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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 236-243

Comparison between topical cyclosporine A 0.05% and oral antioxidant in the treatment of dry eye disease


1 Profossor of Ophthalmology, Faculty of Medicine, Al-Azhar University, Egypt
2 Lecturer of Ophthalmology, Faculty of Medicine, Al-Azhar University, Egypt
3 Assistant Professor of Pathology Faculty of Medicine, Al-Azhar University, Egypt
4 Residant of Ophthalmology, Egypt

Date of Submission19-Mar-2020
Date of Decision08-Apr-2020
Date of Acceptance14-Apr-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
MD Nermien Salah El-Dien Mohammed EL-Haddad
Department of Ophthalmology, Faculty of Medicine for Girls, Al-Azhar University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_40_20

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  Abstract 


Background Dry eye disease is a multifactorial ocular pathology characterized by corneal epithelial lesions, inflammation of ocular surface, and symptoms of discomfort, including irritation, itching, and burning eyes.
Aim The aim of this work is to compare the effect of both topical cyclosporine A 0.05% and oral antioxidant with the preservative-free artificial tears in the treatment of dry eye.
Patients and methods This is a prospective randomized comparative cross-sectional study that included 180 eyes. Schirmer I test, break-up time test (BUT), corneal fluorescein staining score, and impression cytology grade were done.
Results The results showed that there was no significant difference between the cyclosporine and the antioxidant groups after 3 months of treatment in terms of BUT (P=0.245), corneal fluorescein staining score (P=0.9052), and impression cytology grade (P=0.526), and they were significantly different in terms of (P=0.012). In the preservative-free group, although there were highly significant improvements in schirmer I test, BUT, corneal fluorescein staining, and impression cytology grade after 3 months of treatment, the cyclosporine and the antioxidant groups showed highly significant improvement than the preservative-free group.
Conclusion Both topical cyclosporine A 0.05% and oral antioxidant treatments are effective for the treatment of dry eye disorder. However, cyclosporine has better results.

Keywords: antioxidant, dry eye disease, topical cyclosporine


How to cite this article:
Kamel ME, EL-Haddad NDM, Seadah SA, Sahaly MH. Comparison between topical cyclosporine A 0.05% and oral antioxidant in the treatment of dry eye disease. Sci J Al-Azhar Med Fac Girls 2020;4:236-43

How to cite this URL:
Kamel ME, EL-Haddad NDM, Seadah SA, Sahaly MH. Comparison between topical cyclosporine A 0.05% and oral antioxidant in the treatment of dry eye disease. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 26];4:236-43. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/236/288280




  Introduction Top


Dry eye disease (DED) is commonly associated with reduced tear production and/or alteration in tear composition, and this leads to loss of protective and nourishing qualities of tears. The integrity of the outermost layers of the ocular surface is highly dependent on hydration and lubrication, provided by the tear film, as well as on the tear cytokines and growth factors, which promote wound healing and containment of inflammatory responses in the corneal epithelium and stroma [1].

Cyclosporine inhibits T-cell-mediated inflammation by preventing activation of T cells by cytokines and other agents of inflammation [2]. It also can inhibit lymphocytic infiltration, decrease the immune and inflammatory response, and inhibit apoptosis of the lacrimal and conjunctival epithelial cells in DED [3].

Antioxidants protect the cells from free radical damage. The National Eye Institute recommends a diet high in antioxidants, vitamin, and mineral supplements. Antioxidants’ effects on harmful reactive oxygen species may be helpful in the fight against dry eye [4].

The aim of this work is to compare the effect of topical cyclosporine A 0.05% and oral antioxidant with the preservative-free artificial tears in the treatment of dry eye.


  Patients and methods Top


The study was approved by the Scientific and Ethical Committees at Faculty of Medicine, Al-Azhar University. It was carried out from December 2018 to May 2019 at the outpatient clinic of Al-Zahraa University Hospital. Informed consents were obtained from patients participated in this study.

Inclusion criteria

The following were the inclusion criteria:
  1. Schirmer I test (without anesthesia) results less than or equal to 5 mm/5 min in at least one eye.
  2. Low tear film break-up time less than or equal to 5 s.
  3. Mild superficial punctate keratitis, defined as a corneal punctate fluorescein staining score of one or more in either eye [scale, 0 (none) to 3 (severe)].


Exclusion criteria

The following were the exclusion criteria:
  1. History of any ocular disorder, including injury, infection, or ocular inflammation not associated with dry eye.
  2. Trauma or surgery within the previous 6 months.
  3. Patients receiving concurrent treatment that could interfere with the interpretation of the study results.


Study population and procedures

A total of 90 patients (180 eyes) with DED (from 25 to 70 years old) were divided into three groups, with 30 patients each, who were divided randomly.
  • Cyclosporine group was treated twice daily with topical cyclosporine A 0.05% plus preservative-free artificial tears four times daily.
  • Antioxidant group was treated with oral antioxidants once daily plus preservative-free artificial tears four times daily. Each tablet contains selenium yeast (1000 μg/g), vitamin A acetate (500 IU/mg), ascorbic acid (97%), and vitamin E acetate (50%).


Preservative-free group was treated four times daily with preservative-free artificial tears (sodium hyaluronate) alone.

All patients were subjected to local eye assessment, Schirmer I testing (without anesthesia), BUT, and corneal fluorescein staining score, which were performed before treatment and at the first, second, and third months after initiation of treatment. Conjunctival impression cytologic analysis was performed before treatment and third months after initiation of treatment.

The Schirmer I test

A cotton tip was applied in the inferior fornix to remove excess tears, bending the Schirmer strip at the notch, and placing the strip beneath the temporal lid margin. After 5 min, during which the patient was instructed to keep the eyes open and to blink normally, the strip was removed and measured to the point of maximum wetting.

BUT

It indicates adequacy of mucin layer of tear film. It is the time interval between complete blink and appearance of first randomly distributed dry spot on the cornea. Fluorescein was placed in the lower conjunctival sac using a fluorescein-impregnated strip wetted with local anesthesia. It was examined under cobalt blue light of slit lamp. The patient was asked to blink, and the time before the first defect appeared in the stained tear film was measured as the BUT.

Corneal fluorescein staining

The entire cornea was examined by slit-lamp evaluation with cobalt blue illumination. The staining was graded using the Van Bijsterveld Scoring System (from 0 through 3).

Conjunctival impression cytology

It was performed on the lower bulbar conjunctiva using a cellulose acetate filter paper of 0.4-μm pore size, cut into 2×4 mm pieces. The filter paper was applied to the temporal and nasal parts of conjunctiva by pressing on it by the tip of the forceps for 10 s. The filter paper was grasped gently with the forceps. Specimens were fixed in alcohol 90%, stained with hematoxylin and eosin, and examined with a light microscope. The degree of squamous metaplasia was graded from 0 through 3 using the grading scheme of Tseng. The degree of squamous metaplasia was classified according to the morphological changes in the nucleus, the nuclear cytoplasmic ratio, and metachromatic changes in the cytoplasm.

Statistical analysis

Data were collected, revised, coded, and entered to the Statistical Package for Social Science (IBM SPSS), version 23 (Armonk, New York, USA). The quantitative data were presented as mean, SDs, and ranges of their distribution found parametric. Moreover, qualitative variables were presented as number and percentages. So, the P value was considered significant as the following: P value more than 0.05 was nonsignificant, P value less than 0.05 was significant, and P value less than 0.01 was highly significant.


  Results Top


In this study, there was no statistically significant difference regarding age and sex among the three study groups ([Table 1]).
Table 1 Comparison among the three study groups regarding the demographic data

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There were highly significant changes in results of all parameters after 3 months of treatment with cyclosporine A 0.05% plus artificial tears as shown in [Table 2].
Table 2 Comparison of all parameters in the cyclosporine group throughout the study

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AS regard the oral antioxidant plus artificial tears, there were highly significant changes in all parameters after 3 months of treatment as shown in [Table 3].
Table 3 Comparison of all parameters in the antioxidant group throughout the study

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[Table 4] shows the improvements that happened in the preservative-free group throughout the study. Although there were highly significant changes in the results of all parameters, except goblet cell density, which was only significant after 3 months of treatment with preservative-free artificial tears, the cyclosporine and the antioxidant groups showed highly significant improvement than the preservative-free group ([Figure 1],[Figure 2],[Figure 3]).
Table 4 Comparison of all parameters in the preservative-free group throughout the study

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Figure 1 Conjunctival impression cytological finding. (a) A specimen from a patient with dry eye before treatment of 0.05% topical cyclosporine application, shows a goblet cell loss and large, polygonal epithelial cells with a nucleocytoplasmic ratio of 1 : 4 (moderate grade of squamous metaplasia, grade 2). (b) Specimen at 3 months after 0.05% topical cyclosporine application shows some goblet cells (arrow) and round epithelial cells with a nucleocytoplasmic ratio of 1 : 3. (low grade of squamous metaplasia, grade 1) (hematoxylin and eosin staining, ×400).

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Figure 2 Conjunctival impression cytological finding. (a) A specimen from a patient with dry eye before treatment of antioxidant tablets shows marked goblet cell loss, large separated polygonal epithelial cells, and small pyknotic nuclei with a nucleocytoplasmic ratio of 1 : 7 (high grade of squamous metaplasia, grade 3). (b) Specimen at 3 months after antioxidant tablets treatment, shows a goblet cell loss, smaller polygonal epithelial cells, with a nucleocytoplasmic ratio of 1 : 4 (moderate grade of squamous metaplasia, grade 2) (hematoxylin and eosin staining, ×400).

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Figure 3 Conjunctival impression cytological finding. (a) A specimen from a patient with dry eye before treatment of preservative-free artificial tears alone shows some goblet cells (arrow) and round epithelial cells with a nucleocytoplasmic ratio of 1 : 3 (low grade of squamous metaplasia, grade 1). (b) A specimen at 3 months after preservative-free artificial tears treatment alone shows same findings and grade without improvement (low grade of squamous metaplasia, grade 1) (hematoxylin and eosin staining, ×400).

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As regard the comparison among the three study group in Schirmer test results. The cyclosporine group showed the highest increase. The antioxidant group showed slightly lesser results than the cyclosporine group. The preservative-free group showed the least and slowest improvement ([Figure 4]).
Figure 4 A graph comparing the three study groups in terms of Schirmer I test.

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[Figure 5] shows a comparison among the three study groups regarding BUT test results from baseline to the end of the study. The cyclosporine group showed the highest increase. The antioxidant group showed slightly less improvement than the cyclosporine group. The preservative-free group showed the least and slowest improvement.
Figure 5 A graph comparing the three study groups in terms of BUT.

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The corneal fluorescein stainning score among the three study group was shown in [Figure 6]. The cyclosporine and the antioxidant groups showed rapid and equal decrease in their score, whereas in the preservative-free group it was steady after the first month, then it showed a slight decrease through the second month, and then it became steady again.
Figure 6 A graph comparing the three study groups in terms of corneal fluorescein.

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As regard the comparison among the three study group in impression cytology grade. The cyclosporine and the antioxidant groups showed rapid and nearly equal decrease in their grade. However, in the preservative-free group, it was nearly steady after 3 months, it showed a slight decrease, through the treatment period inspite of being statistically significant ([Figure 7]).
Figure 7 A graph comparing the three study groups in terms of impression cytology.

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  Discussion Top


In the present study, we investigated the efficacy of topical 0.05% cyclosporine A and oral antioxidant in the treatment of DED and compared the therapeutic effects of the two agents with preservative-free artificial tears. This study is the first of its kind to compare between the two agents together. Therefore, the discussion will not refer to any other matching study; it will discuss each parameter in each group separately in comparison with the preservative-free group.

Both topical 0.05% cyclosporine A and antioxidant intake treatments improved Schirmer I test results, tear film BUT, corneal staining scores, grades of impression cytologic analysis, and goblet cell densities.

Topical cyclosporine is known to have several mechanisms of action, including the inhibition of epithelial apoptosis and of cytokine production by the activated T lymphocytes that infiltrate the conjunctiva.

Antioxidant intake regulates the proliferation and differentiation of corneal epithelial cells and preserves conjunctival goblet cells.

Schirmer I test measures the basal tear secretion and reflex tears from the main lacrimal gland. The increase in the results of Schirmer I test indicates an improvement in the function of the main lacrimal gland [5].

The results of our study regarding Schirmer test agree with other studies [6],[7],[8],[9],[10],[11],[12],[13],[14]. However, they did not match with the results of the study by Gündüz and Özdemir [15], which investigated the use of topical cyclosporine 2% in olive oil on the dry eye state in patients with secondary Sjögren’s syndrome. Schirmer I test remained unaffected (P>0.05). This may be owing to the small sample size of the patients (15 patients in each group only) and follow-up for 2 months only. Moreover, they used olive oil and a different concentration of cyclosporine 2%.

The better Schirmer test results obtained in our study are owing to the anti-inflammatory effect of the cyclosporine A 0.05% and antioxidants. With less inflammation, the epithelial quality of the ocular surface improves. This results in an increase in the sensory-stimulated reflex tearing, leading to further improvement in the quantity and quality of lacrimal gland tear production.

The better improvement of the cyclosporine group than the antioxidant group (P=0.012) is owing to the different mechanism of action of the two drugs. Cyclosporine acts directly on inflammatory cells, unlike antioxidant. So, cyclosporine A may be more effective for treatment of the ocular surface inflammation caused by dry eye.

The improvement of BUT agrees with the previous studies [6],[7],[8],[9],[10],[11],[12],[13],[14]. This is largely owing to the increase in goblet cell density. The resultant increased mucin production could improve the interface between the hydrophobic corneal epithelium and aqueous tear fluid, leading to better tear film stability.

Corneal fluorescein staining is a valid way of clinical evaluation of corneal health and its barrier function. The improvement in our result matches with several studies [6],[7],[8],[9],[10],[11],[12],[13],[14].

The improvements in BUT and corneal fluorescein staining score indicate increasing tear film stability and decreasing corneal epithelial cell damage [5].Our results did not match with Willen et al. [16], who compared the efficiency of topical cyclosporine in contact lens users with dry eye symptoms and found no statistically significant difference between the treatment and placebo groups in all parameters. This is because the dry eye state in the contact lens wearer is fundamentally different from that of other dry eye states.

The last finding in our study is impression cytology grading. The decrease of impression cytology grade was associated with improvement and increase in goblet cell density. These results agree with previous studies [7],[10],[11],[17].

The cyclosporine and the antioxidant treatments cause an increase in tear production and conjunctival goblet cell densities in patients with chronic DED with better results in cyclosporine group.


  Conclusion Top


In conclusion, both topical cyclosporine A 0.05% and oral antioxidant treatments are effective for the treatment of DED. However, the topical cyclosporine A 0.05% had better results than oral antioxidant as an adjuvant to artificial tears in the treatment of dry eye.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tiulina V, Zernii E, Baksheeva V, Gancharova O, Kabanova E, Sotnikova L et al. Mitochondria-targeted antioxidant SkQ1 improves corneal healing after UV-induced damage in rabbits. FEBS Open Bio 2018; 8:215–215.  Back to cited text no. 1
    
2.
Kunert KS, Tisdale AS, Stern ME, Smith JA, Gipson IK. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 2000;118:1489–1496.  Back to cited text no. 2
    
3.
Yamaguchi T. Inflammatory response in dry eye. Invest Ophthalmol Vis Sci 2018; 59:192–199.  Back to cited text no. 3
    
4.
Hobbs RP, Bernstein PS. Nutrient supplementation for age-related macular degeneration, cataract, and dry eye. J Ophthalmic Vis Res 2014; 9:487–493.  Back to cited text no. 4
    
5.
Huang JY, Yeh PT, Hou YC. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome. Clin Ophthalmol 2016; 10:813–820.  Back to cited text no. 5
    
6.
Huang JY, Yeh PT, Hou YC. Cyclosporine 0.05% ophthalmic emulsion for dry eye in Korea: a prospective, multicenter, open-label, surveillance study. Korean J Ophthalmol 2011; 25:369–374.  Back to cited text no. 6
    
7.
Demiryay E, Yaylal V, Cetin EN, Yldrm C. Effects of topical cyclosporine a plus artificial tears versus artificial tears treatment on conjunctival goblet cell density in dysfunctional tear syndrome. Eye Contact Lens 2011; 37:312–315.  Back to cited text no. 7
    
8.
Wan KH, Chen LJ, Young AL. Efficacy and safety of topical 0.05% cyclosporine eye drops in the treatment of dry eye syndrome: a systematic review and meta-analysis. Ocular Surf 2015; 13:213–225.  Back to cited text no. 8
    
9.
Stonecipher KG, Torkildsen GL, Ousler GW, Morris S, Villanueva L, Hollander DA. The IMPACT study: a prospective evaluation of the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye. Clin Ophthalmol 2016; 10:887–895.  Back to cited text no. 9
    
10.
Othman TM, Mousa A, Gikandi PW et al. Efficacy and safety of using topical cyclosporine A for treatment of moderate to severe dry eye disease. Saudi J Ophthalmol 2018; 32:217–221.  Back to cited text no. 10
    
11.
Peponis V, Papathanasiou M, Kapranou A et al. Protective role of oral antioxidant supplementation in ocular surface of diabetic patients. Br J ophthalmol 2002; 86:13691373.  Back to cited text no. 11
    
12.
Drouault-Holowacz S, Bieuvelet S, Burckel A, Rigal D, Dubray C, Lichon JL et al. Antioxidants intake and dry eye syndrome: a crossover, placebo-controlled, randomized trial. Eur J ophthalmol 2009; 19:337–342.  Back to cited text no. 12
    
13.
Gatell-Tortajada J. Oral supplementation with a nutraceutical formulation containing omega-3 fatty acids, vitamins, minerals, and antioxidants in a large series of patients with dry eye symptoms: results of a prospective study. Clin Intervent Aging 2016; 11:571–578.  Back to cited text no. 13
    
14.
Ziada HEA. Oral versus topical vitamin A antioxidant in treatment of dry eye syndrome. Int J Ophthalmic Res 2017; 3:252–258.  Back to cited text no. 14
    
15.
Gündüz K, Özdemir Ö. Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary Sjögren’s syndrome. Acta Ophthalmol 1994; 72:438–442.  Back to cited text no. 15
    
16.
Willen CM, McGwin G, Liu B. Efficacy of cyclosporine 0.05% ophthalmic emulsion in contact lens wearers with dry eyes. Eye Contact Lens 2008; 34:43–45.  Back to cited text no. 16
    
17.
Blades KJ, Patel S, Aidoo KE. Oral antioxidant therapy for marginal dry eye. Eur J Clin Nutr 2001; 55:589–597.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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