VIRAL CONJUNCTIVITIS

Signs and Symptoms

The two frequently encountered forms of viral conjunctivitis are pharyngoconjunctival fever (PCF) and epidemic keratoconjunctivitis (EKC).1–11 Pharyngoconjunctival fever is characterized by a fever, sore throat, history of recent upper respiratory infection (URI) and follicular conjunctivitis.1,2,4,7,9-11 The condition may be unilateral or bilateral, but classically presents in one eye and is spread to the other.1–8 This may explain why some epidemics are centered around community activity areas like swimming pools.4,7,8 The cornea is rarely affected and infiltrates are uncommon.5 Preauricular lymph nodes may be palpable and tender. The virus has an infectious period of 14 to 30 days that is self-limiting.7,8 The condition is contagious through the entire clinical period.

The principal symptoms include diffuse conjunctival redness, watery discharge, epiphora sometimes leading to a lateral canthal fissure (splitting of the skin at the lateral juncture of the upper and lower eyelids) and irritation.1–11

Epidemic keratoconjunctivitis presents as a unilateral or bilateral inferior palpebral follicular conjunctivitis with epithelial and subepithelial keratitis.12,13 While the entity has a reputation for preserving corneal sensation, recent investigations have demonstrated that transient decreased sensitivity over the middle course of the infection is possible.12-14 Subepithelial infiltrates (SEI) do not occur in every instance. When observed, they are typically concentrated in the central cornea, uniquely sparing the periphery.12–15 These localized gatherings of leukocytes can persist for months or longer; the pockets they create underneath the corneal epithelium are capable of producing permanent corneal opacities.15,16

Diffuse conjunctival injection, tearing, watery discharge, red and edematous eyelids, pinpoint subconjunctival hemorrhages, pseudomembrane (with occasional true membrane) formation on the upper and palpebral conjunctiva and palpable painful swelling of the preauricular, submandibular or submental lymph nodes are fundamental clinical signs.12–17 In severe cases, conjunctival desiccation can initiate scarring of the palpebral and fornix conjunctiva.17 This condition is also contagious.9–12 In many instances, patients present with a history of contact with a person who had red eyes or an upper respiratory infection.

Pathophysiology

Viral conjunctivitis can be caused by a number of different organisms.1–18 Most produce mild, self-limiting disease, while others have the potential to produce severe, disabling symptoms.1-18 Viral conjunctival infections are thought to be transmitted either by airborne respiratory droplets or direct transfer from fingers to the conjunctival surface.1-4,7-16 After an incubation period of five to 15 days, the disease enters an acute phase, during which inciting particles trigger cytokines and chemoattractants, which initiate conjunctival hyperemia, tissue edema and follicle formation.19-21 Follicles are not just reservoirs for extracellular fluid and lymph. Conjunctiva-associated lymphoid tissue (CALT) plays a key role in the protection of the ocular surface by initiating and regulating immune responses.19

Scattered throughout the lamina propria and consisting of components that include immunoglobulins, macrophages, dendritic cells and B-cells, conjunctival follicles enlarge when exposed to toxins, bacteria, viruses and allergens.19 Lymphoid cells (T-cells and B-cells) migrate to these locals from other mucosal regions (mucosal associated lymphoid tissues, or MALT) when defense is required.19

Pharyngoconjunctival fever is commonly caused by adenovirus types 3 and 5, and occasionally by adenoviruses 4 and 7.10 Epidemic keratoconjunctivitis is also caused by adenovirus. Of the 41 serotypes of adenovirus, 19 can produce viral conjunctivitis.21 Types 1-11 and 19 are most common, responsible for the mildest form of EKC.12,21 Acute hemorrhagic conjunctivitis (viral/follicular conjunctivitis with subconjunctival hemorrhage) is a variant produced by adenovirus types 19 and 37 and the picornavirus.15,17

Adenoviruses also have the ability to exert effects on the respiratory, genitourinary and gastrointestinal tracts.1-3 Adenoviruses account for 5% to 10% of respiratory illnesses in children.9,10 Adenovirus 7a has the potential to cause community epidemics via transmission through children.10 There is evidence that adenovirus type 8 can produce a more aggressive response, resulting in extensive keratitis, subepithelial opacities, subconjunctival hemorrhage and pronounced lymphadenopathy.21

Subepithelial infiltrates are caused by viral antigens and lymphocytes collecting in the shallow anterior stroma, just beneath the central epithelium.1-3,23 Confocal biomicroscopic examination provides evidence of an inflammatory response localized to the basal epithelium and anterior stroma of the central cornea.8,23 Some EKC variants include conjunctival membrane formation. Histologically, conjunctival membranes that develop in prolonged cases consist of fibrin, leukocytes, fibroblasts, collagen deposition, elements of the innate and acquired immune response, angiogenic factors and proliferating endothelial cells.24 Pseudomembranes are differentiated from true membranes by the ease with which they are removed, pseudomembrane being distinguished by easier removal.15,24-26

Membrane removal is distinguished by profuse and oozing bleeding, though pseudomembrane removal will also often cause bleeding.24-26 In both instances, as these components accumulate they interdigitate on a cellular level with the palpebral conjunctiva. As a result, when they are stripped from the conjunctival surface, they produce trauma to the underlying membrane, resulting in bleeding.24-26 Cicatrization may ensue following removal, leading to significant permanent mechanical alterations.24,26 The end result is fibrosis.24,26

Management

Differentiating the various causes of conjunctivitis can be challenging. The Rapid Pathogen Screening Adeno Detector (AdenoPlus, Nicox) point-of-care diagnostic test uses technology based on lateral flow immunochromatography to uncover the presence of adenoviral antigens.27,28 This test can minimize misdiagnosis. The detector works by capturing virus in the testing tool and presenting it to antigen-specific monoclonal antibodies inside the apparatus. The sample collector transfers ocular fluid from the lower conjunctiva to the lateral flow immunoassay, located in a plastic cassette.

Once the sample has been transferred, a result is available in 10 minutes.27,28 The test has a control indicator line; when it appears in the result window, the test is valid. The test is best administered within seven days of the patient’s developing a red eye.23 It requires a reasonable viral antigen load to generate a reading; false-negative readings are possible and a negative reading does not exclude other infectious etiologies.28

Viral conjunctivitis is contagious and self-limiting. The primary goal of management is to increase patient comfort by relieving symptoms. The secondary goal is to educate patients so as to limit spread of the condition.21-29-31 Patients should stay home from work or school until the discharge is eliminated.1-3 They should be warned against sharing utensils, glasses, linens or washcloths. Medical management may range from supportive cold compress and tears to topical vasoconstrictors, topical NSAIDs and topical steroids BID to QID.21,29-31 If pseudo- or true membranes are present, they should be removed using a forceps or a moistened cotton-tipped applicator soaked in a combination of antibiotic solution and anesthetic. Topical antibiotic steroidal combination therapy QID can be employed following the removal of the inflammatory membrane.15,21,29-31

Currently, no specific topical antiviral medication is recognized as an effective treatment for viral conjunctivitis.25 Ganciclovir gel (Zirgan, Bausch + Lomb), an antiviral option used in the treatment of herpes simplex dendritic keratitis, has been used successfully to limit the course and expedite healing in these cases, though this is an off-label use.30 Prescribed four to five times a day and then tapered to TID, alone or in combination with other therapies, the agent is gaining acceptance as an option.30 In stubborn cases, a povidone-iodine 5% (Betadine) rinse can be offered. Here, the eye is anesthetized with a topical drop and the patient reclined. Povidone-iodine is placed into the palpebral fissure bathing the conjunctivae for 10 to 30 seconds, then rinsed away. Discomfort is common afterwards and the patient may require analgesia. Patients should be well educated and give consent to this treatment.

Researchers have also been experimenting with off-label povidone-iodine eye drops with or without an incorporated topical steroid for hastening recovery and lessening symptoms.32,33 In the worst cases, cycloplegia can be used for comfort.

Clinical Pearls

When patients present with what is suspected to be viral conjunctivitis, the waiting room, magazines, office equipment and instruments should be sanitized so they do not become a flashpoint for outbreak.

Most practitioners reserve topical steroidal therapy for the severely symptomatic, those exhibiting severe SEI, decreased acuity from lacrimation or SEI on the visual axis, cases exhibiting pseudo- or true membrane formation, and cases recalcitrant to nonsteroidal management.

Epidemic keratoconjunctivitis infiltrates typically resolve without scarring the cornea. Patients should be told to expect their condition to worsen over the first seven to 10 days with slow improvement following over a three- to six-week period.

Steroids should be tapered slowly as the condition remits so that rebound inflammation can be avoided.

The URI that preceded the red eye should not be discounted or ignored; consider referral to the internist.

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10. Mitchell LS, Taylor B, Reimels W, et al. Adenovirus 7a: A community-acquired outbreak in a children’s hospital. Pediatr Infect Dis J 2000;19(10):996–1000.

11. Meyer-Rüsenberg B1, Loderstädt U, Richard G, et al. Epidemic keratoconjunctivitis: the current situation and recommendations for prevention and treatment. Dtsch Arztebl Int. 2011;108(27):475-80.

12. Schrauder A, Altmann D, Laude G, et al. Epidemic conjunctivitis in Germany, 2004. Euro Surveill 2006;11(7):185–7.

13. Uchio E, Takeuchi S, Itoh N, et al. Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1. Br J Ophthalmol 2000;84(9):968–72.

14. Ozturk HE, Sonmez B, Beden U. Corneal sensitivity may decrease in adenoviral epidemic keratoconjunctivitis–a confocal microscopic study. Eye Contact Lens. 2013;39(4):264-8.

15. Murrah WF. Epidemic keratoconjunctivitis. Ann Ophthalmol 1988;20(1):36–8.

16. Janićijević-Petrović MA, Srećković S, Petrović N, Sarenac T. Epidemic keratoconjunctivitis. Srp Arh Celok Lek. 2011;139(5-6):282-5.

17. Karki DB, Shrestha CD, Shrestha S. Acute haemorrhagic conjunctivitis: An epidemic in August/September 2003. Kathmandu Univ Med J (KUMJ) 2003;1(4):234–6.

18. Chang CH, Sheu MM, Lin KH, et al. Hemorrhagic viral keratoconjunctivitis in Taiwan caused by adenovirus types 19 and 37: Applicability of polymerase chain reaction-restriction fragment length polymorphism in detecting adenovirus genotypes. Cornea 2001;20(3):295–300.

19. Steven P, Gebert A. Conjunctiva-associated lymphoid tissue – current knowledge, animal models and experimental prospects. Ophthalmic Res. 2009;42(1):2-8.

20. Kaneko H, Kondo T, Fujiwara T, et al. Clinical and virological studies of nosocomial conjunctivitis infection caused by adenovirus type 37 variant. Nippon Ganka Gakkai Zasshi 2005;109(8):489–96.

21. Rubenstein JB, Virasch V. Allergic conjunctivitis. In: Yanoff M, Duker JS. Ophthalmology. Mosby-Elsevier, St. Loius, MO 2009:237-240.

22. Chang C, Sheu M, Chern C, et al. Epidemic keratoconjunctivitis caused by a new genotype of adenovirus type 8 (Ad8)—a chronological review of Ad8 in Southern Taiwan. Jpn J Ophthalmol 2001;45(2):160–6.

23. Alsuhaibani AH, Sutphin JE, Wagoner MD. Confocal microscopy of subepithelial infiltrates occurring after epidemic keratoconjunctivitis. Cornea 2006;25(9):1102–4.

24. Chintakuntlawar AV1, Chodosh J. Cellular and tissue architecture of conjunctival membranes in epidemic keratoconjunctivitis. Ocul Immunol Inflamm. 2010;18(5):341-5.

25. Rashid S, Dana MR. Cicatrizing and autoimmune diseases. Chem Immunol Allergy 2007;92:195–202.

26. Uchio E. New medical treatment for viral conjunctivitis. Nippon Ganka Gakkai Zasshi 2005;109(12):962–84.

27. Rapid pathogen screening. Point-of-Care Diagnostic Services Adeno Detector instructional insert. RPS Insert 2006:1–2.

28. Sambursky R1, Trattler W, Tauber S, et al. Sensitivity and specificity of the AdenoPlus test for diagnosing adenoviral conjunctivitis. JAMA Ophthalmol. 2013;131(1):17-22.

29. Wilkins MR, Khan S, Bunce C, et al. A randomised placebo-controlled trial of topical steroid in presumed viral conjunctivitis. Br J Ophthalmol. 2011;95(9):1299-1303.

30. Yabiku ST, Yabiku MM, Bottós KM, et al. Ganciclovir 0.15% ophthalmic gel in the treatment of adenovirus keratoconjunctivitis. Arq Bras Oftalmol. 2011;74(6):417-21.

31. Skevaki CL, Galani IE, Pararas MV,et al. Treatment of viral conjunctivitis with antiviral drugs. Drugs. 2011;71(3):331-47.

32. Trinavarat A1, Atchaneeyasakul LO. Treatment of epidemic keratoconjunctivitis with 2% povidone-iodine: a pilot study. J Ocul Pharmacol Ther. 2012;28(1):53-8.

33. Pelletier JS1, Stewart K, Trattler W, et al. A combination povidone-iodine 0.4%/dexamethasone 0.1% ophthalmic suspension in the treatment of adenoviral conjunctivitis. Adv Ther. 2009;26(8):776-83.