ABSTRACT
BACKGROUND: Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas remain incompletely understood. METHODS: A large cohort of 63 conjunctival melanomas was screened for gene mutations known to be important in other melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with patient prognosis. RESULTS: Frequent mutations in genes activating the MAP kinase pathway were identified. NF1 mutations were most frequent (n = 21, 33%). Recurrent activating mutations were also identified in BRAF (n = 16, 25%) and RAS genes (n = 12, 19%; 11 NRAS and 1 KRAS). CONCLUSIONS: Similar to cutaneous melanomas, conjunctival melanomas can be grouped genetically into four groups: BRAF-mutated, RAS-mutated, NF1-mutated and triple wild-type melanomas. This genetic classification may be useful for assessment of therapeutic options for patients with metastatic conjunctival melanoma.
Subject(s)
Conjunctival Neoplasms/genetics , Melanoma/genetics , Mutation , Neurofibromin 1/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cohort Studies , Conjunctival Neoplasms/pathology , DNA Mutational Analysis/methods , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Melanoma/pathology , Middle Aged , Proto-Oncogene Proteins B-raf/genetics , ras Proteins/geneticsABSTRACT
BACKGROUND: Ocular graft-versus-host disease (GvHD) following allogeneic blood stem cell transplantation leads to immunologically induced alterations in many ocular tissues, particularly at the ocular surface. Within the framework of the main topic, this article focuses primarily on corneal complications in chronic ocular GvHD. OBJECTIVE: This article aims to promote understanding of the influencing factors, diagnostics, and therapeutic options pertaining to corneal complications in ocular GvHD. Furthermore, the possibilities for prevention are discussed. MATERIALS AND METHODS: This analysis is based on a literature review as well as on data from the Ophthalmology Clinic at the University Hospital Essen. RESULTS: Corneal complications often occur secondarily in ocular GvHD, as a consequence of severe inflammatory alterations of the conjunctiva or eyelid. Spontaneous corneal perforations associated with only mild symptoms are less common during the course of disease. From the ophthalmologist's perspective, it is important that the inflammatory activity of all the different ocular tissues is considered. Treatment may follow a stepwise scheme that includes substitution, immunosuppression, and surgical rehabilitation. CONCLUSION: Systematic diagnosis of ocular GvHD helps to prevent corneal complications or support early therapeutic intervention. An interdisciplinary approach to diagnosis and treatment planning is recommended, in order to optimize local and systemic immunosuppressive therapy.
Subject(s)
Corneal Diseases/etiology , Eye Diseases/etiology , Graft vs Host Disease/etiology , Adrenal Cortex Hormones/therapeutic use , Chronic Disease , Combined Modality Therapy , Corneal Diseases/diagnosis , Corneal Diseases/therapy , Corneal Ulcer/diagnosis , Corneal Ulcer/etiology , Corneal Ulcer/therapy , Cyclosporine/therapeutic use , Diagnosis, Differential , Eye Diseases/diagnosis , Eye Diseases/therapy , Graft vs Host Disease/diagnosis , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Humans , Interdisciplinary Communication , Intersectoral Collaboration , Keratoplasty, Penetrating , Limbus Corneae/cytology , Ophthalmic Solutions , Tacrolimus/therapeutic useABSTRACT
OBJECTIVE: This study reports the long-term clinical outcome of autologous limbal epithelial cells cultivated ex vivo on intact amniotic membranes (AM) for ocular surface reconstruction in limbal stem cell deficiency (LSCD). PATIENTS AND METHODS: A total of 61 eyes from 57 patients (46 males and 11 females) with LSCD were treated by transplantation of autologous limbal epithelial cells cultivated on intact AM. The etiology of the LSCD was chemical and thermal burns (n = 34), recurrent or primary large-sized pterygium (n = 12), mitomycin C and tumor excision-induced LSCD (n = 9), severe infectious keratitis (n = 3), perforating injury, epidermolysis bullosa and contact lens-associated keratopathy (each n = 1). Only eyes with a follow-up time of at least 12 months were included in the analysis. The main outcome end points were restoration of ocular surface integrity and improvement of visual acuity (VA). RESULTS: The mean follow-up time was 50.8 ± 32.7 months. An entirely stable corneal surface was reconstructed in 46 (75.4%) eyes. Visual acuity significantly increased in 40 (65.6 %) eyes, was stable in 12 (19.7%) eyes and decreased in 9 eyes (14.8%). The mean visual acuity significantly increased (p < 0.0001) from 1.4 ± 0.91 LogMAR preoperatively to 0.8± 0.67 LogMAR postoperatively. CONCLUSION: Transplantation of limbal epithelium cultivated ex vivo on intact AM leads to restoration of a stable corneal surface and resulted in a significant increase of visual acuity in most cases of LSCD. Autologous transplantation of cultivated limbal epithelium showed an excellent prognosis and outcome after long-term follow-up.
Subject(s)
Corneal Diseases/therapy , Epithelium, Corneal/transplantation , Limbus Corneae/surgery , Stem Cell Transplantation/methods , Aged , Autografts , Clinical Trials as Topic , Corneal Diseases/pathology , Epithelium, Corneal/pathology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
BACKGROUND: Radiotherapy of conjunctival melanoma has gained in importance in recent years compared to less invasive therapeutic approaches. This is due to the high recurrence rates achieved by omitting adjuvant therapy and to the increasing availability of suitable radiotherapeutic methods, so that tumors formerly not amenable to organ-preserving therapy can now be treated. OBJECTIVE: This article presents the current radiotherapeutic options for conjunctival melanoma. The aim is to describe the diagnostic and therapeutic strategies and the course of therapy of malignant conjunctival melanoma. It is the authors' intention to justify the necessity of the adjuvant therapy of conjunctival melanoma and to emphasize the need for interdisciplinary cooperation during the course of tumor therapy. METHODS: The article is based on results published in the literature as well as on data collected and experience gained in our centre.
