Isotonic Glycerol and Sodium Hyaluronate Containing Artificial Tear Decreases Conjunctivochalasis after One and Three Months: A Self-Controlled, Unmasked Study

Abstract

Dry eye complaints are ranked as the most frequent symptoms of patients visiting ophthalmologists. Conjunctivochalasis is a common dry eye disorder, which can cause an unstable tear film and ocular discomfort. The severe conjunctivochalasis characterized by high LId-Parallel COnjunctival Folds (LIPCOF) degree usually requires surgical intervention, where a conservative therapy would be highly desirable. Here we examined the efficacy of a preservative-free, inorganic salt-free unit-dose artificial tear, called Conheal containing isotonic glycerol and 0.015% sodium hyaluronate in a prospective, unmasked, self-controlled study involving 20 patients. The regular use of the glycerol/hyaluronate artificial tear in three months caused a significant improvement in the recorded parameters. Conjunctivochalasis decreased from a mean LIPCOF degree of 2.9 ± 0.4 on both eyes to 1.4 ± 0.6 on the right (median decrease of -2 points, 95% CI from -2.0 to -1.0), and to 1.4 ± 0.7 on the left eye (median decrease of -1 points, 95% CI from -2.0 to -1.0) (p<0.001 for both sides). The tear film breakup time (TFBUT) lengthened from 4.8 ± 1.9 seconds on both eyes to 5.9 ± 2.3 seconds (mean increase of 1.1 seconds, 95% CI from 0.2 to 2.0) and 5.7 ± 1.8 seconds (mean increase of 0.9 seconds, 95% CI from 0.3 to 1.5) on the right and left eyes, respectively (p(right eyes) = 0.020, p(left eyes) = 0.004). The corneal lissamine staining (Oxford Scheme grade) was reduced from 1.3 ± 0.6 on the right and 1.4 ± 0.6 on the left eye significantly (p<0.001) to 0.3 ± 0.4 and 0.2 ± 0.4 on the right and the left eyes. The Ocular Surface Disease Index (OSDI) questionnaire score indicating the subjective complaints of the patients also decreased from a mean value of 36.2 ± 25.3 to 15.6 ± 16.7 (p<0.001). In this study, the artificial tear, Conheal decreased the grade of the conjunctivochalasis significantly after one month of regular use already, from the LIPCOF degree 3, considered as indication of conjunctival surgery, to a LIPCOF degree 2 or lower requiring a conservative therapy. Our results raise the possibility that vision-related quality of life can be significantly improved by conservative therapies even in severe conjunctivochalasis.

Trial registration: Controlled-Trials.com ISRCTN81112701 http://www.isrctn.com/ISRCTN81112701.

Fig 1. CONSORT flowchart of the study.

The figure shows the CONSORT flowchart of the study. The TREND checklist (S1 TREND Checklist) and the protocol of the study (S1 Protocol) can be found as supporting information files.

Fig 2. Degree of the conjunctivochalasis in terms of LIPCOF degrees after 1 and 3 months of artificial tear treatment.

Artificial tear treatment and measurement of LIPCOF degree on 20 patients were performed as described in Methods. The artificial tear investigated caused a significant decrease of LIPCOF degree on both eyes after one month of use that advanced further on the right eye (filled diamonds, solid line) significantly, and showed the same tendency on the left eye (open rectangles, dashed line) after three months of use. Means and their standard errors of the LIPCOF degree are shown. Statistical evaluation was performed using the Wilcoxon Signed Rank Test. One and three asterisks note p<0.05 and p<0.001, respectively.

Fig 3. Tear-film breakup time after 1 and 3 months of artificial tear treatment.

Artificial tear treatment and measurement of TFBUT on 20 patients were performed as described in Methods. Tear-film breakup time (TFBUT) showed a significant elongation after one month of regular use of the artificial tears, the effect did not grow further with the longer treatment both on right and left eyes (shown by filled diamonds/solid line, or open rectangles/dashed line, respectively). Means and their standard deviations of the TFBUT value are shown. Statistical evaluation was performed using the Paired T Test. One and two asterisks note p<0.05 or p<0.01, respectively.

Fig 4. Lissamine staining after 1 and 3 months of artificial tear treatment.

Artificial tear treatment and measurement of lissamine staining (in terms of the Oxford Scheme grade) on 20 patients were performed as described in Methods. Lissamine staining significantly decreased on both eyes (right eyes: filled diamonds/solid line, left eyes: open rectangles/dashed line) after one and three months of treatment with the artificial tear product. Means and their standard errors of the Oxford Scheme grade are shown. Statistical evaluation was performed using the Wilcoxon Signed Rank Test. One, two and three asterisks note p<0.05, p<0.01 and p<0.001, respectively.

Fig 5. Impact of 1 and 3 months of artificial tear treatment on the subjective complaints of patients.

Artificial tear treatment and measurement of OSDI score on 20 patients were performed as described in Methods. The OSDI scores showed a significant decrease at the end of the first month, which decreased further significantly at the end of the third month. Means and their standard errors of the OSDI score are shown. Statistical evaluation was performed using the Wilcoxon Signed Rank Test. One and three asterisks note p<0.05 and p<0.001, respectively.

Fig 6. Comparative analysis of the decrease of conjunctivochalasis in various studies.

The figure shows the decrease of the degree of conjunctivochalasis compared to that measure at the start of the treatment in previous studies using a liposome eye spray (dotted arrows) compared to our results using an isotonic glycerol and 0.015% hyaluronate-containing artificial tear (solid lines). Numbers above the arrows represent the different studies on a time scale of their duration in months. 1: current results, 2: Höh et al. [21], 3: group 1 and 2 of Dausch et al. [20], 4: Khaireddin et al. [22], 5: Lee et al. [23].