Effects of pre-instilled mydriatics on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (3)--study on permeability factor]

The authors studied a mechanism of an increase in intraocular concentration of topical 0.1% pranoprofen (PPF) induced by pre-instilled mydriatics (0.5% tropicamide and 0.5% phenylephrine) in rabbit eyes. Ingredient solutions of mydriatics were instilled 60 minutes prior to instillation of PPF. The PPF concentrations in the cornea, aqueous humor and iris-ciliary body did not increase with pre-instilled benzalkonium chloride, chlorobutanol and tropicamide. The PPF concentrations were increased by pre-instilled phenylephrine (PHE), and the concentrations were 2 to 3 times higher than those without mydriatics. The PHE concentration in the aqueous humor was increased about 3 times in the presence of PPF. The octanol/water partition coefficient of PPF was increased in the presence of PHE. These data indicate that the increase of intraocular PPF concentration by the pre-instilled mydriatics was caused by PHE, and the enhancement of transcorneal permeability to PPF may have resulted from the formation of ion-pair complexes between PPF, an anionic drug, and PHE, a cationic drug.     

Effects of pre-instilled mydriatics on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (2)--Study on multiple dosing]

We studied the effects of multiple dosing and pre-instilled mydriatics (0.5% tropicamide and 0.5% phenylephrine) on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (PPF) in rabbit eyes. PPF was applied in a single or multiple doses: 1 to 4 times consecutively at 5-minute intervals with or without pre-instilled mydriatics. PPF concentrations in the aqueous humor increased dose-dependently. The PPF concentrations also increased dose-dependently, and reached the maximal concentration by instillation 3 times in the presence of pre-instilled mydriatics, and the concentrations were 3.4 to 5.8 times higher than those without mydriatics. The PPF concentrations in the cornea, secondary aqueous, and iris-ciliary body increased in a dose-dependent manner, and the concentrations were higher in the presence of mydriatics. PPF reduced the protein rise in the secondary aqueous and miotic responses which were seen after paracentesis. The percent inhibitions ranged from 75 to 83, but the inhibitory actions were not enhanced by increases of intraocular PPF concentrations. These data indicate that the potent anti-inflammatory actions of PPF were obtainable by a single instillation, but it might be useful to instill the drug 3 times consecutively to ensure higher intraocular drug concentrations in combination with pre-instilled mydriatics.     

Topical pranoprofen 0.1% is as effective anti-inflammatory and analgesic agent as diclofenac sodium 0.1% after strabismus surgery.

To compare the anti-inflammatory and analgesic effects of topical pranoprofen 0.1% with diclofenac sodium 0.1% after strabismus surgery, 40 patients were prospectively randomized and assigned into 2 groups. Signs and symptoms of inflammation, as well as intraocular pressure (IOP) of patients, were evaluated at 1 day and 1 and 3 weeks following surgery. Both groups reported reduced inflammation and discomfort at 1 week, as compared to 1 day. There was no statistically significant difference in any measurement of postoperative inflammation (i.e., discomfort, chemosis, secretion, conjunctival hyperemia, and conjunctival gap size) between the 2 groups at any time. None of the patients developed an allergic reaction to the medications and IOP measurements were within the normal limits in both groups. Pranoprofen 0.1% was found to be as effective as diclofenac sodium 0.1% in reducing inflammation and pain after strabismus surgery. Pranoprofen could be used as a safe and effective anti-inflammatory alternative for the treatment of inflammation following strabismus surgery.     

Comparative study of the intraocular pressure effects of fluorometholone 0.1% versus dexamethasone 0.1%.

The intraocular pressure effect of fluorometholone 0.1% was compared with that of dexamethasone 0.1% by performing corticosteroid provocative tests on 24 matched pairs of eyes. Fifteen of the 24 dexamethasone treated eyes, 62.5%, showed a change in intraocular pressure greater than 5 mmHg, with mean delta P = 8.58 mmHg and range 0 to +20 mmHg. Only 2 of the 24 fluorometholone treated eyes, 8.3%, showed a change in pressure greater than 5 mmHg, with mean delta P = 2.96 mmHg and range -2 to +14 mmHg. There was a highly statistically significant difference between the intraocular pressure effects of topical dexamethasone and fluorometholone (correlated t test, p less than 0.001). Fluorometholone would appear to be the topical steroid of choice for patients with glaucoma and other known steroid responders when topical steroid treatment is indicated.     

Reducing angiographic cystoid macular edema and blood-aqueous barrier disruption after small-incision phacoemulsification and foldable intraocular lens implantation: multicenter prospective randomized comparison of topical diclofenac 0.1% and betamethasone 0.1%

PURPOSE: To compare the effectiveness of a topical nonsteroidal drug (diclofenac 0.1%) and a topical steroidal drug (betamethasone 0.1%) in preventing cystoid macular edema (CME) and blood-aqueous barrier (BAB) disruption after small-incision cataract surgery and foldable intraocular lens (IOL) implantation. SETTINGS: Shohzankai Medical Foundation Miyake Eye Hospital, Tokyo, Japan. METHODS: This multicenter interventional double-masked randomized study comprised 142 patients having phacoemulsification and foldable IOL implantation. Seventy-one patients were randomized to receive diclofenac eyedrops and 71, betamethasone eyedrops for 8 weeks postoperatively. The incidence and severity of CME were evaluated by fluorescein angiography. Blood-aqueous barrier disruption was determined by laser flare-cell photometry. RESULTS: Of the patients, 63 were men and 79 were women. Five weeks after surgery, the incidence of fluorescein angiographic CME was lower in the diclofenac group (18.8%) than in the betamethasone group (58.0%) (P<.001). At 1 and 2 weeks, the amount of anterior chamber flare was statistically significantly less in the diclofenac group than in the betamethasone group (P<.05). At 8 weeks, intraocular pressure was statistically significantly higher in the betamethasone group (P = .0003). CONCLUSIONS: Diclofenac was more effective than betamethasone in preventing angiographic CME and BAB disruption after small-incision cataract surgery. Thus, nonsteroidal antiinflammatory agents should be considered for routine treatment of eyes having cataract surgery.     

Effect of topical brinzolamide 1% and brimonidine 0.2% on intraocular pressure after phacoemulsification

PURPOSE: To compare the effectiveness of brinzolamide 1% (Azopt) and brimonidine 0.2% (Alphagan) with a placebo in preventing an early increase in intraocular pressure (IOP) after phacoemulsification. SETTING: Department of Ophthalmology, Baskent University, School of Medicine, Ankara, Turkey. METHODS: In this prospective double-masked study, 90 eyes of 90 patients having clear corneal phacoemulsification were randomly divided into 3 groups of 30 eyes each. One hour before surgery, 1 group received 1 drop of brinzolamide 1%, another received 1 drop of brimonidine 0.2%, and the third received 1 drop of a balanced saline solution (placebo). The IOP was measured preoperatively and 3 and 16 to 20 hours postoperatively. RESULTS: Three hours postoperatively, the mean IOP increased by 4.2 mm Hg +/- 7.0 (SD), 3.2 +/- 6.4 mm Hg, and 5.3 +/- 4.2 mm Hg in the brinzolamide, brimonidine, and placebo groups, respectively. The IOP increase from baseline was significant in all 3 groups (all P<.01), with no difference between the groups (P>.05). The change in IOP at 16 to 20 hours was 0.2 +/- 2.8 mm Hg, 0.2 +/- 2.4 mm Hg, and -0.8 +/- 2.4 mm Hg, respectively. The changes were not significant compared to baseline (all P>.05). Six eyes (20%) in the brinzolamide group, 5 eyes (16.7%) in the brimonidine group, and 7 eyes (23.3%) in the placebo group had an IOP higher than 25 mm Hg 3 hours postoperatively; the difference between groups was not significant (P =.8). CONCLUSION: Prophylactic use of 1 drop of brinzolamide or brimonidine was not more effective than a placebo in controlling early postoperative IOP elevations after clear corneal phacoemulsification.     

Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel

PURPOSE: The objective of this randomized, double-blind, controlled crossover trial was to compare 0.1% timolol hydrogel formulation eyedrops with 0.5% timolol aqueous solution in terms of systemic effects, hypotensive efficacy and pharmacodynamics. METHODS: Twenty-four healthy subjects underwent careful ocular, cardiovascular and pulmonary function evaluation before and after 2 weeks of topical treatment with 0.1% timolol hydrogel or 0.5% aqueous timolol maleate. Intraocular pressure (IOP), heart rate, blood pressure, forced expiratory volume and plasma levels of timolol were measured. RESULTS: There was a statistically significant difference in the systemic absorption of timolol between these two ophthalmic timolol solutions. The peak concentration and mean area under the plasma drug concentration-time curve (AUC) were about 10-fold higher after 0.5% timolol aqueous solution. The mean peak heart rate during exercise was reduced by 19 bpm (SD 6.4 bpm) after 0.5% timolol aqueous solution and by only 4.6 bpm (SD 3.8 bpm) after 0.1% timolol hydrogel (p < 0.0001). There was no difference between the two formulations in efficacy in reducing IOP. No differences between treatments were found in respect of pulmonary function. CONCLUSIONS: The lower timolol concentration in the hydrogel vehicle and its better bioavailability resulted in reduced systemic absorption and side-effects without loss of efficacy.     

Effects of topical mydriatics and vasoconstrictors on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits

We evaluated the effects of topical instillation of mydriatics and vasoconstrictors on prostaglandin E2 (PGE2) induced aqueous flare elevation in pigmented rabbits. Transcorneal diffusion of PGE2 (25 microg/ml) by means of a glass cylinder produced aqueous flare elevation. Mydriatics (atropine sulfate, tropicamide, tropicamide plus phenylephrine hydrochloride, phenylephrine hydrochloride, and cyclopentolate hydrochloride) or vasoconstrictors (naphazoline nitrate and tramazoline hydrochloride) were topically administered before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. One or two instillations of atropine sulfate 1.0%, tropicamide 0.4%, tropicamide 0.5% plus phenylephrine hydrochloride 0.5%, phenylephrine hydrochloride 5.0%, cyclopentrate hydrochloride 1.0%, and naphazoline nitrate 0.05% did not inhibit PGE2-induced aqueous flare elevation. Tramazoline hydrochloride 0.118% inhibited significantly (p < 0.05) PGE2-induced aqueous flare elevation. It is possible that vasoconstriction may be involved partly in inhibition of PGE2-induced aqueous flare elevation by some drugs in pigmented rabbits.     

Topical 0.1% indomethacin solution versus topical 0.1% dexamethasone solution in the prevention of inflammation after cataract surgery. The Study Group

PURPOSE: To compare the efficacy and safety of topical 0.1% indomethacin with 0.1% dexamethasone after cataract surgery. METHODS: 145 patients (indo = 71, dexa = 74) were enrolled in a randomised, double-masked study and received one drop 4 times a day of indomethacin or dexamethasone for 1 month. RESULTS: Proteinic flare and cellular Tyndall decreased with time in both groups, with a difference in favour of indomethacin for cellular Tyndall on day 30 (p = 0.046). Conjunctival hyperaemia was less pronounced in the dexamethasone group on day 30 (p = 0.03). Tolerance of both drugs was good. CONCLUSION: 0.1% Indomethacin solution appears to be as safe and efficient as 0.1% dexamethasone eyedrops in the management of post-operative inflammation and could be a good alternative to the use of steroids.     

Effect of topical 0.1% indomethacin solution versus 0.1% fluorometholon acetate on ocular surface and pain control following laser subepithelial keratomileusis (LASEK)

PURPOSE: To compare the effect of topical 0.1% indomethacin solution versus 0.1% fluorometholon acetate in the early postoperative period after LASEK treatment. METHODS: One hundred thirty-five patients undergoing LASEK, having been randomized in a double-masked manner into 2 groups (1 receiving indomethacin and 1 fluorometholon), were evaluated 2-4 days before and 4 days after treatment. We examined corneal fluorescein staining and corneal esthesiometry; the level of pain experienced was reported by the patient on a visual pain scale. In addition, haze was evaluated at 14 +/- 1 weeks after surgery. RESULTS: The pain level and corneal fluorescein staining were significantly less in the indomethacin group. Corneal esthesiometry was reduced to the same extent in the 2 groups. There were no statistically significant differences in haze presentation between the 2 groups. CONCLUSION: Our study highlights the efficacy of indomethacin solution compared with fluorometholon as a pain reducer after LASEK treatment and suggests that indomethacin is associated with a faster epithelial healing process.     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

Hintergrund: Viele der antiglaukomat?sen Medikamente beeinflussen den okul?ren Blutflu?. Die Blutflu?ver?nderungen in der vorderen Uvea sind in der Literatur beschrieben. über den Effekt von Antiglaukomatosa auf den Blutflu? des hinteren Augenpols wird in neuerer Zeit vermehrt berichtet. Wir pr?sentieren eine Placebo-kontrollierte Studie mit Blick auf den kurz- und mittelfristigen Einflu? von topisch appliziertem Dipivefrin 0,1 % auf den retinalen und papill?ren Blutflu?.     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

PURPOSE: Most of the antiglaucomatous drugs affect ocular blood flow. Blood flow of the anterior uvea under the effect of glaucoma medication has been described in the literature, but measurement of microcirculation at the posterior pole correlated to glaucoma medication is rarely found. We present a placebo-controlled study in which we focused on the short and long-term effects of topical dipivefrine 0.1% on the microcirculation of the retina and optic nerve head. PATIENTS AND METHODS: In a randomized, placebo-controlled double-masked study we examined 40 healthy persons (21 male and 19 female) with a mean age of 35 +/- 4.6 years. Two groups of volunteers (n = 20) were treated either with placebo or dipivefrine 0.1% for 5 days twice a day. Measurement of microcirculation was done at baseline, 30 min after the first application and on days 3 and 5. Microcirculation was evaluated by scanning-laser Doppler flowmetry (SLDF, Heidelberg Engineering; Heidelberg, Germany) [retinal and optic nerve head capillary blood flow (ONH)]. Systemic parameters were checked at all times of blood flow measurement (blood pressure, pulse); intraocular pressure (IOP) was also measured at baseline, 30 min after and on days 3 and 5. RESULTS: Systemic parameters: None of serum medications affected blood pressure or pulse. Dipivefrine 0.1% lowered the IOP significantly (P = 0.01). Microcirculation: dipivefrine 0.1% leads to a significant reduction of retinal capillary blood flow (P = 0.01). ONH blood flow was not significantly affected by dipivefrine 0.1%. CONCLUSION: Retinal capillary perfusion is affected by dipivefrine 0.1% medication. In neuroprotection, it is of interest that glaucoma medication did not alter the microcirculation in a way that leads to an increase of hypoxemia. Therefore, we consider dipivefrine 0.1% not to be useful for long-term glaucoma treatment.     

Effects of topical anaesthetics and repeated tonometry on intraocular pressure

Purpose: To investigate the effects of repeated measurements of intraocular pressure (IOP) using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) to identify mechanisms contributing to the expected IOP reduction. Methods: A prospective, single‐centre study with six healthy volunteers. Consecutive repeated series (six measurements/serie/method) were made alternately on both eyes for 1 hr with oxybuprocaine/fluorescein in the right eye and tetracaine in the left. The left eye was Pentacam^® photographed before and repeatedly for 20 min after the IOP measurements. On a separate occasion, the same volunteers received the same amount of anaesthetic drops for 1 hr but without repeated IOP measurements. Results: A significant IOP reduction occurred with both ART and GAT in the oxybuprocaine‐treated eye, ?4.4 mmHg and ?3.8 mmHg, respectively and with ART in the tetracaine eye, ?2.1 mmHg. There was a significant difference in IOP reduction between the oxybuprocaine and tetracaine eyes with ART. There was a significant drop in anterior chamber volume (ACV) immediately after the IOP measurements, ?12.6 μl that returned to pretrial level after 2 min. After 1 hr of receiving anaesthetic eye drops (without IOP measurements), the IOP decreased significantly in the oxybuprocaine eye for both ART and GAT, ?3.1 and ?1.7 mmHg, respectively, but not in the tetracaine eye (p = 0.72). Conclusion: The IOP reduction cannot be explained solely by aqueous humor being pressed out of the anterior chamber. While significant IOP reduction occurred with both tetracaine and oxybuprocaine after repeated mechanical applanation, the IOP reduction was significantly greater with oxybuprocaine.     

Analgesic effect of topical sodium diclofenac 0.1% drops during retinal laser photocoagulation

AIMS: To evaluate the analgesic effect of topical sodium diclofenac 0.1% during retinal laser photocoagulation. METHODS: 87 patients, 45 with proliferative diabetic retinopathy treated with two sessions of panretinal photocoagulation (group A), and 42 patients with non-proliferative diabetic retinopathy who underwent grid treatment of the posterior pole (19 bilaterally) (group B). Sodium diclofenac 0.1% or sodium chloride 0.9% drops were topically applied 30-135 minutes before laser treatment in a masked fashion. Patients who had two sessions were given the alternate drug in the second one. Pain level was evaluated immediately after laser treatment with the visual analogue scale (VAS). The results were statistically analysed. RESULTS: Patients in group A reported pain in 85/90 sessions (94%). The average pain level was 44.2% with sodium diclofenac 0.1% drops and 53.1% with sodium chloride 0.9% drops (p = 0.011 by paired t test). Patients in group B reported pain in only 16/60 sessions (26. 7%), and the pain level ranged from 10% to 60% regardless of the kind of drops used. There was no correlation in either group between level of pain and time interval from application of the drops to laser treatment (30-135 minutes) or average energy level used (100-500 mW). CONCLUSION: Sodium diclofenac 0.1% is useful for pain reduction and should be applied before panretinal photocoagulation.     

Comparison of topical 0.7% dexamethasone–cyclodextrin with 0.1% dexamethasone sodium phosphate for postcataract inflammation

Background To compare 0.7% dexamethasone–cyclodextrin aqueous eye drop solution applied once daily with 0.1% dexamethasone sodium phosphate eye drops applied three times a day for the control of postoperative inflammation after cataract surgery.Methods Twenty cataract patients who underwent phacoemulsification and intraocular lens implantation were randomly divided into two postoperative treatment groups. Postoperative medication in group I included 0.1% dexamethasone sodium phosphate eye drops three times daily and in group II 0.7% dexamethasone–cyclodextrin eye drop solution once daily. Testing of visual acuity, biomicroscopic examination, applanation tonometry and laser flare cell meter (LFCM) examination were carried out before operation and days 1, 3, 7 and 21 after surgery.Results Preoperative and postoperative visual acuity, aqueous flare and cells in biomicroscopic examination, and the mean intraocular pressure did not show any statistically significant differences between the treatment groups. LFCM examination showed that the mean postoperative photon count values (P=0.032) and the median cell count values on the 1st (P=0.014), 3rd (P=0.031), 7th (P=0.034), and 21st (P=0.0097) postoperative days in group I were more elevated than in group II.Conclusions 0.7% dexamethasone–cyclodextrin eye drops applied once daily is a more effective postoperative anti-inflammatory medication than 0.1% dexamethasone sodium phosphate applied three times a day. In both groups, 3 weeks after the operation the mean visual acuity was normal and intraocular pressure significantly lower than before operation. The use of 0.7% dexamethasone–cyclodextrin eye drops may be useful especially in elderly people who cannot apply themselves the eye drops onto the eye.     

Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome

AIM: To compare safety and efficacy of intravitreal dexamethasone (IVD) implant with topical nepafenac (TN) 0.1% in previously untreated Irvine-Gass syndrome (IGS) in clinical practice. METHODS: This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens (IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study chart (ETDRS), slit-lamp, intraocular pressure (IOP) measurement, fundus examination, spectral-domain optical coherence tomography (OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6mo. RESULTS: The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness (CRT) of IVD group was 266.6±53.5 µm and the mean CRT of TN group was 364.9±56.3 µm in post-treatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. CONCLUSION: IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.