Ocular surface disease (OSD) refers to a series of alterations of the ocular surface such as dry eye disease (DED), Sjögren's syndrome, meibomian gland dysfunction, or allergic processes.
DED is defined by The Tear Film and Ocular Surface Society Dry Eye Workshop as “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”1
Symptoms of dry eye include discomfort, blurred vision, burning sensation, redness, and photophobia, and it may affect activities of daily living, such as driving, reading, or working on a computer, causing a great negative impact both on physical and psychosomatic well-being and consequently a poorer quality of life.2-4
Data from different studies suggest that the prevalence of dry eye symptoms is within a range of 20% to 50% in the adult population, varying depending on the definition used, diagnostic methods and population studied.5 The prevalence of DED increases with age, and a higher incidence is observed in postmenopausal women.6,7
Due to the higher prevalence of dry eye in women compared to men, sex hormones are known to play an important role in the pathogenesis of this disease.8-10 Classically, plasma estrogen levels were thought to be responsible for the onset of age-related DED, although androgens are now known to play an important role in the ocular surface, exercising a protective function. Thus, low androgen levels are the most consistent hormonal factor in the pathophysiology of DED.11-13
The use of validated questionnaires in the detection of this condition is recommended as an initial dry eye diagnostic test.14 The Ocular Surface Disease Index (OSDI) is one of the most widely used questionnaires. The OSDI assesses the presence of symptoms related to eye dryness and the impact of the condition on visual function and quality of life. It was developed in 1997 by the Outcomes Research Group of Allergan Inc (Irvine, CA).15 The questionnaire consists of 12 questions about activities in the week before completion, providing a rapid assessment of DED symptoms.16
The aim of the study was to ascertain the prevalence of OSD symptoms and the possible existence of differences between peri- and postmenopausal women, based on the result of the OSDI in the population of our Obstetrics and Gynaecology Department at the Hospital Universitario Dexeus (Barcelona, Spain).
MATERIALS AND METHODS
A transversal observational study based on the results of an anonymous survey e-mailed to all women who had had a gynecological consultation in our medical center in the last 3 years. The surveys were completed between October 2018 and January 2019. The study was conducted in a group of 1,947 women aged 45 to 79 years who agreed to participate.
The women were sent an e-mail inviting them to participate in an online survey to assess the prevalence of OSD symptoms in peri- and postmenopausal women. The objective and methods of the study were explained in an understandable manner with a link to the questionnaire. Those who agreed to participate, after clicking on the OSD survey, were directed to a secure online portal.
Finally, once all the answers were available, the results were analyzed according to the total OSDI score. This score was analyzed as both a continuous and a categorical variable. Personal information was collected as explained in the following section.
With the data obtained from the survey, the women were divided into three groups based on total OSDI score: normal eye-mild OSD, moderate OSD, and severe OSD, and they were also classified by their menopausal status.
The study was conducted strictly following the international ethical guidelines for medical research involving human subjects in accordance with the principles of the Declaration of Helsinki.
The study protocol of this research was approved by the Hospital's ethics committee.
The personal data in the questionnaire included age, menopausal status, age at menopause, prediagnosis of dry eye by a specialist, already under dry eye treatment, and the OSDI questionnaire in Spanish. Questions originally written in English were translated into Spanish, and the translation was verified by a back translation from Spanish into English, validated by Beltran et al.17
Menopausal status was defined as perimenopausal (period before menopause up to 12 mo after the last period) and postmenopausal (amenorrhea of 1 y or more before the beginning of the study) using Stages of Reproductive Aging Workshop criteria.18
The OSDI questionnaire consists of 12 questions referring to activities in the week before completion. The questions are divided into three subscales that evaluate ocular irritation symptoms, functional limitations of vision, and dry eye-related environmental factors. The answers to the OSDI questionnaire were graded on a score of 0 to 4, where 0 indicates none of the time, 1 some of the time, 2 half of the time, 3 most of the time, and 4 all of the time. The score is assessed on a scale of 0 to 100, with lower scores representing fewer problems and symptoms. The total OSDI score is calculated on the basis of the following formula: OSDI = [(sum of scores for all questions answered) × 100] / [(total number of questions answered) × 4]. According to the final score, women may be classified into three groups: group 1 (0-20 points, considered normal eye or mild dry eye), group 2 (21-45 points, considered moderate dry eye), and group 3 (46-100 points, considered severe dry eye).19
Mean and standard deviation were used for continuous variable and percentage and number for categorical variables. The women were categorized into two groups: perimenopausal and postmenopausal. Continuous variables were compared between the groups with the Student's t test or Wilcoxon-Mann-Whitney according to normality criteria. The chi-square test or the Fisher exact test was applied to compare categorical variables. The odds ratio (OR), with its respective confidence intervals (95% CI), was calculated for univariate logistic regression to estimate the prevalence of OSD symptoms.
A P value less than 0.05 was considered statistically significant for all comparisons. Statistical analyses were performed with IBM SPSS Statistics v 22 (Armonk, NY) and SAS Institute Inc. 2014. Base SAS 9.4 Procedures Guide (SAS Institute Inc, Cary, NC).
The e-mail with the invitation to participate was sent to 31,140 women between 45 and 79 years old. A participation of 6.3% (1,947/31,140) was obtained, of which all the information was analyzed. All women answered the 12 questions so no missing data.
The mean age of the participating women was 54.2 ± 6.8, with a mean age at menopause of 49.5 ± 4.0. According to their menopausal status, 36.9% (719/1,947) were classified as perimenopausal and 63.1% (1,228/1,947) as postmenopausal.
The mean score of the OSDI questionnaire was 29.2 ± 19.4; in perimenopausal women it was 26.8 ± 18.2 and in postmenopausal women it was 30.6 ± 20.0, with a P value less than 0.001 being statistically significant. In women without a prior diagnosis the mean score of the OSDI questionnaire was 39.5 ± 14.2 and in women with a prior diagnosis was 38.2 ± 21.0, with a P = 0.010 being statistically significant.
The survey identified 57.6% (1,121/1,947) of women with OSD symptoms. The test identified 54.4% (391/719) of perimenopausal women and 59.4% (730/1,228) of postmenopausal women, with a P = 0.029 being statistically significant.
Of the 1,947 women included in the study, 25.7% (500/1,947) had already been diagnosed with dry eye before the OSDI test (18.1% [130/719] perimenopausal vs 30.1% [370/1,228] postmenopausal with a P < 0.001), 71.1% (354/498) of whom were on some kind of treatment for DED (60.5% [78/129] perimenopausal vs 74.8% [276/369] postmenopausal, with a P = 0.002). Both results presented significant differences.
The overall prevalence of OSD symptoms was 64% (1,247/1,947), with a prevalence of 59.4% (427/719) in perimenopausal women and of 66.8% (820/1,228) in postmenopausal women, with a P = 0.001 being statistically significant.
The descriptive and inferential statistics of all the comparisons between the perimenopausal and postmenopausal group are shown in Table 1 and Figure 1.
Moreover, 42.4% (826/1,947) of the women of the sample present total OSDI scores within the classification of normal eye-mild OSD, 39.5% (770/1,947) moderate OSD and 18.1% (351/1,947) severe OSD (Fig. 2).
The probability of OSD symptoms prevalence according to age was estimated by means of a univariate logistic regression, it being observed that that the older the women, the greater the probability of prevalence of OSD symptoms (OR: 1.02; 95% CI: 1.01-1.03). The women's age was analyzed as a categorical variable too. We divided the age into two groups (women ≤55 vs women >55). The prevalence of DED was higher in women older than 55 years (OR: 1.26 [95% CI: 1.04-1.53]).
Finally, a logistic regression analysis was performed estimating the probability of OSD symptoms prevalence according to age at menopause as a quantitative variable, it being observed that the probability of dry eye prevalence decreases at an older menopause age (OR: 0.96; 95% CI: 0.93-0.99) (Table 2).
This study presents the prevalence of OSD symptoms in a sample of peri- and postmenopausal Spanish women evaluated with the OSDI questionnaire.
DED is a multifactorial disease of the eye surface, with a variable clinical presentation that generates multiple symptoms with a great impact on women's quality of life.
Peri- and postmenopausal women experience important hormonal changes, particularly in estrogens and androgens, which play a relevant role in the pathophysiology of DED.20 Sex hormone receptors are present in the ocular surface tissues, being target sites for these hormones.21
The intracrine synthesis of sex steroids in peripheral tissues is the major source of estrogens and androgens in women during pre-, peri-, and postmenopause. This intracrine production declines during aging in parallel with the decreased secretion of dehydroepiandrosterone (DHEA; free and sulfated forms) from the adrenal gland. A series of steroidogenic enzymes in these tissues convert the precursor DHEA ultimately into androgens or estrogens.22-24 In ocular surface tissues, the conversion of steroid precursors, especially DHEA, is performed by the aromatase, steroid sulfatase, and hydroxysteroid dehydrogenases present in these tissues.25 Therefore an androgen deficiency would produce a dysfunction in the lacrimal gland and the meibomian gland, causing aqueous tear deficiency, reduction in lipid production, and development of corneal and conjunctival alterations.12,26-28 Thus the hormonal risk factor for the development of the signs and symptoms of DED is the loss of androgens during aging.9 These facts could justify the high prevalence of OSD symptoms found in our study, both in the group of perimenopausal women and in the group of postmenopausal women.
There are several validated questionnaires for assessing the objective symptoms of dry eye and supporting the diagnosis of OSD. The OSDI test was chosen for this study because not only does it include symptoms but it also considers the ability to carry out activities of daily living and the perception of one's own health. The test consists of fewer and easier-to-answer questions than most questionnaires and can be completed quickly, characteristics that could make it the most convenient option for clinical practice. Another one of this test's qualities is that it has a high sensitivity and specificity to distinguish between normal and sick participants.29,30
In our study, the OSDI score was significantly higher in women without a prior diagnosis of OSD versus women with a prior diagnosis, considering that in this group a high percentage were being treated.
Previous studies of dry eye prevalence showed that the incidence of DED increases with age and that it presents a higher incidence in women.31-33 Our results also clearly showed that the prevalence of OSD symptoms increases significantly with age. In fact, the prevalence of OSD symptoms increases with every year of increased age. Interestingly, our study found that early age at menopause was significantly associated with an increased risk of OSD symptoms. This implies that in women of a similar age, the risk of OSD symptoms increases proportionally for each year after the onset of menopause irrespective of age.
The total OSDI test score provides information about the degree of severity of dry eye symptoms. The mean score of the OSDI questionnaire in our study was 29.20, a value considered to be moderate symptomatology in the OSDI test. This value was higher than the total score recorded by Schiffman et al (OSDI score 21)16 but lower than that of Amparo et al34 (OSDI score 48.9), considering that the mean age of these studies is similar to our study.
On studying the severity of eye dryness symptoms using the OSDI questionnaire, we found a greater tendency to present with severe symptoms of eye dryness in postmenopausal women, with a statistically significant association.
From the clinical perspective, the severity of the symptoms produced by OSD is directly related to the loss of physical well-being and potentially to the loss of psychological well-being, due to the difficulty to performing basic activities of daily living. This can result in a greater probability of depression, anxiety, and a loss of feeling of happiness, causing a great impact on their quality of life, particularly in women, who are disproportionately affected by DED. Moreover, neither should the social and healthcare costs caused by dry eye be overlooked. Therefore, early diagnosis and treatment could significantly improve the quality of life of women and reduce healthcare expenditure.10,35,36 The limitations of this study should be considered. The generalization of our findings is limited, first because of the low participation rate and second because the participants were recruited from a specific province in Spain. Future studies are needed to determine the applicability of our findings to populations in other cities. Another limitation of our study was that the study was based on a self-administered questionnaire and did not provide information on the use of systemic medications that promote dry eye, the possible influence of recent ocular surgery, autoimmune diseases, contact lens wear, or allergic processes.
Sixty-four percent of the peri- and postmenopausal women studied had OSD symptoms. There was a correlation between OSD symptoms and age, postmenopause, and earlier age of menopause, and it was associated with increased prevalence. On the strength of our findings, there is a strong relationship between menopausal status and OSD symptoms progression in women.
Based on our results, there is a high prevalence of OSD in peri- and postmenopausal women.
This study was conducted under the auspices of the Chair in Obstetrics and Gynaecological Research of Hospital Universitario Dexeus, Universidad Autónoma de Barcelona.
1. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf
2. O’Brien PD, Collum LM. Dry eye: diagnosis and current treatment strategies. Curr Allergy Asthma Rep
3. García-Catalán MR, Jerez-Olivera E, Benítez-del-Castillo-Sánchez JM. Dry eye and quality of life. Arch Soc Esp Oftalmol
4. Miljanovic B, Dana R, Sullivan DA, Schaumberg DA. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol
5. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf
6. Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM. Prevalence
of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology
7. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence
of dry eye syndrome among US women. Am J Ophthalmol
8. Truong S, Cole N, Stapleton F, Golebiowski B. Sex hormones and the dry eye. Clin Exp Optom
9. Sullivan DA, Rocha EM, Aragona P, et al. TFOS DEWS II sex, gender, and hormones report. Ocul Surf
10. Matossian C, McDonald M, Donaldson KE, Nichols KK, MacIver S, Gupta PK. Dry eye disease: consideration for women's health. J Womens Health (Larchmt)
11. Versura P, Giannaccare G, Campos EC. Sex-steroid imbalance in females and dry eye. Curr Eye Res
12. Sullivan DA, Sullivan BD, Evans JE, et al. Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye. Ann N Y Acad Sci
13. Sriprasert I, Warren DW, Mircheff AK, Stanczyk FZ. Dry eye in postmenopausal women: a hormonal disorder. Menopause
14. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II diagnostic methodology report. Ocul Surf
15. Walt JG, Rowe MM, Stern KL. Evaluating the functional impact of dry eye: the Ocular Surface Disease Index
. Drug Inf J
16. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index
. Arch Ophthalmol
17. Beltran F, Ramos Betancourt N, Martinez J, et al. Mexican Ocular Surface Disease
Study Group. Transcultural Validation of Ocular Surface Disease Index
(OSDI) Questionnaire for Mexican Population. Invest Ophthalmol Vis Sci
18. Harlow SD, Gass M, Hall JE, et al. STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Menopause
19. Özcura F, Aydin S, Helvaci MR. Ocular surface disease index
for the diagnosis of dry eye syndrome. Ocul Immunol Inflamm
20. Peck T, Olsakovsky L, Aggarwal S. Dry eye syndrome in menopause and perimenopausal age group. J Midlife Health
21. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand
22. Luu-The V, Labrie F. The intracrine sex steroid biosynthesis pathways. Prog Brain Res
23. Gibson EJ, Stapleton F, Wolffsohn JS, Golebiowski B. Local synthesis of sex hormones: are there consequences for the ocular surface and dry eye? Br J Ophthalmol
24. Sahu P, Gidwani B, Dhongade HJ. Pharmacological activities of dehydroepiandrosterone: a review. Steroids
25. Schirra F, Suzuki T, Dickinson DP, Townsend DJ, Gipson IK, Sullivan DA. Identification of steroidogenic enzyme mRNAs in the human lacrimal gland, meibomian gland, cornea, and conjunctiva. Cornea
26. Sullivan DA, Sullivan BD, Ullman MD, et al. Androgen influence on the meibomian gland. Invest Ophthalmol Vis Sci
27. Krenzer KL, Dana MR, Ullman MD, et al. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab
28. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci
29. Nichols KK, Smith JA. Association of clinical diagnostic tests and dry eye surveys: the NEI-VFQ-25 and the OSDI. Adv Exp Med Biol
30. Grubbs JR Jr, Tolleson-Rinehart S, Huynh K, Davis RM. A review of quality of life measures in dry eye questionnaires. Cornea
31. Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older population. Optom Vis Sci
32. Uchino M, Nishiwaki Y, Michikawa T, et al. Prevalence
and risk factors of dry eye disease in Japan: Koumi study. Ophthalmology
33. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence
of diagnosed dry eye disease in the United States among adults aged 18 years and older. Am J Ophthalmol
34. Amparo F, Schaumberg DA, Reza Dana R. Comparison of two questionnaires for dry eye symptom assessment: the ocular surface disease index
and the symptom assessment in dry eye. Ophthalmology
35. Kawashima M, Uchino M, Yokoi N, et al. Associations between subjective happiness and dry eye disease: a new perspective from the Osaka study. PLoS One
36. McDonald M, Patel DA, Keith MS, Snedecor SJ. Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review. Ocul Surf