Aflibercept, ranibizumab and bevacizumab upcoming biosimilars: a general overview.

Anti-vascular endothelial growth factors currently are the first-line treatment option for neovascular age-related macular degeneration (nAMD) and other retinal vascular disorders, and their clinical use is associated with high financial burden. Biosimilars are a type of biological product highly similar to referral biologic drugs; they are increasing competition among biologics and have the potential to reduce the overall expenditures on biologics. In this comprehensive literature review, the current investigational biosimilars acting on retinal diseases are discussed. The authors review the results of clinical studies and highlight ongoing trials. Several biosimilar candidates are under evaluation and the pipeline will rapidly change in the future, as soon as each patent expires. Clinicians have to know these new therapeutic agents, which might come in the mainstream clinical practice as a more cost-efficient option.

Razumab -- the role of biosimilars for the treatment of retinal diseases.

Biologics targeting vascular endothelial growth factor (anti-VEGF) are the mainstay treatment of many vascular retinal pathologies. To date, Razumab is the only approved biosimilar for ophthalmic use. Razumab showed no differences compared to the innovator ranibizumab, in terms of VEGF binding activity nor in inhibition of VEGF-induced proliferation. Clinical and preclinical studies have shown a favorable efficacy and safety profile of Razumab. Nonetheless, even if clinical equivalence is expected, randomized controlled clinical trials are needed to directly compare Razumab with the innovator ranibizumab in different retinal diseases.

An update on ripasudil for the treatment of glaucoma and ocular hypertension.

Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hypertension, and several clinical trials are currently investigating its role in the treatment of Fuchs' corneal dystrophy. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.

An update on conbercept to treat wet age-related macular degeneration.

Wet age-related macular degeneration (w-AMD) represents the main cause of vision loss in the elderly in the western countries. The important role displayed by vascular endothelial growth factor (VEGF) in the pathogenesis of this disease has been largely demonstrated. For this reason, anti-VEGF drugs have been developed and currently are considered as the first-line treatment options in the management of w-AMD. Among the novel anti-VEGF agents studied, conbercept is a fusion protein composed of the combination between VEGF receptor domains with the Fc fragment of human immunoglobulin. It was already approved in China in 2014 for treating w-AMD. In this regard, the phase III PHOENIX trial has reported a good clinical efficacy and safety profile of conbercept for w-AMD, also by adopting a quarterly regimen. In this review, we will discuss its pharmacokinetics, pharmacodynamics, clinical efficacy, without neglecting also its safety and tolerability profile.

Omidenepag isopropyl for the treatment of glaucoma and ocular hypertension.

Glaucoma is a main cause of irreversible vision impairment and its prevalence is expected to rise significantly in the near future. Among the current medications, prostaglandin analogues (PGAs) are widely used and considered as a first-line strategy in the management of glaucoma and ocular hypertension (OHT). However, given the non-negligible incidence of adverse ocular effects (conjunctival hyperemia, increase of iris pigmentation and eyelash changes) due to the use of this class of drugs, novel PGAs are being investigated. Omidenepag isopropyl is a selective prostaglandin EP2 receptor agonist which was approved on September 21, 2018, in Japan for the treatment of glaucoma and OHT. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.

Clinical evaluation of BrainTree, a motor imagery hybrid BCI speller.

OBJECTIVE: While brain-computer interfaces (BCIs) for communication have reached considerable technical maturity, there is still a great need for state-of-the-art evaluation by the end-users outside laboratory environments. To achieve this primary objective, it is necessary to augment a BCI with a series of components that allow end-users to type text effectively. APPROACH: This work presents the clinical evaluation of a motor imagery (MI) BCI text-speller, called BrainTree, by six severely disabled end-users and ten able-bodied users. Additionally, we define a generic model of code-based BCI applications, which serves as an analytical tool for evaluation and design. MAIN RESULTS: We show that all users achieved remarkable usability and efficiency outcomes in spelling. Furthermore, our model-based analysis highlights the added value of human-computer interaction techniques and hybrid BCI error-handling mechanisms, and reveals the effects of BCI performances on usability and efficiency in code-based applications. SIGNIFICANCE: This study demonstrates the usability potential of code-based MI spellers, with BrainTree being the first to be evaluated by a substantial number of end-users, establishing them as a viable, competitive alternative to other popular BCI spellers. Another major outcome of our model-based analysis is the derivation of a 80% minimum command accuracy requirement for successful code-based application control, revising upwards previous estimates attempted in the literature.

[Further information on fish parasites from Lake Trasimeno. II. Observations on the population of Scardinius erythrophthalmus L]. / Aggiornamento sui parassiti della fauna ittica del lago Trasimeno. Nota II. Osservazioni sulla popolazione di Scardinius erythrophthalmus L.

An investigation was carried out to identify the actual state of parasitism in the Scardinius erythrophthalmus L. population of Trasimeno lake (Umbria, Italy). Seasonal samples of fishes were taken in different points of the litoral and pelagic zones. The parasites found, together with the somatometric values and the characteristics of their localizations are reported. It has been found: a high number of infested specimens; eleven species of parasites, of which five were not yet known to be in the lake; frequency variations of certain species. The species of parasites observed are distributed in the Paleartic region. The five species, whose presence was not known in the lake, are considered to be allochtonous. The organs most frequently involved were, in descending order, the gills, the ureters, the gonads, the intestinal and mesenteric serous membranes, the liver. The most marked histologic alterations and reactions were observed as a consequence of Ergasilus sieboldi Nord. action and, in several cases, with the presence of Ligula intestinalis L. larvae.

[Current state of fish parasites in lake Trasimeno. I. Observations on the Tinca tinca L. population]. / Aggiornamento sui parassiti della fauna ittica del lago Trasimeno. Nota I. Osservazioni sulla popolazione di Tinca tince L.

An investigation was carried out to identify the actual state of parasitism in the Tinca tinca population of Trasimeno lake (Umbria, Italy). It has been found: a high number of infested specimens, eleven species of parasites, of which four were not yet known to be in the lake, frequency variations of certain species, the absence of others that in the past were present. The species of parasites observed are, in various ways, distributed in the Paleartic region. Some are considered to be of allochthonous origin. The organs most frequently involved were the gills and the ureters followed by the intestine and the liver.

[Parasites of fish in the Chiascio river]. / I parassiti della fauna ittica del fiume Chiascio.

An investigation was carried out to identify the fish parasites in the Chiascio River (Umbria, Italy). Certain physical-chemical factors and the biochemical oxygen demand of the river water were, also, studied in samples taken seasonally. The parasites found, together with the fish species they invested and the organs and apparatuses involved, are listed. The species of parasites observed are, in various degrees, diffused in the Palaearctic region. Some are considered to be of allochthonous origin. The fish species with the highest parasite infestation were, in descending order, Rutilus rubilio, Cyprinus carpio, Leuciscus cephalus cabeda and Barbus plebejus. The organs and apparatuses most frequently involved were the gills, the intestines and the skin.