INTRAVITREAL RANIBIZUMAB IN THE TREATMENT OF FUNGAL ENDOPHTHALMITIS SCAR-RELATED CHOROIDAL NEOVASCULAR MEMBRANE Kasinathan Nachiappan, DNB, FRCS, Aradhana Kadekar, MS, Lingam Gopal, MS, FRCS, Tarun Sharma, MS, FRCS

Purpose: The purpose of this study was to report the efficacious use of intravitreal ranibizumab in the management of postfungal endophthalmitis scar-related choroidal neovascular membrane. Methods: This is an interventional case report. Results: The patient’s visual acuity was stabilized and membrane activity ceased after treatment with three injections of intravitreal ranibizumab at monthly intervals. Conclusion: Intravitreal ranibizumab can be useful in the treatment of inflammatory scar-related choroidal neovascular membrane. RETINAL CASES & BRIEF REPORTS 5:175–178, 2011

in both eyes. Slit-lamp examination showed cells in the anterior chamber (2+) and pigment deposition on the anterior lens capsule. A dilated fundus examination showed numerous ‘‘pearl string’’ ball opacities in the vitreous and irregular fluffy deposits on the posterior pole with an attached retina. A clinical diagnosis of bilateral, endogenous fungal endophthalmitis was made. Blood tests for human immunodeficiency virus and hepatitis B surface antigen and a blood culture were performed and proved to have negative results. A urine culture, however, grew Escherichia coli and Alcaligenes faecalis. The patient was started on systemic itraconazole and topical amphotericin B and natamycin eye drops. She underwent vitrectomy with an intravitreal injection of voriconazole in both eyes sequentially. A vitreous smear showed yeast cells and grew Candida parapsilosis on culture. Sensitivities to fluconazole, voriconazole, ketoconazole, and amphotericin B were established. Multiple injections of intravitreal voriconazole were also administered (50 mmgm/0.1 mL), in the perioperative period in both of the eyes. She was found to be doing well postoperatively, with clearing exudates and an attached retina. Subsequent

From the Shri Bhagawan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India

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34-year-old woman presented with a complaint of painless and acute diminution of vision in both eyes during the previous month. She was known to have well-controlled insulin-dependent diabetes mellitus. Her ocular history was insignificant. The patient correlated her decrease in vision with the surgical procedure of lithotripsy, which had been performed on her for the removal of renal calculi 5 weeks before presentation. Her ocular symptoms had begun 3 days after the lithotripsy. Examination of the records showed that she had developed septicemia a few days after the lithotripsy, which also coincided with the development of her ocular symptoms. On examination, her best-corrected visual acuity (BCVA) was recorded as counting fingers close to face None of the authors have any financial interest in any of the products mentioned. Reprint requests: N. Kasinathan DNB, FRCS, Department of Vitreoretina, Medical Research Foundation, Chennai, Tamil Nadu 600 006, India; e-mail: [email protected]

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follow-ups at regular intervals saw her doing well with resolution of the infection and stable fundii. At 8-month follow-up, she had a BCVA of 2/60, N36 in the right eye, and 20/60, N18 in the left eye. Both eyes showed a scar at the macula, disk pallor, and an attached retina. The patient next presented 2-years postvitrectomy with a complaint that she had noticed sudden decreased vision in her left eye during the previous week. Her left eye BCVA was 20/120, N36. Her right eye fundus was as before (Figure 1), whereas her left eye showed an extrafoveal choroidal neovascular membrane (CNVM) with associated subretinal hemorrhage alongside the preexisting scar (Figure 2). Optical coherence tomography (Figure 3) and fundus flourescein angiography (FFA) were confirmatory of the same, with a classic extrafoveal CNVM seen on FFA that was inferior to the fovea (Figures 4 and 5). After discussing the various treatment options available with the patient, which included laser photocoagulation to the CNVM, photodynamic therapy, and intravitreal antivascular endothelial growth factor (anti-VEGF) injections, we decided to administer intravitreal ranibizumab. The patient underwent 3 injections of intravitreal ranibizumab (0.5 mg/0.05 mL), in her left eye at monthly intervals. Evaluations at monthly intervals showed a stable lesion, substantiated by serial optical coherence tomography scans. After 3 consecutive, monthly injections of intravitreal ranibizumab, the BCVA in her left eye was 20/80, N18. Fluorescein angiography showed staining of the CNVM and optical coherence tomography showed resolution of the lesion (Figures 6 and 7). When last seen, 21 months after the third injection of intravitreal ranibizumab, her left eye BCVA was

C O L O R Fig. 2. Left eye color fundus photograph showing clear media, a macular scar with internal limiting membrane striae and an extrafoveal active CNVM with subretinal hemorrhage.

20/80, N12. Both her eyes were quiet and stable. Her left eye macula showed a scar, with no evidence of activity (Figure 8). Left eye optical coherence tomography showed a scar at the macula with associated retinal pigment epithelium atrophy and a decrease in retinal thickness. Discussion Candida is known to be the most common pathogen isolated in cases of endogenous fungal endophthalmitis.1 Lithotripsy is not directly a risk factor for fungal endophthalmitis, but sometimes patients can develope septicemia as a complication. Our patient is diabetic as well, which definitely increases the risk for fungal endophthalmitis.2 It is known that the grayish white, fluffy lesions situated in the vitreous and the inner retina in candidal endophthalmitis, represent localized fungal abscesses and that candidal colonies may be found between the retinal pigment epithelium and the Bruch membrane.3 The rich vascularity and high-blood flow rates of the choriocapillaris are responsible for the localization of hematogenous, metastatic, septic emboli in

C O L O R

C O L O R Fig. 1. Right eye color fundus photograph showing a clear media and a fibrous scar at the posterior pole involving disk and macula.

Fig. 3. Left eye optical coherence tomography showing a scar at the macula with an adjacent CNVM and increased retinal thickening.

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Fig. 6. Left eye FFA showing staining of the CNVM. Fig. 4. Left eye FFA (arteriovenous phase) showing an active classic, extrafoveal CNVM with adjacent blocked fluorescence because of subretinal hemorrhage.

the choroid and the posterior retina. Similarly, endogenous candidal lesions are known to develop in the outer layers of the choroid and then spread to the choriocapillaris and further inward through the Bruch membrane into the subretinal, retinal, and vitreal space.4 Disturbance of the Bruch membrane and the retinal pigment epithelium is a logical precursor to the development of a CNVM. It is also believed that the continuous subclinical inflammation within the healed chorioretinal scars acts as an angiogenic stimulus.4 Development of choroidal neovascularization associated with candidal chorioretinitis or candidal endophthalmitis-related chorioretinal scars has been reported in two case series.4,5 Patients in both series were either observed,4 treated with laser

Fig. 5. Left eye FFA (late phase) showing increased hyperfluorescence of the CNVM and blocked fluorescence because of subretinal hemorrhage.

photocoagulation,4 or underwent submacular surgery for excision of the CNVM.4,5 Jampol et al4 showed good results with conventional laser photocoagulation for primarily extrafoveal lesions and for one subfoveal CNVM (which had initially been observed). Recchia et al5 showed significant and stable improvement in vision after submacular surgery. Laser photocoagulation has also been used in the treatment of ocular histoplasmosis-related juxtafoveal CNVM with effective outcomes. However, laser scar enlargement with subsequent foveal encroachment is a possible complication,6 which has to be kept in mind. Photodynamic therapy with verteporfin has also been used successfully in the treatment of inflammatory CNVM, including as treatment for a case of Candida endophthalmitis-related choroidal neovascularization.7 A limitation to be considered when treating a CNVM with photodynamic therapy would be the increase in VEGF production that has been documented to accompany the procedure.8 Vascular endothelial growth factor is a cytokine, which is a participant in intraocular inflammatory processes, and is known to contribute to the development and progression of CNVM. In addition, VEGF levels are known to be high in uveitic eyes.9 This is the rationale for the use of anti-VEGF agents in the therapy of inflammatory CNVM. Intravitreal bevacizumab has been used in the treatment of inflammatory ocular neovascularization, including CNVM, spanning different varieties of inflammatory eye diseases with good short-term results.10 We therefore decided to initiate therapy in our patient with an anti-VEGF line of treatment and decided to follow the standard protocol of three monthly injections, as is the accepted norm for CNVM caused by age-related macular degeneration.

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C O L O R

Fig. 8. Left eye color fundus photograph showing a macular scar and a scarred CNVM.

Key words: Candida parapsilosis, choroidal neovascular membrane fungal endophthalmitis, intravitreal ranibizumab, macular scar.

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References

Fig. 7. Left eye optical coherence tomography showing resolution of the CNVM and a substantial decrease in retinal thickening.

Our patient had an active, classic, extrafoveal CNVM that showed up 2 years after vitrectomy. This is in agreement with the observation by Jampol et al4 that the development of chorioretinitis scar-related with CNVM is usually a late complication. The use of the anti-VEGF agent ranibizumab (Genentech, South San Francisco, CA) at three consecutive monthly intervals proved efficacious, with good results for achieving CNVM regression and maintaining visual stability. To the best of our knowledge, this is the first reported case of the use of intravitreal ranibizumab in the therapy of a healed Candida endophthalmitis scar-related CNVM. A good follow-up at 21 months was also obtained with acceptable results, as mentioned earlier.

1. Essman TF, Flynn HW Jr, Smiddy WE, et al. Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 1997;28:185–194. 2. Toshikuni N, Ujike K, Yanagawa T, et al. Candida albicans endophthalmitis after extracorporeal shock wave lithotripsy in a patient with liver cirrhosis. Intern Med 2006;45:1327–1332. 3. Uliss AE, Walsh JB. Candida endophthalmitis. Ophthalmology 1983;90:1378–1379. 4. Jampol LM, Sung J, Walker JD, et al. Choroidal neovascularization secondary to Candida albicans chorioretinitis. Am J Ophthalmol 1996;121:643–649. 5. Recchia FM, Shah GK, Eagle RC, Sivalingam A, Fischer DH. Visual and anatomical outcome following submacular surgery for choroidal neovascularization secondary to Candida endophthalmitis. Retina 2002;22:323–329. 6. Shah SS, Schachat AP, Murphy RP, Fine SL. The evolution of argon laser photocoagulation scars in patients with the ocular histoplasmosis syndrome. Arch Ophthalmol 1988;106: 1533–1536. 7. Tedeschi M, Varano M, Schiano Lomoriello D, Scassa C, Parisi V. Photodynamic therapy outcomes in a case of macular choroidal neovascularization secondary to Candida endophthalmitis. Eur J Ophthalmol 2007;17:124–127. 8. Schmidt-Erfurth U, Schlo¨tzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epitheliumderived factor. Invest Ophthalmol Vis Sci 2003;44:4473–4480. 9. Fine HF, Baffi J, Reed GF, Csaky KG, Nussenblatt RB. Aqueous humor and plasma vascular endothelial growth factor in uveitis-associated cystoid macular edema. Am J Ophthalmol 2001;132:794–796. 10. Mansour AM, Mackensen F, Arevalo JF, et al. Intravitreal bevacizumab in inflammatory ocular neovascularization. Am J Ophthalmol 2008;146:410–416.

Intravitreal ranibizumab in the treatment of fungal endophthalmitis scar-related choroidal neovascular membrane.

The purpose of this study was to report the efficacious use of intravitreal ranibizumab in the management of postfungal endophthalmitis scar-related c...
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