Implants for drug delivery to the posterior segment of the eye: a focus on stimuli-responsive and tunable release systems.

Efficient drug delivery to the posterior segment of the eye is a challenging task for the formulation scientist. Current treatment of chronic back-of-the-eye conditions requires frequent intravitreal injections of drug containing solutions due to the short half-life and limited tissue permeation of the administered molecules. Sustained release ocular delivery systems offering reduced administration frequencies have therefore gained popularity over recent years with a few implants already on the market and many more in the pipeline. However, current implants generally release drug at a predetermined rate without the ability to alter release rates. As required drug concentrations may change over the course of treatment due to the individual patient's clinical response, implants from which release rates can be tuned could optimize treatment efficacy. This article provides an overview of diseases of the posterior segment of the eye, describes currently available implants to treat such conditions and discusses advantages and disadvantages of various implant locations. Finally, stimuli-responsive drug delivery technologies that have been investigated for, or have the potential to be applied to, drug delivery to the back of the eye will be discussed. Emphasis is hereby placed on polymeric implants responsive to an electric current, light or a magnetic field to achieve tunable drug release.

Thoracolumbar kyphosis in treated mucopolysaccharidosis 1 (Hurler syndrome).

STUDY DESIGN: A retrospective radiographical follow-up study of thoracolumbar deformity in 33 children with mucopolysaccharidosis 1 (Hurler syndrome). OBJECTIVE: To report the severity, natural history, risk factors for progression, and results of intervention for thoracolumbar kyphosis in children with Hurler syndrome. SUMMARY OF BACKGROUND DATA: Literature on the subject of thoracolumbar kyphosis in Hurler syndrome and its treatment is limited to small case series. The natural history and thus indications for intervention are unknown. METHODS: Patients who had been treated with bone marrow transplantation and/or enzyme replacement therapy were followed up with erect radiographs of the spine. Mean follow-up period was 3.5 years (range, 2-12 yr). Radiographs were retrieved and analyzed retrospectively. Seven patients underwent varied forms of surgical intervention for progressive deformity, the technique and principles of which are described. RESULTS: The thoracolumbar kyphosis on initial radiographs obtained at a mean age of 17 months measured 38° (95% confidence interval, 34°-42°). Fifteen of the 33 patients (45%) followed for more than 2 years developed a deformity that made a progression of more than 10°. The magnitude of the initial deformity was predictive of whether the deformity progressed (univariate analysis, P < 0.001). An initial kyphosis angle greater than 45° was predictive of progression of more than 10° with sensitivity of 67% and specificity of 88%. All patients who underwent surgical intervention had sustained improvement in the magnitude of thoracolumbar deformity. CONCLUSION: Thoracolumbar kyphosis in Hurler syndrome is of variable severity with an average deformity, in our series, of 38° at a mean age of 17 months. Forty-five percent of patients developed progression of greater than 10°. Patients with an initial deformity greater than 45° seemed to be more likely to progress. Surgical interventions in the form of anterior fusion, combined anterior and posterior surgery and use of the vertical expandable prosthetic titanium rib provided good correction. LEVEL OF EVIDENCE: N/A.