- •Foreword
- •List of contributors
- •Preface
- •Dedication and Acknowledgments
- •Evolving knowledge in pharmacologic treatments
- •MEDICAL TREATMENT
- •VERTEPORFIN
- •ANTI-VEGF TREATMENT
- •OTHER MEDICAL TREATMENTS
- •“PLAYERS” IN OCULAR TREATMENT
- •THE DRUG
- •ROUTE OF ADMINISTRATION
- •Eye drops
- •Soluble ophthalmic drug inserts
- •Ion drug exchange
- •Intravitreal injections
- •Systemic administration
- •Sustained drug delivery system
- •Intraocular implants
- •Microparticles and nanoparticles
- •Liposomes
- •Encapsulated cell technology (ECT)
- •Iontophoresis
- •REFERENCES
- •SECTION 1: Basic Sciences in Retina
- •Retinal anatomy and pathology
- •INTRODUCTION
- •KEY CONCEPTS AND FUNDAMENTALS
- •NORMAL RETINAL ANATOMY
- •RETINAL PATHOLOGY
- •Congenital abnormalities
- •Dystrophies
- •Degenerations
- •Vascular diseases
- •Toxicities
- •Inflammatory diseases
- •Neoplasms
- •Retinal detachment
- •Trauma
- •Involvement of systemic diseases
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Retinal biochemistry, physiology, and cell biology
- •INTRODUCTION
- •VITREOUS BIOCHEMISTRY
- •VITREOUS DEGENERATION WITH AGING
- •PHYSIOLOGICAL AND PATHOLOGICAL CHANGES IN THE VITREORETINAL INTERFACE
- •BLOOD–RETINAL BARRIER
- •TIGHT JUNCTIONS
- •BLOOD–RETINA BARRIER DISRUPTION
- •MECHANISMS OF RETINAL ARTERIOLAR CALIBER CHANGES
- •MECHANISMS OF RETINAL VENULAR CALIBER CHANGES
- •MACULAR PIGMENTS
- •FUNCTIONS OF MACULAR PIGMENTS
- •Antioxidant
- •Optical filter
- •VISUAL CYCLE
- •RETINOID CYCLE
- •Outer segment of photoreceptors
- •Retinal pigment epithelium
- •Re-entry into the outer segment
- •Chaperones
- •PHOTOTRANSDUCTION
- •Activation
- •Inactivation
- •RETINAL PIGMENT EPITHELIUM AND LIPOFUSCIN
- •RETINAL PIGMENT EPITHELIUM
- •LIPOFUSCIN
- •Formation of lipofuscin
- •Lipofuscin and RPE atrophy
- •Stargardt’s disease and lipofuscin
- •Age-related macular degeneration and lipofuscin
- •MATRIX BIOLOGY
- •STRUCTURAL COMPOSITION OF THE BRUCH’S MEMBRANE
- •MACROSCOPIC CHANGES OF THE BRUCH’S MEMBRANE
- •CELL BIOLOGY OF BRUCH’S MEMBRANE
- •LIPID ACCUMULATION
- •MATRIX DYSREGULATION
- •MATRIX METALLOPROTEINASES
- •PHARMACOTHERAPY IMPLICATIONS
- •REFERENCES
- •INTRODUCTION
- •PROMOTERS OF ANGIOGENESIS
- •VEGF in physiologic and pathologic angiogenesis
- •Investigational approaches to VEGF inhibition in ocular neovascularization
- •RNA interference
- •Soluble VEGFR fusion protein: VEGF-Trap
- •Anecortave acetate
- •PLATELET-DERIVED GROWTH FACTOR
- •FIBROBLAST GROWTH FACTOR 2 (FGF2)
- •TUMOR NECROSIS FACTOR-α (TNF-α)
- •EPHS AND EPHRINS
- •NOTCH
- •ANGIOPOIETINS
- •Angiopoietin 1
- •Angiopoietin 2
- •ERYTHROPOIETIN
- •MATRIX METALLOPROTEINASES
- •INTEGRINS
- •COMPONENTS OF THE COMPLEMENT CASCADE
- •INHIBITORS OF ANGIOGENESIS
- •PIGMENT EPITHELIUM-DERIVED FACTOR
- •SOLUBLE VEGF RECEPTOR 1
- •VEGFXXXb ISOFORMS
- •COMPLEMENTARY REGULATORY PROTEIN C59
- •TRYPTOPHANYL-tRNA SYNTHASE FRAGMENT
- •OTHER INHIBITORS
- •SUMMARY
- •REFERENCES
- •Ocular immunity and inflammation
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS AND FUNDAMENTALS IN MOLECULAR BIOLOGY AND BIOCHEMISTRY
- •INNATE IMMUNITY
- •ADAPTIVE IMMUNITY
- •MECHANISMS OF PATHOGENESIS
- •NONINFECTIOUS POSTERIOR AND PANUVEITIS
- •INFECTIOUS RETINITIS AND CHOROIDITIS
- •AGE-RELATED MACULAR DEGENERATION
- •DIABETIC RETINOPATHY
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS IN COMPLEMENT BIOLOGY
- •SUMMARY
- •REFERENCES
- •Genetics of retinal disease
- •INTRODUCTION
- •HISTORY OF RETINAL GENE DISCOVERY
- •KEY CONCEPTS AND FUNDAMENTS OF GENETIC METHODS IN THE STUDY OF RETINAL DISEASE
- •GENETICS: ILLUMINATING MECHANISMS OF PATHOGENESIS, REVEALING COMPLEXITY
- •RP: A “COMPLEX” MONOGENIC DISEASE
- •SHEDDING LIGHT ON AMD
- •DELIVERY OF GENES TO TARGET PATHOGENIC PATHWAYS
- •GENE-INDEPENDENT THERAPY
- •SUMMARY: THE FUTURE IS BRIGHT
- •REFERENCES
- •SECTION 2: Animal Models and Routes for Retinal Drug Delivery
- •Vitamins and supplements for age-related macular degeneration
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS AND PHARMACOLOGY OF CURRENT DIETARY SUPPLEMENTS
- •EPIDEMIOLOGIC DATA OF ASSOCIATION OF FAT AND ω-3 LCPUFAs WITH AMD
- •AVAILABLE SUPPLEMENTS FOR MACULAR DEGENERATION
- •IMPLICATIONS OF RETINAL SUPPLEMENT PHARMACOLOGY
- •FUTURE DIRECTIONS: AREDS2
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Ocular pharmacokinetic, drug bioavailability, and intraocular drug delivery systems
- •INTRODUCTION
- •INTRAVITREAL ADMINISTRATION
- •OCULAR PHARMACOKINETICS
- •TOPICAL FORMULATIONS
- •CONVENTIONAL FORMULATIONS
- •INTRAOCULAR DRUG DELIVERY SYSTEMS
- •NONBIODEGRADABLE IMPLANTS
- •INTRAOCULAR BIODEGRADABLE DRUG DELIVERY SYSTEMS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •INTRODUCTION
- •THE RATIONALE FOR INTRAVITREAL DRUG DELIVERY
- •HISTORY
- •KEY CONCEPTS AND FUNDAMENTAL POINTS IN RETINAL DRUG DELIVERY
- •STRATEGIES AND IMPLICATIONS FOR RETINAL PHARMACOTHERAPY
- •PREOPERATIVE PREPARATION
- •PROPHYLAXIS OF ENDOPHTHALMITIS: LOCAL DISINFECTION AND TOPICAL ANTIBIOTIC THERAPY
- •LOCAL TOPICAL ANESTHESIA
- •SURGICAL TECHNIQUES FOR RETINAL DRUG DELIVERY
- •THE PROCEDURE AND RECOMMENDED TECHNIQUE
- •COMPLICATIONS WITH THE ROUTE FOR DRUG DELIVERY
- •OCULAR COMPLICATIONS
- •PHARMACOKINETICS AND CLEARANCE OF INTRAVITREAL DRUGS
- •PHARMACOKINETICS OF INTRAVITREAL CRYSTALLINE TRIAMCINOLONE ACETONIDE
- •CLINICAL EXPERIENCE AND RESULTS IN VITRECTOMIZED, AIR-FILLED, OR SILICONE OIL EYES
- •VITRECTOMIZED EYES
- •Silicone oil tamponade
- •Gas tamponade
- •PREOPERATIVE DRUG APPLICATIONS
- •INTRAOPERATIVE DRUG APPLICATIONS
- •POSTOPERATIVE DRUG APPLICATIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS
- •ANIMAL MODELS
- •DRUG DELIVERY MODALITIES
- •TOPICAL DRUG DELIVERY
- •TRANSSCLERAL DRUG DELIVERY
- •SUPRACHOROIDAL DRUG DELIVERY
- •INTRAVITREAL GAS-PHASE NANOPARTICLE DRUG DELIVERY
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENT
- •REFERENCES
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS AND FUNDAMENTAL POINTS IN SUSTAINED-RELEASE DRUG DELIVERY
- •EXISTING SUSTAINED-RELEASE DRUG DEVICES
- •BIODEGRADABLE POLYMER IMPLANTS
- •LIPOSOME ENCAPSULATION
- •CELLULAR ENCAPSULATION
- •THE FUTURE
- •SUMMARY
- •ACKNOWLEDGMENT
- •REFERENCES
- •INTRODUCTION
- •PERMEATION BARRIERS AND ANATOMICAL CONSIDERATIONS
- •THEORETICAL BACKGROUND
- •CYCLODEXTRINS
- •ANIMAL TESTING OF ROUTES OF DRUG DELIVERY
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Thermo-sensitive hydrogels
- •INTRODUCTION
- •DELIVERY CHARACTERISTICS
- •POTENTIAL DELIVERY SITE
- •TOXICITY TESTING
- •FUTURE DIRECTION
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Retina and ocular toxicity to ocular application of drugs
- •INTRODUCTION
- •HISTORY
- •MAJOR CLASSES OF DRUGS AND THEIR SAFETY PROFILE AFTER LOCAL OCULAR APPLICATION FOR RETINA THERAPY
- •CORTICOSTEROIDS
- •ANTIBIOTICS
- •NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
- •ENZYMES AND FIBRINOLYTICS
- •MISCELLANEOUS ANTI-INFLAMMATORY AND ANTIANGIOGENIC AGENTS
- •Summary and Key points
- •ACKNOWLEDGMENTS
- •REFERENCES
- •INTRODUCTION
- •KEY CONCEPTS AND FUNDAMENTALS
- •PHARMACOLOGY, BIOCHEMISTRY, AND TYPE OF IMPACT ON THE RETINA
- •DISRUPTION OF THE RETINA AND RETINAL PIGMENT EPITHELIUM
- •Phenothiazines
- •Thioridazine
- •Chlorpromazine
- •Chloroquine derivatives
- •Chloroquine
- •Hydroxychloroquine
- •Quinine sulfate
- •Clofazimine
- •2′,3′-dideoxyinosine (DDI)
- •Deferoxamine
- •Corticosteroid preparations
- •Cisplatin and BCNU (carmustine)
- •Potassium iodate
- •VASCULAR DAMAGE OR OCCLUSION
- •Quinine sulfate
- •Cisplatin and BCNU (carmustine)
- •Talc
- •Oral contraceptives
- •Aminoglycoside antibiotics
- •Interferon
- •Miscellaneous agents
- •CYSTOID MACULAR EDEMA AND RETINAL EDEMA/FOLDS
- •CYSTOID MACULAR EDEMA
- •Epinephrine and dipivefrin
- •Nicotinic acid
- •Prostaglandin analogues
- •Retinal edema/folds
- •Sulfa antibiotics, acetazolamide, ethoxyzolamide, chlorthalidone, hydrochlorothiazide, triamterene, metronidazole
- •Topiramate
- •CRYSTALLINE RETINOPATHY
- •TAMOXIFEN
- •CANTHAXANTHINE
- •METHOXYFLURANE
- •TALC
- •NITROFURANTOIN
- •UVEITIS
- •RIFABUTIN
- •CIDOFOVIR
- •LATANOPROST
- •CARDIAC GLYCOSIDES
- •SILDENAFIL
- •METHANOL
- •VIGABATRIN
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •DISEASE PREVALENCE AND INFLUENCE
- •RISK FACTORS
- •ETIOLOGY/PATHOGENESIS
- •SIGNS AND SYMPTOMS
- •TREATMENT OPTIONS
- •VITAMIN C
- •CAROTENOIDS
- •VITAMIN E
- •MINERALS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Neovascular age-related macular degeneration
- •DISEASE PREVALENCE AND INFLUENCE
- •RISK FACTORS
- •ETIOLOGY/PATHOGENESIS
- •NATURAL HISTORY
- •NONPHARMACOLOGIC THERAPIES
- •PHARMACOLOGIC THERAPIES
- •PDT WITH VERTEPORFIN
- •PEGAPTANIB
- •RANIBIZUMAB
- •BEVACIZUMAB
- •COMBINATION THERAPY
- •TREATMENTS UNDER INVESTIGATION
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Diabetic retinopathy and diabetic macular edema
- •INTRODUCTION
- •DIABETIC RETINOPATHY PREVALENCE
- •RISK FACTORS
- •ETIOLOGY AND PATHOGENESIS
- •SIGNS AND SYMPTOMS
- •TREATMENT OPTIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Retinal vein occlusion
- •INTRODUCTION
- •DISEASE PREVALENCE
- •RISK FACTORS
- •PATHOGENESIS
- •CENTRAL RETINAL VEIN OCCLUSION
- •BRANCH RETINAL VEIN OCCLUSION
- •TREATMENT OPTIONS
- •CENTRAL RETINAL VEIN OCCLUSION
- •BRANCH RETINAL VEIN OCCLUSION
- •TREATMENT OUTCOMES AND PROGNOSIS
- •CENTRAL RETINAL VEIN OCCLUSION
- •TISSUE PLASMINOGEN ACTIVATOR (tPA)
- •CORTICOSTEROIDS
- •BEVACIZUMAB
- •OTHER MEDICATIONS
- •Ranimizumab
- •Coumadin (warfarin)
- •Urokinase
- •Troxerutin
- •Ticlodipine
- •Pentoxifylline
- •Hemodilution
- •Laser treatment
- •Chorioretinal venous anastomosis
- •SURGICAL TREATMENT OF CRVO
- •Radial optic neurotomy (ron)
- •Branch retinal vein occlusion
- •Corticosteroids
- •Bevacizumab
- •Ranimizumab
- •Laser treatment
- •SURGICAL TREATMENT OF BRVO
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Retinal detachment and proliferative vitreoretinopathy
- •INTRODUCTION
- •INCIDENCE OF RETINAL DETACHMENT
- •ETIOLOGY AND RISK FACTORS FOR RETINAL DETACHMENT
- •RISK FACTORS FOR PROLIFERATIVE VITREORETINOPATHY
- •SIGNS, SYMPTOMS, AND DIAGNOSIS
- •TREATMENT OPTIONS
- •PROGNOSIS WITH THE VARIOUS TREATMENT OPTIONS
- •ADJUNCTIVE THERAPIES
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Posterior Uveitis
- •INTRODUCTION
- •DISEASE PREVALENCE AND INFLUENCE
- •RISK FACTORS
- •PATHOGENESIS
- •SPECIFIC DISEASES: DIAGNOSIS AND PHARMACOTHERAPY
- •ADAMANTIADES–BEHÇET DISEASE
- •Diagnostic features
- •Treatment modalities
- •BIRDSHOT RETINOCHOROIDOPATHY
- •Diagnostic features
- •Treatment modalities
- •Treatment modalities
- •SARCOIDOSIS
- •Diagnostic features
- •Treatment modalities
- •SERPIGINOUS CHOROIDOPATHY
- •Diagnostic features
- •Treatment modalities
- •VOGT–KOYANAGI–HARADA SYNDROME
- •Diagnostic features
- •Treatment modalities
- •SYMPATHETIC OPHTHALMIA
- •Diagnostic features
- •Treatment modalities
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •DISEASE PREVALENCE
- •RISK FACTORS
- •MYOPIA
- •PRESUMED OCULAR HISTOPLASMOSIS SYNDROME
- •OTHER INFLAMMATORY CAUSES
- •ANGIOID STREAKS
- •IDIOPATHIC CNV
- •ETIOLOGY AND PATHOGENESIS
- •DIAGNOSIS AND ANCILLARY TESTING
- •MYOPIA
- •PRESUMED OCULAR HISTOPLASMOSIS SYNDROME
- •ANGIOID STREAKS
- •INFLAMMATORY CAUSES
- •DIFFERENTIAL DIAGNOSIS
- •CLINICAL SIGNS AND SYMPTOMS
- •MYOPIA
- •PRESUMED OCULAR HISTOPLASMOSIS SYNDROME
- •ANGIOID STREAKS
- •INFLAMMATORY CAUSES
- •TREATMENT
- •PHOTODYNAMIC THERAPY
- •SURGICAL THERAPY
- •ANTIANGIOGENIC THERAPY
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •DISEASE INCIDENCE
- •RISK FACTORS
- •ETIOLOGY/PATHOGENESIS
- •SIGNS AND SYMPTOMS
- •OCULAR
- •SYSTEMIC
- •TREATMENT OPTIONS
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •Retinopathy of prematurity
- •INTRODUCTION
- •DISEASE PREVALENCE AND INFLUENCE
- •RISK FACTORS
- •ETIOLOGY/PATHOGENESIS
- •ABNORMAL RETINAL VASCULARIZATION IN ROP
- •ROLE OF GROWTH FACTORS IN ROP
- •DIAGNOSIS AND ANCILLARY TESTING/DIFFERENTIAL DIAGNOSIS
- •SIGNS AND SYMPTOMS
- •CLASSIFICATION OF RETINOPATHY OF PREMATURITY
- •TREATMENT OPTIONS FOR RETINOPATHY OF PREMATURITY
- •CRYOTHERAPY AND LASER THERAPY
- •INTRAVITREAL ANTI-VEGF THERAPY FOR ROP
- •Rationale for Treatment
- •Injection Technique
- •Patients
- •Results
- •Other Reported Results
- •Concerns with Intravitreal Anti-VEGF Therapy for ROP
- •Ocular complications
- •Systemic Complications
- •Vitrectomy
- •SUMMARY
- •REFERENCES
- •Idiopathic macular telangiectasia
- •INTRODUCTION
- •THERAPY
- •NONPROLIFERATIVE STAGE
- •PROLIFERATIVE STAGE
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Neovascular glaucoma
- •INTRODUCTION
- •DISEASE PREVALENCE AND INFLUENCE
- •RISK FACTORS
- •ETIOLOGY/PATHOGENESIS
- •CENTRAL RETINAL VEIN OCCLUSION
- •DIABETIC RETINOPATHY
- •DIABETIC NEOVASCULAR GLAUCOMA
- •CAROTID ARTERY OCCLUSIVE DISEASE
- •CENTRAL RETINAL ARTERY OCCLUSION
- •INTRAOCULAR TUMORS
- •Malignant melanoma
- •Retinoblastoma
- •MISCELLANEOUS CAUSES
- •DIAGNOSIS AND ANCILLARY TESTING
- •DIFFERENTIAL DIAGNOSIS
- •SIGNS AND SYMPTOMS
- •TREATMENT OPTIONS
- •TREATMENT OF THE UNDERLYING DISEASE ASSOCIATED WITH NVG
- •Central retinal vein occlusion
- •Diabetic retinopathy
- •Carotid artery occlusive disease
- •Central retinal artery occlusion
- •PHARMACOLOGIC THERAPIES
- •Medical treatment to control high IOP
- •Anti-VEGF therapy
- •Corticosteroid therapy
- •Photodynamic therapy
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •SPECIFIC DISEASES
- •RETINITIS PIGMENTOSA
- •Nutrients and retinitis pigmentosa
- •Cystoid Macular Edema (CME) associated with RP
- •Ciliary Neurotrophic Factor and retinitis pigmentosa
- •REFSUM’S DISEASE
- •Treatment
- •Dietary restriction
- •Plasmapheresis
- •GYRATE ATROPHY
- •Treatment
- •Arginine-restricted diet
- •Vitamin B6 supplementation
- •ABETALIPOPROTEINEMIA (BASSEN–KORNZWEIG SYNDROME)
- •Treatment
- •LEBER CONGENITAL AMAUROSIS
- •Treatment
- •RPE65 gene therapy
- •X-LINKED JUVENILE RETINOSCHISIS
- •Treatment
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •SECTION 4: Drugs and Mechanisms in Retinal Diseases
- •Nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of retinal diseases
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY, DRUG MECHANISM, AND EFFECTS
- •DICLOFENAC
- •KETOROLAC
- •NEVANAC
- •BROMFENAC
- •DICLOFENAC
- •KETOROLAC
- •NEPAFENAC
- •BROMFENAC
- •CONTRAINDICATIONS, COMPLICATIONS, AND TOXICITY
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION
- •PHARMACOLOGY
- •STRUCTURE
- •METABOLISM
- •Dexamethasone
- •Fluocinolone
- •CYSTOID MACULAR EDEMA
- •DIABETIC MACULAR EDEMA
- •RETINAL VEIN OCCLUSION
- •EXUDATIVE AGE-RELATED MACULAR DEGENERATION (AMD)
- •Raised intraocular pressure
- •Infectious, sterile, and pseudoendophthalmitis associated with triamcinolone acetonide
- •Cataract
- •Retinal detachment
- •FUTURE CONSIDERATIONS AND ONGOING STUDIES
- •THE SCORE STUDY
- •STEROID-SUSTAINED RELEASE DEVICES
- •The STRIDE study
- •FLUOCINOLONE ACETONIDE DEVICE
- •NEW-GENERATION FLUOCINOLONE DEVICE
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Anecortave acetate
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •DRUG MECHANISM
- •DRUG EFFECTS IN RETINAL DISEASES
- •PRECLINICAL STUDIES
- •Retinopathy of prematurity
- •Intraocular tumors
- •Choroidal neovascularization
- •CLINICAL STUDIES
- •Exudative AMD
- •Other diseases
- •EFFICACY AND COMPARISON WITH OTHER AGENTS
- •CONTRAINDICATIONS
- •OCULAR COMPLICATIONS AND TOXICITY
- •SYSTEMIC COMPLICATIONS AND TOXICITY
- •DRUG INTERACTIONS
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •DRUG MECHANISM
- •DRUG USE IN RETINAL DISEASES
- •AGE-RELATED MACULAR DEGENERATION
- •DIABETIC RETINOPATHY
- •RETINAL VEIN OCCLUSION (RVO)
- •UVEITIC CYSTOID MACULAR EDEMA (CME)
- •RETINOPATHY OF PREMATURITY (ROP)
- •RETINAL TELANGIECTASIAS
- •NEOVASCULAR GLAUCOMA (NVG)
- •OTHERS
- •CONTRAINDICATIONS
- •OCULAR COMPLICATIONS AND TOXICITY
- •SYSTEMIC COMPLICATION AND TOXICITY
- •DRUG INTERACTIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •PHARMACOLOGICAL DESIGN
- •PHARMACOKINETICS
- •PHARMACODYNAMICS
- •DRUG MECHANISM
- •DRUG USE IN RETINAL DISEASES
- •EFFICACY
- •EFFICACY IN AMD
- •EFFICACY IN OTHER RETINAL DISEASES
- •CONTRAINDICATIONS
- •OCULAR COMPLICATIONS AND TOXICITY
- •DRUG INTERACTIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Pathophysiology of vascular endothelial growth factor and other angiogenic molecules
- •KEY FEATURES
- •INTRODUCTION
- •BIOLOGICAL EFFECTS OF VEGF-A
- •VEGF-A ISOFORMS
- •VEGF RECEPTORS
- •ROLE OF VEGF-A IN INTRAOCULAR NEOVASCULAR SYNDROMES
- •INTRAVITREAL ANTI-VEGF THERAPY FOR NEOVASCULAR AMD: PEGAPTANIB, RANIBIZUMAB AND BEVACIZUMAB
- •OTHER ANTI-VEGF THERAPIES IN CLINICAL DEVELOPMENT FOR AMD
- •OTHER ANGIOGENIC FACTORS
- •FIBROBLAST GROWTH FACTOR FAMILY
- •PLACENTAL GROWTH FACTOR
- •DELTA-LIKE LIGAND 4
- •SUMMARY AND KEYPOINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION
- •TUMOR NECROSIS FACTOR-ALPHA ANTAGONISTS
- •INFLIXIMAB (REMICADE)
- •Pharmacology and mechanism
- •Systemic indications for infliximab
- •Ophthalmic indications for infliximab
- •Contraindications
- •Ocular complications and toxicity
- •Systemic complications and toxicity
- •Drug interactions
- •Summary
- •ADALIMUMAB (HUMIRA)
- •Pharmacology and mechanism
- •Systemic indications
- •Ophthalmic indications
- •Contraindications
- •Ocular toxicity
- •Systemic toxicity
- •Drug interactions
- •Summary
- •ETANERCEPT (ENBREL)
- •Pharmacology and mechanism
- •Systemic indications
- •Ophthalmic indications
- •Contraindications
- •Ocular toxicity
- •Systemic toxicity
- •Drug interactions
- •Summary
- •INTERLEUKIN-2 RECEPTOR ANTAGONIST
- •DACLIZUMAB (ZENAPAX)
- •Pharmacology and mechanism
- •Systemic indication
- •Ophthalmic indications
- •Contraindications
- •Ocular toxicity
- •Systemic toxicity
- •Drug interactions
- •Summary
- •OTHER BIOLOGIC AGENTS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •CALCINEURIN INHIBITORS
- •CICLOSPORIN (CYCLOSPORIN: CsA)
- •Key features, introduction, and history
- •Pharmacology
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Pediatric case series
- •EFFICACY AND COMPARISON WITH OTHER AGENTS
- •Ciclosporin versus tacrolimus
- •TACROLIMUS
- •Key features, introduction, and history
- •Pharmacology
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Summary and key points
- •ANTIMETABOLITES
- •MYCOPHENOLATE MOFETIL (MMF)
- •Key features, introduction, and history
- •Pharmacology
- •Drug mechanism
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Pediatric case series
- •METHOTREXATE
- •Key features, introduction, and history
- •Pharmacology
- •Drug mechanism
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Pediatric case series
- •Intravitreal methotrexate injection
- •AZATHIOPRINE
- •Key features, introduction, and history
- •Pharmacology
- •Drug mechanism
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Pediatric case series
- •Summary and key points
- •ALKYLATING AGENTS
- •CYCLOPHOSPHAMIDE
- •Key features, introduction, and history
- •Pharmacology
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Efficacy and comparison with other agents
- •CHLORAMBUCIL
- •Key features, introduction, and history
- •Pharmacology
- •Drug effects in human nonocular diseases
- •Drug use in retinal diseases
- •Efficacy and comparison with other agents
- •Summary and key points
- •SUMMARY
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •DRUG MECHANISM
- •DRUG EFFECTS IN PRECLINICAL MODELS
- •SYSTEMIC AND OCULAR COMPLICATIONS AND TOXICITY
- •BIOACTIVITY IN HUMAN EYE DISEASES
- •NEOVASCULAR AMD PHASE I
- •NEOVASCULAR AMD PHASE III PROGRAM
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •PHARMACOKINETICS
- •DRUG MECHANISM
- •DRUG USE IN RETINAL DISEASES
- •DIABETIC RETINOPATHY
- •RETINAL VEIN OCCLUSION
- •OTHERS
- •CONTRAINDICATIONS
- •OCULAR COMPLICATIONS AND TOXICITY
- •DRUG INTERACTIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION TO PROTEIN KINASE C
- •PROTEIN KINASE C FAMILY
- •EFFECTS OF ACTIVATED PKC
- •PHARMACOLOGY OF RUBOXISTAURIN
- •EFFECT OF RUBOXISTAURIN IN HUMAN NONOCULAR DISEASES
- •Use of PKC Inhibitors in the treatment of diabetic macular edema and diabetic retinopathy
- •EFFICACY OF RUBOXISTAURIN IN THE TREATMENT OF DIABETIC RETINOPATHY
- •OCULAR AND SYSTEMIC COMPLICATIONS AND TOXICITY OF RUBOXISTAURIN
- •INTERACTION OF RUBOXISTAURIN WITH OTHER DRUGS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY OF SIRNA FOR RETINAL DISEASES
- •PHARMACOLOGY, DRUG MECHANISM, AND DRUG EFFECTS IN NONOCULAR DISEASES
- •DRUG USES IN RETINAL DISEASES
- •BEVASIRANIB FOR SUBFOVEAL CHOROIDAL NEOVASCULARIZATION
- •BEVASIRANIB FOR NEOVASCULAR MACULAR DEGENERATION: RESULTS
- •BEVASIRANIB FOR THE TREATMENT OF DIABETIC MACULAR EDEMA (DME)
- •SIRNA-027 FOR SUBFOVEAL CHOROIDAL NEOVASCULARIZATION
- •REDD14 NP
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENT
- •REFERENCES
- •Ocular gene therapy
- •KEY FEATURES
- •INTRODUCTION TO GENE THERAPY
- •CURRENT VIRAL VECTORS
- •VIRAL VECTOR-ASSOCIATED RISKS
- •VIRAL VERSUS NONVIRAL VECTORS
- •STRATEGIES FOR RECESSIVE VERSUS DOMINANT DISEASE
- •STRATEGIES FOR PROLIFERATIVE AND NEOPLASTIC OCULAR DISEASE
- •RETINOBLASTOMA GENE THERAPY CLINICAL TRIAL
- •GENE THERAPY FOR LEBER’S CONGENITAL AMAUROSIS TRIAL
- •SUMMARY AND KEYPOINTS: THE FUTURE OF GENE THERAPY
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION
- •MECHANISM OF PROTECTION: APPROACHES AND CHALLENGES
- •ANTIOXIDATIVE THERAPY
- •EXCITOTOXICITY
- •NEUROTROPHIC FACTORS
- •ANTIAPOPTOPIC THERAPY
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY
- •DRUG MECHANISM
- •PDT IN ONCOLOGICAL DISORDERS
- •PDT IN IMMUNE (NONONCOLOGICAL) DISORDERS
- •DRUG USE IN RETINAL DISEASES
- •AGE-RELATED MACULAR DEGENERATION
- •PATHOLOGIC MYOPIA
- •OTHER SUBFOVEAL AND JUXTAFOVEAL POSTINFLAMMATORY OR IDIOPATHIC CHOROIDAL NEOVASCULARIZATION
- •POLYPOIDAL CHOROIDAL VASCULOPATHY
- •CENTRAL SEROUS CHORIORETINOPATHY
- •INTRAOCULAR VASOPROLIFERATIVE TUMORS
- •RETINAL ASTROCYTOMA
- •CHOROIDAL OSTEOMA
- •CHOROIDAL MELANOMA
- •RETINOBLASTOMA
- •CONJUNCTIVAL IN SITU SQUAMOUS CELL CARCINOMA
- •EFFICACY AND COMPARISON WITH OTHER AGENTS
- •CONTRAINDICATIONS
- •OCULAR COMPLICATIONS AND TOXICITY
- •DRUG INTERACTIONS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION
- •RETINOBLASTOMA (Tables 44.1 and 44.2)
- •GENERAL CONSIDERATIONS
- •CHEMOREDUCTION
- •AGENTS
- •RESULTS
- •CHEMOREDUCTION FAILURE
- •SIDE-EFFECTS
- •CHEMOTHERMOTHERAPY
- •PERIOCULAR AND SUBCONJUNCTIVAL CHEMOTHERAPY
- •INTRAVITREAL CHEMOTHERAPY
- •INTRA-ARTERIAL CHEMOTHERAPY
- •ADJUVANT CHEMOTHERAPY
- •NO CHOROIDAL, SCLERAL, OR POSTLAMINAR OPTIC NERVE INVOLVEMENT
- •CHOROIDAL INVASION
- •POSTLAMINAR OPTIC NERVE INVASION
- •TUMOR AT CUT OPTIC NERVE MARGIN
- •METASTATIC RETINOBLASTOMA
- •UVEAL METASTASIS
- •GENERAL CONSIDERATIONS
- •CHEMOTHERAPY
- •PROGNOSIS
- •UVEAL MELANOMA
- •METASTATIC UVEAL MELANOMA
- •INTRAOCULAR LYMPHOMA
- •GENERAL CONSIDERATIONS
- •TREATMENT
- •SUMMARY AND KEYPOINTS
- •REFERENCES
- •Antibiotics
- •INTRODUCTION
- •POTENTIAL NEW TREATMENT REGIMENS
- •TOPICAL FLUOROQUINOLONES
- •ORAL AND INTRAVENOUS ANTIBIOTICS
- •NASALLY APPLIED ANTIBIOTICS
- •ORAL, TOPICAL, AND INTRAVITREAL ANTIFUNGAL AGENTS
- •CONCLUSION
- •REFERENCES
- •SECTION 5: Pharmacotherapy and Surgery
- •KEY FEATURES (PHARMACOLOGY)
- •INTRODUCTION AND HISTORY
- •RHEOPHERESIS IN RETINAL DISEASES
- •AGE-RELATED MACULAR DEGENERATION
- •MAC-1 trial
- •Multicenter investigation of rheopheresis for AMD (MIRA-1)
- •DIABETIC MACULOPATHY
- •CENTRAL RETINAL VEIN OCCLUSION
- •UVEAL EFFUSION SYNDROME
- •Complications
- •SUMMARY
- •REFERENCES
- •Enzymatic vitrectomy and pharmacologic vitreodynamics
- •INTRODUCTION AND HISTORY
- •PHARMACOLOGY AND BIOCHEMISTRY
- •INDICATIONS
- •SURGICAL ADJUNCT
- •NONSURGICAL INDICATIONS
- •OPERATIVE TECHNIQUES
- •OUTCOMES
- •SUMMARY
- •REFERENCES
- •KEY FEATURES, INTRODUCTION, AND HISTORY
- •RATIONALE
- •PHARMACOLOGY AND BIOCHEMISTRY
- •INDICATIONS, OUTCOMES, AND COMPLICATIONS – VITAL DYES IN CHROMOVITRECTOMY
- •INDOCYANINE GREEN
- •INFRACYANINE GREEN
- •TRYPAN BLUE
- •PATENT BLUE
- •BRILLIANT BLUE
- •SODIUM FLUORESCEIN (SF)
- •TRIAMCINOLONE ACETONIDE
- •DYE INJECTION
- •MACULAR HOLE PROTECTION
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •KEY FEATURES
- •INTRODUCTION AND HISTORY
- •BIOLOGICAL EFFECTS
- •INDICATIONS
- •CHOROIDAL MELANOMA
- •OTHER OCULAR TUMORS
- •OPERATIVE TECHNIQUES
- •PLAQUE PLACEMENT TECHNIQUE
- •EPIMACULAR BRACHYTHERAPY FOR AGE-RELATED MACULAR DEGENERATION
- •SURGICAL TECHNIQUE
- •OUTCOMES
- •CHOROIDAL MELANOMA
- •BRACHYTHERAPY FOR AGE-RELATED MACULAR DEGENERATION
- •COMPLICATIONS
- •RADIATION RETINOPATHY
- •OPTIC NEUROPATHY
- •LENS TOXICITY
- •SCLERA/CHOROID TOXICITY
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •RPE DISEASE AND INDICATIONS FOR TREATMENT BY TRANSPLANTATION
- •BRUCH’S MEMBRANE AS A SUBSTRATE FOR TRANSPLANTED RPE
- •HISTORICAL DEVELOPMENT OF RPE TREATMENT
- •AUTOLOGOUS TREATMENT
- •IRIS PIGMENT EPITHELIUM
- •RETINAL PIGMENT EPITHELIUM
- •Suspension
- •RPE-BM Choroid Sheet
- •TISSUE ENGINEERING AND RPE REPLACEMENT STRATEGIES
- •PROSTHESIS OR TISSUE ENGINEERING OF BRUCH’S MEMBRANE
- •STEM CELLS
- •Embryonic stem cells
- •Bone marrow-derived cells
- •MANAGING DECONSTRUCTIVE REACTIONS INDUCED BY RETINAL DETACHMENT
- •CONCLUSIONS AND FUTURE DIRECTIONS
- •ACKNOWLEDGMENTS
- •REFERENCES
- •SECTION 6: The Last Words
- •Off-label drugs and the impact of the Food and Drug Administration in the treatment of retinal disease
- •INTRODUCTION
- •OFF-LABEL DRUG USAGE AND THE FOOD AND DRUG ADMINISTRATION
- •HISTORICAL PERSPECTIVES
- •FDA APPROVAL PROCESS
- •THE CONCEPT OF “OFF-LABEL”
- •“INVESTIGATIONAL USAGE OF DRUGS”
- •COMPOUNDING PHARMACIES
- •RISK MANAGEMENT ISSUES
- •INFORMED CONSENT
- •MEDICAL PAYMENT/COVERAGE
- •NATIONAL COVERAGE DETERMINATION
- •CLINICAL TRIALS
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •INTRODUCTION
- •HISTORY
- •KEY CONCEPTS
- •EVIDENCE-BASED MEDICINE
- •TYPES OF PHARMACOECONOMIC ANALYSIS
- •COST MINIMIZATION ANALYSIS
- •COST–BENEFIT ANALYSIS
- •COST-EFFECTIVENESS ANALYSIS
- •Cost-effectiveness analysis
- •COST–UTILITY ANALYSIS
- •Quality of life: Function-based instruments
- •Quality of life: Preference-based instruments
- •Utility gain
- •Value gain
- •Value trumps cost
- •Cost–utility ratio
- •Cost-effectiveness standards
- •Discounting5
- •Value-based medicine
- •Standardization
- •Patient respondents
- •COST PERSPECTIVE
- •SUMMARY AND KEY POINTS
- •REFERENCES
- •Future perspectives:
- •INTRODUCTION
- •KEY FEATURES
- •ANGIOGENESIS AND NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
- •TYROSINE KINASE INHIBITORS
- •PDGF INHIBITORS
- •INTEGRIN INHIBITORS
- •SMALL INTERFERING RNA
- •BIOACTIVE LIPIDS
- •NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION
- •COMPLEMENT INHIBITORS
- •DIABETIC MACULAR EDEMA
- •INHIBITION OF INFLAMMATION
- •SUMMARY AND KEY POINTS
- •ACKNOWLEDGMENT
- •REFERENCES
- •Index
Uveitis• 22 chapPosteriorr
stromal vessels; and (4) disc hyperfluorescence. With treatment, the hypofluorescent spots decrease in number and disappear as disease activity subsides. The other ICGAfindings also diminish with response to treatment. ICGA is useful to detect subclinical choroidal inflammation53 and guide therapy.54 OCT may be utilized to quantify objectively the amount of subretinal fluid and resolution with treatment. Sympathetic ophthalmia (SO) can present similar to VKH, thus any history of penetrating ocular trauma or surgery should be thoroughly elicited.
treatment. Relapses are common with SO, hence the need for prolonged duration of treatment with corticosteroids and gradual tapering of steroid dosage only after prolonged, close follow-up. Good results have been reported on the use of tacrolimus,60 cyclosporine, and/or azathioprine,61,62 combined with corticosteroids for SO. Chlorambucil has also been used for intractable SO with induction of remission.63
Treatment modalities
Corticosteroids constitute the primary treatment for acute disease. VKH responds well to systemic steroids, although some reports suggest that use of immunomodulatory therapy as first-line therapy is associated with a superior visual outcome compared to using corticosteroid alone.55
Treatment of VKH typically requires an average of 6 months or longer, and the addition of a second, steroid-sparing agent allows the corticosteroid dose to be decreased, thereby preventing steroid-related complications. Methotrexate, cyclosporine, tacrolimus, azathioprine, and mycophenolate mofetil are the immunomodulatory agents used to treat VKH in reported series. The use of intravenous immunoglobulin has also been reported.56 In pediatric VKH cases, methotrexate was used as a steroid-sparing agent in steroid-resistant cases, with good results.57 Triple therapy with methotrexate, cyclosporine, and corticosteroid was necessary in one pediatric VKH case reported.58 The aggressive, early use of steroids and maintenance using immunosuppressive agents produces fairly good prognosis, with over half of patients having visual outcomes of 20/30 or better. Poor visual outcomes are associated with increased age of onset, poor response to corticosteroids requiring prolonged treatment, and CNV.
SYMPATHETIC OPHTHALMIA
Diagnostic features
Since its description by William MacKenzie in the mid 19th century, SO has generated much interest and has become one of the most wellknown forms of uveitis among lay people. SO is a rare form of bilateral panuveitis usually following nonsurgical trauma to one eye (the exciting eye) with consequent inflammation of the nontraumatized (sympathizing) eye. SO may also occur after ocular surgery and radiotherapy. The onset of SO occurs within 1 year of the inciting event in 90% of cases, but may occur decades later.
SO presents as granulomatous uveitis with anterior-chamber inflammation, mutton-fat keratic precipitates, vitritis, and posterior-segment abnormalities. Yellow lesions (Dalen–Fuchs nodules) are seen in the periphery of the choroid, sometimes becoming confluent. Secondary glaucoma or cataract may develop.
Classic histopathological features of SO include granulomatous uveal tract infiltration and collections of inflammatory cells under the RPE (Dalen–Fuchs nodules). Monocytes, or T-helper and B lymphocytes, may be the major cellular components in the choroidal infiltrates. The clinical presentation may be similar to VKH, thus it is important to determine if there is any history of penetrating trauma or surgery. ICGA has been used as adjunct to FA in evaluating response to therapy with hypofluorescent spots present in active disease resolving with therapy.59 OCT may be utilized to document decrease in subretinal fluid with treatment.
Treatment modalities
Earlier reports suggested that early enucleation of the inciting eye was beneficial in preventing SO. More recent studies have reported good visual outcomes with aggressive, early, and adequate immunosuppressive therapy. High-dose systemic steroids should be the initial
SUMMARY AND KEY POINTS
Advances in drug development have greatly expanded the spectrum of inflammatory eye diseases amenable to pharmacotherapy. The great majority of patients with noninfectious, posterior-segment uveitis do respond to corticosteroids or currently available immunosuppressive agents. In many instances, early, aggressive, and appropriate treatment of intraocular inflammation makes a huge difference as to whether the patient retains or loses vision. The challenge to clinicians is to diagnose the disease condition correctly and early and enable their patients to have access to specialized care. The chronic, relapsing, insidious nature of posterior uveitis demands careful attention by caregivers. As the pathophysiological processes of these conditions become clearer, promising new treatments will be developed that provide more effective and safer treatments for uveitis patients.
Key points
• Uveitis is a leading cause of visual impairment worldwide. • Pharmacotherapy is the primary means of treating posterior
uveitis.
• Aggressive anti-inflammatory therapy is crucial for sight preservation in autoimmune posterior uveitis.
• Choice of pharmacotherapeutic agent is based on specific disease entity and patients’ clinical profiles.
• Appropriate drug selection and careful monitoring provide safe, effective treatment.
• New immunosuppressive drugs and devices provide alternative modalities for drug resistance or drug intolerance.
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Pharmacotherapy to Amenable Diseases Retinal • 3 section
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