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.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

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.

Pediatric Pars Planitis: A Review.

PURPOSE: To provide an overview of pediatric pars planitis. METHODS: Narrative literature review. RESULTS: Pars planitis refers to the idiopathic subset of intermediate uveitis in which there is vitritis along with snowball or snowbank formation occurring in the absence of an associated infection or systemic disease. It is thought to be a T-cell mediated disease with a genetic predisposition. Pars planitis accounts for 5-26.7% of pediatric uveitis cases. Presentation is commonly bilateral but asymmetric, often with insidious onset of floaters and blurred vision. Although pars planitis is known to be a benign form of uveitis in most cases, severe complications secondary to chronic inflammation may arise, with cystoid macular edema being the most common cause of visual morbidity. Mild vitritis in the absence of symptoms, vision loss, or macular edema may be observed. Patients with severe vitritis and/or associated vision-threatening complications require prompt aggressive treatment. A stepladder approach including corticosteroids, immunosuppressive agents, anti­tumor necrosis factor­alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. CONCLUSION: Timely diagnosis and adequate treatment of pediatric pars planitis and associated complications are crucial in order to improve visual outcomes.

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 Review of Human Ocular RNA Virus Infections Excluding Coronavirus, Human T-Cell Lymphotropic Virus, and Arboviruses.

We provide an updated review of pre-selected RNA viruses causing ocular inflammation in humans. RNA viruses such as coronaviruses and arboviruses are reviewed elsewhere. A Google Scholar search was conducted to identify recent publications on ocular inflammation caused by the RNA viruses specified here. Human RNA viruses target a wide range of ocular tissues from the anterior to the posterior. Influenza, measles and mumps cause anterior segment manifestations including conjunctivitis and keratitis, while retinitis and optic neuritis may be seen posteriorly. Newcastle disease and RSV cause conjunctivitis, whereas HIV causes characteristic anterior uveitis. Cataracts, microphthalmos, and iris abnormalities are common in congenital Rubella, while Rubella virus is associated with Fuchs uveitis syndrome. Newer technologies make it possible to detect more than one pathogen if present simultaneously. RNA viruses may produce significant ocular morbidity, and care should be taken to investigate ocular symptoms during disease outbreaks.

Posterior Herpetic Uveitis: A Comprehensive Review.

PURPOSE: To report and illustrate the main clinical presentations of posterior herpetic uveitis. METHODS: Narrative review. RESULTS: The ocular manifestations of posterior herpetic uveitis include different clinical presentations. Herpes simplex and varicella zoster can cause acute retinal necrosis, progressive outer retinal necrosis, and non-necrotizing herpetic retinopathies. Cytomegalovirus has been associated with fulminant retinitis with confluent areas of retinal necrosis and retinal hemorrhages, indolent/granular retinitis, and frosted branch angiitis. These diverse clinical presentations are often associated with specific risk factors and different immunological profiles of the host. CONCLUSIONS: Herpetic viruses can cause posterior uveitis, presenting various clinical findings. Specific ocular manifestations and the immunological status of the host can help to differentiate the various herpetic entities before laboratory tests confirm the diagnosis.

Optical Coherence Tomography and Optical Coherence Tomography Angiography in Neglected Diseases.

A group of self-limiting and frequently neglected diseases exist in the literature like Rickettsial disease, Malaria, Dengue fever, Chikungunya, West Nile virus infection, Rift Valley fever, Bartonellosis, or Lyme disease which are poorly understood due to lack of proper diagnostic testing. Currently, multimodal imaging has become a critical modality in the diagnosis and management of ocular diseases. Optical coherence tomography (OCT) is one such remarkable imaging modality in the field of ophthalmology providing high-resolution, cross-sectional images of the retina and choroid with the recent advances such as enhanced depth imaging and swept source OCT. Additionally, OCT angiography (OCTA) has further revolutionised dynamic imaging of retinal and choroidal vasculature non-invasively. This review article highlights the OCT and OCTA biomarkers in the diagnosis and prognosis of the aforementioned neglected diseases.

Long-Term Results of Combined Trabeculotomy Trabeculectomy in Primary Congenital Glaucoma.

PRCIS: Primary congenital glaucoma (PCG) in Tunisian children seems to be characterized by a high prevalence of inherited and advanced forms of the disease. Primary combined trabeculotomy trabeculectomy (CTT) allowed satisfactory long-term intraocular pressure (IOP) control and reasonable visual outcome. PURPOSE: To report the long-term outcome of CTT as the initial glaucoma surgery in children with PCG. METHODS: Retrospective analysis of children who underwent primary CTT for PCG between January 2010 and December 2019. The main outcome measures were IOP reduction, corneal clarity, complications, refractive errors, and visual acuity (VA). Success was defined as IOP <16 mm Hg without (complete) or with (qualified) antiglaucoma medication. The WHO criteria of vision loss were used to categorize visual impairment (VI). RESULTS: Of 62 patients, 98 eyes were enrolled. At the last follow-up, the mean IOP was reduced from 22.7 ± 4.0 mm Hg to 9.7 ± 3.9 mm Hg ( P < 0.0001). The complete success rate was 91.6%, 88.4%, 84.7%, 71.6%, 59.7%, and 54.3%, at the first, second, fourth, sixth, eighth, and tenth year, respectively. Follow-up averaged 42.1 ± 28.4 months. Preoperatively, 72 eyes (73.5%) had significant corneal edema versus 11 eyes (11.2%) at the end of the follow-up ( P < 0.0001). Endophthalmitis was encountered in one eye. Myopia was the most common refractive error (80.6%). Data on Snellen VA were available for 53.2% of the patients; 33.3% achieved a VA ≥6/12, 21.2% had mild VI, 9.1% had moderate VI, 21.2% had severe VI, and 15.2% were blind. The failure rate was statistically correlated to the early disease onset (<3 mo) and to preoperative corneal edema ( P = 0.022 and P = 0.037, respectively). CONCLUSION: Primary CTT seems to be a good procedure in a population with advanced PCG at presentation, problematic follow-up visits, and limited resources.

Comments on "Goyal M, Murthy SI and Annum S, Bilateral Multifocal Choroiditis following COVID-19 Vaccination".

The fundus photographs provided show deep yellowish lesions, multifocal exudative retinal detachments, and optic disc hyperemia in both eyes. Spectral domain optical coherence tomography scans shown demonstrate bilateral exudative retinal detachments involving the macula in the right eye. The exudative retinal detachment is characterized by the presence of subretinal fibrin and septa. The B-scan ultrasonography provided shows low- to medium-reflective choroidal thickening predominating around optic nerve head, in association with exudative retinal detachment in the right eye. All these findings are highly suggestive of acute Vogt-Koyanagi-Harada (VKH) disease rather than multifocal choroiditis.

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.

Consensus-based recommendations for optical coherence tomography angiography reporting in uveitis.

BACKGROUND/AIMS: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis. METHODS: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%. RESULTS: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'. CONCLUSIONS: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.

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.

Clinical Features and Outcomes of Congenital Cataract Surgery with Primary Intraocular Lens Implantation in a Tunisian Cohort.

Purpose: To describe the clinical features of congenital cataract (CC) in a Tunisian cohort and to assess the surgical outcomes of primary intraocular lens implantation in two groups based on the age at surgery. Methods: This study was a prospective analysis of children under 5 years with CC that were operated between January 2015 and 2020. The surgery consisted of phacoaspiration with posterior capsulorhexis and primary implantation. Group 1 comprised children operated at <2 years of age and Group 2 comprised children operated between 2 and 5 years. Peri and postoperative surgical events as well as refractive and visual outcomes were compared between both the groups. Results: Fifty-five (84 eyes) infants were enrolled. Group 1 included 30 (48 eyes) children and Group 2 included 25 (36 eyes) patients. The mean follow-up was 27.60 ± 19.89 months. The mean delay between the diagnosis and the cataract surgery was 11.97 ± 13.84 months. Of 14 (16.7%) eyes with postoperative visual axis opacification (VAO), 9 (10.7%) eyes required pars plana membranectomy. The VAO was not statistically associated with the age at surgery (P = 0.112), but significantly correlated with sulcus implantation (P = 0.037). The final mean visual acuity was 0.51 logMAR and comparable between both the groups (P = 0.871). Poor visual outcome was significantly associated with low age at presentation (<6 months; P = 0.039), delay between the diagnosis and time of surgery (P = 0.001), preoperative nystagmus (P = 0.02), and poor parental compliance to amblyopia treatment (P = 0.009). Conclusions: Primary implantation seems to be safe and efficient. VAO appears to become an avoidable occurrence owing to better surgical techniques. Amblyopia remains the biggest barrier to final visual outcome.

Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis.

OBJECTIVE: To report acute multifocal retinitis in association with serologically-proven Coxiella (C) Burnetii infection (Q fever) with endocarditis. MATERIAL AND METHODS: A single case report documented with multimodal imaging. RESULTS: A 67-year-old cattle breeder presented with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20, and there was 1+ vitreous cells in both eyes. Bilateral fundus examination showed multiple small superficial white retinal lesions scattered in the posterior pole and midperiphery associated with a few retinal hemorrhages. These retinal lesions did not stain on fluorescein angiography (FA) and showed focal hyperreflectivity and thickening primarily involving the inner retinal layers on optical coherence tomography (OCT). There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy. Transthoracic echocardiogram (TTE) showed a mobile echodensity on the anterior aortic leaflet consistent with a diagnosis of endocarditis. Elisa assays performed on paired serum samples collected 2 weeks apart showed increase in antibodies against C burnetii from 60 IU/ml to 255 IU/ml. The patient was treated with doxycycline 100 mg twice a day for 18 months, with subsequent resolution of the endocarditis. Sequential ocular examinations showed gradual resolution of all acute retinal findings without visible scars. CONCLUSION: Acute Q fever, caused by C burnetii infection, should be considered in the differential diagnosis of acute multifocal retinitis. A systematic cardiac assessment with echocardiography is essential for early diagnosis of associated endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes.

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.