ACUTE RETINAL NECROSIS IN A NEONATE Christina Hsu, BA,* Nader Moinfar, MD, MPH,*† Brian Lipman, MD,‡ Antonio Capone, MD,§ Michael Trese, MD§
Purpose: To report an unusual case of dizygotic twins, in whom one neonate developed acute retinal necrosis from herpes simplex virus (HSV) type 2. Methods: Retrospective chart review. Results: A 29-week-old premature infant from in vitro fertilization donor egg with negative maternal and fetal history for HSV-1 and HSV-2 developed vesiculopapular rash upon birth. Fundus examination revealed vitritis with retinal hemorrhages, suggestive of retinitis; the twin, however, had a normal funduscopic examination. A presumptive diagnosis of HSV infection was made, and the patient was started on intravenous acyclovir. Polymerase chain reaction of the anterior chamber fluid was positive for HSV-2; serology of both mother and child was HSV-2 IgG(+), IgM(−). Acute retinal necrosis was managed with 360° of bilateral peripheral laser cerclage. A subsequent rhegmatogenous retinal detachment in one eye was successfully treated with a scleral buckle. Retinal reattachment, macular pigmentary disturbances, and mild optic atrophy were noted at 6 months of follow-up. Conclusion: The authors report a case of isolated congenital acute retinal necrosis in an otherwise healthy neonate, and product of a dichorionic, diamniotic in vitro fertilization pregnancy. Clinicians should consider possible HSV transmission from in vitro fertilization donor egg in the differential diagnosis, despite the negative fetal and maternal histories for HSV infection. RETINAL CASES & BRIEF REPORTS 0:1–3, 2013
mouth infection to disseminated infection and neurologic sequelae of encephalitis. Although disseminated or neurologic infection can have up to an 80% risk of mortality without treatment,2 there can be severe consequences to skin, eye, and mouth as well. One serious complication is acute retinal necrosis (ARN), which can lead to retinal detachment (RD) and blindness. Acute retinal necrosis is a rapidly progressing necrotizing retinopathy that exhibits discrete areas of circumferential retinal necrosis, along with signs of uveitis, vitreitis, and retinal vasculitis.3 The authors present a case of isolated congenital retinal necrosis in a dichorionic, diamniotic premature infant. To date, the condition has only once been reported in a neonate and has never been reported in association with an in vitro fertilization donor egg.
From the *University of Central Florida College of Medicine, Orlando, Florida; †Magruder Eye Institute, Orlando, Florida; ‡Winnie Palmer Hospital, Orlando, Florida; and §Associated Retina Consultants, Royal Oak, Michigan.
H
erpes simplex virus (HSV) infection is one of the most common sexually transmitted diseases among women of reproductive age in the United States.1 Genital infection from predominantly HSV-2, and to a lesser extent HSV-1, increases the risk of vertical transmission from mother to neonate in the perinatal period. Neonatal HSV infection occurs in approximately 1 in 3000 cases per year in the United States.1,2 Because of asymptomatic virus shedding and the underdiagnosis of the condition, neonatal HSV infection is associated with significant psychosocial morbidity and complications.1 Clinical presentation ranges from skin, eye, and
Case Report
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Nader Moinfar, MD, MPH, Magruder Eye Institute, 1911 North Mills Avenue, Orlando, FL 32803; e-mail: [email protected]; [email protected]
Our patient is a 29-week-old premature infant, the product of a dichorionic, diamniotic uncomplicated twin pregnancy with no maternal history of any sexually transmitted diseases or herpes; prenatal serological studies, including TORCH titers, were
1
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
2
RETINAL CASES & BRIEF REPORTS´ 2013 VOLUME 0 NUMBER 0
negative. In vitro fertilization with a donor egg was involved. Before delivery, there was a 5-day history of premature rupture of membranes that was treated empirically with broad-spectrum antibiotics. At birth, a vesiculopapular rash was noted on the neonate. These vesicles present on the mouth, nares, eyes, and rectum tested negative for HSV-1 and HSV-2. Funduscopic examination revealed vitritis, retinal hemorrhages, and retinal whitening, selectively involving the retinal periphery (Figures 1 and 2). A presumptive diagnosis of HSV infection was made, and the patient was started on intravenous acyclovir. Polymerase chain reaction of anterior chamber fluid was positive for HSV-2; both mother and child were IgG(+), IgM(−) for HSV-2, suggesting late maternal seroconversion. The neonate’s ARN was managed with 360° of bilateral peripheral laser cerclage. A subsequent rhegmatogenous RD in one eye was successfully treated with a scleral buckle. Retinal reattachment, macular pigmentary disturbances, and mild optic atrophy were noted at 6 months of follow-up.
C O L O R
Fig. 2. RetCam fundus photograph of the left eye showing similar vitreous haze, retinal hemorrhages, and whitening, as well as preretinal fibrous membranes.
Discussion First reported in 1971 by Urayama et al,4 ARN is a serious complication of HSV infection. As described by the American Uveitis Society in 1994, ARN is a necrotizing retinitis with one or more foci that displays circumferential spread, in addition to occlusive vasculopathy.5 The condition has been reported to be most commonly caused by HSV, varicella zoster virus, with some cases reported of Epstein-Barr virus and cytomegalovirus infection. Within the spectrum of rapidly progressing necrotizing retinopathies, ARN can have devastating complications of RD (85%), leading to blindness, and optic atrophy, if left untreated.6 Criteria to make a diagnosis of ARN includes the following: single or multiple areas of retinal necrosis with distinct borders typically located in the peripheral retina, rapid disease progression without antiherpetic treatment, circumferential extension of foci
C O L O R
Fig. 1. RetCam fundus photograph of the right eye with vitreous haze, retinal hemorrhages, peripheral occlusive changes, and pigmentary disturbances.
of retinal necrosis, presence of occlusive vasculopathy with arteriolar involvement, and prominent inflammation of the anterior chamber and vitreous. Affected persons may also report symptoms of optic neuropathy or atrophy, scleritis, and pain, although these symptoms are not necessary for a diagnosis.7 Review of the literature reveals that little data regarding primarily neonatal retinal necrosis exist. All cases of reported neonatal retinal necrosis affect the neonate within the first month of life, with virulent ophthalmic courses, including RD. To our knowledge, this is the first reported case of vertically transmitted isolated ARN to a neonate of a twin gestation. The cases described appear with infants with moderately low birth weight and moderately preterm status. The resulting prematurity of their immune system can explain the immediacy of the disease. As reported by Silva et al,3 prematurity decreases serum IgG and HSV-induced cytokines and leads to a less effective T-cell and monocyte response in the already impaired immune system of the premature newborn. Recalling that our patient was born at 29 weeks, it is possible that this theory explains the rapid onset of disease. Initial therapy for the patient included intravenous acyclovir. The standard treatment for ARN is 10 mg/kg of acyclovir intravenously every 8 hours or 1500 mg/m2 daily for 5 to 10 days, followed by oral acyclovir (800 mg 5 times daily for 6 weeks).5,8 Management following this initial step for patients with ARN includes reliance on diagnostic vitreous biopsy for polymerase chain reaction viral DNA analysis, prophylactic barrier laser posterior to the necrotic retina to prevent rhegmatogenous RD, and vitrectomy for RD repair.9,10 Prophylactic laser prevents RD from extending into the posterior pole; some
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
3
ACUTE RETINAL NECROSIS IN A NEONATE
physicians recommend 360° retinal photocoagulation as soon as the view permits. Other recommendations for management include prophylactic vitrectomy and endolaser, or delaying laser until RD necessitates surgery.8 In our patient, we chose to pursue 360° of bilateral peripheral laser cerclage and use of a scleral buckle for a subsequent rhegmatogenous RD in one eye. At 6 months of follow-up, successful surgery resulted in retinal reattachment; however, macular pigmentary disturbances and mild optic atrophy were also noted. The inability to completely reverse the damage attributed to ARN, despite active management, only further highlights the severity of the condition. Most cases of ARN result in poor visual acuity, regardless of treatment9; in a study of the pediatric population with ARN, mean final visual acuity was 20/400.3 Although the age of the infant prevented us from measuring a formal Snellen acuity, she showed brief moments of fixation only. This case is unusual because both maternal and fetal history were initially negative for HSV-2; but after vesiculopapular rash presented on the mouth, nares, eyes, and rectum and the resulting retinal necrosis, AC tap with polymerase chain reaction was performed, confirming the presence of HSV-2; serology for both mother and child was HSV-2 IgG(+), IgM(−). Additionally, only Twin A of the dichorionic, diamniotic pregnancy was affected by HSV-2; the sibling was clinically and serologically unaffected. Consideration should therefore be made of a contaminated donor source. Isolated ARN in a neonate is a serious, but rare finding. However, roughly 70% of affected neonates are born to mothers who are asymptomatic and unaware of their own HSV-2 seropositive status. Therefore, the clinician who discovers a neonate with ocular findings suspicious for ARN should immediately begin diagnostic testing for HSV-2 and administer prophylactic acyclovir.3 Additionally, because an in vitro fertilization donor egg was involved in
creating the pregnancy, a high degree of suspicion to possible sources of HSV infection is warranted. Key words: retinal necrosis, polymerase chain reaction, neonate, herpes. Acknowledgment The authors acknowledge Drs. Audina Berrocal and John Lehr of Bascom Palmer Institute in Miami for their contributions to this project. References 1. Cherpes TL, Matthews DB, Maryak SA. Neonatal herpes simplex virus infection. Clin Obstet Gynecol 2012;55:938–944. 2. Grose C. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection. Semin Pediatr Neurol 2012;19:115–118. 3. Silva RA, Berrocal AM, Moshfeghi DM, et al. Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review. Graefes Arch Clin Exp Ophthalmol 2012. 4. Urayama A, Yamada N, Sasaki T. Unilateral acute uveitis with retinal periarteritis and detachment [in Japanese]. Jpn J Clin Ophthalmol 1971;25:607–619. 5. Tam PM, Hooper CY, Lightman S. Antiviral selection in the management of acute retinal necrosis. Clin Ophthalmol 2010;4:11–20. 6. Clarkson JG, Blumenkranz MS, Culbertson WW, et al. Retinal detachment following the acute retinal necrosis syndrome. Ophthalmology 1984;91:1665–1668. 7. Holland G. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol 1994;117:663–667. 8. Iwahashi-Shima C, Azumi A, Ohguro N, et al. Acute retinal necrosis: factors associated with anatomic and visual outcomes. Jpn J Ophthalmol 2012. 9. Tibbetts MD, Shah CP, Young LH, et al. Treatment of acute retinal necrosis. Ophthalmology 2010;117:818–824. 10. Hou CH, Chen SN, Ho JD, Ho CL. Surgical treatment of retinal detachment following acute retinal necrosis syndrome: surgical results in four patients. Chang Gung Med J 2003;26:835–842.
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
Purpose: To report an unusual case of dizygotic twins, in whom one neonate developed acute retinal necrosis from herpes simplex virus (HSV) type 2. Methods: Retrospective chart review. Results: A 29-week-old premature infant from in vitro fertilization donor egg with negative maternal and fetal history for HSV-1 and HSV-2 developed vesiculopapular rash upon birth. Fundus examination revealed vitritis with retinal hemorrhages, suggestive of retinitis; the twin, however, had a normal funduscopic examination. A presumptive diagnosis of HSV infection was made, and the patient was started on intravenous acyclovir. Polymerase chain reaction of the anterior chamber fluid was positive for HSV-2; serology of both mother and child was HSV-2 IgG(+), IgM(−). Acute retinal necrosis was managed with 360° of bilateral peripheral laser cerclage. A subsequent rhegmatogenous retinal detachment in one eye was successfully treated with a scleral buckle. Retinal reattachment, macular pigmentary disturbances, and mild optic atrophy were noted at 6 months of follow-up. Conclusion: The authors report a case of isolated congenital acute retinal necrosis in an otherwise healthy neonate, and product of a dichorionic, diamniotic in vitro fertilization pregnancy. Clinicians should consider possible HSV transmission from in vitro fertilization donor egg in the differential diagnosis, despite the negative fetal and maternal histories for HSV infection. RETINAL CASES & BRIEF REPORTS 0:1–3, 2013
mouth infection to disseminated infection and neurologic sequelae of encephalitis. Although disseminated or neurologic infection can have up to an 80% risk of mortality without treatment,2 there can be severe consequences to skin, eye, and mouth as well. One serious complication is acute retinal necrosis (ARN), which can lead to retinal detachment (RD) and blindness. Acute retinal necrosis is a rapidly progressing necrotizing retinopathy that exhibits discrete areas of circumferential retinal necrosis, along with signs of uveitis, vitreitis, and retinal vasculitis.3 The authors present a case of isolated congenital retinal necrosis in a dichorionic, diamniotic premature infant. To date, the condition has only once been reported in a neonate and has never been reported in association with an in vitro fertilization donor egg.
From the *University of Central Florida College of Medicine, Orlando, Florida; †Magruder Eye Institute, Orlando, Florida; ‡Winnie Palmer Hospital, Orlando, Florida; and §Associated Retina Consultants, Royal Oak, Michigan.
H
erpes simplex virus (HSV) infection is one of the most common sexually transmitted diseases among women of reproductive age in the United States.1 Genital infection from predominantly HSV-2, and to a lesser extent HSV-1, increases the risk of vertical transmission from mother to neonate in the perinatal period. Neonatal HSV infection occurs in approximately 1 in 3000 cases per year in the United States.1,2 Because of asymptomatic virus shedding and the underdiagnosis of the condition, neonatal HSV infection is associated with significant psychosocial morbidity and complications.1 Clinical presentation ranges from skin, eye, and
Case Report
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Nader Moinfar, MD, MPH, Magruder Eye Institute, 1911 North Mills Avenue, Orlando, FL 32803; e-mail: [email protected]; [email protected]
Our patient is a 29-week-old premature infant, the product of a dichorionic, diamniotic uncomplicated twin pregnancy with no maternal history of any sexually transmitted diseases or herpes; prenatal serological studies, including TORCH titers, were
1
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
2
RETINAL CASES & BRIEF REPORTS´ 2013 VOLUME 0 NUMBER 0
negative. In vitro fertilization with a donor egg was involved. Before delivery, there was a 5-day history of premature rupture of membranes that was treated empirically with broad-spectrum antibiotics. At birth, a vesiculopapular rash was noted on the neonate. These vesicles present on the mouth, nares, eyes, and rectum tested negative for HSV-1 and HSV-2. Funduscopic examination revealed vitritis, retinal hemorrhages, and retinal whitening, selectively involving the retinal periphery (Figures 1 and 2). A presumptive diagnosis of HSV infection was made, and the patient was started on intravenous acyclovir. Polymerase chain reaction of anterior chamber fluid was positive for HSV-2; both mother and child were IgG(+), IgM(−) for HSV-2, suggesting late maternal seroconversion. The neonate’s ARN was managed with 360° of bilateral peripheral laser cerclage. A subsequent rhegmatogenous RD in one eye was successfully treated with a scleral buckle. Retinal reattachment, macular pigmentary disturbances, and mild optic atrophy were noted at 6 months of follow-up.
C O L O R
Fig. 2. RetCam fundus photograph of the left eye showing similar vitreous haze, retinal hemorrhages, and whitening, as well as preretinal fibrous membranes.
Discussion First reported in 1971 by Urayama et al,4 ARN is a serious complication of HSV infection. As described by the American Uveitis Society in 1994, ARN is a necrotizing retinitis with one or more foci that displays circumferential spread, in addition to occlusive vasculopathy.5 The condition has been reported to be most commonly caused by HSV, varicella zoster virus, with some cases reported of Epstein-Barr virus and cytomegalovirus infection. Within the spectrum of rapidly progressing necrotizing retinopathies, ARN can have devastating complications of RD (85%), leading to blindness, and optic atrophy, if left untreated.6 Criteria to make a diagnosis of ARN includes the following: single or multiple areas of retinal necrosis with distinct borders typically located in the peripheral retina, rapid disease progression without antiherpetic treatment, circumferential extension of foci
C O L O R
Fig. 1. RetCam fundus photograph of the right eye with vitreous haze, retinal hemorrhages, peripheral occlusive changes, and pigmentary disturbances.
of retinal necrosis, presence of occlusive vasculopathy with arteriolar involvement, and prominent inflammation of the anterior chamber and vitreous. Affected persons may also report symptoms of optic neuropathy or atrophy, scleritis, and pain, although these symptoms are not necessary for a diagnosis.7 Review of the literature reveals that little data regarding primarily neonatal retinal necrosis exist. All cases of reported neonatal retinal necrosis affect the neonate within the first month of life, with virulent ophthalmic courses, including RD. To our knowledge, this is the first reported case of vertically transmitted isolated ARN to a neonate of a twin gestation. The cases described appear with infants with moderately low birth weight and moderately preterm status. The resulting prematurity of their immune system can explain the immediacy of the disease. As reported by Silva et al,3 prematurity decreases serum IgG and HSV-induced cytokines and leads to a less effective T-cell and monocyte response in the already impaired immune system of the premature newborn. Recalling that our patient was born at 29 weeks, it is possible that this theory explains the rapid onset of disease. Initial therapy for the patient included intravenous acyclovir. The standard treatment for ARN is 10 mg/kg of acyclovir intravenously every 8 hours or 1500 mg/m2 daily for 5 to 10 days, followed by oral acyclovir (800 mg 5 times daily for 6 weeks).5,8 Management following this initial step for patients with ARN includes reliance on diagnostic vitreous biopsy for polymerase chain reaction viral DNA analysis, prophylactic barrier laser posterior to the necrotic retina to prevent rhegmatogenous RD, and vitrectomy for RD repair.9,10 Prophylactic laser prevents RD from extending into the posterior pole; some
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
3
ACUTE RETINAL NECROSIS IN A NEONATE
physicians recommend 360° retinal photocoagulation as soon as the view permits. Other recommendations for management include prophylactic vitrectomy and endolaser, or delaying laser until RD necessitates surgery.8 In our patient, we chose to pursue 360° of bilateral peripheral laser cerclage and use of a scleral buckle for a subsequent rhegmatogenous RD in one eye. At 6 months of follow-up, successful surgery resulted in retinal reattachment; however, macular pigmentary disturbances and mild optic atrophy were also noted. The inability to completely reverse the damage attributed to ARN, despite active management, only further highlights the severity of the condition. Most cases of ARN result in poor visual acuity, regardless of treatment9; in a study of the pediatric population with ARN, mean final visual acuity was 20/400.3 Although the age of the infant prevented us from measuring a formal Snellen acuity, she showed brief moments of fixation only. This case is unusual because both maternal and fetal history were initially negative for HSV-2; but after vesiculopapular rash presented on the mouth, nares, eyes, and rectum and the resulting retinal necrosis, AC tap with polymerase chain reaction was performed, confirming the presence of HSV-2; serology for both mother and child was HSV-2 IgG(+), IgM(−). Additionally, only Twin A of the dichorionic, diamniotic pregnancy was affected by HSV-2; the sibling was clinically and serologically unaffected. Consideration should therefore be made of a contaminated donor source. Isolated ARN in a neonate is a serious, but rare finding. However, roughly 70% of affected neonates are born to mothers who are asymptomatic and unaware of their own HSV-2 seropositive status. Therefore, the clinician who discovers a neonate with ocular findings suspicious for ARN should immediately begin diagnostic testing for HSV-2 and administer prophylactic acyclovir.3 Additionally, because an in vitro fertilization donor egg was involved in
creating the pregnancy, a high degree of suspicion to possible sources of HSV infection is warranted. Key words: retinal necrosis, polymerase chain reaction, neonate, herpes. Acknowledgment The authors acknowledge Drs. Audina Berrocal and John Lehr of Bascom Palmer Institute in Miami for their contributions to this project. References 1. Cherpes TL, Matthews DB, Maryak SA. Neonatal herpes simplex virus infection. Clin Obstet Gynecol 2012;55:938–944. 2. Grose C. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection. Semin Pediatr Neurol 2012;19:115–118. 3. Silva RA, Berrocal AM, Moshfeghi DM, et al. Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review. Graefes Arch Clin Exp Ophthalmol 2012. 4. Urayama A, Yamada N, Sasaki T. Unilateral acute uveitis with retinal periarteritis and detachment [in Japanese]. Jpn J Clin Ophthalmol 1971;25:607–619. 5. Tam PM, Hooper CY, Lightman S. Antiviral selection in the management of acute retinal necrosis. Clin Ophthalmol 2010;4:11–20. 6. Clarkson JG, Blumenkranz MS, Culbertson WW, et al. Retinal detachment following the acute retinal necrosis syndrome. Ophthalmology 1984;91:1665–1668. 7. Holland G. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol 1994;117:663–667. 8. Iwahashi-Shima C, Azumi A, Ohguro N, et al. Acute retinal necrosis: factors associated with anatomic and visual outcomes. Jpn J Ophthalmol 2012. 9. Tibbetts MD, Shah CP, Young LH, et al. Treatment of acute retinal necrosis. Ophthalmology 2010;117:818–824. 10. Hou CH, Chen SN, Ho JD, Ho CL. Surgical treatment of retinal detachment following acute retinal necrosis syndrome: surgical results in four patients. Chang Gung Med J 2003;26:835–842.
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
