Prognostic models of drug-induced neutralizing antibody formation in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis treated with TNF-α blockersockers.

AIM: This study aimed to construct prognostic mathematical models utilizing multifactorial regression analysis to assess the risk of developing drug-induced neutralizing antibodies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with tumor necrosis factor alpha blockers.

Examining the Safety Profile of Janus Kinase (JAK) Inhibitors in the Management of Immune-Mediated Diseases: A Comprehensive Review.

Janus kinase (JAK) inhibitors have heralded a paradigm shift in the management of immune-mediated diseases. While their efficacy is well-established, the safety concerns associated with these agents, particularly regarding thromboembolic events (TE), remain a focus of extensive research and clinical scrutiny. This comprehensive literature review embarks on an exploration of the multifaceted landscape of JAK inhibitors, providing insights into their safety profiles across diverse immune-mediated diseases. The introduction highlights the transformative influence of JAK inhibitors in the treatment of immune-mediated diseases. Historically, the therapeutic arsenal for these conditions included corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics. The advent of JAK inhibitors has revolutionized this landscape, although concerns about their safety persist. This review strives to comprehensively evaluate their safety, amalgamating knowledge from multiple studies and trials. The subsequent sections delve into the safety of specific JAK inhibitors in the context of rheumatoid arthritis, inflammatory bowel diseases, and dermatologic conditions and their associations with venous thromboembolism. The evolving understanding of TE risk, particularly the intricate relationship between these agents and immune-mediated diseases, is meticulously unravelled. The concluding remarks underscore the dynamic nature of TE risk assessment with regard to immune-mediated diseases involving JAK inhibitors. It underscores that risk assessment is multifactorial, influenced not only by the choice of JAK inhibitor but also by the nuances of the underlying immune-mediated disease and the unique patient characteristics. This review offers a holistic perspective on TE risks associated with JAK inhibitors and contributes to the ongoing dialogue regarding their safety in the realm of immune-mediated diseases.

Celebrating Versatility: Febuxostat's Multifaceted Therapeutic Application.

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat's mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat's primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat's potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat's roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat's multifaceted therapeutic potential.

Trabeculectomy with ExPress - an effective solution to Posner-Schlossman syndrome.

Posner-Schlossman syndrome (PSS) is a unilateral ocular disease, characterized by recurrent non-granulomatous anterior uveitis and increased intraocular pressure (IOP), leading to chronic secondary glaucoma.

Acute retinal necrosis: pathophysiological aspects, diagnosis, and treatment.

Acute retinal necrosis (ARN) is a devastating viral infection commonly associated with varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 (HSV-1, HSV-2). Typically, ARN affects individuals without immune status disorders between the ages of 50-70. In two-thirds of the cases, one-eye involvement is observed and the inflammation can be presented as panuveitis. The most characteristic clinical manifestations are vitreitis, occlusion of the retinal arterioles, and peripheral necrotizing retinitis. Retinitis presents with the appearance of deep, multifocal, yellowish-white foci, typically localized in the peripheral retina. Systemic antivirals are the first treatment of choice for ARN. The goal of the therapy is to stop the viral replication and disease progression in the affected eye, as well as to prevent involvement of the healthy eye. The other eye can be attacked in an interval of 5 days to 30 years. The visual prognosis after illness is poor. Early diagnosis and timely initiation of treatment play an important role in maintaining visual acuity and preventing the other eye from being affected.

Confocal Microscopy of Filtering Blebs after Trabeculectomy.

INTRODUCTION: Filtration surgery is the most effective method of lowering intraocular pressure (IOP) in patients with insufficient medical control. It consists in facilitating the drainage of the intraocular fluid (IOF) from the anterior chamber to the subconjunctival space and subsequent lowering of IOP. The formation of filtration blebs (FB) and the processes of scarring occurring in the conjunctiva are of particular importance in glaucoma surgery. In many cases, the appearance of FB does not match the IOP values, and what causes the failure after trabeculectomy often remains unclear. Often, over time, there is a change in the structure of the FB, as fibrous tissue grows, which prevents the IOF drainage. Laser scanning in vivo confocal microscopy is a non-invasive study allowing the production of layered images at the microstructural level with high resolution of both the cornea and other structures of the anterior ocular surface. AIM: To evaluate the morphological structure and function of filtering blebs after trabeculectomy using in vivo confocal microscopy taking into account the type of implant and when the surgery was performed. MATERIALS AND METHODS: The study included 33 patients, 46 eyes with glaucoma. Twenty-six of the eyes had primary open-angle glaucoma (POAG), 18 eyes had pseudoexfoliative glaucoma and 2 eyes had juvenile glaucoma. All patients underwent trabeculectomy with fornix-based flap, and three of the eyes underwent retrabeculectomy. Mitomicyn C (MMC) was administered intraoperatively to all patients. The study of the filtering bleb was performed by in vivo confocal microscopy (CFM) (Heidelberg Retina Tomograph II (HRT II) /Rostock Cornea Module/ (Heidelberg Engineering GmbH, Heidelberg, Germany), the period from trabeculectomy and examination being from 1 year to 22 years. An Express implant was placed in 14 eyes, Ologen implant in 7 eyes, and 25 eyes had no implant placed. In the analysis of the morphological structure of the filtering blebs, three indicators were evaluated: the type of epithelium, the type of stroma, and blood vessels. RESULTS: Statistical significance was established with regard to the function and morphological structure of the filtering bleb (p=0.009). Blebs with fine collagen mesh and dense collagen mesh demonstrate good function. In the case of blebs with insufficient function, those with a dense collagen network and hyper-reflective tissue predominated and there were no blebs with a fine collagen network, and in non-functioning blebs most common were those with a pronounced collagen network and hyper-reflective tissue. With regard to vascularization, we found that the functioning blebs in the shortest postoperative period were dominated by those with one blood vessel (stage 1) and there was no stage 3, with weak tortuosity, while in non-functioning blebs in the late postoperative period, there was moderate to severe vascularization and tortuosity (p=0.037), (p=0.043), (p=0.047), (p=0.021). The type of implant affects the tortuosity of the blood vessels of the filtering bleb (p=0.026). The blebs with Express implants show a slight tortuosity, followed by the blebs with Ologen implants. The highest percentage of highly kinked blood vessels occurred in blebs without an implant. CONCLUSIONS: In vivo confocal microscopy is an innovative method which allows visualization of the internal structure of the filtering blebs at a cellular level, giving us a new insight into the ongoing healing processes, premising the function of the filtering blebs after glaucoma surgery.

Ocular Hypertension, Glaucoma or Compressive Neuropathy in Patient with Active TED.

INTRODUCTION: Severe cases of thyroid eye disease with high intraocular pressure and visual field defects are a real diagnostic challenge requiring the exclusion of dysthyroid optic neuropathy and differential diagnosis with glaucoma. AIM: To report а case of a patient with active thyroid eye disease (TED), decreased visual acuity and elevated intraocular pressure. MATERIALS AND METHODS: We present a 52-year-old woman with TED in both eyes, class 2c3c4a6a (NOSPECS), with 6 points (by CAS) activity, who received corticosteroid therapy to a maximum cumulative dose of 5750 mg, with non-insulin-dependent diabetes mellitus and topical antihypertensive treatment with tapticom, brizadopt, and luxfen. The patient received full ophthalmological exam, tonometry, exophthalmometry, computer perimetry, optical coherence tomography (OCT) and computed tomography (CT) scan of orbits. RESULTS: The following results were obtained: BCVA of right eye = 0.6, BCVA of left eye = 0.3; TOD = 26 mm Hg and ТОS = 21 mm Hg; exophthalmometry: 30 mm for the right eye and 31 mm for the left one; diplopia in all directions, edema and hyperemia of the eyelids and conjunctiva, eyelids retraction, sluggish pupil reactions, normal color vision, transparent ocular media, indistinct borders of the optic nerve disc, without glaucomatous excavation, tortuosity and dilation of the venules, retina - without diabetic changes, maculas - with normal reflex; CP datа for a localized inferotemporal visual field defect, CT data for thickening of all extraocular muscles, soft tissue orbital edema, and optic nerves compression. CONCLUSION: Our results confirmed the presence of dysthyroid optic neuropathy based on the decreased visual acuity, ophthalmo-scopic evaluation of the optic nerve head, lack of glaucomatous OCT changes, atypical perimetric changes and the CT data. The optic neuropathy is the most severe complication in patients with TED which develops due to the compression of the optic nerve and/or its blood supply from the enlarged extraocular muscles and soft tissues in the orbital apex and due to the mechanical tension of the optic nerve in cases moderate or severe proptosis is present.

Correlation between Intraocular Pressure and Thickness of Extraocular Muscles, the Severity and Activity of Thyroid-associated Orbitopathy.

AIM: To establish the correlation between intraocular pressure (IOP) and thickness of extraocular muscles (EOM), the severity and activity of thyroid-associated orbitopathy (TAO). MATERIALS AND METHODS: 50 patients with TAO were included in the study. They all underwent a thorough ophthalmic examination, Goldmann tonometry (mm Hg) and computer tomography of the orbits, the muscle thickness sum (MTS) of each eye being measured in millimeters. According to the activity of TAO, the patients were divided into two groups - with and without activity, and according to the severity of the disease - into 6 groups: Group 1 ('O') had only subjective symptoms, group 2 ('S') had soft tissue symptoms, group 3 ('P') - proptosis, group 4 ('E') - ocular motility disorders, group 5 ('C') - corneal damage, and group 6 ('Si') - visual impairment; Results: TAO activity was registered in 21 patients (42 eyes, 42%) with MTS 23.39±3.81 and IOP 18.43±4.16. Twenty-nine patients (58 eyes, 58%) with MTS 19±3.21 and IOP 15.98±4.59 showed no TAO activity. The IOP within the groups, in terms of severity, was as follows: group 1 - 19.92+4.05; group 2 - 14.5±2.55; group 3 - 18.04±4.51; group 4 - 18.2±5.05; group 5 - 20.5±4.5; group 6 - 21.5±4.95. A correlation between the IOP and MTS was found. CONCLUSIONS: The IOP in patients with TAO depends on the thickness of the EOM, as well as on the activity and severity of the disease.

Discrepancies between Spectral Domain Optical Coherence Tomography and Fluorescein Angiography in Detecting Uveitic Macular Edema.

AIM: To compare spectral-domain optical coherence tomography (SD-OCT) with fluorescein angiography (FA) in detecting macular edema in patients with uveitis and analyse discrepancies in the findings obtained by the two methods. METHODS: The study included 133 eyes from 117 patients with uveitis that had SD-OCT (RTVue-100/ Optovue) and FA (Topcon TRC 50DX) scans performed to detect or rule out macular edema. RESULTS: Macular edema was found in 57 (42.9%) of the 133 surveyed eyes. In 37 eyes (27.8%) macular edema was confirmed by both imaging methods. In 17 eyes (12.8%) macular edema was detected on SD-OCT but not on FA;in 15 eyes of these the edema was diffuse, and in 2 eyes - serous retinal detachment was verified in the macular area. Focal macular edema was detected on FA in three eyes (2.3%) in which SD-OCT showed normal finding. In 76 eyes (57.1%) no pathological changes in the macula were observed on both SD-OCT and FA. Kappa coefficient was 0.675 at p < 0.001. The agreement rate between the two methods calculated using Kendall's tau-b was 0.693 at p < 0.001. CONCLUSION: Fluorescein angiography and spectral domain optical coherence tomography are highly sensitive methods used in detecting macular edema in patients with uveitis, but they might fail to be efficient in this if used independently. Optical coherence tomography is a more informative method, especially in diagnosing diffuse macular edema.

Macular edema in uveitis.

UNLABELLED: In the present study we have made a review of the relevant literature on pathogenesis and modern diagnostic methods for macular edema (ME) in uveitis. Macular edema is a typical non-specific complication of uveitis, one of the common causes of visual impairment. ME can be found in all types of uveitis. In 85% of cases of intermediate uveitis, the visual impairment is due to the development of cystoid macular edema. The macula is more rarely affected in panuveitis (35%), anterior (20-26%) and posterior (20%) uveitis. The etiological agent is of great importance for the course and treatment of inflammatory diseases. Among the imaging diagnostic methods that are capable of detecting macular edema with fluid accumulation in the retina (either diffuse or distributed in cysts) are the fluorescein angiography (FA) and the optical coherence tomography (OCT). OCT allows a quantitative assessment of retinal thickening and how it changes throughout therapy. FA can be used to determine very precisely the site of a vascular leakage and assess how badly the vascular wall has been affected by the inflammatory process. CONCLUSION: Macular edema occurring during an inflammatory process is one of the causes for visual acuity loss in uveitis. OCT and FA are useful complementary imaging methods for investigation of structural changes in retinal architecture in uveitis patients.

Macular thickness measurements in healthy eyes using spectral optical coherence tomography.

AIM: The aim of the present study was to measure macular thickness in healthy eyes and find whether it changes with age. MATERIAL AND METHODS: We examined 163 healthy eyes of 84 healthy volunteers. In order to measure their macular thickness the patients were examined using spectral-domain optical coherent tomography (SD-OCT - iVue, Optovue). They were allocated into 6 age groups. RESULTS: The mean central macular thickness (inner circle - fovea centralis) was 248.9 +/- 17.9 microm (mean +/- SD), and the mean total macular thickness (an area including 9 subfields as defined by ETDRS) was 286.2 +/- 13.9 microm (mean +/- SD). We found that it correlated negatively with age (r = - 0.18; p = 0.03; Pearson correlation). CONCLUSION: We found a statistically significant decrease of mean macular thickness as age increased.