Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study.

BACKGROUND: Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after. The aim of this study is to evaluate safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops in patients with DED. METHODS: Forty consecutive patients with moderate to severe DED were included in a phase IIa, prospective, open label, multiple-dose, clinical trial to receive rhNGF eye drops at 20 µg/mL (Group 1: G1) or at 4 µg/mL (Group 2: G2) concentrations, two times a day in both eyes for 28 days (NCT02101281). The primary outcomes measures were treatment-emerged adverse events (AE), Symptoms Assessment in Dry Eye (SANDE) scale, ocular surface staining and Schirmer test. RESULTS: Of 40 included patients, 39 completed the trial. Both tested rhNGF eye drop concentrations were safe and well tolerated. Twenty-nine patients experienced at least one AE (14 in G1 and 15 in G2), of which 11 had at least 1 related AE (8 in G1 and 3 in G2). Both frequency and severity of DED symptoms and ocular surface damage showed significant improvement in both groups, while tear function improved only in G1. CONCLUSIONS: The data of this study indicate that rhNGF eye drops in both doses is safe and effective in improving symptoms and signs of DED. Randomised clinical trials are ongoing to confirm the therapeutic benefit of rhNGF in DED. TRIAL REGISTRATION NUMBER: NCT02101281.

Comparison of optical coherence tomography and high frequency ultrasound imaging in mice for the assessment of skin morphology and intradermal volumes.

Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS), two established imaging modalities in the field of dermatology, were evaluated and compared regarding their applicability for visualization of skin tissue morphology and quantification of murine intradermal structures. The accuracy and reproducibility of both methods were assessed ex vivo and in vivo using a standardized model for intradermal volumes based on injected soft tissue fillers. OCT revealed greater detail in skin morphology, allowing for detection of single layers due to the superior resolution. Volumetric data measured by OCT (7.9 ± 0.3 µl) and HFUS (7.7 ± 0.5 µl) were in good agreement and revealed a high accuracy when compared to the injected volume of 7.98 ± 0.8 µl. In vivo, OCT provided a higher precision (relative SD: 26% OCT vs. 42% HFUS) for the quantification of intradermal structures, whereas HFUS offered increased penetration depth enabling the visualization of deeper structures. A combination of both imaging technologies might be valuable for tumor assessments or other dermal pathologies in clinical settings.

Effect of intravitreal bevacizumab (Avastin) in neovascular age-related macular degeneration using a treatment regimen based on optical coherence tomography: 6- and 12-month results.

PURPOSE: To study the effect of intravitreal bevacizumab therapy on visual and anatomical outcomes in patients with neovascular age-related macular degeneration (AMD) within a follow-up period of 6 and 12 months. METHODS: A retrospective analysis of 102 eyes of 102 consecutive patients with neovascular AMD evaluated repeated intravitreal bevacizumab (1 or 2.5 mg) injections. Retreatment was performed following an optical coherence tomography (OCT)-based regimen. Ophthalmic examination included best-corrected visual acuity (BCVA), dilated fundus examination and OCT imaging. Data were analysed at baseline, 6 months (24 weeks) and 12 months (48 weeks) after treatment initiation. RESULTS: BCVA remained stable at 6 months (mean: 0.00+/-0.41 logMAR; p=0.95) and 12 months (mean: +0.02+/-0.43 logMAR; loss of approximately 1 letter; p=0.70) after the first treatment. OCT retinal thickness decreased by a mean of -37.8+/-101.6 microm (p<0.05) compared to baseline at month 6 and -38.6+/-93.3 microm (p<0.05) at month 12. A mean of 2.6+/-1.2 injections were needed to obtain absence of fluid by OCT, and the time to recurrence was 23+/-11 weeks thereafter. There was no difference in BCVA and OCT outcomes between treatment-naive eyes and eyes that had undergone prior treatment. CONCLUSION: The 6- and 12-month follow-up of repeated intravitreal bevacizumab therapy in eyes with neovascular AMD demonstrated stabilization of vision and no safety concerns. An OCT-based retreatment strategy appears appropriate in the management of patients treated with intravitreal bevacizumab.

Influence of Ginkgo biloba on ocular blood flow.

PURPOSE: To investigate the effect of Ginkgo biloba extract (EGb761) on ocular blood flow. METHODS: This randomized, double-masked, placebo-controlled, two-way crossover study included 15 healthy male volunteers. Measurements were taken with laser Doppler flowmetry, laser Doppler velocimetry, a retinal vessel analyser, laser interferometry and applanation tonometry, before and up to 3 hours after oral intake of 240 mg EGb761. RESULTS: At baseline, no significant differences in ocular and systemic haemodynamic parameters were observed between the two study days. Ginkgo biloba significantly decreased retinal venous diameters (p < 0.05 versus baseline), but there was no significant difference between the two groups. Blood pressure, retinal arterial and venous diameters, choroidal blood flow, fundus pulsation amplitude, intraocular pressure and retinal blood flow remained unchanged in both groups and did not differ between groups. Optic nerve head blood flow significantly increased in response to Ginkgo biloba (p < 0.002 versus baseline), but this effect was not significant compared with that of placebo. CONCLUSIONS: The results of this study indicate that a single administration of Ginkgo biloba does not influence ocular blood flow to a relevant degree. Whether the drug may influence ocular blood flow in patients with ocular vascular disease after longterm treatment remains to be investigated in a randomized, placebo-controlled clinical trial.