[Clinical characteristics and research progress of ocular Merkel cell carcinoma].

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: A case report and literature review.

RATIONALE: The most common subtype of primary lymphoma of the ocular adnexa is the mucosa-associated lymphoid tissue (MALT) subtype. MALT lymphoma of the lacrimal gland is relatively rare among the lacrimal gland tumors, and the early clinical symptoms are atypical, which can easily lead to misdiagnosis and missed diagnosis. Here, we report a case of MALT lymphoma of the lacrimal gland and explore its clinical manifestations, pathological characteristics, management, and pathogenesis, with the aim of helping clinicians gain an in-depth understanding of ocular adnexal MALT lymphoma. PATIENT CONCERNS: A 60-year-old man presented to our hospital with proptosis and diplopia. The right eye deviated and shifted toward the lower part of the nose. DIAGNOSIS: Orbital enhanced magnetic resonance imaging suggested a mass with a maximum cross-section of 3.2 × 2.1 cm. T1 weighted image was isointense, and the enhancement was more uniform and obvious. INTERVENTIONS: The right orbital mass was treated surgically, and the final pathology report was MALT lymphoma. After the pathological report was released, the patient was transferred to the hematology department for further diagnosis and no further treatment was given eventually. OUTCOMES: Seven months later, the patient did not complain of discomfort. Whole-body positron emission tomography-computed tomography, superficial lymph node examination and orbital magnetic resonance imaging revealed no abnormal changes. LESSONS: The clinical manifestations of MALT lymphoma are heterogeneous. Imaging examination is important for assessing the size of the tumor and its relationship with adjacent tissues. Postoperative pathological examination may provide further evidence for the evaluation of the patient's surgical efficacy and prognosis. Management of MALT lymphoma of the lacrimal gland requires a multidisciplinary approach involving ophthalmologists, hematologists, and radiotherapists.

[Metastasis in the periocular region]. / Metastase in der periokulären Region.

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.

[Severe Conjunctival and Corneal Epithelial Dysplasia: A Case Series]. / Schwere konjunktivale und korneale epitheliale Dysplasie: eine Fallserie.

BACKGROUND/OBJECTIVES: Ocular surface squamous neoplasia (OSSN) are among the most frequent non-pigmented malignancies of the ocular surface. They have a wide range of histological characteristics - ranging from mild epithelial dysplasia to invasive carcinoma of the squamous cells of the cornea. They may be restricted to the conjunctiva or also involve the cornea. As there are no leading symptoms in the early stages, diagnosis may be very delayed in patients who do not receive regular ophthalmological treatment. The present case series describes clinical and histological data on OSSN and includes clinical and histological data on OSSN, including possible clinical presentations, important risk factors, special histological and cytological features and therapeutic options. METHODS: Retrospective case series of patients with histologically confirmed severe epithelial dysplasia of the conjunctiva and cornea consistent with OSSN who presented to the Department of Ophthalmology in Basel University Hospital. The analysis covered demographic data, symptoms, diagnostic testing (photo documentation, brush biopsy), treatment and cytological and/or histological material and findings. RESULTS: We report on five patients aged between 41 and 92 years at the time of diagnosis. The histological findings in all patients included severe epithelial dysplasia, but with a heterogenous clinical presentation. In all cases, the lesion started in the conjunctiva, but traversed the limbus and extended to the cornea. The primary treatment was always surgical removal. In one patient, this had to be repeated several times due to recurrent metaplasia and was complemented by subsequent mitomycin C therapy. The clinical outcome ranged between total restitution of the original state to inevitable enucleation. CONCLUSION: The clinical presentation of OSSN is highly heterogenous, so that the initial diagnosis is difficult. There are no official guidelines for treatment, so that the treatment of choice varied between clinics. Regular ophthalmological follow-ups are recommended, even after complete surgical excision. Possible relevant concomitant diseases and risk factors must be identified before therapy.

[Clinical approach for solid intraocular metastases]. / Klinisches Vorgehen bei soliden intraokulären Metastasen.

BACKGROUND: Intraocular metastases arising from solid tumors are found in approximately 2% of patients with metastatic tumor diseases and are therefore more frequent than originally assumed. They often affect the uvea and are associated with a poor prognosis. Due to the difficult diagnosis and an inconsistent treatment regimen, ophthalmologists have a special responsibility here. OBJECTIVE: This article gives a summary of the various types of intraocular metastases with respect to clinical features, diagnostics, treatment and prognosis as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the topic of intraocular metastases using PubMed and Google Scholar. RESULTS: Intraocular metastases most frequently affect the uvea, specifically the choroid. In most cases the underlying disease is breast or lung cancer, but other rarer primary tumors have also been reported in the literature. Metastatic lesions can show very different morphological manifestations but can be distinguished based on the corresponding structure of manifestation in the eye and with the aid of targeted staging, thus providing valid information on the type of primary tumor. The treatment is partly experimental and usually depends on the primary tumor and leading symptoms of the patient. A differentiation between a curative or palliative treatment situation must always be made. CONCLUSION: Intraocular metastases are the most frequent intraocular tumor and are usually associated with a poor prognosis. Accurate diagnostics for finding the treatment as well as interdisciplinary collaboration and the presentation of the patient on the tumor board are essential.

Targeted therapy in ophthalmic oncology: The current status.

There have been rapid advancements in the field of ocular oncology for the diagnosis and management of intraocular, adnexal, and orbital tumors. Targeted therapy is in the forefront of medical research in all fields including ocular oncology. Targeted therapy include drugs that target specific genetic mutations, pathways or proteins involved in the development of cancer. In contrast to traditionally used chemotherapy, drugs used in targeted therapy are highly specific for tumor cells and preserve the function of normal cells. This review aims to familiarize ophthalmologists with the drugs that are currently approved or undergoing clinical trials for use in ocular oncology. Targeted therapy is particularly useful for locally advanced or metastatic tumors, including but not limited to eyelid and periocular basal cell carcinoma, periocular cutaneous and conjunctival squamous cell carcinoma, ocular adnexal lymphoma, conjunctival melanoma, and uveal melanoma. The results are promising with improved survival outcomes and better tolerability than chemotherapeutic drugs.

[Staging and systemic treatment of ocular and periocular metastases]. / Staging und Systemtherapie bei okulären und periokulären Metastasen.

Metastases of malignant diseases are the most frequent tumors diagnosed in the human eye. They occur in approximately 5-10% of patients with solid tumors during the course of the disease. Their frequency is particularly high in patients with breast and lung cancer. Many highly sensitive periorbital tissues can be affected by the localization of the metastatic lesions and pose a number of clinical challenges. The main goal of the therapy of ocular metastases consists of the control of tumor growth (including the control of other possible manifestations throughout the body), the preservation of the affected eye and the minimization of potential iatrogenic damage to adjacent tissues. Overall, the purpose of this strategy is also to maintain the quality of life and especially the eyes and vision of the patient. Furthermore, pain should be avoided or at least alleviated. Of special importance is the differentiation between a curative or palliative situation. Patients with ocular metastases usually undergo systemic treatment appropriate for the underlying tumor entity, which is often accompanied by concomitant or sequential radiotherapy. In addition to classical chemotherapy, targeted treatment, treatment with monoclonal antibodies and antibody-drug conjugates as well as immunotherapy with checkpoint antibodies are currently available for many cancer types. This review article gives an overview of the currently available treatment options for patients with ocular metastases of solid tumors.

Intravascular large B-cell lymphoma of the eye: Literature review and new findings.

PURPOSE: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare, aggressive, multi-system disease that can affect the eye. We describe the ophthalmic presentation, multimodal imaging and treatment response of uveal IVLBCL. METHODS: Review and case report. RESULTS: Twenty-five published cases of IVLBCL involving the eye including our own were identified. Of these, 15 patients (60%) had clinically-detectable intraocular involvement, 6 (24%) had extraocular ophthalmic involvement only and 4 (16%) had subclinical, undiagnosed intraocular involvement that was retrospectively detected on post-mortem ocular histopathology. The male to female ratio was 1.08:1 with a mean presenting age of 65.1 ± 11.7 years (range 38-82 years). The majority of cases had bilateral involvement (21/25 patients, 84%). Extraocular manifestations included diplopia, ptosis and ophthalmoplegia. Intraocular manifestations included serous retinal detachment (13/28, 46%), retinal hemorrhages (9/28, 32%), vascular changes (9/28, 32%), retinal pigment epithelial changes (7/28, 25%), thickened choroid (6/28, 21%), vitritis (5/28, 17%), cotton-wool spots (3/28, 10%), and a subretinal lesion (1/28, 3%). Histopathological diagnosis was most commonly confirmed on post-mortem enucleation (8/25 patients, 32%), skin (6/25 patients, 24%) or brain biopsy (6/25 patients, 24%). CONCLUSION: The presence of intra-retinal hemorrhages, cotton wool spots and/or Roth spots help differentiate IVLBCL from other similarly presenting diseases such as central serous chorioretinopathy and Vogt-Koyanagi-Harada disease. New signs not previously described in IVLBCL include macular bacillary layer detachment and hypo-cyanescent spots on ultra-wide field indocyanine green angiography. The diagnosis is elusive and requires tissue biopsy, but systemic chemotherapy and rituximab can lead to rapid improvement of the eye.

A Review of Pediatric Ophthalmic Tumors.

Tumors of the eye, orbit, and ocular adnexa can arise in the pediatric population. These entities can be both vision- and life-threatening and may be associated with systemic disease. Given their relative rarity, pediatricians must be aware of these conditions and understand what findings warrant immediate referral to an ophthalmologist for initiation of further testing. We aimed to review these conditions and highlight clinical features to promote awareness and expedite diagnosis. Tumors are subdivided into the following categories for review: anterior tumors of the eyelid and ocular surface, orbital tumors, and intraocular tumors.

Assessment of Social Vulnerabilities of Care and Prognosis in Adult Ocular Melanomas in the US.

BACKGROUND: Prior works have studied the impact of social determinants on various cancers but there is limited analysis on eye-orbit cancers. Current literature tends to focus on socioeconomic status and race, with sparse analysis of interdisciplinary contributions. We examined social determinants as measured by the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI), quantifying eye and orbit melanoma disparities across the United States. METHODS: A retrospective review of 15,157 patients diagnosed with eye-orbit cancers in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017 was performed, extracting 6139 ocular melanomas. SVI scores were abstracted and matched to SEER patient data, with scores generated by weighted averages per population density of county's census tracts. Primary outcome was months survived, while secondary outcomes were advanced staging, high grading, and primary surgery receipt. RESULTS: With increased total SVI score, indicating more vulnerability, we observed significant decreases of 23.1% in months survival for melanoma histology (p < 0.001) and 19.6-39.7% by primary site. Increasing total SVI showed increased odds of higher grading (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.43) and decreased odds of surgical intervention (OR 0.94, 95% CI 0.92-0.96). Of the four themes, higher magnitude contributions were observed with socioeconomic status (26.0%) and housing transportation (14.4%), while lesser magnitude contributions were observed with minority language status (13.5%) and household composition (9.0%). CONCLUSIONS: Increasing social vulnerability, as measured by the CDC SVI and its subscores, displayed significant detrimental trends in prognostic and treatment factors for adult eye-orbit melanoma. Subscores quantified which social determinants contributed most to disparities. This lays groundwork for providers to target the highest-impact social determinant for non-clinical factors in patient care.

[Chinese expert consensus on the diagnosis and management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)].

Ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) is a common malignant tumor that affects the ocular adnexal region. The incidence of OAML is increasing due to the aging population. The tumor invades the ocular adnexal region, which can result in abnormal ocular appearance and function, thereby reducing the quality of life. Currently, there is no standardized diagnosis and management guideline for OAML. To enhance the standardization of diagnosis and management in OAML, a collaborative effort was undertaken by esteemed organizations in China. The Cellular Immune Therapy Committee of China Association for Promotion of Health Science and Technology, the Ocular Tumor Committee of Chinese Medical Doctor Association for Ophthalmologist Branch, the Imaging Medicine Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare, the Tumor and Microecology Professional Committee of China Anti-cancer Association, and the Lymphoma Immunotherapy Committee of Beijing Cancer Prevention Society jointly convened a panel of experts to develop the inaugural "Chinese Expert Consensus on the Diagnosis and Management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)"..

Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

BACKGROUND: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. METHODS: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. RESULTS: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. CONCLUSIONS: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Ocular tumours.

Ocular tumours may arise from various tissues and therefore present as a heterogeneous group of diseases with unspecific symptoms. Some of the tumours carry a high mortality with a life expectancy less than 50% after ten years. Early diagnosis and treatment are essential for a good outcome, and centralization has led to a decreased morbidity and increased survival in Denmark. Tumour-specific somatic mutations can be used for personalized follow-up programmes and may lead to new treatment modalities, as argued in this review.

Ocular metastasis from renal malignancies - A comprehensive review.

The most common cause of intraocular mass is metastasis from other tumors. Renal malignancies, though rare, have a substantial number of cases with ocular metastasis, few of which were misdiagnosed. Many a times renal malignancies present with ocular manifestations before the primary diagnosis. Here in this article, we comprehensively reviewed 106 cases of ocular metastasis from renal malignancies published till date to the best of our knowledge. The eye is a rare site for distant metastasis because of the lack of a lymphatic system. The most common ocular structures to get involved in distant metastasis are the uveal tract, i.e., choroid, iris, and ciliary body. The most common renal tumor which metastasizes to eyes is renal cell carcinoma (RCC). RCC accounts for less than 2% of all ophthalmic metastases. Out of total 106 cases, the type of renal malignancy was known in 95 cases only, of which 92 had RCC, 1 Wilm's tumor, 1 rhabdoid tumor, and 1 medullary carcinoma. The age ranged widely from 2 weeks old to 81 years old. The male to female ratio was 3.4:1. In total, 67.4% of cases had a previous history of RCC, while the rest 32.6% primarily presented with ophthalmic manifestations first. Treatment modalities included enucleation of the eye, debulking surgery followed by radiotherapy and/or chemotherapy and/or immunotherapy.

PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.

PURPOSE: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. METHODS: Observational case report. RESULTS: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. CONCLUSION: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Posterior segment manifestations of ocular metastasis.

PURPOSE OF REVIEW: This article reviewed and summarized recent published data on ocular imaging findings and treatment of posterior segment manifestations of ocular metastasis. RECENT FINDINGS: Advanced ocular imaging can help differentiate ocular metastases from other mimicking lesions, including primary intraocular tumors or infections. Recently, case reports have demonstrated the successful use of targeted systemic therapy to achieve local control of vitreous and choroidal metastases. SUMMARY: Metastasis can lead to a wide variety of posterior segment ocular manifestations. The choroid is the most common metastatic site, whereas tumor metastasizing to the retina and optic disc are rare. Patients with possible metastatic eye disease are recommended to undergo extensive investigation to determine the underlying primary cancer and ongoing systemic metastases. Currently, there is no consensus on the treatment strategy. Treatment generally includes systemic chemotherapy in combination with local treatment, such as radiotherapy, laser therapy, or anti-vascular endothelial growth factor (anti-VEGF) treatment.