- •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
should be noted, with the following considered:
Is there a single lesion, or is it multifocal? Is the lesion pigmented or amelanotic?
Where is it located—on the bulbar conjunctiva, at the limbus, in the fornix, on the palpebral conjunctiva?
Does the lesion extend onto the cornea? Is the lesion solid or cystic?
Is it flat or elevated?
Is the lesion fixed to the underlying tissues, or is it mobile? Is there a feeder vessel?
The entire ocular surface should be examined, including the entire superior fornix, which requires eyelid eversion. The clinician should document the appearance and extent of the lesion, using either photographs or a detailed diagram. This aids in surgical planning if the lesion is to be removed, or in following the lesion if observation is recommended.
Management of Patients With Conjunctival Tumors
An experienced clinician will often have an opinion about the nature of a conjunctival lesion after completion of the history and physical examination. However, definitive diagnosis almost always requires tissue for histologic evaluation. Lesions that cause concern for possible malignancy are
elevated lesions
extensive pigmented lesions, even if flat lesions fixed to the underlying tissues lesions with a large feeder vessel
These lesions should be managed as described in the following sections.
Many conjunctival lesions are not worrisome for malignancy (eg, inclusion cysts); others will be indeterminate based on the history and the results of the clinical examination. For these cases, observation may be a reasonable option. If observation is elected, regular ophthalmic examinations are essential. If growth or changes in the characteristics of the lesion are documented, one should proceed to surgery.
Surgical Treatment
The standard surgical treatment of a suspicious lesion of the conjunctiva is complete removal of the tumor, including 4 mm of uninvolved tissue surrounding the lesion when possible. The surgeon attempts to avoid touching the tumor during removal (a “no touch” technique) in order to prevent inadvertent seeding of the remaining conjunctiva with tumor cells. Incisional biopsies should be avoided for the same reason, especially in pigmented lesions of the conjunctiva. Involvement of the corneal epithelium is managed using alcohol-assisted epithelial curettage with a surgical blade, with care taken to avoid violation of the Bowman membrane, which is a natural barrier to tumor extension into the corneal stroma. Some lesions may require lamellar sclerectomy for complete removal. Cryotherapy at the time of ocular surface surgery has been shown to improve the prognosis,
especially in conjunctival melanoma.
Once the tumor is removed, additional manipulations should be performed with clean surgical instruments in order to reduce the chance of tumor seeding. Primary conjunctival closure or a conjunctival autograft may be considered if the conjunctival defect is small. Ocular surface reconstruction with amniotic membrane transplantation is useful in the management of conjunctival lesions and allows for wider tumor margins with less risk of postoperative scarring. Amniotic membrane also facilitates reepithelialization and reduces postoperative inflammation. The graft should be cut slightly larger than the defect and may be attached with fibrin-based tissue adhesive. If tissue adhesive is not available, either absorbable (9-0 or 10-0 polyglactin) or nonabsorbable (10-0 nylon) suture may also be used to fixate the graft. If more than two-thirds of the limbus is removed, chronic epitheliopathy may result. Stem cell transplantation using tissue harvested from the fellow eye of the patient may eventually be required.
Once removed from the ocular surface, the lesion can be placed on filter paper and the edges labeled to facilitate histopathologic diagnosis. Care should be taken to avoid damage to the specimen during removal, as any damage could make the lesion more difficult to interpret. The clinical history is relevant to the pathologist’s interpretation of the lesion; thus, the label should include the following information: the age and ethnicity of the patient, the duration of the lesion, and whether the lesion has changed clinically. Diagnosis of conjunctival tumors can be challenging, especially for general pathologists. If possible, conjunctival tumors should be read by an ophthalmic pathologist. Immunostaining can help in distinguishing benign from malignant lesions. Histopathologic findings of various ocular surface tumors are reviewed in BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors.
Topical Chemotherapy
Topical chemotherapy can be used in the management of ocular surface tumors as primary treatment before or instead of surgical tumor removal or, more commonly, as an adjunctive therapy after tumor excision. An advantage of topical chemotherapy is that it treats the entire ocular surface. For squamous lesions, topical interferon-α2b is first-line therapy. Topical mitomycin C (MMC) or 5- fluorouracil (5-FU) may be considered for squamous lesions that do not respond to interferon-α2b. For atypical melanocytic lesions, MMC is the most commonly used agent.
Topical interferon-α2b is very well tolerated. Recent reports have suggested the use of topical interferon-α2b as primary therapy for tumors in the squamous cell family; however, one potential disadvantage of this course of treatment is the lack of histopathologic diagnosis. In addition, the effectiveness of topical interferon-α2b in the treatment of melanotic tumors has not been proven. Since there is some overlap in the appearance of various tumors (eg, amelanotic conjunctival melanoma may resemble squamous cell carcinoma), there is concern that if chemotherapy is elected and the tumor does not respond, valuable time in the management of a potentially deadly lesion may have been lost. Another disadvantage of topical interferon-α2b is that it is expensive and may take several months to work. Some authors advocate using topical interferon-α2b before definitive surgical removal, with the purpose of trying to shrink large ocular surface squamous tumors preoperatively.
The optimal topical chemotherapy regimen has not been determined in controlled studies, but, typically, topical interferon-α2b is given 4 times daily until clinical response occurs, usually within 2 to 4 months. Topical MMC, because of its potential toxicity, is typically administered for short
