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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 2  |  Page : 525-531

Comparative study using cyclosporine A 0.05% eye drops, autologous serum 20% eye drops, and combined use of cyclosporine A 0.05% eye drops and autologous serum 20% eye drops in the treatment of moderate to severe dry eye


Department of Ophthalmology, Faculty of Medicine, Menoufia University, Shebeen Al-Koom, Menoufia, Egypt

Date of Submission19-Aug-2016
Date of Acceptance31-Oct-2016
Date of Web Publication25-Sep-2017

Correspondence Address:
Mohammad A Al-Sayed Ahmad Kasper
3 Sheraton Al-Matar, Area 4, Al-Nozha, Cairo, 11843
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.215461

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  Abstract 

Objectives
A comparative study was carried out between the cyclosporine A 0.05%, the autologous serum, and combined therapy of both in the treatment of moderate to severe dry eye.
Background
Dry eye disease is a common and often underdiagnosed condition.
Patients and methods
A prospective interventional case study was carried out on 30patients attending the ophthalmology outpatient clinic of Menoufia University; these patients were subdivided as follows: groupA received topical autologous serum 20% four times daily for 2months, groupB received cyclosporine A emulsion 0.05% twice daily for 2months, and groupC received topical cyclosporine A emulsion 0.05% two times daily and topical autologous serum 20% four times daily for 2months. The three groups received nonpreserved tears up to five times daily, to be followed 1month after stoppage of treatment, except for nonpreserved tears(Refresh Plus). All patients were subjected to a full assessment of history, slit-lamp examination, lissamine green staining of the ocular surface, the tear break-up time test, Schirmer's test, and conjunctival impression cytology before treatment, at 1 and 2months after treatment, and then 1month after stoppage of treatment. The results obtained were subjected to a statistical analysis.
Results
In our study, we found that autologous serum eye drops had a more delayed onset of action, but more sustained action; topical cyclosporine A had a rapid onset of action, but regression occurred soon after stoppage of treatment. Both autologous serum and cyclosporine 0.05% had additive effects with a rapid sustained action.
Conclusion
Combined topical cyclosporine A emulsion 0.05% and autologous serum eye drops 20% are effective in the treatment of dry eye cases through their combined anti-inflammatory and epitheliotropic effects. Therefore, we recommend the use of combined autologous serum 20% and cyclosporine 0.05% in the treatment of severe dry eye.

Keywords: autologous serum, cyclosporine A, dry eye, keratoconjunctivitis sicca


How to cite this article:
Al-Sayed Ahmad Kasper MA, Farahat HG, Al-Morsy OA, Alhagaa AA. Comparative study using cyclosporine A 0.05% eye drops, autologous serum 20% eye drops, and combined use of cyclosporine A 0.05% eye drops and autologous serum 20% eye drops in the treatment of moderate to severe dry eye. Menoufia Med J 2017;30:525-31

How to cite this URL:
Al-Sayed Ahmad Kasper MA, Farahat HG, Al-Morsy OA, Alhagaa AA. Comparative study using cyclosporine A 0.05% eye drops, autologous serum 20% eye drops, and combined use of cyclosporine A 0.05% eye drops and autologous serum 20% eye drops in the treatment of moderate to severe dry eye. Menoufia Med J [serial online] 2017 [cited 2019 Sep 18];30:525-31. Available from: http://www.mmj.eg.net/text.asp?2017/30/2/525/215461


  Introduction Top


Dry eye syndrome is a common disorder of the tear film that is characterized by a deficiency in the quantity and/or the quality of tears, an unstable tear film, ocular surface damage, and bothersome symptoms such as ocular irritation, dryness, fatigue, and fluctuating visual disturbances[1],[2],[3].

Dry eye disease(DED), also known as keratoconjunctivitis sicca, is a multifactorial disorder of the tears and ocular surface. Risk factors for the development of DED include advanced age, female sex, hormonal imbalance, autoimmune disease, abnormal corneal innervations, vitamin deficiency, environmental stress, contact lens use, infection, medication use, and ophthalmic surgery. The pathogenesis of DED is not fully understood; however, it is recognized that inflammation plays a prominent role in the development and amplification of the signs and symptoms of DED[4],[5],[6].

DED, a chronic inflammatory condition that may be mediated by activated T-cell lymphocytes, affects the ocular surface and lacrimal glands. The damage caused by DED may be irreversible and despite the availability of various tear substitutes, many patients with dry eye syndrome can experience corneal pathology, with a subsequent reduction in vision[7],[8],[9],[10],[11],[12],[13].

Since then, significant advances have been made in the treatment of many facets of dry eye including preservative-free artificial tear preparations, steroids, cyclosporine ophthalmic emulsion, oral pilocarpine, biotears oral formulation, supplementation with omega 3 essential fatty acids, punctal plugs, and iodide iontophoresis. Autologous serum and umbilical cord serum eye drops have been found in clinical trials to be beneficial in patients who have persistent symptoms and signs. In cases refractory to medical treatment, surgery may be necessary[14],[15],[16],[17],[18],[19],[20],[21],[22].

Despite the presence of all these advances in the treatment of dry eye, it remains a disorder of long term maintenance rather than permanent cure.


  Patients and Methods Top


Our study included 30 patients with dry eye, who were subdivided into three groups from among patients attending the outpatient ophthalmology clinic, Menoufia University Hospital. The research protocol adhered to the tenets of the Helsinki Declaration and was approved by the Local Ethics Committee (Ethics Committee at the Faculty of Medicine, Menoufia University, Shebeen Al-Koom, Egypt).

Exclusion criteria

Patients with a history or evidence of ocular surgery or ocular trauma within the previous 6months, pregnancy, or lactation were excluded. Also, patients with proved blood diseases, especially hepatitis B or hepatitis C, were excluded.

Inclusion criteria

Patients with chronic moderate to severe aqueous tear-deficient type dry eye with one or more dry eye-related symptoms including burning, blurred vision, foreign body sensation, dryness, photophobia, itching, and pain, patients with dry eye-related punctate epithelial keratopathy defined as corneal punctate fluorescein staining, Schirmer's test of less than 10mm/5min, andtearbreak-up time(TBUT) of less than 10 s were included.

Examination technique

All patients were subjected to the following:

Pretreatment assessment

Assessment of full medical and ophthalmic history (using Ocular Surface Disease Index), slit-lamp examination, lissamine green staining of ocular surface (according to the van Bjiesterveld scale [23–25]), TBUT test, Schirmer's test with and without topical anesthesia [26], and conjunctival impression cytology [27] (according to Nelson's classification for squamous metaplasia [28],[29]).

Treatment data

The first group (A) received topical autologous serum 20% four times daily for 2 months, the second group(B) received cyclosporine A emulsion 0.05% two times daily for 2months, and the last group (C) received topical cyclosporine A emulsion 0.05% two times daily and topical autologous serum 20% four times daily for 2months. The three groups received nonpreserved tears (Refresh Plus; Allergan Australia Pty Ltd., Pacific Highway, Gordo) up to five times daily up to 1month after stoppage of treatment, except for nonpreserved tears (Refresh Plus; Allergan).

Post-treatment assessment

Assessment of full medical and ophthalmic history (Ocular Surface Disease Index) with a special focus on symptomatic improvement, slit-lamp examination, lissamine green staining of the ocular surface(according to van Bjiesterveld scale), TBUT test, Schirmer's test with and without topical anesthesia and conjunctival impression cytology (according to Nelson's classification for squamous metaplasia were performed at 1, 2, and 3months after treatment).


  Results Top


Demographic data of the studied group

Sex

In the first group, there were six(60%) women and four(40%) men, in the second group, there were six(60%) women and four (40%) men, and in the third group there were three(30%) women and seven(70%) men as shown in [Table1] and [Figure 1].
Table 1: Comparison between the three groups in age and sex distribution

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Figure 1: The mean results according to sex.

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Age

The age of the patients in group(A) ranged from 28 to 75years, with a mean of 51.1years, with an SD of 16.37years, whereas in group(B), the age of the patients ranged from 32 to 73years, with a mean of 52.9years with an SD of 13.5, and in group(C), the age of the patients ranged from 45 to 79years, with a mean of 62.5years with an SD of 10.17 as shown in [Table1].

Comparison between three groups of clinical assessment

In our study, we found that there was a statistically nonsignificant(NS) difference between the three groups in the effect of treatment on symptoms at 1, 2, and 3months as shown in [Table2],[Table3],[Table4].
Table 2: Comparison between groups A and B in symptoms

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Table 3: Comparison between groups B and C in symptoms

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Table 4: Comparison between groups A and C in symptoms

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TBUT, Schirmer's test values, and squamous metaplasia grading 1 and 2months after treatment showed a statistically significant(SS) difference between groupsB and A and a highly significant(HS) difference 3months after treatment as shown in [Figure 2] and [Figure 3]; there was NS difference in 1-month and 2-month post-treatment ocular staining grading and an SS difference at 3months after treatment as shown in [Figure 4].
Figure 2: A comparison between groups B and C in tear break-up time (TBUT).

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Figure 3: A comparison between groups A and C in tear break-up time (TBUT).

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Figure 4: A comparison between groups A and B in the Schirmer test.

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There was NS difference between groupsB and C in TBUT values, Schirmer test values, and lissamine green staining 1month after treatment, with a HS difference 3months after treatment as shown in [Figure 5]. Also, there was an SS difference in squamous metaplasia grading 1 and 3months after treatment.
Figure 5: The adverse effect comparison.

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There was NS difference between groupsA and C in the TBUT values, Schirmer test values, and squamous metaplasia grading 2 and 3months after treatment. There was an SS difference 1month after treatment.

These results showed that autologous serum eye drops had more delayed onset of action, but a more sustained action; topical cyclosporine A had a rapid onset of action, but regression occurred soon after stoppage of treatment. Both autologous serum and cyclosporine 0.05% exerted additive effects as a rapid sustained action.

Also, we found that autologous serum eye drops led to a greater improvement in the degree of keratinization than topical cyclosporine A 0.05% and this can be attributed to the fact that the drops included growth factors, fibronectin, and vitamins.


  Discussion Top


Dry eye is a multifactorial disease of the tears and the ocular surface that results in symptoms of discomfort, visual disturbances, and tear film instability, with potential damage to the ocular surface.

GroupA included 10patients treated with topical autologous serum 20% and preservative-free artificial tears for 2months. Patients were on preservative-free artificial tears only for 1month during the follow-up period.

The age distribution of the patients in our study ranged from 28 to 75years, whereas in Noble etal.'s [22] study, the age of the patientsranged from 30 to 40years, and in Ogawa etal.'s [18] study, the age of the patientsranged from 22 to 43years. This difference in age distribution may be correlated to earlier presentation of patients in studies carried out abroad.

In terms of symptoms, there was a HS difference before treatment and 3months after treatment, with an 80% improvement from severe and disabling(grade3) to mild or no symptoms(grade0). The P- value was 0.007.

In Noble etal.'s [22] study: 32 eyes were assessed; there was 100% significant improvement in symptoms within 1month of treatment.

InOgawa etal.'s [18] study, 14patients were assessed; 93% of the patients reported a significant improvement in their symptoms at the end of the treatment.

This difference from other studies may be related to variations in the severity of the conditions studied, being more severe in our study, and thus a significant improvement started to appear 3months after treatment.

In terms of TBUT and Schirmer's values, there was a SS difference between pretreatment and post-treatment TBUT and a HS difference in Schirmer's values 1month after treatment. Ahighly SS difference was detected between pretreatment and post-treatment TBUT values and Schirmer's values 2 and 3months after treatment.

In the Noble etal.'s [22] study, 32 eyes were assessed; there was a significant improvement in TBUT and Schirmer's test scores within 1month of treatment in all patients.

InOgawa etal.'s [18] study, 14patients were assessed; 95% of the patients experienced a significant improvement in TBUT scores: from 2.8 to 5.8 s, with P less than 0.05. Schirmer's test was not evaluated.

This difference from other studies may be related to variations in the severity of the conditions studied, being more severe in our study, and thus a significant improvement occurred 3months after treatment.

The improvement in ocular surface staining scores in our study started gradually 1month after treatment and continued to improve during 2 and 3months after treatment. This is also in agreement with other studies such as Noble etal.[22], Ogawa etal.[18], in which the improvement in ocular surface staining scores occurred more rapidly 1month after treatment.

No significant difference was detected between the results of our study and other studies such asNoble etal.'s [22] studyandOgawa etal.'s [18] study in the pretreatment results of conjunctival impression cytology.

The squamous metaplasia and distribution of goblet cells showed marked improvement 3months after treatment.

There was a significant difference between groupsB and A in the effect of treatment on the degree of keratinization 1 and 3months after treatment and no significant difference between the three groups2months after treatment.

This was not in agreement with other studies, and this difference may be related to the severity of the conditions studied, being more severe in groupB.

In our study, no significant complications were reported with the use of serum drops, except eczema in a single case, which was treated with topical corticosteroid. Amajor complication that we encountered was the requirement of repeated blood donation and the need for refrigeration of the autologous serum drops as shown in [Table5].
Table 5: Comparison between groups A and B in complications and side effects of treatment

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GroupB included 10patients treated with topical cyclosporine A emulsion 0.05% and preservative-free artificial tears for 2months. Patients were on preservative-free artificial tears only for 1month during the follow-up period.

In our study, the mean age distribution was 52.9±13.5years.

In Brown etal.'s [17] study, the mean age distribution was 45.05years and in Perry etal.'s [21] study, the mean age distribution was 43.17years. Thelowerage incidence in our study may be attributed to the earlier development of dry eye, which might be linked to increased previous ocular surface infections(trachoma).

In terms of symptoms, there was a SS difference before treatment and 1 and 2months after treatment, with a 90% improvement from severe and disabling symptoms(grade3) to mild or no symptoms(grade0), with a P- value of 0.0008. Symptoms worsened in 40% of patients 3months after treatment.

In Brown etal.'s [17] study, 14patients were assessed; of these, 93% of patients showed a significant improvement in symptoms at the end of the treatment.

In Perry etal.'s [21] study, 20patients were assessed; all patients reported a significant improvement in symptoms.

This difference from other studies may be related to variations in the severity of the conditions studied, being more severe in our study, and thus a significant improvement started to appear 3months after treatment.

In our study, there was a statistically HS difference between pretreatment and post-treatment TBUT and Schirmer I test values 1, 2, and 3months after treatment.

There was a SS difference between pretreatment and 1-month and 3-month post-treatment TBUT values in Brown etal.'s [17] study and Perry etal.'s [21] study.

In Brown etal.'s [17] study, there was a SS difference between pretreatment and post-treatment Schirmer's scores (mean±SD=7.55±1.44, P=0.033) and the same result was obtained in Perry etal.'s [21] study, in which mean±SD=7.64±1.12, P=0.012. This is also in agreement with our results.

In our study, there was a SS improvement in staining grade; this effect started gradually 1month after treatment and continued over2 and 3months after treatment. Other studies such as Brown etal.'s [17] study and Perry etal.'s [21] study obtained results similar to ours in terms of the effect of treatment on lissamine green staining of the ocular surface.

No significant difference was detected between our study and other studies such as Brown etal.'s [17] study and Perry etal.'s [21] study in terms of pretreatment results of conjunctival impression cytology.

The most commonly reported side-effect with topical cyclosporine therapy in other studies was mild ocular burning and stinging upon instillation and this occurred in 70% of our patients; the remaining 50% of our patients complained of foreign body sensation, ocular pain, and conjunctival hyperemia as shown in [Table6].
Table 6: Comparison between groups B and C in complications and side effects of the treatment

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GroupC included 10patients treated with combined topical autologous serum 20%, topical cyclosporine 0.05% and preservative-free artificial tears for 2months. Follow-up on preservative-free artificial tears was performed only for 1month.

In our study, the age distribution ranged from 45 to 79years.

In our study, there was a HS difference between pretreatment and 3-month post-treatment symptoms, with an 80% improvement from severe and disabling symptoms (grade3) to mild or no symptoms (grade0), with a P- value of 0.007, which is similar to groupA.

In terms of TBUT and Schirmer's test scores, there was a statistically HS improvement that started 1month after treatment and continued to show improvement over2 and 3months.

In our study, a HS improvement in ocular surface staining started 1month after treatment and reached its maximum 3months after treatment.

There was a SS improvement in the degree of squamous metaplasia and a SS improvement in goblet cell density as shown in [Table7].
Table 7: Improvement in impression cytology in group C

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Summary and recommendations

On the basis of the findings of the present study, we can conclude that combined topical cyclosporine A emulsion 0.05% and autologous serum eye drops 20% are effective in the treatment of dry eye cases through their combined anti-inflammatory and epitheliotropic effects. Also, we found that autologous serum eye drops led to greater improvement in the degree of keratinization than topical cyclosporine A 0.05% and this can be attributed to the fact that the drops included growth factors, fibronectin, and vitamins.

Therefore, we recommend the use of combined autologous serum 20% and cyclosporine 0.05% drops in the treatment of severe dry eye for their combined rapid and sustained effects. Also, further researches are required to determine the effect of topical cyclosporine and topical autologous serum after 3months to ensure either dryness is cured or there is incidence of recurrence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

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

  [Table1], [Table2], [Table3], [Table4], [Table5], [Table6], [Table7]



 

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