Bilateral simultaneous acute angle closure glaucoma triggered by an over-the-counter cold and influenza medication.

A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.

Case report: Topical pilocarpine ameliorated the accommodation loss and pupillary dilation after micropulse transscleral laser treatment.

BACKGROUND: The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision. CASE PRESENTATION: Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1-5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2. CONCLUSION: In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT.

As-Needed Pilocarpine for Radiation-Induced Xerostomia in Head and Neck Cancers.

OBJECTIVES: This study aimed to evaluate the efficacy of as-needed pilocarpine for the management of radiation-induced xerostomia. Additionally, the study sought to assess the side effects associated with an as-needed regimen. METHODS: A randomized, double-blinded, placebo-controlled crossover study was conducted on patients who had undergone radiation therapy for head and neck cancers and developed xerostomia. Participants took pilocarpine or placebo as needed for symptom relief at 2 weeks per treatment, which included a one-week washout period. The primary outcome measure was the severity of dry mouth symptoms, quantified using the Xerostomia Inventory (XI). The primary outcome was the change in the XI score. RESULTS: Among the 20 participants who completed the crossover study, there was a significant reduction in XI scores during the treatment phase with pilocarpine compared to the scores during the placebo phase. The mean difference in XI scores was -18.05 (95% CI: -17.17, -6.13, p < 0.001), with a-49.77 ± 3.22% change (p < 0.001). Only one participant withdrew due to pilocarpine side effects. CONCLUSION: As-needed pilocarpine administration is effective in relieving symptoms of radiation-induced xerostomia, with fewer side effects and reduced treatment costs compared to fixed-dose regimens. This study guides the potential shift toward flexible dosing strategies in clinical practice, promoting enhanced patient-centered, tailored care and adherence. LEVEL OF EVIDENCE: 2: According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines Laryngoscope, 134:4542-4548, 2024.

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms.

INTRODUCTION: Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms. METHODS: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group. RESULTS: First, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced. Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2. CONCLUSION: The current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.

Pilocarpine HCl 1.25% for treatment of presbyopia after laser vision correction: pooled analysis of two phase 3 randomized trials (GEMINI 1 and 2).

PURPOSE: To evaluate the efficacy of topical pilocarpine HCl 1.25% (Pilo) in treating presbyopia in individuals with or without a history of laser vision correction (laser-assisted in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]). SETTING: Multiple clinical sites. DESIGN: Pooled analysis of 2 identically designed prospective, randomized, vehicle-controlled studies (GEMINI 1 and 2). METHODS: Adults aged 40 to 55 years with presbyopia received once-daily Pilo or vehicle bilaterally for 30 days. Responder rates for ≥3-line improvement in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) were determined on day 30. RESULTS: Among participants with a history of LASIK/PRK (n = 39 in the Pilo group, n = 41 in the vehicle group), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.7%, 38.9%, 41.7%, 37.8%, 16.2%, 13.9%, and 8.3% with Pilo and 0.0%, 2.6%, 10.5%, 5.1%, 7.7%, 2.6%, and 0.0% with vehicle. Responder rates in the LASIK/PRK subgroup were significantly higher with Pilo than vehicle at hours 0.25 ( P = .0087), 0.5 ( P = .0001), 1 ( P = .0022), and 3 ( P = .0005). In contrast, there were no significant differences in responder rates between Pilo-treated participants with and without LASIK/PRK. Among non-LASIK/PRK participants in the Pilo group (n = 336), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.8%, 32.7%, 39.0%, 28.0%, 17.4%, 12.6%, and 10.5%. CONCLUSIONS: Pilo treatment effectively and similarly improved DCNVA in presbyopes with or without a history of laser vision correction.

N-Formyl-Methionyl-Leucyl-Phenylalanine Plays a Neuroprotective and Anticonvulsant Role in Status Epilepticus Model.

Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory process. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/µL, 1 µL) followed by fMLP (1 mg/mL, 1 µL) or vehicle (VEH, saline 0.9%, 1 µL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine's Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy. Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).

The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats.

BACKGROUND: Status epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures. METHODS: Twenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated. RESULTS: Centella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments. CONCLUSION: The dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

Safety and efficacy of oral pilocarpine in radiation-induced xerostomia in oropharyngeal carcinoma patients.

Context: Patients with head-and-neck cancers can develop salivary gland hypofunction after radiotherapy. Oral pilocarpine has been shown to be effective treatment for radiation-induced xerostomia, although its usefulness is being discussed. Aims: We aimed to evaluate the efficacy and safety profile of oral pilocarpine in radiation-induced xerostomia. Materials and Methods: Sixty patients with oropharyngeal carcinoma were planned for radiotherapy and divided into two arms randomly: Arm A (30 patients) received oral pilocarpine and Arm B (30 patients) received placebo tablets for 12 weeks after 3 months of completion of radiotherapy. Salivary gland scintigraphy and xerostomia questionnaire (XQ) were obtained from each patient at baseline and at 3 and 6 months of completion of radiotherapy. Results: There was a marked decrease in uptake ratio (UR) and excretion fraction (EF) after 3 months of completion of radiotherapy. There was a statistically significant difference between both the arms in relation to UR, but no significant difference was observed between the two arms in relation to EF after 6 months of completion of radiotherapy. A statistically significant difference was found comparing the XQ results in both the arms. The XQ results did not correlate with salivary gland dysfunction observed by means of salivary scintigraphy. Adverse effects due to xerostomia were generally mild and occasionally of moderate severity. Conclusion: The use of oral pilocarpine did not significantly improve salivary gland excretory function, despite better results on salivary uptake at 6 months. However, oral pilocarpine significantly improved symptoms of xerostomia with minor side effects that were predominantly limited to sweating.

Synergistic effects of applying static magnetic fields and diazepam to improve EEG abnormalities in the pilocarpine epilepsy rat model.

The lithium-pilocarpine rat model is a well-known model of temporal epilepsy. Recently we found that transcranial static magnetic stimulation (tSMS) delay and reduce the signs of EEG in this model. We aim to test the effect of combining the therapeutic action of tSMS and diazepam, a drug used to treat status epilepticus. We induce epilepsy in 12 Sprague-Dawley rats. Animals were classified as "magnet" when a magnetic neodymium cylinder was placed over the skull or "control" when a stainless-steel replica was used. Diazepam was injected 60-min after the second doses of pilocarpine injection. We found a reduction in the number of spikes/minute for magnet condition compared with sham condition, reaching significance at 60 min after diazepam injection. The Root-Mean-Square shown a significant reduction in magnet animals compared with those receiving diazepam (Tukey's-test 30 and 60 min after diazepam injection, p < 0.01; 40 and 50 min after diazepam injection, p < 0.05). Furthermore, the power spectrum analysis shown a reduction in delta, theta, alpha and beta bands, on the diazepam + magnet animals compared to the diazepam + sham group. Analysis of high-frequency oscillations revealed an increased in the ripples due to pilocarpine being reduced by diazepam. Our results demonstrate that application of tSMS previously to diazepam potentiates the effect of the drug by reducing the electroencephalographic pattern associated with epileptiform discharges. We suggest a new synergistic cooperation between pharmacology and neuromodulation as a future treatment for epilepsy.

Comparison of the 1 and 2% pilocarpine mouthwash in a xerostomic population: a randomized clinical trial.

AIMS & BACKGROUND: Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. The present study aimed to compare the effects of 1 and 2% pilocarpine mouthwash on xerostomic participants. METHODS: In this double-blind clinical trial study, 48 subjects with xerostomia were randomly divided into three groups to measure the effects of 1 and 2% pilocarpine and placebo mouthwashes on saliva levels. The amount of saliva in the 1st and 14th days was measured at 0, 45, 60, and 75 mins, while participants used their mouthwash three times a day for 14 days. On the 1st and 14th days, they filled out the information forms on xerostomia and the medicine's side effects before and after the intervention. RESULTS: On the 1st day, the mean salivary flow at 45, 60, and 75 mins in the 2 and 1% pilocarpine mouthwash were significantly higher than in the placebo mouthwash group (p < 0.05). On the 14th day, the mean salivary flow time at 45 mins in the 2% pilocarpine mouthwash group was significantly higher than in the placebo mouthwash group (p = 0.007). Furthermore, the mean salivary flow at 60 and 75 mins in the 2% (p < 0.001) and 1% pilocarpine mouthwash (p = 0.028) was significantly higher than in the placebo group. Moreover, the salivary flow in the 2% pilocarpine mouthwash group was significantly higher than the 1% pilocarpine mouthwash (p < 0.05) during these two times. No side effects were observed in any of the subjects. CONCLUSIONS: The study showed that 5 ml of 2 and 1% pilocarpine mouthwash for 2 weeks increased salivary flow in xerostomic participants compared to placebo without any side effects.

Photophobia as a Presenting Feature in Adie's Tonic Pupil.

A 34 years old female presented with complains of photophobia since 6-7 months. On examination, she had anisocoria of 4 mm in room light which increased in bright light. The left pupil was dilated and unresponsive to direct and indirect light stimuli. It did however, constrict slowly on near fixation followed by slow redilatation on distance fixation. A diagnosis of Adie's tonic pupil was made since left pupil constricted with instillation of dilute pilocarpine 0.1%. Her symptoms of photophobia and blurred vision immediately resolved. Photochromatic glasses and dilute pilocarpine 0.1% three times a day were prescribed. Prompt symptomatic relief of photophobia and blurred vision was observed.

Effects of GABAB receptor positive allosteric modulator BHF177 and IRS-1 on apoptosis of hippocampal neurons in rats with refractory epilepsy via the PI3K/Akt pathway.

The present study was conducted to determine the effects of the γ-aminobutyric acid B (GABAB ) receptor positive allosteric modulator BHF177 on refractory epilepsy (RE). An RE rat model was initially established via treatment with lithium-pilocarpine. The RE rats were then treated with BHF177 or the GABAB receptor antagonist CGP46381, followed by recording of their seizure rate and assessment of their spatial learning in the Morris water maze test. Treatment of BHF177 reduced the seizure intensity, whereas this effect was revered upoj treatment with CGP46381. Immunohistochemistry revealed that BHF177 treatment diminished P-glycoprotein (P-gp) expression in the hippocampal tissues of RE rats. Next, we found that BHF177 activated GABAB receptor, resulting in upregulated expression of insulin receptor substrate 1 (IRS-1) and PI3K, as well as antiapoptotic factors (Bcl-2 and mTOR), along with suppression of the apoptosis factors Bax and cleaved caspase-3 in the hippocampal tissues. Further, activation of GABAB receptors by BHF177 alleviated the inflammatory response in hippocampal tissues of RE rats, as evidenced by reduced VCAM-1, ICAM-1, and tumor necrosis factor-α levels. Next, we treated primary cultured rat hippocampal neurons with BHF177 and the IRS-1 selective inhibitor NT157. BHF177 inhibited hippocampal apoptosis in rat hippocampal neurons by regulating the IRS-1/PI3K/Akt axis through crosstalk between GABAB and insulin-like growth factor-1 receptors. Collectively, our findings indicate that the BHF177 inhibited neuron apoptosis, thus protecting against RE through the IRS-1/PI3K/Akt axis, which may present a new therapeutic channel for RE.

Role of pilocarpine use following laser peripheral iridotomy in eyes with refractory acute angle closure glaucoma: A case report and literature review.

RATIONALE: Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG. PATIENT CONCERNS: A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours. DIAGNOSES: The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination. INTERVENTIONS: The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes. OUTCOMES: No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for >6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed. CONCLUSION: This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.

Pilocarpine 1.25% and the changing landscape of presbyopia treatment.

PURPOSE OF REVIEW: Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). RECENT FINDINGS: Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. SUMMARY: Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Treatment of pilocarpine-induced epileptic seizures in adult male mice.

Epilepsy is one of the most common neurological disorders affecting most social, economic and biological aspects of human life. Most patients with epilepsy have uncontrolled seizures and drug side effects despite the medications. Patients with epilepsy often have problems with attention, memory, and information processing speed, which may be due to seizures, underlying causes, or anticonvulsants. Therefore, improving seizure control and reducing or changing the anti-epileptic drugs can solve these problems, but these problems will not be solved in most cases. In this work, we looked at the effects of pioglitazone, a Peroxisome Proliferator-Activated Receptor agonist used to treat type 2 diabetes, on pilocarpine-induced seizures in mice. The Racine scale was used to classify pilocarpine-induced convulsions. After that, all of the animals were beheaded, and the brain and hippocampus were dissected. Finally, biochemical techniques were used to determine the levels of Malondialdehyde and Catalase activity, as well as Superoxide Dismutase and Glutathione Reductase in the hippocampus. The results of this investigation suggest that pioglitazone's antioxidant action may play a key role in its neuroprotective properties against pilocarpine-induced seizure neuronal damage.

Acute Oropharyngeal Palsy Following Bilateral Adie's Tonic Pupils Associated with Anti-GT1a and GQ1b IgG Antibodies.

A 36-year-old man was admitted to our hospital with complaints of dysphagia and photophobia. A neurological examination showed oropharyngeal palsy and bilateral mydriasis with loss of light reflexes in the absence of external ophthalmoplegia. Bilateral pupils were supersensitive to pilocarpine 0.1%, which was compatible with Adie's tonic pupils. Serum IgG reacted with GQ1b, GT1a, GalNAc-GD1a, and GD3. Intravenous high-dose immunoglobulin therapy improved his neurological symptoms within three weeks. To our knowledge, there is no medical literature describing acute oropharyngeal palsy with Adie's tonic pupils. We recommend evaluating antiganglioside antibodies to clarify the cause of oropharyngeal palsy and Adie's tonic pupils.

Topical Xerostomia Treatment with Hyaluronate Sheets Containing Pilocarpine.

Sjogren's syndrome and radiation therapy for head and neck cancers are often accompanied by xerostomia. Oral pilocarpine (PCP) to treat xerostomia produces systemic side effects, such as runny nose and lacrimation. To improve the therapeutic efficacy of PCP and reduce the aforementioned side effects, we developed a topical delivery system for PCP using freeze-dried sheets of hyaluronic acid (HA). The advantages of HA sheets over conventional oral formulations were examined through in vivo pharmacokinetic and pharmacodynamic studies after their application to oral tissues and salivary glands. The concentration of PCP in the submucosal tissue of the oral cavity was determined using the microdialysis (MD) method after buccal application of HA sheets containing PCP to hamsters. The concentration of PCP in the MD outflow was quite low after gastric administration, whereas the PCP concentration in plasma was high. In contrast, after buccal application of HA sheets containing PCP, the concentration of the drug in the MD outflow increased, despite the negligible concentration in plasma. These findings indicated that both enhancement of saliva secretion and the avoidance of systemic side effects could be achieved through buccal administration of PCP-loaded HA sheets. In addition, the pharmacodynamic study showed that when compared with intravenous and gastric administration, salivary application of HA sheets containing PCP resulted in similar volumes of saliva secretion and reduced lacrimal secretions. In conclusion, freeze-dried HA sheets allow for the development of a novel buccal delivery system with enhanced therapeutic efficacy and safety to treat xerostomia.

Neurogenic keratoconjunctivitis sicca in 34 dogs: A case series.

OBJECTIVE: To describe the clinical findings, imaging features, underlying conditions, treatment, and progression of dogs presented between 2010 and 2019 with neurogenic keratoconjunctivitis sicca (NKCS). METHODS: Dogs diagnosed with NKCS were searched in the clinical database. Inclusion criteria were STT-1 readings <15 mm/min, clinical signs of KCS with concurrent ipsilateral xeromycteria. RESULTS: Thirty-four cases were identified. Mean age at presentation was 8.2 years, median 8.9 years (0.3-14.7). Twenty dogs were male, and 14 dogs were female. Concurrent neurological deficits included facial neuropathy (n = 13, 38%), peripheral vestibular syndrome (n = 10, 29%), and Horner's syndrome (n = 5, 15%). Advanced imaging was acquired in 53% of cases (n = 18). Etiologies included idiopathic (n = 18, 53%), endocrinopathy (n = 6, 18%), otitis interna (n = 4, 12%), head trauma (n = 3, 9%), iatrogenic (post-TECA-LBO, n = 1, 3%), brainstem mass (n = 1, 3%), and an area of inflammation in the pterygopalatine fossa (n = 1, 3%). Treatment for NKCS was initiated in most cases (n = 30, 88%) including: oral pilocarpine 2% and lacrimostimulant (n = 19), oral pilocarpine 2% only (n = 3), or lacrimostimulant only (n = 8). A mean time follow-up of 3.7 months, median 3 months (1-14) was available in 23 cases (68%). Eleven cases with follow-up were responsive (48%) with resolution of the clinical signs in a median time 4 months (1-10), and all of them were treated with oral pilocarpine (±lacrimostimulant). CONCLUSIONS: Most cases presented as idiopathic NKCS; in others, an underlying cause of facial neuropathy was identified. All responsive cases were treated with oral pilocarpine 2%.