Infectious eye disease in the 21st century-an overview.

Infectious diseases affecting the eye often cause unilateral or asymmetric visual loss in children and people of working age. This group of conditions includes viral, bacterial, fungal and parasitic diseases, both common and rare presentations which, in aggregate, may account for a significant portion of the global visual burden. Diagnosis is frequently challenging even in specialist centres, and many disease presentations are highly regional. In an age of globalisation, an understanding of the various modes of transmission and the geographic distribution of infections can be instructive to clinicians. The impact of eye infections on global disability is currently not sufficiently captured in global prevalence studies on visual impairment and blindness, which focus on bilateral disease in the over-50s. Moreover, in many cases it is hard to differentiate between infectious and immune-mediated diseases. Since infectious eye diseases can be preventable and frequently affect younger people, we argue that in future prevalence studies they should be considered as a separate category, including estimates of disability-adjusted life years (DALY) as a measure of overall disease burden. Numbers of ocular infections are uniquely affected by outbreaks as well as endemic transmission, and their control frequently relies on collaborative partnerships that go well beyond the remit of ophthalmology, encompassing domains as various as vaccination, antibiotic development, individual healthcare, vector control, mass drug administration, food supplementation, environmental and food hygiene, epidemiological mapping, and many more. Moreover, the anticipated impacts of global warming, conflict, food poverty, urbanisation and environmental degradation are likely to magnify their importance. While remote telemedicine can be a useful aide in the diagnosis of these conditions in resource-poor areas, enhanced global reporting networks and artificial intelligence systems may ultimately be required for disease surveillance and monitoring.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care. METHODS AND ANALYSIS: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted. ETHICS AND DISSEMINATION: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available. TRIAL REGISTRATION: ISRCTN31474800. Registered 14 April 2020.

Ocular inflammatory events following COVID-19 vaccination: reporting of suspected adverse drug reactions to regulatory authorities in the UK.

BACKGROUND/AIMS: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published suspected adverse drug reactions to vaccines against COVID-19. Ocular inflammatory events following COVID-19 vaccination have been reported worldwide. METHODS: We analysed MHRA data on spontaneous reports of suspected ocular inflammatory events following COVID-19 vaccination between January 2021 and September 2022. RESULTS: The MHRA received 300 UK spontaneous suspected reports of ocular inflammatory events following COVID-19 vaccination, with a calculated prevalence of 6.6 events per 1 000 000 vaccinated individuals. Anterior uveitis was the most common phenotype (58.3%), followed by optic neuritis in 39.3%. Median number of days between vaccination and onset was 8 days. Resolution of the event was seen in 52.3%. CONCLUSION: Ocular inflammatory events following COVID-19 vaccination have a very rare prevalence in the UK. There is no increase in the reporting rate of uveitis, optic neuritis and scleritis following COVID-19 vaccination when compared with the range of incidence in the UK population. The Yellow Card System represents a vital instrument within the domain of pharmacovigilance, empowering patients and healthcare professionals to contribute to the ongoing monitoring of medication safety.

Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.

INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors. CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.

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.

Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis.

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).

Gains in the current understanding of managing neovascular AMD with brolucizumab.

BACKGROUND: Unresolved retinal fluid and high injection burden are major challenges for patients with neovascular age-related macular degeneration. Brolucizumab addresses these challenges by providing robust vision gains and superior fluid resolution, with the potential for longer treatment intervals. Brolucizumab has been associated with adverse events of retinal vasculitis and retinal vascular occlusion typically in the presence of intraocular inflammation (IOI). To define the incidence of the adverse events, Novartis convened an external safety review committee, which found a rate of 4.6% for definite or probable IOI, 3.3% for retinal vasculitis, and 2.1% for retinal vascular occlusion in the HAWK and HARRIER trials. Novartis also established a coalition to explore 4 areas regarding the adverse events: root cause, patient characterization, event mitigation and vigilance, and treatment protocols for the adverse events. Based on the coalition findings, a risk mitigation framework was developed. Prior to initiating treatment with brolucizumab, it is important to weigh the potential benefit against risk of adverse events and to consider patient risk factors such as prior history of IOI and/or retinal vascular occlusion. To mitigate the potential for IOI-related adverse events, it is important to conduct a thorough dilated eye examination before each injection and closely monitor patients throughout treatment. Patients should be educated on symptoms of IOI to monitor for. Brolucizumab should not be injected in the presence of active IOI. If an adverse event is identified, prompt and intensive treatment should be considered. CONCLUSION: Progress has been made in understanding how to mitigate IOI-related adverse events following treatment with brolucizumab.

Ocular sarcoidosis in adults and children: update on clinical manifestation and diagnosis.

Sarcoidosis-associated uveitis, is the predominant ocular sarcoidosis presentation, which affects both adults and children. For adults, international ocular sarcoidosis criteria (IWOS) and sarcoidosis-associated uveitis criteria (SUN) are defined. However, for children they are not yet established internationally. Due to the specificity of pediatric manifestations of sarcoidosis, this task is even more challenging. In children, sarcoidosis is subdivided into Blau syndrome and early-onset sarcoidosis (BS/EOS) affecting younger children (< 5 years) and the one affecting older children with clinical presentation resembling adults. Differential diagnosis, clinical work-up as well as diagnostic criteria should be adapted to each age group. In this article, we review the clinical manifestation of sarcoidosis-associated uveitis in adults and children and the sensitivity and specificity of various ocular sarcoidosis diagnostic modalities, including chest X-ray and CT, FDG PET-CT, gallium-67 scintigraphy, bronchoalveolar lavage fluid, genetic testing for NOD2 mutations and serum biomarkers, such as ACE, lysozyme and IL2R.

Cytomegalovirus anterior uveitis and occlusive retinal vasculitis without retinitis in a patient on immunomodulatory therapy.

PURPOSE: To describe unusual clinical features and therapeutic management of a case of cytomegalovirus (CMV) ocular disease in a patient on immunomodulatory therapy. SETTING/VENUE: Moorfields Eye Hospital NHS Foundation Trust, London, UK. METHODS: Medical history, clinical findings, investigation results, and multimodal imaging were retrospectively collected. RESULTS: A 61-year-old, South-East Asian man, developed CMV-related endotheliitis and occlusive retinal vasculitis, diagnosed by wide-angle fluorescein angiography. No retinitis was present on the fundus examination. Suspicion of CMV etiology was based on anterior segment findings, especially the presence of coin-shaped endothelial lesions. The diagnosis was confirmed by aqueous polymerase chain reaction (PCR) analysis which was positive for CMV DNA. The combined use of topical and systemic valganciclovir resulted in significant improvement of the picture. CONCLUSIONS: CMV can manifest in the eye as occlusive retinal vasculitis without the presence of typical retinitis.

Ocular Inflammatory Events Following COVID-19 Vaccination in the Paediatric Population: A Multinational Case Series.

BACKGROUND: Ocular inflammatory events following COVID-19 vaccination have been reported in the adult population. METHODS: Multinational case series of patients under the age of 18 diagnosed with ocular inflammatory events within 28 days of COVID-19 vaccination. RESULTS: Twenty individuals were included. The most common event was anterior uveitis (n = 8, 40.0%), followed by intermediate uveitis (7 patients, 35%), panuveitis (4 patients, 20%), and posterior uveitis (1 patient, 5%). The event was noticed in the first week after vaccination in 11 patients (55.0%). Twelve patients (60.0%) had a previous history of intraocular inflammatory event. Patients were managed with topical corticosteroids (n = 19, 95.0%), oral corticosteroids (n = 10, 50.0%), or increased dose of immunosuppressive treatment (n = 6, 30.0%). Thirteen patients (65.0%) had a complete resolution of the ocular event without complications. All patients had a final visual acuity unaffected or less than three lines of loss. CONCLUSION: Ocular inflammatory events may happen in the paediatric population following COVID-19 vaccination. Most events were successfully treated, and all showed a good visual outcome.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.

Fundus topographical distribution patterns of ocular toxoplasmosis.

BACKGROUND: To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. METHODS: In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. RESULTS: 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. CONCLUSION: The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease.

The role of a multicentre data repository in ocular inflammation: The Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS).

In the current literature, clinical registry cohorts related to ocular inflammation are few and far between, and there are none involving multi-continental international data. Many existing registries comprise administrative databases, data related to specific uveitic diseases, or are designed to address a particular clinical problem. The existing data, although useful and serving their intended purposes, are segmented and may not be sufficiently robust to design prognostication tools or draw epidemiological conclusions in the field of uveitis and ocular inflammation. To solve this, we have developed the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) Clinical Registry. OASIS collects prospective and retrospective data on patients with all types of ocular inflammatory conditions from centers all around the world. It is a primarily web-based platform with alternative offline modes of access. A comprehensive set of clinical data ranging from demographics, past medical history, clinical presentation, working diagnosis to visual outcomes are collected over a range of time points. Additionally, clinical images such as optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography studies may be uploaded. Through the capturing of diverse, well-structured, and clinically meaningful data in a simplified and consistent fashion, OASIS will deliver a comprehensive and well organized data set ripe for data analysis. The applications of the registry are numerous, and include performing epidemiological analysis, monitoring drug side effects, and studying treatment safety efficacy. Furthermore, the data compiled in OASIS will be used to develop new classification and diagnostic systems, as well as treatment and prognostication guidelines for uveitis.

Choroidal Involvement in a Case of Viral Retinitis.

PURPOSE: To describe a challenging case of acute retinal necrosis. METHODS: Clinical data, including medical history, clinical findings and imaging features were retrospectively collected in a 28-year-old female with unilateral active retinitis. RESULTS: The yellowish area of retinitis surrounding a pigmented chorioretinal scar and the full thickness retinal hyper-reflectivity associated with diffuse increase in choroidal demonstrated a challenging case of necrotising retinitis, where baseline clinical and tomographic features were atypical and misleading towards a toxoplasmic aetiology. The detection of virus genome in ocular samples was necessary to achieve a correct diagnosis of acute retinal necrosis. CONCLUSION: Although rare, choroidal involvement may occur in acute retinal necrosis along with the well-known retinal features.

Glaucoma Drainage Device Surgery Outcomes in Children With Uveitic Glaucoma.

PURPOSE: To evaluate outcomes of glaucoma drainage device (GDD) implantation children with uveitic glaucoma. DESIGN: Retrospective interventional case series. METHODS: Success was defined as intraocular pressure (IOP) ≥5 and ≤21 mm Hg. Failure was defined at final follow-up when the IOP was outside the success criterion, and visual function was no perception of light or if further glaucoma surgery (excluding removal of intraluminal stent suture or needling) was required. RESULTS: Fifty eyes of 36 children with uveitic glaucoma underwent GDD implantation. Mean age at surgery was 10.1±3.1 years (range 5-17) with a mean follow-up of 113±61 months (range 8-228). Mean cumulative probabilities of success (95% CI) were 0.98 (0.86-1.00) at 1 year, 0.87 (0.73-0.94) at 5 years, and 0.59 (0.32-0.78) at 15 years. Fourteen tubes were classified as failed, with 12 due to uncontrolled IOP (11 eyes required a second GDD); 1 eye, removal of the tube due to plate exposure; and 1 eye, lost light perception. Postoperative complications occurred in 36% of patients and included hypotony (22%), tube exposure (6%), tube obstruction (4%), corneal decompensation (2%), and cystoid macular edema (2%). Visual acuity remained stable (preoperation 0.35±0.42 vs postoperation 0.45±0.67, P = .49). IOP was significantly reduced from 31.4±7.5 mm Hg to 14.4±5.1 mm Hg (P < .0001) as were the number of glaucoma medications 3.5±1.0 vs 1.1±1.3 (P < .0001). CONCLUSIONS: Refractory pediatric uveitic glaucoma can be treated successfully by GDD implantation. Further interventions to manage consequences of glaucoma or the underlying disease are common, and visual function is maintained in the majority of cases.

Hellp syndrome-related hypertensive chorioretinopathy: A multimodal imaging and optical coherence tomography angiography (OCTA) study.

INTRODUCTION: Pregnancy may be associated to unique retinal disorders and is associated to worsening of retinal disease that also occurs in non-pregnant females. We report a case of chorioretinopathy caused by pre-eclampsia associated to HELLP (Hemolysis-Elevated-Liver enzymes and Low Platelet count) syndrome. METHODS: Multimodal Imaging features of HELLP syndrome-related hypertensive chorioretinopathy including retinography, Spectral Domain-Optical Coherence Tomography (SD-OCT), Fluorescein angiography (FA), Indocyanine-green angiography (ICG) along with OCT-angiography (OCTA) are presented and discussed. RESULTS: Multimodal imaging and OCTA show both retinal and choroidal involvement by HELLP syndrome, resolved after hypertension treatment. CONCLUSIONS: Multimodal imaging is useful to study HELLP syndrome-related hypertensive chorioretinopathy. Moreover, OCTA is a new technology able to study and follow the circulatory status of the choriocapillaris during the disease.

Resolution of Isolated Subretinal Abscess with Systemic Antibiotic Treatment.

PURPOSE: To describe clinical features and therapeutic management of a case of isolated subretinal abscess (SRA) in an immunocompetent male patient with no predisposing conditions or risk factors. METHODS: Clinical data, including medical history, clinical findings and results of systemic investigations, were retrospectively collected in a 40-year-old man diagnosed with unilateral focal SRA. RESULTS: Systemic investigations did not reveal any extraocular infective focus. Prompt diagnosis of SRA and aggressive systemic antibiotic treatment averted breakthrough into the vitreous cavity and led to clinical resolution with preservation of visual acuity. No local recurrences or distal spread of the infection were found at follow-up. CONCLUSIONS: In isolated SRA, timely systemic antibiotic treatment can lead to an excellent clinical outcome. Close monitoring is essential to prevent potential progression of SRA to a sight-threatening endophthalmitis, which would prompt an urgent shift in the therapeutic approach.