Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia.

Visual and retinal function was measured in a mouse model of chemically induced, sustained dyslipidemia to determine the contribution of dyslipidemia to the pathogenesis of retinopathy in the context of metabolic syndrome. Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, whereas saline was administered at the same rate to control mice using only the subcutaneous route of administration. Total cholesterol (TC) and true triglyceride (TG) levels were quantified from plasma. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal function was determined using Ganzfeld flash electroretinography (ERG). At 32 days, TC for the P-407 IP group was significantly elevated compared to saline controls (169.4 ± 16.5 mg/dl, 0.001 < P < 0.01). TG levels for both the P-407 SQ (59.3 ± 22.4 mg/dl, 0.01 < P < 0.05) and P-407 IP groups (67.7 ± 18.0 mg/dl, 0.001 < P < 0.01) were significantly elevated relative to controls. Electroretinography demonstrated a very significant decline in the b/a ratio (1.80 ± 0.11, P < 0.01) for the P-407 IP group. The b/a ratio exhibited a moderate, significant correlation with TC levels (r = - 0.4425, P = 0.0392) and a strong, very significant correlation with TG levels (r = - 0.6190, P = 0.0021). Delivery of P-407 via osmotic mini-pump resulted in the sustained, significant elevation of plasma TC and TG levels. This elevation in plasma lipid levels was correlated with a decline in inner retinal function.

Visual Field Loss in a Case of Recurrent Cystic Craniopharyngioma During Concomitant Treatment With Pegylated Interferon α-2b.

A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon α-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon α-2b was discontinued. Given the recent interest in interferon α-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery.

Visual Loss After Intraoral Local Anesthesia for the Removal of Circumzygomatic and Circum-Mandibular Wires: A Case Report.

Many types of complications occur after intraoral local anesthesia; however, visual loss is a rare one. There have been only a few case reports of visual disturbance after intraoral local anesthesia. A 67-year-old man with systemic hypertension complained of visual disturbance after a dental local injection for circumzygomatic and circum-mandibular wire removal. Forty-nine days later, he had partly recovered his vision. To date, the exact mechanism of visual loss after dental injection remains unclear. This rare case could provide another clue to the etiology and caution against similar complications.

A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain.

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Drugs with anticholinergic side-effects in primary care.

BACKGROUND: Anticholinergic drugs in elderly people have been associated with some serious side-effects. Patients in Turkey tend to attend primary care centers to have prescriptions of the drugs they chronically use. However, very little are known about how frequent that these drugs are prescribed and their side-effects in Turkish population. We aimed to investigate the usage and side-effects of drugs with anticholinergic properties in patients over 65 years of age attending to primary care centers. MATERIALS AND METHODS: Five hundred and sixty-three subjects were interviewed with a questionnaire of 16 questions inquiring their medication and possible side-effects. Timed up and go test (TUGT) and standardized mini-mental test (SMMT) were also performed. RESULTS: Medical records of 563 individuals were screened to detect anticholinergic medication. Twenty-eight patients were using anticholinergic medication. Mean duration of anticholinergic medication usage was 3.17 years. Mean number of falls occurred in the previous year was 1.14 ± 1.17. Mean SMMT score was 27.20 ± 1.13. Mean TUGT scores mean was 12.4 ± 1.25. Drowsiness in 18 patients (65%), dry mouth in 15 patients (53%), dry eyes in 15 patients (53%), constipation in 11 patients (39%), blurred vision in 11 patients (%39), urinary hesitancy in eight patients (28%), confusion in six patients (21%) were reported. We found that none of the subjects were evaluated in terms of fall risk or mental status by their doctors before the prescription of drugs with anticholinergic effects. CONCLUSIONS: A suggested approach to improve drug safety was reported as to reduce the use of anticholinergic drugs when it is possible. Psychiatrists and family physicians should select less anticholinergic drugs for medication and have to evaluate their patients' fall risk and their cognitive status before prescribing drugs with anticholinergic side effects.

Late effects in survivors of childhood CNS tumors treated on Head Start I and II protocols.

BACKGROUND: Due to the devastating late effects associated with cranial irradiation in young children with central nervous system (CNS) tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. OBJECTIVE: This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. METHODS: Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. RESULTS: Twenty-one survivors (medulloblastoma = 13, sPNET = 4, ATRT = 1, ependymoma = 3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included ≥ grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years), dental (52%; 7.1 years), and no cases of secondary leukemia. Irradiation-free (vs. irradiated) survivors reported low rates of hypothyroidism (0/10 vs. 7/11; P = 0.004) and GH deficiency (2/10 vs. 8/11; P = 0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation was associated with these scores. CONCLUSIONS: Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow-up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.

Partial vision recovery after iatrogenic retinal artery occlusion.

BACKGROUND: To describe the first case of partial vision recovery in a 32-year-old woman with iatrogenic retinal artery occlusion (RAO) following glabella calcium hydroxylapatite (CaHA) injection, and to explore appropriate diagnostic and therapeutic measures according to a literature review. CASE PRESENTATION: A 32-year-old woman had left eye RAO and a bilateral visual field defect after CaHA injection into the glabella region. Topical and systemic intraocular pressure lowering agents, isovolemic hemodilution, globe massage, and anticoagulation with acetylsalicylic acid were prescribed. Carbogen inhalation and oral corticosteroids were also given. In addition to the above therapies, hyperbaric oxygen therapy (HBOT) was implemented as adjuvant treatment. The final best corrected visual acuity (BCVA) of the left eye improved from hand motion at 15 cm to 0.1. Improved retinal circulation and decreased retinal vessel leakage were found in the follow-up fluorescein angiography. However, there were still multiple emboli in the conjunctival and retinal arteries. CONCLUSION: This is the first case report on partial recovery of BCVA after iatrogenic RAO following cosmetic CaHA injection. Because no reliable treatments have been reported for such complications, HBOT may be considered as an alternative adjuvant therapy.

Dilated pupils, dry mouth and dizziness - a case study.

A man, 44 years of age, presented with a 4 hour history of dizziness, blurred vision, dry mouth and dilated pupils. He was previously well and on no medications and there was no history of recent drug use, head injury or focal neurological symptoms. On questioning, the patient said that he had eaten lupini beans for lunch but that he hadn't had enough time to soak them for long enough before eating them. On examination his Glasgow Coma Score (GCS) was 15/15, heart rate 98 bpm, blood pressure 144/98, temperature 37.8°C and respiratory rate 18 breaths/minute. His skin was warm and dry with dry mucous membranes. His pupils were dilated at 6 mm and were nonreactive. Cardiovascular, respiratory, abdominal and neurological examinations were normal. He was unable to pass urine. Electrocardiogram showed normal sinus rhythm with a rate of 98 bpm.

Improved signs, symptoms, and quality of life associated with dry eye syndrome: hydroxypropyl cellulose ophthalmic insert patient registry.

OBJECTIVES: To evaluate the acceptability, ease of use, and efficacy of hydroxypropyl cellulose ophthalmic inserts in reducing signs and symptoms of moderate-to-severe dry eye syndrome (DES), and improving quality of life (QoL) and activities of daily living (ADL). METHODS: The multicenter, prospective, open-label, 4-week registry comprised 520 patients with bilateral DES and a history of artificial tear use, or a desire to use artificial tears within the previous week. Visit 1 encompassed a clinical evaluation and symptom and QoL questionnaires, including the Ocular Surface Disease Index. Patients were trained to use inserts, which were used once daily, thereafter, as monotherapy or with existing therapy. At visit 2, clinical evaluation and questionnaires evaluated changes in signs, symptoms, ADL, and QoL. Adverse events were monitored throughout the registry. RESULTS: There were 418 (80.4%) completers. Statistically significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity, as well as clinical signs of keratitis, conjunctival staining, and tear volume were seen (P<0.05). Mean Ocular Surface Disease Index total scores improved by 21.3% (P<0.05). Blurred vision, affecting 8.7% of patients, was the most commonly reported adverse event leading to discontinuation. CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly improved signs and symptoms of moderate-to-severe DES, as well as ADL and QoL. Benefits were additive to those seen with patients' existing care.

Ocular ischemia and ischemic oculomotor nerve palsy after vascular embolization of injectable calcium hydroxylapatite filler.

A healthy 25-year-old man who received a calcium hydroxylapatite filler injection for nose augmentation by a dermatologist suddenly developed blepharoptosis and orbital pain on the right side, associated with progressive visual disturbance of the right eye. Patchy necrosis at the nose and glabella, limitations of extraocular movements, and anterior segment ischemia, as evidenced by conjunctival injection, chemosis, corneal edema, dilated pupil, hyphema, and hypopyon, were noted. Orbital CT demonstrated linear deposits of a similar density to bone in the right medial orbit and eyelid, suggestive of multiple emboli along the conjunctival vessels. A provisional diagnosis of ocular ischemia and ischemic oculomotor nerve palsy secondary to vascular embolization was made. After 3 months, visual acuity, all intraocular inflammation, oculomotor nerve palsy, and skin necrosis resolved completely except for a dilated pupil.

Blepharoptosis following oxaliplatin administration.

Oxaliplatin is a unique platinum derivative with anti-tumor activity in a number of malignancies, with neurotoxicity being a frequent side effect. Neurotoxicity can manifest in an acute phase and a chronic phase. The acute phase usually presents as dysesthesias of the hands and feet, jaw tightness, and pharyngolaryngo-dysesthesia, triggered and exacerbated by physical contact with cold temperatures. Although various other symptoms have been reported in the literature, little details are available. We report here, in detail, a case of blepharoptosis which appeared after repeated oxaliplatin infusions, and the disappearance of which seemed to be dependent on the infusion rate.

Accidental injection with sodium hypochlorite: report of a case.

AIM: A case is reported in which sodium hypochlorite (NaOCl) was mistaken for anaesthetic solution and infiltrated into the buccal mucosa during routine root canal treatment. SUMMARY: A 1.5% sodium hypochlorite solution, kept in an anaesthetic cartridge, was inadvertently injected in the buccal mucosa of a 56-year-old female during routine root canal treatment. Soft tissue necrosis, labial ptosis and paraesthesia occurred shortly after the injection. Tissues healed with scarring and lip paraesthesia persisted for 3 years. KEY LEARNING POINTS: * NaOCl is highly irritant when introduced into oral tissues. * NaOCl solutions should not be kept in anaesthetic cartridges. * Accidents with NaOCl should be carefully assessed and when appropriate active hospital treatment should be sought. * Early recognition of NaOCl accidents may avert potentially more serious outcomes.

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.

Corneal Toxicity after Self-Application of Calotropis procera (Ushaar) Latex: Case Report and Analysis of the Active Components.

Calotropis procera (ushaar) produces a copious amount of latex, which has both inflammatory and anti-inflammatory pharmacological properties. Local application produces an intense inflammatory response and causes significant ocular morbidity. We report corneal toxicity following self-application of latex from C. procera in a 74-year-old man. He reported painless decreased vision in the affected eye with diffuse corneal edema, and specular microscopy revealed a reduced endothelial cell count. After he was treated with topical corticosteroids, his visual acuity improved from hand motion to 20/80. The composition of the active compounds in the latex was analyzed. When topically administered, the latex may cause severe ocular injuries and a loss of endothelial cells over a period of time. Public education, early recognition of such injuries, and timely intervention may prevent permanent ocular damage.

Treatment Outcome of Overactive Bladder Patients Receiving Antimuscarinic Therapy for More than One Year.

OBJECTIVES: Details on the therapeutic effects of long-term antimuscarinic therapy have not been reported. Thus, the aim of this study is to evaluate the detailed long-term therapeutic effect of antimuscarinic therapy. METHODS: All consecutive patients who visited the urologic outpatient clinics of a medical center for treatment of overactive bladder syndrome and received antimuscarinic therapy of 12 months or more were retrospectively reviewed. All medical records, including the Overactive Bladder Symptom score (OABSS), the modified Indevus Urgency Severity Scale and the International Prostate Symptoms score (IPSS) questionnaires, and uroflowmetry parameters were reviewed at each visit. RESULTS: A total of 140 patients had received 12 months or more of antimuscarinic therapy. Sustained therapeutic effects were observed by persistent decreases of IPSS-storage score, IPSS-total score and OABSS score. Moreover, the maximum flow rate did not change over time. A temporary increase in postvoid residual volume and decrease in voiding efficiency were found, but these parameters improved over long-term visits. Side-effects were observed in 81 patients (57.9%) and included dry mouth (n = 58, 41.4%), constipation (n = 48, 34.3%) and blurred vision (n = 4, 2.9%); all side-effects were tolerable. Patients aged 75 years or more (n = 94) had a higher comorbidity rate (n = 46, 48.9%) before treatment but generally exhibited similar therapeutic effects as overall patients; elderly patients could also tolerate side-effects. CONCLUSION: Sustained therapeutic effects were observed in patients who received 12 months or more of antimuscarinic therapy, even in elderly patients. In addition, side-effects in patients receiving long-term therapy were also common but tolerable.

Seeing Floaters: A Case Report and Literature Review of Intraventricular Migration of Silicone Oil Tamponade Material for Retinal Detachment.

BACKGROUND: Intraocular injection of silicone oil is commonly performed during vitrectomy to tamponade the retina in place for treatment of retinal detachment. Although rare, this intravitreal silicone can migrate through the optic nerve and chiasm and enter the cerebral ventricles. CASE DESCRIPTION: Here we present a case report of a patient presenting with headache and intraventricular hyperdensities on a computed tomography (CT) scan, raising a concern for intraventricular hemorrhage. However, the intraventricular hyperdensities were in a nondependent location and moved to a new nondependent location when repeat imaging was performed with the patient in the prone position. We provide a literature review of this phenomenon and discuss the relevant CT and magnetic resonance imaging findings. CONCLUSIONS: Intraocular silicone can rarely migrate into the cerebral ventricular system. Careful review of the clinical history and imaging findings can help distinguish this from other, more dangerous intracranial pathologies.

Linezolid-induced optic neuropathy: a mitochondrial disorder?

We report a case of bilateral mitochondrial optic neuropathies secondary to long-term linezolid treatment, show the nature of recovery, review the findings in the literature and propose a potential mitochondrial mechanism for linezolid-induced mitochondrial optic neuropathy. This is an observational case report and literature review with presentation of the clinical course of linezolid mitochondrial optic neuropathies through clinical and psychophysical documentation. Main outcome measures included: visual acuity, funduscopical examinations and peripapillary retinal nerve fibre layer (PRNFL) optical coherence tomography (OCT). A 6-year-old boy presented with bilateral optic neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the mandible. On presentation, visual acuities were 20/400 in both eyes, with considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2 weeks after the discontinuation of linezolid, visual acuities returned to 20/25 in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL swelling. 3 months after the discontinuation of linezolid treatment, visual acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL swelling confirmed by OCT, and the development of mild temporal optic disc pallor in both eyes. Doctors should be aware of impairments of vision among patients on long-term linezolid treatment and promptly discontinue treatment to prevent irreversible vision loss. The development and resolution of bilateral optic neuropathies with considerable PRNFL swelling in this patient provide insight into the more general rubric of mitochondrial optic neuropathies.

Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?

OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Transient loss of power of accommodation in 1 eye following inferior alveolar nerve block: report of 2 cases.

Unintended intravascular injection from inferior alveolar nerve blocks can result in frustrating distant complications affecting such structures as the middle ear and eyes. Possible complications affecting the eyes include blurring of vision, diplopia, mydriasis, palpebral ptosis and amaurosis (temporary or permanent). In this article, we present a complication that has been reported only rarely. Two patients developed transient loss of power of accommodation of the eye resulting in blurred vision after routine inferior alveolar nerve blocks on the ipsilateral side. Clear vision returned within 10-15 minutes after completion of the blocks. The possible explanation for this phenomenon is accidental injection into the neurovascular bundle of local anesthetic agents, which were carried via the blood to the orbital region. This resulted in paralysis of a branch of cranial nerve III, the short ciliary nerves that innervate the ciliary muscle, which controls accommodation.