Diagnostic Challenges in Inflammatory Choroidal Neovascularization.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

Use of Optical Coherence Tomography and Optical Coherence Tomography Angiography in the Diagnosis and Follow-Up of Endogenous Candida Endophthalmitis: A Case Report.

Background: Endogenous Candida endophthalmitis (ECE) is a rare but sight-threatening disease. Patients with ECE present with various clinical signs and symptoms, which can complicate the diagnosis. The aim of this report was to demonstrate the outcomes of treatment and to diagnose macular complications caused by intraocular inflammation. Case presentation: A 41-year-old woman with a history of acute intermittent porphyria presented with a progressive vision loss in her left eye. Left-eye OCT revealed findings consistent with a fungal etiology, which was confirmed by the culture of swabs collected from a central vein catheter. The outcomes of intravenous fluconazole treatment were not satisfactory, and the patient developed recurrent attacks of porphyria, suggesting a porphyrogenic effect of systemic antifungal therapy. Repeated intravitreal injections with amphotericin B led to a gradual regression of inflammatory lesions. However, follow-up examinations revealed active macular neovascularization (MNV) on both OCT and OCTA scans. The patient was administered intravitreal bevacizumab. At the 11th month of follow-up, OCT and OCTA scans showed significant inflammatory lesions regression with macula scarring, and no MNV activity was detected. Conclusions: This case highlights the importance of OCT and OCTA as valuable noninvasive imaging techniques for the identification of ECE, the monitoring of its clinical course, and the diagnosis of macular complications.

A Cross-Sectional Survey Reporting on the Value of Patient-Centered Ostomy Programs: A Smooth Transition After Ostomy Surgery.

PURPOSE: The purpose of the study was to evaluate a postsurgical ostomy patient support program in regard to postsurgical experience, education, skin care, pouching system and accessory use, insurance issues, supplier assistance, hospital readmission status, and the benefit of multiple interactions. DESIGN: Cross-sectional design. SUBJECTS AND SETTING: Potential respondents were randomly selected from a group of adults 18 years or older who underwent ostomy surgery within 6 months prior to survey completion. Nine hundred seventy-one individuals met inclusion criteria, and 297 were selected for analysis, based on having 1 or more program interactions. Data were collected between the second and third quarters of 2020. All participants were residents of the United States. METHODS: Participants were contacted by e-mail containing an invitation to participate in a survey; the e-mail also described the intent of the survey. Survey distribution was conducted by the sponsor and linked to a third-party survey management organization for compilation. The survey questionnaire, developed specifically for the purpose of this study, comprised 73 items that queried demographic and pertinent clinical data, participation in an industry-sponsored patient support program, and their post-hospital discharge experiences including unplanned health care provider visits, emergency department visits, and hospital readmissions. RESULTS: Eighty-three percent (n = 237) of respondents did not have postsurgical ostomy-related emergency department visits, 75% (n = 223) did not have related unplanned physician visits, and 90% (n = 268) did not have related hospitalizations. Participants with 2 or more interactions were more likely to contact a program representative for issues of stoma care, leakage and skin care, ostomy products/accessories, and supplier issues than their single-interaction counterparts. CONCLUSIONS: Study findings suggest that patients with new ostomies benefited from engagement in an industry-sponsored patient support program. The benefit appears to arise from personal interactions and respondents; 2 or more interactions were shown to have greater benefit than a single interaction.

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy-From Animal Models to Clinical Trials.

The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Characteristic features of choroidal tumors in Deep Range Imaging Optical Coherence Tomography. / [Cechy charakterystyczne guzów wewnatrzgalkowych w optycznej koherentnej tomografii (DRI-OCT)].

Presentation of literature review and own experience in imaging of characteristic features of choroidal tumors in Deep Range Imaging Optical Coherence Tomography.

Imaging choroidal osteoma with the Deep Range Imaging Optical Coherence Tomography ­ a case report. / Kostniak naczyniówki w badaniu Deep Range Imaging Optical Coherence Tomography ­ prezentacja przypadku.

Choroidal osteoma is a rare, benign tumor which primarily affects young females, occurring at the posterior pole of the eye. Differential diagnosis, based on ophthalmoscopy, ocular ultrasound and modern techniques such as Deep Range Imaging Optical Coherence Tomography, should include amelanotic choroidal melanoma or metastatic tumors. This case report outlines the features of choroidal osteoma imaged using the Deep Range Imaging Optical Coherence Tomography, namely its lamellar and spongy bone structure, sclero-choroidal junction, tumour transparency, parallel horizontal and vertical canals communicating the lesions, as well as the presence of calcified and decalcified regions.

Evaluation of intraocular proton beam irradiation complications after choroidal melanoma treatment. / [Ocena wewnatrzgalkowych powiklan po terapii protonowej czerniaków naczyniówki].

Purpose: The aim of the research was to evaluate of intraocular complications after proton beam therapy of choroidal melanomas Material and methods: A total 105 patients (48 female and 57 male) from Department of Ophthalmology and Ocular Oncology of University Hospital in Cracow, who received proton beam radiation due to choroidal melanoma were enrolled. The mean age was 52.3 years (51.8 y. in females, 52.6 y. in males). Total irradiation dose was 60 cGy and it was applied in 4 fractions per 15 cGy (on 4 consecutive days). We evaluated the incidence of complications classifying patients by age, tumor location, tumor thickness, longitudinal and transversal basal diameter and follow-up period, which ranged between 5 and 57 months. Results: Complications of intraocular irradiation were observed in 33 out of 105 treated patients. Retinopathy occurred in 18 cases, including 4 patients with macular edema. Neuropathy was confirmed in 8 patients, secondary glaucoma in 6 cases; we noted 9 cases of initial or progress existing cataract, 4 cases of dry eye syndrome and 1 patient with central retinal vein occlusion. A statistically significant positive correlation was demonstrated between the length of the follow-up period and the incidence of complications, which were more common and more severe with the longer follow-up period. There was no statistically significant correlation between the incidence of complications and patient's age, tumor location, tumor thickness as well as longitudinal and transversal basal diameter. Conclusion: All forms of radiation therapy used in intraocular tumors are associated with some risk of complications; proton beam radiotherapy is not free of that risk, either.

Uveal melanoma ­ is a biopsy safe and justified? / Czerniak naczyniówki ­ czy biopsja jest bezpieczna i uzasadniona?

Uveal melanoma can be typically diagnosed based on clinical presentation and the A and B mode ultrasound. In some atypical intraocular tumours or for prognostic purposes intraoperative biopsy may be performed. Uveal melanoma biopsy is not safe in 100% and can cause complications (vitreous hemorrhage, retinal detachment and endophthalmitis). Like all biopsies, a biopsy in uveal melanoma biopsy may show limited cellularity and can yield insufficient tissue specimen for histology, cytology and genetic testing. This is most likely in small tumours, below 3 mm in thickness. Another limitation of biopsy-based prognosis is the issue of intratumoural heterogeneity. As a biopsy allows for only a small sample to be removed from the tumour, it is possible to receive false negative results. The most devastating complication of uveal melanoma biopsy is the extraocular spread of the tumour. The study is a review of the current opinions and findings on the role of biopsy in uveal melanoma.

[Merkel cell carcinoma]. / Rak z komórek Merkla.

Merkel cell tumor is a highly aggressive cancer of the skin and mucous membranes. It is most common in elderly patients and in individuals with impaired immunity. Merkel Cell Carcinoma can develop anywhere, but it most frequently affects the heac and neck, as well the skin of the upper limbs. Clinically, it occurs as red, glistening tumor with telangiectasias on the surface At the moment of diagnosis, 50% of patients have already developed metastases, most commonly to regional lymph nodes. The treatment depends on the severity and consists primarily of surgical excision with a margin of healthy tissue followec by possible complementary radiotherapy. Chemotherapy is introduced in advanced cases.

Bilateral choroidal melanoma--case analysis and literature review.

Uveal melanoma is the most common primary intraocular neoplasm in adults. Its bilateral localization is extremely rare. The aim of the paper is analysis of the cases of bilateral uveal melanoma. Five bilateral uveal melanoma patients were diagnosed in the Department of Ophtalmology and Ocular Oncology beetwen 1980 and 2014. Both eyes of four patients were threated with brachytherapy. Final enulcleation of the one eye was performed in three patients. It was the primary treatment in one patient. The presence of uveal melanoma was confirmed by pathological examination in all cases after surgical removal of eyeball and in one after local resection of iris tumor. Metastatic lesions were diagnosed in lungs and liver in two patients. Three patients are still followed-up at our institution. The possibility of bilateral uveal melanoma should considered although it is extremely rare. bilateral uveal melanoma, brachytherapy, enucleation.

[The familial occurrence of choroidal melanoma]. / Rodzinne wystepowanie czerniaka blony naczyniowej.

In 2010 we treated one case of familial choroidal melanoma which was detected in a mother and a daughter at the Department of Ophthalmology and Ocular Oncology University Hospital in Krakow. The enucleation was performed in a daughter, while the mother refused to give an informed consent to the procedure despite the diagnosis of ring melanoma, and was eventually subjected to brachytherapy. In both cases histopathological examination confirmed melanoma. Both patients and their relatives have remained in a follow-up until now. Results: Inheritance may play a role in the etiology of melanoma. Therefore, each time melanoma is diagnosed, the close relatives of the patients should undergo regular eye tests.

Preliminary results of proton radiotherapy for choroidal melanoma - the Kraków experience.

AIM OF THE STUDY: The objective of the study was to present the preliminary results of proton radiotherapy as a method for treating 15 patients with choroidal melanoma. MATERIAL AND METHODS: The proton radiotherapy was administered using beams providing energy levels of 60 MeV, which ensures a clinical range of 28.4 mm. In addition, the beam has a very narrow penumbra of 1.3 mm and a sharp distal dose fall-off. All patients received the dose of 60 CGE (cobalt gray equivalent) given to the PTV (planning target volume). This dose was administered in 4 fractions over 4 successive days of treatment. RESULTS: The tumour had regressed in 8 patients (53.3%) and remained stable in 3 patients (20%). The large tumours in another 3 patients (20%) were removed during vitrectomy (endoresection), which increased the number of patients with tumour regression up to 11 (73.3%). In the case of 1 patient, despite intraocular tumour regression occurring the choroidal melanoma had spread multifocally into the orbit, which necessitated orbit exenteration. The results ensured that the eyeballs of 14 patients (93.3%) could be saved. The follow-up period for the 15 patients ranged between 8 and 26 months (average: 17.4 months, median: 19 months). In this period some side effects were noted: an increase in intraocular pressure, retinal detachment, cataract, maculopathy, neuropathy and vitreous haemorrhaging. CONCLUSIONS: The preliminary results confirm that proton radiotherapy is an effective method for treating patients with choroidal melanoma. This method ensures an eyeball preservation rate of 93%, with the vision function of 80% of the patients being saved.

[Bilateral choroidal osteoma--a case report]. / Obustronny kostniak naczyniówki--opis przypadku.

Choroidal osteoma is a an extremely rare (especially located bilaterally), benign, intraocular tumor, the type of choristoma. It occurs between 2-3 decades of life, women are particularly vulnerable. The main complication in 1/3 cases is a subretinal neovascularization which may cause bleeding. The gradually progressive decalcification develops within the tumour over time, which causes atrophy of the retinal pigment epithelium and Bruch's membrane deformity. The article presents a case of a 26-year-old woman with bilateral choroidal osteoma complicated by subretinal hemorrhage; the diagnosis was based on clinical examination (biomicroscopy and indirect ophthalmoscopy) as well as specialised tests including: ultrasonography, optical coherence tomography, and fluorescein angiography.

[Ultrasound techniques in diagnosis of extrabulbar extension of uveal melanoma]. / Zastosowanie ultrasonografii w diagnostyce zewnatrzgalkowych nacieków czerniaka blony naczyniowej.

PURPOSE: To evaluate the utility of ultrasound examination in detection of extraocular extension of uveal melanoma. METHODS: A retrospective study of 170 enucleated eyes with ciliary body or/and choroidal melanoma and deep intrascleral tumor invasion with extrascleral extension. RESULTS: The extrascleral extension was detectable before enucleation in 31 eyes (18.24%), and tumor sizes varied from 1.5 to 15 mm. Ultrabiomicroscopy used for the anterior tumor assesment, shows the routes of extrascleral extension of uveal melanoma. uveal melanoma, extraocular extension, ultrasonography.

Ophthalmic applicator displacement as a method of treating large diffuse uveal melanomas.

Purpose: The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas. Material and methods: This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023). To achieve appropriate radiation dose distribution for large tumors with a base greater than 18 mm, brachytherapy (106Ru in 7 patients and 125I in 2 patients) with applicator displacement was used as primary treatment. Median follow-up was 2.9 years, and for patients with positive primary treatment results, it was 1.7 months. Median time to local relapse was 2.3 years. Results: In 5 patients, a positive result of local treatment was obtained, out of whom, one patient underwent enucleation due to complications. In the next 4 cases, local recurrence developed. In all tumors, the use of applicator displacement method caused that planning target volume (PTV) was effectively covered with treatment isodose. Conclusions: Brachytherapy with ocular applicator displacement allows for the treatment of tumors with base measurements larger than 18 mm. The application of this method may be considered as an alternative for eye enucleation in particular cases of large diffuse tumors, such as a neoplasm of the eye with vison, or when a patient does not consent to enucleation.

Molecular profiling of primary uveal melanoma: results of a Polish cohort.

There is no published data regarding the molecular alterations of Polish patients with primary uveal melanoma. We performed whole exome sequencing of 20 primary uveal melanomas (UMs), 10 metastasizing and 10 non-metastasizing cases to identify significant molecular alterations. We detected mutations and copy number variants in the BAP1 gene in 50% (10 cases) of the cases. GNA11 mutations were detected in 50% (10 cases) including nine p.Q209L and one p.R183C. GNAQ mutations gene were detected in 40% (8 cases) and all were p.Q209P. SF3B1, EIF1AX, PLCB4 , and PALB2 mutations were detected in one case each. Genetic aberrations of FBXW7 were detected in 55% of cases, with copy number loss of 10 and missense mutation in one. Gain or loss of copy number was observed in 60%, 60%, and 10% of cases in MYC, MLH1 , and CDKN2A genes, respectively. BAP1 and GNAQ tumor suppressor genes are more often mutated in UM with metastasis, while GNA11 mutations are more frequently detected in non-metastasizing tumors. MYC copy gain was present twice as frequently (80% versus 40%) in cases with versus those without metastases. BAP1 mutation correlated with worse overall survival; while GNA11 mutation and CDKN2A loss correlated with better and worse progression-free survival, respectively. We have confirmed BAP1 prognostic potential and documented frequent MYC amplification in metastasizing cases. Although GNA11 mutation and CDKN2A loss significantly correlated with progression-free survival in our study, our sample size is small. The prognostic significance of GNAQ/GNA11 mutation and CDKN2A loss would require further investigation.

Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas.

BACKGROUND: Accurate risk stratification of uveal melanoma (UM) patients is important for determining the interval and frequency of surveillance. Loss of BAP1 expression has been shown to be strongly associated with UM-related death and metastasis. METHODS: In this study of 164 enucleated UMs, we assessed the prognostic role of preferentially expressed antigen in melanoma (PRAME) expression and Ki67 proliferation index measured by digital quantitation using QuPath programme in patients with BAP1-positive and BAP1-loss UMs. RESULTS: In univariate analyses with log-rank tests and Kaplan-Meier curves, PRAME further stratified only overall survival (OS) in BAP1-positive and BAP1-loss tumour groups. However, Ki67 further stratified both OS and disease-free survival (DFS) in BAP1-positive and BAP1-loss tumour groups. In multivariate analyses, Ki67 percentage and BAP1 were independent survival predictors for both OS and DFS, whereas PRAME was not a significant covariate. In model comparisons, combined Ki67 and BAP1 performed better than combined PRAME and BAP1 in risk-stratifying patients for both OS and DFS. Ki67 was better than PRAME in risk stratification of BAP1-positive UMs. Low Ki67 index correlated with significantly prolonged DFS in BAP1-loss UMs. CONCLUSION: A panel of Ki67 and BAP1 could be a helpful risk stratification strategy for UM.

[Proton beam radiotherapy of uveal melanoma--preliminary results]. / Radioterapia protonowa czerniaka blony naczyniowej--wstepne wyniki leczenia.

PURPOSE: Presentation of the proton beam radiotherapy (PBR) as a method of treatment of the uveal melanoma patients in the Department of Ophthalmology and Ocular Oncology and Nuclear Physics Institute in Cracow, Poland and their preliminary results. MATERIAL AND METHODS: Nine patients with only choroidal melanoma were treated using PBR between January and April 2011. There were 4 women (44%) and 5 men (56%), a mean age 56 years (38-72). The mean tumor thickness using ultrasounds was 4.14 mm (1.4-9.6 mm). RESULTS: The mean follow-up was 6 months (5-7). The mean tumor thickness after PBR was 2.47 mm (0-9.3 mm). In 2 patients endoresection of irradiated tumor mass was performed with final flat scar. After exclusion of these patients from analysis, the mean thickness was 3.17 mm (1.5-9.3 mm). In 6 patients the visual function was stable. CONCLUSIONS: The preliminary results show that PBR is highly precise method of uveal melanoma treatment achieving high rates of local control. This method necessitates a close co-operation between ophthalmologist, oncologist, radiotherapists, and medical physicist as well as an elaboration of own procedures of planning and treatment. uveal melanoma, radiotherapy, proton-beam radiotherapy.

Geosynthetics for Filtration and Stabilisation: A Review.

Geosynthetics have been commonly used for the construction of civil engineering structures such as retaining wall, road and railways, coastal protection, soft ground improvement work, and landfill systems since the 1960s. In the past 40 years, the development of polymer materials has helped to prolong the life of geosynthetics. In terms of the practical use of geosynthetics, engineers must understand their appropriate application. The first part of this paper provides a basic description of geosynthetics, including their types, components, and functions. The second part deals with the geosynthetics used as filters. This part briefly presents the mechanism of filtration, the factors affecting the durability of geotextile filters, design concepts, laboratory tests, and case studies. The third part of the study covers the use of geosynthetics for stabilisation. Its mechanism was explained separately for geogrids and for geocells. Several examples of applications with geosynthetics intended for the stabilisation function are described in the last part of this paper.