Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor

Figures & data

Table 1 Demographic and Clinical Data of Study Participants

Collected Data n = 948 Eyes / 894 Patients		Sub-Items	Sample Number (%)
Patients demographic characteristics	Sex	Male	415 (46.2)
		Female	479 (53.8)
	Age - years old	Mean ± SD	62.4 ± 22.8
	Age group	Up to 40	262 (29.2)
		Over 40	632 (70.8)
Anatomical features of the eye	Lens status	Phakic	299 (31.5)
		Pseudophakic	649 (68.5%)
	Pars plana scleral thickness measurements	Up to 550 µm	695 (73.3%)
		More than 550 µm	253 (26.7%)
	Laterality	Bilateral	222 (23.3)
		Unilateral	726 (76.7)
Eye intervention Characteristics	Anti-VEGF type	Ranibizumab	491 (51.8)
		Aflibercept	457 (48.2)
Primary Eye Disease	Chorioretinal Diseases	AMD	318 (33.5)
		DME	461 (48.6)
		RVO	132 (13.9)
		High myopia	37 (3.9)
Operated Eyes	Scleral buckle surgery	Present	42 (4.4)
		No	906 (95.6)
Eye Disorders	History of glaucoma	Present	367 (38.7)
		No	581 (61.3)
	History of severe dry eye	Present	45 (4.7)
		No	903 (95.3)
	Scleral hyaline plaque	Present	255 (26.8)
		No	693 (73.2)
	History of scleritis, episcleritis, and anterior uveitis	Present	18 (1.8)
		No	930 (98.2)
Patients Systemic Disorders	Trigeminal pain	Present	72 (8.1)
		No	822 (91.9)
	History of severe migraine	Present	52 (5.9)
		No	842 (94.1)
	Collagen disease	Present	141 (15.6)
		No	753 (84.4)
	Diabetic neuropathy	Present	356 (39.8)
		No	538 (60.2)
	Fibromyalgia	Present	22 (2.5)
		No	872 (97.5)
	History of other systemic pain disorders	Present	27 (3.1)
		No	867 (96.9)

Abbreviations: n, number of patients and percentage of patients (%); AMD, age-related macular degeneration; DME, diabetic macular edema; RVO, retinal vein occlusion.

Table 2 The Correlation of the Demographic Data with the Level of Ocular Pain

Population Studied 894 Patients			Analog Ocular Pain Scale (AOPS)
			Absent to Mild n= 793 (88.6)	Moderate n = 80 (8.9)	Severe n = 15 (1.6)	Extremely Severe n = 6 (0.7)	P
Demographic Data	Sex	Male	373 (47.1)	34 (42.4)	6 (39.1)	2 (28.5)	0.73^#
		Female	420 (52.9)	46 (57.6)	9 (60.9)	4 (71.5)
	Age	Mean ± SD	59.7 ± 18.9	63.7 ± 11.7	61 ± 15.6	67.1 ± 2.5	0.16*
	Age group	Up to 40 years	221 (27.9)	31 (38.8)	7 (46.7)	3 (50.0)	0.53^‡
		Over 40 years	572 (72.1)	49 (61.2)	8 (53,3)	3 (50.0)

Notes: ^#Chi-square test, ^‡Kruskal–Wallis test, *Student t-test, p-value statistical significance, (%) – sample percentage. Items analyzed as significant data through statistical tests (p < 0.05).

Table 3 The Correlation of Eye Data and Intervention Characteristics with the Level of Ocular Pain

Population Studied 948 Eyes			Analog Ocular Pain Scale (AOPS)
			Absent to Mild n= 840 (88.6)	Moderate n = 85 (8.9)	Severe n = 16 (1.6)	Extremely Severe n = 7 (0.7)	P
Anatomical features of the eye	Lens status	Phakic	251 (35.8)	34 (43.7)	7 (39.1)	3 (42.9)	0.15^#
		Pseudophakic	589 (64.2)	51 (56.3)	9 (60.9)	4 (57.1)
	Pars plana scleral thickness measurements	Up to 550 µm	622 (74.1)	61 (71.7)	9 (81.2)	3 (42.9)	0.09^‡
		More than 550µm	218 (25.9)	24 (21.3)	7(18.8)	4 (57.1)
	Laterality	Unilateral	636 (75.7)	71 (83.6)	13 (81.2)	6 (85.7)	0.16^#§
		Bilateral	204 (24.2)	14 (16.4)	3 (18.8)	1 (14.3)
Intervention characteristics	Anti-VEGF type	Ranibizumab	432 (51.4)	47 (55.2)	9 (56.2)	3 (42.9.)	0.84^#
		Aflibercept	408 (49.6)	38 (44.8)	7 (43.8)	4 (57.1)
Operated eyes	Scleral buckle surgery	Present	31 (3.6)	6 (7.1)	3 (18.8)	2 (28.5)	0.01^#
		No	809 (96.4)	79 (92.9)	13 (86.2)	5 (71.5)
Primary eye diseases	Chorioretinal diseases	AMD	282 (37.1)	30 (38.8)	4 (25.0)	2 (28.5)	0.98^#”
		DME	409 (48.4)	39 (48,2)	9 (60.9)	4 (57.1)
		RVO	118 (14.4)	11 (12.9)	2 (12.5)	1 (14.4)
		High Myopia	31 (3.6)	5 (5.8)	1 (6.25)	0

Notes: ^#”Exact Fisher Test, ^#Chi-square test, ^#§McNemar Chi-square paired test, ^‡Kruskal–Wallis test, p-value statistical significance, (%) – sample percentage. Items in bold analyzed as significant data through statistical tests (p < 0.05).

Table 4 The Correlation of Ocular History Disorders and Findings with Level of Ocular Pain

Population Studied 948 Eyes			Analog Ocular Pain Scale (AOPS)
			Absent to Mild n= 840 (88.6)	Moderate n = 85 (8.9)	Severe n = 16 (1.6)	Extremely Severe n=7 (0.7)	P
Eye history disorders and findings	History of glaucoma	Present	318 (37.8)	36 (41.1)	9 (60.9)	4 (57.1)	0.29^#
		No	522 (62.2)	49 (58.9)	7 (39.1)	3 (42.9)
	History of severe dry eye	Present	32 (3.9)	6 (7.1)	4 (25.0)	3 (42.9)	0.01^#
		No	808 (96.1)	79 (92.9)	12 (75,0)	4 (57.1)
	Scleral hyaline plaque	Present	235 (27.9)	16 (18.8)	4 (25.0)	0	0.35^#”
		No	605 (72.1)	69 (81.2)	12 (75,0)	7 (100)
	History of scleritis, episcleritis, anterior uveitis	Present	14 (1.7)	3 (3.6)	1 (6.3)	0	0.34^#”
		No	826 (98.3)	82 (96.4)	15 (93.7)	7 (100)

Notes: ^#”Exact Fisher Test, ^#Chi-square test, p-value statistical significance, (%) sample percentage. Items analyzed as significant data through statistical tests (p < 0.05).

Table 5 The Correlation of the Systemic Comorbidities with the Level of Ocular Pain

Population Studied 894 Patients			Analog Ocular Pain Scale (AOPS)
			Absent to Mild n= 793 (88.6)	Moderate n = 80 (8.9)	Severe n = 15 (1.6)	Extremely Severe n=6 (0.7)	P
Systemic comorbidities	Trigeminal pain	Present	66 (8.3)	05 (5.9)	1 (12.5)	0	0.99^#”
		No	727 (91.7)	75 (94.1)	14 (87.5)	6 (100)
	History of severe migraine	Present	42 (5.3)	9 (11.3)	1 (12.5)	0	0.98^#”
		No	751 (94.7)	71 (88.7)	14 (87.5)	6 (100)
	Collagen disease	Present	123 (15.6)	13 (16.2)	4 (26.7)	1 (16.7)	0.70^#
		No	670 (84.4)	67 (83.8)	11 (73,3)	5 (83.3)
	Diabetic neuropathy	Present	305 (38.4)	38 (47.5)	10 (66.7)	3 (50.0)	0.06^#
		No	488 (61.6)	42 (52.5)	5 (33.3)	3 (50.0)
	Fibromyalgia	Present	18 (2.2)	2 (2.5)	1 (6.7)	1 (16.6)	0.10^#
		No	775 (97.8)	78 (97.5)	14 (93.3)	5 (83.4)
	History of other systemic pain complaint	Present	21 (2.6)	4 (5.0)	1 (6.6)	1 (16.7)	0.11^#
		No	772 (97.4)	76 (95.0)	14 (93.4)	5 (83.3)

Notes: ^#”Exact Fisher Test, ^#Chi-square test, p-value statistical significance, (%) – sample percentage. Items analyzed as significant data through statistical tests (p < 0.05).