6 Viral conjunctivitis

Viral conjunctivitis is an extremely common ocular disorder, accounting for an estimated 20–30% of all eye related primary care consultations in the UK.1–3 Cases may present sporadically or as part of an epidemic. Epidemic keratoconjunctivitis (EKC) is usually due to adenovirus infection and acute haemorrhagic conjunctivitis (AHC) is most commonly due to picornavirus infection.4

Presentation

Symptoms and signs may include watery discharge, a foreign body sensation, lacrimation, eye discomfort, redness and oedema of the eyelids, sub-conjunctival haemorrhage, conjunctival follicles and palpable preauricular lymphadenopathy.4 Secondary bacterial infection is not uncommon.

Diagnosis

Diagnosis is usually made on clinical grounds, viral cultures rarely being used because of expense, time considerations, and the low sensitivity of the tests commonly employed. Discriminating viral from bacterial conjunctivitis on clinical grounds is often difficult, however, and many cases diagnosed clinically as presumed bacterial conjunctivitis are probably in fact viral in origin. In one study, 50% of cases diagnosed by ophthalmologists as presumed acute bacterial conjunctivitis did not have a bacterial aetiology on culture.2

Prognosis

Viral conjunctivitis is generally a self-limiting condition – acute symptoms typically lasting for between four to seven days before resolution gradually occurs over the following one to three weeks.

Numerous treatments have been used in an attempt to give symptomatic relief, shorten duration of illness and reduce infectivity; these treatments include artificial tears, cold compresses, and topical decongestants, antibiotics, antiviral agents, corticosteroids, interferon, non-steroidal anti-inflammatory drugs (NSAIDs) and povidone-iodine.5

Question

Does treatment for viral conjunctivitis confer benefit (where benefit is defined in terms of either reducing symptoms, shortening duration of illness or reducing infectivity)?

We will examine the evidence for interferon, antiviral agents, topical corticosteroids and topical NSAIDS separately.

Question

Does interferon treatment for viral conjunctivitis confer benefit?

The evidence

We found no systematic reviews. We found five published randomised controlled trials investigating the role of topical interferon.

Wilhelmus et al. undertook a double-blind trial comparing topical human fibroblast interferon with placebo for patients with acute conjunctivitis.6 Of the 50 patients studied, tear-film cultures proved to be positive in only 13 (26%). Outcome data were available for 37 patients. After one week of therapy, the interferon group showed significantly greater improvement in the symptoms and signs severity score than the controls for affected left (mean difference in severity score day 0 to day 7 was 9·4 for interferon and 6·6 for placebo group P = 0·02) but not right eyes (P = 0·5). Transient ocular irritation occurred more often in the treatment group than the control group (81% v 33%, P = 0·001).

Reilly et al. compared interferon with placebo eye drops in 34 patients recruited during an outbreak of EKC.7 Twenty of the 34 patients had positive viral cultures; 26 patients completed the study end-point. There was no significant difference between the groups in duration of symptoms. Summary statistics were not provided.

Adams et al. conducted a double-blind placebo controlled trial investigating the role of interferon alpha-2 for the treatment of adenoviral conjunctivitis in 14 patients.8 No difference was found in either duration or severity of illness between the treatment and placebo groups. No summary statistics were available for these outcome measures.

Stansfield et al. undertook a double-blind placebo controlled trial of human leucocyte interferon (HLI) in 15 subjects with acute haemorrhagic conjunctivitis (AHC).9 They described no difference in the “clinical course” of the illness between the two groups. The use of HLI did, however, appear to reduce the spread of AHC to other household members (secondary cases); three secondary cases were noted in the placebo group and none in the HLI group (P = 0·02).

Sundmacher et al. randomised 14 patients with virologically confirmed adenoviral conjunctivitis to either interferon alfa or placebo (albumin) eye drops.10 The authors reported “no clinically relevant therapeutic effect” for interferon but suggested that interferon may exert a prophylactic effect on uninflamed fellow eyes; no summary data were presented.

Question

Do antiviral agents for viral conjunctivitis confer benefit?

The evidence

We found no systematic review. We found three randomised controlled trials that evaluated the use of antiviral agents.

Dudgeon et al. conducted a double-blind trial comparing 5-iodo-2-deoxyuridine (IDU) with placebo in 70 patients with presumed adenoviral conjunctivitis.11 Adenovirus infection was proven in 35 patients. There was no difference in the severity or duration of symptoms between the two groups. No summary statistics were available.

A UK study compared amantadine with placebo in a conjunctivitis outbreak in a hospital for those with learning difficulties.12 Fifty per cent of subjects had positive viral cultures. The main outcome measures of interest were visual acuity (VA), the period of incapacity, and time required to attend hospital. Data on VA were available for only five patients in each group. The authors suggested that there was a marked difference between the amantadine

and placebo groups in ‘incapacity’ but no summary statistics were presented.

Pavan-Langston et al. compared two antiviral agents: adenine arabinoside (Ara A) and IDU in 22 eyes (15 subjects).13 The average duration of symptoms was 17 days in the Ara A treated group and 16 days in the IDU treated group. The authors concluded that neither treatment had an apparent effect on the course or severity of the conjunctivitis. No summary data were presented.

Question

Do topical corticosteroids for viral conjunctivitis confer benefit?

The evidence

We found no systematic review. We found one doubleblind randomised controlled trial. Ward et al. comparing topical trifluridine, topical dexamethasone and artificial tears in 74 military personnel with viral keratoconjunctivitis.14

Laboratory verification showed positive viral cultures in only 11 of the 74 patients in the study. No significant difference was found between the three groups in duration of symptoms. Mean duration of symptoms was 11 days in the control group (artificial tears), 11 days in trifluridine group and 10 days in dexamethasone group (P = 0·56).

Question

Do topical NSAIDS for viral conjunctivitis confer benefit?

The evidence

We found no systematic review but we found two trials. In an open trial, Kosrirukvongs studied the effect of topical NSAID eye drops combined with antibiotic eye drops for AHC.15 One hundred patients were randomised to either topical antibiotic alone (control group) or topical antibiotic and piroxicam eye drops. Seventy-five patients completed the study. Baseline comparison of symptoms showed pain to be a more common presenting feature in the control group (60·3%) than in the piroxicam group (36·6%). Mean recovery time for the piroxicam group was significantly reduced (4·9 (SD 4·4) versus 5·2 (SD 3·8); P = 0·003). Foreign body sensation, pain and tearing (lacrimation) were also relieved significantly more quickly in the piroxicam group. However, there was no significant difference in resolution of clinical signs and it does not appear that the difference in pain between the groups at recruitment was controlled for in the statistical analysis. A burning sensation

in the eyes was noted significantly more frequently in the

topical piroxicam group than the control group (89·5% v 41·2%; P <0·001).

Shuley et al. reported a double-blind trial of 117 patients diagnosed clinically with viral conjunctivitis.16 Patients were randomised to keterolac 0·5% eye drops four times a day or artificial tears. The 105 subjects were assessed three to four days post-randomisation. No significant difference was found in the change in symptom or sign scores or in the patients’ opinion of the usefulness of treatment between the groups, except for eye redness (which showed greater improvement in the artificial tears group, P = 0·012). Stinging with application of the drops was noted significantly more often in the keterolac group than in the placebo group (59·2% v 18·8%; P <0·001).

Discussion

Viral conjunctivitis is a common self-limiting condition for which various treatments have been investigated. Research into viral conjunctivitis is hampered by difficulties in obtaining confirmatory virological evidence of viral infection.

The evidence for the treatment of viral conjunctivitis is limited. The published RCTs are, in general, of poor quality and insufficiently powered to reliably detect a difference.6–10,13–15 Additionally, confirmation of the clinical diagnosis by virological methods has proved difficult.

On the basis of this limited evidence it appears that none of the treatments studied to date confer benefit in the management of viral conjunctivitis.

Implications for practice

There is insufficient evidence for any of the treatments to evaluate their usefulness for viral conjunctivitis. The evidence suggests that topical antiviral agents and interferon do not significantly alter the course of the disease. The two trials of topical NSAIDs have yielded conflicting results, one suggesting some benefit from piroxicam15 and the other showing no benefit from keterolac.16 However, neither trial showed a significant difference in the resolution of clinical signs and both indicate that a stinging sensation is more common with topical NSAIDs.

Implications for research

Larger, more rigorous trials are needed to clarify whether any of the treatments may be of benefit. Until more sensitive virological tests are developed, pragmatic trials studying those with a clinical diagnosis of viral conjunctivitis are likely to represent the most appropriate way forward.

References

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2.Mahajan VM. Acute bacterial infections of the eye: their aetiology and treatment. Br J Ophthalmol 1983;67:191–4.

3.Wilson A. The red eye: a general practice survey. J R Coll Gen Pract 1987;37:62–4.

4.Donahue S, Khoury J, Kowalski R. Common ocular infections: a prescriber’s guide. Drugs 1996;52:527–39.

5.Isenberg SJ, Apt L, Valenton M et al. A controlled trial of povidoneiodine to treat infectious conjunctivitis in children. Am J Ophthalmol 2002;134:681–8.

6.Wilhelmus K, Dunkel E, Herson J. Topical human fibroblast interferon for acute adenoviral conjunctivitis. Graefe’s Arch Clin Exp Ophthalmol 1987;225:464.

7.Reilly S, Dhillon B, Nkanza K et al. Adenovirus type 8 keratoconjunctivitis – an outbreak and its treatment with topical human fibroblast interferon. J Hyg Camb 1986;96:557–75.

8.Adams C, Cohen E, Albrecht J, Laibson P. Interferon treatment of adenoviral conjunctivis. Am J Ophthalmol 1984;98:429–32.

9.Stansfield S, De La Pena W, Koenig S et al. Human leucocyte interferon in the treatment and prophylaxis of acute haemorrhagic conjunctivitis. J Infect Dis 1984;149:822–3.

10.Sundmacher R, Wigand R, Cantell K. The value of exogenous interferon in adenovirus keratoconjunctivitis. Graefe’s Arch Clin Exp Ophthalmol 1982;218:139–40.

11.Dudgeon J, Bhargava S, Ross C. Treatment of adenovirus infection of the eye with 5-iodo-2-deoxyuridine. Br J Ophthalmol 1969; 53:533.

12.Marmion V. Treatment of adenovirus type 8 keratoconjunctivitis.

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13.Pavan-Langston D, Dohlman CH. A double blind clinical study of adenine arabinosine therapy of viral keratoconjunctivitis. Am J Ophthalmol 1972;74:81–8.

14.Ward J, Siojo L, Waller S. A prospective masked clinical trial of trifluridine, dexamethasone and artificial tears in the treatment of epidemic keratoconjunctivitis. Cornea 1993;12:216–21.

14.Kosrirukvongs M. Topical piroxicam and conjunctivitis. J Med Assoc Thail 1997;80:287–92.

15.Shiuey Y, Ambati B, Adamis AP. A randomized, double-masked trial of topical ketorolac versus artificial tears for treatment of viral conjunctivitis. Ophthalmology 2000;107:1512–17.