Incidence of metformin use in patients with age-related macular degeneration versus normal controls: A population-based study in Olmsted County, Minnesota.

PURPOSE: The purpose of this study is to compare the use of metformin in patients with both exudative and non-exudative age-related macular degeneration (AMD) versus control populations. DESIGN: Retrospective review of three age- and sex-matched cohorts from 1/1/2004 to 12/31/2013: patients with exudative AMD, a cohort of dry AMD patients, and a cohort of patients without AMD. The primary endpoint was the incidence of metformin use in all of the cohorts. RESULTS: There were 1512 patients, with 504 in each of the three cohorts. There was no difference in the prevalence of diabetes between cohorts. Compared to patients with dry AMD, patients with no AMD had increased likelihood of metformin use (p = 0.0168, OR 1.66 (1.09-2.51). There was no difference in the likelihood of metformin use between exudative AMD patients and non-AMD controls. CONCLUSIONS: There appears to be an increased incidence of metformin use in patients without AMD compared to patients with dry AMD. Metformin's current role in the treatment of anti-aging diseases makes it a plausible target for use in the treatment of AMD, particularly dry AMD.

TNF-Alpha Inhibition and Other Immunosuppressants in the Development of Uveal and Cutaneous Melanoma.

OBJECTIVE: To investigate an association between tumor necrosis factors-alpha (TNFα) inhibitors or other immunosuppressants and the development of uveal and cutaneous melanoma. PATIENTS AND METHODS: We performed a retrospective incidence and case-control analysis of patients in Olmsted County, MN, who were diagnosed with uveal or cutaneous melanoma from January 1, 2000, to December 31, 2014. Incidence was adjusted by age and gender to the 2010 US white population. Controls were matched by sex and age to cases at time of diagnosis of melanoma. RESULTS: There were 1221 cases of melanoma (33 uveal, 1188 cutaneous). Combined incidence of uveal and cutaneous melanoma per 100,000 person-years varied by gender (male > female), age (older > younger), and time period: 2010 to 2014 (77.9, 95% confidence interval [CI], 71.1-84.7) ≈ 2005 to 2009 (78.0, 95% CI, 70.9-85.0) > 2000 to 2004 (42.5, 95% CI, 36.9-48.1, P<.001). TNFa inhibitor prescription was not associated with significantly increased risk of melanoma vs controls (1.06% vs 0.41%, P=.06). Immunosuppressive agents, high-dose corticosteroids, and topical immunosuppressants were associated with melanoma (odds ratio [OR] 1.42 CI, 1.03-1.95, 3.30 CI, 2.44-4.48, and 1.87 CI, 1.06-3.28, respectively). An increased number of patients with uveal melanoma received immune modulating agents vs controls, but this was not statistically significant (P=.36). Autoimmune disease itself was not correlated with melanoma (P=.73). CONCLUSION: Exposure to immunosuppressive agents is associated with melanoma. TNFa inhibition and autoimmune disease alone do not significantly increase risk of melanoma. In patients receiving immunosuppressive treatments, physicians should consider monitoring with dilated ophthalmic and full-body skin examinations. Further studies are needed to assess the impact of TNFa inhibitors on development of melanoma, particularly in uveal melanoma.

Classification of Strokes in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor.

BACKGROUND AND OBJECTIVE: The purpose of this study was to identify the differences in the types of strokes seen in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) compared with normal control populations. PATIENTS AND METHODS: We performed a retrospective consecutive review of all patients receiving intravitreal anti-VEGF injections in Olmsted County, Minnesota, from January 1, 2004, to December 31, 2013, for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), or retinal vein occlusion (RVO). A 2-year follow-up period was required for study inclusion. Three age- and sex-matched cohorts were identified. RESULTS: A total of 2,541 patients were examined. There were 690 patients identified during the study period as receiving an intravitreal injection for AMD, DME, PDR, or RVO. Of these patients, 38 (5.8%) suffered a stroke after starting intravitreal injection therapy. Of these strokes, 27 (71.1%) were ischemic, six (15.8%) were embolic, and five (13.2%) were hemorrhagic. There were no differences in the types of strokes identified among the patients receiving intravitreal injections between the case cohort and the control cohorts (P > .05 for all). CONCLUSION: The authors' data suggest there is no predilection to the development of ischemic infarcts or hemorrhagic strokes in those patients receiving intravitreal anti-VEGF compared with control populations. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e140-e157.].

Association of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy With Risk of Stroke, Myocardial Infarction, and Death in Patients With Exudative Age-Related Macular Degeneration.

Importance: Current studies assessing the risk of stroke, myocardial infarction (MI), and death in patients undergoing intravitreal anti-vascular endothelial growth factor (VEGF) therapy are inconclusive. To our knowledge, no population-based studies have been performed to examine these potential risks. Objective: To examine whether patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-VEGF injections have a higher incidence of MI, stroke, or death compared with control populations. Design, Setting, and Participants: This population-based, retrospective cohort study included 504 patients from Olmsted County, Minnesota, identified through the Rochester Epidemiology Project (REP) database as receiving at least 1 intravitreal anti-VEGF injection for exudative AMD from January 1, 2004, to December 31, 2013. Three age- and sex-matched control groups of individuals who did not receive anti-VEGF treatment and were derived from the REP database were also studied: control individuals with exudative AMD in the era before anti-VEGF (January 1, 1990, to December 31, 2003), controls with dry AMD, and controls without AMD. Data analysis was performed from September 1, 2016, to September 1, 2017. Main Outcomes and Measures: Five-year risk of stroke, MI, and death were assessed in patients compared with controls using Kaplan-Meier and multivariate analysis with Cox proportional hazards regression models. Results: The study included 504 patients (321 female [63.7%]; mean [SD] age, 76.5 [10.0] years) who received at least 1 intravitreal anti-VEGF injection for exudative AMD during the study period. Kaplan-Meier analysis revealed a 5-year risk of 7.2% for stroke, 6.1% for MI, and 30.0% for death. Patients who received anti-VEGF had no increased risk of stroke or MI compared with controls with dry AMD (n = 504), controls with exudative AMD (n = 473), or controls without AMD (n = 504). There was an increased risk of mortality compared with controls with exudative AMD in the era prior to anti-VEGF therapy but not the other control groups on multivariate analysis (hazard ratio, 1.63; 95% CI, 1.30-2.04; P < .001). Conclusions and Relevance: This population-based study revealed that intravitreal anti-VEGF therapy for exudative AMD was not associated with consistent increases in the risk of stroke, MI, or death compared with no therapy in patients with or without AMD. It appears to be likely the cardiac events these patients experience are not attributable to their anti-VEGF therapy.

Healthcare Utilization by Glaucoma Patients in a Team Care Model.

PURPOSE: To determine the effect of a glaucoma team care model on resource utilization and efficiency in glaucoma management. METHODS: Retrospective cohort study of 358 patients diagnosed and treated for glaucoma. Analysis included number of patient visits, diagnostic tests, and glaucoma procedures performed before (2005-2007) and after (2008-2010) implementation of a team care model in 2008. Patients not involved in the model served as controls. RESULTS: Number of patient visits did not change significantly after model implementation (p > .05). Diagnostic tests significantly increased in comprehensive ophthalmologist and glaucoma subspecialist groups 25 months after diagnosis (p = .03 and p = .001). Procedures increased for glaucoma subspecialists but was not statistically significant (p = .06). Optometrists used billing codes with significantly lower reimbursement than other providers (p < .001). CONCLUSIONS: Team care model had neutral effect on patient visits and increased testing. Continued evaluation of this model is required to determine its effect on disease progression and outcomes.

Parkinson Disease and Melanoma: Confirming and Reexamining an Association.

OBJECTIVE: To examine an association between melanoma and Parkinson disease (PD). PATIENTS AND METHODS: Phase I: Rochester Epidemiology Project records were used to identify (between January 1, 1976, and December 31, 2013) patients with PD in Olmsted County, Minnesota, with 3 matched controls per case. After review, JMP statistical software with logistic regression analysis was used to assess the risk of preexisting melanoma in patients with PD vs controls. Phase II: All Rochester Epidemiology Project cases of melanoma were identified (between January 1, 1976, and December 31, 2014), with 1 control per case. A Cox proportional hazards model was used to assess the risk of developing PD after the index date in cases vs controls, and Kaplan-Meier analysis was performed to determine the 35-year cumulative risk of PD. A Cox proportional hazards model was used to assess the risk of death from metastatic melanoma in patients with melanoma without PD compared with those with PD. RESULTS: Phase I: Patients with PD had a 3.8-fold increased likelihood of having preexisting melanoma as compared with controls (95% CI, 2.1-6.8; P<.001). Phase II: Patients with melanoma had a 4.2-fold increased risk of developing PD (95% CI, 2.0-8.8; P<.001). Kaplan-Meier analysis revealed an increased 35-year cumulative risk of PD in patients with melanoma (11.8%) compared with controls (2.6%) (P<.001). Patients with melanoma without PD had a 10.5-fold increased relative risk of death from metastatic melanoma compared with patients with melanoma with PD (95% CI, 1.5-72.2) (P=.02). CONCLUSION: There appears to be an association between melanoma and PD. Further study is warranted; but on the basis of these results, physicians may consider counseling patients with melanoma about PD risk and implementing cutaneous and ocular melanoma surveillance in patients with PD.

Analysis of a Physician-led, Team-based Care Model for the Treatment of Glaucoma.

PURPOSE: To determine the effect of a protocol for a new physician-led, team-based glaucoma care model implemented in 2008 at Mayo Clinic's campus in Rochester, Minnesota (MCR), to increase conformance with the American Academy of Ophthalmology (AAO) Preferred Practice Pattern guidelines for treatment of primary open-angle glaucoma. METHODS: Records of 591 patients with newly diagnosed glaucoma were assessed retrospectively for the completion of 9 AAO Preferred Practice Pattern recommended metrics including measured corneal thickness, intraocular pressure (IOP), cup to disk ratio, visual acuity, recorded IOP target, gonioscopy, fundus photos, ocular coherence tomography, and visual field in the 3 years before and 3 years after protocol implementation. Treatment by the glaucoma care team at MCR was compared with treatment at a community-based general ophthalmology practice and with a group of comprehensive ophthalmologists at MCR without team care, which served as controls. RESULTS: Adherence to AAO recommendations increased for the documentation of target IOP (+24%, 42.6% to 66.7%; P=0.007), gonioscopy (+27%, 66.7% to 93.3%; P≤0.001), fundus photos (+29%, 44.4% to 73.3%; P≤0.001), and ocular coherence tomography (+20%, 48.1% to 68.0%; P=0.02) after protocol initiation. No change in pattern of testing occurred in the control groups without team care during the same time period. Type and severity of glaucoma were similar between MCR and community practice. CONCLUSIONS: An increase in compliance with AAO guidelines was found after implementation of our protocol for a physician-led, team-based care model to standardize glaucoma care among providers.

T2 Fluid-Attenuated Inversion Recovery Imaging of Uveal Melanomas and Other Ocular Pathology.

BACKGROUND/AIMS: This study describes patterns of intraocular lesions on T2 fluid-attenuated inversion recovery (FLAIR) imaging, exploring a prospective role of FLAIR imaging sequence in diagnosis and treatment. METHODS: A retrospective study of orbital magnetic resonance imaging (MRI) studies from the years 2000 to 2015 was performed. MRI sequences included: pre-contrast T1-weighted, T2-weighted, T2 FLAIR, and postcontrast T1 and T2 imaging gadolinium, which were evaluated by a neuroradiologist. Two cases of melanoma were correlated to their pathology. RESULTS: Twenty-four patients with intraocular pathology were evaluated. All lesions, regardless of pigmentation, revealed previously described melanotic patterns on T1- and T2-weighted images; 80% of 10 melanomas localized were hyperintense on T2 FLAIR, which better delineated lesion margins. All of the four inflammatory pathologies on T2 FLAIR were hyperintense, as were 80% of the amelanotic neoplasms. Pathology of two large uveal melanomas paralleled the findings seen on T2 FLAIR. CONCLUSIONS: T2 FLAIR appears beneficial in the demarcation of pigmented ocular lesions and may aid in determining protein content or previous treatment. Data also promote previous assertions that blood flow impacts intensity of lesions on T2 FLAIR. Further research is warranted.