An update on non-infectious retinal vasculitis.

BACKGROUND: Retinal vasculitis (RV) signifies the inflammation of various retinal vessels. Non-infectious RV differs from infectious RV with regard to its pathogenesis and treatment. It can have varied clinical presentations and may be associated with systemic vasculitic diseases. SUMMARY: Non-infectious RV can be caused due to type-III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. Non-infectious RV is primarily classified on the basis of the type of retinal vessels involved. It can be further classified as an occlusive or non-occlusive. RV can be a major association of systemic diseases like Behcet's disease, sarcoidosis and systemic lupus erythematosus. Newer modalities, like ultra-widefield fundus fluorescein angiography, can help in the management of RV. Effective treatment of non-infectious RV requires anti-inflammatory and immunosuppressive therapy. The patients may require treatment with high-dose corticosteroids and biological agents. Anti-vascular endothelial growth factor injections and laser photocoagulation may be indicated to treat the occlusive disease. Prompt treatment may prevent complications like vitreous hemorrhage, neovascular glaucoma and tractional retinal detachment. The treatment more often requires a multi-disciplinary approach. KEY MESSAGES: This review provides a comprehensive update on the various causes of non-infectious RV, including both systemic and isolated ocular conditions. It also details various complications and management strategies for this condition.

Vitreoretinal Interface Cells Correlate In Vivo With Uveitis Activity and Decrease With Anti-Inflammatory Treatment.

Purpose: To highlight the utility of en face swept-source optical coherence tomography angiography (SS-OCTA) in assessing vitreoretinal interface cells (VRICs) of patients with active uveitis and their dynamics. Methods: In this prospective, single-center study, 20 eyes from patients with active uveitis were analyzed using six 6 × 6-mm macular scans at three time points: active inflammation (baseline), clinically improving (T1), and resolved inflammation (T2). VRICs were visualized using 3-µm en face OCT slabs on the inner limiting membrane. The variation of VRIC number, density, and size over time was assessed, and VRIC measurements were compared with clinical grading. Results: At baseline, the VRIC count was significantly higher (552.5 VRICs) than that of the healthy controls (478.2 VRICs), with a density of 15.3 cells/mm2. VRIC number decreased significantly to 394.8 (P = 0.007) at T1, with a density of 10.9 cells/mm2 (P = 0.007). VRIC size reduced from 6.8 µm to 6.3 µm at T1 (P = 0.009) and remained stable at T2 (P = 0.3). Correlation coefficients between inflammatory parameters (anterior chamber cells and National Eye Institute vitreous haze), and VRIC count indicated a positive correlation at baseline (r = 0.53), weakening at T1 (r = 0.36), and becoming negative at T2 (r = -0.24). Conclusions: En face SS-OCTA revealed increased VRIC number and size in active uveitis, likely due to monocyte recruitment. Post-inflammation control, VRIC number, size, and density significantly decreased, returning to normal despite residual anterior chamber cells or vitreous haze. Translational Relevance: Visualization of VRICs by in vivo OCT opens up new opportunities for therapeutic targets.

Uveitis-Glaucoma-Hyphema Syndrome Secondary to Implantable Collamer Lens.

Purpose: To report the first case of uveitis-glaucoma-hyphema (UGH) syndrome post implantable collamer lens (ICL).Methods: Case reportResults: A 41-year-old female presented to our clinic complaining of bilateral eye pain and redness for two weeks. Her past medical history was significant for ICL, in both eyes and multiple sclerosis controlled with treatment. She had a long-standing history of bilateral recurrent uveitis and glaucoma. Ultrasound biomicroscopy revealed several sulcus cysts displacing the ICLs haptic into the ciliary body, leading to iris abrasion and uveitis-glaucoma-hyphema syndrome.Conclusion: We present the first published case worldwide about UGH syndrome secondary to ICL. This is an unusual complication, and measures can be taken to avoid it. This provides evidence of the importance of postoperative follow-up by the surgeon and appropriate work-up when such cases are suspected.

Unraveling the Complexities of Severe Acute Respiratory Syndrome Coronavirus 2: A Comprehensive Ophthalmic and Systemic Perspective.

The editorial explores the profound implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which emerged in December 2019 and rapidly evolved into a global health crisis. Despite initial focus on respiratory symptoms, the virus revealed significant ocular implications, prompting a reevaluation of the eye's role in its transmission, diagnosis, and systemic effects. The paradoxical nature of SARS-CoV-2-simultaneously novel and familiar within the coronavirus family-has been central to guiding the global medical response, including the swift development of vaccines. The pandemic has intensified research into the eye's susceptibility to viral infections, enhancing our understanding of virus-host interactions and the systemic impacts of viral diseases. The editorial delves into the pathophysiology of SARS-CoV-2, highlighting its potential to trigger autoinflammatory and autoimmune reactions with significant ocular repercussions. It examines the rapid vaccine development and deployment, the associated ocular side effects, and the ongoing research necessary to mitigate these outcomes. As the World Health Organization declared the end of COVID-19 as a public health emergency, the focus has shifted toward understanding the virus's long-term implications, including its effects on ocular health. This work underscores the critical role of interdisciplinary collaboration in addressing the systemic impacts of viral infections. It emphasizes the importance of ophthalmology in the broader context of public health and highlights the need for continued vigilance, research, and adaptation in a postpandemic world. The editorial calls for an integrated approach to health care, emphasizing the lessons learned from the SARS-CoV-2 pandemic to prepare for future health challenges, with a particular focus on the intersection of virology, immunology, and ophthalmology.

Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

The Humira in Ocular Inflammations Taper (HOT) Study.

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

Description of Macrophage-Like Cells in Active Ocular Toxoplasmosis.

Macrophage-like cells (MLC) have a fundamental role in the maintenance of immunosurveillance, response to inflammation and tissue injury in the retina. MLC can be visualized in vivo with conventional en face optical coherence tomography (OCT). The aim of this study is to describe this population of cells in active toxoplasmosis. We present two cases of active toxoplasma retinochoroiditis imaged at 2 time points, where the MLC were threshold after image processing and averaging for removing background and noise. In both patients the MLC collocated with the area of ischemia at the level of the choriocapillaris and retinal vessels.

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

Purpose: To report a case series of herpetic uveitis following COVID-19 vaccinations. Methods: Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. Results: Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. Conclusion: This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

Optical coherence tomography angiography in birdshot chorioretinopathy.

PURPOSE: To describe the retinal vascular changes in birdshot chorioretinopathy (BSCR) using optical coherence tomography angiography (OCTA) and to compare them with changes in macular thickness. METHODS: In this multicenter study, patients with a diagnosis of BSCR and a positive HLA-A29 underwent fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and OCTA. The foveal avascular zone (FAZ) and the area of capillary non-perfusion were manually measured by two examiners in fluorescein angiography (FA) and 3 × 3-mm OCTA images of the superficial retinal layer. These measurements were compared to central retinal thickness. To calculate normal capillary density, we collected data from 22 controls who had OCTA performed on one visit only. RESULTS: A total of 44 eyes with BSCR were enrolled. The mean automated parafoveal superficial capillary density in BSCR eyes was 0.47 ± 0.03. The differences between the foveal capillary density of BSCR patients and healthy subjects were statistically significant (P < 0.001). The mean area of FAZ manually measured on the 3 × 3 mm unsegmented OCTA images was larger in eyes with BSCR (1.34 ± 0.41 mm2; P < 0.0001). Measurement of FAZ area showed good interobserver (κ 0.88) and intraobserver repeatability (κ 0.79) on OCTA images. The intraclass correlation coefficient for FAZ measurements on FA between the two observers was 0.48. The OCT retinal thickness maps of all BSCR eyes demonstrated statistically significant thinning compared to those of control subjects (P < 0.01). CONCLUSION: Our study demonstrates the potential contribution of OCTA as a new non-invasive imaging technology that monitors disease activity in BSCR patients.

In Vivo Visualization of Macrophage-Like Cells in Patients with Uveitis by Use of En Face Swept Source Optical Coherence Tomography.

AIMS: To detect macrophage-like cells (MLCs) in uveitis patients and describe their characteristics compared to healthy subjects by using en face SS-OCTA. METHODS: Fifteen consecutive patients with "active" uveitis and 11 healthy participants underwent 6 macular scans of 6×6mm using SS-OCTA. The 3µm en face OCT slabs on inner limiting membrane were used to visualize the MLCs. RESULTS: In healthy subjects there was an average of 478.2±149.7 MLCs with a density of 13.28±4.16 cells/mm2. MLCs were larger in patients with "active" uveitis than in controls (891.18±69.46 µm2 vs.885±77.53 µm2). Patients with "active" anterior uveitis had a significantly reduced count and density of MLCs (172±14.68 and 4.77±0.4 cell/mm2) compared to controls, while patients with posterior uveitis had a statistically increased count (546.1±132.4) and area (909.23+/-54.97 µm2) of MLCs compared to controls. CONCLUSIONS: MLCs detected with en face SS-OCTA are increased in number and size in active posterior uveitis eyes compared to controls.

Orbital Perivascular Epithelioid Cell Tumor in a Case of Tuberous Sclerosis.

The aim of the study was to report a case of orbital perivascular epithelioid cell tumor (PEComa) in a known diagnosed patient of tuberous sclerosis and retinal astrocytic hamartoma. 43-year-old female presented with rapid progressive painful proptosis in the left eye, also reported new mass growing in her upper back. The patient past medical history is significant for left renal angiomyolipoma and multiple bilateral lung cysts of which she underwent right nephrectomy and lung biopsy, respectively. The lung biopsy turned diagnostic for lymphangiomyomatosis. On external examination, the left eye was grossly proptotic with hypoglobus. A typical butterfly distribution of sebaceous adenoma was noted across the patient cheeks and nose. Visual acuity in the right eye was 20/20 and the left eye, 20/25. Funduscopic examination identified type 1, 2, and 3 retinal astrocytic hamartomas. MRI brain and orbit was significant for a lesion arising from the lateral orbital wall with extensive bone destruction, displacing the left optic nerve medially. CT chest showed left extrathoracic mass had same radiological features as the orbital lesion; thus, an incisional biopsy performed on the former was diagnostic for PEComa with atypical features. This is the first observed case of PEComa in a known diagnosed patent with TS and retinal astrocytic hamartoma. The association of tuberous sclerosis complex and orbital PEComa is rarely and poorly reported in the literature compared to extraocular PEComa.

Fundus autofluorescence in uveitis: from pathogenesis to imaging interpretation.

PURPOSE: This review aims to summarize the current fundus autofluorescence (FAF) ailment for diagnosis and follow-up of uveitis. METHODS: A thorough literature search was performed in the PubMed database. RESULTS: FAF maps the retinal pigment epithelium's (RPE) health. Therefore, several posterior infectious and non. This fast, easy-to-perform, noninvasive technique can detect and manage infectious uveitis. CONCLUSIONS: FAF serves to understand pathophysiologic mechanisms of uveitis and is a valuable prognostic indicator of themselves.

Focal Posterior Herpetic Retinitis.

Despite having 20/20 vision, a 17-year-old Emirati female presented with central visual changes in her left eye. These changes were attributed to a dull foveal reflex with pigmentary alterations. Retinal pigment epithelium (RPE) mottling at the macula level, attenuating the ellipsoid zone, and a hyper-reflective line connecting the RPE to the outer nuclear layer was observed through spectral domain optical coherence tomography (SD-OCT) of the left eye. In the presence of negative results from laboratory evaluations, the patient was started on oral prednisolone. The medication induced an increased reflectivity of the inner layers on SD-OCT, which turned into a full-thickness macular retinitis with vitreous inflammation, causing a visual decrease to 20/80. A vitreous tap confirmed a positive result for HSV-1, and the patient was prescribed oral valacyclovir 3 g. This treatment led to a resolution of the retinitis and a restoration of the patient's vision to 20/25.

Multimodal Imaging Study of Patients With Vitamin A Deficiency Retinopathy.

OBJECTIVES: To describe multimodal imaging findings of vitamin A deficiency retinopathy. METHODS: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed. RESULTS: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%). CONCLUSIONS: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.].

STELLATE MULTIFORM AMELANOTIC CHOROIDOPATHY: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSION: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."

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.

Tubulointerstitial Nephritis and Uveitis Syndrome in the United Arab Emirates.

PURPOSE: To report the first series of tubulointerstitial nephritis (TINU) syndrome from the Middle East. METHODS: We retrospectively included patients with elevated urine beta-2 microglobulin, and a diagnosis of TINU based on anterior uveitis with or without posterior involvement. Multimodal imaging, duration of follow-up, local and systemic treatment used were recorded. RESULTS: 24 eyes of 12 patients (8 male, mean age 20.3 years) met the criteria for TINU. The most common posterior segment clinical finding was optic nerve head edema (41.7%), while on fluorescein angiography 58.3% and 75% of eyes had peripheral vascular and optic disc leakage, respectively. The mean follow-up was 2.5 years and all patients required immunomodulatory treatment. CONCLUSIONS: Middle Eastern patients with TINU seem to have a male predominance, a bimodal distribution in terms of age, and present with ocular involvement first. Multimodal imaging is paramount in detecting subclinical inflammation and tailoring immunomodulatory treatment.