblyopia and its treatment, the impact of the condition on the child and caregiver views on emerging alternative treatments and clinical trial designs.All responses and comments were visible to participants, who could provide input at any stage during the discussion period.
A combination of open and closed questions was used to initiate participant discussions.Examples of closed questions included 'Have you or your child ever participated in clinical trials for any condition?' or 'What is most important to you, measuring how well your child can see with the amblyopic eye (VA) or how well both eyes work together (stereoacuity)?' Open questions were used to elicit information on matters such as 'How could clinic visits be made easier for parents/carers and children with amblyopia?' and 'Can you explain how satisfied you are with the overall management of your child's amblyopia?' Transcripts were downloaded and analysed to identify patterns in the data, which were coded into categories and labelled in a manner to capture the general meaning of the identified patterns.All data were analysed thematically. 68s this was a qualitative caregiver survey involving thematic analysis, a priori hypothesis was not tested.Closed question results were presented numerically.Representative quotes from the participants are shown.

Participant characteristics
Seven female parents of children with amblyopia participated in the caregiver survey.Parents were from the United States (n = 1), Australia (n = 1), Ireland (n = 1), Japan (n = 1), Brazil (n = 1) and Germany (n = 2).The age of their children ranged from 7 to 15 years and the age of amblyopia diagnosis from 2 to 5 years.Four out of the seven children were female.Two parents reported having amblyopia themselves.Over the round-table period, a total of 645 posts were entered on the platform.
Although the child of each parent had a confirmed diagnosis of amblyopia and thus met the inclusion criteria, the survey team decided to exclude the views and insights from one parent, from Brazil, in the thematic analysis, as they disclosed during the round-table discussions that their child was diagnosed with reduced vision and difficulty fixating due to a retinoblastoma in one eye.Thus, from diagnosis to treatment and follow-up, the process of care for this child was different from the other six children who were diagnosed with amblyopia due to anisometropia or strabismus.
Participating HCPs included one ophthalmologist and one paediatric optometrist.Two patient advocates were also included, bringing experiences and insights from their respective patient communities.They were associated with the National Alliance for Eye and Vision Research (NAEVR/ AEVR) and the International Agency for the Prevention of Blindness (IAPB).Both HCPs and one of the patient advocates are authors on this manuscript.

Understanding the patient and caregiver journey in amblyopia
Parents reported noticing a variety of signs and symptoms prior to their child being diagnosed with amblyopia.These included the eye turning in, eye squinting, head tilting, eye rubbing, tiredness after schoolwork, excessive clumsiness, poor hand-eye co-ordination and failure to excel in ball sports.
Ophthalmologists were the first professional contact and treatment decision-makers in five of the six cases, and full-time spectacles (n = 5) as well as patching (for a range of 1-4 h daily) (n = 4) was the initially prescribed treatment in most cases.Parents communicated that a diagnosis of amblyopia can be emotionally 'overwhelming' and expressed worry that reduced vision in one eye could restrict their child in terms of reading or driving later in life.Both parents with amblyopia also expressed feelings of guilt that their child may have inherited the condition from them.
Following diagnosis, parents felt there was a lack of a definite or defined treatment plan for their child's amblyopia and reported there was limited information provided by their HCP on long-term outcomes or newer therapeutic options for amblyopia.The majority of parents expressed uncertainty and frustration in relation to the duration and success of patching and alternative treatment options.
Left not really knowing what was happening; it was very much let's try this and see what happens next.
Although parents felt that HCPs are highly trusted sources of information, they expressed a need for information from HCPs in lay language, with most participating parents communicating that the medical terminology used by HCPs was difficult to understand.
Information in easy-to-understand flyers would be great [to aid understanding of the diagnoses].
Parents also highlighted the lack of patient support groups and organisations, and felt it was difficult to find reliable information online.One parent reported obtaining support from a local non-profit organisation and endorsed the highly valuable screening and treatment support they received as a family.The remaining parent felt they would benefit from a support website with child-friendly information and noted educating parents plays a major role in understanding the condition, its therapy and potential treatment outcomes.
Post-diagnosis, parent satisfaction with amblyopia management differed depending on the success of treatment.Parents of children whose VA improved with treatment (n = 3) tended to be pleased with the management plan set forth by their eye care professional.I am satisfied because [his] eyesight was maintained and the treatment with the eye patch is finished and was successful.
In contrast, parents of children who showed little improvement (n = 3) appeared frustrated and dissatisfied with the treatment.
No improvement in the years and child very unhappy, constant asking to [take] patch off.
Parents communicated that it is difficult for a young child to understand that wearing glasses and an eye patch should help them in the future, with children often reluctant to follow a therapy when there is no success within a reasonable time frame.
Demotivating when wearing the glasses and eye patching never helped [to improve vision].Patching the healthy eye was exhausting and child often tearful.However, in general, parents are motivated to do whatever it takes and for however long it takes to improve their child's eyesight and noted that early education and acceptance that treatment is long-term is important.
Every parent is motivated to do whatever it takes and for however long it takes to improve their child's eyesight.

The burden of treatment on the child and caregiver
Parents specified that, in general, their child did not notice their eye condition but found the treatment more of a burden.Comments from participants included their child being bullied/teased for wearing glasses, their child reporting feeling ugly or self-conscious wearing the patch and glasses and that the child constantly removed their eye patch.

My daughter has faced teasing wearing her glasses [and is] very self-conscious of this.
Treatment can also be challenging and overwhelming for parents, who are burdened by the constant vigilance in ensuring that their child is patched and wearing their glasses properly.The burden of treatment reported by parents also included the time required attend appointments and the cost of glasses, with parents noting glasses were often lost, broken or ill fitting.
Time required [for appointments and patching] was immense in the first few years.
However, the burden of treatment appeared to lessen when improvements in vision were observed, with one parent noting: His eyesight has improved substantially so the emotional burden is far less than it was when we first found out [and he then] accepted the patch without too much push-back.

Caregiver perspectives on emerging dichoptic binocular therapies and clinical trial designs
The most important result that parents would like to see from amblyopia therapy is an improvement in the VA of the amblyopic eye, followed by improvements in binocular vision and stereoacuity (Figure 1).More specifically, four of the six parents felt measuring best-corrected VA was more important than examining their child's stereoacuity (two of six parents).
One parent noted that treating amblyopia and improving the VA of the amblyopic eye was important in the event of vision loss in the better-seeing eye.Parents recognised that improvements in stereoacuity, hand-eye coordination and fine motor skills should increase their child's ability and confidence when performing sporting activities and other daily life tasks.One parent further noted that parents and patients should be educated on the relationship between stereopsis and vision-related QoL.
Parents reported that a new treatment for amblyopia should be safe, non-invasive and more comfortable (skinfriendly) compared with an eye patch.Treating at home, potentially for a shorter treatment duration, and with a game that entertained their child were the main reasons parents would join a clinical study for an emerging dichoptic binocular therapy.However, the majority of parents communicated they were apprehensive about trying alternative treatments to patching, due to a limited treatment window within the critical period.
My concern would be if therapy is not working does it delay other treatments.
In view of this, parents highlighted they would feel more comfortable joining a clinical trial for a new dichoptic binocular therapy if patching had failed, or if the new treatment was explored as a combination treatment alongside traditional therapy.
I would only want to join the trial if it were an add-on to the traditional patching.
A minority of parents were also concerned about the overuse of digital devices, especially in younger children.One parent highlighted that, in general, there is a conception that screens negatively affect the eyes and children already spend too much time on devices.

I'm worried [about] a short-distance screen, [potentially causing] symptoms such as double vision and dry eye.
In terms of participating in a clinical trial, parents noted that the duration of study visits, number of visits and time spent travelling to appointments were important considerations, with two parents expressing concern regarding the burden of such time commitments on families, alongside the time required to supervise adherence to the dichoptic binocular treatment.In general, parents felt nine 2-h clinic visits were acceptable within 1 year, in a child-friendly, interactive clinic environment.
All parents specified that clinical trial visits, as well as any patient-facing materials and information, should be interesting, engaging and motivating for the child.In order to enhance adherence to treatment, parents specified that the dichoptic therapy game should be fun and enjoyable, and suggested to offer treatment sessions in smaller time blocks if possible (e.g., 1 h/day split into two 30-min sessions).Digital/electronic reminders and a treatment adherence rewards system for the child were also proposed to aid compliance.The option to have regular exchanges with a study coordinator throughout the clinical trial, via a clinical trial support line, was also advocated by parents.

DISCUSSION
Understanding caregiver experiences of amblyopia and its treatment on the child and family, as well as their perspectives on the design and conduct of clinical trials for amblyopia could potentially help in optimising disease management.2]69 To our knowledge, this is the first report of such an interactive, moderated discussion of caregiver perspectives on these aspects.The virtual platform, available 24/7 for a 2week period, enabled the inclusion of diverse perspectives from caregivers across geographies, which may not have been feasible with a traditional, in-person format, particularly as this information was collected during the COVID-19 pandemic.Automatic translation and the interactive format, with all responses and comments visible to all participants and the ability of the moderator to probe for additional information, allowed for more detailed insights and provided context that would not be available using a standard questionnaire.In addition to being relevant to HCPs and the wider amblyopia community, these findings are useful for clinical researchers planning studies in innovative therapies for amblyopia, or qualitative researchers hoping to utilise a similar interactive virtual format.
Parents in our caregiver survey emphasised that the management of amblyopia can pose more of a burden on the child and family than the condition itself. 27,70,71Similar to findings of previous studies, QoL implications of amblyopia typically relate specifically to its treatment, which can impact family life, social interactions or the ability to perform daily activities, as well as feelings and behaviour. 26onsistent with our findings, Koklanis et al. also found patching and glasses were associated with bullying and feelings of self-consciousness and embarrassment among children, 70 while Searle et al. 71 reported that many parents also experience distress related to patching.However, a more recent study found more mixed results, 35 with parents reporting that although treatment can be a source of conflict with their child, it was not significantly associated with social stigma.The absence of social stigma in a more recent study may be because treatment regimens prescribed were less intense than those used in previous studies of younger children and can be potentially carried out at home, since the results from the Pediatric Eye Disease Investigator Group (PEDIG) randomised trials demonstrated that, in cases of moderate amblyopia, patching children for 2 h/day produced the same visual gains as a prescribed dose of 6 h/day 6 ; and in cases of severe amblyopia, 6 h/day patching was as effective as full-time patching. 7Thus, fewer hours of daily patching, or splitting F I G U R E 1 Parents ranked best-corrected visual acuity (BCVA), stereoacuity, binocular vision, ocular alignment and improvement in the performance of daily tasks in the order of the most to the least important result they would like to see from an amblyopia therapy.
patching into shorter periods, for example two 3-h sessions between home and school in more severe cases of amblyopia, should ease the implementation of patching therapy and aid compliance.It should also be noted that treating amblyopia is highly cost-effective compared with other interventions in healthcare, due to the long-lived benefit of improved VA, binocularity and QoL. 32,40Furthermore, lost income from amblyopia, estimated at more than $7 billion/ year in the United States, is substantially higher than the cost of amblyopia treatment, which is estimated as $341 million/year. 32,72hile traditional therapies for amblyopia have been well studied and can be efficacious, suboptimal adherence is one of the main limitations associated with current modalities. 43,73,74However, even with good compliance, there are cases where amblyopia does not fully with patching and a residual interocular difference in VA remains. 36t is therefore unsurprising that in this caregiver survey parents expressed that a new dichoptic binocular therapy for amblyopia should be entertaining and engaging.Rapid advancements in technology have generated considerable interest in the use of dichoptic binocular movies and games as a potential treatment for amblyopia. 37,46,75oor adherence is a known risk in home-based studies, 76 and compliance with many earlier binocular treatments was a concern, due to a lack of interest in the dichoptic games, [77][78][79] with one investigation demonstrating that children had significantly lower gain in VA if their compliance was <50%. 80However, more recent randomised trials have reported better compliance, and also found a significant improvement in VA in the binocular training group compared with patching cohorts. 47,78,81t is interesting to note that most parents indicated they were apprehensive about trying alternative treatments to patching, due to the limited treatment window within the critical period of vision development, and would feel more comfortable joining a clinical trial for a new dichoptic binocular therapy if patching had failed, or if the new treatment was explored as a combination therapy alongside traditional treatment.This raises the question as to whether it would be possible to recruit a representative study population for such a trial to ensure that study outcomes were generalisable to all children with amblyopia, and is a point for consideration in the design of potential trials of novel amblyopia treatments.
In a recent study, adults with anisometropic amblyopia reported having received little or no information from their eye care providers about their condition or regarding available treatment options. 27Similarly, parents in our caregiver survey felt they were provided with limited information from their HCP and highlighted the lack of patient support groups and organisations for families living with amblyopia.Knowledge inadequacy among parents about child eye health will not only impact the lack of understanding of the importance of early detection and intervention, 82 but is of particular concern given the influence parents/ caregivers have on the child's behaviour and choices and in the acceptance of any interventional treatments. 61ducational background, socio-economic status and language barriers are also important considerations that can affect critical aspects of research studies such as enrolment, follow-up and adherence to study procedures.It was encouraging that parents in our caregiver survey appeared committed and motivated to make every effort to improve their child's eyesight, as this will ultimately benefit paediatric eye care, with benefit to their child previously recognised as the most important factor influencing a parent's decision to participate in paediatric clinical research. 57

Strengths and limitations
The strengths of this caregiver survey included using a qualitative method of data collection, which can supplement and provide additional insights to the structured data obtained from quantitative methods such as questionnaires.The novel virtual engagement platform offers numerous advantages versus traditional videoconferencing options, and allowed participants from across geographies to engage in a rich and robust discussion at a time that was convenient for them, with direct language translation.This resulted in obtaining a rich qualitative dataset/transcript over a short period of time.Utilising a user-friendly online platform during the COVID-19 pandemic was especially appreciated by participants.
In terms of limitations, a small number of self-selected participants (all female) took part in the caregiver survey, who may have been more interested and proactive in treating their child's amblyopia.Thus, participants may not adequately represent the experiences and views of all caregivers of amblyopic children.However, the inclusion of patient advocacy group representatives from the IAPB's global community (the overarching alliance for the global eye health sector, with more than 150 organisations in over 100 countries) and NAEVR (a coalition of 50 professional, patient, consumer and industry organisations involved in eye and vision research) sought to incorporate representation of a wider range of views and more robust feedback.Furthermore, the two participating HCPs presented their own views and interpretation of the medical situation, which may not always represent consensus views among eye care providers globally.Although a number of questions in our caregiver survey were structured, the qualitative statements cannot be quantified and the findings will need to be confirmed in further patient engagement activities, preferably using a number of different research methods.Activities that seek to gain feedback directly from children and teenagers living with amblyopia would also be beneficial, as the round-table discussion in this caregiver survey mainly focused on the caregiver perspective.

CONCLUSION
Understanding how amblyopia and its treatment impacts a child's QoL, as well as their families, should be an important premise to guide and evaluate treatment value, both in clinical trials and in routine clinical practice.Parents in our caregiver survey emphasised that the management of amblyopia can pose a greater burden on the child and family than the condition itself.Thus, efforts to minimise any negative emotional and physical associations of treatment should be considered by clinicians and researchers.Patient perspectives and the role of caregivers in the acceptance of any interventional treatments are increasingly recognised, and should be considered when designing and implementing clinical trials for emerging amblyopia treatments.This can serve to enhance recruitment practice, clinical trial retention and implement a methodology designed to improve patient experience, which will ultimately benefit evidencebased paediatric eye care.

AC K N O W L E D G E M E N T S
Medical writing support under the guidance of the authors was provided by Saoirse McCrann, PhD, and Susan Browne, PhD, both of Novartis Ireland Ltd., in accordance with Good