Chapter 9A
Giant Papillary Conjunctivitis
Main Menu   Table Of Contents



Giant papillary conjunctivitis (GPC), first described by Spring1 in 1974, is an inflammatory disorder of the external eye. It is most commonly associated with contact lens wear. It has also been associated with ocular prostheses2 and exposed sutures. Clinically, GPC is characterized by papillary hypertrophy of the upper tarsal conjunctiva, similar in appearance to the papillae seen in vernal conjunctivitis. Itching and burning, discomfort (foreign-body sensation), and increased mucus production are the symptoms of GPC.3 Patients usually report a past ocular history of contact lens wear or ocular surgery (cataract, keratoplasty, enucleation). The signs of GPC include mucous discharge, papillary conjunctivitis consisting of enlarged papillae (Fig. 1), lid swelling, and ptosis and pannus (Fig. 2). Allansmith4 defined giant papillae as those larger than 1 mm. GPC shares other signs with vernal conjunctivitis, including Trantas' dots and limbal gelatinous elevations.5 Apical fibrotic-appearing changes of the papillae have been reported clinically, but it is unclear if these changes are transitory or permanent (Fig. 3).

Fig. 1. Enlarged papillae of upper tarsus in GPC.

Fig. 2. Pannus in patient with GPC.

Fig. 3. Scarring of upper tarsal conjunctiva in a patient with GPC.END

Back to Top
Theories involving immune and mechanical mechanisms have been espoused in the pathophysiology of GPC. Most theories suggest that proteinaceous material must be deposited on the lens surface for either the allergic or the mechanical mechanisms to take effect.


Deposits on Lenses

The adsorption of tear proteins onto the surface of hydrophilic contact lenses6 has been documented by many different methods. The deposits found on spoiled contact lenses include lipids that do not appear to be antigenic,7 and proteins. Many tear proteins that have been identified on contact lenses include lysozyme, lactoferrin, protein G, prealbumin, albumin, and immunoglobulins.8–15 All hydrogel lenses develop a proteinaceous coating that begins almost immediately after insertion.16–18 In a model of protein deposition, a dual layer forms over the contact lens surface immediately after insertion. The first (primary) layer that forms is composed mainly of irreversibly bound denatured proteins. The pellicle, a mucoprotein layer, is partially reversible, is denatured, and tries to equilibrate with the tear film. Lens biocompatibility is largely determined by the primary layer and its biochemical structure because the primary layer is more apt to undergo conformational changes than the second layer. It has been suggested, but not proved, that it is this protein and tear film interaction that ultimately determines whether a contact lens surface is biocompatible. If it is not biocompatible, adverse external ocular responses such as GPC may result.15,19

The type of contact lens may explain how deposits collect on the contact lens surface of patients who develop GPC. The extent to which protein is deposited on the anterior contact lens surface seems to depend on the polymer content, structure, and charge.20,21 Lenses with higher water content tend to develop more deposits than lenses with lower water content.22 The high porosity may allow more tear film components to enter and embed in the contact lens matrix.14,19,23 The net ionic charge of the polymer also influences protein buildup. Lysozyme, a positively charged protein, is attracted to negatively charged ionic materials.24–26 Studies have shown that lenses with both high water content and ionic properties have the greatest deposition of proteinaceous material.6,18,22,27 Furthermore, protein may not deposit uniformly on hydrogels. Some lenses tend to build up protein on the edge, compared with a more uniform distribution on lenses from other groups.28

The hydrogel fabrication process appears to induce a different protein adsorption behavior.29 Lathe-cut lenses tend to adsorb twice the amount of protein as spincast lenses.30 Another study showed lathed hydrogels to have deposits in the lathe marks even after vigorous cleaning.31

It may seem logical to assume that the greater the amount of deposit, the greater the likelihood of developing GPC. However, there has not been a definitive association between GPC with a particular lens type and the amount of protein deposited on the contact lens surface,32 further questioning the importance of proteins. Increased deposition of protein on lenses of some GPC patients may be the result of the inflammatory reaction rather than the cause of the reaction.9,19 Furthermore, the deposits on soft contact lenses of patients with GPC appear no different on scanning electron microscopy from deposits on lenses of asymptomatic wearers.19


The biochemical nature of protein deposits rather than the quantity or appearance of bound protein may be important. For example, once lysozyme is bound irreversibly to the lens surface, it undergoes molecular conformational changes.30,33 Lens-bound protein may be denatured by shearing forces and stresses interacting at the anterior lens surface, such as cyclical drying and rewetting.23 Once lysozyme has been denatured, its interactions with other layers in the tear film are altered and this interaction may play a role in inducing GPC.


Evidence for the allergic theory of GPC includes many studies on the immune reaction in these patients. Most studies have been aimed at immediate hypersensitivity mechanisms. A biopsy study of tissue obtained from a patient with GPC associated with an ocular prosthesis34 found conjunctival plasma cells mostly containing IgE antibody, and to a lesser extent IgG, IgA, and IgM antibody. Another study evaluated tears of 18 patients with GPC and noted the highest level of IgE antibody in the tears of patients with GPC, compared with the IgE tear levels in vernal keratoconjunctivitis. Using transferrin as a marker, these investigators confirmed the suggestion that the IgE antibody was locally produced.35 Contact lens deposits expected to mediate an immunologic response in GPC have also been investigated. Refojo and Holly36 in 1977 suggested that tear protein adsorbed onto the contact lens surface might produce contact lens allergy. Strong anecdotal support for this notion includes the finding of accumulated surface deposits on contact lenses from GPC patients.37 Replacing a worn lens with a new or different lens or cleaning a worn lens often may improve GPC signs and symptoms.38 Asymmetric and unilateral GPC has been observed in the eye wearing the older, dirtier lens.39 In an animal model for GPC, eyes that wore lenses from GPC patients were more likely to develop an inflammatory response akin to GPC than were eyes exposed to unworn soft contact lenses and lenses from asymptomatic wearers.40 An increase in the IgG to IgA deposition ratio has been found on lenses obtained from patients with GPC compared with lenses obtained from asymptomatic contact lens wearers.41 A subsequent study found increased IgM deposition on GPC-associated contact lenses42 but could not confirm the increased IgG to IgA ratio. Eosinophil major basic protein is material elaborated from eosinophils attracted to allergic reactions. This material was not deposited to a significant degree on contact lenses obtained from GPC patients.43,43a


In contrast, and in support of the mechanical theory, investigators have been unable to confirm a direct immunologic role of the contact lens. One animal study suggested that the polymeric composition of one soft contact lens material was not particularly antigenic and therefore unlikely to incite GPC via an immunologic reaction.44 Hypersensitivity testing of contact lens-intolerant patients with contact lens material has revealed infrequent reactivity.45,46 The mechanically induced hypothesis has been supported by the association between GPC and inert objects such as exposed sutures, extruded scleral buckles, cyanoacrylate adhesives, and a keratinized limbal dermoid cyst.4,46a The fact that GPC has produced bloody tears presumably due to conjunctival irritation and friction gives further support to the mechanical theory. Neutrophil chemotactic factors (NCF) thought to originate from damaged conjunctival epithelial cells have been found in the tears of symptomatic GPC patients at 15 times the level of asymptomatic patients.43 In addition, after injection of these factors into the upper tarsal conjunctiva of rabbits for 7 days, a GPC-like inflammatory reaction was observed. It has been suggested that damage necessary to release NCF may come from a continued assault on the tarsal conjunctiva by the contact lens.43,47 As a result, these findings have led to the theory of a combined pathogenesis for GPC involving both mechanical trauma to the upper tarsal conjunctiva and a hypersensitivity reaction to lens-bound antigens.47,48

Back to Top
The epithelium shows a reduction in the number of goblet cells and infiltration with mast cells. Other inflammatory cells, including eosinophils, basophils, and lymphocytes, have also been observed. The stroma has an increased number of inflammatory cells, including lymphocytes and plasma cells, eosinophils and basophils, and degranulating mast cells. In the advanced stages there is proliferation of fibroblasts and deposition of collagen.4
Back to Top


Contact lens wear should be stopped, exposed sutures removed, and adhesive covered or removed.


Drugs that stabilize the mast cell and prevent degranulation have been used to treat GPC. Sodium cromolyn drops have been shown to be effective for the treatment of GPC.49 Alomide, a new mast cell stabilizer effective against vernal conjunctivitis, Acular, a prostaglandin inhibitor effective against allergic conjunctivitis, and Levostin, a new antihistamine, have yet to be tested against GPC.

Specific types of corticosteroids have been developed to maximize potency and decrease side effects. One of these drugs, loteprednol etabonate, is effective in GPC.50 However, this was a short-term study, and the side effects with prolonged use have not been established. The long-term use of corticosteroids is discouraged in the treatment of GPC because of the potential side effects.

Treatment Directed at the Contact Lenses

Cleaning contact lenses, replacing a worn lens with a new one, or switching to a different type of contact lens has given relief from GPC. Fitting disposable contact lenses has successfully allowed continued contact lens wear in some GPC patients. However, GPC has been associated with disposable contact lens wear.48 Disposables are not exempt from protein deposition.47,51 Their advantage over conventional hydrogels in the context of GPC is probably not due to the characteristics of the lenses themselves, but possibly the frequency of replacement that may minimize mechanically induced conjunctival trauma and contact lens deposits.

Rigid gas-permeable (RGP) contact lenses were and still are used as alternative lenses in the therapeutic strategy for GPC. RGP lenses are smaller than soft lenses and thus present a smaller surface area to the conjunctiva. The edge of a gaspermeable lens can be shaped and reshaped to minimize trauma to the conjunctiva. Finally, deposits are removed more easily from hard lenses than from hydrogel lenses.52 However, GPC occurring in wearers of rigid gas-permeable lenses has been reported.53,54 A retrospective study showed an inverse relationship between DK value and the interval of time between RGP contact lens wear and the onset of GPC.54 It was reasoned that higher DK material with poorer wettability over time was apt to collect deposits, with resultant GPC. The wettability of RGPs has since been enhanced with the creation of fluorinated RGP contact lenses.

The difficulty in ascertaining the impact of contact lens type and material on the development of GPC is further hampered by many other variables that may play a role in the pathogenesis of this disorder. They include disinfection methods, cleaning routines, lens thickness, tear pH, blinking mechanisms, lens wettability, and elasticity.19 It is also difficult to control for the effect the external milieu has on the lens/tear interaction in conditions such as blepharitis55,56 and atopic disease.55,57 Other extrinsic factors that may contribute to lens spoilage and GPC include airborne antigens and microbes that adhere to the lens deposits or lens surface.

Supported in part by a Department of Veterans Affairs Research Service Grant (ELS).

Back to Top

1. Spring TF: Reaction to hydrophilic lenses. Med J Aust 1:449, 1974

2. Srinivasan BD, Jacobiec FA, Iwamoto T et al: Giant papillary conjunctivitis with ocular prostheses. Arch Ophthalmol 97:892, 1979

3. Korb DR, Allansmith MR, Greiner JV et al: Prevalence of conjunctival changes in wearers of hard contact lenses. Am J Ophthalmol 90:336, 1980

4. Allansmith MF, Korb DR, Greiner JV et al: Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol 83:697, 1977

5. Meisler DM, Zaret CR, Stock EL: Trantas dots and limbal inflammation associated with soft contact lens wear. Am J Ophthalmol 89:66, 1980

6. Minno GE, Eckel L, Groemminger S et al: Quantitative analysis of protein deposits on hydrophilic soft contact lenses: I. Comparison to visual methods of analysis. II. Deposit variation among FDA lens materials groups. Optom Vis Sci 68:865, 1991

7. Friedlaender MH: Principles of general immunology and mechanisms of immune reactivity. In Tasman W, Jaeger E: Duane's Foundations of Clinical Ophthalmology, Vol 2, p 1. Philadelphia, JB Lippincott, 1993

8. Sack RA, Jones B, Antignani A et al: Specificity and biological activity of the protein deposited on the hydrogel surface. Invest Ophthalmol Vis Sci 28:842, 1987

9. Versura P, Maltarello MC, Roomans GM et al: Scanning electron microscopy, x-ray microanalysis and immuno histochemistry on worn soft contact lenses. Scanning Microsc 2:397, 1988

10. Gudmundsson OG, Woodward DF, Fowler SA et al: Identification of proteins in contact lens surface deposits by immunofluorescence microscopy. Arch Ophthalmol 103: 196, 1985

11. Cheng KG, Kok JHC, van Mil C et al: Selective binding of a 30-kilodalton protein to disposable hydrophilic contact lenses. Invest Ophthalmol Vis Sci 31:2244, 1990

12. Tripathi PC, Tripathi RC: Analysis of glycoprotein deposits on disposable soft contact lenses. Invest Ophthalmol Vis Sci 33:121, 1992

13. Hosaka S, Ozawa H, Tanzawa H et al: Analysis of deposits on high water content contact lenses. J Biomed Mater Res 17:261, 1983

14. Gachon AM, Bilbaut T, Dastugue B: Adsorption of tear proteins on soft contact lenses. Exp Eye Res 40:105, 1985

15. Wedler FC: Analysis of biomaterials deposited on soft contact lenses. J Biomed Mater Res 11:525, 1977

16. Fowler SA, Allansmith MR: Evolution of soft contact lens coatings. Arch Ophthalmol 98:95, 1980

17. Hart DE, DePaolis M, Ratner D et al: Surface analysis of hydrogel contact lenses of ESCA. CLAO J 19:169, 1993

18. Leahy C, Mandell R, Lin S: Initial in vivo tear protein deposition on individual hydrogel contact lenses. Optom Vis Sci 67:504, 1990

19. Hart DE, Schkolnick JA, Bernstein S et al: Contact lens induced giant papillary conjunctivitis: A retrospective study. J Am Optom Assn 60:195, 1989

20. Minarik L, Rapp J: Protein deposits on individual hydrophilic contact lenses: Effects of water and ionicity. CLAO J 15:185, 1989

21. Refojo MF, Leong FL: Microscopic determination of the penetration of proteins and polysaccharides into poly (hydroxyethylmethacrylate) and similar hydrogels. J Polym Sci(C) Polymer Symp 66:227, 1979

22. Fowler SA, Korb DR, Allansmith MR: Deposits on soft contact lenses of various water contents. CLAO J 11:124, 1985

23. Hart DE: Surface interactions on hydrogel contact lenses: Scanning electron microscopy (SEM). J Am Optom Assn 58:962, 1987

24. Franklin V, Horne A, Jones L et al: Early deposition trends on group I (polymacon and tetrafilcon A) and group III (bufilcon A) materials. CLAO J 17:244, 1991

25. Stone RP, Mowrey-McKee MF, Kreutzer P: Protein: A source of lens discoloration. Contact Lens Forum 9:33, 1984

26. Royce FH Jr, Ratner BD, Hobbett TA: Adsorption of proteins from artificial tear solutions to poly (methylmethacrylate-2-hydroxyethyl methacrylate) copolymers. Biomaterials 99:453, 1982

27. Meyers RI, Larsen DW, Tsao M et al: Quantity of protein deposited on hydrogel contact lenses and its relation to visible protein deposits. Optom Vis Sci 68:776, 1991

28. Heiler DJ, Gambacorta-Hoffman S, Groemminger SF et al: The concentric distribution of protein on patient-worn hydrogel lenses. CLAO J 17:249, 1991

29. Tripathi RC, Tripathi BJ, Rubben M: The pathology of soft contact lens spoilage. Ophthalmology 87:365, 1980

30. Castillo EJ, Koenig JL, Anderson JM et al: Protein adsorption on hydrogels. II. Reversible and irreversible interactions between lysozyme and soft contact lens surfaces. Biomaterials 6:338, 1985

31. Fowler SA, Gaertner KL: Scanning electron microscopy of deposits remaining in soft contact lens polishing marks after cleaning. CLAO J 16:214, 1990

32. Barr JT, Dugan PR, Reindel WR et al: Protein and elemental analysis of contact lenses of patients with superior limbic keratoconjunctivitis or giant papillary conjunctivitis. Optom Vis Sci 66:133, 1989

33. Castillo EJ, Koenig JL, Anderson JM et al: Characterization of protein adsorption on soft contact lenses. IV. Comparison of in vivo spoilage with the in vitro adsorption of tear proteins. Biomaterials 7:89, 1986

34. Meisler DM, Krachmer JH, Goeken JA: An immunopathologic study of giant papillary conjunctivitis associated with an ocular prosthesis. Am J Ophthalmol 92:368, 1981

35. Donshik PC, Ballow M: Tear immunoglobulins in giant papillary conjunctivitis induced by contact lenses. Am J Ophthalmol 96:460, 1983

36. Refojo MF, Holly FJ: Tear protein adsorption on hydrogels: A possible cause of contact lens allergy. Contact and Intraocular Lens Med J 3:23, 1977

37. Fowler SA, Greiner JV, Allansmith MR: Soft contact lenses from patients with giant papillary conjunctivitis. Am J Ophthalmol 88:1056, 1979

38. Udell IJ, Meisler DM: Giant papillary conjunctivitis. In Cohen EJ (ed): International Ophthalmology Clinics: Contact Lenses and External Disease, pp 35–41. Boston, Little, Brown & Co, 1986

39. Palmisano PC, Ehlers WH, Donshik PC: Causative factors in unilateral giant papillary conjunctivitis. CLAO J 19: 103, 1993

40. Ballow M, Donshik PC, Rapacz P et al: Immune responses in monkeys to lenses from patients with contact lens induced giant papillary conjunctivitis. CLAO J 15:64, 1989

41. Jones B, Sack R: Immunoglobulin deposition on soft contact lenses: Relationship to hydrogel structure and mode of use and giant papillary conjunctivitis. CLAO J 16:43, 1990

42. Richard NR, Anderson JA, Tasevska ZG et al: Evaluation of tear protein deposits on contact lenses from patients with and without giant papillary conjunctivitis. CLAO J 18:143, 1992

43. Elgebaly SA, Donshik PC, Rahhal F et al: Neutrophil chemotactic factors in the tears of giant papillary conjunctivitis patients. Invest Ophthalmol Vis Sci 32:208, 1991

43a. Trocme SD, Kephart GM, Bourne WM et al: Eosinophil granule major basic protein in contact lenses of patients with giant papillary conjunctivitis. CLAO J 16:219, 1990

44. Allansmith MR, Baird RS: Evidence for lack of antigenicity of polymacon contact lens material in guinea pigs. Ophthalmic Res 12:192, 1980

45. Podmore P, Storrs FJ: Contact lens intolerance; allergic conjunctivitis? Contact Dermatitis 20:98, 1989

46. Dada VK, Kalra VK, Angra SK: Polymethyl methacrylate (PMMA) intolerance. Indian J Ophthalmol 33:57, 1985

46a. Friedlaender M: Some unusual nonallergic causes of giant papillary conjunctivitis. Trans Am Ophthalmol Soc 88: 343, 1990

47. Bucci FA Jr, Lopatynsky MO, Jenkins PL et al: Comparison of the clinical performance of the Acuvue disposable contact lens and CSI lens in patients with giant papillary conjunctivitis. Am J Ophthalmol 115:454, 1993

48. Maguen E, Rosner I, Caroline P et al: A retrospective study of disposable extended wear lenses in 100 patients: Year 2. CLAO J 18:229, 1992

49. Meisler DM, Berzins UJ, Krachmer JH et al: Cromolyn treatment of giant papillary conjunctivitis. Arch Ophthalmol 100:1608, 1982

50. Bartlett JD, Howes JF, Ghormley NR et al: Safety and efficacy of loteprednol for treatment of papillae in contact lens-associated giant papillary conjunctivitis. Curr Eye Res 12:303, 1993

51. Lin ST, Mandell RB, Leahy CD et al: Protein accumulation on disposable extended wear lenses. CLAO J 17:44, 1991

52. Fowler SA, Korb DR, Finnemore VM et al: Surface deposits on worn hard contact lenses. Arch Ophthalmol 102: 757, 1984

53. Hardman Lea SJ, Neugebauer AZ, Smith RG et al: The incidence of ophthalmic problems in the contact lens wearing population. Eye 4:706, 1990

54. Douglas JP, Lowder CY, Lazorik R et al: Giant papillary conjunctivitis associated with rigid gas permeable contact lenses. CLAO J 14:143, 1988

55. Martin NF, Rubinfeld RS, Malley JD et al: Giant papillary conjunctivitis and meibomian gland dysfunction blepharitis. CLAO J 18:165, 1992

56. Mathers WD, Billborough M: Meibomian gland function and giant papillary conjunctivitis. Am J Ophthalmol 114: 188, 1992

57. Begley CG, Riggle A, Tuel JA: Association of giant papillary conjunctivitis with seasonal allergies. Optom Vis Sci 67:192, 1990

Back to Top