Adalimumab for the Treatment of Non-Infectious Uveitis: A Real Life Experience.

OBJECTIVE: To describe the efficacy and safety of adalimumab for the treatment of non-infectious uveitis (NIU) in four Uveitis Units from tertiary Spanish hospitals. METHODS: Multicenter and retrospective clinical cohort study including all patients with NIU treated with adalimumab from January 2012 to October 2022 in four uveitis units was performed. Efficacy was measured with the number of relapses, ocular inflammation and reduction in immunosuppression and corticosteroid dosage before and after adalimumab use. We collected data regarding adverse effects and examined the immunogenicity of adalimumab. RESULTS: One hundred and twenty-two patients (59% females), with a mean age of 48.6 years (SD = 14.8) accounting for 217 eyes were included. The majority (92.6%) were Caucasian. Uveitis analyzed were predominantly panuveitis (34.7%), bilateral (77.9%), acute (41.5%), and non-granulomatous (90%). Most of them were immune mediated (42.6%), and the main reason to initiate adalimumab was refractory disease (96.7%). The analysis was statistically significant due to the reduction in the number of immunosuppressive drugs as well as the dose of oral corticosteroids and the number of relapses during follow-up (p < 0.001). The decrease in ocular inflammation parameters and the improvement in visual acuity (p < 0.05) were also significant. There were no deaths due to the drug and only one reported case of serious infection. In total, 10.9% of 73 patients tested developed anti-adalimumab antibodies and 4.1% lupus-like. CONCLUSIONS: We consider adalimumab as a leading drug in the treatment of NIU with high safety and efficacy.

Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H.

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood-retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.

Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema.

PURPOSE: To assess whether serum cytokine and growth factor levels are associated with diabetic macular edema (DME) and uveitic macular edema (UME) objective severity. METHODS: Cross-sectional observational study of 81 patients (1 eye/patient) with DME (n=48) and UME (n=33). Macular edema (ME) was defined upon central macular thickness (CMT) ≥ 300 µm on spectral domain optical coherence tomography (OCT). Serum samples were obtained from peripheral blood and IL-1ß, IL-6, IL-8, IL-10, MCP-1, TNF-α, and VEGF levels were determined by Luminex analysis. Main outcome measure was the correlation between mediators' levels and CMT and macular volume (MV) on OCT for ME cases. RESULTS: In DME, IL-6 levels were found to significantly correlate with MV (r=0.324; p=0.028) whereas in UME, IL-8 was significantly associated with both CMT (r=0.401; p=0.021) and MV (r=0.391; p=0.024). IL-8 independently correlated with CMT (ß=177.2; p=0.033) and MV (ß=3.17; p=0.008) in UME multivariate model. CONCLUSION: Peripheral blood IL-6 and IL-8 levels could play a role in the severity of DME and UME, respectively. IL-8 even seems to be independently associated with CMT and MV in UME cases. Such systemic implications could enforce DME and UME personalized diagnostic and therapeutic approaches.

Multimodal image characterization of paravenous atrophy.

Objective: The objective is to describe a clinical case of paravenous atrophy using a multimodal image. Methods: A 48-year-old man was visited and followed in the ophthalmology department of Hospital Clinic (Barcelona). Visual acuity, slit-lamp exam, retinography, autofluorescence, visual field, optical coherence tomography, and electrophysiology test were performed. Results: The patient had a history of Behcet's disease. Autofluorescence revealed hypoautofluorescence at the paravenous region, th visual field was also altered and electrophysiologic test were reduced. Conclusion: Paravenous atrophy is a rare entity not well described currently. Patients are frequently misdiagnosed. Multimodal image could help to characterize this condition properly and improve the management.

Nuevas técnicas de imagen en vasculitis retinianas / New imaging techniques in retinal vasculitis

El término vasculitis retinianas (VR) engloba un grupo de entidades potencialmente graves que forman parte de las enfermedades inflamatorias intraoculares que afectan al segmento posterior del ojo. Según la naturaleza del proceso inflamatorio, las VR se clasifican en predominantemente inflamatorias o isquemizantes (VR oclusivas). Su diagnóstico es clínico y su etiología puede ser infecciosa o inmunomediada. Pueden constituir cuadros oculares aislados o bien formar parte de una enfermedad sistémica potencialmente grave, de la que pueden ser la manifestación inicial. Las nuevas técnicas de imagen retiniana, como la angiografía fluoresceínica de campo amplio o la tomografía de coherencia óptica-angiografía, nos ayudarán a clasificar la VR y guiarán la sospecha diagnóstica. Las VR pueden representar un reto diagnóstico y requerir un abordaje multidisciplinar. Por ello, el conocimiento de las VR es importante para que se pueda establecer un diagnóstico temprano e instaurar el tratamiento adecuado (AU)

The term retinal vasculitis (RV) encompasses a heterogeneous group of sight-threatening conditions that are included in the intraocular inflammatory diseases that affect the posterior segment of the eye. Based on the nature of the inflammatory process, RV are classified into predominantly inflammatory or ischaemic (occlusive RV). The diagnosis is clinical and the aetiology can be infectious or non-infectious (immune-mediated). RV can be an isolated ocular syndrome or be associated with a systemic disease, of which they can represent the first manifestation. New retinal imaging techniques such as ultra-wide field fluorescein angiography and optical coherence tomography angiography will help us classify the RV and aid the diagnostic process, which can be challenging and require a multidisciplinary approach. Therefore, clinical knowledge of RV is essential for prompt diagnosis and to establish the appropriate treatment (AU)

New imaging techniques in retinal vasculitis. / Nuevas técnicas de imagen en vasculitis retinianas.

The term retinal vasculitis (RV) encompasses a heterogeneous group of sight-threatening conditions that are included in the intraocular inflammatory diseases that affect the posterior segment of the eye. Based on the nature of the inflammatory process, RV are classified into predominantly inflammatory or ischaemic (occlusive RV). The diagnosis is clinical and the aetiology can be infectious or non-infectious (immune-mediated). RV can be an isolated ocular syndrome or be associated with a systemic disease, of which they can represent the first manifestation. New retinal imaging techniques such as ultra-wide field fluorescein angiography and optical coherence tomography angiography will help us classify the RV and aid the diagnostic process, which can be challenging and require a multidisciplinary approach. Therefore, clinical knowledge of RV is essential for prompt diagnosis and to establish the appropriate treatment.

Evaluation of Objective Vitritis Grading Method Using Optical Coherence Tomography: Influence of Phakic Status and Previous Vitrectomy.

PURPOSE: To evaluate a proposed method for objective measurement of vitreous inflammation using a spectral-domain optical coherence tomography (SD OCT) device in a large cohort of uveitis eyes, including pseudophakic eyes and vitrectomized eyes. DESIGN: Retrospective, observational cohort study. METHODS: One hundred five uveitis eyes (105 patients) with different vitreous haze score grades according to standardized protocols and corresponding SD OCT images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, California, USA) were included. Clinical data recorded included phakic status, previous vitreoretinal surgery, and anterior chamber (AC) cells and flare. SD OCT images were analyzed using custom software that provided absolute measurements of vitreous (VIT) and retinal pigment epithelium (RPE) signal intensities, which were compared to generate a relative optical density ratio with arbitrary units (VIT/RPE-relative intensity) and compared to VHS. RESULTS: VIT/RPE-relative intensity showed a significant positive correlation with vitreous haze score (r = 0.535, P < .001) that remained significant after adjusting for factors governing media clarity, such as AC cells, AC flare, and phakic status (R(2)-adjusted = 0.424, P < .001). Significant differences were also observed between the different vitreous haze score groups (P < .001). Preliminary observation did not observe differences in VIT/RPE-relative intensity values between phakic and pseudophakic eyes (0.3522 vs 0.3577, P = .48) and between nonvitrectomized and vitrectomized eyes (0.3540 vs 0.3580, P = .52), overall and respectively for each vitreous haze score subgroup. CONCLUSIONS: VIT/RPE-relative intensity values provide objective measurements of vitreous inflammation employing an SD OCT device. Phakic status and previous vitrectomy surgery do not appear to influence these values, although these preliminary findings need validation in future studies.

Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer.

Preclinical studies suggest that the isoflavone genistein may have prostate cancer chemopreventive activity. Genistein has been shown to alter cellular levels of protein-tyrosine phosphorylation and is present at high levels in soy. This study was designed to measure the pharmacokinetic parameters of two different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660 (which contain 43% and 90% genistein, respectively), in human subjects with cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein-tyrosine phosphorylation. Cohorts of four patients were given single doses of each preparation; each dose was separated by 1 week. Sequential cohorts received genistein at 2, 4, or 8 mg/kg orally. Pharmacokinetic sampling was performed after each dose, and tyrosine phosphorylation was measured in proteins extracted from peripheral blood mononuclear cells. One of 13 patients treated developed a treatment-related rash. No other toxicities were observed. Maximal plasma concentrations (C(max)) ranged between 4.3 and 16.3 micro M for total genistein and 0.066 and 0.17 micro M for free genistein. For PTI G-2535 and PTI G-4660, half-life was 15.03 and 22.41 h, respectively, and volume of distribution was 189.9 and 653.8 liters, respectively, and there was a trend toward higher area under the concentration curve for PTI G-2535 (P = 0.07 at the 8 mg/kg dose). Treatment-related increases in tyrosine phosphorylation were observed in peripheral blood mononuclear cells. Oral administration of soy isoflavones gives plasma concentrations of genistein that have been associated with antimetastatic activity in vitro.