Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with persistent/recurrent macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study).

PURPOSE: To determine the efficacy of intravitreal ranibizumab 2.0 mg in patients with recalcitrant neovascular age-related macular degeneration (AMD). METHODS: This single-masked, randomized, prospective, pilot study enrolled patients with subfoveal neovascular AMD. All study eyes had persistent subretinal (SRF) or intraretinal fluid (IRF) on spectral-domain optical coherence tomography (SD-OCT) <30 days following at least 6 monthly intravitreal injections of ranibizumab or bevacizumab. Patients were randomized 2 : 1 to receive either ranibizumab 2.0 or 0.5 mg. Following three-loading treatments 4-weeks apart, both groups were treated using a 'treat and extend' regimen guided by eye-tracked SD-OCT through month 12. The primary end point was the mean change in best-corrected visual acuity (BCVA) at month 6. RESULTS: Nine eyes of 9 patients (mean age ± SD, 82.0 ± 5.8 years) were enrolled. Seven eyes received ranibizumab 2.0 mg and two eyes received 0.5 mg. Owing to the small number of patients enrolled, no statistical comparison could be made between the two dosages. At month 6, the mean improvement in BCVA was +6.1 ± 3.7 (W=0, P<0.001) ETDRS letters and +2.0 ETDRS letters in the 2.0 and 0.5 mg groups, respectively. In the 2.0 mg group, there was a statistically significant decline in central foveal thickness, SRF and maximum pigment epithelial detachment height at 6 months compared with baseline. No adverse events were reported in either group. CONCLUSION: Ranibizumab 2.0 mg has the potential to maintain or improve BCVA in some patients with persistent or recurrent SRF or IRF secondary to neovascular AMD despite prior monthly intravitreal anti-vascular endothelial growth factor therapy with the standard dose.

Intraocular pressure control after Nd:YAG laser posterior capsulotomy in eyes with glaucoma.

BACKGROUND AND OBJECTIVES: To evaluate the long-term intraocular pressure (IOP) control of glaucomatous eyes following Nd:YAG laser capsulotomy. MATERIALS AND METHODS: We performed a retrospective study of 69 glaucoma patients who underwent an Nd:YAG laser posterior capsulotomy over a 3 year period, following cataract extraction or a combined cataract-glaucoma procedure. All patients had a minimum follow-up period of at least 6 months and a median follow-up period of 2 years. We assessed IOP control, number of glaucoma medications required and whether the patient needed additional glaucoma surgery following the capsulotomy. Based on these outcome measures, we strictly defined "disease progression" as one of the following: an IOP rise of at least 5 mm Hg on two consecutive visits, addition of one or more glaucoma medications and additional glaucoma surgery following the capsulotomy. We calculated Kaplan-Meier event rate curves for these eyes with "disease progression". RESULTS: The rate of "disease progression" was 11.6% at 4 months, 20.3% at 6 months, 38.1% at 12 months, 46.1% at 24 months, 52.1% at 36 months and 52.1% at 47 months following the capsulotomy. CONCLUSION: Gradual IOP elevation or a need for more aggressive therapy is common in glaucoma patients following Nd:YAG laser posterior capsulotomy. It is unclear whether this progression is related directly to the Nd:YAG laser procedure or whether it is an independent progression of the patient's glaucoma unrelated to the Nd:YAG laser procedure.

Intravitreal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: an optical coherence tomography study.

AIM: To investigate the use of intravitreal triamcinolone acetonide (IVTA) for the treatment of diabetic macular oedema (DMO) unresponsive to previous laser photocoagulation. METHOD: A retrospective, interventional, non-comparative case series. There were 30 eyes of 22 consecutive patients with refractory DMO. An intravitreal injection of triamcinolone acetonide at the dose of 4 mg in 0.1 ml was administered. Best corrected visual acuity was measured at each examination. In addition the central macular thickness was quantitatively measured by optical coherence tomography (OCT) examination at each visit. The amount of hard exudates deposition in the macula was subjectively evaluated using colour fundus photographs. RESULTS: 30 eyes of 22 patients completed 6 months or more of follow up and were included in the study. Mean (SD) visual acuity improved from 0.17 (0.12) at baseline to 0.34 (0.18), 0.36 (0.16), and 0.31 (0.17) at the 1, 3, and 6 month follow up respectively. Mean (SD) OCT macular thickness decreased from 476 (98.32) microm at baseline to 277.46 (96.77) microm, 255.33 (95.73) microm, and 331.25 (146.76) microm at the 1, 3, and 6 month follow up period respectively. 18 and seven eyes completed 12 months and 18 months of follow up, respectively. Mean (SD) visual acuity was 0.36 (0.15) and 0.35 (0.16) at the 12 and 18 month follow up period respectively. 12 eyes received two, seven eyes received three, and two eyes received four IVTA injections. The mean (SD) interval between the first and second IVTA injection was 5.7 (2.67) months and between the second and third was 5.7 (3.25) months. Hard exudates were present in the macula at baseline in all eyes. Progressive reduction in the number and size of the hard exudates was noted after IVTA in all cases. Intraocular pressure was raised above 21 mm Hg in 12 (40%) of 30 eyes. Two eyes developed posterior subcapsular cataract and two developed vitreous haemorrhage. CONCLUSIONS: IVTA is a promising treatment for patients with DMO refractory to laser treatment. IVTA is effective in improving vision, reducing macular thickness, and inducing reabsorption of hard exudates. Further investigation is warranted to assess the safety of IVTA for the treatment of DMO.

Atypical antipsychotic use in treating adolescents and young adults with developmental disabilities.

OBJECTIVE: To study the usage, efficacy, and side effects patterns of atypical neuroleptics (atypicals) in adolescents and young adults with developmental disabilities (DDs) (mental retardation). METHOD: We undertook a chart review of adolescents and young adults (under age 25 years) seen by our specialized mental health team. RESULTS: Risperidone and olanzapine were by far the most frequently prescribed atypicals. Robust clinical effects were noted for both psychotic and nonpsychotic disorders. Most patients tolerated atypicals well, although a significant minority did experience neuroleptic induced movement disorders (NIMDs), particularly dystonias and dyskinesias. Female patients with DDs appear to be at particular risk of NIMDs. CONCLUSIONS: Atypicals are useful in treating various conditions associated with DDs. This population, however, seems particularly sensitive to NIMDs, hence caution and close monitoring are required.

A proposed simple method for measurement in the anterior chamber angle: biometric gonioscopy.

OBJECTIVE: To design a system of gonioscopy that will allow greater interobserver reliability and more clearly defined screening cutoffs for angle closure than current systems while being simple to teach and technologically appropriate for use in rural Asia, where the prevalence of angle-closure glaucoma is highest. DESIGN: Clinic-based validation and interobserver reliability trial. PARTICIPANTS: Study 1: 21 patients 18 years of age and older recruited from a university-based specialty glaucoma clinic; study 2: 32 patients 18 years of age and older recruited from the same clinic. INTERVENTION: In study 1, all participants underwent conventional gonioscopy by an experienced observer (GLS) using the Spaeth system and in the same eye also underwent Scheimpflug photography, ultrasonographic measurement of anterior chamber depth and axial length, automatic refraction, and biometric gonioscopy with measurement of the distance from iris insertion to Schwalbe's line using a reticule based in the slit-lamp ocular. In study 2, all participants underwent both conventional gonioscopy and biometric gonioscopy by an experienced gonioscopist (NGC) and a medical student with no previous training in gonioscopy (JK). MAIN OUTCOME MEASURES: Study 1: The association between biometric gonioscopy and conventional gonioscopy, Scheimpflug photography, and other factors known to correlate with the configuration of the angle. Study 2: Interobserver agreement using biometric gonioscopy compared to that obtained with conventional gonioscopy. RESULTS: In study 1, there was an independent, monotonic, statistically significant relationship between biometric gonioscopy and both Spaeth angle (P = 0.001, t test) and Spaeth insertion (P = 0.008, t test) grades. Biometric gonioscopy correctly identified six of six patients with occludable angles according to Spaeth criteria. Biometric gonioscopic grade was also significantly associated with the anterior chamber angle as measured by Scheimpflug photography (P = 0.005, t test). In study 2, the intraclass correlation coefficient between graders for biometric gonioscopy (0.97) was higher than for Spaeth angle grade (0.72) or Spaeth insertion grade (0.84). CONCLUSION: Biometric gonioscopy correlates well with other measures of the anterior chamber angle, shows a higher degree of interobserver reliability than conventional gonioscopy, and can readily be learned by an inexperienced observer.

Release of endogenous amino acids, including homocysteic acid and cysteine sulphinic acid, from rat hippocampal slices evoked by electrical stimulation of Schaffer collateral-commissural fibres.

This study examined the release of endogenous amino acids from acute hippocampal slices, upon stimulation of the Schaffer collateral-commissural fibres. One-minute samples of superfusate were collected via a cannula placed over the CA1 stratum radiatum, and were analysed by reversed-phase high performance liquid chromatography. Evoked potentials were recorded to ascertain stimulation efficacy. Four minutes of continuous 50 Hz stimulation produced a tetrodotoxin-sensitive release of aspartate and glycine in the second minute of stimulation, as well as a tetrodotoxin-sensitive release of cysteine sulphinic acid, during stimulation and of homocysteic acid, following stimulation. Such 50 Hz stimulation also produced a tetrodotoxin-insensitive decrease in methionine levels, but no significant changes in any of the other 15 amino acids measured. Four minutes of continuous 1 Hz stimulation produced no changes in the levels of any of the amino acids measured, but four 600-ms trains of 100 Hz stimulation, which, unlike the 1 Hz stimulation, produced long-term potentiation, resulted in significant increases in levels of cysteine sulphinic acid and homocysteic acid, but not of any of the other amino acids measured. These results suggest that aspartate, glycine, homocysteic acid, and cysteine sulphinic acid play a role in synaptic transmission in the Schaffer collateral-commissural fibres, and that cysteine sulphinic acid and homocysteic acid may be released specifically by high-frequency stimulation.

The effects of serotonergic compounds on evoked responses in the dentate gyrus and CA1 region of the hippocampal formation of the rat.

The effects of serotonin (5-HT), the 5-HT1A receptor subtype agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor subtype agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on electrophysiological responses in the dentate gyrus and area CA1 were examined in the in vitro hippocampal slice preparation. Superfusion of either serotonin or 8-OH-DPAT in the bath was found to inhibit population responses in a dose-dependent manner in both regions, with a greater effect in the CA1. The effects of 8-OH-DPAT in both regions were attenuated significantly by the serotonergic antagonist methysergide, as were the effects of 5-HT on the population spike in the CA1. The application of DOI did not produce statistically significant effects in either region. These findings support an inhibitory role for the 5-HT1A receptor in both area CA1 and the dentate gyrus.

Modulation of synaptic plasticity in the dentate gyrus of the rat by electrical stimulation of the median raphe nucleus.

The effects of median raphe nucleus (MRN) stimulation on the induction of long-term potentiation (LTP) was investigated in the dentate gyrus (DG) of urethane-anaesthetized rats. LTP of both DG population spike amplitude and population EPSP slope was induced when tetanic electrical stimulation (100 Hz, 1 s) of the perforant path (PP), at an intensity which did not produce significant LTP alone, was presented concurrently with tetanic stimulation of the MRN. Tetanic stimulation of either the PP alone or of the PP and MRN together did not affect the short-term enhancement of population spike amplitude produced by single stimuli to the MRN. These findings suggest that serotonergic afferents from brainstem raphe nuclei may modulate the induction of LTP in the dentate gyrus.

Increased population spike amplitude in the dentate gyrus following systemic administration of 5-hydroxytryptophan or 8-hydroxy-2-(di-n-propylamino)tetralin.

This study investigated the effects of the serotonin (5-HT)precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on population responses in the dentate gyrus evoked by perforant path stimulation. Intraperitoneal injections of either compound into urethane anesthetized rats produced a substantial increase in the amplitude of the population spike, without affecting the granular layer population EPSP. These data suggest that enhanced serotonergic tone facilitates synaptic transmission between the entorhinal cortex and dentate gyrus in vivo, and that this facilitation may be mediated by a 5-HT1A receptor.