José Pinto-Fraga

End-of-day dryness, corneal sensitivity and blink rate in contact lens wearers

PURPOSE To study the relationship among the variables intensity of the end-of-day (EOD) dryness, corneal sensitivity and blink rate in soft contact lens (CL) wearers. METHODS Thirty-eight soft CL wearers (25 women and 13 men; mean age 27.1±7.2 years) were enrolled. EOD dryness was assessed using a scale of 0-5 (0, none to 5, very intense). Mechanical and thermal (heat and cold) sensitivity were measured using a Belmontes gas esthesiometer. The blink rate was recorded using a video camera while subjects were wearing a hydrogel CL and watching a film for 90 min in a controlled environmental chamber. RESULTS A significant inverse correlation was found between EOD dryness and mechanical sensitivity (r: -0.39; p=0.02); however, there were no significant correlations between EOD dryness and thermal sensitivity. A significant (r: 0.56; p<0.001) correlation also was observed between EOD dryness and blink rate, but no correlations were found between blink rate and mechanical or thermal sensitivity. CONCLUSIONS CL wearers with higher corneal sensitivity to mechanical stimulation reported more EOD dryness with habitual CL wear. Moreover, subjects reporting more EOD dryness had an increased blink rates during wear of a standard CL type. The increased blink rate could act to improve the ocular surface environment and relieve symptoms.

Efficacy and Safety of 0.2% Hyaluronic Acid in the Management of Dry Eye Disease.

Objectives: To evaluate the safety and efficacy of a new artificial tear containing 0.2% hyaluronic acid, as compared with 0.9% saline solution, in mild dry eye patients after 1-month use in a crossover study design with washout periods. Methods: Overall, 16 mild dry eye patients were included. After a week of washout, every patient used the experimental product (Visaid 0.2%) and the control product (0.9% saline solution), each for a month (3–8 drops daily). Both products were preservative free. The percentage change for the following variables were calculated and analyzed: Ocular Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular pressure, ophthalmoscopy evaluation, biomicroscopy findings, fluorescein corneal staining and lissamine green conjunctival staining, tear breakup time, contrast sensitivity, Schirmers test, and subject satisfaction. Results: Patients reported an improvement (a significant decrease of −19.5%±27.5%) in OSDI scores after using Visaid 0.2% and a worsening (a significant increase of 19.2%±32.4%) after using 0.9% saline solution; the difference was significant (P=0.0087, Students t test). Significant changes (P⩽0.04, Wilcoxons test) were found comparing Visaid 0.2% with saline solution for bulbar hyperemia (−39.1%±50.8% vs. 7.8%±12.0%, respectively), corneal staining (−26.0%±53.0% vs. 36.5%±73.3%), conjunctival staining (−54.7%±53.4% vs. −7.8%±47.2%), and subjective satisfaction (26.8%±28.5% vs. −13.3%±22.5%). There were no significant differences in the safety parameters for either solution. Conclusion: This clinical trial demonstrates the safety of Visaid 0.2% and its clear benefit over 0.9% saline solution.

Effects of the External Environment on Dry Eye Disease

Dry eye disease (DED) is a chronic multifactorial inflammatory disorder of the lacrimal functional unit (LFU) in which several etiopathogenic mechanisms usually interact to develop into an anomalous LFU, eventually leading to tear film instability and ocular surface damage. Most common symptoms are ocular discomfort, visual disturbance, photophobia, and chronic pain. The general hypothesis, as for many other idiopathic diseases, is that a genetically determined altered immune-based inflammatory response to an insult or a risk factor could initiate the disease, as inflammation is present in virtually all DED types in which it has been searched for. The evidence that inflammation is the pathway used to cause damage in this disease is already unquestionable, but the primary alteration that initiates DED still remains elusive. DED is one of the most common eye disorders for which adult population seeks eye care and its prevalence and incidence varies depending on the criteria used for its diagnosis and the type of DED considered. Thus, reported prevalence ranges from 3.9% in US men to 33.7% in elderly Asians, both men and women. In general, it more often affects women and the elderly population. Its prevalence is on the

Severity, therapeutic, and activity tear biomarkers in dry eye disease: An analysis from a phase III clinical trial

PURPOSE To evaluate the effect of 0.1%-fluorometholone (FML) on tear inflammatory molecule levels after 22-days treatment in dry eye disease (DED) patients exposed to an adverse controlled environment (ACE), identifying different biomarkers. METHODS Analysis of a double-masked randomized clinical trial. Forty-one DED patients received 4-drops daily of topical FML (FML-group) or polyvinyl-alcohol (PA-group) for 22 days. At day 21, patients were exposed to an ACE. Tear samples were collected at V1 (baseline), V2 (pre-ACE), V3 (post-2-h-ACE) and V4 (24-h post-ACE). Concentrations of 18 molecules (EGF, IFN-γ, TNF-α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8/CXCL8, IL-10, IL-12, IL-13, IL-17A, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, RANTES/CCL5 and MMP-9) were analyzed. Similarities among patients in molecule concentrations at V1 were evaluated. A linear-mixed effect model analyzed the influence of different variables on concentrations changes. RESULTS Multidimensional scaling (MDS) divided patients into two groups based on differences in EGF, IFN-γ, IL-8/CXCL8, RANTES/CCL5, and MMP-9 levels at V1. Groups had different clinical severities based on Schirmer test and conjunctival and corneal staining. IL-1RA, IL-2, and TNF-α were differentially affected by time, depending on treatment. Between V2-V3, there were significant changes in EGF, IL-1RA, IL-2, IL-8/CXCL8, IL-13, IP-10/CXCL10, TNF-α, and MMP-9. The strongest biomarker candidates were IFN-γ, RANTES/CCL5, and MMP-9 as DED severity biomarkers; IL-2 as DED therapeutic biomarker; and EGF as DED activity biomarker. CONCLUSIONS This clinical trial design using a controlled environment and the identified tear biomarkers could be useful to objectively select target patients, to define stress response, and to evaluate therapeutic endpoints in clinical trials.

Safety and Efficacy of an Artificial Tear Containing 0.3% Hyaluronic Acid in the Management of Moderate-to-Severe Dry Eye Disease.

Purpose: To evaluate the safety and efficacy of a new 0.3% hyaluronic acid artificial tear compared with 0.9% saline solution (0.9% NaCl) in moderate-to-severe dry eye patients after 1 months use. Methods: A total of 16 patients with moderate-to-severe dry eye were included in this crossover study. After a 1-week washout period, patients used the experimental (Visaid 0.3%) or control solution (0.9% NaCl), selected randomly, applying three to eight drops daily for a month. After another washout period, patients used the other solution in the same way. Percentage of change (&Dgr;Y) was calculated and analyzed for (1) safety variables: visual acuity, intraocular pressure, and ophthalmoscopy evaluation; (2) efficacy variable: Ocular Surface Disease Index (OSDI) questionnaire; and (3) secondary variables: biomicroscopy findings, fluorescein corneal staining, lissamine green conjunctival staining, tear breakup time (TBUT), contrast sensitivity, Schirmer test, and subject satisfaction. Results: There were no significant differences in the safety parameters for either solution. After using Visaid 0.3%, patients showed significant improvements in OSDI score (&Dgr;Y: −9.66%±10.90), tarsal hyperemia (&Dgr;Y: −16.67%±27.89), corneal staining extension (&Dgr;Y: −34.90%±42.41), TBUT (&Dgr;Y: 13.98%±26.19), and subjective satisfaction (&Dgr;Y: 38.06%±47.06). When using 0.9% NaCl, Schirmer test results were significantly worse (&Dgr;Y: −11.47%±19.27). A significant difference between the 2 solutions was found in TBUT (&Dgr;Y: 13.98%±26.19 vs. 10.15%±42.34, respectively; P=0.0214). Conclusion: Visaid 0.3% is a safe product with some benefits over 0.9% NaCl in reducing ocular symptoms and improving some ocular signs in patients with moderate-to-severe dry eye.

Lack of Agreement among Electrical Impedance and Freezing-Point Osmometers.

Purpose To assess the interchangeability of tear osmolarity measurements between electrical impedance and freezing-point depression osmometers and to analyze inter-eye tear osmolarity variability measured with these osmometers in healthy subjects. Methods Tear osmolarity was measured using the TearLab osmometer (OcuSense Inc., San Diego, CA) and the Fiske 210 microsample osmometer (Advanced Instruments Inc., Norwood, MA). We randomly selected one eye in 50 subjects (29 women, 21 men; mean age, 33.16 ± 6.11 years) to analyze whether osmolarity measurements by these osmometers were interchangeable. Both eyes of 25 patients (15 women, 10 men; mean age, 34.32 ± 6.37 years) were included to analyze inter-eye osmolarity variability. Results The mean tear osmolarity values measured with the TearLab osmometer were higher (305.22 ± 16.06 mOsm/L) than those with the Fiske 210 osmometer (293.40 ± 12.22 mOsm/L), with the intraclass correlation coefficient being 0.23 (p = 0.051). A Bland-Altman plot showed that the systems were not interchangeable because there was a systematic difference, with the limits of agreement being −17.93 to 41.57 mOsm/L. There were no statistically significant differences (p = 0.5006 and p = 0.6533, respectively) between an individual’s eyes measured with either osmometer. Conclusions Because the TearLab tear osmolarity measurements were higher than those of the Fiske 210 measurements and the limits of agreement were too wide, the two osmolarity values cannot be used interchangeably. In healthy subjects, there is no difference in tear osmolarity between right and left eyes of the same individual measured with both instruments.

Effect of the osmolarity change in multipurpose solutions induced by an improper contact lens case cleaning procedure

PURPOSE To determine whether variations in multipurpose disinfecting solution (MPDS) storage osmolarity from inappropriate contact lens (CL) case cleaning affect ocular surface integrity and wearer comfort. METHODS There were twenty contact lens cases (study CLCs) in the study group. Ten were filled with ReNu Multiplus(®) and 10 with SoloCare Aqua™ (MPDS-1 and -2, respectively) and kept closed for 8h; the cases were then emptied and kept open for air-drying for 16h. This procedure was carried out every day for two months. Storage solution osmolarity was measured on days 0, 15, 30, 45 and 60. Ten subjects were then fitted with both month-old lenses stored in the study CLCs and with new lenses stored in new cases with fresh solution for 24h (control CLCs). Symptoms, tear osmolarity and percentage of subjects whose conjunctival hyperaemia and ocular surface staining scores changed were determined after 1h of wear. RESULTS Study CLC osmolarity increased in both solutions after two months (p<0.05). For MPDS-1 there were differences in stinging between study CLCs and control CLCs after 10min of CL wear (p=0.04), and in comfort after 10 (p=0.035) and 60min wear (p=0.042). Significant (p<0.05) differences between study CLC and control CLC groups were also found for MPDS-2 in limbal hyperaemia (study: 50% change; control: 0% change) and bulbar and corneal staining (study: 80% change; control: 20% change). CONCLUSION The stored-MPDS osmolarity increase caused by air-drying the CLCs could affect the ocular surface. This increase might reduce lens wear comfort.

Evaluation of safety and efficacy of a new multipurpose disinfecting solution on silicone hydrogel contact lenses

PURPOSE To evaluate the safety and efficacy of a new multipurpose disinfecting solution (MPDS) with a formulation that includes aloe vera on its composition. METHODS This is a prospective, randomized, double-masked clinical trial with a crossover design that included seven examinations. Two different MPDSs, Avizor Alvera® (study solution) and All Clean Soft® (control solution), each were used for 1 month. Comfilcon A silicone hydrogel contact lenses were used during the trial. The main outcome variables were corneal staining and deposits on the surfaces of the contact lenses. Other parameters including ocular surface response, contact lens wettability, user satisfaction, and adverse events, were analyzed according to the International Organization for Standardization (ISO) 11980:2010 guidance for clinical investigation. RESULTS Twenty subjects (10 women, 10 men) (mean age, 27.7±5.6 years; range, 20-41) were included. No differences between both MPDSs were found in the percentage of subjects with corneal staining >0 at day 30 (study: 35%, control: 50%; p=0.46); neither in the percentage of subjects with deposits on the surface of the contact lens >0 at day 30 (study: 26.32%, control: 52.63%; p=0.18). The study MPDS received higher rates in comfort (study: 8.14±1.09, control: 7.94±0.92; p=0.56) and satisfaction at day 30 (study: 8.63±0.91, control: 8.29±0.80; p=0.19), however the scores were not significantly different with the control MPDS. CONCLUSIONS The clinical trial showed that the study MPDS is safe, efficient, and has acceptable physiologic tolerance, according to the ISO 11980:2010 guidance for clinical investigation.