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Background: This study aimed to evaluate mydriasis stability during cataract surgery in patients with systemic comorbidities such as diabetes mellitus (DM) and pseudoexfoliation syndrome (PXF) after a standardised combination of intracameral mydriatics and anaesthetic (SCIMA). Stable mydriasis is crucial for safe and effective phacoemulsification. Methods: Patients were included if they achieved pupil dilation ≥6.0 mm during the qualifying visit. A total of 103 patients were enrolled, divided into three groups: cataract with diabetes (C + DM group, n = 35), cataract with PXF (C + PXF group, n = 32), and cataract without those comorbidities (C group, n = 36). SCIMA was administered, and pupil diameters were measured at key surgical stages. Stability was defined as a pupil diameter of ≥6.0 mm without additional pharmacological intervention and no significant change in its diameter (≥3.0 mm). Results: Stable mydriasis was achieved in 90.3% of patients: 97.1% in the C + DM group, 90.6% in the C + PXF group, and 83.3% in the C group, with no statistically significant differences (p = 0.14). Conclusions: SCIMA effectively maintains mydriasis stability during cataract surgery, even in patients with systemic comorbidities, ensuring greater surgical safety. [ABSTRACT FROM AUTHOR]

MEK inhibitors (MEKi) represent innovative and promising treatments for managing manifestations of neurofibromatosis type 1 (NF1). To mitigate potential ophthalmic side effects, such as MEKi-associated retinopathy (MEKAR), patients undergoing MEKi therapy routinely receive ophthalmology evaluations. Our study aims to assess the necessity of this regular screening within a predominantly pediatric NF1 population by examining the occurrence of ocular adverse events (OAE). A retrospective study evaluated 45 NF1 patients receiving MEKi. Inclusion criteria included baseline and follow-up examinations following the initiation of MEKi therapy. At each assessment, a comprehensive eye evaluation was performed, comprising a dilated fundus examination, ocular coherence tomography of the macula and nerve fiber layer, and Humphrey visual field testing. Twenty-six patients, with an average age of 13 years (range 2–23 years) and an average follow-up duration of 413 days were included in the analysis. Three different MEKi were used: selumetinib (77%), trametinib (23%), and mirdametinib (4%). None of the patients experienced retinopathy at any point during the study. Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication. [ABSTRACT FROM AUTHOR]

Simple Summary: Anticancer drugs can determine alterations in the ocular surface system as side effects that can be referred to by patients as ocular discomfort symptoms and, sometimes, as reduced visual acuity. For this reason, it becomes essential to spread knowledge of the entire spectrum of ocular side effects of these drugs, especially for newer and more recent drugs. This review aims at analyzing the adverse effects on the ocular surface of these innovative anticancer drugs, trying to highlight the physiopathogenetic mechanisms underlying these complications and providing useful indications to clinicians for their proper management. Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactions. Ocular surface side effects are recognized to significantly impact patient's quality of life and quality of vision. Blepharoconjunctivitis is known to be a common side effect caused by oxaliplatin, cyclophosphamide, cytarabine, and docetaxel, while anastrozole, methotrexate, and 5-fluorouracil can all determine dry eye disease. However, the potential processes involved in the development of these alterations are yet not fully understood, especially for novel drugs currently available for cancer treatment. This review aims at analyzing the potential ocular surface and adnexal side effects of novel anticancer medications, trying to provide a better understanding of the underlying pharmacological processes and useful insights on the choice of proper management. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effectiveness of a standardized combination of intracameral mydriatics and anesthetic (SCIMA) on mydriasis in patients with coexisting diseases such as diabetes mellitus (DM) and pseudoexfoliation syndrome (PXF) during phacoemulsification. Methods: Patients with cataract were included in the study if they achieved pupil dilation diameter ≥ 6.0 mm after the administration of mydriatic eyedrops (ME) during the first visit (V1). During the second visit (V2), pupil size measurements were obtained for phacoemulsification surgery with SCIMA. Effective mydriasis was defined as a pupil diameter ≥ 6.0 mm just prior to capsulorhexis without the use of additional pupil dilating agents. The measurements after ME administration during V1 and after SCIMA use during V2 were compared. Results: 103 patients (103 eyes) were divided into 3 groups: cataract and DM (n = 35), cataract and PXF (n = 32), and cataract without DM or PXF (n = 36). SCIMA administration allowed the achievement of effective mydriasis (≥6.0 mm) in all groups (n = 103; 100%). Mydriasis was significantly larger (p ≤ 0.001) after ME (7.3 mm) than after SCIMA (6.8 mm) administration. Conclusions: Patients with cataract and such comorbidities as DM or PXF are likely to achieve effective pharmacological mydriasis during cataract phacoemulsification after SCIMA application. Mydriasis after ME is slower and larger, while SCIMA is faster. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors. [ABSTRACT FROM AUTHOR]

In this study, we characterized diabetic retinopathy in two mouse models and the response to anti-vascular endothelial growth factor (VEGF) injection. The study was conducted in 58 transgenic, non-obese diabetic (NOD) mice with spontaneous type 1 diabetes (n = 30, DMT1-NOD) or chemically induced (n = 28, streptozotocin, STZ-NOD) type 1 diabetes and 20 transgenic db/db mice with type 2 diabetes (DMT2-db/db); 30 NOD and 8 wild-type mice served as controls. Mice were examined at 21 days for vasculopathy, retinal thickness, and expression of genes involved in oxidative stress, angiogenesis, gliosis, and diabetes. The right eye was histologically examined one week after injection of bevacizumab, ranibizumab, saline, or no treatment. Flat mounts revealed microaneurysms and one apparent area of tufts of neovascularization in the diabetic retina. Immunostaining revealed activation of Müller glia and prominent Müller cells. Mean retinal thickness was greater in diabetic mice. RAGE increased and GFAP decreased in DMT1-NOD mice; GFAP and SOX-9 mildly increased in db/db mice. Anti-VEGF treatment led to reduced retinal thickness. Retinas showed vasculopathy and edema in DMT1-NOD and DMT2-db/db mice and activation of Müller glia in DMT1-NOD mice, with some response to anti-VEGF treatment. Given the similarity of diabetic retinopathy in mice and humans, comparisons of type 1 and type 2 diabetic mouse models may assist in the development of new treatment modalities. [ABSTRACT FROM AUTHOR]

Advances in imaging with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technology, including the development of swept source OCT/OCTA, widefield or ultra-widefield systems, have greatly improved the understanding, diagnosis, and treatment of myopia and myopia-related complications. Anterior segment OCT is useful for imaging the anterior segment of myopes, providing the basis for implantable collamer lens optimization, or detecting intraocular lens decentration in high myopic patients. OCT has enhanced imaging of vitreous properties, and measurement of choroidal thickness in myopic eyes. Widefield OCT systems have greatly improved the visualization of peripheral retinal lesions and have enabled the evaluation of wide staphyloma and ocular curvature. Based on OCT imaging, a new classification system and guidelines for the management of myopic traction maculopathy have been proposed; different dome-shaped macula morphologies have been described; and myopia-related abnormalities in the optic nerve and peripapillary region have been demonstrated. OCTA can quantitatively evaluate the retinal microvasculature and choriocapillaris, which is useful for the early detection of myopic choroidal neovascularization and the evaluation of anti-vascular endothelial growth factor therapy in these patients. In addition, the application of artificial intelligence in OCT/OCTA imaging in myopia has achieved promising results. [ABSTRACT FROM AUTHOR]

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs (p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections (p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD. [ABSTRACT FROM AUTHOR]

RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and, in limited cases, RAS mutant cancer. RAS mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy represents the fourth most frequent retinal disorder, occurring especially in young age. Central serous chorioretinopathy is mainly characterized by macular serous retinal detachment and although the clinical course moves frequently toward a spontaneous resolution, the subretinal fluid may persist for a long time, thus evolving to the chronic form, and leading to a potential damage of the retinal pigment epithelium and to photoreceptors. The photodynamic therapy with verteporfin plays an important role in the armamentarium among the many therapeutic options employed in this complex retinal disorder. In this review, the authors aim to summarize data of efficacy and safety of PDT focusing especially on mechanisms of action of the PDT and providing comparative outcomes with the alternative therapeutic approaches, including especially the subthreshold laser treatment. [ABSTRACT FROM AUTHOR]

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen. [ABSTRACT FROM AUTHOR]