Diclofenac drops to treat inflammation after cataract surgery.

PURPOSE: To compare the anti-inflammatory effect of topical diclofenac sodium 0.1% in a fixed combination with gentamicin 0.3% to the anti-inflammatory effect of dexamethasone phosphate 0.1% in a prospective randomized double-masked double-dummy study in patients undergoing cataract surgery. SETTING: Trial performed from June 1991 to April 1992 at the Hôpital Jules Gonin, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland. METHODS: Inclusion of patients scheduled for extracapsular cataract extraction (ECCE) with implantation of an all PMMA intraocular lens (IOL). Double-masked comparison of post-operative inflammation in two randomized treatment groups: (1) fixed diclofenac sodium 0.1%/gentamicin 0.3% and vehicle drops 4X/day until day 12-14 and diclofenac sodium 0.1% 3X/day until day 28. (2) dexamethasone phosphate 0.1% drops 4X/day until postoperative day 12-14 and 3X/day until day 28 and gentamicin 0.3% drops 4X/day until day 12-14. Anterior chamber flare and cells, measured by laser flare-cell photometry, were analyzed as the primary outcomes. RESULTS: Eighty-seven patients were recruited, 45 being assigned to the diclofenac group and 42 to the dexamethasone control group. Diclofenac was significantly better than dexamethasone at controlling flare at day 3 (p< or =0.01) and day 12-14 (p< or =0.002). Mean anterior chamber cells were also significantly lower at day 12-14 (p< or =0.021) and day 28 (p< or =0.012). The commonest adverse event was transient punctate keratitis, which occurred in 15 diclofenac and 3 dexamethasone patients. CONCLUSIONS: While both treatments were effective at controlling post-operative inflammation, the diclofenac-gentamicin combination followed by diclofenac alone was significantly better at suppressing flare and cells but showed a slightly higher incidence of punctate keratitis and eye discomfort.

A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes.

OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study.

OBJECTIVE: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING: Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS: Patients with subfoveal CNV caused by age-related macular degeneration. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.

OBJECTIVES: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

Meta-analysis of six clinical phase III studies comparing lomefloxacin 0.3% eye drops twice daily to five standard antibiotics in patients with acute bacterial conjunctivitis.

BACKGROUND: Lomefloxacin 0.3% ophthalmic solution twice daily has been compared in patients with bacterial conjunctivitis in six randomized double-blind or investigator-masked phase III studies with either chloramphenicol 0.5% 5x/day, gentamicin 0.3% 4x/day, fusidic acid 1% 2x/day, tobramycin 0.3% 4x/day or norfloxacin 0.3% 4x/day. METHODS: A meta-analysis of all individual data of these six studies was performed. A total of 582 patients with clinically diagnosed bacterial conjunctivitis were evaluated by slit-lamp examination with grading of eight key signs and symptoms and by conjunctival swab cultures at baseline, on day 3-5 and on day 7-9. Success of therapy, local tolerance and safety were evaluated at termination. In vitro sensitivity of the ocular isolates to 6-10 antibiotics was evaluated by disk diffusion tests. RESULTS: Two hundred and ninety patients treated with lomefloxacin 0.3% (LF) and 292 patients treated by one of the control antibiotics (combined control group, CCG) were enrolled in the studies. Two hundred and seventy-eight LF and 283 CCG patients were evaluable for the intent-to-treat (ITT) analysis, while 85 LF and 95 CCG patients had bacteria above the pathological threshold and formed the core subpopulation. The mean cumulative sum score in the LF group was 9. 47 on day 1, and decreased by 5.70 on day 3-5 and by 8.10 on day 7-9. In the CCG it decreased significantly less: it was 9.19 at baseline, decreased by 5.15 on day 3-5 and by 7.33 on day 7-9. Swab counts decreased in the LF and CCG group similarly, with the major decrease observed between day 1 and day 3-5. Most of the organisms considered resistant in vitro were still eradicated with the regimen used. Of the few surviving organisms also isolated on the next follow-up visit, one isolate in the LF group and seven in the CCG showed decreased in vitro sensitivity towards the treatment antibiotic used. Local tolerance was good or excellent, without any significant differences except for burning sensation, which lasted significantly longer in the CCG group than in the LF group. Adverse events were observed in 18 LF and 23 CCG patients; four LF and three CCG patients had to be withdrawn. All adverse events were non-serious. CONCLUSION: Lomefloxacin eye drops used with a loading dosage followed by a twice daily regimen proved as effective, safe and well tolerated as five established standard treatments used at a 2, 4 or 5 times daily regimen, caused less discomfort upon instillation, and showed a lower risk to generate or select new resistant strains.

A clinical evaluation of diclofenac-gentamicin combination eye drops in the control of inflammation after cataract surgery. Diclofenac-Gentamicin versus Gentamicin Study Group.

The purpose of this study was to compare the efficacy and safety of diclofenac-gentamicin (DR 1352/1) combination eye drops with gentamicin eye drops in the postoperative management of patients undergoing extracapsular cataract surgery and lens implantation. This was a prospective, randomised, double-masked, parallel-group, four-week, multicentre study with patient visits preoperatively, on the day of surgery, and postoperatively on days 1, 5-8, 12-16, and 26-32. Of the 196 patients (diclofenac-gentamicin 99, gentamicin 97) recruited into the study, 161 (diclofenac-gentamicin 83, gentamicin 78) were available for per-protocol analyses. The two treatment groups were clinically similar at baseline. On days 12-16 postoperatively, diclofenac-gentamicin was significantly more effective (p = 0.002) than gentamicin in reducing intraocular inflammation as assessed by the sum of grades of anterior chamber cells and flare. The level of conjunctival hyperaemia was significantly less in the diclofenac-gentamicin group compared with the gentamicin group on postoperative days 5-8 and 12-16. There was no significant difference between the two study groups in the global assessment of local tolerance. Possibly drug-related adverse events were slightly more in the diclofenac-gentamicin group (22,22%) compared with gentamicin (17,17%); however, all affected study patients normalised with appropriate therapy except one patient with endophthalmitis. In conclusion, diclofenac-gentamicin (DR1352/1) eye drops were more effective than gentamicin eye drops and appeared to be as safe in the control of post-cataract surgery inflammation.

Polyacrylic acid gel in patients with dry eyes: a randomised comparison with polyvinyl alcohol.

PURPOSE: To compare the safety and efficacy of polyacrylic acid 0.2% (PAA) gel and polyvinylalcohol 1.4% (PVA) in the treatment of patients with dry eyes. METHODS: Eighty-nine patients with dry eyes were randomly allocated to treatment with either PAA (48) or PVA (41) in a prospective, investigator-masked study in two centres. The parameters assessed were daily frequency of instillation of the study medications, ocular signs and symptoms, tear film break up time, Schirmer's test values, local tolerance and global assessment of the improvement following treatment. RESULTS: The two groups were similar in patient demographics and study parameters at baseline. The total score of symptoms (gritty or foreign body sensation, burning sensation, dry eye sensation, photophobia, others) and signs (conjunctival hyperaemia, ciliary injection, corneal and conjunctival epithelial staining) was reduced significantly more by treatment with PAA than with PVA at both three and six weeks (p < 0.0001). The daily frequency of instillation of PAA was significantly less than that PVA on 38 of the 41 (93%) study days. Both PAA and PVA were safe and equally well-tolerated except for blurred vision, usually mild and transient, on PAA. On global assessment of the improvement in their dry eye condition, significantly more PAA patients felt better on treatment at six (p = 0.02) weeks compared with those on PVA. CONCLUSIONS: Polyacrylic acid gel was as safe as and more effective than polyvinylalcohol in the treatment of patients with dry eyes.

Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples.

BACKGROUND: Conventional photocoagulation of subfoveal choroidal neovascularization (CNV) is often accompanied by visual loss due to thermal damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular occlusion by selective photochemical destruction of vascular endothelial cells only. In a pilot study we evaluated the use of PDT in CNV. METHODS: In a clinical phase I/II trial, patients with subfoveal CNV were treated with PDT. Benzoporphyrin derivative monoacid ring A (BPD) was used as sensitizer at a drug dose of 6 mg/m2 or 12 mg/m2. Irradiation was performed via a diode laser emitting at 690 nm coupled into a slit lamp. Safe and maximum tolerated light doses were defined by dose escalation from 25 to 150 J/cm2. Photodynamic effects were documented ophthalmoscopically and angiographically. RESULTS: Sixty-one patients received a single course of BPD-PDT. Preliminary results suggest no damage to retinal structures within the treated area clinically. Retinal perfusion was not altered, while CNV demonstrated immediate absence of fluorescein leakage in the majority of lesions subsequent to PDT. At optimized parameters (6 mg/m2 and 50 J/cm2) complete cessation of leakage from classic CNV occurred in 100% of cases at 1 week and in 50% at week 4. In 70-80% of classic CNV, leakage reappeared at week 12, but markedly less than before treatment. CONCLUSION: PDT allows temporary absence of leakage from CNV with preservation of visual acuity. The long-term prognosis of CNV secondary to age-related macular degeneration treated with repeated courses of PDT is being evaluated in a phase III trial.

Topical Lomefloxacin versus Topical Chloramphenicol in the Treatment of Acute Bacterial Conjunctivitis.

We performed a prospective, randomised, investigator-masked and parallel-group study to compare topical lomefloxacin 0.3% instilled twice daily with topical chloramphenicol instilled five times daily in the treatment of acute bacterial conjunctivitis. 191 patients (lomefloxacin 96, chloramphenicol 95) were enrolled in this study with clinically diagnosed acute bacterial conjunctivitis. The two treatment groups were similar at baseline. The treatments were equally effective and significantly (p < 0.001) reduced the Cumulative Sum Score of the clinical signs and symptoms of bacterial conjunctivitis. At the end of the trial, there was no difference between the two treatments in the Cumulative Sum Score of signs and symptoms (p = 0.63), and the investigator (p = 0.28) and patients' (p = 0.50) assessments of the success of therapy. The two drugs were equally well tolerated locally, with no serious systemic or local adverse drug reactions reported in any study patient. Bacteriological confirmation of acute conjunctivitis was possible in 96 patients (lomefloxacin 47, chloramphenicol 49) out of the 191 enrolled. Both treatments significantly (p < 0.001) reduced the conjunctival bacterial colony count score with no difference (p = 0.12) between the two treatment groups. In conclusion, lomefloxacin 0.3% eye drops instilled twice daily were as effective and well tolerated as chloramphenicol 0.5% eye drops instilled 5 times daily in the treatment of acute bacterial conjunctivitis.

Effectiveness of topical diclofenac in relieving photophobia after pupil dilation.

PURPOSE: To test the effectiveness of topical diclofenac in relieving photophobia after pupil dilation. SETTING: Department of Ophthalmology, Newcastle General Hospital, Newcastle-upon-Tyne, United Kingdom. METHODS: Twenty healthy patients and volunteers from the outpatient ophthalmology clinic were enrolled in a prospective, double-blind, placebo-controlled comparison in which the patient's fellow eye served as a control. Photophobia after pupil dilation was tested subjectively using a visual analog scale and a neutralization scale at 30 minute intervals for 2 hours after instillation of topical diclofenac. RESULTS: Both tests show a statistically significant reduction in photophobia in the diclofenac-treated eyes at each time interval (P < or = .05). This difference was also considered clinically relevant. CONCLUSION: Topical diclofenac given at the time of pupil dilation significantly reduced photophobia. The mechanism of action is unknown and requires further evaluation.

Efficacy and safety of topical diclofenac in reducing ocular pain after excimer photorefractive keratectomy.

PURPOSE: To evaluate the efficacy and safety of diclofenac sodium 0.1% ophthalmic solution in patients having myopic photorefractive keratectomy (PRK). SETTING: Corneal Laser Centre, Clatterbridge Hospital, Wirral, United Kingdom. METHODS: We performed a prospective, randomized, double-masked, parallel-group, placebo-controlled study of 50 patients (diclofenac 25, placebo 25) of both sexes who had myopic excimer laser PRK. Results were evaluated by several types of questionnaires and comprehensive clinical examination on the day of the procedure and 1 and 3 to 14 days postoperatively. RESULTS: Diclofenac-treated patients experienced significantly less photophobia, burning/stinging, and ocular pain and took significantly fewer oral narcotic analgesics over the first 24 hours postoperatively than placebo-treated patients. CONCLUSION: Topical diclofenac significantly reduced the ocular pain and discomfort immediately after excimer PRK without any clinically significant complications or adverse effects.

Influence of carteolol and timolol on IOP an visual fields in glaucoma: a multi-center, double-masked, prospective study.

The influences of Carteolol and Timolol eye drops on intraocular pressure (IOP) and visual fields were compared in a multi-center, double-masked, prospective study. Two-hundred and forty eyes of 120 patients were initially included in the study, and 142 eyes of 72 patients fulfilled all the criteria for final statistical analysis. Both drugs significantly reduced IOP. The visual fields in both treatment groups did not change during one year of treatment. In both groups some patients improved slightly, and others deteriorated slightly. This indicates that locally applied beta-blockers may efficiently stop further progression of visual field defects in cases with increased IOP and early visual field damage. There was no difference between Carteolol and Timolol in this regard. The side effects were minimal, and there were no differences in their frequency or intensity in the two treatment groups.