Although it is generally known that vision issues are common in individuals with PWS, there are few reports in the literature on prevalence, and an absence of information regarding corrective vision surgeries. This report on data from a cohort of participants within the Global PWS Registry highlights the breadth of vision issues in PWS, as well as the prevalence of corrective strabismus surgery.
Among participants within the Global PWS Registry who have completed the vision survey, the prevalence of strabismus (40 %) is much higher than that in the general pediatric population, which ranges between 2.1 and 3.6 %, depending on race and ethnicity [13,14,15], and also much higher than the prevalence of strabismus among all age groups in the IRIS registry, which contains over 30 million patients (2.75 %) . Previous reports of strabismus among individuals with PWS range from 28 to 95 % . Most recently, a clinical study of the effect of growth hormone therapy on 355 PWS participants reported a strabismus prevalence of 42 %, which is line with the results reported here . That study also showed a statistically higher prevalence of strabismus in individual with PWS by UPD versus those with the deletion subtype (53 % vs. 39 %) . The current study of data from the Global PWS Registry, with almost 3 times the number of subjects, did not confirm this suggested difference in prevalence of strabismus by genetic subtype.
There are several hypotheses for the high rates of strabismus and other vision problems in PWS, including as a consequence of hypotonia, or alterations in typical facial morphology . A 2019 study suggests a positive impact of GH therapy on strabismus, wherein the prevalence of strabismus was significantly lower in PWS individuals who had received GH therapy . However, that study included a relatively small cohort of patients (N = 64), whereas a significant impact of GH therapy on strabismus was not reported in a larger PWS natural history study , nor in the Registry data represented here. Thus, additional data is needed to understand the impact of GH therapy on strabismus incidence and severity in PWS.
For Registry participants who report strabismus, the vast majority are diagnosed under the age of 5 (91 %). The rate of surgery reported here among PWS individuals with strabismus (42 %) is consistent with a prior study where the percentage was 36 % . Both of these rates are much higher than in the general population where only 5 % of people with a strabismus diagnosis received strabismus surgery . In this report, for those participants who received a corrective strabismus surgery, the majority received their first surgery under the age of 5. This highlights that strabismus in PWS starts at an early age and examination by an ophthalmologist should be a pediatric priority in the PWS population. Importantly, 10.1 % of Registry participants who underwent strabismus surgery went on to experience additional strabismus reoperation in the future, a similar rate to that reported in the IRIS registry (6.72 % reoperation within 1 year of strabismus surgery) .
Additional vision issues captured in the Vision survey of the Global PWS Registry include myopia, hyperopia, astigmatism, and amblyopia. Of these, the incidences of hyperopia and amblyopia were higher in this cohort than reported in the general population. Conversely, the prevalence of myopia was comparable to the general population, and astigmatism was lower. Specifically, the prevalence of hyperopia among Registry participants was higher (25 %) compared to the rates found in a meta-analysis of school-aged children (8.4 % among those 6 years old, 3 % among ages 9–14, and 1 % among those 15 years old) , and higher compared to adults over 20 in an NHANES survey (3.6 %) . The prevalence of myopia among Registry participants (overall: 41 %; Deletion: 44.3 %, UPD: 35.6 %) was relatively similar to both a large pediatric cohort in California (42 %)  and to adults over 20 in an NHANES survey (33.1 %) . Interestingly, the prevalence of astigmatism (overall: 25 %; Deletion: 26.9 %, UPD: 19.1 %) among Registry participants was lower than the 41 % previously reported in individuals with PWS  and lower than the prevalence among adults over 20 in a national NHANES survey (36.2 %) .
The prevalence of amblyopia among Registry participants (16 %) was higher than the amblyopia prevalence in the general pediatric population, which is reported to range between 1.5 and 2.6 %, depending on race and ethnicity [13, 14]. This is an important issue for follow up because amblyopia is typically considered an avoidable complication if strabismus is diagnosed early and if effective treatment is provided. It raises questions about the utilization and efficacy of patching in this population, and whether PWS alone predisposes or increases the risk of amblyopia.
The high prevalence of a myriad of eye and vision problems in PWS may have far-reaching consequences. For a population that struggles with obesity due to a combination of hyperphagia (food-seeking behavior), hypotonia (poor muscle tone), and a lower resting metabolic rate, any additional impairments or challenges to physical activity can further contribute to weight gain. Impaired eye coordination or vision can negatively impact simple activities like walking, balance, and exercise. Moreover, impaired vision can impact learning, presenting additional challenges to a population that already faces intellectual disability, as well as cognitive and developmental delays.
The data from the Global PWS Registry may be limited by the self-reported nature of the surveys, however, the fact that the findings from this patient reported outcomes method correlate well with other, more traditional, sources, suggests that this is a generally robust mechanism for collecting this type of data on a large scale, complementing traditional natural history studies, which can be prohibitively expensive.
Finally, this report highlights that screening for and correcting vision deficits early in individuals with PWS is an important part of their clinical care.