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The Clinical Use of Viscoelastic Artificial Tears and Sodium Chloride in Dry-Eye Syndrome
The Clinical Use of Viscoelastic Artificial Tears and Sodium Chloride in Dry-Eye Syndrome
Abstract
This study was performed to test viscoelastic artificial tears (VAT) based on both subjective and clinical parameters in patients
with keratoconjunctivitis sicca (KCS). Twenty-eight patients were evaluated in a randomized double-blind study. Sodium
hyaluronate was used in two different concentrations (0.4%, 0.25%) and in combination with chondroitin sulfate. Each preparation
was used for one week preceded by another weekly cycle using a sodium chloride solution. Before and after each cycle, clinical
examinations were performed: tear film break-up time, Schirmer’s test, lipid-layer thickness and fluorescein staining. Patients kept a
record of the drop-frequency, subjective response and side effects. After the study, they were asked to give a rating of the various
preparations. The severity of KCS was expressed based on a sicca score and correlated with response to viscoelastic treatment. Both
the subjective and the clinical parameters revealed no statistically significant differences between the various viscoelastic agents or
between the viscoelastics and the sodium chloride solutions. Severe side effects did not occur. There was a positive correlation
of response to viscoelastic treatment with severe KCS (+0.36) but not with mild KCS (0.07). The VAT seems to be indicated
in severe cases of dry-eye syndrome. Sodium chloride solutions may be a useful short-term alternative to other tear formulations.
r 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Dry-eye syndrome; Viscoelastic artificial tears; Sodium chloride; Sicca score
0142-9612/01/$ - see front matter r 2001 Elsevier Science Ltd. All rights reserved.
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3306 J. Nepp et al. / Biomaterials 22 (2001) 3305–3310
The bottles were labeled as A, C, E for NaCl, B for Treatment was discontinued in patients who lacked
Viscoat, D for Hyalodrop and F for Healon, masked by compliance, if the efficacy of VAT application was
the same person. inadequate, or if signs and symptoms of substance
Masking was performed across six groups using Latin intolerance occurred. Patients who prematurely termi-
square randomization. The viscoelastic preparations nated the study were replaced by extending the
were used in weeks 2, 4 and 6. Sodium chloride (NaCl) randomization.
solutions were applied in weeks 1, 3 and 5 both to clean Analyzed parameters included tolerability, symptom
the ocular surface before applying the viscoelastics and scores, the patients’ rating of the agents, and the results
as a ‘‘placebo’’ for control purposes. obtained at the clinical examinations. Based on these
The surface tension and angle of contact of the parameters, the various VAT were compared to each
viscoelastics was compared to that of polyvinylpyrroli- other as well as to NaCl.
done. (Table 1) Examinations at study entry included a To analyze whether there was a correlation between
medical history, slit-lamp microscopy of the lid (espe- severity of KCS and response to VAT treatment, we
cially the orifices of meibomian glands) and an analysis calculated a sicca score. This sicca score is based on a
of foam formation and detritus. comprehensive list of sicca variables to which values
Analysis of the tear film included a Schirmer’s test (II, between 0 (no pathology) and 1 (maximum pathology)
modified by Henderson and Brough), break-up time are assigned. The results are then added up and divided
(BUT), lipid interference test (LIT) and fluorescein by the number of variables used. Thus the sicca score
staining of the corneal surface. Normal values were defines the severity of dry-eye syndrome (1=maximum
Schirmer>10 mm/5 min; BUT>10 s; LIT if red lipids severity). The method is described in detail elsewhere [6].
were seen with the palpebral fissure being reduced by The correlation between severity of dry eyes and
>50% [5], negative fluorescein staining, detritus and response to VAT treatment was expressed along the
foam. range of +1 (maximum positive correlation) through 0
These examinations were performed before treatment (absence of correlation) down to 1 (maximum negative
to obtain baseline values and were repeated every week. correlation).
Patients recorded any symptoms they experienced as Response to VAT treatment was expressed based on
well as the frequency of usage and tolerance. Symptom the patients’ rating of the six agents (1=best, 6=worst),
scores were compiled by the patients classifying their summation of the VAT-rating divided by the number of
complaints as 1=none/minimal, 2=mild, 3=moderate, agents used. Thus the maximum response based on the
4=marked and 5=severe. After the study, patients were three viscoelastic formulations was 1+2+3=6/6. In
asked to give a rating of the six agents (1=best; this way a score of 6–10/6 were considered to a good
6=worst). Patients were also asked about dryness, response to VAT treatment. Correlation was again
foreign-body and burning sensations, or any other expressed as +1 (maximum positive correlation)
symptoms they experienced during the study. through 0 (absence of correlation) down to 1 (max-
Patients were included in the study if they had had dry imum negative correlation).
eyes for more than one year. An informed consent was
obtained from all patients. Exclusion criteria were scars, 2.1. Statistics
lid irregularities, blepharitis, lagophthalmus, use of
contact lenses, any concomitant topical therapy, da- The artificial tears were randomized in Latin squares.
cryocystitis, corneal disease or substance intolerance. Measurements were calculated using variant analysis,
Table 1
Osmolarity, contact angel, surface tension, shear rate and adhesiveness, molecular weight of VAT
repeated measurement and t-test (level of significance preparation was ranked with the various categories
po0:05). The correlation between severity of dry eyes (RANKA, RANKB, etc.). Based on viscoelastic pre-
and response to VAT was expressed along the range of parations, symptoms were seen with F–D–B in descend-
+1 (maximum positive correlation) through 0 (absence ing order. Significant differences in sensation and
of correlation) to 1 (maximum negative correlation). tolerance parameters were observed neither between
any of the VAT nor in comparison with NaCl ðp > 0:05Þ:
Although the viscoelastic preparations were applied less
3. Results frequently than the NaCl, an analysis of usage
frequencies based on a generalized linear design with
Twenty-eight (25 women and 3 men) completed the fixed treatment variables (SAS Proc GLM) yielded no
study after six weeks and could be evaluated. Their significant differences ðp > 0:88Þ:
mean age was 56 (29–77) yr. The results for Viscoats are The symptom scores (1=none to 5=severe) showed
given as B, for Hyalodrops as D and for Healons as F. marked differences at baseline (before study entry) and
The results of the patients’ rating of the six agents are after the initial NaCl cycle. Another striking finding was
summarized in Figs. 1 and 2 (mean values: F:3.15, the small p-values for dryness and foreign-body sensa-
D:3.5, B:3.64). The bar charts show us how often each tion obtained with Hyalodrops and Healons. A total
Fig. 2. Clinical observation: mean values of both eyes (Schirmer, break up time of tear film, lipid layer thickness).
3308 J. Nepp et al. / Biomaterials 22 (2001) 3305–3310
Reported paresthetic events included visual impair- ErlangenFBRD). The NaCl solutions were provided by
ment, itching, foreign-body sensations, redness of the the Vienna General Hospital Pharmacy. This study was
conjunctiva, thermal sensations, dryness, psychological financed in part by the Vienna Municipal Research
effects, spasmastics and general discomfort. None of Fund, Croma and ‘‘Amtsforschung’’. Translation was
these events were severe. Out of 258 events, 137 were performed by translation service (M.P) and corrected by
associated with the viscoelastics and 121 were associated native speakers (C.A).
with NaCl. General discomfort topped the list, with 79
events with viscoelastics and 76 with the NaCl. There
was no statistically significant difference between the References
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