Immune Checkpoint Inhibitor Treatment and Ophthalmologist Consultations in Patients with Malignant Melanoma or Lung Cancer—A Nationwide Cohort Study

Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. Results: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4–1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83–27.31) and men (4.87 (95% CI 1.79–13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29–2.34) and MM (HR 3.21 (95% CI 2.31–4.44). Conclusions: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI.

Role of Janus Kinase (JAK) Inhibitor in Autoimmune Ocular Inflammation: A Systematic Review

Purpose. To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases. Methods. We identified relevant literature by screening the MEDLINE, PubMed, and Cochrane databases for randomized controlled trials, cohort studies, case controls, and case reports. Results. Seven studies, including 11 patients, were included in the final systematic analysis. Of the 11 patients, there were 5 cases of juvenile idiopathic arthritis- (JIA-) associated uveitis, 1 case of rheumatoid arthritis- (RA-) associated keratitis, 1 case of RA-associated scleritis, 1 case of psoriasis-associated conjunctivitis, 2 cases of noninfectious scleritis, and 1 case of uveitis with suspected autoimmune disease. None of these 11 patients responded adequately to conventional treatments, including biological agents; these were all refractory cases and switched to JAK inhibitor therapy. Irrespective of whether they were suffering from uveitis, scleritis, or other types of ocular inflammation, all 11 patients showed an improvement to JAK inhibitors without significant side effects. Different types of JAK inhibitors might be associated with different responses when used to treat ocular inflammation. Conclusions. JAK inhibitors may represent an alternative treatment option for patients with autoimmune ocular inflammation.

Anti-inflammatory Effects of GTE in Eye Diseases

Ocular inflammation is a common complication of various eye diseases with wide consequences from irritations to potentially sight-threatening complications. Green tea is a popular beverage throughout the world. One of the proven health benefits of consuming green tea extract (GTE) is anti-inflammation. Catechins are the biologically active constituents of GTE. In in vitro and in vivo studies, GTE and catechins present inhibition of inflammatory responses in the development of ocular inflammation including infectious, non-infectious or autoimmune, and oxidative-induced complications. Research on the ocular inflammation in animal models has made significant progress in the past decades and several key disease mechanisms have been identified. Here we review the experimental investigations on the effects of GTE and catechins on various ocular inflammation related diseases including glaucoma, age-related macular degeneration, uveitis and ocular surface inflammation. We also review the pharmacokinetics of GTE constituents and safety of green tea consumption. We discuss the insights and perspectives of these experimental results, which would be useful for future development of novel therapeutics in human.

Spiroplasma species as a rare cause of congenital cataract and uveitis: a case series

Background To date, only four cases of ocular spiroplasma infection have been reported in the entire ophthalmic literature. We add two more cases to raise awareness of this sight-threatening congenital disease that manifests as cataract with ocular inflammation. Case presentation Both infants were referred for cataracts associated with ocular inflammation. Case 1, a 3-week-old neonate presented with unilateral cataract, ocular inflammation and elevated intraocular pressure. Case 2 was a 3-month-old infant with bilateral cataract and panuveitis. Lensectomies with or without vitrectomy and subsequent analyses of the specimens were performed. Transmission electron microscopy and multiplex polymerase chain reaction or 16 s rRNA gene polymerase chain reaction revealed spiroplasma species. Conclusions Spiroplasma as a very rare cause for congenital cataract might be underdiagnosed. We recommend performing polymerase chain reaction to probe for spiroplasma species in congenital cataracts with an inflammatory component.

Methotrexate Effectively Controls Ocular Inflammation in Japanese Patients With Non-infectious Uveitis

This single-center retrospective study investigated the clinical characteristics and efficacy of methotrexate (MTX) for the treatment of non-infectious uveitis for more than 6 months at Hiroshima University, from February 2016 to May 2021. Outcome variables included changes in systemic immunosuppressive treatment and intraocular inflammation. Out of 448 patients with non-infectious uveitis, 35 patients (14 male patients and 21 female patients; 65 eyes) treated with MTX for more than 6 months were analyzed. There were 15 patients with anterior uveitis and 20 with posterior and panuveitis. The mean dose of systemic corticosteroids decreased from 12.1 mg/day at baseline to 1.3 mg/day at 6 months and 0.6 mg at 12 months after starting MTX, and approximately 90% of patients were corticosteroid-free at 12 months. The percentage of eyes with inactive uveitis at 6, 12, and 24 months was 49.2%, 59.6%, and 90.0%, respectively. Mean relapse rate score also significantly decreased from 2.88 at baseline to 0.85 at 12 months (p < 0.001). Inflammatory control was achieved with MTX doses of 8–16 mg/week, with a median dose of 12 mg/week. Adverse effects of MTX were observed in 34.3% of patients, and 11.4% required discontinuation; most commonly hepatotoxicity (58.3%), followed by fatigue (25.0%), and hair loss (16.7%). No significant differences were found between the survival curves of patients with anterior uveitis and posterior/panuveitis (Wilcoxon rank-sum test). The percentage of eyes without IOP-lowering eye drops was significantly higher in patients with posterior/panuveitis at 24 months (p = 0.001). Our study suggests that MTX is effective in controlling ocular inflammation for Japanese patients with non-infectious uveitis. Relatively high incidence of MTX-related adverse effects in the Japanese population indicates that careful monitoring and dose adjustments are crucial for the long-term use of this therapy.

Conjunctivitis, episcleritis and anterior uveitis as the first presenting features of granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) is a rare disorder characterised by inflammation of small-sized and medium-sized blood vessels that result in damage to various organ systems, but it most commonly affects the respiratory tract and kidneys. It is one of the few entities that can present with ocular inflammation as well as renal impairment at the same time. We describe a case of a 38-year-old man with conjunctivitis, episcleritis, anterior uveitis as a first manifestation of GPA. His presentation with red eye and anterior uveitis prompted further workup, which revealed acute renal failure (creatinine 442 mmol/L), elevated inflammatory markers (erythrocyte sedimentation rate of 85 mmol/hour and C reactive protein of 72 mg/L), and a c-antineutrophil cytoplasmic antibody titre >8. An urgent renal biopsy was performed demonstrating necrotising crescentic glomerulonephritis, which led to the final diagnosis of GPA. Treatment induction with intravenous methylprednisolone and plasmapheresis followed by an oral prednisone taper and intravenous rituximab infusions leading to resolution of all symptoms and normalisation of kidney function. This report highlights conditions that can present with both ocular inflammation and renal dysfunction with a focus on GPA and its ocular manifestations.