Kirk Bateman (Director, Biostatistics at SDC) presented the poster "A mixed model, repeated measure analysis of demographics and dry eye signs and symptoms in a dry eye population" at the Association for Research in Vision and Ophthalmology (ARVO) 2015 Annual Meeting in Denver, CO on May 6, 2015.

1. Kirk Bateman1, George W. Ousler2, Michael Watson2 , Keith J. Lane2, and Donna L. Welch2
1Statistics and Data Corporation, Tempe, AZ, USA 2Ora, Inc., Andover, MA, USA
A Mixed Model, Repeat Measure Analysis of Demographics and Dry Eye Signs and Symptom
in a Dry Eye Population
PURPOSE
A multitude of risk factors influences the likelihood of developing dry eye signs and
symptoms. A multivariate analysis was used to determine the association between
demographic characteristics of age, gender, and duration of disease with the severity of dry
eye signs and symptoms in a large population of dry eye clinical trial participants. The role
of demographics may be important when designing dry eye clinical trials.
METHODS
Subjects who had successfully completed at least one dry eye study were included in the
analysis (N = 1343). A mixed-model, repeat-measure analysis was performed to assess the
association of age, gender, and duration of disease with the severity of dry eye signs, as
measured by clinician-graded baseline corneal fluorescein staining before and after a
Controlled Adverse Environment (CAE) challenge, and with dry eye symptoms, as measured
by subject diary-reported ocular discomfort and dryness scored during a placebo run-in
period.
Figure 2. Increased duration of disease was associated with a worsening of both signs
and symptoms of dry eye.
Figure 1. Increased age is associated with a worsening of signs, as measured by
an increase in fluorescein staining.
Table 1. Significance of demographic factors and interactions: dry eye symptoms
RESULTS
The demographic criteria evaluated (age, gender, duration of disease) significantly affected
dry eye sign and symptom severity (p < 0.05). Increased age was associated with a
worsening of signs (inferior, superior, and central fluorescein staining). Increased duration
of disease was associated with a worsening of both signs and symptoms of dry eye. Female
gender was associated with a worsening of both clinical signs and a worsening of
symptoms. There was a significant interaction between gender and duration of dry eye
disease, with symptoms worsening with duration of disease among females.
CONCLUSIONS
The results of this study demonstrate clear associations between the demographic
characteristics of age, gender, and duration of disease, and the severity of dry eye signs and
symptoms. The findings of worsening of signs in older patients and with longer duration of
disease are consistent with the literature. Increased severity of dry eye signs and symptoms
in females is also consistent with previous findings. All three demographic criteria should be
carefully considered in clinical trial design.
Table 2. Significance of demographic factors and interactions: dry eye signs
Where there was statistical significance, staining was greater among females and increased as age and duration of disease
increase. †Change in staining increased as duration of disease increased, and decreased slightly as age increased.
†Symptoms increased with duration of disease in females, and remained constant as duration of disease increased in males.
4484-A0110
Staining Region/Time Point Demographic Effect P-value Interactions
Inferior / Pre-CAE
Sex 0.0056
No significant
interactions
Age < 0.0001
Duration of disease 0.0326
Inferior / Post-CAE
Sex 0.0030
No significant
interactionsAge < 0.0001
Duration of disease < 0.0001
Inferior / Change
(Post-Pre) CAE
Sex 0.3632
Age*Duration
(p=0.0161)†Age 0.4045
Duration of disease 0.0110
Superior / Pre-CAE
Sex 0.4163
No significant
interactionsAge 0.7539
Duration of disease < 0.0001
Superior / Post-CAE
Sex 0.3066
No significant
interactionsAge 0.0017
Duration of disease 0.0004
Superior / Change
(Post-Pre) CAE
Sex 0.0007
No significant
interactionsAge < 0.0001
Duration of disease 0.5214
Central / Pre-CAE
Sex < 0.0001
No significant
interactionsAge < 0.0001
Duration of disease 0.0265
Central / Post-CAE
Sex < 0.0001
No significant
interactionsAge < 0.0001
Duration of disease 0.1718
Central / Change
(Post-Pre) CAE
Sex 0.6214
No significant
interactionsAge 0.0039
Duration of disease 0.2185
Symptom Demographic Effect p-value Interactions
Run-in dryness Sex 0.0592 Sex*Duration
(p=0.0149)†
Age 0.0877
Duration of disease 0.0002
Run-in Ocular
Discomfort
Sex 0.1290 Sex*Duration
(p=0.0022)†
Age 0.1975
Duration of disease 0.0117