Summary of the Therapeutic Options for Patients with Dry and Neovascular AMD.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy.

Available Therapeutic Options for Corneal Neovascularization: A Review.

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-ß) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-ß-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

An Analysis of Optical Coherence Tomography Angiography (OCT-A) Perfusion Density Maps in Patients Treated for Retinal Vein Occlusion with Intravitreal Aflibercept.

AIM: The primary goal of this study was to evaluate the reduction in non-perfusion area and improvement in blood flow as well as the reduction in retinal edema on optical coherence tomography angiography (OCT-A) in patients with retinal vein occlusion treated with 2 mg intravitreal injections of aflibercept. MATERIAL AND METHODS: Fifty eyes of nine patients with central retinal vein occlusion (CRVO) and sixteen patients with branch retinal vein occlusion (BRVO), aged 50 to 75 years, were collectively analyzed as retinal vein occlusion (RVO). The following parameters were analyzed: superficial vessel density (VDSF), deep vessel density (VDD), flow area in the outer retina (FAOR), choriocapillaris flow area (FACC), non-flow area (NFA) and the foveal avascular zone (FAZ). RESULTS: OCT-A revealed a reduction in macular edema. The most significant change in central retinal thickness (CRT) was observed between measurement timepoint "5" and the baseline (46%). The non-flow area was also reduced. Following a significant decrease in superficial vessel density 30 days after the first dose of aflibercept, a non-significant increase was noted at the subsequent timepoints. An increase was also found in deep vessel density and choriocapillaris flow area. Improvements in the above OCT-A parameters resulted in increased retinal blood flow and improved visual acuity. CONCLUSIONS: Patients with retinal vein occlusion treated with 2 mg aflibercept exhibited reduced macular edema and FAZ, increased vessel density, improved blood flow, and better visual acuity.

Quality of Life and Mental State After Sight Restoration by Corneal Transplantation.

BACKGROUND: Quality of life has frequently been reported to improve after corneal transplantation. However, mental status before and after surgery has until now been less well investigated. OBJECTIVE: The aim of this study was to investigate quality of life and mental status before and after corneal transplantation including postoperative immunosuppression and visual acuity. METHODS: A total of 45 patients were assessed before, and 3 weeks and 4 months after transplantation using the following questionnaires: Visual Function Questionnaire, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. Assessment included a visual acuity test using the logMAR chart, and recognition of the role of postoperative immunosuppression. Finally, patients were asked if they would be willing to have the surgery again. RESULTS: In the candidates for surgery, quality of life was reduced, and symptoms of depression and anxiety were present. Corneal transplantation improved their quality of life and reduced symptoms of depression and anxiety. Changes in quality of life and in mental state were associated with a change in visual acuity in the grafted eye. Higher doses of prednisone were associated with a worse quality of life and with more severe symptoms of depression and anxiety after transplantation. Further, 82.5% of patients would have the surgery again. CONCLUSION: Assessment for psychiatric symptoms should be considered in individuals facing corneal surgery.

Desipramine administered chronically inhibits lipopolysaccharide-stimulated production of IL-1ß in the brain and plasma of rats.

Nowadays, it is assumed that therapeutic efficacy of antidepressants depends, at least partly, on their anti-inflammatory properties. The present study investigated for the first time the effect of 21-day oral administration of desipramine on the lipopolysaccharide (LPS)-stimulated IL-1ß concentration in the olfactory bulb, hypothalamus, frontal cortex, hippocampus and plasma of rats, and on the LPS-induced IL-1ß mRNA level in the olfactory bulb. Desipramine (15mg/kg/day) reduced significantly the LPS (250 µg/kg i.p.)-induced IL-1ß concentration in the olfactory bulb, hypothalamus and in plasma, and diminished the LPS effect on IL-1ß mRNA in the olfactory bulb. Plasma concentration of desipramine was comparable to its therapeutic range. By using the α1/α2-adrenoceptor antagonist prazosin and the unspecific ß-adrenoceptor antagonist propranolol given prior to LPS, we found that the effect of desipramine on LPS-induced IL-1ß production was partially mediated by both adrenoceptors in the olfactory bulb and plasma, and that ß-adrenoceptors contributed also to its effect on the stimulated IL-1ß concentration in the hypothalamus. The effect of LPS on the cerebral IL-1ß levels was, in part, mediated by ß-adrenoceptors and, in a region-specific manner, by α1/α2-adrenoceptors. The findings provide evidence for central and peripheral anti-inflammatory activity of desipramine and confirm the impact of the noradrenergic system on IL-1ß production induced by an immunostimulatory challenge.

The use of intrastromal corneal ring segments in patients with myopia and keratoconus.

Intrastromal corneal ring segments were primary used for correcting myopia ranging from -0.5 to -3.0 diopters. Nowadays, the most common indication of PMMA insertion in the world is keratoconus-associated astigmatism. The aim of this paper is to provide an overview of using of intracorneal ring segments in myopia and keratoconus. The addressed issues include commercially available ring models, indications and contraindications for ring implantation as well as the recommended surgical techniques. The efficacy of ring implantation in other conditions, such as post-LASIK ectasia and corneal transplantation is also discussed based on literature review. Additionally, the combined procedure of intracorneal ring segment implantation and cor- neal collagen cross-linking is mentioned as one of the latest trends.

The gamma knife in ophthalmology. Part One--Uveal melanoma.

The Gamma Knife was designed by Lars Leksell in the early 1950's. It gave rise to a new discipline of medicine--stereotactic radiosurgery. Primarily dedicated to neurosurgery, the Gamma Knife has become an alternative, widely used surgery technique. According to Elekta's statistics, approximately 60,000 people are treated with Leksell Gamma Knife every year and it is the most extensively studied stereotactic radiosurgery system in the world. The Leksell Gamma Knife can also be used in ophthalmology. The gamma ray beam concentration enables effective treatment of uveal melanoma, choroidal hemangioma, orbital tumors or even choroidal neovascularization. The virtue of Leksell Gamma Knife is its extreme precision, non-invasiveness and the possibility of outpatient treatment, which significantly reduces costs and diminishes post-operative complications. Innovative solutions shorten a single session to a minimum, which is very comfortable and safe for both staff and patients. Advantages and possible side effects of gamma knife radiosurgery are well-documented in the professional literature. The objective of this review is to present the recognized applications of Leksell Gamma Knife in ophthalmology.

The gamma knife in ophthalmology. Part Two--Other ocular diseases.

Gamma Knife was designed by Lars Leksell in the early 1950's. It gave rise to a new discipline of medicine--stereotactic radiosurgery. Main use of Gamma Knife in ophthalmology--discussed in the first part of this paper--is non-invasive treatment of uveal melanoma. Another uses of LGK in ophthalmology cover choroidal hemangioma, orbital tumors and even choroidal neovascularization.

[The application of corneal collagen cross-linking in diseases other than keratoconus]. / Zastosowanie sieciowania wlókien kolagenowych rogówki w schorzeniach innych niz stozek rogówki.

Corneal collagen cross-linking is a method of treatment using ultraviolet radiation UVA and photosensitizing substance riboflavin to strengthen the chemical connections between the collagen fibers of corneal stroma. This treatment is focused on halting the progression of the diasases, called ectasias, characterized by irregular curvature and diminished thickness of the cornea. The most common indication for corneal collagen cross-linking is keratoconus. However, this technique may be also applied to pathologies other than keratoconus. The aim of this paper is to review the applicilcability of corneal collagen cross-linking in other conditions than keratoconus. Specifically, the conditions such as pellucid marginal degeneration, post refractive surgery ectasia as well as combined corneal collagen cross-linking and topography-based photorefractive keratectomy for topographies indicating forme fruste keratoconus are discussed. In addition, the effects of-corneal collagen cross-linking-as an adjunctive therapy in keratitis, corneal ulcers and corneal edema in bullous keratopathy are considered. The authors highlight the importance of treatment in clinical practice and the potential application of the treatment and modification of the protocols in the treatment of corneal diseases other than keratoconus.

[Optical coherence tomography in the imaging of the iridocorneal angle]. / Optyczna koherentna tomografia w obrazowaniu kata przesaczania.

Anterior segment optical coherence tomography (AS OCT), enables visualization and measurements of the anterior segment of the eye. In particular, it is a valuable tool in the imaging of the iridocorneal angle. In this paper, we reviewed parameters used for analysis of the iridocorneal angle in AS OCT and compared changes of these parameters after cataract surgery, laser iridotomy and illumination. Special attention was paid to changes of such quantitative parameters as TISA (trabecular-iris space area), AOD (angle opening distance), and ARA (angle recess area).

Antiapoptotic and neurotrophic effects of antidepressants: a review of clinical and experimental studies.

Recent studies have strengthened the role of the abnormalities in neurotrophic pathways in the pathophysiology of depression. It has been shown that the depletion of growth factors, particularly brain-derived neurotrophic factor, may result in depression-like behavior in animals and may induce cellular changes that are reminiscent of those observed in depressed patients. Some authors even suggested that increased neuronal cell loss may contribute to the pathogenesis of depression. Hence, appreciable interest has been focused on the trophic and antiapoptotic effects of antidepressant drugs. In this paper, we put emphasis on the contribution of hippocampal atrophy, increased cell death and alterations in trophic factors to the pathogenesis of depression and their relationship to the potential of antidepressants to reverse these changes by modulating trophic factor cascades and preventing apoptosis. First, evidences for increased hippocampal atrophy and cell death in depression are discussed, followed by a review of selected studies of special interest that concern antiapoptotic action of antidepressant drugs. Next, depression-related neurotrophic abnormalities and their reversal by antidepressants are depicted. Finally, relationships among neurotrophins, antiapoptotic proteins and antioxidant enzymes in the pathology and treatment of depression are pointed out.

Various patterns of gestes antagonistes in cervical dystonia.

In this study, we evaluated patterns, quantity and effectiveness of gestes antagonistes, the association between the severity of disease and the type of gestes and the clinical implications of the presence of gestes antagonistes in 33 patients with cervical dystonia, 19 patients (58%) presented a classic sensory trick (ST) while 14 subjects (42%) demonstrated a forcible trick (FT). FTs prevailed in patients with more severe dystonia whereas STs were more common among patients with milder disease. These results suggest that at more severe stages of the disease, classic STs are not effective enough and thus patients use FTs.

Effect of chronic treatment with perazine on lipopolysaccharide-induced interleukin-1 beta levels in the rat brain.

In the present study, we sought to determine whether chronic treatment with perazine alters lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) levels in the following rat brain regions: the hypothalamus, frontal cortex, striatum and hippocampus. Male Wistar rats were administered perazine dimaleate (15 or 30 mg/kg/day) in drinking water for 21 days. On day 22, LPS was injected i.p. (125 microg/kg) 2 h before decapitation. Concentrations of perazine and its metabolites in plasma and brain was assessed by HPLC. The levels of IL-1 beta were determined using ELISA. Treatment with perazine (30 mg/kg/day) reduced LPS-stimulated IL-1 beta levels in the hypothalamus, and a tendency to its decrease in the striatum and frontal cortex was observed. This in vivo study suggests for the first time that long-term oral administration of perazine modulates reactivity of cells producing IL-1 beta.

Cytokines in schizophrenia and the effects of antipsychotic drugs.

Growing evidence suggests that the immune, endocrine, and nervous systems interact with each other through cytokines, hormones, and neurotransmitters. The activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous system (CNS) of schizophrenic patients. Numerous studies report that treatment with antipsychotic drugs affects the cytokine network. Hence, it is plausible that the influence of antipsychotics on the cytokine systems may be responsible for their clinical efficacy in schizophrenia. This article reviews current data on the cytokine-modulating potential of antipsychotic drugs. First, basic information on the cytokine networks with special reference to their role in the CNS as well as an up-to-date knowledge of the cytokine alterations in schizophrenia is outlined. Second, the hitherto published studies on the influence of antipsychotics on the cytokine system are reviewed. Third, the possible mechanisms underlying antipsychotics' potential to influence the cytokine networks and the most relevant aspects of this activity are discussed. Finally, limitations of the presented studies and prospects of future research are delineated.