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ARCH SOC ESP OFTALMOL. 2010;85(2):70-75
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ESPAÑOLA DE OFTALMOLOGÍA
www.elsevier.es/oftalmologia
Original article
Analysis of incidence of ocular surface disease index
with objective tests and treatment for dry eye
L. A. Rodríguez-Torres*, D. J. Porras-Machado, A. E. Villegas-Guzmán
and J. A. Molina-Zambrano
La Trinidad Teaching Medical Center, Ophthalmology Dept., Cornea Clinic, Caracas, Venezuela
A RT I C L E I N F O R M AT I O N
A B S T R A C T
Article history:
Objective: To correlate ocular surface disease index (OSDI) with objective tests on patients
Received on July 21, 2008
with dry eye on first consultation and evaluate the efficiency of topical medication
Accepted on Feb. 8, 2010
administered depending on severity of symptoms reported by patients who were evaluated
at 3 months.
Keywords:
Materials and methods: We studied a sample of 144 patients with dry eye who were evaluated
Dry eye
with OSDI and basic diagnostic tests at first consultation: Height of lacrimal meniscus,
Ocular surface disease index
Schirmer II test (with anesthetic), Break-up time test (BUT), and lissamine green staining.
Lissamine green
The sample was divided into four groups depending on clinical severity, taking into
account results of OSDI questionnaire. Treatment was determined for each group taking
into account lubricant viscosity properties: OSDI (mild) = carboxymethylcelullose, OSDI
(moderate) = hidroxypropylmethylcelullose, OSDI (severe) = polyethyleneglycol and OSDI
(very severe) = polyethyleneglycol + cyclosporine A 0.05%. Final OSDI was established for
56 patients who were assessed at 3 months.
Results: Results of objective tests at first consult showed a correlation between the severity
of symptoms and the grade of lissamine green staining (p=0.0421). We found significant
improvement in OSDI values after topical treatment was administered in all groups of
patients (p=0.0066) at three months post treatment.
Conclusions: Conjuntival lissamine green staining is a useful guideline that could be
routinely used to confirm diagnosis in subjective evaluations and patient follow-up.
Patients with dry eye show a decrease in OSDI after being treated with the appropriate
medication prescribed for each particular group, depending on severity.
© 2010 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.
All rights reserved.
*Author for correspondence.
E-mail: [email protected] (L. A. Rodríguez Torres).
0365-6691/$ - see front matter © 2010 Sociedad Española de Oftalmología. Published by Elsevier España, S.L. All rights reserved.
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ARCH SOC ESP OFTALMOL. 2010;85(2):70-75
Relación de índice de enfermedad de la superficie ocular con pruebas
objetivas y tratamiento del ojo seco
R E S U M E N
Palabras clave:
Objetivo: Correlacionar el índice de enfermedad de la superficie ocular (IESO) con las prue-
Ojo seco
bas objetivas de pacientes con ojo seco en la consulta inicial y evaluar la eficacia de la
Índice de enfermedad de la
medicación tópica administrada en relación con la severidad de la sintomatología referida
superficie ocular
en los pacientes que acudieron a control a los 3 meses.
Verde de lisamina
Materiales y métodos: Elegimos una muestra de 144 pacientes con ojo seco a quienes se
aplicó el IESO en la consulta inicial junto a una valoración frente a las pruebas diagnósticas
clásicas: altura del menisco lagrimal, prueba de Schirmer II (con anestesia), tiempo de
ruptura de la película lagrimal (BUT) y tinción con verde de lisamina. La muestra fue dividida en cuatro grupos de severidad clínica, según la puntuación obtenida en el cuestionario IESO. El tratamiento fue asignado para cada grupo según su severidad y tomando en
cuenta las propiedades de viscosidad del lubricante: IESO L (leve) = carboximetilcelulosa,
IESO M (moderado) = hidroxipropilmetilcelulosa, IESO S (severo) = polietilenglicol e IESO
MS (muy severo) = polietilenglicol + ciclosporina A 0,05%. Se estableció el IESO final a
56 pacientes que acudieron a consulta control a los tres meses de iniciado el tratamiento.
Resultados: En cuanto a las pruebas objetivas de la consulta inicial, solo hemos observado
correlación de la severidad de la sintomatología referida con el grado de tinción con verde
de lisamina (p = 0,0421).
Hemos encontrado mejoría significativa en el valor del IESO tras el tratamiento tópico
administrado, para todos los grupos de pacientes (p = 0,0066) que acudieron a control a los
3 meses.
Conclusiones: La tinción conjuntival con verde de lisamina es una medida objetiva útil, que
podría emplearse de rutina para confirmar el diagnóstico realizado en la evaluación subjetiva y como base para el seguimiento del paciente.
Los pacientes con ojo seco presentaron disminución en el IESO después de ser tratados con
la medicación asignada para cada grupo, según el grado de severidad.
© 2010 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.
Todos los derechos reservados.
Introduction
Ocular surface diseases comprise a large group of disorders of
varied etiology, symptoms and clinical findings which damage
and produce inflammation on the ocular surface.1 Dry eye
is the most frequent ocular surface pathology encountered
by the ophthalmologist. This disorder affects between 10%
and 20% of the adult population.2,3 Dry eye is caused by a
heterogeneous group of diseases which share a functional tear
deficit due to reduced production or excessive evaporation,
associated to ocular discomfort symptoms4 which could limit
the day-to-day activities of affected patients.5 The dry eye
prevalence increases in patients with auto-immune diseases,
post-menopause women6 and contact lens users.7 The clinical
diagnostic is variable depending on the degree of involvement
of the ocular surface, and is typically confirmed by tests such
as Schirmer’s test, lacrimal film break up time (BUT) and
conjunctival staining.8 Although the ophthalmologist has
several therapeutic options available for treating this pathology,
such as lacrimal point stops,9 topical steroids,10 topical
cyclosporine,11 autologous solution,12 systemic doxicyclin or
tetracyclin,4 the basis of the treatment continues to be lacrimal
substitutes. These vary in chemical composition, presence of
preservatives, concentrations and time of permanence on
the ocular surface, which depends mainly on the adhesion
capacity and viscosity of the substance.13 We have observed
that the dry eye condition can exist without evidence of
damages on the ocular surface and that the primary goal of
the treatment should be the improvement of symptoms. In
this paper we applied the ocular surface disease index (OSDI)
to determine the severity of the dry eye disease and chose a
medical treatment according to the OSDI classification, taking
into account the viscosity properties of the artificial tear and
the presence of inflammation in the ocular surface.
Material and methods
An experimental, prospective and longitudinal clinical study,
with random sampling, in the period comprised between
January - June 2008. In this period, we selected 144 patients over
25 with dry eye symptoms, able and willing to cooperate with
the study and who exhibited ability to reply all the questions
of the OSDI survey, willingness and ability to administer
themselves eye drops and record every administration as well
as to visit the control practice three months after beginning the
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treatment. Patients under 25 who exhibited mental disability
of were pregnant were excluded from the study, as well as
those who had previous refractive surgery, poor nasolacrimal
drainage, previous use of topical ophthalmological drops,
uncorrected refraction defects or known hypersensitivity to
any of the ingredients of the medication in the study. The study
protocol was reviewed and approved by an institutional review
panel (Bioethics Committee of La Trinidad Teaching Medical
Centre and two specialist ophthalmologists designated by the
Bioethics Committee). The OSDI is the validated Ocular Surface
Disease Index developed by Schiffman et al14 which comprises
12 questions about ocular irritation symptoms related to dry
eye disease and its impact on visual function. The survey was
individually applied to all the patients by the same researcher
in simple and easily understandable terms so that all the
patients were able to score the intensity of their symptoms
from 0 to 4 as well as the survey questions in each visit. Just
as patient symptom-based surveys have demonstrated their
usefulness to study a disease and as a follow-up tool, objective
tests can be more precise to determine lacrimal production
(Schirmer test) and ocular surface alterations (vital stains).15
Before beginning treatment we chose the objective
parameters assessed in the initial visit, i.e., the height of the
lacrimal meniscus, Schirmer’s test 2 (with anesthesia), BUT16,17
and conjunctival stain with lissamine green. The patients
were explored in a softly lit room with a temperature of 25 °C
(77ºF) and a humidity of 40%. Lissamine green staining was
determined according to the Van Bijsterveld scale that divides
the ocular surface in three parts: the internal and external
conjunctival trigons and the middle portion that comprises
the entire length of the cornea. Staining was assessed in
each of said parts with values ranging from 0 to 3, so that the
lowest score for each eye is 0 and the highest is 9.18 In order to
obtain the staining degree of the ocular surface, the eye with
the highest value was measured (i.e., grade 0: without stain,
grade 1: score 1-3; grade 2: score 4-6 and grade 3: score 7-9).
For selecting the treatment, the study population was divided
in 4 clinical severity groups on the basis of the score obtained
in the initial OSDI (table 1), after three years of experience in
the Cornea Clinic of the Trinidad Teaching Medical Centre.19
The OSDI L group was made up by patients with mild dry eye
symptoms who were treated with carboxymethylcellulose
(Refresh Tears®, Allergan). The OSDI M group comprised
patients with moderate dry eye symptoms, who were treated
Table 1 – Ocular surface disease severity levels
according to OSDI scores
Group
OSDI Mi
OSDI M
OSDI S
OSDI VS
OSDI Score
0-0.25
0.26-0.50
0.51-0.75
0.76-1.00
with hydroxypropylmethylcellulose (GenTeal®, Novartis).
The OSDI S group was made up by patients with severe dry
eye symptoms, treated with polyethylene glycol (Systane®,
Alcon). The OSDI MS group comprised patients with very
severe dry eye symptoms and ocular surface inflammation,
treated with polyethylene glycol and cyclosporine A 0.05%
(Restasis®, Allergan). The lubricant dosage administered was
of 4 drops distributed throughout the day in both eyes during
3 months. In the case of cyclosporine A 0.05%, the dosage
was of 1 drop every twelve hours in both eyes. Three months
after initiating treatment, the final OSDI was applied to the
patients who turned up for the control visit. The sample
was also distributed in 20 groups according to the etiological
classification of Madrid.20
The quantitative variables (OSDI, lacrimal meniscus height,
Schirmer II test, BUT, lissamine green staining) were expressed
as mean and standard deviation (SD). To assess the changes in
OSDI after treatment, the t for Student test was used for paired
data. To determine the correlation between the objective tests
and the OSDI, Spearman’s correlation analysis was applied.
Any p value under or equal to 0.05 was taken as statistically
significant. The analysis was made with the Graph Pad Prism®
version 4 statistical package.
Results
In all the 144 patients, the gender distribution was of 36 males
(25%) and 108 females (75%). The mean age was of 45.61±16.26
years with a range of 26-72 years. Table 2 shows the total
number of patients studied as distributed in the various
groups. The global results referring to clinical disease severity
criteria in the initial assessment show that the majority of
patients were in the OSDI M group, followed by the OSDI L,
OSDI S and OSDI MS groups.
On the basis of etiological criteria, it was observed that
the majority of patients were in the hormonal, inflammatory
and immunopathic dry eye group and the other groups, i.e.,
infections, neurodeprivative, traumatic, pharmacological,
etharian and tantalic (table 3) had progressively less patients.
In relation to the objective tests, Table 4 shows the mean values
obtained from the height of the lacrimal meniscus, Schirmer
II test and BUT. Table 5 shows the specific proportions per
lissamine green staining degree as per the Van Bijsterveld
Table 2 – Distribution of patients per ocular surface
disease severity at the initial assessment (n=144)
Severity
leve
mild
moderate
severe
very severe
OSDI: ocular surface disease index; Mi: mild; M: moderate; S: severe;
VS: very severe.
Severity
level
Percentage
CI 95%
Mild
Moderate
Severe
Very severe
36.11%
41.67%
19.44%
2.78%
20.42-51.80
25.56-57.77
6.51-32.37
0,00-8,14
CI 95%: 95% confidence interval.
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1.0
Table 3 – Distribution of patients per etiology (n=144)
0.9
0.8
Percentage
CI 95%
22.22%
8.33%
30.56%
5.56%
5.56%
8.33%
5.56%
11.11%
2.78%
8.64-35.80
0.00-17.36
15.51-45.60
0.00-13.04
0.00-13.04
0.00-17.36
0.00-13.04
0.84-21.38
0.00-8.15
Inflammatory
Neurodeprivative
Hormonal
Pharmacological
Traumatic
Infectious
Age
Immunopathic
Tantalic
CI 95%: 95% confidence interval.
Table 4 – Mean values (standard deviations) before
applying treatment (n=144)
Lacrimal meniscus (mm)
Schirmer test II (mm)
BUT (sec)
Average ± SD
CI 95%
0.48 ± 1.16
6.84 ± 3.40
5.18 ± 2.86
0.07-0.89
5.63-8.04
4.16-6.19
BUT: lacrimal tear time; SD: standard deviation; CI 95%: 95%
confidence interval; mm: millimeters; sec: seconds.
Table 5 – Distribution of patients in the study per stain
rate with lissamine green (n=144)
Staining rates with
lissamine green
Without stain
Grade I
Grade II
Grade III
CI 95%: 95% confidence interval.
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
I
II
Lissamine green
III
Figure 1 - Correlation between lissamine green stain level
and ocular surface disease index (OSDI) (n=144).
scale. In what concerns clinical disease severity criteria, only
lissamine green staining exhibited statistical significance
(p=0.0421), which indicates that with a higher OSDI result the
degree of staining was higher (fig. 1). No statistically significant
correlations were found in the height of the lacrimal meniscus
(p=0.2258), Schirmer II test (p=0.4516) or with BUT (p=0.1076)
with the OSDI values. Of the initial 144 patients, only a subgroup of the sample, comprising 56 patients, turned up for
the control visit after three months. The gender distribution
was of 16 men (28.57%) and 40 women (71.43%). The mean age
was of 49.29±15.50 years with a range of 23-69 years. Table 6
shows the distribution of the 56 patients who completed the
follow-up in the various severity groups, while Table 7 shows
the distribution of patients per etiology criteria. In order to
validate the treatment efficiency, the initial and final OSDI
Objective tests
0.7
OSDI
Etiology group
Percentage
CI 95%
33.33%
30.30%
24.24%
12.12%
22.65-44.00
20.06-40.53
14.98-33.49
5.43-18.80
values were compared (fig. 2), finding a statistically significant
improvement in the index variations for the different clinical
severity groups treated as per the lubricant viscosity rating
(p<0.0001).
Discussion
The ocular surface disease diagnostic begins with the patient
history and the large variety of symptoms related to the
disease.21 Various instruments have been developed for
collecting data. We chose the OSDI questionnaire because
it is a valid and reliable instrument to measure the dry eye
severity and the only one which can evaluate the frequency of
symptoms and their impact on the visual function.14 Clinical
practice has not shown a correlation between the subjective
symptoms and objective findings in assessing the dry eye
patient.22,23 However, regardless of the poor association
between the symptoms and the traditional objective clinical
measures, we have observed that lissamine green conjunctival
staining is closely correlated with the patient’s perception
of the severity of his disease. Considering the large array of
therapeutic lacrimal substitutes for dry eye management, we
established clinical parameters for selecting the treatment on
the basis of the degree of involvement of the ocular surface
disease determined by the measurement of the subjective
symptoms. One of the most important properties of lubricants
is their viscosity, which allows an even distribution and
increases its permanence time on the ocular surface, thus
providing a longer-lasting effect.13 However, even considering
these advantages, it has been observed that many high viscosity
products are poorly tolerated by patients due to discomfort
and damage caused to the ocular epithelium derived from
increased stress during blinking.24 The lacrimal substitutes we
chose as therapeutic alternatives for dry eye management are
carboxymethylcellulose, hydroxipropylmethylcellulose and
polyethylene glycol, which exhibit low, intermediate and high
viscosity, respectively. With higher severity level as determined
by the subjective assessment, the higher was the viscosity
of the lacrimal substitutes administered. We found that the
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Table 6 – Distribution of patients per ocular surface disease severity level at initial and final assessment (n=56)
Severity level
Initial assessment
Mild
Moderate
Severe
Very severe
Final assessment
Percentage
CI 95%
Percentage
CI 95%
42.86%
35.71%
14.29%
7.14%
30.41-55.29%
24.29-47.13%
6.95-21.61%
1.93-12.35%
85.71%
14.29%
0.00%
0.00%
68.69-100
6.95-21.61
0.00-0.00
0.00-0.00
CI 95%: 95% confidence interval.
Table 7 – Distribution de patients per etiology (n=56)
Etiological group
Inflammatory
Neurodeprivative
Hormonal
Pharmacological
Traumatic
Infectious
Etharian
Immunopathic
Tantalic
Percentage
CI 95%
14.29%
0%
35.71%
7.14%
7.14%
7.14%
14.29%
14.29%
0%
6.95-21.61
0.00-0.00
24.29-47.13
1.93-12.35
1.93-12.35
1.93-12.35
6.95-21.61
6.95-21.61
0.00-0.00
CI 95%: confidence interval al 95%.
OSDI
treatment allocated to each group was efficient for improving
dry eye symptoms, as demonstrated when reducing the OSDI
in the follow-up visit for the moderate, severe and very severe
dry eye groups. Even though the mild dry eye did not exhibit
improvements, it remained with mild symptoms during the
three follow-up months and did not worsen in any patient.
On the other hand, the patients referred good treatment
tolerance and none exhibited side effects with the medication
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
of the study. We selected the lacrimal substitute treatment
taking into account viscosity and, in the presence of ocular
surface inflammation in the very severe group, we associated
cyclosporine A to the lubricant due to its immunomodulating
properties.25 However, 0.05% cyclosporine A, as well as topical
steroids, can be utilized in any type of dry eye syndrome with
inflammatory component, regardless of its etiology.
The study limitations include: a) the natural selection of
38.88% of patients who completed the study (56 out of the
initial 144), a small heterogenous group with a large ethareous
range, and b) it is difficult to draw conclusions from the very
severe group, made up by only 4 patients. On the basis of the
results obtained in our study, we support the current tendency
to emphasize the importance of measuring subjective
symptoms and performing diagnostic tests as a supplement
to the questions asked of the patient. In addition, we propose
that patients should benefit from the use of progressively
higher viscosity lubricants in correspondingly higher severity
of the symptoms they refer.
Conflict of interests
The authors state that they do not have any conflict of
interests.
R E F E R E N C E S
Initial
Moment
Final
Slight (n=24)
Moderate (n=20)
Severe (n=8)
Very severe (n=4)
Figure 2 - Variation of ocular surface disease index (OSDI)
per ocular surface disease level (n=56).
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