Ocular Manifestations of Flavivirus Infections.

Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.

A Comparative Study between Occlusive and Non-occlusive Retinal Vasculitis: Data from a Referral Center in Tunisia, North Africa.

PURPOSE: To compare clinical profile and visual outcomes of occlusive versus non-occlusive retinal vasculitis (RV). METHODS: A retrospective comparative study. RESULTS: 284 patients were enrolled, including 124 patients with occlusive RV (ORV) and 160 patients with non-occlusive RV (NORV). Patients with ORV were older (p ≤ 10-3), predominantly male (p ≤10-3), with less bilateral involvement (31.5% vs 53,4%; p ≤ 10-3). Infectious RV was more frequently diagnosed in the ORV group than in the NORV group (48.8% vs 32.9%, p = .006). Behçet disease and ocular tuberculosis were the leading causes of ORV. Idiopathic RV, Behçet disease, and sarcoidosis were the most common causes of NORV. Independent predictive factors of poor visual outcome were worse baseline visual acuity in both groups (p = .006 and p ≤ 10-3, respectively), and retinal hemorrhages (p = .048) and optic atrophy (p = .040) in the ORV group. CONCLUSION: Occlusive and non-occlusive RV have distinctive clinical and etiological profile.

Swept-source Optical Coherence Tomography Angiography in Active and Scarred Toxoplasmic Retinochoroiditis.

PURPOSE: To describe optical coherence tomography angiography (OCTA) findings in eyes with active and scarred toxoplasmic retinochoroiditis. METHODS: OCTA scans in active (25 eyes) and scarred (17 eyes) retinochoroiditis were retrospectively reviewed. RESULTS: In active lesions, OCTA findings included a non-detectable flow signal area in retinal vascular plexuses and choriocapillaris in all 25 eyes (100%), an abnormal intraretinal vascular process in 2 eyes (8%), and an associated area of retinal flow deficit secondary to branch retinal artery occlusion in one eye (4%). In scarred lesions, OCTA findings included a flow deficit area in retinal vascular plexuses and choriocapillaris in all 17 eyes (100%), a visibility of larger deeper choroidal vessels at the level of choriocapillaris in 9 eyes (53%), and a well-defined intraretinal vascular network in one eye (5.9%). Peripapillary scars were associated on OCTA with wedge-shaped loss of radial peripapillary capillaries with corresponding localized retinal nerve fiber layer defect and visual field loss. CONCLUSION: OCTA allows to non-invasively detect retinal and choroidal vascular changes in active and scarred toxoplasmic retinochoroiditis.

Multimodal Imaging of Acute Foveolitis following COVID-19 Vaccination.

PURPOSE: To report a case of unilateral acute foveolitis following COVID-19 vaccination. METHODS: A case report. RESULTS: A 24-year-old woman developed a sudden blurring of vision in the left eye (LE) 5 days after receiving the first dose of COVID-19 vaccine. Examination of the LE showed a visual acuity at 20/40, 2+ cells in the vitreous, and a small yellow-orange foveal subretinal lesion. Late-phase fluorescein angiography showed a mild diffuse retinal vascular leakage and a faint foveal hyperfluorescence. ICG angiography showed in the late-phase hypofluorescence of the centrofoveal lesion. OCT B-scan demonstrated a conical hyperreflective subfoveal lesion on the retinal pigment epithelium associated with disruption of the outer retinal layers. En-face OCT revealed granular hyperreflective specks mainly in the inner nuclear layer. Work-up results were unremarkable. The patient received oral prednisolone with subsequent full functional and anatomic recovery. CONCLUSION: Foveolitis may rarely occur as a complication of COVID-19 vaccination.

Ocular Manifestations of Emerging Arthropod-Borne Infectious Diseases.

PURPOSE: To review the clinical features, diagnosis, treatment modalities, and prognosis of arthropod-borne infectious diseases. METHODS: This is a narrative review on arthropod-borne infectious diseases including general and ophthalmological aspects of these infectious diseases. A comprehensive literature review between January 1983 and September 2020 was conducted in PubMed database. Epidemiology, clinical features, diagnosis, treatment, and prognosis of arthropod-borne infectious diseases were reviewed. RESULTS: Emergent and resurgent arthropod-borne infectious diseases are major causes of systemic morbidity and death that are expanding worldwide. Among them, bacterial and viral agents including rickettsial disease, West Nile virus, Dengue fever, Chikungunya, Rift valley fever, and Zika virus have been associated with an array of ocular manifestations. These include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is confirmed by laboratory tests. Ocular involvement usually has a self-limited course, but it can result in persistent visual impairment. Doxycycline is the treatment of choice for rickettsial disease. There is currently no proven specific treatment for arboviral diseases. Prevention remains the mainstay for arthropod vector and zoonotic disease control. CONCLUSIONS: Emerging arthropod vector-borne diseases should be considered in the differential diagnosis of uveitis, especially in patient living or with recent travel to endemic countries. Early clinical diagnosis, while laboratory testing is pending, is essential for proper management to prevent systemic and ocular morbidity.

Results of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Inflammatory Choroidal Neovascularization.

PURPOSE: To report the visual outcomes of intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) in inflammatory choroidal neovascularization (iCNV). METHODS: A retrospective study of 43 eyes of 38 patients with active choroidal neovascularization (CNV) related to ocular inflammatory disease, treated with IVT injections of anti-VEGF (bevacizumab, ranibizumab, or aflibercept), with or without associated systemic anti-inflammatory therapy, at Fattouma Bourguiba University Hospital, Monastir, Tunisia (24 eyes of 23 patients) and at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (19 eyes of 15 patients) from January 1, 2013, to December 31, 2018. RESULTS: The mean age was 35.5 ± 16.4 years. The sex ratio male:female was 0.27. Seventeen eyes (39.5%) of 17 patients (44.7%) had only anti-VEGF injections, and 26 eyes (60.5%) of 21 patients (45.3%) had anti-VEGF injections and associated systemic anti-inflammatory therapy. Bevacizumab was injected in 36 eyes (83.7%), ranibizumab in six eyes (14%), and aflibercept in one eye (2.3%). Mean follow-up was 20.3 ± 19.2 months (range, 6-106 months). Mean visual acuity improved from 0.8 ± 0.37 logMAR (approximate Snellen equivalent 20/125) to 0.51 ± 0.42 logMAR (approximate Snellen equivalent 20/63) (P < 0.001). Mean central macular thickness on optical coherence tomography decreased from 403.7 ± 121.9 to 293.7 ± 82.8 µm (P < 0.001). Mean gain of vision was 2.9 ± 3.1 lines. The mean number of injections was 2.5. Twenty eyes (46.5%) received a single injection. There were no side effects related to the IVT injections of anti-VEGF. CONCLUSIONS: CNV is a sight-threatening complication of uveitis. IVT anti-VEGF seems to be an effective and safe treatment for iCNV when inflammation is controlled.

Abducens nerve palsy with associated retinal involvement secondary to rickettsia typhi infection.

OBJECTIVE: To report a case of abducens nerve palsy with associated retinal involvement due to rickettsia typhi infection. MATERIAL AND METHODS: A single case report documented with multimodal imaging. RESULTS: A 18-year-old woman with a history of high-grade fever was initially diagnosed with typhoid fever and treated with fluoroquinolone. She presented with a 5-day history of diplopia and headaches. Her best-corrected visual acuity was 20/20 in both eyes. Ocular motility examination showed left lateral gaze restriction. Lancaster test confirmed the presence of left abducens palsy. Fundus examination showed optic disc swelling in both eyes associated with superotemporal retinal hemorrhage and a small retinal infiltrate with retinal hemorrhage in the nasal periphery in the left eye. Magnetic resonance imaging (MRI) of the brain and orbits showed no abnormalities. A diagnosis of rickettsial disease was suspected and the serologic test for Richettsia Typhi was positive. The patient was treated with doxycycline (100 mg every 12 h) for 15 days with complete recovery of the left lateral rectus motility and resolution of optic disc swelling, retinal hemorrhages, and retinal infiltrate. CONCLUSION: Rickettsial disease should be considered in the differential diagnosis of abducens nerve palsy in any patient with unexplained fever from endemic area. Fundus examination may help establish an early diagnosis and to start an appropriate rickettsial treatment.

Sequential bilateral Behçet's neuroretinitis associated with prepapillary vitreous exudate: case report.

OBJECTIVE: To describe a case of Behçet disease (BD) uveitis manifesting with sequential bilateral neuroretinitis associated with prepapillary inflammatory vitreous exudate (PIVE). MATERIAL AND METHODS: A single case report documented with multimodal imaging. RESULTS: A 37-year-old man developed neuroretinitis with associated PIVE in the left eye. He was diagnosed with ocular toxoplasmosis and treated accordingly based on positive serologic testing and negative work-up for other entities, including BD. The disease course was favorable, but 1 year later a similar neuroretinitis developed in the right eye. Extraocular features of BD became evident only at the time of the second eye involvement, and the patient received corticosteroid and immunosuppressive therapy. Swept source (SS) OCT showed at the acute phase in both eyes a typical "mushroom-shaped" prepapillary hyperreflectivity of the PIVE. SS OCT angiography (OCTA) demonstrated a corresponding prepapillary hypointense area due to shadowing effect, decreasing in size while scanning deeper layers. It also detected peripapillary retinal hypervascularity in both eyes and a sectoral area of flow signal loss in the first involved left eye. Visual acuity improved following the resolution of the PIVE and associated acute inflammatory changes in both eyes. The left eye showed residual optic disc pallor and retinal nerve fiber layer defects. CONCLUSION: Sequential bilateral neuroretinitis associated with PIVE may occur before other clinical features of BD become evident. SS OCT and OCTA can provide useful information for the diagnosis and management of this rare, but typical, ocular manifestation of BD uveitis.

Multimodal imaging in IRVAN syndrome presenting with Branch Retinal Artery Occlusion.

PURPOSE: To describe multimodal imaging findings in a patient with idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome presenting with branch retinal artery occlusion (BRAO). CASE DESCRIPTION: A 33-year-old woman presented with acute BRAO in the right eye. A diagnosis of underlying IRVAN syndrome was made based on the presence of arteriolar aneurysms on the optic disc and along major arterioles and faint retinal hard exudates in both eyes. Eight months later, best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. The hard exudates had increased, and there were extensive areas of peripheral retinal capillary nonperfusion without new vessels. Optical coherence tomography (OCT) showed a localized retinal thinning corresponding to the prior BRAO. Fundus autofluorescence showed nodulo-linear periarterial hypoautofluorescence. OCT angiography (OCTA) showed localized ischemic changes, mainly involving the deep capillary plexus, corresponding to the area of resolved BRAO. It also clearly delineated the optic disc aneurysms. The patient received bilateral scatter laser photocoagulation directed to areas of peripheral capillary nonperfusion. Over a 6-month follow-up period, visual acuity remained unchanged, and there was no evidence of disease progression. CONCLUSION: Multimodal imaging, including fundus autofluorescence, OCT, and OCTA can provide additional valuable information in the evaluation of IRVAN syndrome complicated with BRAO.

Acute lymphoblastic leukemia relapse presenting as retinal vasculitis.

Retinal vasculitis may occur as an isolated manifestation of acute lymphoblastic leukemia (ALL) relapse and precede central nervous involvement. Therefore, a high index of suspicion and repeated ocular and neurological evaluations are essential for early diagnosis and prompt appropriate treatment to save life and sight.

Choroidal metastasis as the initial presentation of lung adenocarcinoma: A case report.

Clinical reports of symptomatic choroidal metastasis as the initial presentation of lung cancer are rare. Here, we report such a presentation in a female patient of non small cell lung cancer. She presented with loss of vision in her left eye. On further analyses, the patient was diagnosed with a lung adenocarcinoma.

Update on Bartonella neuroretinitis.

PURPOSE: To review the clinical features, diagnosis, treatment modalities, and prognosis of Bartonella-associated neuroretinitis. METHODS: This is a narrative review on Bartonella-associated neuroretinitis including general and ophthalmological aspects of the disease. A comprehensive literature review between January 1950 and September 2018 was conducted in PubMed database. Epidemiology, clinical features, diagnosis, treatment, and prognosis of Bartonella neuroretinitis were reviewed. RESULTS: Cat scratch disease (CSD) is a worldwide distributed systemic infectious disease caused by a bacterium, Bartonella henselae (B. henselae) which is usually transmitted to humans through contact with infected cats. Ocular manifestations of CSD are diverse, with neuroretinitis and superficial retinal infiltrates being the most common and typical manifestations. Neuroretinitis typically presents as optic disc edema with a partial or complete macular star in association with mild vitritis. Macular star may be absent at the initial presentation, becoming evident 1-2 weeks after the onset of optic disc edema. Diagnosis of CSD is confirmed by reliable laboratory tests. Neuroretinitis usually has a self-limited course. Antibiotic therapy is required for severe systemic disease and vision-threatening ocular involvement. The adjunctive use of oral corticosteroids may further improve the visual outcome. CONCLUSIONS: The diagnosis of Bartonella-associated neuroretinitis is based on typical clinical findings and positive serology. The prognosis is usually favorable in immunocompetent individuals.

Carotid artery dissection following dental extraction revealed by ischaemic optic neuropathy.

AIM: To describe a case of posterior ischemic optic neuropathy (PION) revealing carotid arterial dissection occurring after ipsilateral tooth extraction. CASE REPORT: A 56-year-old patient referred for sudden loss of vision of the left eye (LE) since 3 weeks. Initial visual acuity was 10/10 in the right eye (RE) and limited to light perception in the LE. Ophthalmological examination was without abnormalities in the RE. A relative afferent pupillary defect was noted in the LE. Fundus examination of the LE revealed a papillary pallor, without excavation. Fluorescein angiography revealed no abnormalities in both eyes, including normal choroidal filling. The diagnosis of left PION was retained. A careful questioning of the patient revealed the history of tooth extraction under intra-oral local anesthesia one day before the vision loss. Investigational work up revealed a dissection of the left internal carotid artery. CONCLUSION: Dissection of the internal carotid artery is a rare but possible cause of PION. Ocular involvement may be the only manifestation. Clinicians should be aware of such manifestation especially in case of particular context of micro-trauma, such as dental procedures, and look for an underlying cause that may be potentially fatal.

Atypical white dot syndrome with choriocapillaris ischemia in a patient with latent tuberculosis.

BACKGROUND: White dot syndromes (WDS) are a group of idiopathic multifocal inflammatory conditions that can be recognized and distinguished by lesion morphology, other specific clinical features, imaging findings, and disease course. Our purpose is to describe an atypical case of WDS with choriocapillaris ischemia shown by multimodal imaging including swept-source OCT angiography (OCTA) in a 30-year-old woman with latent tuberculosis. FINDINGS: At presentation, visual acuity in the left eye was 20/500. Clinical findings included macular granularity, diffuse outer retinal discoloration with satellite yellow-white dots, and disc margin blurring. Fluorescein angiography showed early confluent areas of choroidal hypofluorescence and late perifoveal punctate hyperfluorescence. There was choroidal hypofluorescence in a geographic configuration throughout the indocyanine green angiography sequence. OCTA showed confluent geographic areas of loss of signal in the choriocapillaris. Work-up revealed latent tuberculosis. The patient received corticosteroids and prophylactic anti-tubercular treatment. Nine months later, visual acuity had improved to 20/20, and there were some residual retinal pigment epithelium changes. CONCLUSION: Atypical WDS associated with choriocapillaris hypoperfusion may show features of multiple evanescent white dot syndrome and acute posterior multifocal placoid pigment epitheliopathy melting together.

Acute multifocal retinitis: a retrospective review of 35 cases.

BACKGROUND: Acute multifocal retinitis is a rare condition that has been considered to be often idiopathic. The purpose of this study was to analyze clinical features and causes of acute multifocal retinitis. RESULTS: This study is a retrospective review of the charts of 35 patients with acute multifocal retinitis. Patients with three or more retinal lesions in at least one eye, with at least one lesion of less than 500 µm in size were included. All patients had complete ophthalmological examination, fundus photography, and fluorescein angiography. Twelve patients (34.3%) had optical coherence tomography. An extensive work-up was performed including a detailed comprehensive medical history, examination by an internist and an infectious disease specialist, a chest X-ray, Mantoux test, and laboratory tests for syphilis, human immunodeficiency virus, Bartonella, and Rickettsia. Of the 35 patients, 25 (71.4%) had bilateral involvement and 10 (28.6%) had unilateral involvement (total number of eyes: 60). Mean best-corrected visual acuity (BCVA) was 20/25 (range, 20/1000-20/20). Retinal lesions ranged from 3 to more than 20 in number in at least 1 eye, and from 150 to 1500 µm in size. Associated findings included mild anterior chamber inflammation in 5 eyes (8.3%), mild vitritis in 46 eyes (76.7%), optic disc swelling in 9 eyes (15%), macular star in 4 eyes (6.7%), exudative retinal detachment in 6 eyes (10%), and branch retinal artery occlusion in 6 eyes (10%). Acute multifocal retinitis was found to be caused by Rickettsia conorii infection in 20 patients (57.1%), Rickettsia typhi infection in 4 patients (11.4%), cat-scratch disease in 8 patients (22.9%), and syphilis in 1 patient (2.9%). It was idiopathic in two patients (5.7%). Retinal lesions resolved without scarring in 3 to 12 weeks in all but three eyes (5%), in which residual retinal pigment epithelial changes were noted. CONCLUSION: Rickettsial disease was the most common cause of acute multifocal retinitis. Other identified causes included cat-scratch disease and syphilis, and a very small subset of patients was diagnosed with idiopathic multifocal retinitis.

Bilateral acute angle-closure glaucoma following tramadol subcutaneous administration.

BACKGROUND: To report a case of bilateral acute angle closure-glaucoma following the use of subcutaneous Tramadol. CASE PRESENTATION: A 42-year-old healthy man with unremarkable past medical and ocular history, was admitted to the Orthopedic Department for surgical treatment of a bilateral open fracture of the femur following a road accident. Three hoursafterTramadolsubcutaneous injection, the patient complained of a bilateral acute painful visual loss with persistent vomiting. An ocular examination showed bilateral acute angle-closure-glaucoma. The patient was treated with topical anti-glaucoma therapy and intravenous Mannitol 20%.After resolution of ocular hypertension attack, NdYag laser peripheral iridotomy was performed on both eyes. After a follow-up period of 7 days visual acuity improved to 20/20 in both eyes and intraocular pressure returned to normal levels. CONCLUSIONS: This case highlights the risk of developing bilateral acute angle-closure glaucoma after Tramadol administration.

Multimodal imaging in a case of bilateral outer retinitis associated with mumps infection.

PURPOSE: To report the results of multimodal imaging of acute outer retinitis associated to mumps infection. METHODS: A patient with mumps-associated outer retinitis evaluated by color fundus photography, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography, fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA). RESULTS: We report a case of a 12-year-old boy who developed bilateral outer retinitis related to mumps. Ophthalmoscopy showed confluent areas of outer retinitis involving the posterior pole and the periphery with a centrifugal gyrate pattern. SD-OCT revealed a marked disorganization of the outer retinal layers with multiple highly reflective spicules. FA shows diffuse late hyperfluorescence with optic disk staining. ICGA shows macular and peripheral hyperfluorescent lesions with a geographical pattern in the late phases. The patient was treated with acyclovir and oral prednisone. Four weeks after presentation visual acuity remained unchanged, and retinal changes seen at the acute phase had resolved leading to extensive retinal atrophy and optic disk pallor. SD-OCT showed atrophy of the retinal pigment epithelial and outer retinal layers. FAF revealed scattered hyperautofluorescent lesions. Electrophysiology showed generalized retinal dysfunction. CONCLUSIONS: Mumps infection should be considered in the differential diagnosis of bilateral necrotizing outer retinitis in children and young adults. A multimodal imaging approach may help distinguish mumps-associated retinitis from other causes of viral retinitis and facilitate appropriate management.

Ocular involvement associated with varicella in adults.

BACKGROUND: Varicella is a common infectious disease primarily of childhood that is usually benign and self-limited. It is, however, increasingly seen in adults who are at a higher risk of severe infection. Ocular complications of varicella are relatively uncommon and have been rarely described in adults. We describe herein five adults who developed ocular involvement in association with primary varicella-zoster virus infection. FINDINGS: Ocular manifestations included acute anterior uveitis in four eyes, with associated stromal keratitis in one of them, epithelial ulcerative keratitis in the two eyes of one patient, and acute retinal necrosis in one eye. One patient with acute anterior uveitis was treated with topical steroids and cycloplegic agents. The four other patients received topical or systemic antiviral drugs, with subsequent resolution of acute ocular inflammatory disease. CONCLUSIONS: The spectrum of chickenpox-associated ocular complications in adults is wide. Early diagnosis and appropriate management are mandatory to improve visual outcome.