Donshik PC: Contact lens chemistry and giant papillary conjunctivitis. Eye & Contact Lens 29:S37–S39, 2003.

Donshik PC: External wear contact lenses. Ophthalmol Clinic N Amer 16(3):305–309, 2003.

Donshik PC: Giant papillary conjunctivitis. Trans Am Ophthalmol Soc 92:687–744, 1994.

Driebe WT, Jr: Disposable contact lenses. Surv Ophthalmol 34:44–46, 1989.

Ehlers WH, Donshik PC, Suchecki JK: Disposable and frequent replacement contact lenses. Ophthalmol Clinic N Amer 16(3):341–352, 2003.

Ehlers WH, Donshik PC: Allergic ocular disorders: a spectrum of disease. CLAO J 18:117–124, 1992.

Friedlander MH, Howes J: A double-marked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. Am J Ophthalmol 123:455–464, 1997.

Suchecki JK, Donshik PC, Ehlers WH: Contact lens complications. Ophthalmol Clinic N Amer 116:471–484, 2003.

182 LIGNEOUS CONJUNCTIVITIS

372.10

Romain De Cock, MBChB, FRCS, FRCOphth

Canterbury, England

ETIOLOGY/INCIDENCE

Ligneous conjunctivitis is a rare form of recurrent conjunctival inflammation characterized by the formation of thick membranes and pseudomembranes leading to induration of the lids, which assume a woody or ligneous consistency. Usually bilateral, although often asymmetric, it generally affects infants and young children but may occur at any age. There is a slight female preponderance (1.4 : 1). A familial predisposition has been reported, but most cases are sporadic.

Deposition of membrane may also occur in extraocular mucosal sites such as the respiratory tract, vocal cords, gingiva, middle ear, vagina and cervix.

In several cases homozygous or compound heterozygous mutations in the plasminogen gene with decreased immunoreactive plasminogen antigen and decreased functional plasminogen activity (Type I plasminogen deficiency) have been described. In at least two reports tranexamic acid, an antifibrinolytic agent, has been implicated in the formation of conjunctival and/or gingival membranes. Both ocular and extraocular membranes consist of fibrin thus pointing to a failure of fibrinolysis at various mucosal sites of which the conjunctiva are the most common. Fibrin deposition is initiated by an inflammatory stimulus such as infection or trauma (including surgery to remove the membranes) with hypofibrinolysis leading to accumulation and persistence of the fibrinous membranes.

COURSE/PROGNOSIS

●Variable, with more profound decrease in functional and immunoreactive plasminogen levels possibly accounting for more severe disease.

●May persist for many years without severe discomfort or visual loss.

●Usually chronic irritation, redness, discharge and swelling of the lids.

●Mild secondary corneal involvement in 25% of cases; rarely, severe keratopathy.

●Spontaneous resolution in approximately 10% of patients.

●Possible relapse after a prolonged period of quiescence, often at a time of concurrent febrile systemic illness.

DIAGNOSIS

Clinical signs and symptoms

The condition presents most commonly in infancy or childhood as an acute or a subacute conjunctivitis with membrane and pseudomembrane deposition on the upper tarsal conjunctiva, although the lower tarsal and bulbar conjunctiva may also be affected. The membranes are firmly attached at their base and take on a flattened aspect on the surface due to lid movement and compression between the lid and the globe. A fibrinous pseudomembrane that can be readily removed often overlies the membrane. Excision or stripping of the membrane results in bleeding and rapid reformation of the membranous deposit leading to a chronic conjunctivitis. Corneal involvement with secondary neovascularization, scarring and thinning occurs in as many as 25% of patients, but severe keratopathy, including perforation, is rare now.

A systemic febrile illness, upper respiratory tract infection, or local trauma (including ocular surgery) often precedes the onset of the conjunctivitis and can be associated with relapses of the condition after periods of quiescence.

The deposition of membrane in extraocular mucosal sites may lead to life threatening respiratory obstruction. There is an association with occlusive hydrocephalus which in one case has been shown to be related to a craniocervical anomaly though obstruction of the acqueduct remains another possibility.

Laboratory findings

Histologically, the membranes consist of subepithelial deposits of amorphous hyaline material infiltrated to varying extents with lymphocytes, plasmacytes, neutrophils and eosinophils. The overlying epithelium is generally atrophic, and sometimes absent, with areas of epithelial downgrowth into the hyaline material containing goblet cells and mucus. The hyaline material consistently stains positive for fibrin.

Plasminogen activity and plasminogen antigen levels should be measured in all cases of suspected ligneous conjunctivitis.

Differential diagnosis

●Infective membranous and pseudomembranous conjunctivitis: bacterial, viral and chlamydial.

●Chemical burns.

●Stevens–Johnson syndrome.

●Lyell’s syndrome.

●Synthetic fiber granulomatous conjunctivitis (‘teddy bear conjunctivitis’).

●Factitious conjunctivitis.

TREATMENT

Treatment remains difficult. Surgical excision of the conjunctival membranes and excision followed by cautery, cryopexy, irradiation or grafting with conjunctiva or sclera have proved

182 ConjunctivitisCHAPTER Ligneous •

Conjunctiva • 18 SECTION

generally disappointing in the absence of steps to prevent further fibrin deposition. Topical hyaluronidase and alphachymotrypsin have given inconsistent results because mucopolysaccharides are not a major feature of ligneous conjunctivitis.

Topical cyclosporin A used in combination with topical steroids has been used successfully in several cases.

The constant presence of fibrin in ligneous conjunctivitis has prompted the use of topical heparin after excision of the membrane to prevent fibrin reaccumulation, together with a topical steroid to reduce inflammation and a topical antibiotic as prophylaxis against infection until conjunctival epithelial cover has been regained. It is essential with this regimen to achieve complete hemostasis with very meticulous cautery after excision of the conjunctival membrane and to immediately initiate intensive topical heparin and steroid. Once the epithelium has been reestablished, both the concentration and the frequency of the heparin and steroid drops can be tapered, and the topical antibiotic can be stopped. This regimen is very demanding for both patients and medical staff but has been successful in approximately 75% of patients.

More recent treatment modalities have been directed towards re-establishing fibrinolytic activity after excision of membrane with the use of topical plasminogen derived from fresh frozen plasma initially every 2 hours reducing to four times daily after 3 weeks or when re-epithelialization could be confirmed. Alternatively subconjunctival injection of fresh frozen plasma (1 mL) after excision followed by topical fresh frozen plasma 2 hourly for 3 days then four times daily for 2 weeks has been successfully used in one case.

Intravenous administration of lys-plasminogen has proved to be effective in patients with severe systemic disease but is impractical due to the short half-life of lys-plasminogen.

Estrogen and progestrogen oral contraceptives can elevate plaminogen levels and have been associated with clinical improvement of ligneous conjunctivitis in two cases.

The severity and clinical course of this condition is probably related to the degree of underlying hypofibrinolysis and this may well account for the variable results that have been obtained with different forms of treatment. While the optimal treatment regimen remains to be identified a logical approach is to combine efforts to increase local fibrinolysis with steps to prevent fibrin reformation following excision of membranes.

1.Topical plasminogen (ca. 1 mg/mL) every 2 hours to soften membranes.

2.Excise membrane.

3.Achieve complete hemostasis with cautery.

4.Start 5000 IU/mL topical heparin, 1% prednisolone every 30 minutes to 1 hour, and an antibiotic four times daily.

5.When the epithelium is healed, reduce medications to 1000 IU/mL heparin and 0.5%, 0.3%, and 0.1% prednisolone in gradually decreasing frequency according to the degree of conjunctival inflammation. Reduce topical plasminogen to

four times daily for 2–3 weeks.

5.Stop the antibiotic when the epithelium is healed.

6.Take special care to evert the lids for examination very gently so as to keep all microtrauma to a minimum.

Topical ciclosporin and cromoglycate have been successfully used in a few cases; it is possible that they may have a useful role in selected patients in whom the histologic examination confirms abundant lymphocytic or mast cell infiltration, respectively.

REFERENCES

De Cock R, Ficker LA, Dart JG, et al: Topical heparin in the treatment of ligneous conjunctivitis. Ophthalmology 102:1654–1659, 1995.

Heidemann DG, Williams GA, Hartzer M, et al: Treatment of ligneous conjunctvitis with topical plasmin and topical plasminogen. Cornea 22:760–762, 2003.

Hidayat AA, Riddle PJ: Ligneous conjunctivitis: a clinicopathologic study of 17 cases. Ophthalmology 94:949–959, 1987.

Holland EJ, Chan C-C, Kuwabara T, et al: Immunohistologic findings and results of treatment with cyclosporin in ligneous conjunctivitis. Am J Ophthalmol 107:160–166, 1989.

Martinovic E, Ells A: Ligneous conjunctivitis related to a defect in the fibrinolytic system. Can J Ophthalmol 36:147–149, 2001.

Mingers AM, Philapitsch A, Zeitler P, et al: Human homozygous type I plasminogen deficiency and ligneous conjunctivitis. APMIS 107:62–72, 1999.

Schott D, Dempfle C-E, Beck P, et al: Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency. NEJM 339:1679–1686, 1998.

Schuster V, Seregard S: Ligneous conjunctivitis. Surv Ophthalmol 48:369– 388, 2003.

Schuster V, Zeitler P, Seregard S, et al: Homozygous and compound-hetero- zygous Type I plasminogen deficiency is a common cause of ligneous conjunctivitis. Thromb-Haemost 85:1004–1010, 2001.

Tabbara KF: Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol 138:299–300, 2004.

Watts P, Suresh P, Mezer E, et al: Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol 133:451–455, 2002.

183 OPHTHALMIA NEONATORUM

771.6

William V. Good, MD

San Francisco, California

Irene T. Tung, BA

Houston, Texas

DEFINITION

Ophthalmia neonatorum is the traditional term used to indicate conjunctivitis in the newborn period. However, the World Health Organization prefers the more descriptive ‘conjunctivitis of the newborn’ in its communications. With an incidence perhaps as high as 18%, conjunctivitis of the newborn is one of the leading causes of infections in infants. In many cases, the etiology is viral or a low-grade bacterial pathogen, but in some cases, vision-threatening infections can occur. Many variables are responsible for the pathogen, including maternal infection (e.g. herpes simplex conjunctivitis, chlamydia and gonococcal conjunctivitis) and geographic location of the infant and family. In this chapter we describe clinical manifestations of various conjunctivitis entities, their timing of onset, laboratory investigations and treatment.

Signs and symptoms

In most cases, the signs and symptoms of conjunctivitis are non-specific. Timing of onset can offer a rough guide to possible etiologies. Signs of conjunctivitis in the first few days of life are often caused by antibiotic or silver nitrate toxicity. Both may be used to prevent conjunctivitis of the newborn. Gonococcal

183NeonatorumCHAPTER Ophthalmia •

Conjunctiva • 18 SECTION

less pathogenic organisms. Staphylococcus aureus is most common, but other species such as Streptococcus pneumoniae,

Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa may cause conjunctivitis. Cultures for conjunctivitis are negative in a significant number of cases. Given the array of possible pathogens, a broad-spectrum antibiotic should be used to manage conjunctivitis when an etiology cannot be ascertained.

PREVENTION OF CONJUNCTIVITIS OF THE NEWBORN

The best treatment for conjunctivitis of the newborn is prevention. Avoidance of inoculation is a mainstay of prevention, and takes the form of C-section when maternal infection with a sexually transmitted disease is identified. This is especially true in the case of maternal herpes simplex infection, where C-section should be performed. Ironically, the incidence of conjunctivitis of the newborn is the same in vaginal delivery compared to C-section. This fact indicates that most cases of conjunctivitis are mild and are acquired after birth.

Prophylactic treatment for conjunctivitis of the newborn is effective in preventing conjunctivitis, particularly GC. A drop of 2% silver nitrate placed on each eye was the mainstay of treatment until recently. This treatment was introduced by Crede in 1881 and frequently is referred to as ‘Crede prophylaxis.’ Silver nitrate has the disadvantage of occasionally causing a non-infectious (chemical) conjunctivitis.

Topical erythromycin or tetracycline is also effective at preventing conjunctivitis, and has replaced silver nitrate in many regions. Povidone-iodine (one drop in each eye) is also effective, and has the advantage of being inexpensive. This treatment has not been approved in the United States, but could assume importance in developing regions.

Other, milder, causes of conjunctivitis are not always prevented with prophylactic therapy. Chlamydia, too, may not be successfully managed with topical treatment. This raises the question: should prophylaxis be administered in infants whose mothers received good prenatal care? The assumption is that good prenatal care is associated with low risk of sexually transmitted disease, and remains an open question. In some areas, parents are offered the option of not having their infant receive prophylactic treatment, based on the above issues.

Use of other sterile prep solutions as prophylaxis should be avoided. Hibiclens (chlorhexidine) in particular is potentially toxic to the cornea, and can cause corneal ulceration and opacification.

REFERENCES

Crede C: Reports from the obstetrical clinic in Leipzig: prvention of eye infection in the newborn. Archives of Gynaekol 17:50–53, 1881.

Dannevig L, Straume B, Melby K: Ophthalmia neonatorum in northern Norway. II. Microbiology with emphasis on Chlamydia trachomatis. Acta Ophthalmol (Copenh) 70(1):19–25, 1992.

Fransen L, Klauss V: Neonatal ophthalmia in the developing world. Epidemiology, etiology, management and control. Int Ophthalmol 11(3):189– 196, 1988.

Fredricks S: Hibiclens and eye damage. Plast Reconstr Surg 81(3):472, 1988.

Harrison HR, et al: Chlamydia trachomatis infant pneumonitis: comparison with matched controls and other infant pneumonitis. N Engl J Med 298(13):702–708, 1978.

Isenberg SJ, Apt L, Wood M: A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum. N Engl J Med 332(9):562– 566, 1995.

Murthy S, Hawksworth NR, Cree I: Progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate (0.02%). Cornea 21(2):237– 239, 2002.

Schwab L, Tizazu T: Destructive epidemic Neisseria gonorrheae keratoconjunctivitis in African adults. Br J Ophthalmol 69(7):525–528, 1985.

Talley AR, et al: Comparative diagnosis of neonatal chlamydial conjunctivitis by polymerase chain reaction and McCoy cell culture. Am J Ophthalmol 117(1):50–57, 1994.

Zanoni D, Isenberg SJ, Apt L: A comparison of silver nitrate with erythromycin for prophylaxis against ophthalmia neonatorum. Clin Pediatr (Phila) 31(5):295–298, 1992.

184 PTERYGIUM AND

PSEUDOPTERYGIUM 372.40

Larry F. Rich, MS, MD

Portland, Oregon

A pterygium is a triangular elevated mass of thickened bulbar conjunctiva that extends onto the cornea in the interpalpebral zone. Its name is derived from the Greek word for ‘wing,’ which describes its characteristic shape. Within the interpalpebral fissure, a pterygium is most commonly found on the nasal aspect of the globe and less often found on the temporal aspect. If present outside the interpalpebral fissure area, it is considered an atypical pterygium, and other diagnoses, such as phlyctenular keratoconjunctivitis or carcinoma, must be considered (Figure 184.1).

A pseudopterygium is similar in appearance to a true pterygium, but it bridges the limbus such that a probe can be passed beneath the lesion at the limbus. It often is the result of damage to the cornea from a chemical, thermal, or physical insult. Pseudopterygium is more likely to occur in atypical locations (e.g. outside the interpalpebral fissure area) than a true pterygium is. As with a true pterygium, recurrences are more aggressive than the primary lesion.

FIGURE 184.1. Pterygium extending 3 millimeters with moderate vascularity.

Pseudopterygium184 CHAPTERand Pterygium •

Conjunctiva • 18 SECTION

ocular surgery. Subconjunctival injection of lidocaine without hyaluronidase is preferred. Epinephrine may be added to the anesthetic agent to inhibit bleeding. A topical anesthetic, such as cocaine, also may be used to prevent pain when the eye is grasped in an area other than where the lidocaine had been injected. Occasionally, retrobulbar anesthesia is necessary if the patient is unable to control ocular movements; in such patients, akinesia of the eyelids may also be necessary.

After the lesion has been excised, it is wise to submit it to the pathologist for evaluation. Occasionally, malignancies may mimic a pterygium; in these cases, surgery may stimulate growth.

Several adjunctive measures lower the recurrence rate after pterygium excision, but each has significant drawbacks. Stron- tium-90 β-irradiation, applied to the limbus and the adjacent sclera in divided doses totaling 1800 to 2200 rads, decreases the rate of recurrence. However, significant complications may occur, including scleral necrosis, infection, and cataract. Triethylene thiophosphoramide (thiotepa) applied as eyedrops four to six times daily for 6 to 8 weeks after surgery also decreases the probability of recurrence, but depigmentation of the skin and eyelashes around the treated eye limits its use, particularly in dark-skinned individuals. More recently, mito- mycin-C administered as 0.01% to 0.04% solution intraoperatively or 0.02% to 0.04% eyedrops b.i.d. for 5 to 14 days postoperatively has been advocated. Recurrence rates between 0% and 11% have been reported, but serious, potentially blinding complications such as scleral and corneal ulcers with perforation, glaucoma, sudden onset of cataract, corneal edema, and uveitis have occurred. If treatment with mitomycin-C is chose, it is best applied to the excision site with a sponge at the time of surgery rather than dispensing the drug as eyedrops postoperatively.

If symblepharon is present or the remaining conjunctiva is insufficient to permit adequate ocular motility, an amniotic membrane, mucous membrane or conjunctival graft may be needed to cover the bare area. Recurrence rates following the use of amniotic membrane transplantation, however, are disappointingly high. A conjunctival graft may be used from the same or the fellow eye and preferably is taken from a vicinity outside the interpalpebral fissure area. Autologous conjunctival grafting may be superior to adjunctive antimetabolite therapy at preventing recurrence and often provides a significantly better cosmetic result and a much lower incidence of complications. A conjunctival graft incorporating peripheral corneal epithelial stem cells may be of additional value toward prevention of recurrence. It is becoming the treatment of choice for recurrent pterygium.

Corneoscleral grafts with or without mucous membrane or conjunctival grafts have been advocated in cases of recurrent pterygium. Their use is advised in cases in which the limbal architecture has been disturbed by one or more surgical interventions. They are best accomplished with partial-thickness grafts incorporating corneal and scleral donor tissue in the same configuration as the tissue resected from the recipient eye. The grafted area can be trephined or cut freehanded, and the donor tissue is similarly dissected to fit the outline. If corneal and scleral tissue is used, it can be incorporated as a single graft to maintain the architecture of the limbal sulcus. A clear corneal graft that bridges the limbus has also been advocated, but it has the disadvantage of producing a single contour without providing a limbal sulcus. A corneal graft alone is likely to allow vascularization at the graft-host interface, so it is probably best to avoid leaving the edge of the graft

at the limbus. Grafting is necessary if multiple excisions have left the corneal tissue thin and perforation or ocular weakness is imminent.

COMPLICATIONS

●The surgical process and the pterygium itself destroy limbal tissue and predispose the eye to recurrence of the lesion. In addition, the elevation of conjunctiva and the irregular corneal and limbal tissue resulting from surgery may reinitiate the pathologic process of localized dryness, vascularization, and regrowth. Furthermore, an acute inflammatory process after surgery may produce granulation tissue that can contract and stimulate conjunctivalization of the limbus and cornea. Excessive postoperative inflammation and irritation from exposure during the early postoperative period encourage regrowth. Recurrences may be seen as early as 2 weeks or several years after excision.

●Symblepharon formation can occur with or without surgical therapy.

●Temporal displacement of the semilunar fold can occur.

●Astigmatism (with-the-rule) can occur.

●Restriction of ocular motility can occur.

●Diplopia is a possible complication.

COMMENTS

Each surgical intervention can produce a greater cosmetic blemish and a more difficult management situation than the previous lesion. A pterygium is more likely to return after a recurrence than after removal of a primary lesion. Symblepharon is often a sequela of pterygium surgery; restriction of ocular motility and pain with extraocular movements, particularly abduction of the globe, may result.

REFERENCES

Bahrassa F, Datta R: Postoperative beta radiation treatment of pterygium. Int J Rad Oncol Biol Phys 9:679–684, 1983.

Chen PP, Ariyasu RG, Kaza V, et al: A randomized trial comparing mito- mycin-C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol 120:151–160, 1995.

Ehrlich D: The management of pterygium. Ophthalmic Surg 8:23–30, 1977.

Gris O, Guell JL, delCampo Z: Limbal-conjunctival autograft transplantation for the treatment of recurrent pterygium. Ophthalmology 107(2):270–273, 2000.

Jurgenliemk-Schulz IM, Hartman LJC, Roesink JM, et al: Prevention of pterygium recurrence by postoperative single-dose β-irradiation: a prospective randomized clinical double-blind trial. Int J Rad Oncol Biol Phys 59:1138–1147, 2004.

Kleis W, Pico G: Thio-tepa therapy to prevent postoperative pterygium occurrence and neovascularization. Am J Ophthalmol 76:371–373, 1973.

Manning CA, Kloess PM, Diaz MD, et al: Intraoperative mitomycin in primary pterygium excision: a prospective, randomized trial. Ophthalmology 104:844–848, 1997.

Rubinfeld RS, Pfister RR, Stein RM, et al: Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology 99:1647–1654, 1992.

Singh G, Wilson MR, Foster CS: Long-term follow-up study of mitomycin eyedrops as adjunctive treatment for pterygia and its comparison with conjunctival autograft transplantation. Cornea 9:331–334, 1990.

185KeratoconjunctivitisCHAPTER Vernal •

Conjunctiva • 18 SECTION

Eyelid signs include long and thick eyelashes, the mechanism of which is not fully understood. Ptosis may occur in active VKC. Blepharospasm suggests corneal involvement and potentially more severe disease.

Tarsal conjunctival signs, in addition to those mentioned above, include the Maxwell-Lyons sign, a milky coating of fibrinous exudate over the cobblestone papillae that is enhanced by the heat of the slit lamp. Tarsal conjunctival fibrosis is the natural evolution of severe giant papillae. Unlike atopic keratoconjunctivitis, most cases of VKC resolve without tarsal conjunctival scarring.

Bulbar or limbal VKC occurs in about 20% of Mediterranean series and is commoner in patients of African and Asian origin. Usually the superior limbus is more affected. Horner–Trantas’ dots (aggregates of epithelial cells and eosinophils at the limbus) occur in approximately 15% of active VKC.

Epithelial keratopathy is very common and results from epithelial toxicity due to the release of eosinophilic major basic protein. Corneal shield ulcer, a vision threatening complication occurring in 3–11% of VKC, is characteristically a shallow, transversely oval, de-epithelialized area, located in the superior cornea. Mucous and epithelial cell plaque often cover the ulcer base. The surrounding epithelium is smooth and grayish. Superficial peripheral corneal vascularization is common in longstanding cases.

Laboratory findings

Usually, the signs and symptoms are characteristic enough to make the diagnosis without laboratory tests. Conjunctival cytology scrapings are usually positive for eosinophils and free eosinophilic granules. Other immune tests have low sensitivites (negative in >50%) and are therefore not clinically useful for diagnosis of VKC. These include activated eosinophils in conjunctival biopsies, total and specific serum IgE and skin tests. In 2003, Pucci et al showed a positive correlation between giant papillae score and serum eosinophil response, independent of IgE-sensitization, and found serum eosinophil cationic protein to be a useful laboratory marker of disease activity. Limbal VKC has an even lower prevalence of IgE-sensitization than tarsal forms.

Differential diagnosis

●Seasonal and perennial allergic conjunctivitis.

●Atopic keratoconjunctivitis.

●Giant papillary conjunctivitis associated with contact lens wear.

●Giant papillae on the tarsal conjunctiva secondary to an exposed ocular suture or ocular prosthesis.

●Ligneous conjunctivitis may occasionally be confused with large cobblestone papillae in young patients.

●Toxic conjunctivitis secondary to chronic use of ophthalmic preparations: may result in bulbar follicles that may mimic limbal changes. Unlike VKC, the signs are more pronounced inferiorly.

TREATMENT

Because VKC usually resolves without scarring or permanent loss of vision once the disease burns out, treatment should be as conservative as possible to achieve symptomatic relief, prevent structural damage to the ocular surface that may reduce vision, and minimize any iatrogenic complications.

Nonspecific

Although relocating to a cool moist climate is often effective, this is usually impractical. Concurrent blepharitis and dry eye should be treated.

Systemic

Oral antihistamines (e.g. loratidine) and oral nonsteroidal antiinflammatory drugs (NSAIDs) may be useful in mild to moderate cases: the earlier for generalized hyper-reactivity and the latter for the inflammatory aspect of VKC. Oral prednisone 10 mg/day for 3–5 days in a 10-year-old child may be very useful in refractory VKC with corneal damage.

Ocular

Cold compresses decrease itching by reducing superficial vasodilatation and c-fiber stimulation. Artificial tears dilute antigens and immunogenic factors. Refrigerating artificial tears further improves their soothing effect.

Topical vasoconstrictors, such as naphazoline, should be restricted to t.i.d. for only a few days as rebound hyperemia is likely with longer use. Topical antihistamines and H1 antagonists have a rapid onset but short duration. Levocabastine (Livostin) and emedastine (Emadine) may be used 1–4 times daily for long periods. Newer antihistamines (H1 blockers) such as olopatadine (Patanol) also have mast cell-stabilizing properties. Topical NSAIDs, such as ketorolac (Acular), may provide symptomatic relief of itching. Their steroid sparing capability in VKC is yet to be determined. In the presence of any degree of keratitis, vasoconstrictors, antihistamines and NSAIDs alone are inadequate.

Mast cell stabilizers, such as cromolyn (Opticrom, Crolom), lodoxamide (Alomide), nedocromil (Alocril) and pemirolast (Alamast) are the mainstay of therapy for most cases of VKC. Although more severe cases require short courses of topical steroids to control the inflammation, mast cell stabilizers have prophylactic use during quieter phases of the disease and enable steroid sparing. Unpreserved solutions are preferable for longterm use.

Topical corticosteroids are the most effective therapy for VKC, especially with active keratopathy. Steroids inhibit epithelial toxic mediator biosynthesis by eosinophils and neutrophils, thus reversing corneal epithelial damage. Refractory symptoms, cobblestone papillae, limbal thickening, and shield ulcers are indications for steroid use. However, use should be strictly limited as prolonged use may cause cataract, increased intraocular pressure, and superinfection. High frequency intermittent (pulse) therapy (e.g. 2-hourly for 3–5 days) is effective and minimizes steroid complications. The steroid potency, such as 0.1% fluorometholone, 0.2% loteprednol or 1% prednisolone acetate, should be titrated against the severity of the inflammation. Patients and family members should be thoroughly educated regarding steroid complications.

Topical cyclosporin A 2% in olive oil was shown by Pucci et al in a randomized clinical trial to be effective in severe VKC. Most of the therapeutic effect was achieved within 2 weeks. Besides mild irritation on instillation, no ocular or systemic complications were seen. Cyclosporin A binds to cyclophilin, an intracellular protein, inhibiting interleukin-2 production and blocking Th2 lymphocyte proliferation. It also appears to decrease eosinophil recruitment and conjunctival fibroblast proliferation. Effective doses range from 2–4 times/ day for 2–16 weeks. There is no need to check systemic blood levels.

Surgical

Supratarsal injection of steroids is useful in cases refractory to pulsed topical steroids, with non-healing shield ulcers. Dexamethasone, triamcinolone and hydrocortisone are equally effective. Surgical removal of a plaque in the base of a vernal ulcer preventing re-epithelialization, by scraping the base and margins, may promote healing.

Surgical excision, cryotherapy and beta-irradiation of giant papillae of the superior tarsus have been described. These procedures are not recommended as marked scarring and distortion of the upper eyelid often results.

COMPLICATIONS

Up to 6–10% of cases have a complication that causes visual impairment. Complications may be due to the disease itself (corneal vascularization and scarring after shield ulcers) or due to steroid use (cataract and glaucoma). In addition, keratoconus may be a late complication of VKC.

COMMENTS

Mild VKC responds well to topical antiallergics, especially mast cell stabilizers and usually resolves within 2–10 years with no

ocular surface scarring. Severe VKC (giant papillae >1 mm or limbal forms) has fibrosis of the ocular surface, supposedly due to a Th2 lymphocyte driven mechanism, and requires steroid treatment. Continual effort to limit steroid side effects is necessary, such as mast cell stabilizers and cyclosporin A use.

REFERENCES

Bielory L: Update on ocular allergy therapy. Expert Opin Pharmacother 3:541–553, 2002.

Bonini S, Bonini S, Lambiase A, et al: Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 107:1157–1163, 2000.

Bonini S, Coassin M, Aronni S, Lambiase A: Vernal keratoconjunctivitis. Eye 18:345–351, 2004.

Cameron JA: Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis. Ophthalmology 103:985–993, 1995.

Holsclaw DS, Whitcher JP, Wong IG, Margolis TP: Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J Ophthalmol 121:243–249, 1996.

Pucci N, Novembre E, Cianferoni A, et al: Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis.Ann Allergy Asthma Immunol 89:298–303, 2002.

Pucci N, Novembre E, Lombardi E, et al: Atopy and serum eosinophil cationic protein in 110 white children with vernal keratoconjunctivitis: differences between tarsal and limbal forms. Clin Exp Allergy 33:325– 330, 2003.

185KeratoconjunctivitisCHAPTER Vernal •