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Eye exposure to organophosphate (OP) chemical warfare irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. In contrast to the well-documented miotic and ciliary muscle spasm observed following chemical warfare, OP ocular exposure, little is known regarding the ocular surface histopathological insult. The aim of the present study was to determine the degree of the ocular surface insult following sarin or VX ocular exposure and to evaluate potential anti-cholinergic treatments in counteracting this insult. Rats that were whole body exposed to various sarin concentrations (0.049-43 μg/L; 5 min exposure), showed a dose-dependent miotic response and light reflex impairment. Following whole body sarin exposure, a dose dependent ocular surface histopathological insult was developed. A week following exposure to a low concentration of 0.05 μg/L, conjunctival pathology was observed, while corneal insult was noticed only following exposure to a concentration of 0.5 μg/L and above. Both tissues presented poorer outcomes when exposed to higher sarin concentrations. In contrast, eyes topically exposed to 1 μg sarin demonstrated no ocular insult a week following exposure. On the contrary, topical exposure to 1 μg VX resulted in a significant corneal insult. Anticholinergic treatments such as 0.1% atropine or 2% homatropine, given shortly following VX exposure, counteracted this insult. The results of this study show that not only do anti-cholinergic treatments counteract the miotic response, but also prevent the histopathological insult observed when given shortly following OP exposure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To determine whether the addition of phenylephrine 1.0%-ketorolac 0.3% (Omidria) to the irrigation solution during femtosecond laser-assisted cataract surgery (FLACS) reduces surgical time and the need for pupil expansion devices compared with the irrigation solution containing epinephrine., Setting: Wake Forest Baptist Eye Center, Winston-Salem, North Carolina, USA., Design: Retrospective case series., Methods: Data were collected from consecutive patients. One group had epinephrine 1 μg/mL in the irrigating solution and the other group, had phenylephrine and ketorolac 4 mL added to 500 mL irrigation solution instead of epinephrine. All patients received preoperative topical bromfenac 2 days before surgery. The same surgeon performed all procedures using the same laser (Catalys) and operative conditions. Endpoints were surgical time and the use of pupil expansion devices., Results: Data were collected from 200 consecutive patients, 100 in each group. Patient demographics, including a mean baseline pupil size of 7.1 mm, were similar between the groups. Mean surgical times were significantly reduced in the phenylephrine-ketorolac group versus the epinephrine group (8.1 minutes versus 9.4 minutes) (P = .007). When eyes requiring a pupil expansion device were eliminated, there was still a significant reduction in surgical time for phenylephrine-ketorolac versus epinephrine (8.1 minutes versus 9.0 minutes) (P = .018). Two eyes (2%) in the phenylephrine-ketorolac group and 12 eyes (12%) in the epinephrine group required a pupil expansion device (P = .009)., Conclusion: These data support the hypotheses that using phenylephrine and ketorolac reduces FLACS time and the need for pupil expansion devices., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the efficacy of using a nonste-roidal anti-inflammatory drug preoperatively and of applying the re-dilation technique when necessary to minimize pupil size variation when comparing the degree of mydriasis before femtosecond laser pretreatment with that at the beginning of phacoemulsification., Methods: This retrospective study included patients who underwent cataract surgery using the LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Our routine dilating regimen with flurbiprofen, tropicamide, and phenylephrine was used. The re-dilation technique was applied on eyes that manifested with a pupillary diameter that was smaller than the programmed capsulotomy diameter after laser pretreatment. The technique consists of overcoming pupillary contraction by instilling tropicamide and phenylephrine before phacoemulsification. Pupil size was assessed before femtosecond laser application and at the beginning of phacoemulsification., Results: Seventy-five eyes (70 patients) were included. Nine (12%) eyes underwent the re-dilation technique. There was no significant difference in mean pupillary diameter and mean pupillary area between the two studied surgical time points (p=0.412 and 0.437, respectively). The overall pupillary area constriction was 2.4 mm2. Immediately before opening the wounds for phacoemulsification, none of the eyes presented with a pupillary diameter <5 mm, and 61 (85.3%) eyes had a pupillary diameter >6 mm., Conclusion: Preoperative administration of nonsteroidal anti-inflammatory drug and the re-dilation technique resulted in no significant pupil size variation in eyes that were pretreated with the femtosecond laser, when comparing the measurements made before the laser application and at the beginning of phacoemulsification. This approach can avoid the need to proceed with cataract extraction with a constricted pupil.

Introduction: Prevention of intraoperative miosis in hybrid (femtosecond laser-assisted) phacoemulsification is a relevant problem of cataract surgery., Purpose: Development and clinical study of an effective method for preventing intraoperative miosis in hybrid (femtosecond laser-assisted) phacoemulsification., Material and Methods: Hybrid phacoemulsification was performed in 300 patients (300 eyes). The first group (100 eyes) 3 days prior to the surgery was prescribed instillations of 0.1% indomethacin 3 times a day and 3 times in 2 hours before surgery at 30 minute intervals. The second group (100 eyes) 3 days prior to the surgery was prescribed instillations of 0.1% indomethacin 3 times a day, 3 times in 2 hours before the surgery at 30 minute intervals, and 1 hour before the surgery an additional intramuscular injection of diclofenac. The third group (control, 100 eyes) 2 hours before the operation was prescribed instillations of 0.1% indomethacin, 3 times at 30 minute intervals. The diameter of the pupil was evaluated before the beginning of femtosecond laser stage and before the opening of anterior chamber during the second stage of the operation., Results: When the interval between the femtosecond laser stage and emulsification of the nucleus fragments was maintained at less than 15 minutes, pronounced decrease of the pupil (more than 2 mm) was noted in 8.2% of cases in the first group, 6.7% in the second group and 14.1% in third (control) group; mean values of pupil narrowing were 0.68±0.27 mm in the 1st group, 0.63±0.25 mm in the 2nd group, and 0.93±0.39 mm (p<0.05) in the third group., Conclusion: The clinical study showed high efficiency of the proposed methods for prevention of intraoperative miosis in hybrid (femtosecond laser-assisted) phaco surgery. An important factor affecting intraoperative narrowing of the pupil is the time interval between the femtolaser stage of the operation and emulsification of the nucleus fragments, which should not exceed 15 minutes.

Purpose: To determine the effect of phenylephrine 1.0%-ketorolac 0.3% injection (Omidria) on different components of intraoperative floppy-iris syndrome (IFIS)., Setting: Silverstein Eye Centers, Kansas City, Missouri, USA., Design: Prospective case series., Methods: Men treated with tamsulosin having standard cataract extraction surgery were placed in a treatment group that received phenylephrine 1.0%-ketorolac 0.3% injection in the irrigation solution and a control group) that received basic saline solution. Every procedure was video recorded using an endocyclophotocoagulation (ECP) probe and microscopic view. Pupil dilation, iris billowing, and iris prolapse were measured using a micrometer, ECP recording grading scale, and microscopic recordings, respectively., Results: Each group (treatment and control) comprised 25 eyes of 25 patients. Although both groups had a decrease in pupil diameter before and after cataract extraction and before cataract extraction and after intraocular lens implantation, the changes were statistically significantly greater in the treatment group. Iris prolapse occurred in 3 patients (12.0%) in the treatment group and 14 patients (56.0%) in the control group (P < .001). Stage 3 (severe) pupil billowing occurred in 1 eye (4.0%) in the treatment group and 10 eyes (40.0%) in the control group (P < .001)., Conclusions: The use of the phenylephrine 1.0%-ketorolac 0.3% injection combination added to the irrigating solution during cataract surgery in patients at risk for IFIS led to significantly better prevention of miosis, less pupil billowing, and a reduced incidence of iris prolapse. A new grading scale for intraoperative iris abnormalities might be used for future evaluation., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the effect of topical 0.1% bromfenac sodium, a nonsteroidal anti-inflammatory drug (NSAID), on intraoperative pupil dilation maintenance and prostaglandin E 2 (PGE 2 ) inhibition during femtosecond laser-assisted cataract surgery., Methods: Sixty patients (30 each in study and control groups) were included in this study. The patients received 0.1% bromfenac ophthalmic solution or control placebo twice a day for 3 days before surgery. Pupil size was measured at the initiation of femtosecond laser pretreatment and phacoemulsification. Aqueous humor was collected at the beginning of routine cataract surgery. PGE 2 levels were measured with an enzyme-linked immunoassay. Laser flare photometry was measured preoperatively and at 1 day postoperatively., Results: Compared with untreated patients, the change in pupil size and postoperative day 1 aqueous flare were significantly reduced throughout the operation in the patients treated with 0.1% bromfenac (P < 0.001). Mean PGE 2 concentrations were also significantly decreased by treatment with 0.1% bromfenac (P < 0.001). The reduction of the pupil area and postoperative day 1 aqueous flare were significantly correlated with PGE 2 levels (P < 0.001)., Conclusion: NSAID treatment, when administered before femtosecond laser-assisted cataract surgery, was effective in maintaining intraoperative pupil dilation, preventing miosis, and reducing PGE 2 levels.

Purpose: To investigate whether short-term nonsteroidal anti-inflammatory drug (NSAID) pretreatment on the day of surgery inhibits prostaglandin release. Previous studies detected elevated prostaglandin levels after femtosecond laser treatment and identified them as a potential mediator for laser-induced miosis., Methods: Patients underwent either image-guided femtosecond laser cataract surgery or conventional cataract surgery (n = 75). Half of the eyes per group received topical NSAID treatment on the day of surgery. Aqueous humor was collected from all patients. ELISA measurements were performed to detect aqueous humor prostaglandin levels., Results: Femtosecond laser cataract surgery led to higher prostaglandin levels than conventional cataract surgery (P = .007). In both groups, NSAID pretreatment led to reduced prostaglandin release. In the femtosecond laser group, patients pretreated with NSAIDs had significantly lower prostaglandin values (65.3 ± 13.2 pg/mL) than patients not pretreated with NSAIDs (294.4 ± 66.5 pg/mL) (P = .0009)., Conclusions: The short-term NSAID treatment prevented prostaglandin release in patients treated with image-guided femtosecond laser. Therefore, it has potential to limit intraoperative laser-induced miosis., (Copyright 2015, SLACK Incorporated.)

Purpose: To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery., Materials and Methods: A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation., Results: Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30±4.25, 4.87±6.03, and 12.47±12.24 μm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant., Conclusion: Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone.

Objective: To evaluate the usefulness of the Malyugin ring in poor pupil dilation during phacoemulsification assisted with femtosecond laser with 23 gauge pars plana vitrectomy., Method: A 57-year-old female with cataract and vitreous hemorrhage, and poor pupil dilation (5.5mm). The phacoemulsification assisted with femtosecond laser, using Malyugin ring after capsulorrhexis, followed by pars plana vitrectomy, and removing at the end without complications., Results: A successfull intraoperative pupil dilation was achieved without complications, with a final BCVA of 20/40., Conclusions: The Malyugin ring is an effective alternative in cases with poor pupil dilation in femtophacovitrectomy, preserving the anatomical and functional integrity., (Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To compare the effects of topical nonsteroidal anti-inflammatory drugs on pupil dilation maintenance during phacoemulsification cataract surgery and quantify the relationships between pupil size change and nuclear hardness., Methods: This prospective randomized clinical observation study was single centered and double-masked. We studied 239 cases undergoing uneventful phacoemulsification cataract surgery in the absence of significant ocular comorbidity. Cases were randomly assigned to 1 of 6 groups receiving the following treatments: (1) diclofenac (0.1%); (2) pranoprofen (0.1%); (3) control, physiological normal saline solution; (4) diclofenac (0.1%) and epinephrine; (5) pranoprofen (0.1%) and epinephrine; (6) control, physiological normal saline and epinephrine solutions. Pupil diameter was measured at 3 intervals of cataract surgery: before the first incision, at the end of nucleus fragmentation, and at the end of cortex irrigation/aspiration., Results: Compared with patients who were not treated, there was a significant difference in maintaining pupil dilation throughout the operation when the patients were treated with either diclofenac or pranoprofen, P<0.001 and P<0.03, respectively. From the first incision to postnucleus fragmentation, the change in pupil size in both diclofenac and control groups was significantly associated with the hardness of the crystalline lens, P=0.001 and P=0.012, respectively. At the end of irrigation/aspiration, the change in pupil size in only the control groups was significantly associated with the hardness of the crystalline lens, P=0.022. Diclofenac treatment was most effective at inhibiting pupil miosis when the hardness of the nucleus was grade 3, P=0.009. Pupil miosis was not related to the hardness of the nucleus when the patients were treated with epinephrine., Conclusions: Both diclofenac and pranoprofen treatment inhibit surgical-induced miosis. There is a negative correlation between the hardness of the crystalline lens and pupil diameter maintenance at the early stage of phacoemulsification.

Background: A strong association exists between the use of tamsulosin and the occurance of intraoperative floppy iris syndrome. Several methods were advocated to overcome the progressive intraopertive miosis.Our purpose was to investigate the effect of a mydriatic-cocktail soaked cellulose sponge on perioperative pupil diameter in tamsulosin-treated patients undergoing elective cataract surgery., Methods: Patients using tamsulosin were dilated either with mydriatic-cocktail soaked sponge (group 1) or with conventional eyedrop regimen (group 2). Control patients not taking any α1 adrenergic receptor inhibtors were also dilated with mydriatic sponge (group 3).In all groups oxybuprocain 0.4%, cocain 4%, tropicamide 1%, phenylephrine 10%, diclophenac 0.1% along with chloramphenicol 0.5% were used preoperatively.Pupil diameter (mm) was measured preoperatively, after nucleus delivery, and before IOL implantation. Adverse effects associated with the use of sponge, minor and major intraoperative complications, the use of iris retractors and operation time were recorded.Differences in general between groups were analyzed with a one way analysis of variance (ANOVA); differences between groups in proportions were assessed by Fisher's exact test., Results: Mean pupil diameter (mm) was preopertively: 7.52 ± 1.21, 7.30 ± 1.55 and 7.99 ± 0.96 (ANOVA: p = 0.079); after nucleus delivery: 6 ± 1.20, 6.29 ± 1.12 and 6.52 ± 0.81 (ANOVA: p = 0.123); before IOL implantation: 5.46 ± 1.06, 5.83 ± 1.09 and 6.17 ± 0.89 (ANOVA: p = 0.0291).No adverse effect related to sponge use was detected. Frequency of minor complications, and iris hook use was similar in the two tamsulosin treated group. Operation time did not differ significantly in the three groups., Conclusion: We have found that using a mydriatic cocktail-soaked wick - an alternative way to achieve intraoperative mydriasis for cataract surgery - was as effective and safe as the conventional repeated eyedrops regiment for tamsulosin treated patients., Trial Registration: Current Controlled Trials ISRCTN37834752.

Rationale: Pupillometry can be used to characterize autonomic drug effects., Objective: This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function., Methods: Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design., Results: MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function., Conclusions: The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.

Purpose: A prospective, randomized clinical trial was conducted to assess the usefulness of preoperative diclofenac eye drops in maintaining mydriasis during vitrectomy and in reducing postoperative inflammation., Methods: Fifty consecutive patients undergoing vitrectomy were randomly assigned to diclofenac (n = 24) or control (n = 26) groups. All patients received a standard preoperative regimen of cyclopentolate (2%) and phenylephrine hydrochloride (2.5%). The diclofenac group also received diclofenac (1%) preoperatively. Pupillary diameter was recorded at four time points during surgery. Inflammatory indices were measured postoperatively using slit-lamp examination., Results: After induction of anesthesia, the decrease in pupil size was not significantly different between the two groups (P = 0.112), but for the next two stages, it was significantly less in the diclofenac group (P = 0.012 and P = 0.003, respectively). No significant differences were found between the two groups for anterior chamber cells and redness in the eye postoperatively (P = 0.609 and P = 0.123, respectively). However, anterior chamber flare was significantly greater in the control group (P = 0.035), and patients felt significantly more pain in this group (P = 0.001)., Conclusions: Topical administration of diclofenac was effective in maintaining mydriasis during vitrectomy and in reducing postoperative pain and anterior chamber flare as determined by slit-lamp evaluations.

Purpose: To evaluate whether adding perioperative topical ketorolac tromethamine 0.4% improves cataract surgery outcomes relative to topical steroids alone in patients without known risk factors for cystoid macular edema (CME)., Design: Prospective, randomized, investigator-masked, multicenter clinical trial., Methods: Patients scheduled to undergo phacoemulsification and with no recognized CME risks (diabetic retinopathy, retinal vascular disease, or macular abnormality) were randomized to receive either prednisolone acetate 1% 4 times daily (QID) alone (steroid group; n = 278) or prednisolone 1% QID plus ketorolac 0.4% QID (ketorolac/steroid group; n = 268) for approximately four weeks postoperatively. In the ketorolac/steroid group, patients also received topical ketorolac 0.4% QID for three days preoperatively. In both groups, patients received four doses of ketorolac 0.4% one hour before surgery. Patients with capsular disruption or vitreous loss intraoperatively were exited from the study. Outcome measures included CME incidence, retinal thickness as measured by optical coherence tomography (OCT), best-corrected visual acuity, and contrast sensitivity., Results: No patients in the ketorolac/steroid group and five patients in the steroid group had clinically apparent CME (P = .032). Based on OCT, no ketorolac/steroid patient had definite or probable CME, compared with six steroid patients (2.4%; P = .018). In the ketorolac/steroid group, mean retinal thickening was less (3.9 microm vs 9.6 microm; P = .003), and fewer patients had retinal thickening of more than 10 microm as compared with the steroid group (26% vs 51%; P < .001)., Conclusions: This study suggests that adding perioperative ketorolac to postoperative prednisolone significantly reduces the incidences of CME and macular thickening in cataract surgery patients already at low risk for this condition.

Rationale: There is a close relationship between arousal and pupil diameter, decrease in the level of arousal being accompanied by constriction of the pupil (miosis), probably reflecting the attenuation of sympathetic outflow as sedation sets in. Paradoxically, sedation induced by benzodiazepines is not accompanied by miosis., Objective: The objective of this study was to examine the hypothesis that diazepam may attenuate both the sympathetic and the opposing parasympathetic outflow to the iris, which may mask the miosis. Dapiprazole (sympatholytic) and tropicamide (parasympatholytic) were applied topically, together with the cold pressor test (CPT), to manipulate the sympathetic/parasympathetic balance., Materials and Methods: Sixteen healthy male volunteers participated in four weekly sessions according to a balanced double-blind protocol. Diazepam 10 mg (two sessions) and placebo (two sessions), associated with either 0.01% tropicamide or 0.5% dapiprazole eyedrops, were administered orally. Pupil diameter, light and darkness reflexes and pupillary sleepiness waves were recorded with infrared video pupillometry, alertness was measured by critical flicker fusion frequency (CFFF) and visual analogue scales (VAS), blood pressure and heart rate by conventional methods. CPT was applied after post-treatment testing. Data were analysed by analysis of variance, with multiple comparisons., Results: Diazepam caused sedation (reduction in VAS alertness scores and CFFF, increase in sleepiness waves), dapiprazole had a sympatholytic and tropicamide a parasympatholytic effect on the pupil. Diazepam had no effect on pupil diameter and reflexes or their modifications by the antagonists. CPT increased pupil diameter, blood pressure and heart rate, and the increase only in systolic blood pressure was attenuated by diazepam., Conclusions: Diazepam-induced sedation is not accompanied by any change in either the sympathetic or parasympathetic influence on the iris.

The neuroprotective effects of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (180 micro g/kg i.m.; 80% LD(50)) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24h and 7 days following tabun challenge. The results indicate that all oximes studied in combination with atropine allow all tabun-poisoned rats to survive within 7 days following tabun challenge while two non-treated tabun-poisoned rats died within 2h. Both newly developed oximes combined with atropine seem to be effective antidotes for a decrease in tabun-induced neurotoxicity in the case of sublethal poisoning although they are not able to eliminate tabun-induced neurotoxicity completely. The oxime K075 showed a higher neuroprotective efficacy against tabun than K074 according to the number of eliminated tabun-induced neurotoxic signs at 24h as well as 7 days after tabun challenge. The neuroprotective efficacy of obidoxime in combination with atropine is similar to the potency of newly developed oxime K075 but the ability of the oxime HI-6 to counteract tabun-induced acute neurotoxicity is significantly lower at 24h as well as 7 days after tabun poisoning. Due to their neuroprotective effects, both newly developed oximes (especially K075) appear to be more suitable oximes for the antidotal treatment of acute tabun poisonings than the oxime HI-6.

The role of mu3 opioid receptors in morphine-induced intraocular pressure (IOP) lowering effect and miosis was evaluated in conscious, dark-adapted New Zealand white (NZW) rabbits using a masked-design study. IOP and pupil diameter (PD) measurements were taken at just before and 0.5, 1, 2, 4, 6 h after monolateral instillation of morphine (10, 50 and 100 microg/30 microl) as compared to vehicle administered in the contralateral eye. Morphine-induced ocular effects were challenged by a pre-treatment with the non-selective opioid receptor antagonist, naloxone (100 microg/30 microl), the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microl), or the non-selective mu3 opioid receptor inhibitor, reduced L-glutathione (GSH, 1%, 30 microl). Morphine induced a dose-dependent decrease in IOP and PD. Pre-treatment with naloxone totally prevented morphine-induced decrease in IOP and miosis. Ocular administration of L-NAME or GSH alone failed to affect IOP or PD of NZW rabbits. However, pre-treatment with either drugs significantly reduced, but not totally prevented ocular effects of morphine. These results suggest that biochemical mechanisms related to nitric oxide release are involved, at least in part, in morphine effects on the eye. Since the mu3 opioid receptor subtype is able to release nitric oxide and is sensitive to inactivation by GSH, it may be possible that mu3 opioid receptors are involved in morphine-induced miosis and reduction in IOP.

Polymeric nanoparticle suspensions were prepared from Eudragit RS100R and RL100R polymer resins and loaded with flurbiprofen (FLU), with the aim at improving the availability of the drug at an intra-ocular level for the prevention of the myosis induced during extracapsular cataract surgery. Nanosuspensions were prepared by a quasi-emulsion solvent diffusion technique using different formulation parameters (drug-to-polymer ratio, initial polymer concentration, agitation speed, etc.). The resulting nanoparticles showed mean sizes around 100 nm and a fixed positive charge (zeta-potential around +40/+60 mV). Stability tests after mid-time storage (4 degrees C or room temperature) or freeze-drying were carried out to optimise a possible final pharmaceutical preparation. In vitro, dissolution tests showed a controlled release profile of FLU from the nanoparticles. In vivo anti-inflammatory efficacy was assessed in the rabbit eye after induction of an ocular trauma (paracentesis). FLU-loaded nanosuspensions did not show toxicity on ocular tissues. Moreover, an inhibition of the miotic response to the surgical trauma comparable to a control eye-drop formulation was obtained, even though an actual lower concentration of free drug in the conjunctival sac was achieved from the nanoparticle system. Drug levels in the aqueous humour were also higher after application of the nanosuspensions.

Topical application of non-steroidal anti-inflammatory drugs on the eye is a common treatment used to contrast the miosis induced by surgical traumas, such as cataract extraction. With the aim of improving the availability of sodium ibuprofen (IBU) at the intraocular level, IBU-loaded polymeric nanoparticle suspensions were made from inert polymer resins (Eudragit RS100). The nanosuspensions were prepared by a modification of the quasi-emulsion solvent diffusion technique using variable formulation parameters (drug-to-polymer ratio, total drug and polymer amount, stirring speed). Nanosuspensions had mean sizes around 100 nm and a positive charge (zeta-potential of +40/+60 mV), this makes them suitable for ophthalmic applications. Stability tests (up to 24 months storage at 4 degrees C or at room temperature) or freeze-drying were carried out to optimize a suitable pharmaceutical preparation. In vitro dissolution tests indicated a controlled release profile of IBU from nanoparticles. In vivo efficacy was assessed on the rabbit eye after induction of an ocular trauma (paracentesis). An inhibition of the miotic response to the surgical trauma was achieved, comparable to a control aqueous eye-drop formulation, even though a lower concentration of free drug in the conjunctival sac was reached from the nanoparticle system. Drug levels in the aqueous humour were also higher after application of the nanosuspensions; moreover, IBU-loaded nanosuspensions did not show toxicity on ocular tissues.

Purpose: To compare the effect of topical ketorolac tromethamine 0.5% solution and topical diclofenac sodium 0.1% solution on the inhibition of surgically induced miosis., Setting: Tertiary care teaching hospital in South India., Methods: Fifty-one patients were prospectively randomized to receive ketorolac 0.5% or diclofenac 0.1% at 3 intervals preoperatively. Patients with diabetes mellitus, pseudoexfoliation, or local pupil abnormalities were excluded from the study. Mydriatics comprising homatropine 1% plus phenylephrine 10% were instilled in all patients 1 hour before the peribulbar block at 5 intervals. Horizontal pupil diameters were obtained at the beginning of surgery, after capsulotomy, after intraocular lens (IOL) implantation, and at the end of surgery., Results: The mean horizontal pupil diameter was 7.40 mm at the start of surgery in both groups. The ketorolac group showed a consistent trend toward larger pupil diameters at subsequent surgical intervals. Changes from baseline also indicated more significant inhibition of miosis in the ketorolac group., Conclusions: Topical ketorolac was a more effective inhibitor of miosis than topical diclofenac during extracapsular cataract extraction and IOL implantation. It also provided a more stable mydriatic effect throughout surgery.

Surgically-induced miosis commonly occurs during cataract extraction surgery, complicating removal of lens cortex and placement of a posterior chamber intraocular lens. To maintain intraoperative mydriasis, one bolus of epinephrine injection was used in our study. The pupillary response to various doses of intracameral epinephrine (0.1 ml of 1:25,000, 1:50,000, 1:100,000, 1:200,000, 1:400,000) was assessed in 60 consecutive patients. The pupil size was measured just prior to the incision, one min after epinephrine injection, after phacoemulsification and after irrigation/aspiration. There was no significant difference among the mean mydriatic responses to the epinephrine concentrations we tested. The 1:400,000 concentration appeared to be as effective as 1:25,000, but two cases of the 1:400,000 group failed to maintain the pupil diameter after irrigation/aspiration. In addition, we found that blood pressure did not elevate after injection of any concentration of epinephrine. We concluded that one bolus of an extremely dilute concentration of epinephrine (i.e., 1:400,000) injection might be effective in maintaining mydriasis during cataract surgery without systemic side effects.

Purpose: To assess the safety and effectiveness of ketorolac tromethamine 0. 5% (Acular) as a cost-efficient single agent to prevent intraoperative miosis and postoperative inflammation in cataract surgery., Methods: Both eyes of 26 patients were randomized to receive Acular preoperatively and postoperatively or flurbiprofen sodium (Ocufen) preoperatively and prednisolone acetate 1% (Pred Forte) postoperatively. Time scheduled between procedures was from 2 weeks to 1 month. Pupil dilation was measured preoperatively, intraoperatively, and at the end of surgery. Cell and flare were measured 1 day, 1 week, and 1 month postoperatively., Results: A comparison of the Acular and the Ocufen/Pred Forte groups (n=22) showed no statistically significant differences in dilation (preoperative versus postpostoperative) or cell and flare postoperatively., Conclusions: Using Acular as a single agent was as effective as the combination of preoperative Ocufen and postoperative Pred Forte in preventing intraoperative miosis and postoperative inflammation in cataract surgery. The use of Acular as a single agent could save the expense of using separate anti-inflammatory and antimiotic preparations preoperatively and postoperatively, enhancing convenience for the surgeon and surgical facility.

Purpose: To evaluate the effectiveness of phenylephrine 2.5% and flurbiprofen 0.03% combined in inducing and maintaining mydriasis during extracapsular cataract extraction (ECCE)., Methods: One hundred patients undergoing ECCE + intraocular lens (IOL) implantation were randomly divided into four groups. The first group was given phenylphrine 10%, the second group phenylephrine 10% + flurbiprofen, the third group phenylephrine 2.5% and fourth group phenylephrine 2.5% + flurbiprofen. Cyclopentolate 1% was used in all patients. Phenylephrine and cyclopentolate were instilled preoperatively four times during 1 hour and flurbiprofen was given four times the day before surgery and twice with an hour's interval before operation. Pre-operative and post-cortex aspiration horizontal pupil diameters were measured with callipers viewed through the operating microscope., Results: Pupil diameters in pre-operative and post-cortex aspiration were no different in the 2.5% and 10% phenylephrine groups (p>0.05). Both diameters were larger and pupillary constriction was smaller in the flurbiprofen groups (p<0.05)., Conclusions: 2.5% phenylephrine was as effective as 10% phenylephrine, with and without flurbiprofen, in inducing and maintaining pupil dilatation during ECCE surgery.

This multicenter, double-masked, randomized, parallel study compared the efficacy and safety profile of ketorolac tromethamine 0.5% ophthalmic solution with that of its vehicle in the maintenance of pupillary mydriasis during cataract surgery. A total of 176 adult patients scheduled to undergo unilateral extracapsular cataract extraction and posterior-chamber intraocular lens implantation received either ketorolac tromethamine 0.5% (n = 89) or vehicle (n = 87), starting 2 hours before surgery. One drop of study medication was instilled every 30 minutes for a total of 4 drops. No epinephrine was used in the intraoperative irrigating solution. Pupil diameter was measured with a caliper at 3 time points during surgery. To ensure participant safety, biomicroscopy, ophthalmoscopy, intraocular pressure, adverse events, and preoperative and postoperative visual acuity and refractive error were also monitored. The mean change in horizontal and vertical pupil diameter from the time of the first incision to after cortical irrigation and aspiration was significantly less with active ketorolac than with vehicle (P < or = 0.014). Consequently, mean pupil diameter after cortical irrigation and aspiration was significantly greater with ketorolac than with vehicle (P < or = 0.030). No significant between-group differences were observed in the change in pupil diameter between the end of surgery and postoperative administration of a miotic agent, safety variables, or occurrence of adverse events. In this study, ketorolac tromethamine 0.5% ophthalmic solution provided effective and well-tolerated inhibition of surgically induced miosis during cataract surgery.

Purpose: To determine the effect of 0.1% diclofenac sodium (DS) eyedrops made in China on preventing surgically induced miosis and inflammation., Methods: Seventy cases of cataract inpatients were randomly divided into two groups. DS eyedrops and normal saline as placebo were applied respectively 3 h, 1 h, 0.5 h before operation and once every morning for 7 days after operation. The pupil diameter was measured five times at different stages during the extracapsular cataract extraction. The eyepain, photophobia, conjunctival injection, KP, aqueous flare and light reaction of pupil were observed once a day after operation for a week., Results: 37 eyes in DS group and 33 eyes in placebo group were included in the study. 32 of 37 eyes in DS group (86.5%) maintained mydriasis in all stages of operation and 33 eyes (89.2%) did not show any obvious sign of inflammation. There was statistically significant difference between the two groups. No serious side effects occurred in the DS group., Conclusions: The DS eyedrops can prevent surgically induced miosis. Its antiinflammatory effect was significantly better than that of placebo drops.

Purpose: To quantitatively assess pupillary functions after small pupil cataract surgery using the flexible iris retractor., Methods: Subjects were 11 patients (12 eyes) with small pupils who underwent phacoemulsification and intraocular lens implantation. Pupils were enlarged using the flexible iris retractor intraoperatively, and postoperative iriscorder data were compared with the data of 20 normal controls who underwent standard phacoemulsification and intraocular lens implantation., Results: Although pupillary area before light stimulus did not differ between the groups, contraction rate after light stimulus was significantly lower in the small pupil group than in the normal controls. The velocity of contraction and dilation was also significantly slower in the small pupil group. Wider pupillary stretching during surgery resulted in deteriorated pupillary functions after surgery. Eyes of patients on long-term miotic therapy with pilocarpine showed poorer pupillary reaction postoperatively., Conclusion: Inappropriate use of the flexible iris retractor causes an atonic, chronically enlarged postoperative pupil. To avoid postoperative pupillary complications, miotic pupils should not be stretched to larger than a 5.0 x 5.0 mm square.

Purpose: One of the important points in extracapsular cataract extraction with posterior chamber intraocular lens implantation is to maintain mydriasis during the intervention. In this study we compared the efficacy of two topical nonsteroidal anti-inflammatory drugs: diclofenac sodium (Naclof) and indomethacin used before cataract surgery to inhibit surgically induced miosis., Methods: Sixty-four patients were operated (ECCE with IOL) by three experienced surgeons. All patients received dilatating drops and nonsteroidal anti-inflammatory drugs every 30 minutes in five doses beginning 2.5 hours before surgery. 32 patients received diclofenac sodium and 32 patients indomethacin. Pupil diameters were measured three times: first--just before the initial limbal incision, second--at the end of cortical aspiration and the last after implantation of an intraocular lens., Results: In both groups the surgical manipulations induced a decrease in pupil diameter but more in the group treated with indomethacin., Conclusions: Diclofenac sodium appeared to be more potent than indomethacin in maintaining intraoperative mydriasis during cataract surgery.

Objective: To compare the effects of topical 0.5% ketorolac tromethamine ophthalmic solution (Acular, Allergen Pharmaceuticals, Irvine, Calif) with topical 0.03% flurbiprofen sodium ophthalmic solution (Ocufen, Allergen Pharmaceuticals) on the inhibition of surgically induced miosis during phacoemulsification cataract surgery., Design: One hundred eighteen patients were prospectively randomized to receive 0.5% topical ketorolac or 0.03% topical flurbiprofen at 3 preoperative intervals. The flurbiprofen-treated group served as the control group. The surgeon was masked as to patient selection. Horizontal pupillary diameter measurements were obtained at the start of surgery, just before phacoemulsification, before lens implantation, and after lens implantation., Results: Mean horizontal pupillary diameter measurements for both medications were similar at the start of surgery. However, a consistent trend of larger pupillary diameter was seen in all subsequent surgical intervals in the ketorolac-treated group. Changes from baseline measurements also indicated a more significant inhibition of miosis at all subsequent intervals, and a more stable mydriasis throughout the procedure in the ketorolac-treated group., Conclusions: Topical ketorolac is an effective inhibitor of miosis during phacoemulsification cataract surgery, and provides a more stable mydriatic effect throughout the surgical procedure.

Purpose: To compare the bioavailability and pupillary effect of flurbiprofen and indomethacin during phacoemulsification and intraocular lens implantation., Setting: Gimbel Eye Centre, Calgary, Alberta, Canada., Methods: In this prospective, randomized, double-masked study, 236 patients had cataract extraction by phacoemulsification and posterior chamber intraocular lens implantation. They received topical flurbiprofen 0.03% solution or indomethacin 1% suspension applied every 15 minutes for 60 to 75 minutes before surgery. An aqueous humor sample (100 microL) was taken immediately before the corneal incision was made. Pupil diameters (horizontal and vertical) were measured before aqueous humor sampling, after phacoemulsification, after irrigation and aspiration (I/A), and after acetylcholine instillation., Results: Mean concentration of flurbiprofen and indomethacin in the aqueous humor was 59.8 ng/mL and 90.2 ng/mL, respectively (P < .001). The percentage of dose detected in the aqueous humor was 4.38% in the flurbiprofen group and 0.21% in the indomethacin group (P < .001). Pupil diameters were 7.2 and 7.3 mm presurgery and 7.0 and 7.0 mm after I/A in the flurbiprofen and indomethacin groups, respectively (P > .05). No adverse events were reported in either group., Conclusions: Although the absolute concentration of indomethacin was higher, the percentage of dose detected in the aqueous humor was 20 times greater in the flurbiprofen than in the indomethacin group. Flurbiprofen is absorbed 20 times more readily than indomethacin. Both drugs were equally effective in preventing miosis during cataract surgery.

Two hundred consecutive patients were enrolled in a randomized, prospective clinical trial evaluating the efficacy of diclofenac sodium (Voltaren Ophthalmic) in reducing patient discomfort after cataract surgery. Other factors evaluated were the effect of preoperative flurbiprofen (Ocufen) in preventing intraoperative miosis and on postoperative discomfort and the effect of incision size and intraocular carbachol (Miostat) on postoperative comfort. Diclofenac significantly reduced discomfort during the first 24 hours after surgery but not two to three days postoperatively, although there was a trend toward reduction. Flurbiprofen given preoperatively did not affect postoperative discomfort. It also did not affect pupil size at the start of surgery but did reduce intraoperative miosis. Incision size (5.2 mm versus 7.0 mm) had no effect on discomfort. Miostat did not affect discomfort, although there was a trend toward more discomfort. The results indicate that topical diclofenac, given immediately after cataract surgery, significantly reduces discomfort during the first 24 postoperative hours.

Maintenance of pupillary dilatation is necessary for success of scleral buckling procedures. The efficacy of 0.03% flurbiprofen in preventing intraoperative miosis was evaluated by a prospective randomized, double-masked controlled trial of 60 patients. Thirty patients received 0.03% flurbiprofen 6 times at 15 minute intervals 90 minutes preoperatively in addition to the routine dilation regimen. The treated group had a mean pupillary decrease of 1.88 mm and the control group had a decrease of 1.57 mm (p > 0.05). Flurbiprofen did not affect the pupillary size at any step of the surgery. Factors such as age of the patient, lens status, number of cryo applications, duration of surgery, and the size and extent of buckle were assessed. The use of flurbiprofen did not affect the mean pupillary change for any of these groups. Preoperative use of flurbiprofen does not significantly decrease intraoperative miosis during scleral buckling procedures.

A randomized, double-blind study was conducted to compare the effect of 0.1% indomethacin solution versus 0.03% flurbiprofen versus placebo on the maintenance of mydriasis during cataract surgery. Ninety-five patients undergoing extracapsular cataract extraction with posterior chamber lens implantation were enrolled. Pupillary diameters were measured horizontally under operating-microscope visualization before 5 surgical steps: 1. corneo-scleral incision; 2. lens nucleus expression; 3. lens cortex material aspiration; 4. intra-ocular lens implantation; 5. end of surgery. The mydriasis loss during surgery was statistically less in the 2 groups treated by non steroidal anti-inflammatory drugs than in the placebo group. This effectiveness appeared at the time of lens nucleus expression (p = 0.0001) and persisted until the end of surgery. Then, the mydriasis was maintained during 2 crucial surgical steps requiring optimal pupillary dilation: lens cortex material aspiration and intra-ocular lens implantation. No significant difference was found between 0.1% indomethacin and 0.03% flurbiprofen concerning effectiveness and tolerance.

Fifty-six patients who underwent extracapsular cataract surgery were randomized in two groups with 28 patients in each group. Group 1 was treated with standard preoperative dilation regime and group 2 received in addition indomethacin 1% ophthalmic solution. Horizontal and vertical pupil diameter measurements were taken before capsulotomy, before exprimation of the lens nucleus and before lens implantation. The size of the pupil at the time of capsulotomy and at the time just before lens exprimation was greatest in the non-indomethacin treated group, but at the time of lens implantation the pupil of the indomethacin treated group was greatest. It is concluded that even though indomethacin seems to be able to inhibit surgically induced miosis, probably through its inhibitory effect on prostaglandin synthesis, the effect is only marginal and from a clinical point of view it cannot be recommended.

Diclofenac sodium 0.1% (Voltaren) prevents surgically induced miosis during extracapsular cataract extraction in a more long lasting way than indomethacin 1% (Indocid). Just before the IOL-implantation, in eyes treated with diclofenac sodium eye drops, the apparent mean pupil size was constricted by approximately 1 mm less than in the control group (p.01). At the same critical moment, 50% of the pupils treated with diclofenac sodium and only 20% of the pupils in the control and indomethacin groups were larger than 6 mm.

Surgically induced miosis (SIM) frequently occurs during extracapsular cataract extraction (ECCE). A randomized clinical trial was performed to evaluate the effect of 3 nonsteroidal antiinflammatory drugs Indomethacin 1%, Diclofenac 0.1% and Flurbiprofen 0.03%, administered topically before ECCE, on the maintenance of mydriasis during surgery. The patients were grouped based on the type of NSAID given preoperatively in addition to the standard mydriatic agents: 46 patients in group A (Indomethacin), 40 patients in B (Diclofenac), 44 patients in C (Flurbiprofen) and 34 patients formed control group D (no NSAID was instilled). Horizontal pupillary diameter measurements were taken, using a caliper, immediately prior to surgery (step 0), after capsulotomy (step I), after expression of the lens nucleus (step II) and after irrigation-aspiration of the cortical remnants (step III). Differences in pupillary diameter between step 0 and the different surgical steps were used as indices of pupillary constrictions observed in the 4 groups. A significantly less pupillary constriction was found in groups A and C than in D between steps 0 and II (p = 0.01) and in groups A and C than in B and D between steps 0 and III (p = 0.001). Our results show that Indomethacin 1% and Flurbiprofen 0.03%, compared to Diclofenac 0.1% and no NSAID regime, are significantly more effective in maintaining mydriasis during cataract surgery.

Cyclo-oxygenase inhibitors, which are formulated as ophthalmic eyedrop preparations, have recently become commercially available for use by ophthalmologists in the United States to inhibit intraoperative miosis during cataract surgery and to prevent postoperative inflammation. In addition, they are available worldwide as ocular antiinflammatory drugs and are used in the prevention and treatment of pseudophakic and aphakic cystoid macular edema. Understanding the rationale behind the use of these agents requires an understanding of the pathophysiology of the cyclo-oxygenase inhibitors. In this review recent advances in laboratory and clinical science are emphasized. The role of COIs during and following surgery is examined.

The effect of an antiprostaglandin, piroxicam, in preventing surgically induced miosis is studied. Patients undergoing extracapsular cataract surgery were randomly divided into the piroxicam and placebo groups. Intra-operative measurements of the pupillary diameters were performed. The stages of procedure at which they were measured were at the beginning of operation (Stage 1), after anterior capsulotomy (Stage 2), after lens nucleus delivery (Stage 3) and at the end of irrigation and aspiration (Stage 4). It is noted in this Study that the pupillary diameters were larger at stages 2,3 and 4 in the piroxicam group. The increase in the mean pupillary areas of the piroxicam group were statistically significant for Stages 3 and 4.

Topical use of Indomethacin was documented to prevent surgically induced miosis, and it reduced postoperative inflammatory response. We collected 26 consecutive cataract eyes. Seventeen eyes in the study group received topical 0.1% Indomethacin eyedrops from one day before surgery until two weeks after surgery, in addition to the routine medications. Nine eyes belonging to the control group received the routine medications only. The parameters of our study included the measurement of the pupil diameters in surgery, the central corneal thickness, the intraocular pressure, and the anterior chamber reaction before and after surgery. The results revealed that topical use of 0.1% Indomethacin eyedrops could prevent intraoperative miosis and reduce postoperative corneal edema and anterior chamber reaction, but it did not show much influence on intraocular pressure.

The effect of topical Indomethacin 0.5% ophthalmic suspension in preventing surgically induced miosis during planned extracapsular cataract extraction is examined. Eighteen patients received Indomethacin per-operatively while 16 did not and served as controls. Our study failed to show any difference in per-operative pupil size between either group.

Maintenance of wide pupillary dilation during vitreoretinal surgery can be important in successful completion of the operation. This study identified factors associated with intraoperative miosis. Also, flurbiprofen, a topically applied nonsteroidal anti-inflammatory agent, was evaluated for its efficacy in preventing intraoperative miosis in a prospective, randomized study of 99 consecutive patients. Factors associated with intraoperative miosis included duration of surgery greater than 90 minutes, preoperative afferent pupillary defect, and recent previous surgery. Preoperative treatment with flurbiprofen did not decrease the risk of intraoperative miosis.