METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pushing the limit: Globe salvage of Group D retinoblastoma with severe vitreous seeding with intra-arterial chemotherapy and 15 cycles of intravitreal chemotherapy.

Purpose: To report the successful treatment of persistent retinoblastoma vitreous seeding with 6 cycles of intra-arterial chemotherapy and 15 cycles of intravitreal chemotherapy injections. Observations: A three-year-old female presented to the ocular oncology clinic with Group D retinoblastoma with severe vitreous seeding. The patient received 3 cycles of intra-arterial chemotherapy (melphalan, topotecan, and carboplatin) and 15 cycles of intravitreal chemotherapy (melphalan and combined melphalan/topotecan). Complete tumor regression and resolution of vitreous seeding was achieved. The best corrected visual acuity in the affected eye was 20/50. Conclusions and Importance: Intravitreal chemotherapy for retinoblastoma vitreous seeding is often restricted to 8 treatment cycles. Patients who do not respond after 8 cycles face salvage therapy with radiation or enucleation. This is a case in which prolonged intravitreal chemotherapy delivery was well tolerated and resulted in sustained tumor remission, with useful visual acuity in the treated eye.

Clinicopathologic analysis of a case of small cell lung carcinoma metastatic to the retina.

Purpose: Tumor metastases to the retina are a relatively rare occurrence. We report a unique case of retinal metastasis of a systemic malignancy with clinical and histopathologic correlations. Observations: A 62-year-old female with a history of stage IV small cell carcinoma of the lung (SCC, status post chemotherapy and maintenance immunotherapy) presented with hand motions vision and vitreous hemorrhage, status post prior vitrectomy and biopsy that was non-diagnostic. She was found to have unilateral retinal metastatic tumor and underwent a repeat vitrector-assisted biopsy which confirmed the diagnosis. The eye became blind and painful due to recurrent non-clearing vitreous hemorrhage and ghost cell glaucoma and was enucleated. Detailed histopathologic analysis of the globe confirmed small cell carcinoma metastatic to the retina and vitreous cavity and sparing the choroid. Conclusions and importance: This case demonstrates the importance of maintaining a high index of suspicion for metastasis in patients with a known history of malignancy who present with new vitreoretinal lesions.

Next-generation sequencing of a large uveal melanoma with whole genome doubling and a PBRM1 mutation.

Purpose: To report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile. Observations: An 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain. Conclusions and importance: This case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling.

Prognostic Value of BAP1 and Preferentially Expressed Antigen in Melanoma (PRAME) Immunohistochemistry in Uveal Melanomas.

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.

Chorioretinal Findings as the Initial Presentation of Chronic Granulomatous Disease.

To describe a case of chronic granulomatous disease (CGD) with ocular lesions as the presenting findings. An ocular examination of a 4-month-old male infant with poor vision revealed punched-out macular and perivascular chorioretinal fibrosis and atrophy with peripheral retinal nonperfusion. Subsequently, he was hospitalized for recurrent infections and was diagnosed with CGD. Repeated examination demonstrated enlargement of the chorioretinal lesions without evidence of active inflammation or neovascularization. CGD causes recurrent, severe, life-threatening infections in children and should be considered in the differential diagnosis of chorioretinal lesions with peripheral retinal nonperfusion. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):234-238.].

COCCIDIOIDAL ENDOPHTHALMITIS: EXCELLENT RECOVERY OF VISION WITH AGGRESSIVE USE OF INTRAVITREAL ANTIFUNGALS AND VITRECTOMY.

PURPOSE: To report a case of Coccidioides immitis endophthalmitis with severe vision loss and a return to excellent vision after aggressive intervention. METHODS: Case report. RESULTS: A 41-year-old man with a history of solid organ transplantation who complained of floaters and decreased vision in the setting of disseminated Coccidioides infection was found to have presumed coccidioidal endophthalmitis with visual acuities of 20/20 in the right eye and 20/200 in the left eye. The patient was managed with intravenous amphotericin B, oral voriconazole, and intravitreal injections of amphotericin B and voriconazole in the left eye every three days. Five weeks after presentation, his visual acuity remained 20/20 in the right eye and improved to 20/40 in the left eye. The patient was transitioned to twice weekly intravitreal injections and oral voriconazole on hospital discharge. One week later, vision in the left eye decreased to 20/500 with worsening vitritis, prompting vitrectomy. Vision in the left eye subsequently improved to 20/30. Five weeks later, the patient developed a macula-on inferior rhegmatogenous retinal detachment in the left eye and underwent a second vitrectomy, with scleral buckle, laser, and gas injection. Vision in the left eye returned to 20/25. In total, the patient received 22 amphotericin B and 17 voriconazole intravitreal injections in the left eye with two vitrectomies. Vision in the right eye remained 20/20 throughout his treatment course. At four months after presentation, the patient remained on oral voriconazole with no evidence of active intraocular infection on examination. CONCLUSION: Aggressive medical and surgical management can be successful in ocular conservation and restoration of vision in coccidioidal endophthalmitis. Very mild disease may be conservatively monitored and managed with systemic antifungal therapy alone. In severe disease, early diagnosis and prompt and aggressive use of systemic and intravitreal antifungals may spare panophthalmitis and preserve vision.

As the worm turns: An infant with exotropia.

A two-year-old full-term boy with a history of an intermittent exotropia presented to the pediatric ophthalmology clinic for routine follow-up. He was found to have a stable sensorimotor examination however dilated funduscopic examination of the right eye was significant for a dim foveal reflex with a new discrete, white, elevated retinal lesion superotemporal to the fovea with surrounding subretinal exudates. An examination under anesthesia (EUA) was performed two days later that revealed a subretinal posterior pole granuloma with hyperfluorescence and late leakage from the lesion without telangiectatic vessels on fluorescein angiography. A repeat EUA one month later demonstrated an increase in surrounding subretinal and overlying intraretinal fluid. The patient was started on topical 1% prednisolone with a presumed diagnosis of Toxocara granuloma. At EUA, three months later, the subretinal and intraretinal fluid had resolved. The topical steroids were tapered, and the patient continues to be followed closely.

Retinal emboli after cervicopetrous junction internal carotid artery pseudoaneurysm stenting.

PURPOSE: To describe acute and chronic retinal ischemic changes following an internal carotid artery pseudoaneurysm stenting procedure, and to review current evidence for risk factors and management of post-procedural retinal ischemic events. OBSERVATION: A 50-year-old man presented with a 3-month history of pulsatile tinnitus, headache, and intermittent blurry vision. A CT angiogram of head and neck showed bilateral cervicopetrous internal carotid artery (ICA) pseudoaneurysms. The patient underwent successful repair with angioplasty and stenting of the flow-limiting high-grade (>95%) stenosis of his left high cervical ICA. On post-operative day 1, the patient reported monocular vision loss with a large central scotoma. He was found to have a central macular area of retinal whitening and multiple areas of perivascular retinal whitening on exam, concerning for retinal artery occlusions secondary to peri-procedural emboli. Dual antiplatelet therapy was started and a stroke evaluation was performed. Two months later, his visual acuity in the affected eye was counting fingers and his left eye fundus examination was notable for multiple areas of scattered hemorrhages, microaneurysms, and retinal exudates in the distribution of prior retinal ischemia. OCT imaging revealed atrophic changes in the left macula. Subsequently, the patient completed stage-2 repair of the left ICA pseudoaneurysm followed by uncomplicated repair of the right ICA. Four months later, his left eye visual acuity and retinal findings remained stable. CONCLUSIONS AND IMPORTANCE: Post-procedure retinal emboli and ischemia are important, vision threatening possible ocular complications for patients undergoing carotid vascular and endovascular procedures.

Need for Retinal Detachment Reoperation Based on Primary Repair Method Among Commercially Insured Patients, 2003-2016.

PURPOSE: To examine associations between primary repair, patient characteristics, and rhegmatogenous retinal detachment (RRD) reoperation. DESIGN: Retrospective cohort study. METHODS: We used administrative claims to identify enrollees with incident RRD treatment by laser barricade, pneumatic retinopexy (PR), pars plana vitrectomy (PPV), or scleral buckle (SB) between 2003 and 2016. Analysis excluded patients with less than 3 years of continuous enrollment, previous RRD diagnosis, or repair. We determined reoperation frequency (PPV, PR, or SB) within 90 days postrepair and used multivariable logistic regression to identify associations between reoperation and patient and primary repair characteristics. RESULTS: Of 16,190 patients with documented primary RRD repair, 2,918 (18.0%) required reoperation within 90 days. Reoperation was significantly associated with male sex (odds ratio [OR] 1.24, P < .001), pseudophakia (OR 1.25, P < .001), vitreous hemorrhage (OR 1.22, P = .001), and worse systemic health (OR 1.19-1.25, P < .05, for Charlson Comorbidity Index ≥3). Pseudophakia had higher reoperation odds after all primary procedures except PPV. In addition, 28.7% of primary PR cases required reoperation, vs 19.1% of SB and 17.9% of PPV repairs. Adjusting for other patient characteristics, PR had highest odds of reoperation (OR 1.90, P < .001, vs primary PPV). Primary laser barricade had lowest odds of reoperation (OR 0.49, P < .001). PPV was the most frequent reoperation procedure. CONCLUSIONS: Nearly 1 in 5 patients require reoperation within 90 days after primary RRD repair. Cases requiring only primary laser barricade had lowest reoperation odds, likely representing less severe RRDs. Primary PR had highest reoperation odds; PPV and SB were similar to each other. These findings are important for patient education and surgical decision-making.

Systemic Corticosteroid Use after Central Serous Chorioretinopathy Diagnosis.

PURPOSE: To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis. DESIGN: Retrospective claims-based analysis. PARTICIPANTS: A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and 2015. METHODS: We limited the study population to beneficiaries with incident CSC diagnosed by an eye care provider, excluding those with other major ophthalmologic comorbidities. We developed a non-CSC comparison cohort matched to CSC patients by age, sex, general health (Charlson Comorbidity Index), and geographic region. We compared systemic corticosteroid prescriptions before and after CSC diagnosis and by diagnosing provider (optometrist vs. ophthalmologist) and evaluated likelihood of steroids treatment among CSC versus matched control patients using logistic and Cox proportional hazard regression models. MAIN OUTCOME MEASURES: Systemic corticosteroid prescription frequency among CSC patients within 12 months pre-diagnosis and at 6, 12, and 24 months post-diagnosis, median time to steroid initiation and discontinuation, and odds of receiving steroids post-diagnosis among CSC and control patients. RESULTS: We identified 3418 CSC patients. Nearly 39% (n = 1326) were prescribed systemic steroids at some point during the analysis period, versus 23% of controls (4033 of 17 178 patients). Over 12% of CSC patients (n = 430) within 1 year pre-diagnosis, and nearly 12% (n = 404) within 1 year post-diagnosis. Most patients who received steroids after diagnosis were steroid naive (n = 231). Among those receiving steroids, CSC patients demonstrated longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 years for non-CSC patients) and longer time to last steroid prescription (1.62 years vs. 0.35 years for non-CSC patients). Although CSC patients were significantly less likely to receive steroids within 6 months post-diagnosis compared with non-CSC patients (odds ratio, 0.72; 95% confidence interval, 0.59-0.89), they were significantly more likely to receive steroids by 2 years post-diagnosis. Prescribing patterns were similar for patients diagnosed by an ophthalmologist versus optometrist. CONCLUSIONS: Despite evidence showing that steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. Our results suggest a need for greater communication and collaboration among providers to ensure that clinical practice reflects evidence-based recommendations.

Choroidal melanoma overlying scleral buckle evading detection treated with proton beam radiotherapy.

PURPOSE: to present a case of a choroidal melanoma located along a scleral buckle contour and was successfully treated with proton beam radiotherapy, without disturbing the scleral buckle. OBSERVATIONS: A 60-year-old woman presented with photopsias and history of retinal detachment repair with scleral buckle 36 years prior. She had annual dilated exams with her ophthalmologist over the last several years. While initially diagnosis of choroidal detachment, hemorrhage and intraocular buckle intrusion were suspected, the patient was referred to an ophthalmic oncology center and choroidal melanoma was confirmed. The patient underwent tantalum marker placement, trans-retinal biopsy and proton beam radiotherapy. Despite no evidence of metastatic disease on systemic imaging, prognostic genetic testing of the tumor revealed high-risk alterations for future metastasis, and the patient enrolled in an adjuvant clinical trial. CONCLUSIONS: The location of this choroidal melanoma along a scleral buckle contour presented a unique therapeutic challenge. We successfuly treated the tumor with proton beam radiotherapy without disturbing the scleral buckle. IMPORTANCE: chorioretinal elevations adjacent a scleral buckle may be presumed to be due to the buckle element; ultrasound can be helpful in distinguishing an intraocular tumor. Proton beam radiotherapy has the advantage over plaque brachytherapy in this setting as removing the scleral buckle is not needed and placing a plaque over the scleral buckle risks altering the effective radiotherapy dose.

The diagnostic utility of next-generation sequencing on FNA biopsies of melanocytic uveal lesions.

BACKGROUND: Uveal melanoma is highly aggressive, and overall prognosis depends on mutation status. Fine-needle aspiration biopsies (FNABs) play an important role in obtaining fresh tissue for cytologic diagnosis and molecular studies. It has been suggested that, although FNAB usually provides high diagnostic accuracy, there may be limited cellularity, which may compromise diagnostic potential for molecular studies. FNABs of uveal melanocytic lesions were evaluated to assess sample adequacy for both cytologic evaluation and next-generation sequencing (NGS). METHODS: The authors retrospectively evaluated 36 cases of melanocytic uveal lesions from 2015 to 2018. Samples were obtained by ophthalmologist-performed FNAB and aliquoted for cytology and NGS. Various combinations of direct smears, liquid-based cytology slides, cell blocks, and immunohistochemical stains for melanocytic markers were performed. All samples were tested for molecular alterations using hybrid-capture-based NGS. RESULTS: There was sufficient material for cytologic diagnosis in 33 of 36 cases (92%), for NGS testing in 30 of 36 cases (83%), and for both cytologic diagnosis and NGS testing in 28 of 36 cases (78%). Of 7 cases that were cytologically categorized as indeterminate or diagnosed as "atypical" or "nondiagnostic," NGS testing was sufficient and diagnostic for melanoma in 5 cases. Of the cases diagnosed as melanoma on pathology, 20 cases (87%) had concordant NGS testing results, 2 lacked molecular alterations, and 1 was insufficient for testing. CONCLUSIONS: FNA sampling of melanocytic uveal lesions is adequate for both cytologic diagnosis and NGS testing. In a subset of cases in which pathologic findings were indeterminate, NGS testing results were clarifying for diagnosis. In addition, specific molecular alterations identified can aid in evaluating prognosis and guide further management.

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

An audit of retinal lymphoma treatment at the University of California San Francisco.

BACKGROUND/OBJECTIVES: To evaluate retinal lymphoma treatment at the University of California San Francisco. SUBJECTS/METHODS: Prospective observational audit. Patients were treated systemically, usually with: methotrexate, temozolomide, and rituximab induction; etoposide consolidation; and maintenance with lenalidomide or another immunomodulatory agent. Persistent disease was treated initially by ocular radiotherapy or intravitreal melphalan and latterly by vitrectomy. RESULTS: The cohort comprised eight females and two males. The median age was 58 years (range, 38-73). Ocular manifestations were initially unilateral in four patients. Vitreous and subretinal infiltrates were initially present in 16 and 12 eyes, respectively, with three eyes having vision of 20/200 or worse. Four patients had a history of central nervous system (CNS) lymphoma. The median ophthalmic follow-up was 37 months (range, 8-56). Diagnostic and therapeutic vitrectomy were performed in 10 and 2 eyes, respectively. All patients had systemic chemotherapy and eight received maintenance immunotherapy. Four patients underwent ocular radiotherapy, bilaterally in two. One patient received bilateral intravitreal melphalan injections. Two eyes of four patients developed lymphoma during the study and two patients developed CNS disease. At study close, subretinal deposits were subtle in nine eyes and more prominent in two, whereas vitreous infiltrates were minimal in nine eyes, mild in one and moderate in one. The latest visual acuity was significantly worse than at presentation in two eyes and better in two. All patients were alive with no active CNS disease. CONCLUSIONS: Subretinal lymphomatous infiltrates respond to systemic chemotherapy with immunomodulatory maintenance, but dense vitreous infiltrates require therapeutic vitrectomy.

The Relative Impact of Patient, Physician, and Geographic Factors on Variation in Primary Rhegmatogenous Retinal Detachment Management.

PURPOSE: To evaluate geographic variation and characterize the relative contributions of patient characteristics, physician practice, and geographic region on variation in primary rhegmatogenous retinal detachment (RRD) management. DESIGN: Retrospective claims-based analysis. PARTICIPANTS: Commercially insured patients with incident RRD diagnosed between 2008 and 2016 (12 779 patients). METHODS: We determined whether patients underwent primary RRD repair within 60 days of diagnosis and identified repair type. We characterized physicians using physician identifier variables and characterized geography by Combined Statistical Areas or Core-Based Statistical Area. We used multilevel mixed effects logistic regression models to evaluate patient-, physician-, and geographic-level variation in whether patients underwent RRD repair and used multilevel mixed effects multinomial models to characterize variation in repair type. For each model, we evaluated patient fixed effects and physician random effects nested within geographic random effects. We estimated intraclass correlation coefficients and variance partition coefficients, respectively, to compare relative contributions of patient, physician, and geography to overall variation. MAIN OUTCOME MEASURES: Odds ratios for RRD repair and variation estimates for patient, physician, and geography. RESULTS: Most incident RRD patients received treatment within 60 days post-diagnosis. Pars plana vitrectomy was most common (49%), followed by laser barricade (23%), scleral buckle and pneumatic retinopexy (both 11%), and cryotherapy (5%). Physician-level variation showed greater impact on receipt of any treatment than geographic-level variation (estimated variance coefficients of 1.09 and 0.32, respectively). Patient-level characteristics represented approximately 82% of overall variation in receipt of any repair, versus 16% from physician-level and 2% from geographic-level factors. Among RRD patients who underwent repair, estimated variance coefficients were 0.07 for geography and 3.37 for physician. Physician-level factors represented approximately 50% of total variation in repair type, followed by patient-level (49%), and geographic-level (1%) factors. CONCLUSIONS: Rhegmatogenous retinal detachment repair decisions are influenced by patient-level and physician-level factors, less so by geographic variation. Patient characteristics account for most of the variation in receipt of repair, and physician practice accounts for most of the variation in choice of procedure. These findings indicate a need for additional studies to understand drivers behind differences in care and clinical outcomes and to identify barriers in access to care.

THERAPEUTIC VITRECTOMY AS AN ADJUNCT TREATMENT TO SYSTEMIC CHEMOTHERAPY FOR INTRAOCULAR LYMPHOMA.

PURPOSE: To report the outcome of a previously vitrectomized eye having less lymphoma disease burden compared with the contralateral nonvitrectomized eye over the course of 3.5 years while on systemic chemotherapy. METHODS: Case report. RESULTS: A 51-year-old man with vitreoretinal lymphoma with central nervous system involvement underwent vitrectomy in his left eye. Over the following 3.5 years on systemic chemotherapy, the left eye had less lymphoma disease burden compared with the contralateral nonvitrectomized right eye. CONCLUSION: Therapeutic vitrectomy may be a useful adjunct to systemic chemotherapy in vitreoretinal lymphoma, particularly in cases of vitreous predominant disease manifestation.

A Novel Hybrid Fixed and Mobile Ultra-Widefield Imaging Program for Diabetic Teleretinopathy Screening.

PURPOSE: To describe a new approach for telemedicine screening of diabetic retinopathy (DR) using a combination of a mobile ultra-widefield camera, mounted in a van and able to travel to areas of need, and several fixed-location cameras in high-volume clinics and to report predictors of DR in a diverse urban population of 2788 patients. DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand seven hundred eighty-eight patients enrolled in the San Francisco Health Network who underwent DR screening using the novel hybrid telemedicine system. METHODS: The study was carried out at Zuckerberg San Francisco General Hospital in the San Francisco Health Network. A van was specially equipped to allow an ultra-widefield fundus camera to be mounted inside, and the van was sent with a technician to primary care clinics throughout the city on a rotation schedule determined according to clinical need. Additional fundus cameras were placed in several high-volume clinic locations. Patient demographic and clinical information was collected at the time of screening. Photographs were transmitted to a reading center and were graded for DR and other findings by trained readers. MAIN OUTCOME MEASURES: Prevalence of DR subtypes and odds ratios for development of DR and proliferative DR (PDR). RESULTS: The hybrid mobile and fixed-location ultra-widefield camera screening system was able to be deployed to carry out the telemedicine screening program for diabetic patients throughout the city of San Francisco referred for screening during the period of the study. Of 2788 patients screened, 736 (27%) were found to have DR. Of these, 34 (5%) had PDR, and 702 (95%) had nonproliferative DR. In multivariate analysis, factors found to be associated with development of any DR were diabetes duration, hemoglobin A1C level, insulin use, and end-organ damage. Diabetes duration was the only factor associated with PDR. CONCLUSIONS: Diabetic retinopathy screening can be accomplished in an urban setting using a combination of fixed-location and mobile ultra-widefield cameras to extend the reach of the screening opportunity throughout a health network. In a diverse group of patients, factors associated with DR and PDR were identified and support ongoing efforts to screen for retinopathy and maintain diabetic control.