Necrotising fungal scleritis with full-thickness scleral melt and circumferential progression: a novel debridement approach

Abstract

A 44-year-old Asian Indian woman presented with a history of pain and redness in the left eye for 3 weeks. Scleral congestion with a nodular swelling was present inferotemporally. Raised C reactive protein and positive antinuclear and perinuclear antineutrophil cytoplasmic antibodies suggested autoimmune scleritis. The patient was therefore managed with corticosteroids. Nevertheless, the development of severe pain associated with a scleral abscess led to a revised diagnosis of infectious scleritis. Corticosteroids therapy was halted and urgent debridement was performed. Microbiology confirmed fungal scleritis due to Coprinopsis cinerea. Multiple full-thickness circumferential debridements with antifungal therapy resulted in satisfactory anatomical and visual outcomes. This case presented a unique challenge, since laboratory results were misleading, and corticosteroids resulted in a fulminant clinical course. Therefore, aggressive circumferential debridement was performed to achieve the elimination of a rare fungal aetiology of scleritis, which has not been reported previously to cause human infection.

Background

Scleritis is an infrequently encountered entity, presenting with varied clinical morphology ranging from mild episcleritis to vision-threatening and globe-threatening scleromalacia perforans.¹ Scleritis is usually immune-mediated with or without systemic association; however, a majority of the cases are idiopathic with no identifiable aetiology. Although infection remains the least common, yet a significant cause of scleritis, with the incidence ranging from 5% to 18%.^{2 3} Various predisposing factors include trauma,⁴ systemic infection,⁵ use of corticosteroids and immunomodulators^{4 6} or previous ocular surgery.^{7 8} Fungal infection is an important but rare cause of scleritis, previously reported to be occurring variably in about 3%–38% of all cases.6 7 9–11 Aspergillus is the most common fungus seen associated with necrotising infectious scleritis.^{6 7}

The management of fungal scleritis often presents a greater challenge due to a usual delay in diagnosis and lack of consensus on the class of antifungal agents or their route of administration.³ Moreover, it mimics the immune-mediated form, hence often misdiagnosed at presentation and treated with corticosteroids; the latter while beneficial in immune-mediated scleritis worsens infectious scleritis.¹² This could lead to the development of a fulminant clinical picture with full thickness and often circumferentially progressive necrotising scleritis. Early surgical debridement, microbiological analysis, the institution of specific antimicrobial therapy and complete cessation of all forms of corticosteroids remain standard management approaches in such cases.

We report a case of fungal scleritis due to a rare aetiology, with an aggressive clinical course, a unique debridement approach and a counter-intuitive favourable outcome during long-term follow-up.

Case presentation

A 44-year-old Asian Indian woman presented with a history of pain and redness in the left eye for 3 weeks following trivial injury with a tree branch. There was a diminution of vision in the left eye for 10 days. Best-corrected visual acuity (BCVA) was 20/20 in the right eye and 20/50 in the left eye. Pupillary reflexes were normal in both eyes. There was diffuse scleral congestion with a nodular swelling in the inferotemporal quadrant, clear cornea and no discharge or foreign body on examination of the left eye (figure 1A). History of similar episodes was absent and fundus examination was unremarkable. The examination of the right eye was normal. Based on history and examination findings, an initial diagnosis of nodular, anterior, non-necrotising scleritis was made. However, the possibility of infectious aetiology was not ruled out, in view of the history of trauma.

Figure 1.

Left eye anterior segment photograph of the patient. (A) Nodular scleral elevation with yellowish discolouration. (B) Diffuse congestion with an increase in the size of nodular swelling, which had become fluctuant and caused the displacement of the lower lid.

Investigations

Following a review of systems by an internist, a thorough systemic examination and autoimmune workup were carried out. Laboratory investigations revealed raised C reactive protein (4 mg/L), elevated total leucocyte count (10.5×10⁹/L), positive antinuclear antibody (1:40; speckled pattern), positive perinuclear antineutrophil cytoplasmic antibodies, negative HIV and negative tuberculin skin test. Laboratory results and clinical picture pointed to an autoimmune aetiology, and the patient was started on oral and topical corticosteroids (oral prednisolone 1 mg/kg once daily and topical betamethasone 1% 1 hourly) and oral indomethacin (75 mg two times per day) for pain.

Differential diagnosis

Despite adequate corticosteroid therapy, the clinical picture showed transient improvement in the first week of treatment and began worsening thereafter. The patient developed severe pain, diffuse congestion and an increase in the size of swelling, which had become fluctuant and caused the displacement of the lower lid (figure 1B). This mandated a review of our diagnosis to favour an infectious aetiology, due to documented disease progression and hence a paradigm shift in the management approach. Trauma with the vegetative matter was another clue in retrospect, towards an infectious aetiology, possibly fungal.

Treatment

Since the patient was very symptomatic and restless due to severe ocular pain, in addition to the dilemma of an uncertain aetiology, the surgical exploration of the fluctuant swelling and subsequent scleral biopsy and microbiology was urgently considered at this point. Topical and systemic corticosteroids were withdrawn. Before conjunctival incision, aspiration–decompression of the boggy swelling was performed using a 23-gauge needle and syringe. Frank pus was aspirated causing the swelling to flatten completely (video 1). As soon as conjunctiva was opened in the inferotemporal quadrant over the swelling, we noticed full-thickness scleral melt, revealing bare choroid underneath (figure 2). Necrotic sclera having a cheesy consistency was then excised using Westcott’s scissors, advancing circumferentially.

Video 1.

Download video file ^{(8.6MB, mp4)}

DOI: 10.1136/bcr-2020-237586.video01

Figure 2.

Left eye anterior segment photograph of the patient. (A) Image after conjunctival incision in the inferotemporal quadrant over the area of swelling—full-thickness scleral melt with visible bare choroid. (B) Image after surgical debridement showing an annular band of deeply pigmented bare choroid, anteriorly limited to perilimbal 5 mm zone of scleral frill and posteriorly till the insertion of recti muscles (along the spiral of Tillaux).

To achieve this, one blade of the conjunctival scissors was slipped gently between the necrotic sclera and choroid, directly placing it in the suprachoroidal space (video 1). It is noteworthy that once there was a transient clinical improvement after the first debridement, we restarted systemic corticosteroids under adequate antifungal therapy (topical natamycin 5% 2 hourly and oral itraconazole 100 mg two times per day).¹³

Subsequently, we noted the further progression of scleritis with multiple abscesses, despite specific therapy, was attributed to the reintroduction of corticosteroids. This brought about two additional debridement procedures to control the disease process. Hereafter, we refrained from using corticosteroids further in the management.

Consequently, an annular band of pigmented, bare choroid was visible (figure 2B), anteriorly limited by 5 mm of perilimbal scleral frill and posteriorly till the insertion of rectus muscles along the spiral of tillaux—in effect, creating a structural disconnect between anterior and posterior margins of the debrided scleral coat. This radical and necessary surgical approach did not appear to compromise the anatomical integrity of the globe. No event of vitreous loss or choroidal detachment/haemorrhage was encountered. Primary closure was not performed and overlying conjunctiva was excised. Samples of pus and debrided scleral tissue were sent for microbiology, histopathology and PCR testing. Calcofluor-white staining revealed fungal elements (figure 3A), however pus culture did not grow any organisms. Pan-fungal PCR analysis revealed a positive band (figure 3B). Histopathology revealed ulcerated, stratified-squamous epithelium. Underlying stroma showed oedema, fibrocollagenous tissue, mixed inflammatory cells, congested small blood vessels, plump endothelial cells and fibrin along with few areas of necrosis in stromal tissue suggestive of necrotising scleritis. No organisms were identified in the scleral lamellae.

Figure 3.

(A) The image showed hyphae stained with calcofluor white (cat. no. 18909, Sigma), viewed under ultraviolet filter (Olympus BX53F Microscope). (B) The amplified products were run on 2% agarose gel electrophoresis. The product near 600 bp corresponds to the internal transcribed spacer (ITS) region of the panfungal genome.

The National Center for Biotechnology Information blast sequencing revealed that the causative organism was fungal species Coprinopsis cinerea, an unusual and rare fungal aetiology to have caused infection in humans. Antifungal susceptibility testing performed using broth microdilution assay revealed susceptibility for voriconazole. Oral and topical steroids had already been withdrawn and the patient was started on specific oral and topical antifungal treatment (oral voriconazole 200 mg two times per day and topical voriconazole 1% every 2 hourly). Subsequently, lesions showed significant improvement and the patient became comfortable.

Outcome and follow-up

Antifungal therapy was continued for 3 months with topical antiglaucoma (dorzolamide 2% and timolol 0.5%) for 1 month. Routine follow-up visits based on the clinical response were advised and at the end of 1 year, the patient had BCVA of 20/30 in the left eye. Cornea and lens were clear and the fundus was normal. The integrity of the globe was maintained with normal intraocular pressure, without any signs of recurrence of scleritis or ciliary staphyloma. A distinct deep, blue to black, circumferential band of uveal tissue approximately 4–6 mm in width was noticed with healthy epithelisation and vascularisation (figure 4A–D).

Figure 4.

Left eye anterior segment photograph (A: 360° view in diffuse illumination; B-D magnified view of superior, temporal and inferior quadrants respectively) of the patient after 1-year post circumferential debridement, showing a distinct deep – blue to black, circumferential band of uveal tissue (approximately 6 – 8 mm in width) with healthy epithelization and vascularization.

Discussion

Necrotising scleritis is presumably the most severe and destructive form of scleritis.¹ In the case of necrotising scleritis, a strong suspicion for an infectious aetiology needs to be considered, especially when a preceding history of ocular surgery or trauma is present with coexisting scleral abscess.¹²

The undesirable effects of corticosteroids and subsequent delay in scleral debridement have an unfavourable effect on the clinical course and final outcomes in cases of infectious scleritis. Kumar Sahu et al observed in a cohort of 17 patients with infectious scleritis that 15 patients were on topical steroids.¹³ The authors attributed the worsening of infections in corticosteroid exposed patients to the inhibition of lysosomal enzymes and suppression of immunity. The index case also developed a fulminant clinical picture after initial administration of corticosteroids for presumptive autoimmune aetiology and despite revision of therapy later, the lesions continued to progress until circumferential involvement necessitated full-thickness annular scleral debridement.

We also observed that after the first exploratory debridement, reintroducing corticosteroids brought about an unabated progression of infectious scleritis, despite the cover of specific antifungal therapy. This mandated an additional procedure of debridement and we refrained from using corticosteroids further in the management of our case. Tittler et al reported improved functional outcomes of patients with infectious scleritis who were treated with prompt and aggressive scleral debridement and antimicrobial therapy; the authors observed that a delayed debridement was associated with poorer outcomes.¹⁴

Decreased visual acuity at presentation, worsening ocular pain and development of multifocal abscesses with concurrent use of steroids, although non-specific, were potential clues that pointed to an infectious aetiology in our case.⁸ Hodson et al observed that approximately 50% of eyes lost functional vision after infection, with poor presenting visual acuity being the strongest predictor for severe vision loss in cases of infectious scleritis.⁸ This highlights the need for prompt diagnosis and early, aggressive surgical debridement.

Surgical scleral debridement plays an important role in the management of infectious scleritis. The relative avascularity of the sclera and dense structure of the collagen fibres hinder penetration by topical and systemic antibiotics.¹⁵ The picture is further complicated in infectious scleritis of fungal aetiology where hyphae are enmeshed into scleral lamellae extending into the apparently uninvolved tissue. Hence, surgical debridement needs to be aggressive and extensive without sparing the overlying conjunctiva. It must, however, be remembered that one needs to exercise extreme caution while performing full-thickness excision of melted scleral tissue often with circumferential extent, lest the eye may be irreversibly lost. Also, debridement provides samples for microbiological analysis, further aiding the establishment of definitive diagnosis and early institution of targeted therapy. Conjunctival excision is recommended to prevent reorganisation of abscess after surgical debridement, enhance drug penetration and maximise the elimination of infection. Tittler et al demonstrated a 100% globe preservation rate, improved visual rehabilitation and fewer complications by doing a prompt surgical debridement at diagnosis.¹⁴

Extensive scleral debridement has also been shown to require patch graft.^{1 6} However, in our case, scleral patch graft was not resorted to, despite extensive full-thickness debridement. In our experience, the application of preserved/cadaveric, avascular, scleral patch graft at the site of active infection not only lead to the persistence of infectious focus and reorganisation of an abscess but also necrosis of the graft.

The causative fungus C. cinerea has not been reported before to cause ocular infection in humans and therefore makes this a hitherto unreported presentation. Additional reports in the future would help shed more light on its pathogenesis and clinical presentation. For the time being, we can attribute a very severe form of necrotising scleritis with annular progression associated with this rare fungal aetiology. Definitive treatment seems to entail aggressive surgical debridement of sclera while antifungal therapy may be of limited significance per se.

We specifically noted that the progression of scleritis following corticosteroid administration was strictly circumferential and did not involve either the cornea anteriorly or sclera posterior to the insertion of rectus muscles. However, more experience in the management of similar cases will be needed to understand the significance of this observation. Recurrences in case of infectious scleritis are rare after complete resolution as opposed to autoimmune scleritis, where frequent recurrences occur.⁸ We observed similar findings in our case where no recurrence was observed until a follow-up period of 1 year and beyond.

To the best of our knowledge, this is the first case reporting a rare fungal aetiology, C. cinerea, for infectious scleritis and employing a novel technique of full-thickness circumferential scleral debridement, as last resort management. Despite aggressive surgical debridement, the integrity of the globe was maintained and the patient had a satisfactory long-term visual and anatomical outcome.

Learning points.

• Coprinopsis cinerea—a hitherto unreported fungal aetiology—causing necrotising fungal scleritis is worsened by corticosteroid exposure and is a difficult condition to manage, especially when the diagnosis is delayed.

• A high index of suspicion combined with a higher threshold for the use of corticosteroids is required while managing a case of suspected infectious aetiology especially with a history of surgery or trauma.

• Early and liberal scleral debridement plays an important role in achieving specific diagnosis and institution of targeted therapy. Multiple debridements may be needed to achieve the complete elimination of infection.

• In cases of confirmed infectious aetiology, targeted antimicrobial therapy is sufficient to control the disease process without supplemental corticosteroids. Since the latter may cause recurrences and worsen clinical course despite the antimicrobial cover.

• Full-thickness excision of sclera and overlying conjunctiva may be undertaken with favourable anatomical and visual outcomes without the need for any scleral patch graft.