Intravitreal faricimab as an adjuvant in the management of tubercular uveitis.

PURPOSE: To report the use of intravitreal faricimab used as an adjunct in the management of intraocular tuberculosis (IOTB) in a patient with occlusive retinal vasculitis (ORV) and choroiditis. METHODS: A case report. RESULTS: A 27-year-old Asian male presented with bilateral choroiditis and ORV complicated by retinal neovascularization and vitreous hemorrhage in one eye. The patient had a positive tuberculin skin test, indeterminate interferon-gamma release assay, and Ghon's focus on chest radiography. With a diagnosis of IOTB, the patient was treated with anti-tubercular therapy. Due to the significant vitreous hemorrhage, he underwent pars plana vitrectomy in one eye. The patient received bilateral faricimab. Within a week of the injection, he had a near-complete resolution of the extensive choroidal and retinal vascular inflammation. CONCLUSIONS: Intravitreal faricimab, given its angiopoietin-2 (ang2) inhibition and anti-vascular endothelial growth factor action, maybe a helpful adjunct in IOTB. Whether ang2 inhibition provides any additional benefit needs further evaluation in extensive studies.

Impact of adalimumab in patients with active non-infectious intermediate, posterior, and panuveitis in real-life clinical practice: HOPE study.

BACKGROUND/AIM: This study evaluated real-life adalimumab impact in patients with active non-infectious intermediate, posterior, or panuveitis (NIIPPU). METHODS: Adults with active NIIPPU received adalimumab in this prospective, observational study (06/2017-04/2020). Patients were evaluated at baseline (V0) and four follow-up visits over 12 months (V1-V4). PRIMARY ENDPOINT: proportion of patients achieving quiescence (anterior chamber (AC) cells grade and vitreous haze (VH) grade≤0.5+ in both eyes, no new active chorioretinal lesions) at any follow-up visit. Secondary endpoints: proportion of patients achieving quiescence at each visit; proportion of patients maintaining response; and proportion of patients with flares. Workability, visual function, healthcare resource utilisation, and safety were evaluated. RESULTS: Full analysis set included 149 patients. Quiescence at any follow-up visit was achieved by 129/141 (91%) patients. Quiescence at individual visits was achieved by 99/145 (68%), 110/142 (77%), 102/131 (78%), and 99/128 (77%) patients at V1-V4, respectively. Number of patients in corticosteroid-free quiescence increased from 51/147 (35%; V1) to 67/128 (52%; V4; p<0.05). Proportion of patients with maintained response increased from 89/141 (63%; V2) to 92/121 (76%; V4; p<0.05) and proportion of patients with flare decreased from 25/145 (17%; V1) to 13/128 (10%; V4; p=0.092). Workability and visual function improved throughout the study. Proportion of patients with medical visits for uveitis decreased from 132/149 (89%; V0) to 27/127 (21%; V4). No new safety signals were observed. CONCLUSION: These results demonstrated adalimumab effectiveness in improving quality of life while reducing economic burden of active NIIPPU.

Retinal relaxation following membrane peeling: Effect on vision, central macular thickness, and vector analysis of motion.

BACKGROUND: Epiretinal membranes (ERM) form as a result of an inward displacement of retinal structures. Removal of an ERM leads to the outward displacement of retinal vessels and visual improvement. PURPOSE: The aim of the study was to evaluate the direction and extent of displacement of retinal/superficial vascular structures after a membrane peeling procedure by means of image comparison and in selected cases, a vector analysis of displacement. METHODOLOGY: Scanning laser ophthalmoscope images of the retina of eyes undergoing ERM peeling were compared before and 6 months after surgery. Stratification was made between prominent and limited displacement, with assessment of visual acuity (VA), and central macular thickness (CMT). In three cases, using the optic nerve as reference, 50 landmarks were chosen within the posterior pole along large and small vascular structures allowing the construction of a vector map of displacement over 1 year. RESULTS: Nine eyes with prominent and six with limited displacement were assessed. Improvement in VA was similar for both groups, while CMT drop was greatest for the worst group. Vector analysis showed that most vascular movement occurs over the first 6 months, covers most of the posterior retina, is centered around distinct nodes, and may lead to several hundred micrometers of displacement. CONCLUSIONS: Superficial retinal relaxation has no direct implication on visual recovery. It originates in nodes of retinal contraction. Its extent can be significant, covering most of the posterior pole. RELEVANCE FOR PATIENTS: A better understanding of retinal relaxation following the peeling of ERM may help better understand when intervention is required and which part of the membrane is critical to surgical success.

Intravitreal methotrexate in the management of presumed tuberculous serpiginous-like choroiditis.

PURPOSE: To report on the use of intravitreal methotrexate (IVT MTX) as part of treatment of presumed tuberculous serpiginous-like choroiditis progressing despite the use of tuberculostatics. METHODS: Case series of patients suffering from serpiginous-like choroiditis with positive tuberculin skin test who received IVT injections of MTX as part of treatment. Ocular disease was active despite the use of systemic tuberculostatic (isoniazid, rifampicin, pyrazinamide, and ethambutol), and choroidal lesions showed signs of progression. A single injection of IVT MTX (400 µg/0.1 mL) was administered in the eye with macular-threatening features. Change in visual acuity, appearance of the lesion, and staining patterns on angiography were among the main outcome measurements. RESULTS: Three eyes from two patients were included. Both cases presented bilateral involvement with mild vitritis. In all three eyes, choroidal lesions healed within the first month after an IVT MTX injection with visual acuity improvement in two. No adverse reaction was related to the medication or to the procedure. Patients were followed for a mean of 13.5 months after being injected. CONCLUSION: The use of IVT MTX seems effective in the management of the inflammatory component of tuberculous serpiginous-like choroiditis, whereas systemic tuberculostatics are aimed at controlling the infectious one.

Cataract surgery with primary intraocular lens implantation in children with uveitis: long-term outcomes.

PURPOSE: To report long-term outcomes of cataract surgery with primary posterior chamber intraocular lens (IOL) implantation in children with chronic uveitis. SETTING: Department of Ophthalmology, Pitié-Salpêtrière Hospital, Paris, France. DESIGN: Case series. METHODS: This case series comprised patients younger than 16 years with chronic uveitis who underwent phacoemulsification with primary implantation of a heparin surface-modified poly(methyl methacrylate) posterior chamber IOL in the capsular bag. The intraocular inflammation was fully controlled for at least 3 consecutive months before surgery in all cases. The main outcome measures were final corrected distance visual acuity (CDVA), postoperative inflammation, complications, and level of immunosuppressive treatment. RESULTS: Twenty-two eyes of 16 children (7 girls, 9 boys; median age at surgery 9.5 years old) were included. Underlying uveitic entities were juvenile idiopathic arthritis in 9 patients; idiopathic uveitis in 4; and Behçet disease, sarcoidosis, and varicella zoster-associated uveitis in 1 patient each. The final CDVA was 0.3 logMAR or better in all cases. Postoperative complications included posterior capsule opacification requiring laser capsulotomy in 2 eyes, glaucoma in 4 eyes, and cystoid macular edema/macular dysfunction in 3 eyes. The mean dose of oral prednisone was 29.5 mg/day preoperatively and 8.13 mg/day at the last follow-up. The median follow-up was 6 years (range 5 to 19 years). CONCLUSION: The results indicate that uveitis is not a formal contraindication to primary IOL implantation in the management of pediatric cataract surgery in cases with full control of intraocular inflammation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Intravitreal bevacizumab as first local treatment for uveitis-related choroidal neovascularization: long-term results.

PURPOSE: To report long-term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis. METHODS: Files of patients receiving 1.25 mg/0.05 ml bevacizumab as primary local treatment for CNV were retrospectively reviewed. Main outcomes were change in best-corrected visual acuity (BCVA) and central foveolar thickness (CFT), treatment-related adverse events, and number and frequency of injections. RESULTS: Fifteen eyes from fifteen patients were included. Multifocal choroiditis and panuveitis were the diagnosis in seven, ampiginous choroiditis in two, and for six remaining, serpiginous choroiditis, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, punctuate inner choroidopathy, tuberculosis and idiopathic inflammation. In 13 eyes, neovascularization was subfoveal, and peripapillary in two. Intraocular inflammation was strictly controlled in all cases by the time of injections. BCVA improved from logMar 0.53 to logMar 0.29 in 12 eyes (80%), while CFT decreased from 239.06 to 195.2 µm in 13 (87%). Twelve eyes received more than one injection; mean number in this group was 4.25 (2-8), and frequency 1 every 12.97 weeks. There were no adverse events related to bevacizumab or the procedure. Median follow-up was 17.6 months (8-25). CONCLUSIONS: First-intention IVT bevacizumab for inflammatory CNV showed transient improvement in BCVA and CFT, in eyes under controlled inflammation. Reinjection was needed in most cases. Further work should conclude about safety related to repeated injections.

The role of steroids in the management of uveitic macular edema.

PURPOSE: To review the role of steroids in the management of uveitic macular edema. METHODS: Review of recent literature on the physiopathology of macular edema and clinical trials involving steroids as main treatment of uveitic macular edema. RESULTS: The steroid-glucocorticoid receptor complex regulates the action of specific steroids allowing transactivation or repression of a common as well as a unique set of genes. This specificity may help explain differences observed in the side effect profile of commonly used intraocular steroids (dexamethasone, fluocinolone, triamcinolone) whose ability to activate glucocorticoid receptors in model systems is very similar. Sustained delivery devices provide long-term remission of macular edema but with an increased incidence of cataract and glaucoma procedures. The exact incidence is dependent on the specific steroid, the mode of delivery, and the time since injection/placement.Steroid therapy is able to target many important pathways in uveitic macular edema, achieving good clinical results. Secondary adverse effects are still a matter of concern limiting their use. CONCLUSIONS: Steroid therapy remains a mainstay in the management of uveitic macular edema. Local administration precludes systemic adverse effects even though the risk of developing cataract or glaucoma remains an important issue. New slow release devices are thought to improve safety profile while keeping therapeutic advantages.

Uveitis related to juvenile idiopathic arthritis: familial cases and possible genetic implication in the pathogenesis.

PURPOSE: To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis. DESIGN: Retrospective observational case series. METHODS: Clinical data from patients who present familial JIA-associated uveitis are described and possible genetic influence in disease etiology is reviewed. RESULTS: Two sisters, 6- and 7-year-old, developed bilateral anterior uveitis related to oligoarticular JIA. Arthritis in both began by the age of 18 months; uveitis developed simultaneously in one of them and less than one year after arthritis in the other one. Both received topical and systemic treatment to control the ocular disease. Glaucoma occurred in both cases and bilateral cataract in one case. In the other family, a 2-year-old girl developed unilateral uveitis in the context of oligoarticular JIA which was diagnosed by 1-year-old. The disease became soon bilateral and she received topical and systemic immunosuppressive treatment. Her mother suffered from bilateral anterior uveitis associated to oligoarticular inflammatory disease during her infancy, later diagnosed as JIA-associated uveitis. CONCLUSIONS: Familial cases of JIA uveitis, although not very common, support the possible role of genetic influence in the pathogenesis of the disease, with horizontal and vertical inheritance being possible. The evolution of ocular disease is similar to the non-familial cases, except for an earlier age of onset.

Cannabinoid receptors in conjunctival epithelium: identification and functional properties.

PURPOSE: Preservation of the ocular surface barrier requires complex control of epithelial cell proliferation and inflammation mechanisms. The endocannabinoid system may be regulating these processes. Therefore, the authors explored the presence and properties of cannabinoid receptors (CB1 and CB2) in conjunctival epithelial cells. METHODS: The authors used immunohistochemistry to detect CB1 and CB2 in normal mouse conjunctiva, human conjunctival cryosections and impression samples, and IOBA-NHC cells, a human conjunctiva-derived cell line. The presence of CB1 and CB2 proteins and transcripts was studied in IOBA-NHC cells by Western blot and RT-PCR, respectively. The authors also used this cell line to assay cannabinoid ligand-induced changes in cAMP levels, cell growth, and tumor necrosis factor-alpha (TNF-alpha)-induced activation of c-jun N-terminal kinase (JNK) and nuclear factor-kappaB (NF-kappaB). RESULTS: Mouse and human conjunctival epithelial cells displayed CB1 and CB2 proteins and transcripts. Cannabinoid receptor activation decreased cAMP levels in IOBA-NHC cells, and specific CB1 and CB2 antagonists canceled this effect. Cannabinoid ligands also increased cell growth and blocked stress pathways activated by TNF-alpha in vitro. CONCLUSIONS: Cannabinoid receptors are present in mouse and human conjunctival cells. Functional responses, such as decreased cAMP levels, proliferation, and modulation of stress signaling pathways, were mediated by CB1 and CB2 stimulation. Thus, these receptors might be involved in the regulation of epithelial renewal and inflammatory processes at the ocular surface.