The effect of tear supplementation with 0.15% preservative-free zinc-hyaluronate on ocular surface sensations in patients with dry eye

[Purpose]: To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients.[Methods]: Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate.[Results]: After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P 0.05).[Conclusion]: Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.Peer reviewe

The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye.

PURPOSE: To investigate the characteristics of ocular surface sensations and corneal sensitivity during the interblink interval before and after tear supplementation in dry eye patients. METHODS: Twenty subjects (41.88+/-14.37 years) with dry eye symptoms were included in the dry eye group. Fourteen subjects (39.13+/-11.27 years) without any clinical signs and/or symptoms of dry eye were included in the control group. Tear film dynamics was assessed by non-invasive tear film breakup time (NI-BUT) in parallel with continuous recordings of ocular sensations during forced blinking. Corneal sensitivity to selective stimulation of corneal mechano-, cold and chemical receptors was assessed using a gas esthesiometer. All the measurements were made before and 5 min after saline and hydroxypropyl-guar (HP-guar) drops. RESULTS: In dry eye patients the intensity of irritation increased rapidly after the last blink during forced blinking, while in controls there was no alteration in the intensity during the first 10 sec followed by an exponential increase. Irritation scores were significantly higher in dry eye patients throughout the entire interblink interval compared to controls (p0.05). CONCLUSION: Ocular surface irritation responses due to tear film drying are considerably increased in dry eye patients compared to normal subjects. Although tear supplementation improves the protective tear film layer, and thus reduce unpleasant sensory responses, the rapid rise in discomfort is still maintained and might be responsible for the remaining complaints of dry eye patients despite the treatment

Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus.

PURPOSE: To investigate corneal sensitivity to selective mechanical, chemical, and thermal stimulation and to evaluate their relation to dry eye symptoms in patients with keratoconus. METHODS: Corneal sensitivity to mechanical, chemical, and thermal thresholds were determined using a gas esthesiometer in 19 patients with keratoconus (KC group) and in 20 age-matched healthy subjects (control group). Tear film dynamics was assessed by Schirmer I test and by the non-invasive tear film breakup time (NI-BUT). All eyes were examined with a rotating Scheimpflug camera to assess keratoconus severity. RESULTS: KC patients had significatly decreased tear secretion and significantly higher ocular surface disease index (OSDI) scores compared to controls (5.3+/-2.2 vs. 13.2+/-2.0 mm and 26.8+/-15.8 vs. 8.1+/-2.3; p0.05). The mean threshold for selective mechanical (KC: 139.2+/-25.8 vs. control: 109.1+/-24.0 ml/min), chemical (KC: 39.4+/-3.9 vs. control: 35.2+/-1.9%CO2), heat (KC: 0.91+/-0.32 vs. control: 0.54+/-0.26 Delta degrees C) and cold (KC: 1.28+/-0.27 vs. control: 0.98+/-0.25 Delta degrees C) stimulation in the KC patients were significantly higher than in the control subjects (p0.05), whereas in the control subjects both mechanical (r = 0.52, p = 0.02), chemical (r = 0.47, p = 0.04), heat (r = 0.26, p = 0.04) and cold threshold (r = 0.40, p = 0.03) increased with age. In the KC group, neither corneal thickness nor tear flow, NI-BUT or OSDI correlated significantly with mechanical, chemical, heat or cold thresholds (p>0.05 for all variables). CONCLUSIONS: Corneal sensitivity to different types of stimuli is decreased in patients with keratoconus independently of age and disease severity. The reduction of the sensory input from corneal nerves may contribute to the onset of unpleasant sensations in these patients and might lead to the impaired tear film dynamics

Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals

Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; P0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease.This work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER, project SAF2014-54518-C3-1-R (JG, MCA), and in part by SAF2014-54518-C3-2-R (CB), and by the Hungarian Scientific Research Fund – European FP7 Marie Curie Mobility grant Human-MB08A 80372 and OTKA NN106649 (IK, LD).Peer reviewe

Demographic, topographic and tear film characteristics of the control and the keratoconus groups.

<p>Data are mean ± SD values in the control (n = 20) and in the keratoconus groups (n = 19). Note: P: Mann–Whitney U test.</p><p>Demographic, topographic and tear film characteristics of the control and the keratoconus groups.</p

Relationship between age and corneal sensitivity threshold to mechanical (A), chemical (B), heat (C), and cold (D) stimulation in KC patients and in control subjects.

<p>Regression lines (solid: control; dotted: KC) are also plotted (see text for details on R coefficients and P-values).</p

Cumulative distribution of sensation thresholds to selective stimulation of the central cornea in control subjects and keratoconus patients.

<p>(A) air pulses of increasing flow (mechanical stimulation), (B) pulses with increasing CO₂ concentration (chemical stimulation), (C) pulses of air at increasing temperatures (hot thermal stimulation), and (D) pulses of air at decreasing temperatures (cold thermal stimulation), in KC patients (gray line) and controls (black line).</p

Sensation thresholds to selective stimulation of the cornea.

<p>Data are mean ± SD values in the control (n = 20) and in the keratoconus groups (n = 19). Note: P: Mann–Whitney U test.</p><p>Sensation thresholds to selective stimulation of the cornea.</p

Mean irritation scores as a function of time during forced blinking in dry eye and in normal subjects.

<p>(<b>A</b>) Mean values of ocular irritation during the interblink interval in the control and in the dry eye group (*: between-group difference p<0.004) (<b>B</b>) Mean values of ocular irritation scores during the interblink interval after application of saline or HP-guar drops in the control group (*: baseline vs. saline p<0.004; ^#: baseline vs. HP-guar p<0.004) (<b>C</b>) Mean values of ocular irritation scores during the interblink interval after application of saline or HP-guar drops in the dry eye group (*: baseline vs. saline p<0.004; ^#: baseline vs. HP-guar p<0.004) (<b>D</b>) Cumulative distribution of NI-BUT and maximum irritation before and after application of HP-guar from both groups. Note: whisker: pooled variance for 5 sec time frames.</p

Change of irritation scores to selective stimulation of corneal nerves after tear supplementation.

<p>Mean ± SD values of irritation scores to mechanical, chemical and cold stimulation at baseline and after application of saline or HP-guar drops. Note: P compared to baseline, Wilcoxon signed-rank test.</p><p>Change of irritation scores to selective stimulation of corneal nerves after tear supplementation.</p