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 Table of Contents    
Year : 2012  |  Volume : 5  |  Issue : 2  |  Page : 106-108  

Bilateral symmetrical corneal melting following intravesical Bacille Calmette-Guerin therapy for bladder carcinoma

Department of Ophthalmology, Calcutta National Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication4-Aug-2012

Correspondence Address:
Chandana Chakraborty
A/1/1, Pearl Apartment, 50B, Kailas Bose Street, Kolkata-700006, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-620X.99374

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A 63-year-old man with unremarkable previous ocular history presented with bilateral symmetrical corneal ulceration along with mucopurulent conjunctivitis and dry eye 10 days after the fourth dose of intravesical Bacille Calmette-Guerin (BCG) instillation for treatment of bladder carcinoma. Slit lamp examination revealed thinning of the cornea at the base of the ulcer in both eyes. Conjunctival swab and scraping from ulcer sent for Gram and acid fast bacilli stain and culture were negative. On the basis of history, clinical examination, and laboratory investigations, we diagnosed it as bilateral immune mediated sterile corneal ulceration along with mucopurulent conjunctivitis and dry eye. He was treated with topical antibiotics, cycloplegics, cyclosporine, lubricant gel, and bandage contact lens. There was progressive stromal melting, descemetocele formation, and perforation in the inferior part of cornea in both the eyes. He was treated with pulse steroid and paramedian tarsorraphy in both eyes. The patient was subsequently lost to follow-up. We report this case to highlight this rare complication of BCG therapy, in order to improve their management protocol in patients with similar clinical profile. We could not find a similar case after thorough PubMed search.

Keywords: Bacille Calmette-Guerin, bladder carcinoma, corneal ulcer, descemetocele

How to cite this article:
Chakraborty C, Sarkar KC, Majumdar S, Chaudhury KP. Bilateral symmetrical corneal melting following intravesical Bacille Calmette-Guerin therapy for bladder carcinoma. Oman J Ophthalmol 2012;5:106-8

How to cite this URL:
Chakraborty C, Sarkar KC, Majumdar S, Chaudhury KP. Bilateral symmetrical corneal melting following intravesical Bacille Calmette-Guerin therapy for bladder carcinoma. Oman J Ophthalmol [serial online] 2012 [cited 2022 Dec 10];5:106-8. Available from: https://www.ojoonline.org/text.asp?2012/5/2/106/99374

   Introduction Top

Bacille Calmette-Guerin (BCG) is a live attenuated strain of bovine tubercle bacillus. Intravesical BCG therapy is one of the most effective therapies for both prophylaxis and treatment of carcinoma in situ and prophylaxis of primary or recurrent papillary tumors of the urinary bladder. [1] It is also used as an adjunctive therapy for superficial bladder cancer. [2] The mode of action of BCG is probably based on local stimulation of the immune system but the actual mechanism of antitumor activity is not clearly understood. While this treatment is generally well tolerated, both local (cystitis) and systemic infectious complications such as granulomatous hepatitis, pneumonitis and even lethal sepsis can arise. Considerable debate exists in the literature about whether these complications due to BCG represent a hypersensitivity reaction or ongoing active infection. Because it is usually difficult to isolate BCG organisms from affected organs, it is often unclear as to what extent such a reaction is caused by an infectious process versus an inflammatory hypersensitivity reaction, hence the term "systemic BCG reaction." [3]

However, ocular complications are very rare. Ocular complications such as keratitis, uveitis, [1] conjunctivitis, [4] autoimmune retinopathy, [5] panuveitis, [6] endophthalmitis, [7] choroiditis, [8] and chorioretinitis [9] have been documented.

We report a case of bilateral (B/L) sterile corneal ulceration with melting, along with purulent conjunctivitis and dry eye following intravesical BCG therapy.

   Case Report Top

A 63-year-old male presented to the eye emergency on 30 July 2011 with a 10-day history of bilateral (B/L) redness and photophobia. He had no history of ophthalmic ailments before this. Eight weeks prior to presentation he had been diagnosed with superficial transitional cell bladder carcinoma for which transurethral resection of bladder tumor (TURBT) was done, followed by intravesical BCG therapy (one instillation per week). Following the fourth dose of intravesical BCG vaccination, he developed fever, hematuria, and swelling over the parotid and neck glands for which anti-tubercular drugs consisting of rifampicin 450 mg, pyrazinamide 1500 mg, ethambutol 800 mg, isoniazide 300 mg (AKT4), broad spectrum antibiotic, and oral prednisolone (60 mg daily) were started by the treating urologist. Two days after the BCG injection, he developed B/L redness of eyes for which he was treated by a local ophthalmologist with topical antibiotic and lubricant gel, without any improvement.

His best-corrected visual acuity (BCVA) at presentation was 20/80 and 20/200 in the right eye (RE) and left eye (LE), respectively. Eyelashes were matted with thick mucopurulent discharge. After cleaning the eyes with normal saline, slit lamp (S/L) examination was done which showed subconjunctival hemorrhage, conjunctival and ciliary congestion, and corneal ulceration. In both the eyes, the ulcer was in the inferior part of the cornea extending to the limbus with surrounding infiltration [Figure 1] and [Figure 2]. Limbal ischemia adjacent to the ulcer was noted. Multiple Descemet's folds were found radiating towards the central cornea from the ulcer margin (BE). The ulcer bases were clear, devoid of any suppuration. Both cornea and conjunctiva appeared dry and lusterless. Anterior chamber (A/C) was deep and quiet and pupils were regular and reacting to light in BE. Direct and indirect ophthalmoscopy revealed normal fundus in RE, but the LE fundus could not be properly visualized due to corneal haze and mild cataractous change. Conjunctival swab from eyelids, fornices, and scraping from ulcer margin were sent for Gram and acid fast bacilli (AFB) stain and culture, which were bacteriologically negative. Corneal scraping was not done from ulcer base to avoid perforation. Schirmer's test detected severe dry eye (<2 mm BE). Laboratory studies showed an erythrocyte sedimentation rate of 56 mm in 1 st hour with the rest of hematological studies normal. Biochemistry showed raised serum sodium, urea, and creatinine. Tests for antinuclear antibodies and rheumatoid factor were negative. We diagnosed the case as B/L sterile corneal ulcer with mucopurulent conjunctivitis and dry eyes following intravesical BCG instillation. He was treated with moxifloxacin o.5% eye drops eight times daily, timolol eye drops (0.5%) twice daily, cyclosporine eye drops (0.05%) four times daily, atropine sulfate eye drops (1%) thrice daily, and lubricant gel six hourly. AKT4 and oral prednisolone were continued as before.

Follow-up (F/U) on day 1: BCVA was reduced to 20/200 (RE) and finger counting at 2 feet (LE). Conjunctival congestion and discharge decreased but descemetocele developed in both eyes [Figure 3]a and b. Bandage contact lenses (BCL) were inserted in BE and medications were continued as before. He was advised for admission and pulse steroid therapy but he refused.

F/U on day 2: A/C was shallow, pupils irregular, and iris prolapsed through the perforated ulcer bilaterally. The perforation measured 2 mm ΄ 1 mm RE and 3 mm ΄ 2 mm LE. The patient refused to get admitted and received two doses of pulse steroid therapy (intravenous methylprednisolone) as day care basis. Intravenous antibiotic was not given as he was already getting broad spectrum oral antibiotics (Tab cefixime 200 mg bd). Paramedian tarsorraphy was done (BE). The ulcers showed signs of regression but the patient was subsequently lost to follow-up, prior to completion of pulse steroid therapy.
Figure 1: Photograph showing corneal ulceration and mucopurulent conjunctivis in both the eyes

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Figure 2: Slit lamp view of corneal thinning in the left eye

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Figure 3: ( a ) Photograph showing corneal melting in both eyes. ( b ) Photograph showing descemetocele in left eye

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   Discussion Top

BCG has been used for the treatment of bladder cancer for many years. [5] Intravesical BCG is associated with more local and systemic side effects. The frequent local side effects of BCG intravesical instillations include cystitis, irritative voiding symptoms, and haematuria, which occur in approximately 75% of all patients. Rarely, serious local adverse events as a result of BCG infection, such as symptomatic granulomatous prostatitis and epididymo-orchitis, may occur. Systemic side effects like flu-like symptoms, arthalgia, and reactive arthritis may occur. [3],[10]

A similar episode was also seen in our case. Ocular toxicity like bilateral uveitis, [1],[6] endophthalmitis, [7] choroiditis, [8] chorioretinitis, [9] granulomatous uveitis, endogenous endophthalmitis with B\L infiltrative retinitis, and vitritis [5] have been reported.

In our case, the patient developed B/L symmetrical corneal ulcer with melting followed by perforation despite continuing the medications and use of BCL. Although it is not possible to definitely prove that intravesicular BCG caused bilateral corneal melting in our patient, we presume that this was an immune reaction in the absence of any other contributing factor. The possibility of an infective etiology by active mycobacterium must also be considered [1],[8] though AFB stain and culture was negative in our case.

We may not have enough evidence to link the use of intravesical BCG with these ocular changes, but the temporal relation to the BCG therapy suggests that BCG is the most likely triggering factor for the immune reaction.

We believe that this is the first reported case of bilateral symmetrical corneal melting along with mucopurulent conjunctivitis and dry eye caused by intravesical BCG instillation.

   Acknowledgement Top

The authors thank Dr. Jyotirmoy Datta, Professor, Head of Department, Department of Ophthalmology, Calcutta National Medical College and Hospital, Kolkata, for general support.

   References Top

1.Wertheim M, Astbury N. Bilateral uveitis after intravesical BCG immunotherapy for bladder carcinoma. Br J Ophthalmol 2002;86:706.  Back to cited text no. 1
2.Talbot EA, Perkins MD, Silva SF, Frothingham R. Disseminated bacilli Calmette-Guérin disease after vaccination: Case report and review. Clin Infect Dis 1997;24:1139-46.  Back to cited text no. 2
3.Lamm DL, Van Der Meijden PM, Morales A, Brosman SA, Catalona WJ, Herr HW, et al. Incidence and treatment of complications of bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol 1992;147:596-600.  Back to cited text no. 3
4.Tektonidou MG. Reiter's syndrome during intravesical BCG therapy for bladder carcinoma. Clin Rheumatol 2007;26:1368-9.  Back to cited text no. 4
5.Sharan S, Thirkill CE, Grigg JR. Autoimmune retinopathy associated with intravesical BCG therapy. Br J Ophthalmol 2005;89:927-8.  Back to cited text no. 5
6.Uppal GS, Shah AN, Tossounis CM, Tappin MJ. Bilateral panuveitis following intravesical BCG immunotherapy for bladder carcinoma. Ocul Immunol Inflamm 2010;18:292-6. Available from: http://informahealthcare.com/doi/abs/10.3109/09273948.2010.486099. [Last Accessed on 2011 Jul 10].  Back to cited text no. 6
7.Gerbrandy SJ, Schreuders LC, De Smet MD. Mycobacterium bovis endophthalmitis from BCG immunotherapy for bladder cancer. Ocul Immunol Inflamm 2008;16:95-7. Available from: http://informahealthcare.com/doi/abs/10.1080/09273940802056273. [Last Accessed on 2011 Jul 10].  Back to cited text no. 7
8.Gao CQ, Mithani R, Leya J, Dawravoo L, Bhatia A, Antoine J, et al. Granulomatous hepatitis, choroiditis and aortoduodenal fistula complicating intravesical Bacillus Calmette-Guérin therapy: Case report. BMC Infect Dis 2011;11:260.  Back to cited text no. 8
9.Crosier YG, Chamot L, Zografos L. Chorioretinitis induced by intravesical Bacillus Calmette-Guérin (BCG) instillations for urinary bladder carcinoma. Klin Monbl Augenheilkd 2003;220:193-5.  Back to cited text no. 9
10.Sylvester RJ. Bacillus Calmette-Guérin treatment of non-muscle invasive bladder cancer. Int J Urol 2011;18:113-20.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]

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