Search Results (27)

Melanoma occurs in various forms and body areas, not only in the cutis, but also in mucous membranes and the uvea. Rarer subtypes of that cancer differ in genomic aberrations, which cause their minor sensibility to regular cutaneous melanoma therapies. Therefore, it is essential to discover new strategies for treating rare forms of melanoma. In recent years, interest in applying CDK inhibitors (CDKIs) in cancer therapy has grown, as they are able to arrest the cell cycle and inhibit cell proliferation. Current studies highlight selective CDK4/6 inhibitors, like palbociclib or abemaciclib, as a very promising therapeutic option, since they were accepted by the FDA for advanced breast cancer treatment. However, cells of every subtype of melanoma do not react to CDKIs the same way, which is partly because of the genetic differences between them. Herein, we discuss the past and current research relevant to targeting various CDKs in mucosal, uveal and acral melanomas. We also briefly describe the issue of amelanotic and desmoplastic types of melanoma and the need to do more research to discover cell cycle dysregulations, which cause the growth of the mentioned forms of cancer. Full article

Plaque radiotherapy is an effective treatment modality for medium-sized ocular tumors such as uveal melanoma. The authors review the available literature and concisely summarize the current state of the art of ophthalmic plaque brachytherapy. The choice of radioisotope, which includes Ruthenium-106 and Iodine-125, depends on the intended treatment duration, tumor characteristics, and side effect profiles. Ophthalmic plaques may be customized to allow for the delivery of a precise radiation dose by adjusting seed placement and plaque shape to minimize collateral tissue radiation. High dose rate (HDR) brachytherapy, using beta (e.g., Yttrium-90) and photon-emitting sources (e.g., Ytterbium-169, Selenium-75), allows for rapid radiation dose delivery, which typically lasts minutes, compared to multiple days with low-dose plaque brachytherapy. The efficacy of Ruthenium-106 brachytherapy for uveal melanoma varies widely, with reported local control rates between 59.0% and 98.0%. Factors influencing outcomes include tumor size, thickness, anatomical location, and radiation dose at the tumor apex, with larger and thicker tumors potentially exhibiting poorer response and a higher rate of complications. Plaque brachytherapy is effective for selected tumors, particularly uveal melanoma, providing comparable survival rates to enucleation for medium-sized tumors. The complications of plaque brachytherapy are well described, and many of these are treatable. Full article

Neutrophil extracellular traps (NETs) play an essential role in antimicrobial defense. However, NETs have also been shown to promote and mediate a wide spectrum of diseases, including cancer, diabetes mellitus, cardiovascular diseases, and ocular diseases. Data regarding NETs in ocular diseases remain limited. In physiological conditions, NETs protect the eye from debris and cleave proinflammatory cytokines, including several interleukins. On the other hand, NETs play a role in corneal diseases, such as dry eye disease and ocular graft-versus-host disease, where they promote acinar atrophy and delayed wound healing. Additionally, NET levels positively correlate with increased severity of uveitis. NETs have also been described in the context of diabetic retinopathy. Although increased NET biomarkers are associated with an increased risk of the disease, NETs also assist in the elimination of pathological blood vessels and the regeneration of normal vessels. Targeting NET pathways for the treatment of ocular diseases has shown promising outcomes; however, more studies are still needed in this regard. In this article, we summarize the literature on the protective roles of NETs in the eye. Then, we describe their pathogenetic effects in ocular diseases, including those of the cornea, uvea, and retinal blood vessels. Finally, we describe the therapeutic implications of targeting NETs in such conditions. Full article

Histopathologically, uveal melanomas (UMs) can be classified as spindle cell, mixed cell and epithelioid cell type, with the latter having a more severe prognosis. The aim of our study was to assess the correlation between the apparent diffusion coefficient (ADC) and the histologic type of UMs in order to verify the role of diffusion-weighted magnetic resonance imaging (DWI) as a noninvasive prognostic marker. A total of 26 patients with UMs who had undergone MRI and subsequent primary enucleation were retrospectively selected. The ADC of the tumor was compared with the histologic type. The data were compared using both one-way analysis of variance (ANOVA) (assessing the three histologic types separately) and the independent t-test (dichotomizing histologic subtypes as epithelioid versus non-epithelioid). Histologic type was present as follows: the epithelioid cell was n = 4, and the spindle cell was n = 11, the mixed cell type was n = 11. The mean ADC was 1.06 ± 0.24 × 10⁻³ mm²/s in the epithelioid cells, 0.98 ± 0.19 × 10⁻³ mm²/s in the spindle cells and 0.96 ± 0.26 × 10⁻³ mm²/s in the mixed cell type. No significant difference in the mean ADC value of the histopathologic subtypes was found, either when assessing the three histologic types separately (p = 0.76) or after dichotomizing the histologic subtypes as epithelioid and non-epithelioid (p = 0.82). DWI-ADC is not accurate enough to distinguish histologic types of UMs. Full article

The choroid is the main part of the uvea, the vascular layer of the eye that lies between the retina and the sclera. The high vascular component of the choroid makes this structure susceptible to inflammation in multisystemic diseases, as well as the most common site of metastasis in the eye. Therefore, the choroid is involved in many pathological conditions, from uveitis to intraocular tumors. Differentiating between inflammatory and neoplastic lesions deforming the choroidal profile can sometimes be challenging. In addition, scleral disorders can also deform the choroidal profile. Choroidal imaging includes ophthalmic ultrasonography, indocyanine green angiography, and optical coherence tomography (OCT). Recent advances in choroidal imaging techniques, such as enhanced depth imaging optical coherence tomography (EDI-OCT) and swept-source optical coherence tomography (SS-OCT), have facilitated an in-depth analysis of the choroid. The purpose of this review article is to report on and highlight the most common OCT findings to help in the differential diagnosis between inflammatory and neoplastic lesions deforming the choroidal profile. Full article

Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second, tissue biopsy is not routinely recommended due to the risk of extraocular dissemination. Third, UM is an aggressive cancer because it is estimated that about 50% of patients will experience metastatic spread without any curative treatment available at this stage. These challenges better explain the two main objectives in the creation of a dedicated UM biobank. First, collecting UM samples is essential due to tissue scarcity. Second, large-scale translational research programs based on stored human samples will help to better determine UM pathogenesis with the aim of identifying new biomarkers, allowing for early diagnosis and new targeted treatment modalities. Other periocular malignancies, such as conjunctival melanomas or orbital malignancies, also raise specific concerns. In this context, the number of biobanks worldwide dedicated to ocular malignancies is very limited. The aims of this article were (i) to describe the specific challenges raised by a dedicated ocular malignancy biobank, (ii) to report our experience in setting up such a biobank, and (iii) to discuss future perspectives in this field. Full article

The choroid, a multifunctional tissue, has been the focus of research interest for many scientists. Its morphology and morphometry facilitate an understanding of pathological processes within both the choroid and retina. This study aimed to determine the choroidal layer thicknesses in healthy, mixed-breed mesocephalic dogs, both male (M) and female (F), using spectral domain optical coherence tomography (SD-OCT) with radial, cross-sectional, and linear scans. The dogs were divided into two groups based on age: middle-aged (MA) and senior (SN). Thicknesses of choroidal layers, namely RPE–Bruch’s membrane–choriocapillaris complex (RPE-BmCc) with tapetum lucidum in the tapetal fundus, the medium-sized vessel layer (MSVL), and the large vessel layer with lamina suprachoroidea (LVLS), as well as whole choroidal thickness (WCT), were measured manually using the caliper function integrated into the OCT software. Measurement was performed dorsally and ventrally at a distance of 5000–6000 μm temporally and nasally at a distance of 4000–7000 μm to the optic disc on enhanced depth scans. The measurements were conducted temporally and nasally in both the tapetal (temporal tapetal: TempT, nasal tapetal: NasT) and nontapetal (temporal nontapetal: TempNT, nasal nontapetal: NasNT) fundus. The ratio of the MSVL thickness to the LVLS thickness for each region was calculated. In all examined dogs, the RPE-BmCc in the dorsal (D) region and MSVL in the Tt region were significantly thicker than those in the other regions. The MSVL was thinner in the ventral (V) region than in the D, TempT, TempNT and NasT regions. The MSVL was significantly thinner in the NasNT region than in the D region. LVLS thickness and WCT were significantly greater in the D and TempT regions than those in the other regions and significantly lesser in the V region than those in the other regions. The MSVL-to-LVLS thickness ratio did not differ between the age groups. Our results reveal that the choroidal thickness profile does not depend on age. Our findings can be used to document the emergence and development of various choroidal diseases in dogs in the future. Full article

The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases. Full article

Numerous complications following COVID-19 vaccination has been reported in the literature, with an increasing body of evidence reporting vaccination-associated uveitis (VAU). In this systematic review, we searched six electronic databases for articles reporting the occurrence of VAU following COVID-19 vaccination. Data were synthesized with emphasis on patients’ characteristics [age, gender], vaccination characteristics [type, dose], and outcome findings [type, nature, laterality, course, location, onset, underlying cause, and associated findings]. Data are presented as numbers (percentages) for categorical data and as mean (standard deviation) for continuous data. Sixty-five studies were finally included [43 case reports, 16 case series, four cohort, one cross-sectional, and one registry-based study]. VAU occurred in 1526 cases, most commonly in females (68.93%) and middle-aged individuals (41–50 years: 19.71%), following the first dose (49.35%) of vaccination, especially in those who received Pfizer (77.90%). VAU occurred acutely (71.77%) as an inflammatory reaction (88.29%) in unilateral eyes (77.69%), particularly in the anterior portion of the uvea (54.13%). Importantly, most cases had a new onset (69.92%) while only a limited portion of cases had a reactivation of previous uveitis condition. In conclusion, although rare, uveitis following COVID-19 vaccination should be considered in new-onset and recurrent cases presenting with either acute or chronic events. Full article

Honey and propolis have recently become the key target of attention for treating certain diseases and promoting overall health and well-being. A high content of flavonoids and phenolic acids found in both honey and propolis contributes to the antioxidant properties to scavenge free radicals. Honey and propolis also exhibited antibacterial effects where they act in two ways, namely the production of hydrogen peroxide (H₂O₂) and gluconic acids following the enzymatic activities of glucose oxidase, which exerts oxidative damage on the bacteria. Additionally, the anti-inflammatory effects of honey and propolis are mainly by reducing proinflammatory factors such as interleukins and tumor necrosis factor alpha (TNF-α). Their effects on pain were discovered through modulation at a peripheral nociceptive neuron or binding to an opioid receptor in the higher center. The aforementioned properties of honey have been reported to possess potential therapeutic topical application on the exterior parts of the eyes, particularly in treating conjunctivitis, keratitis, blepharitis, and corneal injury. In contrast, most of the medicinal values of propolis are beneficial in the internal ocular area, such as the retina, optic nerve, and uvea. This review aims to update the current discoveries of honey and propolis in treating various ocular diseases, including their antioxidant, anti-inflammatory, antibacterial, and anti-nociceptive properties. In conclusion, research has shown that propolis and honey have considerable therapeutic promise for treating various eye illnesses, although the present study designs are primarily animal and in vitro studies. Therefore, there is an urgent need to translate this finding into a clinical setting. Full article

There are increasing reports that anticancer drugs, especially immunotherapy and specific targeted therapy, can cause uveitis, but it is not fully understood whether the clinical features of this drug-induced uveitis differ from those of other types of uveitis and whether there are differences between these drugs. We retrospectively reviewed the published cases and case series in PubMed, Embase, Web of Science, and Cochrane from January 2011 to October 2020. We analysed the data, including patients’ basic information, medications used, duration of use, time to onset, clinical manifestations, diagnosis, treatment, and prognosis of uveitis. We focused on the differences in uveitis caused by immunotherapy and specific targeted therapy. Altogether 93 cases (43 men, 48 women, and 2 cases whose gender was not mentioned) reported in 55 articles were included in this study. The average age was 59.6 ± 13.5 years. Eighty percent of the patients had bilateral involvement. Sixty cases were caused by immunotherapy (64.5%), and twenty-six were caused by specific targeted therapy (27.9%). No significant difference was found in the mean time from treatment to onset between the two groups. Anticancer drug-induced uveitis can involve all parts of the uvea from anterior to posterior, manifested as anterior chamber flare, anterior chamber cells, papillitis, macular oedema, subretinal fluid, and choroidal effusion. Anterior uveitis (24 cases, 40.0%) was more common in immunotherapy, and intermediate uveitis (8 cases, 30.8%) was more common in specific targeted therapy. The mean LogMAR visual acuity in specific targeted therapy at presentation was lower than in immunotherapy, but it was not statistically significant. Corticosteroid therapy can effectively control uveitis induced by anticancer drugs. However, the survival prognosis was poor. Among the 19 patients with reported cancer prognosis, seven (36.8%) had no cancer progression, eight (42.1%) had further metastases, and four (21.0%) died of cancer. In conclusion, uveitis caused by anticancer drugs involves both eyes and manifests as various types of uveitis. Patients with specific targeted therapy are more likely to have intermediate uveitis and low vision, and immunotherapy patients are more likely to have anterior uveitis. Corticosteroids are effective against uveitis caused by anticancer drugs. Full article

Since 2020, the COVID-19 (Coronavirus Disease 2019) has quickly become a worldwide health problem. Ophthalmologists must deal with symptoms as well. For the positive detection in the conjunctival sac swab in COVID-19 patients hospitalized in Slovakia during March 2021 in four hospital centers, we used a test based on a polymerase chain reaction (PCR). In a group of 484 patients, 264 males (55%) and 220 females (45%) with clinical symptoms were identified with COVID-19 as a clinical diagnosis. The PCR test swab results from the conjunctival sac taken on the same day were positive in 58 patients (12%), 31 males (with a mean age of 74.6 ± 13.59 years) and 27 females (with a mean age of 70.63 ± 14.17 years); negative in 417 patients (86%); and 9 patients (2%) had an unclear result. The cycle threshold values comparing the nasopharynx and conjunctiva were also different in the group of all patients divided by age and gender. In COVID-19 patients the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was detectable using PCR test in the nasopharynx but also in the conjunctival sac swab, where the positivity rate was only 12%. Full article

Ocular tumors are a family of rare neoplasms that develop in the eye. Depending on the type of cancer, they mainly originate from cells localized within the retina, the uvea, or the vitreous. Even though current treatments (e.g., radiotherapy, transpupillary thermotherapy, cryotherapy, chemotherapy, local resection, or enucleation) achieve the control of the local tumor in the majority of treated cases, a significant percentage of patients develop metastatic disease. In recent years, new targeting therapies and immuno-therapeutic approaches have been evaluated. Nevertheless, the search for novel targets and players is eagerly required to prevent and control tumor growth and metastasis dissemination. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system consists of a family of proteins involved in a variety of physiological and pathological processes, including cancer. Indeed, tumor and stroma activation of the FGF/FGFR system plays a relevant role in tumor growth, invasion, and resistance, as well as in angiogenesis and dissemination. To date, scattered pieces of literature report that FGFs and FGFRs are expressed by a significant subset of primary eye cancers, where they play relevant and pleiotropic roles. In this review, we provide an up-to-date description of the relevant roles played by the FGF/FGFR system in ocular tumors and speculate on its possible prognostic and therapeutic exploitation. Full article

Melanoma is an aggressive malignancy that arises from the transformation of melanocytes on the skin, mucosal membranes, and uvea of the eye. SWI/SNF chromatin remodeling enzymes are multi-subunit complexes that play important roles in the development of the melanocyte lineage and in the response to ultraviolet radiation, a key environmental risk factor for developing cutaneous melanoma. Exome sequencing has revealed frequent loss of function mutations in genes encoding SWI/SNF subunits in melanoma. However, some SWI/SNF subunits have also been demonstrated to have pro-tumorigenic roles in melanoma and to affect sensitivity to therapeutics. This review summarizes studies that have implicated SWI/SNF components in melanomagenesis and have evaluated how SWI/SNF subunits modulate the response to current therapeutics. Full article

The deep sclerectomy technique was modified to enhance aqueous humor (AH) outflow via the non-trabecular pathway. A pilot study was carried out to assess its safety and effectiveness. Thirty-eight patients were under observation. After superficial scleral flap (4 × 4 mm), deep scleral layers were divided into three parts by three parallel-to-limbus incisions. Deep sclerectomy without creating a window in the Descemetes’ membrane was carried out in the distal part. A collagen implant was placed under the sclera of the remaining two parts with one end in the intrascleral pool. The third proximal part was excised to expose the uvea and implant. A Nd:YAG laser trabeculotomy at the surgery site was made on postoperative days 7–10. Outcome measures were IOP change, use of hypotensive medication(s), complications, and the need for a second surgery. At six months, the mean IOP decreased from 29.1 ± 9.2 mm Hg to 14.0 ± 4.3 mm Hg (p = 1.4 × 10⁻⁹); hypotensive medication use reduced from 2.9 ± 0.9 to 0.6 ± 1.0 (p = 1.3 × 10⁻¹⁰); complete success was achieved in 68.4% of cases and partial success was achieved in 31.6% of cases. Intraoperative and postoperative complications were rare and manageable. The OCT of the surgery site revealed the absence of bleb in all cases. Lymphatic vessels with characteristic bicuspid valves in their lumen were detected in conjunctiva near the operation site and over it in 32 patients. IOP decrease in the proposed technique was achieved by activation of the uveolymphatic route of AH outflow. Full article