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.

UNASSIGNED: Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare type of non-Hodgkin\'s lymphoma. This report presents a patient with the right lower eyelid ENKTL misdiagnosed as meibomitis repeatedly.
UNASSIGNED: A 48-year-old woman developed recurrent redness and swelling in right eyelid for 2 years. Three eyelid mass removal operations were performed in local hospitals, and the pathological examination suggested meibomitis. Physical examination showed an induration in the lateral lower eyelid of the right eye, local defect of the eyelid margin, mild entropion, redness and swelling of the surrounding tissues, and temporal bulbar conjunctiva hyperemia. The eyelid lesion was resected and ENKTL was diagnosed by specific immunohistochemical staining and in situ hybridization. The lymphoma resolved with chemotherapy and radiotherapy. The patient was still alive forty-one months after the last operation.
UNASSIGNED: Our report demonstrates that recurrent eyelid redness and swelling might be a malignant tumor, and clinicians should be vigilant.

UNASSIGNED: To report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL).
UNASSIGNED: Retrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates.
UNASSIGNED: This study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93-100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity.
UNASSIGNED: External Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20-30 Gy delivered over 10-20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

BACKGROUND: Leukemic infiltration of the eye and ocular adnexal site is rare with unknown risk factors and clinical outcomes.
OBJECTIVE: To describe the clinical characteristics of extramedullary ocular adnexal (OA) leukemia in patients with myeloid malignancies.
METHODS: In a retrospective analysis, we screened all patients treated at our center between 1993 and 2022. We identified 50 patients with myeloid malignancies who presented with vision changes with available magnetic resonance imaging of the orbits.
RESULTS: Among all 50 patients, 38 had their symptoms attributed to an infection, 2 to retinal hemorrhage with thrombocytopenia, 1 to chronic graft-vs-host disease and 1 to dacrocystocele. The remaining 8 patients (7 AML, 1 MDS) had leukemic infiltration of the eye and OA, diagnosed by imaging (7/8) or biopsy (1/8). The median age was 47 years (18-82), 6 (75%) were females. The optic nerve was most frequently affected in 7/8 patients, followed by infiltration of the cranial nerve (CN) III and intraconal soft tissues in 2/8 patients, each. Infiltration of the retina, lateral rectus muscle, CN IV, CN VI, and extraconal soft tissue was seen in 1/8 patient, each. Spinal fluid evaluation identified no evidence of leukemia in all 8 patients. Interestingly, 4/8 patients (50%) had abnormalities in chromosome 3q26 or MDS1 and EVI1 complex locus (MECOM) rearrangements, 2 (25%) had Lysine Methyltransferase 2A (KMT2A) rearrangement and the remaining two had trisomy 8 and a diploid karyotype respectively. Patients with KMT2A rearrangement also had other sites of extramedullary disease, while orbital adnexal involvement was the only extramedullary leukemia site in those with MECOM rearrangements. Intrathecal chemotherapy and concurrent local radiation were given to 6/8 patients while the other 2 received either intrathecal chemotherapy or radiation. Symptoms improved or resolved following these measures in 4/8 patients. These visual findings were detected during salvage therapy (median 4, range 1-9 lines). Overall survival following appearance of these findings was short with a median of 5.8 months (range: 0.4-17.5).
CONCLUSIONS: Leukemic infiltration of the orbital adnexa in myeloid malignancies is rare and associated with an inordinately high proportion of MECOM rearrangements in addition to adverse outcomes.

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features and flow cytometry (FCM) of tumor tissues in ocular adnexal diffuse large B-cell lymphoma (DLBCL).
METHODS: This retrospective, multicenter case study was designed to evaluate the clinical and immunohistochemical features of tumors. DLBCL was diagnosed based on histopathology, immunoglobulin (Ig) heavy chain gene rearrangement, and FCM in all surgically removed periocular tumor tissues. This study involved assessing percentages (%) of B-cell/T-cell markers, a natural killer cell marker, and cell-surface Ig kappa/lambda (κ/λ) expression measured by FCM analysis in tumor tissues.
RESULTS: Eleven DLBCL patients (4 men and 7 women) with 11 tumors were enrolled in this study. The median age at the time of initial presentation was 73 years. The tumor cells were immunohistochemically positive for cluster of differentiation (CD) 20, while CD5 was negative in all 8 cases tested. At the time of ophthalmic diagnosis, two cases already showed systemic dissemination of DLBCL throughout the body. FCM of tumor tissues detected a high percentage of B-cell markers including CD19 and CD20 in all 11 tumors. One case with high CD10 levels in FCM was histologic transformation from follicular lymphoma. One case with a relatively low CD20 population involved a history of systemic treatments including intravenous rituximab.
CONCLUSIONS: Although caution should be exercised when interpreting the data, FCM is useful for not only supportive diagnosis complementary to immunohistochemistry, but also facilitates a better understanding of immunopathology including histologic transformation of follicular lymphoma to DLBCL in the ocular adnexa.

External beam radiotherapy is effective for stage I orbital mucosa-associated lymphoid tissue lymphoma (MALToma). Hence, very-low-dose radiotherapy is increasingly being investigated. We conducted a single-center prospective phase II trial to evaluate the effectiveness of very-low-dose radiotherapy of 4 Gy (2 Gy × 2 fractions) in pathologically confirmed stage I orbital MALToma. In this first prospective trial, patients with complete response were observed after 3-6 months of follow-up. For patients without complete remission, a radiation dose of 24 Gy/12 fractions was additionally delivered. The primary endpoint was complete response rate; secondary endpoints were overall survival, local control, and progression-free survival. Seventeen patients were screened and three patients refused enrollment during October 2018-October 2021. Thus, 14 patients (17 eyes) were analyzed (median follow-up, 28.2 months). The overall response rate was 100% (complete remission: 11 lesions; partial remission: six lesions). In all lesions with residual disease, additional radiation therapy (dose: 24 Gy) was performed. One local failure was observed. Therefore, 4 Gy ultralow-dose radiation therapy for orbital MALToma was safely performed with a planned second-line treatment in patients without complete remission. This is the first prospective study to report the effectiveness of ultralow-dose radiotherapy of 4 Gy for stage I orbital MALToma treatment.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular adnexa, MALT lymphomas represent the most common subtype of lymphoma, accounting for around 8% of all non-Hodgkin lymphomas. These lymphomas are often preceded by inflammatory precursor lesions. Either autoantigens or infectious antigens may lead to disease development by functioning as continuous antigenic triggers. This triggering leads to a constitutive activation of the NF-κB signaling pathway. The role of antigenic stimulation in the pathogenesis of OAMZL is supported by the detection of somatic mutations (partially with further intraclonal diversity) in their rearranged immunoglobulin V genes; hence, their derivation from germinal-center-experienced B cells, by a restricted IGHV gene usage, and the validation of autoreactivity of the antibodies in selected cases. In the established lymphomas, NF-κB activity is further enforced by mutations in various genes regulating NF-κB activity (e.g., TNFAIP3, MYD88), as well as recurrent chromosomal translocations affecting NF-κB pathway components in a subset of cases. Further pathogenetic mechanisms include mutations in genes of the NOTCH pathway, and of epigenetic regulators. While gene expression and sequencing studies are available, the role of differential methylation of lymphoma cells, the role of micro-RNAs, and the contribution of the microenvironment remain largely unexplored.

Sporotrichosis is a subacute or chronic mycosis predominant in tropical and subtropical regions. It is an infection of subcutaneous tissue caused by Sporothrix fungus species, but occasionally resulting in an extracutaneous condition, including osteoarticular, pulmonary, nervous central system, and ocular disease. Cases of ocular sporotrichosis are rare, but reports have been increasing in recent decades. Ocular infections usually occur in hyperendemic areas of sporotrichosis. For its classification, anatomic criteria are used. The clinical presentation is the infection in the ocular adnexal and intraocular infection. Ocular adnexa infections include palpebral, conjunctivitis, and infections of the lacrimal sac. Intraocular infection includes exogenous or endogenous endophthalmitis. Most infections in the ocular adnexal have been reported in Brazil, China and Peru, and intraocular infections are limited to the USA and Brazil. Diagnosis is performed from Sporothrix isolation in the mycological examination from ocular or skin samples. Both sporotrichosis in the ocular adnexa and intraocular infection can mimic several infectious and non-infectious medical conditions. Ocular adnexa infections are treated with potassium iodide and itraconazole. The intraocular infection is treated with amphotericin B. This review describes the clinical findings and epidemiological, diagnosis, and treatment of ocular sporotrichosis.

UNASSIGNED: MED12-related disorders are a rare group of intellectual disability syndromes with a broad range of phenotypic characteristics. The phenotypic spectrum of MED12-related disorders currently includes X-Linked Ohdo Syndrome, Lujan-Fryns Syndrome (LS), and FG syndrome type 1 (FG), also known as Opitz-Kaveggia Syndrome. The MED12 gene encodes the largest component of the mediator complex of RNA polymerase II, which is critical for recruiting activators and repressors to regulate the transcription of genes critical to growth, development, and differentiation.
UNASSIGNED: We performed a systematic literature review of previously published cases to highlight the key ocular features in individuals with MED12-related disorders. In addition, we present a new case of a female patient with a de novo pathogenic c. 3866A>G, p.Q1289R variant. Ocular manifestations are not uncommon in MED12-related disorders, but have not been characterized in literature reports. Commonly reoccurring reported eye and ocular adnexa features within the spectrum include ptosis, downslanting palpebral fissures, and hypertelorism. Other less common findings include strabismus, astigmatism, and optic nerve hypoplasia.
UNASSIGNED: Our patient presented with developmental delay, mild hypotonia and dysmorphic features including frontal bossing, high arched palate, and syndactyly of the 2nd and 3rd toes bilaterally.
UNASSIGNED: Ocular manifestations identified in this patient included intermittent esotropia, hyperopic astigmatism, epicanthal folds and ptosis bilaterally.