Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway.

BACKGROUND: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. METHODS: We performed targeted NGS using a 519-gene panel. RESULTS: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. CONCLUSIONS: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.

Conjunctival Inflammation and Panuveitis as Manifestations of Ig-G4-Related Disease: A Case Report.

PURPOSE: To report a case of isolated conjunctival inflammation as initial manifestation of IgG4-related disease and subsequent development of panuveitis. CASE REPORT: A 75-year-old female presented with a diffuse mass lesion in the temporal area of the left eye, involving the conjunctiva, and an abscessed corneal ulcer. An incisional biopsy was diagnostic of IgG4-related disease with an elevated IgG4/IgG ratio (>40%) and the presence of >10 cells that tested positive for IgG4/CGA. No other ocular, orbital or systemic manifestations were noted at the time of diagnosis. After a year of treatment with topical dexamethasone, oral prednisone, and methotrexate, the patient developed panuveitis, which was controlled by increasing steroids and switching to rituximab. CONCLUSION: IgG4-related disease is a rare entity that can be particularly challenging to diagnose if it manifests in an atypical manner. Continuous follow-up of patients is crucial as relapses and worsening of symptoms can occur despite treatment.

Neurotrophic Keratitis in a Pediatric Patient With Goldenhar Syndrome and Trigeminal Aplasia Successfully Treated by Corneal Neurotization.

Herein, the authors report an unusual case of a 6-year-old boy with right-sided Goldenhar syndrome and trigeminal nerve aplasia who developed neurotrophic keratopathy (NK). Despite the use of therapeutic contact lenses and multiple temporary tarsorrhaphy, NK worsened showing a central corneal scar, neovascularization, and significant stromal thinning, with risk of corneal perforation. Cochet-Bonnet esthesiometry revealed complete corneal anesthesia. To minimize additional corneal complications, the patient underwent indirect corneal neurotization by a sural nerve autograft anastomosed to the contralateral supratrochlear nerve. At 24-month follow up, no epithelial defects, complications, or recurrence were observed. Significant improvements in corneal sensitivity with esthesiometry score of 20 mm and reflex blinking were achieved. This case highlights corneal anesthesia should be suspected among Goldenhar syndrome ophthalmologic abnormalities and monitored before corneal changes become irreversible. Since corneal neurotization can successfully improve corneal sensation, it could be considered as an early therapeutic option to avoid refractory NK.

Sclerouvectomy plus intraoperative ophthalmic brachytherapy for iris-ciliary body melanomas.

BACKGROUND: Partial lamellar sclerouvectomy was designed more than 30 years ago by Jerry and Carol Shields, in order to remove melanomas that involved the ciliary body and/or the choroid, while leaving intact the outer portion of the sclera and the overlying sensory retina [1]. METHODS: We present two cases of iris-ciliary body melanoma with different size. The performed surgery was a partial lamellar sclerouvectomy plus iridectomy, complemented by intraoperative juxtalimbar ruthenium-106 brachytherapy. RESULTS: Both cases achieved anatomical success without developing chronic ocular hypotony in the postoperative period, an infrequent but possible complication [2]. Even one of them reached a best-corrected visual acuity of 0.7 after silicone oil removal and intravitreal implant of dexamethasone because of secondary macular edema. The other remains stable with counting fingers vision. In this case, the poor functional outcome might be influenced by larger size and longer evolution of the tumor, as well as the uncontrolled arterial hypertension and older age of the patient. DISCUSSION: Intraoperative ophthalmic brachytherapy may have a beneficial effect not only over neoplastic activity [2], but also over early choroidal detachments. Its pro-fibrotic/hemostatic stimulus should be further examined by comparative studies with larger cohorts, either prospectively or retrospectively. Other protective factors could be the utilization of equine pericardial grafts for covering scleral defects as well as leaving high-density silicone oil. Another key aspect is to maintain low blood pressure levels during these procedures in order to avoid intraocular hemorrhages [3], especially when the patient exceeds the sixth decade, so the anaesthesiologist will also play a decisive role in the operating room. We prefer to anticipate the likely development of lens opacification after this operation [4], performing cataract surgery at the beginning and using a Cionni capsular tension ring due to a probable zonular instability. Pars plana vitrectomy would also remove peripheral vitreoretinal tractions and seal the retina preventing a detachment. CONCLUSION: As can be observed during the surgical video, a wide range of complications could occur during a partial lamellar sclerouvectomy. Tackle them ahead of time is crucial to achieve anatomical and functional success.

Surgical Approaches for Vitreomacular Tractions.

PURPOSE: The aim is to describe the main characteristics of different approaches in vitreomacular traction surgery. Setting/Venue: The video (see www.karger.com/doi/10.1159/ 000442579) about vitreomacular traction surgery was created at the Department of Ophthalmology, Virgin Macarena University Hospital, Seville, Spain. METHODS: We present the surgical release of vitreomacular tractions in three different pathologies: (1) idiopathic epimacular membrane; (2) proliferative diabetic retinopathy with long-term hemovitreous, and (3) Coats' disease. RESULTS: Although functional success is less common than anatomical success, we will never be able to improve vision without restoring retinal anatomy. CONCLUSIONS: Vitreomacular tractions are perfectly well known by ophthalmologists. However, the method used to release them must be the least aggressive possible in order to avoid retinal tears or macular holes with subsequent visual loss.

Delayed Boston Keratoprosthesis Exchange due to a Preceding Vitreoretinal Surgery with Intraoperative Choroidal Detachment.

PURPOSE: The aim is to describe the main characteristics of an anterior/posterior segment surgery and how to resolve intraoperative complications. Setting/Venue: The anterior and posterior segment surgical video was created at the Department of Ophthalmology, Virgin Macarena University Hospital, Seville, Spain. METHODS: We present the case of a male with Stevens-Johnson syndrome and severe limbal deficiency who needed a Boston type 1 keratoprosthesis, reaching a visual acuity of 0.4 (0.05 before surgery). In the course of follow-up, he developed corneal melting with perforation, immune vitritis, and a large epimacular membrane. We decided to perform a 23-gauge vitrectomy associated with keratoprosthesis exchange. As a consequence of inappropriate anesthesia, the patient woke up during the surgery, provoking a retinal tear besides a choroidal detachment. These damages needed endolaser photocoagulation as well as silicone oil tamponade, forcing us to postpone the exchange. An intravitreal dexamethasone implant was also injected. Two months later, the silicone oil was removed, and the Boston keratoprosthesis was replaced by a new type 1 model with a titanium back plate, which likely improves biocompatibility and retention and may reduce complications such as retroprosthetic membranes and stromal corneal melts. RESULTS: Good anatomical results were achieved, and visual acuity slightly improved to 0.2. CONCLUSIONS: Combined anterior and posterior segment surgery represents a great challenge that can improve not only visual acuity but also quality of life in patients with severe diseases such as Stevens-Johnson syndrome.