|Year : 2015 | Volume
| Issue : 1 | Page : 29-32
Endogenous endophthalmitis following prolong use of methotrexate
Vishal Katiyar, Ankur Yadav, Prateep Phadikar, Sanjiv Kumar Gupta
Department of Ophthalmology, K.G.M.U, Lucknow, Uttar Pradesh, India
|Date of Web Publication||29-Mar-2016|
Department of Ophthalmology, K.G.M.U, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
A 46 yr old male presented to us with a 2 day history of pain, redness and discharge in left eye. The patient was on oral Methotrexate (12.5 mg) weekly with folic acid supplement for the last 1 year for recurrent Uveitis (LE). There was a history of three previous episodes of acute anterior uveitis in left eye 2 years back for which he was prescribed oral steroids. The uveitis attack use to flare up on tapering the steroids. In the hope to reduce the recurrences and to prevent long-term complications, the patient was shifted to oral methotrexate (12.5 mg) weekly with folic acid supplementation. On the basis of clinical examination and B- scan a presumptive diagnosis of endogenous endophthalmitis was made. Vitreous tap revealed a straw colored sample and the culture subsequently grew methicillin sensitive Staphylococcus epidermidis. Intravitreal injection of (Piperacillin+Tazobactum) 225 microgram in 0.1 ml was administered. In addition, intravenous (piperacillin+tazobactum) 4.5 gram BD was given for 3 days. Post intra vitreal injection the symtoms and signs resolved remarkably. Methotrexate has not been previously implicated with endogenous endophthalmitis. Besides, Endogenous endophthalmitis is an ongoing diagnostic and therapeutic dilemma for ophthalmologists as it is relatively rare and often presents like uveitis. It requires a high index of suspicion for prompt diagnosis and treatment. The treatment of EE is still controversial due to a lack of clinical trials. Future large group studies need to be done for validation of the above therapeutic regime.
Keywords: Endogenous, endophthalmitis, methotrexate
|How to cite this article:|
Katiyar V, Yadav A, Phadikar P, Gupta SK. Endogenous endophthalmitis following prolong use of methotrexate. Egypt Retina J 2015;3:29-32
| Introduction|| |
The development of the immunosuppressive drugs has revolutionized the management of chronic inflammatory disorders such as anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, with lesser dependence on the steroids, and thus sparing steroid-induced side effects. Adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs has been an effective modality for the management of inflammatory activity and well tolerated by most patients and seems to convey little risk of serious side effects during treatment.  Specialists prescribing methotrexate should be aware of the unusual and severe clinical presentations that can occur. We report a case of methicillin-sensitive coagulase-negative Staphylococcus causing endogenous endophthalmitis (EE) following prolong methotrexate therapy, getting resolved with intravitreal and intravenous piperacillin + tazobactam. Methotrexate has not been previously implicated with EE. ,
| Case Report|| |
A 46-year-old male presented to us with a 2-day history of pain, redness, and discharge in the left eye. Past history revealed that the patient was a known case of recurrent optic neuritis with optic atrophy (left eye). There was one attack of optic neuritis in right eye 10 years ago and in left eye on 2 occasion 5 years and 1-year back, for which patient was given intravenous methyl prednisolone (intravenous 250 mg 6 hourly for 3 days followed by oral prednisolone 1 mg/body weight for 11 days and a 3 days tapering of oral prednisolone thereafter). The patient underwent uncomplicated cataract surgery (phacoemulsification with posterior chamber intraocular lens) in left eye 1-year back prior to the presentation. No steroid treatment was given pre- or post-cataract surgery. There was a history of three previous episodes of acute anterior uveitis in left eye 2 years back for which he was prescribed oral steroids. The uveitis attack use to flare up on tapering the steroids. In the hope to reduce the recurrences and to prevent long-term complications, the patient was shifted to oral methotrexate (12.5 mg) weekly with folic acid supplementation. The patient was on oral methotrexate for the last 1-year with no recurrences. During this period patient also had recurrent episodes of flu-like symptoms and nocturnal fever. His serum blood gamma interferon level was found raised with sputum positive for tuberculosis bacteria, and the patient was on anti-tubercular drugs (Tab. forecox-2 tablets BD, containing isoniazid 150 mg, rifampicin 225 mg, pyrazinamide 750 mg, and ethambutol 400 mg) since 1-month. No history of ocular trauma. On examination, the vision was 6/12 (OD) on Snellen visual acuity chart, no perception of light (OS). The anterior chamber demonstrated cellular activity with cells Grade 4+, flare++, and 3 mm hypopyon [Figure 1]. There was no view of fundus because of Grade 4 vitritis. B-scan demonstrated extensive vitreous opacities and retina was flat [Figure 2]. A presumptive diagnosis of EE was made. He was admitted to the hospital, a vitreous tap was done using 1 ml dispovan syringe with a 26-gauge needle which revealed a straw colored sample. Intravitreal injection of (piperacillin + tazobactam) 225 μg in 0.1 ml was administered.  Immediate Gram stain of the sample identified moderate Gram-positive cocci, extensive polymorphonuclear cells, and the vitreous culture subsequently grew methicillin-sensitive Staphylococcus epidermidis. In addition to the intravitreal injection intravenous (piperacillin + tazobactam) 4.5 g BD for 3 days and eye drop moxifloxacin QID, eye drop tobramycin QID, and eye drop atropine TDS was given. Post-intravitreal injection the symptoms and signs resolved remarkably after 2 days. The hypopyon resolved completely with no activity in the anterior chamber [Figure 3]. Posterior segment also showed resolution of the exudates, with a faint fundal glow on retroillumination.
|Figure 1: Mixed conjunctival congestion, reaction in anterior chamber, and 3 mm hypopyon|
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|Figure 2: B-scan (left eye) showing vitreous exudates with no retinal detachment|
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|Figure 3: Complete resolution of hypopyon with no activity in anterior chamber after 24 h post-intravitreal injection|
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Further investigations and management were done in consultation with infectious disease specialist [Table 1]. Three sets of blood cultures, urine culture, a chest X-ray, lumbar spine X-ray, and computed tomography scan of orbits and sinuses revealed no significant pathology. A transthoracic echocardiogram was also normal, and thus no primary focus was identified.
| Discussion|| |
EE is a potentially blinding ocular infection resulting from hematogenous spread from a remote primary source. It is relatively rare, accounting for 2 to 8 percent of all cases of endophthalmitis, It usually affects immune-compromised people such as diabetes mellitus, renal failure, AIDS, malignancies, as well as immunosuppressive treatment. 
Candida is the most common organism causing EE.  Among the bacterial causes, Gram-positive bacteria such as Staphylococcus aureus, S. epidermidis, Streptococcus pneumonia, and other streptococcal organisms have also reported the most common causes of EE in the Western world.  S. epidermidis is a Gram-positive, coagulase-negative skin-colonising cocci, which does not usually produce aggressive virulence determinants, and usually requires an obvious breach in the host's defense mechanism to cause severe infection. The gold standard for identification of causative organism is positive culture.  Prolonged therapy with methotrexate lead to immunosuppression in the patient. The patient had recurrent episodes of flu-like symptoms and was positive for tuberculosis, which is more common in immune-compromised.
A detailed ocular history and examination should be performed for patients on prolong immunosuppressive therapy or hospitalized for a debilitating or febrile systemic illness. In this setting, any evidence of intraocular inflammation should be considered EE until proven otherwise. Early detection of EE remains difficult. The gradual onset and relatively indolent course coupled with masquerading signs of uveitis can delay diagnosis. The systemic features of infection such as elevated white cell count may be masked by immunosuppression. The source of infection is identified in the majority of endogenous bacterial endophthalmitis (EBE) cases (93%), most commonly as endocarditis or a gastrointestinal tract infection.  No source of primary infection could be found in this case.
EE is an ongoing diagnostic and therapeutic dilemma for ophthalmologists as it is relatively rare, often presents like uveitis. It requires a high index of suspicion for prompt diagnosis and treatment. The treatment of EE is still controversial due to a lack of clinical trials. The outcome of EE (compared with that of exogenous endophthalmitis) is disappointing. Reports have found that 25% of eyes with EBE end up eviscerated or enucleated.  The greatest prognostic factors in EBE seems to be the infecting bacteria and the timing of initiating treatment. High clinical suspicion, early diagnosis by vitreous biopsy and prompt aggressive treatment are imperative to minimize the risk of losing the eye.
The decision for empirical treatment with intravitreal piperacillin and tazobactam was based on the past institutional experience of high susceptibility of isolated organisms to this antibiotic combination. The organisms isolated from our institution were reported to be sensitive to piperacillin and tazobactam, meropenum and amikacin. Prompt administration of intravitreal antimicrobial followed by systemic antibiotic therapy was the key to the management of acute EE in this case. EE is particularly responsive to intravenous antibiotics while in exogenous, systemic antibiotics are not actually necessary.  Systemic antibiotics also treat distant foci of infection, if any, thereby reducing chances of an invasion of the unaffected eye. Intravitreal antibiotic injections which have revolutionized the treatment of exogenous endophthalmitis might have also showed beneficial results in this case suggested by the prompt resolution of the hypopyon and reaction in the anterior and posterior segment. Systemic antibiotic might have treated any subclinical distant foci besides adding to the therapeutic benefit in the endophthalmitis. Future large group studies need to be done for validation of the above therapeutic regime.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3]