A Prediction Model to Discriminate Small Choroidal Melanoma from Choroidal Nevus

Objective: To develop a validated machine learning model to diagnose small choroidal melanoma. Design: Cohort study Subjects, Participants, and/or Controls: The training data included 123 patients diagnosed as small choroidal melanocytic tumor (5.0-16.0 mm in largest basal diameter and 1.0 mm to 2.5 mm in height; Collaborative Ocular Melanoma Study criteria). Those diagnosed as melanoma (n=61) had either documented growth or pathologic confirmation. 62 patients with stable lesions classified as choroidal nevus, were used as negative controls. The external validation data set included 240 patients managed at a different tertiary clinic, also with small choroidal melanocytic tumor, observed for malignant growth. Methods: In the training data, lasso logistic regression was used to select variables for inclusion in the final model for the association with melanoma versus choroidal nevus. Internal and external validation were performed to assess model performance. Main Outcome Measures: Predicted probability of small choroidal melanoma Results: Distance to optic disc ≥3mm and drusen were associated with decreased odds of melanoma whereas male versus female sex, increased height, subretinal fluid, and orange pigment were associated with increased odds of choroidal melanoma. The area under the receiver operating characteristic (AUROC) “discrimination value” for this model was 0.880. The top four variables that were most frequently selected for inclusion in the model on internal validation, implying their importance as predictors of melanoma, were subretinal fluid, height, distance to optic disc, and orange pigment. When tested against the validation data, the prediction model could distinguish between choroidal nevus and melanoma with high discrimination of 0.861. The final prediction model was converted into an online calculator to generate predicted probability of melanoma. Conclusions: To minimize diagnostic uncertainty, a machine learning based diagnostic prediction calculator can be readily applied for decision making and counselling patients with small choroidal melanoma.

Impact of educational nursing intervention on compression therapy adherence and recurrence of venous leg ulcers: a quasi-experimental study

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 is used, including an intervention, a control group, and before and post-assessments. This study is conducted in one of Egypt's largest teaching hospitals associated with Menoufia University. A 20-month study included 80 adult patients with healed venous leg ulcers. Each participant is randomized to either a control (got regular leg ulcer information) or study (received educational interventions) group. The following tools are used in the study: bio-sociodemographic variables, knowledge evaluation, compression therapy adherence scale, and recurrence follow-up, after three, six, and twelve months of implementation. Furthermore, there is a statistically significant difference between the study groups during the pretest (r=0.885, 0.774, 0.477, p=0.002). The use of nurse 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.

Combination of brachytherapy and intravitreal chemotherapy in the treatment of retinoblastoma with vitreous seeding

Purpose: To report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first line or second line treatment following systemic chemoreduction or intraarterial chemotherapy. Methods: Retrospective data collection of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019. Results: The method described was our first line therapy in 6 patients, whereas it was used as second line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes and 13 group D eyes. The mean follow-up was 19.5 months (range 2 – 53 months). Mean patient age at brachytherapy was 34.0 months (range 15 – 83 months). Median prescribed dose at the tumour base and apex was 574.5 ± 306.7Gy and 88.5 ± 12.2Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of Melphalan was 5.0. Two patients received a simultaneous injection of Topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%) and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow up. Conclusion: Ruthenium-106 plaque therapy in combination with intravitreal chemotherapy is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side effect profile, especially when considering that EBRT and systemic polychemotherapy, or at least the number of cycles needed, with their increased incidence of adverse events can thus be avoided.

Necrotic Uveal Melanoma Mimics Orbital Cellulitis: A Review

<b><i>Background:</i></b> Uveal melanoma is the most common primary intraocular malignancy in adults, often resulting in painless vision loss. We report a case of necrotic uveal melanoma presenting with orbital inflammation mimicking orbital cellulitis and present a comprehensive review of the literature and tabulation of reported cases. <b><i>Summary:</i></b> Our review found 44 published reports of spontaneously necrotic uveal melanoma involving 55 patients. Of these reports, 26 patients (47%) presented with orbital cellulitis. Presenting symptoms of necrotic uveal melanoma with orbital cellulitis included proptosis (82.8%), pain (80.7%), vision loss (61.5%), and restricted extraocular movements (46.2%). <b><i>Key Messages:</i></b> Uveal melanoma can rarely mimic orbital cellulitis. Autoinfarction and tumor necrosis causes secondary orbital inflammation. Intraocular malignancy must remain in the differential for patients with orbital inflammation and vision loss.

Clinical applications of OCTA in ocular oncology: pearls and pitfalls

Background: Optical Coherence Tomography Angiography (OCTA) is a valuable imaging tool for the diagnosis of several retinal and choroidal diseases. Its role in ocular oncology is clinically promising but still controversial. In this review we report the main applications and limits of the use of OCTA for the study of intraocular tumors. Summary: OCTA allows a rapid, safe, low-cost and high-resolution visualization of the retinal and choroidal vasculature. Attempts have been made to use this technology in ocular oncology to differentiate benign and malignant lesions and to assist physicians in the evaluation and monitoring of post-treatment complications. Main limitations include failure in correct segmentation due to tumor inner profile or thickness, poor penetration of laser into the lesion, masking effect from overlying fluid and media opacities and poor fixation. Key messages: The main applications of OCTA in ocular oncology consist in the documentation of tumor-associated choroidal neovascularizations and the study of vascular changes following tumor treatments. In particular, the diffusion of wide-field protocols makes OCTA suitable for the diagnosis and follow-up of radiation chorio-retinopathy allowing a detailed visualoization of both macular and peripheral ischemic changes. Optimistically, future innovations in OCTA technology may offer new perspectives in the diagnosis and follow-up of intraocular tumors.

Single time frame overview of the genetic changes in conjunctival melanoma from, intraepithelial disease to invasive melanoma. A study of 4 exenteration specimens illustrating the potential role of Cyclin D1.

Introduction: Despite advances in the understanding of the molecular pathogenesis of cutaneous melanoma, relatively little is known about the genetic changes that occur in the progression of conjunctival melanocytic from intraepithelial lesions to invasive conjunctival melanoma. Methods: We exposed four exenteration specimens that each contained varying grades of intraepithelial conjunctival melanocytic neoplasia and invasive neoplasia to a combination of various techniques, including array comparative genomic hybridisation (aCGH), RNA seq, fluorescence in-situ hybridisation (FISH) and immunohistochemistry. Results: Three out of four of the invasive melanomas showed gains in 11q13 (CCND1 locus) by aCGH. FISH demonstrated CCND1 gain in invasive melanoma and in conjunctival melanocytic intraepithelial lesions of all grades (Low grade CMIL and in-situ melanoma) and this was paralleled by increased expression of Cyclin D1 protein within the atypical melanocytes by immunohistochemistry, using a double staining method with a red end point for Melan A cytoplasmic staining and a brown end-point for nuclear Cyclin D1 expression. Higher grades of melanocytic intraepithelial lesions showed more cells expressing Cyclin D1 compared to lower grade melanocytic intraepithelial lesions. The Cyclin D1 protein expression was in the same location as the amplified CCND1 signal by FISH. One out of three of these cases also showed amplification of the 12q13-15 locus corresponding to MDM2 and FISH confirmed gains in the conjunctival melanocytic intraepithelial neoplasia and invasive melanoma. The remaining fourth case showed a homozygous deletion of 9p21 (CDKN2A) by aCGH only, with immunohistochemistry showing clonal loss of p16 protein expression in the invasive and conjunctival melanocytic intraepithelial lesion. Two out of four of the invasive melanomas harboured classical driver mutations in NRAS and NF-1respectively. None of the cases showed mutations in BRAF, KIT and TERT mutations. RNAseq data showed secondary mutations in ARAF, PLCB4, MET, EZH2, MAP2K2, CTNNB1, CIITA, NF2, TP53 and MEN1, some of which are implicated in the MAPK pathway. Conclusion: Conjunctival melanocytic intraepithelial lesions harbour amplifications of CCND1 (3 cases), MDM2 (1 case) and loss of CDKN2A (1 case), which are also present when the lesion progresses to invasive melanoma, implicating these amplifications in the early pathogenesis of conjunctival melanocytic intraepithelial lesions. This study represents the first attempt to capture the mutational landscape of at all stages of conjunctival melanoma in a single tissue excision.

Impact of adjuvant ocular interventions on the quality of life of patients with uveal melanoma after proton beam therapy

Introduction Proton beam therapy is an established primary treatment for patients with non-metastasized 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 and QLQ-OPT30 questionnaires at baseline, and at three and twelve months after proton therapy. Patients were grouped by the type of adjuvant treatment. Impact on QOL was analyzed by comparing changes in 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 three and twelve 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 Post-treatment adjuvant interventions had no long-lasting effects on QOL in patients with uveal melanoma.

Improved prognostic precision in uveal melanoma through a combined score of clinical stage and molecular prognostication

Introduction: Prognosis of uveal melanoma (UM) is assessed using clinical staging or molecular testing. Two modalities often used for prognostication are the American Joint Committee on Cancer (AJCC) staging and a tumor gene expression profile (GEP), the outcomes of which are often discordant. This paper discusses a Total Risk Score created to combine the discordant information from both sources. Methods: A retrospective case series was conducted of all patients presenting with UM over six years to two referral centers. Each tumor was classified using the AJCC and the GEP. A Total Risk Score was calculated for each patient using results from both AJCC and GEP. Kaplan-Meier analysis of metastasis free-survival was used to compare groups. Results: A total of 294 patients were included in the study. Kaplan-Meier estimates showed significant curve separation between individual AJCC and GEP risk groups. The combined Total Risk Score provided an accurate estimate of prognosis that incorporated results from both AJCC and GEP. Conclusions: Clinical staging and molecular prognostication of UM can be discordant. There is important information provided by each system that is not provided by the other. The Total Risk Score provides a simple method to combine information from both the AJCC stage and the GEP class in order to provide patients and care teams with a more complete understanding of metastatic risk.

Clinicopathological Features of 19 Eyelid Pilomatrixomas

Introduction: Pilomatrixoma is a relatively rare, benign tumor arising from the hair root matrix. It is found frequently on the head and neck, with most involving the eyebrow in the periocular region. In contrast, eyelid pilomatrixoma is less common, and often clinically misdiagnosed. Here, we present clinical and histological data from 19 pilomatrixomas arising in the eyelid. Methods: The study represents a retrospective study of eyelid pilomatrixoma diagnosed at our institution since 1981. All slides were reviewed, and demographic as well as clinical data obtained. Results: Patient ages ranged from 2 to 63 years (mean 24 years), including 12 (63%) females and 7(37%) males. Eight (42%) and 4 (21%) cases arose in the first and second decades of life, respectively. Upper eyelid involvement was found in 14 (74 %) of cases. Microscopically, the tumors were characterize by basaloid and shadow cells accompanied by calcification and foreign body giant cells. Conclusions: Eyelid pilomatrixoma is rarely suspected clinically, and can be mistaken for cyst, chalazion, sebaceous carcinoma and other tumors. Physicians should consider the possibility of pilomatrixoma in the eyelid area, especially in children or young female patients. Complete excision is curative, and diagnosis can generally be established by histopathological examination.