Epidemiology of Intermediate Uveitis.

Intermediate uveitis is defined as inflammation of the vitreous and pars planitis. Etiology can be infectious, associated with a systemic disease, neoplastic or idiopathic. Pars planitis is the term used for idiopathic intermediate uveitis that presents with snowballs and snowbanks. While relatively rare, intermediate uveitis is present globally and typically affects adult females. Awareness of the presentation and a dilated fundus examination in patients presenting with floaters is essential to the diagnosis. PCR testing has enhanced the ability to diagnose infectious and neoplastic conditions that masquerade as intermediate uveitis. A structured review of systems and focused imaging, and laboratory testing will assist with early diagnosis and initiation of treatment.

Review for Disease of the Year Clinical Features and Ocular Imaging in Intermediate Uveitis and Pars Planitis.

Intermediate uveitis is a relatively common form of intraocular inflammation that can be seen at any age. The vitreous is the primary site of inflammation; and the presence of snowballs or snowbank defines its subtype, pars planitis. Since it is a clinical diagnosis, it is important to recognize the typical clinical features and associated ocular complications. Recent advances in ocular imaging have made significant contributions to the clinical appraisal and studies of intermediate uveitis. This narrative review includes clinical signs, ocular complications, and ocular imaging of intermediate uveitis and pars planitis.

Ocular Complications of Intermediate Uveitis.

Intermediate uveitis (IU) in an intraocular inflammation that predominantly affects the vitreous. It typically manifests as chronic low-grade inflammation, mainly affecting children and young adults. Uncontrolled chronic intraocular inflammation carries a high risk of visual loss. IU, despite being a low-grade inflammation, is among the sight-threatening conditions owing to its intrinsically-associated vision-robbing ocular complications. It can cause early and late-onset ocular complications affecting the anterior and posterior segments of the eye. 40-60% of the patients who suffer from IU will develop at least one ocular complication during the disease course. Prompt management and long-term monitoring are vital for the early detection of ocular complications and timely intervention. Proactive screening programs are essential in children because of the occult nature of IU in the pediatric age group and the high prevalence of complications at the initial visit. This review provides a comprehensive panorama of anterior segment complications, namely, band keratopathy, corneal endotheliopathy, posterior synechiae, and cataract as well as of posterior segment complications including macular edema, retinoschisis, retinal detachment, vitreous hemorrhage, vasoproliferative tumor, optic neuritis, and papillitis, in addition to glaucoma and hypotony.

[Uveitis and multiple sclerosis : Clinical aspects, diagnostics, management and treatment]. / Uveitis und multiple Sklerose : Klinik, Diagnostik, Management und Therapie.

Approximately 0.5-1% of patients with multiple sclerosis (MS) have co-existing uveitis. Both intraocular inflammation and MS mainly affect women in younger adulthood. The MS in patients is most frequently associated with an often bilateral intermediate uveitis with typical concomitant retinal vasculitis. Both diseases share similar characteristics with chronic inflammatory diseases with a relapsing course and an immune-mediated pathogenesis; however, it is still unclear whether the co-occurrence of uveitis and MS in the same patient represents a coincidence of two separate disease entities or whether uveitis is a rare clinical manifestation of MS. In the differential diagnostics of intermediate uveitis, clinical symptoms and signs of MS should be considered. As both diseases are considered to be immune-mediated, immunotherapy is the main treatment option. In recent years the range of medications has expanded and includes several disease modifying drugs (biologics). When selecting the active substance it must be taken into account that tumor necrosis factor (TNF) alpha blockers are contraindicated in patients with MS.

Presentation of Adult-onset Asthma and Periocular Xanthogranuloma with Intermediate Uveitis and Hodgkin's Lymphoma: A Case Report.

Purpose: To report a case of adult-onset asthma and periocular xanthogranuloma (AAPOX) in a patient with intermediate uveitis and a history of Hodgkin's lymphoma (HL). Case Report: A 51-year-old man with a past medical history of HL presented with blurred vision, asthma, and bilateral yellowish eyelid lesions. The eyelid lesions and asthma appeared 10 years after being diagnosed with HL. Physical examination was significant for multiple subcutaneous and firm eyelid masses in addition to the presence of pre-auricular and submandibular lymphadenopathies. Ophthalmic examination revealed bilateral intermediate uveitis and mild macular edema. Further systemic evaluations, including laboratory testing and imaging, were normal. Excisional biopsy of the eyelid lesions was performed and the histopathologic examination was consistent with the diagnosis of AAPOX. Conclusion: The presence of AAPOX in a patient with intermediate uveitis and history of HL suggests that immunological dysfunction may play a role in the pathogenesis of adult orbital xanthogranulomatous disease.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

Intermediate Uveitis with Cystoid Macular Edema as Presentation of Retained Caterpillar Hair in the Vitreous Cavity.

PURPOSE: To report an unusual case of retained caterpillar hair in the vitreous cavity presenting as recurrent Intermediate Uveitis with cystoid macular edema. METHOD: Case Report. RESULTS: A 40-year-old male presented to our uveitis clinic with recurrent episodes of redness and diminution of vision in his left eye for 3 years. He was diagnosed and treated elsewhere as a case of recurrent intermediate uveitis and was referred to our center for a second opinion to initiate immunosuppressive therapy. A detailed history revealed that a caterpillar had fallen into his left eye 3 years back, followed by severe irritation, pain, and redness. He received topical antibiotics and corticosteroids, and retained caterpillar hair was removed from the ocular surface. During the last 3 years, the patient had multiple episodes of inflammation despite being treated with oral and topical corticosteroids. At the current visit, a meticulous clinical examination at our centre revealed multiple, migrated, retained caterpillar hair in the vitreous cavity. The patient was diagnosed with Ophthalmia Nodosa (Type V) and managed with surgical intervention (vitreous surgery). The case highlights an unusual presentation of ON and the role of pars plana vitrectomy in its successful management. CONCLUSION: We highlight a rare and unusual presentation of ophthalmia nodosa and its successful management.

A case report of pediatric-onset MS associated uveitis.

BACKGROUND: To report a case of Pediatric-onset MS associated uveitis managed with local and systemic medications. CASE PRESENTATION: An 11-year-old boy who was diagnosed with Pediatric-onset MS (POMS) with the first presentation of left optic neuritis in another center, was referred to our clinic with the complaint of non-improved vision in the left eye despite receiving IV 5gr methylprednisolone. After the ophthalmologic examinations, the patient was diagnosed as bilateral POMS-associated intermediate uveitis, and local treatment with corticosteroid was administered to both eyes. He was continued on systemic therapy such as Rituximab and five sessions of plasmapheresis. After four months, the patient's vision improved from FC at 50cm to 9/10 in the left eye. The intensity of intraocular inflammation decreased in both eyes. In fluorescein angiography findings, the optic disc, as well as vascular leakage, subsided bilaterally. CONCLUSION: Despite its rarity, POMS-associated uveitis presents a considerable challenge that necessitates the collaborative efforts of neurologists and ophthalmologists to achieve the most effective treatment outcomes.

Prevalence, clinical characteristics, and independent predictors of uveitic macular edema in an Asian population: a retrospective cohort study.

BACKGROUND: To determine the prevalence, clinical characteristics, and independent predictors of uveitic macular edema (UME) in patients with intermediate, posterior and panuveitis. METHODS: We retrospectively reviewed the records of patients with intermediate, posterior, and panuveitis who underwent macular assessment using optical coherence tomography between January 2015 and February 2020. The prevalence of UME and clinical characteristics of the patients were described. Predictors of UME were identified using multivariate regression analysis. RESULTS: A total of 349 patients were included. The mean age was 41 years, female: male ratio was 1.3:1. The prevalence of UME was 51.9%. UME was found in 33.9%, 56.9%, and 54.1% of the intermediate, posterior, and panuveitis cases, respectively. Among patients with UME, 47% had infectious uveitis, 32.6% had idiopathic uveitis, and 20.4% had immune-mediated uveitis. Diffuse macular edema was the most frequently observed pattern (36.5%). Multivariate analysis showed that factors independently associated with UME included age at uveitis onset (adjusted odds ratio [aOR] 1.01, 95% confidence interval [CI] 1.00-1.03, P = 0.036), PU and panuveitis compared with intermediate uveitis (aOR 2.09, 95% CI 1.14-3.86, P = 0.018), and infectious uveitis compared with noninfectious uveitis (aOR 2.13, 95% CI 1.34-3.37, P = 0.001). CONCLUSIONS: Increasing age at uveitis onset, posterior/panuveitis, and infectious etiology are predictive factors for UME in patients with intermediate, posterior and panuveitis.

Vasoproliferative Tumor Secondary to Sarcoidosis-Associated Intermediate Uveitis.

We report the visual and clinical outcomes of a middle-aged woman who presented with exudative retinal detachment (ERD) secondary to a vasoproliferative tumor (VPT) in an eye with sarcoidosis-associated intermediate uveitis. A 55-year-old woman previously diagnosed with sarcoidosis presented with decreased vision in the left eye (LE). Visual acuity in the LE was counting fingers. She had active vitritis, and a peripheral retinal vascular mass was noted in the superotemporal periphery. The mass was associated with ERD involving the posterior pole. The patient was managed with systemic and intravitreal steroids, and cyclosporine was subsequently added as a steroid-sparing agent. Because of recurrence of ERD, the patient underwent pars plana vitrectomy, and cryotherapy and laser photocoagulation were applied to the VPT. Two months postoperatively, visual acuity in the LE improved to 6/10. There was marked regression of the VPT and total resolution of the ERD. In conclusion, we report a favorable visual and clinical outcome in a patient with VPT-associated ERD who responded to a combination of medical therapy and surgical intervention. VPT may lead to different remote complications, so timely diagnosis of these tumors and proper management of their complications is warranted.

Evaluation of Optical Coherence Tomography Angiography Findings in Pars Planitis and Multiple Sclerosis Associated Intermediate Uveitis in Remission.

PURPOSE: To evaluate the microvasculature during remission in patients with pars planitis (PP-IU) and multiple sclerosis-associated intermediate uveitis (MS-IU) using optical coherence tomography angiography (OCT-A). METHODS: Single-center, descriptive, case-control study was conducted. Adult patients (≥16 years) with IU in remission (PP-IU and MS-IU) and healthy age-sex matched healthy controls (HC) were enrolled to the study. Demographic/clinical features, best-corrected visual acuity (BCVA), ocular findings, neurological symptoms and preferred treatments were recorded. The presence of cystoid macular edema (CME) during follow-up was recorded. All IU patients in remission and HC subjects were scanned with OCT-A. Foveal avascular zone (FAZ) areas of superficial and deep capillary plexus (SCP/DCP) and vascular densities of SCP, DCP and choriocapillaris were obtained from OCT-A and compared between the groups. RESULTS: Sixty-nine eyes of 37 IU patients in remission and 20 HC were included (44 eyes/23 patients in PP-IU, 25/14 in MS-IU, 40/20 in HC). No statistically significant differences were observed in terms of demographic or clinical characteristics of the patients. The vascular density in the SCP was significantly reduced in the PP-IU and MS-IU groups compared to the HC group (p < .05). Nevertheless, there were no significant changes in any of the OCTA parameters between the IU groups. Uveitis duration was found to be correlated with enlargement of the FAZ area in PP-IU (p = .039). CONCLUSION: OCTA may not be useful in differentiating between PP-IU and MS-IU. Nevertheless, the primary implication in SCP potentially elucidates the pathogenesis of these two subtypes of IU, which are characterized by a shared pathogenesis. The monitoring of the FAZ area in the PP-IU group is valuable in terms of chronicity.

Retinal Vasoproliferative Tumours in Uveitis.

PURPOSE: To describe a cohort of patients with retinal vasoproliferative tumours (RVPT) seen in the uveitis clinic of a single tertiary eye care institute in India. METHODS: Retrospective Chart Review. RESULTS: In our study of 17 patients with 18 eyes affected by RVPTs, 94.1% showed unilateral involvement, one patient had bilateral RVPTs, and another had two RVPTs in the same eye. The mean age was 36.3 ± 15.1 years (range: 12-63 years), with a male majority (76.4%). The most common location was inferotemporal quadrant (44.4%). The most common associated uveitic condition was intermediate uveitis (50%). Patients were treated with oral corticosteroid (in 94.1%) and immunosuppressive (35.2%) in addition to transconjunctival cryotherapy (in 52.9%) or laser photocoagulation (in 41.1%). Regression of the RVPT was achieved in all cases except one. Visual acuity at time of detection of RVPT ranged from 6/6 to HM. No significant change was noted in the mean best corrected visual acuity pre and post treatment in the study group. CONCLUSION: RVPTs, rare peripheral retinal lesions often associated with intermediate uveitis, require early diagnosis with targeted therapy to prevent vision loss and achieve favorable long-term outcomes with rare recurrences.

Uveitis in the Setting of Co-Existing Systemic Sarcoidosis and Multiple Sclerosis.

We report a case of intermediate uveitis in the setting of both systemic sarcoidosis and multiple sclerosis. A 68-year-old female was diagnosed with bilateral granulomatous intermediate uveitis and cystoid macular edema. Initial systemic work-up was unrevealing. The uveitis was treated successfully with local corticosteroid injections. Eighteen months after presentation, the patient developed new systemic symptoms. Additional testing revealed systemic lymphadenopathy, with biopsy showing non-caseating granulomas, leading to a diagnosis of sarcoidosis. However, MRI of the brain and spinal cord along with cerebrospinal fluid analysis was consistent with MS. The management of the uveitis and systemic inflammation was co-managed by ophthalmology, neurology, and rheumatology, and eventually controlled with leflunomide and rituximab. Patients can rarely have co-existing systemic sarcoidosis and multiple sclerosis. Although challenging to diagnose, radiographic findings and cerebrospinal fluid analysis can be helpful to differentiate multiple sclerosis and neurosarcoidosis. Management of these patients requires coordination between multiple specialties.

Pediatric Pars Planitis: A Review.

PURPOSE: To provide an overview of pediatric pars planitis. METHODS: Narrative literature review. RESULTS: Pars planitis refers to the idiopathic subset of intermediate uveitis in which there is vitritis along with snowball or snowbank formation occurring in the absence of an associated infection or systemic disease. It is thought to be a T-cell mediated disease with a genetic predisposition. Pars planitis accounts for 5-26.7% of pediatric uveitis cases. Presentation is commonly bilateral but asymmetric, often with insidious onset of floaters and blurred vision. Although pars planitis is known to be a benign form of uveitis in most cases, severe complications secondary to chronic inflammation may arise, with cystoid macular edema being the most common cause of visual morbidity. Mild vitritis in the absence of symptoms, vision loss, or macular edema may be observed. Patients with severe vitritis and/or associated vision-threatening complications require prompt aggressive treatment. A stepladder approach including corticosteroids, immunosuppressive agents, anti­tumor necrosis factor­alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. CONCLUSION: Timely diagnosis and adequate treatment of pediatric pars planitis and associated complications are crucial in order to improve visual outcomes.

SER recommendations for the treatment of uveitis.

OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.

Effects of non-medical infliximab biosimilar switching in ocular inflammatory diseases: A case series from a tertiary care center.

PURPOSE: To describe the course of care and outcomes for 3 uveitis patients formerly on Remicade that were non-medically switched to Inflectra. DESIGN: Retrospective observational case series. METHODS: •Setting: Tertiary care clinical practice.•Patient population: 3 Uveitis patients, observing both eyes for inflammation as applicable. Patients included if they had been on Inflectra for ≥2 infusions and history of Remicade use. Patients described herein had at least 1 adverse reaction to Inflectra and were switched to Remicade for medical necessity. Patients excluded if they were lost to follow-up or not examined for over 6 months during therapy.•Observation procedures/Interventions: Patients observed for adverse changes in clinical course while on Inflectra. Patients developing these changes on Inflectra were started or restarted on Remicade. RESULTS: The 3 patients described herein developed adverse complications while on Inflectra that required switching to Remicade. They were originally on Remicade, and their clinical course worsened beyond what had been controlled with Remicade alone. Our findings are limited by our small sample size, and further investigation is necessary to explore the scope of effects of non-medical biosimilar switching. CONCLUSION: Non-medical biosimilar switching from Remicade to Inflectra may induce detrimental side-effects and significant worsening of inflammation in patients with uveitis. Non-medical biosimilar switching from Remicade to Inflectra should be discouraged, and physician input should be sought in establishing an effective and medically-necessary treatment plan for patients with uveitis.

Clinical characteristics of intermediate uveitis in adults according to criteria of the SUN working group.

PURPOSE: To analyse the clinical characteristics of adult patients with pars planitis (PP-IU), non-pars planitis (NPP-IU) and multiple sclerosis-associated intermediate uveitis (MS-IU) and distinguish between groups. METHODS: Seventy-three adult patients with intermediate uveitis (IU) reviewed retrospectively and divided as PP-IU, NPP-IU and MS-IU according to 'The standardization of uveitis nomenclature working group classification criteria.' Demographic and clinical characteristics, OCT and fluorescein angiography (FA) findings, complications and treatments were recorded. RESULTS: A total of 134 eyes of 73 patients were included, and 42 of the patients were classified as PP-IU, 12 as NPP-IU, and 19 as MS-IU. If a patient presenting with blurred vision, or tent-shaped vitreous band/snowballs/snowbank on examination, or vascular leakage on FA and accompanying neurological symptoms, the frequency of demyelinating plaque detection on cranial MRI and the risk of MS-IU increased. Mean BCVA was increased from 0.22 ± 0.30 logMAR to 0.19 ± 0.31 logMAR (p = 0.021). Gender, initial BCVA, snowbank formation, disc oedema and periphlebitis on examination, and disc leakage/occlusion on FA were found predictive of decreased BCVA at final visit (p < 0.05). CONCLUSIONS: The clinical features of these three groups are similar, some features that can guide the differential diagnosis. It may be recommended to periodically evaluate "suspicious" patients with MRI for MS.

Bilateral exudative retinal detachment, unusual pattern of uveitis with multiple sclerosis.

MS (Multiple sclerosis) associated uveitis used to have limited phenotypes. Bilateral exudative retinal detachment has never been recognized as a pattern of MS-associated uveitis. We are reporting a patient with multiple sclerosis who presented initially with the usual pattern of intermediate uveitis and later developed bilateral exudative retinal detachment.

Correlation between Morphological Characteristics of Macular Edema and Visual Acuity in Young Patients with Idiopathic Intermediate Uveitis.

Background and Objectives: Macular edema (ME) is a common complication of intermediate uveitis (IU). It is often responsible for a decrease in visual acuity (VA). Three distinct patterns of macular edema have been described in intermediate uveitis, namely, cystoid macular edema (CME), diffuse macular edema (DME), and serous retinal detachment (SRD). The current study aims to describe the characteristics of macular edema in young patients with idiopathic intermediate uveitis and to correlate its features with VA using spectral domain optical coherence tomography (SD-OCT). Materials and Methods: A total of 27 eyes from 18 patients with idiopathic IU complicated by ME were included in this retrospective study. All patients underwent SD-OCT; data were gathered at the onset of ME. Best-corrected VA (BCVA) was correlated with the morphological features of ME. Results: BCVA was negatively correlated with Ellipsoid Zone (EZ) disruption (p = 0.00021), cystoid pattern (p = 0.00021), central subfield thickness (CST) (p < 0.001), and serous retinal detachment (0.037). Conclusions: In ME secondary to idiopathic IU, VA negatively correlates with Ellipsoid Zone disruption and increases in CST. Moreover, vision is influenced by the presence of cysts in the inner nuclear and outer nuclear layers and by the neuroepithelium detachment.

Macular vessel densities by optical coherence tomography angiography in patients with intermediate uveitis.

Purpose: To evaluate the macular microvascular changes in patients with intermediate uveitis (IU) using optical coherence tomography angiography (OCT-A) and to determine the relationship of OCT-A measurements with disease duration and activity. Methods: This cross-sectional study was performed at the uvea department of a tertiary hospital. Patients with IU (8 women, 8 men; mean age: 28.80 ± 12.80 years) were included in the study. The macular thickness measurements obtained by optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering, Heidelberg, Germany) and macular superficial and deep vessel density (VD) parameters obtained by OCT-A (Avanti RTVue-XR; Optovue, Fremont, CA, USA) were compared with healthy subjects (12 men, 22 women; mean age: 28.40 ± 8.32 years). Eyes with pathology including marked obvious edema in the macula were not included in the study. Results: The macular thickness was found to be higher in the patient group (p < 0.001). The deep and superficial VD measurements in almost all quadrants in both superficial and deep layers were significantly lower in the IU patient group (p < 0.05). Macular thickness was increased in the active state of IU (p = 0.03), however, none of the OCT-A parameters showed a significant difference between active and inactive IU patients (p > 0.05). No correlation was observed between OCT-A parameters and total IU disease duration. Conclusion: Quantitative analyses of macular vascular structures demonstrate significantly reduced VD in both superficial and deep retinal layers in IU patients. Considering the importance of the macula in visual prognosis, OCT-A can provide crucial data for the monitoring and follow-up of IU patients.