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ORIGINAL ARTICLE
Year : 2001  |  Volume : 49  |  Issue : 4  |  Page : 241-5
 

Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis.


Department of Ophthalmology, Pt. B.D. Sharma PGIMS, Rohtak, India

Correspondence Address:
S Singh
Department of Ophthalmology, Pt. B.D. Sharma PGIMS, Rohtak
India
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PMID: 12930116

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   Abstract 

PURPOSE: To study and compare the efficacy of supratarsal injection of dexamethasone sodium phosphate, triamcinolone acetonide and hydrocortisone sodium succinate in treating refractory vernal keratoconjunctivitis (VKC). METHODS: Prospective randomized, double-masked, case control trial, including 90 eyes of 45 patients with refractory VKC. Both eyes of each patient were randomly assigned to receive supratarsal injection of one of three compounds under study: dexamethasone sodium phosphate (2 mg), triamcinolone acetonide (10.5 mg), and hydrocortisone sodium succinate (50 mg). RESULTS: All the three drugs were equally effective with no statistically significant difference in the time of resolution of cobblestone papillae, lid oedema, conjunctival discharge and chemosis, Tranta's dots and shield ulcers. There was no statistically significant difference in the severity and rate of recurrence of disease following supratarsal injection of all the three drugs. But recurrence of disease to same severity was seen within 6 months of injection in all cases irrespective of compounds used. CONCLUSION: Supratarsal injection of corticosteroids is very effective for temporary suppression of severe inflammation associated with VKC.


Keywords: Anti-Inflammatory Agents, administration & dosage, Conjunctivitis, Allergic, drug therapy, Dexamethasone, administration & dosage, analogs & derivatives, Double-Blind Method, Eyelids, Humans,


How to cite this article:
Singh S, Pal V, Dhull C S. Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis. Indian J Ophthalmol 2001;49:241

How to cite this URL:
Singh S, Pal V, Dhull C S. Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis. Indian J Ophthalmol [serial online] 2001 [cited 2014 Oct 21];49:241. Available from: http://www.ijo.in/text.asp?2001/49/4/241/14694


Vernal keratoconjunctivitis (VKC) is a bilateral, recurrent, interstitial inflammation of the conjunctiva that occurs in warm weather in young patients predisposed to atopy.[1] Eighty percent of patients are below 14 years of age. Boys are usually more affected at 2:1 ratio.[2] The chief symptoms of this disease include severe itching, photophobia, redness, tearing and tenacious discharge.[3] The clinical signs in conjunctiva include cobblestone papillae in the upper tarsal conjunctiva, limbal conjunctival thickening with gelatinous nodules and Tranta's dots. Corneal involvement can occur in the form of shield ulcers and pannus.[4] In majority of children the disease resolves spontaneously between 2 and 10 years. Eyes with refractory and frequently recurrent VKC often develop potentially blinding disease or iatrogenic complications. These eyes often demonstrate corneal shield ulcers, vascularisation, plaque formation, corneal opacity or signs of corticosteroid abuse.

Recently a number of new therapeutic agents have been attempted in refractory VKC. They include topical non-steroidal anti-inflammatory agents (Suprofen),[6] topical mast cell stabilizers (Nedocromil, Lodoxamide),[7] topical immunomodulators (Cyclosporine),[8] topical antihistamines (Levocabastine),[9] and ganglioside derivatives (Miprogoside).[10] However, most of these newer treatment modalities have been found relatively ineffective. Systemic therapy with high doses of aspirin relieve some signs and symptoms, but tarsal cobblestone papillae and shield ulcers remain relatively unaffected.[11] More recently, successful use of supratarsal injection of corticosteroids has been reported in severe and refractory VKC. [12,13] We report the results of a prospective study comparing hydrocortisone, triamcinolone and dexamethasone in treatment of refractory VKC.


   Materials and Methods Top


This prospective, randomized, double masked case control study included 90 eyes of 45 patients. The study included patients with advanced and refractory VKC not responding or inadequately responding to month-long maximum topical therapy. The combination medical therapy consisted of non-steroidal anti-inflammatory drug (NSAID), mast cell stabilizer, antihistamine and corticosteroid. The eyes with active ocular infection and those patients who were concurrently treated for other allergic disorders were excluded from the study. Patients were randomly allocated to three groups of equal size and informed consent was obtained. Group A eyes received supratarsal injection of 2 mg dexamethasone, Group B eyes received supratarsal injection of 10.5 mg triamcinolone, and Group C eyes received supratarsal injection of 50 mg hydrocortisone. Thus corticosteroids given were in equivalent anti-inflammatory doses. All patients had a wash off period of two weeks prior to the administration of study drugs. In this period all topical medications were discontinued, and patients were maintained on frequent cold compresses and disodium cromoglycate 2% eye drops four times daily. The symptoms (itching, tearing, photophobia and redness) and the signs (lid oedema, tarsal papillae, conjunctival chemosis, conjunctival discharge, Tranta's dots and keratopathy) were subjectively graded by the patient and the treating physician respectively [Table - 1]. The grading was done at entry into the study, and at all subsequent follow-up visits.

The score for all these symptoms and signs was added to get the score at time of entry into the study and subsequently at each follow-up visit. Both eyes of a patient were injected with the same corticosteroids and were treated 3 weeks apart. After the supratarsal injection patients were advised frequent cold compresses and topical disodium cromoglycate 2% four times daily. The treating physician (who injected the drug) and the evaluating physician grading the symptoms and signs were masked during the study period. Each eye was evaluated at the third day, every week thereafter up to four weeks and then every month up to 6 months. All patients were observed for any side effects of corticosteroid injection such as ptosis, depigmentation of eyelid skin, infections, motility disturbances, conjunctival scarring and raised intraocular pressure (IOP).

Recurrence of disease was graded and scored. Moderate to severe disease was considered to be an indication for repeat supratarsal injection of corticosteroid. The results were statistically analysed and the p-value of <0.05 was taken as statistically significant.


   Injection technique Top


A method of staged anaesthesia was used to allow the injection to be easily tolerated. First, a drop of 4% xylocaine was instilled into the eye. A cotton-tipped applicator soaked in 2% xylocaine was held on the upper tarsal border of superior tarsus of the everted eyelid for approximately one minute. A 26G needle was used to inject 0.25ml of 2% xylocaine with epinephrine (1:200,000) while the superior tarsus was lifted away with a lid hook. The needle was placed subconjunctivally approximately 1mm above the superior tarsal border to avoid the marginal arcade blood vessels. This produced ballooning of the potential space between the conjunctiva and Muller's muscle. After 2 minutes, the time for the anaesthetic to take effect, a 26G, 5/8 inch needle was positioned in the supratarsal subconjunctival space and the intended corticosteroid was injected.


   Results Top


The patients enrolled included 40 (88.9%) males and 5 (11.1%) females with a mean age of 12.56 years (range 5 years to 23 years). The disease was bilateral in all patients and the mean age of onset of disease was 8.31 years. Twenty six (57.8%) patients had other systemic atopic features (asthma, hay fever, eczema) and 15 (33.3%) patients had a family history of allergic disorders. Twenty three (51.1%) patients demonstrated palpebral, 18 (40%) patients demonstrated mixed and 4 (8.9%) patients demonstrated the bulbar form of the disease. Thirty six patients (80%) had seasonal variation in severity of disease. Ten (22%) patients had shield corneal ulcers. There was no statistically significant difference in the mean age, mean age of onset, type of disease and corneal shield ulcers in the three groups. Group B had no female patient while group C had only one female patient [Table - 2].

Significant symptomatic improvement (p<0.001) was noticed in all patients within three days of the supratarsal corticosteroid injection. This response was independent of the severity or duration of disease. Improvement of symptoms preceded the resolution of signs. Among symptoms the itching was first to disappear and the photophobia was the last to disappear in all three groups (p<0.001). Mild symptoms recurred at 12 weeks' follow-up in all three groups. Photophobia was least in severity among the symptoms that recurred during follow-up.

Improvement in signs was noticed by 2 weeks. The lid oedema nearly disappeared (p<0.001) in 2 weeks and the size of cobblestone papillae reduced by 50% (p<0.01) at 2 weeks' follow up in all the three groups. There was reduction in conjunctival chemosis, discharge and Tranta's dots (p<0.001). The corneal shield ulcers healed completely by 3 weeks in all eyes in three groups. Clinical signs recurred in all the three groups. Lid oedema and conjunctival chemosis were the first to reappear. Cobblestone papillae started increasing in size at 12 weeks' follow-up. All eyes developed moderate to severe papillae (p<0.001) at the 5 months' follow-up visit. The conjunctival discharge recurred in all the three groups and no eye was completely free of discharge at the 4 months' follow-up visit. But there was no recurrence of corneal shield ulcer in any eye in any group. The recurrence was independent of the type of corticosteroid used.

Thus after initial rapid clinical improvement, clinical symptoms and signs recurred in all the three groups starting at 12 weeks' follow-up and the severity of recurrence of disease gradually increased enough by 5 months [Figure - 1] and [Figure - 2] to require repeat injection. No statistically significant difference was observed in the initially rapid improvement and recurrence rate among the three groups. No complication was seen in any eye in the three groups.


   Discussion Top


While VKC has wide geographical distribution, it is common in the tropics, including Mediterranean area, Balkans, North and South Africa, and the Indian subcontinent. Some patients develop severe recalcitrant disease which is unresponsive to standard treatment. These patients develop disease-related and/or iatrogenic complications with irreparable ocular morbidity and even blindness.[14] Many patients with advanced VKC remain markedly symptomatic and debilitated despite the most aggressive medical management including topical antihistamines, tear substitutes, NSAIDs, mast cell stabilizers and corticosteroids.[15-17] Such cases pose a great challenge. Surgical excision and cryotherapy of large papillae have been considered and abandoned due to extensive scarring. Topical cyclosporine brings in temporary symptomatic relief, but has very little effect on cobblestone papillae and shield corneal ulcers.[18]

There is a great need to devise a safe and effective treatment modality for such refractory cases. Holsclaw et al[12] in 1996 reported their initial experience in managing 12 such patients with supratarsal injection of corticosteroids. They noticed significant symptomatic and clinical improvement in all patients irrespective of type of corticosteroid used. Only one patient developed elevated IOP. More recently Saini et al[13] have observed similar beneficial results with this treatment modality.

In this series, we noticed a significant symptomatic improvement in all patients within 1-3 days of receiving supratarsal injection of each of the three corticosteroids: hydrocortisone, dexamethasone and triamcinolone. The response was independent of the severity of disease and was found to be statistically significant. A reduction of 50% or more in size of cobblestone papillae was noticed after 2 weeks in all patients and was independent of the type of corticosteroid used. But mild recurrence of symptoms was noticed after 12 weeks and after 5 months moderate to severe symptoms and signs reappeared in all patients in the three groups. Thus, at five months' follow-up most patients had developed crippling disease requiring a repeat injection. There was no statistically significant difference in the recurrence of symptoms and signs in the three corticosteroid treated groups. Significantly, none of the eyes showed recurrence of corneal shield ulcers by 6 months. Also no patient in either group developed any side effects of the therapy, including increased IOP.

Supratarsal injection of corticosteroids provides initial symptomatic relief by reducing the inflammation locally.[19] Intra-lesional depot steroid injections do not raise significant blood cortisol levels to exert systemic anti-inflammatory activity or cause remission of inflammation at another site in the body.[20] In our study, the initial response to treatment was consistent with reports of Holsclaw et al[12] and Saini et al.[13] They also observed maximal reduction in size of papillae in 2 weeks and healing of shield ulcers in 3 weeks. But in our study the symptoms and signs recurred during the follow-up period in all patients. Holsclaw et al[12] and Saini et al[13] have reported mild to moderate recurrence in 16% and 23% of patients respectively. This could be because of climatic variations in habitat of patients. Our patients came from arid and sandy areas, a climate which poses an important risk factor for VKC.

Based on the outcome of this study, we conclude that supratarsal injection of corticosteroids can be used for initial quick suppression of inflammation in patients with severe refractory disease in tropical areas. But a curative treatment for refractory VKC still remains elusive.

 
   References Top

1.Theodore FH, Schlossnan A. Vernal conjunctivitis. In: Ocular Allergy. Baltimore: Waverly Press Inc., 1958: pp 98-137.  Back to cited text no. 1    
2.Allansmith MR, Ross RN. Ocular allergy and mast cell stabilizers. Surv Ophthalmol 1986;30:229-44.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Jones BR. Vernal keratitis. Trans Ophthalmol Soc UK 1961;81:215-28.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Friedlaender MH. Current concept in ocular allergy. Ann Allergy 1991;67:5-13.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Buckley RJ. Vernal keratopathy and its management. Trans Ophthalmol Soc UK 1981;101:234-38.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Buckley DC, Caldwell DR, Reaves TA. Treatment of vernal conjunctivitis with suprofen, a topical non-steroidal anti-inflammatory agent. Invest Ophthalmol Vis Sci 1986;27:29-37  Back to cited text no. 6    
7.Caldwell DR, Verin P. Efficacy and safety of lodoxamide 0.1% versus cromolyn sodium 4% in patients with vernal keratoconjunctivitis. Am J Ophthalmol 1992;113:632-37.  Back to cited text no. 7    
8.Benezra D, Pe'er J, Brodsky M, Cohen E. Cyclosporine eye drops in the treatment of severe vernal conjunctivitis. Am J Ophthalmol 1986;101:278-82.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Smith LM, Southwick PC, Derosia DR, Abelson MB. The effects of levocabstine, a new highly potent and specific histamine H1, receptor antagonist, in the ocular allergen challenge model of allergic conjunctivitis. ARVO abstracts.Invest Ophthalmol Vis Sci 1989;30:503.  Back to cited text no. 9    
10.Centofeuti M, ShivVone M, Lambaise A. Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis. Eye 1996;10:422-24.  Back to cited text no. 10    
11.Abelson MB, Butrus SI, Weston JH. Aspirin therapy in vernal conjunctivitis. Am J Ophthalmol 1983;95:502-5.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Holsclaw DS, Witcher JP, Wong IG, Morgolis TP. Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J Ophthalmol 1996;121:243-49.  Back to cited text no. 12    
13.Saini JS, Gupta A, Pandey SK, Gupta V, Gupta P. Efficacy of supratarsal dexamethasone versus triamcinolone injection in recalcitrant vernal keratoconjunctivitis. Acta Ophthalmol Scand 1999;77:515-18.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Buckley RJ. Vernal keratoconjunctivitis. Int Ophthalmol Clin 1988;28:303-8.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Dahan A, Appel R. Vernal keratoconjunctivitis in the black child and its response to therapy. Br J Ophthalmol 1983;67:638-92.  Back to cited text no. 15    
16.Foster SC, Duncan J. Randomized clinical trial of topically administered cromolyn sodium for vernal keratoconjunctivitis. Am J Ophthalmol 1980;90:175-81.  Back to cited text no. 16    
17.Meyer E, Krans E, Zonis S. Efficacy of anti-prostaglandin therapy in vernal keratoconjunctivitis. Br J Ophthalmol 1987;71:497-99.  Back to cited text no. 17    
18.Secchi AG, Tognon MS, Leonard A. Topical use of cyclosporine in the treatment of vernal keratoconjunctivitis. 1990;110:641-645.  Back to cited text no. 18    
19.Nussenblatt RB, Whitcup SM, Palestine AG. In: Uveitis-Fundamentals and Clinical Practice. Mosby Year Book Inc; 1996. pp 99-102.  Back to cited text no. 19    
20.Guzzo CA, Lazarus GS, Werh VP. Dermatologic pharmacology. In Hurdman JG, Limbird LE, Motinoff PB, Rudon DW, editors:Goodman and Gilman's Pharmacological Basis of Therapeutics. New York: McGraw Hill; 1996.p.1597.  Back to cited text no. 20    


    Figures

[Figure - 1], [Figure - 2]

    Tables

[Table - 1], [Table - 2]


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