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.

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.

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.

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.

Hyperbaric Oxygen Therapy for Mumps-Associated Outer Retinitis with Frosted Branch Angiitis.

PURPOSE: To describe a case of outer retinitis with frosted branch angiitis associated with mumps infection treated with hyperbaric oxygen (HBO) therapy. METHODS: Observational case report. CASE REPORT: A four-year-old boy with bilateral blindness was diagnosed with necrotizing outer retinitis with frosted branch angiitis associated with serologically confirmed mumps virus infection. He was treated with HBO therapy. Visual acuity subsequently improved to 20/40 in the right eye and to 20/320 in the left eye. Sequential follow-up optical coherence tomography examinations showed progressive recovery of the outer retinal layers in the right eye. CONCLUSION: HBO therapy appears to be a feasible and safe treatment that might improve the anatomical and functional outcome in patients with mumps retinitis.

Is There a True Neuroretinitis in Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis (IRVAN) Syndrome ?

PURPOSE: To clarify whether a true neuroretinitis is part of  idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. METHODS: Critical literature review. RESULTS: Neuroretinitis has been considered as a prominent feature of IRVAN syndrome. It has been described as late diffuse optic  disc staining on fluorescein angiography. However, patients with IRVAN syndrome usually do not present with visual function alterations consistent with optic neuropathy or neuroretinitis. The typical stellate exudative maculopathy seen in IRVAN syndrome is primarily caused by leakage from retinal arteriolar aneurysms at or near the optic disc, and it could be misinterpreted as a feature of neuroretinitis. CONCLUSION: There is no clinical evidence of true neuroretinitis at any of the disease stages in patients with IRVAN syndrome. The acronym « IRVARE ¼ (Idiopathic Retinal Vasculitis, Aneurysms, and Retinal Exudates) is proposed to better characterize this syndrome.

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.

Corticosteroids Versus Cyclosporine for Subepithelial Infiltrates Secondary to Epidemic Keratoconjunctivitis: A Prospective Randomized Double-Blind Study.

PURPOSE: To compare efficiency and tolerance between topical 0.5% cyclosporine A (CSA) and fluorometholone (FML) for subepithelial infiltrates (SEI) complicating epidemic keratoconjunctivitis. METHODS: We conducted a prospective double-blind randomized study involving 72 eyes with SEI. Thirty-eight eyes were treated with topical FML (FML group) and 34 eyes with CSA 0.5% eye drops (CSA group). Treatment was considered successful in case of SEI reduction and visual acuity improvement. Tolerance was evaluated by Schirmer test value, burning on eye drops instillation, and conjunctival injection. RESULTS: Baseline characteristics of both groups were similar (P > 0.05). After 3 months of the regimen, resolution of SEI was 3 times more observed in the FML group than that in the CSA group (P = 0.026). After 6 months, resolution of SEI was observed in 70% of the FML group and in 47% of the CSA group (P = 0.068). The recurrence of SEI was almost twice higher in the FML group than that in the CSA group (16% vs. 9%). FML was better tolerated during the first 3 months: a higher Schirmer test value (P = 0.0003), less burning on instillation (P = 0.242), and less conjunctival injection (P = 0.003). For the rest of the follow-up period, the 2 groups were comparable in tolerance. No ocular hypertension was noted. CONCLUSIONS: Epidemic keratoconjunctivitis can evolve favorably under both FML and CSA. The effect of FML is faster and CSA is more durable with fewer recurrences. Both are safe therapeutic options for long-term control of SEI.

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.

Ocular Manifestations of West Nile Virus.

Ocular manifestations are a feature of West Nile virus infection. They mostly occur in association with severe neuroinvasive disease. Linear chorioretinitis is suggestive of the diagnosis and may raise diagnostic suspicion when associated with evocative systemic signs, and in an epidemic context. Various other less specific inflammatory ocular manifestations have been reported, including anterior uveitis, occlusive retinal vasculitis, optic neuritis, and diplopia. The pathophysiology of ocular disease remains unclear, but it reflects the neuroinvasiveness of the disease. Although ocular involvement most often resolves without visual sequelae, some patients may have permanent loss of vision, adding to the need for the development of a specific treatment and/or vaccines.

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.

Swept-source OCT findings in shaken baby syndrome: case report.

BACKGROUND: Our purpose was to document the swept source optical coherence tomography (SSOCT) findings in a patient with Shaken baby syndrome (SBS). CASE PRESENTATION: SSOCT was obtained without sedation in a six-month-old girl with bilateral multilayered retinal hemorrhages due to SBS. It documented vitreoretinal interface abnormalities, including internal limiting membrane (ILM) detachment with retinal traction, in association with other specific changes in the inner and outer retinal layers. Six weeks later, retinal hemorrhages had substantially resolved, and there was optic disc pallor. OCT showed ILM reattachment with release of retinal traction and the development of severe diffuse retinal atrophy involving the fovea. CONCLUSIONS: SS OCT can provide useful information in SBS, revealing a wide variety of vitreoretinal interface, inner, and outer retinal changes not detected by clinical examination. It also may have a prognostic value over follow-up.

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.

Post-fever retinitis - Newer concepts.

Post-fever retinitis (PFR) is an infectious or para-infectious uveitic entity caused by bacterial or viral agents and seen mainly in tropical countries. Systemic symptoms such as joint pain, skin rash are common during the febrile stage. On the basis of only clinical presentation, it is difficult to pin-point the exact etiology for PFR. Serological investigations, polymerase chain reaction, and knowledge of concurrent epidemics in the community may help to identify the etiological organism. Bacterial causes of PFR such as rickettsia and typhoid are treated with systemic antibiotics, with or without systemic steroid therapy, whereas PFR of viral causes such as chikungunya, dengue, West Nile virus, and Zika virus have no specific treatment and are managed with steroids. Nevertheless, many authors have advocated mere observation and the uveitis resolved with its natural course of the disease. In this article, we have discussed the clinical features, pathogenesis, investigations, and management of PFR.