Anti-inflammatory effect of curcuminoids and their analogs in hyperosmotic human corneal limbus epithelial cells.

BACKGROUND: To assess the efficacy of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin [BDC]) and their analogs (tetrahydrocurcumin [THC], tetrahydrodemethoxycurcumin [THDC], tetrahydrobisdemethoxycurcumin) in reducing inflammatory cytokines and their toxicity to primary human corneal limbal epithelial cells, these cells were cultured and exposed to these compounds. METHODS: The PrestoBlue assay assessed cell viability after treatment. Anti-inflammatory effects on hyperosmotic cells were determined using real-time polymerase chain reaction and significance was gauged using one-way analysis of variance and Tukey's tests, considering p-values < 0.05 as significant. RESULTS: Curcuminoids and their analogs, at 1, 10, and 100 µM, exhibited no effect on cell viability compared to controls. However, cyclosporin A 1:500 significantly reduced cell viability more than most curcuminoid treatments, except 100 µM curcumin and BDC. All tested curcuminoids and analogs at these concentrations significantly decreased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-17 A, matrix metallopeptidase-9, and intercellular adhesion molecule-1 after 90 mM NaCl stimulation compared to untreated cells. Furthermore, proinflammatory cytokine levels from hyperosmotic cells treated with 1, 10, and 100 µM curcumin, 100 µM BDC, 100 µM THC, 1 and 100 µM THDC mirrored those treated with cyclosporin A 1:500. CONCLUSION: The anti-inflammatory efficiency of 1 and 10 µM curcumin, 100 µM THC, 1 and 100 µM THDC was comparable to that of cyclosporin A 1:500 while maintaining cell viability.

Efficacy of Interleukin-1ß Inhibitor on Dry Eye Disease in Patients with Degenerative Arthritis.

Purpose: To evaluate diacerein (interleukin-1ß inhibitor) efficacy on ocular surface disease (OSD). Patients and Methods: This prospective observational study included patients who received diacerein for osteoarthritis and had dry eye (DE). The primary outcome was corneal staining score. Secondary outcomes were ocular surface disease index (OSDI) score, tear breakup time (TBUT), tear osmolarity (Osm), Schirmer's test results, interleukin-1α (IL-1α), interleukin-1ß (IL-1ß), and interleukin-1 receptor antagonist (IL-1Ra) levels in tears. All measurements were done at baseline and 2-month follow-up visits. Linear mixed models were used to examine the effect of all parameters, and log-transformed models were used for IL-1α, IL-1ß, and IL-1Ra analyses. Results: Thirty-four patients (31 females and 3 males) were enrolled. The corneal staining score improved by 1.29 points (P=0.022, 95% confidence interval [95% CI] 0.19 to 2.40) after 2 months, and the OSDI score improved by 17.2 points (P<0.001, 95% CI 10.82 to 23.58) but TUBT decreased by 0.66 seconds (P=0.021, 95% CI 0.10 to 1.22). No significant differences were observed in the tear Osm and Schirmer's test. IL-1Ra demonstrated no statistical difference, IL-1α was significantly increased by 80% (P=0.260), and IL-1ß was significantly decreased by 99.21% (P<0.001). Conclusion: Diacerein can improve corneal staining and decrease IL-1ß levels in tears, which reflects better DE symptoms. Diacerein may be a promising alternative treatment for patients with OSD and osteoarthritis.

Dry Eye Disease in Hemifacial Spasm Patients Treated with Botulinum Toxin Type A.

PURPOSE: To assess the impact of botulinum toxin type A (BTX-A) on signs and symptoms of dry eye (DE) in affected eye of hemifacial spasm (HFS) patients and to compare the prevalence of DE between affected and non-affected eye in HFS patients. PATIENTS AND METHODS: This prospective study included participants with unilateral HFS, who received BTX-A injection as a treatment. The eyes ipsilateral to the spasm side were used as studied eyes and the contralateral eyes were used as controls. The Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer I test were measured at baseline, 1 and 3 months after BTX-A injection. Fluorescein clearance test (FCT) was evaluated at baseline and at 1 month after BTX-A injection. RESULTS: Thirty-one participants (6 males and 25 females; mean age 61±10 years) were included. The prevalence of DE according to the Asia Dry Eye Society was not significantly different between affected (37.93%) and non-affected eyes (27.6%); P=0.083. At baseline, there was no significant difference in TBUT, Schirmer test, basal tear secretion, presence of delayed tear clearance, and presence of reflex tear secretion between affected and non-affected eyes, while significant difference in Oxford scheme grade was observed (P=0.031). OSDI score, TBUT, Oxford scheme grade, and Schirmer test at 1 month (P=0.817, 0.796, 0.534, 0.556), and 3 months (P=0.803, 0.904, 0.936, 0.684) after BTX-A injection did not significantly change from baseline in affected eyes. FCT results were not significantly different between baseline and at 1-month follow-up in both groups. All findings were corresponding in both naïve and long-term botulinum toxin injection groups. CONCLUSION: We found no significant effect of BTX-A on signs and symptoms of DE in patients with HFS. Moreover, there was no significant association between HFS and DE. However, we found significant corneal surface damage in the affected eyes, which emphasized importance of ocular surface evaluation and prompt treatment in HFS patients.

Effectiveness and Safety of Combined Application of Three Modes of 2940-nm Erbium:YAG and 1064-nm Neodymium:YAG Lasers in Treatment of Meibomian Gland Dysfunction.

PURPOSE: To study the effectiveness and safety of upper and lower eyelid treatment with combined application of three modes of 2940-nm erbium-doped yttrium aluminium garnet (Er:YAG) and 1064-nm neodymium-doped yttrium aluminium garnet (Nd:YAG) lasers in patients with baggy eyelids (formed by intraorbital fat herniation) who exhibited meibomian gland dysfunction (MGD). PATIENTS AND METHODS: In this prospective cohort study, patients with baggy eyelid who exhibited MGD received combined laser treatment at baseline, as well as at the 4-, 8-, and 12-week follow-ups. The primary endpoint was meibum quality score at 16- and 24-week follow-ups; secondary endpoints were ocular surface index scores, tear film lipid layer thicknesses, tear break up times (TBUTs), Oxford scheme grades, and meibography grades at 16- and 24-week follow-ups. Adverse events, uncorrected visual acuities, best-corrected visual acuities, and intraocular pressures were also recorded. RESULTS: Sixteen patients (four men and 12 women; mean age, 56.38 ± 8.64 years) were included. Meibum quality scores at the 16-week follow-up were significantly lower than scores at baseline (p=0.043) and at the 24-week follow-up (p=0.015). TBUT was significantly exacerbated at the 24-week follow-up, compared with baseline (p=0.001) and the 16-week follow-up (p=0.006). There were no significant changes in other parameters. All adverse events were mild and resolved without additional treatment. CONCLUSION: Combined application of three modes of 2940-nm Er:YAG and 1064-nm Nd:YAG lasers on upper and lower eyelids significantly improved meibum quality in patients with MGD; it ameliorated symptoms and signs of dry eye disease at 4 weeks after completion of laser treatment.

Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye.

This study evaluated human papillomavirus's (HPV) role in pterygium pathogenesis, its autoinoculation from genitalia to ocular surface, potential cytokines involved, and crosstalk cytokines between pterygium and dry eye (DE). This cross-sectional study enrolled 25 healthy controls (HCs) and 116 pterygium patients. Four subgroups of pterygium and DE were used in cytokine evaluations. Conjunctival and pterygium swabs and first-void urine samples (i.e., genitalia samples) were collected for HPV DNA detection using real-time polymerase chain reaction. Tear cytokines interleukin (IL)-6, IL-18, and vascular endothelial growth factor (VEGF) in tears were evaluated. No HPV DNA was detected in conjunctival or pterygium swabs. No association was found between HPV DNA in urine samples and that from conjunctival or pterygium swabs. Tear VEGF levels were significantly higher in pterygium patients than in HCs, with no markedly different levels between primary and recurrent pterygia. Tear IL-6, IL-18, and tear VEGF were significantly higher in participants with DE, regardless of pterygium status. In conclusion, HPV infection was not a pathogenic factor of pterygia. The hypothesis of HPV transmitting from the genitals to ocular surfaces was nullified. Tear VEGF was involved in both pterygia and DE, whereas tear IL-6 and IL-18 played roles only in DE.

Efficacy of topical bevacizumab 0.05% eye drops in dry eye disease: A double-masked, randomized trial.

The objective of this double-masked, placebo-controlled, randomized trial was to assess the efficacy and safety of bevacizumab 0.05% eye drops in dry eye patients. This study included Dry Eye Workshop Study (DEWS) Grade 3-4 dry eye participants (n = 31) whose tear break-up time (TBUT) was ≤5 seconds(s). Participants were randomized to undergo treatment with either bevacizumab 0.05% eye drops (n = 19) or placebo (n = 12). The primary outcome was TBUT, and the proportion of responders (increase of ≥3s in TBUT at week 12), ocular surface disease index (OSDI) score, Schirmer test, and Oxford scheme grade were secondary outcomes. All outcomes were measured at 1-, 4- and 12 weeks. TBUT in bevacizumab group differed significantly from TBUT in placebo group within 12 weeks (P = 0.001). Moreover, the improvement of TBUT in bevacizumab group versus placebo group at 4- and 12 weeks differed significantly from that difference at baseline (P = 0.002 and P = 0.003, respectively). The proportion of participants achieving increase of 3 seconds or more of TBUT at week 12 in the bevacizumab group was significantly greater than that in the placebo group (P = 0.02). Oxford scheme grade at 1-, 4- and 12 weeks differed significantly from the values at baseline in bevacizumab group (P = 0.001, P = 0.01, and P = 0.03, respectively). OSDI scores at 1-, 4- and 12-week follow-ups were significantly lower than that at baseline in bevacizumab group (P<0.001 at each follow-up). Schirmer test were not significantly different within or between groups (the lowest P = 0.92). No adverse events occurred in this study. Patients treated with bevacizumab 0.05% eye drops showed significant improvement in tear film stability, corneal staining and symptoms.