New Treatment Horizons in Uveal and Cutaneous Melanoma.

Melanoma is a complex and heterogeneous malignant tumor with distinct genetic characteristics and therapeutic challenges in both cutaneous melanoma (CM) and uveal melanoma (UM). This review explores the underlying molecular features and genetic alterations in these melanoma subtypes, highlighting the importance of employing specific model systems tailored to their unique profiles for the development of targeted therapies. Over the past decade, significant progress has been made in unraveling the molecular and genetic characteristics of CM and UM, leading to notable advancements in treatment options. Genetic mutations in the mitogen-activated protein kinase (MAPK) pathway drive CM, while UM is characterized by mutations in genes like GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Chromosomal aberrations, including monosomy 3 in UM and monosomy 10 in CM, play significant roles in tumorigenesis. Immune cell infiltration differs between CM and UM, impacting prognosis. Therapeutic advancements targeting these genetic alterations, including oncolytic viruses and immunotherapies, have shown promise in preclinical and clinical studies. Oncolytic viruses selectively infect malignant cells, inducing oncolysis and activating antitumor immune responses. Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic virus for CM treatment, and other oncolytic viruses, such as coxsackieviruses and HF-10, are being investigated. Furthermore, combining oncolytic viruses with immunotherapies, such as CAR-T cell therapy, holds great potential. Understanding the intrinsic molecular features of melanoma and their role in shaping novel therapeutic approaches provides insights into targeted interventions and paves the way for more effective treatments for CM and UM.

Role of arterial hypertension and angiotensin II in chronic kidney disease (Review).

Chronic kidney disease (CKD) is a major public health issue, due to its effect on the quality of life of patients and by the huge costs incurred in treating this disease. It is an irreversible process, characterized by the progressive loss of functional nephrons. CKD ultimately requires the support of renal function by dialysis or even renal transplantation. It has a multiple etiology, but the most common causes remain arterial hypertension and diabetes. High arterial blood pressure affects the target organs (kidneys) and this leads to a vicious circle involved in maintaining high blood pressure. Arterial hypertension is closely related to the renal pathology of CKD. The result of excessive activation of the renin angiotensin system (RAS) is increased angiotensin II (Ang II), which acts upon the systemic circulation and especially upon the kidneys. The outcome is high blood pressure and also the stimulation of proinflammatory and profibrotic effects in the kidneys. Collectively these ultimately lead to CKD. The aim of this review was to provide a brief overview of the pathophysiological associations between CKD, arterial hypertension, and Ang II.

Micropulse Transscleral Cyclophotocoagulation for Glaucoma after Penetrating Keratoplasty.

The main objective of the article was to assess the surgical outcome of micropulse transscleral cyclophotocoagulation in patients presenting with glaucoma after penetrating keratoplasty. We conducted a retrospective study that included 26 eyes of 26 patients who presented with glaucoma after penetrating keratoplasty, and who were treated using micropulse transscleral cyclophotocoagulation between January 2017 and December 2020. The surgeries were performed using the Iridex Cyclo G6 MicroPulse P3 Probe. The intraocular pressure, mean number of antiglaucoma medications, visual acuity, corneal status, and postoperative complications were analyzed. The minimum follow-up period was 12 months. The success rate after 12 months was 76.9%. The baseline median intraocular pressure was 29 mm Hg and decreased to 18 mm Hg after 12 months. The median number of antiglaucoma medications was also reduced from three preoperatively to one after one year. In seven cases (29.92%), the visual acuity decreased and, in four cases (15.38%), the corneal graft was not transparent. We concluded that micropulse transscleral cyclophotocoagulation is an effective and safe method for the treatment of glaucoma after penetrating keratoplasty.

Mucocutaneous lesions associated with SARS-CoV-2 infection (Review).

The ongoing COVID-19 pandemic, declared by the World Health Organisation in March 2020, with the emergence of new, possibly more contagious and more virulent strains, remains a research subject, with the complex systemic involvement better described and understood, but also with a variety of skin and mucosal lesions described in the literature. Mucocutaneous lesions associated with SARS-CoV-2 infection are still under investigation, due to their polymorphic clinical aspect and incompletely understood pathogenic mechanism. The cutaneous inflammatory, exanthematous and purpuric rashes, erythemato-purpuric enanthems, oral ulcers, lichenoid oral lesions, conjunctivitis, conjunctival pseudomembranes, or corneal lesions have been described in patients with COVID-19. Several classifications have been proposed based on the clinical pattern, histological findings, and possible pathogenic mechanisms. The pathogenic mechanism, the diagnostic criteria, the prognostic importance of these lesions are still being debated. The diverse clinical aspects of dermatological manifestations render the diagnosis difficult. However, several clinical patterns strongly associated with COVID-19, such as chilblains, papulovesicular exanthems, and febrile rash require increased awareness and changes to the investigation protocols for these conditions, to include testing for SARS-CoV-2. In the present review, the mucocutaneous findings associated with the novel coronavirus infection, reported thus far in the literature, was provided.

Phototherapy in dermatological maladies (Review).

Since the introduction of modern phototherapy in 1903 by Nobel Prize-winner Niels Ryberg Finsen, the usage of this therapy in the medical field has grown, techniques have been refined and developed, and it has gained widespread acceptance. Psoriasis vulgaris, parapsoriasis, lichen planus, atopic dermatitis, neonatal jaundice, urticaria, morphea, vitiligo, granuloma annulare and cutaneous T cell lymphoma are only a few dermatological indications that come along with satisfactory results. Most often, it is a 2nd or 3rd line therapy being an alternative in more severe or refractory diseases. Despite the side effects that may occur after phototherapy, which are often minor, the benefits can be significant. Unfortunately, the absolute contraindications limit the use of this type of treatment and implicitly the management of these patients. The current review aimed to combine the recommendations of phototherapy in dermatology, the types of phototherapy that can be suitable for certain dermatological diseases and to emphasize its importance in certain conditions that are associated with significant remission rates.

Micropulse vs. continuous wave transscleral cyclophotocoagulation in neovascular glaucoma.

Neovascular glaucoma (NVG) is a refractory form of glaucoma, associated with important morbidity, for which no consensus exists regarding the optimal choice of therapy. The primary aim of our study was to compare the performances of micropulse transscleral cyclophotocoagulation (MP-TSCPC) and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) in the treatment of neovascular glaucoma (NVG). A total of 24 eyes for MP-TSCPC and 22 eyes for CW-TSCPC, all with NVG were included. The procedures were performed using either the Iridex Cyclo G6 (IRIDEX Laser System), the MP3, or the G-Probe devices. Intraocular pressure (IOP), visual acuity (VA), the mean number of antiglaucoma medications, and postoperative complications were monitored. The minimum follow-up was 12 months. The success rate at 12 months was 54.5% in the CW-TSCPC group and 33.3% in the MP-TSCPC group. The mean IOP at baseline was 35.82 mm Hg for CW-TSCPC and 34.71 mm Hg for MP-TSCPC. The change from baseline in IOP at 12 months was 11.95 mm Hg in the CW-TSCPC group and -8.04 mm Hg in the MP-TSCPC group. There was a significant difference in the occurrence of serious complications (worsening of VA, hypotony, and phthisis bulbi) between the two methods, with CW-TSCPC associated with more important adverse effects (P=0.045). There was a decrease in the number of topical antiglaucoma medications in both groups: in the MP-TSCPC group from a mean number of 2.6 at baseline, to 1.7 at 3 months, followed by a slight increase to 2.1 at 12 months and in the CW-TSCPC group from 2.8 at baseline, to 1.4 at 3 months and 1.9 at 12 months. Our study concluded that both MP-TSCPC and CW-TSCPC could manage NVG, but, while CW-TSCPC revealed higher IOP control in the long term (which did not reach statistical significance), it also had a significantly lower safety profile.

Update on the etiopathogenesis of psoriasis (Review).

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, involving hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages, and neutrophils. Multiple factors appear to play important roles in the pathogenesis of psoriasis. These environmental (e.g., infectious agents and trauma), genetic, and immunologic factors are reviewed in this article. Although the pathogenesis of psoriasis remains to be established, data suggesting immune cell dysregulation in the skin are available. The involvement of the immune system, particularly T cells, in the etiopathogenesis of psoriasis is discussed in this review, indicating a potential justification for innovative treatment intervention. Besides describing pathogenic T cells, the aim of the review was to assess the function of newly identified antimicrobial peptides (AMPs), interleukin (IL)-23, IL-17, and tissue resident memory cells (TRMs), and their role in psoriasis. Furthermore, new insights were presented regarding TRMs, a recently identified subset of memory T cells, and the role they play in the local memory of disease, making them a potential new therapeutic target in psoriasis. Finally, current developments in T-cell research and cytokine-targeted therapy for psoriasis treatment are reviewed.

Diagnostic methods for the etiological assessment of infectious corneal pathology (Review).

Infectious keratitis is a leading cause of visual morbidity, including blindness, all across the globe, especially in developing countries. Prompt and adequate treatment is mandatory to maintain corneal integrity and to recover the best possible final visual acuity. Although in most of the cases practitioners chose to employ empirical broad-spectrum antimicrobial medication that is usually effective, in some instances, they face the need to identify the causative agent to establish the appropriate therapy. An extensive search was conducted on published literature before December 2020 concerning the main laboratory investigations used to identify the microbial agents found in infectious keratitis, their indications, advantages, and disadvantages, as well as the results reported by other studies concerning different diagnostic tools. At present, the gold standard for diagnosis is still considered to be the isolation of microorganisms in cultures, along with the examination of smears, but other newer techniques, such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and in vivo confocal microscopy (IVCM) have gained popularity in the last decades. Currently, these newer methods have proved to be valuable adjuvants in making the diagnosis, but technological advances hold promise that, in the future, these methods will have increased performance and availability, and may become the new gold standard, replacing the classic cultures and smears.

Adult female acne: Clinical and therapeutic particularities (Review).

Acne is a chronic inflammatory condition affecting the pilosebaceous unit that was traditionally viewed as a disease of the adolescence. However, over the past several years, an increasing number of adult women have been reported to suffer from this condition. The prevalence of adult female acne ranges between 12 and 54%. Two clinical types can be distinguished in this population, a 'retentional' and an 'inflammatory' type, which usually tend to overlap. In terms of evolution, three main subtypes can be identified: Persistent acne, which is the most frequent subtype, late-onset acne and recurrent acne. This type of acne is mainly mild-to-moderate in severity and may be refractory to conventional treatment. The etiopathogenesis is complex and has yet to be fully elucidated. It appears to involve an interaction among genetic predisposition, hormonal factors, and chronic activation of the innate immune system overlapping with external factors, such as daily stress, Western-type diet, use of tobacco and cosmetics. The treatment may be challenging and a holistic approach is required, with special attention to the individual needs and particularities of adult women. Both topical and systemic treatments are available, with hormonal therapies being of special value in this population. The aim of the present article was to provide up-to-date, evidence-based information on the clinical presentation, etiopathogenesis and treatment of adult female acne.

Cardiovascular comorbidities in psoriasis (Review).

Long considered a skin-limited condition, psoriasis is currently defined as a chronic, immune-mediated inflammatory disease, presenting, besides the skin changes, important systemic manifestations, the most common being: psoriatic arthritis, cardiovascular disease, metabolic syndrome, diabetes, inflammatory bowel disease and nonalcoholic steatohepatitis. It is a disease with a strong psycho-emotional and social impact, both through skin changes such as pruritic, scaly erythematous plaques, and through the association of comorbidities that influence morbidity and mortality. It has been shown that psoriasis is an independent cardiovascular risk factor, with patients developing ischemic heart disease/acute coronary syndrome, hypertension, peripheral arterial disease, or stroke. The chronic inflammatory status of psoriasis and the production of specific cytokines may be the etiopathogenic link to atherosclerosis and cardiovascular disease. Biological therapy may affect atherosclerosis, leading to the arrest of the evolution or even regressing the changes in the atheromatous plaque. The aim of this review was to re-evaluate the current knowledge regarding the cardiovascular comorbidities associated with psoriasis for optimal management of the patients.

Metabolic comorbidities of psoriasis (Review).

Psoriasis is a chronic inflammatory and immune-mediated condition, which is no longer considered as being limited to the skin, but may affect the entire body. Epidemiological studies have shown that certain disorders, including obesity, diabetes, liver abnormalities, elevated lipid levels in the blood and metabolic syndrome, may occur more frequently in patients with psoriasis compared with the general population. As psoriasis is a chronic disease, the frequently associated comorbidities must be identified early to ensure timely treatment and, possibly, their prevention. Comorbidities often manifest clinically 1-2 years after the onset of psoriasis and are commonly seen in patients with severe forms of the disease. The association between psoriasis and its comorbidities is not coincidental, but rather based on common pathophysiological mechanisms and risk factors that underlie the increased frequency of comorbidities in patients with psoriasis. The aim of the present review was to emphasize the important role of dermatologists in the early recognition of comorbidities in patients with psoriasis, with a focus on metabolic comorbidities, precisely because the dermatologists are usually the first medical contact due to the predominance of skin lesions. Therefore, these specialists have the responsibility to inform patients on the association between psoriasis and possible multiple comorbidities, devise prevention and treatment plans, or even redirect patients to other specialists.

Current trends in gene therapy for retinal diseases (Review).

The eye is considered an effective target for genetic therapy, as it has a privileged immune status, it is easily accessed for medication delivery and it is affected by a number of inherited disorders. In particular, the retina is considered for gene therapy due to the fact that it can be visualized with ease, it does not have lymphatic vessels, nor a direct blood network for the outer layers and its cells do not divide after birth, and thus transgene expression is not affected. As gene therapy is currently on a continuously progressive development trend, this emerging field of gene manipulation techniques has yielded promising results. This involves the development of treatments for a number of debilitating and blinding diseases, which were to date considered intractable. However, numerous unanswered questions remain as regards the long-term efficacy and safety profile of these treatments. The present review article discusses the current research status regarding genetic manipulation techniques aimed at addressing visual impairment related to retinal disorders, both inherited and degenerative.

Uveal melanoma diagnosis and current treatment options (Review).

Uveal melanoma is a rare condition accounting for only 5% of all primary melanoma cases. Still, it is the most frequently diagnosed primary intraocular malignant tumor in adults. Almost 90% of the tumors involve the choroid and only a small percentage affects the ciliary body or the iris. There is a consistent difference in incidence between different regions with individuals of northern European descent having a significantly higher risk as compared to Hispanics, Asians, and Blacks. Among the many risk factors, mutations in the G protein subunit alpha Q (GNAQ) or G protein subunit alpha 11 (GNA11) genes and different receptors are highly suggestive. While iris melanoma can easily be noticed by the patient itself or diagnosed at a routine slit-lamp evaluation, a consistent percentage of posterior uveal tumors are incidentally diagnosed at funduscopic evaluation as they can evolve silently for years, especially if located in the periphery. Uveal melanoma classifications rely on the tumor size (thickness and basal diameter) and also on intraocular and extraocular extension. The differential diagnosis with pseudomelanomas is carried out according to the tumor aspect and position. Iris melanoma has a better prognosis and a lower mortality rate as compared to choroidal melanoma that has a much higher rate of metastasis (50% of the patients) and a subsequent limited life expectancy from 6 to 12 months. While conservative therapeutic options for the primary tumor, relying on different surgical excision techniques and/or irradiation therapies, offer good local tumor control, the treatment options for metastatic disease, although numerous, are still inadequate in preventing a fatal outcome.

Management of psoriasis in children (Review).

Psoriasis is a common long-lasting, inflammatory disease that mainly affects the skin. The incidence of this condition has increased significantly over time and at this point, it affects approximately 1% of children. Psoriasis can appear at any age, including childhood and adolescence, with a higher frequency in girls, an earlier onset being associated with severe psoriasis. The pathology is the result of the interaction between genetics and trigger factors such as infections, stress, diet, obesity, and chemical irritants. Paradoxically, tumor necrosis factor (TNF)-α inhibitors (infliximab, adalimumab) may induce psoriasis in children. Psoriasis is a long-term condition with periods of exacerbation; thus, the quality of life can be affected and patients should receive psychosocial support. Although most children have mild disease and topical treatment is efficient, some cases are challenging to treat. The aim of this review was to provide an overview of the current knowledge concerning the epidemiology, etiology, pathogenesis, clinical features, comorbidities, and treatment of psoriasis in children and also to emphasize the need for a multidisciplinary approach to this complex pathology.

Hypersensitivity reactions to monoclonal antibodies: Classification and treatment approach (Review).

The present paper aims to review the topic of adverse reactions to biological agents, in terms of the incriminating mechanisms and therapeutic approach. As a result of immunomodulatory therapy, the last decade has achieved spectacular results in the targeted treatment of inflammatory, autoimmune, and neoplastic diseases, to name a few. The widespread use of biological agents is, however, associated with an increase in the number of observed adverse drug reactions ranging from local erythema to systemic reactions, including life-threatening immunologically mediated events, which justifies the need for a deeper understanding of this subject. Rapid desensitization to biological agents emerges as a treatment strategy for anaphylactic (immediate or delayed) hypersensitivity reactions as well as for severe infusion reactions. Drug desensitization is the administration of progressively increasing doses of the specific preparation until reaching the therapeutic dose in order to induce immunological tolerance and is indicated when the drugs are indispensable to the therapeutic regimen of individuals with hypersensitivity reactions to the preparation, with no reasonable alternatives.

Accelerated vs. conventional collagen cross-linking for infectious keratitis.

Infectious keratitis represents a serious concern for ophthalmologists, with a progressively growing incidence in the last few years. In this prospective comparative study, we evaluated two groups of patients with infectious keratitis or corneal ulcer resistant to antimicrobial and antifungal therapy, treated respectively with conventional and accelerated photoactivated chromophore collagen cross-linking. Eight patients were assigned to each group and they were monitored for 12 months. We investigated the differences between groups, comparing on one side the mean of the quantitative variables using the t-test and on the other side the frequencies of qualitative variables using the Fisher exact test. The time to healing for the group treated with conventional cross-linking was 2 days longer than for the group undergoing accelerated cross-linking (34.9±11.4 vs. 32.9±9.4 days), a difference that did not reach statistical significance (P=0.708). We conclude that the accelerated protocol is as safe and efficient as the classic procedure. The accelerated protocol has an important advantage, both for the doctor and the patient, of being time sparing (the time for accelerated cross-linking is 3 times shorter than in the case of the conventional protocol).

Immunohistochemical study of CD117 in various cutaneous melanocytic lesions.

The aim of the present study was to carried out a comparative immunohistochemical evaluation of CD117 (c-Kit), a biomarker that evaluates both tumor progression and prognosis, in different melanocytic lesions, to emphasize the significance of this biomarker in malignant melanoma (MM). The study was performed on 55 cases, represented by a control group, which included 5 cases of simple nevi and 5 cases of dysplastic nevi, as well as a study group consisting of 35 cases of primary MM and 10 metastases (one intestinal, 3 cutaneous - one satellite and two distant as well as 6 in the lymph nodes). The study group included 15 cases of superficial spreading melanoma (SSM), 10 cases of nodular melanoma (NM), 3 lentigo maligna melanoma (LMM), 3 cases of acral lentiginous melanoma (ALM) and 4 cases of amelanotic MM. CD117 was found to be massively involved in the process of tumorigenesis of cutaneous malignancies, being immunohistochemically undetectable in benign neural lesions, but densely expressed in dysplastic lesions and in situ melanoma areas. In invasive cutaneous MMs, CD117 expression tended to decrease with neoplasia progression proceding into the tumorigenic, vertical growth phase, being lower in the profound dermal component of tumors and in nodular MMs. To eliminate the epidermal barriers and gain a proliferative advantage to allow the transition to the vertical growth phase, it seems that MM should lose expression of c-Kit. Cutaneous metastases were found to express CD117 at a level comparable to their primary tumors, suggesting that other mechanisms interfere directly with the metastatic process and not loss of c-Kit expression by itself. CD117 overexpression in cutaneous melanocytic lesions correlates significantly with increased immunostaining intensity, suggesting that the immunohistochemical evaluation of CD117 may be a good method for screening patients, who could benefit from personalized therapy with tyrosine kinase inhibitors.

Intraocular pressure changes during and after silicone oil endotamponade (Review).

Silicone oil (SIO) has rapidly become an indispensable adjunct in vitreoretinal surgery. Constant improvements in purity and also in viscosity have not totally prevented specific complications that may occur during endotamponade. Results of in vitro studies that suggested that higher viscosity silicone oil might be superior in terms of stability and safety are confirmed in real life only if endotamponade lasts for more than 6 months. Intraocular pressure changes induced by the silicone oil endotamponade or oil extraction are documented from its very first use and are potentially threatening vision. The purpose of this review is to update current knowledge on the incidence, risk factors, pathogenesis, and management of secondary silicone oil glaucoma. Also, in a retrospective evaluation on cases with complex retinal detachments that underwent 23G vitrectomy and high viscosity SIO endotamponade, we have noticed that a considerable number of cases developed significant intraocular pressure changes during SIO endotamponade and after SIO removal, especially in early postoperative period.

Subretinal alteplase injections in massive subretinal hemorrhage due to age-related macular degeneration: A case report series.

This report describes a series of cases with massive subretinal hemorrhage (SRH) due to age-related macular degeneration (AMD) treated by subretinal alteplase injections. In all cases, the surgical technique consisted in 25-gauge pars plana vitrectomy (PPV) and alteplase injection under the retina using a 38-gauge cannula. After the fluid-gas exchange, bevacizumab injection was performed in all patients. Three cases of SRH in which this technique was used, as well as their evolution at one week and one month postoperatively are described. Visual acuity was hand motion in all three cases at presentation. After surgery, a significant anatomical and functional improvement was noted in all cases. One month postoperatively, none of the patients had blood under the macula, and visual acuities significantly improved to 0.8, 0.2 and 0.16 (decimal fraction). A consistent reduction of central retinal thickness was observed on optical coherence tomography (OCT) from the first week postoperatively. No intra and postoperative complications were noted. Subretinal alteplase injection proved as a viable solution in these severe SRH with early presentation. There was no need to change the systemic anticoagulant and antiaggregant therapy. Bevacizumab intravitreal injection at the end of surgery has an important role in preventing further bleeding.

Influence of unilateral intravitreal bevacizumab injection on the incidence of symptomatic choroidal neovascularization in the fellow eye in patients with neovascular age-related macular degeneration (Review).

Neovascular age-related macular degeneration (neovascular ARMD) represents only 10% of ARMD cases but is responsible, if untreated, for quick and severe central vision loss due to major macular changes. The presence of choroidal neovascularization (CNV) in one eye is associated with an approximately 10% risk of CNV development in the fellow eye each year. Intravitreal anti-VEGF therapy has quickly evolved as the standard treatment in neovascular ARMD in the last decade due to significant anatomical and functional improvements, especially in the early stages. In many reports an improvement in the untreated fellow eye was mentioned and systemic exposure was soon confirmed for all anti-VEGF agents after unilateral intravitreal injection. In particular, bevacizumab intravitreal injection is followed by a consistent reduction of serum VEGF levels and the drug was shown to have the longest serum half-life raising important debates about its safety. Once bevacizumab was detected in the fellow eye of an animal model after unilateral injection, the possible influence on fellow eye conversion rate into neovascular ARMD was questioned. Although comparative studies have not found statistically significant differences between drugs regarding the incidence of symptomatic CNV in the fellow eye during treatment, we observed, on a retrospective 36-month evaluation, a reduced incidence of symptomatic CNV in the fellow eye that might be explained by the consistent systemic exposure of bevacizumab.