Abstract
PURPOSE:
Children with autism spectrum disorder and intellectual disability often cannot tolerate wearing spectacles or contact lenses, which are the standard-of-care for treating ametropia.1,2 We aimed to assess the impact of refractive surgery on social functioning and vision-specific quality-of-life (VSQOL) in this population.
DESIGN:
Prospective, before-and-after case series.
METHODS:
Setting:
Single, academic tertiary care center.
Study population:
18 children with autism spectrum disorder and/or intellectual disability, ametropia, and spectacle nonadherence were included in the analysis.
Procedure:
Participants underwent refractive surgery with either intraocular lens implantation or keratectomy. Parents completed the Social Responsiveness Scale (SRS-2) and Pediatric Eye Questionnaire (PedEyeQ) at baseline and 1, 6, and 12 months postsurgery.3,4
Main outcome measures:
Median change in SRS-2 T-scores and PedEyeQ scores 12 months after surgery, compared to baseline. The minimum clinically important difference was set at 5 points for the SRS-2 and 10 points for the PedEyeQ.
RESULTS:
At 12 months after surgery, statistically significant improvements were observed in the SRS-2 domains of Social Awareness (8 points, 95% CI 2–13, P =.03) and Social Motivation (7 points, 95% CI 2–15, P =.03). Total SRS-2 T-score improved in a clinically important manner for 56% (10/18) of patients, but the median change was not statistically significant (5 points, 95% CI −1 to 9, P =.10). VSQOL showed statistically significant improvements in the domains of Functional Vision (40 points, 95% CI 7–73, P =.02) and Bothered by Eyes/Vision (23 points, 95% CI 3–45, P =.02).
CONCLUSIONS:
Refractive surgery led to clinically and statistically significant improvements in domains of social functioning and VSQOL at 12 months after surgery. A narrow majority of patients demonstrated a clinically important improvement in overall social functioning, but these changes were not statistically significant. The results suggest that refractive surgery in children with neurodevelopmental disorders, ametropia, and spectacle nonadherence may provide developmental and quality-of-life benefits. Larger, controlled studies are required to validate these findings.
INTRODUCTION
The prevalence of visual disorders including ametropia, strabismus, and amblyopia is higher among children with neurodevelopmental disorders (NDD).1,2 This report focuses on children with intellectual disability (ID) and/or autism spectrum disorder (ASD), which affects approximately 2% to 5% of children in the United States.3,4 The standard-of-care for managing ametropia is spectacle correction. However, a significant subset of these children, many with visual impairment (VI, visual acuity worse than 20/60), cannot tolerate spectacle wear.5,6 Uncorrected ametropia, secondary to spectacle nonadherence, places these children at risk for irreversible vision loss from refractive amblyopia and results in additional developmental burden due to VI.
The association of VI and abnormal development is well established in the literature.5,6 In a Swedish retrospective study of 150 congenitally blind children, 53% had ID and 31% had ASD, a prevalence rate that is 30 times higher than that of visually-normal children in the same population.7 Longitudinal cohort studies support the hypothesis that VI contributes to poor developmental outcomes, especially among children with existing NDDs. In a 1997 mixed prospective/retrospective study of 186 children with VI, including 39% with concurrent ID or developmental delay, the Battelle Developmental Inventory was used longitudinally to calculate developmental growth curves from age 1 to 4 years.8 Developmental trajectory varied with the degree of visual function and the presence of co-occurring disabilities, such as ID. ID and VI were found to decrease developmental growth in an additive manner, supporting the hypothesis that children with both ID and VI suffer from a dual impairment of development. A 2002 retrospective cohort study of 69 children with ‘simple’ congenital disorders of the peripheral visual system used the Reynell–Zinkin scales to measure developmental trajectory and the Near Detection Vision scale to assess visual acuity between ages 10 to 16 months and 27 to 54 months.9 Participants with profound VI were at higher risk than those with severe VI for global learning difficulties, developmental delay, and developmental regression between the two timepoints.10 VI can thus be understood to impair developmental growth and, when comorbid with an existing NDD, compound psychosocial disability.
The correction of visually significant ametropia in children with NDDs may benefit their developmental outcomes. A 1980 study found that provision of new spectacles to 75 children with ID and uncorrected ametropia led to greater improvements in social behavior and motor skills when compared to 212 controls provided Plano spectacles or no spectacles.11 In recent years, refractive surgery has been shown to successfully treat refractive error in children and evaluated as a treatment option for ametropic, spectacle nonadherent children at risk for refractive amblyopia.12 In a nonrandomized, uncontrolled trial of intraocular collamer lens implantation in 13 spectacle nonadherent children with NDDs, our group found that 85% of patients exhibited improved visual awareness, attentiveness, or social interactions after surgery, as reported by an unmasked, non-parent observer using an nonvalidated assessment of social behavior.13 A recent study of photorefractive keratectomy in 16 children with severe isoametropia, ID, and spectacle nonadherence showed clinically important improvements in communication and interpersonal skills 6 months after surgery, using the Vineland Adaptive Behaviors Scale II, a behavioral assessment tool.14
The objective of this pilot study was to quantify changes in social functioning following refractive surgery in a prospective, nonrandomized cohort of children with ID and/or ASD, visually significant ametropia, and spectacle nonadherence. We hypothesized that social functioning, as measured by the Social Responsiveness Scale, 2nd Edition (SRS-2), would improve after refractive surgery.15 We also investigated changes in vision-specific quality-of-life (VSQOL), refractive error, and visual acuity as secondary outcomes. Our results build upon a prior publication that reported improved VSQOL 1 month after refractive surgery in a subset of the cohort used in the present study, but which did not analyze changes in social functioning.16
METHODS
This prospective, before-and-after case series took place at a single tertiary academic medical center. Participants were children planning to undergo refractive surgery between December 2020 and December 2023. Inclusion criteria were: (1) age 3 to 18 years, (2) community clinician diagnosis of ID or ASD documented in the electronic health record, (3) moderate to high refractive error,17 and (4) nonadherence to prescribed spectacle, and contact lens wear for at least 1 year. Refractive surgeries performed included keratectomy (photorefractive or limbal relaxing incision), phakic intraocular lens implantation, and clear lens exchange.
This study received approval from the Washington University Human Research Protection Office (IRB #202001151), ensuring that all procedures and protocols adhered to ethical standards for research involving human subjects. The research conducted in this study adhered to the tenets of the Declaration of Helsinki, ensuring the ethical treatment and protection of all participants. Informed consent was obtained from each participant’s parent or legal guardian prior to their inclusion in the study and verbal assent was also secured from the participant when appropriate. No patients were able to self-consent due to age and limited capacity.
Two questionnaires were administered to each participant’s parent/caregiver before surgery and at 1, 6, and 12 months after surgery: (1) the SRS-2 and (2) the Pediatric Eye Questionnaire (PedEyeQ).15,18 The SRS-2 quantifies social impairment involving autistic traits (ie, aspects of social communication impairment and restricted interests and repetitive behaviors) on a continuous scale, providing a total T-score and five subscale T-scores with a mean of 50 and a standard deviation of 10, based on a representative normative sample. Lower scores correspond to better social functioning relative to these traits. The SRS-2 treatment subscales, which can be used to design and evaluate treatment programs, consist of Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests, and Repetitive Behavior. Responses with > 20% of items unanswered were considered invalid and excluded from the analysis. For valid responses, unanswered items were imputed with the sample’s median presurgery value for the item, as recommended by the instrument publisher. The PedEyeQ evaluates VSQOL in children. We utilized the Proxy and Parent forms, which evaluate the parent’s perspective on the child’s vision and the parent/family experience, respectively. Higher scores represent better VSQOL. Domain raw scores were computed using all answers provided. Rasch scores, adjusted to a scale from 0 to 100, were determined for each domain of the PedEyeQ using the published reference tables. An additional questionnaire, the Adaptive Behavior Assessment System, Third Edition (ABAS-3), was used to assess baseline adaptive functioning but was not analyzed longitudinally. The ABAS-3 provides standardized scores, with a mean of 100 and standard deviation of 15, in three adaptive domains and for a General Adaptive Composite.
Participants’ demographic and clinical characteristics were derived from the electronic health record retrospectively, including from standard-of-care eye examinations before and 1, 6, and 12 months after surgery. Refractive error was assessed using retinoscopy or autorefraction. Visual acuity was measured using Snellen charts, then converted to Logarithm of the Minimum Angle of Resolution (Log-MAR) for analysis. As refractive error and Snellen visual acuity measurements are dependent on patient cooperation and not conducted at every visit, we report these outcomes using pooled data from 6 to 12 months after surgery. Myopia was defined as spherical equivalent ≤–1 diopter, hyperopia as spherical equivalent ≥2 diopters, and astigmatism as cylinder ≥2 diopters. The goal refractive error after surgery was spherical equivalent within 1 diopter of Plano.
The primary outcome measure was the change in SRS-2 T-scores at 12 months after surgery compared to baseline. Secondary outcomes were: (1) change in the SRS-2 T-scores at 1 and 6 months after surgery and (2) change in the PedEyeQ Rasch scores at 1, 6, and 12 months after surgery. The minimum clinically important difference was set for the SRS-2 at 0.5 standard deviations (5 points when using T-score, equivalent to a moderate Cohen’s d effect size) and for the PedEyeQ using the difference between the maximum score (100 points) and the 5th percentile of normal thresholds reported by Leske.19–21
Descriptive statistics were presented as medians with interquartile ranges. For inferential statistics, the Wilcoxon matched-pair signed-rank test was used for within-sample comparisons, and the Kruskal–Wallis test was used for between-sample comparisons. Pearson correlation was employed to examine linear associations between continuous variables. Analyses were performed using IBM SPSS Statistics for Windows (Version 29.0: IBM Corp).
RESULTS
Demographic and clinical characteristics:
The analysis dataset consisted of 18 participants who completed the SRS-2 at baseline, underwent refractive surgery, and repeated the SRS-2 at 12 months after surgery. A total of 12 patients meeting inclusion criteria were excluded: 7 did not complete the baseline SRS-2, 2 aged out of the cohort prior to surgery, 1 did not undergo surgery, and 2 did not complete the SRS-2 at 12 months postsurgery. No difference was detected in clinical or demographic characteristics between those who were included/excluded in the analysis. The 18 participants in the analysis dataset were 83% male, 17% female, 11% Black race, 6% Hispanic or Latino ethnicity, and 89% White race. Neurodevelopmental disorder diagnosis was ID in 83% (15/18) of participants, ASD in 72% (13/18), and both ID and ASD in 56% (10/18). 15/18 (83%) participants completed the ABAS-3 before surgery. Median baseline ABAS-3 adaptive domain percentiles were 0.2 (IQR 0.08–1) for General Adaptive Composite, 0.3 (IQR 0.1–0.6) for Conceptual, 1 (IQR 0.3–12.3) for Social and 0.1 (IQR 0–2) for practical nonrefractive ocular conditions included strabismus in 78% (14/18) of participants, amblyopia in 89% (16/18), optic neuropathy in 22% (4/18), and cortical VI in 22% (4/18). The types of ametropia treated with refractive surgery included combined myopia/astigmatism (40%, 14/35 eyes), combined hyperopia/astigmatism (3%, 1/35), hyperopia only (31%, 11/35), myopia only (17%, 6/35) and astigmatism only (9%, 3/35). The median age at the time of surgery was 7.9 years (range 3.7–18.0). 94% (17/18) of participants had both eyes treated, using the same surgical technique in each eye, and 6% (1/18) had only one eye undergo refractive surgery. The surgical technique used was phakic intraocular lens implantation in 51% (18/35) of eyes, keratectomy in 43% (15/35), and clear lens exchange in 6% (2/35) (Table 1).
TABLE 1.
Participant Characteristics
| Demographics | n = 18 Participants |
|---|---|
| Age at surgery, y (median) | 7.9 (range 3.7–18.0) |
| Female | 3 (17%) |
| Male | 15 (83%) |
| Black | 2 (11%) |
| Hispanic or Latino | 1 (6%) |
| White | 16 (89%) |
| Developmental disorders | n = 18 participants |
| Intellectual disability | 15 (83%) |
| Autism spectrum disorder | 13 (72%) |
| Cerebral palsy | 8 (44%) |
| Attention-deficit hyperactivity disorder | 8 (44%) |
| Genetic disorder confirmed or clinically suspected | 10 (56%) |
| Baseline adaptive functioning percentilea | n = 15 participants |
| General adaptive composite (median) | 0.2 (IQR 0.08–1) |
| Conceptual (median) | 0.3 (IQR 0.1–0.6) |
| Social (median) | 1 (IQR 0.3–12.3) |
| Practical (median) | 0.1 (IQR 0–2) |
| Ametropia type | n = 35 eyes |
| Myopia and astigmatism | 14 (40%) |
| Hyperopia and astigmatism | 1 (3%) |
| Hyperopia only | 11 (31%) |
| Myopia only | 6 (17%) |
| Astigmatism only | 3 (9%) |
| Refractive surgery type | n = 35 eyes |
| Phakic intraocular lens implant | 18 (51%) |
| Keratectomyb | 15 (43%) |
| Clear lens exchange | 2 (6%) |
| Other visual disorders | n = 18 participants |
| Strabismus | 14 (78%) |
| Amblyopia | 16 (89%) |
| Optic neuropathy or dysplasia | 4 (22%) |
| Cortical visual impairment | 4 (22%) |
IQR = interquartile range.
Measured with Adaptive Behavior Assessment System, Third Edition. Percentile scores reported as median (IQR). Higher percentiles indicate better adaptive functioning.
Keratectomy techniques included photorefractive keratectomy and limbal relaxing incisions.
Refractive error and visual acuity:
The median absolute spherical equivalent was 5.3 (IQR 3.3–8.8) diopters at baseline (n = 35 eyes), 1.0 (IQR 0.5–1.1) diopters at 1 month after surgery (n = 21 eyes), 1.0 (IQR 0.8–1.5) diopters at 6 months after surgery (n = 27 eyes), and 0.8 (IQR 0.5–1.1) diopters at 12 months after surgery (n = 18 eyes). Using the last refractive measurement available at least 6 months after surgery, 72% (21/29) of eyes met the treatment goal of 1 diopter within Plano, and a further 21% (6/29 eyes) were outside of the treatment goal but within 2 diopters of Plano. 1 participant (2/29 eyes) had a large reduction in refractive error but experienced hyperopic regression and did not meet our treatment target at 6 and 12 months after surgery (Figure 1). Five participants (9 eyes) were tested using Snellen visual acuity charts at baseline. A total of 13 participants could not participate in Snellen visual acuity testing due to disability or limited cooperation. The median LogMAR, converted from Snellen visual acuity, was 0.42 (IQR 0.20–0.91) at baseline, 0.36 (IQR 0.08–0.36) at 1 month after surgery (n = 3 eyes), 0.32 (IQR 0.30–0.72) at 6 months after surgery (n = 8 eyes), and 0.17 (IQR 0.12–0.31) at 12 months after surgery (n = 4 eyes). Using the last Snellen visual acuity test available at least 6 months after surgery, 44% (4/9) of eyes improved by 2 lines or greater on the LogMAR chart, 22% (2/9) improved by 1 line, and 33% (3/9) eyes had no change (Table 2).
FIGURE 1.
Refractive error in spherical equivalent before and after surgery.
TABLE 2.
Refractive Error and Visual Acuity Before and After Refractive Surgery
| Patient ID | OD | OS | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Surgery Type | Before Surgery | 1 Mo After Surgery | 6 Mo After Surgery | 12 Mo After Surgery | Surgery Type | Before Surgery | 1 Mo After Surgery | 6 Mo After Surgery | 12 Mo After Surgery | |||||||||||||||||||||||||
| Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | Sph | Cyl | SE | VA | |||
| 1 | PIOL | −9.50 | 6.00 | −6.50 | FF | 0.00 | 1.50 | 0.75 | 20/80 | 0.00 | 2.50 | 1.25 | FF | 0.00 | 1.50 | 0.75 | FF | PIOL | −9.00 | 5.50 | −6.25 | FF | −0.50 | 2.00 | 0.50 | FF | 0.00 | 2.00 | 1.00 | FF | −0.50 | 2.00 | 0.50 | FF |
| 2 | PIOL | −3.00 | 3.75 | −1.13 | FF | 0.00 | 0.00 | 0.00 | FF | – | – | – | FF | – | – | – | FF | PIOL | −2.75 | 3.75 | −0.88 | FF | 0.00 | 0.00 | 0.00 | FF | – | – | – | FF | – | – | – | FF |
| 3 | PRK | −8.25 | 2.25 | −7.13 | FF | 1.50 | 0.50 | 1.75 | FF | 1.00 | 0.50 | 1.25 | FF | 1.25 | 0.00 | 1.25 | FF | LRI | 1.75 | 2.25 | 2.88 | FF | 0.50 | 1.25 | 1.13 | FF | 1.75 | 0.00 | 1.75 | FF | 1.25 | 0.00 | 1.25 | FF |
| 4 | PIOL | −19.75 | 6.75 | −16.38 | 20/200 | – | – | – | 20/125 | – | – | – | 20/125 | – | – | – | – | PIOL | −18.50 | 5.00 | −16.00 | 20/225 | – | – | – | – | – | – | – | 20/125 | – | – | – | – |
| 5 | PRK | −0.25 | 2.50 | 1.00 | 20/50 | −0.75 | 0.25 | −0.63 | – | −0.75 | 0.25 | −0.63 | 20/40 | −1.00 | 0.00 | −1.00 | 20/40 | PRK | −0.25 | 2.50 | 1.00 | 20/40 | −0.50 | 0.00 | −0.50 | FF | −0.50 | 0.00 | −0.50 | 20/30 | −0.75 | 0.00 | −0.75 | 20/30 |
| 6 | PRK | 5.50 | 0.00 | 5.50 | FF | – | – | FF | −0.75 | 0.50 | −0.50 | F | 0.00 | 0.25 | 0.13 | F(F) | PRK | 4.50 | 0.00 | 4.50 | FF | – | – | – | 20/40 | −0.75 | 0.50 | −0.50 | F | 0.00 | 0.25 | 0.13 | F(F) | |
| 7 | PIOL | 4.50 | 0.00 | 4.50 | 20/40 | 0.50 | 0.00 | 0.50 | 20/40 | −0.25 | 1.00 | 0.25 | 20/40 | – | – | – | – | PIOL | 5.00 | 0.50 | 5.25 | 20/60 | 0.25 | 0.50 | 0.50 | FF | 0.00 | 1.00 | 0.50 | 20/40 | – | – | – | – |
| 8 | PIOL | 3.25 | 0.00 | 3.25 | FF | – | – | – | FF | 0.75 | 0.00 | 0.75 | FF | – | – | – | – | PIOL | 3.25 | 0.00 | 3.25 | FF | – | – | – | – | 0.75 | 0.25 | 0.88 | FF | – | – | – | – |
| 9 | PIOL | −18.00 | 4.00 | −16.00 | FF | 1.00 | 0.00 | 1.00 | – | 1.00 | 0.00 | 1.00 | 20/70 | – | – | – | – | PIOL | −17.00 | 5.00 | −14.50 | FF | 1.00 | 0.00 | 1.00 | – | 1.00 | 0.00 | 1.00 | 20/250 | – | – | – | – |
| 10 | PIOL | −6.75 | 3.00 | −5.25 | FF | 1.00 | 0.00 | 1.00 | – | 1.00 | 0.00 | 1.00 | 20/180 | 0.50 | 0.00 | 0.50 | – | PIOL | −7.75 | 4.00 | −5.75 | FF | 1.00 | 0.00 | 1.00 | HM at 1 foot | 1.00 | 0.00 | 1.00 | 20/180 | 0.50 | 0.00 | 0.50 | – |
| 11 | CLE | −14.00 | 0.00 | −14.00 | F | – | – | – | FF | 1.50 | 0.00 | 1.50 | FF | – | – | – | – | CLE | −13.00 | 1.00 | −12.50 | F | – | – | – | 10/250 | 1.50 | 0.00 | 1.50 | FF | – | – | – | – |
| 12 | PIOL | −13.00 | 0.00 | −13.00 | F(F) | – | – | – | FF | 1.25 | 1.25 | 1.88 | FF | – | – | – | FF | PIOL | −17.00 | 0.00 | −17.00 | FF | – | – | – | FF | 0.75 | 0.50 | 1.00 | FF | – | – | – | FF |
| 13 | PIOL | −8.25 | 2.00 | −7.25 | F | 1.50 | 1.25 | 2.13 | FF | 0.75 | 0.75 | 1.13 | FF | 0.25 | 1.25 | 0.88 | FF | PIOL | −10.00 | 2.50 | −8.75 | F | 1.00 | 1.00 | 1.50 | 20/25 | 0.75 | 0.00 | 0.75 | FF | 0.00 | 1.00 | 0.50 | FF |
| 14 | PRK | 2.25 | 0.50 | 2.50 | 20/25 | 0.25 | 0.00 | 0.25 | 20/25 | – | – | – | 20/60 | −0.25 | 1.00 | 0.25 | 20/25 | PRK | 3.50 | 0.50 | 3.75 | 20/25 | −0.50 | 0.50 | −0.25 | FF | – | – | – | – | 1.00 | 0.00 | 1.00 | 20/25 |
| 15 | PRK | −6.00 | 3.00 | −4.50 | – | – | – | – | – | – | – | – | – | – | – | – | – | PRK | −4.00 | 3.50 | −2.25 | – | – | – | – | FF | – | – | – | – | – | – | – | – |
| 16 | PRK | 6.25 | 0.25 | 6.38 | FF | – | – | – | FF | 2.25 | 0.50 | 2.50 | 20/250 | 2.25 | 4.00 | 4.25 | 20/300 | PRK | 6.00 | 0.25 | 6.13 | FF | – | – | – | 20/40 | 2.25 | 0.75 | 2.63 | 20/25 | 2.75 | 1.50 | 3.50 | 20/20 |
| 17 | None | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | PRK | 4.25 | 0.50 | 4.50 | 20/125 | 1.25 | 0.25 | 1.38 | FF | 1.75 | 0.00 | 1.75 | 20/40 | – | – | – | – |
| 18 | PRK | −4.50 | 0.00 | −4.50 | FF | 1.00 | 0.25 | 1.13 | 20/80 | 1.00 | 0.25 | 1.13 | FF | 1.00 | 0.00 | 1.00 | FF | PRK | −4.25 | 0.50 | −4.00 | FF | 1.00 | 0.00 | 1.00 | FF | 1.00 | 0.00 | 1.00 | FF | 1.00 | 0.00 | 1.00 | FF |
CLE = clear lens exchange; Cyl = cylinder; F(F) = fix, intermittently follow; F = fix; FF = fix, follow; HM = hand motion; PIOL = phakic intraocular lens; PRK = photorefractive keratectomy; SE = spherical equivalent; Sph = sphere.
Social functioning:
The median SRS-2 total T-score at baseline was 78 (IQR 71–83). Treatment subscale T-scores were 78 (IQR 72–83) for Social Communication and Interaction, 76 (IQR 66–83) for Social Awareness, 76.0 (IQR 71–83) for Social Cognition, 76 (IQR 10–84) for Social Communication, 68 (IQR 62–76) for Social Motivation, and 73 (IQR 64–79) for Restricted and Repetitive Behaviors. 1 month after surgery (n = 12), significant improvements were seen in: total T-score (–5 points, 95% CI −9 to −1, P =.02), Social Communication and Interaction (–5 points, 95% CI −8 to −2, P =.01), Social Awareness (–8 points, 95% CI −13 to −2, P =.02), Social Communication (–5 points, 95% CI −8 to −1, P =.02), and Social Motivation (–7 points, 95% CI −15 to −2, P =.01). At 6 months after surgery (n = 12), Social Communication and Interaction had improved by a median 4 points (95% CI −6 to 0, P =.05) and Social Cognition by 5 points (95% CI −9 to 0, P =.06).
At 12 months after surgery (n = 18), clinically meaningful median improvements were observed in Social Awareness (–8 points, 95% CI −13 to −2, P =.03) and Social Motivation (–7 points, 95% CI −10 to −2, P =.03), compared to baseline. We did not detect a significant median score change in total T-score at 12 months after surgery (− 5 points, 95% CI −9 to 1, P =.10) (Table 3). Clinically important improvements were observed in 56% (10/18) of participants in overall social functioning, 61% (11/18) in Social Awareness, and 61% (11/18) in Social Motivation (Figures 2 and 3). There was a strong correlation between baseline Social Awareness T-score and the improvement in Social Awareness T-score at 12 months postsurgery (r = −0.7, 95% CI −0.9 to −0.4, P <.001), whereas there was no significant correlation between baseline Social Motivation score and the change in Social Motivation at 12 months after surgery (r = −0.3, 95% CI −0.7 to 0.2, P =.24).
TABLE 3.
Social Functioning and Vision-Specific Quality-of-Life Before and After Refractive Surgery
| Median (IQR) | Median Difference From Baseline (95% CI) | |||
|---|---|---|---|---|
| SRS-2 T-Scoresa | Baseline(n = 18) | 1 Mo After Surgery (n = 12) | 6 Mo After Surgery (n = 12) | 12 Mo After Surgery (n = 18) |
| Total | 78 (71–83) | −5 (−9 to −1)d | −5 (−8 to 2) | −5 (−9 to 1) |
| Social Communication and Interaction | 78 (72–83) | −5 (−8 to −2)d | −4 (−6 to 0) | −4 (−9 to 1) |
| Social Awareness | 76 (66–83) | −8 (−13 to −2)d | −5 (−14 to 3) | −8 (−13 to −2)d |
| Social Cognition | 76 (71–83) | −1 (−5 to 4) | −5 (−9 to 0) | −3 (−7 to 4) |
| Social Communication | 76 (70–84) | −5 (−8 to −1)d | −3 (−6 to 3) | −4 (−7 to 3) |
| Social Motivation | 68 (62–76) | −7 (−15 to −2)d | −4 (−9 to 3) | −7 (−10 to −2)d |
| Restricted and Repetitive Behaviors | 73 (64–79) | −4 (−10 to 1) | −5 (−13 to 3) | −3 (−9 to 3) |
| PedEyeQ Proxy Form Domainsb | Baseline (n = 15) | 1 Mo After Surgery (n = 10) | 6 Mo After Surgery (n = 9) | 12 Mo After Surgery (n = 9) |
| Functional Vision | 40 (15–51) | 20 (0–40) d | 32 (0–65) d | 40 (7–73) d |
| Bothered by Eyes/Vision | 58 (49–86) | 9 (−5 to 27) | 22 (0–42) d | 23 (3–45) d |
| Social | 88 (73–100) | −7.7 (−31 to 11) | 4 (−3 to 13) | 4 (0–9) |
| Frustration/worry | 100 (48–100) | −5 (−30 to 25) | 5 (−20 to 30) | 5 (0–28) |
| Eye-care | 50 (17–83) | −4 (−21 to 24) | 25 (−4 to 58) | 18 (−8 to 50) |
| PedEyeQ Parent Form Domainsc | Baseline (n = 16) | 1 Mo After Surgery (n = 11) | 6 Mo After Surgery (n = 10) | 12 Mo After Surgery (n = 9) |
| Impact on Parent/Family | 75 (51–87) | 6 (−14 to 23) | 13 (−7 to 25) | 20 (−3 to 43) |
| Worry Regarding Child’s Eye Condition | 37 (26–60) | 28 (2–47) d | 32 (2–55) d | 25 (−2 to 56) |
| Worry Regarding Child’s Self-Perception/Interactions | 79 (64–86) | −4 (−32 to 18) | 4 (−11 to 21) | 9 (−11 to 25) |
| Worry Regarding Child’s Visual Function | 19 (12–54) | 29 (6–56) d | 43 (6–80) d | 28 (0–63) d |
IQR = interquartile range; SRS-2 = Social Responsiveness Scale, 2nd Edition; PedEyeQ = Pediatric Eye Questionnaire. Bold values indicate statistically significant improvement.
Lower scores on the SRS-2 indicate better social functioning.
Higher scores on the PedEyeQ Proxy form indicate better child vision-specific quality-of-life-based on parent observation.
Higher scores on the PedEyeQ Parent form indicate better parent/family quality-of-life related to child’s eye condition.
Indicates a statistically significant improvement.
FIGURE 2.
SRS-2 social awareness T-score before and after surgery.
FIGURE 3.
SRS-2 social motivation T-score before and after surgery.
VSQOL:
83% (15/18) of participants completed the PedEyeQ Proxy form and 89% (16/18) completed the parent form at baseline. At 1 month after surgery, there were clinically important median improvements in Functional Vision (20 points, 95% CI 0–40, P =.05), Worry Regarding Child’s Eye Condition (28 points, 95% CI 2–47, P =.02) and Worry Regarding Child’s Visual Function (29 points, 95% CI 5–56, P =.02). At 6 months after surgery, Functional Vision had improved by a median 32 points (95% CI 0–65, P =.04), Bothered by Eyes/Vision by 22 points (95% CI 0–42, P =.03), Worry Regarding Child’s Eye Condition by 32 points (95% CI 2–55, P =.05), and Worry Regarding Child’s Visual Function by 43 points (95% CI 6–80, P =.04) compared to baseline. At 12 months after surgery, clinically meaningful improvements were observed in Functional Vision (40 points, 95% CI 7–73, P =.02), Bothered by Eyes/Vision (23 points, 95% CI 3–45, P =.02), and Worry Regarding Child’s Visual Function (28 points, 95% CI 0–63, P =.04) (Table 3). Overall, 78% (7/9) of participants demonstrated clinically meaningful improvements in Functional Vision, 56% (5/9) in Bothered by Eyes/Vision, 78% (7/9) in Worry Regarding Child Eye Condition, and 67% (6/9) in Worry Regarding Child Visual Function.
DISCUSSION
In this observational pilot study of 18 children with ID and/or ASD, significant ametropia, and spectacle nonadherence, improvements in social functioning, and VSQOL were observed following refractive surgery. At 12 months after surgery, we observed statistically significant changes in social awareness, Social Motivation, and quality-of-life related to Functional Vision and bother from eye/vision symptoms which were compatible with clinically important improvements, but we did not detect a statistically significant change in overall social functioning.
Our findings align with previous studies on the developmental impact of refractive surgery published by Paysse, who reported developmental improvements postphotorefractive keratectomy in children with ID,14 and Tychsen, who observed enhanced Functional Vision and social behaviors after refractive surgery in a group of children with neurobehavioral disorders.13 Our study builds on prior literature by employing the SRS-2 for quantification of social functioning changes and the PedEyeQ to explore the quality-of-life effects of refractive surgery. The magnitude of improvement on the SRS-2 observed in our study is comparable to that demonstrated in other trials of behavioral22,23 and pharmacological24 therapeutics for the treatment of ASD. Our findings support the notion that treatment of medical comorbidities may improve developmental outcomes in children with NDDs, such as has been previously shown after the surgical treatment of epilepsy in children with severe ASD.25 Additionally, the VSQOL domains we observed improvements in following surgery correspond to those previously reported in a cross-sectional study to be correlated with visual acuity in children.26 This provides evidence to support our hypothesis that refractive surgery, by improving visual acuity, leads to meaningful quality-of-life benefits for patients.
This pilot study’s sample size, while small, is favorably comparable to existing studies on the developmental impacts of refractive surgery in children with NDD.13,14 By measuring both psychosocial and functional outcomes, we offer a more comprehensive evaluation of the benefits of refractive surgery in this population. We included both children with ASD and with ID in our study because these conditions are commonly associated with spectacle nonadherence and are highly comorbid with each other. The SRS, as a continuous measure of core autistic trait burden, is elevated in children with ASD and in some children with ID who do not meet full criteria for ASD,27–29 indicating that each condition can independently contribute to social impairment. Most of our participants also had other visual disorders, such as strabismus and amblyopia, or other NDD, such as ADHD. Thus, our participants were severely disabled, as reflected in the low ABAS-3 scores, and had high clinical heterogeneity. This fact reflects the complex medical needs of children who are spectacle nonadherent but also contributes to the variability in our results. Importantly, the 12-month SRS-2 and PedEyeQ offer the strongest evidence that refractive surgery may provide social and VSQOL benefits in this population. The observed loss of significant improvements in some subscores of the SRS-2 and PedEyeQ at 12 months, as compared to the 1- and 6-month outcomes, may be attributed to a diminution of benefits over time as participants adjust to new visual acuity or possibly to a regression to the mean effect as the measures were repeated and sample size increased.
Important limitations must be considered when interpreting the results. The small sample of 18 participants may not represent the full range of findings and possible effects from surgery and the analysis was not powered to detect smaller effects in social functioning, which may still be clinically important. Additionally, participants in our study were not randomized and we did not include a parallel control group, which restricts our ability to ascertain the natural trend of social functioning and VSQOL of our study population independent of visual correction. This is particularly important because parent-reported outcomes, such as the SRS-2 and PedEyeQ, may be susceptible to observer bias. Our group plans to address these limitations in a future study by utilizing a delayed-treatment control group and including an observational assessment of development by an assessor masked to surgery status, in addition to collecting the parent-reported SRS-2. This study was also limited by incomplete data collection at intermediate time points and the attrition of participants, which may introduce bias in the estimation of treatment effects. The limited visual acuity data also precluded direct testing of our underlying hypothesis that visual acuity improvements after surgery lead to social functioning benefits. Our primary aim in this pilot study was to detect a signal indicating the potential effects of refractive surgery, which would justify further investigation. We thus accepted a higher potential for type I error, opted to not adjust the p-values for multiple comparisons, and used a distribution-based method to set a threshold for clinical importance. As refractive surgery carries significant risks, future larger, controlled trials are needed to make a definitive conclusion regarding the benefit of this intervention for children in this population.
Building upon the promising outcomes of this pilot study, future trials are needed to validate the positive impact of refractive surgery on development and quality-of-life in spectacle nonadherent children with NDD. Employing mixed-methods approaches that combine observational behavioral assessments with parent-reported outcomes could provide deeper insights into the value of this intervention for affected children. Ophthalmologists, neurologists, and pediatricians are encouraged to develop comprehensive care models that address the multifaceted needs of children with NDD to maximize their potential for developmental gains and improved outcomes.
Funding/Support:
This project was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number TL1TR002344, the Doris Duke Charitable Foundation Fund to Retain Clinical Scientists under Grant 2020144, and an Unrestricted Grant from Research to Prevent Blindness. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The sponsors or funding organizations had no role in the design or conduct of this research.
Footnotes
MEETING PRESENTATION: An abstract for this paper has been submitted for consideration as a paper/poster for the American Academy of Ophthalmology Annual Meeting, 2024. Intermediate results (6 month outcomes) from a subset of patients included in this study were presented at the American Association for Pediatric Ophthalmology and Strabismus Annual Meeting, 2024.
CREDIT AUTHORSHIP CONTRIBUTION STATEMENT
Jacob Strelnikov: Writing – review & editing, Writing – original draft, Visualization, Validation, Investigation, Formal analysis, Data curation. Alexandra Zdonczyk: Writing – review & editing, Formal analysis, Data curation. John R. Pruett Jr.: Writing – review & editing, Methodology. Susan Culican: Writing – review & editing, Methodology, Conceptualization. Lawrence Tychsen: Writing – review & editing, Conceptualization. Mae Gordon: Writing – review & editing, Supervision. Natasha Marrus: Writing – review & editing, Methodology. Alexandre Todorov: Methodology, Formal analysis. Margaret Reynolds: Writing – review & editing, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Data curation, Conceptualization.
Financial Disclosures: No financial disclosures. No conflicts of interest.
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