Influence on ocular surface after cataract surgery and effect of topical diquafosol on postoperative dry eye: a multicenter prospective randomized study

Figures & data

Table 1 Demographics of the observational study subjects

Background factors	Total (%)
Number of patients analyzed	433 (100.0)
Sex
Male	199 (46.0)
Female	234 (54.0)
Age (year), mean ± SD	71.9±7.5
Site of incision
Cornea	159 (36.7)
Sclerocornea	102 (23.6)
Transconjunctival sclerocornea	172 (39.7)
Width of incision, mm (phacoemulsification), mean ± SD	2.32±0.14
Anesthetic procedure
With eye drops	413 (95.4)
With retrobulbar injection	2 (0.5)
With tenon injection	18 (4.2)
Surgical time, minutes, mean ± SD	8.6±3.4

Abbreviation: SD, standard deviation.

Table 2 Change of signs and symptoms according to the category of dry eye diagnosis

Category of dry eye diagnosis before surgery	Examination point		Comparison within-group, P-value
	Before surgery	4 weeks after surgery
Tear breakup time (seconds)
Total			0.036a,*
Mean ± SD	4.75±2.63	4.50±2.67
Number of patients	433	433
Non-dry eye			<0.001a,**
Mean ± SD	7.02±2.62	5.74±2.95
Number of patients	131	131
Probable			0.269a
Mean ± SD	3.96±2.10	4.14±2.41
Number of patients	217	217
Definite			0.169a
Mean ± SD	3.24±1.32	3.53±2.13
Number of patients	85	85
Probable + definite			0.105a
Mean ± SD	3.76±1.94	3.96±2.35
Number of patients	302	302
Corneal and conjunctival fluorescein staining scores
Total			0.012a,*
Mean ± SD	1.5±1.4	1.6±1.3
Number of patients	433	433
Non-dry eye			<0.001a,**
Mean ± SD	0.7±0.8	1.2±1.2
Number of patients	131	131
Probable			<0.001a,**
Mean ± SD	1.1±1.0	1.5±1.2
Number of patients	217	217
Definite			<0.001a,**
Mean ± SD	3.5±1.0	2.6±1.2
Number of patients	85	85
Probable + definite			0.720a
Mean ± SD	1.8±1.5	1.8±1.3
Number of patients	302	302
Schirmer I test
Total			0.209a
Mean ± SD	11.8±9.0	12.3±9.9
Number of patients	433	433
Non-dry eye			0.205a
Mean ± SD	14.7±9.4	15.7±10.5
Number of patients	131	131
Probable			0.252a
Mean ± SD	10.5±8.9	11.2±9.3
Number of patients	217	217
Definite			0.388a
Mean ± SD	10.4±7.6	9.8±8.8
Number of patients	85	85
Probable + definite			0.534a
Mean ± SD	10.5±8.5	10.8±9.2
Number of patients	302	302
Total score of 12 subjective symptoms
Total			<0.001b,**
Mean ± SD	8.8±5.5	4.5±4.6
Number of patients	431	431
Non-dry eye			<0.001b,**
Mean ± SD	6.8±5.4	3.6±4.2
Number of patients	131	130
Probable			<0.001b,**
Mean ± SD	9.2±5.1	4.5±4.4
Number of patients	216	216
Definite			<0.001b,**
Mean ± SD	11.1±5.6	5.8±5.2
Number of patients	84	85
Probable + definite			<0.001b,**
Mean ± SD	9.7±5.3	4.9±4.7
Number of patients	300	301

Notes:

a One-sample t-test.

b One-sample Wilcoxon rank-sum test, corneal and conjunctival fluorescein staining scores were evaluated in three areas (the temporal bulbar conjunctiva, nasal bulbar conjunctiva, and cornea), scored on a 0- to 3-point scale (0: no damage to 3: damage in the entire area) and then totaled (maximum =9 points). Subjective symptom score; score 0= never, score 1= rarely, score 2= sometimes, score 3= all of the time.

* P<0.05;

** P<0.001.

Abbreviation: SD, standard deviation.

Table 3 The prevalence and the change of diagnostic classification of dry eye before and 4 weeks after cataract surgery

			Classification of dry eye diagnosis before surgery
			Non-dry eye (%)	Dry eye patient			Total (%)
				Probable (%)	Definite (%)	Probable + definite (%)
The prevalence of dry eye before cataract surgery			131 (30.3)	217 (50.1)	85 (19.6)	302 (69.7)	433 (100.0)
Number of patients analyzed			131 (100.0)	217 (100.0)	85 (100.0)	302 (100.0)	433 (100.0)
Classification of dry eye diagnosis 4 weeks after surgery	Non-dry eye		90 (68.7)	83 (38.2)	19 (22.4)	102 (33.8)	192 (44.3)
	Dry eye patient	Probable	30 (22.9)	100 (46.1)	38 (44.7)	138 (45.7)	168 (38.8)
		Definite	11 (8.4)	34 (15.7)	28 (32.9)	62 (20.5)	73 (16.9)
		Probable + definite	41 (31.3)	134 (61.8)	66 (77.6)	200 (66.2)	241 (55.7)

Table 4 Risk analysis for dry eye 4 weeks after cataract surgery according to patient demographics and the result of the dry eye test before surgery

Background factors	Category	Univariate logistic regression analysis
		Odds ratio	95% confidence interval	P-value
Demographics
Sex	Male	Reference	–	–
	Female	3.149	2.122–4.674	<0.001**
Age (years)	<60	Reference	–	–
	≥60, <70	0.689	0.284–1.672	0.410
	≥70, <80	0.718	0.304–1.697	0.450
	≥80	0.617	0.238–1.596	0.319
Site of incision	Cornea	Reference	–	–
	Sclerocornea	1.570	0.948–2.600	0.080
	Transconjunctival sclerocornea	1.406	0.911–2.171	0.124
Surgical time (minutes)	<10	Reference	–	–
	≥10, <20	1.214	0.771–1.911	0.402
	≥20	0.830	0.236–2.921	0.771
The result of the dry eye test before surgery
Tear breakup time (seconds)	>5	Reference	–	–
	≤5	3.959	2.585–6.062	<0.001**
Corneal and conjunctival	Score 0	Reference	–	–
Fluorescein staining	Score 1, 2	2.980	1.893–4.693	<0.001**
Score	≥ Score 3	4.822	2.784–8.351	<0.001**
Schirmer I test (mm)	≤5	Reference	–	–
	>5	0.756	0.497–1.149	0.190
Subjective symptom score before surgery
Eye fatigue	Score 0, 1	Reference	–	–
	≥ Score 2	2.130	1.417–3.202	<0.001**
Eye pain	Score 0, 1	Reference	–	–
	≥ Score 2	3.271	1.304–8.203	0.012*
Eye discharge	Score 0, 1	Reference	–	–
	≥ Score 2	1.505	0.792–2.860	0.212
Foreign body sensation	Score 0, 1	Reference	–	–
	≥ Score 2	2.109	1.157–3.846	0.015*
Tearing	Score 0, 1	Reference	–	–
	≥ Score 2	0.930	0.560–1.546	0.780
Blurred vision	Score 0, 1	Reference	–	–
	≥ Score 2	1.129	0.758–1.682	0.551
Itchy eye	Score 0, 1	Reference	–	–
	≥ Score 2	1.596	0.924–2.756	0.094
Heaviness	Score 0, 1	Reference	–	–
	≥ Score 2	2.709	1.459–5.030	0.002
Red eye	Score 0, 1	Reference	–	–
	≥ Score 2	2.249	1.020–4.960	0.045*
Eye discomfort	Score 0, 1	Reference	–	–
	≥ Score 2	2.815	1.726–4.591	<0.001**
Dryness	Score 0, 1	Reference	–	–
	≥ Score 2	2.885	1.609–5.174	<0.001**
Photophobia	Score 0, 1	Reference	–	–
	≥ Score 2	2.177	1.471–3.220	<0.001**

Notes:

* P<0.05,

** P<0.001, corneal and conjunctival fluorescein staining scores were evaluated in three areas (the temporal bulbar conjunctiva, nasal bulbar conjunctiva, and cornea), scored on a 0- to 3-point scale (0: no damage to 3: damage in the entire area) and then totaled (maximum =9 points). Subjective symptom score: score 0= never, score 1= rarely, score 2= sometimes, and score 3= all of the time.

Table 5 Patient background of prospective randomized study

Background factor	Randomized group		Comparison among groups
	DQS (%)	AT (%)
Number of patients analyzed	75 (100.0)	79 (100.0)	–
Sex
Male	30 (40.0)	23 (29.1)	Fisher’s exact test, P=0.177
Female	45 (60.0)	56 (70.9)
Age (years)
Mean ± SD	71.7±7.4	70.3±7.1	t-test, P=0.227
Site of incision
Corneal incision	25 (33.3)	26 (32.9)	Fisher’s exact test, P=0.899
Sclerocorneal incision	23 (30.7)	22 (27.8)
Transconjunctival sclerocorneal incision	27 (36.0)	31 (39.2)
Width of incision (mm) (phacoemulsification)
Mean ± SD	2.31±0.14	2.30±0.16	t-test, P=0.603
Anesthetic procedure
With eye drops	70 (93.3)	72 (91.1)	Fisher’s exact test, P=1.000
With retrobulbar injection	0 (0.0)	1 (1.3)
With tenon injection	5 (6.7)	6 (7.6)
Surgical time (minutes)
Mean ± SD	8.6±3.3	8.2±3.2	t-test, P=0.495
Schirmer I test (mm) (4 weeks after surgery)
Mean ± SD	11.6±9.6	12.5±10.9	t-test, P=0.592

Abbreviations: AT, artificial tears; DQS, diquafosol ophthalmic solution; SD, standard deviation.

Table 6 Change of tear breakup time (seconds) in prospective randomized study

	Examination point		Amount of change	Comparison within-group one-sample t-test (P-value)
	Before treatment (4 weeks after surgery)	After treatment (8 weeks after surgery)
Total patients
DQS
Mean ± SD	3.32±1.62	3.92±1.87	0.60±2.11	0.015*
Median	3.33	3.67	0.67
Number of patients	75	75	75
AT
Mean ± SD	3.13±1.69	3.48±1.69	0.35±1.76	0.085
Median	3.00	3.33	0.33
Number of patients	79	79	79
Comparison between groups two-sample t-test (P-value)	0.489	0.125	0.410
The definite dry eye patient before surgery
DQS
Mean ± SD	3.25±1.27	4.18±1.82	0.93±1.61	0.018*
Median	3.33	4.17	1.00
Number of patients	20	20	20
AT
Mean ± SD	3.00±1.94	2.99±1.71	−0.01±1.88	0.972
Median	2.67	3.00	0.00
Number of patients	25	25	25
Comparison between groups two-sample t-test (P-value)	0.622	0.028*	0.081

Note:

* P<0.05.

Abbreviations: AT, artificial tears; DQS, diquafosol ophthalmic solution; SD, standard deviation.

Table 7 Change of corneal and conjunctival fluorescein staining scores in prospective randomized study

	Examination point		Amount of change	Comparison within-group one-sample t-test (P-value)
	Before treatment (4 weeks after surgery)	After treatment (8 weeks after surgery)
Total patients
DQS
Mean ± SD	2.1±0.9	1.6±1.2	−0.6±1.2	<0.001**
Median	2.0	1.0	−1.0
Number of patients	75	75	75
AT
Mean ± SD	2.4±1.1	1.8±1.3	−0.6±1.2	<0.001**
Median	2.0	2.0	0.0
Number of patients	79	78	78
Comparison between groups two-sample t-test (P-value)	0.169	0.322	0.826
The definite dry eye patient before surgery
DQS
Mean ± SD	2.9±0.9	2.3±1.3	−0.6±1.3	<0.077
Median	3.0	2.0	−0.5
Number of patients	20	20	20
AT
Mean ± SD	2.8±1.3	2.5±1.2	−0.4±1.2	<0.153
Median	2.0	2.5	0.0
Number of patients	25	24	24
Comparison between groups two-sample t-test (P-value)	0.887	0.674	0.653

Notes:

** P<0.001, corneal and conjunctival fluorescein staining scores were evaluated in three areas (the temporal bulbar conjunctiva, nasal bulbar conjunctiva, and cornea), scored on a 0- to 3-point scale (0: no damage to 3: damage in the entire area) and then totaled (maximum =9 points).

Abbreviations: AT, artificial tears; DQS, diquafosol ophthalmic solution; SD, standard deviation.

Table 8 Change of total score of 12 subjective symptoms in prospective randomized study

	Examination point		Amount of change	Comparison within-group one-sample the Wilcoxon rank-sum test (P-value)
	Before treatment (4 weeks after surgery)	After treatment (8 weeks after surgery)
Total patients
DQS
Mean ± SD	7.5±4.4	7.1±5.5	−0.6±5.5	0.170
Median	7.0	5.0	−1.0
Number of patients	74	73	72
AT
Mean ± SD	7.8±5.0	6.1±5.1	−1.7±4.8	<0.001**
Median	6.0	5.0	−1.0
Number of patients	79	78	78
Comparison between groups two-sample the Wilcoxon rank-sum test	P=0.996	P=0.177	P=0.248
The definite dry eye patient before surgery
DQS
Mean ± SD	8.8±5.4	8.3±4.3	−0.6±4.9	0.599
Median	8.5	7.0	−1.0
Number of patients	20	19	19
AT
Mean ± SD	8.3±4.4	8.3±6.6	0.0±5.6	0.100
Median	7.0	7.0	−1.0
Number of patients	25	25	25
Comparison between groups two-sample the Wilcoxon rank-sum test	P=0.827	P=0.584	P=0.867

Notes:

** P<0.001, subjective symptom score; score 0= never, score 1= rarely, score 2= sometimes, score 3= all of the time.

Abbreviations: AT, artificial tears; DQS, diquafosol ophthalmic solution; SD, standard deviation.