ABSTRACT
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.
Subject(s)
Melanoma , Uveal Neoplasms , Adult , Humans , Prognosis , Immunohistochemistry , Retrospective Studies , Tumor Suppressor Proteins/genetics , Melanoma/pathology , Uveal Neoplasms/metabolism , Ubiquitin Thiolesterase/genetics , Antigens, NeoplasmABSTRACT
PURPOSE: To evaluate the risk factors for retinal tear (RT) or rhegmatogenous retinal detachment (RRD) associated with acute, symptomatic posterior vitreous detachment (PVD) in a large comprehensive eye care setting. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 8305 adult patients in the Kaiser Permanente Northern California Healthcare System (KPNC) during calendar year 2018 who met inclusion criteria. METHODS: The KPNC electronic medical record was queried to capture acute, symptomatic PVD events. Each chart was reviewed to confirm diagnoses and capture specific data elements from the patient history and ophthalmic examination. MAIN OUTCOME MEASURES: Presence of RT or RRD at initial presentation or within 1 year thereafter. RESULTS: Of 8305 patients who presented with acute PVD symptoms, 448 (5.4%) were diagnosed with RT and 335 (4.0%) were diagnosed with RRD. When considering variables available before examination, blurred vision (odds ratio [OR], 2.7; confidence interval [CI], 2.2-3.3), male sex (OR, 2.1; CI, 1.8-2.5), age < 60 years (OR, 1.8; CI, 1.5-2.1), prior keratorefractive surgery (OR, 1.6; CI, 1.3-2.0), and prior cataract surgery (OR, 1.4; CI, 1.2-1.8) were associated with higher risk of RT or RRD, whereas symptoms of flashes were mildly protective (OR, 0.8; CI, 0.7-0.9). Examination variables associated with a high risk of RT or RRD included vitreous pigment (OR, 57.0; CI, 39.7-81.7), vitreous hemorrhage (OR, 5.9; CI, 4.6-7.5), lattice degeneration (OR, 6.0; CI, 4.7-7.7), and visual acuity worse than 20/40 (OR, 3.0; CI, 2.5-3.7). Late RTs or RRDs occurred in 12.4% of patients who had vitreous hemorrhage, lattice degeneration, or a history of RT or RRD in the fellow eye at initial presentation but only 0.7% of patients without any of these 3 risk factors. Refractive error had an approximately linear relationship with age at presentation of PVD, with myopic patients presenting at a younger age (r = 0.4). CONCLUSIONS: This study, based in a comprehensive eye care setting, found the rate of RT and RRD associated with acute PVD to be lower than rates previously reported by retina subspecialty practices. Several patient features strongly predicted the presence of initial and late complications of acute PVD.
Subject(s)
Retinal Detachment/etiology , Retinal Perforations/etiology , Vitreous Detachment/complications , Acute Disease , Aged , Electronic Health Records , Female , Humans , Male , Middle Aged , Odds Ratio , Retinal Detachment/diagnosis , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/etiology , Retinal Perforations/diagnosis , Retrospective Studies , Risk Factors , Vision Disorders/diagnosis , Vision Disorders/etiology , Visual Acuity , Vitreous Hemorrhage/diagnosis , Vitreous Hemorrhage/etiologyABSTRACT
INTRODUCTION: Trans-scleral biopsy of uveal melanoma (UM) poses an inherent risk of tumor and possibly retinal perforation. We describe a novel technique for trans-scleral biopsy of UM and evaluate its safety and efficacy in an initial cohort of patients. METHODS: A retrospective, consecutive observational case series was conducted from October 14, 2019, to April 15, 2020, at Kaiser Permanente, San Francisco, CA among patients with UM of the ciliary body or anterior choroid undergoing trans-scleral fine-needle aspiration biopsy using a novel guarded needle technique. RESULTS: A total of 6 patients were included in the study, with a mean age of 64.3 (range 35-77) years (5 women 83%). Mean (±SD) tumor thickness and maximal basal diameter were 6.4 (±2.66) and 11.9 (±2.13) mm, respectively. Five out of 6 patients achieved a successful biopsy with reliable gene expression profiling (GEP) results. The only failure to obtain specimen occurred in the first attempted patient and, after a minor technique modification, all subsequent biopsies were successful. No intraoperative or short-term postoperative complications were observed in any patient. CONCLUSION: This novel trans-scleral biopsy technique appears to be safe and effective when obtaining UM tissue for GEP. This method may provide a more controlled biopsy depth thereby minimizing the risk of tumor perforation and its associated complications while still obtaining adequate biopsy yield.
ABSTRACT
IMPORTANCE: This case series describes events associated with errors in intravitreous injections. Given the volume of injections performed worldwide, it is important to identify the factors associated with these wrong events to try to reduce their occurrences. OBJECTIVE: To evaluate a series of errors in intravitreous injections within Kaiser Permanente Northern California (KPNC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective small case series of a convenience sample at KPNC between January 1, 2019, and December 30, 2020, cases of errors in intravitreous injection were identified either as part of a formal institutional quality review or by self-report of the involved surgeon during quality improvement discussions. MAIN OUTCOMES AND MEASURES: Description of the medical errors and the circumstances surrounding these errors. RESULTS: During the 2 years of this evaluation, there were more than 147â¯000 injections performed within KPNC. Four cases of errors in intravitreous injection were identified. Mistakes were associated with inaccurate review of the electronic medical record, poor surgeon and staff focus, and inconsistent use of surgical checklists and timeouts. No long-term ocular morbidity occurred following any of these errors. CONCLUSIONS AND RELEVANCE: Medical errors related to intravitreous injections have occurred within KPNC. We trust these events are not unique to our practice. A standardized teams-based approach that incorporates rigorous safety protocols will likely be needed to reduce the risk of future wrong intravitreous injections.
Subject(s)
Checklist , Medical Errors , Humans , Injections , Intravitreal Injections , Retrospective StudiesSubject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Blindness/etiology , Intravitreal Injections/adverse effects , Macular Edema/drug therapy , Retinal Perforations/etiology , Retinal Vein Occlusion/drug therapy , Aged , Blindness/diagnosis , Blindness/physiopathology , Female , Glaucoma, Open-Angle/complications , Humans , Macular Edema/etiology , Retinal Perforations/diagnostic imaging , Retinal Perforations/physiopathology , Retinal Vein Occlusion/complications , Subretinal Fluid/diagnostic imaging , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiologyABSTRACT
Conjunctival examination for trachomatous inflammation-follicular (TF) guides public health decisions for trachoma. Smartphone cameras may allow remote conjunctival grading, but previous studies have found low sensitivity. A random sample of 412 children aged 1-9 years received an in-person conjunctival examination and then had conjunctival photographs taken with 1) a single-lens reflex (SLR) camera and 2) a smartphone coupled to a 3D-printed magnifying attachment. Three masked graders assessed the conjunctival photographs for TF. Latent class analysis was used to determine the sensitivity and specificity of each grading method for TF. Single-lens reflex photo-grading was 95.0% sensitive and 93.6% specific, and smartphone photo-grading was 84.1% sensitive and 97.6% specific. The sensitivity of the smartphone-CellScope device was considerably higher than that of a previous study using the native smartphone camera, without attachment. Magnification of smartphone images with a simple attachment improved the grading sensitivity while maintaining high specificity in a region with hyperendemic trachoma.
Subject(s)
Photography/instrumentation , Photography/methods , Smartphone , Trachoma/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Male , Sensitivity and SpecificityABSTRACT
BACKGROUND: Treatment planning for I-125 plaque therapy for uveal melanoma has advanced significantly since the Collaborative Ocular Melanoma Study trial, with more widely available image-guided planning and improved dosimetry. OBJECTIVE: We evaluated real-world practice patterns for I-125 plaque brachytherapy in the United States by studying practice patterns at centers that comprise the Ocular Oncology Study Consortium (OOSC). METHODS: The OOSC database and responses to a treatment practice survey were evaluated. The database contains treatment information from 9 institutions. Patients included in the database were treated between 2010 and 2014. The survey was conducted in 2018 and current treatment planning methods and prescriptions were queried. RESULTS: Examination of the OOSC database revealed that average doses to critical structures were highly consistent, with the exception of one institution. Survey responses indicated that most centers followed published guidelines regarding dose and prescription point. Dose rate ranged from 51 to 118 cGy/h. As of 2018, most institutions use pre-loaded plaques and fundus photographs and/or computed tomography or magnetic resonance imaging in planning. CONCLUSIONS: While there were differences in dosimetric practices, overall agreement in plaque brachytherapy practices was high among OOSC institutions. Clinical margins and planning systems were similar among institutions, while prescription dose, dose rates, and dosimetry varied.
ABSTRACT
We report a case of a 51-year-old Caucasian female who presented with a ciliary body melanoma of the right eye leading to focal resorption of the crystalline lens and inducing posterior subcapsular cataract. She underwent successful enucleation, and histopathology demonstrated a ciliary body melanoma with a predominance of epithelioid cells and focal scleral extension. Genetic testing revealed a heterozygous, pathogenic mutation of BAP1 (c.1717delC, p.Leu573fs). Crystalline lens resorption is a rare but potentially important finding in ciliary body melanoma, as early detection of malignancy can be lifesaving.
ABSTRACT
PURPOSE: To study the relationship between gene expression profile (GEP) subclass and American Joint Committee on Cancer (AJCC) stage in patients with uveal melanoma (UM). METHODS: A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Three hundred sixty eligible patients had UM and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with GEP testing between January 1, 2010, and October 28, 2014. Patient demographics and UM features were analyzed by both GEP and AJCC status. RESULTS: Gene expression profile class divided the cohort into three groups: Class 1a (n = 186), Class 1b (n = 77), and Class 2 (n = 113). When classified using AJCC staging criteria, we found the following: Stage I in 91 cases (25.3%), Stage IIA in 143 cases (39.7%), Stage IIB in 89 cases (24.7%), Stage IIIA in 36 cases (10%), and Stage IIIB in 1 case (0.3%). There were no Stage IV cases, as lymph node and metastatic data were not collected as a part of this study. Among Stage I tumors, both high tumor height and high largest basal diameter were associated with a higher frequency of Class 2 status (P < 0.05). As UMs progress to a larger AJCC tumor group (T1-T4), the odds ratio of having a worse prognosis based on GEP class was 1.75 (95% CI, 1.36-2.25; P < 0.001). Similarly, as UMs progress to a higher AJCC stage, the odds ratio of having a worse prognosis based on GEP class was 1.69 (95% CI, 1.36-2.10; P < 0.001). CONCLUSION: This report details the differences in clinical features between GEP subclasses and how they are distributed among the AJCC stages. When the tumors were grouped by AJCC staging criteria, both larger AJCC tumor (T) group and worsening AJCC stage were associated with worsening predicted prognosis, based on GEP subclass.
Subject(s)
DNA, Neoplasm/genetics , Gene Expression Profiling/methods , Melanoma/genetics , Neoplasm Staging , Ophthalmology , Societies, Medical , Uveal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle , Female , Humans , Male , Melanoma/diagnosis , Melanoma/metabolism , Middle Aged , Retrospective Studies , United States , Uveal Neoplasms/diagnosis , Uveal Neoplasms/metabolism , Young AdultABSTRACT
PURPOSE: To investigate the relationship between surgical approach for intraocular tumor biopsy of uveal melanoma and tumor morphologic features such as size and intraocular location and the effect of these variables on diagnostic yield and biopsy outcome. METHODS: Consecutive patients from nine Ocular Oncology centers with uveal melanoma (UM) undergoing tumor biopsy immediately preceding I125 plaque brachytherapy with tissue sent for gene expression profiling (GEP) testing were reviewed retrospectively. RESULTS: Three hundred sixty patients were included (50% men, mean age 60.2 years). Overall biopsy yield was 99% and 83% for GEP and cytopathology, respectively. Surgeon choice of biopsy approach (trans-vitreal vs. trans-scleral) was found to associate with both tumor location and tumor thickness. A trans-scleral rather than trans-vitreal approach was used more commonly for anteriorly located tumors (92% vs. 38% of posterior tumors, p < 0.001) and thicker tumors (86% vs. 55% of thin tumors, p < 0.001). When performing trans-vitreal biopsies, ocular oncologists with previous vitreoretinal surgery fellowship training were more likely to use wide-field surgical viewing systems, compared with indirect ophthalmoscopy (82.6% vs. 20.6%, p < 0.001). Surgical complications were rare and occurred more frequently with trans-vitreal biopsies (3.6% vs. 0.46%, p = 0.046). CONCLUSIONS: In this multi-center analysis of UM tumor biopsy, surgical yield was high for obtaining tumor tissue for GEP and cytopathology analysis with both trans-scleral and trans-vitreal techniques. Fellowship-trained ocular oncologists' preferred intraocular biopsy techniques associated strongly with tumor location, tumor thickness, and fellowship training of the surgeon. Short-term complication rates were low.
Subject(s)
Biopsy, Fine-Needle/methods , Brachytherapy/methods , Gene Expression Profiling/methods , Melanoma/diagnosis , Ophthalmologic Surgical Procedures/methods , Uvea/pathology , Uveal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Melanoma/genetics , Melanoma/therapy , Middle Aged , Prognosis , Retrospective Studies , Uveal Neoplasms/genetics , Uveal Neoplasms/therapy , Young AdultABSTRACT
Using multimodal imaging, we demonstrate a classic iris melanocytoma presenting with recurrent, spontaneous hyphema in a young female patient. The patient has been observed without tumor growth. Hyphema has not been previously reported to occur with iris melanocytoma.
ABSTRACT
PURPOSE: Surgical intervention is indicated for large primary iris pigment epithelial cysts that significantly affect vision or compromise adjacent structures. Methods described in the literature include laser photocoagulation, needle aspiration, and complete resection. METHODS: We describe a novel surgical technique in which a surgical cystotomy is created for a large, symptomatic iris pigment epithelial cyst using microsurgical instruments for a patient in whom needle aspiration was unsuccessful. RESULTS: The patient's visual symptoms had largely resolved within 1 week postoperatively, no complications were encountered, and there was no clinical or sonographic evidence of cyst recurrence after 14 months. CONCLUSION: Surgical cystotomy with microinstrumentation may be an effective tool for management of primary iris pigment epithelial cysts, especially as an alternative after needle aspiration fails.
Subject(s)
Choroid Neoplasms/metabolism , Lipofuscin/metabolism , Melanoma, Amelanotic/metabolism , Melanoma/metabolism , Aged , Choroid Neoplasms/diagnostic imaging , Choroid Neoplasms/pathology , Humans , Male , Melanoma/diagnostic imaging , Melanoma/pathology , Melanoma, Amelanotic/diagnostic imaging , Melanoma, Amelanotic/pathology , Tomography, Optical CoherenceSubject(s)
Diabetic Retinopathy/diagnosis , Hypertension, Malignant/diagnosis , Papilledema/diagnosis , Pregnancy in Diabetics/diagnosis , Vision Disorders/diagnosis , Acute Disease , Blood Pressure/physiology , Diabetes Mellitus, Type 1/diagnosis , Diabetic Retinopathy/physiopathology , Female , Heart Rate/physiology , Humans , Hypertension, Malignant/physiopathology , Papilledema/physiopathology , Pregnancy , Pregnancy in Diabetics/physiopathology , Respiratory Rate/physiology , Vision Disorders/physiopathology , Visual Acuity/physiology , Young AdultSubject(s)
Leukemia/complications , Retinal Diseases/pathology , Adolescent , Anemia/complications , Humans , MaleABSTRACT
PURPOSE: To evaluate the images produced in an initial surgical series of intraoperative near-real-time volumetric swept-source (SS) OCT imaging. DESIGN: Prospective translational study. PARTICIPANTS: Forty-one consecutive adult patients undergoing vitreoretinal surgery between July 22, 2014, and July 1, 2015, at the Duke University Eye Center who agreed to participate. METHODS: A novel microscope-integrated SS-OCT prototype captured volumetric renderings of imaging of macular surgery in near-real-time and showed them to the surgeon via a heads-up display through the microscope oculars. Then the images were analyzed formally after surgery. MAIN OUTCOME MEASURES: Image quality, successful capture of surgical instruments, maneuvers and associated retinal deformation volumetrically over time, and qualitative image analysis. RESULTS: Volumetric SS-OCT images were graded as acceptable in 92% of patients. Volumetric imaging of scraping and peeling procedures was achieved in 75% and 78% of patients in whom it was performed, respectively. Imaging provided the surgeon with near-real-time volumetric visualization of the position of the instrument relative to the retinal surface, flap initiation, flap removal, and retinal deformation during instrumentation via a heads-up display. CONCLUSIONS: This volumetric, microscope-integrated SS-OCT prototype seems to provide high-detail, near-real-time volumetric imaging of delicate maneuvers during macular surgery.