Necrotizing retinitis in a patient with syphilis: A case report.

RATIONALE: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. Necrotizing retinitis is a rare manifestation of ocular syphilis and mimics ARN. PATIENT CONCERNS: We report a male patient who presented with bilateral dense vitritis obscuring fundus details similar to ARN, as a rare reported manifestation of syphilis, who was initially given intravitreal ganciclovir. DIAGNOSIS: After the results for herpes viral PCR disclosed negative, the diagnosis of syphilitic necrotizing retinitis was made based on positive RPR. INTERVENTION AND OUTCOMES: With the clinical diagnosis of ocular syphilis, treatment with intravenous penicillin was promptly initiated. His visual acuity improved to 20/100 in the right eye and still light perception in the left. Pars plana vitrectomy with silicon oil tamponade was performed in his left eye. LESSONS: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. However, whenever ARN is clinically suspected, empiric treatment against herpetic viruses should be promptly administered while awaiting further infectious disease study results. Recognition of syphilitic retinitis and prompt initiation of intravenous penicillin is of critical important for clinicians.

Necrosis retiniana como manifestación de aspergilosis invasiva en un paciente tratado con ruxolitinib / Invasive aspergillosis manifesting as retinal necrosis in a patient treated with ruxolitinib

Varón de 30 años de edad con leucemia mieloblástica aguda y síndrome mielodisplásico secundario que desarrolló una enfermedad injerto contra huésped. El paciente fue tratado con ruxolitinib, un inhibidor de la Janus quinasa. A los 3 meses de haber iniciado el tratamiento se produjo una necrosis retiniana por Aspergillus, sin respuesta al tratamiento. El tratamiento con inhibidores de la Janus quinasa favorecería un aumento en la incidencia de infecciones oportunistas. El uso de estos fármacos podría dar lugar a una menor eficacia de los tratamientos empleados

A 30 year-old man with acute myeloblastic leukaemia and secondary myelodysplastic syndrome developed graft-versus-host disease. The patient was treated with ruxolitinib. After being treated for 3 months with ruxolitinib, an inhibitor of Janus kinase, he developed Aspergillus retinal necrosis resistant to common treatment. Treatment with Janus kinase inhibitors may lead to an increased incidence of opportunistic infections. Janus kinase inhibitor administration may result in poor treatment efficacy

Ocular Syphilis Presenting as Bilateral Acute Retinal Necrosis in an Immunocompetent Host.

Given the recent rise in reported cases of syphilis, clinicians must maintain a high index of suspicion for this great masquerader when evaluating patients with symptoms and signs of ocular inflammation. Ocular syphilis can present a diagnostic dilemma for ophthalmologists due to its myriad ofmanifestations. We report a case of ocular syphilis presenting as bilateral acute retinal necrosis (BARN) that we recently saw in Connecticut and review clinical signs, appropriate serum testing sequence, and specialized ophthalmic testing, as well as treatment of ocular syphilis.

Síndrome de necrosis retiniana aguda tras primoinfección por varicela / Acute retinal necrosis syndrome following chickenpox

Caso clínico: Varón de 34 años que desarrolló una necrosis retiniana aguda en su ojo izquierdo tres semanas después de padecer varicela. Con tratamiento sistémico precoz con aciclovir intravenoso (10 mg/kg/8 horas) y corticoides sistémicos (1 mg/kg/día) la retinitis fue controlada y el paciente no sufrió pérdida de agudeza visual. Discusión: La necrosis retiniana aguda es una complicación inusual de la varicela que necesita atención. Se ha descrito una forma leve durante el curso de la primoinfección por varicela zoster. Se recomienda un tratamiento adecuado y precoz durante la fase aguda de la enfermedad con aciclovir intravenoso para conseguir una buena agudeza visual y prevenir complicaciones

Case report: A 34-year-old male patient developed acute retinal necrosis in his left eye about three weeks after the onset of chickenpox. Systemic antiviral treatment with intravenous acyclovir (10 mg/kg/8hours) and systemic corticosteroids (1 mg/kg/day) controlled the retinitis and the patient suffered no loss of visual acuity. Discussion: Acute retinal necrosis is an unusual complication of chickenpox. A mild form of this entity has been described during the course of primary varicella-zoster infection. Adequate and early therapy during the acute phase of the disease with intravenous acyclovir and systemic corticosteroids is recommended to achieve a satisfactory visual acuity and prevent complications

The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS.

BACKGROUND: The progressive outer retinal necrosis syndrome is a recently recognized variant of necrotizing herpetic retinopathy. This report characterizes more fully its clinical features and course. METHODS: Using standardized clinical criteria, patients with progressive outer retinal necrosis syndrome from four institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, presenting symptoms, physical findings, course, responses to treatment, and outcomes. RESULTS: Thirty-eight patients (65 involved eyes) were studied. All had acquired immune deficiency syndrome. A known history of cutaneous zoster was documented in 22 (67%) of 33 patients. Median CD4 lymphocyte count was 21/mm3 (range, 0-130/mm3). Median follow-up was 12 weeks. The most common presenting symptom was unilateral decreased vision (35 of 65 eyes, 54%); median visual acuity at presentation was 20/30 (range, 20/20 to no light perception [NLP]). Anterior chamber and vitreous inflammatory reactions were absent or minimal in all patients. Typical retinal lesions were multifocal, deep opacities scattered throughout the periphery, although macular lesions also were present in 21 eyes (32%) at diagnosis. Lesions progressed rapidly to confluence. Initial intravenous antiviral therapy appeared to reduce disease activity in 17 (53%) of 32 eyes, but treatment did not alter final visual outcome. Visual acuity was NLP in 42 (67%) of 63 eyes within 4 weeks after diagnosis. Retinal detachment occurred in 43 (70%) of 61 eyes, including 13 (93%) of 14 eyes that received prophylactic laser retinopexy. CONCLUSION: The progressive outer retinal necrosis syndrome is characterized by features that distinguish it from cytomegalovirus retinopathy, acute retinal necrosis syndrome, and other necrotizing herpetic retinopathies. Visual prognosis is poor with current therapies.

Retinal necrosis in X-linked lymphoproliferative disease.

BACKGROUND: X-linked lymphoproliferative disease is a hereditary disease that renders the males susceptible to fatal infectious mononucleosis, aplastic anemia, malignant lymphoma, and hypogammaglobulinemia after infection by the Epstein-Barr virus. METHODS: The authors examined the clinical and pathologic findings in an 8-year-old boy with bilateral retinal necrosis who died with aplastic anemia as a complication of X-linked lymphoproliferative disease. RESULTS: Results of histopathologic examination of the eyes disclosed retinal necrosis, and examination using the polymerase chain reaction technique showed Epstein-Barr virus genomic DNA in the left eye. CONCLUSION: Retinal necrosis may be part of the expanding spectrum of X-linked lymphoproliferative disease. It is unknown if the retinal necrosis is due directly to Epstein-Barr virus infection or a host inflammatory response.

Detection of intraocular antibody production to herpesviruses in acute retinal necrosis syndrome.

In order to improve the determination of the causative agent in acute retinal necrosis syndrome, we evaluated the detection of intraocular antibody production to herpesviruses in 28 patients with this disease. Intraocular antibody production was determined by calculation of the Goldmann-Witmer coefficient whereby specific antibody titers in the inflamed eye and circulation are related to the total IgG content in ocular fluid and serum. Specific antibody titers to herpesviruses and Toxoplasma were determined by the indirect immunofluorescence technique. Thirty-five patients with ocular toxoplasmosis, cataract, or proliferative vitreoretinal disorders were tested as controls. By this technique, intraocular antibody production to varicella zoster virus or herpes simplex virus could be established in 16 (57%) of the patients with the typical clinical features of acute retinal necrosis, compared to none of the controls. Of the 33 affected eyes, 21 (64%) had a visual outcome of less than 20/200. We concluded that detection of intraocular antibody production to herpesviruses may be a useful diagnostic tool in establishing the causative agents in acute retinal necrosis.

Treatment of outer retinal necrosis in AIDS patients.

We report a patient with AIDS who developed rapidly progressive, acute outer retinal necrosis. Cytomegalovirus etiology was proposed as a possibility in view of the histopathologic identification of the virus in the fellow concomitantly affected eye. Treatment with ganciclovir resulted in disappearance of the posterior pole lesions and inactivation of the peripheral lesions. We suggest that ganciclovir be used as soon as this condition is suspected in order to optimize the outcome.

Induction of bilateral retinal necrosis in mice by unilateral intracameral inoculation of a glycoprotein-C deficient clinical isolate of herpes simplex virus type 1.

Herpes simplex virus can cause acute retinal necrosis, a blinding retinal disease in man. A unilateral intracameral inoculation of herpes simplex virus type 1 (HSV-1) in mice induces retinal necrosis primarily in the contralateral eye and provides an experimental model for the disease. Previous studies suggested that a major envelope glycoprotein of HSV-1, glycoprotein C (gC), is required for retinal necrosis. We studied HSV-1 strain TN-1, a gC-deficient clinical isolated from a lesion of herpetic keratitis, for its pathogenicity in mice with an intracameral inoculation of the virus and found that TN-1 could induce severe necrotizing retinitis in both inoculated and uninoculated eyes of BALB/c mice. Inoculation with a lower dose of TN-1 resulted in a unilateral necrotizing retinitis in the uninoculated eyes. Tissue virus titration of infected mice killed at various times after inoculation detected an infectious virus in various organs including the eyeballs, trigeminal ganglia, brain and adrenal glands. Anterior chamber-associated immune deviation (ACAID) was observed in TN-1-inoculated mice as well as in mice inoculated with gC-positive laboratory strain KOS 7 days postinoculation. Our findings suggested that gC of HSV-1 is not necessary for either the induction of retinal necrosis, neural spread of the virus, or ACAID.

Polymerase chain reaction for the detection of the varicella-zoster genome in ocular samples from patients with acute retinal necrosis.

We used the polymerase chain reaction to detect the virus genome in ocular samples from patients with clinically diagnosed acute retinal necrosis. Four samples from four patients with acute retinal necrosis, and five samples from three patients with other ocular diseases (sarcoidosis, rhegmatogenous retinal detachment, and epiretinal membrane of unknown origin) were evaluated. The samples consisted of aqueous humor, vitreous, or subretinal fluid. Primers were specific for varicella-zoster virus, herpes simplex virus, or cytomegalovirus. The varicella-zoster virus genome was detected in three of the four samples from patients with acute retinal necrosis. Among these three positive samples, two had PstI-site-less point mutation, strains that have been described only in Japan and of low prevalence. Samples from patients with diagnoses other than acute retinal necrosis yielded negative results when varicella-zoster virus primer was used. No sample was positive for herpes simplex virus or cytomegalovirus primers.

Herpesvirus antibody levels in the etiologic diagnosis of the acute retinal necrosis syndrome.

Quantitative antibody levels to three herpesviruses in acute and chronic sera from six patients with clinical signs of the acute retinal necrosis syndrome were consistent with a specific etiologic diagnosis only in the two cases associated with cutaneous herpes zoster. Available data on acute and convalescent antibody titers to herpes group viruses from these six patients in addition to data from 27 acute retinal necrosis cases from the literature disclosed that only 13 of the 33 patients (39%) had a diagnostic increase or decrease in herpes group viral antibody levels on serial sampling. Three patients had nondiagnostic changes in viral antibody levels despite positive vitreous cultures for herpesviruses. In contrast, a review of 25 cases from the literature with paired antiviral serum and intraocular fluid antibody levels suggested a more promising approach to the etiologic diagnosis of the acute retinal necrosis syndrome. By calculating the ratio of antiviral antibodies in intraocular fluid and serum, an etiologic diagnosis could be made in 12 of 14 (86%) of subacute and convalescent samples. The sensitivity of this method decreased to 72% (13 of 18) when fluids were obtained earlier in the course of the disease.

Diagnosis and management of the acute retinal necrosis syndrome.

The acute retinal necrosis (ARN) syndrome is an increasingly occurring entity characterized by the triad of acute confluent peripheral retinitis with papillitis and anterior-chamber uveitis. We present case reports on four patients (age, 12-65 years) with an ARN syndrome caused by herpes simplex or varicella zoster virus and discuss diagnostic and therapeutic modalities. Immediate antiviral therapy in three patients exhibiting the typical clinical features reduced the intraocular inflammation. However, due to proliferative vitreoretinopathy with peripheral retinal necrosis, vitrectomy with encircling band and silicone oil instillation was necessary in all patients. The suspected diagnosis of an ARN syndrome induced by herpes simplex virus (HSV) was confirmed in one case during the early stage of the disease by the detection of increased levels of HSV-IgA in the vitreous and in another case by the measurement of increased titers of HSV-IgG in the vitreous. For the first time, we found intraocular HSV DNA sequences using the polymerase chain reaction (PCR) in one of these patients. In a fourth patient intraocular varicella zoster virus (VZV) infection was confirmed by the detection of elevated VZV-IgA levels and by positive PCR in the intraocular fluids. Two patients who were diagnosed and treated early retained a visual acuity of 0.4 and 0.5, respectively, whereas in the other two patients, whose diagnosis and therapy were delayed (> 6 weeks), visual acuity was reduced to light perception. We conclude that use of the PCR in the intraocular fluids together with detection of autochthonous antibodies in the vitreous seem to be the most important diagnostic laboratory tools.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of herpetic encephalitis with acute retinal necrosis syndrome.

Bilateral acute retinal necrosis syndrome developed shortly after a severe acute encephalitis in two previously healthy adults. The clinical and laboratory data suggested that herpes simplex virus was the cause of the encephalitis and acute retinal necrosis in these patients. To the authors' knowledge, this is the first report of an association of herpetic encephalitis with acute retinal necrosis in the literature.

Evidence that precursor cytotoxic T cells mediate acute necrosis in HSV-1-infected retinas.

Following uniocular anterior chamber injection of HSV-1 (KOS) in BALB/c and A/J mice, it is paradoxical that (a) acute retinal necrosis (ARN) develops only in the uninjected eyes, and (b) ARN occurs only in mice that are immunocompetent, event though these mice invariably display anterior chamber associated immune deviation (ACAID), wherein delayed hypersensitivity to HSV antigens is grossly impaired. Previous studies have revealed that ARN develops only if the titer of infectious virus in the contralateral eye exceeds 4 Log10 PFU, indicating that virus infection is essential to ARN. However, HSV-1 titers in contralateral eyes of similarly infected athymic mice also exceed 4 Log10 PFU, even though these mice never develop ARN - implying that virus alone is insufficient to cause retinal cell destruction. In an effort to define the pathogenic immune component of ARN, we have evaluated in vitro viral antigen-specific T cell responses in mice with ARN and ACAID. We found that T cells, harvested from draining ipsilateral cervical lymph nodes and contrateral eye proliferate in response to viral antigens, express IL-2 receptors, and include HSV-1-specific precursor cytotoxic T cells (pTc), but not direct cytotoxic T cells (Tc). Since the time of appearance of HSV-specific pTc in the contralateral eye coincides with entry of infectious virus into that eye, and since their mutual appearance heralds the onset of retinal necrosis, we conclude that destruction of the retina is initiated by virus-specific cytotoxic T cells that lyse HSV-infected retinal cells.