Ocular Oncology and Pathology最新文献

Background: Over the last few decades, chemotherapy has become the main treatment of retinoblastoma, delivered through various routes: intravenous, intra-arterial, and intravitreal. Despite its efficacy, chemotherapy-related toxicity (ocular and systemic) and recurrences due to resistant tumor clones are common, highlighting the need for novel therapeutic agents. Summary: Recent advances in our understanding of the molecular drivers of Rb1 tumorigenesis and mechanisms of tumor resistance have afforded opportunities to explore novel targets such as the MDMX-p53 pathway (nutlin-3), histone deacetylase inhibitors, spleen tyrosine kinase inhibitors, and genetic and immune modulatory drugs. In this review, we discuss the limitations of current therapeutic strategies, candidate cellular pathways, current evidence for newer targeted drugs, and offer a look toward the future. Key Messages: Advances in the understanding of the molecular drivers of the RB pathway have provided opportunities to explore novel drugs with targeted effects, improved bioavailability, and reduced chemotoxicity.

Introduction: Iodine-125 brachytherapy is an effective eye-sparing treatment for uveal melanoma. Previous work has shown that uveal melanomas cluster into distinct molecular classes based on gene expression profiles - discriminating low-grade from high-grade tumors. Our objective was to identify clinical and molecular predictors of local recurrence (LR) and progression-free survival (PFS).

Methods: We constructed a retrospective database of uveal melanoma patients from the University of Miami's electronic medical records that were treated between January 8, 2012, and January 5, 2019, with either COMS-style or Eye Physics plaque. Data on tumor characteristics, pretreatment retinal complications, post-plaque treatments, LR, and PFS were collected. Univariate and multivariate Cox models for cumulative incidence of LR and PFS were conducted using SAS version 9.4.

Results: We identified 262 patients, with a median follow-up time of 33.5 months. Nineteen patients (7.3%) had LR, and 56 patients (21.4%) were classified as PFS. We found that ocular melanocytosis (hazard ratio = 5.55, p < 0.001) had the greatest impact on PFS. Genetic expression profile did not predict LR outcomes (hazard ratio = 0.51, p = 0.297).

Conclusion: These findings help physicians identify predictors for short-term brachytherapy outcomes, allowing better shared decision making with patients preoperatively when deciding between brachytherapy versus enucleation. Patients stratified to higher risk groups based on preoperative characteristics such as ocular melanocytosis should be monitored more closely. Future studies must validate these findings using a prospective cohort study.

Introduction: The aim of the study was to analyze the results of intraocular surgery in treated retinoblastoma eyes and to assess the long-term results with a priority on local recurrences, secondary enucleation, and metastases. Methods: Retrospective noncomparative case series. Results: From March 1964 to January 2020, 42 eyes of 40 retinoblastoma patients underwent intraocular surgery. Time interval between the last therapy and surgery was 9.5 years (mean: 114 months; median: 54.5 months). 31 eyes were treated for radiogenic cataract formation with a gain in visual acuity of 61.3%. One child developed an upper eyelid metastasis, 3 showed second primary malignancies (SPM), one a late recurrence, and 2 eyes were enucleated. Retinal surgery was performed in 17 eyes; 6 eyes were done as a combined procedure. Indications were radiogenic complications in the sense of a vitreous hemorrhage in 11 eyes and a rhegmatogenous retinal detachment in 6 eyes. 41.2% of the treated eyes had a postoperative gain in visual acuity, whereas 9.5% of the eyes could not be preserved in the long term. Regarding systemic involvement 2 patients developed late recurrences and one a SPM. Conclusion: Surgical therapy in treated retinoblastoma is necessary in isolated cases. In our series, cataract surgery was a safe procedure with a good option of a significant increase in visual acuity. As expected, vitreoretinal treated eyes showed a limited gain in visual acuity, a higher risk of late recurrences, and a lower globe retention rate. Therefore, a careful indication and individual risk-benefit analysis are mandatory.

Introduction: The presenting symptoms of retinoblastoma in Ethiopia, as well as their relationship to the stage of the disease, are poorly understood, but they could be important as background knowledge for creating early detection initiatives. This study aimed to describe the clinical and histopathological characteristics of retinoblastoma among Ethiopian patients. Methods: A hospital-based cross-sectional analysis of all children with newly diagnosed retinoblastoma during the study period of May 2015 to December 2019, inclusive, who presented to a tertiary referral center during were included. Demographic, clinical, and histological characteristics were collected and descriptive statistics were done using SPSS Version 20.0 software. Results: A total of 217 patients (unilateral 84.3%, bilateral 15.7%) were studied. The median age at presentation was 29 months (34 months vs. 19.5 months in unilateral and bilateral cases, respectively, p < 0.001). Among all patients, 57.8% were male. Leukocoria was the most common presenting sign (37.3%) and followed by fungating mass (31.8%). Tumors were extraocular in 40.1% of cases. From the intraocular cases, 73.3% were advanced International Intraocular Retinoblastoma Classification Group D or E disease. Sixty-two (54.4%) of the eyes had high-risk pathological features. The median lag time was significantly shorter for intraocular versus extraocular cases (5 months vs. 12 months, respectively, p < 0.001). Conclusion: Our results show that the majority of Ethiopian children with retinoblastoma have delayed presentation and late stage at diagnosis. This suggests that national health promotion campaigns to increase public knowledge on the presenting signs of retinoblastoma may be critical to achieving early diagnosis. Furthermore, the development of standard management guidelines informed by this study will be helpful in managing the complex and advanced cases currently observed.

Following the healing of venous leg ulcers, the primary problems for nursing and patients are adhering to compression therapy and preventing ulcer recurrence. As a result, it is important that patients comprehend their situation. The purpose of this study is to see how an educational nursing intervention affected compression therapy adherence and recurrence of venous leg ulcers in patients with chronic venous leg ulcers. A quasi-experimental design was used, including an intervention, a control group, and before and after assessments. This study was conducted in one of Egypt's largest teaching hospitals associated with Menoufia University. The 20-month study included 80 adult patients with healed venous leg ulcers. Each participant was randomized to either a control (got regular leg ulcer information) or study (received educational interventions) group. The following tools were used in the study: bio-sociodemographic variables, knowledge evaluation, compression therapy adherence scale, and recurrence follow-up, after 3, 6, and 12 months of implementation. Furthermore, there is a statistically significant difference between the study groups during the pretest (r = 0.885, 0.774, and 0.477, p = 0.002). The use of nursing education increased patients' understanding and adherence to compression treatment substantially. As a consequence, those with chronic venous leg ulcers may be able to avoid recurrent venous leg ulcers.

Introduction: Proton beam therapy is an established primary treatment for patients with nonmetastasized uveal melanoma. Adjuvant local interventions, like intravitreal injections or surgery, were shown to improve long-term eye preservation; however, their impact on the patient's quality of life (QOL) remains unknown.

Methods: In a post-radiotherapeutic follow-up, we prospectively collected data on QOL, visual acuity, and interventional adjuvant procedures. QOL was measured with QOL-C30 questionnaire and quality of life questionnaire OPT30 at baseline, and at 3 and 12 months after proton therapy. Patients were grouped by the type of adjuvant treatment. The impact on QOL was analyzed by comparing changes in the mean score values and visual acuity for different interventional subgroups, with generalized linear mixed models and Wilcoxon signed-rank tests.

Results: We received 108 (100%) and 95 (88.0%) questionnaires at 3 and 12 months post-therapy, respectively. Adjuvant interventions included observation (n = 61, 56.5%), intravitreal injections (n = 17, 15.7%), and an intraocular surgical procedure (n = 30, 27.8%). In the latter group, several QOL items significantly declined after the 3-month adjuvant interval, but they partially recovered at the 12-month follow-up. In all adjuvant-intervention groups, global QOL scores returned to baseline levels at 12 months.

Conclusion: Posttreatment adjuvant interventions had no long-lasting effects on QOL in patients with uveal melanoma.

Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and despite treatment of the primary tumor, approximately 15%-50% of patients will develop metastatic disease. Based on gene expression profiling (GEPs), UM can be categorized as Class 1A (low metastatic risk), Class 1B (intermediate metastatic risk), or Class 2 (high metastatic risk). PReferentially expressed Antigen in MElanoma (PRAME) status is an independent prognostic UM biomarker and a potential target for immunotherapy in metastatic UM. PRAME expression status can be detected in tumors using reverse-transcription polymerase chain reaction (RT-PCR). More recently, immunohistochemistry (IHC) has been developed to detect PRAME protein expression. Here, we employed both techniques to evaluate PRAME expression in 18 UM enucleations.

Methods: Tumor material from the 18 UM patients who underwent enucleation was collected by fine-needle aspiration before or during enucleation and sent for GEP and PRAME analysis by RT-PCR. Histologic sections from these patients were stained with an anti-PRAME monoclonal antibody. We collected patient demographics and tumor characteristics and included this with our analysis of GEP class, PRAME status by RT-PCR, and PRAME status by IHC. PRAME IHC and RT-PCR results were compared.

Results: Twelve males (12/18) and 6 females (6/18) with an average age of 60.6 years underwent enucleation for UM. TNM staging of the UM diagnosed Stage I in 2 patients (2/18), Stage II in 7 patients (7/18), Stage III in 8 patients (8/18), and Stage IV in 1 (1/18). GEP was Class 1A in 6 tumors (6/18), Class 1B in 6 tumors (6/18), and Class 2 in 6 tumors (6/18). PRAME IHC showed diffusely positive labeling of all UM cells in 2/18 enucleations; negative IHC labeling of UM cells in 9/18 enucleations; and IHC labeling of subsets of UM cells in 7/18 enucleations. Eleven of the 17 UMs tested for PRAME by both RT-PCR and IHC had consistent PRAME results. In the remaining 6/17 cases tested by both modalities, PRAME results were discordant between RT-PCR and IHC.

Conclusions: We find that PRAME IHC distinguishes PRAME-positive and PRAME-negative UM tumor cells. Interestingly, IHC reveals focal PRAME expression in subsets of tumor cells consistent with tumor heterogeneity. PRAME RT-PCR and IHC provide concordant results in most of our cases. We suggest that discordance in PRAME results could arise from spatial or temporal variation in PRAME expression between tumor cells. Further studies are required to determine the prognostic implications of PRAME IHC in UM.