The purpose was to examine the incidence of allergic reactions and side effects of glaucoma treatment in asymptomatic individuals with early POAG. The glaucoma treatment studies were identified from MEDLINE, Cochrane Library and from HUCS Skin and allergy Hospital. The database search about possible adverse effects to various glaucoma medications consisted of 224 abstracts and titles from 1998 to 2004.
There are no high quality prospective studies concerning adverse effects and the adverse effects are often told as secondary outcomes in big glaucoma treatment studies.
There are only few studies, where the allergic reactions are verified by allergy tests. Another problem is that we may have an allergic reaction in the eye caused by glaucoma medication but the skin tests used for eye drops are not sensitive enough compared to the eye. Further problems are test medications, which usually are eye drops used by the patients. They are tested in most instances "as is" on the back skin. The back skin 5mm thick and the lid skin 0.5mm. This causes a fundamental difference in sensitivity, which is further amplified by very sensitive cornea and conjunctiva.
The treatment options include topical medications, systemic medications, laser surgery, and incisional surgery, alone or in combination. No data exists about sensitivity and specificity in suspected ocular allergies caused by topical glaucoma medication.
Contact allergy is caused by almost all topical glaucoma medications; pilocarpin, beta blockers: timolol, befunolol, betaxolol, levobunolol, carteol, metipranolol, carboanhydrase inhibitors, adrenergics, prostaglandin analoques, preservatives (BAK, bentsalkon chloride), parabens, thimerosal 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Our own results in HUCS Skin and allergy Hospital varies from 1.1% to 5.5 %. The suspected allergic reactions to adrenergic apraclonidine and brimonidine are about 50 % among all users 17 .
Adverse effects are common. In the Collaborative Normal-Tension Glaucoma Study (CNTGS) 12 23 of 66 treated eyes (35 %) developed cataract, compared with 11 of 79 eyes in the control group (14 %) (p = 0.0011), relative risk (RR) 2.5, CL 1,32-4,75. The highest incidence of cataracts (16 of 33) occurred in surgically treated eyes, RR 3,48, CL 1,82-6,68. The rate of cataract formation in untreated eyes was lower than surgically treated eyes (p=0.0001) but was not different from medically treated eyes (p=0.18). In another study the risk of cataract formation was compared in medically treated vs. untreated eyes. In the EMGT 15 study, cataract development was more likely in the group treated with ALT (Argon Laser Trabeculoplasty) plus betaxolol than in untreated subjects (p=0.002), and the risk of cataracts related to treatment increase over time (p=0.02).
Ocular symptoms, such as dryness, tearing and itching, were frequently reported. In the Ocular Hypertension Treatment Study (OHTS) 13 ocular symptoms occurred in 57 % of treated patients and 47 % of control subjects, NNH (number needed to harm) 10, p<0.001. Other symptoms such as darkening of the eyelids or eyelash growth, were reposted in 23 % of treated patients vs. 18 % of control subjects (NNH 10, p<0.001). Patients were treated by prostaglandinanaloques, most often by latanoprost and betablockers.
The CIGTS 14 trial reported intraoperative and postoperative complication for surgical trabeculectomy in 524 participants. Intraoperative complication included bleeding in the anterior chamber (7.1 %) and conjunctival buttonhole defects (1.0 %). Complications within 30 days postoperative were: shallow or flat anterior chamber (14.2 %); failed or encapsulated filtering bleb (11.9 %); ptosis (11.9 %); serous choroidal detachment (11.3%); and anterior chamber bleeding oor hyphema (10.9 %). Over time, the cataract extraction rate in the surgery group remained significantly higher than in the medication group (p=0.0001).
In the Finnish study there were examined complications of Neodymium YAG laser goniopuncture after deep sclerectomy in 31 patients. Three patients had spontaneous iris prolapse but there were no signs of severe hypotension 16 .
In the EMGT 15 study there are also reported serious systemic adverse effects. In this study, more participants died in the group treated with topical medication and ALT (15 of 22) than in the untreated control group (7 of 22, p=0.08), RR 2.14, CL 1.09-4.21. Most of these deaths occurred among men in the first 2 years of the study. The patterns of cause specific mortality, primarily cardiovascular events and malignancy, were similar those expected in a population of the same age and gender.
In the OHTS 13 study, there were no observed differences between the treated and untreated participants in total hospitalizations, worsening of pre existing conditions, or mortality. Serious psychiatric adverse effects were reported in 5,5 % (44 of 800) vs. 3.4 % (27 of 802) in the control group (p=0.05), RR 1.63, CL 1.02-2.61. Serious genitourinary adverse effects occurred in 1.5 % (12 of 800) of the treatment group vs. 0.5 % (4 of 802) in the control group (p=0.04), RR 3.01, CL 0.97-9.29.
1. Holdiness MR. Contact dermatitis to topical drugs for glaucoma. Am J Contact Dermat 2001 Dec;12(4):217-9. [PMID:11753897]
2. Butler P, Mannschreck M, Lin S, Hwang I, Alvarado J. Clinical experience with the long-term use of 1% apraclonidine. Incidence of allergic reactions. Arch Ophthalmol 1995 Mar;113(3):293-6. [PMID:7887842]
3. Costagliola C, Prete AD, Incorvaia C, Fusco R, Parmeggiani F, Di Giovanni A. Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol 2001 Nov;239(11):809-14. [PMID:11789860]
4. Jerstad KM, Warshaw E. Allergic contact dermatitis to latanoprost. Am J Contact Dermat 2002 Mar;13(1):39-41. [PMID:11887105]
5. Cusano F, Luciano S, Capozzi M, Verrilli DA. Contact dermatitis from pilocarpine. Contact Dermatitis 1993 Aug;29(2):99. [PMID:8365189]
6. Gaspari AA. Contact allergy to ophthalmic dipivalyl epinephrine hydrochloride: demonstration by patch testing. Contact Dermatitis 1993 Jan;28(1):35-7. [PMID:8428443]
7. Manni G, Centofanti M, Sacchetti M, Oddone F, Bonini S, Parravano M, Bucci MG. Demographic and clinical factors associated with development of brimonidine tartrate 0.2%-induced ocular allergy. J Glaucoma 2004 Apr;13(2):163-7. [PMID:15097264]
8. Aalto-Korte K. Contact allergy to dorzolamide eyedrops. Contact Dermatitis 1998 Oct;39(4):206. [PMID:9817238]
9. Vilaplana J, Romaguera C. Contact dermatitis from parabens used as preservatives in eyedrops. Contact Dermatitis 2000 Oct;43(4):248. [PMID:11011947]
10. Tosti A, Tosti G. Thimerosal: a hidden allergen in ophthalmology. Contact Dermatitis 1988 May;18(5):268-73. [PMID:3416589]
11. Hätinen A, Teräsvirta M, Fräki JE. Contact allergy to components in topical ophthalmologic preparations. Acta Ophthalmol (Copenh) 1985 Aug;63(4):424-6. [PMID:4050363]
12. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 1998 Oct;126(4):487-97. [PMID:9780093]
13. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002 Jun;120(6):701-13; discussion 829-30. [PMID:12049574]
14. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP, CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology 2001 Nov;108(11):1943-53. [PMID:11713061]
15. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002 Oct;120(10):1268-79. [PMID:12365904]
16. Vuori ML. Complications of Neodymium:YAG laser goniopuncture after deep sclerectomy. Acta Ophthalmol Scand 2003 Dec;81(6):573-6. [PMID:14641256]
17. Gross RL, Pinyero A, Orengo-Nania S. Clinical experience with apraclonidine 0.5%. J Glaucoma 1997 Oct;6(5):298-302. [PMID:9327348]
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