INTRODUCTION
Scleritis refers to a severe painful inflammatory condition of sclera, which may involve cornea, uveal tissue, and adjacent episclera. Scleritis due to infective etiology is a rare entity which accounts for 5%–10% of all cases of scleritis.[1] The initial clinical picture of infectious scleritis may be identical to that caused by immune-mediated scleritis. Therefore, in a patient presenting with scleritis, an infectious etiology is many a times not suspected resulting in unusual delay in the diagnosis and consequently worsened outcome. Infectious scleritis may follow accidental or surgical trauma, severe endophthalmitis, or may occur as an extension of a primary corneal infection.[2] Systemic illness, use of corticosteroid and immunomodulators, or previous history of scleritis may also be predisposing factor.[3] Pseudomonas aeruginosa has been the most commonly reported causative agent in various series followed by fungus.[456] Other causative organisms such as Staphylococcus species, Streptococcus species, haemophilus influenza, Stenotrophomonas maltophilia, Serratia marcescens, Mycobacterium species, Nocardia, fungus, and virus have also been reported.[3] However, reports from India have stated fungi to be more common in tropical regions.[1] Sclera being an avascular structure with dense collagenous framework limits the penetration of traditional topical antibiotics. The clinical outcome in cases of infectious scleritis is generally poor and most cases required evisceration in many series.[27] Furthermore, very often misdiagnosis of autoimmune scleritis or postsurgical inflammatory scleritis with vigorous corticosteroid regime worsens condition and delays timely intervention.[8] However, a review of more recent reports clearly suggests that infectious scleritis can be managed successfully with good visual and anatomical outcome as a result of early diagnosis with combined antibiotic therapy and early surgical intervention.[456]
MATERIALS AND METHODS
We retrospectively reviewed the medical and microbiological records of all patients with microbiologically proven infectious scleritis examined from January 2016 to December 2019 in Department of Cornea and refractive surgery services in our hospital. Information including patient's age, gender, the predisposing factors, pathogenic organisms, duration of presentation, clinical presentation, methods of diagnosis, treatment, and outcomes were abstracted from the medical records. At presentation, all patients were examined in detail under slit lamp. With proper consent of patient, suspected infective scleral lesions with ulceration were subjected to scraping with scleral knife under topical anesthesia and smeared on glass slides for Gram's staining and potassium hydroxide mount. All the cases were subjected to incision and drainage with scleral debridement under peribulbar anesthesia in the operating room. Materials collected from the lesions were smeared on glass slides and stained with potassium hydroxide and Grams stain and were sent for culture on blood agar, chocolate agar, potato dextrose agar, and nonnutrient agar with an Escherichia coli overlay. Significant growth was defined as confluent growth on solid media, and/or there was growth of the same organism on more than one medium, and/or growth in one medium was accompanied by the presence of similar organism in smears. Microbiologically culture-proven cases of scleral ulcer and/or abscess were included in the study, while cases with no growth in culture were excluded from the study. All bacteria and fungi grown were identified and were tested for antibiotic susceptibility by Kirby-Bauer disc diffusion method. Initial therapy was based on either the clinical suspicion or results of microscopic examination of smears. Treatment was later modified depending on the clinical response and the results of culture and sensitivity. Resolution was defined as absence of symptoms, congestion, or active infiltrate.
RESULTS
We included 12 cases (12 eyes) of infectious scleritis, among which 9 were males and 3 were females [demographic features, clinical presentation, and etiology are detailed in Table 1, treatment and outcome are detailed in Table 2]. Age ranged from 32 years to 76 years (mean 52.4 ± 13.3 years, median 49.3 years). The mean duration from onset of symptoms to presentation was 12.16 ± 9.5 days (range of 4–30 days). The mean follow-up period was 16.3 ± 14.4 weeks (range of 3–46 weeks). Average duration of healing of lesion with appropriate treatment was 4.9 ± 3.2 weeks (range of 1–12 weeks).
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Table 1: Demographic features, clinical presentation, and etiology
Table 2: Treatment and outcome
Trauma was the most common predisposing factor (41.6%, n = 5) followed by previous history of cataract surgery (25%, n = 3), all of which were manual small incision cataract surgery. In four patients (33%), no history of trauma or surgery could be elicited, but all these cases were on topical steroids for a prolonged duration before presenting to us. The interval from trauma to presentation of infectious scleritis ranged from 4 days to 1 month (mean = 19.6 days) while that of preceding ocular surgery to presentation ranged from 15 days to 6 years. Six patients (50%) were using topical corticosteroids at the time of reporting to us. Only one patient was diabetic in this series. Rest patients did not have any significant systemic illness. Most common presenting symptoms were redness (83%) and moderate-to-severe pain (in all the cases) in the affected eye. The presenting visual acuity varied from light perception present (PL) to a normal vision of 6/6. Five (41.6%) patients presented with a vision of 6/60 or worse.
Microbiological profile included fungus (50%, n = 6), P. aeruginosa (25%, n = 3), Nocardia (n = 1), Staphylococcus species (n = 1), and Klebsiella species (n = 1). One was a case of mixed Aspergillus and Streptococcal viridans infection (Case 5). Aspergillus species was the most common (83%, n = 5) of all fungal isolates. Nodular scleral lesion with pus point [Figure 1] was the most common (n = 11, 91.6%) presenting sign except one with scleral wound melt at scleral tunnel site (Case 12). Corneal involvement was seen in 16% cases (n = 2), and pseudomonas was the causative organism in both the cases. Multifocal abscess was noticed in 25% (n = 3) cases at presentation and 16% (n = 2) cases presented as unifocal abscess and progressed to multifocal during the course of treatment [Figure 2]. Severe anterior chamber reaction was seen in 4 cases (33%).
Figure 1: (a) Unifocal scleral abscess of fungal etiology (Case 8). (b) Unifocal scleral abscess 2-month posttreatment (Case 8)
Figure 2: Unifocal scleral abscess progressing to multifocal scleral abscess after initial debridement (Case 2). Scleral abscess progressing to multifocal scleral abscess after initial debridement (Case 2)
All cases underwent scleral debridement except one case with postcataract surgery wound melt [Figure 3]. Nearly 25% (n = 3) cases underwent multiple debridements due to recurrence at different location of sclera during the course of treatment. The surgical debridement was diagnostic in all cases. This also facilitated debulking of the infected scleral tissue and improved the drug penetration. During the surgical debridement, the actual area of involvement was usually found to be larger than that visible on slit-lamp examination. One case (Case 12) with post small incision cataract surgery scleral wound melt received scleral patch graft as primary procedure along with intraocular antibiotic in view of suspected postoperative endophthalmitis.
Figure 3: Postcataract surgery scleral wound melt (Case 12)
All cases with proven fungal etiology were treated with topical natamycin and topical fluoroquinolones, with additional systemic antifungal, in case of poor response. All cases due to culture-proven bacterial etiology were treated with topical antibiotics and systemic medication, based on antibiotic susceptibility testing [Table 3]. All cases of proven Pseudomonas infection received intravenous amikacin, while staphylococcal infection received oral ciprofloxacin. Tapering doses of topical steroids were given in scleritis of bacterial etiology after active infection subsided. Eighty-three percent (n = 10) of cases had complete resolution of infection and globe architecture was preserved, while 2 eyes underwent evisceration. Posterior segment examination with B scan was normal in all the eyes except one eye with panophthalmitis (Case 12).
Table 3: Antibiotic susceptibility of isolated organisms (Kirby-Bauer disc test)
Among the eyes which underwent evisceration, one patient (Case 1) [Figure 4] with culture-proven fungal infection, showed poor response with antifungal treatment, progressed to develop secondary glaucoma and painful blind eye and had to be eviscerated. Another case (Case 12) with postcataract surgery scleral melt underwent scleral patch graft and intravitreal antibiotics, subsequently developed panophthalmitis and was eviscerated. Three (25%) cases resolved with progression of cataract while one among them was complicated with choroidal detachment during the course of treatment which resolved with oral steroids.
Figure 4: Mixed fungal and nocardial scleritis postsurgical debridement (Case 1)
In our series, 41.6% (n = 5) patients had final best-corrected visual acuity (BCVA) of better than 6/18 while 25% (n = 3) had worse than 6/60 and 33% (n = 4) had fair visual outcome in between <6/18 and ≥6/60. Seventy-one percent of patients with presenting BCVA better than 6/60 had improved to 6/18 and better.
DISCUSSION
As reported earlier, trauma or prior history of ocular surgery raises the suspicion of infectious scleritis in all cases of scleral inflammation presenting as scleral abscess or ulceration.[159] Pterygium excision has been reported to be the most common surgical procedure in many series.[45610] Cataract surgery was seen to be the most common in another series.[1911] In our series, 50% cases had trauma while 25% cases had history of cataract surgery, while no case of prior pterygium surgery was seen. This difference of more number of cases due to trauma may be due to rural and agricultural background of our patients. Compared to rest of the world, small incision cataract surgeries are more often performed in India, which accounts for it being the most common ocular surgery responsible for the same.[9] It is unusual for the scleral site to be infected long after surgery but surgical-induced necrotizing scleritis (SINS) has been seen to be activated long after surgery.[12] Lin et al.[6] postulated that after initiation of SINS, microorganisms caused late-onset postsurgical infective scleritis. One of the cases in our series had post-SICS wound melt with infiltrate (Case 12). Melt in this case may be attributed to infective agent rather than SINS. None of our patients with late-onset scleritis had systemic vasculitis. Similar experience was reported by Altman et al.[13] and Jain et al.[1] in their case series. Meallet in 2006 proposed that the use of adjunctive therapies such as mitomycin and beta irradiation also likely compromise the integrity of episcleral conjunctival vessels and underlying tissue, inhibiting adequate wound healing, and leaving the sclera vulnerable to infection.[14] Often corticosteroids given before diagnosis of infective origin have been seen to increase the infection.[1] In our series, 6 cases had a history of steroid use. With no predisposing history of trauma or surgery, immunosuppression due to human immunodeficiency virus or chemotherapy may be a risk factor for spontaneous cases of infectious scleritis.[415] There were 4 cases in our series with no predisposing trauma or surgical history. None of the four cases had any endogenous infection or immunosuppression but were under prolonged usage of topical steroids.
P. aeruginosa is reported as the most common causative organism and rarely fungus for infective scleritis.[4516] Infection due to fungus, mostly Aspergillus, was found to be most common in our series. In India, fungus is reported to be the most common in many series with Aspergillus species being the most common[1911] too. High incidence of fungal infection in India is due to agriculture being the most common occupation among the masses and the tropical hot and humid climatic conditions. Infective scleritis often presents with multifocal nodules, Pseudomonas being most commonly reported with such presentation due to its proteolytic activity leading to intrascleral dissemination.[4569] Another series[1] saw all cases of multifocal presentation due to fungi. Our case series saw multifocal abscess (25%) at presentation in both pseudomonas (n = 2) and fungal scleritis (n = 1). Some studies have reported.[1456] that multifocal presentation is due to the load of infection and not due to the organism causing it, which can be well correlated to our findings.
As in autoimmune scleritis, patients with infectious scleritis commonly present with redness, pain, and epiphora.[11] Mild-to-moderate pain is generally associated with diffuse and nodular scleritis whereas severe pain is more frequently associated with necrotizing scleritis,[17] suggesting that pain out of proportion to examination findings may indicate underlying possible infectious etiology.[8] Hodson et al.[15] reported scleral necrosis (93%) as the most common clinical sign, 67% with adjacent ocular structures such as cornea and extraocular muscle involvement. An anterior chamber reaction >1+ grade is usually present at the initial encounter.[5] In our series, 33% (n = 4) had anterior uveitis and 16% (n = 2) had corneal infiltrate. Endophthalmitis has also been documented as the presenting finding.[161113] Progressive inflammation leads to pupillary membrane, cataract, glaucoma, retinal and choroidal detachment, and endophthalmitis. In our series, 25% cases resolved with cataract, other complications being choroidal detachment (n = 1), absolute glaucoma (n = 1), and panophthalmitis (n = 1).
Pyogenic infection of sclera is difficult to treat because of poor antimicrobial penetration. Abscess exploration with systemic and topical antimicrobial therapy yields superior result.[161819] Some studies found that surgical debridement improves visual outcome[20] while some showed that it shortens the course of treatment.[456] Pradhan and Jacob[9] showed that chances of globe preservation were better with prompt surgical debridement. Medical therapy was adequate as the sole treatment in only 18% of patients, with most requiring surgical debridement in a large case series studied by Hodson et al.[15] A higher rate of enucleation or evisceration was seen in those treated solely with medical methods.[2] Tittler et al.[20] showed a 100% globe preservation rate, with fewer complications and shorter hospital stays with prompt surgical debridement at diagnosis (within 2.5 days). We did surgical debridement within a mean duration of 6 days for all our cases expecting a better outcome in terms of globe preservation and were able to achieve the same in 83% of the cases. Scleral patch graft was done in one case (Case 12) in view of large defect postscleral debridement. In addition to surgical debridement and topical and systemic antibiotics, adjunctive procedures such as subconjunctival injections of antibiotic at both ends of the scleral lesion and wound irrigation with antibiotic solution one to two times a day followed by normal saline after improvement were shown to be beneficial.[6] Meallet[14] could achieve success in treating 6 cases of infective scleritis with the use of continuous subpalpebral lavage antibiotics. In our series, betadine 5% lavage was done in all cases after scleral debridement. Review literature revealed poor outcome in cases of fungal scleritis,[456] while 2 studies[911] showed good outcome in fungal scleritis with prompt surgical debridement and medical management similar to our study. Useful vision of ≥6/60 was retained in 61% eyes in series by Hsiao et al.,[5] 33% by Jain et al.,[1] and 83% by Kumar Sahu et al.[11] Vision ≥6/60 was retained in 75% of our patients. Seventy one of eyes with presenting visual acuity of >6/60 improved to 6/18 and better. Four out of 18, 3 out of 21, and none out of 17 eyes underwent evisceration in the above studies, respectively. Two out of 12 eyes underwent evisceration in our series. None of our cases showed recurrence once infection resolved completely although 3 cases underwent multiple debridements during active infection. Although the appearance of recurrences after achieving full resolution of scleritis is generally rare,[1520] still cases should be closely followed up for an extended period of time after resolution.
CONCLUSION
Trauma is a common predisposing factor for infectious scleritis apart from ocular surgery. Fungus is the most common organism responsible followed by Pseudomonas in countries with agricultural occupational background. Although difficult to differentiate from autoimmune scleritis, subtle differences in clinical features highlighted above should be kept in mind while dealing with any case of scleritis. Any case of scleritis worsening with steroid use should raise high suspicion of infective etiology. Prompt surgical debridement along with medical treatment plays a major role in early identification of infective agent as well reducing the infective load, thereby it helps in good visual outcomes and better chances of preservation of the globe.
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Conflicts of interest
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REFERENCES
1. Jain V, Garg P, Sharma S. Microbial
scleritis-experience from a developing country Eye (Lond). 2009;23:255–61
2. Reynolds MG, Alfonso E. Treatment of
infectious scleritis and keratoscleritis Am J Ophthalmol. 1991;112:543–7
3. Reddy JC, Murthy SI, Reddy AK, Garg P. Risk factors and clinical outcomes of bacterial and
fungal scleritis at a tertiary eye care hospital Middle East Afr J Ophthalmol. 2015;22:203–11
4. Huang FC, Huang SP, Tseng SH “Management of
infectious scleritis after pterygium excision,” Cornea. 2000;19:34–9
5. Hsiao CH, Chen JJ, Huang SC, Ma HK, Chen PY, Tsai RJ. Intrascleral dissemination of
infectious scleritis following pterygium excision Br J Ophthalmol. 1998;82:29–34
6. Lin CP, Shih MH, Tsai MC. Clinical experiences of
infectious scleral ulceration: A complication of pterygium operation Br J Ophthalmol. 1997;81:980–3
7. Sevel D. Necrogranulomatous
scleritis. Clinical and histologic features Am J Ophthalmol. 1967;64:1125–34
8. Ramenaden ER, Raiji VR. Clinical characteristics and visual outcomes in
infectious scleritis: A review Clin Ophthalmol. 2013;7:2113–22
9. Pradhan ZS, Jacob P.
Infectious scleritis: Clinical spectrum and management outcomes in India Indian J Ophthalmol. 2013;61:590–3
10. Cunningham MA, Alexander JK, Matoba AY, Jones DB, Wilhemus KR. Management and outcome of microbial anterior
scleritis Cornea. 2011;30:1020–3
11. Kumar Sahu S, Das S, Sharma S, Sahu K. Clinico-microbiological profile and treatment outcome of
infectious scleritis: Experience from a tertiary eye care center of India Int J Inflam. 2012;2012:753560
12. O'Donoghue E, Lightman S, Tuft S, Watson P. Surgically induced necrotising sclerokeratitis (SINS)--precipitating factors and response to treatment Br J Ophthalmol. 1992;76:17–21
13. Altman AJ, Cohen EJ, Berger ST, Mondino BJ.
Scleritis and
Streptococcus pneumoniae Cornea. 1991;10:341–5
14. Meallet MA. Subpalpebral lavage antibiotic treatment for severe
infectious scleritis and keratitis Cornea. 2006;25:159–63
15. Hodson KL, Galor A, Karp CL, Davis JL, Albini TA, Perez VL, et al Epidemiology and visual outcomes in patients with
infectious scleritis Cornea. 2013;32:466–72
16. Okhravi N, Odufuwa B, McCluskey P, Lightman S.
Scleritis Surv Ophthalmol. 2005;50:351–63
17. Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with
scleritis and episcleritis Ophthalmology. 2012;119:43–50
18. Bernauer W, Allan BD, Dart JK. Successful management of
Aspergillus scleritis by medical and surgical treatment Eye (Lond). 1998;12(Pt 2):311–6
19. Helm CJ, Holland GN, Webster RG Jr., Maloney RK, Mondino BJ. Combination intravenous ceftazidime and aminoglycosides in the treatment of pseudomonal
scleritis Ophthalmology. 1997;104:838–43
20. Tittler EH, Nguyen P, Rue KS, Vasconcelos-Santos DV, Song JC, Irvine JA, et al Early surgical debridement in the management of
infectious scleritis after pterygium excision J Ophthalmic Inflamm Infect. 2012;2:81–7
