Ocular Pathology and Occasionally Detectable Intraocular Severe Acute Respiratory Syndrome Coronavirus-2 RNA in Five Fatal Coronavirus Disease-19 Cases.

INTRODUCTION: In December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract. However, further studies documented other systemic involvement. This study investigates histopathologic eye changes in postmortem material of coronavirus disease 2019 (COVID-19) patients. METHODS: Sections of formalin-fixed, paraffin-embedded eyes from 5 patients (10 eyes) who died of COVID-19 at the University Hospital in Basel were included. Gross examination and histological evaluation were performed by 3 independent ophthalmopathologists. Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3, and ACE-2. Five enucleated eyes of patients not infected with SARS-CoV-2 served as control group. All cases have been studied for presence of SARS-CoV-2 RNA by means of reverse transcription PCR and RNA in situ hybridization (ISH). The choroidal vessels of one case were analyzed with electron microscope. RESULTS: Ophthalmopathologically, 8 eyes from 4 patients displayed swollen endothelial cells in congested choroidal vessels. No further evidence of specific eye involvement of SARS-CoV-2 was found in any of the patients. In the 8 eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina, and choroidea and displayed significantly lower amounts of stained cells as in COVID-19 eyes. SARS-CoV-2 RNA was detectable in both bulbi of 2/5 patients, yet ISH failed to visualize viruses. Electron microscopy showed no significant results due to the artifacts. DISCUSSION/CONCLUSION: As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, that is, hypercoagulation and vasculopathy most probably due to endothelial damage. A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. The expression of ACE-2 receptors in the conjunctiva hints toward its susceptibility to infection. To what extend eyes, function is disrupted by SARS-CoV-2 is subject to further studies, especially in the clinic.

Optical coherence tomography angiography findings in patients with COVID-19.

OBJECTIVE: To examine the changes in choriocapillaris and retina caused by coronavirus disease 2019 (COVID-19) by comparing optical coherence tomography angiography (OCTA) findings of COVID-19 patients and healthy controls. METHODS: The study and control groups consisted of 54 eyes of 27 participants, each. Patients and controls underwent OCTA examination. Foveal zone vessel density and parafoveal zone vessel density (for 4 quadrants: nasal, temporal, superior, inferior) were calculated for both superficial and deep capillary plexuses. Additionally, choriocapillaris flow and foveal avascular zone areas were calculated. RESULTS: For the parafoveal area in the study group, vessel density was significantly lower in the superior and nasal quadrants of the superficial capillary plexus and in all quadrants of the deep capillary plexus compared with controls (p < 0.05 for all). The study group had significantly higher choriocapillaris flow area values compared with controls (p = 0.042). CONCLUSION: Reduced vessel density of the retinal capillary plexus was detected in COVID-19 patients who may be at risk for retinal vascular complications.

Viral Kerato-Uveitis with Choroidal Vitiligo.

Purpose: To describe unusual fundus findings in typical varicella zoster (VZV) kerato-uveitis.Methods: Observational, retrospective case study of five patients diagnosed with VZV kerato-uveitis.Results: Four out of five cases had a history of typical herpes zoster ophthalmicus skin rash over the forehead. All five patients had stromal keratitis, granulomatous keratic precipitates, and mild-moderate anterior chamber reaction, and two cases had typical VZV-iris atrophic changes. All cases demonstrated clear vitreous and multiple hypopigmented choroidal lesions (MHCL) with indistinct borders only in the affected eyes. Imaging studies failed to demonstrate evidence of active or resolved choroiditis. MHCL remained status quo in all including two cases who had recurrences of kerato-uveitis.Conclusion: We describe previously unreported novel fundus finding, MHCL in typical VZV-kerato-uveitis cases. We presume MHCL are due to loss of melanin from choroidal melanocytes secondary to the VZV infection and propose a term "choroidal vitiligo" to describe these novel fundus findings.

Acute unilateral maculopathy associated with adult onset of hand, foot and mouth disease: a case report.

BACKGROUND: To report the case of a 31-year-old patient with Hand, Foot and Mouth Disease (HFMD) and concurrent acute monocular maculopathy, and to describe multimodal imaging findings never before described including optical coherence tomography angiography (OCT-A). CASE PRESENTATION: Nine days after the onset of clinically highly probable but not laboratory-verified HFMD, a 31-year old male noticed a central scotoma, distorted lines and loss of visual acuity (Snellen visual acuity 20/400) in his right eye. Funduscopy revealed focal alterations in the retinal pigmented epithelium (RPE) and yellow retinal dots corresponding to focal dots of decreased fundus autofluorescence (FAF) surrounded by increased FAF. Spectral domain optical coherence tomography (SD-OCT) demonstrated irregularities in the ellipsoide zone, hyperreflective dots above the RPE and RPE thickening. Fundus fluorescein angiography (FAG) revealed central hypofluorescence in the macular area in the early phase, as well as increasing focal hyperfluorescence in the late phase corresponding with RPE defects observed in FAF. Indocyanine green angiography (ICGA) showed central hypofluorescence in the early and late phase, corresponding with areas of reduced flow in the choroidea and choriocapillaris as apparent in OCT-A. Visual acuity improved within 3 months without any systemic or local therapy. At his three-month follow-up, SD-OCT revealed subtle subretinal fluid that resolved spontaneously over time. No signs of choroidal neovascularization were observed. Twelve months following the onset of symptoms Snellen visual acuity was 400/400. Multimodal imaging revealed subtly changed, decreased FAF while the choroidal architecture recovered completely as demonstrated by OCT-A. CONCLUSIONS: HFMD-associated maculopahty is an uncommon but important differential diagnosis of chorioretinitis with macular involvement. The prognosis can be good and the initially observed morphological pathologies such as impaired perfusion of the choroidal vessels can recover spontaneously over a period lasting 12 months. OCT-A can be employed as a non-invasive tool to detect the reduced perfusion of the choroidal vessels and for monitoring the disease course.

Observed positive correlation between Epstein-Barr virus infection and focal choroidal excavation.

PURPOSE: To evaluate a possible correlation between focal choroidal excavation and Epstein-Barr virus (EBV) infection. METHOD: Three eyes of three patients underwent a comprehensive ophthalmologic examination including visual field testing, color fundus photography, optical coherence tomography (OCT), fluorescein angiography and indocyanine green angiography. In addition, hematological and viral infectivity were also evaluated. PATIENTS: Two females and one male with a mean age of 53.6 ± 5.6 years were studied. RESULTS: In all patients, both the anterior and posterior segment evaluations were unremarkable except for the presence of a spot with focal retinal pigment epithelium (RPE) alteration. In patients 1 and 2, OCT disclosed a normal neuroretinal structure above the lesion and a focal 'punch-out' choroidal lesion with total absence of the RPE coupled with a localized hyporeflectivity in the subretinal space. In two of the three patients, OCT showed normal outer retinal layers, including the photoreceptor layer and the external limiting membrane with a hyporeflective space under the inner segment/outer segment (IS/OS) junction. In one patient, the retinal structure appeared to descend down into the choroidal excavation with an absence of the IS/OS junction and RPE. Moreover, the outer retinal layers appeared to be deformed. In all three patients, the choriocapillaris and choroid showed significant defects as if 'punched out' and the scleral boundary was more evident. In all three patients, an active EBV infection was confirmed by hematological investigation. CONCLUSIONS: In all our patients with focal choroid anomalies, such as choroidal excavation observed by OCT, a systemic infection by the EBV was detected. A larger number of similar cases are necessary to corroborate these preliminary observations.

Choroidal and optic nerve infarction in hepatitis C-associated polyarteritis nodosa.

A 39-year-old man presented with headache, weight loss, bilateral subdural hematomas, pansinusitis, and visual loss. The neuro-ophthalmologic examination disclosed deep choroidal lesions and bilateral optic disc edema. Orchiectomy for testicular torsion showed acute vasculitis consistent with polyarteritis nodosa (PAN). Polymerase chain reaction (PCR) testing revealed hepatitis C. This is the first reported case of PAN due to hepatitis C with early findings of choroidal and optic nerve infarction.

Ocular manifestations of dengue fever.

PURPOSE: To evaluate ocular manifestations associated with dengue fever. DESIGN: Retrospective case series and literature review. METHODS: Clinical records of patients with dengue fever who subsequently had ocular symptoms and signs develop were reviewed. The clinical presentation and ocular complications were evaluated. RESULTS: Six patients, 5 females and 1 male, were seen with a sudden decrease in vision 6 to 7 days after the initial manifestations of dengue fever were identified. The diagnosis was confirmed by detection of dengue-specific IgM antibodies (IgM enzyme-linked immunoassay). The presenting best-corrected visual acuity ranged from 20/30 to counting fingers, and ocular involvement was bilateral but asymmetric in 5 cases and unilateral in 1 case. Fundus findings included small, intraretinal, whitish lesions, with localized retinal and retinal pigment epithelium (RPE) disturbance, small dot hemorrhages, and vascular sheathing around the macula and the papillomacular bundle. Fluorescein angiography showed arteriolar focal knobby hyperfluorescence at the macula with mild staining of the vascular walls and leakage at the level of the RPE. All 5 cases that had indocyanine green angiography done showed early diffuse choroidal hyperfluorescence with late silhouetting of the larger choroidal vessels. Five patients received steroid therapy: 1 topical, 2 periocular, and 2 oral. Over 2 to 4 months, RPE discoloration was observed over the affected areas. After the acute episode, 3 patients showed partial recovery of vision, and in the remaining patients, the visual acuity remained stable. CONCLUSIONS: Ocular complications associated with dengue fever are rare but may result in permanent visual impairment.

Ocular manifestations of human T-cell lymphotropic virus type 1 infection.

PURPOSE OF REVIEW: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is endemic in Japan, the Caribbean islands, and parts of Central Africa and South America. Known ophthalmic manifestations of HTLV-1 include malignant infiltrates in patients with adult T-cell leukemia/lymphoma, retinal degeneration, neuroophthalmic disorders, and keratoconjunctivitis sicca in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, and HTLV-1-associated uveitis. This report reviews the recent developments and ocular findings reported in patients with HTLV-1-related diseases. RECENT FINDINGS: Most of the knowledge of the ocular manifestations of HTLV-1 comes from southwestern Japan, which has the highest incidence of infection worldwide. During the past few years, however, ocular disease associated with HTLV-1 has been described in patients from other endemic areas genetically distinct and geographically distant from Japan. The most interesting of these was the recognition of corneal pathology in Brazilian and Caribbean patients with HTLV-1 that have not been described in Japanese patients. Other developments include the use of molecular techniques in the diagnostic evaluation of ocular tissues from HTLV-1 patients, and clinical studies demonstrating choroidal involvement by indocyanine green angiography in patients with HTLV-1-associated uveitis, and suggesting that retinal vasculitis unresponsive to corticosteroid therapy maybe a poor prognostic sign. SUMMARY: The spectrum of ocular disease related to HTLV-1 continues to expand. Routine evaluation of HTLV-1-infected patients is important because immune-mediated or neoplastic ocular involvement may occur during the disease course. Genetic and environmental factors may play a role in the ocular manifestations of HTLV-1 in different populations.

Intrauterine West Nile virus: ocular and systemic findings.

PURPOSE: To report the first documented case of intrauterine transmission of West Nile virus (WNV) with resulting congenital chorioretinal scarring and central nervous system malformation in a newborn. DESIGN: Case report. METHODS: Ophthalmic findings and laboratory data in an otherwise presumed healthy 2-day-old female are presented. The infant's mother developed paraplegia due to WNV during the second trimester of her pregnancy. The newborn's external and general physical examination were unremarkable. RESULTS: Ophthalmic examination disclosed marked chorioretinal changes, and magnetic resonance imaging of the brain demonstrated severe abnormalities. Serology for WNV was positive. Other causes of congenital chorioretinal changes were ruled out with the appropriate serology. CONCLUSIONS: Intrauterine transmission of WNV may result in significant ocular and neurologic morbidity. Titers for this important and emerging viral pathogen should be obtained when standard serologies are negative in an infant with congenital chorioretinal scarring.

Indocyanine green angiography in patients with human T cell-lymphotropic virus type 1 uveitis.

PURPOSE: To determine the indocyanine green (ICG) angiographic features and to evaluate the choroidal involvement of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis. METHODS: We performed ICG angiography using scanning laser ophthalmoscopy in 54 eyes of 27 patients (8 men and 19 women) diagnosed with HTLV-1 uveitis. The patient's mean age was 51.5 years with a range of 24-65 years. RESULTS: The early phase of ICG angiography revealed ICG leakage from the choroidal vessels in the posterior pole, hyperfluorescent spots that which were not detected with fluorescein angiography, and small hypofluorescent lesions in the macula which most likely corresponded to microcirculatory disturbances in the choriocapillaris. CONCLUSIONS: We suggest that the ICG angiographic findings reflect choroidal lesions such as infiltration with leukocytes and edema. ICG angiography may provide useful information on choroidopathy in HTLV-1 uveitis.

Chorioretinal post-transplant lymphoproliferative disorder induced by the Epstein-Barr virus.

BACKGROUND: The Epstein-Barr virus (EBV) is responsible for the lymphoproliferative disorders observed in transplanted patients. METHODS: The case history is described of a 59 year old man with a chorioretinal lesion who had received a single lung transplant and was on immunosuppressive treatment. Immunoglobulin gene rearrangement and EBV detection by polymerase chain reaction (PCR) with semiquantification were used on the vitreous material. RESULTS: A proliferation of B lymphocytes with a monoclonal subpopulation was found by PCR on the vitreous sample. The large amounts of EBV genomes found in the vitreous suggest that EBV was the cause of the lymphoproliferation. Healing of the lesion was achieved by a decrease in immunosuppressive treatment and the use of nucleotide analogues. CONCLUSION: The diagnosis of ocular post-transplant lymphoproliferative disorder (PTLD) can be made by PCR on vitreous material. Early diagnosis and treatment can lead to regression of limited monoclonal lesions.