Increased Retinal Vessel Tortuosity Associated With Crimean-Congo Hemorrhagic Fever in Children.

BACKGROUND: To evaluate the ocular symptoms and findings of children diagnosed with Crimean-Congo hemorrhagic fever (CCHF). METHODS: In this prospective study, children diagnosed with CCHF who underwent a complete ophthalmologic examination during the hospitalization period were included. RESULTS: Twenty-four children with a mean age of 12.4 ± 3.6 years were included study. The most common ocular finding was conjunctival hyperemia and was observed in 50% of patients. Nine (37.4%) children had abnormalities in fundus examination. Two (8.3%) of them had dilated retinal veins, and 7 (29.1%) had tortuous retinal vessels. No significant difference was found between mild to moderate and severe disease groups in terms of ocular symptoms and ophthalmologic examination findings (P > 0.05, for all). CONCLUSIONS: The increased retinal vessel tortuosity was detected as a fundus examination finding in children with CCHF. Both ophthalmologists and pediatricians should be aware of the various ocular manifestations of CCHF for rapid diagnosis and management.

Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes-Implications for Retinopathy.

Purpose: To investigate the expression of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 in human retina. Methods: Human post-mortem eyes from 13 non-diabetic control cases and 11 diabetic retinopathy cases were analyzed for the expression of ACE2. To compare the vascular ACE2 expression between different organs that involve in diabetes, the expression of ACE2 was investigated in renal specimens from nondiabetic and diabetic nephropathy patients. Expression of TMPRSS2, a cell-surface protease that facilitates SARS-CoV-2 entry, was also investigated in human nondiabetic retinas. Primary human retinal endothelial cells (HRECs) and primary human retinal pericytes (HRPCs) were further used to confirm the vascular ACE2 expression in human retina. Results: We found that ACE2 was expressed in multiple nonvascular neuroretinal cells, including the retinal ganglion cell layer, inner plexiform layer, inner nuclear layer, and photoreceptor outer segments in both nondiabetic and diabetic retinopathy specimens. Strikingly, we observed significantly more ACE2 positive vessels in the diabetic retinopathy specimens. By contrast, in another end-stage organ affected by diabetes, the kidney, ACE2 in nondiabetic and diabetic nephropathy showed apical expression of ACE2 tubular epithelial cells, but no endothelial expression in glomerular or peritubular capillaries. Western blot analysis of protein lysates from HRECs and HRPCs confirmed expression of ACE2. TMPRSS2 expression was present in multiple retinal neuronal cells, vascular and perivascular cells, and Müller glia. Conclusions: Together, these results indicate that retina expresses ACE2 and TMPRSS2. Moreover, there are increased vascular ACE2 expression in diabetic retinopathy retinas.

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.

Vascular Damage May Mimic Retinitis and Optic Neuritis in COVID-19.

Ophthalmologic nvolvement in SARS-CoV-infected patients is variegated. One of the ophthalmologic pathologies is optic neuritis. Optic neuritis in SARS-CoV-infected patients may precede the classical pulmonary manifestations of COVID-19 and can be unilateral or bilateral. Optic neuritis has been repeatedly reported in COVID-19 patients and may occur with or without affection of other cranial nerves. Since cerebro-spinal fluid parameters can be abnormal in COVID-19 associated optic neuritis, these patients require a spinal tap. Before diagnosing SARS-CoV-2 associated optic neuritis various differentials need to be excluded. Since SARS-CoV-2 causes endothelial damage complicated by thrombus formation and thromboembolism, ophthalmologic vascular complication due to an infection with SARS-CoV-2 such as anterior ischemic optic neuropathy (AION), central retinal artery occlusion (CRAO), and retinal vein occlusion need to be excluded. CRAO may result from arterial hypertension, myocarditis, heart failure, Takotsubo syndrome, atrial fibrillation, or atrial flutter, frequent cardiac complications of COVID-19. Since CRAO can be accompanied by ischemic stroke, patients with SARS-CoV-2 associated optic neuritis need to undergo a cerebral MRI.

Varicella Zoster-related Occlusive Retinal Vasculopathy--A Rare Presentation.

PURPOSE: To report a case of occlusive retinal vasculopathy following varicella zoster infection in an immunocompetent adult. DESIGN: Observational case report. METHODS: A patient with defective vision following chickenpox was evaluated with fluorescein angiography, spectral domain optical coherence tomography and fundus auto fluorescence. RESULTS: Fundus showed multiple cotton wool spots and a well-demarcated zone of retinal ischemia in the posterior pole with normal optic disc without any evidence of anterior or posterior uveitis. Fluorescein angiography, spectral domain optical coherence tomography and fundus auto fluorescence findings revealed occlusive vasculopathy as the cause of defective vision. CONCLUSIONS: We report a hitherto undescribed case of purely occlusive vasculopathy following varicella zoster infection without features of vasculitis or anterior and posterior uveitis in an immunocompetent individual.

Elevated anti-human T-cell lymphotropic virus type I antibody in serum of patients with retinal vasculitis and uveitis living in Izumo area.

Four patients with human T-lymphotropic virus type I associated myelopathy (HAM) were examined ophthalmologically, and serum titers to human T-lymphotropic virus type I (HTLV-I) in 11 patients with nonspecific retinal vasculitis or uveitis were determined. All of the patients lived in the Izumo area. All 4 patients with HAM (Cases 1 to 4) had vitreous opacities. Of the 11 patients with nonspecific retinal vasculitis or uveitis, 3 (Cases 5 to 7) had elevated titers to HTLV-I. We believe that HTLV-I infection may be involved in the causes of retinal vasculitis and uveitis in patients living not only in the endemic area but also outside the endemic area.