Prospective evaluation of intense pulsed light and meibomian gland expression efficacy on relieving signs and symptoms of dry eye disease due to meibomian gland dysfunction

Figures & data

Figure 1 Study flow diagram.

Notes: Withdrawn case in site 2 received one IPL treatment but was withdrawn because it was discovered, after the treatment, that the patient has a history of migraines.
Abbreviations: FU, follow-up; LFU, lost to follow-up; Tx, treatment session.

Table 1 Demographic information

	N	Age (µ ± SD)	Gender (male)	Skin type (Fitzpatrick scale)	Baseline rosacea (0= none; 3= severe)
Site 1	19	53.6±15.7	58%	2.8±0.5	1.36±0.67
Site 2	21	61.0±13.9	43%	2.6±0.7	0.57±0.67
Sites 1+2	40	57.5±15.1	50%	2.7±0.6	0.95±0.78
Site 1 vs site 2 (P-value)		0.08	0.41	0.38	<0.0001

Notes: Site 1 vs Site 2 were compared with two-tail t-test. A P-value less than the α level (0.05) implies that the two sites are different.

Abbreviation: SD, standard deviation.

Figure 2 Longitudinal analysis of tear breakup time.

Notes: Error bars: standard error of the mean values. ***Wilcoxon signed rank test against BL (P<0.001). (A) Site 1 and (B) site 2.
Abbreviations: BL, baseline; FU, follow-up.

Table 2 Numerical analysis

Outcome measure	Sites	N	BL	FU1			FU2			FU3			Pwithin_pt
			Mean (SD)	Mean (SD)	Change vs BL (%)	P	Mean (SD)	Change vs BL (%)	P	Mean (SD)	Change vs BL (%)	P
TBUT (s)	1	38	5.8 (2.3)	9.3 (3.5)	60	<0.0001	9.6 (3.2)	66	<0.0001	11.2 (4.2)	93	<0.0001	<0.0001
	2	42	10.2 (10)	32 (17)	218	<0.0001	41 (22)	300	<0.0001	54 (26)	425	<0.0001	<0.0001
SPEED	1+2	80	12.9 (4.9)	6.6 (4.4)	−49	<0.005	6.3 (4.3)	−51	<0.005	5.8 (4.2)	−55	<0.001	<0.0001
MGS	1+2	80	20.3 (7.2)	13.4 (5.5)	−34	<0.01	12.4 (5.2)	−39	<0.01	12.9 (6.0)	−36	<0.05	<0.0001
CFS	1	38	7.8 (4.6)	3.3 (2.9)	−57	<0.0001	4.5 (3.5)	−43	<0.0001	3.3 (3.3)	−58	<0.0001	<0.0001
	2	42	0.2 (0.9)	1.0 (4.7)	340	0.32	0.1 (0.4)	−50	0.74	0.5 (0.2)	100	0.35	0.07
TFO (mOsm/L)	1+2	20	322.2 (19)	298.5 (12)	−7	<0.0001	297.9 (11)	−7.5	<0.0001	297.8 (9)	−8	<0.0001	<0.005
ΔTFO (mOsm/L)	1+2	24	17.8 (19)	8.6 (5.4)	−52	<0.0001	8.8 (6.9)	−51	<0.005	6.3 (4.2)	−65	<0.0001	0.06
LLT (nm)	1	38	79.3 (19)	80.7 (20)	1.8	0.89	81.1 (22)	2.3	0.73	79.4 (21)	0.2	0.93	0.88

Notes: Change vs BL was calculated by subtracting the BL from the FU means and dividing by the BL mean. P = probability that FU and BL are similar (two-tail Wilcoxon signed rank test): P<0.05 suggests that the distributions are different. P_{within_pt} = probability that there was no change within subjects (repeated measures, MANOVA test). TBUT and CFS were analyzed per each site separately. TFO was analyzed only for eyes with an abnormally elevated TFO value (≥310 mOsm/L) at BL. ΔTFO, the difference of osmolarity between both eyes of a patient, was analyzed for patients with an abnormally elevated ΔTFO (≥8 mOsm/L) at BL.

Abbreviations: BL, baseline; CFS, corneal fluorescein staining; FU, follow-up; LLT, lipid layer thickness; MANOVA, multivariate analysis of variance; MGS, meibomian gland score; SD, standard deviation; SPEED, Standard Patient Evaluation of Eye Dryness; TBUT, tear breakup time; TFO, tear film osmolarity.

Table 3 Categorical analysis

Outcome measure	Normality criterion	Sites	N	BL, n (%)	FU1, n (%)	FU2, n (%)	FU3, n (%)
TBUT (s)	>10	1	38	1 (2.6)	11 (29)	15 (39)	20 (53)
		2	42	15 (36)	39 (93)	40 (95)	42 (100)
SPEED	<10	1+2	80	18 (22)	65 (81)	61 (76)	67 (84)
MGS	≤10	1+2	80	7 (8.8)	24 (30)	31 (39)	28 (35)
CFS	<10	1	38	24 (63)	38 (100)	34 (89)	36 (95)
		2	42	42 (100)	40 (95)	42 (100)	42 (100)
TFO (mOsm/L)	<310	1+2	20	0 (0)	17 (85)	17 (85)	17 (85)
ΔTFO (mOsm/L)	<8	1+2	24	0 (0)	13 (54)	14 (58)	16 (67)
LLT (nm)	<60	1	38	29 (76)	31 (82)	31 (76)	28 (74)

Notes: In this analysis, outcome measures were dichotomized to “normal” or “consistent with DED”, according to the criteria listed under the column “Normality criterion”. n, number of eyes with normal values.

Abbreviations: BL, baseline; CFS, corneal fluorescein staining; DED, dry eye disease; FU, follow-up; LLT, lipid layer thickness; MGS, meibomian gland score; SPEED, Standard Patient Evaluation of Eye Dryness; TBUT, tear breakup time; TFO, tear film osmolarity.

Figure 3 Forest plot of odds ratios for study measures.

Notes: Outcome measures were dichotomized as detailed in Table 3. Open circles and bars represent ORs and 95% confidence intervals, respectively. Green, blue, and black symbols show FU1 vs BL, FU2 vs BL, and FU3 vs BL, respectively. ORs for which the 95% confidence interval do not cross OR =1 are statistically significant. Undefined ORs are missing from this plot.
Abbreviations: BL, baseline; CFS, corneal fluorescein staining; FU, follow-up; LLT, lipid layer thickness; MGS, meibomian gland score; ORs, odds ratios; SPEED, Standard Patient Evaluation of Eye Dryness; TBUT, tear breakup time.

Figure 4 Subgroup analysis of TBUT (site 1).

Notes: In each panel, the dotted line shows the TBUT data for the complete cohort (38 eyes). (A) Effect of age. Solid squares: patients aged <58 years (n=18); open circles: patients aged >58 years (n=20). (B) Effect of baseline skin rosacea. Solid squares: patients with no or mild skin rosacea at BL (n=24); open circles: patients with moderate or severe skin rosacea at BL (n=14). (C) Effect of BL TBUT. Solid squares: eyes with TBUT ≥6 s (n=20); open circles: eyes with TBUT <6 s (n=18). (D) Effect of gender. Solid squares: females (n=16); open circles: males (n=22).
Abbreviations: BL, baseline; FU, follow-up; TBUT, tear breakup time.