Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

Patient preferences for diabetes-related complications in Taiwan

Background: As the prevalence of diabetes mellitus (DM) continues to increase rapidly, there has been a rising need not only to assess the clinical outcomes but also the impact of DM on the health-related quality of life (HRQoL) of affected individuals. Most previous studies have found that having complications is strongly associated with decreased HRQoL in DM patients. As such, it is crucial to measure individuals’ preferences for DM-related complications in order to assess the magnitude of complications’ effect on overall HRQoL. In addition, preference scores are an essential component of cost–utility analyses (CUAs), which studies can incorporate healthcare costs, HRQoL and clinical outcomes of DM into one analysis.

Objective: The aims of this study were to assess the preference scores of DM-related complications using both the standard gamble (SG), a choice-based method, and visual analogue scale (VAS), a scaling method. We also aimed to assess several possible factors that might be associated with the preference scores of the complications.

Methods: This is a cross-sectional interview-administered survey, and 213 patients with type 2?DM were interviewed. The respondents’ preference scores of eleven DM-related complications were obtained using VAS and SG techniques. Demographic information, clinical characteristics and risk attitudes were also collected to explore factors that may affect patients’ preference scores.

Results: Nearly one quarter of participants in Taiwan ranked at least one of the complications worse than death. The mean VAS scores ranged from 0.004 (amputation) to 0.47 (nocturnal hypoglycemia) while the mean adjusted SG scores ranged from 0.30 (blindness) to 0.66 (nocturnal hypoglycemia). There were significant differences in all of the complications’ preference scores depending on risk attitudes.

Conclusion: Both the VAS and SG methods were used to elicit the preference scores of DM-related complications, and the preference scores derived could be useful for future cost utility analyses.     

The need for new control strategies for particulate matter in parenterals

An undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affect patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: (1) visible particulate matter; (2) lyo-cake collapse traces; and (3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmission mode release testing since the particles may enter the interior of the lyo-cake. A theoretical explanation of the observed impurity locations is provided.     

Symptom improvement in dry eye subjects following intranasal tear neurostimulation: Results of two studies utilizing a controlled adverse environment

PurposeTo evaluate the safety and effectiveness of the intranasal tear neurostimulator (ITN) in improving dry eye symptoms assessed in a controlled adverse environment (CAE®).MethodsStudy 1: Multicenter, subject-masked, randomized-sequence, crossover design. Single intranasal (active) and extranasal (control) ITN administration during CAE exposure. Study 2: Single-arm, open-label design. Intranasal ITN administration ≥2 times/day for 45 days, CAE assessment at days 0 and 45. In both studies, upon CAE entry, and every 5 min thereafter, subjects assessed eye dryness score (visual analog scale, 0–100 mm; EDS-VAS), and ocular discomfort score (ODS; Ora Calibra™, 0–4), for ≈2 h. Study 1: when ODS was ≥3 at 2 consecutive timepoints, subjects applied ITN intranasally or extranasally for ≈3 min, and again when achieving the same ODS criteria in randomized sequence. Study 2: days 0 and 45, ITN was applied for ≈3 min employing the same ODS criteria as Study 1.ResultsStudy 1: Significantly greater pre- to post-application reductions in mean [SEM] EDS (−16.5 [1.7] vs −3.1 [1.7], P < 0.0001) and ODS (−0.93 [0.08] vs −0.34 [0.08], P < 0.0001; n = 143) with intranasal vs extranasal stimulation. Study 2: On day 0 (n = 52) and day 45 (n = 48), significant pre- to post-application reductions in mean [SEM] EDS (−15.9 [2.7] and −15.2 [2.4]; P < 0.0001), and ODS (−1.3 [0.2] and −1.3 [0.1]; P < 0.0001). Few device-related adverse events were reported, none serious.ConclusionsAcute symptom relief is significant with the ITN and remains undiminished after daily use.