A novel technique of full-thickness scleral debridement in fulminant necrotising infectious scleritis and its outcomes—a consecutive case series

To report the outcomes of a novel technique of scleral debridement in five consecutive cases of relentlessly progressive and fulminant infectious scleritis following corticosteroid exposure. Five consecutive patients of infectious scleritis with a common history of corticosteroids exposure, resulting from either an initial misdiagnosis of autoimmune scleritis or as anti-inflammatory adjunct to specific antimicrobial therapy. Data collection included presentation details such as photographs, clinical findings, microbiological analysis, treatment details and audit of surgical videos. Cases with undisputed diagnosis of infectious scleritis with microbiological evidence, without corticosteroid use, were excluded from the study. After full-thickness scleral debridement and cessation of corticosteroids, favourable anatomical and visual outcome was observed in all cases; however, two patients required multiple scleral debridements due to progressive scleritis. Scleral patch graft was not used in any case. Microbiology detected infective organisms in two cases, while the remaining revealed negative results. Therefore, specific antimicrobial therapy was initiated in former, whereas empirical broad-spectrum regimen in patients with repeatedly negative microbiological results. No recurrence of scleritis or development of ciliary staphyloma was noted and anatomical integrity was maintained with normal intraocular pressure during follow-up. This study highlights the fulminant and relentlessly progressive clinical course, that infectious scleritis can metamorphose into, despite specific antimicrobial therapy, if inadvertent corticosteroid therapy is administered. Full-thickness debridement without scleral patch graft, could achieve elimination of infectious foci, with favourable long-term anatomical and visual outcome. This technique could offer a potential last-resort approach in such cases where standard therapeutic modalities have not been successful.


Introduction
Scleritis is an uncommon, painful and sight threatening ocular inflammatory condition with a prevalence of 6 cases per 100,000 [1,2]. Scleritis is more commonly associated with autoimmune disorders and infectious scleritis accounts for only 5-10% of all the scleritis cases [3][4][5][6]. The initial presentation of infectious scleritis can mimic its immune-mediated counterpart [7,8]. Topical and systemic steroids, while beneficial in immune-mediated scleritis, worsen infectious scleritis. The latter may occur post-trauma, ocular surgery, endophthalmitis or from a primary corneal infection [9]. The most common organisms responsible for infectious scleritis are Pseudomonas aeruginosa and fungi [7,10,11].
Infectious scleritis follows an aggressive course and the clinical outcome is poor in most cases with various series reporting the need for evisceration in severe cases [9,12]. Early initiation of topical and systemic antimicrobial therapy along with surgical debridement can help in salvaging these eyes with improved anatomical success [7,11]. Surgical debridement also aids in the penetration of topical medications while debulking the infected scleral tissue [8].
In this study, we report five consecutive cases of infectious scleritis with relentless progression despite medical management and focal debridement. These cases were successfully managed by full thickness, and when required-circumferential, scleral debridement procedure.

Materials and methods
Five consecutive patients of infectious scleritis were analysed in a retrospective review conducted at a tertiary eye hospital in central India during one-year period . Diagnosis was based on proven microbiology and/or worsened clinical course following corticosteroid administration. There was a common history of corticosteroid use, resulting from either an initial misdiagnosis of autoimmune scleritis or as an adjunct to specific antimicrobial therapy. Initial misdiagnoses were attributed to either an overlap of clinical characteristics between infectious and autoimmune scleritis, with an unclear history of trauma, or a negative microbiological yield. All cases had a documented worsening of clinical picture after corticosteroid therapy and were managed by full-thickness scleral debridement at our institute. This was carried out only as a last resort procedure where the disease was relentlessly progressive despite focal debridement procedures and culture specific antimicrobial therapy. Patient's referral notes were reviewed for details of medical therapy, microbiological evidence or any previous surgical procedure. The study adheres to tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients for the surgical procedure and potential complications and outcome. Consent was also obtained for use of clinical data 'without identifiers' for potential future academic use or research publications.

Data analysis
Clinical records of five patients with infectious scleritis who underwent full-thickness scleral debridement were retrospectively reviewed. Data collection included details of clinical picture at presentation including photographs, best corrected visual acuity (BCVA), intraocular pressure (IOP), detailed ocular examination including fundus, anterior segment photographs and audit of surgical videos. Debrided scleral tissue was subjected to microbiological analysis and histopathological examination (HPE). Microbiological assessment included grams stain, KOH/Calcofluor white stain and Ziehl-neelsen staining. Acid-fast staining was done if Gram stain was negative, and the clinical picture strongly suggested microbial/ infective origin. The samples from scleral scraping were cultured on blood agar, chocolate agar, Sabouraud's dextrose agar and non-nutrient agar with an E. coli overlay. Details of the type of antimicrobial agents and their doses were noted. Treatment and surgical procedure details of patients referred from elsewhere were also recorded. All patients included in the study had a documented follow-up period of at least one year.

Technique of Scleral Debridement
All procedures were performed under local peribulbar anaesthesia. After standard preparation of the surgical field with 5% povidone iodine and draping, a lid speculum was placed. Conjunctiva was opened using scissors, initially at the location of the most prominent, yellowish nodular elevation which often led to the drainage of frank pus and subsidence of swelling, thus confirming the presence of a sub-conjunctival abscess. Using a surgical blade (15 no.) mounted on Bard-Parker handle, necrotic sclera was debrided until the underlying healthy scleral tissue was visible and fresh bleeding was encountered. In a few areas upon excision of overlying conjunctiva, bare choroid was exposed; this was suggestive of full-thickness scleral necrosis.
In cases with a more aggressive clinical picture, full-thickness scleral necrosis was noticed (360 degrees) and necrotic sclera was excised using conjunctival scissors, advancing in a circumferential fashion. In order to achieve this, one blade of the conjunctival scissors was slipped gently between the cheesy necrotic sclera and choroid-directly placing it in the supra-choroidal space. After excising the necrotic melted scleral tissue off the underlying uveal tissue, an annular band of deeply pigmented, bare choroid was visible; anteriorly limited to perilimbal 5 mm-zone of scleral frill and posteriorly till the insertion of rectus muscles (along the spiral of Tillaux). No event of globe rupture with vitreous loss or choroidal haemorrhage was encountered in any of the cases. Primary closure was not performed and the conjunctiva overlying the area of scleral necrosis was excised in order to ensure better penetration of medications, to prevent re-organization of abscess and to maximize elimination of infection. Before patching, the wound and debrided area were thoroughly irrigated using broad-spectrum antibiotic solution.

Results
Of the five patients enrolled in the study, two were females. Three patients presented with scleritis which was initially misdiagnosed as autoimmune and started on corticosteroids. However, when the clinical picture worsened into fulminant necrotising full-thickness scleritis with relentless progression despite initial management, the diagnosis was revised to consider infectious aetiology and corticosteroids stopped henceforth. Remaining two patients had a microbiologically proven aetiology of infectious scleritis, but were given steroids as an adjunct, to control scleral inflammation under cover of specific antimicrobial therapy. Corticosteroids in these cases were started after clinical resolution was documented and a minimum intervening period of one week between both therapies. The individual case details, clinical course, management and outcomes have been described below.

Case 1
A 55-year-old male presented with complaints of redness and pain in the left eye for two months. (Fig. 1a) BCVA was 20/100 in left eye (OS). Patient had undergone focal superficial debridement outside, one month prior to presentation. Specimens sent for microbiological analysis had not yielded any positive results. Patient was being treated with high-dose systemic steroids along with empirical broad-spectrum antimicrobial therapy. Systemic history and examination were not contributory and without any history of risk factors like previous surgery and trauma. However, he had continued to worsen with severe pain and was referred to our centre. On examination, diffuse conjunctival congestion with multiple scleral abscesses was noted, and the site of earlier debridement revealed an adjacent pus point. Smear and culture reports from abscess were inconclusive. Serum rheumatoid arthritis (RA) factor, antinuclear antibody (ANA), and cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (c-ANCA and p-ANCA) were negative. Based on worsening clinical course while on corticosteroid therapy and multiple scleral abscesses, a diagnosis of infectious scleritis was made despite negative microbiological testing and a 360-degree scleral debridement was performed. (Fig. 1b) All forms of steroids were immediately stopped, and the patient was started empirically on intravenous third-generation cephalosporin (cefotaxime 1 g every 8 h) with fortified topical vancomycin (5%) and tobramycin (1.4%) every 2 h. Anti-glaucoma medication was added to the regimen. At one-week follow-up, patient had become pain free and the eye was less congested with minimal discharge. At one month, complete epithelialization of bare choroid was visible without any staphylomatous bulge. (Fig. 1c-d) Intraocular pressure was normal with a formed anterior chamber. Systemic antibiotics and anti-glaucoma therapy were withdrawn at the end of one month.

Case 2
A 60-year-old male presented with complaints of pain, redness and discharge in the left eye for 15 days. BCVA was finger counting close to face. Patient had undergone an uneventful manual-small incision cataract surgery, two months prior to presentation. The patient was stable post-operatively. Examination revealed focal necrotising scleritis at the incision site, hypopyon and dense vitritis. A diagnosis of postsurgical infectious scleritis with endophthalmitis was made. Topical moxifloxacin 0.5% and intravitreal antibiotics (vancomycin 1 mg/0.1 ml & ceftazidime 2.25 mg/0.1 ml) were administered and vitreous tap was subjected to microbiological analysis, which did not reveal any organisms. Topical therapy was continued and oral steroids were also initiated as per standard regimen (tablet prednisolone 0.5 mg/kg once a day) for endophthalmitis along with oral antibiotics (tablet ciprofloxacin 500 mg two times a day). Next follow-up review after one week revealed a superior perilimbal uveal show with surrounding necrotic scleral tissue, congestion, increased pain and discharge. Several new lesions of active scleritis had also developed with multifocal abscesses. Gram stain and culture results of focal superficial debridement revealed Pseudomonas aeruginosa. In view of culture results and progressive necrotising scleritis-fortified topical tobramycin (1.4%) was added, systemic antimicrobials based on sensitivity (similar to Patient 1) were initiated, and corticosteroids were withdrawn. Despite treatment revision, the lesions continued to progress; hence, full-thickness circumferential scleral debridement was performed to save the eye and prevent evisceration (Fig. 2a). Progressive clinical improvement was noted post-operatively and on subsequent follow-up visits. At one-year follow-up, the patient had a BCVA of 20/160; all medications were stopped and had a normal IOP with posterior capsular opacification, without any recurrence or evidence of ciliary staphyloma. (Fig. 2b).

Case 3
A 44-year-old female presented with complaints of redness, pain and swelling in her left eye for two weeks. (Figure 3a) There was an unclear history of trauma by vegetative matter two weeks prior to presentation. Examination revealed a BCVA of 20/80. No signs of trauma or foreign body was found and a provisional diagnosis of autoimmune diffuse anterior scleritis was made and the patient was initiated on topical corticosteroids with oral indomethacin. Due to inadequate improvement in clinical picture, the patient was started on oral corticosteroids on subsequent visits, followed by a transient The systemic vasculitis/rheumatologic workup was negative, and hence, the patient was continued on systemic corticosteroids. At two-week follow-up, the clinical picture had rapidly deteriorated, and examination revealed a well-defined, boggy swelling at the site of initial congestion with worsened pain. An abscess was suspected, and the patient was taken up for exploration. Bare choroid with full-thickness scleral melt was noted on conjunctival incision. (Fig. 3b) Microscopy revealed septate fungal hyphae, and culture report showed Fusarium spp. Oral steroids were urgently withdrawn while the patient was started on oral and topical antifungal treatment (topical voriconazole 1% every 2 h and oral voriconazole 200 mg two times day). Following specific antifungal therapy, lesions showed significant resolution; therefore, corticosteroid adjunctive therapy was also added to this regimen to prevent collateral damage due to persistent scleral inflammation However, two weeks later patient returned with new lesions-identified as multifocal scleral abscesses (Fig. 3c). Multiple scleral debridement procedures were undertaken, since the lesions continued to progress in an annular fashion, until total 360-degree band of scleral tissue was excised. Antifungal therapy could be withdrawn at the end of three months. At one-year follow-up, patient had BCVA of 20/30. The integrity of the globe was maintained with a normal IOP and no signs of recurrence or ciliary staphyloma. A distinct deep blue to black, circumferential band of uveal tissue (approximately 6-8 mm in width) is noticed with healthy epithelization and vascularization. (Fig. 3d). A 50-year-old female presented with complaints of redness and pain in her left eye for five days. Examination revealed a BCVA of 20/40, circumcorneal congestion, anterior chamber cells and normal posterior segment. (Figure 4a) Patient was prescribed topical corticosteroids (prednisolone acetate 1% every two hours) and cycloplegics (atropine sulphate 1% three times a day) and was asked to return after one week. A week later, vision had dropped to 20/500 with fibrin in the anterior chamber and no view of the fundus, ultrasonography (USG B-scan) revealed normal posterior segment study. Rheumatology workup and serology testing were inconclusive with regard to associated systemic vasculitis. Provisional diagnosis of acute-fibrinous anterior uveitis with diffuse anterior scleritis was made and systemic corticosteroids (tablet prednisolone 1 mg/kg once a day) were initiated in addition to topical therapy. There was progressive deterioration of clinical picture on further follow-up, while still being on adequate corticosteroid therapy. On review and reassessment, the possibility of an infectious aetiology was considered, which was further corroborated by the development of a scleral abscess. However, smear and culture results were negative, yet all forms of corticosteroids were withdrawn, and empirical antimicrobials were initiated.
Due to continued annular progression of necrotising scleritis and appearance of multifocal abscesses, with inconclusive microbiology results, the patient was taken up for circumferential scleral debridement. (Figure 4b) Broad-spectrum antimicrobials (similar to Patient 1) were continued. Patient was symptomatically better during subsequent visits. (Figure 4c) Eight months following full-thickness surgical debridement, the patient underwent an uneventful phacoemulsification with IOL implantation. The phacodynamics were titrated to low-flow/vacuum settings and chamber stability was ensured with appropriate interventions throughout surgery. At one-year followup, patient achieved a BCVA of 20/80 with a quiet eye, normal fundus and no signs of recurrence or ciliary staphyloma. Anatomical integrity of the globe was preserved, and intraocular pressure was 16 mm Hg. (Fig. 4d).

Case 5
A 50-year-old male presented with complaint of pain in the left eye for 15 days. He was initially diagnosed as having nodular episcleritis based on presenting clinical picture and was treated with topical steroids (prednisolone acetate 1% every two hours) and cycloplegics (atropine sulphate 1% three times a day). His presenting BCVA was 20/40. On subsequent follow-ups, his condition worsened; thus, systemic corticosteroids (tablet prednisolone 1 mg/kg once a day) were added to the regimen (Fig. 5a), despite which the condition continued to worsen and developed a violaceous raised lesion with tortuous conjunctival vessels, appearing in the perilimbal area. The patient was taken up for scleral debridement. A 180°t emporal full-thickness scleral debridement was performed in view of total scleral melt in the affected area. (Figure 5b) Further progression necessitated additional debridement of the upper-nasal sclera. Gram staining revealed the presence of neutrophils with no detectable organisms. Broad-spectrum antibiotics were empirically added (similar to Patient 1). One week post-debridement, the patient improved symptomatically. (Figure 5c) A month after the debridement, the patient had a BCVA of 20/100 with minimal discharge and conjunctival congestion. Topical antibiotics and anti-glaucoma medications were continued. Three months after debridement, the patient was maintaining a BCVA of 20/80 with uveal show, no evidence of congestion and an IOP of 10 mm Hg. (Figure 5d).
In three out of the five cases (cases 1, 4 & 5), microbiology was inconclusive. (Table 1) No microorganisms/fungal hyphae were observed on HPE of the debrided scleral tissue; however, all cases revealed features suggestive of necrotising inflammation. Case 1 was suspected to be infectious scleritis based on clinical picture; however due to lack of microbiological evidence, the autoimmune aetiology was considered and corticosteroids were started. In contrast to case 1-cases 4 & 5 were initially misdiagnosed as autoimmune scleritis based on mimicking clinical presentation and negative microbiological yield but progressive worsening on corticosteroid therapy confirmed otherwise. In cases 2 & 3, corticosteroids were started as anti-inflammatory adjunct to specific antimicrobial therapy and still caused unabated progression of disease. All patients had improved after debridement and presented a stable clinical course without recurrence, upto a minimum of one-year follow-up. Anti-glaucoma therapy was given in all cases to achieve target IOP of 10-12 mm of Hg, in view of lack of scleral support during the initial one month post-operatively. We observed that patients worsened on corticosteroids therapy and acquired a relentless clinical course, despite a microbiologically proven aetiology and concurrent specific/culture-sensitive antimicrobial therapy (cases 2 & 3). This aggressive clinical metamorphosis led to full-thickness necrotising scleritis and could eventually only be managed by full-thickness debridement.

Discussion
Scleritis is more commonly associated with autoimmune disorders than with infectious etiologies [13].
Owing to the overlap of presenting clinical features, infectious scleritis is often initially misdiagnosed and treated with corticosteroids, leading to worsening of the disease into a fulminant and relentlessly progressive clinical course. Aggressive surgical management may often be required for globe salvage in these cases. Pseudomonas, Staphylococcus and Herpes zoster are common agents that can cause infectious scleritis which mimics autoimmune disease [8,14]. All five patients in our study had a common history of treatment with systemic steroids that may have led to worsening of their scleritis. (Table 1) Sahu et al. observed that in their cohort of 17 patients with infectious scleritis, 15 were on topical steroids. The authors have attributed the worsening of infections in these patients to the inhibition of lysosomal enzymes and suppression of immunity [15].
Patient 1 presented to us after focal debridement and abscess drainage carried out at another facility and was treated with systemic steroids throughout because the microbiology was non-revealing. In view of the fulminant clinical picture, the patient was promptly taken up for surgical debridement. 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 [16]. Patient 2 presented two months after cataract surgery with a surgical wound infection. Infectious scleritis has been reported after various surgical procedures like pterygium excision, cataract and vitreoretinal surgery [11,17,18]. Patients with a prior history of ocular surgery and then presenting with necrotising scleritis at the site of tissue penetration should be suspected to have infectious scleritis. The presentation at two months is similar to that observed by Hodson et al.,who noted that fastidious organisms had a longer time between symptoms and diagnosis than the non-fastidious ones [17].
Patient 3 gave a history of trauma by vegetative matter. Reddy et al. noted a history of trauma in 22% of scleritis due to infectious aetiology [19]. Ahn et al. observed a poorer prognosis amongst eyes with fungal scleritis, most likely due to delay in diagnosis and its  [20]. Jain et al. observed that fungal scleritis was more commonly seen in areas of hot, humid climate and found Aspergillus and Nocardia to be the most common pathological agents.
Of the eight cases of fungal scleritis, four eyes were eviscerated and only one retained useful vision despite adequate antifungal therapy and surgical debridement in their series. This highlights the need for prompt diagnosis and early, aggressive surgical debridement [7]. Multiple scleral debridements were performed in our cases, which are frequently needed in fungal scleritis due to the increased incidence of recurrence as reported by Reddy et al. [19]. Patient 4 initially presented with a clinical picture of acute anterior uveitis with diffuse anterior scleritis, which worsened on corticosteroids and led to the formation of scleral abscess. These abscesses are most commonly located along an arc 3-4 mm from the limbus as observed by Hsiao et al. [11]. The patient underwent an uneventful phacoemulsification and had a stable post-operative course, reaffirming the anatomical stability of the globe after circumferential debridement.
Patient 5 presented with a condition mimicking nodular episcleritis. This case also highlighted the fact that infectious scleritis may be confused initially with its autoimmune counterpart and the administration of corticosteroids may be considered in a step-wise fashion. However, once the misdiagnosed infectious aetiology was exposed to systemic steroids, the progression was unabated, only to culminate in a full-thickness necrotising involvement of scleral tissue-thus mandating an aggressive surgical approach.
Surgical debridement plays an important role in the management of infectious scleritis. The relative avascularity of the sclera and the dense structure of the collagen fibres hinder penetration by topical and systemic antibiotics [20]. The picture is further complicated in infectious scleritis of fungal aetiology, where the hyphae are enmeshed into scleral lamellae extending into the apparently uninvolved tissue. Whereas in bacterial aetiology, 'biofilm' formation could play a role in infectious scleritis' resistance to medical treatment. Bacterial colonies are contained in an extracellular matrix of exopolysaccharides inside the biofilm architecture, which protects them from hostile conditions and reduces their susceptibility to antibiotics, making them more resistant to standard medical treatment [21]. Early surgical debridement decreases the pathogenic burden and removes the proteases and 'biofilm' along with necrotic tissue, hence expediting wound healing [22,23]. Therefore, surgical debridement needs to be aggressive and extensive without sparing the overlying conjunctiva. The procedure also provides samples for microbiological analysis, further aiding the establishment of definitive diagnosis and early institution of targeted therapy.
Conjunctival excision is recommended in order to prevent re-organization of abscess after surgical debridement, enhance drug-penetration and maximize elimination of infection. Tittler et al. demonstrated a 100% globe preservation rate, and improved visual rehabilitation and fewer complications by doing a prompt surgical debridement at diagnosis [16]. We performed a full-thickness surgical debridement in all cases, since it has been reported that aggressive, early debridement not only debulks the infected scleral tissue, but also aids in antibiotic penetration [15,19].
It must, however, be remembered that one needs to exercise extreme caution while performing full-thickness excision of necrosed and melted scleral tissue (often with circumferential extent and cheesy consistency in steroid exposed cases) as discussed in our study. One blade of the scissors is circumferentially slid into the supra-choroidal space as far as no resistance is encountered and the affected tissue is then cut along the junction of infected and normal sclera both anteriorly and posteriorly. It has also been shown that the extent of involved sclera is better delineated intraoperatively than on clinical examination, and often the actual extent is greater, than that observed on clinical examination.
Extensive scleral debridement has also been shown to require patch graft [7,15]. However, in our series, scleral patch graft was not resorted to, despite extensive full-thickness debridement. In our experience, application of preserved/cadaveric, avascular, scleral patch graft at the site of active infection not only leads to persistence of infectious focus and reorganization of abscess, but also leads to necrosis of the graft. Epithelisation of the bare choroid/uveal tissue in early post-operative period was observed.
All patients were maintained on anti-glaucoma medications for an initial one month, in order to prevent spikes in intraocular pressure due to inflammation. This was necessary to prevent the dehiscence of bare choroid in early post-operative period, and formation of ciliary staphyloma in late post-operative period-which may occur due to circumferential lack of scleral support.
Recurrences in case of infectious scleritis are rare after complete resolution as opposed to autoimmune scleritis, where frequent recurrences occur [17]. We observed similar findings in our series where none of the patients had recurrence after scleral debridement until a minimum follow-up period of one year. The integrity of the globe was maintained as demonstrated by an uneventful phacoemulsification with intraocular lens implantation in one patient and stable postoperative course in all patients. Thus, good anatomical and visual outcome after the procedure was achieved without the use of a scleral patch graft in any case.
It is worth noting that while dealing with cases of infectious scleritis, greater emphasis must be laid on the role of medical therapy aided by focal debridements. Extensive full-thickness scleral debridement, on the other hand, could offer a last-resort advantage in managing extraordinary clinical situations, that are frequently encountered in tertiary care referral centres. These would include cases with proven infectious scleritis, demonstrating relentless progression, despite being on specific antimicrobial treatment. Various referral cases have usually been through multiple consultations and received cocktail treatments, before presenting with a morphed clinical picture. And cases of infectious scleritis misdiagnosed as autoimmune scleritis-which were treated with escalating dosages of corticosteroids and immunosuppressive drugs and therefore turned fulminant-are not uncommon.
Infectious scleritis should be considered in patients showing inadequate clinical response to steroid therapy, reactivation/non-resolution of an existing lesion or appearance of new lesion/lesions. History of trauma may not be forthcoming in all cases especially when a trivial trauma has gone unnoticed. Full-thickness removal of infected and necrosed sclera appears to be a safe procedure in managing such cases of infectious scleritis, especially following steroid exposure. This study highlights the fulminant and relentlessly progressive clinical course, that infectious scleritis can metamorphose into-despite specific antimicrobial therapy-if inadvertent corticosteroid therapy has been administered. Full-thickness debridement without scleral patch graft, could achieve elimination of infectious foci with favourable longterm anatomical and visual outcomes. This technique could offer a potential last resort approach in such cases where standard therapeutic modalities have not been successful.