Factors associated with the use of botulinum toxin injections for adult strabismus in the IRIS Registry

Abstract

This cross-sectional study used data from a large nationwide registry to describe the factors associated with use of botulinum toxin injections for adults with strabismus in the United States. Botulinum toxin injections were performed on 3.1% of adults undergoing an intervention for strabismus between 2013 and 2020. Adults treated with botulinum toxin injections were more likely to be older and female. Compared to non-Hispanic White patients, non-Hispanic Black patients were three times less likely to receive treatment with botulinum toxin after adjusting for age, sex, geographic region, and type of insurance. Efforts to understand the factors contributing to disparities in the use of botulinum toxin for strabismus may lead to opportunities for more equitable access to this intervention.

Botulinum toxin injection is a versatile technique for the management of strabismus first reported by Alan Scott in 1980. It can provide temporary relief of diplopia, guide future surgical intervention, and in some cases circumvent the need for incisional surgery.^1–3 The most common indications for botulinum toxin in adults include acute acquired comitant esotropia, smaller-angle esotropia, acute-onset abducens nerve palsy, or use as an adjunct to surgery for large-angle esotropia.^2,3 The costs associated with the medication and the frequent need for prior authorization may be barriers to utilization of this treatment.⁴ Challenges to medication access may disproportionately affect individuals from financially disadvantaged backgrounds, who may have insurance coverage with high out-of-pocket costs or lack the advocacy support to successfully navigate the prior-approval process. In this study, we used a large nationwide registry to analyze the factors associated with strabismus management using botulinum toxin injections.

Subjects and Methods

This cross-sectional study was performed using electronic health record data of patients in the Intelligent Research in Sight (IRIS) Registry. The study was approved by the Massachusetts General Brigham Institutional Review Board and adhered to STROBE reporting guidelines.

We included all adults (age ≥18 years) in the IRIS Registry undergoing an intervention for strabismus between January 1, 2013, and December 31, 2020. Strabismus procedures were identified using Current Procedural Terminology (CPT) codes (CPT 67311–67399). The primary outcome was receipt of botulinum toxin injection (CPT 67345) during the study interval. Data collected from the registry included age, sex, race, ethnicity, geographic location, and type of insurance. Age was treated as a continuous variable. Sex was categorized into male, female, and not reported. Race and ethnicity were categorized into non-Hispanic White, non-Hispanic Black, Hispanic, and other race and ethnicity. Geographic location was categorized based on the US census region of the zip code of residence. Insurance type was categorized into Medicaid, Medicare, Commercial, and other (including military insurance, unspecified government insurance, and no insurance).

Chi-square testing was used to compare the prevalence of botulinum toxin across the sociodemographic strata in the univariate analysis. Multivariable logistic regression models were used to estimate the associations between receipt of botulinum toxin injection and age, sex, race and ethnicity, geographic location, and type of insurance. Odds ratios (OR) with 95% confidence intervals (CI) were obtained from the multivariable logistic regression models. All statistical tests were two-sided, and significance was defined as P < 0.05. Analyses were performed using R, version 4.2.0 (R Core Team, 2022).

Results

Strabismus procedures were performed on 52,717 adults during the study period. Of these, 3.1% (1566/52,717) were treated with botulinum toxin chemodenervation of the extraocular muscles. In univariate analyses, patients treated with botulinum toxin injections were more likely to be older (median, 62 vs 54 years [P < 0.001]) and female (3.6% vs 2.1% [P < 0.001]). Compared to non-Hispanic White patients, Black patients were less likely receive treatment with botulinum toxin (1.2% vs 3.2%; P < 0.001). These procedures were more likely to be performed in the South (3.4%) and Northeast (4.4%) regions, and less likely in the West (2.2%) and Midwest (1.2%) regions (P < 0.001). Patients covered by Medicare (4.0%) and Medicaid (2.7%) were more likely to receive botulinum toxin injections compared to those covered by commercial insurance plans (2.2%; P < 0.001) (Table 1).

Table 1.

Factors associated with receipt of botulinum toxin injection among adults in the IRIS Registry undergoing intervention for strabismus

	Overall	Botulinum toxin injection			Multivariable model
	N = 52,717a	No, n = 51,151a	Yes n = 1,566a	P valueb	OR	95% CI	P value
Age, years				<0.001
18–29	8,885 (17%)	8,743 (98%)	142 (1.6%)		1.00	—
30–39	7,192 (14%)	7,071 (98%)	121 (1.7%)		1.08	0.84, 1.38	0.6
40–49	6,966 (13%)	6,799 (98%)	167 (2.4%)		1.56	1.25, 1.97	<0.001
50–59	8,211 (16%)	7,942 (97%)	269 (3.3%)		2.17	1.77, 2.68	<0.001
60–69	10,069 (19%)	9,697 (96%)	372 (3.7%)		2.32	1.88, 2.87	<0.001
70+	11,394 (22%)	10,899 (96%)	495 (4.3%)		2.64	2.12, 3.30	<0.001
Sex				<0.001
Female	29,721 (56%)	28,652 (96%)	1,069 (3.6%)		1.00	—
Male	22,791 (43%)	22,301 (98%)	490 (2.1%)		0.58	0.52, 0.65	<0.001
Unknown	205 (0.4%)	198 (97%)	7 (3.4%)		0.82	0.35, 1.63	0.6
Race and ethnicity				<0.001
White Non-Hispanic	36,238 (69%)	35,084 (97%)	1,154 (3.2%)		1.00	—
Black Non-Hispanic	3,928 (7.5%)	3,882 (99%)	46 (1.2%)		0.36	0.27, 0.49	<0.001
Hispanic	3,519 (6.7%)	3,400 (97%)	119 (3.4%)		1.16	0.94, 1.40	0.15
Other	792 (1.5%)	766 (97%)	26 (3.3%)		1.19	0.78, 1.74	0.4
Unknown	8,240 (16%)	8,019 (97%)	221 (2.7%)		0.90	0.77, 1.04	0.2
US census region				<0.001
South	21,214 (40%)	20,503 (97%)	711 (3.4%)		1.00	—
Northeast	11,172 (21%)	10,682 (96%)	490 (4.4%)		1.34	1.19, 1.51	<0.001
West	7,941 (15%)	7,769 (98%)	172 (2.2%)		0.58	0.49, 0.68	<0.001
Midwest	11,279 (21%)	11,131 (99%)	148 (1.3%)		0.37	0.31, 0.44	<0.001
Unknown	1,111 (2.1%)	1,066 (96%)	45 (4.1%)		1.21	0.88, 1.63	0.2
Insurance type				<0.001
Commercial	18,195 (35%)	17,802 (98%)	393 (2.2%)		1.00	—
Medicare	16,833 (32%)	16,156 (96%)	677 (4.0%)		1.29	1.10, 1.52	0.002
Medicaid	7,492 (14%)	7,291 (97%)	201 (2.7%)		1.37	1.15, 1.63	<0.001
Other	5,418 (10%)	5,309 (98%)	109 (2.0%)		0.90	0.72, 1.11	0.3
Unknown	4,779 (9.1%)	4,593 (96%)	186 (3.9%)		2.03	1.69, 2.43	<0.001

CI, confidence interval; OR, odds ratio.

^aResults provided as no. (%).

^bPearson’s χ² test.

In the multivariable model, greater odds of receiving treatment with botulinum toxin injection were associated with older age and female sex. After adjusting for age, sex, geographic region, and type of insurance, Black patients with strabismus were less likely to receive treatment with botulinum toxin injection than non-Hispanic White patients (OR = 0.36; 95% CI, 0.27–0.49; P < 0.001). The adjusted model also showed that adults who underwent treatment for strabismus with government insurance, including Medicare (OR = 1.29; 95% CI, 1.10–1.52; P = 0.002) and Medicaid (OR = 1.37; 95% CI, 1.15–1.63; P < 0.001), were more likely to have received botulinum toxin injections compared to commercially insured patients (Figure 1).

FIG 1.

Multivariable logistic regression demonstrating the association between sociodemographic factors and receipt of botulinum toxin injection for strabismus.

Discussion

After adjusting for type of insurance and regional practice patterns, Black adults with strabismus had a three times lower likelihood of receiving treatment with botulinum toxin. Differences in the utilization patterns for botulinum toxin injections for extraocular muscles by race and insurance type have not been previously described. The underlying factors contributing to these disparities and implications of these findings on equitable access to this versatile tool in strabismus management deserve further investigation, especially given the potential quality of life improvement in adults treated with botulinum toxin.⁵

With an array of clinical applications beyond strabismus,⁶ botulinum toxin use has been associated with regional, racial, and socioeconomic factors in several other specialties. In a study of commercially insured patients diagnosed with refractory overactive bladder, non-White individuals with a lower education level, and lower income had a decreased likelihood of receiving advanced therapies, including botulinum toxin injection.⁷ Evidence of regional differences in botulinum toxin in use for spasticity have been reported,⁸ and socioeconomic factors have also been associated with the frequency of injections for spasmodic dysphonia.⁹ Patients with spasmodic dysphonia treated with botulinum toxin injections had higher income and education levels, and were more likely to speak English as a primary language.⁹

Commercial insurance plans in this cohort were associated with a lower likelihood of receiving treatment with botulinum toxin injection. The larger hurdles for reimbursement imposed by private payers compared to government payers may be responsible for this difference; however, shifts in government payer prior authorization requirements may alter this relationship in the future.¹⁰ Although there is likely a large variation in the prior authorization barriers associated with botulinum toxin use among private insurance carriers, we were unable to explore this using the IRIS Registry, because granular information on specific carriers, prior authorization requirements, provider reimbursement, and out-of-pocket costs was unavailable. Further investigation using a multipayer insurance claims database may reveal further insight into the range of reimbursement and association with utilization.

Several other limitations of the IRIS Registry are important to consider. First, although patients are sampled from over 70% of eye care practices across the United States, certain types of practices such as academic medical centers may be underrepresented in the registry. Although the IRIS Registry is a large and nationwide database, botulinum toxin injections are relatively infrequently performed thus limiting statistical power for subgroup analyses of individual indications for injections such as abducens nerve palsy. The relationship between patient demographics and use of botulinum toxin may be confounded by other clinical factors such as strabismus type that were not included in this multivariable analysis. In addition, there may be differences in the severity of underlying ocular misalignment, patient knowledge regarding options and indications for treatment, and overall interest in intervention, which cannot be assessed using this large database. Finally, the complex relationship between race, insurance, and access to treatment may have many potential confounders that are unaccounted for in this registry-based analysis, including, for example, unconscious physician bias and patient preference.

In summary, geographic and demographic variation exists in the utilization patterns of botulinum toxin for strabismus in the IRIS Registry. Black race was associated with a lower likelihood of receiving treatment with botulinum toxin. Large clinical registries may provide insight into subtle inequities in access to ophthalmic interventions. Efforts to understand the factors contributing to disparities in the use of botulinum toxin for strabismus may lead to novel opportunities to address barriers and enable equitable access to this intervention.

Literature Search

MEDLINE was queried for research articles related to access to botulinum toxin injections for strabismus. The query was performed in November 2023, restricted to English language articles, and used the following keyword search strategy: ((botulinum toxin) OR (botox) OR (onabotulinumtoxinA) OR (abobotulinumtoxinA) OR (chemodenervation)) AND ((disparities) OR (equity) OR (race) OR (ethnicity) OR (insurance)) AND ((strabismus) OR (eye muscle) OR (ophthalmology)).