CLEAR - Contact lens optics.

The most fundamental aspect of a contact lens is its optics; the manner in which the refraction of light is managed to optimise vision to the clinical benefit of the lens wearer. This report presents contemporary information on the optical structure of the eye and the optical models employed to understand the correction of refractive error. The design, measurement and clinical assessment of spherical, aspheric, toric, multifocal and myopia control contact lenses are described. The complexity and variety of multifocal lenses is recognised and detailed information is provided for alternating, simultaneous, diffractive, annular, aspheric and extended depth of field lens designs. In terms of clinical assessment, a contemporary review is provided for the measurement of: visual acuity, contrast sensitivity, through focus curves, reading performance, peripheral refraction, toric displacement realignment and patient reported outcomes. Overall, the paper aims to serve as a resource for the prescribing clinician, who can optimise contact lens corrections for patients by building on the optical rationale of these devices; and also highlights future opportunities for research innovation.

IMI - Industry Guidelines and Ethical Considerations for Myopia Control Report.

Purpose: To discuss guidelines and ethical considerations associated with the development and prescription of treatments intended for myopia control (MC). Methods: Critical review of published papers and guidance documents was undertaken, with a view to carefully considering the ethical standards associated with the investigation, development, registration, marketing, prescription, and use of MC treatments. Results: The roles and responsibilities of regulatory bodies, manufacturers, academics, eye care practitioners, and patients in the use of MC treatments are explored. Particular attention is given to the ethical considerations for deciding whether to implement a MC strategy and how to implement this within a clinical trial or practice setting. Finally, the responsibilities in marketing, support, and education required to transfer required knowledge and skills to eye care practitioners and academics are discussed. Conclusions: Undertaking MC treatment in minors creates an ethical challenge for a wide variety of stakeholders. Regulatory bodies, manufacturers, academics, and clinicians all share an ethical responsibility to ensure that the products used for MC are safe and efficacious and that patients understand the benefits and potential risks of such products. This International Myopia Institute report highlights these ethical challenges and provides stakeholders with recommendations and guidelines in the development, financial support, prescribing, and advertising of such treatments.

Bioequivalence of inhaled drugs: fundamentals, challenges and perspectives.

Interest in bioequivalence (BE) of inhaled drugs derives largely from the desire to offer generic substitutes to successful drug products. The complexity of aerosol dosage forms renders them difficult to mimic and raises questions regarding definitions of similarities and those properties that must be controlled to guarantee both the quality and the efficacy of the product. Despite a high level of enthusiasm to identify and control desirable properties there is no clear guidance, regulatory or scientific, for the variety of aerosol dosage forms, on practical measures of BE from which products can be developed. As more data on the pharmaceutical and clinical relevance of various techniques, as described in this review, become available, it is likely that a path to the demonstration of BE will become evident. In the meantime, debate on this topic will continue.

Pulmonary and nasal deposition of ketorolac tromethamine solution (SPRIX) following intranasal administration.

Ketorolac tromethamine is a racemic, non-steroidal, anti-inflammatory drug (NSAID). An intra-nasal (IN) formulation, SPRIX(®), is approved for the treatment of short term (up to 5 days) acute moderate to moderately severe pain. The primary objective of this study was to determine whether (99m)Tc-diethylenetriaminepenta acetic acid (DTPA) radiolabelled ketorolac tromethamine formulation (31.5 mg) was deposited in the lungs of healthy subjects (4 men and 9 women) following nasal inhalation of different intensities (gentle or vigorous sniff) and under different postural conditions (upright or semi-supine). The secondary objectives were to determine the deposition pattern of radiolabelled ketorolac solution in the nasal cavity and the clearance of the radiolabel over a 6h period post-administration. The nasal spray pump delivery device used showed a droplet size distribution with a volume mean diameter (VMD) of 50 µm and approximately 85% of the aerosol mass contained in droplets >10 µm diameter. The fraction of the dose recorded from the lung regions averaged <0.5%, and was considered to represent scattered radiation rather than true pulmonary deposition. This fraction was not affected by posture or by inhalation manoeuvre. The majority of the radiolabelled intranasal dose was deposited in the nasal cavity. The visual spread patterns within the nasal cavity were most uniform following administration in the upright position regardless of inhalation manoeuvre. Clearance from the nasal cavity was initially very rapid, with only 16-30% of the dose remaining after 10 min and 6-14% after 6 h. Retention was greatest following gentle inhalation.

Deposition, imaging, and clearance: what remains to be done?

Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.

International Society for Aerosols in Medicine, 17th congress, 10-14 May 2009, Monterey, California, USA.

The 17th biennial congress of the International Society for Aerosols in Medicine (ISAM) was held in Monterey, California, between 10 and 14 May 2009. The congress was attended by approximately 300 delegates from 18 countries. Podium presentations were focused on advances in pulmonary drug delivery, but clearance of materials from the lungs by a variety of processes and the potential harmful effects of inhaled particles were also covered. There were > 100 proffered posters, and a commercial exhibition in which 20 companies displayed their products. There were excellent networking opportunities, and the inauguration of more formal networking groups will allow dialogue to continue. Abstracts of podium and poster presentations were provided in the Journal of Aerosol Medicine and Pulmonary Drug Delivery, and it is likely that some of the podium presentations will appear as full papers in that journal in due course. The next conference in this series takes place in Rotterdam, The Netherlands, in June 2011.

Management of retrobulbar hematoma.

BACKGROUND: Retrobulbar hematoma (RH) is a complication that can result from both otolaryngic and ophthalmologic procedures. RH can occur during endoscopic sinus surgery and improper treatment can result in several morbidities, including visual loss. Despite serious consequences, management for RH is not well evaluated. However, lateral canthotomy with cantholysis is generally recommended. The objective of this study is to review the management for RH. METHODS: A retrospective study was performed at our tertiary hospital from 1979 to 2006 for patients with the ICD-9 code for orbital hematoma. The demographic information, comorbidities, presentation, management, follow-up period, and outcomes were evaluated. Data were analyzed. RESULTS: Twenty-two patients were identified with 13 male patients and an average age of 43 years (range, 11-80 years). The RH was broken into three categories: iatrogenic, six cases; trauma, eight cases; and spontaneous, eight cases. The most common symptom was diplopia followed by orbital pain. The average pretreatment and posttreatment tonometric pressures were 25.3 mm Hg (range, 11-60 mm Hg) and 14.5 mm Hg (range, 10-22 mm Hg), respectively. The average proptosis was 4.3 (range: 0-8) mm. Treatments were observation (13 cases), medical treatment alone (4 cases), and surgical treatment with and without medical treatment (5 cases). Sixty-eight percent of the patient's visual acuity improved with these treatments. Twenty-seven percent had no visual changes from the RH. The average follow-up was 5 years. CONCLUSION: Traditionally, lateral canthotomy with cantholysis is recommended for the treatment for RH. However, in certain patients and settings, there may be an acceptable alternative option for the management of RH.

The rejuvenated pressurised metered dose inhaler.

The pressurised metered-dose inhaler (pMDI) has now been available for 50 years. Once regarded as an inefficient and difficult-to-use device, the technology has evolved significantly over the last few years, particularly since the introduction of novel formulations containing hydrofluoroalkane (HFA) propellants. Many modern HFA pMDIs deposit drug more efficiently in the lungs, impact less forcefully on the back of the throat and feel less cold than their chlorofluorocarbon pMDI counterparts. An improved understanding of technical factors makes it possible to design HFA pMDIs to have specific spray properties, particularly in terms of fine particle dose and spray velocity. Device technology has also progressed with the introduction of compact and convenient breath-actuated, breath-coordinated and velocity-modifying devices, which help patients to achieve a reliable lung dose. Although it faces competition from dry powder inhalers and possibly from novel soft-mist inhalers containing liquid formulations, the rejuvenated HFA pMDI is a device with a significant future for asthma, chronic obstructive pulmonary disease and wider treatment indications.

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: a review.

The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CI-generated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

Respiratory Drug Delivery X. Boca Raton, FL, USA, 24-27 April 2006.

There were approximately 700 delegates who attended Respiratory Drug Delivery X (RDD-X) at the Boca Raton Resort and Club in Boca Raton, Florida, between the 24th and 27th April 2006. Participants from North America, Europe and many other parts of the world came together to hear a series of invited podium presentations covering the latest scientific developments in pulmonary and nasal drug delivery, along with regulatory and quality control issues. A total of 150 proffered posters were also presented, and a Technology Exhibition involved the products of 78 companies. The conference also provided unparalleled networking opportunities. The proceedings of RDD-X will prove to be an invaluable resource for years to come.

High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma.

OBJECTIVE: To examine the deposition and pharmacokinetics of ciclesonide administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) in patients with asthma. METHODS: Twelve patients with mild asthma (FEV1, 95% predicted) inhaled a single dose of 99mtechnetium (Tc)-ciclesonide 320 microg ex-actuator (400 microg ex-valve). Deposition of ciclesonide in the lung and oropharynx was quantified using two-dimensional (2D)-gamma scintigraphy. Three-dimensional single photon emission computed tomography (3D SPECT) was used to assess the regional distribution of ciclesonide in the lung. The pharmacokinetics of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC), were determined by liquid chromatography-tandem mass spectrometry. Ciclesonide and des-CIC concentrations were determined in mouth-rinsing solutions. RESULTS: 2D-gamma scintigraphy indicated that ciclesonide deposition was higher in the whole lung (52%) than in the oropharynx (32.9%). Furthermore, 3D SPECT revealed that ciclesonide deposition within the lungs was highest in the peripheral regions that contain the small airways and alveoli. The pharmacokinetic profile of Tc-labeled ciclesonide and des-CIC was similar to that obtained after inhalation of non-labeled formulations in previous studies. Des-CIC accounted for 14.9% of the total molar concentration of ciclesonide/des-CIC in mouth-rinsing solutions obtained between 7 and 12min after inhalation. CONCLUSION: Inhalation of ciclesonide via HFA-MDI results in high pulmonary deposition, especially in the peripheral regions of the lung. High pulmonary deposition contributes to ciclesonide's ability to maintain lung function and control symptoms in patients with asthma. Deposition and activation of ciclesonide in the oropharynx is low, consistent with previous reports of low oropharyngeal deposition and a reduced incidence of local side effects in patients receiving ciclesonide therapy.

Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler.

Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.