Prevalence and Risk Factors of Blindness Among Primary Angle Closure Glaucoma Patients in the United States: An IRIS^® Registry Analysis

Abstract

Purpose:

To assess the prevalence and risk factors of blindness among patients newly diagnosed with primary angle closure glaucoma (PACG) in the United States (US).

Design:

Retrospective cross-sectional study.

Methods:

Eligible patients from the American Academy of Ophthalmology (AAO) IRIS^® Registry (Intelligent Research in Sight) had newly diagnosed PACG, defined as: 1) observable during a 24-month lookback period from index date of PACG diagnosis; 2) no prior history of eye drops, laser, or cataract surgery unless preceded by a diagnosis of anatomical narrow angle (ANA); 3) no prior history of glaucoma surgery. Logistic regression models were developed to identify risk factors for any (one or both eyes) or bilateral (both eyes) blindness (visual acuity ≤ 20/200) at first diagnosis of PACG.

Results:

Among 43,901 eligible patients, overall prevalence of any and bilateral blindness were 11.5% and 1.8%, respectively. Black and Hispanic patients were at higher risk of any (OR=1.42 and 1.21, respectively; p<0.001) and bilateral (OR=2.04 and 1.53, respectively; p<0.001) blindness compared to non-Hispanic White patients adjusted for ocular comorbidities. Age <50 or >80 years, male sex, Medicaid or Medicare insurance product, and Southern or Western practice region also conferred higher risk of blindness (OR>1.28; p≤0.01).

Conclusions and Relevance:

Blindness affects 1 out of 9 patients with newly diagnosed PACG in the IRIS^® Registry. Black and Hispanic patients and Medicaid and Medicare recipients are at significantly higher risk. These findings highlight the severe ocular morbidity among PACG patients and the need for improved disease awareness and detection methods.

Précis

Blindness affects 1 out of 9 patients with newly diagnosed primary angle closure glaucoma (PACG) in the IRIS^® (Intelligent Research In Sight) Registry. Black and Hispanic patients and Medicaid and Medicare recipients are more vulnerable.

Introduction

Primary angle closure glaucoma (PACG) is a visually devastating disease and leading cause of irreversible blindness worldwide.^1–3 The current global prevalence of PACG is approximately 23 million, although this number is projected to rise to approximately 32 million by 2040 due to the aging of the world’s population.¹ Any rise in the prevalence of PACG is problematic due to high rates of blindness associated with the disease; it is estimated that blindness affects 27.0% of those with PACG worldwide.³ Quality of life (QoL), defined as an individual’s experience of health, comfort, and happiness, is significantly diminished by blindness, especially when bilateral.^4–6 Blindness also has a profound impact on the global economy; the economic burden of vision loss has been estimated to be $134.2 billion annually in the United States (US) alone.⁷ Therefore, there exists an urgent need to better understand the burden and risk factors of blindness associated with treatable ocular diseases, such as PACG, in diverse patient populations.

While primary open angle glaucoma (POAG) is twice as common as PACG, PACG confers a two-fold higher risk of blindness.³ Therefore, POAG and PACG are associated with a similar number of cases of blindness worldwide.⁸ The visually devastating nature of PACG stems from severely obstructed aqueous outflow and elevated intraocular pressure (IOP), which can lead to rapid and extensive glaucomatous damage. Laser and surgical treatments help alleviate angle closure, which effectively delay or even prevent the onset of elevated IOP and PACG.^9,10 Therefore, many cases of irreversible blindness associated with PACG could be avoided if high-risk patients are identified and treated earlier in the disease course.

There are an estimated 700,000 people with PACG in the US.¹ While there is abundant data on PACG outside of the US, little is known about the visual morbidity associated with PACG within the US.¹¹ In this study, we use data from the IRIS^® Registry (Intelligent Research in Sight) to assess the prevalence of blindness among patients newly diagnosed with PACG in the US. We speculate there may be lower ocular morbidity associated with PACG in the US compared to other regions of the world given high health expenditures per capita in the US.^12–18 We also assess sociodemographic factors to identify groups of patients with newly diagnosed PACG that appear more vulnerable to blindness and could benefit from improved provider awareness and detection methods.

Methods

The American Academy of Ophthalmology IRIS^® Registry is a comprehensive clinical registry that includes data on approximately 441 million patient visits for over 73 million unique patients as of April 1, 2022. Available eye-level clinical data (with specified laterality) included dates of clinical diagnoses, visual acuity (VA), intraocular pressure (IOP), and dates of procedures including laser peripheral iridotomy (LPI) and cataract and glaucoma surgeries. Available patient-level clinical data included history of IOP-lowering medications (without specified laterality). Available patient-level sociodemographic data included age, race, sex, insurance category, and practice region. Race and ethnicity, which are cultural constructs with biological contribution through genetic heritage, were self-reported by patients and combined into a single variable in the IRIS^® Registry.¹⁹ This study was approved by The University of Southern California Institutional Review Board. The study adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act.

Study Population Selection and Definitions

Patients with a diagnosis of PACG based on International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) codes (Supplementary Table 1) between the years of 2015 to 2019 were identified from the IRIS^® Registry. PACG diagnoses were analyzed on the eye level. The index date of diagnosis was defined as the date of the first visit associated with a PACG diagnosis. Eligible patients were aged 18 years and older with newly diagnosed PACG, defined as: (1) observable in the IRIS^® Registry for at least 24 months prior to the index date of PACG diagnosis; (2) no prior history of IOP lowering drops, LPI, cataract surgery, or a diagnosis of pseudophakia in either eye unless preceded by a diagnosis of anatomical narrow angles (ANA; also referred to as primary angle closure without glaucoma) based on ICD or Current Procedural Terminology (CPT) codes (Supplementary Table 1); (3) no history of glaucoma surgery (defined as trabeculectomy, glaucoma shunt, and cyclophotocoagulation) in either eye based on CPT codes (Supplementary Table 1). Criterion 1 was implemented to ensure that cases of PACG were newly diagnosed, based on the standard-of-care practice of monitoring PACG patients at least once per year. Criterion 2 was implemented to ensure that patients who had potentially received angle closure interventions for a diagnosis of ANA rather than PACG would not be excluded from the analyses. Criterion 3 was implemented to ensure that patients who had previously received glaucoma interventions would not be designated as newly diagnosed PACG.

Visual acuity data from the index date of diagnosis was analyzed on the eye level. Blindness was defined as VA ≤ 20/200 in at least one eye (any blindness) or in both eyes (bilateral blindness) on or within 90 days prior to the index date of diagnosis. Both any and bilateral blindness were assessed as bilateral vision loss is less common but has a greater impact on quality of life.²⁰ If multiple VAs were documented within that time frame, the VA closest to the index date was utilized. Patients without VA data from at least one eye with PACG on or within 90 days prior to the index date of diagnosis were excluded from the analysis. Only patients with bilateral VA data were eligible for analyses on bilateral blindness.

Statistical Analysis

Continuous data were expressed as means and standard deviations. Categorical data were expressed in proportions and percentages. Univariable and multivariable logistic regression analyses were performed to determine odds ratios (OR) for any and bilateral blindness. Multivariable analyses were adjusted for ocular comorbidities (cataracts, diabetic retinopathy, and macular degeneration) identified based on ICD codes (Supplementary Table 1). Variables significant at p < 0.15 in univariable analysis were included in multivariable analysis. A separate multivariable analysis of any blindness was performed while additionally adjusting for IOP to assess whether higher IOP in certain populations contributed to higher risk of blindness. Thresholds for statistical and clinical significance were set at OR ≥ 1.20 or OR < 0.80 and p ≤ 0.01 to avoid interpretation of weak associations due to large sample size. All statistical analyses were performed using R (The R Foundation for Statistical Computing, Vienna, Austria).

Results

A total of 223,029 unique patients with an eye-level diagnosis of PACG from 2015 to 2019 were identified in the IRIS^® Registry (Figure 1). There were 43,901 unique patients who met criteria for newly diagnosed PACG after patients were excluded based on the lack of a minimum 24-month lookback period (116,535 patients excluded), presence of prior treatment and surgical history (48,326 patients excluded), or the absence of VA data from at least one eye with PACG on or within the 90 days prior to the index date of diagnosis (14,267 patients excluded).

Figure 1.

Attrition diagram of patients with newly diagnosed PACG in the IRIS^® (Intelligent Research in Sight) Registry.

Out of 43,901 patients with newly diagnosed PACG and VA data for at least one eye, 5,064 (11.5%, 5064/43,901) were blind in at least one eye; out of 41,904 patients with bilateral VA data, 736 (1.8%, 736/41,904) were blind in both eyes (Table 1). The association of age and race with prevalence of any blindness and bilateral blindness were similar. The proportion of any and bilateral blindness were highest in patients < 40 (31.0% [224/722] and 9.5% [63/662], respectively) and > 80 (18.6% [1,527/8,211] and 3.6% [280/7,783], respectively) years of age; higher in males (13.7% [2,000/14,589] and 2.0% [271/13,865], respectively) compared to females (10.4% [3,026/29,061] and 1.7% [462/27,801], respectively); and higher in Black patients (14.2% [632/4,452] and 2.9% [122/4,167] respectively) and Hispanic patients (12.3% [703/5,610] and 2.3% [121/5,349], respectively) compared to non-Hispanic White patients (11.2% [3031/27,077] and 1.6% [403/26,003], respectively) (Table 1 and Supplementary Table 2).

Table 1.

Proportion of blindness in newly diagnosed PACG cases stratified by race and age.

Age	ANY* BLINDNESS
	Non-Hispanic White			Black			Hispanic			Asian			Unknown			Overall
	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%
<40	393	119	30.28%	88	34	38.64%	117	41	35.04%	27	4	14.81%	97	26	26.80%	722	224	31.02%
40–49	880	104	11.82%	156	35	22.44%	229	37	16.16%	90	1	1.11%	222	23	10.36%	1577	200	12.68%
50–59	3267	259	7.93%	670	77	11.49%	809	87	10.75%	334	29	8.68%	692	64	9.25%	5772	516	8.94%
60–69	7584	639	8.43%	1471	155	10.54%	1689	144	8.53%	704	48	6.82%	1321	114	8.63%	12769	1100	8.61%
70–79	9343	883	9.45%	1422	193	13.57%	1926	216	11.21%	750	65	8.67%	1409	140	9.94%	14850	1497	10.08%
80+	5610	1027	18.31%	645	138	21.40%	840	178	21.19%	353	53	15.01%	763	131	17.17%	8211	1527	18.60%
Overall	27077	3031	11.19%	4452	632	14.20%	5610	703	12.53%	2258	200	8.86%	4504	498	11.06%	43901	5064	11.54%
Age	BILATERAL BLINDNESS
	Non-Hispanic White			Black			Hispanic			Asian			Unknown			Overall
	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%	N (PACG)	n (Blind)	%
<40	367	34	9.26%	80	12	15.00%	112	14	12.50%	23	0	0.00%	80	3	3.75%	662	63	9.52%
40–49	825	13	1.58%	141	8	5.67%	214	10	4.67%	85	1	1.18%	213	0	0.00%	1478	32	2.17%
50–59	3146	41	1.30%	615	12	1.95%	769	12	1.56%	321	1	0.31%	662	5	0.76%	5513	71	1.29%
60–69	7331	71	0.97%	1376	26	1.89%	1615	26	1.61%	662	5	0.76%	1249	19	1.52%	12233	147	1.20%
70–79	9001	64	0.71%	1349	35	2.59%	1844	25	1.36%	693	7	1.01%	1348	12	0.89%	14235	143	1.00%
80+	5333	180	3.38%	606	29	4.79%	795	34	4.28%	331	12	3.63%	718	25	3.48%	7783	280	3.60%
Overall	26003	403	1.55%	4167	122	2.93%	5349	121	2.26%	2115	26	1.23%	4270	64	0.10%	41904	736	1.76%

PACG = primary angle closure glaucoma; N and n = number of patients.

^*Any refers to uni- or bilateral blindness.

Multivariable logistic regression analysis showed significant associations between any blindness and the following parameters (Table 2): age groups < 40 (OR = 3.54, 95% CI 2.93–4.26), 40–49 (OR = 1.41, 95% CI 1.18–1.68), and ≥ 80 years (OR = 1.79, 95% CI 1.60–2.02) compared to 50–59 years; Black race (OR = 1.42, 95% CI 1.29–1.57) or Hispanic ethnicity (OR = 1.21, 95% CI 1.10–1.33) compared to non-Hispanic White race; Southern (OR = 1.34, 95% CI 1.23–1.46), Western (OR = 1.31, 95% CI 1.19–1.44), and unknown (OR = 1.23, 95% CI 1.06–1.44) practice regions compared to the Northeast practice region; Medicaid (OR = 2.06, 95% CI 1.75–2.42), Medicare fee-for-service (FFS) (OR = 1.51, 95% CI 1.37–1.65), or Medicare Managed (OR = 1.28, 95% CI 1.13–1.46) insurance category compared to private insurance; history of cataract (OR = 1.57, 95% CI 1.45–1.69) or macular degeneration (OR = 1.37, 95% CI 1.18–1.60); and PACG diagnosis without prior ANA diagnosis (OR =1.78, 95% CI 1.66–1.90). Female sex (OR = 0.75, 95% CI 0.71–0.80) was associated with significantly lower odds of any blindness compared to male sex.

Table 2.

Univariable and multivariable analysis of risk factors for any^* blindness in PACG.

		Any* Blindness (+)	Any Blindness (−)	Univariable Analysis		Multivariable Analysis
		N (%)	N (%)	OR (CI)	P value	OR (CI)	P value
Total # PACG patients:		5,064 (11.54%)	38,837 (88.46%)
	43,901
Age [years]
50–59		516 (8.94%)	5,256 (91.06%)	REF		REF
<40		224 (31.02%)	498 (68.98%)	4.58 (3.82–5.50)	<0.001	3.54 (2.93–4.26)	<0.001
40–49		200 (12.68%)	1,377 (87.32%)	1.48 (1.24–1.76)	<0.001	1.41 (1.18–1.68)	<0.001
60–69		1,100 (8.61%)	11,669 (91.39%)	0.96 (0.86–1.07)	0.467	0.84 (0.75–0.95)	0.004
70–79		1,497 (10.08%)	13,353 (89.92%)	1.14 (1.03–1.27)	0.013	0.92 (0.82–1.04)	0.169
80+		1,527 (18.60%)	6,684 (81.40%)	2.33 (2.10–2.59)	<0.001	1.79 (1.60–2.02)	<0.001
Sex
Male		2,000 (15.64%)	12,589 (84.36%)	REF		REF
Female		3,026 (10.41%)	26,035 (89.59%)	0.73 (0.69–0.78)	<0.001	0.75 (0.71–0.80)	<0.001
Not Reported		38 (15.14%)	213 (84.86%)	1.12 (0.79–1.59)	0.514	1.12 (0.78–1.60)	0.530
Race
Caucasian		3,031 (11.19%)	24,046 (88.81%)	REF		REF
Asian		200 (8.86%)	2,058 (91.14%)	0.77 (0.66–0.90)	0.001	0.82 (0.70–0.96)	0.014
Black or African American		632 (14.20%)	3,820 (85.80%)	1.31 (1.20–1.44)	<0.001	1.42 (1.29–1.57)	<0.001
Hispanic		703 (12.53%)	4,907 (87.47%)	1.14 (1.04–1.24)	0.004	1.21 (1.10–1.33)	<0.001
Unknown		498 (11.06%)	4,006 (88.94%)	0.99 (0.89–1.09)	0.787	1.00 (0.90–1.11)	0.967
Practice Region
Northeast		995 (9.41%)	9,578 (90.59%)	REF		REF
Midwest		1,138 (11.52%)	8,741 (88.48%)	1.25 (1.15–1.37)	<0.001	1.05 (0.96–1.16)	0.306
South		1,847 (12.86%)	12,520 (87.14%)	1.42 (1.31–1.54)	<0.001	1.34 (1.23–1.46)	<0.001
West		845 (11.87%)	6,275 (88.13%)	1.30 (1.18–1.43)	<0.001	1.31 (1.19–1.44)	<0.001
Unknown		239 (12.18%)	1,723 (87.82%)	1.34 (1.15–1.55)	<0.001	1.23 (1.06–1.44)	0.007
Insurance Category
Private		828 (8.43%)	8,998 (91.57%)	REF		REF
Government		63 (9.18%)	623 (90.82%)	1.10 (0.84–1.44)	0.491	1.12 (0.85–1.48)	0.407
Medicaid		249 (17.29%)	1,191 (82.71%)	2.27 (1.95–2.65)	<0.001	2.06 (1.75–2.42)	<0.001
Medicare FFS		3,250 (12.76%)	22,224 (87.24%)	1.59 (1.47–1.72)	<0.001	1.51 (1.37–1.65)	<0.001
Medicare Managed		445 (10.62%)	3,747 (89.38%)	1.29 (1.14–1.46)	<0.001	1.28 (1.13–1.46)	<0.001
Military		29 (12.29%)	207 (87.71%)	1.52 (1.03–2.26)	0.037	1.35 (0.90–2.03)	0.141
Unknown/Missing		200 (9.77%)	1,847 (90.23%)	1.18 (1.00–1.38)	0.049	1.12 (0.95–1.33)	0.168
Ocular comorbidities
Cataract	No	3,746 (10.51%)	31,899 (89.49%)	REF		REF
	Yes	1,318 (15.96%)	6,938 (84.04%)	1.63 (1.52–1.74)	<0.001	1.57 (1.45–1.69)	<0.001
Diabetic Retinopathy	No	4,728 (11.28%)	37,173 (88.72%)	REF		REF
	Yes	336 (16.80%)	1,664 (83.20%)	1.58 (1.40–1.78)	<0.001	1.04 (0.89–1.22)	0.626
Macular Degeneration	No	4,659 (11.16%)	37,096 (88.84%)	REF		REF
	Yes	405 (18.87%)	1,741 (81.13%)	1.83 (1.64–2.05)	<0.001	1.37 (1.18–1.60)	<0.001
ANA prior to PACG
	Yes	1,406 (8.33%)	15,476 (91.67%)	REF		REF
	No	3,658 (13.54%)	23,361 (86.46%)	1.72 (1.62–1.84)	<0.001	1.78 (1.66–1.90)	<0.001

ANA = anatomic narrow angle; CI = confidence interval; N = number of patients; OR = odds ratio; FFS = fee-for-service; PACG = primary angle closure glaucoma.

^*Any refers to uni- or bilateral blindness.

Statistically significant multivariable p-values and odds ratios with OR ≥ 1.20 and p ≤ 0.01 are bolded.

Multivariable analyses were adjusted for ocular comorbidities (cataract, diabetic retinopathy, and macular degeneration).

Multivariable logistic regression analysis showed associations between bilateral blindness and the following parameters (Table 3): age group < 40 (OR = 5.58, 95% CI 3.89–8.00), age group 70–79 years (OR = 0.52, 95% CI 0.35–0.71) and age group > 80 (OR = 1.82, 95% CI 1.35–2.45) years of age compared to 50–59 years; Black race (OR = 2.04, 95% CI 1.64–2.53) or Hispanic ethnicity (OR = 1.53, 95% CI 1.23–1.90) compared to non-Hispanic White race; Southern (OR = 1.41, 95% CI 1.14–1.74;) practice region compared to the Northeast practice region; Medicaid (OR = 3.85, 95% CI 2.71–5.48), Medicare fee-for-service (FFS) (OR = 2.70, 95% CI 2.07–3.51), or Medicare Managed (OR = 1.84, 95% CI 1.27–2.65) insurance categories compared to private insurance; history of cataract (OR = 1.48, 95% CI 1.23–1.78) or macular degeneration (OR = 1.74, 95% CI 1.25–2.40); and PACG diagnosis without prior ANA diagnosis (OR = 1.64, 95% CI 1.39–1.94) (Table 3).

Table 3.

Univariable and multivariable analysis of risk factors for bilateral blindness in PACG.

		Bilateral Blindness (+)	Bilateral Blindness (−)	Univariable Analysis		Multivariable Analysis
		N (%)	N (%)	OR (CI)	P value	OR (CI)	P value
Total # PACG patients:		736 (1.76%)	41,168 (98.24%)
	41,904
Age [years]
50–59		71 (1.29%)	5,442 (98.71%)	REF		REF
<40		63 (9.52%)	599 (90.48%)	8.06 (5.68–11.44)	<0.001	5.58 (3.89–8.00)	<0.001
40–49		32 (2.17%)	1,446 (97.83%)	1.70 (1.11–2.59)	0.014	1.63 (1.07–2.50)	0.024
60–69		147 (1.20%)	12,086 (98.80%)	0.93 (0.70–1.24)	0.630	0.71 (0.52–0.96)	0.024
70–79		143 (1.00%)	14,092 (99.00%)	0.78 (0.58–1.04)	0.085	0.52 (0.38–0.71)	<0.001
80+		280 (3.60%)	7,503 (96.40%)	2.86 (2.20–3.72)	<0.001	1.82 (1.35–2.45)	<0.001
Sex
Male		271 (1.95%)	13,594 (98.05%)	REF		REF
Female		462 (1.66%)	27,339 (98.34%)	0.85 (0.73–0.99)	0.032	0.89 (0.76–1.04)	0.134
Not Reported		3 (1.26%)	235 (98.74%)	0.64 (0.20–2.01)	0.446	0.57 (0.18–1.83)	0.344
Race
Caucasian		403 (1.55%)	25,600 (98.45%)	REF		REF
Asian		26 (1.23%)	2,089 (98.77%)	0.79 (0.53–1.18)	0.249	0.93 (0.62–1.41)	0.742
Black or African American		122 (2.93 %)	4,045 (97.07%)	1.92 (1.56–2.35)	<0.001	2.04 (1.64–2.53)	<0.001
Hispanic		121 (2.26%)	5,228 (97.74%)	1.47 (1.20 – 1.81)	<0.001	1.53 (1.23–1.90)	<0.001
Unknown		64 (1.50%)	4,206 (98.50%)	0.967 (.074–1.26)	0.802	1.00 (0.76–1.32)	0.990
Practice Region
Northeast		133 (1.32%)	9,916 (98.68%)	REF		REF
Midwest		160 (1.67%)	9,408 (98.33%)	1.27 (1.01–1.60)	0.045	0.952 (0.74–1.22)	0.701
South		290 (2.12%)	13,379 (97.88%)	1.62 (1.31–1.99)	<0.001	1.41 (1.14–1.74)	0.001
West		111 (1.64%)	6,647 (98.36%)	1.25 (0.97–1.61)	0.091	1.21 (0.93–1.57)	0.157
Unknown		42 (2.26%)	1,818 (97.74%)	1.72 (1.21–2.45)	0.002	1.49 (1.05–2.13)	0.027
Insurance Category
Private		83 (0.88%)	9,348 (99.12%)	REF		REF
Government		4 (0.61%)	648 (99.39%)	0.70 (0.25–1.90)	0.479	0.69 (0.25–1.91)	0.479
Medicaid		60 (4.45%)	1,287 (95.55%)	5.25 (3.75–7.36)	<0.001	3.85 (2.71–5.48)	<0.001
Medicare FFS		499 (2.05%)	23,810 (97.95%)	2.36 (1.87–2.98)	<0.001	2.70 (2.07–3.51)	<0.001
Medicare Managed		53 (1.33%)	3,930 (98.67%)	1.52 (1.07–2.15)	0.018	1.84 (1.27–2.65)	0.001
Military		6 (2.71%)	215 (97.29%)	3.14 (1.36–7.28)	0.008	2.71 (1.15–6.36)	0.022
Unknown/Missing		31 (1.58%)	1,930 (98.42%)	1.81 (1.19–2.74)	0.005	1.82 (1.19–2.78)	0.005
Ocular comorbidities
Cataract	No	529 (1.55%)	33,580 (98.45%)	REF		REF
	Yes	207 (2.66%)	7,588 (97.34%)	1.73 (1.47–2.04)	<0.001	1.48 (1.23–1.78)	<0.001
Diabetic Retinopathy	No	667 (1.67%)	39,299 (98.33%)	REF		REF
	Yes	69 (3.56%)	1,869 (96.44%)	2.18 (1.69–2.80)	<0.001	1.28 (0.91–1.81)	0.153
Macular Degeneration	No	656 (1.65%)	39,186 (98.35%)	REF		REF
	Yes	80 (3.88%)	1,982 (96.12%)	2.41 (1.90–3.05)	<0.001	1.74 (1.25–2.40)	0.001
ANA prior to PACG
	Yes	204 (1.26%)	16,024 (98.74%)	REF		REF
	No	532 (2.07%)	25,144 (97.93%)	1.66 (1.41–1.96)	<0.001	1.64 (1.39–1.94)	<0.001

ANA = anatomic narrow angle; CI = confidence interval; N = number of patients; OR = odds ratio; FFS = fee-for-service; PACG = primary angle closure glaucoma.

Statistically significant multivariable p-values and odds ratios with OR ≥ 1.20 and p ≤ 0.01 are bolded.

Multivariable analyses were adjusted for ocular comorbidities (cataract, diabetic retinopathy, and macular degeneration).

The multivariable logistic regression model for any blindness was additionally adjusted for IOP (Supplementary Table 3). Results were similar to those from the multivariable model for any blindness without adjustment for IOP (Table 2); however, associations with Western and unknown practice regions and Medicare Managed insurance product were no longer significant. Diabetic retinopathy (OR = 2.00, 95% CI 1.65–2.42) also became significantly associated with higher odds of any blindness.

Discussion

In this study, we used data from the IRIS^® Registry to assess the prevalence of any and bilateral blindness among patients with newly diagnosed PACG in the US, which were 11.5% and 1.8%, respectively. There were significant racial disparities in blindness risk, with Black and Hispanic patients having 1.42 and 1.21 times higher odds, respectively, compared to non-Hispanic White patients. Other sociodemographic factors conferring higher risk of blindness included age < 40 or > 80 years, male sex, Medicaid or Medicare insurance, and Southern or Western practice region. Detection of ANA prior to PACG was associated with lower risk of any and bilateral blindness. Although conclusions about causation should be made cautiously given limitations of IRIS Registry data, these findings highlight the high prevalence of blindness among patients with PACG and the need for increased provider awareness and improved detection methods.

The prevalence of any blindness among patients with newly diagnosed PACG (11.5%) is substantially higher than the prevalence of any blindness in the US overall (0.8%).²¹ It is well-established that PACG is a visually devastating disease: a meta-analysis of 23 population-based studies estimated the prevalence of blindness in PACG to be 27.0%.³ However, prevalence of blindness, in most studies analyzed as blindness in at least one eye, varies widely by geographic region.^{3,12,14,15,22–24} For example, studies conducted in more developed countries and/or urban regions reported lower prevalence of blindness: 5.3% in the Tajimi Study, 6.1% in the Kumejima Study, and 10.2% in the Singapore Chinese Eye Study.^14,22,23 Conversely, studies conducted in China consistently reported higher prevalence of blindness regardless of the degree of urbanization: 25.0% in the Beijing Eye Study, 25.5% in the Handan Eye Study, 42.9% in the Liwan Eye Study, and 71.7% in the Yunnan Minority Eye Study.^12,15,24,25 However, prior to our study, there was sparse information on visual morbidity in PACG among the different racial and ethnic populations in the US. Our findings provide evidence that the US does not have substantially lower prevalence of blindness among patients with PACG compared to other developed countries.

There are significant racial and ethnic disparities in the burden of blindness among PACG patients in our study; in this study, Black (14.2%, 1 per 7.0 cases) and Hispanic patients (12.5%, 1 per 8.0 cases) were disproportionately affected compared to non-Hispanic White (11.2%, 1 per 8.9 cases) and Asian patients (8.9%, 1 per 11.2 cases). These racial disparities were magnified for bilateral blindness: 1 in 34.5 Black patients (2.9%) and 1 in 43.5 Hispanic patients (2.3%) were bilaterally blind compared to 1 in 64.5 non-Hispanic White patients (1.6%) and 1 in 81.3 Asian patients (1.2%). Furthermore, these disparities appear to be independent of IOP and ocular comorbidities. There are several likely explanations for these observations. First, it is widely recognized that PACG is most common among Asian individuals, with approximately half of global cases occurring in China.^8,16,17,26 In contrast, there is sparse information about the prevalence of PACG among other races and ethnicities, with the assumption being that prevalence is low.²⁷ Therefore, provider-level biases about racial or ethnic differences in PACG prevalence may contribute to greater vigilance in detecting angle closure among Asian individuals. It is important to note that such biases should not contribute to differences in angle closure detection between Black and non-Hispanic White patients, as both racial groups are believed to have low PACG prevalence. Second, there may be racial and ethnic differences in ocular biometry, such as anterior chamber depth, that could influence the likelihood of eye care providers performing gonioscopy to detect angle closure.^28,29 Finally, differences in access to eye care services between racial and ethnic groups may influence visual outcomes independent of any effect by PACG. Although our findings do not ascribe causality, they do support the need for additional research on racial and ethnic differences in anatomical mechanisms and clinical outcomes of PACG.

Age over 80 years and age under 40 years were both risk factors for blindness. While older age is a well-established risk factor for PACG, PACG tends to be rare in younger populations.^13,30 We speculate that the anatomical mechanisms underlying PACG differ between younger and older patients.^30–32 Patient sex, practice region, and insurance category were identified as additional risk factors. We identified male sex as a risk factor for any blindness, which could be attributed to lower utilization of medical care among men.³³ Patients seeking care in Western and Southern regions were at higher risk for any and bilateral blindness, which could be attributed to differences in regional screening methods. Finally, patients with Medicaid, Medicare FFS, or Medicare Managed were at higher risk for any blindness compared to patients with private insurance, which may reflect the effects of confounding socioeconomic factors.

Diagnosis of ANA prior to the diagnosis of PACG was associated with lower risk of any and bilateral blindness, providing evidence that earlier detection of ANA yields more favorable clinical outcomes. This serves as a reminder about the importance but also underutilization of gonioscopy, the current clinical standard for detecting angle closure.³⁴ In addition, more than half of patients with newly diagnosed PACG in the US do not have a prior diagnosis of ANA. Higher prevalence of blindness among Blacks appears related to later detection of ANA, rather than more rapid conversion from ANA to PACG.^35,36 While there are automated non-contact methods utilizing anterior segment OCT (AS-OCT) imaging and artificial intelligence (AI) to detect gonioscopic angle closure, these methods are not widely available for clinical use.^37–40 Our findings highlight the continued need to develop and implement more convenient clinical methods to detect and risk-stratify patients for PACG.^41,42

Our study has several limitations. First, our analyses relied on clinical diagnoses of PACG provided by a large number of practicing ophthalmologists, some of whom may not adhere to formal definitions of PACG established for scientific studies. While identifying glaucoma cases based on claims codes appears to be reliable, it is feasible that some cases of ANA and POAG were misclassified as PACG, thereby lowering blindness estimates. However, we intentionally avoided applying additional criteria to narrow the definition of PACG, which could introduce systematic biases toward higher blindness estimates. Second, our definition of newly diagnosed PACG excluded a large number of PACG patients from the analysis. While some of these may have been newly diagnosed PACG patients, we could not differentiate between these patients and established PACG patients without imposing a lookback period. In addition, excluding established PACG patients would likely bias our findings toward the null given PACG is an irreversible, progressive disease. Third, we did not have access to visual field data. Therefore, we could not adopt a more comprehensive definition of blindness that includes <20 degrees of visual field, which leads to further underestimation of the visual impact of PACG. Fourth, the duration of our lookback period to establish PACG cases as newly diagnosed was at minimum two years. As the IRIS^® Registry was recently launched in 2014, this substantially reduced our study sample size, which could limit the generalizability of our findings. We also cannot rule out that underlying racial and ethnic disparities in ocular health amplified differences in the prevalence of blindness in our study.⁴³ Finally, it is important to reiterate that while our findings suggest an association between PACG and blindness, they do not prove causation, and further study of this relationship using more detailed clinical data is needed.

Our findings suggest that PACG is a visually devastating disease, even in the US. Historical epidemiological studies on PACG have shaped perception that the burden of PACG falls primarily on Asian patients, yet Black and Hispanic patients newly diagnosed with PACG have significantly higher risk of blindness. These findings highlight the importance of renewed efforts to increase awareness about PACG and associated ocular morbidity. They also call into question the utilization of healthcare resources and the effectiveness of current practice patterns for detecting and managing patients at risk for PACG. We propose the development of more convenient and precise clinical tools for detecting and evaluating patients with angle closure, especially given the projected rise in PACG prevalence worldwide.

Supplementary Material

1

Supplementary Table 1. Diagnosis, procedure, and treatment codes used in the study.

2

Supplementary Table 2. Proportion of blindness in newly diagnosed PACG cases stratified by sex and age.

3

Supplememtary Table 3. Univariable and multivariable analysis of risk factors for any blindness in PACG additionally adjusted for IOP.