Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning.

Purpose: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. Design: Retrospective multicenter study. Participants: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). Methods: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with fivefold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under precision-recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10 000 bootstrap samples with replacement and results. Main Outcome Measures: Area under receiver operating curve and AUPRC for each ML model. Results: There were 2870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top-performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (95% CI: 0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (95% CI: 0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow-up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 [95% CI: 0.655-0.657]). The top 5 features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. Conclusions: We demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease.

Artificial intelligence methods in diagnosis of retinoblastoma based on fundus imaging: a systematic review and meta-analysis.

BACKGROUND: Artificial intelligence (AI) algorithms for the detection of retinoblastoma (RB) by fundus image analysis have been proposed as a potentially effective technique to facilitate diagnosis and screening programs. However, doubts remain about the accuracy of the technique, the best type of AI for this situation, and its feasibility for everyday use. Therefore, we performed a systematic review and meta-analysis to evaluate this issue. METHODS: Following PRISMA 2020 guidelines, a comprehensive search of MEDLINE, Embase, ClinicalTrials.gov and IEEEX databases identified 494 studies whose titles and abstracts were screened for eligibility. We included diagnostic studies that evaluated the accuracy of AI in identifying retinoblastoma based on fundus imaging. Univariate and bivariate analysis was performed using the random effects model. The study protocol was registered in PROSPERO under CRD42024499221. RESULTS: Six studies with 9902 fundus images were included, of which 5944 (60%) had confirmed RB. Only one dataset used a semi-supervised machine learning (ML) based method, all other studies used supervised ML, three using architectures requiring high computational power and two using more economical models. The pooled analysis of all models showed a sensitivity of 98.2% (95% CI: 0.947-0.994), a specificity of 98.5% (95% CI: 0.916-0.998) and an AUC of 0.986 (95% CI: 0.970-0.989). Subgroup analyses comparing models with high and low computational power showed no significant difference (p=0.824). CONCLUSIONS: AI methods showed a high precision in the diagnosis of RB based on fundus images with no significant difference when comparing high and low computational power models, suggesting a viability of their use. Validation and cost-effectiveness studies are needed in different income countries. Subpopulations should also be analyzed, as AI may be useful as an initial screening tool in populations at high risk for RB, serving as a bridge to the pediatric ophthalmologist or ocular oncologist, who are scarce globally. KEY MESSAGES: What is known Retinoblastoma is the most common intraocular cancer in childhood and diagnostic delay is the main factor leading to a poor prognosis. The application of machine learning techniques proposes reliable methods for screening and diagnosis of retinal diseases. What is new The meta-analysis of the diagnostic accuracy of artificial intelligence methods for diagnosing retinoblastoma based on fundus images showed a sensitivity of 98.2% (95% CI: 0.947-0.994) and a specificity of 98.5% (95% CI: 0.916-0.998). There was no statistically significant difference in the diagnostic accuracy of high and low computational power models. The overall performance of supervised machine learning was best than unsupervised, although few studies were available on the second type.

Description and Characteristics of Ocular Tumor Lysis Syndrome.

Introduction: The aim of the study was to describe and evaluate characteristics of ocular tumor lysis syndrome (OTLS) in eyes with uveal melanoma. Methods: Retrospective chart review of all patients with OTLS at the University of Colorado from 2009 to 2021. Data collected included patient demographics, tumor characteristics, radiation dosimetry, gene expression profiling (GEP), OTLS characteristics, management, and outcomes. Results: Seven eyes of seven patients with uveal melanoma treated with I-125 brachytherapy developed OTLS. Average age was 59 years (range 32-83). Mean apical height was 8.6 mm (range 6-11); mean diameter was 12.7 mm (range 8.5-15.3). All tumors were treated with plaques ≥16 mm in diameter. On presentation, 5/7 tumors had subretinal fluid, and 6/7 had collar-button configuration. OTLS presented as extensive pigment dispersion in the vitreous in all eyes, subretinal pigment and/or retinal detachment in 4/7 eyes, vitreous hemorrhage in 2/7 eyes, and anterior chamber pigment in 3/7 eyes. Four tumors were GEP class 1, two were class 2, and one was unclassified. Biopsy route was trans-scleral in 4/7 eyes and trans-vitreal in 3/7 eyes. OTLS occurred 2-4 weeks after an intraocular procedure in 5/7 eyes. All underwent pars plana vitrectomy. Cytology of the vitreous, obtained in five cases, showed pigment laden macrophages and hemorrhage, but only 1/5 eyes had viable malignant cells. Four eyes were stable at the last follow-up, two were enucleated, and one had no light perception from pigmentary glaucoma. Poor vision (<20/200) occurred in 6/7 cases. Three patients died from metastasis (tumors were GEP class 2, GEP class without subclassification, and no GEP classification performed). Conclusions: OTLS is a rare but devastating complication of uveal melanoma. Common characteristics included large plaque diameter, presence of subretinal fluid, and collar-button shape. The extensively dispersed pigment is typically not malignant. Though poor vision is common, enucleation may be avoided in most eyes through vitreoretinal surgical repair.

Geographic Patterns of Ocular Oncologist Supply and Patient Demand for Uveal Melanoma Treatment in the United States: A Supply and Demand Analysis.

Purpose: To study geographic patterns of supply and demand for uveal melanoma and other ocular oncology healthcare by ocular oncology physicians in the United States. Methods: Google search interest data was obtained through trends.google.com. The combined-state density of ocular oncology physicians was calculated by dividing the number of practicing ocular oncologists in each state and its surrounding states by the state population. Relative search volume (RSV) values were divided by ocular oncology physician density to calculate the Google relative demand index (gRDI) for each state. Medicare (mRDI) and IRIS® Registry (iRDI) relative demand indices were calculated using prevalence data obtained through the Vision and Eye Health Surveillance System (VEHSS). Data from the US Census Bureau and Centers for Disease Control (CDC) databases were also utilized to analyze associations with poverty rates, percent living in urban or rural areas, vision screening rates, and ocular neoplasm rates. Results: Alabama showed the highest RSV (100), while the lowest was reported in New Mexico (20). Vermont had the highest density of combined-state ocular oncology ophthalmologists (1.85 per 100,000 residents). New Mexico had the lowest RDI (0.013 gRDI, 0.015 mRDI, 0.018 iRDI) with 32 combined-state ocular oncologists and a population of 2,114,371. Ocular neoplasm prevalence rates ranged between 1.32% and 5.40% and significantly correlated with RSV. Single-state gRDI correlated with rural status and negatively correlated with urban areas (≥50,000 individuals). Single-state ophthalmologist density correlated positively with percent living in urban areas and vision screening rates, and negatively with rural status. Conclusion: This study uncovered significant heterogeneity in the geographical distribution of ocular oncology physicians and RDI throughout the United States, highlighting potential undersupply scenarios. This may guide efforts to increase ocular oncology physician and surgeon availability in areas of need.

Bevacizumab and External Beam Radiation Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome: A Case Report.

Introduction: Sturge-Weber syndrome, a congenital vascular disorder, is associated with diffuse choroidal hemangiomas in which the current mainstay of treatment is radiation therapy, including external beam radiation therapy (EBRT). The purpose of this case report was to present a novel combination of treatments for diffuse choroidal hemangioma. Case Presentation: A 37-year-old man with a history of Sturge-Weber-associated glaucoma presented with an acute-onset decrease in vision in the right eye. Best-corrected visual acuity (BCVA) at the presentation was 20/400 in the right eye. Examination revealed a total macula-off, bullous, folded exudative retinal detachment and findings consistent with diffuse choroidal hemangioma. The patient was treated with a single injection of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent bevacizumab and 10 fractions of EBRT of the right eye. Follow-up examination at 17 months demonstrated complete resolution of subretinal fluid and no evidence of choroidal elevation on B-scan. Final BCVA in the right eye was 20/1,000. Conclusion: This case uses simultaneous treatment with EBRT and bevacizumab in the treatment of diffuse choroidal hemangioma and associated exudative retinal detachment. Clinicians may use anti-VEGF agents early in the course of the disease in determining whether they may assist in preventing visual decline.

Managing vitreoretinal complications in uveal melanoma: Surgical treatment and practical considerations.

BACKGROUND: In the past few decades, the primary management for uveal melanoma has evolved from enucleation to eye-preserving treatments. However, despite achieving a high rate of local tumour control, complications following eye-preserving treatments still occur and are partly responsible for functional loss and secondary enucleation. METHODS: A literature review by a broad international panel. RESULTS: We summarised the current literature on utilizing vitreoretinal (VR) surgery for managing the complications of uveal melanoma. We also provided insights from the authors' personal experience and practical recommendations for clinical care. CONCLUSIONS: With the advancement of VR instruments and surgical techniques and the combination of VR and ocular oncology knowledge ("Onco-VR"), it is now possible to manage or even prevent complications such as vitreous haemorrhage, retinal detachment, and toxic tumour syndrome.

Primary orbital apocrine adenocarcinoma: case report and literature review.

Primary apocrine adenocarcinoma (PAA) originating from the orbit is a rare malignant neoplasm. We present the case of a 61-year-old-male with PAA of the orbit. The patient underwent a right orbital exenteration, neck dissection, and adjuvant radiotherapy. Orbital exenteration is commonly performed as the primary intervention for PAA of the orbit. The role of adjuvant radiotherapy to prevent local recurrence is unclear and may be determined on a case-by-case basis.

Transient Bacillary Layer Detachment During the Disease Course of Primary Vitreoretinal Lymphoma.

PURPOSE: To report the clinical course and the retinal imaging features of a case of cytology-proven primary vitreoretinal lymphoma (PVRL) presenting with a transient bacillary layer detachment (BALAD) during the disease course. METHODS: Observational case report. RESULTS: A 50 year-old woman was referred to us with a 2-month history of vitritis in both eyes, poorly responding to oral prednisolone. After discontinuation of oral prednisolone, worsening of vitritis and the appearance of multiple creamy-like subretinal infiltrates in the mid-peripheral retina of both eyes, along with the exclusion of common causes of intermediate/posterior uveitis, made us consider PVRL. Aqueous humor sampling detected MYD88 L265P mutation, and subsequent diagnostic pars plana vitrectomy in the left eye yielded a positive cytology for large B cell lymphoma consistent with PVRL. During the disease course, optical coherence tomography of the macula showed a BALAD in the right eye, which resolved during follow-up. CONCLUSION: Our case indicates that BALAD is a possible rare manifestation of PVRL, and this should be considered in the differential diagnosis process in order to avoid diagnostic delays.

Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature.

Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.

Posterior Uveitis in Ocular-Involving Chronic Lymphocytic Leukemia and the Utility of Negative MYD88 L265P Testing in the Diagnosis.

Introduction: The aim of this study was to investigate if a negative test result for MYD88 L265P mutation, associated with vitreoretinal lymphoma (VRL) and primary CNS lymphoma, in liquid biopsies from intraocular fluids can be a useful adjuvant test to diagnose chronic lymphocytic leukemia in clinically challenging cases. Case Presentations: We selected patients with a past medical history or examinations findings suspicious for intraocular lymphoma. We evaluated both vitreous and aqueous humor-derived (AHD) MYD88 L265P mutation from patients that had suspected intraocular lymphoma that warranted a liquid biopsy procedure. Gold-standard cytopathology, flow cytometry, and gene rearrangement studies were also performed. All 4 patients had negative AHD MYD88 L265P mutation testing. Gold-standard testing (cytology) either showed paucicellular specimens (1/4) or specimens with high background inflammation (3/4). One case showed a rare B-cell clonal population (CD5+, Kappa-restricted by flow cytometry), but this was not sufficient to make any definitive diagnosis. All patients were subsequently initiated on systemic therapy and had improvement in their disease burden. Conclusions: Negative AHD MYD88 L265P mutation testing can serve as an adjuvant molecular test to diagnose difficult cases of intraocular CLL.

Conjunctival Intraepithelial Neoplasia Mimicking a Pigmentary Lesion in an HIV-Seropositive Indian Male.

We present the case of a 27-year-old male who presented to our ophthalmology outpatient clinic with a pigmented lesion on the conjunctiva of his right eye. There was no history of ocular trauma or familial ocular complaints, and a thorough evaluation revealed the patient's seropositive status for HIV for the past eight years. The presentation resembled a conjunctival pigmentary lesion, with typical features of ocular surface squamous neoplasia (OSSN) being absent and a demographic incongruent with typical OSSN cases as OSSN typically affects the elderly population. Given the patient's HIV status and the lesion's recent increase in size, a more aggressive treatment approach was warranted. Mass excisional biopsy surgery confirmed conjunctival intraepithelial neoplasia with one positive margin. Adjuvant treatment with mitomycin eye drops (0.04%) resulted in no lesion recurrence at the one-month follow-up. Conjunctival intraepithelial neoplasia can mimic pigmentary lesions in young HIV-positive patients with obvious signs of OSSN being absent. In such cases, the history of seropositivity should be sufficient to suspect it as OSSN and aggressive management measures should be adopted to get best possible outcomes.

Evidence in Focus: The Sparse Landscape of Randomized Trials on Retinoblastoma Treatment.

Background: Retinoblastoma, although rare, is one of the most common intraocular malignancies worldwide. Its prognosis has improved significantly in the past few decades, thanks to modern treatments, like systemic, intra-arterial, and intravitreal chemotherapy. However, regarding survival, there are significant differences between high- and low-income countries, eye salvage is still a challenge worldwide, and treatment-related toxicity needs to be carefully and sufficiently managed. Summary: To appraise the strength of supporting evidence, we performed a systematic review of randomized controlled trials investigating any therapeutic protocol for retinoblastoma. Four trials with 174 participants (188 eyes) were eligible, all pertaining to different intravenous chemotherapy regimens. Vincristine, etoposide, and carboplatin (VEC) appear superior to a 5-drug combination for stage III retinoblastoma. Moreover, etoposide and carboplatin as neoadjuvant chemotherapy followed by thermochemotherapy seem to offer better local control than vincristine and carboplatin. However, increasing carboplatin dose in the VEC protocol failed to improve treatment efficacy. Key Messages: Retinoblastoma is a success story of modern medicine. However, only intravenous chemotherapy has been studied through randomized trials, while evidence for the most novel retinoblastoma treatments has mainly stemmed from observational studies. International collaborations for multicenter randomized trials could overcome difficulties and increase certainty and precision in the field.

Topical 5-Fluorouracil 0.5% as primary treatment for Ocular Surface Squamous Neoplasia.

PURPOSE: To evaluate the efficacy of topical treatment with 5-Fluorouracil (5-FU) 0.5% in cases of Ocular Surface Squamous Neoplasia (OSSN), and to assess the tolerance of patients undergoing treatment. METHODS: Patients with clinical diagnosis of OSSN referred to the Ocular Oncology division from the Federal University of Sao Paulo, Brazil, were recruited for the current study. Patients were treated with topical 5-FU 0.5% using a regimen of 4 times daily for 10 days, followed by a 3-week drug holiday, continued up to 3 cycles before an alternative treatment. Lesions were evaluated at baseline and throughout treatment. Treatment adherence was assessed using the Morisky Medication Adherence scale. Any adverse events along the treatment were noted. RESULTS: A total of 30 eyes of 30 patients adherent to the treatment were included in the study. Among the total cases treated with 5-FU 0.5%, 24 patients achieved therapeutic success after a mean treatment duration of 21.71 ± 7.77 days, representing a success rate of 80.00% (95% CI: 60.75-91.18%). For each 1 mm2 increase in the lesion area, the odds of treatment success decrease by 6% (OR: 0.94; 95%CI: 0.88-0.99; p = 0.033). Only mild adverse events such as ocular discomfort, ocular burning and tearing were observed along the treatment in 8 patients. CONCLUSIONS: Topical 5-FU 0.5% is an effective therapeutic option in the treatment of OSSN, with an 80% therapeutic success rate, showing good tolerability. The size of the lesion was identified as a factor influencing treatment success, therefore it should be taken into consideration when defining treatment approaches.

CyberKnife Stereotactic Radiosurgery for Uveal Melanoma: First Case Series in Central America.

Introduction: Uveal melanoma is the most common primary intraocular malignancy in adults, affecting primarily the choroid of the eye. Plaque brachytherapy is the most common procedure for the treatment of small choroidal melanoma, especially in posteriorly located tumors. However, modern radiotherapy techniques, such as CyberKnife or Gamma knife stereotactic radiosurgery (SRS) and proton beam radiotherapy, have shown better results in tumor control and eye retention. Recent studies have indicated that SRS is a promising non-invasive, single-session treatment option, with most studies reporting the best outcomes when using ≥21-22 Gy. However, there is no consistent protocol for managing this pathology using CyberKnife, not only in terms of dose but also fractions. Case Presentations: Here, we report the first case series of patients (n = 4, age range 38-64 years, median age 52.5 years) with choroidal UM in Central America who were treated with CyberKnife SRS (22 Gy in one session). During the follow-up (range 25-29 months, median 27.5 months), a 100% control rate with no systemic metastatic disease has been achieved. We found a statistically significant reduction in the largest basal diameter at 24 months for all tumors. However, visual acuity has progressively decreased in most patients. Notably, two of our patients developed radiation maculopathy, and the other two developed radiation retinopathy after SRS. Conclusions: Our findings suggest that future studies should evaluate the use of different prophylactic therapies to prevent the development of side effects. The clinical management of toxicities presented in our report can serve as a reference in the clinical practice of other centers. Our report supports the growing body of evidence showing that CyberKnife radiosurgery is a safe and effective therapeutic option for the treatment of UM.

Ocular metastases profile in a tertiary hospital in São Paulo, Brazil.

OBJECTIVE: Ocular metastases are the most common intraocular tumours in adults. Data regarding the occurrence of these tumours in the Brazilian population is scarce. We aimed to investigate the profile of ocular metastases of patients referred to tertiary hospital service in São Paulo, Brazil. DESIGN: Retrospective study. PARTICIPANTS: Patients referred to the Ocular Oncology service of the Federal University of São Paulo with initial diagnostic hypothesis of ocular metastasis. METHODS: Data was retrospectively collected from medical records from June 2017 to June 2023. Age, sex, primary tumour site, previous knowledge of the systemic diagnosis, laterality, initial visual acuity (VA), local or systemic treatment and mean follow-up period were obtained. RESULTS: A total of 37 cases were referred to the ocular oncology division due to a suspected ocular metastasis, 15 (40.5%) were confirmed. Mean age at diagnosis was 53.47 ± 16.01 years old, the majority (86.7%) of patients already knew the systemic diagnosis. Breast cancer (66.7%) was the most common primary site, followed by Lung cancer (26.7%). Both eyes were affected in 66.67% of the cases, all patients had metastases at the choroid (100.0%), and the mean initial VA was 1.37 ± 1.04 logMAR. Chemotherapy was the main systemic treatment modality (73.3%), and most patients had no ocular treatment (53.3%). The mortality rate along the follow-up period was 30.0%. CONCLUSIONS: Considering the number of new patients absorbed by the Ocular Oncology service over the study period, the frequency of ocular metastases was relatively low. The patients' characteristics was comparable to data published in the international literature.

Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Melanocytic Nevus of the Superior Conjunctival Fornix: A Case Report.

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

Ptosis secondary to orbital metastasis undetected by magnetic resonance imaging: A case report.

We report a patient with isolated ptosis secondary to orbital metastasis but no evidence of a neoplastic process on magnetic resonance imaging (MRI). A 69-year-old male was referred to our hospital with ptosis of the right upper eyelid and secondary frontalis muscle overaction on the left side for six months. The palpebral fissure was 3mm on the right and 16mm on the left, and levator function was 6mm and 19mm respectively. Three years previously, he had undergone surgical resection of the left lower lobe of the lung due to a T1 N0 M0 adenocarcinoma, and no recurrence had since been observed. An MRI was performed to rule out ptosis secondary to metastasis. Thyroid dysfunction and myasthenia were also ruled out. The ptosis was attributed to an isolated microvascular third nerve palsy. A standard external levator advancement was performed. Six months after the surgery, the patient presented with intense pain, minimal ptosis, edema and diplopia. A new MRI revealed an orbital metastasis measuring 2.4×1.0×1.6cm in the superior orbit, exerting mass effect on the superior rectus and the levator palpebrae superioris muscle. A positron emission tomography scan revealed a recurrence of the lung cancer with multiple bony metastases. The patient underwent chemotherapy consisting of the taxol-carboplatin protocol. Our report highlights the importance of a high index of suspicion of a neoplastic etiology in patients with mild symptoms and a history of cancer even if imaging does not initially reveal a mass or infiltration.

Exploring vismodegib: A non-surgical breakthrough in the management of advanced periocular basal cell carcinoma.

The management of periocular basal cell carcinoma (BCC) is challenging due to its proximity to the eyeball. Vismodegib, a Hedgehog pathway inhibitor, has emerged as a therapeutic option for locally advanced and metastatic BCC. To critically appraise the relevant evidence, we conducted a systematic review of observational and experimental studies assessing the efficacy and safety of vismodegib for periocular BCC. Thirty-seven trials, including 435 patients, were eligible. No randomized trials were retrieved. Complete and overall clinical response rates were 20-88 % and 68-100 %, respectively. Disease progression was observed at a maximum rate of 14 %. Recurrence rates varied between 0 % and 31 %. The most common side effects were muscle cramps, dysgeusia, weight loss and alopecia. Treatment with vismodegib improved health-related quality of life. In conclusion, vismodegib represents an important novel treatment for advanced periocular BCC, with good response rates and acceptable tolerability profile. Nevertheless, its full potential needs clarification through randomized controlled trials.