Satellite Faculty in an Academic Ophthalmology Department: Junior, Clinical, and Female.

Purpose: To evaluate the perception of physicians at satellite offices of a large academic ophthalmology department. Methods: A survey was sent to the 32 physician faculty members working at the satellite offices in the Ophthalmology Department of the University of Michigan. The ophthalmologists answered 44 survey questions on staffing, wait times, physician satisfaction, patient satisfaction, compensation, administrative help, research, and operations management. Results: Seventeen (53%) satellite ophthalmologists responded. The majority were satisfied with work at satellites, which they felt operated efficiently and believed to feature high patient satisfaction. A minority of ophthalmologists had concerns about salary, volume, marketing support, and geographic location. Some respondents did not understand the compensation structure, satellites' finances, or contribution to the overall department. Most described a lack of research and resident teaching opportunities at satellites. Conclusions: The perceptions of ophthalmologists who work in satellite offices are important because of the growth of these offices in academic medical centers and the ability for satellite doctors to offer care comparable with and sooner than doctors at the main hospital at locations convenient for patients. Satellite ophthalmologists at this academic center would appreciate increased transparency of compensation and financial structures; administrative help with marketing and maintaining efficiency, which doctors and patients enjoy at satellite offices; and more teaching and research opportunities, which are the basis of academic advancement. Such efforts may help retain satellite doctors, who tend to be junior in rank, female, nontenured faculty, and who experience a higher turnover rate than faculty at the main campus.

Comparative Molecular Analysis of Primary Central Nervous System Lymphomas and Matched Vitreoretinal Lymphomas by Vitreous Liquid Biopsy.

Primary Central Nervous System Lymphoma (PCNSL) is a lymphoid malignancy of the brain that occurs in ~1500 patients per year in the US. PCNSL can spread to the vitreous and retina, where it is known as vitreoretinal lymphoma (VRL). While confirmatory testing for diagnosis is dependent on invasive brain tissue or cerebrospinal fluid sampling, the ability to access the vitreous as a proximal biofluid for liquid biopsy to diagnose PCNSL is an attractive prospect given ease of access and minimization of risks and complications from other biopsy strategies. However, the extent to which VRL, previously considered genetically identical to PCNSL, resembles PCNSL in the same individual with respect to genetic alterations, diagnostic strategies, and precision-medicine based approaches has hitherto not been explored. Furthermore, the degree of intra-patient tumor genomic heterogeneity between the brain and vitreous sites has not been studied. In this work, we report on targeted DNA next-generation sequencing (NGS) of matched brain and vitreous samples in two patients who each harbored VRL and PCSNL. Our strategy showed enhanced sensitivity for molecular diagnosis confirmation over current clinically used vitreous liquid biopsy methods. We observed a clonal relationship between the eye and brain samples in both patients, which carried clonal CDKN2A deep deletions, a highly recurrent alteration in VRL patients, as well as MYD88 p.L265P activating mutation in one patient. Several subclonal alterations, however, in the genes SETD2, BRCA2, TERT, and broad chromosomal regions showed heterogeneity between the brain and the eyes, between the two eyes, and among different regions of the PCNSL brain lesion. Taken together, our data show that NGS of vitreous liquid biopsies in PCNSL patients with VRL highlights shared and distinct genetic alterations that suggest a common origin for these lymphomas, but with additional site-specific alterations. Liquid biopsy of VRL accurately replicates the findings for PCNSL truncal (tumor-initiating) genomic alterations; it can also nominate precision medicine interventions and shows intra-patient heterogeneity in subclonal alterations. To the best of our knowledge, this study represents the first interrogation of genetic underpinnings of PCNSL with matched VRL samples. Our findings support continued investigation into the utility of vitreous liquid biopsy in precision diagnosis and treatment of PCNSL/VRL.

Quantification of Retinal Nonperfusion and Neovascularization With Ultrawidefield Fluorescein Angiography in Patients With Diabetes and Associated Characteristics of Advanced Disease.

Importance: Quantification of nonperfusion (NP) and neovascularization (NV) in diabetic retinopathy (DR) may identify better biomarkers of disease progression. Objective: To identify demographic risk factors and markers of advanced DR that are associated with increased areas of NP and NV in eyes with disease ranging from no DR but diagnosed as having diabetes to proliferative DR (PDR) and to calculate a threshold total area of NP that may be associated with an increased risk of PDR. Design, Setting, and Participants: This retrospective case series was performed on ultrawidefield fluorescein angiography (UWF FA) images from January 2009 to May 2018 at the University of Michigan Kellogg Eye Center. A total of 363 participants (651 eyes) diagnosed as having type 1 or 2 diabetes receiving UWF FA were included. Exclusion criteria included previous panretinal photocoagulation (PRP) and poor-quality images (eg, vitreous hemorrhage and significant cataract). Main Outcomes and Measures: The surface areas in millimeters squared of the foveal avascular zone; total NP; NP at posterior pole, midperiphery, and far periphery; total NV; NV at posterior pole, midperiphery, and far periphery were measured. Results: Of 363 patients, most were male (205 patients [56.5%]) and white (247 [68%]) or black (77 [21.2%]). The mean (SD) age was 59.4 (13.7) years. Seventy-six eyes with no DR, 92 with mild NPDR, 144 with moderate NPDR, 101 with severe NPDR, 220 with PDR, and 18 with DR of unknown severity were included. Male sex had a positive association with total NP (difference, 15.72; 95% CI, 4.83-26.61; P = .005); black race/ethnicity with total NV (difference, 2.32; 95% CI, 0.09-4.55; P = .04); and vitreous hemorrhage with total NP (difference, 30.00; 95% CI, 5.26-54.75; P = .02). A threshold total NP area of 77.48 mm2 (95% CI, 54.24-92.66 mm2) was identified, at greater than which patients may have an increased risk of developing PDR (sensitivity of 59.5% and specificity of 73.6%). Conclusions and Relevance: Our results indicate NP and NV can be quantified on UWF FA. These biomarkers interpreted with demographic risk factors may help predict disease progression. Conclusions are limited by ascertainment and information biases because the results are from retrospective data.

Scleral necrosis after plaque radiotherapy of uveal melanoma: a case-control study.

PURPOSE: To identify risk factors and outcome of scleral necrosis after plaque radiotherapy of uveal melanoma. DESIGN: Case-control study. PARTICIPANTS: A total of 73 cases with scleral necrosis and 73 controls without necrosis after plaque radiotherapy. Controls were matched for anteroposterior tumor epicenter and follow-up duration. INTERVENTION: Plaque radiotherapy with iodine-125, cobalt-60, iridium-192, or ruthenium-106. MAIN OUTCOME MEASURES: Scleral necrosis. RESULTS: Of 5057 patients treated with plaque radiotherapy for uveal melanoma, 73 (1%) developed radiotherapy-induced scleral necrosis. Scleral necrosis occurred in <1% of patients (3/1140) when plaque radiotherapy was used for tumors <3 mm in thickness, 1% of patients (33/3155) with 3- to 8-mm tumor thickness, and 5% of patients (37/762) with >8-mm-thick tumors. On the basis of tumor location, scleral necrosis was detected after plaque radiotherapy of iris melanoma in 0% of patients (0/91), ciliary body melanoma in 29% of patients (67/235), and choroid melanoma in <1% of patients (6/4731). The mean time interval between plaque radiotherapy and scleral necrosis was 32 months (median, 23 months; range, 4-126 months). The mean basal dimension of scleral necrosis was 4 mm (median, 3 mm; range, 1-15 mm), equivalent to 29% of mean tumor base (median, 24%; range, 6%-100%) and 22% of mean plaque size (median, 19%; range, 5%-75%). Multivariate analysis of factors that predicted clinically evident scleral necrosis included ciliary body (P = 0.0001) and pars plana to ora serrata (P < 0.0001) locations of anterior tumor margin, tumor thickness ≥ 6 mm (P = 0.0001), and radiation dose ≥ 400 Gy to the outer sclera (P = 0.0455). Scleral necrosis remained stable in 48% of patients (35/73), increased in size/severity in 48% of patients (35/73), or progressed to scleral perforation in 4% of patients (3/73) over a mean follow-up of 79 months (median, 54 months; range, 5-351 months). Treatment of scleral necrosis included observation in 81% of patients (59/73), scleral patch graft in 14% of patients (10/73), and enucleation in 5% of patients (4/73). CONCLUSIONS: Scleral necrosis after plaque radiotherapy of uveal melanoma was detected in 1% of cases. Factors predictive of scleral necrosis included increasing tumor thickness, ciliary body and peripheral choroidal location, and higher radiation dose to sclera. Most patients (81%) did not require treatment, and 4% evolved to full-thickness perforation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.