Vascular actions of peripheral CGRP in migraine-like photophobia in mice.

BACKGROUND: Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice. METHODS: Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay. RESULTS: Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion. CONCLUSION: We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

Stimulation of Posterior Thalamic Nuclei Induces Photophobic Behavior in Mice.

OBJECTIVE: A hallmark of migraine is photophobia. In mice, photophobia-like behavior is induced by calcitonin gene-related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. DESIGN: We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and acute CGRP injections in wild-type mice. Since the light/dark assay has historically been used to investigate anxiety-like responses in animals, we measured anxiety in a light-independent open field assay and asked if stimulation of a brain region, the periaqueductal gray, that induces anxiety would yield similar results to posterior thalamic stimulation. The hippocampus was used as an anatomical control to ensure that light-aversive behaviors could not be induced by the stimulation of any brain region. RESULTS: Optogenetic activation of neuronal cell bodies in the posterior thalamic nuclei elicited light aversion in both bright and dim light without an anxiety-like response in an open field assay. Injection of CGRP into the posterior thalamic region triggered similar light-aversive behavior without anxiety. In contrast to the posterior thalamic nuclei, optogenetic stimulation of dorsal periaqueductal gray cell bodies caused both light aversion and an anxiety-like response, while CGRP injection had no effect. In the dorsal hippocampus, neither optical stimulation nor CGRP injection affected light aversion or open field behaviors. CONCLUSION: Stimulation of posterior thalamic nuclei is able to initiate light-aversive signals in mice that may be modulated by CGRP to cause photophobia in migraine.

Electroretinographic abnormalities associated with pregabalin: a case report.

PURPOSE: Pregabalin binds to the α2-δ1/α2-δ2 subunits of the voltage-gated L-type calcium channel (LTCC), which is expressed in rod/cone photoreceptor terminals. The purpose of this report was to describe electroretinographic abnormalities associated with pregabalin treatment. CASE PRESENTATION: This is an observational case report. A 49-year-old female reported photophobia and night blindness in her left eye after 10 months of pregabalin administration. One month after the symptoms, ophthalmic examinations were performed, which revealed good visual acuity and no remarkable fundus findings. However, full-field electroretinography (ERG) of the left eye revealed a decreased b-wave in rod ERG, a slightly decreased a-wave and severely decreased b-wave (negative ERG) in bright flash ERG, decreased a- and b-waves in cone ERG, and decreased b-waves in 30-Hz flicker ERG. These findings are similar to those seen in incomplete congenital stationary night blindness, whereas the right eye ERG showed normal responses, except for a square a-wave in cone ERG. The ERG gradually improved from 1 to 12 months after discontinuing pregabalin. Finally, b-waves in bright flash ERG and cone ERG responses largely recovered, but b-waves in rod ERG and a-waves in bright flash ERG only partially recovered in the left eye. The square a-wave recovered to normal in the right eye. CONCLUSIONS: This is the first report to indicate that ERG abnormalities might be associated with pregabalin treatment. Our results suggest that pregabalin may affect LTCC function via the α2-δ1/α2-δ2 subunits, which leads to defective synaptic transmission from rod/cone photoreceptors to bipolar cells.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study.

BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

First-in-human trial of an anti-5T4 antibody-monomethylauristatin conjugate, PF-06263507, in patients with advanced solid tumors.

Background The antibody-drug conjugate PF-06263507 targets the cell-surface, tumor-associated antigen 5T4 and consists of a humanized IgG1 conjugated to the microtubule-disrupting agent monomethylauristatin-F by a non-cleavable maleimidocaproyl linker. In this first-in-human, dose-finding trial (NCT01891669), we evaluated safety, pharmacokinetics, and preliminary antitumor activity of PF-06263507 in pretreated patients with advanced solid tumors, unselected for 5T4 expression. starting at 0.05 mg/kg, with 25, 56, and 95% dose increments, depending on observed dose-limiting toxicities (DLTs), applying a modified continual reassessment method. Results Twenty-six patients received PF-06263507 at 0.05 to 6.5 mg/kg. The first DLT, grade 3 photophobia, occurred at 4.34 mg/kg and two additional DLTs, grade 2 keratitis and grade 1 limbal stem cell deficiency (> 2-week dosing delay), at 6.5 mg/kg. The most common adverse events (AEs) were fatigue (38.5%), photophobia (26.9%), and decreased appetite, dry eye, nausea, and thrombocytopenia (23.1% each). No treatment-related grade 4-5 AEs were reported. Systemic exposure of PF-06263507 increased in a dose-related manner. At the maximum tolerated dose (MTD, 4.34 mg/kg), mean terminal half-life for PF-06263507 and unconjugated payload were ~6 and 3 days, respectively. Payload serum concentrations were substantially lower compared with PF-06263507. No objective responses were observed. Conclusions The MTD and recommended phase II dose were determined to be 4.34 mg/kg. Ocular toxicities accounted for the DLTs observed, as previously reported with monomethylauristatin-F payloads. Further studies are warranted to investigate clinical activity of this agent in patients with 5T4-expressing tumors.Trial registration ID: NCT01891669.

Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats.

BACKGROUND: This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. METHODS: Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. RESULTS: The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. CONCLUSIONS: These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.

Modulation of CGRP-induced light aversion in wild-type mice by a 5-HT(1B/D) agonist.

The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.

Incidence of Adverse Events Induced by Atropine in Myopic Children: A Meta-Analysis.

A large number of studies have evaluated the efficacy of low-dose atropine in preventing or slowing myopic progression. However, it is challenging to evaluate the ocular safety from these studies. We aimed to evaluate the incidence of adverse events induced by atropine in children with myopia. We performed a systematic literature search in several databases for studies published until November 2022. The incidence of adverse events induced by atropine was pooled by a common-effect (fixed-effect) or random-effects model. Subgroup analyses were conducted according to drug doses, types of adverse events, and ethnicity. A total of 31 articles were ultimately included in the study. The overall incidence of adverse events for atropine was 5.9%, and the incidence of severe adverse events was 0.0%. The most commonly reported adverse events were photophobia (9.1%) and blurred near vision (2.9%). Other adverse events including eye irritation/discomfort, allergic reactions, headache, stye/chalazion, glare, and dizziness occurred in less than 1% of the patients. The incidence of atropine-induced adverse events varied depending on the drug doses. A lower dose of atropine was associated with a lower incidence of adverse events. There was no significant difference in the incidence of adverse events for low-dose atropine between Asian and White children. Our study suggests photophobia and blurred near vision are the most frequently reported adverse events induced by atropine. Low-dose atropine is safer than moderate- and high-dose atropine. Our study could provide a safe reference for ophthalmologists to prescribe atropine for myopic children.

Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (PAC1, VPAC) are present in sensory neurons and vascular smooth muscle. PACAP infusion was found to trigger migraine-like headache in humans and we showed its central pro-nociceptive function in several mouse pain models. Nitroglycerol (NTG)-induced pathophysiological changes were investigated in this study in PACAP gene-deleted (PACAP(-/-)) and wildtype (PACAP(+/+)) mice. Chemical activation of the trigeminovascular system was induced by 10 mg/kg i.p. NTG. Light-aversive behavior was determined in a light-dark box, meningeal microcirculation by laser Doppler blood perfusion scanning and the early neuronal activation marker c-Fos with immunohistochemistry. NTG-induced photophobia both in the early (0-30 min) and late phases (90-120 min) due to direct vasodilation and trigeminal sensitization, respectively, was significantly reduced in PACAP(-/-) mice. Meningeal blood flow increased by 30-35% during 4 h in PACAP(+/+) mice, but only a 5-10% elevation occurred from the second hour in PACAP(-/-) ones. The number of c-Fos expressing cells referring to neuronal activation in the trigeminal ganglia and nucleus caudalis significantly increased 4h after NTG in PACAP(+/+), but not in PACAP(-/-) animals. Similar PAC1 receptor immunostaining was detected in both groups, which did not change 4 h after NTG treatment. PACAP-38 (300 µg/kg, i.p.) produced photophobia similarly to NTG and 30% meningeal vasodilatation for 30 min in PACAP(+/+), but not in PACAP(-/-) mice. It significantly increased neural activation 4h later in the trigeminal ganglia of both groups, but in the nucleus caudalis of only the PACAP(+/+) mice. We provide the first experimental results that PACAP is a pivotal mediator of trigeminovascular activation/sensitization and meningeal vasodilation related to migraine.

Anterior Uveitis Due to Intracameral Moxifloxacin: A Case Report.

Purpose: To report a case of a drug-induced anterior uveitis secondary to the use ofintracameral moxifloxacin.Case report: A 64-year-old Colombian male patient presented with severe ocular pain and photophobia in his left eye 15 days after cataract surgery. In the ophthalmology and glaucoma specialist evaluation, pigment dispersion in the anterior chamber and camerular angle, severe anterior segment inflammation, and elevated intraocular pressure were observed. Poor response to treatment for a suspected viral origin and exclusion of other possible etiologies, led to the conclusion of intracameral moxifloxacin induced anterior uveitis.Conclusion and importance: We present the second published case worldwide about anterior uveitis secondary to intracameral moxifloxacin, which may rarely cause hypertensive uveitis that may be confused with viral uveitis. This provides evidence on the importance of postoperative follow-up by the surgeon for an early referral and treatment of these cases.

Effects of 0.05% racanisodamine on pupil size and accommodation.

PURPOSE: To investigate the effect of a new non-selective muscarinic antagonist, 0.05% racanisodamine eye drop, on pupil size and accommodative response in children. METHODS: Twenty healthy myopic children aged between 9 and 12 years were enrolled in the study. They were given two successive drops of 0.05% racanisodamine solution in one eye. Scotopic pupil sizes of both eyes were evaluated with an infrared open-field autorefractor before and 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min after treatment. Accommodative responses to a Maltese cross at a distance of 50, 33, and 20 cm were measured at the same time intervals as pupil sizes. Subjective evaluation of photophobia and reading difficulty were recorded by questionnaires. Pupil sizes and accommodative responses were compared across time using repeated measurements of analysis of variance. RESULTS: The minimum pupil size of the treated eye came at 10 min after the second drop and maintained for the next 20 min. Then, it recovered to baseline value at 45 min and continued to enlarge to a peak size of about 0.75 ± 0.22 mm larger than baseline value at 120 min (p = 0.036), followed by a recovering process. No significant change occurred to the contralateral untreated eye. Accommodative responses to near targets did not significantly change at any time during the procedure for both eyes. Only one subject experienced photophobia in the treated eye at the 120 and 180 min time points after treatment. None reported reading difficulty at any time. CONCLUSIONS: As a non-selective muscarinic antagonist, 0.05% racanisodamine has a significant but clinically moderate impact on pupil size and no effect on accommodative response.

Premonitory symptoms in glyceryl trinitrate triggered migraine attacks: a case-control study.

ABSTRACT: Spontaneous and pharmacologically provoked migraine attacks are frequently preceded by nonheadache symptoms called premonitory symptoms. Here, we systematically evaluated premonitory symptoms in migraine patients and healthy controls after glyceryl trinitrate (GTN) infusion. In women with migraine without aura (n = 34) and age-matched female controls (n = 24), we conducted systematically a semistructured interview assessing 21 possible premonitory symptoms every 15 minutes in the 5 hours after GTN infusion (0.5 µg/kg/min over 20 minutes). Migraine-like headaches occurred in 28/34 (82.4%) migraineurs (GTN responders). After GTN, 26/28 (92.9%) responders, 6/6 (100%) nonresponders, and 13/24 (54.2%) controls reported at least one possible premonitory symptom. Concentration difficulties (P = 0.011), yawning (P = 0.009), nausea (P = 0.028), and photophobia (P = 0.001) were more frequently reported by those migraineurs who developed a migraine-like attack vs healthy controls. Importantly, concentration difficulties were exclusively reported by those who developed a migraine-like attack. Thus, our findings support the view that GTN is able to provoke the naturally occurring premonitory symptoms and show that yawning, nausea, photophobia, and concentration difficulties are most specific for an impending GTN-induced migraine-like headache. We suggest that these symptoms may also be helpful as early warning signals in clinical practice with concentration difficulties exclusively reported by those who develop a migraine-like attack.

Ocular toxicity by latex of Calotropis procera (Sodom apple).

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further.

Ocular surface response and subjective symptoms associated to lens care solutions in Palestine.

PURPOSE: To compare the biocompatibility and subjective symptoms of four multipurpose solutions marketed in Palestine with hydrogel contact lenses. METHODS: 50 habitual soft contact lens wearers were recruited in this interventional crossover study. Subjects were asked to attend the optometry clinic five times. A new pair of hydrogel lenses (Bioxifilcon-B) were fitted each time. This pair was soaked randomly overnight in one of the following four-multipurpose solutions (NEOPLUS®, AvizorUnicaSensitive®, ReNuMultiPlus® and COMPLETERevitaLens®) which contain different disinfecting agents (PHMB, Phx, PAPB, and PQ-1+Alexidine, respectively), or non-preserved saline. At each visit, corneal staining, ocular redness and subjective symptoms were assessed. RESULTS: The percentage of corneal staining increased significantly (P≤0.050) after soaking the lenses with PHMB (86%), PAPB (64%) and Phx (32%) based-solutions. However, a non-significant increase was noticed after the use of PQ-1+Alexidine based solution (30%, P=0.083). Ocular redness evaluation showed a significant increase (P≤0.050) in limbal hyperemia after the use of all solutions, while bulbar redness was significantly increased after the use of biguanide-based solutions (P≤0.050). The subjective assessment analysis showed a non-significant change in comfort, dryness, photophobia and scratchiness (P≥0.050) at 2-h intervention using all solutions, except for the PHMB based solution which showed a significant change in subjective symptoms (P≤0.050). CONCLUSION: The combination of Bioxifilcon-B hydrogel contact lenses and solution containing PHMB, PAPB and Phx-disinfectants induced a significant increase in corneal staining after 2h of CL-wear with a higher severity when the PHMB-based solution was used, while the PQ-1+Alexidine-based solution did not. Only the PHMB-based solution triggered a significant change in subjective symptoms which might which suggests that it might be related to the severity of staining rather than the induction of staining.

Toxic Keratitis After Application of Custard Apple Seed for Head Lice Infestation.

PURPOSE: To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation. METHODS: Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented. RESULTS: Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2). CONCLUSIONS: Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.

Dental inflammation and central retinitis--it is important to protect the retina from the harmful sunlight.

During 3-year study of 73 patients with dental inflammation, sinusitis, otitis and 5 cases with granuloma, in 9 cases we observed the development of central retinitis. All patients were medicated with the same antibiotics and parabulbar depo of Prednisolonacetate. To 50% of these patients, we suggested eye protection with Yellow Medical filters during two months. In the first group with medication we observed better vision in 69%, but in the second group with eye protection with Yellow Medical filters we observed normalization of vision in 100%.

A rare complication of topical atropine for treatment of eccrine hidrocystoma: Pharmacological fixed dilated pupils.

Multiple eccrine hidrocystoma (EH) has been treated with topical atropine with variable results. However, in rare cases, anticholinergic side effects have been seen after the use of the topical form of this drug. We presented a 50-year-old woman who developed recent onset of visual disturbance and photophobia from 2 weeks prior. The diagnosis of topical atropine-induced bilateral mydriasis was made. We reported a recognized but often overlooked case of bilateral mydriasis caused by application of topical 1% atropine for treatment of multiple EH.

Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy.

In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min (P < 0.05), phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction.

A case of accidental mydriasis.

A 42-year-old man presented with a three-day history of progressive bilateral blurred vision, photophobia and headaches. There was no history of trauma. He was emmetropic with visual acuity of 6/60 (pinhole 6/24) in both eyes, no ptosis and full range of eye movements. His pupils were in fixed mydriasis. The pupils were unreactive to light or accommodation. His optic discs and fundi were normal. Pilocarpine failed to constrict his pupils. Initially, he strongly denied using any topical ocular medications but later remembered that 10 days previously his eyes had felt 'gritty' and his wife had instilled their son's old atropine penalisation drops into both his eyes. His signs and symptoms had resolved over the next two days.