Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model

There is no approved antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced “minimal” to “practically non-irritating” Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II

Importance: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). Background: Different prostaglandin analogues have been commercially approved, with differences in tolerability. Design: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. Participants: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. Methods: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. Main outcome measures: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. Results: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost ( p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. Conclusions and relevance: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy. ClinicalTrials.gov Identifier NCT02471105.

In vitro efficacy of ganciclovir against feline herpesvirus type 1 and assessment of ocular tolerability in healthy cats

Objectives Feline herpesvirus-1 (FHV-1) is a prevalent cause of ocular disease in cats and limited topical options for treatment currently exist. The first objective of this study was to confirm the efficacy of ganciclovir against FHV-1 in vitro. The second objective was to assess the safety and ocular tolerability of topically applied ganciclovir eye gel (GEG) in healthy cats. Methods FHV-1 was used to infect tissue culture wells covered in maximally confluent Crandall–Rees feline kidney cells prior to the addition of three molarities of ganciclovir (8.9 µM, 17.8 µM and 89 µM) before being incubated for 48 h. Ganciclovir efficacy in vitro was then assessed using standard plaque reduction assay. Commercially available GEG (0.15%) was applied q8h to one randomly chosen eye of four healthy cats for 7 days. Commercially available lubricating eye gel (LEG) was applied to the opposite eye q8h. Complete blood counts (CBC), blood chemistry panels (CHEM) and urinalysis (UA) were performed on all cats before and after the study period. Ocular lesions were assessed daily using a standardized scheme. Results Ganciclovir led to a significant reduction in FHV-1 plaque number, area and diameter at all tested molarities in vitro. The highest molarity assessed (89 µM) caused a 100% reduction in viral plaque number. There was no significant difference in lesion scores between eyes receiving GEG and LEG. Animals remained healthy throughout the study period with CBC, CHEM and UA showing no clinically significant alterations. Conclusions and relevance Based on the in vitro results, ganciclovir appears to be effective against FHV-1 in vitro. When applied q8h as a commercial 0.15% gel to a small group of cats with normal eyes, this medication was well tolerated. Taken together, these data suggest this medication warrants further investigation in cats with ocular disease caused by FHV-1.

BrightOcular® Cosmetic Iris Implant: A Spectrum from Tolerability to Severe Morbidity

Purpose: The BrightOcular® implants are the newest model of cosmetic iris devices that are currently advertised as safe. The previous generation known as NewColorIris® have had severe ocular side effects and were subsequently withdrawn from the market. There is little literature on the safety profile of BrightOcular® implants. Case Report: Herein we describe two cases with varying degrees of ocular tolerability. The first case had a normal ocular exam 1 year after implantation, whereas the second case had unilateral severe corneal edema requiring explantation of the iris device and Descemet membrane endothelial keratoplasty 9 months after bilateral implantation. Conclusions: These two cases attest to the unpredictability of the results of these cosmetic surgeries. Patients should be counseled about the vision-threatening complications of iris implants.

Ocular Tolerability of Preservative-Free Tafluprost and Latanoprost: in vitro and in vivo Comparative Study

Objective: Detrimental effects of the preserved prostaglandin analogs (PGAs) have been thoroughly documented in the published literature. The current work studied two preservative-free (PF) prostaglandin eye drops: PF tafluprost and PF latanoprost. The aim of the study was to compare these two PF formulations in vitro for viability of the human corneal epithelial (HCE-T) cells and in vivo for ocular tolerability of the rabbit eye. Method: Viability of the HCE-T cells was measured by the MTS assay. The SV40-immortalized HCE-T cells were exposed to 100 µL of the drug solutions (at their commercial concentrations) or the culture medium. Ocular irritation was evaluated after repeated instillation of the drug solutions in Japanese white rabbits (Kbl:JW). Results: A significant loss of HCE-T cell viability was observed in vitro immediately after the exposure to PF latanoprost formulation but not immediately after the exposure to PF tafluprost formulation. Congruently, PF latanoprost induced in vivo more irritation on the rabbit eye than PF tafluprost. Conclusion: Comparing these two PF formulations in vitro and in vivo, it is considered that ocular tolerability of PF tafluprost is better than PF latanoprost. Taking into account the composition of these two PF PGA formulations, the solubilizing agent macrogolglycerol hydroxystearate 40 (MGHS40) contained in PF latanoprost formulation is a plausible cause for the negative effects.