Effectiveness of sodium hyaluronate eye gel in patients with dry eye disease: A multi-centre open label uncontrolled study.
Objective: To assess the effectiveness of sodium hyaluronate Eye Gel in Dry Eye Disease (DED) patients Methods: A Multi-center Open-label Uncontrolled clinical trial was conducted in different centers of Pakistan. Ten ophthalmologists conducted this study in which 250 diagnosed patients with dry eye disease were enrolled after obtaining a written informed consent.
Ten patients were dropped out during the study period. All patients were assessed as per following criteria for enrolling a patient into the study: Tear Film Break up time (TBUT) = 10 seconds Schirmer Test 1 = 6 mm / 5 minutes and Positive Corneal Staining. Tolerability/safety was assessed by the monitoring and recording of all adverse events. The physical examination was done at baseline 4th week and 8th week.
Results: The mean age of the patients was 43.4 17.8 years and out of 240 patients 117 (48.7%) were males and 123 (51.3%) females. The Mean duration of symptoms was 19.323.9. At the initial visit the foreign body sensation was 50.6% itching 35.9% burning 50.6% watering 42.9% photophobia 25.3% and feeling of dryness in 14.7% of patients.
After 4 weeks (2nd visit) the symptoms were decreased to 47.1% foreign body sensation 32.4% itching 48.2% burning 41.8% watering 25.3% photophobia and 13.5% feeling of dryness. At the 3rd visit (after 8 weeks) the frequency of symptoms were: 45.3% foreign body sensation 30.6% itching 45.9% burning 40% watering 24.7% photophobia and 13.5% feeling of dryness.
Conclusion: Sodium Hyaluronate can provide a suitable alternate in the treatment of dry eye disease due to its reported efficacy on foreign body sensation itching burning watering photophobia and feeling of dryness
KEY WORDS: Fluorescein eye stain Schirmer's test Tear Film Break up Time.
The Dry eye disease (DED) is a common health problem which has an effect on the quality of life.1 The new definition of Dry Eye was developed in the International Dry Eye Workshop (DEWS) 2007 and is based on etiology mechanism and severity of the disease. The dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort visual disturbance and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface".2
Dry eye is a common ocular problem and also an important public health problem. DED patients are having problems in daily routine activities such as reading working on a computer and car driving. DED also increases the risk of ocular infections ocular discomfort fatigue and visual disturbance .34
Only a few population based studies are available regarding the magnitude of the problem. The studies conducted in US to determine the prevalence of DED showed 14.6% (Salisbury Eye Study).5
The reported frequency of dry eye syndrome was found 16%.in adult patients attending the eye clinic of tertiary care hospital in Pakistan.6
The important risk factors for DED are older age female sex reduced androgen levels exogenous estrogen use and an imbalance in the dietary intake of essential fatty acids as identified by the studies over the past decade.7-8
A study conducted on elderly Korean population found that female sex age and hormonal influence were risk factors for both DED and depression.9
Wang et al and Galor et al reported a relationship between depression and DED.1011
Hyaluronan (HA) has distinctive viscoelastic and hygroscopic properties and plays many important roles in the human body. It is a naturally occurring lubricant and is made up of biocompatible polysaccharide It is because of its excellent water-retaining properties that it is used in ophthalmic products.12-14
HA is found mainly in the connective tissue of the skin inside the umbilical cord synovial fluid in joints and eye. In eye it is found in the vitreous lacrimal gland cornea conjunctiva and tear fluid. HA has an anti-inflammatory and wound healing property. HA inhibits free radicals thus prevents oxidative damage to cells.15 16
The objective of this study was to assess the effectiveness of sodium hyaluronate Eye Gel in diagnosed patients of DED. METHODS
A Multi-center Open-label Uncontrolled clinical trial was conducted in different centers of Pakistan. Ten ophthalmologists conducted this study in which 250 diagnosed patients with dry eye disease were included after obtaining a written informed consent.
All patients were assessed as per following criteria for enrolling a patient into the study: Presence of at least 2 of the 6 symptoms (Foreign Body Sensation Itching Burning Watering Photophobia and Feeling of Dryness in the eye) and at least one of the 3 tests Tear Film Break up time (TBUT) = 10 seconds 2) Schirmer Test 1 = 6 mm / 5 min and Positive Corneal Staining. Patients with Entropion Ectropion Trichiasis or using Cortico-steroids drugs were excluded from the study.
Sodium hyaluronate Eye Gel 2-4 times a day was prescribed to patients for 8 weeks. Tolerability/ safety was assessed by the monitoring and recording of all adverse events. The physical examination was performed at baseline 4th week and 8th week. The confidentiality of data and patient anonymity was protected by the codes given in the study documents.
Demographic and baseline variables were described by mean + standard deviation for continuous data and frequency and percentages were calculated for categorical data. One Way ANOVA was performed and p value less than 0.05 was considered as significant.
Ten patients dropped out during the study period from a total of 250 diagnosed patients of Dry Eye and the response rate was 96%. The mean age of the patients was 43.4 17.8 years. Out of 240 patients 117 (48.7%) were males and 123 (51.3%) females. The Mean duration of symptoms was 19.3 23.9 months. At the baseline foreign body sensation 50.6% itching 35.9% burning 50.6% watering 42.9% photophobia 25.4% and feeling of dryness 14.7%.
After 4 weeks (2nd visit) the results showed that the foreign body sensation 47.1% itching 32.4% burning 48.2% watering 41.8% photophobia 25.3% and feeling of dryness 13.5%. After 8 weeks (3rd visit) the changes in ocular symptoms were: foreign body sensation 45.3% itching 30.6% burning 45.9% watering 40% photophobia 24.7% and feeling of dryness 13.5%.
The Mean TBUT was 6.62.2 in the first visit 8.32.2 second visit and 10.12.3 seconds in the third visit (p-value less than 0.05). Schirmer's test was 9.1 5.7 in the first visit 10.6 5.3 in the second visit and 11.84.1 in the third visit (p-value less than 0.05).The above results showed a significant difference in the ocular symptoms between the visits.
Table-I: Change in Ocular symptoms and signs with visit (N = 240)
Ocular History###Visit-1 (Baseline)###Visit-2 (Week 4)###Visit-3 (Week 8)
###N %###N%###N %
###Foreign Body sensation###121###50.6%###113###47.1%###109###45.3%
###Feeling of Dryness###35###14.7%###32###13.5%###32###13.5%
Table-II: Change in Tear film breakup time and Schirmer's Test with visits (N = 240)
###Tear film breakup time (sec)###Schirmer's Test mm/5 min (Without Anesthesia)
###Visit-1 (Baseline) Visit-2 (Week 4) Visit-3 (Week 8)###Visit-1 (Baseline) Visit-2 (Week 4) Visit-3(Week 8)
###p-value###less than 0.05###less than 0.05
The results of this study showed that sodium hyaluronate-containing eye gel reduces the ocular symptoms in patients with dry eye.
Treatment with 0.4% hyaluronic acid hypotonic solution drops gave better results in relieving symptoms along with a statistically significant improvement (p less than 0.001) in the state of the corneo-conjunctival epithelium than the isotonic solution.16
Pasquale et al found that sodium hyaluronate significantly improved signs and symptoms in patients with moderate to severe dry eye independently from the saline composition of the ophthalmic solutions.17
In vitro hyaluronate promotes cell migration and can stabilize ocular surface epithelial barrier suggesting that it may be directly involved in the process of epithelial repair by activation of the CD44 (the hyaluronate receptor).1819
Brignole and associates found that comfort was better in Sodium hyaluronate (SH) group as compared to carboxym-ethylcellulose (CMC) group. SH group also showed faster recovery in keratitis (type extent and depth) and symptoms than in the CMC group.20
A comparative study between diquafosol group and sodium hyaluronate group also showed that the SH group had lower adverse reactions such as eye discharge and eye irritation than in the other group.21
Johnson and coworkers compared the effect of saline and 0.1% and 0.3% HA on TBUT. A significant improvement was found in TBUT up to 6 hours. They also noticed that the 0.3% HA had greater effect on TBUT as well as on symptoms (P less than 0.04).22
Our study also showed the improvement of mean TBUT from 6.6 second (SD2.2) in the first visit to 10.1 seconds (SD2.3) in the third visit (p-value less than 0.05). Prabhasawat and coworkers also found the increase in TBUT in HA group at 30 and 60 minutes (P less than 0.04 and P less than 0.005 respectively).23
Our study found that the foreign body sensation itching burning watering photophobia and feeling of dryness decreased after 8 weeks of treatment with HA. Dumbleton and associates also reported the efficacy of HA with a significant difference in subjective symptoms in the group using HA.24
Literature review showed that HA is found throughout the body and can be used to mimic the natural tears in such products as artificial tears. Previous studies also show that HA-based ophthalmic preparations can serve as natural tears.25
In conclusion this study suggests that sodium hyaluronate Eye Gel has a beneficial effect on the foreign body sensation itching burning watering photophobia and feeling of dryness in a well defined and homogeneous population of patients with dry eye selected by using stringent inclusion criteria. No adverse event with sodium hyaluronate eye gel was reported by the patients.
Limitations of the Study: The limitations of this study were lack of control group and also the open label nature of the study. The equal number of male and female patients will have an effect on the results because some of the factors e.g. gender and menopause is associated with female gender. The duration (8 weeks) of the study was also a limitation to observe the long-term effects of the treatment.
The authors would like to thank Dr. Khalid Mahmood Dr. Khurram Mirza Dr. Khalid Waheed Dr. Javed Chaudhry Dr. M. Ayub Dr. Sabih Uddin Dr. Aamir Asrar for their help and assistance in conducting this study. We would also like to thank all investigators for their support in data collection.
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2. International Dry Eye Workshop (DEWS). The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop. Ocul Surface. 2007;5:7592.
3. Miljanovic' B Dana R Sullivan DA Schaumberg DA. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007;143(3):409-415.
4. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):93-107.
5. Munoz B West SK Rubin GS. Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study. Arch Ophthalmol 2000;118:819-25
6. Malik TA Naqvi SAH Shahid M. Dry eye syndrome; frequency in adult patients attending the eye clinic in Military hospital Rawalpindi. Professional Med J. 2009;16(1):145-158.
7. Schaumberg DA Buring JE Sullivan DA Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001;286(17):2114-2119.
8. Schaumberg DA Sullivan DA Buring JE Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136(2):318-326.
9. Han SB Hyon JY Woo SJ Lee JJ Kim T-H Kim K-W. Prevalence of dry eye disease in an elderly Korean population. Arch Ophthalmol. 2011;129:633638.
10. Wang TJ Wang IJ Hu CC Lin HC. Comorbidities of dry eye disease: a nationwide population-based study. Acta Ophthalmol. 2012;90(7):663-668.
11. Galor A Feuer W Lee DJ. Prevalence and risk factors of dry eye syndrome in a United States Veterans Affairs population. Am J Ophthalmol. 2011;152:377384.
12. Milas M Rinaudo M. Characterization and properties of hyaluronic acid (hyaluronan). In: Dumitriu S ed. Polysaccharides Structural Diversity and Functional Versatility. New York NY: Marcel Dekker; 2005:535-549.
13. Stuart JC Linn JG. Dilute sodium hyaluronate (Healon) in the treatment of ocular surface disorders. Ann Ophthalmol. 1985;17:190-192.
14. Fonn D. Targeting contact lens induced dryness and discomfort: what properties will make lenses more comfortable. Optom Vis Sci. 2007;84:279-285.
15. Lapcik L Jr Lapcik L DeSmedt S. Hyaluronan: preparation structure properties and applications. Chem Rev. 1998;98:2663-2684.
16. Troiano P Monaco G. Effect of hypotonic 0.4% hyaluronic acid drops in dry eye patients: a cross-over study. Cornea. 2008;27(10):1126-1130
17. Pasquale Ar Vincenzo P Antonio M Marcello S Giovanni M. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye.Br J Ophthalmol. 2002;86(2):181184.
18. Lerner LE Schawrtz DM Hwang DG. Hyaluronan and CD44 in the human cornea and limbal conjunctiva. Exp Eye Res. 1998;67:481484.
19. Baudouin F Brignole F Dupas B. Reduction in keratitis and CD44 expression in dry eye patients treated with a unique 0.18% sodium hyaluronate solution. Invest Ophthalmol Vis Sci. 2001;42:S32 abstract no 180.
20. Brignole F Pisella PJ Dupas B Baeyens V Baudouin C. Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis. Graefes Arch Clin Exp Ophthalmol. 2005;243(6):531-538.
21. Takamura E Tsubota K Watanabe H Ohashi Y. A randomised double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96(10):13101315.
22. Johnson ME Murphy PJ Boulton M. Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye. Graefes Arch Clin Exp Ophthalmol. 2006;244:109-112.
23. Prabhasawat P Tesavibul N Kasetsuwan N. Performance profile of sodium hyaluronate in patients with lipid tear deficiency: randomised double-blind controlled exploratory study. Br J Ophthalmol. 2007;91:47-50.
24. Dumbleton K Woods C Fonn D. An investigation of the efficacy of a novel ocular lubricant. Eye Contact Lens. 2009;35:149-155.
25. Marjorie R. Hyaluronan: A Review of its Properties Ophthalmic Uses and Research. contact lens spectrum. 2010 April: 30-32.
CONFLICT OF INTEREST:
Non-Financial Conflict of Interest: In this study the integrity of the study was not be compromised by any financial interests. To assure that investigators did not have financial arrangements that reward a particular study outcome proprietary interest in the intervention being tested significant equity in the manufacturer of the intervention or significant payments of other sorts.
The investigators were paid for the data filling and the examination of patient during the study period. Since this was a non interventional study so patients were observed in real life setting and no support for any laboratory test or drug supply was provided to investigators.
Prof. Dr. Nasir Saeed: Design drafting data collection critical review.
Dr. ZA Qazi: Data collection writing the results drafting.
Dr. Nadeem H Butt: Writing the discussion Drafting Data collection.
Dr. Ahson Siddiqi: Design critical review.
Dr. Neeta Maheshwary: Data collection Data analysis.
Dr. Muhammad Athar Khan: Data analysis writing the results.
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|Publication:||Pakistan Journal of Medical Sciences|
|Date:||Aug 31, 2013|
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