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  1. Book: Retina and optic nerve imaging

    Ciulla, Thomas A.

    2003  

    Author's details ed. Thomas A. Ciulla
    Keywords Retina / physiopathology ; Optic Nerve / physiopathology ; Diagnostic Imaging / methods ; Diagnostic Techniques, Ophthalmological ; Eye Diseases / diagnosis ; Retina/Imaging ; Optic nerve/Imaging
    Subject code 617.730754
    Language English
    Size X, 369 S. : Ill.
    Publisher Lippincott Williams & Wilkins
    Publishing place Philadelphia, Pa. u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT013811323
    ISBN 0-7817-3433-9 ; 978-0-7817-3433-2
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2003 A 3703 order for loan Magazin

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  2. Article ; Online: The complement system: a novel therapeutic target for age-related macular degeneration.

    Shughoury, Aumer / Sevgi, Duriye D / Ciulla, Thomas A

    Expert opinion on pharmacotherapy

    2023  Volume 24, Issue 17, Page(s) 1887–1899

    Abstract: Introduction: With the recent FDA approvals of pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (IZERVAY, Astellas Pharmaceuticals), modulation of the complement system has emerged as a promising therapeutic approach for slowing ... ...

    Abstract Introduction: With the recent FDA approvals of pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (IZERVAY, Astellas Pharmaceuticals), modulation of the complement system has emerged as a promising therapeutic approach for slowing progression of geographic atrophy (GA) in AMD.
    Areas covered: This article reviews the current understanding of the complement system, its role in AMD, and the various complement-targeting therapies in development for the treatment of GA, including monoclonal antibodies, aptamers, protein analogs, and gene therapies. Approved and investigational agents have largely focused on interfering with the activity of complement components 3 and 5, owing to their central roles in the classical, lectin, and alternative complement pathways. Other investigational therapies have targeted formation of membrane attack complex (a terminal step in the complement cascade which leads to cell lysis), complement factors H and I (which serve regulatory functions in the alternative pathway), complement factors B and D (within the alternative pathway), and complement component 1 (within the classical pathway). Clinical trials investigating these agents are summarized, and the potential benefits and limitations of these therapies are discussed.
    Expert opinion: Targeting the complement system is a promising therapeutic approach for slowing the progression of GA in AMD, potentially improving visual outcomes. However, increased risk of exudative conversion must be considered, and further research is required to identify clinical criteria and best practices for initiating complement inhibitor therapy for GA.
    MeSH term(s) Humans ; Macular Degeneration/drug therapy ; Macular Degeneration/metabolism ; Geographic Atrophy/drug therapy ; Geographic Atrophy/etiology ; Geographic Atrophy/metabolism ; Immunologic Factors/therapeutic use ; Therapies, Investigational ; Pharmaceutical Preparations
    Chemical Substances Immunologic Factors ; Pharmaceutical Preparations
    Language English
    Publishing date 2023-09-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1080/14656566.2023.2257604
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Molecular Genetic Mechanisms in Age-Related Macular Degeneration.

    Shughoury, Aumer / Sevgi, Duriye Damla / Ciulla, Thomas A

    Genes

    2022  Volume 13, Issue 7

    Abstract: Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the ... ...

    Abstract Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the development of AMD. However, our ability to predict disease risk and personalize treatment remains limited by our nascent understanding of the molecular mechanisms underlying AMD pathogenesis. Research into the molecular genetics of AMD over the past two decades has uncovered 52 independent gene variants and 34 independent loci that are implicated in the development of AMD, accounting for over half of the genetic risk. This research has helped delineate at least five major pathways that may be disrupted in the pathogenesis of AMD: the complement system, extracellular matrix remodeling, lipid metabolism, angiogenesis, and oxidative stress response. This review surveys our current understanding of each of these disease mechanisms, in turn, along with their associated pathogenic gene variants. Continued research into the molecular genetics of AMD holds great promise for the development of precision-targeted, personalized therapies that bring us closer to a cure for this debilitating disease.
    MeSH term(s) Complement Factor H/genetics ; Humans ; Macular Degeneration/genetics ; Molecular Biology ; Polymorphism, Single Nucleotide ; Proteins/genetics
    Chemical Substances Proteins ; Complement Factor H (80295-65-4)
    Language English
    Publishing date 2022-07-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13071233
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  4. Article ; Online: Advancements in ocular gene therapy delivery: vectors and subretinal, intravitreal, and suprachoroidal techniques.

    Kovacs, Kyle D / Ciulla, Thomas A / Kiss, Szilárd

    Expert opinion on biological therapy

    2022  Volume 22, Issue 9, Page(s) 1193–1208

    Abstract: Introduction: Ocular gene therapy represents fertile ground for rapid innovation, with ever-expanding therapeutic strategies, molecular targets, and indications.: Areas covered: Potential indications for ocular gene therapy have classically focused ... ...

    Abstract Introduction: Ocular gene therapy represents fertile ground for rapid innovation, with ever-expanding therapeutic strategies, molecular targets, and indications.
    Areas covered: Potential indications for ocular gene therapy have classically focused on inherited retinal disease (IRD) but more recently include acquired retinal diseases, such as neovascular age-related macular degeneration, geographic atrophy, and diabetic retinopathy. Ocular gene therapy strategies have proliferated recently, and include gene augmentation, gene inactivation, gene editing, RNA modulation, and gene-independent gene augmentation. Viral vector therapeutic constructs include adeno-associated virus and lentivirus and continue to evolve through directed evolution and rationale design. Ocular gene therapy administration techniques have expanded beyond pars plana vitrectomy with subretinal injection to intravitreal injection and suprachoroidal injection.
    Expert opinion: The success of treatment for IRD, paired with the promise of clinical research in acquired retinal diseases and in administration techniques, has raised the possibility of in-office gene therapy for common retinal disorders within the next 5 to 10 years.
    MeSH term(s) Dependovirus/genetics ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors ; Humans ; Intravitreal Injections ; Retinal Diseases/genetics ; Retinal Diseases/therapy
    Language English
    Publishing date 2022-09-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1080/14712598.2022.2121646
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6094: Show issues Location:
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  5. Article: Molecular Genetic Mechanisms in Age-Related Macular Degeneration

    Shughoury, Aumer / Sevgi, Duriye Damla / Ciulla, Thomas A.

    Genes. 2022 July 12, v. 13, no. 7

    2022  

    Abstract: Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the ... ...

    Abstract Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the development of AMD. However, our ability to predict disease risk and personalize treatment remains limited by our nascent understanding of the molecular mechanisms underlying AMD pathogenesis. Research into the molecular genetics of AMD over the past two decades has uncovered 52 independent gene variants and 34 independent loci that are implicated in the development of AMD, accounting for over half of the genetic risk. This research has helped delineate at least five major pathways that may be disrupted in the pathogenesis of AMD: the complement system, extracellular matrix remodeling, lipid metabolism, angiogenesis, and oxidative stress response. This review surveys our current understanding of each of these disease mechanisms, in turn, along with their associated pathogenic gene variants. Continued research into the molecular genetics of AMD holds great promise for the development of precision-targeted, personalized therapies that bring us closer to a cure for this debilitating disease.
    Keywords angiogenesis ; blindness ; complement ; diet ; extracellular matrix ; genes ; genetic background ; lipid metabolism ; macular degeneration ; molecular genetics ; oxidative stress ; pathogenesis ; risk factors ; stress response ; tobacco use
    Language English
    Dates of publication 2022-0712
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13071233
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Triamcinolone Acetonide Suprachoroidal Injectable Suspension for Uveitic Macular Edema: Integrated Analysis of Two Phase 3 Studies.

    Yeh, Steven / Henry, Christopher R / Kapik, Barry / Ciulla, Thomas A

    Ophthalmology and therapy

    2022  

    Abstract: Introduction: Macular edema, a common complication of uveitis, may result in vision loss. The aim of this analysis was to report integrated phase 3 trial data for triamcinolone acetonide injectable suspension for suprachoroidal use (SCS-TA) in the ... ...

    Abstract Introduction: Macular edema, a common complication of uveitis, may result in vision loss. The aim of this analysis was to report integrated phase 3 trial data for triamcinolone acetonide injectable suspension for suprachoroidal use (SCS-TA) in the treatment of macular edema secondary to noninfectious uveitis using strict inclusion criteria.
    Methods: This analysis included patients with central subfield thickness (CST) ≥ 300 µm and best-corrected visual acuity (BCVA) of ≥ 5 and ≤ 70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at both screening and baseline who received ≥ 1 study treatment in either PEACHTREE (randomized, double-masked SCS-TA or sham control) or AZALEA (open-label SCS-TA). Patients received SCS-TA 4.0 mg (0.1 ml of 40 mg/ml) or control at baseline and week 12.
    Results: In the SCS-TA group (n = 95), 47.4% of patients gained ≥ 15 ETDRS letters from baseline to week 24 versus 16.7% of patients in the control group (n = 60; P < 0.001). Mean change in BCVA in the SCS-TA group was 9.6 letters at week 4 and 13.9 letters at week 24. CST also improved rapidly in the SCS-TA group (mean change: - 158.4 µm at week 4), with sustained reduction throughout the study (mean change: - 163.9 µm at week 24 versus - 19.3 µm in the control group; P < 0.001). No treatment-related serious adverse events (AEs) were reported. Incidence of AEs pertaining to elevated intraocular pressure was 12.6% and 15.0% in the SCS-TA and control groups, respectively; incidence of cataract formation/worsening AEs was 7.4% and 6.7%, respectively.
    Conclusion: In this integrated analysis utilizing strict inclusion criteria, SCS-TA was found effective in the treatment of patients with macular edema associated with noninfectious uveitis and was generally well tolerated.
    Trial registration: ClinicalTrials.gov identifier: NCT02595398, NCT03097315.
    Language English
    Publishing date 2022-11-18
    Publishing country England
    Document type Journal Article
    ISSN 2193-8245
    ISSN 2193-8245
    DOI 10.1007/s40123-022-00603-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Suprachoroidal delivery enables targeting, localization and durability of small molecule suspensions.

    Kansara, Viral S / Hancock, Shelley E / Muya, Leroy W / Ciulla, Thomas A

    Journal of controlled release : official journal of the Controlled Release Society

    2022  Volume 349, Page(s) 1045–1051

    Abstract: Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after the 2021 FDA approval of CLS-TA, a triamcinolone acetonide injectable suspension for suprachoroidal use (XIPERE®), administered via a microneedle-based device, the SCS ... ...

    Abstract Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after the 2021 FDA approval of CLS-TA, a triamcinolone acetonide injectable suspension for suprachoroidal use (XIPERE®), administered via a microneedle-based device, the SCS Microinjector®. Suprachoroidal (SC) delivery facilitates targeting, compartmentalization, and durability of small molecule suspensions, thereby potentially addressing some of the efficacy, safety, and treatment burden limitations of current retinal therapies. Herein, the design features of the SCS Microinjector are reviewed, along with the biomechanics of SC drug delivery. Also presented are preclinical evaluations of SC small molecule suspensions from 4 different therapeutic classes (plasma kallikrein inhibitor, receptor tyrosine kinase inhibitor, corticosteroid, complement factor D inhibitor), highlighting their potential for durability, targeted compartmentalization, and acceptable safety profiles following microinjector-based SC delivery. The clinical evaluations of the safety, tolerability and efficacy of SC delivered triamcinolone further supports potential of SC small molecule suspensions as a clinically viable strategy for the treatment of chorioretinal diseases. Also highlighted are current limitations, key pharmacological considerations, and future opportunities to optimize the SC microinjector platform for safe, effective, and potentially long-acting drug delivery for the treatment of chorioretinal disorders.
    MeSH term(s) Choroid ; Complement Factor D/pharmacology ; Plasma Kallikrein/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Suspensions ; Triamcinolone Acetonide
    Chemical Substances Protein Kinase Inhibitors ; Suspensions ; Plasma Kallikrein (EC 3.4.21.34) ; Complement Factor D (EC 3.4.21.46) ; Triamcinolone Acetonide (F446C597KA)
    Language English
    Publishing date 2022-09-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2022.05.061
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  8. Article ; Online: Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits.

    Kansara, Viral S / Muya, Leroy W / Ciulla, Thomas A

    Translational vision science & technology

    2021  Volume 10, Issue 7, Page(s) 19

    Abstract: Purpose: Axitinib, a tyrosine kinase inhibitor, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptors -1, -2 and -3. Suprachoroidal (SC) delivery of axitinib, combined with pan-VEGF inhibition activity of axitinib, has the ... ...

    Abstract Purpose: Axitinib, a tyrosine kinase inhibitor, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptors -1, -2 and -3. Suprachoroidal (SC) delivery of axitinib, combined with pan-VEGF inhibition activity of axitinib, has the potential to provide additional benefits compared to the current standard of care with intravitreal anti-VEGF-A agents. This study evaluated the ocular pharmacokinetics and systemic disposition of axitinib after SC administration in rabbits.
    Methods: Rabbits received axitinib as either a single SC injection (0.03, 0.10, 1.00, or 4.00 mg/eye; n = 4/group) or a single intravitreal injection (1 mg/eye; n = 4/group) in three separate studies. Axitinib concentrations were measured in several ocular compartments and in plasma at predetermined timepoints for up to 91 days. The pharmacokinetics parameters were estimated by noncompartmental analysis.
    Results: A single SC injection of axitinib suspension (1 mg/eye) resulted in an 11-fold higher mean axitinib exposure in the posterior eye cup, compared with intravitreal injection. Sustained levels of axitinib in the retinal pigment epithelium-choroid-sclera (RCS) and retina were observed throughout the duration of studies after a single SC axitinib injection (0.1 and 4.0 mg/eye), with low exposure in the vitreous humor, aqueous humor, and plasma. Axitinib levels in the RCS were 3 to 5 log orders higher than the reported in vitro (VEGF receptor-2 autophosphorylation inhibition) 50% inhibitory concentration value after 0.1 and 4.0 mg/eye dose levels throughout the 65-day and 91-day studies, respectively.
    Conclusions: This study demonstrates that SC axitinib suspension has a favorable pharmacokinetics profile with potential as a long-acting therapeutic candidate targeted to affected choroid and retinal pigment epithelium in neovascular age-related macular degeneration.
    Translational relevance: Suprachoroidal axitinib suspension has potential to decrease the treatment burden in neovascular age-related macular degeneration, as a long-acting therapeutic candidate, and could yield greater efficacy, as a potent tyrosine kinase pan-VEGF inhibitor, compared with current standard anti-VEGF-A therapies.
    MeSH term(s) Animals ; Axitinib ; Choroid ; Intravitreal Injections ; Rabbits ; Retina ; Vascular Endothelial Growth Factor A
    Chemical Substances Vascular Endothelial Growth Factor A ; Axitinib (C9LVQ0YUXG)
    Language English
    Publishing date 2021-06-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2674602-5
    ISSN 2164-2591 ; 2164-2591
    ISSN (online) 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.10.7.19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Genetic Testing Prevalence, Guidelines, and Pitfalls in Large, University-Based Medical Systems.

    Neiweem, Ashley E / Hariprasad, Seenu M / Ciulla, Thomas A

    Ophthalmic surgery, lasers & imaging retina

    2021  Volume 52, Issue 1, Page(s) 6–10

    MeSH term(s) Genetic Testing ; Humans ; Prevalence ; Universities
    Language English
    Publishing date 2021-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2701167-7
    ISSN 2325-8179 ; 2325-8160
    ISSN (online) 2325-8179
    ISSN 2325-8160
    DOI 10.3928/23258160-20201223-02
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 756: Show issues Location:
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  10. Article ; Online: RPE65 Mutation-associated Inherited Retinal Disease and Gene Therapies.

    Camp, David A / Falabella, Paulo / Ciulla, Thomas A

    International ophthalmology clinics

    2021  Volume 61, Issue 4, Page(s) 125–132

    MeSH term(s) Eye Proteins/genetics ; Genetic Therapy ; Humans ; Mutation ; Retina ; Retinal Degeneration ; Retinal Diseases/genetics ; Retinal Diseases/therapy ; cis-trans-Isomerases/genetics
    Chemical Substances Eye Proteins ; cis-trans-Isomerases (EC 5.2.-)
    Language English
    Publishing date 2021-09-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207382-1
    ISSN 1536-9617 ; 0020-8167
    ISSN (online) 1536-9617
    ISSN 0020-8167
    DOI 10.1097/IIO.0000000000000381
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