|Year : 2018 | Volume
| Issue : 1 | Page : 32-36
Associations between dry eye symptoms with tear film stability, volume, and osmolarity in a sample of young adults in Kuala Lumpur
Mohamad Hanif Hajar-Maidin1, Bariah Mohd-Ali2, Asmah Ahmad2, Zainora Mohammed2, Jamaluddin Mohamed3
1 Optometry and Vision Science Program, Faculty of Health Sciences, 50300 Kuala Lumpur; School of Optometry, Faculty of Medicine and Health Sciences, UCSI University, No. 1, Jalan Menara Gading, UCSI Heights, 56000 Kuala Lumpur, Malaysia
2 Optometry and Vision Science Program, Faculty of Health Sciences, 50300 Kuala Lumpur, Malaysia
3 Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia
|Date of Web Publication||4-Sep-2018|
Faculty of Health Science UKM, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur
Context: Dry eyes (DE) are common ocular problems and any abnormalities in tear film are a concern to eye care practitioners. However, the association between DE symptoms with clinical tests is controversial. Aim:This study aims to investigate the associations between DE symptoms with tear film stability, volume, and osmolarity in a sample of young adults living in Kuala Lumpur. Methodology: A total of 107 healthy young adults, 35 males and 72 females participated in this study with a mean age of 23.06 ± 2.63 years. DE symptoms were screened using McMonnies DE questionnaire (MDEQ); tear stability was evaluated using tear break-up time test (TBUT); tear volume was measured using phenol red thread test (PRT); and tear osmolarity was measured with micro osmometer. The MDEQ score classified 36 subjects as having DE and 71 as non-DE (NDE). Results: Mean score for DE was 16.49 ± 1.74 and 7.23 ± 3.09 for NDE. Mean TBUT for DE and NDE was 4.76 ± 1.58 s and 5.69 ± 1.61 s, respectively. Mean PRT was 7.97 ± 5.60 mm for DE and 12.59 ± 5.70 mm for NDE. Mean tear osmolarity for DE and NDE was 322.42 ± 36.94 Osm/L and 286.35 ± 21.31Osm/L accordingly. Analysis using independent t-test showed a significant difference in TBUT and osmolarity between two groups (P < 0.05). Mann–Whitney sum rank test shown that there were significant differences in PRT measurement between two group (P = 0.00). Significant correlations were noted between MDEQ score with tear osmolarity (r = 0.42, n = 107, P = 0.00), PRT (r = −0.36, n = 107, P = 0.00) and TBUT (r = −0.28, n = 107, P = 0.00). Conclusion: This study demonstrated that significant associations between DE symptoms with TBUT, PRT, and tear osmolarity. MDEQ should be considered by eye care practitioners to confirm the diagnosis of dry eye.
Keywords: Tear break-up time, tear film, tear osmolarity, tear volume
|How to cite this article:|
Hajar-Maidin MH, Mohd-Ali B, Ahmad A, Mohammed Z, Mohamed J. Associations between dry eye symptoms with tear film stability, volume, and osmolarity in a sample of young adults in Kuala Lumpur. Sudanese J Ophthalmol 2018;10:32-6
|How to cite this URL:|
Hajar-Maidin MH, Mohd-Ali B, Ahmad A, Mohammed Z, Mohamed J. Associations between dry eye symptoms with tear film stability, volume, and osmolarity in a sample of young adults in Kuala Lumpur. Sudanese J Ophthalmol [serial online] 2018 [cited 2019 Feb 21];10:32-6. Available from: http://www.sjopthal.net/text.asp?2018/10/1/32/240541
| Introduction|| |
Dry eye (DE) is a disorder of the tear film due to excessive evaporation or deficiency in production that leads to symptoms and signs of damaged ocular surface. It is one of the most frequently encountered ocular morbidities. Around 25% of patients who visits the eye clinic report symptoms of dry eye, making it a growing public health problem. In the recent international Dry Eye Workshop II (DEWS II) 2017, the definition of “dry eye” was revised 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”. In addition, DE can also be classified into episodic or chronic depending on etiology, mechanism, and severity of the condition. DE prevalence is 7% in women and 4% in men over the age of 50 years in the US, 17% in China, and 27.5% in Indonesia. Hospital and population-based studies in Malaysia reported between 14% and 33% of the sample population had dry eye.,, The wide range of prevalence is due to different study population and different methods used for data collection.
Patients may complain of symptoms of DE in the presence or absence of signs of the disease. Symptoms include soreness, grittiness, burning, or scratchy sensation. In addition, DE may be diagnosed based only on the signs observed by a healthcare professional in the absence of symptoms/complaints by the patients. Several tools normally used in clinical settings to evaluate DE include tear film stability test, tear volume test, and ocular surface staining. Tear osmolarity test is a laboratory test that slowly adapted into clinical setting especially with invention of a nanofluid lab-on-a-chip osmolarity device which uses electrical impedance to measure solute in the tears., This lead to faster tear sample collection and almost instantaneous osmolarity measurement.
The previous studies have shown controversial findings in associations between reported symptoms and clinical signs of DE using few clinical tests.,, Meta-analysis of 34 studies by Bartlett concluded that most of the clinical signs and symptoms have correlations in the range of − 0.4–0.4 indicating low-to-moderate correlation. Among all investigative tools, osmolarity was found to have better correlation with symptoms of DE compared to tear volume and tear stability. To the best of our knowledge, there is only one study that investigated the changes in tears osmolarity in Malaysian contact lens wearers, and their results showed insignificant change in tears osmolarity after 6 months of wearing silicone hydrogel contact lenses.
It is well known that Asians have lower tear stability than Caucasians.,,, Nevertheless, no study has shown that the association between tear stability and DE symptoms in Asian population. This study investigates the associations between tear stability, tear volume and tear osmolarity with the McMonnies Dry Eye Questionnaire (MDEQ) score in sample of young adults in Kuala Lumpur.
| Methodology|| |
This is a cross-sectional study using cluster sampling method. Participants were screened using self-administrated MDEQ. The questionnaire was invented by Charles McMonnies in 1986 and consisted of 12 questions that focused on clinical risk factors of DE. The questions employ answer options that vary in number and type and provide score from 0 to 45. Each question has a weighted scoring scale. Participants must answer all questions, and the score of each question was calculated. Scores above 14.5 are consistent with DE. The reliability and validity studies of MDEQ have been carried out, and the results are consistent for clinical use., MDEQ is quite popular among eye care practitioners and has been used in studies involving local participants.,
This study was conducted in an optometry clinic in Kuala Lumpur. The sample size was calculated using G * Power version 184.108.40.206 (Heinrich Heine University Düsseldorf, Germany) for comparison between two group with two-tails test, test power was set at 0.8, significance level at 0.05, and ratio between group was set at 0.5 with medium effect size. Total sample size required was 100. To ensure sufficient data, advertisements were placed on bulletin boards around the campus. The inclusion criteria include age between 19 and 30 years, had never worn contact lens before participation in this study, free from any ocular diseases and systemic illnesses, and not pregnant and not smoking. This study was approved by the Medical Ethics Committee (NN-115-2013) and followed the tenets of the Declaration of Helsinki on the use of human participants in research.
Before any measurements were taken in the clinic, participants were left for 10 min to adapt to the clinical environment. This is to minimize the effects of environment such as room temperature and humidity on tears assessment. All measurements were conducted in the same room with room temperature between 23°C and 25°C and humidity level between 45% and 50%. Tear break up time test (TBUT) was measured following a technique described by Pult and Riede-Pult In this method, volume of fluorescein entering the eye is controlled by limiting the contact area of the fluorescein strip (1 mm × 10 mm) to the eye globe. A drop of normal saline was instilled on the fluorescein strip then shaken off so that no visible drop remained. The participant was asked to look up before the introduction of the fluorescein to the inferior conjunctival fornix on the eye. Participant was told to close the eye for approximately 10 s, then to open the eye, blink twice, and to keep the eye naturally opened while looking straight ahead in primary position as long as they could. The time from the last blink to the appearance of random dark spots or streaks in the tear film was taken as TBUT. This was achieved using full aperture of cobalt blue light from slit lamp. Once TBUT was observed, the patient was instructed to blink freely. Three readings were taken, and the mean was recorded.
Tear volume was measured using phenol red thread test (PRT). This method was much less invasive and did not require the application of anesthetic. Vashinit and Singh reported a strong agreement between Schirmer test and PRT. Phenol red is a pH-sensitive indicator. The yellow thread will turn into red upon contact with alkaline tears. The total length of the thread that changed was measured as the PRT value. The cutoff point for tear volume was at 10 mm/15 s. Three measurements were taken for every subject and the mean recorded.
Tear sample was collected using 20 μl microcapillary glass tube (Haematokrit-Kapillaren, Hirschman Laborgerate, Eberstadt German) for osmolarity measurement. Minimum contact with tears caused the capillary effect that slowly filled up the tube and stopped once the other end was closed. It is important not to touch the ocular surface as this will induce any tear reflects which multiply the production of aqueous and this could modify tear composition. In the event of tear reflex, subject was asked to rest until it stop before continue with tear recollection. Samples were then transferred into Eppendorf tube and stored in a freezer with –20°C until it was ready for analysis.
Osmolarity was measured using micro osmometer machine Advance 2020 (Advance Instrument, Norwood, USA) at the Pathology Unit in Hospital Kuala Lumpur. Before the analysis, samples were allowed to thaw at room temperature for 30 min before the Eppendorf tubes were vortexed. This machine comes with twenty samples slot, allowed it to measure sample continuously with each measurement take about 2 min. It worked based on freezing depression techniques which temperature of the freezing point was directly proportional to the total solute in tears. The machine requires volume of 20 μL sample for every measurement. Three reading measurements were taken from sample of each participant.
| Results|| |
A total of 107 participants were recruited in this study. Around 89.7% participants were Malays and 10.3% were Chinese. Thirty-six of them were classified as DE and the remaining 71 as nondry eye (NDE). [Table 1] summarized the demographical data of the participants. Mean TBUT for DE participants was 4.76 ± 1.58 s and for NDE was 5.69 ± 1.61 s. Mean PRT for DE and NDE were 7.87 ± 5.60 mm and 12.59 ± 5.70 mm, respectively. Mean tear osmolarity for DE was 322.42 ± 36.94 mOsm/Lm, and NDE was 286.35 ± 21.31 mOsm/L. The Shapiro–Wilk test shown data in both groups were found to be normally distributed (P > 0.05) except for PRT in DE (P = 0.00). Independent sample t-test in [Table 2] showed significant difference in measurements between DE and NDE for TBUT (P = 0.01) and osmolarity (P = 0.00). Mann–Whitney sum rank test shown that there were significant differences in PRT measurement between two groups (P = 0.00).
|Table 2: Summary of measurements for dry eye and nondry eye participants|
Click here to view
Pearson's correlation coefficients were measured and summarized in descending order on [Table 3]. Highest correlation found was between MDEQ and osmolarity (r = 0.45, P = 0.00) followed by MDEQ and PRT (r = −0.36, P = 0.00) and then between MDEQ and TBUT (r = −0.28, P = 0.00). Significant correlation was found between osmolarity and PRT (r = −0.27, P = 0.00) and between TBUT and PRT (r = 0.21, P = 0.03). No correlation was found between osmolarity and TBUT (r = −0.10, P = 0.29).
|Table 3: Summary of correlation test between clinical measurements and dry eye symptoms|
Click here to view
| Discussion|| |
DE symptoms are quite difficult to manage due to objective clinical signs often conflicting with patient-reported symptoms., The symptoms included ocular discomfort, redness, fatigue, blurred vision, photophobia, dryness, irritation and foreign body sensation, and each of these symptoms may vary in frequency and intensity. Following DEWS Report in 2007, symptoms are considered as essential components of DE. Nevertheless, in a clinical setting, symptom assessment will be followed by a combination of objective tests before a diagnosis is being made. If patients are solely diagnosed based on presenting symptoms, this might result in failure to identify patients with mild problems who could be candidates for early intervention to prevent or delay onset of overt symptoms. Therefore, the purpose of this study was to evaluate the relationship between DE symptoms with tear film stability, volume, and osmolarity in sample of young healthy adults living in Kuala Lumpur. The symptoms of DE were evaluated using MDEQ score which was developed based on the risk factors of DE and frequently used by local optometrists.
The results of this study showed that around 33% of the participants had MDEQ score of higher than 14.5, which was consistent with DE. This was later confirmed with the clinical and laboratory measurements that demonstrated a significant difference in results between DE and NDE groups. Results from PRT was consistent with earlier findings but slightly lower when compared to hospital-based population study. This is probably due to the use of anesthetic before measurement in the hospital. With regard to TBUT, the results of this study reaffirmed earlier findings that Asians have lower TBUT compared to proposed diagnostic value which was <10 s., Yeh et al. found that although the sensitivity and specificity of TBUT were similar in Asians and non-Asians, their thresholds were noticeably different (6.7 s for Asians and 9.2 s for non-Asians). As TBUT is one of the common clinical methods of assessing tears, the threshold for Asian patients should be set much lower than 10 s. This is because many of our participants have TBUT lower than 10 s but do not complain of DE symptoms. The observations on lower TBUT were similar to findings from earlier works in Asian populations.,,,
Measurement of tear osmolarity is considered as a gold standard in DE diagnosis.,, Using micro osmometer, this study showed that the tear osmolarity for normal NDE participants was around 286 mOsm/L and for the DE was around 322 mOsm/L. To the best of our knowledge, this is the first reported tear osmolarity measurement in a normal healthy population in Malaysia. The results are within the range suggested by Versura et al. who used the TearLab Osmolarity system and found value of 305 mOsm/L as cutoff value for DE, 309 mOsm/L for moderate DE, and 318 mOsm/L for severe DE. Significant positive correlation was also noted between MDEQ score and tear osmolarity. Higher MDEQ symptoms score (>14.5) indicates DE which is linked to tear hyperosmolarity. An increase in tear osmolarity is thought to be the central mechanism in the pathogenesis of ocular surface damages. Significant correlation between osmolarity and PRT explains increase reaction of inflammatory cytokine with reduce of tear volume which than lead to loss of goblet cell. Tear stability dependent on ocular surface mucin which probably affected at the end of the inflammatory cycle., This explains why no correlation found between osmolarity and TBUT. Same insignificant correlation between osmolarity and TBUT was also found in Saudi and Korean study.,
Negative correlations were noted between MDEQ and PRT and between MDEQ and TBUT. These trends suggest that participants with inadequate tear volume and unstable tear film report more symptoms of DE. The results support that earlier findings by Begley et al., who showed associations between ocular surface symptoms with TBUT, Schirmer test, and overall conjunctival staining. The results of this study also showed that MDEQ symptom score is a reliable screening tool for DE. Tang et al. recently evaluated the accuracy of MDEQ as a screening tool for DE among 27718 Chinese ophthalmic outpatients. Their results showed that MDEQ is an effective screening tool and should be considered by eye care practitioners.
| Conclusion|| |
This study showed good correlation between MDEQ symptoms score with clinical and laboratory tests results in a sample population of young adults in Kuala Lumpur. The questionnaire should be considered by eye care practitioners to confirm the diagnosis of DE in young adults.
We would like to thank Hospital Kuala Lumpur Pathology unit for cooperation and assistance for micro osmolarity testing.
| References|| |
Doughty MJ, Fonn D, Richter D, Simpson T, Caffery B, Gordon K, et al.
A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada. Optom Vis Sci 1997;74:624-31.
Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al.
TFOS DEWS II definition and classification report. Ocul Surf 2017;15:276-83.
Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003;136:318-26.
Liu NN, Liu L, Li J, Sun YZ. Prevalence of and risk factors for dry eye symptom in Mainland China: A systematic review and meta-analysis. J Ophthalmol 2014;2014:748654.
Lee AJ, Lee J, Saw SM, Gazzard G, Koh D, Widjaja D, et al.
Prevalence and risk factors associated with dry eye symptoms: A population based study in Indonesia. Br J Ophthalmol 2002;86:1347-51.
Jamaliah R, Fathilah J. Prevalence of dry eye in university Malaya medical centre. Med J Malaysia 2002;57:390-7.
Mohd Ali B, Leong SF, Abdul Mutalib H, Mohidin N. Incidence of dry eye in a sample population in Kuala Lumpur. Int J Collab Res Intern Med Public Health 2011;3:839-45.
Muna'aim MA, Tey YY, Mohamad Zafarullah AA, Saleh RM, Omar N. Dry eye among patients at the eye clinic of a secondary referral hospital. Malays J Med Sci 2016;12:30-7.
McMonnies CW. Key questions in a dry eye history. J Am Optom Assoc 1986;57:512-7.
Masmali A, Alrabiah S, Alharbi A, El-Hiti GA, Almubrad T. Investigation of tear osmolarity using the TearLab osmolarity system in normal adults in Saudi Arabia. Eye Contact Lens 2014;40:74-8.
Kim M, Kim HS, Na KS. Correlation between tear osmolarity and other ocular surface parameters in primary Sjögren's syndrome. Korean J Ophthalmol 2017;31:25-31.
Nichols KK, Smith JA. Association of clinical diagnostic tests and dry eye surveys: The NEI-VFQ-25 and the OSDI. Adv Exp Med Biol 2002;506:1177-81.
Cardona G, Marcellán C, Fornieles A, Vilaseca M, Quevedo L. Temporal stability in the perception of dry eye ocular discomfort symptoms. Optom Vis Sci 2010;87:1023-9.
Lin PY, Cheng CY, Hsu WM, Tsai SY, Lin MW, Liu JH, et al.
Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: The Shihpai Eye Study. Invest Ophthalmol Vis Sci 2005;46:1593-8.
Bartlett JD, Keith MS, Sudharshan L, Snedecor SJ. Associations between signs and symptoms of dry eye disease: A systematic review. Clin Ophthalmol 2015;9:1719-30.
Ahmad A, Ishak B, Mohd Ali B. PH8: Tear film osmolarity in young malay after wearing contact lens for 6 months. Med J Malays 2017;72 Suppl 2:28.
Mohidin N, Ramli A. Fluorescein tear break-up time in Malays. Malays J Med Sci 2004;2:65-73.
Mohammed Z, Hajar Maidin MH, Mohd Ali B. Lid wiper epitheliopathy in subjects with and without dry eye symptoms in Kuala Lumpur – A pilot study. Arch Des Sci 2012;65:585-90.
McMonnies C, Ho A, Wakefield D. Optimum dry eye classification using questionnaire responses. Adv Exp Med Biol 1998;438:835-8.
Tang F, Wang J, Tang Z, Kang M, Deng Q, Yu J, et al.
Accuracy of McMonnies questionnaire as a screening tool for Chinese ophthalmic outpatients. PLoS One 2016;11:e0153047.
Ali M, Nguan DK, Bashirah I, Chan KM. Tear proteomics in young Malays with dry eyes. Int Med J Malays 2013;12:39-43.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007;39:175-91.
Pult H, Riede-Pult BH. A new modified fluorescein strip: Its repeatability and usefulness in tear film break-up time analysis. Cont Lens Anterior Eye 2012;35:35-8.
Vashisht S, Singh S. Evaluation of phenol red thread test versus Schirmer test in dry eyes: A comparative study. Int J Appl Basic Med Res 2011;1:40-2.
Farris RL. Tear osmolarity – A new gold standard? In: Sullivan DA, editor. Lacrimal Gland, Tear Film, and Dry Eye Syndromes. Advances in Experimental Medicine and Biology. Boston, MA: Springer; 1994.
Sullivan BD, Whitmer D, Nichols KK, Tomlinson A, Foulks GN, Geerling G, et al.
An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010;51:6125-30.
Fuentes-Páez G, Herreras JM, Cordero Y, Almaraz A, González MJ, Calonge M, et al.
Lack of concordance between dry eye syndrome questionnaires and diagnostic tests. Arch Soc Esp Oftalmol 2011;86:3-7.
Sullivan BD, Crews LA, Messmer EM, Foulks GN, Nichols KK, Baenninger P, et al.
Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: Clinical implications. Acta Ophthalmol 2014;92:161-6.
Methodologies to diagnose and monitor dry eye disease: Report of the diagnostic methodology subcommittee of the International Dry Eye workshop (2007). Ocul Surf 2007;5:108-52.
Tsubota K, Yokoi N, Shimazaki J, Watanabe H, Dogru M, Yamada M, et al.
New perspectives on dry eye definition and diagnosis: A consensus report by the Asia dry eye society. Ocul Surf 2017;15:65-76.
Yeh TN, Graham AD, Lin MC. Relationships among tear film stability, osmolarity, and dryness symptoms. Optom Vis Sci 2015;92:e264-72.
Cho P, Yap M. Age, gender, and tear break-up time. Optom Vis Sci 1993;70:828-31.
Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: Determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006;47:4309-15.
Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res 2010;35:553-64.
Narayanan S, Manning J, Proske R, McDermott AM. Effect of hyperosmolality on beta-defensin gene expression by human corneal epithelial cells. Cornea 2006;25:1063-8.
Utine CA, Bıçakçıgil M, Yavuz S, Çiftçi F. Tear osmolarity measurements in dry eye related to primary sjögren's syndrome. Curr Eye Res 2011;36:683-90.
Baudouin C. A new approach for better comprehension of diseases of the ocular surface. J Fr Ophtalmol 2007;30:239-46.
Begley CG, Chalmers RL, Abetz L, Venkataraman K, Mertzanis P, Caffery BA, et al.
The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci 2003;44:4753-61.
[Table 1], [Table 2], [Table 3]