To compare the safety and intraocular pressure (IOP)-lowering efficacy of once-daily travoprost (0.0015% and 0.004%) to twice-daily timolol 0.5%.
Prospective, 6-month, randomized, controlled, multicenter, double-masked, phase III study.
Six hundred five patients with open-angle glaucoma or ocular hypertension.
Patients with an 8 AM IOP between 24 to 36 mmHg in at least one eye (the same eye) at two eligibility visits received either travoprost 0.0015%, travoprost 0.004% (dosed every day), or timolol 0.5% (dosed twice daily).
Mean IOP at 8 AM, 10 AM, and 4 PM in the patient's eye with the higher baseline IOP.
The mean IOP was significantly lower for both concentrations of travoprost compared with timolol. Travoprost was statistically superior to timolol at 9 of 13 visits, with differences in IOP reductions ranging from 0.9 to 1.8 mmHg (0.0015%) and 10 of 13 visits with differences in IOP reductions from 0.9 to 2.4 mmHg (0.004%). Mean IOP changes from baseline ranged from -6.0 to -7.5 mmHg (0.0015%), -6.5 to -8.0 mmHg (0.004%), and -5.2 to -7.0 mmHg for timolol. Hyperemia was experienced at rates of 29.2% (59 of 202) for travoprost 0.0015%, 42.8% (86 of 201) for travoprost 0.004%, and 8.9% (18 of 202) for timolol. Iris pigmentation changes were observed in 1.0% (2 of 200) of patients receiving travoprost 0.004% with no changes noted in the travoprost 0.0015% group or the timolol group. A decrease in pulse and systolic blood pressure was observed in the timolol group. There were no other clinically relevant or statistically significant changes from baseline in ocular signs or laboratory values, and no serious, related, unexpected adverse events were reported for any group.
Travoprost (0.0015% and 0.004%), dosed once daily in the evening, is statistically superior or equal to timolol 0.5% dosed twice daily at all treatment visits during this 6-month study. IOP reductions of up to 2.0 mmHg greater than timolol were found in the travoprost 0.004% pooled data group. Travoprost is safe and well tolerated in patients with open-angle glaucoma or ocular hypertension.
To compare efficacies of adjunctive therapy with brimonidine 0.15% and adjunctive therapy with brinzolamide 1% in combination with travoprost 0.004%.
Three-month randomized, parallel-group, double-masked, multicenter clinical trial.
Patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension with intraocular pressure (IOP) > 18 mmHg on monotherapy with travoprost (N = 163).
Patients were randomized to receive adjunctive therapy with twice-daily brimonidine (N = 79) or twice-daily brinzolamide (N = 84). Treatment efficacy was assessed after 1 and 3 months of combination therapy. Intraocular pressure was measured at 8 am, noon, and 4 pm at baseline (on travoprost monotherapy) and after 3 months of combination therapy. Mean diurnal IOP was defined as the average of the IOP measurements at these 3 time points. Adverse events were recorded at each visit.
Difference between treatment groups in mean diurnal IOP at month 3, adjusted for difference in baseline IOP, using analysis of covariance.
Mean diurnal IOPs (+/- standard error of the mean) at baseline were 21.7+/-0.33 mmHg in the brimonidine group and 21.1+/-0.29 mmHg in the brinzolamide group (P = 0.16). Mean diurnal IOPs at month 3 were 19.6+/-0.41 mmHg in the brimonidine group and 18.4+/-0.33 mm Hg in the brinzolamide group (P = 0.019). At month 3, mean diurnal IOPs, adjusted for difference in baseline IOP, were 19.3+/-0.27 in the brimonidine group and 18.6+/-0.25 in the brinzolamide group (P = 0.035).
The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain.
To evaluate and compare the effects of latanoprost 0.005% once daily and brimonidine tartrate 0.2% twice daily in patients with normal-tension glaucoma (NTG).
A randomized, open-label, crossover study.
Twenty-eight NTG patients with progressive visual field defects/optic disc excavation, new disc hemorrhage, or field defects that threatened fixation.
Patients were randomly allocated to one of two groups. Patients in group 1 were treated with latanoprost, lubricant, and brimonidine for 4 weeks each, whereas patients in group 2 were treated with brimonidine, lubricant, and latanoprost for 4 weeks each.
Intraocular pressure (IOP), pulse rate, and blood pressure were measured at 8 am, 12 noon, and 4 pm after each 4-week treatment. Ocular perfusion pressure (OPP) was calculated.
Latanoprost and brimonidine reduced the average IOP by 3.6 +/- 1.9 mmHg (P < 0.001) and 2.5 +/- 1.3 mmHg (P < 0.001), respectively, with a significant difference between the two regimens (P = 0.009). Both drugs significantly reduced IOP at each time point. Latanoprost decreased IOP significantly more than did brimonidine at 8 am (11.7 +/- 2.2 mmHg vs. 13.7 +/- 2.1 mmHg, P = 0.004) and 4 pm (11.4 +/- 2.1 mmHg vs. 13.2 +/- 2.9 mmHg, P = 0.004), but IOP was equal between the two agents at 12 noon (11.5 +/- 2.6 mmHg vs. 11.5 +/- 2.3 mmHg, P = 0.967). IOP was maintained at 12 mmHg or lower in 18 (66.7%) of 27 patients after treatment with latanoprost and in 9 (33.3%) of 27 patients after treatment with brimonidine. Latanoprost monotherapy reduced IOP by 30% in 8 patients (29.6%), but brimonidine monotherapy did not reduce IOP by that much in any of the patients. OPP increased after latanoprost treatment (P < 0.001) but did not increase after brimonidine treatment (P = 0.355). There was no significant change in pulse rate or blood pressure.
Both latanoprost and brimonidine reduce IOP in NTG patients. Brimonidine has a peak IOP-lowering effect equal to that of latanoprost but produces a higher mean diurnal IOP than does latanoprost because of its shorter effect. Latanoprost might favorably alter optic disc blood perfusion by increasing OPP.
To evaluate the efficacy and safety of commercially available latanoprost 0.005% given every evening versus timolol 0.5% and dorzolamide 2% fixed combination (TDFC) given twice daily to white Greeks with primary open-angle glaucoma and ocular hypertensive patients.
A single-masked, two-center, crossover comparison with two 6-week treatment periods occurring after at least a 3-week medicine-free period. Diurnal curve intraocular pressures were taken at 2:00 AM, 6:00 AM, 10:00 AM, 2:00 PM, 6:00 PM, and 10:00 PM.
Thirty-four subjects with primary open-angle glaucoma or ocular hypertension were enrolled.
Latanoprost 0.005% given every evening and TDFC twice daily.
The primary efficacy variable was diurnal intraocular pressure.
Thirty-three patients completed the study. On the last day of treatment, the mean diurnal intraocular pressure for latanoprost was 15.9 +/- 2.3 mmHg and for TDFC was 15.3 +/- 2.0 mmHg (P = 0.05). Individual time points for intraocular pressure were not statistically different between groups except at the 10:00 PM time point, when the mean for TDFC was 14.6 +/- 2.7 mmHg and for latanoprost was 16.6 +/- 3.1 mmHg (P < 0.006). Eighteen patients overall preferred latanoprost versus 2 patients for the fixed combination, generally because of the greater convenience of once daily dosing. Adverse events were not significantly different between groups except that a bitter taste was found more frequently with TDFC (n = 9) than with latanoprost (n = 0; P = 0.009). Despite screening to exclude intolerance to beta-blockers, a single patient had to discontinue the TDFC because of new-onset asthma.
This study indicates that the 24-hour diurnal intraocular pressure is lowered more, by a small but statistically significant amount, with TDFC compared with latanoprost in primary open-angle glaucoma and ocular hypertensive patients.
To compare the effect on intraocular pressure (IOP) over 24 hours after 4 weeks of treatment with latanoprost 0.005% and timolol gel 0.5%.
Randomized, open, crossover single-center study.
Twenty-seven patients with ocular hypertension.
The patients were randomly assigned to 4 weeks of latanoprost 0.005% once daily or timolol gel 0.5% once daily, with a 4-week washout period before switching therapy.
Measurement of IOP during 24 hours of hospitalization. Blood pressure and heart rate were also measured repeatedly over the 24 hours. Daytime mean IOP, nighttime mean IOP, and 24-hour mean IOP were calculated as IOP area under the curve (AUC) divided by time in hours.
The mean IOP during daytime (7 AM to 10 PM) was 13.5 +/- 0.4 mmHg (daytime IOP, AUC/15 hours, least square mean +/- standard error of the mean [SEM]) in the latanoprost group, and 14.8 +/- 0.4 mmHg in the timolol gel group. This difference of 1.3 +/- 0.3 mmHg was statistically significant in favor of latanoprost (P < 0.001; 95% confidence interval [CI], 0.7, 2.0). The mean IOP at night (10 PM to 7 AM) was 13.7 +/- 0.4 mmHg for latanoprost (nighttime IOP, AUC/9 hours, least square mean +/- SEM) and 15.9 +/- 0.5 mmHg for timolol gel, with a difference of 2.2 +/- 0.3 mmHg (P < 0.001; 95% CI, 1.5, 2.8). At every measured time point during the 24 hours, latanoprost reduced IOP more than timolol. There was no difference between the two treatment groups regarding blood pressure and heart rate.
Latanoprost reduced mean 24-hour IOP, mean daytime IOP, and mean nighttime IOP statistically significantly more than timolol. Also, latanoprost reduced IOP more effectively at every measured time point over the 24 hours compared with timolol gel.
To evaluate latanoprost versus bimatoprost given each evening over the 24-hour diurnal curve.
Double-masked, 2-center, crossover comparison.
Forty-two of 44 patients with primary open-angle glaucoma (POAG) completed the study.
Consecutive patients were not treated during a baseline 24-hour curve after a glaucoma medicine-free period. They then were randomized to either latanoprost or bimatoprost for a 7-week treatment period. Diurnal curve intraocular pressures (IOPs) were measured at treatment period end at 2 am, 6 am, 10 am, 2 pm, 6 pm, and 10 pm. After the first treatment period, patients were changed to the opposite medicine without a medicine-free period. Diurnal curve measurements were performed again at the end of the second 7-week treatment period.
The 24-hour diurnal IOP.
On the last day of treatment, mean 24-hour IOPs were 17.3+/-2.8 mmHg for latanoprost and 16.7+/-2.4 mmHg for bimatoprost (P = 0.01). The 6 pm individual time point for IOP was statistically lower for bimatoprost after a Bonferroni correction (P = 0.008). The largest IOP difference at any time point was 0.9 mmHg at 6 pm. The most common side effect was conjunctival hyperemia, which occurred less with latanoprost (n = 6) than with bimatoprost (n = 15) (P = 0.004). Two patients had their treatments discontinued while on bimatoprost, one due to conjunctival hyperemia and the other due to ocular intolerance.
This study indicates that the 24-hour diurnal IOP is statistically lower in POAG with bimatoprost, compared with latanoprost, among patients who tolerated bimatoprost. However, the IOP difference between groups was small and may not be clinically meaningful. In contrast, conjunctival hyperemia seems statistically greater with bimatoprost. The exact clinical importance of conjunctival hyperemia, if any, needs to be clarified further.
To compare the effect on intraocular pressure (IOP) and side effects of 0.005% latanoprost applied once daily, morning or evening, with 0.5% timolol applied twice daily.
A 6-month randomized, double-masked, multicenter study with three parallel groups was undertaken. Two hundred sixty-seven patients were randomized, 84 to timolol, 89 to latanoprost in the morning for 3 months and then in the evening for another 3 months, and 94 to latanoprost with the treatment schedule reversed.
After 6 months, timolol reduced diurnal IOP from 24.6 to 17.9 mmHg (27%); latanoprost applied in the morning, from 25.5 to 17.7 mmHg (31%); and latanoprost applied in the evening, from 24.8 to 16.2 mmHg (35%). The efficacy of latanoprost applied in the evening was statistically superior to latanoprost applied in the morning and to timolol (P < 0.001). Latanoprost induced a slight increase in conjunctival hyperemia in 31.4% of treated patients, compared with 15.9% for timolol. Sporadic episodes of mild punctate corneal epithelial erosions were three times as frequent in latanoprost-treated eyes as in timolol-treated eyes. The most significant ocular side effect was increased pigmentation of the iris observed in five and suspected in seven more latanoprost-treated eyes. All these eyes had a mixed green-brown or blue/gray-brown iris color. Timolol reduced heart rate by 3 beats/minute (P < 0.005).
The effect on diurnal IOP of latanoprost applied once daily in the evening is superior to that of timolol. The main difference in side effects is increased pigmentation of the iris induced by latanoprost, most likely due to stimulation of melanogenesis in iris stromal melanocytes.
Our previous study, Atropine for the Treatment of Myopia 1 (ATOM1), showed that atropine 1% eyedrops were effective in controlling myopic progression but with visual side effects resulting from cycloplegia and mydriasis. The aim of this study was to compare efficacy and visual side effects of 3 lower doses of atropine: 0.5%, 0.1%, and 0.01%.
Single-center, double-masked, randomized study.
A total of 400 children aged 6-12 years with myopia of at least -2.0 diopters (D) and astigmatism of -1.50 D or less.
Children were randomly assigned in a 2:2:1 ratio to 0.5%, 0.1%, and 0.01% atropine to be administered once nightly to both eyes for 2 years. Cycloplegic refraction, axial length, accommodation amplitude, pupil diameter, and visual acuity were noted at baseline, 2 weeks, and then every 4 months for 2 years.
Myopia progression at 2 years. Changes were noted and differences between groups were compared using the Huber-White robust standard error to allow for data clustering of 2 eyes per person.
The mean myopia progression at 2 years was -0.30±0.60, -0.38±0.60, and -0.49±0.63 D in the atropine 0.5%, 0.1%, and 0.01% groups, respectively (P=0.02 between the 0.01% and 0.5% groups; between other concentrations P > 0.05). In comparison, myopia progression in ATOM1 was -1.20±0.69 D in the placebo group and -0.28±0.92 D in the atropine 1% group. The mean increase in axial length was 0.27±0.25, 0.28±0.28, and 0.41±0.32 mm in the 0.5%, 0.1%, and 0.01% groups, respectively (P < 0.01 between the 0.01% and 0.1% groups and between the 0.01% and 0.5% groups). However, differences in myopia progression (0.19 D) and axial length change (0.14 mm) between groups were small and clinically insignificant. Atropine 0.01% had a negligible effect on accommodation and pupil size, and no effect on near visual acuity. Allergic conjunctivitis and dermatitis were the most common adverse effect noted, with 16 cases in the 0.1% and 0.5% atropine groups, and no cases in the 0.01% group.
Atropine 0.01% has minimal side effects compared with atropine at 0.1% and 0.5%, and retains comparable efficacy in controlling myopia progression.
To compare the long-term outcome of pterygium surgery and the long-term effect on endothelial counts after mitomycin C (MMC) or limbal conjunctival autograft (LCAU) in pterygium surgery.
We performed a 10-year follow-up study of a randomized controlled trial.
A total of 115 eyes of 114 patients with primary pterygium were treated with intraoperative MMC (n = 63) or LCAU transplants (n = 52). A total of 76 patients completed the current 10-year long-term follow-up (47 in the MMC group, 29 in the LCAU group).
This is a follow-up study of a randomized controlled trial of a cohort of 114 patients in 2 groups that was performed at the Prince of Wales Hospital 10 years ago: group 1, intraoperative 0.02% MMC for 5 minutes; group 2, LCAU. Consecutive patients enrolled in the original study (recruitment began in February 2001) were invited back for a detailed clinical examination to document the long-term outcome of both surgical groups.
The main outcome measures included the recurrence rate, residual conjunctival bed status, complications, and corneal endothelial cell density (ECD) differences.
A total of 115 eyes of 114 patients were enrolled and randomized in our previous study. For the current study, 76 of the 114 patients (47 in the MMC group, 29 in the LCAU group) were contacted, whereas 18 patients were lost to follow-up and 20 patients had died. The mean follow-up period was 138±2 months in the MMC group and 137±2 months in the LCAU group. Twelve of 47 patients (25.5%) in the original MMC group and 2 of 29 patients (6.9%) in the LCAU group had recurrent pterygium (P = 0.021). The mean ECD was 2392±342 cells/mm(2) in the MMC group and 2390±388 cells/mm(2) in the LCAU group (P = 0.978). There was no significant difference in the ECD between the operated eyes and the fellow eyes in both groups (P = 0.926 MMC, P = 0.468 LCAU). No other significant ocular complications were observed in either group at the 10-year postoperative follow-up.
Limbal conjunctival autograft was more effective than intraoperative MMC in minimizing pterygium recurrence at the 10-year follow-up. Treatment with intraoperative MMC was not associated with long-term corneal endothelial cell loss.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
To evaluate the short-term efficacy and safety of topical cyclosporin A 0.05% in the treatment of patients with severe, steroid-resistant atopic keratoconjunctivitis (AKC).
Multicenter, placebo-controlled, double-masked, randomized trial.
Twenty-two patients with AKC refractory to topical steroid treatment.
Patients were randomly assigned (1:1) to treatment with topical 0.05% cyclosporin A eyedrops or a placebo (artificial tears) for a period of 28 days, 6 times daily during the first 2 weeks and 4 times daily during the last 2 weeks.
Symptoms (itching, tearing, discomfort, mucous discharge, and photophobia) and signs (bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) of AKC recorded on the day of enrollment and at the end of the treatment period.
A composite score computed by summing the severity grade over all 5 symptoms and 6 signs of AKC for each patient indicated a greater improvement in the cyclosporin A group relative to the placebo at the end of the 4-week treatment period (P = 0.048 and P = 0.002, for symptoms and signs, respectively). No adverse effects of the treatment with cyclosporin A 0.05% eyedrops were observed.
Topical cyclosporin A 0.05% seems to be safe and have some effect in alleviating signs and symptoms of severe AKC refractory to topical steroid treatment.
This study was conducted to evaluate the efficacy of 0.05% levocabastine compared with 4% cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge.
Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits (n = 50) received placebo in one eye and cromolyn in the fellow eye, four times daily for 2 weeks. On day 18, subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye. Subjects were challenged and evaluated after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and evaluated after 3, 5, and 10 minutes.
Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05).
These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours.
The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model.
Randomized, double-blind, placebo-controlled, paired-eye study.
Adults with a history of allergic conjunctivitis (>/=2 years) who were asymptomatic throughout the trial, had a positive skin test (cat dander, grass, or ragweed pollen within the last year), and had a positive conjunctival reaction (score 2+ or more for itching and redness in both eyes on a 0-4 scale) during two separate conjunctival provocation tests (CPT) before randomization.
Eighty patients underwent a 2-week screening period (visits 1 and 2) that included a CPT during visit 1 to establish the allergen threshold dose and a second confirmatory CPT performed at visit 2. Eye symptom assessments for itching (evaluated by patient) and conjunctival redness (evaluated by physician) were performed 5 and 10 minutes after CPT using a 5-point scale (from 0 = none to 4+ = severe). Qualified patients were randomized to receive one drop of AZE (0.015 mg of azelastine hydrochloride) in one eye and one drop of placebo in the other eye 20 minutes before CPT at visit 3 (onset) and 8 or 10 hours before CPT at visit 4 (duration).
Individual severity scores for itching (evaluated by patient) and conjunctival redness (evaluated by physician) for each eye at 3, 5, and 10 minutes after CPT at visits 3 and 4 using a 5-point scale (0 = none to 4+ = very severe).
Each of the 80 randomized patients completed the trial. Mean itching and conjunctival redness scores at visit 3 (onset) were significantly lower (P: < 0.001) in the AZE-treated eyes than in the placebo-treated eyes. At visit 4 (duration), mean itching and conjunctival redness scores (P: </= 0.003) for the 8-hour group and mean itching scores (P: </= 0.001) for the 10-hour group were significantly lower in the AZE-treated eyes than in the placebo-treated eyes. Significant differences in mean tearing and chemosis severity scores were also seen at visit 3 (onset) and visit 4 (duration) in the AZE-treated eyes when compared with the placebo-treated eyes. Treatment with AZE was well tolerated.
Therapy of experimentally induced allergic conjunctivitis with AZE was highly effective, with an onset of action seen within 3 minutes and a duration of effect of at least 8 to 10 hours.
To assess the incidence of immunologic corneal graft rejection episodes in a prospective case series of patients treated 4 times a day with topical cyclosporine 0.05%.
Prospective, single-center, institutional review board-approved study.
Fifty-two cornea transplant recipients considered low risk for graft rejection.
Primary indications for transplantation were keratoconus, Fuchs' dystrophy, or nonherpetic, nonvascularized scars. Subjects completely tapered off prednisolone acetate 1% by 13 weeks after transplantation and used topical cyclosporine 0.05% 4 times a day, beginning either 1 or 10 weeks posttransplant, with use continued until 1 year posttransplant. One subgroup supplemented cyclosporine use with pulsed prednisolone acetate 1% dosing, 4 times a day for 4 days every 6 weeks. The incidence of immunologic corneal graft rejection episodes was compared with that in Fuchs' and keratoconus historical control subjects, who used topical steroids a median of 7 months after penetrating keratoplasty.
Incidence of immunologic graft rejection episodes.
Graft rejection episodes occurred earlier and with higher incidence in subjects using cyclosporine 0.05% compared with historical control subjects who used steroids for a longer period of time (P<0.0001). Cyclosporine subjects who pulse-dosed prednisolone had a significantly higher incidence of graft rejection compared with those who did not pulse steroids (P = 0.04).
The results suggest that 4 times daily dosing with topical cyclosporine 0.05% is not as effective as use of topical prednisolone acetate 1% for prevention of graft rejection episodes in low-risk corneal transplants, and that periodic pulsing with corticosteroids may increase the risk of rejection episodes.
To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% (Xibrom) for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction (CE).
Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled clinical trials were conducted under a common protocol. Data were pooled for analyses.
Five hundred twenty-seven subjects were sequentially assigned, according to a computer-generated randomization list (2:1), to bromfenac (n = 356) or a placebo (n = 171).
Subjects who underwent cataract surgery without prior antiinflammatory treatment with a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or the placebo, instilled twice daily for 14 days in the study eye, and observed for an additional 14 days for safety evaluation.
Cleared ocular inflammation with a SOIS of 0 (cells< or =5 and absence of flare after 14 days of treatment). Secondary outcomes included time to resolution of ocular inflammation, time to resolution of ocular pain, proportion of subjects with photophobia, and ocular adverse events.
Baseline characteristics were comparable between groups for age, gender, and race. The baseline mean SOIS was 3.7 in both groups. A greater proportion of bromfenac (64.0%) than placebo subjects (43.3%) achieved complete clearance of ocular inflammation at study day 15 (P<0.0001). The effect of bromfenac on clearance of ocular inflammation was as early as study day 3 after initiation of treatment, compared with the placebo (8.4% vs. 1.2%, P = 0.0012). The median time to resolution of ocular pain was 2 days (bromfenac) versus 5 days (placebo) (P<0.0001). Numbers of most ocular adverse events were lower for the bromfenac group than for the placebo group. Eye irritation was reported in a lower percentage of subjects for bromfenac (2.5%) versus placebo (4.7%), as were burning and stinging (1.4% vs. 2.5%), and photophobia (2.0% vs. 11.1%).
Bromfenac ophthalmic solution 0.09% effectively and rapidly cleared ocular inflammation and reduced ocular pain after CE. There were no serious ocular adverse events, and fewer adverse events were reported for the bromfenac group.
To evaluate cyclosporine 0.1% ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients.
Nonrandomized, multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials.
Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05% or 0.1% in prior phase III trials.
Patients instilled ophthalmic cyclosporine 0.1% twice daily into both eyes for up to 3 consecutive 12-month extension periods.
Corneal staining, Schirmer tests, and symptom severity assessments were conducted during the first 12-month extension, with a patient survey during the second 12-month extension. Biomicroscopy and visual acuity (VA) examinations, intraocular pressure (IOP) measurements, and adverse effects queries occurred at 6-month intervals.
Mean duration of treatment was 19.8 months. Improvements in objective and subjective measures of dry eye disease were modest, probably because of prior treatment with cyclosporine. Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials. At study exit, VA decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by > or =2 lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760), 7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common treatment-related adverse events were burning (10.9% of patients [45/412]), stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious treatment-related adverse events occurred. Most patients (95.2% [140/147]) said they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to other dry eye patients.
Therapy of chronic dry eye disease with cyclosporine 0.1% ophthalmic emulsion for 1 to 3 years was safe, well tolerated, and not associated with systemic side effects. The results supplement the safety record of the commercially available cyclosporine 0.05% ophthalmic emulsion.
In a prospective study, the addition of dipivefrin hydrochloride 0.1% twice daily to one eye of 32 patients with early primary open-angle glaucoma or ocular hypertension, maintained on a bilateral beta 1-, beta 2-blocker twice daily, resulted in a significant decrease of mean intraocular pressure (IOP) from 22.7 +/- 3.9 to 20.2 +/- 3.4 mmHg at 1 week (P = 0.0001) and to 21.0 +/- 3.8 mmHg at 12 weeks (P less than 0.02) in the dipivefrin-treated eyes. On the other hand, no significant change was noted in the fellow eyes (from 21.7 +/- 4.1 to 21.6 +/- 4.0 mmHg at 1 week and to 21.3 +/- 4.2 mmHg at 12 weeks). The addition of dipivefrin resulted in an IOP reduction of 2 mmHg or more in 50% and 3 mmHg or more in 19% of the eyes throughout the 12-week therapy. The result of the current study provides a realistic guideline as to what to expect from the common practice of adding dipivefrin hydrochloride to a beta 1-, beta 2-blocker regimen.
To compare nerve growth factor (NGF) levels in tears and on the ocular surfaces of normal control and non-Sjögren's type keratoconjunctivitis sicca subjects, and to investigate the effect of 0.1% prednisolone eyedrops on NGF levels in keratoconjunctivitis sicca patients.
Prospective, double-masked, randomized, comparative clinical trial.
Forty-one keratoconjunctivitis sicca patients and 23 age- and gender-matched healthy subjects.
Baseline tear NGF levels were measured in keratoconjunctivitis sicca patients and healthy control subjects using enzyme-linked immunosorbent assays. Keratoconjunctivitis sicca patients received 0.1% prednisolone drops in one eye and 0.1% hyaluronic acid drops in the other, 3 times a day for 28 days. Also, impression cytology (IC) and immunostaining for NGF on conjunctival epithelium were performed on both groups.
Tear NGF/total tear protein (TP) concentration ratio, IC and NGF immunocytologic staining, subjective symptom scale, tear breakup time, and Schirmer values.
Keratoconjunctivitis sicca patients were found to have baseline tear NGF concentrations higher than those of age- and gender-matched healthy control subjects (65.9+/-14.5 vs. 122.1+/-45.3 pg/mug, P<0.0001). In keratoconjunctivitis sicca patients, prednisolone treatment for 28 days resulted in a decrease in tear NGF levels, symptom scores, and IC scores, whereas hyaluronic acid treatment had no such effect (68.2+/-25.0 pg/mug vs. 108.0+/-43.4 pg/mug, P<0.0001 for tear NGF/TP ratio; 2.16+/-1.01 vs. 3.39+/-1.50, P = 0.0014 for symptom scale; 1.05+/-0.67 vs. 1.61+/-0.86, P = 0.0317 for IC). Measurements taken at both 14 and 28 days indicated that neither prednisolone nor hyaluronic acid treatment affected breakup time or Schirmer values.
Keratoconjunctivitis sicca patients showed elevated levels of tear NGF, which were decreased by treatment with 0.1% prednisolone. These data suggest that ocular surface NGF may play an important role in ocular surface inflammation processes associated with dry eyes.
To investigate the efficacy of 2% rebamipide ophthalmic suspension compared with 0.1% sodium hyaluronate ophthalmic solution for the treatment of patients with dry eye.
Randomized, multicenter, active-controlled parallel-group study.
One hundred eighty-eight patients with dry eye.
Following a 2-week screening period, patients were allocated randomly to receive 2% rebamipide or 0.1% sodium hyaluronate, administered as 1 drop in each eye 4 or 6 times daily, respectively, for 4 weeks.
Main outcome measures:
There were 2 primary end points: changes in the fluorescein corneal staining (FCS) score to determine noninferiority of 2% rebamipide and changes in the lissamine green conjunctival staining (LGCS) score to determine superiority. Secondary objective end points were Schirmer's test results and tear film breakup time (TBUT). Secondary subjective end points were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and the patients' overall treatment impression score.
In the primary analysis, the mean change from baseline in FCS scores verified noninferiority, indicated significant improvement, and, in LGCS scores, verified the superiority of 2% rebamipide to 0.1% sodium hyaluronate. Values for the Schirmer's test and TBUT were comparable between the 2 groups. For 2 dry eye-related ocular symptoms--foreign body sensation and eye pain--2% rebamipide showed significant improvements over 0.1% sodium hyaluronate. Patients had a significantly more favorable impression of 2% rebamipide than of 0.1% sodium hyaluronate; 64.5% rated treatment as improved or markedly improved versus 34.7%, respectively. No serious adverse events were observed.
Administration of 2% rebamipide was effective in improving both the objective signs and subjective symptoms of dry eye. Those findings, in addition to the well-tolerated profile of 2% rebamipide, clearly show that it is an effective therapeutic method for dry eye.
Proprietary or commercial disclosure may be found after the references.
To compare the efficacy of brimonidine, dorzolamide, and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to a prostaglandin analog (PGA).
Randomized, controlled, investigator-masked, single-site, parallel-group clinical trial.
One hundred twenty eyes of 120 patients with open-angle glaucoma or ocular hypertension who had inadequate IOP control after at least 6 weeks of monotherapy with a once-daily PGA (bimatoprost, latanoprost, or travoprost).
Study eyes were assigned randomly to adjunctive treatment with thrice-daily brimonidine tartrate 0.15% (n = 41), dorzolamide hydrochloride 2% (n = 40), or brinzolamide 1% (n = 39) for 4 months.
Efficacy was evaluated by IOP measured at 10 am and 4 pm at baseline, month 1, and month 4.
The mean IOP at each hour at PGA-treated baseline was comparable among treatment groups. After initiation of adjunctive therapy, the mean IOP was lower and the mean change from baseline IOP was greater in the brimonidine group than in either the dorzolamide group or the brinzolamide group at 10 am and 4 pm at months 1 and 4 (P<0.001). After 4 months of adjunctive treatment, the mean IOP reduction from baseline at 10 am and 4 pm was 4.8 mmHg (21%) and 3.8 mmHg (19%) with brimonidine, 3.4 mmHg (16%) and 2.8 mmHg (14%) with dorzolamide, and 3.4 mmHg (16%) and 2.6 mmHg (13%) with brinzolamide (P<0.001 for brimonidine vs. dorzolamide and brinzolamide at each time point). Each of the study drugs was well tolerated, and all patients completed the study.
The addition of brimonidine to a PGA provided greater IOP lowering than the addition of either dorzolamide or brinzolamide. Further studies are needed to evaluate the relative long-term efficacy and tolerability of these medications as adjunctive therapy to a PGA.
Proprietary or commercial disclosure may be found after the references.
To assess whether iris color and eyelash changes occur with the use of unoprostone for 2 years.
The 2 clinical trials described herein were prospective, randomized, double-masked, active-controlled, parallel group, multicenter studies.
A total of 1131 patients with primary open-angle glaucoma or ocular hypertension participated in 2 clinical trials and received either unoprostone isopropyl 0.15% (659), timolol maleate 0.5% (331), or betaxolol hydrochloride 0.5% (141), 1 drop per eye twice daily for up to 24 months.
Color photographs (1:1 magnification) were taken of the iris and eyelid of each patient at baseline and at regular intervals thereafter through month 24 using a standardized camera system. Photography included 7 views of each eye plus a calibration photograph and a patient identification photograph, for a total of 16 photographs per patient per visit. Two independent (masked) readers subjectively compared baseline iris colors to subsequent visits. Side view photographs of the upper and lower eyelashes were used for the eyelash length analysis, with each having sufficient depth of field and a sufficient number of eyelashes in focus. Similarly, frontal eyelash views were used for the eyelash density analysis.
Changes from baseline in iris color and eyelash length and density within and between treatment groups.
Seven cases of iris color change (1.06%) were confirmed in patients treated with unoprostone for up to 24 months; no confirmed cases were reported in the timolol or betaxolol groups. In the unoprostone group, cases of iris color change were confirmed at months 12 (1 case), 18 (2 cases), and 24 (4 cases). No clinically relevant differences were observed among treatment groups for changes from baseline in eyelash length or density.
Although iris hyperpigmentation and abnormal eyelash changes may occur after treatment with unoprostone, the incidence of these events appears to be low in the 2-year clinical study.
The safety and intraocular pressure (IOP)-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1 were evaluated and compared with brimonidine tartrate 0.15% preserved with chlorine dioxide in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Randomized, double-masked, parallel group, multicenter equivalence study.
Eight hundred forty-two patients randomized to the study treatments.
Patients with OAG or OHT and with qualifying IOP (22-36 mmHg at 8 am on 2 eligibility visits after an appropriate washout period from previous treatment) were assigned randomly to either brimonidine tartrate 0.15% preserved with polyquaternium-1 (brimonidine PQ) or brimonidine tartrate 0.15% preserved with chlorine dioxide (brimonidine P) dosed 3 times daily and were followed up for 6 months. Approximately one half of the study sites continued to follow up their patients for an additional 6 months to obtain longer-term safety data.
Brimonidine PQ produced statistically significant and clinically relevant reductions from baseline ranging from 4.3 to 6.5 mmHg, which were statistically and clinically equivalent to brimonidine P at all 18 visit days and times. No safety concerns were identified based on an assessment of ocular and cardiovascular parameters. Patient discontinuations resulting from adverse events were similar for both groups and most of these were a result of signs or symptoms of ocular allergic reaction.
Brimonidine PQ is equivalent in IOP-lowering efficacy and safety to brimonidine P.
To determine the vitreous concentration of brimonidine after topical administration of Alphagan.
Prospective observational case series.
Eighteen patients scheduled for elective pars plana vitrectomy.
Brimonidine tartrate, 0.2%, was topically administered twice or three times daily for 4 to 14 days preoperatively in 13 patients. Four patients served as controls, without application of brimonidine. A dry, undiluted vitrectomy specimen obtained intraoperatively was collected, frozen, and sent to an independent bioanalytical facility for quantitative determination of vitreous concentration of brimonidine using gas chromatography/mass spectrometry.
The concentration of brimonidine in human vitreous.
All patients treated with brimonidine measured above the lower limit of quantitation with a mean vitreous concentration of 185 +/- 500 nM. All patients not treated with brimonidine measured at or below the lower limit of quantitation of 0.05 nM. There was a trend toward higher concentration in patients who were either aphakic or pseudophakic compared with those that were phakic.
Topically applied brimonidine results in vitreous levels at or above 2 nM, the concentration shown to activate alpha(2)-receptors.
To evaluate the clinical efficacy and tolerability of brimonidine tartrate 0.2% twice daily as adjunctive therapy for glaucoma patients inadequately controlled with otherwise maximal tolerated medical therapy.
Retrospective, noncomparative, case series.
Ninety-six patients were identified from the authors' tertiary glaucoma practice who were treated with brimonidine. Their glaucoma was uncontrolled despite maximal tolerated medical therapy before receiving brimonidine, and some had previously undergone argon laser trabeculoplasty or filtration surgery. The patients were subdivided according to their glaucoma diagnosis: open-angle (OAG), angle-closure (ACG), mixed mechanism, and congenital glaucoma. Both the short- (about 2 weeks) and long-term results were evaluated. Twenty-two patients were excluded because additional medication changes were made at the time of introduction of brimonidine.
Brimonidine was added to the existing regimen of glaucoma medication.
Intraocular pressure (IOP) was recorded at all follow-up dates, together with visual field examination and optic disc evaluation twice yearly.
There were 44 OAG, 20 ACG, 6 mixed mechanism, and 4 congenital glaucoma patients. Mean pretreatment IOP, mean short-term post-treatment IOP, and mean short-term IOP reduction (percentage) were 23.10 +/- 5.21 mmHg, 18.49 +/- 4.77 mmHg, and 4.6 mmHg (20%) for OAG; 22.80 +/- 5.70 mmHg, 18.65 +/- 5.75 mmHg, and 4.15 mmHg (18%) for ACG; 25.00 +/- 10.32 mmHg, 21.00 +/- 12.12 mmHg, and 4.0 mmHg (16%) for mixed mechanism; and 26.00 +/- 4.97 mmHg, 17.75 +/- 4.57 mmHg, and 8.25 mmHg (32%) for congenital glaucoma, respectively. Mean long-term follow-up was 204 days for OAG and 213 days for ACG. Of the initially controlled OAG and ACG patients, at 3 months 96% and 100%, at 6 months 80% and 77%, and at 9 months 58% and 44%, respectively, were still controlled. Six patients discontinued brimonidine, three of these owing to allergy.
As adjunctive therapy, brimonidine achieved a short-term IOP reduction of 16%-32% in this patient population; 77%-80% of initially controlled patients were still controlled after 6 months. Brimonidine was well tolerated.
To compare the long-term safety and ocular-hypotensive efficacy of brimonidine tartrate 0.2% with timolol maleate 0.5% administered twice daily in patients with glaucoma or ocular hypertension.
A double-masked, parallel-group, active-controlled, multicenter clinical trial of 12 months' duration.
Four hundred eighty-three patients with glaucoma or ocular hypertension were enrolled. Of these, 463 were evaluated according to the protocol criteria (280 in the brimonidine tartrate group and 183 in the timolol group).
Brimonidine tartrate 0.2% or timolol maleate 0.5% was administered twice daily.
The primary efficacy variable was intraocular pressure (IOP).
Brimonidine and timolol produced significant (P < 0.001) and sustained mean reductions in IOP throughout the 1-year follow-up when measured at hour 0 (trough) and at hour 2 (peak). At weeks 1 and 2 and month 12, significantly greater mean decreases in IOP measured at peak (P < or = 0.007) were observed in patients treated with brimonidine as compared to timolol, whereas the mean decreases in IOP measured at trough was significantly greater in patients treated with timolol as compared to brimonidine (P < 0.001) at all follow-up visits. Both drugs were well-tolerated. The incidence of adverse events was similar in both treatment groups, except for ocular allergy, oral dryness, and conjunctival follicles, which occurred more frequently in the brimonidine group, and burning-stinging, which occurred more frequently in the timolol group. Patients receiving timolol experienced significant decreases in heart rate at all follow-up visits.
Topically applied twice daily for 12 months, brimonidine tartrate 0.2% was safe and effective in lowering IOP in patients with glaucoma or ocular hypertension.
To compare the efficacy of brimonidine 0.2% with apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery.
Double-masked, randomized clinical trial.
Sixty-six patients underwent either laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:yttrium-aluminum-garnet laser capsulotomy.
Eyes received either one drop of brimonidine 0.2% or apraclonidine 0.5% before laser surgery.
Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery.
Before the laser treatment, 33 patients (50.0%) received brimonidine 0.2% and 33 patients (50.0%) received apraclonidine 0.5%. Eight of 33 patients (24.2%) in the brimonidine-treated group and 9 of 33 patients (27.3%) in the apraclonidine group had postoperative IOP increases of 5 mmHg or more. This was not statistically different (P = 0.80). By the time of last follow-up examination, 3 of 33 patients (9.1%) in the brimonidine-treated group and 3 of 33 patients (9.1%) in the apraclonidine group had IOP increases of 10 mmHg or more. This was also not statistically different (P > or = 0.95). The mean IOP reduction from baseline in the brimonidine group (-2.8 +/- 2.8 mmHg) was not statistically different (P = 0.55) compared with the mean IOP reduction in the apraclonidine group (-3.6 +/- 3.3 mmHg). There were no statistically significant changes in mean heart rate or blood pressure in either group except for a slight reduction in diastolic blood pressure at 1 hour (P = 0.005) in the brimonidine group (-5.2 +/- 7.4 mmHg) compared with the apraclonidine group (-0.2 +/- 6.4 mmHg). There were no clinically significant side effects noted in either group.
A single preoperative drop of brimonidine 0.2% is as effective as apraclonidine 0.5% in preventing IOP elevation immediately after anterior segment laser surgery.
To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis.
Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration.
A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated.
All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days.
Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured.
A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0-3 scale) and itching (3.4 vs. 3.0 units on a 0-4 scale) over the first 2 weeks. The treatment effect by these measures was -0.5 and -0.4 units in favor of LE (P < or = 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment.
Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.
To determine whether brimonidine 0.2% can control intraocular pressure (IOP) spikes as well as apraclonidine 1.0% can in those patients undergoing argon laser trabeculoplasty (ALT).
Prospective, randomized, double-masked, clinical trial.
A total of 56 eyes of 41 patients with open-angle glaucoma or ocular hypertension were entered in the study; 46 eyes of 41 patients were eventually used for the final analysis.
Patients were randomized to receive either brimonidine 0.2% or apraclonidine 1.0% before and after 360 degrees ALT. Both patient and physician were masked as to which agent each patient received.
Intraocular pressure measurements were recorded before surgery and at 1, 2, and 4 hours after surgery. The difference between the preoperative IOP (baseline) and the highest recorded postoperative IOP was recorded as the maximum IOP change. The mean of the maximum IOP change for each group was analyzed using a two-sample, one-tailed t test.
The mean of the maximum IOP change in the brimonidine 0.2% group was -2.6+/-3.6 mmHg, and the mean for the apraclonidine 1.0% group was -2.3+/-3.7 mmHg (P = 0.8). No patient had a pressure spike greater than 10 mmHg.
Brimonidine 0.2% appears to be as effective as apraclonidine 1.0% in preventing IOP spikes after argon laser trabeculoplasty.
The authors evaluated the efficacy of once-daily treatment with levobunolol in patients with primary open-angle glaucoma or ocular hypertension in an open-labeled, two-phase titration clinical trial. All patients started the study using 0.25% levobunolol administered once daily for 3 months (phase I). If a patient's intraocular pressure (IOP) was not controlled with this concentration of levobunolol, the concentration was increased to 0.5% administered once daily for 3 months (phase II). During phase I, a significant reduction in IOP was observed in 21 of the 29 patients (72%), with an average IOP reduction of 24%. During phase II, in six patients whose IOP was reduced inadequately with 0.25% levobunolol, one had a significant reduction in IOP with 0.5% levobunolol. The authors concluded that levobunolol, instilled once daily at a concentration of 0.25%, was effective in significantly reducing IOP in the majority of the patients evaluated.
Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed.
A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication.
All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication.
Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.
To measure the achievable perioperative aqueous concentration of the commercially available topically administered fourth generation fluoroquinolones, moxifloxacin 0.5% ophthalmic solution, and gatifloxacin 0.3% ophthalmic solution, and to correlate this concentration with the agents' biological efficacy in the aqueous humor of patients undergoing routine cataract surgery.
Prospective, randomized, parallel, double-masked, clinical trial.
Fifty patients undergoing cataract extraction.
Patients (n = 25) were given perioperative topical moxifloxacin 0.5% or topical gatifloxacin 0.3% (n = 25). One drop of antibiotic was administered every 10 minutes for 4 doses beginning 1 hour prior to surgery. Aqueous humor was sampled via paracentesis and antibiotic concentrations were determined using validated high performance liquid chromatography (HPLC) procedures. Dilution analyses were performed to determine the biological efficacy of the agents in the aqueous against Staphylococcus epidermidis, the most common cause of postcataract endophthalmitis.
Aqueous humor antibiotic concentrations were measured using HPLC and microdilution bioassay techniques. Biological activity was measured as minimal inhibitory dilution and minimal bactericidal dilution.
Aqueous humor concentrations for moxifloxacin via HPLC analysis were 1.80 (+/-1.21) microg/ml, whereas those for gatifloxacin were 0.48 (+/-0.34) microg/ml. This 3.8-fold difference in aqueous humor antibiotic concentrations was statistically significant (P = 0.00003). Similarly, the biological dilution analysis of the aqueous humor samples showed that moxifloxacin attained an estimated activity of 2.1 microg/ml, whereas the gatifloxacin activity was approximately 0.4 mug/ml, which represented a 4.9-fold difference.
This study demonstrated that after topically administered perioperative antibiotics with cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in aqueous humor compared with gatifloxacin (P = 0.00003). Results from the broth dilution analysis showed that moxifloxacin 0.5% was biologically more active against S. epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. There were no adverse events reported, and incision wounds healed quickly and as expected.
The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers.
This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria.
Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01).
Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.
To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (QUIXIN) with 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis.
Prospective, randomized, active-controlled, double-masked, multicenter study.
Four hundred twenty-three patients with a clinical diagnosis of bacterial conjunctivitis were enrolled.
Patients were randomly assigned to receive either 0.5% levofloxacin (n = 211) or 0.3% ofloxacin (n = 212) for 5 days (every 2 hours on days 1 and 2 and every 4 hours on days 3-5). Conjunctival cultures were obtained, and ocular signs and symptoms were evaluated on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). End point was defined as the last evaluable observation.
Primary microbial and clinical outcomes were based on culture results and resolution of cardinal signs, respectively. Secondary efficacy assessments included evaluations of ocular signs and symptoms.
Two hundred eight patients (levofloxacin, n = 109; ofloxacin, n = 99) were evaluated for efficacy. Microbial eradication rates were significantly greater in the 0.5% levofloxacin treatment group compared with the 0.3% ofloxacin group at both the final visit (89% vs. 80%, P = 0.034) and at end point (90% vs. 81%; P = 0.038). Treatment with 0.5% levofloxacin was significantly more effective in resolving photophobia than was 0.3% ofloxacin treatment (94% vs. 73%, P = 0.006). Both study medications were well tolerated, with a low incidence of adverse events.
Although clinical cure rates in the 0.5% levofloxacin and 0.3% ofloxacin treatment groups were similar, a 5-day treatment regimen with 0.5% levofloxacin achieved microbial eradication rates that were statistically superior to those attained with 0.3% ofloxacin. Despite the higher concentration of active drug in 0.5% levofloxacin versus 0.3% ofloxacin, there was no difference between treatment groups in the incidence of treatment-related adverse events.
To investigate the aqueous penetration of 3 commercially available ophthalmic fluoroquinolones.
Prospective, double-masked, clinical study.
Fifty-two eyes of 52 patients.
Fifty-two patients undergoing cataract surgery were given preoperative topical gatifloxacin 0.3% (Zymar), moxifloxacin 0.5% (Vigamox), or ciprofloxacin 0.3% (Ciloxan). The patients were instructed to use their antibiotic drops 4 times a day for 3 days before surgery. On the day of surgery, patients were given their assigned antibiotic every 15 minutes for 3 doses, 1 hour before their procedure. At the time of surgery, 0.1 ml of aqueous fluid was aspirated from the anterior chamber with an air cannula needle attached to a tuberculin syringe. The aspirate was immediately stored at -70 degrees C.
Fluoroquinolone concentrations were determined by reverse-phase high-pressure liquid chromatography assay technique with ultraviolet detection at a wavelength of 275 nm.
Mean aqueous concentration of gatifloxacin in 16 eyes was 0.63 microg/ml (standard deviation [SD], 0.30), moxifloxacin in 14 eyes was 1.31 microg/ml (SD, 0.46), and the mean concentration of ciprofloxacin in 22 eyes was 0.15 microg/ml (SD, 0.11).
Both moxifloxacin (P<0.001) and gatifloxacin (P<0.005) penetrated the aqueous humor at significantly higher levels than ciprofloxacin. Moxifloxacin penetrated into the aqueous humor at significantly higher levels than gatifloxacin (P<0.05). The anterior chamber levels of moxifloxacin and gatifloxacin may be due to the difference in antibiotic concentration.
To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of moxifloxacin ophthalmic solution 0.5% for the treatment of bacterial conjunctivitis.
Multicenter, randomized, double-masked, parallel-group, active-controlled, noninferiority study.
Patients 1 year of age or older with clinical manifestations of bacterial conjunctivitis.
Eligible patients were randomized to either besifloxacin suspension or moxifloxacin solution, instilled in the infected eye(s) 3 times daily for 5 days, and participated in study visits on days 1, 5 (+/-1 day), and 8 (+1 day). Assessments included clinical evaluation of signs and symptoms, visual acuity, biomicroscopy, and culture of the infected eye(s) at each visit, as well as direct ophthalmoscopy on days 1 and 8.
The primary efficacy end points were clinical resolution and microbial eradication of baseline bacterial infection on day 5 in patients with culture-confirmed bacterial conjunctivitis. Secondary end points included clinical resolution and microbial eradication on day 8, individual clinical outcomes, microbial and clinical outcomes by bacterial species, and safety.
A total of 1161 patients (533 with culture-confirmed bacterial conjunctivitis) were randomized. Based on the 95% confidence interval (CI) of the difference, besifloxacin was noninferior to moxifloxacin for clinical resolution on day 5 (58.3% vs. 59.4%, respectively; 95% CI, -9.48 to 7.29) and day 8 (84.5% vs. 84.0%, respectively, 95% CI, -5.6% to 6.75%) and for microbial eradication on day 5 (93.3% vs. 91.1%, respectively, 95% CI, -2.44 to 6.74) and day 8 (87.3% vs. 84.7%; 95% CI, -3.32 to 8.53). There was no statistically significant difference between the 2 treatment groups for either efficacy end points on days 5 or 8 (P>0.05). Besifloxacin and moxifloxacin were well tolerated. The cumulative frequency of ocular adverse events was similar between treatments (12% and 14% with besifloxacin and moxifloxacin, respectively). However, eye irritation occurred more often in moxifloxacin-treated eyes (0.3% for besifloxacin vs. 1.4% for moxifloxacin; P = 0.0201).
Besifloxacin ophthalmic suspension was non inferior to moxifloxacin ophthalmic suspension and provided similar safety and efficacy (clinical and microbiological) outcomes when used for the treatment of bacterial conjunctivitis.
Proprietary or commercial disclosure may be found after the references.
To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD).
Twenty-four-month, open-label, multicenter, phase IV extension study.
Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study.
Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion).
Main outcome measures:
Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections.
Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline.
The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.
Proprietary or commercial disclosure may be found after the references.
To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME).
Twenty-four-month, open-label, multicenter, Phase IIIb extension study.
Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension.
All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension.
Main outcome measures:
Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA.
Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 μm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 μm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 μm, and 4.3, respectively), with an average of 4.1 ranibizumab injections.
Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year.
Proprietary or commercial disclosure may be found after the references.
To compare the efficacy and safety of ketorolac 0.5% ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation.
Multicenter clinical study.
One hundred four patients were prospectively randomized, 52 patients in treatment group, 52 patients in control group.
Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospective, double-masked, randomized, parallel group study. Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled.
The main outcome measures include inflammation (cell, flare, ciliary flush), intraocular pressure and visual acuity.
Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation, including: anterior chamber cells (P: = 0.002) and flare (P: = 0.009), conjunctival erythema (P: = 0.010), ciliary flush (P: = 0.022), photophobia (P: = 0.027), and pain (P: = 0.043). Five times as many patients were dropped from the study for lack of efficacy from the vehicle group (22/52) than from the ketorolac group (4/52; P: = 0.001). Ketorolac was found to be equally as safe as vehicle in terms of adverse events, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables.
Ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery, while being as safe as vehicle.
The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.
To report the early success of the use of topical cyclosporine A 0.5% drops to treat Theodore's superior limbic keratoconjunctivitis (SLK).
A retrospective noncomparative case series.
Five patients diagnosed with SLK.
All five patients were treated with topical cyclosporine A 0.5% drops as primary or adjunctive therapy after treatment failure in some of prednisolone acetate 1% drops and topical silver nitrate 0.5% application. Topical cyclosporine A 0.5% drops were used four times a day in both eyes.
Resolution of symptoms (foreign body sensation and irritation) and signs (rose bengal staining, tarsal papillary reaction, and injection).
All five patients had long-term (6 months to 3 years) improvement of irritation and foreign body sensation, as well as improvement of injection and filamentary keratitis. Aside from burning on instillation, there were no complications related to this therapy.
Topical cyclosporine A 0.5% is helpful as primary or adjunctive therapy for SLK. It may also be used as a maintenance drug to prevent recurrence. Further study may delineate the specific role and treatment parameters for the use of topical cyclosporine A 0.5% in the treatment of SLK.
To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy.
This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery.
Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine).
The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.
To evaluate the 24-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly or as needed (pro re nata [PRN]) in patients with neovascular age-related macular degeneration (wet AMD).
Twenty-four-month, multicenter, randomized, double-masked, active treatment-controlled phase 3 trial.
Patients (n = 1098) ≥ 50 years of age with treatment-naïve subfoveal wet AMD.
Patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or 2.0 mg monthly or PRN after 3 monthly loading doses.
Main outcome measures:
The primary efficacy end point was the mean change in best-corrected visual acuity (BCVA) from baseline at month 12. Key secondary end points included mean change in BCVA from baseline at month 24, proportion of patients who gained ≥ 15 letters in BCVA, mean number of ranibizumab injections, and mean change in central foveal thickness from baseline over time by spectral-domain optical coherence tomography. Ocular and systemic safety events also were evaluated through month 24.
At month 24, the mean change from baseline in BCVA was (letters) +9.1 (0.5 mg monthly), +7.9 (0.5 mg PRN), +8.0 (2.0 mg monthly), and +7.6 (2.0 mg PRN). The change in mean BCVA from month 12 to 24 was (letters) -1.0, -0.3, -1.2, and -1.0, respectively. The proportion of patients who gained ≥ 15 letters from baseline in BCVA at month 24 was 34.5%, 33.1%, 37.6%, and 34.8%, respectively. The mean number of ranibizumab injections through month 24 was 21.4, 13.3, 21.6, and 11.2, respectively; 5.6 and 4.3 mean injections were required in year 2 in the 0.5 mg and 2.0 mg PRN groups, respectively. The average treatment interval in the 0.5 mg PRN group was 9.9 weeks after 3 monthly loading doses, and 93% of these patients did not require monthly dosing. Ocular and systemic safety profiles over 2 years were similar among all 4 treatment groups and were consistent with previous ranibizumab trials in AMD.
At month 24, mean BCVA improvements were clinically meaningful and similar among all 4 ranibizumab treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 13.3 injections (5.6 injections in year 2). No new safety events were identified over 24 months.
To compare the safety and intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination with brinzolamide 1% or timolol 0.5% alone in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Randomized, double-masked, parallel group, multicenter study.
Five hundred twenty-three patients were randomized to the study treatments.
Patients with OAG or OHT were recruited to the study. Qualifying eyes had IOPs of 24 to 36 mmHg at 8 am and 21 to 36 mmHg at 10 am on 2 eligibility visits after an appropriate washout period from previous treatment. Patients were assigned randomly to either brinzolamide 1%/timolol 0.5%, brinzolamide 1% (Azopt; Alcon Laboratories, Fort Worth, TX), or timolol 0.5%, dosed twice daily and were followed up while receiving therapy for 6 months. At selected sites, additional IOP measurements were performed at 12 pm, 4 pm, and 8 pm during the 2 eligibility visits, at month 3, and at month 6.
Brinzolamide 1%/timolol 0.5% produced statistically significant and clinically relevant reductions from baseline ranging from 8.0 to 8.7 mmHg, which were statistically and clinically superior to that of either brinzolamide 1% (5.1-5.6 mmHg) or timolol 0.5% (5.7-6.9 mmHg). No safety concerns were identified based on an assessment of ocular and cardiovascular parameters and a review of adverse events.
Brinzolamide 1%/timolol 05% is superior in IOP-lowering efficacy to either brinzolamide 1% or timolol 0.5%.
To compare the equivalence of moxifloxacin 0.5% with a combination of fortified cefazolin sodium 5% and tobramycin sulfate 1.3% eye drops in the treatment of moderate bacterial corneal ulcers.
Randomized, controlled, equivalence clinical trial.
Participants and controls:
Microbiologically proven cases of bacterial corneal ulcers were enrolled in the study and were allocated randomly to 1 of the 2 treatment groups.
Group A was given combination therapy (fortified cefazolin sodium 5% and tobramycin sulfate) and group B was given monotherapy (moxifloxacin 0.5%).
Main outcome measures:
The primary outcome variable for the study was percentage of the ulcers healed at 3 months. The secondary outcome variables were best-corrected visual acuity and resolution of infiltrates.
Of a total of 224 patients with bacterial keratitis, 114 patients were randomized to group A, whereas 110 patients were randomized to group B. The mean ± standard deviation ulcer size in groups A and B were 4.2 ± 2 and 4.41 ± 1.5 mm, respectively. The prevalence of coagulase-negative Staphylococcus (40.9% in group A and 48.2% in group B) was similar in both the study groups. A complete resolution of keratitis and healing of ulcers occurred in 90 patients (81.8%) in group A and 88 patients (81.4%) in group B at 3 months. The observed percentage of healing at 3 months was less than the equivalence margin of 20%. Worsening of ulcer was seen in 18.2% cases in group A and in 18.5% cases in group B. Mean time to epithelialization was similar, and there was no significant difference in the 2 groups (P = 0.065). No serious events attributable to therapy were reported.
Corneal healing using 0.5% moxifloxacin monotherapy is equivalent to that of combination therapy using fortified cefazolin and tobramycin in the treatment of moderate bacterial corneal ulcers.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Ketorolac tromethamine solution 0.5% (1 drop 3 times daily) was more effective than the placebo vehicle solution in suppressing postoperative anterior ocular inflammation after extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation in this multicenter, double-masked, randomized study. Four of 60 ketorolac-treated patients compared with 25 of 58 placebo-treated patients required supplemental corticosteroid therapy to suppress inflammation in the postoperative period which was statistically significant (P less than 0.001). Even though these supplemental steroid-treated patients were kept in the analysis, the placebo-treated group showed more evidence of anterior ocular inflammation as measured by anterior segment fluorophotometry. This was consistent with slit-lamp observations of increased anterior ocular inflammation. This study supported previous studies that suggested ketorolac tromethamine ophthalmic solution 0.5% was effective and safe as a nonsteroidal anti-inflammatory agent for topical use after ECCE and IOL implantation.
To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD).
Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study.
A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy.
In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections.
The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining ≥ 10 and ≥ 15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area.
At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained ≥ 10 and ≥ 15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups.
In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified.
Botulinum toxin was used to treat 20 patients with strabismus after retinal detachment surgery. Preinjection motility deviations ranged from 10 to 60 prism diopters (D). Postinjection deviations ranged from 0 to 20 prism D, with 75% being 10 D or less. Eighty-five percent achieved fusion that persisted, with 73% requiring only one or two injections. Only muscles in the eye that had undergone retinal reattachment surgery were injected. The average period of follow-up was 12 months. Complications were rare and all resolved spontaneously. Botulinum toxin appears to be useful as a primary treatment modality for persistent strabismus following retinal detachment surgery, possibly obviating the need for complicated strabismus surgery.