Abstract
Purpose
Optic disc drusen (ODD) are calcified deposits in the prelaminar portion of the optic nerve head. Although often asymptomatic, it can damage optic nerve fibers, resulting in irreversible vision loss. This study evaluates rates of structural changes in children with ODD and risk factors associated with faster rates of retinal nerve fiber layer (RNFL) thinning.
Design
Retrospective cohort study.
Subjects
Forty eyes of 22 children with ODD and 40 eyes of 20 age-, gender-, and race-matched glaucoma-suspect children.
Methods
Children were required to have ≥3 OCT RNFL tests and a minimum of 18 months between the first and last OCT. Linear mixed models estimated RNFL changes over time. Univariable and multivariable models assessed the effect of clinical variables on rates of change.
Main Outcome Measures
The primary outcome was the rates of RNFL change over time, which was compared to the glaucoma-suspect group. The secondary outcome was to investigate the clinical factors associated with faster RNFL thinning.
Results
Children with ODD were followed for an average of 4.1 ± 2.5 years (median 3.2). Eyes with ODD had rates of RNFL change significantly faster than the glaucoma-suspect group (–2.01 ± 1.53 μm/year versus –0.07 ± 0.47 μm/year; P < 0.001). The multivariable model revealed older age and higher RNFL at baseline were significantly associated with faster rates of RNFL thinning, with 0.37 μm/year faster loss for each year older (P = 0.040) and 0.07 μm/year faster loss for each μm higher RNFL at baseline (P = 0.030).
Conclusions
Children with ODD demonstrate significant rates of RNFL thinning over time. Knowing the distribution of RNFL change attributable to ODD in children will enable clinicians to identify rapid progressors and alternative etiologies of optic nerve injury.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
Keywords: Children, Optical coherence tomography, Optic disc drusen, Optic nerve, Retinal nerve fiber layer
Optic disc drusen (ODD) are acellular deposits of calcium, mucopolysaccharides, and nucleic and amino acids located in the prelaminar portion of the optic nerve head.1 These structures are usually buried and noncalcified early in life, making the diagnosis challenging in the pediatric population and possibly contributing to the underestimation of the prevalence previously reported as 0.4%.2 In some cases, ODD can cause mechanical compression of the retinal nerve fibers and decreased optic nerve head perfusion, placing eyes with ODD at risk of retinal nerve fiber damage and subsequent vision loss.3
The longitudinal visual field changes in eyes with ODD have been previously reported. Estrela et al4 assessed rates of changes in the visual field of adults with ODD and found a mean rate of change of –0.23 ± 0.26 decibels/year. Gise et al5 investigated visual field changes in a cohort of 208 eyes of children with ODD and found repeatable visual field defects in 11.5% of the eyes. In contrast, there are limited data on structural changes in children with ODD over time. This information is especially important given the challenges of performing perimetry in young children and the fact that structural changes of the optic nerve precede both measurable visual loss and detectable changes in the optic nerve appearance.6
In the present study, we evaluate the rates of retinal nerve fiber layer (RNFL) change in a cohort of children with ODD and compare them with rates of RNFL change in a glaucoma-suspect children. In addition, we assess clinical factors associated with faster rates of RNFL thinning in eyes with ODD.
Methods
This retrospective cohort study included children evaluated by the ophthalmology department at Boston Children's Hospital between 2018 and 2024. Given the retrospective nature of this study, the institutional review board approved the research protocol with a waiver of consent. All methods adhered to the tenets of the Declaration of Helsinki for research involving human subjects and were conducted following the regulations of the Health Insurance Portability and Accountability Act.
Children with ODD were identified using the International Classification of Diseases (ICD) 10 codes for ODD (“H47.321,” “H47.322,” “H47.323,” and “H47.329”), and the diagnosis of ODD was further confirmed by a manual review of medical records based on the identification of ODD in ≥1 of the following methods: ophthalmoscopy, B-scan ultrasound, autofluorescence imaging, computerized tomography scan, or OCT. Because the rates of RNFL change have not been described in healthy children, we included as a control group children followed under ophthalmology care as glaucoma suspects because this is a group followed longitudinally with serial OCTs. The control group was identified as glaucoma suspects based on ICD codes and chart review (ICD10 codes: H40.00, H40.01, H40.001, H40.011, H40.002, H40.012, H40.003, and H40.013) based on the presence of large cup-to-disc ratio or cup-to-disc asymmetry ≥0.2 per the Childhood Glaucoma Research Network classification.7
For ODD and glaucoma-suspect groups, children were included in the study if they were ≤18 years of age at baseline and had ≥3 OCT tests across a minimum of 18 months follow-up. The study baseline was defined as the date of the first OCT test and the endpoint as the last OCT during follow-up. Patients were excluded if they had any concurrent ocular or systemic disease that could affect the afferent visual function and if they had a refractive error >5 diopters (spherical equivalent). Because ischemic optic neuropathy can occur in the setting of ODD, we excluded eyes with the diagnosis of ischemic optic neuropathy, according to clinicians' notes. Also, based on clinician notes, we excluded eyes with optic atrophy at baseline because the floor effect on OCT could confound the quantification of progression. A matching technique was used to randomly select the glaucoma-suspect eyes with clinical characteristics similar to those of the eyes with ODD. The groups were matched for age, gender, and race.
Baseline clinical information was extracted from medical records. The peripapillary RNFL and macula thickness and volume were acquired using the Spectralis spectral domain-OCT Nsite Analytics Module (Heidelberg Engineering) with the automatic real-time eye tracker to eliminate motion artifacts. Measurement maps were automatically generated and transferred from HEYEX (Heidelberg Eye Explorer Version 1.7). The peripapillary RNFL OCT circle report scans show a global average, average thickness of 6 sectors, and also for the 4 main sectors: temporal, nasal, superior, and inferior. For simplification, we used the global and 4 sector averages. Scans with a quality score of ≥15 were included.8 The macular 20° × 20° scan was used, and high-quality images were defined as those with individual retinal layers that could be identified. The macular scans were then automatically segmented for the ganglion cell layer (GCL) volume analysis, and final GCL volume measurement was extracted. Scans were manually reviewed for segmentation errors and were corrected as needed. All scans meeting the quality criteria acquired during patients' follow-ups were included in the analysis.
Reliable standard automated perimetry mean deviation (MD) acquired with the Humphrey Field Analyzer and OCT macular GCL volume at the last follow-up were recorded when available. Reliable standard automated perimetry was defined as any 24-2 Swedish Interactive Threshold Algorithm tests with size III white stimulus, with <33% fixation losses, 15% false-positives, and 15% false-negatives.
Statistical Analysis
Linear mixed models were used to estimate rates of RNFL loss over time. In brief, this standard technique takes into account that each patient may contribute with 2 eyes for the analyses as well the natural correlation of such data over time. The differences in rates of change between eyes and between subjects are considered by introducing random slopes and random intercepts. To estimate the individual slopes for each eye of change more precisely, the best linear unbiased prediction was used. As the number of tests increases, the best linear unbiased prediction estimates become essentially identical to those obtained from ordinary least squares regression.9,10
Linear mixed models were also used to assess the effect of clinical parameters such as baseline age, RNFL thickness, spherical equivalent, and gender on rates of RNFL loss. Multivariable Linear mixed models included clinical factors significantly related to a faster progression in the univariate models. The Bonferroni correction was performed to adjust for multiple comparisons. In addition, the Pearson correlation test was used to assess the correlation between rates of RNFL change and final MD and GCL volume. Thereafter, variables with normal distribution were compared between ODD and glaucoma-suspect groups using Student t test and are presented as mean ± standard deviation. Variables with non-normal distribution (Shapiro–Wilk test) were compared between groups using the Wilcoxon signed-rank test and are presented as median and interquartile range (IQR).
All statistical analyses were completed in Stata (version 17, StataCorp LP).
Results
Out of 396 children with ICD10 codes for ODD, the diagnosis was confirmed in 181 eyes from 94 children. Thirty-six eyes were excluded because they had concomitant ocular conditions (6 retinitis pigmentosa; 6 brain tumors; 14 idiopathic intracranial hypertension; 6 membrane frizzled-related protein–related ocular disorder; 1 optic nerve hypoplasia; and 3 anterior ischemic optic neuropathy). One hundred five eyes did not match the criteria of follow-up or the number of OCT tests. Of the 40 eyes from 22 children who met the inclusion criteria for this study, 11 children (50.0%) were female, and 19 (86.4%) were identified as White. The mean age at the first OCT tests was 11.9 ± 3.3 years (median 12.1; IQR: 9.0, 15.2). Children with ODD were followed for a mean of 4.1 ± 2.5 years (median 3.2; IQR: 2.1, 5.6). The median number of OCT tests per eye was 4 (IQR: 3, 5; range: 3, 11). The median global RNFL at baseline was 108 μm (IQR: 96 117), and at the last OCT was 98 μm (IQR: 83, 111), significantly decreased compared with baseline (P < 0.001). When analyzing the OCT algorithm classification at the last follow-up, 11 eyes (27.5%) had global RNFL below normal limits, and 1 had RNFL thickness borderline below normal limits. Among the eyes with global RNFL within normal limits, 4 eyes had sectoral thinning below normal limits, and 5 had borderline thinning below normal limits.
All patients were evaluated by a pediatric neuro-ophthalmologist who confirmed the diagnosis based on clinical examination and review of ancillary imaging when available. A total of 29 eyes (72.5%) had ODD visualized on OCT (either enhanced depth imaging or swept-source). Of these, 24 eyes (60%) also had ODD documented by an additional modality, including fundoscopy or B-scan ultrasound, while 5 eyes (12.5%) had ODD identified by OCT alone. In the 11 eyes (27.5%) without available OCT imaging, 4 eyes (10%) were diagnosed by B-scan ultrasound alone, 2 (5%) by fundoscopy alone, 3 (7.5%) by a combination of fundoscopy and fundus autofluorescence, and 2 (5%) by both B-scan ultrasound and fundoscopy.
Forty eyes from 20 matched children carrying a diagnosis of “glaucoma suspect” were analyzed for comparison. Demographic and clinical characteristics of ODD and glaucoma-suspect eyes are compared in Table 1. There was no statistically significant difference in age, gender, race, or OCT test number between the ODD and glaucoma suspects. The median global RNFL thickness at baseline for glaucoma-suspect eyes was 100 μm (IQR: 91, 108), which was significantly different from ODD eyes (P = 0.021), and the median global RNFL thickness for the last OCT was 100 μm (IQR: 92, 108), which was unchanged compared with baseline (P = 0.58).
Table 1.
Comparison of Demographic and Baseline Clinical Characteristics between Children with Optic Disc Drusen and Glaucoma Suspects
| ODD | Glaucoma Suspects | P | |
|---|---|---|---|
| Subjects | 22 | 20 | |
| Age, yrs | 12.1 (9.0, 15.2) | 10.8 (8.1, 12.8) | 0.179 |
| Female, n (%) | 11 (50%) | 11 (55%) | 0.990 |
| Self-identified race, n (%) | 19 (86.4%) | 10 (50%) | 0.870 |
| White | 1 (4.6%) | 3 (15%) | |
| Asian | 0 | 2 (10%) | |
| African American not identified | 2 (9.0%) | 5 (25%) | |
| Eyes | 40 | 40 | |
| OCT tests per eye, n | 4 (3, 5) | 3 (3, 4) | 0.100 |
| Follow-up, yrs | 3.2 (2.1, 5.6) | 4.6 (3.3, 6.1) | 0.034 |
| Global RNFL thickness, μm | 108 (96, 117) | 100 (91, 108) | 0.021 |
| Superior RNFL thickness, μm | 141 (118, 153) | 126 (113, 141) | 0.063 |
| Inferior RNFL thickness, μm | 142 (125, 151) | 130 (120, 148) | 0.203 |
| Temporal RNFL thickness, μm | 78 (69, 88) | 69 (63, 79) | 0.007 |
| Nasal RNFL thickness, μm | 78 (67, 86) | 67 (59, 85) | 0.280 |
| Spherical equivalent | 0 (–1.25, 0.50) | –1.75 (–3.75, 0) | <0.001 |
n = number; ODD = optic disc drusen; RNFL = retinal nerve fiber layer.
Values represent the median and interquartile range unless otherwise indicated.
Bold indicates a significant P value (<0.05).
Over the follow-up period, eyes with ODD had a mean global RNFL change rate of –2.01 ± 1.53 μm/year (median –1.90; IQR: –0.99, –2.84 μm/year), significantly faster compared with the rates of change of the glaucoma-suspect group (mean = –0.07 ± 0.47 μm/year; coefficient = 2.03, P < 0.001). Table 2 shows the global and sectorial RNFL rates of change for the eyes with ODD and glaucoma suspects. Eyes with ODD had significantly faster rates of change in the superior (coefficient = 4.09, P < 0.001), nasal (coefficient = 1.83, P = 0.005), and temporal (coefficient = 1.16, P = 0.014) optic nerve sectors compared with the glaucoma-suspect eyes, with a larger difference in the superior quadrant. For the inferior sector, there was no significant difference in rates of change between ODD and glaucoma-suspect eyes (coefficient = 1.41, P = 0.111). Figure 1 shows representative follow-up fundus photos and OCT tests of 2 eyes with ODD included in the study. In the (A-B) images, it is an eye with rates of RNFL thinning of –5.83 μm/year over time with RNFL below normal limits at the last follow-up, and in the (C-D) images, an eye with RNFL thinning of –2.06 μm/year and RNFL within normal limits at the last follow-up.
Table 2.
Rates of Change for Spectral-Domain OCT RNFL Thickness Global and per Optic Nerve Sector for Eyes with ODD and Glaucoma Suspects Included in the Study
| RNFL | Rates of Global RNFL Change (μm/Yr) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| ODD |
Glaucoma Suspects |
||||||||||
| Mean | SD | Median | IQR | Mean | SD | Median | IQR | P | |||
| Global | –2.10 | 1.53 | –1.90 | –0.99 | –2.84 | –0.07 | 0.47 | –0.05 | 0.23 | –0.32 | <0.001 |
| Superior | –4.18 | 3.29 | –4.26 | –1.62 | –6.21 | –0.09 | 1.12 | –0.02 | 0.65 | –1.02 | <0.001 |
| Inferior | –1.53 | 2.17 | –1.31 | –0.78 | –2.24 | –0.12 | 0.70 | –0.14 | 0.12 | –0.58 | 0.111 |
| Temporal | –0.92 | 0.81 | –0.78 | –0.39 | –1.27 | 0.24 | 0.55 | 0.10 | 0.76 | –1.39 | 0.014 |
| Nasal | –1.97 | 2.22 | –1.49 | –0.75 | –2.39 | –0.14 | 1.08 | –0.10 | 0.49 | –0.98 | 0.005 |
IQR = interquartile range; ODD = optic disc drusen; RNFL = retinal nerve fiber layer; SD = standard deviation.
Bold indicates a significant P value (<0.05).
Figure 1.
A representative example of 2 eyes with ODD included in the study. A, Enhanced depth imaging OCT B-scan showing ODD (yellow arrows), (B) fundus photo, and (C) peripapillary OCT of the left eye of a 10-year-old boy with ODD followed for 8 years. The estimated RNFL rate of loss was –5.83 μm/year. D, Enhanced depth imaging OCT B-scan showing ODD (yellow arrows), (E) fundus photo, and (F) peripapillary OCT of the left eye of a 13-year-old girl with ODD also followed for 8 years. The estimated RNFL rate of loss was –2.06 μm/year. Respective follow-up periods are listed. G = global; N = nasal; NI = nasal inferior; NS = nasal superior; N/T = nasal/temporal; ODD = optic disc drusen; PMB = papillomacular bundle; RNFL = retinal nerve fiber layer; T = temporal; TI = temporal inferior; TS = temporal superior.
Univariable and multivariable regression models were used to investigate the association of age, gender, and baseline RNFL with rates of RNFL change over time (Table 3). In the univariable models, none of these variables was significantly associated with faster rates of RNFL loss. Nevertheless, given the known effect of age, baseline RNFL thickness, and gender on rates of RNFL change over time in other pathologies, such as glaucoma,11, 12, 13 we built a multivariable model that included these variables.
Table 3.
Univariable and Multivariable Models Investigating the Effect of Each Clinical Characteristic on the Rate of gRNFL Change Over Time in the Eyes of Children with Optic Disc Drusen
| Characteristic | Univariable Models |
Multivariable Model |
||
|---|---|---|---|---|
| Coefficient (CI) | P Value | Coefficient (CI) | P Value | |
| Age, per 1 yr older | –0.24 (–0.57, 0.10) | 0.173 | –0.37 (–0.72, –0.02) | 0.040 |
| Gender, male | –1.40 (–3.40, 0.58) | 0.165 | –1.31 (–3.33, 0.712) | 0.204 |
| Baseline gRNFL (μm), per 1 μm higher | –0.03 (–0.09, 0.03) | 0.372 | –0.07 (–0.14, –0.07) | 0.030 |
| Spherical equivalent | –0.18 (–0.73, 0.36) | 0.515 | - | - |
CI = confidence interval; gRNFL = global retinal nerve fiber layer thickness.
Bold indicates a significant P value (<0.05).
We found that age and baseline RNFL became significant when controlling for each other and for gender, with 0.37 μm/year faster rates of RNFL thinning for each year older (P = 0.040) and 0.07 μm/year faster thinning for each μm higher RNFL at baseline (P = 0.030).
At the last follow-up visit, 32 eyes had a GCL volume measurement, and 30 eyes had a reliable standard automated perimetry. The mean GCL volume was 1.1 ± 0.11 mm3 (IQR: 1.0, 1.2 mm3), and the mean MD was –3.5 ± 2.6 decibels (IQR: –4.8, –1.6 decibels). We further evaluated the correlation between rates of RNFL change and GCL volume and MD at the last follow-up (Fig 2). Ganglion cell layer volume was moderately correlated with faster rates of RNFL loss corresponding to lower GCL volume at the last follow-up (R = 0.54, P = 0.001) and strongly correlated with RNFL at last follow-up (R = 0.71, P < 0.001). The MD was not significantly correlated with faster rates of RNFL thinning (R = –0.02, P = 0.90) but was correlated with final RNFL (R = 0.38, P = 0.03).
Figure 2.
Scatterplots showing the relationship between rates of RNFL change over time and GCL volume (left) and between rates of RNFL change and standard automated perimetry MD (right). Correlation coefficients are reported. dB = decibels; GCL = ganglion cell layer; MD = mean deviation; RNFL = retinal nerve fiber layer.
Discussion
In this study, we assessed longitudinal rates of RNFL changes in children with ODD, which, to our knowledge, has not been reported previously. In our cohort, children with ODD had a change in RNFL thickness over time of a mean –2.01 ± 1.53 μm/year. Age and RNFL at baseline were associated with faster RNFL thinning rates. Importantly, these rates of change led to global or sectoral RNFL below normal limits in 37.5% of the eyes and to borderline below normal limits in 15% of the eyes, underscoring the clinical significance of the change observed.
The mechanism by which ODD causes optic nerve damage is still unclear. It has been hypothesized that ODD can cause mechanical compression over retinal vessels, leading to decreased blood flow and consequent optic nerve damage.14 An alternative explanation is that these calcified bodies compress adjacent ganglion cell axons, leading to ganglion cell death and axonal degeneration.15 Structural changes of the optic nerve detected by OCT in the setting of ODD have been previously studied. Gili et al16 cross-sectionally compared RNFL in patients with ODD and healthy subjects. Except for the temporal quadrants, eyes with ODD had significantly lower global and sectorial RNFL thickness than the healthy subjects. Pilat et al17 assessed the short-term progression of the optic disc in patients with ODD and found significant thinning in RNFL after 12 months. However, the rates of RNFL change were not quantified.
In our study, we focused specifically on children (≤18 years) and evaluated changes in RNFL over a longer mean follow-up time. Our finding of faster changes in the superior sector and slower in the temporal sector agrees with the findings of Gili et al,16 who found no significant difference in temporal quadrant RNFL thickness between ODD subjects and glaucoma-suspect group, indicating that either ODD is less common in this quadrant or this area may be less susceptible to damage from ODD. In addition, we estimated the rates of RNFL thinning over time, and because “physiologic” rates of change in RNFL in the pediatric population have not been described, as a comparison, we included a glaucoma-suspect group with similar demographic characteristics and for which significant rates of RNFL thinning over time are not expected. In fact, the glaucoma-suspect eyes had an average RNFL thinning over time of 0.07 μm/year, which was not significant (P 0.628). In contrast, eyes with ODD had approximately 2 microns faster RNFL thinning rates than glaucoma-suspect eyes (P < 0.001). Eyes with ODD had significantly higher RNFL at baseline compared with glaucoma-suspect eyes, which agreed with prior studies showing that RNFL in eyes with ODD is higher than in healthy children.18
When evaluating the clinical factors associated with faster rates of RNFL thinning, the multivariable model revealed mutually suppressive effects of age and baseline RNFL thickness on the progression of thinning over time. The nature of progressive RNFL thinning in ODD explains how older age and higher baseline thickness would conflict in the univariate model. Thicker baseline RNFL may reflect an increased susceptibility to accelerated damage as a marker for greater crowding or drusen burden. Older age within a pediatric cohort may signify that teenagers progress faster than young children. A sustained rate of RNFL thinning of 2.01 μm/year from 108 μm at age 18 would yield a 45 μm RNFL thickness at age 48, much lower than that reported in adult cohorts.19 Reconciliation of our results with the fact that such profound degrees of RNFL thinning are not seen in adults with ODD would indicate that ODD-induced RNFL thinning likely peaks in late childhood and tapers through adulthood. However, this hypothesis remains to be tested in future longitudinal studies.
In addition, we found that rates of RNFL thinning in the setting of ODD correlated with GCL volume loss, validating that changes in RNFL reflect axon damage rather than changes in optic nerve head structure with aging, as in glaucoma.20 Visual field MD did not correlate with the rate of RNFL change, but it did correlate with the final RNFL. It may also be, as in glaucoma, that eyes with ODD only manifest measurable visual field defects with more substantial RNFL loss.21 Indeed, our pediatric population, though followed for >4 years on average, maintained a final mean RNFL that would not reliably result in visual field defects. Another consideration is that pediatric patients harbor a greater capacity for neuroplasticity that may compensatory mitigate functional deficits resulting from a given degree of RNFL injury. It is also possible that the anatomical location of the ODD interferes in the manifestation of measurable visual field defect in the 24-2 visual field, accounting for the patients in our cohort who presented decreased MD. Further studies should assess the relationship between the anatomical location of ODD and the presence and severity of the visual field defects.
Our study has limitations. The children included in the study were followed at a referral center; therefore, there may be an overrepresentation of more severe cases. It is also important to note that the findings may be most applicable to cases with ODD that were visible on ultrasound, autofluorescence, fundoscopy, or OCT, potentially limiting the generalizability to patients with deeply buried or less well-visualized drusen. In addition, this was a retrospective study, and children were managed at the discretion of their ophthalmologists during follow-up. Clinical features at the presentation may have influenced the decision regarding how often to perform OCT tests, limiting the number of tests available and our sample size. However, this would be expected to influence the baseline measurement and not necessarily the rate of RNFL change, which would only be determined through regular follow-up. Additionally, the retrospective nature of the study led to variability in OCT imaging protocols, as many scans were acquired before the establishment of the ODD Consortium's standardized guidelines;22 consequently, not all imaging adhered to uniform acquisition parameters, which may impact consistency in ODD detection and characterization. Finally, it is important to acknowledge that the Spectralis OCT algorithm classification is based on an adult's normative database. Therefore, when reporting the classification of RNFL thickness of our cohort based on this algorithm, we are likely underestimating the significance of our results because it has been demonstrated that the healthy pediatric population has thicker RNFL than adults.23
In this longitudinal analysis of our cohort of children with ODD, we observed progressive thinning of RNFL over time. By characterizing these early changes, our data contribute to the understanding of the disease trajectory in pediatric populations and may aid in more accurate prognostication and the distinction of other potential causes of optic nerve injury in the context of ODD. In addition, our findings support the potential value of including pediatric populations in future neuroprotection trials. Early identification of at-risk individuals could allow for timely intervention before irreversible damage occurs. Further research is warranted to better define structure-function relationships and to place these findings within the broader context of aging and disease progression.
Manuscript no. XOPS-D-25-00222.
Footnotes
Disclosure(s):
The Article Publishing Charge (APC) for this article was paid by Boston Childrens Hospital.
All authors have completed and submitted the ICMJE disclosures form.
The author made the following disclosures:
E.G.: Scientific advisor – Luminopia, Inc.; Patents planned, issued, or pending – Luminopia, Inc.; Equity – Luminopia, Inc.; Consultant – Stoke Therapeutics, Inc., Neurofieldz, Inc.
HUMAN SUBJECTS: Human subjects were included in this study. This retrospective cohort study included children evaluated by the ophthalmology department at Boston Children's Hospital between 2018 and 2024. Given the retrospective nature of this study, the Institutional Review Board approved the research protocol with a waiver of consent. All methods adhered to the tenets of the Declaration of Helsinki for research involving human subjects and were conducted following the regulations of the Health Insurance Portability and Accountability Act.
No animal subjects were used in this study.
Author Contributions:
Conception and design: Estrela, Gaier, Gise
Data collection: Estrela, Jeon-Chapman, Zhang, VanderVeen
Analysis and interpretation: Estrela
Obtained funding: N/A
Overall responsibility: Estrela, Jeon-Chapman, VanderVeen, Gaier, Heidary, Elhusseiny, Gise
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