Dr.bidisha mahapatra

Dr.SHIVANANDA NARAYANA, Dr. KUNAL MANDLIK

Abstract

Aim: To study the clinico-microbiological profile and treatment outcome of infectious scleritis.

Method: All cases of infectious scleritis between January 2016 and December 2019 were reviewed and demographical, clinico-microbiological data and treatment outcome was analysed.

Results: 12 cases of infectious scleritis identified. All except 4 cases had history of trauma(41.6%) or cataract surgery(25%).Redness with pain was most common presenting complaint.Most common organism was fungus(50%,n=6), followed by Pseudomonas (25%,n=3).Microbe specific medical treatment and scleral debridement was done for all cases.Globe was preserved in 83.3% cases. 41.6% had BCVA ≥6/18 at the end of 3 months

Conclusion: Trauma is the commonest predisposing factor followed by surgery.Fungi are the commonest causative agent followed by Pseudomonas.Early surgical debridement helps in early identification of the organism and reduction of infective load,thus, playing major role in visual and anatomical success.

Full Text

Abstract: 

Aim: To study the clinico-microbiological profile and treatment outcome of infectious scleritis. Method: All cases of infectious scleritis between January 2016 and December 2019 were reviewed and demographical, clinico-microbiological data and treatment outcome was analysed. Results: 12 cases of infectious scleritis were identified. All except 4 cases had history of trauma (41.6%) or cataract surgery (25%). Redness with pain was most common presenting complaint. Most common causative organism was fungus (50%, n=6), followed by Pseudomonas (25%, n=3). Microbe specific medical treatment and scleral debridement was done for all cases. Globe was preserved in 83.3% cases. 41.6% had BCVA ≥6/18 at the end of 3 months. Conclusion: Trauma is the commonest predisposing factor for infectious scleritis followed by surgery. Fungi are the commonest causative agent followed by Pseudomonas. Early surgical debridement helps in early identification of the organism and reduction of infective load, thus playing a major role in visual and anatomical success.

 Keywords- infectious; scleritis; trauma; fungal 

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 and accounts for 5–10% of all cases of scleritis¹. 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 often 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 infection². Systemic illness, use of corticosteroid and immunomodulators or previous history of scleritis may also be predisposing factor³. Pseudomonas aeruginosa has been the most commonly reported causative agent in various series followed by fungus^4-6. Other causative organisms like Staphylococcus species, Streptococcus species, Hemophilus influenza, Stenotrophomonas maltophilia, Serratia marcescens, Mycobacterium species, Nocardia, fungus, and virus have also been reported³. However, reports from India have stated fungi to be more common in tropical regions¹. 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^2,7.  Also, very often misdiagnosis of autoimmune scleritis or post surgical inflammatory scleritis with vigorous corticosteroid regime worsens the condition and delays timely intervention ⁸. But, a review of more recent reports clearly suggests that if early diagnosis is combined with prompt institution of antibiotic therapy and early surgical intervention, infectious scleritis can be managed successfully with good visual and anatomical outcome ^4-6.

 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 anaesthesia 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 anaesthesia in the operating room. Materials collected from the lesions were smeared on glass slides and stained with Potassium hydroxide and Gram’s stain and were sent for  culture on blood agar, chocolate agar, potato dextrose agar (PDA) and nonnutrient agar with an Escherichia coli overlay.  Significant growth was defined as confluent growth on solid media, and/or growth of the same organism on more than one medium, and/or growth in one medium was accompanied by 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 females (Demographic features, clinical presentation and etiology are detailed in Table I, treatment and outcome are detailed in Table II). 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 to 30days). The mean follow up period was 16.3 ± 14.4 weeks (range of 3 to 46 weeks). Average time taken for healing of lesion with appropriate treatment was 4.9 ± 3.2 weeks(range of 1 to 12 weeks).

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 4 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 4days to 1month(mean=19.6days), while that of preceding ocular surgery to presentation ranged from 15days to 6years. Six patients (50%) were using topical corticosteroids at the time of reporting to us. Out of twelve patients only 1 had diabetes mellitus while the remaining eleven patients didn’t 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 positive) to a normal vision of 6/6. Five (41.6%) patients presented with a visual acuity of 6/60 or worse.

Microbiological profile included fungus (50%, n=6), Pseudomonas 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 commonest (83%, n = 5) of all fungal isolates. Nodular scleral lesion with pus point^(Fig1) was the commonest(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^(fig2).Severe anterior chamber reaction was seen in 4 cases(33%).

All cases underwent  scleral debridement except one case who had post cataract surgery wound melt^(fig3). 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 post operative endophthalmitis.

All cases with proven  fungal etiology were treated with topical natamycin and topical fluoroquinolones, with additional systemic antifungal drugs, 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 III). All cases of proven pseudomonas infection received intravenous amikacin, while staphylococcal infection received oral ciprofloxacin. Tapering doses of topical steroids, was given in scleritis of bacterial etiology after active infection had subsided.  83%(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 ultrasound was normal in all the eyes except one eye with panophthalmitis(case 12).

Among the eyes which underwent evisceration, one patient(case 1)^{(Fig 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 post cataract surgery scleral melt underwent scleral patch graft and intravitreal antibiotics, but 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.

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. 71% 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^1,5,9 . Pterygium excision has been reported to be the most common surgical procedure in many series^4,5,6,10. Cataract surgery was seen to be the commonest in another series^1,9,11. 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 in our series 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 same⁹. It is unusual for the scleral site to be infected long after surgery but surgical induced necrotising scleritis (SINS) has been seen to be occur long after surgery¹². Lin et al⁶ postulated that after initiation of SINS, microorganisms caused late onset post-surgical 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 al¹³ and Jain et al¹ 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 infection¹⁴. Often corticosteroids given before diagnosis of infective origin, has been seen to increase the infection¹. In our series, 6 cases had 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^4,15. There were 4 cases in our series with no predisposing trauma or surgical history. None of the four cases had any endogenous focus of infection or immunosuppression, but were under prolonged usage of topical steroids.

Pseudomonas aeruginosa is reported as the most common causative organism and rarely fungus for infective scleritis^4,5,16.  Infection due to fungus, mostly Aspergillus, was found to be commonest in our series. In India, fungus is reported to be the most common in many series with Aspergillus species being the commonest causative agent^1,9,11. High incidence of fungal infection in India is due to agriculture being the most common occupation among the population 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^4,5,6,9. In another series¹ all cases of multifocal presentation were 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^1,4-6, 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 epiphora¹¹.  Mild to moderate pain is generally associated with diffuse and nodular scleritis whereas severe pain is more frequently associated with necrotizing scleritis¹⁷, suggesting that pain out of proportion to examination findings may indicate underlying possible infectious etiology⁸. Hodson KL et al¹⁵ reported scleral necrosis (93%) as the most common clinical sign, 67% had involvement of adjacent ocular structures like cornea and extraocular muscle. An anterior chamber reaction greater than 1+ grade is usually present at the initial encounter⁵. 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^1,6,11,13. 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 are difficult to treat because of poor antimicrobial penetration. Abscess exploration with systemic and topical antimicrobial therapy yields superior results^1,6,18,19. Some studies found that surgical debridement improves visual outcome²¹  while some showed that it shortens the course of treatment^4-6. Pradhan ZS et al⁹ showed that chances of globe preservation was 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 KL et al¹⁵. A higher rate of enucleation or evisceration was seen in those treated solely with medical methods². Tittler et al²⁰ 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 post scleral 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 was shown to be beneficial⁶.  Meallet¹⁴ could achieve success in treating 6 cases of infective scleritis with use of continuous subpalpebral lavage antibiotics. In our series, betadine 5% lavage was done in all cases after scleral debridement. Review of literature revealed poor outcome in cases of fungal scleritis^4-6, while 2 studies^9,11 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 al⁵ ,33% by Jain V et al¹ and 83% by Sahu SK et al¹¹. Vision ≥6/60 was retained in 75% of our patients. 71% of eyes with presenting visual acuity of >6/60 improved to 6/18 and better. 4 out of 18, 3 out of 21 and none out of 17 eyes underwent evisceration in the above studies respectively. 2 out of 12 eyes underwent evisceration in our series. None of our cases showed recurrence once infection resolved completely, though 3 cases underwent multiple debridements during active infection. Though the appearance of recurrences after achieving full resolution of scleritis is generally rare^15,20, 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 for infectious scleritis followed by Pseudomonas in countries with agricultural occupational background. Though 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 helping in attaining good visual outcomes and better chances of preservation of the globe.

References

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Table I: Demographic features, clinical presentation and etiology

Case no	Age/sex		Eye involved	Predisposing factor	Steroid use	Complains (days)	Associated features	Foci	Smear	Culture
1	48/M		OS	TRAUMA(sugarcane 1month)	–	7	SA	M	nocardia	Aspergillus flavus
2	60/M		OD	TRAUMA (stick 1month)	Y	30	SA	U	ND	Aspergillus flavus
3	40/M		OS	CATARACT SX(6yrs)	–	7	SA,scleral thinning,adherent leucoma	U	ND	Klebsiella pneumoniae
4	50/M		OD	NIL	Y	4	SA,AC reaction	U	ND	Pseudomonas aeruginosa
5	32/F		OS	NIL	Y	5	SA	U	fungus+GPC	Aspergillus flavus,Streptococcus pneumoniae
6	68/M		OS	TRAUMA (insect 14days)	–	14	SA	U	ND	Aspergillus flavus
7	36/M		OD	TRAUMA (insect 4days)	–	4	SA,corneal scar	U	GPC	Staphylococcus epidermidis
8	46/M		OS	NIL	Y	7	SA	U	no org	Fusarium
9	49/F		OS	NIL	Y	7	SA, corneal infiltrate,AC reaction	M	ND	Pseudomonas aeruginosa
10	60/M		OD	TRAUMA(dust 20days)	–	20	SA, AC reaction	U	no org	Nocardia
11	64/F		OD	CATARACT SX(3yrs)	–	30	SA	U	no org	Aspergillus flavus
12	76/M		OS	CATARACT SX(15days)	Y	11	Scleral melt,wound gaping, corneal infiltrate,AC exudates	M	GNB	Pseudomonas aeruginosa
		M- multifocal, U- unifocal, SA-scleral abscess, ND- not done, GPC- Gram positive cocci, GNB- Gram negative bacilli, org- organism, Y-yes

Table II: Treatment and outcome

Case no	V/A at presentation	Medical treatment (topical)	Medical treatment         ( systemic)	Surgical treatment	Final V/A	Complications	Outcome	Duration of healing(weeks)
1	6/18	Natamycin,itraconazole,amikacin	amikacin,TMX-SMZ	SD*,cryo,E	NPL	absolute glaucoma, painful blind eye	E	–
2	6/24p	natamycin,gatifloxacin	ketoconazole	SD*	6/24	cataract	R	12
3	6/60	gatifloxacin	Amikacin	SD	6/24		R	2
4	6/12	gatifloxacin,amikacin	Amikacin	SD*	6/12p		R	6
5	6/6	natamycin,moxifloxacin		SD	6/6		R	1
6	5/60	natamycin,gatifloxacin		SD	6/36		R	2
7	6/60	gatifloxacin,tobramycin	ciprofloxacin	SD	6/24	RCS thickening, ST fluid, cataract	R	2
8	6/12	natamycin,moxifloxacin		SD	6/18	cataract	R	6
9	3/60p	amikacin,moxifloxacin	Amikacin	SD	4/60		R	4
10	6/9	amikacin,moxifloxacin		SD	6/9		R	6
11	6/18p	natamycin,moxifloxacin		SD	6/18		R	8
12	PL+	amikacin,moxifloxacin	Amikacin	SPG, IOAB, E	NPL	panophthalmitis	E	–
SD-scleral debridement, *- multiple debridements, TMX-SMZ- trimethoprim sulphamethoxazole, E-evisceration, R-resolved, IOAB-intraocular antibiotics, SPG-scleral patch graft, cryo= cyclocryotherapy, RCS thickening = retinochoroidal scleral thickening, ST fluid= subtenon’s fluid

Table III: Antibiotic susceptibility of isolated organisms (Kirby Bauer disc test)

Antibiotic susceptibility

SL NO

Case no

Organism

Chlor

Cefa

Vanco

Cipro

Gati

Oflo

Amik

Tobra

1 2 3   4   5 6 7

3 4 5   7   9 10 12

Klebsiella Pseudomonas Streptococcus viridans Staphylococcus aureus Pseudomonas Nocardia Pseudomonas

R S S   S   I R S

ND ND R   R   ND S ND

ND ND S   S   ND S ND

S S S   S   S S S

S S S   R   S S S

S S S   S   S S S

S S ND   ND   S S S

S S S   S   S S S

Chlor- Chloramphenicol Cefa- Cefazolin Oflo- Ofloxacin Amik-amikacin

Tobra-Tobramycin Vanco-Vancomycin Gati-gatifloxacin Cipro-Ciprofloxacin

ND-Not done R-Resistant S-Sensitive