opthalmic pathology-conjunctival-pathology

1Conjunctival pathology

CHAPTER 4. CONJUCTIVAL PATHOLOGY

Anatomy of the conjunctiva

Definition: Thin mucous membrane lining the inner surface of the eyelid, and covers the anterior surface of the globe● Gross picture:

○ Parts: The conjunctiva is formed of five parts named according to related structures: – Palpebral conjunctiva – Marginal conjunctiva– Transitional zone between skin and sulcus subtarsalis (Stratified squamous epithelium)– Lacrimal puncti open in marginal conjunctiva– Tarsal conjunctiva: vascular, tightly adherent to the back of the tarsus

○ Fornical conjunctiva:– Represents the reflection of the conjunctiva at the corners – Four in numbers (superior, inferior, medial and lateral)– Superior fornix is the deepest. It reaches the superior orbital margin at 8-10 mm from the limbus – Inferior fornix extends 8 mm from the limbus. Superior and inferior fornices are adherent to expan-

sions of from the sheaths of the levator and rectus muscles via areolar tissue. These adhesions deep-en the fornices

– Medial fornix is the shallowest ○ Bulbar conjunctiva:

– Loose over the sclera– It becomes firmly adherent to episclera within 3 mm from the limbus

○ Plica semilunaris: – Crescentic conjunctival fold at the inner canthus representing remnant of the nictitating membrane

of animals– The epithelium is nonkeratinized squamous with goblet cells– Contains fatty tissue, skin appendages and accessory lacrimal glands

○ Caruncle:– Dense fibrovascular triangular elevation at the inner canthus covered by stratified squamous epithe-

lium – Represents a muco-cutaneous ovoid transition zone between conjunctival epithelium and the skin

epidermis– Contains hair, sebaceous and sweat glands, lobules of lacrimal gland and striated muscles

● Microscopic picture:○ Conjunctival epithelium:

– Origin: Surface ectoderm which also forms the epidermis of the skin, the corneal and lens epithelia– Type: Nonkeratinized stratified squamous epithelium with goblet cells, which are abundant near the

fornices – Conjunctival melanocytes are found at the limbus, fornix, plica, caruncle and the sites of perforation

of anterior ciliary vessels– Langerhans cells: dendritic cells found mainly in tarsal conjunctiva, fornix and bulbar conjunctiva

○ Accessory lacrimal glands:– Glands of Krause: located in the deep conjunctival tissue in:

□ Upper fornix: 42 in number □ Lower fornix: 6-8 in number

IHAB-ch4_CS3ME.indd 1IHAB-ch4_CS3ME.indd 1 28-1-2009 13:46:2828-1-2009 13:46:28

Chapter 42

□ Their ductules unite into a single duct which opens in the fornix – Glands of Wolfring: larger than glands of Krauze and located in:

□ Above mid-superior tarsus: 2-5 in number □ Lower edge of inferior fornix: 2 in number

○ Substantia propria: – Loose connective tissue stroma with scattered lymphocytes (predominantly T-cells), lymphoid fol-

licles (correspond to mucosa associated lymphoid follicles of the gut and bronchi), plasma cells and Langerhans’ cells (dendritic cells expressing class II antigen)

– Substantia propria of bulbar conjunctiva is loose and areolar, thus permitting chemosis. It contains a network of perilimbal capillaries giving nutrition to peripheral cornea

● Conjunctival cytology:○ Normal epithelium shows the following:

– Epithelial cells have a round nucleus and homogeneous cytoplasm– Cells are flat squamous epithelial cells – In smear, they appear cuboidal and clump in sheet – Goblet cells: Contain clump of pale staining mucus containing flake shaped cells displacing the nu-

cleus toward the edge of cell membrane giving the cell a ‘signet-like ring appearance’ ○ Epithelial abnormalities: Abnormal epithelium may be due to abnormal cellular morphology or pres-

ence of abnormal cells. Abnormal epithelium can be obtained through impression cytology or exfolia-tive cytology (stained with Giemsa and Gram stain): – Presence of polymorph nuclear leucocytes indicates bacterial conjunctivitis – Presence of eosinophils suggests allergic conjunctivitis– Presence of lymphocytes indicates viral conjunctivitis – Presence of polymorph nuclear leucocytes, and lymphocytes points to Chlamydia trachomatis con-

junctivitis with presence of basophilic intracytoplasmic inclusion bodies – In alcohol fixed Pap stained smear, squamous dysplasia or malignancy is indicated by nuclear hyper-

chromasia and high nuclear/cytoplasmic ratio and pleomorphism● Vascular supply:

○ Arterial supply:– Posterior conjunctival arteries:

□ Origin: Palpebral arteries from the tarsal arcades □ Distribution: Conjunctiva-limbus

– Anterior conjunctival arteries:□ Origin: Anterior ciliary arteries□ Distribution: Limbal conjunctiva

○ Venous drainage:– Anterior conjunctival veins drain into anterior ciliary veins– Posterior conjunctival veins drain into palpebral veins

○ Lymphatics: drain into the preauricular and submandibular lymph nodes● Nerve supply:

○ Same as palpebral nerve supply ○ Long ciliary nerves supply the circumcorneal conjunctiva and cornea

Vascular abnormalities

1. HyperemiaPrimary: Active vasodilatation in response to inflammation



Secondary:● Passive (vascular congestion due to venous obstruction):

○ Space occupying orbital lesions○ Increased blood viscosity

● Active: increased filling of arterial system: ○ Arterializations in carotid-cavernous fistula○ External carotid shunting in internal carotid occlusion

● Paroxysmal: associated with simultaneous lacrimation and rhinorrhea○ Charlin’s syndrome (migrainous nasociliary neuritis)○ Horton’s cephalgia○ Sluder’s syndrome (neuralgia of the sphenopalatine ganglion)

2. Vascular sludgingIncreased blood viscosity or decreased circulatory velocity

3. ChemosisEdema due to increased permeability of conjunctival vessels

4. Subconjunctival hemorrhageDifferential diagnosis:● Idiopathic (spontaneous without sequelae)● Traumatic● Inflammation:

○ Viral conjunctivitis○ Febrile illness○ Subacute bacterial endocarditis○ Trichinosis

● Vascular:○ Hypertension and arteriosclerosis○ Orbital stasis○ Hemorrhagic diathesis: vitamin C deficiency (scurvy)

NB: Kaposi’s sarcoma can mimic subconjunctival hemorrhage

5. Telangiectasia● Rendu-Osler-Weber syndrome ● Louis-Bar syndrome ● Fabry’s disease● Sturge-Weber syndrome

6. Microaneurysms Definition: Saccular dilatation of the capillary network Etiology: ● Diabetes● Hypertension● Arteriosclerosis● Carotid occlusion● Sickle hemoglobinopathy (Hb-SS disease): Paton’s sign: comma-shaped conjunctival microaneurysms


Chapter 44

Congenital lesions

1. Cryptophthalmos

2. Epitarsus

3. Congenital ectropion

4. Congenital lymphedema

5. Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)

6. Epidermoid (see eyelid pathology section)

7. Congenital dermoidDefinition: Choristoma formed of variety of tissues including fat, muscle, hair follicles, cartilageEtiology: ● Isolated finding ● Associated with syndromes:

○ Goldenhar syndrome ○ Treacher-Collins syndrome ○ Nevus sebaceous of Jadassohn

Pathology: ● Smooth yellowish subconjunctival nodules ● Inferotemporal quadrant ● Encroaching on cornea ● Dermoid are commonly solid and may be cystic ● Dermoids are formed of interweaving, coarsely thickened collagen fibers covered by skin-like epi the-

lium● Contains epidermal appendages (hair, sebaceous and sweat glands)

8. Dermolipomas● Soft mobile subconjunctival nodules seen in adults superotemporal conjunctiva● Choristoma of fat and connective tissue● Can extend deep within orbit (should be excised carefully)

9. Complex choristomaAlso contains cartilage, fat and lacrimal gland elements

Immunological disorders with conjunctival findings

1. Ataxia telangiectasia (Louis-Bar syndrome)

2. Hereditary angioneurotic edema● Autosomal dominant● C1 esterase inhibitor deficiency

3. Toxic epidermal necrosis (Yell’s syndrome)

4. Weskit-Aldrich syndrome



Conjunctival inflammation

1. Acute conjunctivitisDefinition: Acute self-limited infection of conjunctival surface of less than 3 weeks durationEtiology: ● Bacterial:

○ Streptococcus pneumoniae○ Staphylococcus aureus ○ Hemophilus influenza

Pathology: ● Hyperemia, chemosis and purulent discharge● Presence of polymorph nuclear leucocytes in substantia propria and epithelium ● Mucopurulent discharge ● Petechial hemorrhages● Outcome:

○ Resolution○ Chronicity

● Complications:○ Superficial crescentic marginal ulcer○ Iridocyclitis (pneumococci)

2. Purulent conjunctivitisDefinition: An acute severe suppurative form of conjunctivitis with generalized manifestationsEtiology: ● Forms:

○ Purulent conjunctivitis of adults○ Ophthalmia neonatorum

● Onset: Explosive (few hours to few days)● Organisms:

○ Gram-negative cocci: – Neisseria gonorrhea (60- 80%) – Staphylococci– Streptococci

○ Gram-positive bacilli: DiphtheriaPathology: ● Massive purulent discharge ● Severe hyperemia and chemosis ● Eyelid edema ● Membrane formation ● Complications:

○ Corneal ulceration:– Gonococci invade corneal epithelium– Keratitis: 15-40%

□ Diffuse epithelial infiltration □ Marginal infiltrates □ Corneal ulcers:

▪ Marginal ulcer▪ Ring ulcer▪ Central ulcer


Chapter 46

○ Iridocyclitis○ Spastic ectropion○ Chronicity

3. True membranous conjunctivitisDefinition: Acute infective conjunctivitis characterized by true membrane formationEtiology:● Organism: Corynebacterium diphtheria bacilli

○ Age: 2-5 years ○ Season: Winter○ Gonococcus○ Beta-hemolytic streptococci○ Stevens-Johnson syndrome

Pathology: ● Characteristics of membrane:

○ Formed as a result of toxin diffusion ○ Composition: necrotic epithelium, exotoxin and diphtheria bacilli entangled in fibrin and dense neutro-

phils ○ Adherent to basement membrane ○ Peeling results in a raw bleeding surface○ The underlying tissues are markedly congested and infiltrated with heavy neutrophils

● Local complications result from excessive fibrosis and include the following:○ Eyelid: Trichiasis, entropion○ Conjunctiva: Symblepharon, xerosis○ Cornea: Ulcers, pseudopterygia

● General complications result from exotoxin production which circulates in the blood stream, causing:○ Toxic myocarditis○ Toxic glomerulonephritis and albuminuria○ Toxic neuritis:

– Cranial nerve palsies (3,4,6) result in paralytic squint – Parasympathetic nerve palsy results in loss of accommodation

4. Pseudomembranous conjunctivitis Definition: ● Pseudomembrane is formed of fibrin network entangling PNLs, deposited on the surface epithelium● The pseudomembrane is less adherent and peels without bleedingEtiology: Pseudomembrane formation is associated with the following:● Viral conjunctivitis:

○ Herpes simplex virus○ Adenovirus 8 (epidemic keratoconjunctivitis, EKC)○ Adenovirus 3 (pharyngo-conjunctival fever, PCF)

● Bacterial○ Staphylociccus aureus○ Streptococcus pneumoniae○ Meningococcus○ Pseudomonas○ Coiliforms

● Chemical burn● Ocular pemphigoid



● Foreign body● Ligneous conjunctivitisPathology: ● Table 1 shows the main differences between true and pseudomembranous conjunctivitis

Table 1. Differences between membranous and pseudo-membranous conjunctivitis

Membranous conjunctivitis Pseudo-membranous Conjunctivitis

Etiology Diphtheria bacilli Pneumococci, viruses, fungiCaustics, atropine allergy

Membrane composition Necrotic epithelium, fibrin, bacilli Coagulated discharge rich in fibrin

Adhesions to BM Firmly adherent Loosely adherent

Removal Results in a raw bleeding surface No bleeding

5. Viral conjunctivitisEtiology: ● Papillomavirus: inducing the following:

○ Conjunctival papilloma ○ Conjunctival intraepithelial neoplasia ○ Squamous cell carcinoma

● Human herpes virus type-8 involved in: Kaposi sarcoma ● Adenoviral keratoconjunctivitis:

○ Definition: Contact infection by adenovirus subgroups inducing: – Simple follicular conjunctivitis: mild, transient – Pharyngo-conjunctival fever (serotypes 3 or 7)– Epidemic keratoconjunctivitis (serotypes 8, 19, 37):

□ Associated upper respiratory tract infection□ Bilateral conjunctivitis

Pathology: ● Severe follicular conjunctivitis ● Conjunctival petechial hemorrhages ● Pseudomembrane formation ● Cornea:

○ Multifocal subepithelial infiltrates ○ Large central corneal erosion

Complications: ● Subepithelial conjunctival scarring ● Symblepharon formation● Dry eyes

Chronic conjunctivitis

Definition: Unilateral or bilateral conjunctivitis, persisting more than 4 weeks 1. Follicular conjunctivitisDefinition: Non-specific inflammation representing a reactive hyperplasia of conjunctival resident popula-tion of lymphocytes (specially at fornices)(well-circumscribed focus of lymphoid hyperplasia)


Chapter 48

Pathology: ● Gross picture: Gray-white round to oval elevations or granularity● Microscopic picture:

○ Follicles containing a mixture of centrocytes, centroblasts, lymphocytes and macrophages– More mature lymphocytes and vessels at periphery– Overlying epithelium is usually thinned

○ Healing is without fibrosis (except in trachoma)Differential diagnosis:● Infectious-acute:

○ Adenoviruses (type 3-PCF; type 8-EKC)○ Herpes simplex virus: Newcastle virus (swimming pool conjunctivitis)○ Enterovirus 70 (acute hemorrhagic conjunctivitis)○ Inclusion conjunctivitis of adults (paratrachoma)○ Blood-borne (measles, German measles)

● Infectious-chronic: Trachoma, psittacosis, moraxella and infectious mononucleosis● Non-infectious:

○ Pseudo-trachoma○ Topical medications (IDU, eserine, atropine)○ Cosmetics○ Antigenic meterial (e.g., ‘crab’ droppings)○ Allergy (exogenous agents)○ Physiological folliculosis of childhood

2. Papillary hypertrophy (conjunctival papillae)Definition: Nonspecific change in the tarsal conjunctiva characterized by presence of papillary hypertro-phyPathology: ● Papillae are more common in inferior tarsal conjunctiva● Papillae are characterized by:

○ Central vascular tuft, rich vascular stroma with chronic inflammatory cells (lymphocytes, plasma cells and eosinophils) and granulation tissue

○ Pale avascular valleys○ Hyperplastic epithelium, thrown into folds ○ Stromal hyperplasia ○ Deep infoldings of epithelium

3. Pseudoglands of HenleGland-like invaginations formed by proliferating tarsal conjunctival epithelium and goblet cells, lymphocytes and plasma cells in stroma

4. Parinauds oculoglandular syndromeDefinition: Granulomatous conjunctivitis with regional lymphadenopathy (preauricular node)Differential diagnosis:● Acute conjunctivitis:

○ Bacterial conjunctivitis○ Viruses (especially Epstein-Barr virus, infectious mononucleosis)

● Chronic conjunctivitis:○ Cat scratch fever (silver stain for bacteria Bartonella henselae)○ Tularemia



○ Actinomycosis○ Leptotrichosis○ Tuberculosis○ Syphilis○ Rickettsia○ Chlamydia (lymphogranuloma venereum)○ Sarcoidosis

Ligneous conjunctivitis

Definition: Bilateral, chronic fibrinous pseudomembranous conjunctivitisEtiology:● Begins in childhood● Recurrent● Caused by heritable mutations in plasminogen with severe deficiency in type I plasminogen ● Systemic form have similar lesions in vagina, other mucosal membranesPathology: ● Yellowish plate-like masses overlying palpebral conjunctiva ● Massive accumulation of fibrin and granulation tissue● Microscopic picture: Thick fibrin associated with epithelial cells, inflammatory membrane and

mononuclear cells

Angular conjunctivitis

Definition: Acute infection of the eyelid canthi Etiology: ● Morax Axenfeld, gram negative diplobacilli● The organism produces proteolytic enzymes which have a predilection to the canthi due to deficient

lysozymes present in tears at canthiPathology: ● Gross picture:

○ Inner and outer canthi show white and foamy angular discharge○ Maceration, redness of skin and conjunctiva○ Marginal corneal ulcers

● Microscopic picture: ○ Thin epithelium with parakeratosis○ Eyelid edema ○ Conjunctiva shows increase in goblet cells, with diffuse stromal infiltration by polymorph nuclear leu-

cocytes and plasma cells ○ Organism is seen extracellularly

● Outcome: Chronicity

Viral conjunctivitis (trachoma)

1. Chlamydial conjunctivitisTRIC agents (trachoma, inclusion conjunctivitis) are gram-negative, basophilic, small obligate intracellular parasites sensitive to antibiotics. Infected cells contain elementary bodies and initial inclusions bodies.Definition: Chronic conjunctivitis caused by Chlamydia trachomatis characterized by initial epithelial infection followed by subepithelial inflammation with follicles, papillae and pannus formation in substantia


Chapter 410

propria and healing by fibrosis leading occasionally to eyelid deformity and visual disabilityEtiology: Trachoma is caused by a gram-negative basophilic organism which is considered an atypical virus. It is an obligate intracellular organism. Three species exist:● Chlamydia trachomatis● Chlamydia psittaci● Chlamydia pneumoniaThe organism is similar to viruses being an obligate intracellular organism, with the following differences:● Larger in size (250 μ) ● Contains both DNA and RNA● Replicates by binary fission● No long lasting immunity after infection (being epitheliotropic)● Responds to antibiotics (sulfacetamide)● Giemsa stain shows basophilic inclusion bodyTrachoma is the leading cause of preventable blindness worldwide. It affects more than 400 million people in endemic areas (Africa, India and Middle East). Nearly all children are infected by age 2 in endemic areas:● Human acts as a reservoir with infected mucosa (GIT, URT)● Trachoma may spread via feces, airborne particles and fliesTransmission:● Direct contact with ocular secretions● Vectors: Flies that land on infected mucosaPathology: ● The organism is strictly epitheliotropic. It affects substantia propria by toxin diffusion ● Conjunctival smear shows:

○ Polymorph nuclear leucocytes, plasma cells and lymphocytes○ Epithelial cells contain initial bodies, basophilic intracytoplasmic inclusions of Halberstaedter and

Prowazek (Giemsa stain)○ Free elementary bodies ○ Immunohistochemical stains help in diagnosis

● WHO classification: This is a generalized classification system for non-specialists in the field to study the epidemiologic aspect of the disease. Patients must have two criteria to make the diagnosis: ○ TF: Trachomatous inflammatory follicles: ≥5 in upper tarsal conjunctiva○ TI: Trachomatous inflammation-intense: Pronounced inflammatory thickening of upper tarsal con-

junctiva○ TS: Trachomatous scarring (Arlt's line) ○ TT: Trachomatous trichiasis○ CO: Corneal opacity

● MacCallan’s classification (1908): Conjunctival manifestations.Trachoma is an epitheliotropic organism affecting conjunctival, corneal and lacrimal system epithelium. It secretes toxins that diffuse into deeper structures inducing a chronic inflammatory reaction (follicles). Healing occurs by fibrosis.

○ Stage I: (T1) incipient trachoma:– Immature follicles in palpebral conjunctiva and fornix– Follicles are < 1mm, flat with the conjunctival surface and not expressible– Follicles are surrounded by dilated capillaries

○ Stage II (T2):– T2a: Typical florid follicular conjunctivitis with follicular hypertrophy and necrosis:

□ Mature superficial tarsal follicles



□ Raised above conjunctival surface□ Increase in size of follicles results in compression of blood vessels with central necrosis and

pouting out of expressible gelatinous material □ Limbal keratitis and vascular pannus formation

– T2b: Papillary conjunctivitis (no scarring): Conjunctival epithelial hyperplasia on top of follicles → papillae formation□ Fine, pink, finger-like projections□ Increase weight of the eyelid results in mechanical ptosis□ Velvety appearance of the lid□ Stage T2b is further subdivided into:

▪ T2b1:Typical papillary trachoma▪ T2b2: T2b1 + spring catarrh▪ T2c: T2b1 + chronic gonococcal conjunctivitis▪ T2v: Plasma cell infiltration added to hyaline degeneration of papillae results in Stellwag Brawny

edema○ Stage III (T3): Cicatrizing stage: Dense fibrosis replace inflammatory infiltrate

– Necrotic follicles involute and scar resulting in white lines of fibrosis– Loss of mucin-secreting goblet cells leading to xerophthalmia, and scarring of lymphoid follicles– Arlt’s line: white line of fibrosis at sulcus subtarsalis– Hyaline degeneration: secretions and desquamated epithelium is retained inbetween papillae with

formation of post-trachomatous degenerations (PTDs) which may be calcified giving post-tracho-matous calcifications (PTCs)

○ Stage IV (T4): Inactive trachoma:– Inflammation resolved– Conjunctival scarring with entropion, trichiasis, lagophthamos

● Corneal manifestations:○ Corneal follicles: The upper cornea shows:

– Herbert’s rosettes: Yellow follicles, represent aggregation of inflammatory cells at the end of blood vessels between epithelium and Bowman’s membrane

– Herbert’s pits: Depressed pits due to healing of the rosettes○ Trachomatous pannus:

– Definition: Chronic inflammation characterized by superficial vascularization and cellular infiltra-tion of cornea

– Stages:□ Progressive stage: Infiltration followed by vascularization□ Regressive stage: Cellular infiltrate regress. Blood vessels do not regress and remain anterior to

the cellular infiltrate□ Healing stage (Pannus siccus): A superficial scar is seen in upper cornea showing obliterated blood

vessels and Herbert’s pitsNB Other types of trachomatous pannus include:a. Pannus tenius (thin): characterized by mild vascularization and infiltrationb. Pannus carnosus (thick): associated with excessive infiltrationc. Pannus vasculosus: presents with excessive vascularizationd. Pannus annulosus: seen as ring infiltration around the cornea

– Fate:□ Complete resolution without sequelae occur if Bowman’s membrane is intact□ Healing by fibrosis occur if Bowman’s membrane is destroyed □ Keratectasia: due to corneal thinning


Chapter 412

2. Trachomatous ulcers:● Typical ulcers:

○ Linear, horizontal, and superficial○ Related to pannus (on surface or at the edge)

● Atypical ulcers: Produced mechanically by PTDs and rubbing lashes ● Complications of trachomaMost complications result from scarring of the conjunctiva, eyelids, and cornea.

○ Eyelids:– Eyelid margin fibrosis results in:

□ Maldirected lashes□ Trichiasis□ Cicatricial entropion

– Multiple chalazia result from duct fibrosis with increase weight of the eyelids leading to mechanical ptosis

– Scaphoid deformity, boat shaped deformity ○ Conjunctiva:

– Posterior symblepharon– Conjunctival xerosis:

□ Atrophy of goblet cells□ Obstruction of lacrimal ducts by fibrosis□ Stellwag Brawny edema

○ Cornea:– Opacities: ulcer followed by scarring– Keratectasia

○ Lacrima:– Dacryoadenitis, dacryocystitis– Epiphora: punctual obstruction– Mucocele formation– Pyocele formation

Inclusion conjunctivitis (paratrachoma)

● Inclusion blenorrhea in infants is a major cause of acute purulent conjunctivitis in newborn● Inclusion conjunctivitis in adults (venereal disease) manifests with follicles in lower fornix

Mycotic and parasitic conjunctivitis

1. RhinosporidosisDefinition: A form of chronic conjunctivitis due to infection by a large round encapsulated spore-forming fungus (Rhinosporidum seeberi) Pathology: ● Infectious strawberry-like papilloma studded with white microabscesses● Episcleral necrosis and perforation● Pathognomonic histology: the sporangium is encapsulated by fibrous wall and filled with numerous

spherule-containing endospores● Common in India

2. Allergic conjunctival granuloma (Ashton)Definition: Presumed parasitic granulomas characterized by eosinophilic deposits of antigen-antibody complexes (Splendore-Hoeppli phenomenon)



3. Filarial conjunctivitis

Chronic foreign body reaction conjunctivitis

1. Ophthalmia nodosaDefinition: Chronic foreign body conjunctivitis due to Caterpillar hairs (setae)Pathology: ● Foreign body granulomatous conjunctivitis ● May invade anterior chamber

2. Synthetic fiber granulomaDefinition: Epibulbar foreign body granuloma in response to synthetic fabric ‘fuzz balls’Pathology: Mimics ophthalmia nodosa

Allergic conjunctivitis

1. Acute allergic conjunctivitisDefinition: Contact hypersensitivity due to exposure to allergensEtiology: Hay fever (seasonal), animal dander and topical drugs Pathology: ● IgE-mediated immediate hypersensitivity reaction● Acute anaphylactic reaction due to mast cell degranulation and histamine release ● Chemosis, itching and eyelid dermatitis● Esinophils are found in smear

2. Vernal conjunctivitis: Spring catarrh Definition: Bilateral, recurrent, IgE hypersensitivity reaction of adolescents with history of atopyEtiology:● Exogenous allergens: Pollen, animal dander with seasonal exacerbation ● Endogenous allergens:

○ The condition is aggravated by exposure to ultraviolet rays○ More common in keratoconus patients and in males

Pathology: Giant papillae, limbal papillae, Tranta’s spots, corneal involvement ● Gross picture:

○ Conjunctiva: Chronic papillary hypertrophy, up to cobblestone formation○ Papillae:

– Flat topped regular size – Occur in upper tarsal conjunctiva more commonly than the lower – Upper fornix is characteristically free – Giant papillae may develop in severe cases

● Microscopic picture: ○ Fibrovascular papillary core proliferation with perivascular infiltration of lymphocytes, plasma cells,

mast cells, numerous eosinophils and basophils ○ Epithelial hyperplasia, hypertrophy, then atrophy○ Hyaline degeneration of stroma ○ Thick ropy whitish discharge formed of mucus, epithelial cells, polymorphs and a large number of

eosinophils ○ Limbal vernal keratoconjunctivitis:

– Thickened gelatinous appearance of limbus with vascular injection– More common in Blacks


Chapter 414

○ Tranta spots: – Grayish limbal papillae with white spots on top – Intra- and subepithelial collection of eosinophils, cellular debris associated with marked epithelial

proliferation. – Balloon degeneration of epithelium results in localized pocket formation containing epithelial debris

and esinophils ○ Corneal involvement:

– Direct spread: pannus formation with destruction of Bowman’s layer – Keratitis epithelialis vernalis of Tobgy:

□ Central corneal infiltration with grayish white discrete epithelial dots. Stain with rose Bengal □ Common with palpebral form

– Vernal ulcerative keratitis: □ Noninfectious epithelial ulcer □ Transverse oval ulcer □ Affects upper cornea□ Stromal opacification

3. Giant papillary conjunctivitisDefinition: A condition similar to vernal catarrh seen in soft and hard contact lenses wear and post-enucle-ation ocular prosthesesEtiology: Immune-related response to: ● Repeated mechanical trauma ● Hypersensitivity to foreign material itself● Dry eyeMicroscopic picture: ● Accumulation of mast cells, basophils and eosinophils ● High levels of IgE, IgG and IgM● May represent a cell-mediated hypersensitivity reaction

4. Phlyctenular conjunctivitisDefinition: Local corneal or conjunctival inflammatory condition characterized by nodular affection of the conjunctiva and cornea Etiology: ● Delayed hypersensitivity to bacterial and fungal proteins:

○ Cell wall of staphylococcus in blepharitis○ Pneumococcal and Koch Weeks bacillus ○ Candida albicans

● Association to tuberculoprotein and intestinal parasites (Ascaris lumbricoides, Ancylostoma duodenale) is of historical interest

Pathology: ● Gross picture:

○ Conjunctival phlycten: – Unilateral – 2-3 mm whitish inflammatory nodules on bulbar conjunctiva surrounded by zone of dilated vessels– Epithelial ulceration– Healing occurs with no fibrosis

○ Corneal phlycten: – Superficial phlycten:

□ In front of Bowman’s layer



□ Ulceration results in fascicular ulcer: Moon shaped and tends to move centrally across the cornea with a leash of parallel vessels

– Deep phlycten: □ Deep to Bowman’s layer □ Destruction of anterior corneal lamellae and Bowman’s layer □ Deep and superficial vascularization

– Phlyctenular pannus: vascularized granulation tissue □ Affects any part of the cornea□ Thin with vessels straight and deep to Bowman’s layer

● Microscopic picture: ○ Stroma shows lymphocytes aggregation with endothelial proliferation of neighboring blood vessels ○ Epithelial shedding results in ulcer formation with PNLs, plasma cells, histiocytes and mast cells infil-

tration○ Local thrombosis and edema ○ Corneal involvement may result in a characteristic wedge-shaped corneal scar

5. Ocular cicatricial pemphigoid Definition: Chronic cicatrizing conjunctivitis of autoimmune natureEtiology: ● More common in middle-aged females ● Cytotoxic (type II) hypersensitivity with IgG autoantibodies directed against basement membrane● Autoantibodies activate complement resulting in breakdown of conjunctival membrane ● Other mucous membranes (mouth, oropharynx, genitalia and anus) are affected Pathology: ● Conjunctival hyperemia, edema, ulceration ● Stages:

○ Stage I: Subepithelial fibrosis ○ Stage II:

– Bullous conjunctivitis – Loss of Goblet cells – Shortened fornices (inferior fornix < 8 mm is suspicious)

○ Stage III: Symblepharon formation ○ Stage IV: Restricted ocular motility from adhesions between lid and globe

● Microscopic picture: ○ Destruction of conjunctival basement membrane ○ Chronic inflammatory cells○ C3, IgG, IgM ,and/or IgA localized to conjunctival basement membrane by immunohistochemistry

● Complications: ○ Goblet cell destruction ○ Conjunctival keratinization ○ Fibrosis results in trichiasis, entropion ○ Corneal vascularization

Differential diagnosis of cicatrizing conjunctivitis

● Infectious conjunctivitis: ○ Trachoma ○ Adenoviral conjunctivitis ○ Streptococcal conjunctivitis


Chapter 416

● Autoimmune conditions: ○ Sarcoidosis ○ Atopic blepharoconjunctivitis ○ Stevens-Johnson syndrome ○ Ocular cicatricial pemphigoid ○ Graft-versus-host disease (severe keratoconjunctivitis sicca)

● Trauma

Conjunctival degenerations

1. PingueculumDefinition: Raised yellowish-white mass of degenerated subepithelial connective tissue near nasal limbus in interpalpebral spaceEtiology: Related to environmental light damage inducing actinic stromal degeneration Pathology:● Microscopic picture:

○ Subepithelial elastotic degeneration of deep stroma ○ Solar elastosis, acellular homogeneous deposit (hyaline degeneration), basophilia, thickened vermi-

form collagen fibers ○ Elastotic material stains positively with Verhoeff-van Gieson elastic stain, but is not sensitive to elastase

digestion○ Epithelium may be thinned (atrophy) or thickened (reactive proliferation)○ Similar findings to pterygium

2. PterygiumDefinition: Degenerative condition in which there is a triangular encroachment of the conjunctiva on the cornea Etiology: unknown● Environmental factors: Ultraviolet light, dust, wind may be claimed ● Occurs in interpalpebral fissure, most common nasallyPathology: ● Gross picture:

○ Conjunctival epithelium and fibrovascular tissue encroach on the cornea disrupting Bowman’s layer and superficial stroma

○ Components: – Apex:

□ Over the cornea□ Preceded by fine corneal opacities □ Stocker’s line is a pigmented line of iron deposition in epithelium in front of apex of pterygium

– Neck: Over the limbus with an upper and lower fold – Body: Over the sclera, covered with stretched conjunctiva

○ Types:– Stationary: Thin, less vascular, non-progressive– Progressive: Thick, more vascular– Recurrent: Following surgery, characterized by more fibrosis and symblepharon formation

● Microscopic picture: ○ Resembles pinguecula histologically but involves the cornea○ Vesicle-like swelling at sites of perforation of BM by corneal nerves○ Subepithelial elastotic degeneration of deep stroma



○ Solar elastosis, acellular homogeneous deposit (hyaline degeneration), basophilia, thickened vermi-form collagen fibers

○ Basement membrane and superficial stromal lamellae damaged● Differential diagnosis: Table 2 demonstrates main differences between true and pseudo-pterygium

Table 2. Main differences between true and pseudo-pterygium

True pterygium Pseudo-pterygium

Nature Degenerative condition of unknown etiology A fold of conjunctiva attached to the base of a healed ulcer

Site Nasal Anywhere

Side Bilateral Unilateral

Hook test Cannot pass under neck Can pass

Course Stationary or progressive Stationary

3. AmyloidosisDefinition: A pathological process where a proteinaceous substance is deposited in the stroma in various tissues and organs of the body in a variety of clinical settings Etiology: ● Localized amyloidosis:

○ Lid amyloidosis ○ Pingueculum and pterygium ○ Corneal lattice degeneration○ Orbital deposits: proptosis ○ External and internal ophthalmoplegia (muscle infiltrate) ○ Vitreous infiltration

● Systemic amyloidosis: ○ Primary amyloidosis: Immunocytes dyscrasia as in plasma cell dyscrasia of multiple myeloma○ Secondary (reactive) amyloidosis:

– Systemic affection: □ Autoimmune disorders: rheumatoid arthritis, ankylosing spondylitlis, Crohn’s disease and

ulcerative colitis □ Chronic infection: Tuberculosis, bronchiectasis, chronic osteomyelitis

Pathology: ● Pathogenesis: Abnormal folding of proteins which are deposited as fibrils in extracellular tissues and

interfere with local tissue function ● Gross picture: Yellowish soft tissue mass appearing subconjunctival, with eyelid thickening● Microscopic picture: Homogenous hyaline-like or ‘starch-like’ acellular eosinophilic material showing

the following triad:○ Positive reaction to Congo Red○ Apple-green birefringence by polarizing microscope ○ Dichroism with polarization microscopy

Conjunctival cysts

These include: Congenital cysts; cystic nevi; cysts with microphthalmos; cystic epibulbar dermoid; epithelial inclusion cysts; ductal cysts


Chapter 418

1. Epithelial inclusion (implantation) cystsDefinition: Clear fluid-filled cyst lined by conjunctival epitheliumEtiology: ● Small cysts are formed by apposition of conjunctival folds ● Traumatic or surgical implantation results in a large single cystPathology: ● Gross picture: Translucent cyst with viscid contents ● Microscopic picture:

○ Cysts are lined by conjunctival epithelium○ Lumen filled with mucous○ Multiple conjunctival inclusion cysts are found commonly occur in association with conjunctival

nevi

2. Ductal cystsOrigin: Arise from accessory lacrimal glandsAnalogue to suderiferous cysts in skinDual layer of epithelium

Conjunctival neoplasms

There are three basic categories:Squamous: Proliferation of conjunctival squamous epitheliumLymphoid: Proliferation of normal resident population of lymphocytesMelanocytic: Proliferation of normal resident melanocytes

Squamous lesions

1. Squamous papillomaDefinition: Benign sessile and pedunculated proliferation of conjunctival epithelium seen as single or multiple cauliflower-like masses with central fibrovascular coresEtiology: ● Many are viral lesions (human papova virus types 16, 18 and human papilloma virus) as detected by

DNA hybridization● In children they are multiple and recurrentPathology: ● Gross picture:

○ Vascular grayish red soft fleshy masses○ Sessile or pedunculated ○ Cauliflower surface ○ Affecting inner canthus of bulbar conjunctiva or palpebral conjunctiva and limbus

● Microscopic picture:○ Each frond has a central vascularized core formed of connective tissue usually showing acute and

chronic inflammatory cells ○ Epithelium is acanthotic, non-keratinizing, stratified squamous epithelium with goblet cells ○ Papilloma can show marked hypercellularity with cellular atypia, nuclear hyperchromatism and atyp-

ical mitoses to be differentiated from carcinoma in situ vs squamous cell carcinoma○ Two types exist (see Table 3 for the main differences):

– Pedunculated type – Sessile type



● Differential diagnosis of papilloma includes pyogenic granuloma (fibrovascular proliferation) that has the following characteristics:○ Fleshy red mass of exuberant granulation tissue (‘proud flesh’)○ Aberrant inflammatory repair response○ May form after surgery (as in chalazion excision or strabismus surgery) or trauma

Table 3. Differences between pedunculated and sessile conjunctival papilloma

Pedunculated conjunctival papilloma Sessile conjunctival papilloma

Age Children Adults

Etiology HPV-6, 11 HPV-16, 18

Site Inferior fornix , semilunar fold Limbus, may spread on cornea

Shape Multiple branching fronds originating from a narrow base

Regular spaced fibrovascular fronds originating from a broad base

Recurrence +++ +/-

Dysplasia +/- +++

Invasive carcinoma

- +

2. Actinic (solar) keratosisDefinition: Focal, leukoplakic patches that may develop over a pre-existing pingueculum or pterygiumEtiology: Chronic ultraviolet light damage Pathology:● Microscopic picture:

○ Acanthotic atypical epithelium with parakeratosis○ Stroma shows actinic elastosis of the stroma○ Rarely recurs

3. Hereditary benign intraepithelial dyskeratosis Definition: Nonmalignant, bilateral vascularized elevated plaques on limbal conjunctiva Etiology: Autosomal dominant inherited disorder of triracial Haliwa Indians in North Carolina affecting conjunctiva and other mucous membranesPathology:● Acanthosis, parakeratosis, with absent nuclear atypia ● Progression leads to corneal vascularization and opacification

4. Conjunctival intraepithelial neoplasia (CIN, conjunctival dysplasia)Definition: A disease spectrum characterized by a replacement of the conjunctival epithelium by atypical squamous cellsEtiology: ● Some cases are caused by viral infection with human papillomavirus HPV 16/18 ( as detected by in situ

DNA hybridization)● In young adults, it is associated with immunosuppression (HIV infection a.o.)Pathology: ● Gross picture:

○ Ill-defined gelatinous lesions that blend with surrounding normal conjunctiva ○ Keratinization (leukoplakia) represents a clinical marker for squamous lesion with the following

changes:


Chapter 420

– Hyperkeratosis– Parakeratosis – Dyskeratosis

○ Papilliform: sessile papilloma with severe dysplasia ○ Frequent recurrence (incomplete excision):

– 30 % at 10 years with complete surgical excision – 50% at 10 years with positive margins

○ Differs from actinic keratosis in that they often occur outside interpalpebral limbal location● Microscopic picture:

○ Basal germinative layer involved first○ Characteristically abrupt transition between normal and acanthotic dysplastic epithelium○ Acanthosis, and cellular dysplasia which may be:

– Mild dysplasia: < 50% of epithelium replaced– Severe dysplasia: >50% of epithelium replaced

5. Carcinoma in situDefinition: Full thickness replacement of epithelium by frankly malignant cells; epithelial basement membrane is intact, no invasion into substantia propriaPathology:● Gross picture:

○ Opalescent papillary masses at limbus○ Minimal leukoplakia

● Microscopic picture: ○ Loss of polarity (random orientation in relation to basement membrane)○ The cells show increased nuclear/cytoplasmic ration, hyperchromatic pleomorphic nuclei with fre-

quent mitoses ○ Leukoplakic tumors show epithelial hyperkeratosis○ Transparent or translucent tumors show absent keratin on the surface○ Variants include: spindle and epidermoid variants

6. Invasive squamous cell carcinomaDefinition: Malignant cells have broken through epithelial basement membrane invading substantia propriaEtiology: ● Predisposing factors:

○ Actinic keratosis○ Conjunctival dysplasia ○ Xeroderma pigmentosa ○ More common in younger age groups Africa and Middle East

Pathology:● Gross picture:

○ Papillary masses appearing at limbus ○ Feeder vessels are seen supplying the mass○ Initially mobile conjunctiva then becomes fixed to the globe○ Growth pattern:

– Exophytic or papillary growth pattern with growth in interpalpebral fissure– Endophytic growth pattern with invasion of cornea, sclera, interior of globe, and posteriorly to the

orbit● Microscopic picture:

○ Atypical epithelial cells invading the substantia propria and sclera



○ Cells are arranged in lobules, nests, sheets or cords with or without keratinization○ Alcohol fixed Pap stained smear:

– Nuclear hyperchromasia– High nuclear/cytoplasmic ratio

○ Spindle cell carcinoma represents an aggressive variant ○ Mucoepidermoid carcinoma:

– Rare variant with squamous cells, mucus-secreting cells, and intermediate cells– Behaves more aggressively with early invasion and recurrence

● Spread: ○ Local:

– Lateral spread over the conjunctival surface covering the globe to the orbit – Deep spread: Infiltrating corneal BM and Descemet’s membrane, and sclera – Intraocular extension:

□ Schlemm’s canal: angle involvement □ Perivascular and perineural spread to the suprachoroidal space

○ Orbital and intraocular infiltration occur specially with incompletely excised and recurrent lesions ○ Lymph node metastasis to the preauricular, submandibular and upper deep cervical lymph nodes○ Systemic metastasis: Rare

Lymphoid lesions (see further discussion in orbit section)

Origin:● Arise from conjunctival resident population of lymphocytes in substantia propria ● ‘Salmon-patch’ or fish-flesh appearance clinically● Readily movable over epibulbar surface Types: ● Reactive lymphoid hyperplasia● Atypical lymphoid hyperplasia● Malignant lymphomas:

○ Stage IE well-differentiated lymphocytic lymphomas○ MALT lymphomas

● Systemic malignant lymphoma rarely presents as a conjunctival lesion● Associated systemic disease in 20% (prior, concurrent or subsequent)Pathology: ● Benign lesions have following histopathological features:

○ Follicular appearance ○ Germinal centers○ Abundant capillaries with plump endothelial cells○ Polymorphous infiltrate containing mixtures of cells, i.e., mature lymphocytes, plasma cells, and esino-

phils○ Polyclonal infiltrate with immunohistochemical markers (recent studies suggest this is not always the

case!)● Malignancy includes:

○ Monomorphic infiltrate with cytological atypia○ Monoclonality

● Mucosa associated lymphoid tissue (MALT):○ Immunoregulatory system of conjunctiva ○ Found also in other mucosal surface epithelia:

– Respiratory tract


Chapter 422

– Gastrointestinal tract – Genitourinary tract

○ Common immunologic features: – Rich population of antigen presenting cells – Specialized structures for localized antigen processing – Unique effectors cells:

□ Intraepithelial T cells □ Mast cells

– MALT sites share expression of specific-cell adhesion molecules on effector T and B cells

Melanocytic tumors

These include:● Benign melanocytic lesions:

○ Benign epithelial melanosis○ Ocular melanocytosis ○ Conjunctival nevi

● Preinvasive melanocytic tumors : ○ Primary acquired melanosis

● Malignant melanocytic tumors: ○Conjunctival melanoma

1. Benign epithelial melanosisDefinition: Flat, uninflamed, non-vascularized and finely to coarsely granular brown pigmentation generally occurring in the interpalpebral zone of the conjunctiva Etiology: ● The condition may be:

○ Congenital ○ Acquired:

– Seen in dark skin persons: □ Racial melanosis□ Climactic or chronic conjunctival irritation

– Irradiation – Arsenic poisoning – Addison’s disease – Chloasma of pregnancy

● Bilateral and may be asymmetrical Pathology: ● Light brown pigmentation of perilimbal and interpalpebral bulbar conjunctiva ● The pigmentation moves with the conjunctiva ● Heavy pigmentation restricted to the basal cell layer of conjunctival epithelium ● The clear melanocytic cells are difficult to demonstrate ● Absent nest formation ● Minimal inflammation of substantia propria with normal lymphocytic population and scattered histiocytic

melanophages NB: Squamous tumors in Blacks may be pigmented due to secondary acquired melanosis

2. Conjunctival neviDefinition: Nests of benign nevus cells along epithelial base and/or within substantia propria



Etiology: ● Congenital lesions: Manifest during the first two decades of life ● Typically enlarge or become more pigmented at puberty or during pregnancy● May be amelanotic in 35% of cases with variable melanin contents Pathology: ● Elevated mass● Site:

○ Interpalpebral area: – Limbus: flat – Bulbar conjunctiva and caruncle: elevated

● Color: ○ Pigmented (65%)○ Amelanotic (35%)

● Mobile with conjunctiva (located in substantia propria)● Intralesional epithelial inclusion cysts:

○ Clear areas within pigmented or solid areas ○ Found more in compound and subepithelial types

● Variants:○ Junctional nevi:

– Nevus cells: □ Rounded or polyhedral cells □ Scanty cytoplasm with deep stained nuclei and inconspicuous nucleoli □ Melanin is present as intracytoplasmic golden or brown fine granules □ Nevus cells confined to epithelial-subepithelial junction

– Outcome: □ Remain stationary □ Develop into compound nevi □ Undergo malignant change (if junctional activity exists)

– DD: Include primary acquired melanosis of elderly. Age and clinical history are important diagnos-tic clues

– A junctional nevus of the conjunctiva in an adult is considered primary acquired melanosis until proven otherwise

○ Compound nevi:– Most conjunctival nevi are compound intraepithelial and subepithelial – Nevus cells are present in both locations– Cystic or solid epithelial inclusions are very common in compound conjunctival nevi; they suggest

nevus clinically but do not rule out melanoma– Cellular proliferation results in secondary lymphocytic inflammation – Prognosis:

□ Rapid enlargement at puberty: hormonal influence□ Junctional activity: rare malignant transformation

○ Subepithelial nevi:– Cells are entirely in the substantia propria– Equivalent to intradermal nevus of skin – Rare entity – Nevoid nests confined to substantia propria

○ Spindle/epithelioid cell nevus (Spitz nevus) ○ Blue and cellular blue nevi


Chapter 424

3. Nevus of Ota (congenital oculodermal melanocytosis)Definition: Congenital melanosis of episclera with cutaneous involvement Etiology: ● Incidence: 1/2500 of population ● More common in Hispanic, Asian and Black races Pathology: ● Congenital slate gray periocular flat cutaneous pigmentation● Associated episcleral, orbital and uveal pigmentation● Episcleral pigmentation does not move with movement of conjunctiva ● Microscopic picture:

○ Superficial focal proliferation of subepithelial melanocytes with no cytological atypia ○ Prognosis:

– 0.4% develop uveal melanoma (1 in 400 cases)– Slightly more risk of orbital and brain (meningeal) melanoma– Eyelid and conjunctival melanoma are extremely rare

4. Primary acquired melanosis (PAM, Reese’s cancerous melanosis) Definition: Acquired proliferation of melanocytes situated within the epithelium of the conjunctiva Etiology: ● Middle-aged or elderly Whites (rare in Blacks) ● Unilateral Pathology: ● Multiple or single flat brown patches of superficial conjunctiva (rarely amelanotic)● Move with movement of the conjunctiva ● Insidious onset, waxes and wanes● Anywhere in conjunctiva ● Abnormal melanocytic proliferation in basal conjunctival epithelium ● PAM can be amelanotic (primary acquired melanosis sine pigmento) and can occur in blacks (rare)● 20% develop malignant melanoma:

○ Nodularity ○ Increase vascularity

● Types of PAM: ○ PAM without atypia:

– Epithelial hyperpigmentation with melanocytic hyperplasia– Restricted to basilar region of epithelium without nuclear hyperchromatism or prominent nucleoli– Low risk for conjunctival melanoma

○ PAM with atypia: – Atypical melanocytic hyperplasia or malignant melanoma in situ involving conjunctival epithelium – High risk for developing conjunctival melanoma:

□ 75% if PAM contains epithelioid cells□ 90% if intraepithelial pagetoid spread is present□ 20% if atypical melanocytes are confined to the basilar part of the epithelium

– Atypical cells confined to epithelium constitute radial growth phase – Vertical growth phase: Represent invasive malignant melanoma

● UV (Wood’s light) may highlight subtle pigmentation Management: Observe carefully with photographic documentation.

Management: Observe carefully with photographic documentation● Zimmerman’s classification of PAM:

○ Stage I. Benign acquired melanosis



– With minimal melanocytic hyperplasia (increased melanin within epithelium)– With atypical melanocytic hyperplasia

□ Mild to moderate□ Severe (‘in situ’ malignant melanoma)

○ Stage II. Malignant acquired melanosis– With superficially invasive melanoma (tumor thickness < 1.5 mm) – With more deeply invasive melanoma (tumor thickness > 1.5 mm)

5. Malignant melanoma of the conjunctivaDefinition: Relatively uncommon malignant conjunctival tumor arising from conjunctival melanocytesEtiology: ● Incidence: 1 in 2 million in fair complexion population ● Uveal/conjunctival melanoma ratio: 10/1● Predisposing lesions:

○ Primary acquired melanosis (75% of cases)○ Pre-existing nevus (junctional or compound) (25%)○ De novo (nodular melanoma)

Pathology: ● Gross picture:

○ Site: – Bulbar conjunctiva – Limbus – Palpebral conjunctiva – Caruncle

○ Shape: – Nodular mass – Variable pigmentation

○ Highly vascularized: bleeds easily ○ Feeder vessels: dilated and tortuous○ Spread:

– Local: invades the globe and orbit – Lymphatic spread common (preauricular and intraparotid nodes)-poor prognosis– In lymph nodes tumor cells gain access to blood vessels via anastomoses between lymphatics and

blood vessels– Risk factors for metastasis:

□ Younger age group □ Large tumor size □ Multicentricity □ Epithelioid cell type □ Lymphatic invasion

○ Behavior: – Unpredictable behavior– Behaves like skin melanomas (Clarke’s classification is not applicable to conjunctival melanomas) – Mortality rate: 26%

Table 4 shows the main clinical differences between pigmented epibulbar and conjunctival masses.


Chapter 426

Table 4. Differential diagnosis of pigmented epibulbar lesions

Congenital melanosis

Primary acquired melanosis

Nevus Malignant melanoma

Location Episcleral Intraepithelial Intraepithelial Subepithelial

Movement with conjunctiva

No Yes Yes Variable

Pigmentation Slate gray Variable Variable Variable

Special features Heterochromia iridis

Pseudocysts Cystic contents Feeder vessels

Course Stationary Waxes and wanes Stationary Progressive

Inflammation - + + ++

Kaposi’s sarcoma

Definition: ● Multicentric vascular neoplasm affecting the skin, mucous membrane, lymph nodes and viscera, and

commonly affecting immunocompromised patients (HIV)● Lesions affect eyelid and conjunctiva of 5% of immunosuppressed individuals (HIV patients)Pathology: See Eyelid pathology section

References

Anatomy of the conjunctivaAbdel-Khalek LMR, Williamson J, Lee WR. Morphological changes in the human conjunctival epithelium in the normal elderly

population. Br J Ophthalmol 1978; 62: 792-799 Allansmith MR, Greiner JV, Baird RS. Number of inflammatory cells in the normal conjunctiva. Am J Ophthalmol 1978; 86:

250-254 Gipson IK. The epithelial basement membrane zone of the limbus. Eye 1989; 3: 132-136 Kessing SV. Mucous gland system of the conjunctiva. A quantitative normal anatomical study. Acta Ophthalmol Suppl 1968;

95: 1-14 Steuhl KP, Sitz U, Knorr M, et al. Age-dependent distribution of Langerhans cells within human conjunctival epithelium.

Ophthlamologe 1995; 92: 21-27 Wei ZG, Sun TT, Lavker RM, et al. Conjunctival goblet cells have proliferative capabilities. Invest Ophthalmol Vis Sci 1990;

32: 734-739

Congenital anomalies Benjamin SN, Alien HF. Classification for limbal dermoid choristomas and branchial arch anomalies. Presentation of an unusual

case. Arch Ophthalmol 1972; 87: 305-314Dutton JJ, Fowler AM, Proia AD. Dermoid cyst of conjunctival origin. Ophthal Plast Reconstr Surg 2006; 22: 137-139Katowitz JA, Yolles EA, Yanoff M. Ichthyosis congenita. Arch Ophthalmol 1974; 91: 208-210

Vascular tumors and tumor-like conditionsHolland GN, Pepose JS, Pettit TH, Gottlieb MS, Yee RD, Foos RY. Acquired immune deficiency syndrome. Ocular manifestations.

Ophthalmology 1983; 90: 859-873Jampol ML, Nagpal KC. Hemorrhagic lymphangiectasia of the conjunctiva. Am J Ophthalmol 1978; 85: 419-420Lieberman PH, Liovera IN. Kaposi’s sarcoma of the bulbar conjunctiva. Arch Ophthalmol 1972; 88: 44-45Minoda H, Usui N, Sata T, Katano H, et al. Human herpesvirus-8 in Kaposi’s sarcoma of the conjunctiva in a patient with AIDS.

Jpn J Ophthalmol 2006; 50: 7-11Nicholson DH, Lane L. Epibulbar Kaposi sarcoma. Arch Ophthalmol 1978; 96: 95-96



Palestine AG, Rodriguez MM, Macher AM, et al. Ophthalmic involvement in acquired immunodeficiency syndrome. Ophthalmology 1984; 91: 1092-1099

Rootman J, Hay E, Greab D, Miller R. Orbital-adnexal lymphangiomas. A spectrum of hemodynamically isolated vascular hamartomas. Ophthalmology 1986; 93: 1558-1570

Shields JA, Eagle RC Jr, Shields CL, De Potter P, Shapiro RS. Orbital varix presenting as a subconjunctival mass. Ophthalmol Plast Reconstr Surg 1995; 11: 37-38

Ullman SS, Nelson LB, Shields JA, Choi HY, Arbizo V. Cavernous hemangioma of the conjunctiva. Orbit 1988; 6: 261-265Weiter JJ, Jakobiec FA, Iwamoto T. The clinical and morphologic characteristics of Kaposi’s sarcoma of the conjunctiva. Am J

Ophthalmol 1980; 89: 546-522Wright JF, Sullivan JT, Garner A, et al. Orbital venous anomalies. Ophthalmology 1997; 104: 905-913

Acute conjunctivitisDushku N, Hatcher SLS, Albert DM, et al. Expression and relation to human papillomavirus infection in pingueculae, pterygia,

and limbal tumors. Arch Ophthalmol 1999; 1117: 1593-1599Laibson PR, Dhiri S, Oconer J, et al. Corneal infiltrates in epidemic keratoconjunctivitis. Arch Ophthalmol 1970; 84: 36-40Lee JS, Choi HY, Lee JE, Lee SH, et al. Gonococcal keratoconjunctivitis in adults. Eye 2002; 16: 646-649 Peacock SJ, Anita Justice D, Griffiths GD, et al. Determinants of acquisition and carriage of Staphylococcus aureus in infancy. J

Clinic Microbiol 2003; 41: 5718-5725Shanmuganathan VA, Armstrong M, Buller A, et al. External ocular infections due to methicillin-resistant Staphylococcus aureus

(MRSA). Eye 2005; 19: 284-291

Chronic conjunctivitis Bobo L, Munoz B, Viscidi R, et al. Diagnosis of Chlamydia trachomatis eye infection in Tanzania by polymerase chain reaction/

enzyme immunoassay. Lancet 1991; 338: 847-850Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: A study of 100 cases. Tram Am Ophthalmol Soc 1989; 87:

327-343Foster CS, Allansmith MR. Chronic unilateral blepharoconjunctivitis caused by sebaceous carcinoma. Am J Ophthalmol 1978;

86: 218-220Holland MJ, Hayes LJ, Whittle HC, et al. Conjunctival scar ring in trachoma is associated with depressed cell-mediated immune

responses to chlamydial antigens. J Infect Dis 1993; 168: 1528-1531MacCallan AF. The initial signs of trachoma. Rev Int Trach 1950; 27: 115-117Matoba AY. Ocular disease associated with Epstein-Barr virus infection. Surv Ophthalmol 1990; 35: 145-150 (Review)Raithinam S, Fritsche TR, Srinivascan M, et al. An outbreak of trematode-induced granulomas of the conjunctiva. Ophthal-

mology 2001; 108: 1223-1229 Reacher MH, Pe’er J, Rapoza PA, et al. T cells and trachoma. Ophthalmology 1991; 98: 334-341Risco JM, Al-Dosari F, Millar L. Sheep nasal botfly (Oestrusovis) larvae infestation of the conjunctiva. Arch Ophthalmol 1995;

113: 529-530 Taylor HR, Rapoza PA, West S, et al. The epidemiology of infection in trachoma. Invest Ophthalmol Vis Sci 1989; 30:

1823-1833Thygeson P. Historical review of oculogenital disease. Am J Ophthalmol 1971; 71: 975-985

Ligneous conjunctivitisBatemen JB, Pettit TH, Isenberg SJ, Simons KB. Ligneous conjunctivitis: an autosomal recessive disorder. J Pediatr Ophthalmol

Strabismus 1986; 23: 137-140Eagle RC Jr, Brooks JSJ, Katowitz JA, et al. Fibrin as a major constituent of ligneous conjunctivitis. Am J Ophthalmol 1986;

101: 493-494Girard LJ, Veselinovic A, Font RL. Ligneous conjunctivitis after pinguecula removal in an adult. Cornea 1989; 8: 7-14Hidayat AA, Riddle PJ. Ligneous conjunctivitis; a clinicopathologic study of 17 cases. Ophthalmology1987; 94: 949-959Holland BI, Holland EJ, de Smet MD, et al. Immunohistologic findings and results of treatment with cyclosporine in ligneous

conjunctivitis. Am J Ophthalmol 1989; 107: 160-166Kraft J, Lieb W, Zeitler P, Schuster V. Ligneous conjunctivitis in a girl with severe type I plasminogen deficiency. Graefes Arch

Clin Exp Ophthalmol 2000; 238: 797-800Spencer LM, Straatsma BR, Foos RY. Ligneous conjunctivitis. Arch Ophthalmol 1968; 80: 365-377Tabbara KF. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol 2004;

138: 299-300


Chapter 428

Allergic and autoimmune conjunctivitisAnderson DF, MacLeod JD, Baddeley SM, et al. Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers

in the absence of leucocyte infiltration. Clin Exp Allergy 1997; 27: 1060-1066Bernauer W, Wright P, Dart JK et al. The conjunctiva in acute and chronic mucous membrane pemphigoid. Ophthal mology 1993;

100: 339-346Cameron JA, Al-Rajhi AA, Badr LA. Corneal ectasia in vernal keratoconjunctivitis. Ophthalmology 1989; 96: 1615-1623Friedlaender MH. Immunologic aspects of diseases of the eye. JAMA 1992; 268: 2869-2873Greiner JV, Covington HI, Allansmith MR. Surface morphol ogy of giant papillary conjunctivitis in contact lens wearers. Am J

Ophthalmol 1978; 85: 242-252Lambiase A, Bonini S, Bonini S et al. Increased plasma levels of nerve growth factor in vernal keratoconjunctivitis and rela-

tionship to conjunctival mast cells. Invest Ophthalmol Vis Sci 1995; 36: 2127-2132Pisella PJ. The cellular players in allergy. J Fr Ophthalmol 2007; 30: 283-287Power WJ, Neves RA, Rodriguez A et al. Increasing the diag nostic yield of conjunctival biopsy in patients with suspected/ocular

cicatricial pemphigoid. Ophthalmology 1995; 102: 1158-1163 Trocme SD, Kephart GM, Bourne WM et al. Eosinophil granule major basic protein deposition in corneal ulcers associ ated with

vernal keratoconjunctivitis. Am J Ophthalmol 1993; 115: 640-643

Conjunctival degenerationsGedik S, Akova YA, Gur S. Secondary bacterial keratitis associated with shield ulcer caused by vernal conjunctivitis. Cornea

2006; 25: 974-976 Levine RA, Rabb MF. Bitot’s spot overlying a pinguecula. Arch Ophthalmol 1971; 86: 525-528Nolan TM, DiGirolamo N, Sachdev NH, et al. The role of ultraviolet irradiation and heparin-binding epidermal growth factor-

like growth factor in the pathogenesis of pterygium. Am J Pathol 2003; 162: 567-574Perra MT, Colombari R, Maxia C, et al. Finding of conjunctival melanocytic pigmented lesions within pterygium. Histopathology

2006; 48: 387-393Stern ME, Siemasko KF, Gao J, et al. Evaluation of ocular surface inflammation in the presence of dry eye and allergic conjunctival

disease. Ocul Surf 2005; 3: S161-164 Touhami A, Di Pascuale MA, Kawatika T, et al. Characterization of myofibroblasts in fibrovascular tissues of primary and

recurrent pterygia. Br J Ophthalmol 2005; 89: 269-274

Conjunctival amyloidosis: Borodic GE, Beyer-Mechule CK, Millin J, et al. Immunoglobulin deposition in localized conjunctival amyloidosis. Am

Ophthalmol 1984; 98: 617-622Brownstein S, Rodrigues MM, Fine BS et al. The elastotic nature of hyaline corneal deposits: A histochemical, fluorescent and

electron microscopic examination. Am J Ophthalmol 1973; 75: 799-809Chumbley LC, Peacock OS. Amyloidosis of the conjunctiva-an unusual complication of trachoma. A case report. S Afr Med J

1977; 52: 897-898Ciulla TA, Tolentino F, Morrow JF et al. Vitreous amyloidosis in familial amyloidotic polyneuropathy: Report of a case with the

ValsoMet transthyretin mutation. Surv Ophthalmol 1995; 40: 197-206Demirci H, Shields CL, Eagle RC Jr, et al. Conjunctival amyloidosis: report of six cases and review of the literature. Surv

Ophthalmol 2006; 51: 419-433 Gertz MA, Kyle RA. Primary systemic amyloidosis: A diagnostic primer. Mayo Clin Proc 1989; 64: 1505-1519Glass R, Scheie HG, Yanoff M. Conjunctival amyloidosis aris ing from a plasmacytoma. Ann Ophthalmol 1971; 3: 823-825Gorevic PD, Rodrigues MM. Ocular amyloidosis (Perspective). Am J Ophthalmol 1994; 117: 529-532Hill VE, Brownstein S, Jordan DR. Ptosis secondary to amyloi dosis of the tarsal conjunctiva and tarsus. Am J Ophthalmol 1997;

123: 852-854Leibovitch I, Selva D, Goldberg RA, et al. Periocular and orbital amyloidosis: clinical characteristics, management, and outcome.

Ophthalmology 2006; 113: 1657-1664 Marsh WM, Streeten BW, Hoepner JA, et al. Localized con junctival amyloidosis associated with extranodal lymphoma.

Ophthalmology 1987; 94: 61-64Meisler DM, Stock El, Wertz RD, et al. Conjunctival inflammation and amyloidosis in allergic granulomatosis and angiitis

(Churg-Strauss syndrome). Am J Ophthalmol 1981; 91: 216-219Moorman CM, McDonald B. Primary (localized non-familial conjunctival amyloidosis): three case reports. Eye 1997; 11:

603-606Rodrigues MM, Cullen G, Shannon G. Primary localized conjunctival amyloidosis following strabismus surgery. Can J

Ophthalmol 1976; 11: 177-179



Sandgren O. Ocular amyloidosis with special reference to the hereditary forms with vitreous involvement. Surv Ophthalmol 1995; 40: 1173-1196 (Major review)

Smith ME, Zimmerman LE. Amyloidosis of the eyelid and conjunctiva. Arch Ophthalmol 1966; 75: 42-50

Conjunctival depositsBrothers DM, Hidayat AA: Conjunctival pigmentation associ ated with tetracycline medication. Ophthalmology 1981; 88:

1212-1215Donoso LA, Shields JA. Epibulbar lesions simulating extraocular extension of uveal melanomas. Ann Ophthalmol 1982; 14:

1120-1123Fong DS, Frederick AR, Krichter CU, et al. Adrenochrome deposit. Arch Ophthalmol 1993; 3: 1142-1143Fraunfelder FT, Garner A, Barras TC. Subconjunctival and episcleral lipid deposits. Br J Ophthalmol 1976; 60: 532-535Shields JA, Marr BP, Shields CL, et al. Conjunctival mascaroma masquerading as melanoma. Cornea 2005; 24: 496-497Yanoff M, Scheie HG. Argyrosis of the conjunctiva and lacrimal sac. Arch Ophthalmol 1964; 72: 57-58

Conjunctival cystsDesai V, Shields CL, Shields JA. Orbital cyst in a patient with Stevens Johnson syndrome. Cornea 1992; 11: 592-594Jahnle R, Shields JA, Bernardino V, et al. Pigmented conjunctival inclusion cyst simulating a malignant melanoma. Am J

Ophthalmol 1985; 100: 483-484Lieb WE, Shields JA, Shields CL, et al. Postsurgical hematic cyst stimulating a conjunctival malignant melanoma. Retina 1990;

10: 63-67McCarthy RW, Beyer CK, Dallow RL. Conjunctival cysts of the orbit following enucleation. Ophthalmology 1981; 88: 30-35Shapiro A, Tso MOM, Putterman AM, et al. A clinicopathologic study of hematic cysts of the orbit. Am J Ophthalmol 1986; 102:

237-241

Conjunctival neoplasm Benign tumors of the conjunctival epitheliumLass JH, Grove AS, Papale JJ, et al. Detection of human papillomavirus DNA sequences in conjunctival papillomas. Am J

Ophthalmol 1983; 96: 670-674Lass JH, Henson AB, Papale JJ, et al. Papillomavirus in human conjunctival papillomas. Am J Ophthalmol 1983; 95: 364-368McDonnell PJ, McDonnell JM, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia.

Arch Ophthalmol 1986; 104: 1801-1805McLean IW, Riddle PJ, Scruggs JH, et al. Hereditary benign intraepithelial dyskeratosis. Ophthalmology 1981; 88: 164-168Minchiotti S, Masucci L, Serapiao Dos Santos M, et al. Conjunctival papilloma and human papillomavirus: identification of

HPV types by PCR. Eur J Ophthalmol 2006; 16: 473-477Shields CL, Shields JA, Eagle RC Jr. Hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1987; 105: 422-423Streeten BW, Carillo R, Jamison R, et al. Inverted papilloma of the conjunctiva. Am J Ophthalmol 1979; 88: 1062-1066Premalignant and malignant tumors of the conjunctival epitheliumCha SB, Shields CL, Shields JA, et al. Massive precorneal extension of squamous cell carcinoma of the conjunctiva. Cornea

1993;12: 537-540Dark AJ, Streeten BW. Preinvasive carcinoma of the cornea and conjunctiva. Br J Ophthalmol 1980; 64: 506-514Erie JC, Campbell RF, Liessegang TJ. Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology 1986;

93: 176-183Evans WH. Tumor of the lacrimal caruncle. A study of 200 collected cases. Arch Ophthalmol 1940; 24: 83-90Glasson WJ, Hirst LW, Axelsen RA et al. Invasive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1994; 112:

1342-1345Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea

1987; 6: 78-116Iliff WJ, Marback R, Green WR. Invasive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1995; 93: 119-122Jakobiec FA, Harrison W, Aronian D. Inverted mucoepidermoid papillomas of the epibulbar conjunctiva. Ophthalmology 1987;

94: 283-287Karp CL, Scott IU, Chang TS et al. Conjunctival intraepithe lial neoplasm: A possible marker for human immunodeficiency virus

infection? Arch Ophthalmol 1996; 114: 257-261Kiire CA, Dhillon B. The aetiology and associations of conjunctival intraepithelial neoplasia. Br J Ophthalmol 2006; 90:

109-113Lauer SA, Matter JS, Meier JR. Human papillomavirus type 18 in conjunctival intraepithelial neoplasia. Am J Ophthalmol 1990;

110: 23-27Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol 1995; 39: 429-450


Chapter 430

Lewallen S, Shroyer KR, Keyser RB, et al. Aggressive conjunctival squamous cell carcinoma in three young Africans. Arch Ophthalmol 1996; 114: 215-218

Mahmood MA, Al-Rajhi A, Riley F, et al. Sclerokeratitis. An unusual presentation of squamous cell carcinoma of the con-junctiva. Ophthalmology 2001; 108: 553-558

McDonell JM, Mary AJ, Martin WG. DNA of human papillomavirus type 26 in dysplastic and malignant lesions of the conjunctiva and cornea. N Engl J Med 1089; 320: 1442-1446

McDonnell JM, McDonnell PJ, Sun YY. Human papillomavirus DNA in tissues and ocular surface swabs of patients with conjunctival epithelial neoplasia. Invest Ophthalmol Vis Sci 1992; 33: 184-189

Nicholson DH, Herschler J. Intraocular extension of squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1977; 95: 843-846

Odrich MG, Jakobiec FA, Lancaster WD et al. A spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16. Ophthalmology 1991; 98: 628-635

Rao NA, Font RL. Mucoepidermoid carcinoma of the conjunctiva with intraocular invasive. Ophthalmology 1981; 88: 1126-1130

Roberson MC. Corneal epithelial dysplasia. Ann Ophthalmol 1987; 16: 1147-1150Rodman RC, Frueh BR, Finer VM. Mucoepidermoid carci noma of the caruncle. Am J Ophthalmol 1997; 123: 564-565Spencer WH. Conjunctiva. In: Spencer WH (ed.) Ophthalmic pathology. An atlas and textbook, vol. 1, pp. 112-113. 4th ed.

Philadelphia: WB Saunders 1996Tabin G, Levin S, Snibson G, et al. Recurrences and necessity for long-term follow-up in corneal and conjunctival intraepithelial

neoplasia. Ophthalmology 1997; 104: 485-492

Lymphoid tumors of the conjunctiva Bardenstein DS. Ocular adnexal lymphoma: classification, clinical disease, and molecular biology. Ophthalmol Clin North Am

2005; 18: 187-197Ferry JA, Fungi CY, Zukerberg L, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol 2007; 31:

170-184 Jakobiec FA, Bilyk JR, Font RL. Orbit. Lymphoid tumors. In: Spencer WH (ed.) Ophthalmic pathology. An atlas and textbook

vol. 4, pp. 2686-2736. 4th ed. Philadelphia: WB Saunders 1996Loo H, Forman WB, Levine MR, et al. Periorbital ecchymoses as the initial sign in multiple myeloma. Ann Ophthalmol 1982;

14: 1066-1068Sullivan TJ, Whitehead K, Williamson R, et al. Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study

with statistical analysis of 69 patients. Ophthal Plast Reconstr Surg 2005; 21: 177-188 Benign melanocytic tumorsBuckman G, Jakobiec FA, Folberg F, et al. Melanocytic nevi of the palpebral conjunctiva. An extremely rare location usually

signifying melanoma. Ophthalmology 1988; 95: 1053-1057Folberg R, Jakobiec FA, Bernardion VB, et al. Benign conjunctival melanocytic lesions. Clinicopathologic features. Ophthalmology

1989; 96: 436-461Folberg R, McLean IW, Zimmerman LE. Conjunctival melanosis and melanoma. Ophthalmology 1984; 91: 673-678Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum Pathol 1985; 16: 129-135Folberg R, McLean IW. Primary acquired melanosis and melanoma of the conjunctiva: terminology, classification, and biologic

behavior. Hum Pathol 1986; 17: 652-654Folberg R. Melanocytic lesions of the conjunctiva. In: Spencer WH (ed.) Ophthalmol pathology. An atlas and textbook, vol. 1,

pp. 125-137.4th ed. Philadelphia: WB Saunders 1996Gloor P, Alexandrakis G. Clinical characterization of primary acquired melanosis. Invest Ophthalmol 1995; 36: 1721-1729Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea

1987; 6: 78-116Jakobiec FA, Folberg R, Iwamoto T. Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the

conjunctiva. Ophthalmology 1989; 96: 147-166McDonnell JM, Carpenter JD, Jacbos P, et al. Conjunctival melanocytic lesions in children. Ophthalmology 1989; 96: 986-993Pfaffenbach DD, Green WR, Maumenee AE. Balloon cell of the conjunctiva. Ophthalmology 1972; 87: 192-195Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983; 90: 1459-1461Sugiura M, Colby KA, Mihm MC Jr, et al. Low-risk and high-risk histologic features in conjunctival primary acquired melanosis

with atypia: Clinicopathologic analysis of 29 cases. Am J Surg Pathol 2007; 31: 85-92

Malignant melanocytic tumorsCiblin ME, Shields CL, Shields JA, Eagle RC. Primary eyelid malignant melanoma associated with primary conjunctival

malignant melanoma. Aust N Z J Ophthalmol 1988; 16: 127-131



De Potter P, Shields CL, Shields JA, et al. Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases. Br J Ophthalmol 1993; 77: 624-630

Esmaeli B, De Martelaere S, Ozkan Y, et al. Surgical specimen handling for conjunctival melanoma: implications for tumor thickness determination and sentinel lymph node biopsy.Ophthal Plast Reconstr Surg 2006; 22: 238-239

Keijser S, Missotten GS, Bonfrer JM, et al. Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions. Br J Ophthalmol 2006; 90: 213-217

Kurli M, Finger PT. Melanocytic conjunctival tumors. Ophthalmol Clin North Am 2005; 18: 15-24Liesegang TJ, Campbell RJ. Mayo Clinic experience with conjunctival melanomas. Arch Ophthalmol 1980; 98: 1385-1389Missotten GS, Keijser S, De Keizer RJ, et al. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol

Vis Sci 2005; 46: 75-82Shields JA, Shields CL. Tumors of the conjunctiva and cornea. In: Smolin G, Thoft RA (eds.) The Cornea, pp. 588-589. 3rd ed.

Boston: Little, Brown and Co. 1993

Tumors of the caruncleBiggs SL, Font RL. Oncocytic lesions of the caruncle and other ocular adnexa. Arch Ophthalmol 1977; 95: 474-478Bonuik M, Zimmerman LE. Sebaceous carcinoma of the eyelid, eyebrow, caruncle, and orbit. Trans Acad Ophthalmol Otolaryngol

1968; 72: 619-642Greer CH. Oxyphil cell adenoma of the lacrimal caruncle. Br J Ophthalmol 1969; 53: 198-202Gritz DC, Rao NA. Metastatic carcinoid tumor diagnosis from a caruncular mass. Am J Ophthalmol 1991; 112: 470-471Kaeser PF, Uffer S, Zografos L, et al. Tumors of the caruncle: a clinicopathologic correlation. Am J Ophthalmol 2006; 142:

448-455Luthra CL, Doxanas MT, Green WR. Lesions of the caruncle. A clinicopathologic study. Surv Ophthalmol 1978; 23: 183-195Morand B, Bettega G, Bland V et al.: Oncocytoma of the eyelid: An aggressive benign tumor. Ophthalmology 1998; 105:

2220-2224Ostergaard J, Prause JU, Heegaard S. Caruncular lesions in Denmark 1978-2002: a histopathological study with correlation to

clinical referral diagnosis. Acta Ophthalmol Scand 2006; 84: 130-136Rennie IG. Oncocytomas (oxyphil adenomas) of the lacrimal caruncle. Br J Ophthalmol 1980; 64: 935-939Santos A, Gomez-Leal A. Lesions of the lacrimal caruncle: Clinicopathologic features. Ophthalmology 1994; 101: 943-949Shields CL, Shields JA, Arbizo V, et al. Oncocytoma of the caruncle. Am J Ophthalmol 1986; 102: 315-319Shields CL, Shields JA, White D, et al. Types and frequency of lesions of the caruncle. Am J Ophthalmol 1986; 102: 771-778Shields RS, Lomeo MD, Kirchgraber PRN, et al. Caruncular malignant melanoma in a black patient. Ophthalmol Surg 1995;

26: 139-141Stern K, Jakobiec FA, Harison WG. Caruncular dacryops with extruded secretory globoid bodies. Ophthalmology 1983; 90:

147-151Wilson RP. Tumors and cysts of lacrimal caruncle. Trans Ophthalmol Soc NZ 1958; 11: 23-28LeukemiaFont RL, Mackay B, Tang R. Acute monocytic leukemia recurring as bilateral perilimbal infiltrates. Ophthalmology 1985; 92:

1681-1685Kincaid MC, Green WR. Ocular and orbital involvement in leukemia. Surv Ophthalmol 1983; 27: 211-232

Metastatic tumors of the conjunctiva Grossniklaus HE, Green WR, Lukenbach M, Chan CC. Conjunctival lesions in adults. A clinical and histopathologic review.

Cornea 1987; 6: 78-116Kiratli H, Shields CL, Shields JA, et al. Metastasis tumors to the conjunctiva. Report of ten cases. Br J Ophthalmol 1996; 80:

5-8

NeurilemomaCharles NC, Fox DM, Avendano JA, et al. Conjunctival neurilemoma. Report of 3 cases. Arch Ophthalmol 1997; 115: 547-549

Fibrous histiocytoma Font RL, Hidayat AA. Fibrous histiocytoma of the orbit. A clinicopathologic study of 150 cases. Hum Pathol 1982; 13:

199-209Jakobiec FA. Fibrous histiocytoma of the corneoscleral limbus. Am J Ophthalmol 1974; 78: 700-706Kim HJ, Shields CL, Eagle RC Jr, et al. Fibrous histiocytoma of the conjunctiva. Am J Ophthalmol 2006; 142: 1036-1043 Mietz H, Severin M, Arnold G, Kirchhof B, Krieglstein GK. Management of fibrous histiocytoma of the corneoscleral limbus:

report of a case and review of the literature. Graefes Arch Clin Exp Ophthalmol 1997; 235: 87-91


Chapter 432

Fibroma and juvenile xanthogranuoma Austin P, Jakobiec FA, Iwamoto T, Hornblass A. Elastofibroma oculi. Arch Ophthalmol 1983; 101: 1575-1579Herschorn BJ, Jakobiec FA, Hornblass A, et al. Epibulbar subconjunctival fibroma: a tumor possibly arising from Tenon’s

capsule. Ophthalmology 1983; 90: 1490-1494Jakobiec FA, Sacks E, Lisman RL, Krebs W. Epibulbar fibroma of the conjunctival substantia propria. Arch Ophthalmol 1988;

106: 661-664Zimmerman LE. Ocular lesions of juvenile xanthogranuloma (neoxanthoendothelioma). Trans Am Acad Ophthalmol Otolaryngol

1965; 69: 412-442

Myxoma, lipoma and reticulohistiocytoma Allaire GS, Hidayat AA, Zimmerman LE, et al. Reticulohistiocytoma of the limbus and cornea. A clinicopathologic study of two

cases, Ophthalmology 1990; 97: 1018-1022Evans WH. Tumor of the lacrimal caruncle. A study of 200 collected cases. Arch Ophthalmol 1940; 24: 83-90


opthalmic pathology-conjunctival-pathology

Health & Medicine