[Anti-VEGF-therapy of fibrovascular and serous-vascularized pigment epithelial detachment in neovascular AMD : A retrospective five-year-analysis]. / Anti-VEGF-Therapie bei fibrovaskulärer und serös-vaskularisierter Pigmentepithelabhebung bei neovaskulärer AMD : Eine retrospektive Fünf-Jahres-Analyse.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is the most frequent cause of pigment epithelial detachment (PED). In the clinical routine the treatment of fibrovascular PED (fPED) and serous vascularized PED (svPED) with intravitreal vascular endothelial growth factor (VEGF) inhibitors has a restricted prognosis. OBJECTIVE: There are limited data on the long-term outcome of PED under anti-VEGF therapy. Therefore, this study recorded the course of treated PEDs in nAMD eyes over a period of 5 years. METHODS: All eyes with fPED or svPED that underwent anti-VEGF medication between 2006 and 2015 were retrospectively analyzed regarding the clinical course and the morphology seen on optical coherence tomography (OCT). The inclusion criteria were the detection of a PED on OCT, the angiographic verification of nAMD, a documented clinical history over 5 years and a good image quality. RESULTS: A total of 23 eyes from 22 patients met the inclusion criteria. After 5 years a significant deterioration of visual acuity (VA) was seen in all eyes (p = 0.007) and in the subgroup of cases with fPED (p = 0.045). In the eyes with svPED the decline of VA was not significant (p = 0.097). In the collective study group a statistically significant reduction of PED height (p = 0.006) and an increase of PED diameter was measured (p = 0.002). In the subgroup analysis the decrease of PED height and increase of PED diameter were significant for cases with svPED (p = 0.004, p = 0.013, respectively) but were not statistically significant for fPED eyes (height: p = 0.616; diameter: p = 0.097). In 17 (74%) eyes fibrosis or atrophy were seen on the final assessment of OCT images. DISCUSSION: After 5 years of anti-VEGF therapy for nAMD-associated PED the VA declined in half of the eyes and the OCT showed an unfavorable morphology in 3/4 of the cases. The average number of visits and injections was distinctly lower than in clinical trials and other real-life analyses. In summary, we observed an undertreatment with a worse functional and anatomical outcome in our clinical routine compared to other studies.

Scintigraphic comparison of budesonide deposition from two dry powder inhalers.

Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been identified as being deleterious to the environment leading to a ban on their production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One disadvantage of DPIs is that in vivo lung deposition can be influenced by the patient's inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler (AM-MDPI) has been designed to offer low resistance on inhalation, so that asthmatic patients can achieve inhaled flow rates of approximately 90 L x min(-1). The aim of the study was to evaluate the in vivo deposition of budesonide from the AM-MDPI at different flow rates and to compare this with delivery from a Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized, crossover study in which 13 healthy volunteers inhaled a single 200 microg dose of radiolabelled budesonide on four separate occasions with a minimum 44-h washout period between dosings. At the lowest flow rate of 54 L x min(-1), comparable to that for the Turbuhaler (58 L x min(-1)), a similar percentage of the metered dose was delivered to the lung (AM-MDPI median 19.9%; Turbuhaler median 21.4%). At high flow rate (peak inspiratory flow rate 99 L x min(-1)) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L x min(-1) or 54 L x min(-1) (median 25.0% and 19.9% of metered dose, respectively), thus demonstrating flow rate dependence. The pattern of regional lung deposition from the AM-MDPI was similar for all three inhalation manoeuvres. It was concluded that the ASTA Medica multi-dose dry powder inhaler achieves at least as much deposition of budesonide in the lungs as a Turbuhaler when used at similar inspiratory flow rates.

Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury.

Contrast-enhanced MRI in patients with MS shows that increased permeability of the blood-brain barrier (BBB) commonly occurs. The changes in capillary permeability often precede T2-weighted MRI evidence of tissue damage. In animal studies, intracerebral injection of the matrix metalloproteinase (MMP) 72-kDa type IV collagenase (gelatinase A) opens the BBB by disrupting the basal lamina around capillaries. Steroids affect production of endogenous MMPs and tissue inhibitors to metalloproteinases (TIMPs). To determine the role of MMP activity in BBB damage during acute exacerbations of MS, we measured MMPs in the CSF of patients with MS. Patients (n = 7) given steroids to treat an acute episode of MS had CSF sampled before and after 3 days of methylprednisolone (1 g/day). Patients had a graded neurologic examination and gadolinium-enhanced MRI before treatment. CSF studies included total protein, cell count, and a demyelinating profile. We measured levels of MMPs, urokinase-type plasminogen activator (uPA), and TIMPs by zymography, reverse zymography, and Western blots. The MMP, 92-kDa type IV collagenase (gelatinase B), fell from 216 +/- 70 before steroids to 54 +/- 26 relative lysis zone units (p < 0.046) after treatment. Similarly, uPA dropped from 3880 +/- 800 to 2655 +/- 353 (p < 0.03). Four patients with gadolinium enhancement on MRI had the most pronounced drop in gelatinase B and uPA. Western immunoblots showed an increase in a complex of gelatinase B and TIMPs after treatment, suggesting an increase in a TIMP (p < 0.05). Reverse zymography of CSF samples showed that steroids increased a TIMP with a molecular weight similar to that of mouse TIMP-3 (p = 0.053). Our results suggest that increased gelatinase B is associated with an open BBB on MRI. Steroids may improve capillary function by reducing activity of gelatinase B and uPA and increasing levels of TIMPs.