Risk Factors for Glaucoma Diagnosis and Surgical Intervention following Pediatric Cataract Surgery in the IRIS^® Registry

Abstract

Purpose:

To compare demographic and clinical factors associated with glaucoma following cataract surgery (GFCS) and glaucoma surgery rates between infants, toddlers, and older children using a large ophthalmic registry.

Design:

Retrospective cohort study.

Participants:

Patients in the IRIS^® Registry (Intelligent Research in Sight) who underwent cataract surgery at ≤17 years old and between January 1, 2013 and December 31, 2020.

Methods:

Glaucoma diagnosis and procedural codes were extracted from the electronic health records of practices participating in the IRIS Registry. Children with glaucoma diagnosis or surgery before cataract removal were excluded. The Kaplan-Meier estimator was used to determine the cumulative probability of GFCS diagnosis and glaucoma surgery after cataract surgery. Multivariable Cox regression was used to identify factors associated with GFCS and glaucoma surgery.

Main Outcome Measures:

Cumulative probability of glaucoma diagnosis and surgical intervention within five years after cataract surgery.

Results:

The study included 6,658 children (median age 10.0 years; 46.2% female). The five-year cumulative probability of GFCS was 7.1% (95% CI 6.1%−8.1%) and glaucoma surgery was 2.6% (95% CI 1.9%−3.2%). The five-year cumulative probability of GFCS for children <1 year old was 22.3% (95% CI 15.7%−28.4%). Risk factors for GFCS included aphakia (HR 2.63; 95% CI 1.96–3.57), unilateral cataract (HR 1.48; 95% CI 1.12–1.96), and Black race (HR 1.61; 95% CI 1.12–2.32). The most common surgery was glaucoma drainage device (GDD) insertion (32.6%), followed by angle surgery (23.3%), cyclophotocoagulation (15.1%), and trabeculectomy (5.8%).

Conclusions:

GFCS diagnosis in children in the IRIS Registry was associated with young age, aphakia, unilateral cataract, and Black race. GDD surgery was the preferred surgical treatment, consistent with the World Glaucoma Association 2013 consensus recommendations for GFCS management.

In the IRIS^® Registry, one in five children less than one year old developed glaucoma within five years of cataract surgery. Aphakia and unilateral cataract were associated with increased risk of glaucoma diagnosis and surgery.

Introduction:

Glaucoma following cataract surgery (GFCS) is the most common vision-threatening complication after congenital cataract removal. In the United States, the incidence of congenital cataracts is about 2–5 per 10,000 live births.^1,2 While GFCS can be a potentially blinding complication, visually significant congenital cataracts are a major cause of dense amblyopia, and therefore, congenital cataract removal still remains a time sensitive issue.^3,4 The Infant Aphakia Treatment Study (IATS) group found that 22% of children undergoing unilateral infantile cataract surgery developed glaucoma within 10 years of surgery.^3,4 Common risk factors for GFCS include younger age at cataract removal and microcornea, while other possible risk factors include aphakic status, persistent fetal vasculature (PFV), posterior capsulotomy, and subsequent lens remnant removal.^3–7

An important distinction of GFCS is that the glaucoma develops after pediatric cataract removal. This process is different than diseases with concomitant cataract and glaucoma development such as Lowe syndrome or prenatal rubella infection, which are rare. In fact, GFCS is one of the most common types of childhood glaucoma, along with primary congenital glaucoma.^8–10 The chronology of GFCS implies that the pathogenesis is related to either the surgery itself or from post-surgical changes to an infant’s eye. In prior pediatric multicenter studies, GFCS is more common after surgery in early infancy, and uncommon in older children.^3,4,8 From the IATS, Toddler Aphakia and Pseudophakia Study (TAPS), and IOLunder2 studies, the strongest risk factor for GFCS has been young infants, particularly those under 4 months of age at time of surgery.^3,4,11–13 While the World Glaucoma Association/Childhood Glaucoma Research Network (WGA/CGRN) 2013 consensus group defined GFCS as following cataract removal during childhood, older children with cataract removal do not seem to have an increased association with glaucoma.^8,14

The American Academy of Ophthalmology’s IRIS^® Registry (Intelligent Research in Sight) is a nationwide eye disease registry of over 73 million patients under the care of 15,000 ophthalmologists.¹⁵ The IRIS Registry has been most useful for comparing practice patterns that utilize billable codes. As the largest nationwide subspecialty registry, data is also not limited by academic cohorts or regional differences. Previous GFCS studies have been limited by small cohorts from a few centers. Since childhood glaucoma is a rare group of diseases, of which GFCS is the most common iatrogenic cause, we investigated the IRIS Registry, the largest ophthalmologic registry, to compare nationwide demographic, clinical, and surgical patterns that were associated with GFCS between infants, toddlers, and older children.

Methods:

This was a retrospective cohort study performed using electronic medical record data of patients followed in practices participating in the IRIS Registry. The version of the database that this study uses was frozen on December 20, 2021 and accessed on June 9^th, 2022. The data collection methodology of the IRIS Registry has been described previously.¹⁵ The investigation was approved by the Massachusetts General Brigham Institutional Review Board with the exemption of informed consent. This research adhered to the Declaration of Helsinki and the United States’ Health Insurance Portability and Accountability Act.

Records of all children (0 to ≤17 years old) in the IRIS Registry who underwent cataract surgery between January 1, 2013 and December 31, 2020 were included in this study. Follow-up data was available up until December 31, 2020 in this version of the database. Pediatric cataract surgeries were identified using Current Procedural Terminology (CPT) codes for cataract extraction (Table S1). Surgical procedures missing laterality specifications of the CPT code were excluded. Children with glaucoma diagnosis or surgery on or before the date of cataract surgery were excluded (Table S1).

The dates of glaucoma diagnosis after cataract surgery and surgical intervention for glaucoma were identified through International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/ICD-10) and CPT codes; no glaucoma suspect codes were used. Missing ICD code laterality was not used as an exclusion criteria since laterality was not used in ICD coding prior to ICD-10. For this study, we made the assumption that incident glaucoma occurred in the eye that had cataract surgery. It would be rare for a child to have cataract surgery in one eye and then develop glaucoma only in their non-operative eye.¹⁶ The type of surgical intervention was categorized into glaucoma drainage device (GDD) insertion, angle surgery (ab interno or ab externo), laser cyclophotocoagulation (CPC), and trabeculectomy (Table S1). Office-based laser procedures including laser trabeculoplasty and peripheral iridotomy were also recorded. We obtained the total length of follow-up and most recent visual acuity converted to the Logarithm of the Minimum Angle of Resolution (LogMAR) scale. The main study outcomes were the cumulative probability of glaucoma diagnosis and surgical intervention within five years of cataract surgery obtained using the Kaplan-Meier estimator of survival. Cox regression models were used to quantify the association of glaucoma diagnosis and surgery with several risk factors. The risk factors investigated were patient age at cataract surgery, sex, race and ethnicity, geographic location, type of insurance, cataract laterality, presence of PFV, presence of microcornea, and intraocular lens (IOL) placement during cataract surgery. Age was categorized into 0 to <1, 1 to ≤4, and 5 to ≤17 years old. Race and ethnicity were treated as a categorical covariate with four groups: White non-Hispanic, Black non-Hispanic, Hispanic, and other. Geographic location was also a categorical covariate where the state of residence was categorized into one of four US census regions: Northeast, Midwest, South, and West. Insurance type was categorized into private versus non-private. For all analyses, cataract laterality was defined as bilateral if the initial surgery was performed bilaterally or if the second eye was operated within 90 days of the initial surgery. Presence of PFV and microcornea were identified by ICD diagnosis (Table S1). IOL placement during surgery was identified using CPT codes (Table S1).

All statistical tests were two-sided, and significance was defined as p < 0.05. Medians and interquartile ranges (IQR) are reported. Log-rank tests were used to compare survival patterns in the Kaplan-Meier plots for the overall cohort and by baseline demographic factors. Hazard Ratios (HR) with 95% confidence intervals (CI) are reported from multivariable regression models. All analyses were performed at the individual level with an eye selected at random for patients undergoing bilateral cataract surgery or sequential cataract surgery within 90 days using statistical software. All analyses were performed using R, version 4.2.0 (R Core Team, 2021) with the MICE package, version 3.13.0.10.¹⁷

Results:

In total, 6,658 children had cataract removal in the IRIS Registry in the study period (Figure S1). Two hundred fifty children developed glaucoma within 5 years, and 86 required a glaucoma surgery or procedure. The median age at the time of cataract removal was 10.0 years (IQR 5.0 – 14.0 years) while median length of follow-up was 1.7 years (IQR 0.4 – 3.7 years). Compared to the group with cataract removal at age 5–17 years (6.0%) and 1–4 years (6.3%), the group with cataract surgery prior to age 1 year had a higher five-year cumulative probability of developing glaucoma (22.2%, p < 0.001). Furthermore, microcornea (18.6% vs 7.1%, p = 0.019), aphakia (16.5 vs 5.2%, p < 0.001), Black race (11.8%, p=0.016), and unilateral cataract surgery (8.4 vs 5.4%, p = 0.004) were also associated with higher five-year cumulative probability of GFCS diagnosis (Table 2).

Table 2:

Relationship between Baseline Patient Demographics and Clinical Factors with Five-Year Cumulative Probability of Glaucoma Diagnosis and Surgery Following Pediatric Cataract Surgery

	Entire cohort, N = 6,658	Glaucoma diagnosis, N = 250	5-year cumulative probability (95% CI)	p-value*	Glaucoma Surgery, N = 86	5-year cumulative probability (95% CI)	p-value*
Age category, n (%)				<0.001			<0.001
5 to ≤17	5,119	160 (3.1)	5.949 (4.892 to 6.995)		49 (1.0)	2.034 (1.345 to 2.719)
1 to ≤4	1,112	38 (3.4)	6.278 (4.061 to 8.443)		17 (1.5)	2.490 (1.128 to 3.834)
<1	427	52 (12)	22.27 (15.66 to 28.35)		20 (4.7)	8.882 (4.432 to 13.13)
Sex, n (%)				0.2			0.3
Female	3,075	108 (3.5)	7.000 (5.543 to 8.434)		34 (1.1)	2.352 (1.427 to 3.268)
Male	3,540	142 (4.0)	7.301 (5.911 to 8.670)		51 (1.4)	2.791 (1.874 to 3.700)
Not Reported	43	0 (0)	0 (0 to 0)		1 (2.3)	2.439 (0 to 7.048)
Cataract laterality, n (%)				<0.001			0.009
Bilateral	2,634	76 (2.9)	5.352 (3.962 to 6.722)		24 (0.9)	1.725 (0.885 to 2.557)
Unilateral	4,024	174 (4.3)	8.432 (7.019 to 9.823)		62 (1.5)	3.229 (2.284 to 4.164)
Operative eye, n (%)				0.7			0.6
Left	3,209	118 (3.7)	7.487 (5.936 to 9.013)		44 (1.4)	2.760 (1.791 to 3.719)
Right	3,449	132 (3.8)	6.801 (5.510 to 8.075)		42 (1.2)	2.424 (1.556 to 3.285)
Race and ethnicity, n (%)				0.016			0.3
White Non-Hispanic	3,266	122 (3.7)	6.333 (5.103 to 7.548)		37 (1.1)	1.790 (1.176 to 2.400)
Black Non-Hispanic	812	42 (5.2)	11.81 (7.653 to 15.79)		13 (1.6)	4.384 (1.358 to 7.318)
Hispanic	1,046	42 (4.0)	8.115 (5.302 to 10.84)		19 (1.8)	3.731 (1.786 to 5.637)
Other	218	4 (1.8)	3.524 (0 to 7.177)		3 (1.4)	2.136 (0 to 4.505)
Unknown	1,316	40			14
Type of insurance, n (%)				0.7			0.074
Non-private	1,796	60 (3.3)	6.779 (4.716 to 8.798)		29 (1.6)	3.782 (2.019 to 5.514)
Private	3,899	162 (4.2)	6.951 (5.807 to 8.081)		49 (1.3)	2.188 (1.493 to 2.878)
Unknown	963	28			8
US census regions, n (%)				0.033			0.5
West	986	39 (4.0)	7.211 (4.762 to 9.597)		14 (1.4)	2.837 (1.127 to 4.518)
South	3,005	123 (4.1)	7.997 (6.334 to 9.631)		41 (1.4)	2.697 (1.711 to 3.673)
Midwest	1,455	36 (2.5)	5.173 (3.306 to 7.003)		14 (1.0)	2.017 (0.797 to 3.222)
Northeast	1,043	43 (4.1)	6.937 (4.648 to 9.170)		12 (1.2)	2.285 (0.686 to 3.858)
Unknown	169	9			5
PFV, n (%)				>0.9			0.3
No	6,534	245 (3.7)	7.092 (6.086 to 8.088)		83 (1.3)	2.515 (1.870 to 3.157)
Yes	124	5 (4.0)	8.853 (0.216 to 16.74)		3 (2.4)	5.881 (0 to 12.42)
Microcornea, n (%)				0.019			<0.001
No	6,624	246 (3.7)	7.061 (6.063 to 8.049)		83 (1.3)	2.445 (1.826 to 3.059)
Yes	34	4 (12)	18.55 (0 to 35.67)		3 (8.8)	26.34 (0 to 50.76)
Lens type, n (%)				<0.001			<0.001
aphakic	1,111	103 (9.3)	16.50 (13.07 to 19.79)		38 (3.4)	7.067 (4.477 to 9.586)
IOL	5,547	147 (2.7)	5.183 (4.212 to 6.145)		48 (0.9)	1.627 (1.078 to 2.173)
Overall			7.129 (6.129 to 8.118)			2.588 (1.940 to 3.232)

Abbreviations: N = total number of patients, CI = confidence interval, n = number of patients, US = United States, PFV = persistent fetal vasculature, IOL = intraocular lens implant

^*log-rank test

The most common choice for initial glaucoma surgery after cataract surgery was GDD insertion (32.6%). Other glaucoma surgeries performed were angle surgery (23.3%), CPC (15.1%), and trabeculectomy (5.8%). The remaining procedures included other types of glaucoma surgery and office-based laser procedures (23.3%). Compared to the group with cataract removal at age 5–17 years (2.0%) and 1–4 years (2.5%), the group with cataract surgery prior to age 1 year had a greater five-year cumulative probability of receiving glaucoma surgery (8.9%, p < 0.001). Patients with microcornea (26.3 vs 2.4%, p < 0.001), aphakia (7.1 vs 1.6%, p < 0.001), and unilateral cataract surgery (3.2 vs 1.7%, p = 0.009) were also associated with a greater five-year cumulative probability of receiving glaucoma surgery (Table 2).

Using the Kaplan-Meier estimator, the five-year cumulative probability for GFCS overall was 7.1% (95% CI 6.1% – 8.1%) and for glaucoma surgery was 2.6% (95% CI 1.9% – 3.2%). Figure 2 shows the cumulative probability of GFCS diagnosis by age at cataract surgery. Using multivariable Cox regression models, higher risk of GFCS diagnosis was associated with cataract surgery before age 1 year (HR 2.33, 95% CI 1.60 – 3.40, p < 0.001; reference: age group 5–17 years at cataract removal). There was no statistical difference between GFCS risk in those who had cataract removal at age 1–4 years versus at 5–17 years (p = 0.35). Higher risk of GFCS was also associated with aphakia (HR 2.63; 95% CI 1.96 – 3.57, p < 0.001), Black race (HR 1.61; 95% CI 1.12 – 2.32, p = 0.010), unilateral cataract (HR 1.48; 95% CI 1.12 – 1.96, p = 0.006), and lower risk of GFCS was associated with presence of PFV (HR 0.35; 95% CI 0.14 – 0.88, p = 0.025). Higher risk of glaucoma surgery after cataract removal was associated with age < 1 year at cataract removal (HR 2.55, 95% CI 1.34 – 4.85; p = 0.004), aphakia (HR 2.56, 95% CI 1.56 – 4.35, p < 0.001), and unilateral cataract (HR 1.72 (1.05 – 2.83, p = 0.031; Table 3).

Figure 2:

Cumulative Probability of Glaucoma Following Cataract Surgery by Age Group.

Notes: Shaded areas = corresponding 95% confidence intervals.

Table 3:

Multivariable Cox Regression Analysis of Glaucoma Diagnosis and Surgery following Pediatric Cataract Surgery

	Glaucoma diagnosis		Glaucoma surgery
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age group (years)
5 to ≤17	1.00		1.00
1 to ≤4	0.84 (0.57 to 1.21)	0.35	1.13 (0.62 to 2.06)	0.69
<1	2.33 (1.60 to 3.40)	<0.001	2.55 (1.34 to 4.85)	0.004
Female	0.90 (0.69 to 1.16)	0.40	0.74 (0.47 to 1.16)	0.19
Cataract laterality
Bilateral	1.00		1.00
Unilateral	1.48 (1.12 to 1.96)	0.006	1.72 (1.05 to 2.83)	0.031
Race and ethnicity
White Non-Hispanic	1.00		1.00
Black Non-Hispanic	1.61 (1.12 to 2.32)	0.010	1.42 (0.73 to 2.78)	0.31
Hispanic	0.89 (0.62 to 1.28)	0.54	1.29 (0.72 to 2.31)	0.39
Other	0.48 (0.18 to 1.30)	0.15	1.21 (0.37 to 3.97)	0.76
Unknown	0.90 (0.61 to 1.32)	0.59	1.05 (0.54 to 2.04)	0.88
US census region
West	1.00		1.00
South	1.01 (0.70 to 1.46)	0.95	1.00 (0.54 to 1.87)	>0.99
Midwest	0.61 (0.39 to 0.97)	0.038	0.78 (0.37 to 1.68)	0.53
Northeast	0.90 (0.58 to 1.39)	0.63	0.75 (0.34 to 1.64)	0.47
Private insurance
Non-private	1.00		1.00
Private	1.13 (0.84 to 1.53)	0.42	0.68 (0.43 to 1.09)	0.11
Unknown	1.12 (0.70 to 1.78)	0.64	0.49 (0.20 to 1.20)	0.12
PFV	0.35 (0.14 to 0.88)	0.025	0.62 (0.18 to 2.09)	0.44
Microcornea	1.53 (0.56 to 4.18)	0.41	2.96 (0.89 to 9.86)	0.077
IOL placement	0.38 (0.28 to 0.51)	<0.001	0.39 (0.23 to 0.64)	<0.001

Abbreviations: HR = Hazard Ratio, CI = confidence interval, US = United States, PFV = persistent fetal vasculature, IOL = intraocular lens implant

Figure 3 shows the cumulative probability of glaucoma between aphakes and pseudophakes by age group. Five-year cumulative probability of GFCS diagnosis was higher in aphakes than pseudophakes for those in the cataract surgery at age 5–17 year group (p < 0.001) while it was not in the age 0–1 and 1–4 year groups (p ≥ 0.16). Five-year cumulative probability of glaucoma surgery was also higher in aphakes than pseudophakes for those in the cataract surgery at age 5–17 year group (p < 0.001), but not in the age 0–1 and 1–4 year groups (p ≥ 0.23). Similarly, there was a higher proportion of GFCS patients with eye trauma in the age 5–17 year group than in the age 0–1 and 1–4 year groups at time of cataract surgery (p < 0.001). There were no proportional differences in GFCS patients who also had uveitis between the three age groups (p = 0.45).

Figure 3:

Cumulative Probability of Glaucoma Following Cataract Surgery and Surgical Intervention in Aphakes versus Pseudophakes by Age Group. Notes: Age group in years. Shaded areas = corresponding 95% confidence intervals. Proportion of patients with aphakia by age group: 70.0% in cataract surgery at age < 1 year group, 29.9% in 1–4 year group, and 9.4% in 5–17 year group.

Discussion:

In the IRIS Registry, GFCS was an overall uncommon diagnosis at 5 years after pediatric cataract removal, except in those < 1 year of age at the time of surgery. GFCS diagnosis was also associated with unilateral cataract, aphakia, and Black race. In the subgroup analysis, aphakia was associated with GFCS in older children, but not in infants or toddlers. We also found that the most common choice for glaucoma surgery following cataract surgery was GDD insertion, followed by angle surgery, CPC, and then trabeculectomy. Lastly, glaucoma surgery was associated with young age, unilateral cataract, and aphakia.

Although overall GFCS cumulative probability was 7.1% at 5 years, GFCS cumulative probability at 5 years was as high as 22.3% in those < 1 year old at the time of surgery. Historically, overall GFCS incidence in children has been between 6–15%.^18,19 For infants, other studies have estimated GFCS incidence to be between 17–75% by 6 years.^3,4,16,20 In the IATS study, the authors found higher odds of GFCS in those with cataract removal before 7 weeks old compared to after 7 weeks.⁴ However, the IATS study authors still emphasize the importance of early cataract removal due to the higher risk of vision loss from cataract-related amblyopia. GFCS incidence in the IATS study was found to be 17% and 22% at 5 and 10 years, respectively, based on optic disc or OCT RNFL progression.^3,4 Similar to the IATS study, our study found that the largest increase of new cases in the youngest age group occurred in the first year after cataract surgery. This further supports a temporal relationship with the cataract surgery event and GFCS pathogenesis, likely from trabecular meshwork injury. Both the TAPS and IOLunder2 multicenter cohort studies investigated cataract surgery outcomes in infants younger than 2 years old. GFCS incidence at 5 years was between 2–20% in TAPS and between 12–20% in IOLunder2, which is similar to our study.^11–13 Our study utilized ICD-9 and ICD-10 billing codes to estimate GFCS diagnosis rates, which may tend to overestimate glaucoma incidence since providers may code for glaucoma in patients in whom there is a high suspicion. In contrast, CPT coding for glaucoma surgery is less prone to overestimation errors. We also compared glaucoma surgery rates after GFCS, which was as high as 8.9% in the age < 1 year group, and as low as 2.0% in the age 5–17 year group at cataract removal. Therefore, glaucoma surgery within 5 years of pediatric cataract surgery was uncommon in this cohort.

Children who had cataract removal after 1 year of age in the IRIS Registry were unlikely to acquire GFCS. Walton postulated that release of lens epithelial cells in congenital cataract surgery contributed to post-operative inflammation and injury of the trabecular meshwork, leading to GFCS.²¹ Other theories include anatomical collapse of the trabecular meshwork in the absence of the phakic lens.¹⁴ We suspect that the risk of these pathological changes decreases with age, which may explain the relative lack of GFCS in older children. Trauma was more common in the age 5–17 year group at cataract removal, which may account for some of the glaucoma in this age group. In a study from Toronto, Canada, the three most common types of secondary glaucoma with a mean age of onset > 5 years old were from trauma, steroid response, and uveitis.⁹ Trauma also may account for why aphakia was associated with GFCS in the age 5–17 year group at cataract removal, but not in the 0–1 or 1–4 year groups. In a prospective registry study of children aged less than 13 years at time of cataract surgery by the Pediatric Eye Disease Investigator Group, the incidence of glaucoma plus glaucoma suspect diagnoses at 5 years was also low for children older than 1 year of age at time of surgery (6–11% for pseudophakes between 3–12 years old), but was also noted to be higher in the aphakic group (25% for aphakes in the 2–12 year group).²² Their study did include some patients with ocular disorders that were usually excluded in clinical trials. In our study, we did not include glaucoma suspect diagnoses due to the higher risk of overcoding errors from a billing code registry.

Some risk factors that were associated with GFCS in this study corresponded with the current literature, while others did not. Aphakia and unilateral cataract surgery are usually related with younger age at cataract removal.^13,23 However, we found that aphakia was mainly associated with higher odds of GFCS in the age 5–17 year group in the subgroup analysis. Adult aphakia has also been associated with glaucoma in previous studies.²⁴ Unilateral cataract surgery has also been associated with GFCS in some studies likely due to its association with PFV and earlier cataract surgery.²⁵ In contrast, bilateral cataract surgery has also been found to be associated with GFCS in other studies, likely because it may also be associated with systemic syndromes that have higher risk for glaucoma.^7,22 Interestingly, presence of microcornea and PFV were not associated with GFCS diagnosis here. In fact, PFV was found to associated with lower risk of GFCS after adjusting for age in the multivariable analysis. Both the overall prevalence of PFV and microcornea diagnosis codes in this cohort was very small (likely due to undercoding), which may explain these two unusual findings in the multivariable analysis. Previous studies have produced mixed results on whether aphakia and PFV are associated with GFCS.^4,5,13,26 Many studies have shown a strong association between microcornea and GFCS.^3,4,11,19

We found a novel association between Black race and GFCS diagnosis. In the US National Birth Defects Prevention Study, race was not statistically associated with increased congenital cataract prevalence, but low birth weight was.²⁷ Other historical risk factors for congenital cataracts have included intrauterine infection, genetic and metabolic disorders, and Down syndrome.²⁸ However, in a separate US National Birth Defects Prevention Study analysis on primary congenital glaucoma (PCG), Black race was associated with increased PCG prevalence.²⁹ In the US, Black race has also been associated with juvenile- and adult-onset primary open angle glaucoma.³⁰ As big data registries make demographic and socioeconomic information more available, we must consider how social determinants of health might explain racial differences in disease prevalence, especially given the iatrogenic nature of GFCS. Given the propensity for GFCS and amblyopia after cataract removal and the need for lifelong monitoring, social determinants of health that limit follow-up or medication adherence may explain some of these health inequities.

Glaucoma surgery after cataract surgery was significantly associated with cataract removal at age < 1 year, further supporting that GFCS is more aggressive with younger age. We found that GDD insertion was more common than angle surgery for GFCS. At the time of the WGA/CGRN 2013 consensus statement, GDD insertion or trabeculectomy were the recommended first line treatments for GFCS.¹⁴ However, subsequent studies have shown great success with angle surgery for GFCS, which may be related to the wider adoption of 360 degree trabeculotomy techniques.^31,32 In a survey of worldwide CGRN members, CPC (41.7%) was the most common first line surgery performed for GFCS, followed by angle surgery (26.7%) and GDD insertion (26.7%).⁸ CPC is often reserved for glaucoma patients with poor vision, so it is possible that regions with dense amblyopia after cataract surgery may be using CPC earlier in the disease course. Challenging angle anatomy that may occur after cataract removal may also dissuade those with less experience in angle surgery. Furthermore, surgical preferences may vary depending on training, which further supports the need for databases such as the IRIS Registry to highlight these discrepancies.

There are several limitations to this large retrospective database study. As the IRIS Registry relies on diagnosis and procedural coding, data extraction may be limited by miscoding or missing data. For example, secondary diagnoses such as PFV and microcornea are likely to be undercoded, which may account for the lack of associations found in this study. Short follow-up length for the overall cohort may have also underpowered estimations of cumulative probability. While the IRIS Registry is a comprehensive national database, information from academic centers and children are less represented in this registry. However, this trait may better reflect nationwide GFCS rates among non-academic providers in the United States, who may have been previously underrepresented in the literature. Although we excluded those with previous glaucoma diagnosis or surgery before cataract surgery, we cannot exclude the possibility that some cases, especially older children, developed secondary glaucoma related to something other than their cataract surgery such as uveitis or trauma.

Conclusion:

In summary, we found the 5-year cumulative probability of GFCS in children was less than ten percent in the IRIS Registry, but was higher than twenty percent in those who had cataract surgery prior to 1 year of age. Due to our study’s size and age range, we were able to examine how GFCS rates differ between infants, toddlers, and older children. This study shows that GFCS is quite uncommon in older children and older toddlers. Potential risk factors such as race require further study, especially in the context of social determinants of health. GDD insertion was most often the initial choice for GFCS surgical treatment, but future comparative studies between different surgeries for GFCS and their outcomes may be warranted. This study underscores the IRIS Registry’s capacity to highlight nationwide risk factors and practice pattern differences that may not be captured in smaller multicenter studies.

Supplementary Material

1

Figure S1: Flow chart of study inclusion and exclusion criteria.

Appendix:

Members of the IRIS^® Registry Analytic Center Consortium:

Suzann Pershing, MD¹; Leslie Hyman, PhD²; Julia A. Haller, MD²; Aaron Y. Lee, MD, MSCI^3,4; Cecilia S. Lee, MD, MS⁴; Flora Lum, MD⁵; Joan W. Miller, MD⁶; Alice C. Lorch, MD, MPH⁶

1. Stanford University, Palo Alto, CA, USA

2. Wills Eye Hospital, Philadelphia, PA, USA

3. eScience Institute, University of Washington, Seattle, WA, USA

4. Department of Ophthalmology, University of Washington, Seattle, WA, USA

5. American Academy of Ophthalmology, San Francisco, CA, USA

6. Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA