Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.     

Incidence of brimonidine allergy in patients previously allergic to apraclonidine

PURPOSE: This study was performed to determine the incidence of allergic reaction to brimonidine in patients who have previously demonstrated an allergic reaction to apraclonidine. METHODS: A retrospective chart review was performed to identify patients who had demonstrated an allergic reaction to apraclonidine of sufficient severity to result in drug discontinuation. Within this group, those patients subsequently treated with brimonidine were isolated and analyzed, and the incidence of allergy to brimonidine was determined. RESULTS: Forty-five patients were identified with a significant allergic reaction to apraclonidine that resulted in drug discontinuation. Of these patients, 22 subsequently received brimonidine. Follow-up on all patients was obtained for at least 15 months. All but two of the 22 patients were taking additional topical glaucoma medications, ranging from one to three additional agents with an average of 1.8+/-0.8 medications. Seventeen patients incurred no allergic reaction to brimonidine. Only five patients (22.7%) previously allergic to apraclonidine developed an allergic reaction to brimonidine. Three of these patients demonstrated only a follicular conjunctival reaction, one had conjunctival hyperemia, and one patient developed a periocular dermatitis. The allergic reactions developed at 8.2+/-1.2 months after initiation of brimonidine therapy. CONCLUSIONS: In this study, the risk of developing an allergic reaction to brimonidine in patients known to be allergic to apraclonidine is 22.7%. This lack of a strong cross-reactive allergic response possibly suggests different allergic mechanisms for these two medications. Therefore, brimonidine therapy in patients previously identified as being allergic to apraclonidine is safe and does not result in a cross-reactive response in the great majority of patients (or in nearly four of five patients).     

Reversal of intraocular pressure increases with 0.5% apraclonidine after dilated fundus examination in patients with chronic open-angle glaucoma.

BACKGROUND: Apraclonidine 1.0% has been shown to reverse the potential intraocular pressure (IOP) increase after pupil dilation IOP increases in patients with chronic open-angle glaucoma. However, it is only approved for preventing IOP spikes after laser surgery. The purpose of this study is to determine the effectiveness of 0.5% apraclonidine in reversing IOP increases after pupillary dilation in patients with chronic open-angle glaucoma. METHODS: Twenty-two patients with chronic open-angle glaucoma were found to have an increase in post-dilation IOP of at least 4 mmHg from pre-dilated levels (baseline) in both eyes. IOP was measured 1 hour after dilation, after which two drops of 0.5% apraclonidine were instilled in one eye and the IOP was remeasured 15 minutes later in both eyes. Instillation of 0.5% apraclonidine in one eye was continued every 15 minutes and IOP was measured 15 minutes after each instillation, until the pressure returned to baseline levels. RESULTS: The IOP of the initially treated eye of all 22 patients returned to within levels clinically insignificant from baseline IOP within 90 minutes. By comparison, the IOP of the control group (untreated eye) remained elevated. Once the initial treatment eye returned to baseline levels, the control group was then treated with 0.5% apraclonidine, resulting in a lowering effect of the IOP in similar fashion to the initial treated group. CONCLUSIONS: Apraclonidine 0.5% appears to be effective in reduction of post-dilated IOP increases in patients with chronic open-angle glaucoma.     

Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery

PURPOSE: To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma. DESIGN: Interventional study. METHODS: A total of 83 consecutive patients (83 eyes) awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for listing were inadequate intraocular pressure (IOP) control despite medical therapy and documented progression of visual field loss. All patients discontinued the previous treatment and were switched to bimatoprost 0.03% QD (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90 of treatment; less than 20% IOP reduction was considered as a failure. RESULTS: An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained IOP readings 20% lower than baseline after 60 and 90 days. In these patients, visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). CONCLUSIONS: This preliminary study shows that bimatoprost 0.03% could represent a useful therapeutic tool that might defer filtration surgery.     

Adjunctive glaucoma therapy. A comparison of apraclonidine to dipivefrin when added to timolol maleate

The authors compared the additive intraocular pressure (IOP)-lowering effects of two different topical medications, apraclonidine hydrochloride and dipivefrin hydrochloride, when used in conjunction with timolol maleate. Eighteen patients with elevated IOPs entered a randomized, double-masked, cross-over study. Each used apraclonidine 1.0%, dipivefrin 0.1%, or placebo, twice daily for 3 weeks each, in addition to timolol 0.5% twice daily. Only apraclonidine produced a significant additional IOP lowering over timolol treatment alone at all time intervals (P less than 0.001). Its additive effect was significantly greater than that seen with dipivefrin at all time intervals (P less than 0.01), with the exception of day 22 (P = 0.061). No significant change in pulse rate or blood pressure was seen during apraclonidine administration. Apraclonidine may be a useful adjunctive agent in patients with poorly controlled glaucoma.     

False negative apraclonidine test in two patients with Horner syndrome

BACKGROUND: Because of denervation supersensitivity, a miotic pupil in a sympathetically-denervated eye dilates in response to a dilute or weak alpha-1-agonist drug. A reversal of anisocoria after topical apraclonidine is considered as a positive test result that diagnoses a unilateral Horner syndrome. HISTORY AND SIGNS: Two women aged 34 and 46 years with a cocaine-confirmed oculosympathetic defect (Horner syndrome) were tested with 1 % topical apraclonidine on separate days. THERAPY AND OUTCOME: In one patient, her miotic Horner pupil dilated marginally but not enough to reverse the baseline anisocoria. Additionally, the upper lid on the same side retracted. There was no discernable effect of apraclonidine on the normal, contralateral eye. In the second patient, there was no pupillary response to apraclonidine but there was resolution of her ptosis. CONCLUSIONS: Neither patient demonstrated a reversal of anisocoria, the current criterion for diagnosing a Horner syndrome using apraclonidine. Thus, these two patients with an established oculosympathetic defect were said to have a "negative test" for Horner syndrome. Yet both women showed subtle pupil and/or lid changes in response to apraclonidine that were consistent with sympathetic denervation supersensitivity. Reversal of anisocoria following topical apraclonidine does not occur in all patients with a unilateral oculosympathetic defect and more specific parameters for defining a positive test result might optimize apraclonidine's utility as a diagnostic test for Horner syndrome.     

Efficacy of apraclonidine ophthalmic solution (lopidine) in presumed silicon oil-induced glaucoma and primary open-angle glaucoma

Background: This pilot study evaluated the acute effects of topical ocular apraclonidine 1% (Iopidine) in 10 patients with presumed silicone oil-induced secondary glaucoma (SOIG) and in 10 patients with high-pressure primary open-angle glaucoma (POAG) despite maximum tolerated medical therapy. Methods: Intraocular pressure (TOP) measurements were carried out before and 1, 2 and 3 h after a single drop of apraclonidine. Results: Patients with SIOG presented with a mean IOP of 30.0 ± 2.8 mmHg, which was reduced to 21.7 ± 2.9 mmHg (P<0.001) after 1 h, to 20.4 ± 2.3 mmHg (P<0.001) after 2 h and to 20.0±2.5 mmHg (P<0.001) after 3 h. In the POAG group, TOP was reduced from 25.9±1.9 mmHg before treatment to 18.9±1.4 mmHg after 1 h (P<0.001), 17.7±1.2 mmHg after 2 h (P<0.001) and 16.9±0.9 mmHg after 3 h (P<0.001). There were no significant changes in blood pressure or pulse rate. Conclusion: This study confirmed the activity of apraclonidine as an TOP suppressant.This study was presented in abstract at the 1993 ARVO meeting, Sarasota, Florida (poster 2422)     

Sublingual timolol--an alternative to topical medication in glaucoma?

AIMS--To assess whether timolol drops lower a raised intraocular pressure (IOP) when given sublingually. This route of administration would be useful for glaucoma patients who are unable to instil their own drops--for example, because of stroke, poor vision, arthritis, poor coordination, or blepharospasm. METHODS--A placebo controlled randomised, double masked, crossover study was undertaken in the glaucoma clinic of a large teaching hospital. Twelve patients with ocular hypertension with IOPs over 21 mm Hg, normal optic discs, and full visual fields were examined by Humphrey perimetry. Single dose units of timolol maleate 0.5% drops and normal saline drops were given by instillation in one eye or sublingually. The IOP of both eyes, pulse rate, and blood pressure were all measured before and after each type of drop and route of administration. RESULTS--Two hours after instillation of timolol in one eye, the IOP in the treated eye was reduced by a mean of 8.5 mm Hg (p = 0.0000), and by 1.66 mm Hg in the fellow eye (p = 0.03). Two hours after sublingual instillation of timolol, the IOP was reduced by 7.55 mm Hg in the study eye (p = 0.0000) and by 7.7 mm Hg in the fellow eye (p = 0.0000). There was an equal amount of reduction in pulse rate by either route, but there was no significant change in blood pressure. CONCLUSIONS--The results show that, at least after 2 hours, sublingual treatment is almost as effective as topical treatment in lowering a raised IOP.     

The one-month effects of topical betaxolol, dorzolamide and apraclonidine on ocular blood flow velocities in patients with newly diagnosed primary open-angle glaucoma

PURPOSE: This double-masked, prospective and randomized clinical trial was planned to investigate with color Doppler imaging the 1-month vascular effects of betaxolol, dorzolamide and apraclonidine treatment on patients with newly diagnosed primary open-angle glaucoma (POAG). METHODS: 22 consecutive patients with newly diagnosed POAG between the ages of 46 and 72 years were enrolled in this study. All patients were newly diagnosed cases and had not received any antiglaucoma medication before. Patients who had a systemic vascular disease (including systemic hypertension) or were taking beta-blockers, nitrates or calcium channel blockers were excluded from the study. The patients were randomly divided into three groups. Groups A and B contained 7 patients, group C contained 8 patients. Group A patients were treated with topical betaxolol, group B patients received topical dorzolamide eye drops, and group C patients were treated with topical apraclonidine eye drops. Peak systolic velocities (PSV), end-diastolic velocities (EDV) and resistive indices (RI) in the right ophthalmic arteries (OA), central retinal arteries (CRA) and posterior ciliary arteries (PCA) were measured at baseline by using color Doppler imaging on a masked basis. On days 15 and 30 of treatment, the same measurements were repeated. The inter- and intragroup results were compared statistically. RESULTS: Compared to pretreatment measurements, topical betaxolol therapy significantly decreased PSV only in the PCA and only on day 30 of treatment (p = 0.011). On days 15 and 30, dorzolamide decreased RI measurements in the PCA compared to pretreatment measurement (p = 0.013 and p = 0.011, respectively). Apraclonidine also decreased PSV in the OA on days 15 and 30 of treatment when compared to pretreatment values (p = 0.013 and p = 0.012, respectively). When 15-day measurements were compared between the groups, PSV in the OA were significantly higher in dorzolamide-treated patients compared to other groups (p = 0.01 and p = 0.011). On day 30 of treatment, PSV in the OA was also higher in the dorzolamide-treated group than the other groups (p = 0.012 and p = 0.01). Additionally, apraclonidine-treated patients had a significantly lower EDV in the OA than the other groups (p = 0.013 and p = 0.01). The RI in the OA was also significantly lower in the apraclonidine-treated group compared to the other groups (p = 0.01 and p = 0.011). CONCLUSION: Our study suggests that dorzolamide has the most advantageous 1-month effects on blood flow velocity in the retrobulbar arterial circulation of POAG patients. Betaxolol seems superior to apraclonidine in this regard. Our data may help the clinician when treating patients with POAG medically. Further studies using a larger population size may clarify our results.     

External trabecular excision--alternative to filtering glaucoma operation in patients with open angle glaucoma

BACKGROUND: Postoperative complications concerning glaucoma filtering surgery (trabeculectomy, goniotrepanation) often include hypotonia that may lead to athalamia or choroidal detachment, which are difficult to handle. Cystic non filtering blebs are due to postinflammatory reactions, and may limit the success of filtering surgery. Aim of the study was to compare the success and the complications of a new operating technique, which will be described, with those of usual glaucoma filtering surgery. PATIENTS AND METHODS: In 24 open angle glaucoma patients with mean intraocular pressure of 28.12 mm Hg (+/- 8.6) we performed external trabecular excision in 25 eyes since June 1997. Preoperative visual acuity and peak intraocular pressure were compared retrospectively in all eyes with the values of the first postoperative day, in 22 eyes after one month and in 17 eyes after 3 months. RESULTS: Intraocular pressure measured between 0 mm Hg and 16 mm Hg on the first postoperative day (7.64 mm Hg +/- 4.3), after one month between 10 mm Hg and 30 mm Hg (17.81 mm Hg +/- 5.5) and after 3 months between 9 mm Hg and 26 mm Hg (15.29 mm Hg +/- 4.2). After 1 month 10 of 22 (45%) and after 3 months 7 of 17 eyes (42%) required antiglaucomatous drugs; 3 eyes needed gonitrepanation (2 weeks, 1 month, 3 months after ETE). Concerning postoperative complications, we observed 6 choroidal detachments, once erythrocoytes in the anterior chamber, twice hyphemata, twice inflammatory reaction in the anterior chamber, two flat anterior chambers and twice a positive seidel test. CONCLUSION: Complications after ETE are similar to those after filtering surgery. Postoperative intraocular pressure dip after ETE in most eyes was not as pronounced as after goniotrepanation or trabeculectomy, and postoperative complications were all reversible. 45% of the eyes again needed antiglaucomatous drugs after one month and 42% after 3 months. A prospective long-term study has to verify the success respectively the complications of ETE.     

Acute aphakic pupil block glaucoma: an alternative surgical approach.

In a series of 7 cases of acute aphakic pupil block glaucoma a surgical approach designed to break adhesions between the iris and the anterior hyaloid face was uniformly successful. Reasons for the success of the method are discussed and comparisons made with other surgical approaches.     

Visual field defects in patients with normal-tension glaucoma and patients with high-tension glaucoma.

We compared the automated visual field test results of 24 patients with normal-tension glaucoma and 24 patients with high-tension glaucoma who were closely matched for the amount of visual field loss to determine any differences in the characteristics of visual field defects between the two groups. Patients were matched with a maximum allowable difference in mean deviation of 0.3 dB. Although the normal-tension group had a greater amount of focal visual field loss (pattern standard deviation), the difference was not statistically significant (P = .628). Additionally, there was no statistically significant difference in the amount of diffuse or focal visual field damage in the superior hemifields between the two groups; however, the patients with normal-tension glaucoma had a significantly greater amount of localized visual field loss in the inferior hemifield than the patients with high-tension glaucoma (P = .015). Our data support the hypothesis that a vascular mechanism may have a greater role in the pathogenesis of optic nerve damage and visual field loss in patients with normal-tension glaucoma than in patients with high-tension glaucoma.     

Knowledge and awareness of glaucoma in Mexican patients with and without glaucoma diagnosis in an Ophthalmology Referral Center

AIM: To assess and compare knowledge and awareness of glaucoma in subjects with and without glaucoma diagnosis attending an Ophthalmology Referral Center. METHODS: This cross-sectional study was conducted at Asociación Para Evitar la Ceguera in Mexico City, using a questionnaire formulated by a group of experts following the Delphi panel rules, and pre-tested in a pilot study. The questionnaire was applied and compared between: glaucoma patients, relatives of glaucoma patients and patients without glaucoma. Socio-demographic data was collected to assess correlation with the level of knowledge using Logistic regression models, estimating the odds ratios (OR), 95% confidence intervals, and P<0.05. RESULTS: Three hundred and ninety-four subjects were enrolled; with a median age of 61y. One hundred and thirty-four (34%) were patients with glaucoma, 152 (38.6%) patients without glaucoma, and 108 (27.4%) relatives of patients with glaucoma. Two hundred and ninety-one (73.9%) participants were aware of the term “glaucoma”. Regarding knowledge 46.7% had moderate knowledge, 37.8% had poor knowledge, and 15.5% good knowledge. Overall, relatives of glaucoma patients had the highest scores, and patients without glaucoma got the lowest scores. A positive correlation was found between better knowledge and frequent ophthalmological examinations OR 2.24 (P=0.02), higher education level OR 4.17 (P=0.00) and having a family member with glaucoma OR 3.28 (P=0.00). CONCLUSION: Awareness and knowledge of glaucoma in subjects attending an Ophthalmology Referral Center is predominantly moderate or poor. This has important implications regarding attitudes that can result in lack of follow up in ophthalmological care.