Stephen G Schwartz

University of Miami, كورال غيبلز، فلوريدا, Florida, United States

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Publications (104)268.3 Total impact

  • Brian S. McKay · Stephen G. Schwartz

    No preview · Article · Jan 2016 · Journal of Ocular Pharmacology and Therapeutics
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    ABSTRACT: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 [times] 10-8) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 [times] 10-10). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
    Full-text · Article · Dec 2015 · Nature Genetics
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    ABSTRACT: Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. © 2015, Society for Biomedical Diabetes Research. All rights reserved.
    No preview · Article · Dec 2015 · The Review of Diabetic Studies

  • No preview · Article · Dec 2015 · Ophthalmology
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    Full-text · Article · Dec 2015 · Ophthalmology
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    ABSTRACT: Background: Age-related Macular Degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell-type involved in AMD, the retinal pigment epithelium expresses a g-protein coupled receptor that, in response to its ligand, L-DOPA, upregulates pigment epithelia derived factor, while downregulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD. Methods: We used retrospective analysis to compare the incidence of AMD between patients taking vs. not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (∼17,000 and ∼20,000) and the Truven MarketScan outpatient and databases (∼87 million) patients. We used ICD-9 codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription. Results: In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3 and 71.3 in three independent retrospective cohorts. AMD occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (OR=0.78;CI=0.76-0.80;P<0.001). Similar results were observed for neovascular AMD, p<0.001. Conclusion: Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues such as the retinal pigment epithelium as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor, it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease.
    Full-text · Article · Nov 2015 · The American journal of medicine
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    ABSTRACT: Purpose: To determine predictors of reoperation and abnormal binocularity outcomes (including amblyopia and diplopia) following pediatric strabismus surgery. Design: Retrospective cross-sectional study. Methods: Setting: Review of a national insurance database. Study population: Children under age 18 years having strabismus procedures between 2007 and 2013. Interventions: Adjustable or fixed suture strabismus surgery, or botulinum toxin injection. Outcome measures: Reoperation or diagnosis of abnormal binocularity in the first postoperative year. Results: Of 11,115 children having strabismus procedures, 851 (7.7%) underwent reoperation. The reoperation rate was 7.4% for fixed suture surgeries, 9.6% for adjustable suture surgeries (p=0.18), and 44.9% for botulinum injections (p<0.001). Age under 2 years was associated with higher reoperation and abnormal binocularity rates (p<0.001). For horizontal strabismus, the postoperative abnormal binocularity rate was 12.8% for fixed suture surgery and 26.5% for botulinum injection (p=0.005). Reoperation rates tended to be higher with adjustable sutures (odds ratio [OR] 1.69, 95% confidence interval [CI] 0.94 to 3.03, p=0.08), or botulinum toxin injection (OR 10.36, 95% CI 5.75 to 18.66, p<0.001) and lower with 3- or 4-muscle surgery (p=0.001). Esotropia, hyperopia, and botulinum injection were independently associated with higher rates of postoperative abnormal binocularity (p<=0.005). For vertical surgeries, predictors of reoperation were adjustable suture use (OR 2.51, p=0.10) and superior oblique surgery (OR 2.36, p<0.001). Conclusions: Adjustable sutures were not associated with a lower reoperation rate in children. Younger age, esotropia, hyperopia, and botulinum injection were associated with postoperative abnormal binocularity. Superior oblique surgery and botulinum injection were associated with higher rates of reoperation.
    No preview · Article · Nov 2015 · American Journal of Ophthalmology
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    ABSTRACT: Purpose: To evaluate rates of reoperation and retinal detachment (RD) after macular hole surgery. Design: Retrospective cross-sectional study. Participants: Patients in the insurance claim-based MarketScan databases from 2007 through 2013 with a record of macular hole surgery. Methods: Patients with macular hole surgery were identified. Cases of definite (the same eye was coded both times) and presumed (the eye laterality was not coded) macular hole reoperations within 2, 3, and 12 months were queried. In addition, cases of postoperative RD within 2, 3, and 12 months were captured. Main outcome measures: Rates of macular hole reoperation and postoperative RD, including subgroup analysis based on presence or absence of internal limiting membrane (ILM) peeling. Results: Records of 23465 macular hole surgeries among 20 764 patients were analyzed. Among presumed reoperations, the rates of reoperation were 4.3% (4.1% after ILM peeling and 5.0% after no ILM peeling; P = 0.01) within 2 months of surgery, 5.5% (5.3% after ILM peeling and 6.2% after no ILM peeling; P = 0.03) within 3 months of surgery, and 9.5% (9.0% after ILM peeling and 11.0% after no ILM peeling; P = 0.01) within 12 months of surgery. The rates for definite reoperations were 1.3% (1.2% after ILM peeling and 1.8% after no ILM peeling; P = 0.04) at 2 months, 1.7% (1.6% after ILM peeling and 2.5% after no ILM peeling; P = 0.004) at 3 months, and 4.1% (3.3% after ILM peeling and 7.5% after no ILM peeling; P < 0.001) at 12 months. The cumulative rate of postoperative RD was 1.81±0.09% to 2.18±0.5% after 2 months, 2.27±0.10% to 3.18±0.67% after 3 months, and 3.92±0.16% to 5.70±1.1% after 12 months. Internal limiting membrane peeling was associated negatively with postoperative RD at 2 months (2.3% vs. 1.7%; P = 0.007), 3 months (2.8% vs. 2.1%; P = 0.004), and 12 months (4.7% vs. 3.3%; P < 0.001). Conclusions: In this sample, reoperations for macular hole were performed at low rates. Internal limiting membrane peeling was associated with lower rates of reoperation and RD.
    No preview · Article · Oct 2015 · Ophthalmology
  • Stephen G Schwartz · Harry W Flynn · Taraprasad Das · William F Mieler
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    ABSTRACT: Endophthalmitis is characterized by marked inflammation of intraocular fluids and tissues. Infective endophthalmitis may be categorized by the cause of the infection, which helps predict the underlying etiology and most likely causative organisms. The major category remains acute-onset postoperative endophthalmitis. Infective endophthalmitis is a clinical diagnosis but is confirmed by evaluation of intraocular fluid specimens. The Endophthalmitis Vitrectomy Study offered important guidelines for the initial management of endophthalmitis, and these guidelines remain relevant to this day. Prompt initiation of empiric broad-spectrum antimicrobial therapy is important in achieving best outcomes.
    No preview · Article · Oct 2015 · Developments in ophthalmology
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    ABSTRACT: Glaucoma involves a characteristic optic neuropathy, often with elevated intraocular pressure. Before 1850, poor vision with a normal eye appearance, as occurs in primary open-angle glaucoma, was termed amaurosis, gutta serena, or black cataract. Few observers noted palpable hardness of the eye in amaurosis. On the other hand, angle-closure glaucoma can produce a green or gray pupil, and therefore was called, variously, glaucoma (derived from the Greek for glaucous, a nonspecific term connoting blue, green, or light gray) and viriditate oculi. Angle closure, with palpable hardness of the eye, mydriasis, and anterior prominence of the lens, was described in greater detail in the 18th and 19th centuries. The introduction of the ophthalmoscope in 1850 permitted the visualization of the excavated optic neuropathy in eyes with a normal or with a dilated greenish-gray pupil. Physicians developed a better appreciation of the role of intraocular pressure in both conditions, which became subsumed under the rubric "glaucoma".
    Full-text · Article · Oct 2015 · Opthalmology and Eye Diseases
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    ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10 % of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45 % and 70 %. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD’s heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. In a case–control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. We found that 19 previously associated AMD risk SNPs contributed to 13.3 % of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7 % of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8 % and 17.9 %, respectively), with other pathways showing no significant effects (0.3 % – 4.4 %). Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5 % additional risk for each pathway. From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs.
    Full-text · Article · Oct 2015 · BMC Bioinformatics
  • Stephen G Schwartz · Harry W Flynn · Andrzej Grzybowski
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    ABSTRACT: Endophthalmitis following intravitreal injection is uncommon. There are currently no randomized clinical trials evaluating the role of prophylactic topical antibiotics in this setting. Many large series have reported that topical antibiotics do not decrease, and may in fact increase the rate of endophthalmitis. The reason for this apparent paradoxical finding is unknown but may be due to changes in conjunctival flora due to repeated exposure to antibiotics. At this time, antiseptics (specifically povidone-iodine), rather than antibiotics, are preferred for the majority of patients undergoing intravitreal injections.
    No preview · Article · Sep 2015 · Current pharmaceutical design
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    ABSTRACT: Several medications are associated with retinal vascular toxicity. These include intraocular aminoglycosides, oral contraceptives, interferon alpha, several other agents, and talc, which occurs as a vehicle in some oral medications that may be abused intravenously. As a group, these entities represent a small but clinically relevant category of retinal toxicity from medications. Some of the manifestations (e.g., retinal vascular occlusion) are nonspecific, but others are more specific, including clinically visible talc emboli in retinal vessels. Toxicity may be asymptomatic or may cause irreversible visual loss. By maintaining a high index of suspicion, the correct diagnosis can usually be made.
    No preview · Article · Sep 2015 · Current pharmaceutical design
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    Full-text · Article · Sep 2015 · The British journal of ophthalmology
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    Christopher Leffler · Stephen G. Schwartz · Andrzej Grzybowski
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    ABSTRACT: The word “tamponade” is commonly used in the ophthalmic literature, generally referring to the surgical use of intravitreal gas or silicone oil. This unusual word is derived from “tampon”, which appears to have been imported directly from French to English in both medical and non-medical contexts. “Tamponade” was used in an obstetric textbook as early as 1856, and in the context of retinal detachment surgery as early as 1938. Its modern use in vitreoretinal surgery evolved during the late 1960s through the early 1970s, and peaked in use in 1987, during a period of intense research into vitrectomy.
    Full-text · Article · Aug 2015
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    ABSTRACT: To assess the incidence and outcomes of infectious endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. Patient records at the Bascom Palmer Eye Institute (BPEI) from January 1, 2005, through December 31, 2014, were reviewed. The largest commercial claims and encounters database in the U.S. (MarketScan) was utilized to calculate the population-based endophthalmitis rate for 2011 to 2013. The population-based rate of endophthalmitis after anti-VEGF injections for 2011 to 2013 was 391/740,757 (0.053%). BPEI's rate was 20/121,285 (0.016%) during the study period: eight after bevacizumab (0.012%), six after ranibizumab (0.018%), and six after aflibercept (0.031%) injection. Nine BPEI cases (45%) were culture-positive: Streptococcus species (5), coagulase-negative Staphylococcus (3), and non-anthracis Bacillus (1). Final visual acuity varied from 20/25 to no light perception. Endophthalmitis after anti-VEGF injection was uncommon in our institution and in the population-based database. Treatment outcomes were variable but generally fared better in the culture-negative cases. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:643-648.]. Copyright 2015, SLACK Incorporated.
    Full-text · Article · Jun 2015 · Ophthalmic Surgery Lasers and Imaging Retina
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    ABSTRACT: To determine the association of strabismus surgery reoperation rates with adjustable or conventional sutures. Retrospective cross-sectional study. Setting. Review of a large national private insurance database. Adults age 18 to 89 having strabismus surgery between 2007 and 2011. Adjustable versus conventional suture strabismus surgery. Reoperation rate in the first postoperative year. Overall, 526 of 6178 surgical patients had a reoperation (8.5%). Reoperations were performed after 8.1% of adjustable suture surgeries and after 8.6% of conventional suture surgeries (p=0.57). Of the 4357 horizontal muscle surgeries, reoperations were performed after 5.8% of adjustable suture surgeries, and after 7.8% of conventional suture surgeries (p=0.02). Of the 1072 vertical muscle surgeries, reoperations were performed after 15.2% of adjustable suture surgeries, and after 10.4% of conventional suture surgeries (p=0.05). Younger age (18 to 39 years) was associated with a lower reoperation rate (p ≤ 0.02). The significant multivariable predictors of reoperation for horizontal surgery were adjustable sutures (odds ratio, OR 0.69, 95% confidence interval 0.52 to 0.91), monocular deviation (OR 0.64), complex surgery (OR 1.63), and unilateral surgery on two horizontal muscles (OR 0.70, all p ≤ 0.01). Adjustable sutures were not significantly associated with reoperation rates after vertical muscle surgery (multivariable OR 1.45, p=0.07). Adjustable sutures were associated with significantly fewer reoperations for horizontal muscle surgery. Adjustable sutures tended to be associated with more reoperations for vertical muscle surgery, but this observation was not statistically significant in the primary analysis after controlling for age. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · May 2015 · American Journal of Ophthalmology
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    Blake M Hampton · Jaclyn L Kovach · Stephen G Schwartz
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    ABSTRACT: The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.
    Preview · Article · May 2015 · Clinical ophthalmology (Auckland, N.Z.)
  • Stephen G Schwartz · J William Harbour
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    ABSTRACT: The retinal tumor provisionally referred to as presumed solitary circumscribed retinal astrocytic proliferation (PSCRAP) is a rare, benign lesion of unknown pathogenesis and histopathology. The authors present a case of PSCRAP that was analyzed with spectral-domain optical coherence tomography (OCT), which demonstrated a demarcation between the mass and the retinal nerve fiber layer. This finding stands in contrast to previous descriptions using time-domain OCT, suggesting that this tumor may originate from mid-retinal layers rather than the nerve fiber layer. In addition, the OCT of PSCRAP is distinct from that of astrocytic hamartoma associated with tuberous sclerosis complex. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:586-588.]. Copyright 2015, SLACK Incorporated.
    No preview · Article · May 2015 · Ophthalmic Surgery Lasers and Imaging Retina
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    ABSTRACT: To report the 3-month incidence rates of postoperative suprachoroidal hemorrhage after glaucoma filtration surgeries and to examine the subsequent surgical treatments in these eyes. This is a retrospective study using the nationally pooled, insurance claim-based MarketScan databases from the years 2007-2011. Patients with records of trabeculectomy and/or tube shunt procedures were identified, and all cases of "definite" (ie, properly coded) and "suspected" (possibly miscoded) postoperative suprachoroidal hemorrhage occurring within 3 months of their glaucoma filtration procedures were captured along with the surgical interventions used for this condition. Kaplan-Meier survival analysis was used to evaluate the 3-month incidence rates of suprachoroidal hemorrhage, and regression analysis was applied to calculate the odds ratios, confidence intervals, and P-values. There were 17,843 trabeculectomies and 9,597 tube shunt surgeries identified. Among these, there were 107 cases (247 including "suspected" cases) of postoperative suprachoroidal hemorrhage within 3 months of trabeculectomy and 113 cases (255 including "suspected" cases) within 3 months of tube shunt procedures. The 3-month cumulative incidence rate of postoperative suprachoroidal hemorrhage ranged from 0.6%±0.06% to 1.4%±0.09% after trabeculectomy and 1.2%±0.11% to 2.7%±0.16% after tube shunt surgery. Postoperative suprachoroidal hemorrhage was almost twice as likely to occur after tube shunt surgeries than after trabeculectomies for both "definite" and "definite" plus "suspected" cases (odds ratio, 1.98; 95% confidence interval, 1.51-2.58; P<0.001; and odds ratio, 1.95; 95% confidence interval, 1.63-2.32; P<0.001, respectively). Among the 502 "definite" and "suspected" cases of postoperative suprachoroidal hemorrhage, 32.9% (165 cases) had a treatment record of choroidal tap and 8.8% (44 cases) had a treatment record of pars plana vitrectomy. In this sample, the 3-month cumulative incidence rate of postoperative suprachoroidal hemorrhage was 0.6%-1.4% after trabeculectomy and 1.2%-2.7% after tube shunt procedures, and the majority of the cases appeared to be managed without further surgery. Postoperative suprachoroidal hemorrhage was almost twice as likely to occur after tube shunt surgeries as after trabeculectomies.
    Preview · Article · Apr 2015 · Clinical Ophthalmology

Publication Stats

1k Citations
268.30 Total Impact Points

Institutions

  • 2009-2015
    • University of Miami
      كورال غيبلز، فلوريدا, Florida, United States
  • 2006-2015
    • Bascom Palmer Eye Institute
      Miami, Florida, United States
  • 2013
    • Miami University
      Оксфорд, Ohio, United States
  • 2007-2010
    • University of Miami Miller School of Medicine
      Miami, Florida, United States
  • 2003
    • Virginia Commonwealth University
      • Department of Ophthalmology
      Ричмонд, Virginia, United States
  • 2002
    • Baylor College of Medicine
      • Department of Ophthalmology
      Houston, TX, United States