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Abstract
Purpose
The changes in tear film lipid layer thickness (LLT) after artificial tears application using LipiView® II interferometer were assessed.
Methods
We performed a prospective study of patients with dry eye disease. All subjects underwent measurement of tear film break-up time, Schirmer test, ocular surface staining, meibomian gland evaluation, and subjective score assessment using the Ocular Surface Disease Index. All subjects were randomly assigned to 1 of 3 groups using table of random numbers (group 1, sodium hyaluronate [HA] 0.1% eye drops without preservatives; group 2, HA 0.3% eye drops without preservatives and group 3, HA 0.1% with benzalkonium chloride 0.003%). LLT was measured before, immediately after and 1 hr, 3 hrs, and 6 hrs after artificial tears application. Additionally, the patients were divided into 2 subgroups depending on the presence of meibomian gland dysfunction (MGD) and further evaluated.
Results
Significant change in LLT was observed at 3 hrs after artificial tears instillation. LLT in groups 1 and 2 showed significant changes over time (p < 0.01 and p < 0.01, respectively). However, LLT in group 3 showed no change. LLT was unchanged in patients without MGD. Conversely, in MGD patients, a significant difference in LLT between groups 1 and 2 was observed immediately after and 1 hr and 3 hrs after instillation of artificial tears (p = 0.04, p < 0.01 and p = 0.02, respectively) but not at 6 hrs. However, no significant difference in LLT between groups 1 and 3 was observed in MGD patients.
Conclusions
LLT after instillation of artificial tears measured using LipiView® II interferometer was affected by artificial tear concentration and presence of preservatives. Additionally, the presence of MGD can impact the pattern of LLT changes induced by artificial tear instillation. Therefore, LLT measurements using LipiView® II interferometer require at least a 6-hrs interval after use of eye drops, especially for patients with MGD or using artificial tears with preservatives.
References
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Figure 1.
Schematic diagram of the study protocol. 84 patient were screened and total 56 patients were included. All subjects underwent measurement of tear film break-up time (TBUT), Schirmer test, ocular surface staining, meibomian gland evaluation, and subjective score assessment using Ocular Surface Disease Index (OSDI). Patients were randomly assigned to 1 of 3 groups using table of random numbers. Lipid layer thickness (LLT) was measured before, immediately after and 1 hr, 3 hrs, and 6 hrs after artificial tears application. HA = sodium hyaluronate; h(s) = hour(s).
Figure 2.
The analyzed image by Lipiview®II interferometer. The values are given in interferometric color units (ICUs) where in 1 ICU approximately reflects 1nm of the tear lipid layer thickness (LLT). The average LLT of this patient was 99 ICUs.
Figure 3.
Box plot of lipid layer thickness (LLT) stratified by (A) non-Meibomian gland dysfunction (MGD) group and (B) MGD group. Horizontal lines in the boxes indicate the median; box limits show third quartile and first quartile. Maximum and minimum values are indicated by the top and the bottom whisker ends, respectively. Overall p-values were calculatedby linear mixed model. h(s) = hour(s).
Figure 4.
Box plots of lipid layer thickness (LLT) for comparison between two groups of Meibomian gland dysfunction patients. Figure (A) shows comparision between Group 1 and 2 and figure (B) shows Comparision berween Group 1 and 3. Horizontal lines in the boxes indicate the median; box limits show third quartile and first quartile. Outliers (1.5 × 3 interquartile ranges) are indicated as circles. Maximum and minimum values are indicated by the top and the bottom whisker ends, respectively. p-values were calculated by Linear mixed model. h(s) = hour(s).
Table 1.
Clinical characteristics of subjects
| Variables | Group 1 | Group 2 | Group 3 | p-value* |
|---|---|---|---|---|
| N (eyes) | 18 | 20 | 18 | |
| Age (years) | 26.56 ± 1.85 | 27.62 ± 3.67 | 27.11 ± 2.90 | 0.54 |
| (24–29) | (23–41) | (24–32) | ||
| BUT (sec) | 6.56 ± 1.65 | 5.33 ±1.56 | 6.00 ± 2.26 | 0.13 |
| (4–11) | (3–9) | (3–11) | ||
| Schirmer test (mm) | 14.11 ± 3.05 | 12.00 ± 2.17 | 13.11 ± 3.09 | 0.07 |
| (10–20) | (8–16) | (8–18) | ||
| Corneal staining score | 0.89 ± 0.90 | 0.52 ± 0.60 | 0.58 ± 0.51 | 0.22 |
| (0–3) | (0–2) | (0–1) | ||
| Subjective score (OSDI) | 17.67 ± 16.57 | 16.93 ± 15.77 | 14.75 ± 16.29 | 0.85 |
| (8–70) | (4.2–60) | (4.2–60) | ||
| MGD grade | 0.94 ± 0.73 | 1.10 ± 0.94 | 1.11 ± 0.99 | 0.83 |
| (0–2) | (0–2) | (0–2) | ||
| Baseline LLT | 64.76 ± 25.56 | 67.71 ± 23.72 | 61.15 ± 24.88 | 0.70 |
| (26–100) | (30–100) | (31–100) |
Values are presented as mean ± SD (range) unless otherwise indicated. ‘Group 1’ is ‘Sodium hyaluronate (HA) 0.1% eye drops without preservatives’, ‘Group 2’ is ‘HA 0.3% eye drops without preservatives’, and ‘Group 3’ is ‘HA 0.1% with Benzalkonium chloride 0.003%’. BUT = tear film break-up time; OSDI = ocular surface disease index; MGD = Meibomian gland dysfunction; LLT=Lipid layer thickness.
Table 2.
Tear film lipid layer thickness after application of artificial tears
| Time |
LLT (nm) |
Overall P* Post | t-hoc p-value* for time | ||
|---|---|---|---|---|---|
| Group 1 | Group 2 | Group 3 | |||
| Baseline | 64.76 ± 25.56 | 67.71 ± 23.72 | 61.15 ± 24.88 | P group = 0.09 | Reference† |
| (26–100) | (30–100) | (31–100) | |||
| Immediate | 65.11 ± 21.95 | 79.14 ± 25.03 | 58.53 ± 15.17 | 0.29 | |
| (39–100) | (39–100) | (36–95) | |||
| After 1 h | 51.35 ± 15.51 | 73.76 ± 23.60 | 58.89 ± 18.09 | P time = 0.02 | 0.35 |
| (31–80) | (28–100) | (38–100) | |||
| After 3 hs | 52.41 ± 17.57 | 65.00 ± 25.09 | 55.57± 15.26 | P(group × time) < 0.01 | 0.03 |
| (26–100) | (29–100) | (33–100) | |||
| After 6 hs | 64.82 ± 22.94 | 60.57 ± 23.95 | 62.42 ± 19.83 | 0.52 | |
| (31–100) | (26–100) | (30–100) | |||
| p-value | <0.01 | <0.01 | 0.71 | ||
Values are presented as mean ± SD (range) unless otherwise indicated. ‘Group 1’ is ‘Sodium hyaluronate (HA) 0.1% eye drops without preservatives’, ‘Group 2’ is ‘HA 0.3% eye drops without preservatives’, and ‘Group 3’ is ‘HA 0.1% with Benzalkonium chloride 0.003%’. LLT = lipid layer thickness; h(s) = hour(s).
Table 3.
Clinical variables of two subgroups: non-meibomian gland dysfunction (MGD) and MGD group
| Variables |
Non-MGD group (n = 19) |
MGD group (n = 39) |
||||||
|---|---|---|---|---|---|---|---|---|
| Group 1 | Group 2 | Group 3 | p-value* | Group 1 | Group 2 | Group 3 | p-value* | |
| N (eyes) | 5 | 8 | 6 | 13 | 12 | 12 | ||
| Age (years) | 27.08 ± 0.84 | 29.00 ± 4.96 | 25.67 ± 1.37 | 0.22 | 26.08 ± 1.93 | 26.77 ± 2.46 | 27.77 ± 3.22 | 0.26 |
| (27–29) | (26–41) | (24–27) | (24–29) | (23–29) | (24–32) | |||
| BUT (sec) | 5.60 ± 1.82 | 5.50 ± 1.77 | 5.67 ± 2.66 | 0.99 | 6.92 ± 1.50 | 5.23 ± 1.48 | 6.15 ± 2.15 | 0.06 |
| (4–8) | (4–9) | (3–9) | (5–11) | (3–8) | (3–11) | |||
| Schirmer test (mm) | 13.60 ± 2.30 | 12.13 ± 2.10 | 14.33 ± 2.81 | 0.24 | 14.31 ± 3.35 | 11.92 ± 2.29 | 12.54 ± 3.15 | 0.12 |
| (10–16) | (10–16) | (11–18) | (10–20) | (8–15) | (8–17) | |||
| Corneal staining score | 1.20 ± 0.84 | 0.75 ± 0.71 | 0.50 ± 0.55 | 0.28 | 0.77 ± 0.93 | 0.38 ± 0.56 | 0.62 ± 0.51 | 0.36 |
| (0–2) | (0–2) | (0–1) | (0–3) | (0–1) | (0–1) | |||
| Subjective score (OSDI) | 24.11 ± 25.73 | 11.72 ± 10.0 | 10.03 ± 2.26 | 0.25 | 15.20 ± 12.02 | 20.15 ± 18.07 | 16.93 ± 19.49 | 0.75 |
| (10–70) | (4.2–27.0) | (7.3–60) | (8–54.16) | (6.3–60) | (4.2–60) | |||
| Baseline LLT (nm) | 43.60 ± 22.12 | 72.13 ± 23.96 | 52.50 ± 28.49 | 0.14 | 64.76 ± 25.56 | 67.71 ± 23.72 | 61.15 ± 24.88 | 0.65 |
| (26–81) | (30–100) | (31–100) | (26–100) | (30–100) | (31–100) | |||
| MGD grade | 0 | 0 | 0 | 1.31 ± 0.48 | 1.77 ± 0.44 | 1.62 ± 0.77 | 0.13 | |
| (1–2) | (1–2) | (1–2) | ||||||
Values are presented as mean ± SD (range) unless otherwise indicated. ‘Group 1’ is ‘Sodium hyaluronate (HA) 0.1% eye drops without preservatives’, ‘Group 2’ is ‘HA 0.3% eye drops without preservatives’, and ‘Group 3’ is ‘HA 0.1% with Benzalkonium chloride 0.003%’. BUT = tear film break-up time; OSDI = ocular surface disease index; LLT = lipid layer thickness; MGD = Meibomian gland dysfunction.
Table 4.
Changes of tear film lipid layer thickness after application of artificial tears in meibomian gland dysfunction (MGD) group
| Time | Baseline | Immediate | After 1 h | After 3 hs | After 6 hs | p-value* | |
|---|---|---|---|---|---|---|---|
| Group 1 | LLT (nm) | 64.76 ± 25.56 | 65.11 ± 21.95 | 51.35 ± 15.51 | 52.41 ± 17.57 | 64.82 ± 22.94 | <0.01 |
| (26–100) | (39–100) | (31–80) | (26–100) | (31–100) | |||
| Post-hoc P | Reference† | 0.48 | <0.01 | <0.01 | 0.74 | ||
| Group 2 | LLT (nm) | 67.71 ± 23.72 | 79.14 ± 25.03 | 73.76 ± 23.60 | 65.00 ± 25.09 | 60.57 ± 23.95 | 0.01 |
| (30–100) | (39–100) | (28–100) | (29–100) | (26–100) | |||
| Post-hoc P | Reference† | 0.05 | 0.09 | 0.89 | 0.22 | ||
| Group 3 | LLT (nm) | 61.15 ± 24.88 | 58.53 ± 15.17 | 58.89 ± 18.09 | 55.57 ± 15.26 | 62.42 ± 19.83 | 0.45 |
| (31–100) | (36–95) | (38–100) | (33–100) | (30–100) |
Values are presented as mean ± SD (range) unless otherwise indicated. ‘Group 1’ is ‘Sodium hyaluronate (HA) 0.1% eye drops without preservatives’, ‘Group 2’ is ‘HA 0.3% eye drops without preservatives' and ‘Group 3’ is ‘HA 0.1% with Benzalkonium chloride 0.003%’. h(s) = hour(s); LLT = lipid layer thickness.
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