This report highlights the administration of upadacitinib in four adolescents with idiopathic chronic refractory panuveitis who showed an inadequate response to systemic glucocorticoids, immunosuppressive agents, and anti-TNF biologic therapy. We present four cases: two 13-year-old boys, one 15-year-old boy, and one 14-year-old girl, each with a history of idiopathic panuveitis that persisted for 4, 8, 4, and 5 years, respectively. Upadacitinib effectively reduced ocular inflammation in all four cases during the first month of treatment. Following upadacitinib treatment, adalimumab was discontinued or extended, and the immunosuppressive agents were gradually tapered. In two cases, it led to complete resolution of the anterior segment and vitreous inflammation and significant improvement in the posterior segment. However, two patients developed upper respiratory tract symptoms at the second and fifth months, respectively, both of which were associated with recurrence of ocular inflammation and required high-dose glucocorticoids for control. No other serious adverse events were documented in the four patients during the nine to ten months follow-up period. These cases indicate that upadacitinib may be an effective treatment strategy for adolescents with idiopathic chronic refractory panuveitis. However, the potential risk of infections should be considered and monitored.

Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging. The objective of this study was to evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis. A retrospective chart review of non-infectious PGU occurring in children before the age of 16 years (recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023) was undertaken. We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with JIA, and 1 with Vogt-Koyanagi-Harada disease. The median age at diagnosis was 9.8 years (range 7.2-12.5). The M:F sex ratio was 0.52. The most common types of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%), particularly in cases of panuveitis. The most commonly used treatments were systemic CSs (72%) and MTX (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years. We report the largest cohort of PGU. The cases of PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.

To report primary vitreoretinal lymphoma after surgical 0.59 mg fluocinolone acetonide implant (FAi) exchange in a patient treated with adalimumab for idiopathic bilateral panuveitis. Retrospective case review. A 37-year-old woman with bilateral idiopathic panuveitis, who had favorable responses to previous FAi surgical implants, presented with right eye recurrent intraocular inflammation and cystoid macular edema that partially responded to systemic adalimumab. Her FAi was replaced, given her previous favorable response. She developed postoperative ocular inflammation transiently responsive to two serial vitreous taps and injections of intravitreal antimicrobials and then worsening inflammation and new layered flocculant material. Diagnostic vitrectomy showed a few atypical lymphocytes and cultures were negative. At postdiagnostic vitrectomy Month 1, flocculant material recurred. Aqueous cytology and flow cytometry revealed large CD45-positive B cells suspicious for lymphoma. Postoperatively, she revealed that she was pregnant. She was treated with eight monthly intravitreal methotrexate injections and postpartum consolidation radiotherapy. Subsequent repeat cytology, flow cytometry, and corneal pathologic examination revealed large B cells that were CD20 positive, and next-generation sequencing detected a dominant monoclonal B-cell population, diagnostic of PVRL. Nineteen months after FAi exchange, she developed an area of enhancement in the lateral aspect of the right frontal lobe on brain MRI, consistent with central nervous system involvement. The authors present a unique case of PVRL masquerading as postoperative endophthalmitis after FAi exchange in an eye with chronic panuveitis treated with adalimumab immunosuppressive therapy. The authors hypothesize that there may be a causal relationship between adalimumab and PVRL.

A 40-year-old Asian Indian woman, diagnosed as having idiopathic panuveitis (elsewhere) 3 years earlier and being treated with oral steroids (20 mg/day) and methotrexate (25 mg/week), presented to us with worsening vision in both eyes. Her best corrected visual acuity (BCVA) was perception of light in her right eye and counting fingers close to face in her left eye. A slit lamp examination showed an anterior chamber (AC) reaction (1+) in both eyes with posterior synechia, a total cataract in her right eye, and pseudophakia in her left eye. The left fundus showed vitritis, vitreous membranes, chorioretinitis, multifocal areas of retinitis, and retinal vascular sheathing. A systemic examination showed extensive multifocal areas of tinea corporis on the hands and torso. Owing to the leukocytosis (22,000 cells/mm3), diagnostic vitrectomy was initially deferred and 100 mg of oral itraconazole was given twice a day for 3 months. The vitritis improved a little and her total white blood cell (WBC) count improved with treatment of the skin infection. Following a diagnostic vitrectomy later in her left eye, resolving areas of retinitis were seen. Complete resolution of eye inflammation was seen at the end of 6 weeks. At the 6-month follow-up, her BCVA was 6/18 in left eye and she was off oral steroids and methotrexate, with no recurrence of inflammation. We speculate a probable association between the ocular inflammation and extensive tinea corporis based on the therapeutic response to itraconazole.

We report 2 patients with chronic panuveitis who were treated with fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals Inc, Watertown, MA) intended to control ocular inflammation long term without interfering with systemic immunity. The first case was a man in his 50s referred for ocular complaints in the setting of ongoing immunotherapy for the treatment of metastatic melanoma. He was diagnosed with bilateral drug-induced panuveitis. Treatment objectives were outlined as reduction of inflammation, prevention of uveitis recurrence, and continuation of systemic immunomodulatory therapy in order to maintain malignancy remission; the patient was treated with fluocinolone acetonide intravitreal implant bilaterally and at 18 months' follow-up had 20/20 bilateral visual acuity and no inflammation. In case 2, a woman in her 70s, presented with a 2-month history of worsening floaters and blurry vision. She was phakic, with bilateral nuclear sclerotic cataracts, 1+ vitreous cells and 2+ haze, diffuse vasculitis, and central leakage around the optic nerve and posterior pole. She was diagnosed with bilateral idiopathic panuveitis with retinal vasculitis. The patient continued to do well at 1 year following intravitreal implantation with fluocinolone acetonide.