Case for conservative management of adenoviral pseudomembranous conjunctivitis
- Kenneth McNair Gilmour and
- Kanna Ramaesh
- Ophthalmology, Tennent Institute of Ophthalmology, Glasgow, UK
- Correspondence to Dr Kenneth McNair Gilmour; kenneth.gilmour2@nhs.scot
Abstract
The clinical course of adenoviral pseudomembranous conjunctivitis is mostly self-limiting and requires only supportive management measures; however, a minority of patients may develop severe inflammation in response to the virus, which can present as subepithelial infiltrates and pseudomembranes. In its most severe form, symblepharon can result from the inflammatory response resulting in longer-term clinical sequelae. The optimal management of adenoviral pseudomembranous conjunctivitis is poorly defined and while debridement is commonly recommended, there is limited evidence base to support this practice. In this paper, we present two cases of PCR-proven adenoviral pseudomembranous conjunctivitis managed conservatively with topical lubricants and corticosteroids rather than debridement to good effect.
Background
Adenoviral conjunctivitis is common and represents up to 62% of all acute infectious conjunctivitis.1 The clinical course in the majority of cases is self-limiting and requires only supportive measures. A minority of patients may develop complications such as subepithelial infiltrates and pseudomembranes.2 Formation of pseudomembrane represents severe inflammation within the conjunctiva and can be associated with secondary complications such as subepithelial infiltration, corneal epithelial punctate keratopathy, epithelial erosions and late formation of conjunctival scarring.3–5 The pathophysiology has been attributed to exudation of fibrin and leucocytes from inflamed conjunctiva and clinically appears as a thin pale membrane covering both the palpebral and tarsal conjunctiva.3
The management of pseudomembrane is not well documented in the ophthalmic literature. While topical steroids to target the inflammatory response have been advocated, some authors have suggested removing the pseudomembrane.3 6–9 In this paper, we present the outcome of two cases of PCR-proven adenoviral pseudomembrane managed conservatively with topical steroids only.
Case presentation 1
An otherwise fit male patient in his 40s presented with a 7-day history of red eyes, foreign body sensation, profuse watery discharge and itch in the left eye, following a recent upper respiratory tract infection. Two days prior to presentation, his symptoms spread from the left to the right eye. The clinical examination showed bilateral follicular conjunctivitis, conjunctival hyperaemia and tender pre-auricular lymph nodes. Visual acuity was 6/6 in the right eye and slightly reduced to 6/12 in the left eye due to the presence of subepithelial infiltrate. There was evidence of a pseudomembrane on the upper and lower conjunctival fornices of the left eye (figure 1). PCR swab was positive for adenovirus. Topical fluorometholone 0.1% was commenced two times per day for 2 weeks alongside as-required topical lubricants. Follow-up at days 4 and 14 (figures 2 and 3, respectively) showed a gradual improvement in symptoms followed by complete resolution. Two weeks following commencement of treatment, the visual acuity was 6/6 in both eyes and the patient was discharged.
Day of presentation of case 1 showing left eye superior and inferior fornix pseudomembrane.
Day 4 following presentation of case 1 showing resolution of superior fornix and improvement of inferior fornix pseudomembrane.
Fourteen days after presentation, showing resolution of all pseudomembranes.
Case presentation 2
A man in his 20s was referred via the optician with unresolving bilateral conjunctivitis and reduced vision to 6/36 in the right eye and 6/9 in the left eye. On examination, there was conjunctival injection and superficial punctuate staining of both corneas. Initial management included viral and bacterial swabs, oral co-amoxiclav and ofloxacin drops. Three days later, vision declined to count fingers and 6/15 in the right and left eyes, respectively. There was evidence of membranes on all tarsal conjunctival surfaces, as well as a central corneal abrasion and subepithelial infiltrates in the right eye. Adenovirus was detected on PCR.
The patient initially underwent removal of the left lower lid membrane but was unable to tolerate the debridement due to pain and distress, and the procedure was abandoned. He was commenced on chloramphenicol ointment 1% and two times per day preservative-free dexamethasone 0.1%. At day 5, the epithelial defect had resolved and his symptoms were much improved. His final visual acuity at 3 weeks was 6/6 and the patient was discharged. Neither patients had evidence of symblepharon upon discharge.
Outcome and follow-up
Both patients were discharged after 3–4 weeks of follow-up.
Discussion
Viral conjunctivitis is the most common cause of infectious conjunctivitis, and adenovirus comprises up to 90% of viral cases. Serotypes 8, 19 and 37 are considered the most severe variants with propensity to cause longer-term complications such as corneal scarring secondary to subepithelial infiltrates and symblepharon formation.2 Adenovirus invades the epithelial cells and results in cytopathic cell damage, and an inflammatory response is mounted to limit viral invasion. This inflammatory response can manifest in a spectrum of clinical manifestations. Macroscopic clinical manifestations include conjunctival hyperaemia, conjunctival chemosis, formation of follicles and a formation of a pale exudation that is adherent to the underlying conjunctiva.3 This exudation may clinically look like a ‘membrane’. Careful consideration should be given to describe the nature of this ‘membrane’. What clinically appears like a ‘membrane’ may have a spectrum of microscopic pathological features ranging from fibrin meshwork with entangled leucocytes to more severe involvement of the epithelium. In the severe spectrum, the fibrin mesh and the inflammatory cells involve the epithelium and become strongly adherent to the epithelium. The epithelium may undergo coagulative necrosis. Healing takes place by granulation tissue formation underneath the membrane and epithelial migration, and the membrane is ultimately cast off resulting in the restoration of the conjunctival epithelium.3 6
In his monumental Text Book of Ophthalmology, Duke Elder gives a clear description of conjunctival membrane formation.10 He attributes the original description of conjunctival membrane formation to Bouissin in 1847. The original description of this ‘membrane’ is in the context of pathological findings resulting from diphtheria that was prevalent in the 19th century. The original pathological description was historically surrogated to describe clinical features of adenoviral conjunctivitis.10 Both pseudomembranes and true membranes have been demonstrated in adenoviral conjunctivitis.3 Pathologically, the pseudomembrane consists of a fibrin-rich network enmeshed with leucocytes and other exudative products, which lack blood supply and lymphatics. Translucent and pearl-like in appearance, clinically, it may be peeled off easily leaving the underlying epithelium intact, although it may quickly reform.11 True membranes are thought to represent an extension in the degree and severity of the inflammatory process whereby exudate permeates the superficial layers of the epithelium so that the fibrinous network becomes entangled among the epithelial cells. Any attempt at debridement tears the epithelium itself to leave a denuded bleeding surface.3 11 One has to bear in mind that an attempt to peel an adherent exudative inflammatory membrane is not a satisfactory diagnostic test, and invariably causes discomfort, pain and may even delay healing.
Debridement of pseudomembranes is a widely accepted and recommended treatment to improve symptoms and reduce true membrane or symblepharon formation, as table 1 demonstrates.4 6–9 However, to the best knowledge of the authors, no prospective or retrospective comparative study exists that demonstrates this treatment is effective at reducing complications and the evidence base is limited to anecdotal retrospective case series.4 6–9 Additionally, as case 2 highlights that the clinical distinction between true and pseudomembranes may not be apparent until debridement is attempted and should a true membrane exist, its removal has potential to be painful and poorly tolerated. Symblepharon as a complication of adenoviral conjunctivitis is an uncommon phenomenon. One retrospective case series from a UK tertiary centre investigated 54 patients with adenoviral conjunctivitis over 6 years and found 13 patients (25%) had evidence of membranes or pseudomembranes and 2 patients (4%) had evidence of long-term symblepharon formation, despite all membranes being treated with debridement.4 Considering debridement is so widely employed, there is a lack of evidence base to support its use.
A summary of recommended management plans for pseudomembrane in adenoviral conjunctivitis from core ophthalmology texts
| Source reference | Recommended management |
| American Academy of ophthalmology, Basic and clinical science course, External Disease and cornea, 2021–2022 | No management recommendation |
| Cornea 3rd Edition Vol 1, editors Krachmer JH, Mannis M | Recommends removal with cotton buds or forceps. No references quoted |
| The Wills Eye Manual 8th Edition | Recommends treatment with topical steroids and gentle removal of pseudomembrane. No references quoted |
| Kanski’s Clinical Ophthalmology. Salmon JF, 9th Edition | Recommends removal. No references quoted |
| Oxford Handbook of Ophthalmology, 4th edition, 2018 | No management recommendation |
The evidence for using conservative management alone, such as topical corticosteroids, ocular lubricants and observation, is also limited. In these cases, after clinical consideration of the reduction of vision and severity of inflammation of the patients, both topical fluorometholone and dropodex were used to good effect although no treatment protocol exists.12 However, it should be considered that even in its severe presentation, adenoviral conjunctivitis is predominantly a self-limiting condition with spontaneous resolution. Additionally, topical corticosteroids are routinely used to safely manage multiple forms of ocular inflammation.12 Case 1 above demonstrates a likely case of pseudomembranous conjunctivitis, while case 2 likely represents a true conjunctival membrane, due to the presence of haemorrhage and difficulty peeling the membrane, which resulted in debridement being abandoned. Both case reports demonstrate that even in the severe spectrum of the disease, spontaneous resolution is achievable with conservative management. In juxtaposition to treatment with debridement, there is prospective evidence to support the use of conservative treatment measures. A blinded randomised controlled trial (RCT) by Kovalyuk et al demonstrated that povidone and dexamethasone in combination showed a statistically significant faster resolution of symptoms than dexamethasone and artificial tears in isolation.13 Additionally, a prospective RCT by Asena et al demonstrated symptom reduction when topical corticosteroids were used in conjunction with ciclosporin A.14 There remains no definitive treatment for adenoviral conjunctivitis and further research would be valuable to guide management. However, considering the self-limiting nature of the condition in most cases, the authors of this paper advocate a conservative management approach as a logical and effective first-line treatment.
Learning points
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Evidence to determine optimal management of adenoviral pseudomembranous conjunctivitis is lacking.
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Considering the high prevalence of adenoviral conjunctivitis, future comparative studies to investigate optimal management would be of value.
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The two case reports highlight the potential for successful outcomes and full resolution with conservative management.
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The authors advocate that considering the underlying inflammatory pathophysiology and the absence of evidence to support debridement of pseudomembrane, anti-inflammatory treatments should be recommended in the first instance.
Ethics statements
Patient consent for publication
Footnotes
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Contributors Both KMG and KR claim authorship of the paper and they agree that they undertook the following: conception and design, acquisition of data or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version published; agreement to be accountable for the article and to ensure that all questions regarding the accuracy or integrity of the article are investigated and resolved.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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