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.

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.

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.

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.

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.

The Collaborative Ocular Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis.

OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.

Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness.

Imaging-based Assessment of Choriocapillaris: A Comprehensive Review.

PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.

Hypotony in uveitis: an overview of medical and surgical management.

Hypotony is a well-recognised, sight-threatening complication of uveitis. It can also be the final common endpoint for a multitude of disease entities. Multiple mechanisms underlie hypotony, and meticulous clinical history alongside ocular phenotyping is necessary for choosing the best intervention and therapeutic management. In this narrative review, a comprehensive overview of medical and surgical treatment options for the management of non-surgically induced hypotony is provided. Management of ocular hypotony relies on the knowledge of the aetiology and mechanisms involved. An understanding of disease trajectory is vital to properly educate patients. Both anatomical and functional outcomes depend on the underlying pathophysiology and choice of treatment.

Ocular Toxoplasmosis.

INTRODUCTION: Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide, affecting individuals acrossdifferent age groups. The key to reducing vision loss includes prompt diagnosis and treatment. However, despite the prevalence of ocular toxoplasmosis, there has been little consensus regarding its pathophysiology,clinical features, diagnosis, and especially management. METHODS: The data sources were literature reviews, including Pub Med and Medline databases. Search terms included toxoplasmosis, retinitis, vasculitis, vitritis, uveitis alone or in combination with, serum, aqueous, vitreous eye, ocular and review. RESULTS: In this review paper, we have sought to provide an overview of the pathophysiology, epidemiology, and clinical features of the disease, both based on current literature and our own clinical experience. We have also discussed the use of serology, ocular fluid, and ophthalmic investigations that could further facilitate the diagnosis of ocular toxoplasmosis.Different management strategies have been reported worldwide, including newer approaches such as local therapy. CONCLUSION: A better understanding of critical aspects of ocular toxoplasmosis will hopefully lead to reduced morbidity, including blindness associated with this condition.

Subretinal abscess: causative pathogens, clinical features and management.

PURPOSE: To review the literature on endogenous subretinal abscess (SRA). METHODS: We searched in the literature for the terms 'subretinal abscess', 'chorio-retinal abscess' and 'choroidal abscess'. RESULTS: A total of 122 patients were identified, of whom 20 patients (22 eyes) had no identified systemic infective foci (group 1) and 102 (120 eyes) had systemic infective foci (group 2). The mean age for group 1 was 44.6 years (range 2 weeks-82 years) and for group 2 was 43.2 years (range 1-89 years). The responsible pathogen was identified in 90% and 95% of cases, respectively. In group 1 the most frequent causative agents were Aspergillus and Nocardia, while in group 2 were Nocardia, Mycobacterium Tuberculosis and Klebsiella. In both groups the most common symptoms were reduced vision (70% and 72.5%, respectively), pain (65% and 29.4%, respectively) and redness (35% and 17.6%, respectively). For group 1 there was no difference between mean initial and final visual acuity (1.7 logMAR, range 0-3 logMAR), while for group 2 mean initial and final visual acuities were 0.8 logMAR and 0.6 logMAR, respectively. Final visual acuity was significantly better in group 2 (p = 0.003). Anterior segment inflammation was seen in 77.3% of cases of group 1 and 66.7% of cases of group 2. In both groups the abscess most common locations were posterior pole (45.4% and 32.5%, respectively) and temporal periphery (13.6% and 13.3%, respectively). Clinical features included hemorrhages (76.5% and 76.3%, respectively) and subretinal fluid (75% in both groups). Diabetes mellitus (20% and 25.5%) and immunosuppressive drug intake (35% and 23.5%) were the main predisposing factors for SRA. Combination of systemic and intravitreal antibiotics/antifungals and vitrectomy was the main therapeutic strategy for both groups. Systemic treatment alone was used mainly for cases of tubercular etiology. The timing of vitrectomy differed between the two groups, as it more commonly followed the use of systemic and intravitreal antibiotics in the forms associated with systemic infective foci. Additional abscess drainage or intralesional antibiotics were performed in 23.8% of cases. CONCLUSION: At present no guideline exists for the treatment of subretinal abscess. Systemic broad-spectrum antibiotic treatment is of primary importance and should be used in all cases unless contraindicated. Combination of systemic and local treatment is the most frequently adopted strategy.

Ocular inflammatory events following COVID-19 vaccination: a multinational case series.

BACKGROUND: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine's immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. METHODS: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. RESULTS: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19-84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1-14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). CONCLUSION: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome.

Severe Hypotony-induced Intraocular Inflammation after Removal of Ripcord Suture from a Glaucoma Drainage Device in Uveitis Patient.

PURPOSE: To report a case of exuberant anterior chamber inflammation post partial removal of supramid® stent. METHODS: Case report. RESULTS: The sudden intraocular pressure drop induced by partial removal of ripcord suture from a glaucoma drainage device can result in blood-retinal and blood-aqueous barrier breakdown, inducing uveitis. CONCLUSIONS: Intensive inflammatory prophylaxis prior to maneuvers to reduce intraocular pressure may reduce the risk of severe intraocular inflammation in patients with a previous history of uveitis as a consequence of sudden hypotony.

Clinical Features and CD4+ T Cells Count in AIDS Patients with CMV Retinitis: Correlation with Mortality.

PURPOSE: To explore the all-cause mortality in patients with acquired immune deficiency syndrome (AIDS) and Cytomegalovirus (CMV) retinitis. METHODS: A retrospective cohort study of patients with CMV retinitis (CMVR) presented to a tertiary referral center in Singapore from January 1, 2004, through December 31, 2015. RESULTS: A total of 144 patients were studied (87 survived, 11 lost to follow up, 46 died). Patients with bilateral CMVR and six-month follow up CD4 + T cell count < 50 cells/mm3 have shorter time to mortality, compared to patients with CD4 + T cell count > 50 cells/mm3 (p < .001) and unilateral disease (p = .043). Baseline CD4 + T cell count, size and zone of initial primary retinitis lesions, recurrences of retinitis, and timing of combined antiretroviral therapy (cART) are not significantly associated with mortality. CONCLUSION: Bilateral ocular involvement and lack of immune recovery in patients with AIDS and CMVR are associated with shorter survival time.

Evaluation of fluocinolone acetonide 0.19 mg intravitreal implant in the management of birdshot retinochoroiditis.

PURPOSE: To report treatment outcomes and efficacy of the fluocinolone acetonide 0.19 mg intravitreal implant (Iluvien) in controlling retinal and choroidal inflammation in 11 patients with birdshot retinochoroiditis. METHODS: A single-centre, retrospective, interventional case series. The primary efficacy end point was improvement in vascular leakage on fluorescein angiography (FA), effect on cystoid macular oedema (CMO) and resolution of hypofluorescent lesions on indocyanine green angiography (ICGA); secondary measures were improvements on pattern and full-field electroretinogram (PERG; ERG) parameters. Safety outcome measures were intraocular elevation and cataractogenesis. RESULTS: Fifteen eyes received Iluvien implant with an average follow-up of 31 months (range 12-36 months). Prior to the implant, 5 (33.3%) eyes had received dexamethasone intravitreal implant 0.7 mg (Ozurdex). FA showed evidence of vascular leakage in all eyes at baseline. Between month 6 and 12, FA showed that 73.4% of eyes had no leakage, this increased to 84.6% by month 24. Three eyes in our study had CMO at baseline. 6 months after Iluvien implant, all eyes achieved complete CMO resolution. One year after insertion of the implant, the characteristic hypofluorescent lesions on ICGA were unchanged in all cases. There was baseline ERG evidence indicating a high incidence of peripheral cone system dysfunction and most showed PERG evidence of macular dysfunction. Retinal function improved and macular function improved or was stable in the majority following treatment. CONCLUSIONS: The results show the possible therapeutic effect of Iluvien in the management of Birdshot-related vascular leakage, CMO and retinal dysfunction. However, choroidal lesions seem to persist with no detectable response to treatment.

Diagnostic value of culture results from aqueous tap versus vitreous tap in cases of bacterial endophthalmitis.

OBJECTIVE: To investigate the concordance between aqueous and vitreous tap culture results among different types of bacterial endophthalmitis. METHODS AND ANALYSIS: This retrospective cohort analysis included all cases diagnosed with endophthalmitis at Moorfields Eye Hospital between January 2008 and March 2020. Aqueous and vitreous samples obtained simultaneously at presentation. Samples were evaluated for sensitivity, specificity, negative and positive predictive values. RESULTS: A total of 217 patients (217 eyes) were included in the study. Postsurgical endophthalmitis was the most common type of endophthalmitis and diagnosed in 35.9% of the cases. The rate of positive culture results was 32.2% from vitreous tap and 21.7% from aqueous tap. The culture yield through vitreous sampling was 15.7% when aqueous culture results were negative, and in 5.1%, the aqueous sample was positive when the vitreous tap results were negative. Considering the vitreous tap as the gold standard, aqueous sample culture results showed a statistically significant high specificity and positive predictive values in cases of postsurgical endophthalmitis, late-onset endophthalmitis associated with glaucoma procedures, postintravitreal injection and endophthalmitis associated with bacterial keratitis. Coagulase Negative Staphylococcus was the most common organism isolated from vitreous and aqueous samples. CONCLUSIONS: Even though the sensitivity and specificity of aqueous tap are low, our results show that in a few cases it identified important organisms, otherwise missed by vitreous sampling alone. Culture of vitreous sample remains the gold standard for isolation of pathogen in bacterial endophthalmitis, but aqueous samples should also be obtained as an adjunct for the diagnosis.