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Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 412-414

Double trouble – Acute kidney injury complicating pediatric acute retinal necrosis

Department of Retina and Vitreous, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India

Date of Submission11-Dec-2022
Date of Acceptance16-Jan-2023
Date of Web Publication28-Apr-2023

Correspondence Address:
Arthi Mohankumar
Vitreoretinal Consultant, Rajan Eye Care Hospital, 5, Vidyodaya Second Street, T. Nagar, Chennai - 600 017, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_3232_22

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Acute retinal necrosis (ARN) occurs due to secondary reactivation of previous herpes simplex or varicella zoster infection. In children, ARN is rare and challenging to manage due to late presentation caused by difficulty in the communication of symptoms to caregivers and lack of treatment guidelines.[1] Acyclovir used for treatment can cause direct tubular injury or crystal deposit in the tubules, causing acute kidney injury (AKI). Prompt management of AKI is required to avoid lethal complications. In this case report, we describe the case of a 14-year-old boy with ARN secondary to primary varicella infection developing AKI following intravenous acyclovir.

Keywords: Acute retinal necrosis, acyclovir, acyclovir-induced nephrotoxicity, chicken pox, varicella zoster virus

How to cite this article:
Thomas NR, Mohankumar A, Gautam SD, Rajan M. Double trouble – Acute kidney injury complicating pediatric acute retinal necrosis. Indian J Ophthalmol Case Rep 2023;3:412-4

How to cite this URL:
Thomas NR, Mohankumar A, Gautam SD, Rajan M. Double trouble – Acute kidney injury complicating pediatric acute retinal necrosis. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 2];3:412-4. Available from: https://www.ijoreports.in/text.asp?2023/3/2/412/375028

Varicella (chicken pox) is a childhood exanthematous infection caused by the varicella zoster virus (VZV). It remains dormant in the trigeminal and dorsal root ganglia and can reactivate to cause herpes zoster.[2] Ocular involvement in cases of primary VZV infection is a rare occurrence that can result in conjunctivitis, keratitis, uveitis, retinitis, optic neuritis, and internal ophthalmoplegia.[3] Acute retinal necrosis (ARN) is a rare, vision-threatening necrotizing herpetic retinopathy with devastating visual outcomes if not accurately diagnosed and treated.[4] Since the first documented application of acyclovir by Blumenkranz et al.,[5] the American Academy of Ophthalmology recommended a loading dose of intravenous acyclovir followed by oral acyclovir, which has been the standard treatment for herpetic ARN.[6] Acyclovir is excreted by the kidneys via glomerular filtration and tubular secretion. It is insoluble in urine and rapidly accumulates in the distal tubules, causing intratubular precipitation of crystals and kidney damage. Herein, we report a case of unilateral ARN secondary to chicken pox complicated by acyclovir-induced nephrotoxicity in a 14-year-old boy.

  Case Report Top

A 14-year-old boy presented with complaints of cloudy vision in the left eye (OS) for 3 days. He gave a history of chickenpox during an epidemic at school 3 weeks back, which had resolved uneventfully. On examination, his best corrected visual acuity (BCVA) was 20/20 in both eyes (OU). Slit-lamp examination of OS revealed fine keratic precipitates with 2+ cells in the anterior chamber. The fundus revealed grade 1 vitritis, retinal vasculitis, and multiple yellow-white areas of retinitis in the peripheral retina temporally [Figure 1]a, [Figure 1]b, [Figure 1]c. The right eye (OD) was normal. Optical coherence tomography (OCT) macula of both eyes was normal. Serological analysis using chemiluminescence immunoassay technology showed positive VZV IgM (2.04 index) and IgG (2155.0 mIU/ml) values. Serological tests for human immunodeficiency virus (HIV) type 1, toxoplasma, herpes simplex virus (HSV), and cytomegalovirus (CMV) were negative. Baseline liver and renal function tests were done as a part of the uveitis workup and were found to be normal. All forms of immunosuppression including HIV were ruled out. The patient was started on intravenous acyclovir (10 mg/kg every 8 h for 10 days) along with topical steroids and cycloplegics. After 48 h of initiation of treatment, the margins of retinitis began to regress, and oral steroids (1 mg/kg/day) were started. On the fifth day of intravenous antiviral therapy, the patient began to complain of abdominal pain. The patient was evaluated, and serum creatinine was elevated (3 mg/dl). Pediatrician's opinion was obtained and acyclovir-induced crystal nephropathy was suspected; systemic antiviral therapy was discontinued, and the patient was started on aggressive intravenous fluids. The patient received two doses of intravitreal ganciclovir (2 mg/0.1 ml) with dexamethasone (4 mg/0.1 ml) at an interval of 3 days. The patient's creatinine normalized in 3 days. The areas of retinitis regressed with residual atrophy [Figure 1]d. Prophylactic laser barrage photocoagulation was done posterior to the areas of retinitis. The patient was discharged and started on oral famciclovir 500 mg thrice a day, which was continued for 3 months. The dose of oral steroids was tapered and stopped at 8 weeks. Complete resolution of ARN was noted at 3 weeks with a final BCVA of 20/20 in both eyes. The patient has been followed up for the past 2 years without any recurrence of inflammation.
Figure 1: (a) Color fundus photo of the left eye showing posterior pole with mild haze suggestive of mild vitritis. (b) Arterial (black arrow) and venous sheathing (yellow arrow) suggestive of peripheral retina vasculitis. (c) Yellow-white areas of retinitis in the peripheral retina from 2 o' clock to 4 o' clock hours (white arrow). (d) Complete resolution of retinitis with barrage laser marks posterior to the atrophic retina 3 months after treatment

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  Discussion Top

ARN is a fulminant panuveitis that occurs secondary to reactivation of VZV or HSV infection in immunocompetent as well as immunocompromised individuals. It is characterized by extensive confluent peripheral necrotizing retinitis, vitritis, and retinal vasculitis, and may culminate, in retinal detachment, with a poor visual outcome.

ARN developing in the context of a primary varicella infection has been reported in adult and pediatric patients, with severe manifestations in children. Poor visual outcomes in pediatric patients have been suggested to be due to an immature immune system as well as delayed complaints of their ocular symptoms resulting in delayed diagnosis.[7]

Treatment with intravenous acyclovir at a dose of 10 mg/kg every 8 h for 7–10 days followed by an oral antiviral has been the most established treatment regimen for ARN. Higher maximal acyclovir concentration and faster time to peak concentration have been demonstrated with intravenous dosing. Acyclovir is known to be nephrotoxic, and nephrotoxicity due to acyclovir may occur in 12%–48% of patients. Risk factors include higher doses (>1500 mg/m2/day), dehydration, and preexisting renal dysfunction. It is characterized by a rapid elevation in serum creatinine levels within 12–48 h of drug administration. Immediate detection of acute kidney injury is vital to prevent morbidity. The risk of acyclovir-induced crystal nephropathy can be minimized with intravenous fluids before drug administration, slower infusion of the drug over 1–2 h, and dose adjustment for renal function if required. Treatment of acyclovir nephrotoxicity includes discontinuation of the drug, hydration using intravenous fluids, and usage of loop diuretics. In cases of progressive damage, patients may require hemodialysis or renal transplant.[8] Administration of intravitreal ganciclovir with dexamethasone addresses the viral infection as well as accompanying inflammation in the posterior segment. This approach is effective in cases where systemic treatment is not tolerated, as noted in our case.[9]

Newer oral antivirals which achieve target concentration in the posterior segment, such as valaciclovir and famciclovir, have replaced intravenous acyclovir and are used as the first-line treatment with the added advantage of economical outpatient care. These are equally effective in achieving complete resolution of retinitis, reducing the incidence of complications like retinal detachment and fellow eye involvement. They help achieve comparable visual outcomes and reduce systemic adverse effects.[5]

  Conclusion Top

Our report highlights a case of management of ARN due to chicken pox in a pediatric patient who developed acyclovir-induced nephropathy. The patient was managed successfully using intravitreal ganciclovir injections followed by oral famciclovir. The identification of nephropathy due to acyclovir treatment in children is equally challenging as making a diagnosis of ARN. Timely intervention aided in avoiding systemic and ocular morbidity. When intravenous acyclovir is used, the importance of adequate hydration to prevent acyclovir-induced nephrotoxicity should be stressed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Mapelli C, Milella P, Donà C, Nassisi M, Osnaghi S, Viola F, et al. Acute retinal necrosis: Clinical features, diagnostic pitfalls, treatment, and outcome of an insidious disease in children. Case report and review of the literature. Front Pediatr 2022;10:854325. doi: 10.3389/fped. 2022.854325.  Back to cited text no. 1
Freer G, Pistello M. Varicella-zoster virus infection: Natural history, clinical manifestations, immunity and current, and future vaccination strategies. New Microbiol 2018;41:95-105.  Back to cited text no. 2
Gargouri S, Khochtali S, Zina S, Khairallah M, Zone-Abid I, Kaibi I, et al. Ocular involvement associated with varicella in adults. J Ophthalmic Inflamm Infect 2016;6:47.  Back to cited text no. 3
Shin YU, Kim J, Hong EH, Kim J, Sohn JH, Cho H. Varicella zoster virus-associated necrotizing retinitis after chickenpox in a 10-year-old female: A case report. Pediatr Infect Dis J 2017;36:1008-11.  Back to cited text no. 4
Blumenkranz MS, Culbertson WW, Clarkson JG, Dix R. Treatment of the acute retinal necrosis syndrome with intravenous acyclovir. Ophthalmology 1986;93:296-300.  Back to cited text no. 5
Schoenberger SD, Kim SJ, Thorne JE, Mruthyunjaya P, Yeh S, Bakri SJ, et al. Diagnosis and treatment of acute retinal necrosis: A report by the american academy of ophthalmology. Ophthalmology 2017;124:382-92.  Back to cited text no. 6
Tajunisah I, Reddy SC. Acute retinal necrosis complicating chickenpox in a healthy adult--a case report and review of the literature. Compr Ther 2007;33:25-31.  Back to cited text no. 7
Fleischer R, Johnson M. Acyclovir nephrotoxicity: A case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy. Case Rep Med 2010;2010:602783. doi: 10.1155/2010/602783.  Back to cited text no. 8
Patel CV, Kishore K. Concomitant intravitreal ganciclovir and dexamethasone therapy in the management of acute retinal necrosis in a patient previously treated with oral famciclovir. Case Rep Ophthalmol Med 2017;2017:4613624. doi: 10.1155/2017/4613624.  Back to cited text no. 9


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