New insights in pathogenic mechanism of hydroxychloroquine retinal toxicity through optical coherence tomography angiography analysis.

INTRODUCTION: There is only a unique report with a small sample size studying hydroxychloroquine (HCQ) retinal toxicity with swept-source (SS) optical coherence tomography angiography (OCTA). The aim of this study was to quantify OCTA quantitative parameters in patients who underwent HCQ therapy. METHODS: We conducted a retrospective study. The study included 43 eyes of 22 patients taking HCQ for more than 5 years (high-risk group), 57 eyes of 29 patients taking HCQ for 5 years or less (low-risk group) and 25 eyes of 50 age-matched healthy controls. OCTA quantitative parameters (vessel density (VD) and foveal avascular zone (FAZ) area in superficial capillary plexus (SCP), middle capillary plexus (MCP), deep capillary plexus (DCP), total capillary plexus (TCP), and choriocapillaris (CC)) were recorded. RESULTS: In the low-risk group, VD in the SCP and MCP was increased compared to control group (p value <.05). In the high-risk group, VD in the SCP, MCP and TCP was increased (p value <.05). The subgroup analysis revealed an increased VD at SCP in systemic lupus erythematosus (SLE) high-risk patients, an increased VD at TCP and CC in rheumatoid arthritis (RA) high-risk subjects, and a decreased VD at CC level in the high-risk group patients with Sjögren's syndrome (SS) and connective tissue disease (CTD) (p value <.05). Furthermore, we demonstrated a significant enlargement of FAZ area at MCP level in the high-risk group patients with SS and CTD (p value <.05). CONCLUSION: We demonstrated an increase of VD in patients who underwent HCQ treatment, so we suggest that HCQ retinal toxicity is not vascular mediated.

Case Report: Ipilimumab-induced Multisystem Autoimmune-like Toxicities Suggestive of Vogt-Koyanagi-Harada-like Syndrome.

SIGNIFICANCE: The emergence of new cancer therapies has dramatically improved outcomes in metastatic melanoma. Immune checkpoint inhibitors have been the most effective treatment. Although, as a direct consequence of the immune dysregulation induced by them, adverse effects termed immune-related adverse events are observed in more than 60% of the patients. PURPOSE: We describe the clinical presentation of Vogt-Koyanagi-Harada-like syndrome in a patient with concomitant systemic melanoma treatment with ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 blocker. METHODS: This study aimed to report a case of ipilimumab-induced vitritis, papillitis, and skin and auditory signs suggestive of Vogt-Koyanagi-Harada-like syndrome. CASE REPORT: A 64-year-old woman with metastatic melanoma presented with bilateral blurred vision and hearing loss upon completion of three cycles of treatment with ipilimumab. Ophthalmologic examination revealed a bilateral granulomatous uveitis with intense vitritis and papillitis. The result of optical coherence tomography was normal, and fluorescein angiography confirmed the bilateral papillary edema. Ipilimumab was withdrawn, and treatment with oral and systemic steroids led to a rapid improvement in the ophthalmologic and auditory manifestations. Three months after initial presentation, the patient developed vitiligo and poliosis. CONCLUSIONS: Vogt-Koyanagi-Harada-like syndrome can develop in the process of immunological deregulation by ipilimumab in the treatment of metastatic melanoma and can correlate temporally with the efficacy of the drug in tumor regression. These observations may help elucidate the underlying mechanism of Vogt-Koyanagi-Harada syndrome as well as the relation between tumor-associated tolerance and autoimmunity.

Rituximab in the treatment of Susac's syndrome: Report of a case.

SIGNIFICANCE: Susac's syndrome is a rare retinocochleocerebral immune-mediated endotheliopathy and clinically manifests as a pathognomonic triad of encephalopathy, hearing loss, and branch retinal artery occlusion. This triad is rarely present at symptom onset, thus, it is often initially misdiagnosed. To date, Susac's syndrome has persisted as an elusive entity and there are numerous treatment regimens proposed with varying effectiveness mainly based on case series. PURPOSE: To report our 12-month follow-up experience in the treatment of Susac's syndrome with rituximab. CASE REPORT: A 25-year-old female presenting with headache, paresthesias, tinnitus, peripheral vertigo, and a branch retinal artery occlusion. The patient had a personal history of anxiety-depressive disorder. After discarding other infectious/autoimmune conditions and magnetic resonance imaging suggestive findings of Susac's syndrome, we observed a prompt response to the combination of intravenous immunoglobulin, corticosteroids, and rituximab. CONCLUSION: A standard treatment paradigm is lacking in Susac's syndrome as randomized controlled trials do not exist. There are no definitive scores to predict its outcome, and early diagnosis is important as the organs involved can easily become irreversibly damaged. Thus, patients with Susac's syndrome must be treated promptly and aggressively. Our report highlights the possibility of positive long-term prognosis with an early use of rituximab. However, a systematic therapeutic approach on the basis of controlled trials is mandatory to develop a consensus.

CRMP-5-IgG Antibody: role in the bilateral uveitis with swollen disc.

Autoimmunity against collapsin response-mediator protein-5 (anti-CRMP-5) has been associated with ocular inflammation in paraneoplastic syndrome. We present a 59-year-old Caucasian man with optic neuritis and vitreous cells in both eyes (OU), at different stages. Despite the fact that the patient did not have any systemic disease, we suspected a paraneoplastic syndrome and requested CRMP-5-IgG and a mediastinoscopy. After performing the tests, a small cell lung carcinoma was diagnosed. Autoantibody CRMP-5-IgG positivity and optic neuritis combined with vitreous inflammation was defined as a paraneoplastic entity, avoiding vitreous biopsy and allowing us to suspect malignancy before systemic symptoms appeared.

Aqueous Humor Levels of Different Interleukins 1-ß, 2, 6 and 10, Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in Uveitis Treated with Adalimumab.

PURPOSE: To assess changes in aqueous humor levels of different interleukins (IL), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients with uveitis treated with adalimumab. METHODS: In this study, 24 aqueous humor samples including 12 pre- and post-treatment samples from 6 patients with uveitis treated with subcutaneous adalimumab and 12 samples from patients with cataracts (serving as controls) were evaluated. The levels of IL-1ß, IL-2, IL-6, IL-10, TNF-α and VEGF were measured using a Luminex(®) 200™ flow cytometer (Merckmillipore, Merck KGaA, Darmstadt, Alemania) and a highly sensitive ELISA system. RESULTS: The levels of IL-1ß, IL-2, IL-6 and IL-10 in the aqueous humor before and after treatment with adalimumab did not show significant differences. Aqueous VEGF levels significantly reduced after treatment with adalimumab (P = 0.028). Aqueous TNF-α levels did not significantly change after treatment with adalimumab, however the post-treatment level was significantly higher in patients as compared to control subjects (P = 0.032). IL-2 showed significantly higher levels in uveitis patients before treatment as compared to controls (P = 0.024), while its post-treatment levels were almost normalized. CONCLUSION: Decrease in the aqueous humor levels of VEGF and IL-2 after treatment with systemic adalimumab indicates that anti-TNF-α therapy induces modifications of some inflammatory mediators involved in the pathogenesis of uveitis. Aqueous humor samples may be useful to assess the effect of adalimumab on intraocular inflammation through measurement of cytokines.