Fluorometholone Research Articles

A Comparative Study of the Novel Ratio Difference Method versus Conventional Spectrophotometric Techniques for the Analysis of Binary Mixture with Overlapped Spectra

The smart novel ratio difference spectrophotometric method was developed and validated for the determination of a binary mixture of Sodium cromoglicate (SCG) and Fluorometholone (FLU) in presence of benzalkonium chloride without prior separation. The results were compared to that of the conventional methods (dual wavelength and first derivative of ratio spectra). The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of SCG and FLU in their laboratory prepared mixtures and commercial ophthalmic solution. The novel method showed significant advantages over the conventional methods regarding simplicity, minimal data manipulation and maximum reproducibility and robustness; which enabled the analysis of binary mixtures with overlapped spectra for routine quality control testing with quite satisfactory.

Effects of GM6001 on haze formation after excimer laser epithelial keratomileusis in rabbit

Background More and more attentions are paid to the effect of matrix metalloproteinases (MMPs) in the process of wound healing after excimer laser.Objective The present study was to investigate the effects of GM6001,a matrix metalloproteinases inhibitor,on haze formation after excimer laser epithelial keratomileusis (LASIK).Methods LASEK of -10.00 diopter was bilaterally performed on 27 New Zealand white rabbits and then divided randomly into the GM6001 group,Fluorometholone (FML) group and normal control group.Corneal haze was graded under dim light at 2 weeks,4 weeks and 8 weeks after operation,and the number of eyes in different grades of haze were compared among the three groups.Six corneal samples were harvested in each group for confocal microscope examination at 2,4,8 weeks.The corneal histopathological examination was carried out with the optical microscope,and the ultrastructure of the cornea was examined under the transmission electron microscope.Results The numbers of eyes of different corneal grades of haze at 2,4 or 8 weeks after surgery were significantly different among the three groups (P＜0.05).Compared with the normal control group,the corneal haze grades in the GM6001 group and FML group were apparently lower (P＜0.01),but there was no significant difference in the numbers of eyes of different corneal grades of haze between the GM6001 group and FML group (P＞0.01).The numbers of keratocytes in the GM6001 group were apparently lower than those in the normal control group and FML group in 2,4 or 8 weeks after operation (P＜0.05).No significant difference in the keratocytes was seen between the normal control group and FML group at various time points (P＞0.05).Corneal epithelial cell morphology,disordered arrangement of collagen fibers in GM6001 group and in FML group were less pronounced than in the negative control group.Conclusion GM6001 has an inhibitory effect on the formation of corneal haze after LASEK which suppresses proliferation and production of keratocytye with the similar efficacy as FML. Key words: Cornea; Matrix metalloproteinases; Matrix metalloproteinases inhibitor; Excimer laser in situ keratomilusis; Haze

Inhibition Effect of Tetrandrine on Haze Formation after Epi-LASIK Surgery in Rabbits

Purpose: To observe the inhibitory effect of tetrandrine on haze formation after Epi-LASIK surgery in rabbits.Materials and Methods: Twenty-seven healthy New Zealand rabbits were selected and underwent Epi-LASIK surgery. According to a self comparison principle, these rabbits were randomly divided into three groups. The first group was treated with tetrandrine eye drops (Tet), the second (negative control, NC) group was treated with pure solvent, and the third group was treated with fluorometholone (FML) solvent. Haze grades of each group were respectively observed by slit lamp exam at half-month, one month, and two months after surgery. After corneal tissues were extracted, optical microscopy, Sirius Red staining, immunohistochemistry, and semi-quantitative RT-PCR tests were conducted, in order to test collagen formation of operated eyes after surgery and expression of transformation growth factor beta 2 (TGF-β2) in corneal stroma.Results: At a half month and one month after surgery, haze grades and type III collagen expression in Tet and FML groups were significantly lower than that in NC groups (P < 0.01). No statistical difference was observed between Tet and FML groups. Immunohistochemistry showed that, at each time point after surgery, expressions of TGF-β2 protein in Tet and FML groups were significantly lower than that in the NC group (P < 0.01), whereas there was no statistical difference between Tet and FML groups. The expression level of TGF-β2 protein increased, reaching its peak one month after surgery. RT-PCR also showed that, at each point after surgery, the TGF-β2 mRNA expression in Tet and FML groups was lower than that in the NC group (P < 0.01), nevertheless no statistical difference was observed between Tet and FML groups.Conclusions: Like FML, Tet could inhibit haze formation in rabbits after Epi-LASIK surgery, possible through TGF-β2-collagen-III pathway.

Do reducing regimens of fluorometholone for paediatric ocular surface disease cause glaucoma?

Background/aimsAlthough fluorometholone (FML) is considered a steroid of minimal ocular penetration, reports in children have shown dose-dependent intraocular pressure (IOP) rise. The authors aimed to assess whether reducing regimens of...

A rabbit model of age‐dependant ocular hypertensive response to topical corticosteroids

To investigate the ocular hypertensive response to topical dexamethasone (DEX), rimexolone (RIM), loteprednol etabonate (LOT) and fluorometholone (FML) in rabbits of different ages. Seventy-five rabbits of three age groups (7 weeks, 6 months and 1-year old) received topical administration of 0.1% DEX, 1% RIM, 0.5% LOT, 0.1% FML or balanced salt solution four times daily for 1 month. Intraocular pressure (IOP) was monitored at regular time intervals. After a month, eyes were harvested for histological study with haematoxylin and eosin (H&E), periodic acid Schiff and Masson trichrome staining. Trabecular meshwork changes were graded by masked ocular pathologists. Topical DEX caused the greatest increase in IOP, followed by RIM and FML. LOT caused the least IOP increase. Similar pattern of IOP response to the four corticosteroids was observed in the three studied age groups. Young rabbits (7 week) were the most responsive to corticosteroids among the age groups. Extracellular matrix thickening in the trabecular meshwork region and loss of trabecular meshwork cells were observed after DEX, FML or RIM treatments. Young rabbits are more susceptible to steroid induced increase in IOP, even for milder steroids such as fluorometholone and rimexolone.

Comparison of Efficacy of Bromfenac Sodium 0.1% Ophthalmic Solution and Fluorometholone 0.02% Ophthalmic Suspension for the Treatment of Allergic Conjunctivitis

Bromfenac sodium (BF) 0.1% was compared with fluorometholone (FML) 0.02% for the treatment of seasonal allergic conjunctivitis when concomitantly used with disodium cromoglycate (DSCG) 2.0%. Eighty-six patients with seasonal allergic conjunctivitis were treated with DSCG four times a day, and BF was concomitantly administered twice a day in one eye and FML was administered four times a day in the contralateral eye for 1 week. Ocular signs were scored on a four-graded severity. Patients recorded symptoms using visual analog scale. Patients were asked which concomitant treatment was more suitable for them and scored global evaluation. All subjective symptom scores were decreased in both concomitant treatment groups compared with baseline (P < 0.05). Objective signs were significantly improved with the concomitant use of BF or FML with DSCG (P < 0.05). Neither symptoms nor signs differed significantly between the concomitant use of BF and FML. Fifteen patients selected BF and 29 patients selected FML as the more preferred concomitant eye drops, 42 patients judged no difference in efficacy between the groups. No significant difference was observed in patient's global evaluation between the groups. Bromfenac sodium for allergic conjunctivitis was effective, with efficacy equivalent to that of FML when used with DSCG.

Comparison of Topical Dry Eye Medications for the Treatment of Keratoconjunctivitis Sicca in a Botulinum Toxin B-Induced Mouse Model

To compare the effects of topical dry eye medications including anti-inflammatory agents and lubricant eyedrops for the treatment of keratoconjunctivitis sicca (KCS) in a botulinum toxin B (BTX-B)-induced mouse model. CBA mice were randomized into 10 groups. The first 5 groups received a transconjunctival injection of saline into the lacrimal gland, and the remaining groups were injected with 0.05 mL of 20 mU BTX-B. Each group received treatment with 0.1% fluorometholone (FML), 0.05% cyclosporine A (CsA), a 50:50 combination of FML and CsA, artificial tears, or saline 3 days after injections. Tear production, corneal staining, and blink rate were compared in each of the 10 groups. Tear production in BTX-B-injected CsA-treated, FML-treated, and combined-treated groups started to return to baseline level within 2 weeks of treatment, whereas those treated with saline or artificial tears still exhibited reduction of lacrimation up to 4 weeks after injection. Topical FML significantly reversed the staining score within 1 week of treatment. The improvement of corneal staining in BTX-B-challenged combined-treated and CsA-treated groups occurred later within 2 weeks after treatment. No significant improvement in corneal staining was observed for the BTX-B-injected mice treated with artificial tears or saline. No significant changes were noted in blink frequency between the control and study groups undergoing the various dry eye therapies. The therapeutic effects of dry eye medications in a BTX-B-induced mouse model of KCS are similar to the human response.

A prospective study on ocular hypertensive and antiinflammatory response to different dosages of fluorometholone in children

Objective To investigate the ocular hypertensive and antiinflammatory response to different dosages of fluorometholone (FML). Design Prospective clinical trial with randomization of fellow eyes to different postoperative treatment. Participants Thirty-one consecutive children undergoing bilateral symmetrical strabismus operation. Intervention Among 31 children who received bilateral squint operations, one eye was randomized to receive topical FML six times daily (group 1), whereas the other eye received topical FML three times daily (group 2), both for 4 weeks. Intraocular pressure (IOP) and antiinflammatory response were measured serially in the postoperative period for 8 weeks. Main outcome measures Intraocular pressure was measured on the day before surgery and on postoperative days 1, 3, 6, 13, 20, 27, 41, and 55. The antiinflammatory response was also assessed subjectively and objectively at days 6, 13, 20, and 27 after the operations. Peak IOP, net increase in IOP, and antiinflammatory responses in the two study groups were analyzed. Results Thirty-one children, age 3 to 9 years, (mean ± standard deviation [SD], 5.52 ± 1.81) participated in the study. Intraocular pressure increased significantly in both groups compared with the preoperative values ( P < 0.001). The peak IOP ranged from 12.00 to 31.00 mmHg and 12.30 to 25.00 mmHg in groups 1 and 2, respectively. The mean peak IOP (19.00 ± 5.06 mmHg vs. 17.13 ± 3.32 mmHg) was significantly higher in group 1 ( P < 0.001). The net increase in IOP was similar (mean ± SD, 4.37 ± 4.79 vs. 2.57 ± 3.32 mmHg; P = 0.005). Ranges of the net IOP increase were −1.00 to 16.00 mmHg and −2.50 to 10.30 mmHg in groups 1 and 2, respectively. Children in group 1 reached the peak IOP earlier than those in group 2 (median, 6 vs. 13 days; P = 0.033). However, there was no significant difference in antiinflammatory response between the two groups. Conclusions Ocular hypertension occurs in a dose-dependent manner in children treated with FML. Children in group 1 had a quicker onset and more severe ocular hypertensive response than those in group 2. It would be desirable to monitor the IOP regularly when FML is used with a high frequency and for a long duration in children.

Polymer blend implant for ocular delivery of fluorometholone.

Ocular implants containing fluorometholone (FLM) were prepared using blends of poly (DL-lactic acid) (PLA) and polyvinyl pyrrolidone (PVP). The effect of the fraction of PVP content on the release of FLM from the implant was investigated in vitro. The drug was released from the device by approximately following first order kinetics within the period of 40 d. The release rate gradually increased with an increase in the PVP content. The in vivo study after implantation in the anterior chamber of rabbit eyes indicated that the PLA-PVP implant showed a good correlation between the in vitro and in vivo release of FLM. The present polymer blend implant demonstrated a constant level of FLM in the aqueous humor for one month.

Ocular-hypertensive Response to Topical Steroids in Children

The purpose of the study is to investigate the rate and degree of ocular-hypertensive response to topical steroids in Chinese children. The study design was an institutional, randomized, clinical trial. A total of 19 consecutive patients were studied. Topical steroids were administered to Chinese children younger than 10 years of age who underwent bilateral strabismus surgery. One eye was randomized to receive topical 0.1% dexamethasone (DMS), whereas the fellow eye received 0.1% fluorometholone (FML) six times per day for up to 4 weeks. Intraocular pressure (IOP) was measured on the day before operation and at postoperative days 1, 3, 6, 10, 13, and 27, then every 2 weeks thereafter until the IOP fell to preoperative levels. Topical steroids would be stopped if IOP was 30.00 mmHg or greater. Peak IOP and maximal change of IOP from baseline were measured and categorized into low, intermediate, and high levels. Time to peak IOP also was studied. A total of 16 patients were included. The peak IOP for DMS-treated eyes was 30.66 +/- 8.35 mmHg (range, 13.00-48.00 mmHg), whereas that in FML-treated eyes was significantly lower at 20.66 +/- 6.03 mmHg (range, 11.30-36.30 mmHg) (P = 0.001). The maximal change in IOP ranged from -2.60 to +31.00 mmHg in DMS-treated eyes (mean, 15.48 +/- 8.71 mmHg), almost double that of FML-treated eyes (range, +1.00 to +17.00 mmHg; mean, 5.83 +/- 4.96 mmHg) (P = 0.001). When the ocular-hypertensive responses of both DMS and FML groups were categorized into three levels of severity, significant differences were found between the two treatment groups (P = 0.001). In the DMS group, nine patients (56.25%) were high responders and six patients (37.5%) were intermediate responders. In the FML group, only one patient (6.25%) was a high responder. The ocular-hypertensive response to topical DMS in children occurs more frequently, more severely, and more rapidly than that reported in adults. A total of 56% of the studied children, all younger than 10 years of age, were high responders to topical DMS. Of these, 89% attained their peak IOP within 8 days. Its use in children should best be avoided if possible. It would be desirable to monitor the IOP when it is being used. Conversely, FML produced a much less ocular-hypertensive effect and therefore poses an acceptable risk of clinically significant pressure elevation.

Effects of antiglaucoma drugs and corticosteroids on the cellular glucose uptake in cultured porcine corneal endothelial cells.

In this study, various commercially used antiglaucoma drugs and corticosteroids were investigated in their effects on porcine corneal endothelial cells especially in cellular glucose uptake. Cellular glucose uptake directly affects the pumping efficiency in corneal endothelial cells. Following the cells' treatment with various antiglaucoma eyedrops for 100 min, the 3H-2-deoxyglucose uptake in cultured porcine corneal endothelial cells was affected by betaxolol from 3.1% (1.6 mM), 181% (0.16 mM) to 158% (0.016 mM), by timolol from 93% (0.79 mM), 227% (0.079 mM) to 151% (0.0079 mM), by carteolol from 141% (3.4 mM), 180% (0.34 mM) to 97% (0.034 mM), by levobunolol from 80% (1.5 mM), 98% (0.15 mM) to 90% (0.015 mM), by dipivefrin from 116% (0.2 mM), 176% (0.02 mM) to 108% (0.002 mM) and by pilocarpine from 115% (9.6 mM), 210% (0.96 mM) to 210% (0.096 mM) when the cells were compared with a control medium. In the presence of various corticosteroids, the glucose uptake in corneal endothelial cells was affected by fluorometholone from 160% (0.26 mM), 139% (0.026 mM) to 107% (0.0026 mM), by dexamethasone from 85% (0.25 mM), 117% (0.025 mM) to 109% (0.0025 mM) and by betamethasone from 95% (0.25 mM), 96% (0.025 mM) to 99% (0.0025 mM). These results show that the commercial eyedrops of antiglaucoma drugs and corticosteroids will not decrease the cellular glucose uptake in cultured porcine corneal endothelial cells except when incubated with high concentrations of betaxolol, levobunolol and dexamethasone.

Loteprednol Etabonate: Comparison with Other Steroids in Two Models of Intraocular Inflammation

Loteprednol etabonate (LE) is a novel steroid with a low tendency to raise IOP. It is metabolized in the eye to an inactive metabolite. The current study was undertaken to assess the intra-ocular anti-inflammatory activity of LE in two models of experimental uveitis in rabbits. In the endotoxin induced rabbit model, LE was effective at reducing measures of inflammation, but less so that either fluorometholone (FML) or dexamethasone. In the Freunds adjuvant chronic uveitis model, FML was also very effective with LE and dexamethasone showing similar activity. The data demonstrate that LE is effective at reducing intra-ocular inflammation.

The metabolism of fluorometholone by bovine cornea

Isolated bovine cornea was found to reduce the 20 ketone group in fluorometholone (FML) to produce a mixture of 20α- and 20β-dihydrofluorometholone (DHFML). Incubation of FML with bovine cornea at pH 7.4 in phosphate buffer produced an increase in the amount of reduction products up to 8 h; after this time the rate of reduction decreased. The reduced products were quantified by GC—MS against [ 2H 3] 20α-DHFML. Variable amounts of 20β-DHFML were detected in six samples of human aqueous humour following topical application of 50 μg of FML to the eye. The rapid metabolism of the side chain of FML may account for the unexpected low concentrations of FML which are found in human aqueous humour following its application to the surface of the eye.

Effect of fluorometholone (FML) on the intraocular pressure of corticosteroid responders.

Steroid responsiveness to dexamethasone was determined in a large family with an established dominant form of chronic simple glaucoma. The high and intermediate steroid responders were then tested with fluorometholone--a steroid which is claimed to have a reduced risk of increasing intraocular pressure. It was found that fluorometholone had a much less pronounced ocular hypertensive effect than dexamethasone. However, one patient showed a comparable response on both drugs, and this suggests that some caution must still be exercised when using the drug on susceptible individuals. Fluorometholone was also found to be more irritable to the eye than dexamethasone.