Individualized Significance of 24-Hour Intraocular Pressure Curves for Therapeutic Decisions in Primary Chronic Open-Angle Glaucoma Patients

Figures & data

Figure 1 Study approach, and patients subgroups, glaucoma parameters and abbreviations. (A) An overview of all parameters analyzed in this 24-hour intraocular pressure curve (IPC) study. They are separated into IPC dependent (IPCd) and IPC independent (IPCi). (B) presents the subgroups created for detailed analysis, based on patients’ age, therapy intensity (number of antiglaucomatous agents), and glaucoma stage.

Figure 2 The 24-hour intraocular pressure curve. The figure presents an example of the 24-hour intraocular pressure curve (IPC) like it was performed for this study. Principal IPC-related parameters are also represented: IOPmean is the mean of all measured intraocular pressure (IOP) values, IOPmax is the peak IOP, IOPmin the lowest measured IOP, and IOPampl the amplitude of IOP (defined as the difference between IOPmax and IOPmin). IOPday and IOPnight are the mean IOP measured during daytime (10 AM, 1 PM, 4 PM) or during nighttime (9 PM, midnight, 7 AM), respectively. IOPini (first IOP measured on the day of admission for IPC) is considered IPC independent.

Table 1 Epidemiologic and General Ophthalmologic Characteristics of Patients

General Epidemiologic Data
Gender, Male : female (%)		41.6 : 58.4
Age, Mean±SD (y)		65.8±12.7
Eye, Right : left (%)		52.5 : 47.5
Age of disease, Mean±SD (y)		5.1±5.6
Follow-up period, Mean±SD (m)		5.7±14.5
Therapy intensity, Mean±SD (n)		2.9 ±1.2
Therapy frequency, Mean±SD (n)		3.7±1.6
BCVA, Median (CL) (LogMAR)		0.2 (95.4%)
IOPmean, Mean±SD (mm Hg)		14.6±2.9
IOPmean (raw), Mean±SD (mm Hg)		15.0±2.7
GS, Median (CL)		Stage 1 (95.4%)
CDR, Median (CL)		0.8 (95.8%)
CCT, Mean±SD (µm)		561.7±36.8

Note: The table presents the main characteristics of patients included in the study. Therapy intensity refers to the number of topical antiglaucomatous agents used by patients. Therapy frequency represents the number of eye drop applications per day.

Abbreviations: GS, glaucoma stage; CCT, central corneal thickness; CDR, cup-to-disc- ratio; IOP, intraocular pressure; IOPini, first intraocular pressure measurement at day of admission for 24-hour IOP curve; SD, standard deviation; CL, actual confidence level; y, years; m, months; mm Hg, millimeter of mercury.

Table 2 Comparison of Glaucoma Parameters in Relation to the IPC-Related Outcome

		No Therapy Change (NC)	Therapy Change (TC)	p-value
(A) – IPC-Dependent Parameters
Patients, n (%)		46 (45.5%)	55 (54.5%)	n/n
IOPampl, Mean±SD (mm Hg)		7.3±2.1	9.3±3.3	<0.01
IOPmean, Mean±SD (mm Hg)		13.2±2.2	15.8±3.0	<0.01
IOPmean (raw), Mean±SD (mm Hg)		13.7±2.2	16.2±2.5	<0.01
IOPmax, Mean±SD (mm Hg)		17.0±2.7	20.8±3.8	<0.01
IOPday, Mean±SD (mm Hg)		13.0±2.3	15.5±3.0	<0.01
IOPnight, Mean±SD (mm Hg)		13.3±2.3	16.1±3.3	<0.01
Highest IOP at night, n (%)		6 (22.2%)	21 (77.8%)	<0.01
(B) – IPC-Independent Parameters
Age, Mean±SD (y)		65.8±10.6	65.8±14.3	1.00
Therapy intensity, Mean±SD (n)		2.8±1.2	2.9±1.3	0.67
GS, Median (CL)		1 (97.4%)	2 (97.0%)	<0.01
GS worse, n (%)		1 (7.1%)	13 (92.9%)	<0.01
BCVA, Median (CL) (LogMAR)		0.20 (97.4%)	0.20 (97.0%)	0.54
CDR, Median (CL)		0.8 (96.9%)	0.9 (96.0%)	<0.01
CDR progression, n (%)		9 (42.9%)	12 (57.1%)	0.78
VF deterioration, n (%)		16 (45.7%)	19 (54.3%)	0.38
RNFL progression, n (%)		7 (24.1%)	22 (75.9%)	0.01
IOPini, Mean±SD (mm Hg)		13.4±3.0	16.9±4.3	<0.01

Notes: Table 2A shows differences of IPC-dependent parameters related to the therapeutic decision after IPC. Daytime IOP measurements took place at 10 AM, 1 PM, 4 PM, nighttime measurements at 9 PM, midnight and 7 AM Raw IOPmean corresponds to the mean IOP without correction for central corneal thickness. Table 2B presents differences of IPC-independent parameters related to the therapeutic decision after IPC. Therapy intensity refers to the number (n) of topical antiglaucomatous agents used by patients.

Abbreviations: GS, glaucoma stage; BCVA, best-corrected visual acuity; CDR, cup-to-disc ratio; CL, actual confidence level; SLP, scanning laser polarimetry; IOP, intraocular pressure; IOPampl, amplitude of IOP; IOPmax, highest IOP; IOPday, mean daytime IOP; IOPnight, mean nighttime IOP; IOPini, first IOP measurement at admission for IPC; OCT, optical coherence tomography; RNFL, retinal nerve fiber layer; SD, standard deviation; VF, visual field; y, years; m, months; p-value statistically significant when p<0.05 (bold).

Table 3 Subgroup Analysis of Glaucoma Parameters in Relation to IPC Outcome

(A) – IPC-Dependent Parameters in Subgroups of Patients
	IOPmax Mean±SD (mmHg)			IOPmean Mean±SD (mmHg)			IOPampl Mean±SD (mmHg)
	No Change (NC)	Therapy Change (TC)	p-value	No Change (NC)	Therapy Change (TC)	p-value	No Change (NC)	Therapy Change (TC)	p-value
Age_low	17.2±2.5	19.5±3.5	0.05	13.3±1.8	15.5±2.9	0.02	7.6±2.1	8.3±2.7	0.44
Age_medium	17.1±2.9	21.8±3.9	<0.01	13.3±2.2	16.1±3.4	<0.01	7.2±2.0	10.2±3.2	<0.01
Age_high	15.8±2.2	20.4±3.6	0.02	11.7±3.2	15.7±1.5	0.02	7.3±2.6	9.0±4.2	0.38
Therapy_low	17.6±2.8	20.8±4.3	<0.01	13.6±2.0	15.8±3.3	<0.01	7.1±2.0	9.2±3.8	0.02
Therapy_max	16.4±2.6	21.4±3.3	<0.01	12.7±2.5	16.3±2.7	<0.01	7.6±2.3	9.6±2.6	0.01
GS_low	17.1±2.7	20.9±3.7	<0.01	13.3±2.1	16.0±3.0	<0.01	7.4±2.2	9.2±2.7	<0.01
GS_high	16.2±3.4	20.6±4.1	0.03	12.4±2.5	15.5±3.0	0.04	6.8±1.0	9.6±4.3	0.21
(B) – IPC-Independent Parameters in Subgroups of Patients
	IOPini Mean±SD (mmHg)			GS Median (CL)			CDR Median (CL)
	No Change (NC)	Therapy Change (TC)	p-value	No Change (NC)	Therapy Change (TC)	p-value	No Change (NC)	Therapy Change (TC)	p-value
Age_low	13.2±3.2	16.0±3.6	0.04	1 (96.1%)	1 (98.1)	0.02	0.75 (97.7)	0.8 (97.7%)	0.049
Age_medium	13.9±2.8	17.1±4.7	<0.01	1 (95.7%)	2 (98.1)	<0.01	0.8 (98.1%)	0.9 (97.1%)	<0.01
Age_high	10.8±2.9	18.1±4.3	<0.01	2 (87.5%)	2 (96.1%)	0.58	0.9 (87.5%)	1.0 (96.9%)	0.22
Therapy_low	13.1±3.5	16.6±5.0	<0.01	1 (97.6%)	2 (95.7%)	0.02	0.75 (97.7%)	0.8 (97.7%)	0.048
Therapy_max	13.8±2.4	17.0±4.0	<0.01	1 (95.1%)	2 (95.7%)	0.01	0.8 (95.1%)	0.9 (95.7%)	<0.01
GS_low	13.6±3.0	17.4±4.0	<0.01	1 (96.2%)	1 (95.3%)	0.02	0.8 (96.2%)	0.9 (95.3%)	0.02
GS_high	12.7±3.4	16.8±4.3	0.052	3 (96.9%)	4 (96.9%)	0.04	0.9 (93.8%)	1.0 (95.1%)	0.050

Notes: Table 3A shows results for representative 24-hour IOP curve-dependent parameters (IPCd): IOPmax (highest intraocular pressure), IOPmean (mean IOP), IOPampl (amplitude of IOP throughout IPC) in the subgroups of patients (age_low (up to 60 years of age); age_medium (60 to 80 years of age); age_high (older than 80 years); therapy_low (up to 3 active antiglaucomatous agents); therapy_max (4 active antiglaucomatous agents); GS_low (glaucoma stage 0 to 2); GS_high (GS 3 to 5). Table 3B shows results for representative IPC-independent parameters (IPCi) in the patient subgroups: GS, the cup-to-disc ratio of the optic nerve head (CDR), and IOPini (first intraocular pressure measurement at day of admission for 24-hour IOP curve). Statistically significant results when p<0.05 (bold).

Table 4 Logistic Regression Analysis of Selected IPC-Independent Parameters for the IPC Outcome

	IOPini			GS Worse			Progression of RNFL Thinning			Multiple Regression
	OR	95% CI	p-value	OR	95% CI	p-value	OR	95% CI	p-value	R^2	p-value
Entire cohort	1.3	1.1–1.5	<0.01	12.7	1.6–102.8	<0.01	6.3	2.1–19.2	<0.01	0.46	<0.0001
Age_low	1.3	1.0–1.6	0.03	n/n			n/n			n/n
Age_medium	1.3	1.1–1.5	<0.01	6.9	0.8–63.5	0.05	8.4	1.6–44.1	<0.01	0.45	0.0006
Age_high	n/n			n/n			n/n			n/n
Therapy_low	1.3	1.1–1.5	<0.01	n/n n/n			n/n n/n			0.39	0.0019
Therapy_max	1.4	1.1–1.7	<0.01							n/n
GS_low	1.3	1.1–1.5	<0.01	15.6	1.9–129.5	<0.01	5.8	1.7–19.3	<0.01	0.44	<0.0001
GS_high	1.4	1.0–2.0	0.03	n/n			n/n			n/n

Notes: Table 4 presents the odds ratio (OR), 95% confidence interval (95% CI) and p-value (statistically significant when p<0.05; bold) of the univariate logistic regression analysis for IOPini (first intraocular pressure measurement at day of admission for 24-hour IOP curve), the presence of worsening of glaucoma stage (GS worse), and the progression of RNFL thinning (by OCT and/or SLP) in the whole cohort of patients as well as for several subgroups (age_low (up to 60 years of age); age_medium (60 to 80 years of age); age_high (older than 80); therapy_low (up to 3 active antiglaucomatous agents); therapy_max (4 active antiglaucomatous agents); GS_low (GS 0 to 2); GS_high (GS 3 to 5). R² and the p-value (statistically significant when <0.05, bold) of the Log-likelihood ratio test of the multivariate logistic regression analysis using all three above parameters are also presented for the entire cohort as well as for the mentioned subgroups.

Table 5 Comparison of the Predictive Potential of IPC-Dependent and Independent Parameters for the IPC Outcome

	Sensitivity (%)	Specificity (%)	AUC	Sensitivity (%)	Specificity (%)	AUC	Sensitivity (%)	Specificity (%)	AUC	Sensitivity (%)	Specificity (%)	AUC
IPCd	IOPmax			IOPmean			IOPampl			Multivariate Regression
Entire cohort	78	61	0.79	72	70	0.76	69	57	0.71	0.77	0.72	0.80
Age_low	74	42	0.70	78	58	0.73	100	0	0.59	67	58	0.70
Age_medium	67	77	0.83	62	83	0.74	67	80	0.80	81	77	0.85
Age_high	89	50	0.89	89	50	0.92	100	0	0.65	89	75	0.97
Therapy_low	70	76	0.71	62	69	0.68	63	66	0.70	66	69	0.73
Therapy_max	84	71	0.88	83	71	0.84	76	41	0.72	88	82	0.90
GS_low	65	78	0.80	65	75	0.76	54	78	0.72	68	75	0.79
GS_high	89	33	0.79	94	67	0.85	100	0	0.68	94	67	0.90
IPCi	IOPini			GS worse			RNFL worse			Multivariate regression
Entire cohort	72	69	0.75	22	98	0.60	67	76	0.71	77	79	0.88
Age_low	83	33	0.73	n/n			57	70	0.64	n/n
Age_medium	69	79	0.71	19	97	0.58	64	82	0.73	79	76	0.89
Age_high	n/n			n/n			n/n			n/n
Therapy_low	66	69	0.73	15	97	0.56	54	68	0.61	69	89	0.87
Therapy_max	83	50	0.77	n/n			75	90	0.83	n/n
GS_low	68	82	0.74	29	98	0.63	68	73	71	75	77	0.88
GS_high	94	50	0.78	n/n			n/n			n/n

Note: The table shows sensitivity, specificity and area under the receiver operating characteristic curve (AUC) values of univariate and multivariate logistic regression using selected IPC-dependent (IPCd) and- independent (IPCi) parameters in the entire cohort as well as in several patient subgroups.

Abbreviations: IOPmax, peak intraocular pressure; IOPmean, mean IOP; IOPampl, amplitude of IOP; IOPini, first IOP at day of admission for IPC; GS worse, worsening of the glaucoma stage; RNFL worse, decrease of RNFL thickness in OCT and/or SLP; age_low, up to 60 years of age; age_medium, 60 to 80 years of age; age_high, older than 80; therapy_low, up to 3 active antiglaucomatous agents; therapy_max, 4 active antiglaucomatous agents; GS_low, GS 0 to 2; GS_high, GS 3 to 5.