- •Uveitis
- •Foreword
- •Preface
- •Dedication
- •Acknowledgments
- •Elements of the Immune System and Concepts of Intraocular Inflammatory Disease Pathogenesis
- •Elements of the immune system
- •Macrophages/monocytes
- •Dendritic cells
- •T cells
- •Major subsets of T cells
- •Cytokines
- •T-cell subsets
- •T-regulatory cells
- •T-cell receptor
- •Chemokines
- •Thymic expression and central immune tolerance
- •B cells
- •Classes of Immunoglobulin
- •Other cells
- •Mast Cells
- •Eosinophils
- •Neutrophils
- •Resident Ocular Cells
- •Complement system
- •Cellular interactions: hypersensitivity reactions
- •Classic immune hypersensitivity reactions
- •Type I
- •Type II
- •Type III
- •Type IV
- •Type V
- •Concepts of disease pathogenesis
- •Immune characteristics of the eye
- •Absence of lymphatic drainage
- •Intraocular microenvironment
- •Anterior Chamber-Associated Immune Deviation (ACAID)
- •Fas-Fas Ligand Interactions and Programmed Cell Death (Apoptosis)
- •Resident Ocular Cells and Immune System
- •Cytokines and Chemokines and the Eye
- •Oral Tolerance
- •Choroidal circulation and anatomy
- •Retina
- •Immunogenetics
- •Class I antigens
- •Class II and class III antigens
- •Histocompatibility lymphocyte antigens
- •Single-nucleotide polymorphisms (SNPs)
- •Epigenetics
- •Immune complex-mediated disease
- •Gene expression profiling
- •Tissue damage in the eye
- •T-cell responses and autoimmunity
- •T-cell receptor and the expression of disease
- •Ocular autoimmunity
- •Uveitogenic antigens
- •Retinal S-Antigen (Arrestin)
- •Interphotoreceptor Retinoid-Binding Protein
- •Recoverin
- •Bovine Melanin Protein
- •Rhodopsin
- •Phosducin
- •Tyrosinase
- •Other Antigens
- •Endotoxin and Other Bacterial Antigens
- •Importance of Antigen Studies
- •Cell adhesion molecules and their role in lymphocyte homing and in disease
- •Immune responses to invading viruses and parasites
- •Suggested Readings
- •References
- •Medical History in the Patient with Uveitis
- •References
- •Sample Uveitis Questionnaire
- •FAMILY HISTORY
- •SOCIAL HISTORY
- •PERSONAL MEDICAL HISTORY
- •MEDICAL HISTORY
- •Examination of the Patient with Uveitis
- •Visual acuity
- •External examination
- •Pupils and extraocular muscles
- •Intraocular pressure measurement
- •Slit-lamp biomicroscopy
- •Conjunctiva
- •Cornea
- •Keratic Precipitates
- •Other Corneal Findings
- •Anterior chamber
- •Iris
- •Anterior chamber angle
- •Lens
- •Vitreous
- •Retina and choroid
- •Optic nerve
- •References
- •Development of a Differential Diagnosis
- •Forming a differential diagnosis
- •Classifying uveitis
- •Is the disease acute or chronic?
- •Is the inflammation granulomatous or nongranulomatous?
- •Is the disease unilateral or bilateral?
- •Where is the inflammation located in the eye?
- •What are the demographics of the patient?
- •What associated symptoms does the patient have?
- •What associated signs are present on physical examination?
- •What is the time course of the disease and response to previous therapy?
- •Case 4-1
- •Case 4-2
- •References
- •Diagnostic Testing
- •Pretest likelihood of disease
- •Receiver operating characteristic (ROC) curve
- •Diagnostic tests for uveitis
- •Laboratory tests
- •Image analysis
- •Skin testing
- •Tissue samples
- •Ancillary ophthalmic tests
- •Electrophysiology
- •Laser interferometry
- •Fluorescein angiography
- •Indocyanine green
- •Laser flare photometry
- •Optical coherence tomography
- •High-frequency ultrasound biomicroscopy and multifrequency ultrasound
- •Fundus autofluorescence
- •Other diagnostic tests
- •Polymerase chain reaction (PCR)
- •Rapid tests for herpes simplex and herpes zoster
- •Bone mineral density studies
- •Genetic testing for steroid-induced glaucoma
- •Neurologic tests
- •References
- •Evidence-Based Medicine in Uveitis
- •Study design
- •Clinical trials in uveitis
- •References
- •Philosophy, Goals, and Approaches to Medical Therapy
- •Goals and philosophy
- •Pain, photophobia, and discomfort
- •Degree and location of inflammatory disease
- •Evaluation of visual acuity and prospect of reversibility
- •Follow-up procedures and standardization of observations
- •General health and age of patient
- •Patient reliability, preferences, and understanding
- •Nonsurgical therapeutic options
- •Corticosteroids
- •Mode of Action
- •Preparations, Dosage Schedules, and Complications
- •Ozurdex.
- •Secondary Effects
- •Cytotoxic agents
- •Alkylating agents
- •Mode of Action
- •Indications and Dosages
- •Secondary Effects
- •Antimetabolites
- •Azathioprine
- •Mode of Action
- •Indications and Dosages
- •Secondary Effects
- •Mycophenolate mofetil
- •Methotrexate
- •Mode of Action
- •Indications and Dosages
- •Secondary Effects
- •Ciclosporin
- •Mode of Action
- •Dosages and Indications
- •Secondary Effects
- •Tacrolimus
- •Mode of Action
- •Indications and Dosages
- •Secondary Effects
- •Lx 211 (Voclosporin)
- •Rapamycin
- •Mode of Action
- •Indications and Dosages
- •Toxicity
- •Antibodies and monoclonal antibodies
- •Daclizumab
- •Etanercept
- •Infliximab (Remicade)
- •Adalimumab (Humira)
- •Efalizumab (Raptiva)
- •Rituximab (Rituxan)
- •Anakinra (Kineret)
- •Alemtuzumab (Campath-1H)
- •Abatacept (Orencia)
- •Intravenous immunoglobulin therapy
- •Oral tolerance
- •Interferon-α
- •Antiviral therapy
- •Aciclovir
- •Ganciclovir
- •Valaciclovir
- •Famciclovir
- •Foscarnet
- •Combined ganciclovir and foscarnet
- •Cidofovir
- •Fomivirsen
- •Colchicine
- •Mode of Action
- •Indications and Dosages
- •Secondary Effects
- •Mydriatic and cycloplegic agents
- •Antitoxoplasmosis therapy
- •Other therapeutic approaches
- •Immunostimulators
- •Plasmapheresis
- •Nonsteroidal antiinflammatory agents
- •References
- •Role of Surgery in the Patient with Uveitis
- •Considerations
- •Removal of band keratopathy
- •Corneal transplantation
- •Cataract surgery
- •Glaucoma surgery
- •Treatment of vitreoretinal disease
- •Laser treatment
- •Photodynamic therapy
- •Diagnostic surgery
- •Anterior chamber paracentesis
- •Chorioretinal biopsy
- •Subretinal surgery
- •Case 8-1
- •References
- •Bacterial and Fungal Diseases
- •Introduction
- •Leprosy
- •Clinical findings
- •Immunology and pathology
- •Therapy
- •Tuberculosis
- •Systemic disease
- •Ocular disease
- •Diagnosis
- •Therapy
- •Other bacterial infections
- •Brucellosis
- •Whipple’s disease
- •Treatment and prognosis
- •Chronic granulomatous disease
- •Fungal disease
- •Neuroretinitis
- •References
- •Spirochetal Diseases
- •Spirochetal infections and the eye
- •Spirochetes
- •Definition
- •Venereal treponemal diseases
- •Syphilis
- •Etiology and Epidemiology
- •Clinical Manifestations
- •Primary syphilis.
- •Secondary syphilis.
- •Latent syphilis.
- •Tertiary syphilis.
- •Benign tertiary syphilis.
- •Cardiovascular syphilis.
- •Neurosyphilis.
- •Congenital syphilis.
- •Ocular Manifestations
- •Diagnosis
- •Prognosis
- •Treatment
- •General recommendations.
- •Approach to Syphilis in Patients with AIDS
- •Nonvenereal treponematoses
- •Endemic syphilis
- •Etiology and Epidemiology
- •Clinical Manifestations
- •Ocular Manifestations
- •Diagnosis
- •Prognosis
- •Treatment
- •Yaws and pinta
- •Ocular Manifestations
- •Diagnosis
- •Prognosis
- •Treatment
- •Borrelia infection
- •Lyme disease
- •Etiology and Epidemiology
- •Clinical Manifestations
- •Ocular Manifestations
- •Diagnosis
- •Prognosis
- •Treatment
- •Relapsing fever
- •Etiology and Epidemiology
- •Clinical Manifestations
- •Ocular Manifestations
- •Diagnosis
- •Prognosis
- •Treatment
- •Leptospirosis
- •Etiology and Epidemiology
- •Clinical Manifestations
- •Ocular Manifestations
- •Weil’s disease
- •Diagnosis
- •Prognosis
- •Treatment
- •Case 10-1
- •References
- •Acquired Immunodeficiency Syndrome
- •Human immunodeficiency virus
- •Epidemiology
- •Diagnosis
- •HIV disease
- •HIV therapy
- •Ocular manifestations of HIV infection
- •Ocular infection
- •Cytomegalovirus retinitis
- •Progression
- •CMV retinitis in the era of highly active antiretroviral therapy
- •Treatment
- •Intravitreal ganciclovir implant
- •Current therapeutic approach to CMV retinitis in the era of HAART
- •Retinal detachment
- •Prognosis
- •Immune recovery uveitis
- •Herpes zoster
- •Pneumocystis jirovecii choroiditis
- •Mycobacterium avium-intracellulare choroiditis
- •Other diseases
- •Drug-related ocular inflammation
- •Case 11-1
- •Case 11-2
- •References
- •Acute retinal necrosis
- •Epidemiology
- •Clinical features
- •Etiology
- •Differential diagnosis
- •Therapy
- •Progressive outer retinal necrosis
- •Diagnosis
- •Differential diagnosis
- •Etiology
- •Therapy
- •Case 12-1
- •Case 12-2
- •References
- •Other Viral Diseases
- •Herpes simplex virus kerititis and keratouveitis
- •Pathogenesis
- •Diagnosis
- •Treatment
- •Herpes zoster ophthalmicus
- •Treatment
- •West Nile virus
- •Epidemiology
- •Diagnosis
- •Clinical description
- •Ophthalmic manifestations
- •Treatment
- •Prognosis
- •Other viral infections
- •Human T-lymphotropic virus type I
- •Case 13-1
- •References
- •Ocular Toxoplasmosis
- •Organism
- •Clinical manifestations
- •Systemic
- •Ocular
- •Decreased Vision
- •Loss of Vision
- •Effects in immunocompromised host
- •Histopathology and immune factors
- •Immune response
- •Inflammatory response
- •Methods of diagnosis
- •Pregnancy
- •Other methods
- •Congenital versus acquired disease
- •Therapy
- •Additional therapeutic approaches
- •Case 14-1
- •Case 14-2
- •Case 14-3
- •Case 14-4
- •References
- •Ocular Histoplasmosis
- •Systemic findings
- •Ocular appearance
- •‘Histo’ spots
- •Maculopathy
- •Peripapillary pigment changes
- •Clear vitreous
- •Etiology and immunology
- •Nonsurgical therapies
- •Laser therapy
- •Subretinal surgery
- •References
- •Toxocara canis
- •Ocular manifestations
- •Histopathology and immune factors
- •Enzyme-linked immunoabsorbent assay
- •Treatment
- •Case 16-1
- •References
- •Onchocerciasis and Other Parasitic Diseases
- •Onchocerciasis
- •Clinical appearance
- •Immune characteristics
- •Therapy
- •Giardiasis
- •Ophthalmomyiasis
- •Cysticercosis
- •Caterpillar hairs
- •Amebiasis
- •Diffuse unilateral subacute neuroretinitis (DUSN)
- •Malaria
- •Seasonal hyperacute panuveitis (SHAPU)
- •References
- •Postsurgical Uveitis
- •Acute bacterial endophthalmitis
- •Chronic bacterial endophthalmitis
- •Fungal endophthalmitis
- •Endogenous endophthalmitis
- •Lens-induced uveitis
- •Toxic anterior segment syndrome (TASS)
- •Laser-induced uveitis
- •Case 18-1
- •References
- •Anterior Uveitis
- •Epidemiology
- •Clinical description
- •Idiopathic anterior uveitis
- •Diagnostic workup
- •Treatment
- •HLA-B27–associated anterior uveitis
- •Epidemiology
- •Demographics and clinical findings
- •Etiology
- •HLA-B27–associated anterior uveitis with systemic disease
- •Ankylosing spondylitis
- •Etiology
- •Treatment
- •Reactive arthritis (Reiter’s syndrome)
- •Juvenile idiopathic arthritis
- •Diagnosis
- •Pathology
- •Differential diagnosis
- •Treatment and prognosis
- •Psoriatic arthropathy
- •Inflammatory bowel disease
- •Whipple’s disease
- •Disease associations
- •Fuchs’ heterochromic iridocyclitis
- •Etiology
- •Treatment and prognosis
- •Kawasaki disease
- •Tubulointerstitial nephritis and uveitis syndrome (TINU)
- •Pathogenesis
- •Glaucomatous cyclitic crisis
- •Schwartz syndrome
- •Anterior segment ischemia
- •Lens-induced uveitis
- •Anterior uveitis associated with AIDS
- •Other disease associations
- •References
- •Scleritis
- •Episcleritis
- •Scleritis
- •Disease associations
- •Other causes of scleritis
- •Diagnostic testing
- •Pathogenesis
- •Differential diagnosis
- •Treatment
- •References
- •Intermediate Uveitis
- •Epidemiology
- •Clinical manifestations
- •Prognosis
- •Differential diagnosis
- •Multiple sclerosis
- •Etiology
- •Treatment
- •Corticosteroids
- •Immunosuppressive agents
- •Surgery
- •Case 21-1
- •Case 21-2
- •References
- •Sarcoidosis
- •Epidemiology
- •Etiology
- •Clinical manifestations
- •Anterior uveitis
- •Posterior segment findings
- •Systemic involvement
- •Pathology
- •Diagnosis
- •Treatment
- •Case 22-1
- •References
- •Sympathetic Ophthalmia
- •Clinical appearance and prevalence
- •Classic presentation
- •Sequelae
- •Tests and immunologic characteristics
- •Dalen–fuchs nodules
- •Preservation of the choriocapillaris
- •Therapy
- •Corticosteroids
- •Immunosuppressive agents
- •Case 23-1
- •Case 23-2
- •References
- •Vogt–Koyanagi–Harada Syndrome
- •Clinical aspects
- •Systemic findings
- •Ocular findings
- •Course of disease
- •Laboratory tests, etiology, and histopathology
- •Antigen-specific and immune responses
- •Vogt–Koyanagi–Harada syndrome versus sympathetic ophthalmia
- •Therapy
- •Cataract extraction
- •Case 24-1
- •Case 24-2
- •References
- •Birdshot Retinochoroidopathy
- •Clinical manifestations
- •Ocular examination and ancillary clinical tests
- •Tests, histology and etiology
- •Therapy
- •Case 25-1
- •Case 25-2
- •References
- •Behçet’s Disease
- •Clinical manifestations
- •Oral aphthous ulcers
- •Skin lesions
- •Genital ulcers
- •Ocular disease
- •Retinal disease
- •Complications
- •Minor criteria
- •Arthritis
- •Vascular alterations
- •Neurologic involvement (neuro-Behçet’s disease)
- •Immunologic and histologic considerations
- •Role of T cells (but other cells count too!)
- •HLA typing and single nucleotide polymorphisms (SNPs)
- •Therapy
- •Systemic corticosteroids
- •Cytotoxic and antimetabolic agents
- •Colchicine
- •Interferon-α
- •Ciclosporin and tacrolimus (FK506)
- •Anti-TNF therapy (infliximab)
- •Other approaches
- •Case 26-1
- •Case 26-2
- •Case 26-3
- •References
- •Retinal Vasculitis
- •Clinical characteristics
- •Ocular vasculitic disorders without systemic disease
- •Eales’ disease
- •Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN syndrome)
- •Frosted branch angiitis
- •Scleritis
- •Ocular vasculitic disorders with systemic disease
- •Systemic lupus erythematosus
- •Polyarteritis nodosa
- •Wegener’s granulomatosis
- •Whipple’s disease
- •Inflammatory bowel disease
- •Autoantibodies to Sjögren’s syndrome A antigen
- •Retinal vein occlusion
- •Relapsing polychondritis
- •Viral diseases
- •Multiple sclerosis
- •Tuberculosis
- •Rheumatoid arthritis
- •Kikuchi–Fujimoto disease
- •Susac syndrome
- •Sweet syndrome
- •References
- •Serpiginous Choroidopathy
- •Clinical features
- •Pathology
- •Etiology
- •Differential diagnosis
- •Therapy
- •Case 28-1
- •Case 28-2
- •Case 28-3
- •References
- •White-Dot Syndromes
- •Multiple evanescent white-dot syndrome
- •Clinical findings
- •Laboratory findings
- •Therapy
- •Multifocal choroiditis and panuveitis
- •Clinical findings
- •Punctate inner choroidopathy
- •Laboratory findings
- •Therapy
- •Acute retinal pigment epitheliitis
- •Clinical findings
- •Laboratory findings
- •Therapy
- •Acute posterior multifocal placoid pigment epitheliopathy
- •Clinical findings
- •Etiology
- •Therapy
- •Subretinal fibrosis and uveitis syndrome
- •Clinical findings
- •Laboratory findings
- •Therapy
- •Acute zonal occult outer retinopathy (AZOOR) and the azoor complex diseases
- •Case 29-1
- •Case 29-2
- •Case 29-3
- •References
- •Masquerade Syndromes
- •Intraocular lymphoma
- •Non-Hodgkin’s lymphoma of central nervous system
- •Diagnosis
- •Treatment
- •Systemic Non-Hodgkin’s lymphoma metastatic to eye
- •Lymphoid hyperplasia of uvea
- •Other malignant processes manifesting as uveitis
- •Paraneoplastic syndromes
- •Multiple sclerosis
- •Other nonmalignant conditions
- •References
- •Introduction
- •Age-related macular degeneration
- •Animal work
- •Animal laser model
- •Ccl2 and Ccr2 knockout model
- •Ccl2 and Cx3cr1 double knockout model
- •CEP induced AMD-like disease
- •Human data
- •Autoimmunity
- •Gene associations
- •Macrophages and other cells
- •Histopathology
- •The downregulatory immune environment
- •Should we consider immunotherapy?
- •Diabetic retinopathy
- •Diabetes and the immune process
- •Animal work
- •Human observations
- •Can we begin to think about immune therapy for diabetes and diabetic retinopathy?
- •Glaucoma
- •Autoantibodies and glaucoma
- •Cellular immunity and glaucoma
- •Can immune intervention help alter the course of glaucoma?
- •References
- •Index
Part 4 • Infectious Uveitic Conditions
Chapter 12 Acute Retinal Necrosis and Progressive Outer Retinal Necrosis
With the discovery of the viral etiology of ARN, specific therapy has been employed for the treatment of this disease. Nevertheless, many questions about ARN remain. We still do not know why certain individuals are more susceptible to developing the disease, because ARN is relatively rare but herpes virus infection is quite common. Finally, although aciclovir, valaciclovir, and famciclovir and corticosteroids are used to treat patients with ARN, there are still no randomized, masked, clinical trials definitively showing the benefits of therapy.
Progressive outer retinal necrosis
A syndrome characterized by rapidly progressive outer retinal necrosis (PORN) was initially described in immunocompromised patients. This syndrome seems to be different from ARN in immunocompromised patients and the prognosis is extremely poor. Unfortunately, it is thought to be the second most frequent opportunistic retinal infection in patients with AIDS in North America.52
Diagnosis
PORN is thought to be a variant of a necrotizing herpetic retinopathy in immunocompromised patients. The syndrome was described by Forster and colleagues in 199053 in two patients seropositive for human immunodeficiency virus (HIV). Margolis and coworkers54 similarly described varicellazoster virus retinitis in patients with AIDS, and also noted a rapidly progressive necrotizing retinitis with early patchy choroidal and deep retinal lesions which progressed relentlessly until patients were left with atrophic and necrotic retinas and pale optic nerves. Unlike typical ARN there is little or no vasculitis and less vitritis, and in many patients posterior pole involvement occurs early in the course of disease (Fig. 12-5).
Engstrom and colleagues52 recently reviewed the cases of 38 AIDS patients with PORN. A definite history of cutaneous herpes zoster was documented in 22 of 33 patients (67%). The median CD4+ lymphocyte count in these patients was 21/mm3, with a range of 0–130/mm3. Most patients had a unilateral decrease in visual acuity, although about onequarter of them had a presenting complaint of reduced
Figure 12-5. Diffuse retinitis involving posterior pole in patient with progressive outer retinal necrosis. Retinitis appears to involve the outer retina with little evidence of retinal vasculitis. (Courtesy of Chris Walton, MD.)
peripheral vision or constriction of visual field. Asymptomatic disease was noted in seven of 65 eyes (11%). The median visual acuity at presentation was 20/30, but some patients had no light perception (NLP) vision at presentation. Anterior chamber and vitreous inflammation was minimal or absent in all patients. Multifocal, deep retinal lesions were typically found in the periphery; however, macular lesions were noted in 21 eyes (32%) at the time of diagnosis. Optic nerve involvement was present in 11 of 65 eyes (17%), and an afferent pupillary defect was noted in 11 of 29 patients (38%). Characteristic of this syndrome, the lesions rapidly progressed to confluence. Interestingly, although the syndrome is described as involving the outer retina, pathologic evidence suggests that the disease can cause substantial destruction of the inner retina late in its course.53
Differential diagnosis
The differential diagnosis for PORN is similar to that of ARN, and a comparison of their diagnostic criteria is noted in Table 12-1. It is important to differentiate these two disorders. Retinal lesions in PORN appear to predominantly involve the deep retina, whereas lesions in ARN appear to be full thickness. Posterior retinal lesions are more common in PORN, whereas anterior chamber inflammation and dense vitritis are characteristic of ARN but rare in PORN.
Table 12.1 Diagnostic criteria
Progressive Outer Retinal
Necrosis Syndrome
Multifocal lesions characterized by deep retinal opacification without granular borders; there may be areas of confluent opacification
Acute Retinal Necrosis
Syndrome
One or more foci of fullthickness retinal necrosis with discrete borders
Lesions located in the peripheral |
Lesions located in the peripheral |
retina with or without macular |
retina* |
involvement |
|
|
|
Extremely rapid progression of |
Rapid progression of disease† |
lesions |
Circumferential spread of |
No consistent direction of disease |
disease around the peripheral |
spread |
retina |
|
|
Absence of vascular inflammation |
Evidence of occlusive |
|
vasculopathy, with arteriolar |
|
involvement |
|
|
Minimal or absent intraocular |
|
inflammation |
|
|
|
Characteristics that support, but are |
Prominent inflammatory |
not required, for diagnosis |
reaction in the vitreous and |
|
anterior chamber |
|
|
Perivenular clearing of retinal |
Characteristics that support, but |
opacification |
are not required, for diagnosis |
|
|
|
Scleritis |
|
|
|
Pain |
|
|
From Engstrom RE Jr, Holland GN, Margolis TP, et al.: The progressive outer retinal necrosis syndrome: a variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 1994; 101: 1488–1502.
*Involving the area adjacent to, or outside, the major temporal vascular arcades.
†Progression can be successfully halted in most patients with intravenous aciclovir therapy.
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