Tear cytokine response to multipurpose solutions for contact lenses

Figures & data

Figure 1 Baseline tear cytokine concentrations (mean ± standard deviation) of subjects who used RNF in Phase I or OFR in Phase I.

Abbreviations: CCL, cc chemokine ligand; CXCL, cxc motif ligand; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; FGF, fibroblast growth factor; IL, interleukin; INF, interferon; OFR, Opti-Free RepleniSH; PDGF-BB, plasma-derived growth factor; TNF, tumor necrosis factor; RNF, ReNu Fresh; VEGF, vascular endothelial growth factor.

Figure 2 Tear levels of representative cytokines of subjects using different MPS in Phase I and Phase II.

Note: *Indicates a statistically significant change (P < 0.01) from baseline.
Abbreviations: INF, interferon; IL, interleukin; MPS, multipurpose solution; OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Table 1 Statistical analysis of tear cytokine concentration changes from baseline

Cytokine	RNF Phase I					OFR Phase I
	Phase I day 1 (RNF)	Phase I day 28 (RNF)	Washout	Phase II day 1 (OFR)	Phase II day 28 (OFR)	Phase I day 1 (OFR)	Phase I day 28 (OFR)	Washout	Phase II day 1 (RNF)	Phase II day 28 (RNF)
CCL3	§	§	§	§	§	0.0006	§	0.0011	0.0099	§
CCL5	§	§	§	§	0.0091*	0.0014	§	0.0090	§	§
CCL11	§	§	§	§	§	0.0006	0.0057	0.0002	§	§
GM-CSF	§	§	§	§	§	0.0003	§	0.0079	§	§
IFN-γ	§	§	§	§	§	0.0043	0.0078	0.0036	§	§
IL-2	§	§	§	§	§	0.0021	§	0.0097	§	§
IL-4	§	§	§	§	§	0.0015	§	§	§	§
IL-5	§	§	§	§	§	0.0010	§	0.0042	§	§
IL-6	§	§	§	§	§	§	0.0087	0.0066	§	§
IL-13	§	§	§	§	§	0.0038	§	0.0042	§	§
IL-15	§	§	§	§	§	§	§	0.0096	§	§
IL-17	§	§	§	§	§	§	§	0.0078	0.0088	§
PDGF-BB	§	§	§	§	§	§	§	§	§	0.0033
TNF-α	§	§	§	§	§	0.0064	§	0.0023	§	§

Notes: *P-value by paired t-test; ^§P > 0.01 by paired t-test.

Abbreviations: CCL, cc chemokine ligand; GM-CSF, granulocyte macrophage colony-stimulating factor; IL, interleukin; INF, interferon; OFR, Opti-Free RepleniSH; PDGF-BB, plasma-derived growth factor; TNF, tumor necrosis factor; RNF, ReNu Fresh.

Table 2 Conjunctival surface hyperemia score (mean ± standard deviation, scale 0–100)

Hyperemia	RNF Phase 1					OFR Phase 1
	Baseline	Phase I day 1 (RNF)	Phase I day 28 (RNF)	Phase II day 1 (OFR)	Phase II day 28 (OFR)	Baseline	Phase I day 1 (OFR)	Phase I day 28 (OFR)	Phase II day 1 (RNF)	Phase II day 28 (RNF)
Bulbar	33.5 ± 3.9	29.8 ± 3.7*	31.6 ± 3.6*	31.0 ± 3.5*	31.7 ± 3.1	33.1 ± 4.6	30.2 ± 4.8	30.8 ± 3.7	30.1 ± 3.0*	32.0 ± 4.1
Limbal	27.2 ± 4.5	26.2 ± 3.7	28.1 ± 3.8	27.6 ± 4.5	28.2 ± 3.8	27.7 ± 4.5	26.8 ± 3.6	29.1 ± 7.7	29.0 ± 3.7	30.0 ± 3.89

Notes:

* Statistically significant change from baseline, P < 0.01 by paired t-test.

Abbreviations: OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Figure 3 Ocular surface sensitivity thresholds of subjects using different MPS in Phase I and Phase II.

Abbreviations: MPS, multipurpose solution; OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Table 3 Corneal surface chemical and mechanical sensitivity

Sensitivity tested	RNF Phase I baseline	OFR Phase I baseline	P-value (unpaired Student t-test)
Corneal mechanical threshold (air flow mL/minute)	49.2 ± 23.7	39.9 ± 15.4	0.26
Corneal chemical threshold (% CO2 added)	21.7 ± 6.7	21.8 ± 8.8	0.97
Conjunctival mechanical threshold (air flow mL/minute)	51.4 ± 22.1	52.1 ± 18.9	0.94
Conjunctival chemical threshold (% CO2 added)	50.6 ± 10.6	49.36 ± 19.6	0.84

Abbreviations: OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Table 4 Corneal surface staining score (mean ± standard deviation), severity scale 0–4, extent scale (0%–100%)

Staining	RNF Phase 1					OFR Phase 1
	Baseline	Phase I day 1 (RNF)	Phase I day 28 (RNF)	Phase II day 1 (OFR)	Phase II day 28 (OFR)	Baseline	Phase I day 1 (OFR)	Phase I day 28 (OFR)	Phase II day 1 (RNF)	Phase II day 28 (RNF)
Severity	0.3 ± 0.3	0.9 ± 0.2*	0.7 ± 0.3*	0.6 ± 0.2	0.4 ± 0.3	0.1 ± 0.2	0.3 ± 0.3	0.7 ± 0.3*	0.8 ± 0.2*	0.9 ± 0.1*
Extent	2.4 ± 3.4	53.8 ± 32.3*	26.7 ± 26.6*	7.4 ± 10.6	6.3 ± 12.4	1.1 ± 2.2	2.5 ± 2.0	11.9 ± 13.1	48.3 ± 24.8*	45.6 ± 32.2*

Notes:

* Statistically significant change from baseline, P < 0.01 by paired t-test.

Abbreviations: OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Figure 4 Subjective responses of subjects using different MPS in Phase I and Phase II.

Notes: Subjects reported subjective scores in the morning (AM) afternoon (AN) and evening (PM). *Indicates a statistically significant change (P < 0.01) from morning score.
Abbreviations: AM, morning; AN, afternoon; MPS, multipurpose solution; PM, evening; OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Table 5 Statistical analysis of subjective symptom score changes from morning score; P-value by paired t-test

Subjective measurement	RNF Phase 1								OFR Phase 1
	Phase 1 day 1 AN (RNF)	Phase 1 day 1 PM (RNF)	Phase 1 day 27 AN (RNF)	Phase 1 day 27 PM (RNF)	Phase II day 1 AN (OFR)	Phase II day 1 PM (OFR)	Phase II day 27 AN (OFR)	Phasell day 27 PM (OFR)	Phase 1 day 1 AN (OFR)	Phase 1 day 1 PM (OFR)	Phase 1 day 27 AN (OFR)	Phase 1 day 27 PM (OFR)	Phasell day 1 AN (RNF)	Phase II day 1 PM (RNF)	Phase II day 27 AN (RNF)	Phase II day 27 PM (RNF)
Comfort	§	§	§	0.009	§	§	§	§	§	§	§	§	§	§	§	§
Dryness	§	§	§	§	§	§	0.008	§	§	0.010	§	0.004	§	0.007	§	§
Blurry vision	§	§	§	§	§	§	§	§	§	§	§	§	§	§	§	§

Note: ^§P > 0.01 by paired t-Test

Abbreviations: AN, afternoon; PM, evening; OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.

Table 6 Scores for stinging or burning upon CL/MPS insertion (mean ± standard devation), scale 0 (severe) to 100 (negligible)

Insertion sensation	RNF Phase I				OFR Phase I
	Phase I day 1 (RNF)	Phase I day 27 (RNF)	Phase II day 1 (OFR)	Phase II day 27 (OFR)	Phase I day 1 (OFR)	Phase I day 27 (OFR)	Phase II day 1 (RNF)	Phase II day 27 (RNF)
Stinging	91.9 ± 23.8	97.8 ± 3.6	99.2 ± 2.7	97.1 ± 5.4	95.0 ± 9.8	97.2 ± 6.6	93.8 ± 9.4	96.8 ± 4.3
Burning	91.9 ± 24.7	97.7 ± 3.7	99.2 ± 2.7	97.5 ± 4.6	98.5 ± 3.0	98.3 ± 4.1	96.0 ± 8.3	97.5 ± 3.7

Abbreviations: CL/MPS, contact lens/multipurpose solutions; OFR, Opti-Free RepleniSH; RNF, ReNu Fresh.