Tear Cytokines as Predictive Biomarkers of Success in Contact Lens Discomfort Management.

PURPOSE: To analyze changes in tear levels of inflammatory mediators in symptomatic contact lens (CL) wearers after refitting with daily disposable CLs and to identify potential biomarkers of success in CL discomfort (CLD) management. METHODS: Symptomatic CL wearers (CLDEQ-8 ≥ 12) were refitted (V1) with daily disposable CLs (Delefilcon A). After one month (V2), participants were classified into the post-fitting non-symptomatic (CLDEQ <12) and symptomatic (CLDEQ ≥12) groups. At each visit, the participants were clinically evaluated, tears were collected, and 20 inflammatory mediators and substance P (SP) were measured using multiplex immunobead analysis and ELISA, respectively. The detection rates and concentrations were compared between visits and groups, and logistic regression models were performed. RESULTS: Forty-three subjects (32 women/11 men; mean age: 23.2 ± 4.9 years) were enrolled. The IL-1ß and IL-9 detection rates were higher at V2 (p ≤ 0.044). The detection rates of IL-1ß, IL-9, MIP-1α/CCL3, and MMP-9 at V1 (p ≤ 0.045) and IL-17A at V2 (p ≤ 0.014) were higher in the post-fitting symptomatic group. The tear IL-9 concentration was increased at V2 (p = 0.018). The tear concentrations of fractalkine/CX3CL1, IL-2, IL-6, IL-10, MCP-3/CCL7, MIP-1ß, NGF, RANTES/CCL5, and TNF-α were higher in the post-fitting symptomatic group (p ≤ 0.044). Additionally, levels of fractalkine/CX3CL1, IL-2, IL-6, IL-10, RANTES/CCL5, and TNF-α at V1 were significantly associated with the post-fitting grouping (p ≤ 0.044). CONCLUSIONS: Low tear concentrations of specific inflammatory mediators may be used as a predictive biomarker of success for refitting symptomatic CL wearers with daily disposable CLs. However, complementary treatments might be required for symptomatic CL wearers with higher levels of these inflammatory molecules.

Visual Performance and Higher Order Aberrations Obtained With Omafilcon A Dual-Focus and Single-Vision Contact Lens Designs.

OBJECTIVE: The purpose of this study was to assess the visual performance and monochromatic higher-order aberrations (HOAs) obtained while wearing a MiSight dual-focus (DF) contact lenses (CL) in comparison with a single-vision contact lens (SVCL). METHODS: A randomized, double-masked, cross-over study was performed. Participants were fitted with a DFCL and a SVCL composed of the same material (omafilcon A) and parameters. Logarithm of the Minimum Angle of Resolution high-contrast (100%) and low-contrast (10%) visual acuity (VA) and contrast sensitivity (CS) for 3, 6, 12, and 18 cycles per degree were measured. Higher-order aberrations were also evaluated using a Hartmann-Shack aberrometer with the CLs on. RESULTS: Twenty-four subjects (21 females and 3 males) with a mean age of 21.9±1.9 years (range: 18-27) were included. Low-contrast VA was significantly lower with the DFCL regarding the SVCL design (0.39±0.23 vs 0.25±0.18, P=0.002). However, there were no differences in high-contrast VA between both CLs (-0.03±0.10 vs -0.09±0.14, P=0.187). Contrast sensitivity was lower with the DFCL under all spatial frequencies (P≤0.048). Second-, third-, fourth-, and fifth-order aberrations were significantly (P<0.001) higher for the DFCL. There were also significant differences between DFCL and SVCL in defocus (0.87±0.28 vs 0.16±0.35, P<0.001), oblique trefoil (-0.16±0.27 vs -0.01±0.08, P=0.005), vertical coma (0.13±0.17 vs 0.00±0.08, P=0.002), and spherical aberration (0.09±0.11 vs -0.02±0.05, P=0.002). CONCLUSION: Visual performance for detecting low-contrast targets is reduced when wearing MiSight DFCL compared with a SVCL with the same material. The main reason might be the induction of second-order and HOAs by the DFCL design.

Effect of a single vectored thermal pulsation treatment of Meibomian gland dysfunction patients under controlled environmental conditions.

To assess the prophylactic effect of LipiFlow treatment in Meibomian gland dysfunction (MGD) patients exposed to an adverse environmental humidity. MGD patients were exposed to normal (23 °C; 50% relative humidity; 30 min) and adverse (23 °C; 10% relative humidity; 2 h) controlled environments consecutively during baseline and follow-up visits (3, 6, and 12 months) after a single LipiFlow treatment. Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), fluorescein tear break-up time (TBUT), corneal and conjunctival staining, change in dry eye symptoms questionnaire (CDES-Q), and Meibomian gland yielding liquid secretion (MGYLS), were assessed. Linear mixed-effects and cumulative logit mixed models were fitted to assess the effect of the LipiFlow treatment over time and within the controlled environments. Seventeen females and 4 males (59.6 ± 9.4 years) completed the study. LLT and TBUT did not vary significantly (p > 0.05) after LipiFlow treatment. OSDI, corneal and conjunctival staining, and MGYLS scores were improved (p ≤ 0.01) 12 months after treatment. After the adverse exposure, corneal staining increased at all visits (p = 0.01), and there was no significant improvement in CDES-Q scores after LipiFlow treatment (p ≥ 0.07). One LipiFlow treatment improved objective and subjective outcomes in MGD disease for at least one year. Further studies are needed to support that LipiFlow might also help as an adjuvant to avoid acute flares against an adverse environmental humidity.

Is contact lens discomfort related to meibomian gland morphology?

PURPOSE: To examine the relationship between contact lens (CL) discomfort and meibomian gland (MG) morphology assessed by a semi-objective software in subjects without an alteration of MG function (meibum quality and expressibility). METHODS: Nineteen symptomatic (CLDEQ-8 ≥ 12) CL wearers, 19 asymptomatic (CLDEQ-8 < 12) wearers, and 22 non-wearers were recruited. Upper and lower eyelid meibography images were taken and the following parameters were analysed using a semi-objective software in the central 2/3 of each eyelid: number of MG, number of partial MG, percentage of MG loss and percentage of tortuosity. One-way ANOVA or Kruskal-Wallis H test were used for comparisons among groups. The relationships between CLDEQ-8 and MG morphology parameters were analysed using the Spearman correlation coefficient and multivariable linear regression models. RESULTS: No significant differences were found among groups in the MG morphology of the upper or lower eyelids. In all CL wearers, a significant correlation with CLDEQ-8 was found in the upper eyelid for the number of MG (rho = 0.47, p = 0.003). In symptomatic wearers, significant correlations with CLDEQ-8 were found in the lower eyelid for the number of partial MG (rho = 0.49, p = 0.03) and the percentage of partial MG (rho = 0.61, p = 0.005). In all CL wearers, multivariable models were fitted to explain CLDEQ-8 score including the number of MG, the number of partial MG and the percentage of MG loss from the lower eyelid (R2 = 0.19; p = 0.007), and the number of MG from the upper eyelid (R2 = 0.19; p = 0.001). In symptomatic wearers, a model was fitted including the percentage of MG loss from the lower eyelid (R2 = 0.30; p = 0.016). CONCLUSIONS: Alterations of MG morphology, without clinically apparent alteration of MG function, can be involved in causing CL discomfort and influence the degree of symptoms. The differences in findings between eyelids indicate the need to monitor both eyelids, especially the lower one, in CL wearers.

Inflammation-related molecules in tears of patients with chronic ocular pain and dry eye disease.

The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = -0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = -0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = -0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions.

Usefulness of a global rating change scale for contact lens discomfort evaluation.

OBJECTIVES: To evaluate the usefulness of a global rate of change scale (GRCS) to detect variations in contact lens discomfort (CLD). METHODS: Symptomatic contact lens (CL) wearers were recruited according to the 'Contact Lens Dry Eye Questionnaire-8' (CLDEQ-8). At the baseline visit, subjects scored their comfort following insertion of their habitual CL using a 0-100 visual analogue scale (VAS). After 4-10 h of CL wear, comfort was again self-evaluated with the VAS and with a GRCS (range, -50 to +50). Then, a daily disposable CL (DDCL) was fitted. After one month of DDCL wear, a follow-up visit was conducted where the same evaluations as the baseline visit were performed. Changes in comfort were estimated using a Student's t-test for normal variables and the Friedman test for multiple comparisons of non-parametric variables. Internal responsiveness was measured by calculating the standardised response mean. Agreement between scales was estimated by the intraclass correlation coefficient (ICC). RESULTS: Twenty-nine (22 females and 7 males) CL wearers with a mean age of 23.4 ± 5.4 years participated in the study. There was a significant decrease in comfort at both visits detected by the GRCS (baseline = -13.58 ± 17.48, p < 0.001; follow up = -6.86 ± 12.69, p = 0.007). However, the VAS did not detect that change, either at baseline (insertion = 64.28 ± 18.72 vs removal = 52.89 ± 17.64, p = 1.000) or follow-up visit (insertion = 81.97 ± 12.91 vs removal = 76.48 ± 16.02, p = 1.000). Comfort at insertion and removal times was significantly higher with the DDCL (p = 0.008 at insertion and p = 0.004 at removal). The standardised response mean was greater with the GRCS than the VAS at baseline (0.78 vs 0.63) and follow-up (0.54 vs 0.37) visits. Agreement between both scales was moderate and significant (p < 0.001) for both visits, ICC: 0.674 (95 % confidence interval (CI):0.411-0.833) (baseline) and 0.652 (95 % CI:0.377-0.821) (follow-up visit). CONCLUSIONS: The GRCS can detect slight changes in CL wear comfort and shows higher responsiveness than the VAS. This subjective scale can allow detection of changes in comfort in a simple and quick way.

Does placebo effect exist in contact lens discomfort management?

PURPOSE: To study the effect of daily disposable contact lens (DDCL) refitting in monthly contact lens (CL) wearers suffering from contact lens discomfort (CLD), and to assess if there is a placebo effect associated with this CLD intervention. METHODS: Symptomatic CL wearers, according to the Contact Lens Dry Eye Questionnaire 8 (CLDEQ-8 ≥ 12 points), were divided into two groups. The study group was provided with DDCLs (delefilcon A) and the control group with a masked pair of their habitual monthly CLs (placebo effect) and were assessed after one month. Then, the control group was provided with the same DDCLs and evaluated one month later. The symptoms were recorded with the CLDEQ-8 and global rating of change scale (GRCS). Non-invasive tear break-up time (NITBUT), conjunctival hyperaemia, fluorescein staining, and lid wiper epitheliopathy (LWE) were evaluated. Changes between visits, groups, and the effect of each intervention were analysed. RESULTS: Thirty-one participants (mean age: 23.2 ± 5.3 years) were recruited. The study group (n = 14) showed an improvement of -39.6 ± 25.8 % (p < 0.001) in CLDEQ-8 and 31.3 ± 14.6 points in GRCS (p < 0.001) after one month of DDCL use, while no changes in clinical tests were found. In the control group (n = 17), symptoms improved significantly after wearing the masked monthly CL (CLDEQ-8: -26.1 ± 31.0 %, p = 0.03; GRCS: 14.9 ± 17.0, p = 0.002), however a worsening in bulbar (26.5 ± 40.0 %; p = 0.02) and limbal hyperaemia (21.6 ± 34.7 %, p = 0.02) and an improvement of -19.1 ± 37.0 % (p = 0.049) in LWE was found. When the control group was fitted with the DDCL, improvements in GRCS (20.5 ± 25.5, p = 0.02), NITBUT (37.9 ± 42.3 %, p = 0.002), and conjunctival staining (-47.1 ± 59.9 %, p = 0.005) were noted. CONCLUSIONS: Refitting symptomatic monthly CL wearers with Delefilcon A DDCL is effective in reducing symptoms related to CLD. However, clinicians and researchers must be aware of the existence of a placebo effect when assessing the effectiveness of any CL refitting.

Contact Lens Discomfort Management: Outcomes of Common Interventions.

PURPOSE: To assess the consecutive implementation of habitual contact lens discomfort (CLD) management strategies: lid hygiene, daily disposable CL (DDCL) fitting, and artificial tear (AT) supplementation. METHODS: Contact lens (CL) wearers with CLD symptoms (CLDEQ-8 ≥12 points) were included in the study. Subjects with Meibomian gland dysfunction (MGD) were instructed to perform lid hygiene. All participants were fitted with a DDCL (delefilcon A) and evaluated 1 month later. After, half of them were randomly assigned to use AT (Povidone-2%) at least three times/day, and all participants were evaluated 1 month later. Tests performed were: lower tear meniscus area (LTMA), bulbar, limbal, and tarsal hyperemia, noninvasive tear break-up time (NITBUT), and corneal and conjunctival staining. Weighted combined clinical scores (CS) were created to analyze signs. Changes in symptoms (CLDEQ-8) and CS were analyzed using linear mixed models. RESULTS: Forty-two subjects (mean age: 23.2±4.9 years) completed the study. Two CS were created, CS 1 was composed of bulbar, limbal, and tarsal hyperemia and corneal staining, and CS 2 by NITBUT, LTMA, and conjunctival staining. CLDEQ-8 was reduced after lid hygiene (mean: -2.73±2.13; P=0.012) and DDCL use (mean: -10.1±3.54; P<0.01), but not after AT use (P=0.62). CS 1 did not change after any intervention. CS-2 was higher (P=0.04) in DGM subjects after lid hygiene, it decreased (P=0.04) after DDCL use. CONCLUSIONS: Lid hygiene is effective for reducing CLD symptoms in MGD patients. Refitting subjects with delefilcon A is an effective intervention for CLD to reduce symptoms and achieve a healthier ocular surface. Simultaneous administration of AT did not further improve CLD.

Therapeutic Instruments Targeting Meibomian Gland Dysfunction.

The most prevalent type of meibomian gland dysfunction (MGD), which is obstructive, is the main cause of evaporative dry eye and is characterized by changes in the meibum composition and duct obstruction. Eyelid hygiene has usually been the most common clinical approach. However, alternative therapies for MGD are emerging on the market. Some warming and humidity devices have led to an improvement in the signs and symptoms in MGD patients. Likewise, eyelid massaging and cleaning devices are also beneficial for ocular signs and symptoms; however, patients usually need more than one session to maintain the therapeutic effect. Thermal pulsation has been reported to be more efficient than other strategies, and the effects can last up to 12 months. Moreover, intense pulsed light therapy has been demonstrated to improve ocular signs and symptoms alone and in combination with other therapies. Proper counseling of clinicians considering MGD status and patient compliance will help patients to undergo the adequate technique that best suits their condition.