Systemic and Ocular Manifestations of Arboviral Infections: A Review.

PURPOSE: To provide an overview of pre-selected emerging arboviruses (arthropod-borne viruses) that cause ocular inflammation in humans. METHODS: A comprehensive review of the literature published between 1997 and 2023 was conducted in PubMed database. We describe current insights into epidemiology, systemic and ocular manifestations, diagnosis, treatment, and prognosis of arboviral diseases including West Nile fever, Dengue fever, Chikungunya, Rift Valley fever, Zika, and Yellow fever. RESULTS: Arboviruses refer to a group of ribonucleic acid viruses transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. They mostly circulate in tropical and subtropical zones and pose important public health challenges worldwide because of rising incidence, expanding geographic range, and occurrence of prominent outbreaks as a result of climate change, travel, and globalization. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or non-specific, but they may include serious, potentially disabling or life-threatening complications. A wide spectrum of ophthalmic manifestations has been described including conjunctival involvement, anterior uveitis, intermediate uveitis, various forms of posterior uveitis, maculopathy, optic neuropathy, and other neuro-ophthalmic manifestations. Diagnosis of arboviral diseases is confirmed with either real time polymerase chain reaction or serology. Management involves supportive care as there are currently no specific antiviral drug options. Corticosteroids are often used for the treatment of associated ocular inflammation. Most patients have a good visual prognosis, but there may be permanent visual impairment due to ocular structural complications in some. Community-based integrated mosquito management programs and personal protection measures against mosquito bites are the best ways to prevent human infection and disease. CONCLUSION: Emerging arboviral diseases should be considered in the differential diagnosis of ocular inflammatory conditions in patients living in or returning from endemic regions. Early clinical consideration followed by confirmatory testing can limit or prevent unnecessary treatments for non-arboviral causes of ocular inflammation. Prevention of these infections is crucial.

SS OCT and OCT-A Findings in Convalescent Inactive Vogt-Koyanagi-Harada Disease.

PURPOSE: This study aimed to determine predictive factors for low final visual acuity in patients with inactive Vogt-Koyanagi-Harada (VKH) disease using Swept-source OCT and OCT-angiography (OCT-A). METHODS: We conducted a prospective longitudinal study, including 21 patients (42 eyes), who were followed up for the first 24 months after disease onset. Patients were included at the acute phase and subsequently treated. Sequential qualitative and quantitative changes in OCT and OCT-A were assessed. Analytical statistical methods were employed to determine predictive factors for final visual acuity. RESULTS: Structural alterations including focal parafoveal outer nuclear layer atrophy, ellipsoid zone disruption, interdigitation zone disruption, and irregular and thickened retinal pigment epithelium line were observed in 57.1% of eyes at month 3, with no significant improvement over time. The presence of flow voids at months 6, 12, and 24 was significantly associated with low final visual acuity. Serous retnal detachment at presentation emerged as an independent risk factor for structural changes detected by SS-OCT during the first 2 years of the disease. Optic disc edema was predictive factor for both structural SS-OCT and OCT-A changes. CONCLUSION: This study underscores the importance of monitoring flow voids to predict final visual acuity and highlights the impact of serous retinal detachment at presentation on structural changes in patients with inactive VKH disease.

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.

Heterozygous factor V Leiden mutation manifesting with combined central retinal vein occlusion, cilioretinal artery occlusion, branch retinal artery occlusion, and anterior ischaemic optic neuropathy: a case report.

BACKGROUND: Our purpose was to describe a patient who developed combined central retinal vein occlusion (CRVO), cilioretinal artery occlusion, branch retinal artery occlusion (BRAO), and anterior ischaemic optic neuropathy (AION) followed by CRVO in the second eye because of the heterozygous factor V Leiden (FVL) mutation. CASE PRESENTATION: A 39-year-old female with a history of recurrent pregnancy losses presented with acute blurred vision in the right eye (RE), with visual acuity limited to counting fingers. She was diagnosed with combined impending CRVO, cilioretinal artery occlusion, BRAO, and AION. The results of thrombophilia testing, not including the FVL mutation, were negative. Retinal atrophy with vascular attenuation and optic disc pallor developed after resolution of acute retinal findings. Nine months after initial presentation, the patient developed an impending CRVO in the left eye (LE), with a secondary progression to a complete CRVO causing a decrease in best corrected visual acuity (BCVA) to 20/40. The patient was determined to be heterozygous for the FVL mutation. She subsequently was treated with acenocoumarol. At the last follow-up visit, the BCVA was 20/400 in the RE and 20/20 in the LE, and there was a complete resolution of the acute CRVO findings in the LE. CONCLUSION: Our case shows that the heterozygous FVL mutation may manifest with combined retinal vascular occlusion involving multiple sites in both eyes. Early recognition of such an inherited thrombophilic disorder is important because it implies the need for long-term anticoagulative therapy to reduce the patient's risk of recurrent, sight-threatening and life-threatening thrombotic events.

Distinguishing swept-source optical coherence tomography findings in active toxoplasmic retinochoroiditis.

OBJECTIVE: To define the swept-source optical coherence tomography (SS-OCT) features which distinguish ocular toxoplasmosis (OT) from other forms of retinochoroiditis. METHODS: This is a prospective diagnostic study enrolling 43 eyes of 43 patients with active toxoplasmic (TOXO) retinochoroiditis matched to 54 eyes (54 lesions) with non-TOXO retinochoroiditis evaluated by structural SS-OCT. RESULTS: The finding of retinal hyper-reflective round deposits, sub-lesional choroidal thickening, and sub-lesional retinal pigment epithelium elevation were more likely to be found in TOXO lesions with a positive likelihood ratio of 45.2 (95% CI: 6.45-316.56), 23.86 (95% CI: 6.09-93.36), and 9.79 (95% CI: 4.22-22.7), respectively. The presence of each of these findings was associated with a high level for positive predictive value (PPV) (88.63-97.29), negative predictive value (NPV) (88.3-92.45), sensitivity (83.72-90.69), and specificity (90.74-98.14). Two-parameter model binary logistic regression suggested that sub-lesional retinal pigment epithelium elevation and sub-lesional choroidal thickening were significant predictors of the diagnosis of OT (Wald = 11.905, p < 0.001; Wald = 14.881, p < 0.001; respectively). By adding hyper-reflective round deposits along the posterior hyaloid or the retinal surface the model improved its performance with very good diagnostic accuracy with area under the curve (AUC) values of 0.96 (95% CI: 0.9-0.99) for two parameters model and 0.98 (95% CI: 0.93-0.99) for the three parameters model. CONCLUSIONS: Our results show that three OCT findings including retinal hyper-reflective round deposits, sub-lesional choroidal thickening, and sub-lesional retinal pigment epithelium elevation are more likely to occur in OT patients as compared with non-OT patients.

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.

Rickettsial disease: An underestimated cause of posterior uveitis.

Rickettsioses are worldwide distributed infectious disease caused by intracellular small Gram-negative bacteria transmitted to humans by the bite of contaminated arthropods, such as ticks. Systemic disease typically consists of a triad of high fever, headache, and skin rash. It usually has a self-limited course, but severe, life-threatening complications can sometimes occur. It may be clinically difficult to differentiate rickettsial diseases from other febrile illnesses. Rickettsial infection has been largely underestimated as a cause of infectious uveitis for long decades in the past. Conversely, recent data show that ocular involvement is much more common than previously thought, with retinitis, retinal vasculitis, and neuroretinitis being the most typical and frequent findings. Early clinical diagnosis of rickettsial disease, while awaiting laboratory test results, is essential for prompt initiation of appropriate antibiotic treatment to prevent systemic and ocular morbidity. The prevention remains the mainstay of rickettsial infection control.

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.

Hypopyon: Is-it Infective or Noninfective?

Hypopyon usually corresponds to the sedimentation of white blood cells, and it signifies severe intraocular inflammation. This key clinical sign may occur in association with a wide variety of infectious, inflammatory, and neoplastic conditions that may be sight- and, occasionally, life-threatening. A careful history and thorough clinical examination are the cornerstones for orienting the differential diagnosis, identifying the causative agent, and initiating prompt and appropriate treatment. This review outlines the clinical characteristics and management of hypopyon in relation with the underlying causative infectious or noninfectious ocular or systemic diseases.

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.

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.

Cytomegalovirus retinitis following corticosteroid overdose for Vogt-Koyanagi-Harada disease.

A 33-year-old patient was diagnosed with acute Vogt-Koyanagi-Harada (VKH) disease and was prescribed prednisolone (1 mg/kg/day) and azathioprine (2.5 mg/kg/day). She mistakenly took an excessively high dose (4 mg/kg/day) of prednisolone for 14 days. The erroneous dose of corticosteroids was progressively corrected. Several weeks after initial presentation, the patient developed a polymerase chain reaction-proven bilateral cytomegalovirus retinitis, with extensive occlusive arteritis in the right eye. Systemic immunosuppressive therapy was temporarily discontinued and viral retinitis was successfully managed with systemic and intravitreal ganciclovir. Corticosteroids were reintroduced to control recurrent VKH disease. Final visual acuity was 20/1000 in the right eye and 20/50 in the left eye.

Swept-Source Optical Coherence Tomography Angiography Shows Choriocapillaris Flow Reduction in Multiple Evanescent White Dot Syndrome.

PURPOSE: To report two cases of typical multiple evanescent white dot syndrome (MEWDS), in which swept-source optical coherence tomography angiography (SS-OCTA) revealed transient areas of flow deficit at the level of the choriocapillaris. METHODS: The SS-OCTA images of two female patients with typical MEWDS were analyzed at the onset of the disease and during follow-up. RESULTS: The patients were aged 24 and 25 years, respectively. Previous medical history was unremarkable in both cases. The diagnosis of MEWDS was made on the basis of typical clinical findings and results of fundus autofluorescence, fluorescein angiography, and optical coherence tomography. At presentation, SS-OCTA showed a few small hypointense areas of flow deficit at the level of the choriocapillaris in both cases. During follow-up, SS-OCTA showed complete resolution of choriocapillaris flow voids. CONCLUSION: Both our patients with typical acute MEWDS showed SS-OCTA multifocal small areas of flow reduction at the level of the choriocapillaris, with full recovery during the follow-up. This finding supports the hypothesis of transient, primary, or secondary choriocapillaris hypoperfusion in typical MEWDS.

Changing pattern of clinical manifestations of Behçet's disease in Tunisia: comparison between two decades.

OBJECTIVES: To investigate the changes over time in extraocular and ocular manifestations of Behçet's disease (BD) in Tunisian patients. MATERIAL AND METHODS: Retrospective study of 246 patients divided into two groups: group 1 (147 patients examined from 1995 to 2005) and group 2 (99 patients examined from 2006 to 2017). RESULTS: Active or scarred genital ulcers observed by physician at presentation were significantly less frequent in group 2 (47.2% vs. 29.6%; p = 0.007), as were articular involvement (50.3% vs. 34.7%; p = 0.016) and erythema nodosum (18.4% vs. 8.1%; p = 0.024). One hundred-seven patients (43.5%) developed ocular manifestations during the 23-year study period. Intermediate uveitis was significantly more frequent in group 2 than in group 1 (11.7% vs. 28.4%; p = 0.003), and posterior uveitis less frequent in group 2 than in group 1 (34.2% vs. 19.7%; p = 0.016). Patients from group 2 were more likely to have macular edema (19.8% vs. 45.6%; p = 0.001). However, better visual prognosis, with a lower rate of legal blindness, was noted in group 2. CONCLUSIONS: Changes over time included a decrease in the rate of articular involvement and cutaneous involvement. There was an increase in the rate of intermediate uveitis and a decrease in the rate of posterior uveitis over time. Despite an increase in the rate of macular edema, there was an improvement in visual prognosis, with less legal blindness over time.

Panuveitis revealing Melkersson Rosenthal syndrome: a case report.

AIM: To describe a case of panuveitis revealing Melkersson Rosenthal syndrome (MRS). CASE REPORT:   A 35-year-old female with a history of bilateral chronic idiopathic panuveitis was referred for work up. On examination, her visual acuity was 3/10 in the right eye and limited to hand motion in the left eye. Slit lamp examination revealed posterior synechiae and vitritis more severe in the left eye. Fundus examination showed bilateral vascular sheathing with no retinitis or choroiditis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. A careful questioning of the patient revealed the history of relapsing facial paralysis with palpebral edema. The work up ruled out an underlying infectious disease, especially ocular tuberculosis. Examination of the internist revealed a cheilitis and a fissured tongue. The diagnosis of MRS was made and the patient was treated with systemic corticosteroids and scatter laser treatment of retinal nonperfusion areas. CONCLUSION: MRS is a rare disorder. Ocular involvement, especially uveitis, is uncommon. Clinicians should be aware of this syndrome to avoid misdiagnosis and extensive work up.

Swept-source Optical Coherence Tomography Angiography Findings in Uveitic Cystoid Macular Edema.

Purpose: To describe swept-source optical coherence tomography angiography (OCTA) findings in uveitic cystoid macular edema (CME).Methods: Prospective study of 36 eyes.Results: Cystoid black spaces were shown in the deep capillary plexus (DCP) in 36 eyes (100%) and in the superficial capillary plexus (SCP) in 6 eyes (16.7%). Grayish areas of capillary non perfusion/hypoperfusion were seen in 69.4% of eyes in the DCP (vs 25% in the SCP, p < .001). The foveal avascular zone was larger than in the control healthy eyes in the DCP (p < .001). Capillary density was lower than in the control group in the SCP (p = .001) and the DCP (p < .001). Of 11 eyes with resolved CME on OCT, 4 eyes showed complete recovery of both plexuses on OCTA. There was a persistence of areas of capillary rarefaction in 4 eyes, and of hypoperfusion/nonperfusion in 3 eyes.Conclusion: OCTA visualizes perifoveal microvascular changes in uveitic CME.

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.