Multiple ocular manifestations in a patient diagnosed with herpes zoster ophthalmicus: case report.

Objective: Our purpose was to present a case of a patient diagnosed with herpes zoster ophthalmicus with multiple ocular manifestations. Case presentation: A 70-year-old Caucasian male presented to the hospital for headache and skin hyperesthesia on the scalp and forehead on the left side. The diagnoses of herpes zoster ophthalmicus and acute conjunctivitis were made for the left eye. The patient was followed up for 6 months and during that period the following diagnoses were made for the same eye: peripheral sterile corneal infiltrates, episcleritis, and hypertensive anterior uveitis. Discussions: Herpes zoster ophthalmicus occurs when the reactivation of the dormant virus involves the ophthalmic division of the trigeminal nerve. The most frequent ocular presentations are conjunctivitis, keratitis, uveitis, episcleritis, and scleritis. The standard therapy consists of antivirals, such as acyclovir, valacyclovir, and famciclovir to limit the replication of the virus. The patient's risk factors, the course of treatment, and the severity of the disease, all affect the prognosis, which is highly variable. Prevention of the disease consists of vaccination with one of the following two vaccines, Zostavax and Shingrix. Conclusions: Final visual acuity for the left eye remained 1 despite numerous manifestations of the disease. Abbreviations: VZV = Varicella-zoster virus, BCVA = best-corrected visual acuity, OU = both eyes, OD = right eye, OS = left eye, IOP = intraocular pressure, NCT = non-contact tonometer, ZVX = Zostavax vaccine.

Serum Biomarkers of Vascular Involvement in Childhood Uveitis.

Purpose: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. Methods: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. Results: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. Conclusions: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. Translational Relevance: Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.

Postoperative Inflammation After Anterior Segment Surgery.

A 71-year-old woman had 2 months of worsening vision and pain in her right eye. Examination revealed retrocorneal plaque, peaking of the pupil, and temporal prominent scleral vessels with inferotemporal scleral thinning. What would you do next?

Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study.

BACKGROUNDS: Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). OBJECTIVES: The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period. METHODS: In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis. RESULTS: Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU. CONCLUSIONS: AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.

Establishing the Normative Data Set Necessary for Imaging-Based Childhood Uveitis Surveillance: A Cross-Sectional Study.

Purpose: Anterior segment optical coherence tomography (AS-OCT) is an emerging diagnostic and monitoring tool for anterior uveitis. We investigated AS-OCT findings in the eyes of a large, diverse population of children free of uveitis to establish its potential to "rule out" accurately those without disease. Methods: In this cross-sectional observational study, image acquisition was performed with swept source AS-OCT (Heidelberg Anterion), using a protocol of 13 B-scans per volume, from 217 children (434 eyes) aged 5 to 15 years, with analysis of acquired images (identification of apparent inflammatory cells, or "cell events") by multiple graders. Outcomes of interest were median and maximum cell event count (MEDCC, MAXCC) per B-scan from each eye and the total cell event count (TCC) per volume scan. Results: At least one cell event was detected in volume scans of 76% of eyes (329/434) and 87% of children (189/217). The maximum number (MAXCC) per scan ranged from 0 to 6 (median, 2). There was a strong positive association between increasing age (years) and the number of cell events detected within a volume scan following adjustment for gender and iris color (adjusted regression coefficient for TCC 0.5; P < 0.0001; 95% confidence interval, 0.4-0.7). Conclusions: Our findings demonstrate that apparent inflammatory cells are detectable on AS-OCT in the apparently healthy eyes of children and furthermore suggest early life developmental changes in blood-iris barrier stability that merit further exploration. We provide the foundation for the normative data set necessary for establishing the clinical utility of AS-OCT for surveillance of children with inflammatory eye diseases.

The Presence of Pigmentation on Central Anterior Lens Capsule in the Human Leukocyte Antigen B27-Associated Anterior Uveitis and Its Value in Clinical Diagnosis.

PURPOSE: To report on the value of presence of pigmentation on central anterior lens capsule (PioLe) in HLA B27- associated anterior uveitis (HLA B27-AU). METHODS: 268 patients (320 eyes) with AU were reviewed. Two diagnostic models to predict probability of HLA-B27-AU were developed. The first model included 6 variables (age, gender, unilaterality, presence of non-granulomatous keratic precipitates, hypopyon, and intraocular pressure (IOP). The second model was developed to investigate the added value of PioLe into the first model. RESULTS:      Unilaterality, presence of hypopyon, IOP <21 mmHg and PioLe were characteristic for HLA-B27 positive patients (P≤0.003 for all). All of 6 variables had area under receiver operating characteristic curves (AuROC) ≤ 60, but PioLe reached even higher value (65.5). Diagnostic model I and II had AuROC 76.3% (95%CI, 68.4%-84.2%) and 80.0% (95%CI, 72.6%-87.5%), respectively. CONCLUSIONS: Unilaterality, hypopyon, IOP <21 mmHg and presence of PioLe are clinical signs suggesting HLA B27- AU.

Monkeypox Infection Causing Conjunctival Vesicles and Anterior Uveitis.

Human monkeypox is a zoonosis caused by an orthopoxvirus and the clinical presentation resembles that of smallpox and chickenpox. The disease may start with a prodrome that includes lymphadenopathy, headache, fatigue, and fever, followed by a vesiculo-pustular rash. Ocular manifestations such as conjunctivitis and edema are present in approximately 20% of affected people, with a greater incidence among unvaccinated patients. Corneal involvement has also been reported and can result in corneal scarring and severe forms of keratitis. The natural course of the disease is most often benign and self-limiting, however, in some individuals, especially immunocompromised patients, there is a risk of complications such as bronchopneumonia, encephalitis, and vision loss. Herein, we present a case of a patient with monkeypox which caused conjunctival vesicles and anterior uveitis.

Diagnosis, Treatment, and Prevention of Noninfectious Acute Anterior Uveitis with or without Human Leukocyte Antigen B27 in Adults - Expert Consensus in Taiwan.

BACKGROUND: Anterior uveitis is the most common anatomical type of uveitis. Patients with noninfectious anterior uveitis may develop various ocular complications and eventually visual impairment. Appropriately differentiating the etiologies can help clinicians to predict the outcome, arrange clinical follow-up, and decide the treatment or prevention strategy. Adequate treatment and effective prevention strategies can reduce the frequency of recurrence and the risk of developing complications. Human leukocyte antigen (HLA)-B27 is the most common positive finding in patients with noninfectious AAU in many countries including Taiwan. PURPOSE: To report a consensus from experienced uveitis specialists and rheumatologists was made in Taiwan. METHODS: A panel of nine ophthalmologists from nine different referral centers with expertise in the management of uveitis and an experienced rheumatologist was held on January 16, 2022. A comprehensive literature review was performed. Differential diagnoses for etiologies, general treatments, and prevention strategies were discussed. Each statement in the consensus was made only if more than 70% of the experts agreed. RESULTS: A flow chart and seven statements regarding the differential diagnoses for etiologies, treatments and preventions, and co-management with rheumatologists were included in the consensus. CONCLUSIONS: This article discusses the general diagnosis, treatment, and prevention of noninfectious acute anterior uveitis, with or without HLA-B27, in adults for general ophthalmologists to improve overall outcomes of these patients.

Wide-Field Fluorescein Angiography in Patients with Idiopathic Acute Anterior Uveitis.

PURPOSE: To elucidate whether wide-field fluorescein angiography (WFFA) can yield additional information in patients with newly diagnosed idiopathic acute anterior uveitis (AAU). METHODS: The WFFA was performed in patients with idiopathic AAU, and the findings were analyzed according to the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Forty-four eyes of 30 patients (22 eyes of 13 patients in the pediatric group and 22 eyes of 17 patients in the adult group) were studied. The mean age was 12.41 ± 3.92 (range, 5-18) years in the pediatric group and 42.36 ± 32.07 (range, 24-68) years in the adult group. Thirteen eyes (59%) of pediatric patients and 12 eyes (54%) of adult patients showed some evidence of posterior segment activity on the WFFA (p = .764).     Systemic treatment was administered in 53.8% of the pediatric and 5.9% of adult patients, depending on the disease severity. CONCLUSION: Pediatric patients with idiopathic AAU may have subtle posterior segment manifestations more than adult patients, and posterior segment findings may affect the treatment preferences of physicians.

Comment on "Monkeypox Infection Causing Conjunctival Vesicles and Anterior Uveitis" - A Concern on Possible Co-Infection.

This correspondence discusses on the monkeypox infection and conjunjunctival problem with uveitis. The other possible causes of the problme are mentioned.

HLA-B27-positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management, and treatment.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Demyelinating plaque-associated uveitis.

PURPOSE: To report the clinical and fluorescein angiographic (FA) features of demyelinating plaque-associated uveitis (DPU), a subset of uveitis in which patients have demyelinating plaques on the brain/cervical magnetic resonance image (MRI) but do not meet the criteria for multiple sclerosis (MS). METHODS: In this retrospective observational study, Persian Patients were diagnosed with DPU and included if (1) they never satisfied the MS criteria, (2) all other possible etiologies were excluded, and (3) they were followed for at least 2 years. RESULTS: After a median follow-up of 3 years (interquartile range, 2.0-5.3), 8 out of 40 (20%) patients diagnosed with DPU were excluded as they subsequently met the MS criteria. Of remaining 32 patients studied, the mean age was 36.3±9.9 (range 20-56 years), and 30 (93.8%) were female. Twenty-four (75.0%) showed bilateral involvement and 27 (84.4%) had insidious-chronic course. Uveitis was classified as intermediate (with or without anterior uveitis) in 29 (90.6%) and isolated anterior in 3 (9.4%) patients. Nine (28.1%) patients had at least one systemic neurological complaint. Ocular findings were: granulomatous keratic precipitates in 43/44 (97.7%) eyes; snowballs in 25/52 (48.1%) eyes; snowbanks in 4/52 (7.7%) eyes; cystoid macular edema in 20/56 (35.7%) eyes; and optic neuritis in 5/56 (8.9%) eyes. Visual acuity was ≥ 20/40 in 39 eyes (69.6%) at presentation which improved to 46 eyes (81.2%) at 2-year follow up. The two most frequent findings in FA were optic disc leakage/staining in 44/52 (81.5%) eyes, and peripheral retinal perivascular leakage in 39/52 (76.9%) eyes, which in 14/52 (26.9%) eyes extended beyond the equator. CONCLUSION: DPU usually presents as a bilateral chronic granulomatous intermediate and, less often, isolated anterior uveitis, especially in females. Most are neurologically asymptomatic. Visual outcome is generally favorable. In FA, peripheral retinal perivascular leakage is common. DPU patients have an increased tendency to develop MS and should be prohibited from anti-TNF treatment.

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.

Recurrent and chronic anterior uveitis: Long-term outcome and treatment strategies.

PURPOSE: To study the long-term clinical outcome and treatment strategies of recurrent and chronic non-infectious anterior uveitis. METHODS: Multicenter study of anterior uveitis patients from 2001 to 2022. Outcome measures included ocular complications, medical and surgical therapies, and visual acuity measured at the beginning of follow-up and at 1, 2, and 5 years thereafter. RESULTS: In total, 76 patients were included, with a mean follow-up of 6.8 years. Idiopathic anterior uveitis was the most common etiology (56%). Immunomodulatory agents (IMAs) were used in almost half of the cohort. Early initiation of IMAs was associated with a lower risk of developing glaucoma ( P = 0.019). Mean best corrected visual acuity (BCVA) improved after 5 years in both groups. Early use of immunomodulation was correlated with a better visual outcome at 2 years ( P = 0.024). CONCLUSION: Chronic and recurrent anterior uveitis were associated with greater risk than expected for ocular complications, surgeries, and vision impairment. Early initiation of immunomodulation should be strongly considered to improve clinical course and outcome.

Effectiveness and Safety of Weekly Adalimumab for Non-Infectious Chronic Anterior Uveitis in Children.

PURPOSE: Non-infectious chronic anterior uveitis (CAU) remains a therapeutic challenge. The purpose of this study was to analyze the effectiveness and safety of weekly dosing of adalimumab in children with non-infectious refractory CAU. Methods: Demographic and clinical data of children followed by non-infectious CAU treated with adalimumab were retrospectively reviewed. RESULTS: Of the 42 children with CAU, 27/42 (64.3%) were treated with adalimumab. Escalation to weekly dosing of adalimumab was necessary for 11/27 children (40.7%). After 3 and 6 months, 7/11 children (63.6%) met the composite endpoint of inflammation control improvement. Children requiring weekly adalimumab had initially more severe uveitis: anterior chamber cells (p = 0.02), aqueous flare (p = 0.02), and presence of macular edema (p = 0.007). No children had serious systemic side effects. CONCLUSION: Weekly adalimumab in children with refractory CAU appears to be an effective and safe treatment for inflammation control and corticosteroid sparing, and an alternative before biologic switching. Controlled studies are needed.

Tonic pupil in child after chicken pox.

This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient had red and irritated eyes and photophobia. Ophthalmological findings included anterior uveitis and tonic pupil accompanied by reduced vision and accommodation. An MRI of the cerebrum was normal. To ease the symptoms the patient was prescribed photophobia glasses with correction of hyperopia. Tonic pupil due to VZV infection is a rare complication, but may have long-term consequences, why patients with eye-involving VZV infection need to be examined by an ophthalmologist.

Iris depigmentation and cytomegalovirus in aqueous humor as predictors of uveitic activity and recurrence in chronic and recurrent anterior uveitis.

PURPOSE: To examine the clinical outcomes in chronic or recurrent anterior uveitis in the presence or absence of cytomegalovirus (CMV) and investigate the predictive factors for uveitic activity and recurrence. METHODS: Polymerase chain reaction (PCR) was performed in a prospective cohort of immunocompetent adults with recurrent or chronic anterior uveitis to detect CMV in aqueous humor. The clinical outcomes were compared between eyes with and without CMV DNA. Logistic regression was performed to evaluate associations between iris depigmentation, CMV-PCR status, uveitic activity, and recurrence. RESULTS: Thirty-eight eyes of 38 subjects with a mean age of 61.1 ± 11.2 years old were analyzed. Fifteen eyes were positive for CMV. More eyes with CMV developed recurrences and remained actively inflamed at 6, 12, and 24 weeks though the differences were insignificant. The presence of iris depigmentation was predictive of a greater odd of uveitic recurrences by 12 and 24 weeks (Odds ratio (OR) = 9.17 and 5.72, P = 0.007 and 0.034 respectively), whereas positive CMV-PCR predicts a greater odd of uveitic activity at postoperative 12 and 24 weeks (OR = 13.08, 34.30; P = 0.027, 0.007). CONCLUSION: Eye with and without detectable CMV behaved similarly in their clinical course. Our findings suggested that iris depigmentation was predictive of more frequent uveitic recurrence, regardless of the PCR status, whereas the presence of CMV in aqueous humor was associated with persistent uveitic activity. Iris changes may be present during the earlier phase of the disease and precede the detection of virus from the aqueous humor at a later stage of CMV infection.