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.

Presentation, Diagnostic Testing and Initial Treatment of Vitreoretinal Lymphoma.

PURPOSE: Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes presentation, diagnostic testing, and first treatment approaches in a recently diagnosed and treated patient cohort. DESIGN: Clinical registry-based observational study. SUBJECTS: Forty-eight women and 32 men (age range, 32-91 years; median age, 64 years) diagnosed with vitreoretinal lymphoma. METHODS: An international network of ophthalmologists reported clinical features and management of patients presenting with vitreoretinal lymphoma between January 1, 2020 and December 31, 2022 via an electronic platform. MAIN OUTCOME MEASURES: Visual acuity at presentation (logarithm of the minimum angle of resolution [logMAR]); basis for diagnosis; first treatment. RESULTS: Vitreoretinal lymphoma was bilateral at presentation in 65% of patients (n = 52) and an initial site of lymphoma in 78% (n = 62). Of 127 eyes with lymphoma at presentation, vitreous was involved in 89% (n = 113) and was the only involved eye tissue in 40% (n = 51), and retina was involved in 46% (n = 59) and was the only involved eye tissue in 9% (n = 11). Median logMAR visual acuity of the worse-seeing eye was 0.50. The lymphoma was diagnosed from ocular specimens in 80% of patients (64/80), usually vitreous (57/64 patients [89%]), and on other clinical information in 20% of patients (16/80). Cellular studies were performed on ocular specimens from 59 of 64 patients (92%), most often cytology. Tumor gene analysis was used in 21 of 64 patients (33%), and cytokine assays were used in 13 of 64 patients (20%). For 76 patients (95%), treatment was initiated within 6 months of diagnosis and included ocular (38/76 [48%]), extraocular (17/76 [21%]), and ocular plus extraocular (21/76 [26%]) approaches. Intravitreal methotrexate was the most common ocular treatment (83/87 eyes [95%]). CONCLUSIONS: Using data collected from 80 patients diagnosed with vitreoretinal lymphoma since 2020, we show that visual impairment is common, and that management often involves diagnosis by cellular tests and treatment with intravitreal chemotherapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[Molecular diagnostics for vitreoretinal lymphoma]. / Molekulare Diagnostik des vitreoretinalen Lymphoms.

Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered a special form of primary diffuse large cell lymphoma (DLBCL) of the CNS (central nervous system) (PCNSL) and arises primary or secondary to PCNSL. According to the cell of origin (COO) classification of DLBCL, PVRL largely belongs to the activated B­cell (ABC) type of DLBCL. Based on a recently established genetic-biological classification of DLBCL, PCNSL and thus also PVRL belong to a group of DLBCL of the MYD88/CD79B-mutated (MCD) or cluster 5 subtype, which often shows extranodal manifestations and MYD88 and CD79A mutations as well as CDKN2A deletions.PVRL diagnostics is often complicated as it represents a classic masquerade syndrome. Due to the usually limited material with often large numbers of reactive lymphocytes and/or degenerative changes in the cells, the results of diagnostic tests are difficult to interpret. Classic diagnostic tests include cytology on vitreous aspirates, immunocytochemistry, and clonality analysis.New insights into the spectrum of genetic alterations of vitreoretinal lymphomas (VRL) confirm the close relationship to PCNSL and could significantly improve pathological diagnosis. Next-generation sequencing panel-based diagnostics allow VRL diagnosis confirmation with little DNA in almost 100% of patients in cases with insufficient cytological evidence or lack of clonality detection. PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.

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.

[Research progress in the diagnosis of primary vitreoretinal lymphoma].

Primary vitreoretinal lymphoma (PVRL), the most prevalent intraocular lymphoma, is a subtype of primary central nervous system lymphoma (PCNSL) that often clinically mimics uveitis. It is a rare intraocular malignancy characterized by a dismal prognosis. The gold standard for PVRL diagnosis remains cytopathological examination. Additionally, auxiliary tests, such as clonal detection of tumor cells and cytokine analysis, have been employed. Moreover, recent years have witnessed the gradual development of novel molecular biomarkers and detection techniques. To optimize diagnostic strategies for PVRL patients, a comprehensive approach that integrates clinical manifestations, cytological examination, immunological assessment, and molecular biology analysis is indispensable. This article provides a comprehensive review of recent advancements in the diagnosis of primary vitreoretinal lymphoma.

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.

Vitreoretinal lymphoma: a diagnostic challenge.

A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented. Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone, biological treatment with Adalimumab was established. During follow-up, the patient developed bilateral subretinal lesions compatible with Vitreoretinal Lymphoma (VRL), so vitrectomy was performed, confirming the diagnosis of large B-cell lymphoma. Treatment with systemic chemotherapy with BRAM-Carmustine, Metrotexate, Ara C, and Rituximab was started with a good answer. Two years later, the patient remains without ocular or systemic recurrences. Vitreoretinal Lymphoma is a rare type of primary central nervous system lymphoma. The diagnosis is frequently delayed due to the nonspecific symptoms, which mimic chronic posterior uveitis, hence the importance with a diagnostic suspicion.

Iridial melanocytoma in a ferruginous hawk (Buteo regalis): A case report and review of avian melanocytic neoplasia.

A 21-year-old, suspected female captive ferruginous hawk (Buteo regalis) was followed for 3 years due to an iridial mass of the left eye (OS) that progressively increased in size. Enucleation of OS was eventually recommended due to the iridial mass taking up approximately 75% of the anterior chamber, and the bird seemed less active. A complete physical examination, complete blood cell count, biochemistry, and survey radiographs were performed pre-surgery with no findings indicating metastasis. A subconjunctival enucleation was performed and the globe was submitted for histopathology through the Comparative Ocular Pathology Lab of Wisconsin. The histopathologic evaluation determined the mass to be consistent with an iris melanocytoma, which has not been previously reported in this species. The patient recovered well from surgery and has remained comfortable and active for 117 days post-surgery. This case report aimed to review the current available information on avian ocular neoplasms as well as describe the clinical presentation, medical management and surgical procedure, and long-term follow-up for this patient to enhance clinical understanding of the behavior of iris melanocytic tumors in avian species.

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.

Promotor methylation in ocular surface squamous neoplasia development: epigenetics implications in molecular diagnosis.

INTRODUCTION: Cancer is heavily influenced by epigenetic mechanisms that include DNA methylation, histone modifications, and non-coding RNA. A considerable proportion of human malignancies are believed to be associated with global DNA hypomethylation, with localized hypermethylation at promoters of certain genes. AREA COVERED: The present review aims to emphasize on recent investigations on the epigenetic landscape of ocular surface squamous neoplasia, that could be targeted/explored using novel approaches such as personalized medicine. EXPERT OPINION: While the former is thought to contribute to genomic instability, promoter-specific hypermethylation might facilitate tumorigenesis by silencing tumor suppressor genes. Ocular surface squamous neoplasia, the most prevalent type of ocular surface malignancy, is suggested to be affected by epigenetic mechanisms, as well. Although the exact role of epigenetics in ocular surface squamous neoplasia has mostly been unexplored, recent findings have greatly contributed to our understanding regarding this pathology of the eye.

Lamellar Keratoplasty Using Microkeratome-Assisted Anterior Lamellar Graft in the Management of Deep Limbal Dermoid: A Case Report.

Limbal dermoid is a congenital benign tumor of the limbus which is often managed by surgery if necessary. In dermoid lesions involving the deep stroma, tumor excision and reconstruction of the anterior segment with amniotic membrane transplantation or keratoplasty may be required. Herein, we present a case of deep limbal dermoid treated with surgical resection and lamellar keratoplasty using microkeratome-assisted anterior lamellar graft.

Artificial intelligence for ocular oncology.

PURPOSE OF REVIEW: The aim of this article is to provide an update on the latest applications of deep learning (DL) and classical machine learning (ML) techniques to the detection and prognostication of intraocular and ocular surface malignancies. RECENT FINDINGS: Most recent studies focused on using DL and classical ML techniques for prognostication purposes in patients with uveal melanoma (UM). SUMMARY: DL has emerged as the leading ML technique for prognostication in ocular oncological conditions, particularly in UM. However, the application of DL may be limited by the relatively rarity of these conditions.

Localized Recurrence of Multiple Myeloma in the Lacrimal Gland.

The authors report the case of a multiple myeloma recurrence isolated to the lacrimal gland. The patient is a 54-year-old man with a medical history of IgA kappa multiple myeloma status post multiple lines of chemotherapy and stem cell transplantation (×2) who was presumed to be without evidence of disease. Six years following the transplant, he presented with a lacrimal gland tumor with a biopsy consistent with multiple myeloma. Systemic disease evaluation at that time, including positron emission tomography scan, bone marrow biopsy, and serum analysis, were negative. To the best of the authors' knowledge, no prior reports exist describing an isolated lacrimal gland recurrence of multiple myeloma with ultrasound and MRI imaging.

Corneal squamous neoplasia: masquerades and management outcomes at a rural eyecare centre.

The authors describe two cases of corneal ocular surface squamous neoplasia (OSSN), presenting at our rural eyecare centre, which were initially misdiagnosed as viral epithelial keratitis and corneal pannus with focal limbal stem cell deficiency. Both the cases were refractory to initial treatment and corneal OSSN was suspected. Anterior segment-optical coherence tomography (AS-OCT) revealed a thickened, hyper-reflective epithelium with abrupt transition and an underlying cleavage plane, features typical of OSSN. Topical 1% 5-fluorouracil (5-FU) therapy was initiated and in two cycles (first case) to three cycles (second case), complete resolution was noted both clinically and on AS-OCT, with no significant side effects. Both patients are currently free of tumour at the 2-month follow-up period. The authors report the rare, atypical presentations of corneal OSSN, discuss the masquerades and highlight the role of primary topical 5-FU in managing corneal OSSN in limited resource settings.

Role of vitreous cytology in the diagnosis of primary central nervous system lymphoma: A report of an unusual presentation.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma confined to the brain, spinal cord, meninges, intraocular compartment, and cranial nerves. Intraocular lymphoma (IOL) is a rare subtype of PCNSL. Intravitreal involvement by a PCNSL is an infrequent but potentially fatal event. The role of vitreous cytology in diagnosing IOLs is vital but has been sporadically described in the literature due to its variable sensitivity. Herein, we present a case of PCNSL, who primarily presented with ocular symptoms and could be accurately diagnosed based on vitreous cytology and subsequently confirmed on stereotactic brain biopsy.

[Tic douloureux sustained by an eye tumor].

Cancer is a major cause of morbidity and mortality in solid organ transplantation. Nonmelanoma skin cancer (NMSC) such as basocellular (BCC) and spinocellular (SCC) carcinoma, are common in renal transplant recipients. We report a case of an SCC affecting a lacrimal gland in a subject with kidney transplantation. A man aged 75 years who had suffered from glomerulopathy since 1967 and subsequently started haemodialysis, in 1989 was transplanted from a living donor. In 2019, he suffered paresthesia and pain in his right eyebrow arch and he was diagnosed to have neuralgia of the fifth cranial nerve. The failure of medical treatment and the development of a mass in his eyelid plus exophthalmos induced healthcare professionals to perform a magnetic resonance. The latter showed a retrobulbar mass measuring 39×22×16 mm3. Biopsy revealed an SCC and the patient underwent eye exenteration. Although NMSC of the eye is an extremely rare condition, risk factors such as male sex, history of glomerulopathy, and duration of immunosuppression should be taken into consideration at the time of the onset of eye symptoms.