Zika virus induces neuronal and vascular degeneration in developing mouse retina.

Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease and even blindness in newborns. However, ZIKV-induced retinal lesions have not been studied in a comprehensive way, mechanisms of ZIKV-induced retinal abnormalities are unknown, and no therapeutic intervention is available to treat or minimize the degree of vision loss in patients. Here, we developed a novel mouse model of ZIKV infection to evaluate its impact on retinal structure. ZIKV (20 plaque-forming units) was inoculated into neonatal wild type C57BL/6J mice at postnatal day (P) 0 subcutaneously. Retinas of infected mice and age-matched controls were collected at various ages, and retinal structural alterations were analyzed. We found that ZIKV induced progressive neuronal and vascular damage and retinal inflammation starting from P8. ZIKV-infected retina exhibited dramatically decreased thickness with loss of neurons, initial neovascular tufts followed by vessel dilation and degeneration, increased microglia and leukocyte recruitment and activation, degeneration of astrocyte network and gliosis. The above changes may involve inflammation and endoplasmic reticulum stress-mediated cell apoptosis and necroptosis. Moreover, we evaluated the efficacy of preclinical drugs and the safety of ZIKV vaccine candidate in this mouse model. We found that ZIKV-induced retinal abnormalities could be blocked by a selective flavivirus inhibitor NITD008 and a live-attenuated ZIKV vaccine candidate could potentially induce retinal abnormalities. Overall, we established a novel mouse model and provide a direct causative link between ZIKV and retinal lesion in vivo, which warrants further investigation of the underlying mechanisms of ZIKV-induced retinopathy and the development of effective therapeutics.

Retinal vein occlusion in COVID-19: A novel entity.

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the "cytokine-storm" as the pathogenesis for systemic manifestations of COVID-19.

Human Adenovirus: An Unusual Causative Agent for Acute Retinal Necrosis Presented with Central Retinal Vascular Occlusion.

PURPOSE: We describe a case of acute retinal necrosis (ARN) with central retinal vascular occlusion caused by human adenovirus (HAdV). CASE REPORT: A 41-year-old man presented with a sudden decrease of visual acuity in his right eye since seven days. Visual acuity was hand movements and ophthalmic examination of the right eye revealed diffuse hemorrhagic retinal vasculitis with panuveitis. He was clinically diagnosed as ARN with central retinal vascular occlusion. An anterior chamber paracentesis and intravitreal ganciclovir injection were performed and intravenous ganciclovir has been initiated immediately. Polymerase chain reaction (PCR) analysis of aqueous humor identified HAdV DNA as a causative agent. Oral prednisolone was added to treatment 5 days after antiviral therapy. After 10 days of intravenous ganciclovir therapy, oral valganciclovir was given for 6 months. No recurrence or retinal detachment occurred during follow-up. CONCLUSION: HAdV known to cause acute epibulbar infections of the eye may also cause intraocular inflammation such as ARN.

Varicella-zoster virus necrotising retinitis, retinal vasculitis and panuveitis following uncomplicated chickenpox in an immunocompetent child.

A 4-year-old girl presented with acute left visual loss 4 weeks after uneventful chickenpox. She was found to have left necrotising retinitis and profound retinal vasculitis and vitritis. Aqueous humour was PCR positive for varicella-zoster virus. Combined intravenous and intravitreal antiviral treatment led to rapid improvement with settled retinitis, no vascular occlusion and good recovery of vision. Her recent coinfection with Epstein-Barr virus may have acted to provoke the retinitis.

Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

RETINAL VASCULITIS ASSOCIATED WITH EPSTEIN-BARR VIRUS INFECTION, A CASE REPORT.

PURPOSE: To report a case of retinal vasculitis associated with Epstein-Barr virus infection. METHODS: Case report. RESULTS: A 26-year-old woman came with blurry vision. Funduscopy illustrated vasculitis with frosted branch-like appearance. The patient was treated with systemic acyclovir and topical steroid. Circulating polymerase chain reaction was positive for Epstein-Barr virus antibodies. Two months of treatment resolved the clinical manifestations. CONCLUSION: Epstein-Barr infection should be considered as the etiology of retinal vasculitis with similar clinical manifestations.

Bilateral idiopathic retinal vasculitis following coxsackievirus A4 infection: a case report.

BACKGROUND: Coxsackieviruses are members of a group of viruses called the enteroviruses, which may cause respiratory and gastrointestinal symptoms, erythema, meningoencephalitis, myocarditis, pericarditis, and myositis. Unilateral acute idiopathic maculopathy caused by coxsackievirus A16 has been associated with hand, foot, and mouth disease, but only a few reports describe retinitis associated with coxsackievirus serotype B3 or B4. We report a case of bilateral multifocal obstructive retinal vasculitis that developed after coxsackievirus A4 infection. CASE PRESENTATION: A 60-year-old woman was referred to our department with bilateral visual disturbance that developed following flu-like symptoms. At the initial examination, best corrected visual acuity was 20/200 in the right eye and 20/50 in the left eye. The critical flicker frequency (CFF) was 23 Hz in the right eye and 27 Hz in the left eye. Fine white keratic precipitates with infiltrating cells were presented in the anterior chamber of both eyes, and multifocal retinal ischemic lesions were observed in the macula and posterior pole of both eyes. The retinal lesions corresponded with scotomas observed in Goldmann visual field test. On spectral domain-optical coherence tomography (SD-OCT), retinal lesions were depicted as hyper-reflective regions in the inner retina layers in both eyes, and disruption of ellipsoid line in the left eye., Fluorescein angiography exhibited findings indicative of multifocal obstructive retinal vasculitis. The patient had a history of current hypertension treated with oral therapy and glaucoma treated with latanoprost eye drops. Blood test for coxsackievirus antibody titers revealed that A4, A6, A9, B1, B2, B3, and B5 were positive (titers: 8-32). Abdominal skin biopsy of necrotic tissue suggested vascular damage caused by coxsackievirus. The general symptoms improved after 6 weeks, and the multifocal retinal ischemic lesions were partially resolved with residual slightly hard exudates. Only coxsackievirus A4 antibody titer increased from 4 to 32-fold after 14 months. However, hyper-reflective regions and disruption of the inner retinal layers on SD-OCT persisted especially in the right eye, and residual paracentral scotoma was observed in the right eye. CONCLUSION: The present case suggests that coxsackievirus A4 causes bilateral multifocal obstructive retinal vasculitis with irreversible inner retinal damage.

Progressive outer retinal necrosis associated with occlusive vasculitis in acquired immunodeficiency syndrome.

A 45-year-old man, a case of acquired immunodeficiency syndrome, received a highly active antiretroviral therapy at the outpatient service for 4 years without regular follow-up. He experienced progressively blurred vision for 6 months and a cutaneous zoster on his back 3 months ago. He was diagnosed with progressive outer retinal necrosis by polymerase chain reaction-restriction fragment length polymorphism using an aqueous humor sample, which revealed an existence of varicella zoster virus. He was given a combination of systemic, intravitreal antiviral and a highly active antiretroviral therapy. Occlusive vasculitis, an unusual finding for progressive outer retinal necrosis, developed in both eyes 1 week after the secondary intravitreal injection. Unfortunately, his vision deteriorated to no light perception in both eyes within 2 weeks. Progressive outer retinal necrosis is characterized clinically as showing minimal or no inflammation in the aqueous and vitreous humors, absence of retinal vasculitis, and patches of yellowish spots located deep in the retina. Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment.

Posterior segment findings of ocular cytomegalovirus infection in immunocompetent patients.

PURPOSE: We sought to investigate and describe the clinical spectrum of posterior segment abnormalities in immunocompetent patients presenting with CMV-associated anterior uveitis. METHODS: This was a prospective study conducted at the Singapore National Eye Centre, a tertiary referral centre, from August 2010 to June 2011. Eleven eyes of eleven patients with CMV anterior uveitis confirmed by polymerase chain reaction on aqueous humor sampling were recruited based on the study criteria. Patients were recruited from a single uveitis specialist clinic and underwent aqueous humor sampling and fluorescein and indocyanine green angiography as well as optical coherence tomography. They were further evaluated by the Infectious Disease physician for immunocompetence. RESULTS: Mean presenting visual acuity was logMAR 0.35 ± 0.29. The main presenting complaints were blurring of vision, eye redness, and pain. Anterior chamber cellular activity was present in all cases. Fine diffuse keratic precipitates (KPs) were present in 10 eyes, and the remaining one eye had mutton fat KPs. Iris changes were present in three eyes. Intraocular pressure (IOP) was elevated in nine eyes (mean presenting IOP was 40.2 ± 16.8 mmHg). In the posterior segment, none of the eyes had evidence of retinitis or hemorrhage. Posterior segment abnormalities were present in six eyes (macular edema, disc leakage, epiretinal membrane, phlebitis). Eight eyes also had prolonged arm to retina time (mean 24.8 ± 10.6 s) on fluorescein angiography. Indocyanine green angiography was unremarkable. CONCLUSION: Posterior segment manifestations can be seen in a proportion of immunocompetent patients with CMV anterior uveitis. The underlying mechanism remains to be determined.

Human herpesvirus 6-associated uveitis with optic neuritis diagnosed by multiplex PCR.

PURPOSE: Human herpesvirus 6 (HHV-6), which is usually responsible for exanthem subitum in children, can be reactivated from its latent state. We report a case of unilateral optic disc edema and retinal vasculitis associated with HHV-6 infection. CASE: A healthy 63-year-old man noted a decrease in the vision of his left eye. On examination, his left eye had moderate mutton-fat keratic precipitates, vitreous opacities, significant optic disc edema surrounded by yellowish-white swelling in the inner retina, retinal arteritis, and cotton-wool-like exudates. He was started on corticosteroid therapy and aspirin. After 1 month, the disc edema was reduced, the cotton wool-like exudates had decreased, and his visual acuity had improved to 10/20 OS. Multiplex polymerase chain reaction (PCR) of an aqueous humor sample revealed the presence of genomic DNA of HHV-6 but not of the other HHVs. CONCLUSIONS: The HHVs are known to infect the ocular tissues, but the differential diagnostic signs of HHV-6 are still not well known. We recommend that multiplex PCR of the aqueous humor be performed to search for the genomic DNA of HHV-6 in suspected cases of herpesviral infection.

Mannose-binding lectin as part of the complement pathway: characterization in non-inflamed and inflamed human eyes.

BACKGROUND: Mannose-binding lectin plays a central effector role in the lectin pathway of complement activation. Frequently occurring MBL2 polymorphisms result in mannose-binding lectin deficiency, which increases susceptibility to infection. We characterized mannose-binding lectin levels and function in non-inflamed and inflamed human eyes, and evaluated its relationship to blood mannose-binding lectin levels and function. DESIGN: Prospective, observational clinical study with controls and cases. PARTICIPANTS: Twenty-seven patients with paired blood and ocular samples (aqueous and/or vitreous) including 15 controls (non-inflamed) and 12 cases (inflamed). METHODS: Blood and ocular samples were collected from controls (n = 15) with quiet eyes during elective cataract surgery and cases with inflamed eyes including proven/suspected endophthalmitis (n = 11) and herpetic retinal vasculitis (n = 1). Mannan-binding and C4 deposition enzyme-linked quantify mannose-binding lectin levels and function. MAIN OUTCOME MEASURES: Blood and ocular mannose-binding lectin levels and function. RESULTS: Of 27 patients, 10 (37%) were mannose-binding lectin-deficient (defined as blood mannose-binding lectin levels <500 ng/mL). Blood mannose-binding lectin levels (P= 0.16) or function (P= 0.43) were not significantly different between controls and cases. As expected, there was a high correlation between blood mannose-binding lectin levels and function (r(2) = 0.74). However, there was significantly more mannose-binding lectin in inflamed eyes than non-inflamed eyes measured as level (P < 0.01) or C4 deposition function (P < 0.01). CONCLUSIONS: Our study demonstrated that mannose-binding lectin is significantly elevated in inflamed human eyes but virtually undetectable in non-inflamed control eyes, suggesting a role in sight-threatening ocular inflammation.

[HIV retinal vasculitis]. / Vasculitis retiniana por VIH.

CASE REPORT: We present a case of a 47 year-old woman, infected with human immunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, who had floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed by an angiography. No source of infection was found, antiretroviral and corticosteroid treatment was given, with a complete resolution of the vasculitis. DISCUSSION: From 70-80% of positive untreated HIV patients develop ocular complications, with intraocular inflammation in more than half of them. Intraocular inflammation can be associated with opportunistic infections, tumours and as in our case, secondary to the HIV. Antiretroviral therapy is the proper treatment in these patients.