Pediatric Optic Pathway Gliomas Resource Utilization and Prevalence in the Optum Labs Data Warehouse

Optic pathway gliomas (OPGs) are a central nervous system (CNS) malignancy that occur within the visual pathway and surrounding structures. Many OPGs are linked to neurofibromatosis-1 (NF-1), which has an incidence of approximately 3 cases per 10,000 births.¹ OPGs comprise 3–5% of total CNS tumors and 1% of intracranial tumors in children.² However, OPGs represent a significant portion (86.6%) of all visual pathway lesions and thus are an important cause of vision loss in children.³ Typically, OPGs are diagnosed between one and eight years of age, but some may be asymptomatic and are discovered incidentally later in life.⁴

The clinical prognosis of OPGs may vary depending on various factors, including the presence of NF-1. Children with NF-1-associated OPGs tend to have a better long-term visual function if their initial exam was normal.⁵ In contrast, pediatric patients with sporadic OPGs often suffer long-term visual impairment.⁶ Upon diagnosis for pediatric OPG patients, active surveillance without treatment is often the first-line option. To maintain the best vision possible, it is crucial to regularly monitor with neuro-ophthalmologic testing and neuroimaging. Monitoring will also inform decisions about whether to continue without treatment or pursue active interventions using chemotherapy, surgery, or radiation. The combined responsibility of clinical diagnosis, monitoring, and management creates a challenging burden of care for both OPG patients and their families. Although recent studies have shed light on treatment, survival rates, and long-term outcomes of patients with OPG, there is little published data that describes how these patients are continuously monitored.^{3 7} The goal of our study was to provide prevalence, demographic, frequency of surveillance, and treatment data for pediatric OPG patients using a large insurance claims dataset from 2016 to 2021.

Methods

This cross-sectional study of de-identified subjects using a commercial insurance claims database from the Optum Labs Data Warehouse (OLDW) was exempt from review by the Institutional Review Board at the University of California, Los Angeles. The research was conducted in accordance with the tenets of the Declaration of Helsinki. OLDW contains health information for de-identified enrollees in the United States.⁸

All enrollees born in 1999 or later in the OLDW member coverage table were extracted and queried for medical claims from 1/1/2016 to 6/30/2021. The presence of an OPG claim was defined by an International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes of C72.30, C72.31, or C72.32.⁹ The date and age of the first OPG claim in the database were recorded. Patients were included if they were under 18 years of age at the first OPG claim. The duration of follow-up was calculated using the dates of the first OPG claim and the last follow-up. Patients were excluded if they had less than 6 months of follow-up. Data on the characteristics of eligible OPG patients were then extracted, including race and ethnicity (classified as Asian, Black/African American, Hispanic, White, and Unknown), region of residency (Midwest, Northeast, South, West), and form of insurance (HMO vs. commercial).

Surveillance imaging and ophthalmologic testing captured magnetic resonance imaging (MRI), computed tomography (CT), visual field (VF) testing, and optical coherence tomography (OCT). Age at the first claim for radiation, surgery, and ten chemotherapy medications (procarbazine, bevacizumab, lomustine, vincristine, etoposide, cisplatin, carboplatin, selumetinib, refametinib, trametnimb, cobimetinib) was also calculated. Monitoring and treatment modalities were identified using Current Procedural Terminology (CPT) and HCFA Common Procedural Code System (HCPCS) codes (Supplemental Table). Finally, to examine the association between OPG and strabismus, strabismus claims were extracted, as well as age and type of strabismus (esotropia, exotropia, hypertropia, and not specified strabismus) and age at strabismus surgery (Supplemental Table).

Statistical analysis

The data extractions were conducted using SQL Software DBVisualizer Pro 10.0.15 (DbVis Software AB, Stockholm, Sweden), and all statistical analyses were performed using R (3.5.3) (R Foundation for Statistical Computing: https://www.R-project.org). Descriptive statistics were calculated for study variables. Per the data use agreement with OLDW to preserve data privacy and confidentiality, results with a count of less than 11 were either not reported or reported as a combined number with other groups or as < 11. The prevalence was calculated by dividing the number of OPG cases by the projected total number of children in OLDW. The overall estimated prevalence was based on a sample size derived from previous studies utilizing the same database.¹⁰ The distributions of demographic characteristics were shown and compared between the total children population and pediatric OPG patients.

Results

Our study analyzed health insurance claims from 2016 to 2021, studying children under 18 years with at least one OPG claim. Out of 9–11 million enrollees born in 1999 or later, 551 unique children had OPG claims, resulting in a prevalence of 4.6 ± 0.1 per 100,000. Excluding children with less than 6 months of follow-up, 476 pediatric OPG patients were included in subsequent analysis. The mean follow-up time was 2.8 ± 1.5 years, ranging from 0.5 to 5.5 years.

On average, the first OPG claim was 9.4 ± 4.6 years, with a range from 0 to 17.0 years. The majority (64.7%) were diagnosed between the ages of 5 and 15 years. The demographic characteristics of these children were similar to the overall OLDW database (Table 1).

Table 1.

Demographic characteristics of children with optic pathway gliomas (OPG) compared to pediatric patients in the Optum Labs Data Warehouse (OLDW) utilizing historical data. Age is listed as the age of first OPG claim. The number of Asian patients was less than 11, so it is combined with Unknown race and ethnicity.

Demographics	Children with OPG (N = 476)	OLDW Children (N=9,500,000+)
Age
< 5 years	84 (17.6%)	28%
5 - <10 years	158 (33.2%)	26%
10 - <15 years	150 (31.5%)	29%
15 - <18 years	84 (17.6%)	18%
Sex
Male	232 (48.7%)	51%
Female	244 (51.3%)	49%
Race / Ethnicity
Asian or Unknown	190 (39.9%)	37%
Black/African American	22 (4.6%)	7%
Hispanic	37 (7.8%)	9%
White	227 (47.7%)	48%
Census Region
Mid-West	134 (28.2%)	26%
North-East	23 (15.5%)	12%
South	59 (40.3%)	44%
West	23 (15.9%)	18%
Insurance
Commercial	455 (95.6%)	95%
HMO	21 (4.4%)	6%

We found that 133 (27.9%) of children with OPG claims had claims for strabismus. Among OPG children with claims for strabismus, 59 (44.3%) had esotropia, 66 (49.6%) with exotropia, 28 (21.0%) with hypertropia, and 15 (11.2%) not specified (Table 2). The mean age of first strabismus claim was 8.6 ± 4.4 years, occurring on average 6 months after first OPG claim. Demographically, there were no differences in age, gender, race, and insurance status between children with and without strabismus. However, we did find a difference in census region (p = 0.01) with an overrepresentation of strabismus in the MidWest (36.4%) and an underrepresentation in the West (13.6%). Among subtypes of strabismus, we found no difference in the age between exotropia and esotropia (p = 0.50). Additionally, a few strabismus patients (n < 11) underwent strabismus surgery at a mean age of 11.8 ± 6.0 years. Strabismus patients were over twice as likely to receive either OPG surgical or radiation treatment (12.8%, p < 0.001) and chemotherapy (21.1%, p = 0.006).

Table 2.

Percentages of strabismus type, mean age of strabismus at first OPG claim, strabismus surgery, and OPG treatment among children with optic pathway gliomas (OPG).

	Children with Strabismus (N = 133)	Mean Age (SD)
Strabismus		8.6 (4.4)
Esotropia	59 (44.3%)	8.2 (4.5)
Exotropia	66 (49.6%)	8.7 (4.0)
Hypertropia	28 (21.0%)	9.7 (5.0)
Unspecified	15 (11.2%)	10.2 (4.6)
Strabismus Surgery	<10 (NA%)	11.8 (6.0)
OPG Surgery/Radiation	17 (12.8%)**
OPG Chemotherapy	28 (21.1%)*

^**p < 0.001

^*p < 0.01

Of the OPG patients analyzed, 15.3% had at least one CT scan and 88.9% had at least one MRI scan. There were no demographic differences among children with CT scans. However, patients receiving MRI scans were younger than those without MRI scans with mean ages of 9.2 and 11.6 years respectively (p < 0.001).

For neuro-ophthalmic testing, 52.9% of children had at least one VF or OCT claim, with a mean of 2.6 ± 4.7 claims and a range of 0–35 claims throughout follow-up (Table 4). OCT scans were billed at least once in 40.1% of OPG children, with a mean age of 9.2 ± 4.2. For VF testing, 36.3% of children had at least one VF claim with an average age of 11.7 ± 3.7 years. OCT was used at similar rates to VF testing with an average of 0.5 tests per year. Additional analyses for rates of VF and OCT testing are included in Table 4. When examining children who only received one modality of neuro-ophthalmic testing, OCT was performed in younger children than VF testing with a mean age of 6.6 years and 12.7 years respectively (p < 0.001). Additional analyses for the age distribution of VF and OCT testing are included in Table 5.

Table 4.

Total number, range, and yearly rates of insurance claims for visual field (VF) and optical coherence tomography (OCT) testing among children with optic pathway gliomas (OPG). Number of claims and yearly claims are listed as claims since first OPG claim.

	Neuro-ophthalmic Testing (VF or OCT)	Visual Field (VF) Testing	Optical Coherence Tomography (OCT)
Children with claims	252	173	191
Claims per child (SD)	2.6 (4.7)	1.6 (3.1)	1.3 (2.4)
Range of total claims	0 – 35	0 – 28	0 – 17
Claims per year for all patients (N=476) (SD)	1.0 (1.8)	0.5 (1.2)	0.5 (0.9)
Claims per year for those with testing (SD)	2.0 (2.1)	1.5 (1.7)	1.2 (1.1)

Table 5.

Mean ages and age distribution for all neuro-ophthalmic testing (NO) including visual fields (VF) and optical coherence tomography (OCT). Mean age is listed as the age of first OPG claim.

	Any NO testing (n = 252)	Any VF (n = 173)	Any OCT (n = 191)	OCT and VF (n = 112)	VF only (n = 61)	OCT only (n = 79)	None (n = 224)
Age, Mean (SD)	10.1 (4.4)	11.7 (3.7)	9.2 (4.2)	11.1 (3.5)	12.7 (3.7)	6.6 (3.7)	8.76 (4.7)
< 10 yrs	118 (46.8%)	55 (31.8%)	104 (54.4%)	41 (36.6%)	~(25%)	~(70%)	124 (55.4%)
10 - < 15 yrs	81 (32.1%)	70 (40.5%)	60 (31.4%)	49 (43.8%)	~(35%)	~(15%)	69 (30.8%)
15 - <18 yrs	53 (21.0%)	48 (27.7%)	27 (14.1%)	22 (19.6%)	~(40%)	~(15%)	31 (13.8%)

Regarding the management of children with OPGs, 14.1% of children had at least one claim for chemotherapy, 6.1% had a claim for surgery or radiation, and 81.7% had no intervention (Table 3). Among patients requiring surgery or radiation, the vast majority underwent surgery alone. For chemotherapy use, 7.6% received one medication, 6.5% received two medications, and no child received three or more medications. Though our analysis searched for 12 chemotherapy agents, insurance claims for only three were found in the database. The most common medication submitted to insurance was carboplatin in 8.0% of children at a mean age of 6.8 ± 4.2 years. Vincristine, a vinca alkaloid, was documented in 7.1% of children at an average age of 6.5 ± 4.4 years. Bevacizumab, a VEGF inhibitor, was administered to 6.7% of children at an average age of 8.6 ± 3.6 years. There were no claims for procarbazine, lomustine, etoposide, cisplatin, carboplatin, or MAPK pathway inhibitors (selumetinib, refametinib, trametinib, cobimetinib). It is important to note that MAPK inhibitors were only used in clinical trials during the time period analyzed, and therefore, were not expected to be captured in OLDW insurance claims. No patients had claims for the combination of chemotherapy, radiation, and surgery together.

Table 3.

Percentage of children with optic pathway gliomas (OPG) with insurance claims for computed tomography (CT), magnetic resonance imaging (MRI), surgery or radiation treatment, and chemotherapy.

	Children with OPG (N = 476)	Mean Age (SD)
Neuroimaging
CT Brain	73 (15.3%)	9.2 (5.1)
MRI Brain	423 (88.9%)	9.5 (4.5)
Treatment
No treatment	389 (81.7%)
Surgery or radiation	29 (6.1%)	10.1 (5.3)
Any chemotherapy	67 (14.1%)
1 Agent	36 (7.6%)
2 Agents	31 (6.5%)
3 Agents	0 (0%)
Carboplatin	38 (8.0%)	6.8 (4.2)
Vincristine	34 (7.1%)	6.5 (4.4)
Bevacizumab	32 (6.7%)	8.6 (3.6)

Conclusions

We estimate the prevalence of pediatric OPGs to be 4.6 per 100,000, with 14% of children receiving chemotherapy and 6% receiving surgery or radiation. Although this estimate of prevalence relies on insurance claims in place of broad population-level studies, similar methods have shown consistent results in estimating the prevalence of rare diseases.^{10 11}

To our knowledge, the first study that examined a large number of children with OPG was a 1994 review article based on thousands of cases reported before 1992. From these data, Dutton et al. estimated the median age of OPG diagnosis to be seven years old, with approximately 90% of patients diagnosed before adulthood.² More recent studies using larger datasets have also provided important insights into OPG epidemiology. Using publicly available SEER data of children and adults from 2000–2018, Liu et al. estimated that 83.7% of OPG patients were less than or equal to 19 years old, with approximately 45% of patients under the age of 4 years.³

Previous research has suggested that OPG prevalence may be higher among girls, while others did not observe differences by sex (Table 1).^{3 12 13} Girls have also been shown to lose more vision and require more treatment than boys.¹² While we did observe increased strabismus prevalence rates in children with an OPG (27.9%) when compared to the general population (2–3%), the claims data did not include measures of visual acuity so we cannot answer sex disparities in vision loss.¹⁰ We did observe, however, that OPG children with strabismus received surgery or radiation at over double the rate of their strabismus-free peers, possibly suggesting more advanced disease. As strabismus was diagnosed on average only 6 months after OPG diagnosis, providers must advocate for more careful monitoring of strabismus in OPG patients. This is especially important when examining regional policy as we found that strabismus occurred more frequently in the MidWest (36%) and least frequently in the West (14%) (p = 0.01). Further studies will be helpful to further elucidate disparities in OPG patients.

Monitoring OPGs typically involves visual acuity assessment every 3 months for the first year, then every 6 months until age 8 years, and then annually until at least 18 years, with supplemental VF/OCT testing.¹⁴ Surprisingly, we found that only 52.9% of OPG patients had a claim for VF or OCT testing during their care, with patients averaging 1.0 VF or OCT claims per year (Table 4). It is unclear why this number was so low, but it may be related to poor cooperation due to age, poor visual acuity, and provider comfort with testing children. We found that 54% of OCT claims were for children diagnosed before the age of 10, compared to only 32% of claims for VF (Table 5). These age differences may be due to challenges in younger children as a high degree of attention is required; poor cooperation can mimic the pathological effects or mask underlying deficiencies.¹⁵

Although neuroimaging monitors the OPG size, extent, and shape, changes in imaging do not exclusively drive treatment decisions. Instead, time since diagnosis, degree of impairment, and disease progression determine the frequency of neurologic, imaging, and ophthalmological assessment.¹⁶ In our study, MRI was performed more frequently than CT.

Of those children treated with chemotherapy, most patients received a combination of carboplatin and vincristine, with a smaller number receiving bevacizumab in addition to either agent. No child received all three chemotherapy agents. Although recent clinical trials of MAPK inhibitors have shown promise, there were no claims for MAPK inhibitors as OLDW does not record medications used in clinical trials.¹⁷

Examining OPG patients under 5 years of age, Metzger et al. have shown much higher rates of surgical intervention in Switzerland. However, the proportion of children treated surgically decreased over time, from 94% in the 1990s to 84% in the 2010s. They also reported that radiotherapy treatment has remained relatively stable at approximately 40%.⁷ Liu et al. found that from 2000 to 2018, only 12.4% of children required radiation therapy or surgical resection and 63.1% of patients were monitored with observation only.³ In the present study from 2016 to 2021 there was a lower percentage of children treated with surgery or radiation (6.1%) and a higher percentage not requiring any treatment (81.7%). While not directly comparable, these findings may indicate a trend to more conservatively manage OPGs, underscoring the importance of appropriate monitoring.

While providing a valuable benchmark for demographic makeup and resource utilization in OPG management, this study has important limitations. The study was performed using limited data extraction which did not provide all demographic characteristics, most notably whether OPG patients had NF-1. Understanding the differences in resource utilization between NF-related OPGs and sporadic OPGs is critical to elucidating treatment burden and warrants future study. This study was performed utilizing historical data from previous OLDW studies as a comparison. Therefore, prevalence and demographic comparisons to the overall population were extrapolated and could not be directly determined.¹⁰

Our findings are also limited due to the use of insurance claim data; improper coding and unclear or incomplete data in large datasets may underestimate the prevalence and burden of treatment. These data did not capture care outside of commercial insurance or claims prior to enrollment within the system. These limitations skew the ages of children to be older and therefore underestimate rates of testing, burden, and cost to patients. Furthermore, this data does not distinguish between primary care provider diagnoses and referral to a tertiary center or by an eye care specialist. Reliance on insurance claims also limits the generalizability of these findings to specific populations (i.e., uninsured children and children ensured with Medicaid/Children’s Health Insurance Program). A lack of Medicaid patient data may also skew these findings, as many states contain a large proportion of children insured through Medicaid that may contain important differences in income and demographics.

While the majority of pediatric OPG patients are managed with observation alone, we found that only 53% of children undergo OCT or VF testing at least once a year. While frequent clinic visits and testing can be stressful for families, our research underscores the significance of implementing consistent, age-appropriate monitoring strategies for young children. Such strategies should involve early screening for visual impairment and strabismus, as well as regular neuro-ophthalmologic testing. We hope that advancements in capability will ultimately decrease the treatment burden and improve the long-term outcomes for these children.