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Three Part Question

In [patients with allergic conjunctivitis] are [topical antihistamines better than systemic antihistamines] at [relieving ocular symptoms]

Clinical Scenario

A 14 yr old patient comes into the accident and emergency eye centre with red, sore, itchy eyes. He had been out in the countryside on an activities day with school and has a clear case of allergic conjunctivitis. His eyes have become incredible swollen and itchy and you want to give him some relief as quickly as possible and you wonder if topical antihistamines might be more effective than systemic tablets.

Search Strategy

Using the ovid interface
Ovid MEDLINE(R) 1966 to June Week 2 2006
Embase 1980 to 2006 Week 25
CINAHL 1982 to June Week 3 2006
{[exp rhinitis, allergic, perennial OR exp rhinitis, allergic, seasonal OR hayfever.mp.] AND [Antihistamines.mp. or exp Histamine H1 Antagonists OR exp Ophthalmic Solutions]} LIMIT to [humans and english language]
Chrochrane
Antihistamines AND Allergic conjunctivitis

Search Outcome

174 Papers were found in Medline of which 167 did not answer the three part question. The remaining 7 are listed in the table below.
No further Papers were gained from searching Embase, CINHAL and Cochrane databases.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
The Livostin Study Group Oct 1993 DENMARK	A total of 128 adult patients with a two year history of birch-pollen-provoked allergic rhinoconjunctivitis Topical (ocular and nasal) levocabastine v Oral terfenadine antihistamines	RCT	Ocular symptom control	No significant difference in the scores given by both the investigator and the patients between the two treatments. Both are deemed as good as each other in controlling ocular symptoms of allergic conjunctivitis.	Small sample group
Sohoel, P et al July 1993 UNITED STATES	115 patients with documented birch pollen allergy Topical and nasal levocabastine verses orally administered terfenadine for the prophylaxis and treatment of seasonal allergic rhinoconjunctivitis	RCT	Ocular symptom control	Overall a lower rate of symptoms reported in topical levocabastine group.	Small Study group
			Investigators assessment	Levocabastine v Terfenadine
			Red eye results favour topical and nasal levocabastine	p <0.01 at week 4. No further statistical significant results were gained.
			Worst eye results favour topical and nasal levocabastine	p <0.05 at week 4. No further statistical significant results were gained.
			From patient diaries of symptoms over entire treatment period. Scores favour levocabastine verses terfenadine.
			Itchy eyes	p<0.05 in favour of levocabastine
			Lacrimation	p<0.01 in favour of levocabastine
Abelson, M B. Welch, D L 2000 DENMARK	29 patients with no symptoms of allergic conjunctivitis were subjected to an allergen challenge Panatol (olopatadine hydrochloride ophthalmic solution 0.1%) Verses Claritin (loratadine 10 mg) tablets	RCT	Itchy Eyes - 1st allergen challenge. Allergen given 1 hour after medication	3min - p=0.002 in favour of panatol	Very small test group
				7min - p=0.001 in favour of panatol
				10min - p=0.004 in favour of panatol
			Itchy Eyes - 2nd allergen challenge. Allergen given 8 hours after medication	3min - No difference
				7min - p=0.0052 in favour of panatol
				10min - statistical trend present
Abelson, M B. Lanier, R Q 1999 DENMARK	A topical ocular antigen challenge induced allergic conjunctivitis in 15 subjects. To determine whether Patanol in combination with the systemic antihistamine Claritin (loratadine) reduces the ocular itching associated with allergic conjunctivitis more effectively than Claritin alone. Two separate allergen challenges on separate occasions. On the first occasion the allergen was instilled one hour after dosing with medications to look at the onset of action of the drugs, and ocular itching was graded at 3, 7, 10 and 20 minutes thereafter. The second allergen challenge was performed eight hours after dosing looking at the duration of action of medications, and itching graded after 3, 7, 10 and 20 minutes	RCT	Onset of action - Allergen given 1 hour after medication		Small Study group
			Patient eyes treated with Patanol/Claritin combination were significantly less itchy than those treated with systemic Claritin alone.	3, 7, 10min p=0.002
			Duration of action - allergen given 8 hours after medication
			Patient eyes treated with Patanol/Claritin combination were significantly less itchy than those treated with systemic Claritin alone.	3 and 7 mins p=0.05
				Statistical trend at 10 min 0.05
Lanier, B Q. Gross, R D. Marks, B B. Cockrum, P C. Juniper, E F June 2001 United States	95 patients with known allergy to birch pollen Olopatadine ophthalmic solution adjunctive to loratadine compared to loratadine alone - 7 day trial Both patient and investigator gave a score to severity of ocular symptoms	RCT	Overall mean score for ocular itching		Single blinded so patients knew whether they were on one drug or the combination Small study group
			Investigators found patients receiving olopatadine twice daily in addition to loratadine once daily exhibited less ocular itching	(P = 0.0436)
			Patients receiving olopatadine rated their ocular condition as more improved compared with those receiving loratadine alone	(P < 0.0022)
			Overall redness	No statistical significance. Results favoured combination therapy
			Immediate itching and redness scores also favoured the combination therapy
			Investigators impression	3, 10 20 mins p<0.05 for both itching and redness scores in favour of Olopatadine adjunctive to loratadine
			Quality of life was assessed by questionnaire
			Overall result favoured combination therapy	Statistically significant result p<0.05
Spangler, Dennis L. Abelson, Mark B. Ober, Andrew. Gotnes, Paulo J Aug 2003 United States	Seventy-three subjects were screened and randomised to treatment. Two subjects did not complete the study. The study compared the clinical signs and symptoms induced by Conjunctival Allergen Challenge and the Nasal Allergen Challenge. The effects of drugs administered by 3 different routes and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. Subjects who qualified were randomised to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-microg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray.	RCT	Conjunctival Allergen Challenge - Ololopatadine 0.1% ophthalmic solution Vs fexofenadine hydrochloride 180-mg tablets		Small study group
			Ocular itching reduced at	3 mins V's fexofenadine hydrochloride 180-mg tablets p=0.008
				5 mins V's fexofenadine hydrochloride 180-mg tablets p=0.0013
			Ocular redness	No statistical significance between treatments but overall trend favoured olopatadine ophthalmic solution at reducing redness.
Swedish GP Allergy Team Sept 2004 DENMARK	95 patients with a one year history of seasonal allergic conjunctivitis Topical (ocular and nasal) levocabastine compared with oral loratadine for treating seasonal allergic conjunctivitis Both patient and investigator gave a score to severity of symptoms	RCT	Mean ocular symptoms	No statistical difference between the two treatments was found.	Small study group
				Results favoured topical levocabastine
			Side effects	No statisically significant difference

Comment(s)

The treatment of seasonal allergic conjunctivitis can be done several different ways. This bet looks at whether topical antihistamines or oral systemic antihistamines provide better relief from ocular sysmptoms. All the papers studied found slightly different methods and results with most favouring a topical ocular preparation. From one of the papers we know that the flow of the nasolacrimal duct is unilateral[3]. This means that ocular instilled drugs can have a secondary effect on the nasal symptoms of allergic conjunctivitis but not the other way round. Some of the other studies [4,6,7] gave patients both ocular and nasal topical antihistamines and compared them to a systemic antihistamine. So because we know nasal treatment does not effect the eyes we can say that the treatment given into the eye acted alone and nasal treatment had no effect on the ocular symptoms due to the unilateral flow of the nasolacrimal duct. In paper [3] olopatadine 0.1% ophthalmic solution was directly compared with fexofenadine hydrochloride 180-mg tablets. This study showed great results in favour of olopatadine solution for the immediate relief of itching compared to that of systemic fexofenadine hydrochloride tablets. A study of 115 patients [4] found topical levocabastine was also better at relieving ocular itching than systemic terfenadine. It showed that from patient diaries scores eye itching and lacrimation were both statistically reduced over the entire treatment period and the investigators measurements also found topical levocabastine worked better. In a study by the Livostin Study Group [6] of 128 adult patients they to compared topical levocabastine verses terfenadine. they found that there was no significant difference in the treatments and found they were both as good as each other. The Swedish GP Allergy Team [7] did a study of 95 subjects lasting 5 weeks comparing topical levocabasine with oral loratadine, again it showed no statistical difference in the effect of topical verses systemic anihistamine treatment for allergic conjunctivitis. They did say that results favoured topical treatment with levocabastine. A different study [3] compared ocular olopatadine 0.1% ophthalmic solution with systemic loratidine. This found that both the immediate effect and duration of the topical olopatadine was greater than that of systemic treatment with loratidine. Two further studies [1,5] looked to see if olopatadine in combination with the systemic antihistamine loratadine reduces the ocular itching associated with allergic conjunctivitis more effectively than loratadine alone. Study [1] had 15 patients in it. Although it was a small sample group it found a tatistical trend in favour of the olopatadine in combination with the systemic loratadine for both the onset and duration of the medication compared to just sytemic loratadine. The final paper [5] looked at 95 patients. This also found that over the 7 day trial a combination of olopatadine in with systemic loratadine worked better than loratadine alone at relieving ocular itching. The combination therapy also gave better immediate relief from ocular itching. A quality of life questionaire filled out by the patients also concluded that the patients with the olopatadine / loratadine combination had a better quality of life than those on loratadine alone. Overall the studies results definately favour the use of topical antihistamine treatment over systemic treatment for immediate control of ocular itching. Results for the long term management for allergic conjunctivitis are not as conclusive but still favour topical antihistamines.

Clinical Bottom Line

Topical antihistamines are favoured to that of systemic antihistamines in the treatment of allergic conjunctivitis.

References

1. The Livostin Study Group A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis Allergy 1993 Oct. Vol 48(7):530-4
2. Sohoel, P et al Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis Journal of Allergy & Clinical Immunology 1993 Jul. Vol 92(1 Pt 1):73-81,
3. Abelson, M B. Welch, D L An evaluation of onset and duration of action of patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin (loratadine 10 mg) tablets in acute allergic conjunctivitis in the co Acta Ophthalmologica Scandinavica Supplement 200. Vol (230):60-3,
4. Abelson, M B. Lanier, R Q The added benefit of local Patanol therapy when combined with systemic Claritin for the inhibition of ocular itching in the conjunctival antigen challenge model Acta Ophthalmologica Scandinavica Supplement 1999. Vol (228):53-6
5. Lanier, B Q. Gross, R D. Marks, B B. Cockrum, P C. Juniper, E F Olopatadine ophthalmic solution adjunctive to loratadine compared with loratadine alone in patients with active seasonal allergic conjunctivitis symptoms Annals of Allergy, Asthma, & Immunology 2001 Jun. Vol 86(6):641-8,
6. Spangler, Dennis L. Abelson, Mark B. Ober, Andrew. Gotnes, Paulo J Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen ch Clinical Therapeutics Aug 2003. Vol 25(8):2245-67
7. Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis Allergy 1994 Sep. Vol 49(8):611-5