Theodoros Empeslidis, Vasileios Konidaris, Periyasami Kumar, Somnath Banerjee, James Deane and Konstantinos T Tsaousis*
Ophthalmology Department, Leicester Royal Infirmary, Leicester LE1 5WW, UK
Received: June 25, 2014; Accepted: July 14, 2014; Published: July 16, 2014
Konstantinos T Tsaousis, Ophthalmology Department, Medical Retina, Leicester Royal Infirmary, Infirmary Square, Leicester, Leicestershire, LE1 5WW, UK, Tel: +44116 258 5928; Fax: +44 258 6763; Email: firstname.lastname@example.org
Empeslidis T, Konidaris V, Kumar P, Banerjee S, Deane J, et al. (2014) Valacyclovir as a Therapeutic Agent in Acute Retinal Necrosis: Two Case Reports. J Clin Res Ophthalmol 1(1): 016-018. DOI: 10.17352/2455-1414.000004
© 2014 Empeslidis T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Valacyclovir; Acute retinal necrosis; Chorioretinitis; Herpetic infection
Introduction: Acute retinal necrosis (ARN) is a rare, rapidly progressive viral retinitis. The current standard of care for ARN consists of intravenous acyclovir for 5-10 days, followed by oral acyclovir for an additional 6-12 weeks. Valacyclovir has superior plasma bioavailability to acyclovir as an oral preparation. The aim of this study is to add to the evidence of treating ARN with valacyclovir with 2 additional cases.
Methods: 2 patients diagnosed with ARN received treatment with valacyclovir either as a monotherapy, or in combination with intravenous acyclovir.
Results: All patients had significant improvement in visual acuity within 4 weeks of the initiation of treatment. In the sixth month follow-up none of them developed retinal detachment, which is one of the commonest sight-threatening complications of ARN.
Conclusions: Valacyclovir proved effective at treating retinitis in both patients. The 2 g t.i.d. dose was well tolerated and neither patient developed systemic adverse effects associated with the treatment.
Acute retinal necrosis (ARN) is a rare, but potentially blinding disease, characterized by the clinical trial of vitreous inflammation, occlusive vasculopathy, and progressive peripheral retinal necrosis . It took more than a decade after its first description for its herpetic aetiology to be discovered and antiviral therapy to become the main stay of treatment [2,3]. ARN usually presents unilaterally, however, bilateral disease has been reported in up to 35% of patients . The incidence in the UK is approximately 1 case per 1.6 to 2.0 million of population per year . It usually affects immune-competent hosts, although it may occur in immuno-compromised individuals. As the outcome is often poor, prompt diagnosis and treatment prevents visual loss and involvement of the fellow eye. The clinical diagnosis is based on the standard diagnostic criteria proposed by the American Uveitis Society . More recently, testing of aqueous or vitreous samples for viral DNA has identified varicella zoster virus (VZV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) and occasionally cytomegalovirus (CMV) as the common causative agents of ARN [6,7]. Using polymerase chain reaction (PCR) methodologies, human herpes virus 6 (HHV6) has been recently implicated in ocular inflammation . The state-of-the-art pattern of treatment for ARN involves intravenous acyclovir 10 mg/kg every 8 h for 5–10 days, subsequently oral acyclovir 400-800 mg 5 times daily for another 6-12 weeks, to decrease the possibility of second eye involvement . Recent studies have reported that treatment with oral valacyclovir as the sole antiviral therapy resulted in favorable outcomes, with complete resolution of retinitis, a restoration of visual acuity, and a retinal detachment rate comparable with previously reported outcomes for intravenous acyclovir . Moreover, high dosage of oral valaciclovir (2g 3 times/day) was suggested as an alternative treatment of varicella zoster acute retinal necrosis syndrome, with good anatomic and functional results .
Valacyclovir and famciclovir have superior plasma bioavailability to acyclovir as oral preparations . The aim of the present study is to add to this evidence with 2 additional cases of ARN treated with valacyclovir . Written informed consent was obtained from the patients for publication of these case reports and any accompanying images.
Case report 1
A 22-year-old white male was referred to our Department with a 1 day history of floaters and blurred vision in his right eye. His medical history was remarkable following a diagnosis of glandular fever 4 weeks previously. Additionally, 10 days prior to presentation the patient had presented to the Neurology Department with widespread macular pruritic rash, sore throat, nausea, fever, headache, unsteadiness, weakness on the left leg, and binocular diplopia. At that time serology had confirmed an acute EBV infection with increased titres for EBV-IgM antibodies. Serological testing for Human Immunodeficiency Virus (HIV), hepatitis B and C, syphilis, HSV, VZV, and CMV was negative. A computerized tomography (CT scan) of the brain was unremarkable. However, analysis of cerebrospinal fluid (CSF) had revealed 97% lymphocytic cells, a protein level of 1.44 g/L and PCR had showed positive for HHV6 viral DNA (365 DNA copies/mL). CSF testing for HSV, VZV, EBV, CMV, and enterovirus was negative. In this setting, the patient had been diagnosed with HHV6 encephalitis and left fourth 4th nerve palsy. He had been admitted under neurological care and treated with intravenous acyclovir (1 g 3 times daily for 10 days) and pulsed intravenous methylprednisolone (1g daily for 3 days).
On presentation, his best-corrected visual acuity (BCVA) was LogMAR 0.50 in the right eye and LogMAR 0.00 in the left eye with an intraocular pressure of 16 mmHg and 17 mmHg respectively . Additionally, a right relative afferent pupillary defect (RAPD) was present. Anterior segment examination revealed fine corneal precipitates on both eyes. The vitreous in the right eye showed minimal cellular infiltration. Fundoscopy of the right eye showed a well-demarcated creamy area of retinal necrosis in the lower periphery, and some oval-shaped confluent necrotic lesions scattered throughout the entire peripheral fundus (Figure 1). Inflammatory sheathing of retinal blood vessels was also evident. In the left eye some smaller multifocal whitish lesions and retinal vasculitis were identified. Since the patient was diagnosed with bilateral ARN and left post-viral 4th nerve neuropathy in the setting of HHV6 encephalitis, a diagnostic vitrectomy or anterior chamber tap was not performed, because this would have no therapeutic consequences. Given that the patient had already received intravenous acyclovir for 10 days, treatment was switched to oral valacyclovir (1g 3 times daily for 1 month) and oral prednisolone (60mg/day) for 10 days.
- Gartry DS, Spalton DJ, Tilzey A, Hykin PG (1991) Acute retinal necrosis syndrome. Br J Ophthalmol 75: 292-297.
- Blumenkranz MS, Culbertson WW, Clarkson JG, Dix R (1986) Treatment of the acute retinal necrosis syndrome with intravenous Acyclovir. Ophthalmology 93: 296-300.
- Culbertson WW, Blumenkranz MS, Haines H, Gass DM, Mitchell KB, et al. (1982) The acute retinal necrosis syndrome. Part 2: Histopathology and etiology. Ophthalmology 89: 1317-1325.
- Muthiah MN, Michaelides M, Child CS, Mitchell SM (2007) Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK. Br J Ophthalmol 91: 1452-1455.
- Holland GN (1994) Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol 117: 663-667.
- Hillenkamp J, Nolle B, Bruns C, Rautenberg P, Fickenscher H, et al. (2009) Acute retinal necrosis: clinical features, early vitrectomy, and outcomes. Ophthalmology 116: 1971-1975.
- Lau CH, Missotten T, Salzmann J, Lightman SL (2007) Acute retinal necrosis features, management, and outcomes. Ophthalmology 114: 756-762.
- Sugita S, Shimizu N, Watanabe K, Ogawa M, Maruyama K, et al. (2012) Virological analysis in patients with human herpes virus 6-associated ocular inflammatory disorders. Invest Ophthalmol Vis Sci 53: 4692-4698.
- Taylor SR, Hamilton R, Hooper CY, Joshi L, Morarji J, et al. (2012) Valacyclovir in the treatment of acute retinal necrosis. BMC Ophthalmol12: 48.
- Guex-Crosier Y, Meylan PR (2006) High dosage of oral valaciclovir as an alternative treatment of varicella zoster acute retinal necrosis syndrome. Eye (Lond) 20: 247.
- Soul-Lawton J, Seaber E, On N, Wootton R, Rolan P, et al. (1995) Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of Acyclovir, following oral administration to humans. Antimicrob Agents Chemother 39: 2759-2764.
- Aizman A, Johnson MW, Elner SG (2007) Treatment of acute retinal necrosis syndrome with oral antiviral medications. Ophthalmology 114: 307-312.
- Aslanides IM, De Souza S, Wong DT, Giavedoni LR, Altomare F, et al. (2002) Oral valacyclovir in the treatment of acute retinal necrosis syndrome. Retina22: 352-354.
- Empeslidis T, Konidaris V, Brent A, Vardarinos A, Deane J (2013) Kyrieleis plaques in herpes zoster virus-associated acute retinal necrosis: a case report. Eye (Lond) 27: 1110-1112.
- Fisher JP, Lewis ML, Blumenkranz M, Culbertson WW, Flynn HW Jr, et al. (1982) The acute retinal necrosis syndrome. Part 1: Clinical manifestations. Ophthalmology 89: 1309-1316.
- Martinez J, Lambert HM, Capone A, Sternberg P Jr, Aaberg TM, et al. (1992) Delayed bilateral involvement in the acute retinal necrosis syndrome. Am J Ophthalmol113: 103-104.
- Carney MD, Peyman GA, Goldberg MF, Packo K, Pulido J, et al. (1986) Acute retinal necrosis. Retina6: 85-94.
- Meghpara B, Sulkowski G, Kesen MR, Tessler HH, Goldstein DA (2010) Long-term follow-up of acute retinal necrosis. Retina 30: 795-800.
- Sims JL, Yeoh J, Stawell RJ (2009) Acute retinal necrosis: a case series with clinical features and treatment outcomes. Clin Experiment Ophthalmol 37: 473-477.
- Tibbetts MD, Shah CP, Young LH, Duker JS, Maguire JI, et al. (2010) Treatment of acute retinal necrosis. Ophthalmology 117: 818-824.
- Wong R, Pavesio CE, Laidlaw DA, Williamson TH, Graham EM, et al. (2010) Acute retinal necrosis: the effects of intravitreal foscarnet and virus type on outcome. Ophthalmology 117: 556-560.
- Guex-Crosier Y, Rochat C, Herbort CP (1997) Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host. Ocul Immunol Inflamm 5: 259-265.
- Bell WR, Chulay JD, Feinberg JE (1997) Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore)76: 369-380.
- Vigil KJ, Chemaly RF (2010) Valacyclovir: approved and off-label uses for the treatment of herpes virus infections in immunocompetent and immunocompromised adults. Expert Opin Pharmacother11: 1901-1913.