AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Giant papillary conjunctivitis (GPC) is a common complication of contact lens (CL) wear. Spring first described GPC in association with CL use in 1974.¹ Papillary changes can occur in the ocular tarsal palpebral conjunctivae as part of an immunoglobulin E (IgE)-mediated hypersensitivity reaction.

Prior to the popularization of hydrogel (soft) CLs in the past 4 decades, this reaction primarily was seen as allergic conjunctivitis (AC) or vernal keratoconjunctivitis (VKC). VKC is a seasonal atopic disease in young people (more common in boys), which occasionally becomes severe and leads to shield corneal ulcers and other complications. GPC related to CL wear never leads to the severe tissue morbidity of VKC.

Papillary changes in the tarsal conjunctiva have been associated with the use of all types of CLs (eg, rigid, hydrogel, scleral, prosthetic). Similar reactions have been noted with ocular prostheses, extruding scleral buckles, exposed ocular sutures, and even elevated corneal scars. When the small papillae coalesce with expanding internal collections of inflammatory cells and when the lesions reach a diameter of at least 1.0 mm, the condition is referred to as giant.

Pathophysiology

The antigens responsible for GPC have not been identified. From circumstantial evidence, the initiating event is believed to be mechanical irritation of the tarsal conjunctiva of the upper lids, followed by histologic changes in the tissue (mast cell degranulation and typical secondary inflammatory cascade).

Frequency

United States

Hydrogel CLs appear to result in an overall prevalence of GPC of approximately 20%. Silicone hydrogel CLs may be more prone to GPC development, perhaps because of their mechanical stiffness or their higher propensity for deposition. Heat sterilization, poor cleaning, rough CL edges, and extended wearing times favor development of GPC. Increased frequency of CL replacement (especially daily disposables), rigorous cleaning (particularly with enzymes), peroxide disinfection, and decreased wear times appear to reduce the prevalence of GPC among users of hydrogel CLs. Rigid CL wear appears to result in a prevalence of approximately 5%; increased enzyme cleaning appears prophylactic.

International

No differences are reported; the prevalence is similar to that in the United States.

Mortality/Morbidity

GPC is not associated with any mortality.

• Ptosis of the upper lids and decreased CL tolerance can occur.
• GPC has been a common cause for permanent CL intolerance.

Race

No racial differences have been described.

Sex

Both sexes develop GPC.

Age

GPC can be more aggressive in children who wear CLs.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Patients often report decreasing CL tolerance and mechanical stability, ocular itching, and mucous discharge in the tears, as well as blurred vision and conjunctival injection.

Physical

• Clinicians commonly note protein-laden CLs. Also, CLs appear to ride more under the upper lids than expected.
• With eversion of the lids, inflammation of the vasculature (hyperemia) and papillary hypertrophy are noted.
• Mucous strands are seen both in the tears and between the papillae.
• Papillae can range from small uniform lesions (uniform cobblestone appearance [UCA]) to irregular changes (nonuniform cobblestone appearance [NUCA]) to clusters of giant lesions with whitish centers that can ulcerate and stain with sodium fluorescein dye.
• • Originally, the papillae of the upper tarsal conjunctiva were thought to have to be at least 1 mm to diagnose GPC.
  • Today, the clinical sign is generally accepted as follows: the papillae are at least 0.3 mm diameter on the upper palpebral conjunctiva in association with the classic symptoms.
• GPC that is associated with hydrogel CLs appears more commonly at the fold of the everted lid, spreading over the entire tarsal conjunctival surface.
• GPC that is associated with rigid CL wear shows an opposite pattern, corresponding to the position of the CL edge meeting the lid tissues. This is evidence for the mechanical etiological hypothesis.

Causes

All forms of ocular prostheses, including rigid and hydrogel CLs, artificial glass eyes, extruding scleral buckles, exposed portions of sutures, filters, and knots (even corneal scars), can cause GPC.

• Other diagnostic considerations
• • Distinguish from other diseases that cause conjunctivitis and ocular itching/mucus - Typically ocular allergies (hay fever conjunctivitis) but also viral and bacterial conjunctivitis and blepharitis
  • Distinguish from other diseases that cause papillary changes in the tarsal conjunctiva of the lids, especially vernal and atopic conjunctivitis
  • Distinguish from other giant papillary forming disorders by the creamy white appearance of the giant papillae center/top (a clinical pearl)
  • Distinguish from other diseases that cause follicular changes, which can easily be confused with papillary changes, in the palpebral conjunctivae of the lids - Viral conjunctivitis (adenovirus and herpes); chlamydial infections; and Gel-Coombs type IV hypersensitivity and toxic reactions, particularly to CL solutions
  • Distinguish from other causes of CL intolerance, such as poor fit, dry eyes, and blepharitis

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No lab studies are necessary, although some authors advocate screening patients who wear CLs for increased levels of IgE in their tears.
• Because of the high prevalence of this complication to CL wear, every patient who wears CLs should be considered as a potential patient with GPC.
• • Attending eye doctors should routinely invert and visually inspect lids, especially if a patient who wears CLs has any ocular complaints.
  • Subjective ocular itching; mucus; CLs with significant protein deposits; and CLs that become less comfortable, more mobile, or ride higher underneath the upper lids should all raise suspicion of GPC.

Histologic Findings

Quantitative histologic findings on biopsy specimens from the upper tarsal conjunctivae of patients with either VKC or GPC suggest abnormalities. Mast cells are found in the epithelium, and eosinophils and basophils are found in the epithelium and substantia propria.

Common tear abnormalities include elevated levels of immunoglobulin G (IgG), IgE, and immunoglobulin M (IgM), as well as complement factors, such as C3, factor B, and C3 anaphylatoxin. Specific antigens are thought to cause local production of these mediators. Another feature includes reduced lactoferrin levels in tears (also present in VKC). The significance of these findings is yet to be determined.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• For severe GPC, patients who wear CLs purely for cosmesis should discontinue CL wear for 2-4 weeks (the interval during which symptoms may begin to reverse and signs improve).  Steroids can be used for these cases.  Combination mast cell stabilizers and antihistamine ophthalmic medications can sometimes suffice. Most patients do not require more aggressive treatment.
• For mild-to-moderate GPC or when CL wear is resumed after discontinuing CL wear in severe cases, refit patients into new CLs. Refit wearers of hydrogel CLs into disposable CLs, especially daily disposable CLs. If daily disposable CLs are not available, wearers of hydrogel CLs should use peroxide disinfecting solutions with their frequently disposable CLs. Reemphasize CL cleaning techniques, especially rubbing with "no-rub" labeled solutions; also educate patients about the nature of this allergic disease.  
• Wearers of rigid and hydrogel CLs should use some form of enzyme cleaning, at least twice per week or as frequently as every night. This measure is unnecessary for patients who use daily disposable hydrogel CLs.
• Topical mast cell stabilizers and antihistamine combination solutions (eg, olopatadine, Elestat) may offer a pharmacological alternative for these patients, although CL cessation is the most effective treatment.
• Cool compresses can be added to improve symptoms.
• Considering the efficacy and safety of most modern keratorefractive procedures (eg, LASIK), patients who refuse conservative management may consider refractive surgery to avoid CLs.
• Symptoms may be more important than signs.
• • Therapeutic effect is evidenced by the subjective return of CL tolerance, suppression of ocular itching, decreased objective hyperemia of the tarsal conjunctivae, decreased inflammation of the giant papillae, and lessened mucus in the tears.
  • The lids of some patients return to normal appearance, while other lids retain small, white, capped scars of the giant papillary lesions for long periods of time, sometimes indefinitely.

MEDICATION

Section 7 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Pharmacological management is a mildly to moderately effective, adjunctive treatment when patients with GPC cannot or will not discontinue wearing CLs. GPC is a Gel-Coombs type 1 disease with degranulated conjunctival mast cells as the chief histologic feature; therefore, drugs that inhibit mast cell degranulation are effective.

The most commonly used topical medications are combination dual acting H1 receptor antagonists and inhibitors of histamine release from mast cells (ie, olopatadine hydrochloride, ketotifen fumarate). Topical mast cell stabilizers, nonsteroidal anti-inflammatory drugs (NSAIDs), and antihistamines are also used. Steroids can be useful for severe cases.

Topical ophthalmic medications should be used cautiously with CL wear, because these medications are commonly preserved with benzalkonium chloride (BAK). BAK is associated with corneal epithelial toxicity episodes (a greater concern with hydrogel CLs).

If medication must be administered concomitantly with hydrogel CLs, application should be restricted to a maximum of 3 times a day (ie, 1 gtt just prior to CL wear, 1 gtt immediately upon CL removal, 1 gtt hs).  Once-daily and twice-daily ophthalmic medications are now available (eg, Pataday, Zaditor) for increased patient compliance and convenience, especially for CL wearers. Patients should wait at least 10 minutes after medication instillation before CL insertion.

Drug Category: Mast cell stabilizers

GPC primarily appears to be a Gel-Coombs type 1 hypersensitivity disease. The primary pathological event is inappropriate degranulation of the conjunctival mast cells, which release many inflammatory mediators, such as histamine (resulting in itch).  Pure mast cell stabilizers are indicated for long-term use after the acute phase of symptoms is abated.

Drug Category: Antihistamines

These agents are used for the temporary relief of the signs and symptoms (itching) of allergic conjunctivitis. 

Drug Category: Corticosteroids

These agents inhibit many aspects of the inflammatory response to inciting agents: edema, capillary dilation and proliferation, leukocyte migration, and fibroblast proliferation.

Drug Category: Antihistamine/Mast Cell Stabilizer

These agents are used to treat symptoms of itching and to prevent future symptoms by controlling the degranulation of mast cells.  Mast cell-stabilizing medications/antihistamine combination drops are most likely to achieve the therapeutic effect with minimal complications. 

Drug Category: Nonsteroidal Anti-inflammatory Drug (nsaid), Ophthalmic

The inhibition of prostaglandin synthesis results in vasoconstriction, a decrease in vascular permeability, leukocytosis, and a decrease on intraocular pressure (IOP). However, these agents have no significant effect on IOP.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Approximately 80% of patients who develop GPC with CL use can return to comfortable CL wear with appropriate treatment. Frequent encouragement by the clinician can be essential, because the symptoms may take a while to subside.
• The patient should be frequently monitored while GPC is active, perhaps every few weeks to few months.
• Once GPC successfully is managed, patients should receive follow-up care as indicated by other aspects of their ophthalmic and medical situation.
• Patients should be educated about the chronic nature of this disease and its symptoms (eg, ocular itch, mucous discharge, CL intolerance). Patients should be counseled to present within a week of any relapsing symptoms.

Deterrence/Prevention

• Optimal CL cleaning, replacement, and appropriate/timely professional supervision will minimize occurrence and result in minimal patient symptoms and tissue morbidity.

Complications

• Decreased CL tolerance and lid ptosis

Prognosis

• The prognosis is good. Approximately 80% of patients can return to comfortable CL wear with appropriate treatment.

Patient Education

• Patients should be educated about appropriate CL cleaning and follow-up care. Patients should be advised to return for regular professional evaluations (perhaps once or twice a year if no other complications) but to additionally appoint if they experience any increasing ocular itching, mucous discharge, or dirty CLs.
• For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education articles Pinkeye and Contact Lenses.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Use of topical steroid drops, especially for more than a few weeks, is associated with glaucoma, cataracts, and decreased ocular resistance to infection.
• • Topical steroid use is a particular concern in patients with past history of herpetic eye disease.
  • Although topical corticosteroid use is not associated with induction or facilitation of viral recurrence, a fulminant infection could occur if the herpes virus recurs during topical corticosteroid treatment. Increased concerns exist regarding de novo fungal and other viral infections and potentiating bacterial infections.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Very large papillae in the everted upper lid of a patient who wears hydrogel (soft) contact lenses.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Spring TF. Reaction to hydrophilic lenses. Med J Aust. Mar 23 1974;1(12):449-50. [Medline].
2. Aakre BM, Ystenaes AE, Doughty MJ, Austrheim Ø, Westerfjell B, Lie MT. A 6-month follow-up of successful refits from daily disposable soft contact lenses to continuous wear of high-Dk silicone-hydrogel lenses. Ophthalmic Physiol Opt. Mar 2004;24(2):130-41. [Medline].
3. Allansmith MR, Korb DR, Greiner JV. Giant papillary conjunctivitis induced by hard or soft contact lens wear: quantitative histology. Ophthalmology. Aug 1978;85(8):766-78. [Medline].
4. Allansmith MR, Korb DR, Greiner JV, Henriquez AS, Simon MA, Finnemore VM. Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol. May 1977;83(5):697-708. [Medline].
5. Chang WJ, Tse DT, Rosa RH, Huang A, Johnson TE, Schiffman J. Conjunctival cytology features of giant papillary conjunctivitis associated with ocular prostheses. Ophthal Plast Reconstr Surg. Jan 2005;21(1):39-45. [Medline].
6. Donshik PC, Ballow M. Tear immunoglobulins in giant papillary conjunctivitis induced by contact lenses. Am J Ophthalmol. Oct 1983;96(4):460-6. [Medline].
7. Donshik PC, Ballow M, Luistro A, Samartino L. Treatment of contact lens-induced giant papillary conjunctivitis. CLAO J. Oct-Dec 1984;10(4):346-50. [Medline].
8. Korb DR, Greiner JV, Finnemore VM, Allansmith MR. Treatment of contact lenses with papain. Increase in wearing time in keratoconic patients with papillary conjunctivitis. Arch Ophthalmol. Jan 1983;101(1):48-50. [Medline].

Article Last Updated: Nov 2, 2007