Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis.

PURPOSE: To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. METHODS: This retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting. RESULTS: A strong correlation was seen between human and software counts. Pearson's correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; P<0.001 each). IL-6 levels correlated with both vitreous cell counts and cell counts observed on macular WOCT (human-counted group +0.339, P = 0.04; software-counted group +0.349, P = 0.03). Infectious uveitis showed higher IL-6 levels (P = 0.016) and high cell counts compared with non-infectious uveitis (P = 0.04). CONCLUSIONS: Vitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.

Alirocumab-associated unilateral posterior uveitis.

A man in his mid-40s who had been recently started on alirocumab (a human monoclonal antibody which inhibits proprotein convertase subtilisin/kexin type 9) due to his strong familial cardiovascular risk and refractory hypercholesterolaemia presented with a few-hour history of acute-onset left-sided blurred vision. The best-corrected visual acuities were 6/6 bilaterally and slit-lamp examination was normal. However, optical coherence tomography revealed serous subretinal fluid in the left macula. Optos ultra-widefield retinal imaging and fundus autofluorescence, along with a set of blood tests, did not reveal any alternative causes. A diagnosis of alirocumab-associated uveitis was diagnosed. Alirocumab was stopped and he was followed up in uveitis clinic. Within 4 months following alirocumab cessation, the subretinal fluid resolved completely. This case report emphasises the importance of early multidisciplinary team involvement, since novel therapeutic agents can have unexpected adverse events.

Serous macular detachment in ocular toxoplasmosis: A review.

Ocular toxoplasmosis, a disease of the eye caused by the protozoan parasite Toxoplasma gondii, represents a common cause of posterior uveitis. The Authors review the current Literature regarding the uncommon presentation of ocular toxoplasmosis as macular serous retinal detachment (SRD). It is imperative to keep in mind that inflammatory SRD is a possible presentation of toxoplasmic retinochoroiditis. Underestimation of this clinical scenario and treatment with steroids alone without appropriate antiparasitic drugs, could lead to devastating consequences.

[Intermediate and Posterior Uveitis - Disease entities]. / Intermediäre und posteriore Uveitis ­ Teil 2.

Intermediate and posterior uveitis can have multiple infectious and noninfectious causes, and posterior uveitis in particular is clinically multifaceted. Some entities require prompt initiation of therapy to ensure visual prognosis. This article presents typical characteristics of intermediate and posterior uveitides and explains special features of their treatment.

Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) - Report 6: Dengue Uveitis at a Tertiary Eye Institution in Singapore.

OBJECTIVES: To identify the characteristics, treatment, and visual outcomes of dengue uveitis at a tertiary eye care centre in Singapore. METHODS: Retrospective case record review of all consecutive dengue uveitis patients (2004 to 2015) from the Ocular Autoimmune Systemic Inflammatory and Infectious Study (OASIS) database. RESULTS: Fifty-four patients were identified from the OASIS database. The most common ocular symptom was blurring of vision (n = 41, 75.9%), followed by floaters (n = 9, 17.0%), scotoma (n = 5, 9.3%), and metamorphopsia (n = 3, 5.7%). Scotoma based on history, Amsler grid, and perimetry accounted for 27 (50%) patients. Majority presented with either a posterior uveitis or retinal vasculitis (n = 51, 94.4%). Treatments ranged from close observation for spontaneous improvement, to the use of high-dose corticosteroids. CONCLUSIONS: Dengue uveitis may present with a spectrum of disease manifestations including posterior uveitis, vasculitis, and macula edema. Scotoma is significant and may be found on history taking, Amsler charting, and perimetry.

Assessment of choriocapillaris and choroidal vascular changes in posterior uveitis using swept-source wide-field optical coherence tomography angiography.

PURPOSE: To evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA). METHOD: Consecutive patients with posterior uveitis were evaluated using 3×3 mm and 12×12 mm OCTA scan patterns and montage images of 5×12×12 mm or 2×15×9 mm, covering approximately 70°-90° of the retina. The images were quantitatively and qualitatively analysed and compared with healthy controls. RESULTS: Eighty-six eyes of 56 patients with posterior uveitis (mean age 45.2±19.9 years; 58.9% female), and 38 eyes of 19 age-matched healthy controls (57.9% female) were included. The mean perfusion density (PD) in 3×3 mm and 12×12 mm CC scans was significantly lower in eyes with posterior uveitis compared with those of healthy controls. However, no significant difference in the mean PD of choroidal scans was found comparing eyes with posterior uveitis and healthy controls. The mean PD in eyes with active disease was significantly higher compared with the inactive eyes on 12×12 mm choroidal scans (55.61% vs 51.25%, p=0.02), while no difference was found in the CC slabs. CONCLUSION: CC and choroidal assessment using OCTA provides useful information in patients with posterior uveitis. SS-OCTA metrics of the CC and choroidal slabs are promising tools in uveitis patients in the future. TRIAL REGISTRATION NUMBER: NCT02811536.

Epiretinal membrane in uveitis: Rate, visual prognosis, complications and surgical outcomes.

BACKGROUND: Epiretinal membrane (ERM) is a common finding in patients with uveitis that contributes to visual impairment. We describe the long-term visual acuity (VA) and morphometric progression in patients with uveitis and epiretinal membrane (ERM). METHODS: Retrospective cohort study of patients with uveitic ERM from a tertiary centre database. Multivariate analysis of risk factors for ERM progression was calculated using a marginal Cox regression model to estimate hazard ratios (HR). RESULTS: Two hundred and sixteen eyes (4%) of a total 5450 eyes with uveitis were identified to have an ERM. The most common diagnosis was idiopathic uveitis in 45 patients (28.7%), followed by sarcoidosis in 21 (13.4%), HLAB27-related uveitis in 15 (9.6%) and toxoplasmosis in 15 (9.6%). Risk factors for ERM development include age (HR 1.03), intermediate uveitis (HR 2.33), posterior uveitis (HR 1.53) and ERM fellow eye (HR 18.28). Anterior uveitis (HR 0.53) and alternating disease (HR 0.53) were protective. Median VA was 20/40 at diagnosis of ERM and 20/40 at final follow up. Progression of ERM grade occurred in 17 eyes (7.9%) during the study period. ERM peel was performed in 44 eyes (20.4%). Median VA was 20/60 and 20/40 at baseline and 12 months after surgery, respectively. Improvement in visual acuity occurred in 23 eyes (60.5%) following surgery. CONCLUSIONS: In addition to intermediate and posterior uveitis, fellow eye involvement is a strong risk factor for ERM development. In treated uveitis, the majority maintain their long-term vision and rates of ERM progression are low.

Pediatric Posterior Infectious Uveitis.

PURPOSE: To describe the most important cause of infectious posterior uveitis in pediatric patients. METHODS: Review of the literature. RESULTS: The most important causes of infectious uveitis in pediatric patients are: cat-scratch disease, toxocariasis, tuberculosis, viral diseases and toxoplasmosis. Ocular manifestations include retinitis, neuroretinitis, choroidal granulomas, peripheral granulomas and posterior pole granulomas. CONCLUSION: Infectious posterior uveitis is a challenging subject and should be considered in the differential diagnosis of any posterior uveitis in children. Infectious uveitis must be excluded before initiating immunosuppressive therapy.

Epidemiology of Pediatric Uveitis.

Uveitis is uncommon in children and its diagnosis and treatment are challenging. Little is known of the epidemiology of pediatric uveitis. Indeed, population-based studies in the literature are rare. However, there are many tertiary referral center reports that describe the patterns of uveitis in childhood, although few are from developed countries, and their comparison presents some issues. Anterior uveitis is the most frequent entity worldwide, especially in Western countries, where juvenile idiopathic arthritis is diffuse. Most cases of intermediate uveitis do not show any association with infectious or noninfectious systemic diseases. In low- and middle-income countries, posterior uveitis and panuveitis are prevalent due to the higher rates of infectious etiologies and systemic diseases such as Behçet disease and Vogt-Koyanagi-Harada disease. In recent decades, idiopathic uveitis rate has decreased thanks to diagnostic improvements.

[Intermediate and Posterior Uveitis - Classification, diagnostics, complications, and therapeutic algorithms]. / Intermediäre und posteriore Uveitis ­ Teil 1.

Intermediate and posterior uveitis describes a broad variety of different types of intraocular inflammation. Before starting treatment of intermediate or posterior uveitis, a differentiation between infectious or non-infectious uveitis must always be made. Pathognomonic symptoms do not exist, visual loss and vitreous floaters are the most common symptoms. The indication for therapy is influenced by the anatomical localization, the degree of inflammation, an association, complications and the activity of the inflammation. In addition to clinical ophthalmological standard examination, angiography and OCT are the most important investigations to classify and assess the course of inflammation. Macular edema is the most common complication of intermediate or posterior uveitis and should be treated at first onset, recurrence, or worsening. Oral, intravenous, or intravitreal corticosteroids are usually the primary therapy for intermediate or posterior uveitis. Systemic immunosuppression is indicated after steroid failure in non-infectious uveitis.

Vitreoretinal lymphoma: a diagnostic challenge.

A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented. Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone, biological treatment with Adalimumab was established. During follow-up, the patient developed bilateral subretinal lesions compatible with Vitreoretinal Lymphoma (VRL), so vitrectomy was performed, confirming the diagnosis of large B-cell lymphoma. Treatment with systemic chemotherapy with BRAM-Carmustine, Metrotexate, Ara C, and Rituximab was started with a good answer. Two years later, the patient remains without ocular or systemic recurrences. Vitreoretinal Lymphoma is a rare type of primary central nervous system lymphoma. The diagnosis is frequently delayed due to the nonspecific symptoms, which mimic chronic posterior uveitis, hence the importance with a diagnostic suspicion.

Bilateral macular hole in a patient with CAPN5-related neovascular inflammatory vitreoretinopathy.

PURPOSE: To characterize the genotype and phenotype of a patient with CAPN5-related neovascular inflammatory vitreoretinopathy (NIV) who have undergone surgery for macular holes. METHODS: We observed a patient presenting with retinitis pigmentosa and posterior uveitis who later developed vitreoretinal macular traction and a macular hole. Genetic testing was performed using a targeted gene panel. Fundus photography and spectral-domain optical coherence tomography were also performed. RESULTS: In a targeted gene panel, a monoallelic pathogenic variant, c.750G > T, p.Lys250Asn, in the CAPN5 gene was identified, and CAPN5-NIV was diagnosed. At the first visit, peripheral retinal degeneration and mild posterior uveitis were observed. At that time, neovascularization, epiretinal or fibrous membranes were not observed. After 5 years, vitreomacular traction developed and progressed to a full-thickness macular hole in both eyes. After pars plana vitrectomy, the macular hole was successfully closed without aggravation of uveitis. CONCLUSION: In this case, a pathogenic variant of CAPN5 lead to a distinct phenotype of retinitis pigmentosa, posterior uveitis, vitreomacular traction, and macular hole without typical inflammatory neovascularization or tractional membranes. Therefore, the clinical variability of CAPN5-NIV and genetic diagnosis should be considered in cases of atypical retinitis pigmentosa with bilateral macular hole.

Diagnostic efficacy of elevated serum angiotensin-converting enzyme and lymphopenia between presumed sarcoid uveitis and presumed tubercular uveitis.

PURPOSE: To evaluate the diagnostic efficacy of elevated serum angiotensin-converting enzyme (sACE) and lymphopenia in presumed sarcoid and tubercular uveitis. METHODS: A single-centre retrospective study was conducted on a cohort of 755 adult patients with uveitis between January 2019 and June 2020. Demographic, clinical and laboratory data were retrieved from our hospital database. Measurements of serum angiotensin-converting enzyme (sACE) and lymphocyte counts were analysed. RESULTS: The mean age of the patients was 41 ± 13 years. Presumed sarcoid uveitis was diagnosed in 50 (7%) patients, presumed tubercular uveitis in 222 (29.4%) and other uveitic entities noted in 483 (64%). Intermediate and posterior uveitis were the most common anatomical diagnosis in presumed sarcoid uveitis (59% and 20%, respectively) and in presumed tubercular uveitis (46% and 38%, respectively). Elevated sACE was noted in 76% of presumed sarcoid uveitis and 46% in presumed tubercular uveitis. The combination of high serum angiotensin-converting enzyme along with lymphopenia was only in 17% in presumed sarcoid uveitis and 9.7% in presumed tubercular uveitis. sACE was found to be a significant risk factor for presumed sarcoid uveitis with an odds ratio of 3.603 (p < 0.002), and in presumed tubercular uveitis odds ratio was not significant with odds ratio of 1.19. Lymphopenia was not found to be a significant factor in both groups. CONCLUSION: Elevated sACE activity was an independent risk factor for presumed sarcoid uveitis over lymphopenia alone or in combination with lymphopenia.

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.

Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China.

BACKGROUNDS: To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China. METHODS: In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed. RESULTS: Among the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences. CONCLUSION: Posterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.

[Noninfectious posterior uveitis : Clinical aspects, diagnostics, management and treatment]. / Nichtinfektiöse posteriore Uveitis : Klinik, Diagnostik, Management und Therapie.

Noninfectious posterior uveitis (NPU) comprises a heterogeneous group of vision-threatening, immune-mediated ocular and systemic diseases. It is predominantly bilateral and recurrent and, if not treated properly, leads to severe tissue damage that threatens the eyesight. In industrialized countries ca. 10-20% of all cases of blindness are caused by NPU. An NPU can occur at any age but is most common between the ages of 20 and 50 years. Laboratory diagnostic and imaging procedures enable an increasingly better differentiation of the disease spectrum. This makes it possible to better assess the course and prognosis of individual disease entities. An increasing repertoire of systemic and intravitreal forms of treatment has already led to more favorable long-term treatment outcomes. It can be expected that further progress can be achieved with better knowledge of the pathophysiology of the different clinical disorders and appropriate, targeted treatment.

Stepwise approach for fundus imaging in the diagnosis and management of posterior uveitis.

An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.

Relationship between ultra-widefield optical coherence tomography and ophthalmoscopy for detecting posterior inflammation in posterior uveitis and panuveitis.

PURPOSE: To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis. METHOD: We retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT. RESULTS: This study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (p<0.01). Compared to "Ophthalmoscopic findings", "W-OCT VO" offered 78.6% sensitivity and 30% specificity for all cases (p = 0.19). In addition, "W-OCT Cells" did not differ significantly from "FAG findings" for all cases (P = 0.424). CONCLUSION: W-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.

Pediatric Non-Infectious Uveitis: Long-Term Outcomes and Complications.

PURPOSE: To describe the long-term prevalence of ocular complications and visual prognosis in patients with pediatric uveitis. METHODS: Demographics, etiology and location of uveitis, type of complications, treatment and visual outcomes were recorded in 296 children at first examination and at 1-, 2-, 3-, 5- and 10-year time points. RESULTS: Αnterior uveitis represented 53.4% of cases, followed by intermediate (28.0%), posterior uveitis (11.1%) and panuveitis (7.4%). The leading diagnoses were idiopathic uveitis (31.1%), juvenile idiopathic arthritis (27.0%) and pars planitis (22.6%). Posterior synechiae was the most frequent complication of anterior uveitis and panuveitis, cystoid macular edema and disc edema of intermediate and posterior uveitis respectively. Posterior uveitis and panuveitis had more severe final vision loss (23.1% and 20% respectively). CONCLUSIONS: This study provides clinical characteristics and main complications in a longitudinal long-term follow-up of a large non-infectious pediatric uveitis Greek population. Early diagnosis and close monitoring remain of fundamental importance.