Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics

Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics provides a review of the basic anatomy, physiology, biochemistry and pathology of the eye with a focus drug therapy, drug delivery and use of therapeutic medical miniature devices. An understanding of the pharmacological actions of drugs acting on the eye requires the student and health care practitioner to learn additional principles in basic and clinical sciences that are unique to this organ. As a sensory organ, the eye is relatively inaccessible to the systemic circulation due to the blood-vitreous, blood-aqueous and blood-retinal barriers. Consequently, the administration of drugs for therapeutic effects in the eye necessitates an understanding of physico-chemical properties of the molecules and pharmacokinetic principles involved in the access to its site of action via topical, intracameral and intravitreal administration. This book includes information on the general principles of pharmacokinetics and pharmacodynamics of drugs as it pertains to the eye and in combating ocular disorders and diseases. Using a disease-themed approach, the book discusses basic and clinical pharmacological principles involved in the therapy of these diseases including the ocular side effect of systemically-administered drugs, drugs used in ophthalmic surgery and miscellaneous agents, the therapeutic utility of biologics, drug conjugates, combination products, gene and cellular therapy are also covered. Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics is useful as a primary and secondary source of reference for up-to-date information about the pharmacological mechanisms of action, pharmacokinetics, side effects, drug-drug interactions and therapeutic indications of drugs for pharmacologists, pharmaceutical scientists, students in the health care disciplines (nursing, pharmacy, optometry, medical), and practitioners in optometry and ophthalmology.

• Explains the mechanisms of action, side-effects and therapeutic uses of drugs, biologics, miniature devices, gene and cellular therapies for the eye
• Provides a comprehensive review of the anatomy, physiology, biochemistry, pharmacology, microbiology, genetics and pathology of parts of the eye involved in drug therapy to combat eye disorders and diseases
• Explores the pharmacological and clinical basis of drugs, drug conjugates, combination products used in the treatment of anterior and posterior segment diseases

Table of Contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of contributors
• Preface
• Acknowledgments
• Chapter 1. The eye as a target for drugs and other treatment modalities
• Subchapter 1. 1. Anatomy and pathology
• Introduction
• Anatomy and overview of eye diseases
• Subchapter 1. 2. Ocular biochemistry
• Abstract
• Aqueous humor
• Vitreous humor
• Retina
• References
• Subchapter 1. 3. Physiology
• Abstract
• Anterior segment of the eye
• Posterior segment of the eye
• References
• Subchapter 1. 4. Receptors, ion channels, and signal transduction pathways as targets for drug intervention to mitigate ocular diseases
• Abstract
• Introduction
• Phospholipase-C-coupled receptors, janus kinase pathway, transcription, and immunogenic factors in mediating conjunctivitis
• Role of multiple of receptor-signaling pathways involved in causing and treating glaucoma
• Receptor-tyrosine-kinase signaling pathways causing age-related macular degeneration
• Concluding remarks
• References
• Chapter 2. Ocular autonomic physiology and pharmacology
• Abstract
• Introduction
• Structure of the ocular autonomic nervous system
• Function of the ocular autonomic nervous system
• Autonomic control of pupil diameter
• Mechanisms of autonomic contractions of pupillary muscles
• Autonomic regulation of ocular accommodation
• Autonomic regulation of ocular blood flow
• Autonomic regulation of intraocular pressure
• Summary
• References
• Chapter 3. Ocular drug discovery and development
• Subchapter 3. 1. Drug discovery in ophthalmology: creating new chemical entities in new classes of drugs
• Introduction/overview
• Modern ophthalmic drug discovery—rho kinase inhibitors
• Conclusion
• Further reading
• Subchapter 3. 2. Screening strategies for drug discovery-focus on ocular hypertension
• Abstract
• Introduction
• In vitro assays for screening potential ocular hypotensive compounds
• Ex vivo ocular models for drug characterization
• Animal models of OHT disease and in vivo studies
• Conclusions
• References
• Further reading
• Subchapter 3. 3. Therapeutic modality aspects in safety and efficacy of ocular drugs
• Abstract
• Pharmacokinetics of ocular drugs
• Drug residence and sustained delivery
• Pharmacodynamics of ocular drugs
• Safety of ocular drugs
• Overview
• Conclusion
• References
• Subchapter 3. 4. Investigational new drug-enabling studies for ocular and other therapeutics
• Abstract
• Introduction
• Investigational new drug study applications
• Studies and data to permit investigational new drug application filing
• Conclusions
• References
• Subchapter 3. 5. Preclinical ocular regulatory science—investigational new drug-enabling studies
• Abstract
• References
• Subchapter 3. 6. Ocular clinical regulatory sciences
• Abstract
• References
• Chapter 4. Drug formulation, delivery, and ocular pharmacokinetics
• Subchapter 4. 1. Ocular formulation and novel drug delivery systems
• Introduction
• Routes of ocular drug administration and associated barriers
• Key considerations in the development of ophthalmic formulations
• Ophthalmic formulations
• Subchapter 4. 2. Ocular pharmacokinetics
• Abstract
• Introduction
• Anatomy/physiology
• Topical ocular administration
• Intravitreal administration
• Other routes of administration
• Systemic administration
• Ocular metabolism
• Conclusion
• References
• Chapter 5. Pharmaco-devices therapy for glaucoma
• Subchapter 5. 1. The importance of distal outflow resistance in the regulation of intraocular pressure
• Introduction
• Intraocular pressure regulation
• Distal outflow regulation
• Clinical relevance of the distal portion of the outflow pathway
• Summary and future directions
• Subchapter 5. 2. Various forms of glaucoma and their treatments
• Abstract
• Introduction
• Primary open-angle glaucoma and its treatment
• Normotensive glaucoma and its treatment
• Primary closed-angle glaucoma and its treatment
• Pharmaceutical treatment options for glaucomas
• Laser treatments to reduce intraocular pressure
• Surgical procedures to lower intraocular pressure
• Minimally invasive glaucoma surgeries-based devices for lowering intraocular pressure
• Neuroprotection for glaucoma treatment
• Conclusions
• References
• Further reading
• Subchapter 5. 3. Glaucoma pharmacology
• Abstract
• Definition
• Types and pathophysiology
• Epidemiology
• Presentation
• Diagnosis
• Treatment
• Lasers and surgeries
• References
• Subchapter 5. 4. Minimally invasive glaucoma surgical devices
• Abstract
• Acknowledgments
• References
• Subchapter 5. 5. Gene therapy for ocular hypertension and glaucoma treatment
• Abstract
• Introduction
• Application of gene therapy to lower intraocular pressure
• Gene therapy for neuroprotection in glaucoma
• Conclusions
• References
• Subchapter 5. 6. Retina–brain axis and neuroprotection
• Abstract
• Retina–brain axis
• Neuroprotection
• References
• Chapter 6. Pharmacotherapy of retinal diseases
• Subchapter 6. 1. Pharmacotherapy of retinal diseases
• Basic science
• Therapeutic strategies for treatment of retinal diseases
• Pharmacology of agents used in the therapy of retinal diseases
• Subchapter 6. 2. Age-related macular degeneration and its treatment options
• Abstract
• Epidemiology
• Clinical characteristics
• Diagnosis
• Etiology and pathogenesis of age-related macular degeneration
• Treatments
• Concluding remarks
• References
• Subchapter 6. 3. Pharmacotherapy of diabetic retinopathy
• Abstract
• Introduction
• Systemic therapy
• Local therapy
• Future directions
• References
• Subchapter 6. 4. Inherited retinal dystrophies
• Abstract
• Inherited retinal dystrophies
• Retinitis pigmentosa
• Leber congenital amaurosis
• Usher syndrome
• X-linked retinoschisis
• Achromatopsia
• Choroideremia
• Stargardt
• Optogenetics
• References
• Chapter 7. Pharmacotherapy of inflammatory eye diseases
• Subchapter 7. 1. Pharmacotherapy of inflammatory eye diseases
• Introduction
• Blepharitis
• Keratitis
• Uveitis
• Subchapter 7. 2. Noninfectious anterior, posterior, and panuveitis and their treatments
• Abstract
• Epidemiology
• Etiology and pathogenesis
• Clinical characteristics and diagnosis
• Treatments
• Concluding remarks
• References
• Chapter 8. Etiology and pharmacotherapy of ocular surface allergic diseases
• Abstract
• Introduction and overview
• Epidemiology and etiology of human conjunctivitis
• Short history of drug discovery for seasonal allergic conjunctivitis and perennial allergic conjunctivitis
• Pharmacotherapeutics for seasonal allergic conjunctivitis and perennial allergic conjunctivitis treatment
• Other types of allergic conjunctivitis and their treatments
• Conclusion
• References
• Chapter 9. Pharmacotherapy of dry eye disease and ocular pain
• Abstract
• Dry eye disease and ocular pain, their manifestations and impact on the daily life of patients
• Animal and cell-based models for dry eye disease
• Clinical aspects of dry eye disease
• Ocular pain (dry eye symptoms and injuries)
• Conclusion
• References
• Chapter 10. Pharmacotherapies for myopia and ocular refractive errors
• Subchapter 10. 1. The pharmocotherapy of myopia—animal studies and clinical trials
• Introduction
• Animal studies of pharmacological agents
• Clinical studies of pharmacological agents
• Subchapter 10. 2. Cataracts and presbyopia
• Abstract
• Lens structure and functions
• Presbyopia and cataract: age-related degeneration of lens function
• Dysfunctional lens syndrome: an intermediate stage of lens aging
• Pharmacological treatment approaches
• Preclinical models of presbyopia and cataracts
• Imaging modalities, assessments, and endpoints for presbyopia and cataracts
• Summary and Outlook
• References
• Chapter 11. Pharmacotherapy of ocular infectious diseases
• Abstract
• Introduction
• Bacterial and viral infections and their treatments
• Ocular fungal diseases and treatments
• Conclusion
• References
• Chapter 12. Ocular side effects of drugs administered systemically for treatment of nonocular diseases
• Abstract
• Introduction
• Drugs acting on the cardiovascular system
• Drugs acting on the central nervous system
• Antiinflammatory drugs
• Antiviral and antimicrobial drugs
• Anticancer drugs
• Drugs used for skin diseases
• Summary
• References
• Chapter 13. Current and emerging techniques/technologies in ocular research and drug/device development
• Subchapter 13. 1. Genome-wide association studies to unravel genetics of ocular diseases
• Introduction
• Specific examples of GWAS for different forms of glaucoma
• GWAS for myopia
• Conclusions
• Further reading
• Subchapter 13. 2. Single-cell genetics approach in ophthalmology
• Abstract
• Cells in the eye
• Cell characterization by single-cell mRNA expression profiling
• Retinal cell subtype identification
• Cell numbers and read numbers
• Single-cell analysis of retinal diseases
• Future development of mRNA expression profiling technology
• References
• Subchapter 13. 3. Muller glia-derived exosomes and their microRNA cargo–potential for glaucoma therapies
• Abstract
• Introduction
• Extracellular vesicles
• Potential of extracellular vesicles derived from Müller glia for the development of neuroprotective strategies in glaucoma
• Micro-RNAs and their potential for neuroprotective glaucoma therapies
• Conclusions and future trends
• References
• Subchapter 13. 4. Genetics and other techniques to create novel animal models for ocular research
• Abstract
• Introduction
• Corneal and conjunctival diseases—animal models
• Ocular hypertension/glaucoma and animal models
• Cataracts and animal models
• Age-related macular degeneration and animal models
• Diabetic retinopathy and animal models
• Conclusions
• References
• Further reading
• Subchapter 13. 5. Imaging of apoptosing retinal cells for early diagnosis
• Abstract
• Rationale to detection of apoptosing retinal cell technology
• The detection of apoptosing retinal cell technique
• Applications
• References
• Subchapter 13. 6. Optogenetic approaches to gene therapy for vision restoration in retinal degenerative diseases
• Abstract
• Introduction
• Optogenetics
• Applications of optogenetics for vision restoration
• Gene delivery methods
• Nonopsin optogenetic strategies
• Optogenetic clinical trials
• Concluding remarks and future directions
• References
• Subchapter 13. 7. Multispecific biologics in opthalmology
• Abstract
• Strategies in developing bispecific or multispecific biologics
• Design and development of bispecific biologics
• Development through preclinical and clinical phases
• Conclusion
• References
• Subchapter 13. 8. CRISPR–Cas9: current and future utilities in ocular diseases
• Abstract
• Introduction to genome editing
• Tools for genome editing: ZFNs, TALENs, and CRISPR
• Overview of the CRISPR/Cas9 system
• Types of CRISPR–Cas enzymes
• DNA repair: nonhomologous end-joining versus homology-directed repair
• CRISPR–Cas9: current utility in ocular research
• Glaucoma
• Ocular angiogenesis
• Leber congenital amaurosis
• CRISPR–Cas9: clinical trials
• Conclusions
• References
• Subchapter 13. 9. DNA methylation: its role in retinal health and diseases
• Abstract
• DNA methylation
• DNA methylation writers
• DNA methylation erasers
• DNA methylation readers
• Roles of DNA methylation in retina development
• DNA methylation and eye diseases
• DNA methylation and uveitis
• DNA methylation and age-related macular degeneration
• DNA methylation and diabetic retinopathy
• DNA methylation and glaucoma
• Conclusions
• Acknowledgment
• References
• Index

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