contrast, zonular granulomas are characterized by a spe-cific architecture. The pathogenic substrate (e.g., a for-eign body) is located in the center, surrounded by a ringof epitheloid cells and giant cells. The outermost zoneof the granuloma is made up of lymphocytes, plasmacells, and eosinophilic granulocytes. Various forms ofconjunctivitis associated with the formation of eitherdiffuse or zonular granuloma are shown in Table 2.6.

Conjunctival Inflammation in Ocular AllergyBased on the underlying pathomechanism, severalforms of chronic conjunctivitis can be classified as re-lated to allergy, as shown in Table 2.7.

Perennial and seasonal conjunctivitis represent the mostfrequent manifestations of ocular allergy. These disor-ders are characterized by relatively benign pathologicalchanges with mild epithelial hyperplasia and increasednumber of goblet cells. A characteristic, scant inflam-

22 F.E. Kruse

Figure 2.4. Giant papillary con-junctivitis of the upper tarsuswith mucoid discharge in ver-nal keratoconjunctivitis.

Table 2.5. Ocular surface disease associated with formationof symblepharon.

Immunological disordersCicatricial pemphigoidStevens–Johnson syndrome (Erythema multiforme majus)Toxic epidermal necrolysis (Lyell’s syndrome)Herpetiform dermatitis (Duhring)Linear IgA diseaseAcquired epidermolysis bullosaAtopic keratoconjunctivitis

BacteriaCorynebacterium diphtheriaeBorrelia burgdorferi

ChlamydiaChlamydia trachomatis

Viral (rare, severe forms of inflammation)AdenovirusHerpes zoster

Chemicals, drugs, physical injuryChemical burnThermal burnDrug-induced pseudopemphigoid

Table 2.6. Ocular surface disease associated with formationof granuloma.

BacteriaMycobacterium leprae or tuberculosisTreponema pallidumHemophylus ducreiiYersiniaCat scratch disease (Afipia felis, Bartonella henselae)ListeriaFranciscella tularensisRickettsia

ChlamydiaViral

Epstein–Barr VirusOther infectious organisms

ActinomycosisBlastomycosisSporotrichosisLeptospirosis

Systemic diseaseSarcoidosisWegener’s granulomatosis

Allergic granulomasParasites (toxocara canis, shistosoma, onchocerca)Caterpillar hairsAllergic granulomas without detectable antigen

Foreign-body granulomasOrganic material (plants, insects)Nonorganic materialSuturesPlastics (e.g., stuffed toys)

matory infiltrate is found in the substantia propria consisting of mast cells and esosinophils. The tarsal con-junctiva undergoes papillary hypertrophy. Upon contactwith antigens, a type I hypersensitivity reaction resultsin synthesis of antibodies by B-lymphocytes. IgE andspecific antibodies are increased in serum and tears.49,50

Upon renewed contact, antigens are bound to IgE on thesurface of mast cells, which leads to degranulation andthe release of inflammatory mediators such as hista-mine, leucotriene and prostaglandins. These mediatorscause dilation of vessels and secondary tissue damageby recruitment of inflammatory cells. The identificationof the role of mast cells and the release of inflammatorymediators has enabled the development of powerfuldrugs for the treatment of seasonal/perennial conjunc-tivitis, such as mast cell stabilizers and antihistamines.

Atopic conjunctivitis is a chronic disease that is basedon a number of deviations of the immune system, suchas delayed hypersensitivity responses to pathogens (e.g.,Candida albicans)51 and defective T-cell function thatinclude a possible failure to terminate the production ofIgE in response to specific antigens.52 In chronic type Iand IV reactions, the conjunctival epithelium andstroma contain (degranulating) mast cells and eosino-

phils, as well as activated T-lymphocytes with an in-creased proportion of helper cells.53 Inflammatory me-diators induce the expression of MHC class II antigensas well as pseudoglandular hyperplasia.54 The clinicalpicture is characterized by giant papillary conjunctivi-tis of the lower tarsus that can lead to linear tarsal scars,fornix foreshortening, and symblepharon. Trantas dotsat the limbus represent focal accumulations of eosino-phils. Keratitis associated with atopic dermatitis can besevere, including scarring and vascularization.

Vernal keratoconjunctivitis shares several clinical char-acteristics of atopic disease, and the immunologicalchanges are also indicative of type I and IV hypersensi-tivity reactions. Similar to atopic disease, one of the mostimportant pathophysiological mechanisms is the releaseof inflammatory mediators by degranulating mast cellsand eosinophils (e.g., histamine or major basic protein).55

Conjunctival plasma cells synthesize IgA, IgG and IgE.56

Changes of the vascular endothelium such as hyperpla-sia, hypertrophy, and necrosis, together with the exis-tence of basophilic granulocytes in epithelium andstroma, suggest a basophilic hypersensitivity reaction.57

Increased vascular permeability, deposition of fibrin,and fibrovascular hypertrophy of subepithelial tissueleads to the formation of giant papillary changes that arepredominantly located in the tarsal conjunctiva. In lim-bal vernal conjunctivitis, papillae are smaller and in-flammatory degenerations of the epithelium cause for-mation of pseudocysts containing degenerated epithelialcells and eosinophilic granulocytes (Trantas dots) (Fig-ure 2.5). Corneal changes include superficial keratitis,formation of (shield) ulcers, and stromal opacities thatare frequently located at the limbus.

2. Classification of Ocular Surface Disease 23

Table 2.7. Conjunctival inflammation in ocular allergy.

Seasonal conjunctivitisPerennial conjunctivitisAtopic keratoconjunctivitisVernal keratoconjunctivitisGiant papillary conjunctivitisContact dermatitis

Figure 2.5. Limbal form of ver-nal keratoconjunctivitis.

104 T. Kim and B.A. Khosla-Gupta

Mild

Perilimbal ischemia None

Stromal haze Faint

Perilimbal ischemia Little or none

Stromal haze Moderate

Moderate

Perilimbal ischemia �1/3

Stromal haze Blurs iris detail

Moderate to severe

Perilimbal ischemia 1/3 - 2/3

Stromal haze Blurs pupil Cornea often marbleized

Severe

Perilimbal ischemia �2/3

Stromal haze Pupil not visible Cornea often marbleized

Very severe