Patent Application: US-47374003-A

Abstract:
after refractive surgery to reduce ametropy an average percentage of patients between 15 . 8 % after prk and 33 % after lasik shows a poor night sight due to the presence of halos , glare and coma . a comparable disorder is present in a percentage of patients that underwent lensectomy with intra ocular lens implant and iol implants in phakic patients to reduce ametropy . thanks to the effect on pupillary kinetics , diluted low concentrations of aceclidine were surprisingly found to effectively reduce and / or eliminate night sight problems for about 6 hours .

Description:
the following clinical trail has been performed in order to demonstrate the activity of aceclidine at different concentrations on patients who underwent refractive surgery . a double - masked randomized clinical trial with 14 patients ( 27 eyes ) has been organized by dividing the patients in three different groups : 8 patients were treated with placebo , 10 patients were treated with a first ophthalmic composition ( i dilution ), 9 patients were treated with a second ophthalmic composition ( ii dilution ). the patients belonging to this trial had to go through an ophthalmic examination : of the haze grading and of natural and corrected visual acuity , intra ocular pressure ( iop ), pupillometry in mesopic conditions with split lamp and examination of corneal maps . the anamnestic data about the surgical operation were collected : the refractive surgery technique employed ( prk / lasik ), the date of the surgical operation , data about the corrected optical zone and the ametropy kind . the night sight problems had to be stable for at least three months after the surgical operation for the patient to be included in the trial . in order to render the clinical trial as much as possible objective and reproducible , the values of halos and coma perceived by the patients were graduated using eight images got from the web site www . surgical . com and elaborated with the photoshop program ; a value of halos and coma ( on a scale from 1 to 4 ) was assigned to each image , as showed in fig1 and 2 . the patients had to identify the image they perceived before and during the pharmacological treatment , with follow - up examinations fixed every 15 - 30 days . at the end of the clinical trial the patients had to provide information about the efficacy and duration ( in terms of hours ) of the treatment , onset time of the effect , changes of the visual capabilities and side effects , if any . i dilution , 4 iu of aceclidine 2 % were diluted in 5 ml of hyaluronic acid ( 0 . 200 g / 100 ml ) ii dilution , 8 iu of aceclidine 2 % were diluted in 5 ml of hyaluronic acid ( 0 . 200 g / 100 ml ) placebo consisted in 5 ml of hyaluronic acid ( 0 . 200 g / 100 ml ). the two ophthalmic compositions , i and ii dilution , were administered firstly to a group of healthy people : one eye was treated with the i dilution composition ( 0 . 016 %), the second eye with the ii dilution composition ( 0 . 032 %), measuring the pupillary diameter in the same light conditions at 30 minutes , 1 - 2 - 3 - 4 - 5 - 6 hours after the first instillation . fig3 shows the behavior of the pupillary diameter . a mean reduction of the pupillary diameter of 2 . 5 mm is showed within the first 30 minutes following the instillation and with a trend to disappear after 5 - 6 hours . the three ophthalmic compositions ( i dilution , ii dilution and placebo ) were administered to the 14 patients belonging to the clinical trial in a blind way . the results showed that 18 out of 19 eyes treated with diluted aceclidine ophthalmic compositions ( i and ii dilution ) versus 2 out of 8 treated with placebo showed an improvement in night vision problems ( 95 % vs 25 %; p = 0 . 04 ). the efficacy in terms of hours has been reported to 6 hours with the onset after 15 - 20 minutes following the instillation . mean improvement was 1 . 4 (± 0 . 6 ) for coma and 1 . 14 (± 0 . 4 ) for halos ; 61 % of patients reported a night vision acuity improvement . the reported side effect is a modest and transient conjunctival hyperemia lasting for about 10 - 15 minutes . none reported headache , myopia enhancement or other alterations . moreover no differences have been reported on the iop or the pupillary kinetics during the follow - up examinations . 1 . paoletti r ., nicosia s ., clementi f ., fumagalli g ., in farmacologia oculare , a cura di : filippo drago e nicola orzatesi , ed . utet , 1998 . 2 . rossetti l ., randazzo a ., fogagnolo p ., orzalesi n ., comparison of prk vs lasik for correction of myopia . the results of meta - analysis of published literature , arvo 2001 . 3 . martin l . computerized method to measure glare and contrast sensitivity in cataract patients , j . cataract refract . surg . 1999 mar ; 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