- •Contents
- •General Introduction
- •Objectives
- •Anatomy
- •Eyelids
- •Conjunctiva
- •Lacrimal Functional Unit
- •The Tear Film
- •Cornea
- •Sclera
- •2 Examination Techniques for the External Eye and Cornea
- •Evaluation of Vision in the Patient With an Abnormal Cornea
- •External Examination
- •Slit-Lamp Biomicroscopy
- •Direct Illumination Methods
- •Indirect Illumination Methods
- •Clinical Use
- •Stains
- •Fluorescein
- •Rose Bengal and Lissamine Green
- •Evaluation of the Tear Film and Tests of Tear Production
- •Tear Composition Assays
- •Imaging Technologies
- •Impression Cytology
- •Corneal Pachymetry
- •Measurement of Corneal Biomechanics
- •Measurement of Corneal Curvature
- •Zones of the Cornea
- •Shape, Curvature, and Power
- •Keratometry
- •Computerized Corneal Topography
- •Corneal Tomography
- •Indications
- •Ultrasound Biomicroscopy
- •Anterior Segment Optical Coherence Tomography
- •Confocal Microscopy
- •External and Slit-Lamp Photography
- •Specular Microscopy
- •Anterior Segment Fluorescein Angiography
- •Esthesiometry
- •Retinoscopy
- •3 Clinical Approach to Ocular Surface Disorders
- •Common Clinical Findings
- •Conjunctival Signs
- •Corneal Signs
- •Clinical Approach to Dry Eye
- •Mechanisms of Dry Eye
- •Aqueous Tear Deficiency
- •Evaporative Dry Eye
- •Treatment of Dry Eye
- •Rosacea
- •Seborrheic Blepharitis
- •Staphylococcal Blepharitis
- •Hordeola and Chalazia
- •Exposure Keratopathy
- •Floppy Eyelid Syndrome
- •Superior Limbic Keratoconjunctivitis
- •Recurrent Corneal Erosion
- •Neurotrophic Keratopathy and Persistent Corneal Epithelial Defects
- •Trichiasis and Distichiasis
- •Factitious Ocular Surface Disorders
- •Dellen
- •Limbal Stem Cell Deficiency
- •Sjögren Syndrome
- •Ichthyosis
- •Ectodermal Dysplasia
- •Xeroderma Pigmentosum
- •Vitamin A Deficiency
- •4 Infectious Diseases of the External Eye: Basic Concepts and Viral Infections
- •Defense Mechanisms of the External Eye
- •Normal Ocular Flora
- •Pathogenesis of Ocular Infections
- •Virulence
- •Inoculum
- •Host Defense
- •Ocular Microbiology
- •Diagnostic Laboratory Techniques
- •Specimen Collection
- •Staining Methods
- •Virology and Viral Infections
- •DNA Viruses: Herpesviruses
- •Herpes Simplex Eye Diseases
- •Varicella-Zoster Virus Dermatoblepharitis, Conjunctivitis, and Keratitis
- •Epstein-Barr Virus Dacryoadenitis, Conjunctivitis, and Keratitis
- •Cytomegalovirus Keratitis and Anterior Uveitis
- •DNA Viruses: Adenoviruses
- •DNA Viruses: Poxviruses
- •Molluscum Contagiosum
- •Vaccinia
- •DNA Viruses: Papovaviruses
- •RNA Viruses
- •Bacteriology
- •Gram-positive Cocci
- •Gram-negative Cocci
- •Gram-positive Rods
- •Gram-negative Rods
- •Gram-positive Filaments
- •Chlamydia Species
- •Spirochetes
- •Mycology
- •Yeasts
- •Septate Filamentous Fungi
- •Nonseptate Filamentous Fungi
- •Parasitology
- •Protozoa
- •Helminths
- •Arthropods
- •Prions
- •Staphylococcal Blepharitis
- •Fungal and Parasitic Infections of the Eyelid Margin
- •Bacterial Conjunctivitis in Children and Adults
- •Parinaud Oculoglandular Syndrome
- •Microbial and Parasitic Infections of the Cornea and Sclera
- •Contact Lens–Related Infectious Keratitis
- •Bacterial Keratitis
- •Atypical Mycobacteria
- •Fungal Keratitis
- •Acanthamoeba Keratitis
- •Corneal Stromal Inflammation Associated With Systemic Infections
- •Microsporidiosis
- •Loiasis
- •Microbial Scleritis
- •6 Ocular Immunology
- •Overview of the Ocular Surface Immune Response
- •Tear Film
- •Immunoregulation of the Ocular Surface
- •Angiogenesis and Lymphangiogenesis in the Cornea
- •Tissue-Specific Patterns of Immune-Mediated Ocular Disease
- •Conjunctiva
- •Cornea
- •Sclera
- •Diagnostic Approach to Immune-Mediated Ocular Disorders
- •Immune-Mediated Diseases of the Eyelid
- •Contact Dermatoblepharitis
- •Atopic Dermatitis
- •Immune-Mediated Disorders of the Conjunctiva
- •Hay Fever Conjunctivitis and Perennial Allergic Conjunctivitis
- •Vernal Keratoconjunctivitis
- •Atopic Keratoconjunctivitis
- •Ligneous Conjunctivitis
- •Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
- •Mucous Membrane Pemphigoid
- •Ocular Graft-vs-Host Disease
- •Other Immune-Mediated Diseases of the Skin and Mucous Membranes
- •Immune-Mediated Diseases of the Cornea
- •Thygeson Superficial Punctate Keratitis
- •Interstitial Keratitis Associated With Infectious Diseases
- •Reactive Arthritis
- •Cogan Syndrome
- •Marginal Corneal Infiltrates Associated With Blepharoconjunctivitis
- •Peripheral Ulcerative Keratitis Associated With Systemic Immune-Mediated Diseases
- •Mooren Ulcer
- •Corneal Transplant Rejection
- •Immune-Mediated Diseases of the Episclera and Sclera
- •Episcleritis
- •Scleritis
- •8 Clinical Approach to Neoplastic Disorders of the Conjunctiva and Cornea
- •Approach to the Patient With a Neoplastic Conjunctival Lesion
- •Management of Patients With Conjunctival Tumors
- •Surgical Treatment
- •Topical Chemotherapy
- •Tumors of Epithelial Origin
- •Benign Epithelial Tumors
- •Preinvasive Epithelial Lesions
- •Malignant Epithelial Lesions
- •Management of Atypical Epithelial Tumors
- •Other Malignant Epithelial Lesions
- •Glandular Tumors of the Conjunctiva
- •Oncocytoma
- •Sebaceous Gland Carcinoma
- •Tumors of Neuroectodermal Origin
- •Benign Pigmented Lesions
- •Preinvasive Pigmented Lesions
- •Malignant Pigmented Lesions
- •Neurogenic and Smooth-Muscle Tumors
- •Vascular and Mesenchymal Tumors
- •Benign Tumors
- •Malignant Tumors
- •Lymphatic and Lymphocytic Tumors
- •Lymphangiectasia and Lymphangioma
- •Lymphoid Hyperplasia
- •Lymphoma
- •Metastatic Tumors
- •9 Basic and Clinical Concepts of Congenital Anomalies of the Cornea, Sclera, and Globe
- •Developmental Anomalies of the Globe and Sclera
- •Cryptophthalmos
- •Microphthalmos
- •Nanophthalmos
- •Blue Sclera
- •Developmental Anomalies of the Anterior Segment
- •Anomalies of Size and Shape of the Cornea
- •Abnormalities of Corneal Structure and/or Clarity
- •Secondary Abnormalities Affecting the Fetal Cornea
- •Intrauterine Keratitis: Bacterial and Syphilitic
- •Congenital Corneal Keloid
- •Congenital Corneal Anesthesia
- •Congenital Glaucoma
- •Birth Trauma
- •Arcus Juvenilis
- •10 Corneal Dystrophies and Ectasias
- •Corneal Dystrophies
- •Epithelial and Subepithelial Dystrophies
- •Bowman Layer Corneal Dystrophies
- •Stromal Corneal Dystrophies: TGFBI Dystrophies
- •Stromal Dystrophies: Non-TGFBI Dystrophies
- •Endothelial Dystrophies
- •Ectatic Disorders
- •Keratoconus
- •Pellucid Marginal Degeneration
- •Keratoglobus
- •11 Systemic Disorders With Corneal Changes
- •Disorders of Carbohydrate Metabolism
- •Mucopolysaccharidoses
- •Diabetes Mellitus
- •Disorders of Lipid Metabolism and Storage
- •Hyperlipoproteinemias
- •Hypolipoproteinemias
- •Sphingolipidoses
- •Mucolipidoses
- •Disorders of Amino Acid Metabolism
- •Cystinosis
- •Tyrosinemia
- •Alkaptonuria
- •Disorders of Protein Metabolism
- •Amyloidosis
- •Disorders of Immunoglobulin Synthesis
- •Noninflammatory Disorders of Connective Tissue
- •Ehlers-Danlos Syndrome
- •Marfan Syndrome
- •Disorders of Nucleotide Metabolism
- •Gout
- •Porphyria
- •Disorders of Mineral Metabolism
- •Wilson Disease
- •Hypercalcemia
- •Hemochromatosis
- •Corneal and External Disease Signs of Systemic Neoplasia
- •Enlarged Corneal Nerves
- •Appendix
- •12 Clinical Approach to Depositions and Degenerations of the Conjunctiva, Cornea, and Sclera
- •Degenerative Changes of the Conjunctiva
- •Age-Related (Involutional) Changes
- •Pinguecula
- •Pterygium
- •Conjunctival Concretions
- •Conjunctival Inclusion Cysts
- •Conjunctivochalasis
- •Conjunctival Vascular Tortuosity and Hyperemia
- •Degenerative Changes in the Cornea
- •Age-Related (Involutional) Changes
- •Epithelial and Subepithelial Degenerations
- •Stromal Degenerations
- •Endothelial Degenerations
- •Scleral Degenerations
- •Drug-Induced Deposition and Pigmentation
- •Corneal Epithelial Deposits
- •Stromal and Descemet Membrane Pigmentation
- •Endothelial Manifestations
- •13 Clinical Aspects of Toxic and Traumatic Injuries of the Anterior Segment
- •Injuries Caused by Temperature and Radiation
- •Thermal Burns
- •Ultraviolet Radiation
- •Ionizing Radiation
- •Chemical Injuries
- •Alkali Burns
- •Acid Burns
- •Management of Chemical Injuries
- •Toxic Keratoconjunctivitis From Medications
- •Pathogenesis
- •Clinical Presentation
- •Management
- •Animal and Plant Substances
- •Insect Injuries
- •Vegetation Injuries
- •Concussive Trauma
- •Subconjunctival Hemorrhage
- •Corneal Changes
- •Traumatic Mydriasis and Miosis
- •Traumatic Iritis
- •Iridodialysis and Cyclodialysis
- •Traumatic Hyphema
- •Nonperforating Mechanical Trauma
- •Conjunctival Laceration
- •Conjunctival Foreign Body
- •Corneal Foreign Body
- •Corneal Abrasion
- •Perforating Trauma
- •Evaluation
- •Management
- •Surgical Trauma
- •Corneal Epithelial Changes From Intraocular Surgery
- •Descemet Membrane Changes During Intraocular Surgery
- •Corneal Endothelial Changes From Intraocular Surgery
- •Conjunctival and Corneal Changes From Extraocular Surgery
- •14 Treatment of Ocular Surface Disorders
- •Surgical Procedures of the Ocular Surface
- •Limbal Transplantation
- •Autologous Conjunctival Transplantation
- •Pterygium Excision
- •Mucous Membrane Grafting
- •Conjunctival Flap
- •Conjunctival Biopsy
- •Conjunctivochalasis Excision
- •Therapeutic Interventions for Corneal Disease
- •Superficial Keratectomy and Corneal Biopsy
- •Management of Descemetocele, Corneal Perforation, and Corneal Edema
- •Corneal Tattoo
- •Tarsorrhaphy
- •15 Clinical Approach to Corneal Transplantation
- •Corneal Transplantation
- •Eye Banking and Donor Selection
- •Criteria Contraindicating Donor Cornea Use
- •Surgical Approach to Corneal Disease
- •Preoperative Evaluation and Preparation
- •Penetrating Keratoplasty
- •Surgical Technique for Penetrating Keratoplasty
- •Combined Procedures
- •Intraoperative Complications
- •Postoperative Care and Complications
- •Control of Postoperative Corneal Astigmatism and Refractive Error
- •Diagnosis and Management of Graft Rejection
- •Pediatric Corneal Transplantation
- •Corneal Autograft Procedures
- •Keratoprosthesis
- •Lamellar Keratoplasty
- •Anterior Lamellar Transplantation
- •Surgical Technique
- •Postoperative Care and Complications
- •Endothelial Keratoplasty
- •DSEK Surgical Technique and Complications
- •Descemet Membrane Endothelial Keratoplasty
- •Basic Texts
- •Related Academy Materials
- •Requesting Continuing Medical Education Credit
pedunculated papillomatous or polypoid lesions in the conjunctiva, which may be associated with similar lesions in the nose and nasopharynx.
Septate Filamentous Fungi
A significant majority of external ocular mold infections are caused by septate fungi. Fusarium species (eg, Fusarium solani and Fusarium oxysporum) are common pathogens encountered in warm, humid environments as a cause of fulminant keratitis. Among the genera that have been isolated from the external eye are Aspergillus, Alternaria, Curvularia, Paecilomyces, Scedosporium, and
Phialophora. Some filamentous fungal corneal infections are more indolent. Most cases of oculomycosis occur following trauma with vegetative matter and, less frequently, with contact lens usage.
Nonseptate Filamentous Fungi
Nonseptate filamentous fungi include the Mucor, Rhizopus, and Absidia species in class Zygomycetes, order Mucorales, family Mucoraceae. These ubiquitous fungi are an uncommon cause of external ocular infections, but they can cause life-threatening infections of the paranasal sinuses, brain, and orbit in immunocompromised patients, with particular predilection for those with failure of normal phagocytic responses due to acidosis from diabetes mellitus or renal failure. Fungal invasion of blood vessels results in ischemic necrosis (blackened char) of affected tissues.
Pneumocystis jiroveci (previously Pneumocystis carinii) was formerly classified as Protozoa, but gene sequencing has placed the organism firmly in the Fungi kingdom. P carinii is an important cause of choroiditis in HIV-infected individuals, the incidence of which is declining in the era of antiretroviral therapy.
Thomas PA, Geraldine P. Oculomycosis. In: Collier L, Balows A, Sussman M, eds. Topley & Wilson’s Microbiology and Microbial Infections. 10th ed. Medical Mycology, ed Merz WG, Hay RJ. London: Hodder Arnold; 2005:chap 16.
Parasitology
Protozoa
Acanthamoeba species are protozoa (unicellular eukaryotes) that can cause an isolated infection of the human cornea as their primary disease in humans. Other conditions have been described, such as disseminated dermatitis, visceral infestation, and encephalitis unrelated to ocular disease. The Acanthamoeba life cycle includes a motile trophozoite form (15–45 μm in diameter) and a dormant cyst form (10–25 μm in diameter) (Fig 5-7). The cysts are double-walled and very hardy, resistant to most environmental extremes and toxins, including chlorine. Classification of Acanthamoeba species has been based on morphology, but molecular methods are more accurate and increasingly utilized.
Figure 5-7 Acanthamoeba cyst. (Diff-Quick stain ×100.) (Courtesy of Elmer Y. Tu, MD.)
Microsporidia are obligate intracellular parasites and have recently been linked to fungi. Their spores enter eukaryotic cells through a polar tube that opens a hole in the eukaryotic cell membrane. Growth and differentiation of the sporoplasm result in the formation of intracellular spores that may be liberated by lysis of the host cell. Of the phylum Microspora, the following genera have been implicated in human infection: Nosema, Encephalitozoon, Pleistophora, Vittaforma (formerly Nosema corneum), Trachipleistophora, Enterocytozoon, and unclassified microsporida.
Toxoplasma gondii causes one of the most common parasitic infections of humans and is a common cause of chorioretinitis (see BCSC Section 9, Intraocular Inflammation and Uveitis). Cats shed oocysts in their feces after ingestion of T gondii. Oocysts may be ingested by human-food animals such as swine; the cyst-containing meat of these animals is then eaten by humans. Alternatively, cysts may be ingested directly by human contact with cat feces or feces-contaminated water. Transplacental transmission to the fetus of T gondii tachyzoites can result in a devastating fetal infection. See BCSC Section 6, Pediatric Ophthalmology and Strabismus, for discussion of the consequences of maternal transmission of toxoplasmosis.
Leishmania species
Cutaneous leishmaniasis is transmitted by the bite of its vector, the female sandfly, in endemic areas of tropical Asia, Africa, and Latin America. Leishmania organisms hide within the phagolysosomal system of macrophages. An infected eyelid ulcer may become granulomatous. Scrapings or biopsy material can show intracellular parasites by Giemsa or immunofluorescent stains. The parasites can sometimes be isolated on blood agar or insect tissue culture medium.
Helminths
Onchocerciasis is caused by onchocercal filariae transmitted by the bite of the blackfly (Simulium), which lays its eggs on vegetation in fast-flowing rivers (hence the common name river blindness) and is endemic in parts of sub-Saharan Africa, the Middle East, and Latin America. Microfilariae penetrate the skin and mature in nodules at the site of the bite for approximately 1 year, after which mating produces microfilariae offspring (≈300 μm in length)—up to 1500 a day per female (100 cm in length). These worms can live as long as 15 years in the human host; thus, diagnosis can be made
with skin snips demonstrating the microfilariae.
Migration of microfilariae to the skin and eye results in clinical onchocerciasis, and subsequent blackfly bites can carry the organism to other individuals. Microfilariae enter the peripheral cornea, where they can be visualized by slit-lamp examination, and may reach the inner eye. Keratitis (including punctate keratitis and “snowflake” and sclerosing peripheral corneal opacities), anterior uveitis, and chorioretinitis occur upon death of the microfilariae. The intense, blinding inflammatory keratitis has been shown to be a reaction less to the microfilariae than to a bacterial endosymbiont, Wolbachia, which is essential for filariae reproduction. Antifilarial therapy can produce a systemic inflammatory response, but prior treatment with systemic doxycycline has been shown to reduce this response. Treatment by nodulectomy, oral ivermectin, and control of local blackfly populations has been successful in selected areas.
Loa loa larvae enter the skin at the bite of an infected Chrysops (mango horsefly). Adult worms may grow to 6 cm in length and migrate through the connective tissues, causing transient hypersensitivity reactions. Loa loa may appear beneath the conjunctiva.
Visceral larval migrans is a multisystem disease in young children and is caused by the migrating larvae of Toxocara canis and Toxocara cati, natural residents of dogs and cats, respectively. Toxocara larvae develop and mate in the intestines of their natural host; human ingestion of fertilized eggs in pet feces results in infection. Toxocara larvae in the human intestine do not receive the proper environmental signals and migrate throughout the body, invading and destroying tissues as they go. Ocular larval migrans occurs in older children, and the viscera are typically spared.
Taenia solium, the pork tapeworm, is transmitted to humans from ingestion of undercooked pork containing the larval stage (cysticercus). In the stomach, proteolytic enzymes dissolve the cysticercus capsule. Adult worms attach to the intestinal wall by means of suckers at the head (scolex) and release eggs that then disseminate. A hydatid cyst can subsequently form in various tissues, including the eye and orbit, to cause cysticercosis.
Arthropods
Phthirus pubis
Phthiriasis is a venereally acquired crab louse (Phthirus pubis) infestation of coarse hair in the pubic, axillary, chest, and facial regions. Adult female crab lice (Fig 5-8) and immature nits on the eyelashes cause blepharoconjunctivitis.
Figure 5-8 Crab louse (Phthirus pubis). (Wet mount ×200.)
