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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 106  |  Issue : 3  |  Page : 206-209

Autologous serum eyedrops versus systemic doxycycline and topical corticosteroids in the treatment of recurrent corneal erosion


Department of Ophthalmology, Zagazig Faculty of Medicine, Zagazig, Egypt

Date of Submission05-Jun-2013
Date of Acceptance06-Jul-2013
Date of Web Publication28-Feb-2014

Correspondence Address:
Haitham Y Al-Nashar
Zagazig Faculty of Medicine, 44519, Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2090-0686.127406

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  Abstract 

Purpose
The aim of the study was to evaluate the efficacy of autologous serum eyedrops for the treatment of recurrent corneal erosion when compared with systemic doxycycline and topical steroids.
Patients and methods
In this prospective study, 27 eyes of 20 patients with recurrent corneal erosion were divided into two groups. In group A (14 eyes), the patients were treated with autologous serum eyedrops and in group B (13 eyes), the patients were treated with systemic doxycycline and topical steroids. In group A, autologous serum eyedrops were administered five times daily. Serum eyedrops were prepared by obtaining 50 ml of patient's blood and allowing it to clot, and the serum was obtained by centrifugation for 15 min. Detailed informed consent was obtained from all patients before the study. Patients in group B received oral doxycycline (50 mg) twice daily and topical fluoromethalone (0.1%) three times daily. The two groups were followed up for 6 months and were compared for the signs of relapse or recurrence of corneal symptoms and for any ocular complications.
Results
The study included 27 eyes of 20 patients (age range: 10-45 years). Eleven eyes in group A (78.5%) had complete healing of erosions with no relapse of the disease during the follow-up period. Two eyes (14.3%) presented with a recurrence after the end of the treatment and one eye (7.1%) failed to heal. No ocular complications were detected during the follow-up. In group B, eight eyes (61.5%) showed complete healing with no relapse of the disease during the follow-up period and one eye (7.7%) failed to heal. Four eyes (30.7%) presented with a recurrence after the end of the treatment, with a significant difference compared with group A (P = 0.02). One patient in group B showed an increase in intraocular pressure in the follow-up period.
Conclusion
This study suggests that the treatment of recurrent corneal erosion with autologous serum eyedrops gives the same results as with the treatment with systemic doxycycline and topical steroids, with low recurrence rate and less complication.

Keywords: Autologous serum; corneal erosion; doxycycline; epithelial defect; serum eyedrops


How to cite this article:
Al-Nashar HY, Shahien EA, Atya MA. Autologous serum eyedrops versus systemic doxycycline and topical corticosteroids in the treatment of recurrent corneal erosion. J Egypt Ophthalmol Soc 2013;106:206-9

How to cite this URL:
Al-Nashar HY, Shahien EA, Atya MA. Autologous serum eyedrops versus systemic doxycycline and topical corticosteroids in the treatment of recurrent corneal erosion. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2020 Jun 5];106:206-9. Available from: http://www.jeos.eg.net/text.asp?2013/106/3/206/127406


  Introduction Top


Recurrent corneal erosion syndrome (RCES) is a common cause of disabling ocular symptoms [1]. It is a chronic relapsing disease characterized by repeated episodes of pain, photophobia, redness, and lacrimation. These symptoms, usually occurring upon awakening, are related to corneal de-epithelialization in the areas of weakly adhered corneal epithelium [2].

RCES may be either primary or secondary; trauma is the initiating factor for erosion in many patients, especially trauma from a scratch that damages or destroys the corneal basement membrane. Secondary causes that may lead to recurrent erosion include chemicals, thermal injuries, previous herpetic keratitis,  Meibomian gland More Details dysfunction, ocular rosacea, diabetes mellitus, Salzmann's nodular degeneration, band keratopathy, previous bacterial ulceration, keratoconjunctivitis sicca, and epidermolysis bullosa [3].

Abnormal formation of hemidesmosomes or anchoring filaments at the basal layer of corneal epithelium is believed to play an important role in the pathogenesis of recurrent corneal erosions [4]. The ultrastructural changes that reduce adhesion of the corneal epithelium include a deficient epithelial basement membrane, the absence and abnormality of hemidesmosome, and the loss of anchoring fibrils [5].

A possible cause for these pathologic changes is degradation of the epithelial attachment complexes by matrix-degrading enzymes. Increased level or activity of several members of the matrix metalloproteinase (MMP) enzyme family, including MMP-2 and MMP-9, have been reported in patients with recurrent erosion [6].

On the basis of biochemical evidence implicating increased MMP activity in the pathogenesis of this condition, there is a rationale for using therapy aimed at inhibiting the activity of these enzymes. Corticosteroids and tetracyclines have been reported to inhibit one or more metalloproteinases [7].

Autologous serum supplies the eye surface with several substances that are essential for the recovery of the damaged epithelium, such as vitamin A, epidermal growth factor, transforming growth factor, fibronectin, and many other cytokines [8]. In the last few years, autologous serum has been frequently used for topical therapy in patients with ocular surface disorders, as serum contains a mixture of growth factors, nutritional factors, and other mediators involved in wound-healing regulation [9].

Autologous serum extracted from patients' own blood is a nonallergenic, nonconserved drug that is similar to natural tears in many aspects such as biochemistry, viscosity, or epitheliotrophy [10].

The aim of this study was to evaluate the efficacy and safety of autologous serum eyedrops for the treatment of recurrent corneal erosions when compared with systemic doxycycline and topical steroids.


  Patients and methods Top


In this study, 27 eyes of 20 patients with recurrent corneal erosion were included. They were divided into two groups: In group A (14 eyes), the patients were treated with autologous serum eyedrops and in group B (13 eyes), the patients were treated with systemic doxycycline and topical steroids.

Detailed history was taken from all patients, including age, sex, previous medical and ocular diseases, history of trauma, duration of symptoms, and frequency of the erosions. In all patients, routine ophthalmic examination was performed. Slit-lamp biomicroscopy and corneal fluorescein staining were also performed.

In group A, the serum eyedrops were prepared after informed consent was obtained. For preparation of the autologous serum, 50 ml blood sample was drawn from the antecubital vein and was left to clot spontaneously for 1 h; after that, it was centrifuged at 1500 rpm for 5 min (Nüve NF 200 Bench top Centrifuge, Birkan Izgin, Germany). Then, the serum was separated and was diluted to 50% with sterile saline in a ratio of 1 : 1. The obtained solution was then transferred into a bottle with ultraviolet light protective coating on its surface. The final preparation was introduced in 5-ml eyedrops bottles with ultraviolet light protective coating to avoid vitamin A degradation by light. Patients were instructed to refrigerate (4°C) the bottle that they were using and to store the rest of the bottles in a freezer (−20°C) until required. The patients were instructed to use the autologous serum eyedrops five times daily.

Patients in group B received a combined therapy of oral doxycycline (50 mg) twice daily and topical fluoromethalone (0.1%) three times daily.

The two groups were followed up for 6 months. They were followed up after 2, 4, and 6 weeks, and then every month. They were compared for erosion healing, relapse of signs, recurrence of corneal symptoms, and for any ocular complications.


  Results Top


A total of 27 eyes of 20 patients diagnosed as recurrent corneal erosion were included in this study. The mean age of the patients was 24.8 years (range 10-45 years). The study included 12 male patients and eight female patients. The patients were randomly divided into two groups; patients in group A (14 eyes) were treated with autologous serum eyedrops and those in group B (13 eyes) were treated with both systemic doxycycline (50 mg) twice daily and fluoromethalone eyedrops (0.1%) three times daily. All patients were followed up for 6 months.

In group A, eight eyes (57.5%) showed complete healing within 2 weeks, four eyes (28.4%) within 1 month, and one eye (7.1%) healed completely within 6 weeks; only one eye (7.1%) failed to heal.

In group B, seven (53.8%) eyes showed complete healing within 2 weeks, three eyes (23.1%) within 1 month, and two eyes (15.4%) healed completely within 6 weeks; only one eye (7.7%) failed to heal.

These results are shown in [Table 1], and there is no statistically significant difference between the two groups in the healing time.
Table 1: Healing of erosion

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Eleven eyes in group A showed complete healing without any relapse or recurrence during the whole follow-up period, whereas only two eyes (14.3%) showed relapse with a recurrence of the erosion within 3 months after initial complete healing. One of the eyes healed after 2 weeks and then showed recurrence after 9 weeks of the end of the treatment. The other eye healed after 4 weeks and then showed recurrence after 11 weeks of the initial complete healing and after end of the treatment. They were retreated with the same autologous drop, and both of them showed complete healing again.

In group B, eight eyes showed complete healing without any relapse or recurrence during the whole follow-up period, whereas four eyes (30.7%) in the same group showed recurrence of corneal erosion; two of them showed recurrence after 7 weeks, one eye after 10 weeks, and the fourth after 12 weeks of initial complete healing. They were retreated with the combined therapy of both topical steroid and systemic doxycycline; two of them responded to the treatment and showed complete healing, whereas the other two eyes failed to heal and other line of treatment was tried.

One eye (7.7%) in group B showed elevation of intraocular pressure (IOP) (28 mmHg) after 1 month of treatment; hence, the topical steroid was stopped and replaced by other line of treatment (artificial tears eyedrops).

These data are shown in [Table 2], with a significant difference between the two groups (P = 0.02).
Table 2: Recurrence and complications

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  Discussion Top


RCES is commonly encountered in ophthalmic practice. It is characterized by disturbance of the epithelial basement membrane resulting in defective adhesion and recurrent breakdown of the epithelium. The condition most commonly follows superficial corneal trauma, especially a scratch. It may also occur in certain corneal dystrophies [11]. Various treatment modalities have been tried to alleviate the symptoms as well as to prevent further recurrences. New conservative modalities including autologous serum eyedrops can help a vast majority of patients with RCES [12].

In this study, 27 eyes with recurrent corneal erosion were divided into two groups; patients in group A (14 eyes) were treated with autologous serum eyedrops and patients in group B (13 eyes) were treated with topical steroid and systemic doxycycline. In group A, eight eyes (57.8%) showed complete healing within 2 weeks, four eyes after 1 month, and one eye after 6 weeks, whereas one eye failed to heal and other line of treatment was tried for it.

Nikolaos et al. [13] studied the effect of autologous serum for the treatment of recurrent corneal erosions on 33 eyes of 33 patients (mean age 49.3 ± 9.8). Autologous serum drops were administered for a 6-month period, six times daily for the first 3 months and four times daily for the remaining 3 months The mean follow-up period was 30 ± 6.3 months. They found that none of the patients experienced a recurrence during the treatment period. Twenty-eight patients (85%) had complete healing of erosions, with no relapse of the disease during the whole follow-up period. Five patients (15%) presented a single recurrence 3-12 months after the end of the treatment. No sight-threatening complications were reported during the follow-up. There was no statistically significant difference in the IOP measurements (P < 0.38) between the pretreatment and post-treatment patient groups.

Chiang et al. [14] studied the efficacy and safety of allogeneic serum in the treatment of persistent corneal epithelial defect. Thirty-six patients with persistent corneal epithelial defect (PED) used the serum eyedrops every hour. The epithelial defect healed in six patients (16.7%) within 1 week with an additional nine patients (25%) in 1-2 weeks. Twenty-one patients (58.3%) did not completely heal in the second week. In agreement with our study, none of the 36 patients reported any adverse events during therapy.

To investigate the efficacy of umbilical cord serum eyedrops for the treatment of patients with recurrent corneal erosions, Kyung et al. [15] studied 35 eyes of 35 patients (mean age was 46.6 ± 13.4 years). Eighteen eyes were treated with 20% umbilical cord serum eyedrops in addition to artificial tears (group A), and 17 eyes received artificial tears only (group B). Frequency of recurrence of corneal erosions was compared between the two groups, with a mean follow-up duration of 14.7 ± 2.5 months. No significant differences in age, sex, and follow-up duration were observed between the two groups. In group A, recurrence occurred two times in three eyes, one time in three eyes, and did not occur in 12 eyes. In group B, recurrence occurred five times in one eye, three times in five eyes, two times in eight eyes, one time in two eyes, and did not occur in one eye. The mean frequency of recurrence was 0.50 ± 0.79 per month in group A and 2.24 ± 1.09 in group B (P = 0.01). No significant complications associated with serum use were observed.

Patients in group B (13 eyes) in this study were treated with topical steroid and systemic doxycycline. Seven eyes showed complete healing after 2 weeks, three eyes after 1 month, two eyes after 6 weeks, and one eye failed to heal. Four eyes showed recurrence after healing, with a significant difference from group A (P = 0.02); only one case in group B showed increased IOP.

Louis et al. [16] studied the effect of using the combination of oral doxycycline and topical corticosteroid on the treatment of RCES. Twenty-one patients received oral doxycycline (50 mg) twice daily and topical fluoromethalone (0.1%) three times daily. After 8 weeks, 15 patients (71%) were symptom free. They reported that treatment of RCES with the combination of oral doxycycline and topical corticosteroid is effective.

To evaluate the effect of inhibitors of MMP-9, Dilek et al. [17] used oral doxycycline (50 mg, two times a day) for 2 months along with a topical corticosteroid (either methylprednisolone 1%, prednisolone acetate 1%, or fluoromethalone 0.1%), three times a day, for 2-3 weeks. In the treatment of recalcitrant recurrent corneal erosions, they found that there were no recurrences of this condition when treated with these therapies.


  Conclusion Top


Autologous serum eyedrops are effective as topical steroid, and systemic doxycycline is effective in the treatment of recurrent corneal erosion. The serum eyedrops have lower recurrence rate with less complication than the combined therapy of steroid and doxycycline.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Dua HS, Lagnado R, Raj D, Singh R, Mantry S, Gray T, Lowe J. Alcohol delamination of the corneal epithelium: an alternative in the management of recurrent corneal erosions. Ophthalmology 2006; 113:404-411.  Back to cited text no. 1
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2.Singh RP, Raj D, Pherwani A, Lagnado R, Abedin A. Eatamadi H et al.Alcohol delamination of the corneal epithelium for recalcitrant recurrent corneal erosion syndrome: a prospective study of efficacy and safety. Br J Ophthalmol 2007; 91:908-911.  Back to cited text no. 2
    
3.Di Girolamo N, Chui J, Coroneo MT, Wakefield D. Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res 2004; 23:195-228.  Back to cited text no. 3
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4.Friberg TR, Ohji M, Scherer JJ, Tano Y. Frequency of epithelial debridement during diabetic vitrectomy. Am J Ophthalmol 2003; 135:553-554.  Back to cited text no. 4
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5.Ogawa Y, Okamoto S, Mori T, Yamada M, Mashima Y, Watanabe R, et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant 2003; 31:579-583.  Back to cited text no. 5
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6.Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. Am J Ophthalmol 2001; 132:8-13.  Back to cited text no. 6
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7.Wang L, Tsang H, Coroneo M. Treatment of recurrent corneal erosion syndrome using the combination of oral doxycycline and topical corticosteroid. Clin Experiment Ophthalmol 2008; 36:8-12.  Back to cited text no. 7
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8.Akyol-Salman I. Effects of autologous serum eye drops on corneal wound healing after superficial keratectomy in rabbits. Cornea 2006; 25:1178-1181.  Back to cited text no. 8
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9.Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol 2001; 85:1188-1197.  Back to cited text no. 9
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10.Del Castillo JM, de la Casa, JM, Sardiña RC, Fernández RM, Feijoo JG, Gómez AC, et al. Treatment of recurrent corneal erosions using autologous serum. Cornea 2002; 21:781-783.  Back to cited text no. 10
    
11.Das S, Seitz B. Recurrent corneal erosion syndrome. Surv Ophthalmol 2008; 53:3-15.  Back to cited text no. 11
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12.Watson SL, Secker GA. The effect of therapeutic human serum drops on corneal stromal wound-healing activity. Curr Eye Res. 2008; 33:641-652.  Back to cited text no. 12
    
13.Ziakas NG, Boboridis KG, Terzidou C, Naoumidi TL, Mikropoulos D, Georgiadou EN, Georgiadis NS. Long-term follow up of autologous serum treatment for recurrent corneal erosions. Clin Experiment Ophthalmol 2010; 38:683-687.  Back to cited text no. 13
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14.Chiang CC, Chen WL, Lin JM, Tsai YY. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect. Eye (Lond). 2009; 23:290-293.  Back to cited text no. 14
    
15.Yoon KC, Choi W, You IC, Choi J. Application of umbilical cord serum eyedrops for recurrent corneal erosions. Cornea 2011; 30:744-748.  Back to cited text no. 15
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16.Wang L, Tsang H, Coroneo M. Treatment of recurrent corneal erosion syndrome using the combination of oral doxycycline and topical corticosteroid. Clin Experiment Ophthalmol 2008; 36:8-12.  Back to cited text no. 16
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17.Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. Am J Ophthalmol 2001; 132:8-13.  Back to cited text no. 17
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Introduction
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