Transitioning from a COMS-based plaque brachytherapy program to using eye physics plaques and plaque simulator treatment planning system: A single institutional experience.

The aim of this work is to describe the implementation and commissioning of a plaque brachytherapy program using Eye Physics eye plaques and Plaque Simulator treatment planning system based on the experience of one institution with an established COMS-based plaque program. Although commissioning recommendations are available in official task groups publications such as TG-129 and TG-221, we found that there was a lack of published experiences with the specific details of such a transition and the practical application of the commissioning guidelines. The specific issues addressed in this paper include discussing the lack of FDA approval of the Eye Physics plaques and Plaque Simulator treatment planning system, the commissioning of the plaques and treatment planning system including considerations of the heterogeneity corrected calculations, and the implementation of a second check using an FDA-approved treatment planning system. We have also discussed the use of rental plaques, the analysis of plans using dose histograms, and the development of a quality management program. By sharing our experiences with the commissioning of this program this document will assist other institutions with the same task and act as a supplement to the recommendations in the recently published TG-221.

Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography.

PURPOSE: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA). DESIGN: Prospective cross-sectional study. PARTICIPANTS: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center. METHODS: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes. MAIN OUTCOME MEASURES: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC. RESULTS: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm2; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00). CONCLUSIONS: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.

CHOROIDAL TUMOR BIOPSY: A Review of the Current State and a Glance Into Future Techniques.

PURPOSE: To review the indications for and the methods of obtaining biopsies in eyes with uveal melanoma. In addition, this review provides recommendations for avoiding biopsy-related complications and discusses the future directions of biopsy techniques for uveal melanoma. METHODS: This review is based on a presentation by the authors (PM and MM) at the 2017 Duke Advanced Vitreoretinal Surgery Course and an extensive literature review using PubMed. RESULTS: Transscleral and transvitreal fine-needle aspiration biopsy, and transvitreal vitrectomy-assisted biopsy techniques are described. The use of 25- and 27-gauge needles and vitreous cutters through a transvitreal approach are most commonly used. Complications are uncommon but may include vitreous hemorrhage, retinal detachment, and rarely, extraocular extension. Proper technique and precautions will minimize the occurrence of these rare complications. CONCLUSION: Biopsy of uveal melanoma either using a needle or vitrectomy-assisted procedures is safe and these techniques continue to improve with new vitreoretinal surgical advances.

Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.

Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

NCCN Guidelines Insights: Melanoma, Version 3.2016.

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

Melanocytic Nevus of the Superior Conjunctival Fornix: A Case Report.

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

A CASE OF HIGH-RISK CILIARY BODY MELANOMA ARISING IN AN EYE AFTER RESECTION OF AN IRIDOCILIARY MELANOCYTOMA.

PURPOSE: To report a case of a benign iridociliary melanocytoma recurring as malignant melanoma after excision. METHODS: Observational case report with clinical data, slit-lamp examination findings, ultrasound biomicroscopy results, and histopathological and genetic analyses. RESULTS: A 40-year-old African American woman initially presented with a superonasal iridociliary mass with a maximal thickness of 2.5 mm. Visual acuity of the involved eye was 20/25, intraocular pressure was 52 mmHg on maximal pressure-lowering medications, and Humphrey visual field testing revealed an inferior altitudinal defect. Fine-needle aspiration biopsy and incisional biopsy followed by tumor excision confirmed a benign melanocytoma. After 5 years of stability, possible recurrence was detected on ultrasound biomicroscopy as an increase in ciliary body thickness. The new lesion grew to a thickness of 5.1 mm over the next 18 months of observation. Fine-needle aspiration biopsy and gene expression profile of the recurrent lesion diagnosed a malignant melanoma with high metastatic potential (Class 2). The patient underwent plaque brachytherapy and has ongoing regression of the tumor. CONCLUSION: Transformation of benign iridociliary melanocytoma to melanoma is rare. To the best of the authors' knowledge, this is the first documented case of a melanoma arising in an eye after initial excision of a melanocytoma. Close monitoring of these patients is warranted even years after the initial excision.

Sector laser photocoagulation for the prevention of macular edema after plaque radiotherapy for uveal melanoma: a pilot study.

OBJECTIVE: To investigate the role of sector laser photocoagulation for prevention of macular edema after plaque radiotherapy for uveal melanoma. METHODS: Noncomparative, pilot interventional case series. The main outcome measure was optical coherence tomography-evident macular edema. RESULTS: A total of 29 patients had sector laser photocoagulation (sector panretinal photocoagulation) and sub-Tenon triamcinolone injection. The median tumor thickness and base was 3.3 mm and 10.0 mm. The median radiation dose and rate to the macula was 2,944 cGy and 31.0 cGy/hour. At the 12-month and 24-months follow-up, cystoid macular edema was found in 17% and 24% of the sector panretinal photocoagulation group. There were no major side effects registered. CONCLUSION: Sector panretinal photocoagulation in combination with sub-Tenon triamcinolone appears to show potential as a safe and beneficial intervention for the prevention of macular edema after plaque radiotherapy for uveal melanoma in this series.

Dual-source strength seed loading for eye plaque brachytherapy using eye physics eye plaques: A feasibility study.

Purpose: This study quantifies the dosimetric impact of incorporating two iodine-125 (125I) seed source strengths in Eye Physics eye plaques for treatment of uveal melanoma. Material and methods: Plaque Simulator was used to retrospectively plan 15 clinical cases of three types: (1) Shallow tumors (< 5.5 mm) with large base dimensions (range, 16-19 mm); (2) Tumors near the optic nerve planned with notched plaques; and (3) Very shallow (< 3.0 mm) tumors with moderate base dimensions (range, 13.5-15.5 mm) planned with larger plaques than requested by the ocular oncologist. Circular plaques were planned with outer ring sources twice the source strength of inner sources, and notched plaques with the six seeds closest to the notch at twice the source strength. Results: In cases of type (1), the dual-source strength plan decreased prescription depth, and doses to critical structures were lower: inner sclera -25% ±2%, optic disc -7% ±3%, and fovea -6% ±3%. In four out of five cases of type (2), the dual-source strength plan decreased prescription depth, and dose to inner sclera was lower (-22% ±5%), while dose to optic disc (17% ±7%) and fovea (20% ±12%) increased. In cases of type (3), a smaller dual-source strength plaque was used, and scleral dose was lower (-45% ±3%), whereas dose to optic disc (1% ±14%) and fovea (5% ±5%) increased. Conclusions: Dual-source strength loading as described in this study can be used to cover tumor margins and decrease dose to sclera, and therefore the adjacent retina, but can either decrease or increase radiation dose to optic disc and fovea depending on location and size of the tumor. This technique may allow the use of a smaller plaque, if requested by the ocular oncologist. Clinical determination to use this technique should be performed on an individual basis, and additional QA steps are required. Integrating the use of volumetric imaging may be warranted.

Preliminary Results of Uveal Melanoma Treated With Iodine-125 Plaques: Analysis of Disease Control and Visual Outcomes With 63 Gy to the Target Volume.

Purpose: Our purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach. Methods and Materials: This was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis. Results: Sixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse. Conclusions: In patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes.

Ocular neoplastic disease.

Ocular neoplasms, both primary and metastatic, may present with visual disturbance or vision loss and often are asymptomatic. Clinical ophthalmologic examination may demonstrate leukocoria, abnormal pupillary light reflex, or a mass lesion with or without retinal detachment or hemorrhage. Retinoblastoma in children and uveal melanoma and ocular metastases in adults are the most important ocular malignant neoplasms referred for imaging to aid with diagnosis and staging. Familiarity with their common imaging appearances, the common patterns of spread, and the diagnostic findings of greatest concern to the ocular oncologist will enhance accuracy of imaging interpretation. Clinical ophthalmologic examination and imaging using B-scan ultrasound, A-scan ultrasound, fluorescein angiography, computed tomography and magnetic resonance imaging have complementary roles in ocular tumor staging and treatment assessment.

Choroidal nevus with retinal invasion, clinical and imaging features.

PURPOSE: To report a clinically challenging case of a choroidal nevus with retinal invasion with accompanying ancillary testing. OBSERVATIONS: A 60-year-old Caucasian female was referred for a suspicious melanocytic choroidal lesion in her left eye. Ophthalmoscopic examination revealed a melanocytic choroidal lesion, measuring 10 mm × 10 mm in basal diameter. The lesion had a clinically evident area of retinal invasion seen as a protruding choroidal mass at its center, darker in appearance compared to the rest of the lesion, obscuring retinal vessels. The choroidal nevus had associated chronic retinal changes and the absence of overlying orange pigment or subretinal fluid. On fundus autofluorescence, there was a hypoautofluorescent area showing the site of retinal invasion. Fluorescein angiography at the lesion site exhibited central blocked perfusion corresponding to the area of retinal invasion. Ultrasonography showed a dome-shaped choroidal lesion that was optically dense with a medium-high internal reflectivity measuring 3.3mm in thickness. The optical coherence tomography showed a choroidal mass extruding through a break in Bruch's membrane with inner retinal invasion. A watchful waiting strategy was adopted, and at 28 months follow-up, the choroidal lesion did not show growth or presence of new suspicious features of malignant transformation. CONCLUSION AND IMPORTANCE: This case highlights the importance of recognizing the key features of choroidal nevi with retinal invasion, which can prevent the treatment of a benign condition and assist in the arrival of a correct diagnosis. These lesions should be monitored for long-term.

Optical Coherence Tomography Angiography Microvascular Variations in Pre- and Posttreatment of Retinoblastoma Tumors.

INTRODUCTION: The purpose of this study is to describe variations in microvasculature before and after treatment of treatment-naive lesions and during consolidation therapy of retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system. METHODS: This study is a single-center, prospective, observational case series. Recruited subjects were either undergoing surveillance for retinoblastoma or had newly detected retinoblastoma. Nine tumors from 7 eyes in 6 patients were included. During exams under anesthesia, the tumors were imaged with an investigational portable OCTA system. OCTA images were analyzed to assess vascular changes before and after treatment. RESULTS: In all 6 presented cases, OCTA imaging revealed distinctive vascular patterns, such as dilated feeder arteries and draining veins, disorganized and complex branching patterns, irregular vessel calibers, and dilation and tortuosity of vessels. After treatment, OCTA imaging revealed decreased intrinsic tumor vascularity and reduced dilation of draining and feeder vessels. Tumor relapse demonstrated prominent vascularity (n = 1) that resolved on repeat OCTA after transpupillary thermotherapy treatment. Type 2 (n = 1), 3 (n = 6), and 4 (n = 1) tumor regression patterns were seen in our patients after treatment, and OCTA findings were consistent with a previously published report. Interestingly, in one of the presented cases, OCTA demonstrated clear feeder, draining, and intrinsic tumor vessels that were not as evident on fluorescein angiography. CONCLUSIONS: OCTA may offer a noninvasive and sensitive technique to evaluate the vasculature of both the tumor and the surrounding retina in retinoblastoma. With additional research and development into its use in patients with retinoblastoma, OCTA may one day be useful in assessing treatment response and residual tumor activity.

Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial.

OBJECTIVE: To determine the efficacy and safety of periocular triamcinolone acetonide (40 mg) for the prevention of macular edema in patients undergoing plaque radiotherapy for uveal melanoma. DESIGN: Prospective, randomized, controlled clinical trial. PARTICIPANTS AND CONTROLS: One-hundred sixty-three patients with newly diagnosed uveal melanoma undergoing iodine 125 plaque radiotherapy were entered into the study. Fifty-five patients were randomized to the control group and 108 to the triamcinolone group. Eighteen-month data were available for 143 (88%) of the 163 patients. INTERVENTION: Periocular injection of triamcinolone acetonide (40 mg in 1 ml) at the time of plaque radiotherapy and 4 months and 8 months later. Optical coherence tomography was performed at each patient evaluation. MAIN OUTCOME MEASURES: Optical coherence tomography-evident macular edema, moderate vision loss, and poor final visual acuity. RESULTS: Optical coherence tomography-evident macular edema occurred significantly less often in the triamcinolone group compared with the control group up to 18 months after plaque radiotherapy (hazard estimate, 0.45; 95% confidence interval, 0.19-0.70; P = 0.001). At the 18-month follow-up, moderate vision loss (loss of 3 lines or more of best-corrected visual acuity [BCVA]) and severe vision loss (BCVA <5/200 Snellen) occurred significantly less frequently in the triamcinolone group than in the control group (31% vs. 48% [P = 0.039] and 5% vs. 15% [P = 0.048], respectively). Rates of elevated intraocular pressure and cataract progression were similar in both groups. CONCLUSIONS: Periocular triamcinolone is beneficial in reducing the risk of macular edema up to 18 months after plaque radiotherapy for uveal melanoma and significantly reduces the risk of moderate vision loss and poor visual acuity in these patients.

Hyperreflective Vitreous Opacities on Optical Coherence Tomography in a Patient With Bilateral Retinoblastoma.

An investigational, portable spectral-domain optical coherence tomography (SD-OCT) unit revealed small hyperreflective opacities in both eyes of a patient with bilateral retinoblastoma. There was no evidence of vitreous seeding on ophthalmoscopy of either eye. Although the opacities may initially raise concern for potential vitreous seeding, this report suggests alternate potential etiologies for such opacities, which were also seen on imaging of a cohort of normal eyes in pediatric patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:50-52.].

Microvascular Features of Treated Retinoblastoma Tumors in Children Assessed Using OCTA.

BACKGROUND AND OBJECTIVE: To describe the microvascular features of treated, clinically regressed, or reactivated retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system. PATIENTS AND METHODS: Single-center, prospective, cross-sectional, consecutive case-series of children with previously treated retinoblastoma who underwent portable OCTA of posterior retinoblastoma lesions. RESULTS: Eight tumors from seven eyes of five children with retinoblastoma were included. Tumors with types 1 (calcified remnant, n = 3), 2 (non-calcified remnant, n = 1), and 3 (both calcified and noncalcified remnants, n = 1) regression revealed persistent intrinsic superficial vasculature on OCTA (five of five lesions; 100%). Lesions with type 4 regression (atrophic scar, n = 2) had complete vascular flow voids in the involved retina and underlying choriocapillaris. A reactivated tumor (n = 1) showed a distinct area of vascularity with prominent feeder/draining vessels. CONCLUSIONS: OCTA revealed that significant vascularity exists in inactive retinoblastoma lesions. Dilated feeder vessels may suggest continued disease activity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:43-49.].

Regression of uveal melanoma after plaque radiotherapy and thermotherapy based on chromosome 3 status.

PURPOSE: To evaluate regression rates after plaque radiotherapy and thermotherapy of uveal melanoma with chromosome 3 monosomy versus disomy. DESIGN: Noncomparative case series. PARTICIPANTS: Two hundred and seventy patients with uveal melanoma. METHODS: Fine needle aspiration biopsy was used at the time of plaque radiotherapy to sample tumor cells for genetic testing. MAIN OUTCOME MEASURES: Tumor thickness regression based on chromosome 3 status. RESULTS: At the time of plaque radiotherapy, the median tumor thickness was 4.0 mm for melanomas with chromosome 3 monosomy and 3.5 mm for those with disomy 3. The median tumor thickness (% original thickness) at 4, 8, 12, 15, and 18 months after radiotherapy for melanoma with monosomy 3 was 77%, 67%, 58%, 55%, and 50% and for those with disomy 3 was 82%, 70%, 69%, 67%, and 61%. The median monthly regression rate was 3.1% for tumors with monosomy 3 and 2.7% for those with disomy 3. The overall regression and monthly rate of regression was statistically greater at 12 months (P < 0.001) and 15 months (P = 0.003) for melanomas with monosomy 3 compared with disomy 3. CONCLUSIONS: Uveal melanomas with chromosome 3 monosomy showed faster and greater tumor thickness regression at 12 and 15 months after plaque radiotherapy and thermotherapy than melanomas with disomy 3.