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.
Author(s): Sunny E. Ohia, Naj Sharif
Publisher: Academic Press
Year: 2022
Language: English
Pages: 671
City: London
Front Cover
Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics
Copyright Page
Dedication
Contents
List of contributors
Preface
Acknowledgments
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
Anatomy
Brief overview of eye diseases with clinico-pathologic correlation
Ocular surface and selected corneal diseases
Inflammation
Refractive diseases
Glaucoma
Retinal diseases
Neovascularization
References
Subchapter 1.2 Ocular biochemistry
Aqueous humor
Production of aqueous humor
Composition of aqueous humor
Vitreous humor
Retina
Structure and function of neural pathway of the retina
Phototransduction
Oxidative stress in the retina
References
Subchapter 1.3 Physiology
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 ocula...
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
2 Ocular autonomic physiology and pharmacology
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
Mydriatic and miotic agents
Autonomic regulation of ocular accommodation
Autonomic regulation of ocular blood flow
Autonomic regulation of intraocular pressure
Summary
References
3 Ocular drug discovery and development
Subchapter 3.1 Drug discovery in ophthalmology: creating new chemical entities in new classes of drugs
Introduction/overview
Type 3B ophthalmic drug discovery— prostaglandin analogs and ROCK inhibitors
Modern ophthalmic drug discovery—rho kinase inhibitors
Related investigations of ROCK inhibitors
Other companies’ ROCK inhibitor efforts
Conclusion
References
Further reading
Subchapter 3.2 Screening strategies for drug discovery-focus on ocular hypertension
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
Pharmacokinetics of ocular drugs
Bioavailability of topical drugs
Bioavailability of periocular drugs
Permeability
Clearance
Bioavailability of intraocular drugs
Permeability
Clearance
Drug residence and sustained delivery
Pharmacodynamics of ocular drugs
Safety of ocular drugs
Aggregation
Impurities
Antidrug antibodies
Overview
Conclusion
References
Subchapter 3.4 Investigational new drug-enabling studies for ocular and other therapeutics
Introduction
Investigational new drug study applications
Studies and data to permit investigational new drug application filing
Pharmaceutical agent quality
Primary pharmacology of the active product ingredient
Secondary pharmacology/safety pharmacology
Pharmacokinetic studies
Toxicological evaluation studies
Genotoxicity studies
Conclusions
References
Subchapter 3.5 Preclinical ocular regulatory science—investigational new drug-enabling studies
References
Subchapter 3.6 Ocular clinical regulatory sciences
References
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
Physical properties of the drugs
Role of excipients
Sterility
Ophthalmic formulations
Conventional ocular dosage forms
Eye drops
Ointments
Emulsions
Suspensions
Punctal plug
Novel controlled release ophthalmic formulations
Nanosuspensions
Nanoparticles
Nanomicelles
Hydrogels
Composite hydrogel systems
Microneedles
Intravitreal implants
References
Subchapter 4.2 Ocular pharmacokinetics
Introduction
Anatomy/physiology
Topical ocular administration
Transcorneal absorption
Absorption kinetics
Conjunctival/scleral absorption
Topical ocular distribution
Distribution within the anterior segment
Distribution to the posterior segment
Elimination following topical ocular administration
Ocular pharmacokinetic models—front of the eye delivery
Intravitreal administration
Intravitreal drug distribution and elimination
Vitreal pharmacokinetic models
Other routes of administration
Systemic administration
Ocular metabolism
Hydrolytic enzymes
Cytochrome P450 enzymes
Phase II metabolism
Other metabolizing enzymes
Transporters
Conclusion
References
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
Aqueous humor outflow
Proximal–distal outflow communication
Distal outflow regulation
Anatomy
Collector channels
Aqueous veins
Intrascleral venous plexus
Episcleral veins
Resident macrophages
Distal innervation
IOP homeostasis
Evidence for distal resistance
Distal vessel regulation
Collector channel morphology
Aqueous humor flow patterns
Clinical relevance of the distal portion of the outflow pathway
Structural and functional outflow imaging
Outflow imaging and glaucoma therapeutics
Minimally invasive glaucoma surgeries
Pharmacological interventions
Summary and future directions
References
Subchapter 5.2 Various forms of glaucoma and their treatments
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
Definition
Types and pathophysiology
Epidemiology
Presentation
Diagnosis
Treatment
Pharmacokinetics
Prostaglandins
Beta-adrenergic blockers
Carbonic anhydrase inhibitors
Sympathomimetics
Parasympathomimetics
Rho-associated protein kinase inhibitor
Hyperosmotic agents
Combination medications
Preservative agents
Lasers and surgeries
References
Subchapter 5.4 Minimally invasive glaucoma surgical devices
References
Subchapter 5.5 Gene therapy for ocular hypertension and glaucoma treatment
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
Retina–brain axis
Neuroprotection
Memantine
Brimonidine
Citicoline
Coenzyme Q10
Ginkgo biloba
Neurotrophins
Future directions
References
6 Pharmacotherapy of retinal diseases
Subchapter 6.1 Pharmacotherapy of retinal diseases
Basic science
Overview of the retina
Therapeutic strategies for treatment of retinal diseases
Intravitreal route
Periocular routes
Implants
Other routes
Pharmacology of agents used in the therapy of retinal diseases
Vascular endothelial growth factors inhibitors
Corticosteroids
Ganciclovir
Verteporfin
Voretigene
References
Subchapter 6.2 Age-related macular degeneration and its treatment options
Epidemiology
Clinical characteristics
Diagnosis
Etiology and pathogenesis of age-related macular degeneration
Treatments
Bevacizumab
Ranibizumab
Aflibercept
Brolucizumab
Faricimab
Concluding remarks
References
Subchapter 6.3 Pharmacotherapy of diabetic retinopathy
Introduction
Systemic therapy
Control of blood glucose
Control of dyslipidemia
Control of hypertension
Control of systemic inflammation/oxidative stress
Local therapy
Antiangiogenesis therapy
Efficacy of intravitreal antivascular endothelial cell growth factor therapy for proliferative diabetic retinopathy with an...
Efficacy of intravitreal antivascular endothelial cell growth factor therapy for diabetic macular edema
Complications of intravitreal vascular endothelial cell growth factor
Antiinflammatory strategies
Neuroprotection for diabetic macular edema
Pharmacotherapy as an adjunct to surgery
Combination pharmacotherapy
Clinical pathways
Future directions
References
Subchapter 6.4 Inherited retinal dystrophies
Inherited retinal dystrophies
Retinitis pigmentosa
Leber congenital amaurosis
Usher syndrome
X-linked retinoschisis
Achromatopsia
Choroideremia
Stargardt
Optogenetics
References
7 Pharmacotherapy of inflammatory eye diseases
Subchapter 7.1 Pharmacotherapy of inflammatory eye diseases
Introduction
Blepharitis
Anatomical structures involved in blepharitis
Drugs
Pharmacokinetics
Pharmacodynamics
Side effects and Interactions
Keratitis
Anatomical structures involved in keratitis
Drugs
Pharmacodynamics
Pharmacokinetics
Side effects and interactions
Uveitis
Anatomical structures involved in uveitis
Drugs
Pharmacokinetics
Pharmacodynamics
Side effects and interactions
References
Subchapter 7.2 Noninfectious anterior, posterior, and panuveitis and their treatments
Epidemiology
Etiology and pathogenesis
Clinical characteristics and diagnosis
Anterior uveitis
Posterior segment uveitis (intermediate, posterior, and panuveits)
Treatments
Topical corticosteroids
Cycloplegics
Nonsteroidal anti-inflammatory drugs
Periocular corticosteroids
Intravitreal corticosteroids
Systemic corticosteroids
Systemic immunosuppressive agents
Biologic agents
Concluding remarks
References
8 Etiology and pharmacotherapy of ocular surface allergic diseases
Introduction and overview
Epidemiology and etiology of human conjunctivitis
Short history of drug discovery for seasonal allergic conjunctivitis and perennial allergic conjunctivitis
Screening strategies for ocular antiallergic compounds
Pharmacotherapeutics for seasonal allergic conjunctivitis and perennial allergic conjunctivitis treatment
Current pharmacotherapy for seasonal allergic conjunctivitis and perennial allergic conjunctivitis
Other types of allergic conjunctivitis and their treatments
Conclusion
References
9 Pharmacotherapy of dry eye disease and ocular pain
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
Sjögren syndrome model
Desiccation stress model
Meibomian gland dysfunction model
Miscellaneous model
Clinical aspects of dry eye disease
Anti-inflammatory treatments
Ocular pain (dry eye symptoms and injuries)
Conclusion
References
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
Muscarinic acetylcholine receptors and antagonists
Transcription factor ZENK
Dopamine
Role of D1 and D2-receptors
Nitric oxide
Adenosine receptor
Gamma-aminobutyric acid
Clinical studies of pharmacological agents
Muscarinic receptor antagonists
Atropine
Tropicamide
Cyclopentolate
Pirenzepine
Beta-adrenergic receptor antagonists
Timolol
Labetalol
Adenosine receptor antagonist
Summary
References
Subchapter 10.2 Cataracts and presbyopia
Lens structure and functions
Presbyopia and cataract: age-related degeneration of lens function
Presbyopia
Cataract
Dysfunctional lens syndrome: an intermediate stage of lens aging
A closer look at the aging lens
Pharmacological treatment approaches
Crystallin conformation correctors in presbyopia and cataract
Miotics for transient correction of presbyopia
Preclinical models of presbyopia and cataracts
Hereditary cataract models
Wild type model animals with naturally occurring cataracts
Induced models of cataract
Animal models of presbyopia
Imaging modalities, assessments, and endpoints for presbyopia and cataracts
Summary and Outlook
References
11 Pharmacotherapy of ocular infectious diseases
Introduction
Bacterial and viral infections and their treatments
Ocular fungal diseases and treatments
Conclusion
References
12 Ocular side effects of drugs administered systemically for treatment of nonocular diseases
Introduction
Drugs acting on the cardiovascular system
Drugs acting on the central nervous system
Antiinflammatory drugs
Nonsteroidal antiinflammatory drugs
Corticosteroids
Antiviral and antimicrobial drugs
Antiviral Drugs
Antimicrobial drugs
Anticancer drugs
Drugs used for skin diseases
Summary
References
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
References
Further reading
Subchapter 13.2 Single-cell genetics approach in ophthalmology
Cells in the eye
Cell characterization by single-cell mRNA expression profiling
Next-generation sequencing
Single-cell isolation technology
Bioinformatical analysis methods
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
Introduction
Neurotrophins and their protective roles in maintaining retinal ganglion cell survival
Contribution of oxidative stress to glaucomatous damage—considerations for antioxidant therapies
Experimental and clinical approaches for glaucoma neuroprotection based on the application of neurotrophic factors
Stem cell transplantation as a neuroprotective approach to treat glaucoma
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
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
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
Introduction
The retina
Inherited retinal degenerations
Macular degeneration
Vision restoration technologies
Gene replacement
Stem cells
Electrodes
Optogenetics
Opsins
Mechanism of phototransduction
Applications of optogenetics for vision restoration
Mammalian versus microbial opsins
Kinetics
Preclinical studies of native and engineered opsins
Deactivation and recovery
Gene delivery methods
Viral delivery
Routes of administration
Viral serotypes and tropism
Engineered adeno-associated virus capsids
Laser gene delivery
Electroporation
Nonopsin optogenetic strategies
Optogenetic retinal prostheses
Upconversion nanoparticles
Chemical photoactivable switches
Photoisomerizable switches
Photovoltaic switches
Optogenetic clinical trials
Concluding remarks and future directions
Engineering complexity into restored retinal circuitry
Developing better retina degeneration model
Nonviral delivery of opsin-genes to targeted retinal cells and regions(s) of interest
References
Subchapter 13.7 Multispecific biologics in opthalmology
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
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
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
References
Index
Back Cover
