Ocular Sporotrichosis

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.

The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways

A comprehensive constellation of somatic nonsilent mutations and copy-number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors, we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NF-κB, NOTCH, and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets. Significance: We report systematic application of whole-exome sequencing and CN variations in OAMZL, revealing common alterations in regulation of NFAT signaling pathway that may facilitate identification of new therapies.

Human Papillomavirus Related Neoplasia of the Ocular Adnexa

Human papillomaviruses (HPV) are a large group of DNA viruses that infect the basal cells of the stratified epithelium at different anatomic locations. In the ocular adnexal region, the mucosa of the conjunctiva and the lacrimal drainage system, as well as the eyelid skin, are potential locations for HPV-related neoplasia. The role of HPV in squamous cell neoplasia of the ocular adnexa has been debated for several decades. Due to the rarity of all these tumors, large studies are not available in the scientific literature, thereby hampering the precision of the HPV prevalence estimates and the ability to conclude. Nevertheless, increasing evidence supports that defined subsets of conjunctival papillomas, intraepithelial neoplasia, and carcinomas develop in an HPV-dependent pathway. The role of HPV in squamous cell tumors arising in the lacrimal drainage system and the eyelid is still uncertain. Further, the potential of HPV status as a diagnostic, prognostic, or predictive biomarker in these diseases is a topic for future research.

Follicular lymphoma of the ocular adnexa: Clinicopathological findings with flow cytometry analysis of eight cases

Purpose: Flow cytometry (FCM) is used to evaluate cell surface markers of various leukocyte populations quantitatively. However, little is known about the usefulness of FCM in follicular lymphoma (FL) of the ocular adnexa. The aim of this study was to evaluate the clinicopathological features and FCM results in ocular adnexal FL. Materials: This is a retrospective multicenter case study on clinical and immunohistochemical features. All tumors, surgically excised, were diagnosed based on histopathology, immunoglobulin heavy chain gene rearrangement, and FCM. The percentages (%) of B-cell markers, T-cell markers, a natural killer cell marker, and cell surface kappa/lambda measured by FCM analysis in tumor tissues were searched based on medical records. Results: This study enrolled nine tumors in eight FL patients (three men and five women). The median age at the time of initial presentation was 74 years. All the tumors surgically excised histologically exhibited cluster of differentiation (CD)10, CD20, and BCL2-positive cells. At the time of ophthalmic diagnosis, lymphomas were already disseminated throughout the body in five cases. FCM demonstrated high percentage of B-cell markers including CD10, CD19, CD20, and CD23 in all nine tumors. CD10 population was 73.5% ± 11.9% in seven out of nine tumors, while that in the other two tumors was particularly low being 11.7% ± 1.13%, which showed the relatively high T-cell lineages compared to the other seven tumors. Conclusion: For ophthalmologists involving managements of ocular adnexal tumors, FCM can provide useful information for complementing the diagnosis and understanding pathophysiology of FL.