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Simple Summary: Conjunctival melanoma (CM) is an aggressive cancer with an unmet need for prognostic biomarkers and more effective treatments. In recent years, a rapid increase in available epigenetic technologies and epigenetic modulation-based treatment options has led to the development/implementation of various epi-drugs in the cancer field. Like other cancers, CM occurrence and prognosis are also believed to be influenced by multiple genetic and epigenetic factors. While the genetic understanding of CM has been significantly improved in recent decades, the epigenetic understanding of CM remains limited. A relatively small number of CM epigenetics studies published to date have revealed some potential biomarkers and/or therapeutic targets; however, their results warrant replication in independent and larger studies/samples. Furthermore, not all epigenetic aspects of CM have been investigated in published studies; hence, an in-depth understanding of CM epigenetics remains largely incomplete. Additional studies are therefore urgently needed to advance our epigenetic understanding of CM and improve clinical outcomes by taking advantage of new therapy options driven by epigenetic knowledge. The purpose of this article is to provide a literature review of the epigenetic understanding of conjunctival melanoma (CM), with a primary focus on current gaps in knowledge and future directions in research. CM is a rare aggressive cancer that predominantly affects older adults. Local recurrences and distant metastases commonly occur in CM patients; however, their prediction and management remain challenging. Hence, there is currently an unmet need for useful biomarkers and more effective treatments to improve the clinical outcomes of these patients. Like other cancers, CM occurrence and prognosis are believed to be influenced by multiple genetic and epigenetic factors that contribute to tumor development/progression/recurrence/spread, immune evasion, and primary/acquired resistance to therapies. Epigenetic alterations may involve changes in chromatin conformation/accessibility, post-translational histone modifications or the use of histone variants, changes in DNA methylation, alterations in levels/functions of short (small) or long non-coding RNAs (ncRNAs), or RNA modifications. While recent years have witnessed a rapid increase in available epigenetic technologies and epigenetic modulation-based treatment options, which has enabled the development/implementation of various epi-drugs in the cancer field, the epigenetic understanding of CM remains limited due to a relatively small number of epigenetic studies published to date. These studies primarily investigated DNA methylation, ncRNA (e.g., miRNA or circRNA) expression, or RNA methylation. While these initial epigenetic investigations have revealed some potential biomarkers and/or therapeutic targets, they had various limitations, and their findings warrant replication in independent and larger studies/samples. In summary, an in-depth understanding of CM epigenetics remains largely incomplete but essential for advancing our molecular knowledge and improving clinical management/outcomes of this aggressive disease. [ABSTRACT FROM AUTHOR]

Uveal melanoma is the most common intraocular malignant tumor in adults. For patients presenting with cataracts and glaucoma, it is recommended to assess whether an intraocular lesion is present as the primary cause. The present study describes the case of a 52-year-old man with primary intraocular malignant melanoma. The patient experienced painless vision loss in the right eye for 1 year, with recent onset of eye swelling and pain in the week prior to seeking medical attention. A slit-lamp examination revealed a shallow anterior chamber in the right eye, a visibly opaque lens and a faint reflection of the tumor surface in the vitreous humor. In addition, the intraocular pressure of this eye was >60 mmHg. Magnetic resonance imaging revealed a large tumor behind the lens measuring 16x18x14 mm. Pathological examination confirmed the diagnosis of malignant melanoma. No BRCA-associated protein-1 somatic mutation was detected, whereas germline mutations of MutL protein homolog 1, RAD54 like, and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 were identified. Extensive systemic examination excluded the possibility that the tumors originated from another part of the body. The present case report highlights the crucial role of slit-lamp examination in the detection of ocular tumors. It is advocated that for patients presenting with cataracts, attention should be paid to the possibility of intraocular tumors. Meticulous slit-lamp microscopy may reveal a reflection of the surface of a malignant melanoma, preventing misdiagnosis. [ABSTRACT FROM AUTHOR]

Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual‐level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127–5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391–7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675–11.099) were significantly associated with overall survival. For non‐SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087–0.651) and combined therapy (HR, 0.133; 95% CI, 0.017–0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new‐generation tyrosine kinase inhibitors (TKIs) are preferred. [ABSTRACT FROM AUTHOR]

The ocular surface and orbit constitute unique microenvironments in the human body. Current advances in molecular research have deepened our understanding of tumor development in these regions. Tumors exhibit greater heterogeneity compared to normal tissues, as revealed by pathological and histological examinations. The tumor microenvironment (TME) plays a crucial role in the proliferation and progression of cancer cells. Factors from the external environment or the body's own inflammation and microcirculation interact within the TME, maintaining a delicate balance. Disruption of this balance, through uncontrolled signal pathway activation, can transform normal or benign tissues into malignant ones. In recent years, various systemic immunotherapies have been developed for cancer treatment. This study reviews the epidemiology of ocular surface and orbital tumors include squamous cell carcinoma, basal cell carcinoma, sebaceous carcinoma and lymphoma in conjunction with their occurrence, growth, and underlying mechanisms. We propose that by examining clinical histopathological images, we can identify specific and shared microscopic features of tumors. By collecting, classifying, and analyzing data from these clinical histopathological images, we can pinpoint independent diagnostic factors characteristic of tumors. We hope this study provides a basis for future exploration of the mechanisms underlying different ocular diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a common eye malignancy and is managed by surgery, brachytherapy or external beam radiation for early-stage disease. Proton therapy is a newer form of radiation therapy and is especially suited to treat large uveal melanoma because of its unique physical characteristics. This review describes the physics, radiobiology, treatment techniques, and clinical outcomes when using proton therapy to treat uveal melanoma, with a focus on choosing between brachytherapy and proton therapy. Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated whether the anatomical location of metastases from posterior uveal melanoma affects survival. We found that patients with newly diagnosed metastatic posterior uveal melanoma who only have extrahepatic metastases had a significantly longer survival compared to patients with liver metastases. This insight could help clinicians improve the prediction of patient outcomes and enhance the selection of patients in clinical trials. Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate nnU-net's performance in automatically segmenting and volumetrically measuring ocular adnexal lymphoma (OAL) on multi-sequence MRI. Methods: We collected T1-weighted (T1), T2-weighted and T1-weighted contrast-enhanced images with/without fat saturation (T2_FS/T2_nFS, T1c_FS/T1c_nFS) of OAL from four institutions. Two radiologists manually annotated lesions as the ground truth using ITK-SNAP. A deep learning framework, nnU-net, was developed and trained using two models. Model 1 was trained on T1, T2, and T1c, while Model 2 was trained exclusively on T1 and T2. A 5-fold cross-validation was utilized in the training process. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), sensitivity, and positive prediction value (PPV). Volumetric assessment was performed using Bland-Altman plots and Lin's concordance correlation coefficient (CCC). Results: A total of 147 patients from one center were selected as training set and 33 patients from three centers were regarded as test set. For both Model 1 and 2, nnU-net demonstrated outstanding segmentation performance on T2_FS with DSC of 0.80–0.82, PPV of 84.5–86.1%, and sensitivity of 77.6–81.2%, respectively. Model 2 failed to detect 19 cases of T1c, whereas the DSC, PPV, and sensitivity for T1_nFS were 0.59, 91.2%, and 51.4%, respectively. Bland–Altman plots revealed minor tumor volume differences with 0.22–1.24 cm3 between nnU-net prediction and ground truth on T2_FS. The CCC were 0.96 and 0.93 in Model 1 and 2 for T2_FS images, respectively. Conclusion: The nnU-net offered excellent performance in automated segmentation and volumetric assessment in MRI of OAL, particularly on T2_FS images. [ABSTRACT FROM AUTHOR]

Background: With the advent of targeted therapies, the survival prognosis for metastatic tumors has extended, and it has become necessary to diagnose and consider treatment that takes into account Quality of Life for metastatic tumors of the eye. The reports of checking tumor marker in the aqueous humor for diagnosis of metastatic intraocular tumors are few. Here, we report a case of masquerade syndrome with secondary glaucoma in which a high carcinoembryonic antigen (CEA) level in the aqueous humor could assist diagnosis, and continuing targeted therapy and trabeculectomy were effective. Case presentation: A 73-year-old man was referred to us for iritis and high intraocular pressure (IOP) with severe eye pain in the left eye. He had Stage IVB lung adenocarcinoma treated with a molecularly targeted drug, Osimertinib. His best corrected visual acuity was 0.15, and IOP was 52 mmHg in the left eye. Anterior chamber cells (+), numerous small nodules in the iris, and small masses in the inferior angle were observed. In the aqueous humor, the CEA level was higher than in the blood. Napsin A and Thyroid Transcription Factor-1 (TTF-1) positive cells showed in the resected tissue at iridectomy performed during trabeculectomy. The pathological diagnosis of metastatic iris tumor of the lung adenocarcinoma was made, and we injected bevacizumab intravitreally once and continued Osimertinib. His IOP lowered to 8–10 mmHg, and the iris masses disappeared. He lost vision by metastasis to the left optic nerve after termination of Osimertinib one and a half years later. The metastasis shrank after restarting the drug. He passed away from an exacerbation of his primary lung cancer two years and nine months after the first visit. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his quality of life was maintained without any pain in his eye. Conclusions: Checking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients' Quality of Life. [ABSTRACT FROM AUTHOR]

Simple Summary: Conjunctival melanoma (Co-M) is a rare and aggressive eye surface cancer. It is often misdiagnosed or overlooked, leading to late diagnosis. Co-M can cause sight loss and even eye loss, impacting quality-of-life. The numbers of new cases globally are rising at alarming rates. There is no standard treatment for Co-M and management varies between eye cancer centres. In ~25% of cases the cancer spreads elsewhere in the body, which can lead to death. The aim of this review is to concisely present what is currently known about Co-M presentation, its development and progression, clinical management and outcomes, and finally summarise future directions for research into novel therapies. 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. [ABSTRACT FROM AUTHOR]

We present a case series of eight patients with ocular tuberculosis (OTB), latent tuberculosis (TB) or sarcoidosis, some of whom were receiving anti-tumor necrosis factor alpha (anti-TNF-a) therapy for various systemic diseases. Only one patient had a positive QuantiFERON®-TB test (QFT), and only one case showed a positive acid-resistant bacilli (ARB) test result. In a third case, brain imaging provided valuable assistance. Ocular tuberculosis should not be overlooked during clinical examination, as it remains a relevant diagnosis even in nonendemic regions. Over the last decade, the use of anti-TNF-α inhibitors for treating resistant uveitis has increased significantly. Consequently, it is essential to closely monitor patients for immunosuppression and remain vigilant about the risk of TB. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of the evaluation and management of orbital mass lesions in a tertiary hospital. It explains that these lesions can be either benign or malignant and can originate from different tissues in the orbit. The article emphasizes the importance of a thorough clinical evaluation and radiological imaging for accurate diagnosis and management. Surgical intervention is often necessary for symptomatic or malignant lesions, and the article highlights the need for a multidisciplinary approach. It also includes case studies that demonstrate the diverse presentations and outcomes of these lesions, underscoring the importance of tailored management plans. Radiological imaging, particularly MRI, is crucial for evaluation and diagnosis, and long-term follow-up is essential for complex cases involving systemic conditions like neurofibromatosis. [Extracted from the article]

To review the characteristics of all Slovenian patients with ocular adnexal lymphoma (OAL) in the period of 24 years with the aim of evaluating demographic data, lymphoma location and type, disease stage, treatment modality, local control rate and survival rate. All patients with histologically diagnosed OAL in the main tertiary centre of Slovenia, Eye Hospital, University Medical Centre Ljubljana, who were treated at Institute of Oncology Ljubljana were included in the study. Patients' data were collected from October 1995 through April 2019. Seventy-four patients were included in the study having a median age of 68 years at diagnosis. The majority of lymphomas were of B-cell origin (98.6%). The most frequent type was the extranodal marginal zone B-cell lymphoma (MALT) (71.6%). Orbital lymphomas were diagnosed in 56 cases (75.7%) and conjunctival in 18 cases (24.3%). Ocular manifestation was the first sign of the disease in 78.4% of patients and in 67.6% of patients ocular adnexa were the only disease location. Fifty-one patients (68.9%) were treated with radiotherapy, 7 patients (9.4%) with systemic treatment, 5 patients (6.8%) with combined radiotherapy and systemic treatment and in 11 patients, biopsy and active surveillance strategy was applied (14.9%). Local control of the disease was achieved in 96.6% of treated patients. Median overall survival of the whole study group has not been reached yet. Five-year overall survival rate was 80.1% (95% CI 68.1% – 88.5%) and 5-year lymphoma specific survival rate was 87.2% (95% CI 83.2%−91.2%). OALs comprise a group of heterogeneous diseases with variable outcomes depending predominately on the patient's age and lymphoma type, with low grade lymphomas carrying good prognosis even in elderly patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Adenoid cystic carcinoma is a rare but devastating disease. Currently, treatment options are very poor, and ACC does not respond well to conventional chemotherapy or radiation therapy and has a high rate of recurrence or metastasis. The molecular drivers that govern disease pathology are currently poorly understood. We conducted a molecular analysis of adenoid cystic carcinoma of the salivary and lacrimal glands in order to better understand these mechanisms and pave the way for the development of future therapeutics. Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo determine the incidence and clinical characteristics of ocular adnexaltumors in Olmsted County, Minnesota.Retrospective population-based cohort study of all patients residing in Olmsted County, Minnesota diagnosed with any ocular tumor from January 1, 2006, to December 31, 2015. The medical records of all patients with an incident diagnosis of any ocular adnexal tumor were reviewed using the Rochester Epidemiology Project medical record linkage system for patient demographics, tumor type, and histopathologic confirmation. Incidence rates were calculated per 100,000 person-years. Poisson regression analysis was used to analyze changes in incidence over time.There were 717 patients diagnosed with ocular adnexal tumors during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 59.7 per 100,000 (95% CI 55.4 to 64.0, p < 0.05) per year. In total, 764 tumors were diagnosed. Most tumors were eyelid lesions (N = 756, 99.0%), which were mostly benign (N = 512, 67.8%) with epidermal inclusion cysts (N = 275, 36.0%), hidrocystoma (N = 70, 9.2%), and eyelid sebaceous cysts (N = 46, 6.1%) accounting for the majority. Malignant eyelid lesions (N = 244, 31.9%) were relatively common with basal cell carcinoma (N = 184, 24.1%) and squamous cell carcinoma (N = 49, 6.4%) having the highest frequencies. Orbital tumors (N = 8, 1.0%) were infrequent. Of the orbital tumors, the most common was lacrimal gland adenoidcystic carcinoma (N = 2, 25.0%).In a population-based setting, most ocular adnexal tumors were benign eyelid lesions. Understanding the epidemiology of ocular adnexal tumors is important to aid providers in diagnosing and facilitating appropriate referrals of potentially vision- and life-threatening malignancies. [ABSTRACT FROM AUTHOR]

To describe the epidemiology, incidence, mortality and survival of ocular cancer in Cali between 1962 and 2019. Ecological population-based study analyzing data of incidence, mortality, and 5-years survival of malignant ocular tumors from the Populational Cancer Registry of Cali between 1962 and 2019. Between 1962 and 2019, 586 ocular tumors were found, 50.5% occurred in females, the mean age at diagnosis was 45 years (standard deviation = 25), 70.3% of ocular malignancies occurred in >14 years. The average annual incidence rate was 7.8 per million for male and 6.9 per million for females. Retinoblastoma (21%), squamous cell carcinoma (20%), melanoma (16%) and lymphoma (8%) were the most common neoplasm. In those <15 years, the most frequent malignant tumors were retinoblastomas (85.7%), followed by non-specified malignant neoplasm (NOS, 7.9%), and rhabdomyosarcoma (3.6%). In those >14 years, there were NOS (30%), followed by squamous cell carcinomas (28%), melanomas (23%), and lymphomas (9.7%). Conjunctiva (38.2%), retina (21%) and orbit (10%) constituted the majority of anatomical sites of ocular tumors. The survival rate was about 83.2% and mortality did not show a decreasing trend over time (p >.05). The incidence of ocular cancer in Cali has a slightly increasing trend, with stable behavior in the last decades. Squamous cell carcinoma, retinoblastoma, melanoma and lymphoma are the most frequent ocular cancers, with being retinoblastoma more frequent than melanoma. In general, ocular cancer had good survival rates in Cali. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. Basic procedures: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015–2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. Main findings: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54–77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). Conclusions: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN. [ABSTRACT FROM AUTHOR]

Retinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA methylation analysis from 61 retinoblastomas, we identify a MYCN-driven cluster of subtype 2 retinoblastomas characterized by DNA hypomethylation and high expression of genes involved in protein synthesis. Subtype 2 retinoblastomas outside the MYCN-driven cluster are characterized by high expression of genes from mesodermal development, including NKX2-5. Knockdown of MYCN expression in retinoblastoma cell models causes growth arrest and reactivates a subtype 1-specific photoreceptor signature. These molecular changes suggest that removing the driving force of MYCN oncogenic activity rescues molecular circuitry driving subtype 1 biology. The MYCN-RB gene signature generated from the cell models better identifies MYCN-driven retinoblastoma than MYCN amplification and can identify cases that may benefit from MYCN-targeted therapy. MYCN drives tumor progression in a molecularly defined retinoblastoma subgroup, and inhibiting MYCN activity could restore a more differentiated and less aggressive tumor biology. DNA methylation analysis identifies a MYCN-driven subgroup of aggressive retinoblastoma that may benefit from MYCN-targeted therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites. [ABSTRACT FROM AUTHOR]

Pediatric tumors of the eye and orbit can be benign or malignant as well as congenital or acquired and are usually distinctively different than those seen in adults. Although most of these neoplasms are benign (eg, dermoid cyst, chalazion, molluscum), their location near and within a vital organ can result in serious dermatologic and ophthalmologic sequelae. Lesions discussed include vascular lesions, retinoblastomas (the most common primary pediatric intraocular malignancy), rhabdomyosarcoma (the most common primary pediatric orbital malignancy), Langerhans cell histiocytosis, and metastatic lesions to the orbit (neuroblastoma, Ewing sarcoma). Although cysts and ocular melanoma can occur within the pediatric population, these conditions are covered in other contributions in this issue of Clinics in Dermatology. [ABSTRACT FROM AUTHOR]

Metastatic tumors to the eye and eyelid are generally seen in patients with disseminated metastases in the setting of advanced disease. Occasionally, they can present as the first sign of occult malignancy. The choroid is the most common site of intraocular metastases secondary to its dense vascular supply. Similar to the eye, metastatic tumors to the eyelid can present with a variety of clinical findings and are most often seen in patients with a known history of cancer. The most common skin malignancy that can spread to ocular structures is cutaneous melanoma, whereas the most common noncutaneous malignancy is breast cancer followed by lung cancer. In pediatric patients, metastatic disease to the eye is rare and can be seen in neuroblastoma and Ewing sarcoma. The overall prognosis of metastatic lesions involving the eye and eyelid is typically poor, with a mean survival of months. Ophthalmologists play an important role in the diagnosis of metastatic disease of the eye and eyelid; therefore, it is imperative for patients to undergo a complete ophthalmic examination and systemic workup if they have new-onset vision changes and a known history of cancer. Early diagnosis and management with systemic and local therapies can maximize quality of life and preserve vision. [ABSTRACT FROM AUTHOR]

Benign tumors of the eye and eyelid are common in children and adults, and they rarely undergo malignant transformation. Their workup and management have evolved over the years with increasing advancements in surgical and laser therapies. This contribution focuses on describing the following benign eye and eyelid tumors and their diagnostic and treatment approaches: congenital and acquired melanocytic nevi; nevus of Ota (Hori nevus); conjunctival papilloma; seborrheic keratosis; epidermoid cyst; dermoid cyst; milium; xanthelasma; hemangioma (cherry angioma and pyogenic granuloma); neurofibroma; neurilemmoma (schwannoma); and fibroepithelial polyp. Surgical removal is the primary treatment approach for many of these benign tumors. With advancements in laser technologies, there are now several laser types that can be used in the treatment of these benign eye and eyelid tumors. Other treatment modalities include cryosurgery, electrosurgery, and topical or intralesional medications. We hope this review will provide a reference to dermatologists and ophthalmologists in their approach to evaluation and management of benign eye and eyelid tumors. [ABSTRACT FROM AUTHOR]

Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails. [ABSTRACT FROM AUTHOR]

Simple Summary: Orbital and ocular adnexal lymphoma (OAL) refers to a type of cancer affecting the eye and its surrounding structures. It typically originates from lymphoid tissue and can manifest with different variants, including the non-Hodgkin subtype. While prognosis is generally favorable, this relies on different factors, including early detection, prompt treatment, and cancer subtype. This observational study on diagnostic and prognostic factors in OAL aims to provide significant information about the relationship between imaging and disease outcomes. We conclude that by analyzing radiological features such as subtype, fluorodeoxyglucose avidity, and bone marrow involvement, researchers can identify potential prognostic indicators, ultimately helping clinicians in predicting disease progression, refining diagnostic protocols, and improving patient outcomes. Orbital and ocular adnexal lymphoma (OAL) affects the orbit and the surrounding structures and can arise as several subtypes with variable prognoses. We performed an observational study on the relationship between OAL subtype, diagnostic features, and prognosis to offer valuable insights into imaging techniques, such as Positron Emission Tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with Computed Tomography (18F-FDG PET-CT), in predicting outcomes. With this aim, we retrospectively reviewed 99 patients with OALs, recording demographics, cancer subtype, location and treatment, 18FDG avidity, and bone marrow positivity. We divided patients into Group 1 (those presenting with extranodal marginal zone lymphoma—EMZL) and Group 2, including all other subtypes. The primary outcome was long-term cancer-specific survival (CSS) based on key predictors, performed through Kaplan–Meier curves and the log-rank test, with a p < 0.05 significance threshold. The mean patient age was 67 years (57–75.5). The most frequent histopathologic subtypes were EMZL lymphoma in 69 patients (69.7%), small lymphocytic lymphoma (11.1%) and diffuse-large B-cell lymphoma (10.1%). Patients of Group 1 showed a better prognosis (CSS = 80%) compared to those of Group 2 (CSS = 60%) (p = 0.01). In patients with high-grade lymphoma, the occurrence of 18FDG avidity (p = 0.003) and bone marrow positivity (p = 0.005) were related to a worse prognosis. In our group, EMZL was the most prominent subtype of OALs and exhibited the best prognosis, low 18FDG avidity, and bone marrow negativity. By observing specific patterns in radiological findings, it is possible to increase our understanding of disease progression, treatment response, and the overall prognosis in OAL patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The differential diagnosis between small melanocytic lesions and choroidal nevus is challenging. We usually rely on clinical risk factors to establish the need for immediate treatment vs. close monitoring followed by treatment if the lesion grows. We aimed to describe the features of small indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. Our findings show that the vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors. In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness (p = 0.00), greatest basal diameter (p = 0.00), number of risk factors (p = 0.00), symptoms (p = 0.001; relative risk [RR]: 4.3), orange pigment (p = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); p = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm (p = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter (p = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors. [ABSTRACT FROM AUTHOR]

Objective: Eye plaque radiation therapy is the treatment of choice for small‐ and medium‐sized choroidal melanomas. This study investigated the dose distribution around eye plaques containing 125I seeds to treat ocular melanoma using Monte Carlo N‐Particle eXtended (MCNPX) and Plaque Simulator (PS) software. Methods: Dosimetry evaluation and comparison of the resulting isodose curves for 125I COMS plaques were performed using the MCNPX code. The isodose curves and dose distributions were calculated using PS treatment planning for a 125I COMS plaque. Results: In the validation, the maximum relative difference between the results of this study and those reported in other literature was approximately 9%–10% for the COMS plaques. The dose distributions of MCNPX were lower than those of PS with a relative difference of approximately 27.7%–35.4%. The dose distribution may differ depending on the 125I source spectra and seed design used in the two methods. In addition, the dose algorithm used in PS made a major contribution to the relative differences between the results. Conclusion: The PS did not provide accurate details of dose distribution near the surface of the plaque insert. The source parameters used in each program should be studied more carefully to determine the source of the differences in the estimated dose values. [ABSTRACT FROM AUTHOR]

AIM: To explore the role of positron emission tomography-computed tomography (PET-CT) examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma (OAML). METHODS: The general clinical data, postoperative PET-CT results, treatment regimens, and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected. Among the 21 patients, five patients underwent surgical treatment alone, 13 patients underwent surgical treatment combined with radiotherapy, and three patients underwent surgical treatment combined with chemotherapy. RESULTS: The follow-up period ranged from 8 to 79mo, with four cases of recurrence and no deaths. Through PET-CT examination, two patients exhibited both local ocular metabolic elevation and systemic metastasis, and one of these patients had cervical lymph node metastasis, while the other had submandibular and parotid gland metastasis. Nine patients showed only local ocular metabolic elevation, while 10 patients had no abnormal metabolic activity locally. CONCLUSION: PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection, aiding in precise disease staging, and facilitating the development of personalized treatment plans, ultimately improving patient prognosis.

Choroidal melanoma (CM) is the most common malignant ocular tumor in adults. The current treatment of metastatic CM is limited by the intrinsic resistance of CM to conventional systemic therapies. Immunotherapy alone or in association with cytotoxic treatment became a realist option treatment. Advancements in molecular biology have resulted in the identification of a number of promising prognostic and therapeutic targets. Herein, we report a rare case of 36-year-old patient with metastatic CM who presented a good long response to treatment with double immunotherapy reaching 3 years of overall survival, which has never been described in the literature. [ABSTRACT FROM AUTHOR]

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Orbital tumors are the most common eye tumors that affect people all over the world. Early detection prevents the progression to other regions of the eye and the body. Also, early identification and treatment could reduce mortality. A computer-assisted diagnosis (CAD) system to help physicians diagnose tumors is in great demand in ophthalmology. In recent years, deep learning has demonstrated promising outcomes in computer vision systems. This work proposes a CAD system for detecting various forms of orbital tumors using convolutional neural networks. The system has three stages: preprocessing, data augmentation and classification. The proposed system was evaluated on two datasets of magnetic resonance imaging (MRI) images containing 1404 MRI T1-weighted images and 1560 MRI T2-weighted images. The results have shown that the system is capable of detecting and classifying the tumor in each image type, and the recognition rate for the T1-weighted image is 98% and for the T2-weighted image is 97%. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study is crucial for understanding the rare occurrence of ocular and periocular metastasis in breast cancer. By exploring demographics and clinical aspects, we aim to improve the management of this condition. Our focus is on enhancing treatment strategies, predicting outcomes, and ultimately improving the quality of life for breast cancer patients with ocular metastasis. This study addresses the gaps in knowledge regarding the intricacies of this manifestation, driving progress toward more effective interventions and better patient outcomes. Background: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. Methods: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. Results: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. Conclusions: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis. [ABSTRACT FROM AUTHOR]

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Purpose: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. Methods: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. Results: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2–39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4–9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12–84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30–60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25–50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P < 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10–24) months, in which, 3 (17%) patients needed a second surgery. Conclusion: Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis. [ABSTRACT FROM AUTHOR]

While digital ocular fundus images are commonly used for diagnosing ocular tumors, interpreting these images poses challenges due to their complexity and the subtle features specific to tumors. Automated detection of ocular tumors is crucial for timely diagnosis and effective treatment. This study investigates a robust deep learning system designed for classifying ocular tumors. The article introduces a novel optimizer that integrates the Caputo fractional gradient descent (CFGD) method with the cuckoo search algorithm (CSA) to enhance accuracy and convergence speed, seeking optimal solutions. The proposed optimizer's performance is assessed by training well-known Vgg16, AlexNet, and GoogLeNet models on 400 fundus images, equally divided between benign and malignant classes. Results demonstrate the significant potential of the proposed optimizer in improving classification accuracy and convergence speed. In particular, the mean accuracy attained by the proposed optimizer is 86.43%, 87.42%, and 87.62% for the Vgg16, AlexNet, and GoogLeNet models, respectively. The performance of our optimizer is compared with existing approaches, namely stochastic gradient descent with momentum (SGDM), adaptive momentum estimation (ADAM), the original cuckoo search algorithm (CSA), Caputo fractional gradient descent (CFGD), beetle antenna search with ADAM (BASADAM), and CSA with ADAM (CSA-ADAM). Evaluation criteria encompass accuracy, robustness, consistency, and convergence speed. Comparative results highlight significant enhancements across all metrics, showcasing the potential of deep learning techniques with the proposed optimizer for accurately identifying ocular tumors. This research contributes significantly to the development of computer-aided diagnosis systems for ocular tumors, emphasizing the benefits of the proposed optimizer in medical image classification domains. [ABSTRACT FROM AUTHOR]

Malignant melanoma of the conjunctiva is a rare tumor of the ocular surface with potential fatal consequences and a high likelihood of recurrence. Although routes for extending the tumor, including local, hematogenous, and lymphatogenous, are pretty straightforward, the indirect extension through free-floating tumoral cells to the nasolacrimal duct is not described thoroughly. We report a case of malignant melanoma of the conjunctiva which presented with local recurrence in the intranasal cavity and lacrimal sac two years after the primary surgery (without involvement of the ocular surface and punctum on the second occasion). However, there was no evidence of distant metastasis on either occasion. This case demonstrates the possible noncontiguous spreading route of melanoma tumoral cells and highlights the need for attention to the surgical technique, and careful follow-up to detect further disease activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurate diagnosis of early-stage choroidal melanoma, the most commonly occurring malignancy of the eye, is extremely important yet highly challenging. Unfortunately, due to challenges in obtaining adequate sampling and the risk of vision loss, intraocular melanoma remains largely a clinical diagnosis, which can be subjective. Most of the existing tools and diagnostic methods lack definitive discriminative features, leading to uncertainties in clinical diagnoses. In this work, we present and evaluate a novel, contrast-free ultrasound-based method for quantitative assessment of microvascular characteristics of choroidal tumors, aiming at distinguishing malignant lesions based on the complex and irregular microvessel formations within them. Using this method, we visualize intratumoral microvascular networks, estimate their morphological features using objective quantitative metrics, and perform statistical analyses demonstrating differences between lesions based on their malignancy status. The results of this preliminary study show promise for further assessment of the method as a complementary diagnostic tool for ocular tumors. Angiogenesis has an essential role in the de novo evolution of choroidal melanoma as well as choroidal nevus transformation into melanoma. Differentiating early-stage melanoma from nevus is of high clinical importance; thus, imaging techniques that provide objective information regarding tumor microvasculature structures could aid accurate early detection. Herein, we investigated the feasibility of quantitative high-definition microvessel imaging (qHDMI) for differentiation of choroidal tumors in humans. This new ultrasound-based technique encompasses a series of morphological filtering and vessel enhancement techniques, enabling the visualization of tumor microvessels as small as 150 microns and extracting vessel morphological features as new tumor biomarkers. Distributional differences between the malignant melanomas and benign nevi were tested on 37 patients with choroidal tumors using a non-parametric Wilcoxon rank-sum test, and statistical significance was declared for biomarkers with p-values < 0.05. The ocular oncology diagnosis was choroidal melanoma (malignant) in 21 and choroidal nevus (benign) in 15 patients. The mean thickness of benign and malignant masses was 1.70 ± 0.40 mm and 3.81 ± 2.63 mm, respectively. Six HDMI biomarkers, including number of vessel segments (p = 0.003), number of branch points (p = 0.003), vessel density (p = 0.03), maximum tortuosity (p = 0.001), microvessel fractal dimension (p = 0.002), and maximum diameter (p = 0.003) exhibited significant distributional differences between the two groups. Contrast-free HDMI provided noninvasive imaging and quantification of microvessels of choroidal tumors. The results of this pilot study indicate the potential use of qHDMI as a complementary tool for characterization of small ocular tumors and early detection of choroidal melanoma. [ABSTRACT FROM AUTHOR]

Background: Canine transmissible venereal (TVT) is a transplantable tumor usually transmitted to genital organs during coitus. Tumor cell inoculation is also possible in extragenital sites via licking or sniffing of the vaginal or preputial discharge. Metastases occur predominantly in males involving mainly the regional lymph nodes. On rare occasions, TVT metastases may affect kidney, spleen, tonsils, pancreas, lung, eye, brain, pituitary gland and musculature. Primary ocular involvement of TVT is not commonly reported in dogs, with few cases cited in the literature. The purpose of this study is to describe the ocular manifestations, histological features and immunohistochemical analysis in a canine intraocular TVT. Case: A 8-year-old male dog of mixed breed weighing 14.3 kg, was presented because red protrusion from both eyes. After of clinical examination, the dog was submitted to bilateral enucleation. In the histopathological examination was observed tumor cells uniformly round, arranged in solid sheets by delicate connective-tissue stroma. The cells have centrally located round nuclei that contain 1 or 2 prominent nucleolus. The cytoplasm was scant, sometimes contain brown pigment. Immunohistochemical staining with commercially available antibodies such as lysozyme, CD3, CD45R, PAX5 and PNL2 was performed to obtain a more accurate diagnosis. Immunohistochemical staining revealed strong cytoplasmic reactivity to lysozyme in about 90% cells. Weak cytoplasmic immunoreactivity of CD45R was detected in 80-90% of cells and negative immunoreactivity was observed in the CD3, PAX-5, PNL2 antibodies. Discussion: The use of imunohistochemical markers excluded other types of round cell tumors, such as lymphomas, melanomas, amelanotic melanomas, poorly differentiated carcinomas and mast cell tumors. However, some authors described similar immunostaining in histiocitomas, but the specific staining for Lysozyme, histopathological analisys and immunohistochemical evaluation was fundamental for this diagnosis. As a differential diagnosis for ophthalmic lesions, there are malignant and benign and non-neoplastic neoplastic processes. As malignant neoplasms of intraocular location, there are melanomas, poorly differentiated carcinomas, mast cell tumors. In the case of benign variants, adenomas are highlighted. Round cell neoplasms are also important differential diagnoses, including mast cell tumor, histiocioma, and lymphoma. Non-neoplastic processes, such as granulomatous lesions caused by Leishmaniasis, should also be considered. Linked to this, the performance of immunohistochemistry, due to the range of possible tumor markers, becomes essential for the diagnostic conclusion by excluding other types of round cell tumors, such as lymphoma, melanoma, poorly differentiated carcinomas and mast cell tumors. The prognosis for ocular TVT is good in situations where enucleation occurs, as in this case. That the patient was healthy and in the absence of neoplastic cells due to being affected only in the eye region. Finally, histopathological and imunohistochemistry are examination are confirmatory are the definitive diagnosis. Despite the specific labeling for Lysozyme, it was present in 90% of the cells, and the non-sensitivity of imunoreactivity to CD3 and PAX-5, similar results already described. Thus, and due to the fact that the importance of immunohistochemistry is observed, it suggests - if the use of this technique can validate the confirmation of marking of primary cells of the tumor, in this case reported here. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is the most prevalent ocular tumor of childhood, and its extraocular invasion significantly increases the risk of metastasis. Nevertheless, a single-cell characterization of RB local extension has been lacking. Here, we perform single-cell RNA sequencing on four RB samples (two from intraocular and two from extraocular RB patients), and integrate public datasets of five normal retina samples, four intraocular samples, and three extraocular RB samples to characterize RB local extension at the single-cell level. A total of 128,454 qualified cells are obtained in nine major cell types. Copy number variation inference reveals chromosome 6p amplification in cells derived from extraocular RB samples. In cellular heterogeneity analysis, we identified 10, 8, and 7 cell subpopulations in cone precursor like cells, retinoma like cells, and MKI67+ photoreceptorness decreased (MKI67+ PhrD) cells, respectively. A high expression level of SOX4 was detected in cells from extraocular samples, especially in MKI67+ PhrD cells, which was verified in additional clinical RB samples. These results suggest that SOX4 might drive RB local extension. Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, improving our understanding of RB local extension at the single-cell resolution and providing potential therapeutic targets for RB patients. Single-cell transcriptomic characterization of intraocular and extraocular retinoblastoma suggests that SOX4 may drive the local extension of retinoblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy is the gold‑standard treatment for choroidal melanoma. This study evaluated iodine‑125 brachytherapy by using Ocuprosta seeds with indigenous non‑collimated plaques in Asian patients. Methods: Retrospective single‑center study in a tertiary care hospital of 12 eyes with choroidal melanoma in 12 Asian patients who underwent brachytherapy with Ocuprosta seeds fixed on non‑collimated plaques and had a follow‑up of at least 32 months (mean: 42.4 ± 9.5 months; median: 40 months). Radiotherapy was planned after developing the digital 3D model of the tumor within the eye by using radiological images and clinical pictures. Ocuprosta iodine‑125 seeds were used on indigenous non‑collimated gold plaques to deliver the radiation for precalculated time. “Successful outcome” was taken as a decrease in the volume of the tumor, and “unsuccessful outcome” was defined as no change in the tumor volume or increase in the tumor volume at 24 months after brachytherapy. Results: The mean decrease in tumor volume was 21% (914.5 ± 912.2 mm³ to 495.7 ± 633.6 mm³ ) after brachytherapy, which correlated with the baseline volume of the tumor. Ten eyes (83.3%) showed a reduction in tumor volume, whereas two eyes showed an increase in the volume of the tumor after brachytherapy. One of the cases with a reduction in tumor size developed neovascular glaucoma. Enucleation was done in three eyes. A globe salvage rate of 75% and tumor regression rate of 83% were seen in the present study using Ocuprosta seeds. Conclusions: Iodine‑125 brachytherapy with uncollimated indigenous gold plaques is an effective treatment modality for choroidal melanomas in Asian patients. [ABSTRACT FROM AUTHOR]

Hemangiosarcomas are tumors of mesenchymal origin, potentially deleterious, associated with areas of high vascularization. Tumor progression and growth are associated with these tumors' ability to retain blood and give rise to tortuous blood vessels. They have a vast metastatic capacity, often occurring in organs such as the spleen, liver, and aorta artery. However, other sites may be affected, although less frequently, such as the third eyelid and the conjunctiva and cutaneous regions. This article aims to report the case of an 8-year-old female dog with a history of conjunctival hemangiosarcoma, in the medial region of the left eye, with a hemorrhagic appearance. The animal was submitted to the surgical procedure of enucleation after the involvement of the surgical margins in a previous histopathological examination. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features. Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes – compound, subepithelial, and junctional – depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium. Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient's young age helped render a final diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant melanoma is a highly aggressive malignancy, accounting for the majority of skin cancer deaths. Its global incidence rate has been increasing rapidly over the past few decades, and accurate disease diagnosis is crucial for optimal patient management. Imaging modalities, such as positron emission tomography (PET), play a pivotal role in accomplishing this objective. Based on current guidelines, [18F]F-FDG PET is recommended for the assessment of distant metastases in advanced-stage melanoma patients. In addition, it is indicated in patient follow-up. However, to our knowledge, there is no comprehensive investigation in the literature reporting the real-world performance of [18F]F-FDG PET in melanoma patients across a broad spectrum of clinical scenarios. Thus, we aimed to describe the performance of [18F]F-FDG PET in a wide range of detection-based clinical scenarios (e.g., initial staging, re-staging, locoregional detection, distant metastasis diagnosis) by conducting a systematic review and meta-analysis of the existing literature. We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18F]F-FDG-PET and compared it with a valid reference standard were considered eligible. The pooled measurements were calculated based on the data level (patient/lesion-based). Regarding sub-groups, diagnostic performances were calculated for local, regional and distant involvement. The bivariate model was employed to calculate sensitivity and specificity. The initial search resulted in 6678 studies. Finally, 100 entered the meta-analysis, containing 82 patient-based (10,403 patients) and 32 lesion-based (6188 lesions) datasets. At patient level, overall, [18F]F-FDG-PET had pooled sensitivity and specificity of 81% (95%CI: 73–87%) and 92% (95%CI: 90–94%), respectively. To detect regional lymph node metastasis, the pooled sensitivity and specificity were 56% (95%CI: 40–72%) and 97% (95%CI: 94–99%), respectively. To detect distant metastasis, they were 88% (95%CI: 81–93%) and 94% (95%CI: 91–96%), respectively. At lesion level, [18F]F-FDG-PET had a pooled sensitivity and specificity of 70% (95%CI: 57–80%) and 94% (95%CI: 88–97%), respectively. Thus, [18F]F-FDG-PET is a valuable diagnostic modality for melanoma assessment. It was accurate in various clinical scenarios. However, despite its high specificity, it showed low sensitivity in detecting regional lymph node metastasis and could not replace lymph node biopsy. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphomas are rarely localized in the ocular and orbital regions. Although their diagnosis is often complicated due to the similarity with other pathologies of this anatomical district, they are characterized by a good prognosis in the vast majority of cases. This article reports our clinical experience in the field, associating it with a review of the main therapeutic options, placing greater attention on the role of radiotherapy in the treatment of these tumors. Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient's clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy is the gold-standard treatment for choroidal melanoma. This study evaluated iodine-125 brachytherapy by using Ocuprosta seeds with indigenous non-collimated plaques in Asian patients. Methods: Retrospective single-center study in a tertiary care hospital of 12 eyes with choroidal melanoma in 12 Asian patients who underwent brachytherapy with Ocuprosta seeds fixed on non-collimated plaques and had a follow-up of at least 32 months (mean: 42.4 ± 9.5 months; median: 40 months). Radiotherapy was planned after developing the digital 3D model of the tumor within the eye by using radiological images and clinical pictures. Ocuprosta iodine-125 seeds were used on indigenous non-collimated gold plaques to deliver the radiation for precalculated time. "Successful outcome" was taken as a decrease in the volume of the tumor, and "unsuccessful outcome" was defined as no change in the tumor volume or increase in the tumor volume at 24 months after brachytherapy. Results: The mean decrease in tumor volume was 21% (914.5 ± 912.2 mm3 to 495.7 ± 633.6 mm3) after brachytherapy, which correlated with the baseline volume of the tumor. Ten eyes (83.3%) showed a reduction in tumor volume, whereas two eyes showed an increase in the volume of the tumor after brachytherapy. One of the cases with a reduction in tumor size developed neovascular glaucoma. Enucleation was done in three eyes. A globe salvage rate of 75% and tumor regression rate of 83% were seen in the present study using Ocuprosta seeds. Conclusions: Iodine-125 brachytherapy with uncollimated indigenous gold plaques is an effective treatment modality for choroidal melanomas in Asian patients. [ABSTRACT FROM AUTHOR]

To investigate the effect of using non‐uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter‐seed and inhomogeneity effects. For standard plaque configurations, uniformly and non‐uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2 Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95 Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non‐uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye‐cancer‐busy centers. [ABSTRACT FROM AUTHOR]

Radiation retinopathy (RR) and radiation maculopathy (RM) can occur as a result of uveal melanoma radiation treatment and after irradiation of other head and neck extraocular tumors, even with precise targeting techniques, such as stereotactic or proton beam radiotherapy. This review provides an overview of the current understanding of potential radiation damage to ocular tissues, and how recent developments in ophthalmic multimodal imaging techniques and treatment modalities have improved managing options. Several treatment strategies have been employed so far for the management of RR, including laser photocoagulation, intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents or glucocorticosteroids and surgery. The use of intravitreal anti-VEGFs or dexamethasone implants have significantly altered the final visual outcome for uveal melanoma patients. As a prophylaxis, a few different strategies were proposed, but still there is a lack of large randomized clinical trials supporting these approaches and clear clinical guidelines for daily practice. Early detection and proper treatment are crucial in preventing or reducing vision loss, and improving patients’ quality of life. Close monitoring and timely intervention are essential for successful management.

This article discusses the case of a 25-year-old Caucasian male with tuberous sclerosis complex (TSC) who was referred for evaluation of multifocal retinal tumors in both eyes. The patient had a history of cardiac rhabdomyoma and subependymal giant cell astrocytoma. The examination revealed nodular, cream-colored tumors in both eyes, as well as congenital hypertrophy of the retinal pigmented epithelium and a punched-out retinal pigmented epithelium lesion. The diagnosis of retinal astrocytic hamartoma (RAH) was made, and observation was advised. The article also provides information on the classification of RAH and the differentiation between RAH and retinoblastoma using optical coherence tomography (OCT). [Extracted from the article]

Simple Summary: This study investigates whether lens-sparing electron irradiation of low-grade, conjunctival lymphomas prevents cataract formation while ensuring high disease control rates. This study presents the data of 65 eyes of 56 patients with low-grade Ann Arbor stage I conjunctival lymphomas that were treated with either lens-sparing or non-lens-sparing electron irradiation. After a median follow-up of 65 months, the cumulative incidences of 5- and 10-year outfield progression were 10.4% and 13.4% while the cataract incidence was significantly lower in patients treated with a lens-shielding technique. The presented data underline the status of radiotherapy as first line therapy for low-grade conjunctival lymphomas. Irradiation with electrons is the primary treatment regime for localized conjunctival low-grade lymphomas. However, radiation-induced cataracts are a major cause of treatment-related morbidity. This study investigates whether lens-sparing electron irradiation produces sufficient disease control rates while preventing cataract formation. All consecutive patients with strictly conjunctival, low-grade Ann Arbor stage IE lymphoma treated with superficial electron irradiation between 1999 and 2021 at our department were reviewed. A total of 56 patients with 65 treated eyes were enrolled with a median follow-up of 65 months. The median dose was 30.96 Gy. A lens-spearing technique featuring a hanging rod blocking the central beam axis was used in 89.2% of all cases. Cumulative incidences of 5- and 10-year infield recurrences were 4.3% and 14.6%, incidences of 5- and 10-year outfield progression were 10.4% and 13.4%. We used patients with involvement of retroorbital structures treated with whole-orbit photon irradiation without lens protection—of which we reported in a previous study—as a control group. The cumulative cataract incidence for patients treated with electrons and lens protection was significantly lower (p = 0.005) when compared to patients irradiated without lens protection. Thus, electrons are an effective treatment option for conjunctival low-grade lymphomas. The presented lens-sparing technique effectively prevents cataract formation. [ABSTRACT FROM AUTHOR]