bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo evaluation of corneal biomechanics in clinical practice; why, when and how?
Authors: Rechichi Miguel 
Published: December 2022

AbstractThe study of corneal biomechanics in vivo has been evolving fast in recent years. While an organized corneal structure is necessary for its transparency, resistance to occasional external insults and bearing the intraocular pressure (IOP), which several clinically relevant events can disturb.While significant technological advances have been made for the detection of morphologic markers of keratoconus, these findings are of later sequalae of the disease. Keratoconus is thought to begin with a focal biomechanical weakening of the cornea, followed by a cycle of decompensation resulting in corneal thinning and increased curvature [39, 40]. With the increasing number of corneal refractive surgeries being performed, the identification of the earliest form of the disease, before any morphologic changes have occurred, has become of paramount importance. This has led to efforts directed at measuring the in vivo biomechanical properties of the cornea.I will speak about techniques currently available for clinical use.The principles will be discussed along with their strategies to improve accuracy in the IOP measurement, corneal ectasia diagnosis, evaluation of corneal cross‐linking procedures, and planning of corneal refractive surgeries.
Biomechanical profile of refractive procedures; is there a biomechanical privilege?
Authors: Balidis Miltos 
Published: December 2022

AbstractThe cornea shows regional in‐plane variation in strain and deformation. Paracentral and peripheral cornea is stiffer than the central cornea due to differing orientation and number of collagen fibrils. Corneal elastic strength is a function of depth, with decreasing strength from the anterior to the posterior stroma.During central myopic ablation, an immediate circumferential severing of corneal lamellae is produced. resulting in a forward herniation. Additionally central ablation also relaxes lamellar tension in residual peripheral lamellar segments, which decreases local resistance to swelling leading to peripheral stromal thickening. Expansion of the peripheral stroma may generate centripetal stress in underlying lamellae through dense interlamellar connections at the margin of the ablation zone, resulting central flattening.Empirically, the hyperopic response is dominant when ablation is limited to the anterior stroma, and progressively deeper circumferential insults result in a shift towards corneal steepening. Central flattening response augments the effects of a myopic procedure but impedes efforts to correct hyperopia.
Preservatives, generics and ocular surface
Authors: Kolko Miriam 
Published: December 2022

AbstractMost eye drops sold in many European countries are generic. While one would expect generic drugs to be a true copy of the original eye drop, there are surprisingly few requirements for the introduction of a copy eye drop on the market. Thus, only the concentration of the active ingredients should be identical to the concentration of the original product. Since many other factors such as bottle material, bottle shape and size and lid colour, droplet size, pH, viscosity, buffer capacity can affect the effect, there is concern about whether generics are identical to their original variants. In addition to the few requirements for the introduction of generic drugs, the replacement of preservatives in eye drops with the same active substance is legal. In general, preservatives have a negative effect on the surface of the eye due to their toxic effect on, among other things, the ocular surface cells and on the tear film. Here, a brief overview of the concerns and facts about generics and the use of preservatives in eye drops will be given.
IOP measurement in abnormal corneas
Authors: Grieshaber Matthias 
Published: December 2022

AbstractElevated intraocular pressure still the major surrogate and risk factor for development and progression of glaucoma. For decades the Goldmann applanation tonometry has been the gold standard for measuring intraocular pressure; however, there are newer methods of measuring intraocular pressure, each one has advantages and disadvantages and depends on the corneal biomechanics parameters. This talk will focus on the different methods and their limitations with regard to measuring intraocular pressure in abnormal corneas.
Development of 3D‐printed devices for the study of transscleral drug delivery on freshly excised whole porcine eyes
Authors: González‐Fernández Felipe M. , Cauzzi Daniele A. , Nicoli Sara , Gasco Paolo , Pescina Silvia 
Published: December 2022

AbstractPurpose: Ex vivo ocular models are a valuable tool for quick screening ophthalmic formulations through permeation and retention studies. We hereby present a 3D‐printed set‐up consisting of a combination of two devices, allowing for the ex vivo study of transscleral drug delivery with fresh whole swine eyes.Methods: The two devices were drafted on a CAD (computer aided design) software and 3D printed with three different printing techniques: selective laser sintering (SLS), fused deposition modelling (FDM) and masked stereolithography (MSLA). The first device was designed to guarantee the contact between drug formulation (liquid or semisolid) and the scleral surface in a defined permeation area for up to 24 h. The second device was then designed to maintain up to three ocular bulbs at constant temperature (37°C) and humidity values.Results: MSLA 3D printing technique was selected due to its versatility, superior print detail and a low unitary cost. In addition, the other two explored techniques delivered relatively porous prints that do not guarantee the required water and air tightness of the devices. The first device was optimized in order to maximize adherence onto the scleral surface and thus anatomically adjusted to porcine scleral curvature. Firm anchorage onto the ocular surface was achieved through a ring‐shaped vacuum chamber easily controlled with a syringe. The second device allowed to immobilize the ocular bulb during the experiment, preserve ocular hydration, and maintain a fixed working temperature by placement into a water bath.Conclusions: The developed ex vivo set‐up, based on the whole porcine eye, could be suitable to perform permeation and accumulation studies of transscleral applied ocular formulations.
In vivo identification of Schlemm's canal and response to SLT
Authors: Gupta Shikha 
Published: December 2022

AbstractASOCT has been used to demonstrate a lack of Schlemm's canal (SC) or its dysgenesis in many Primary Congenital Glaucoma (PCG) eyes, and nearly half of Juvenile Open Angle Glaucoma (JOAG) eyes. There is an increasing evidence that even in adult‐onset POAG, apart from the trabecular meshwork (TM), the post TM structures like the SC and collector channels are also affected which may contribute to the outflow resistance. Absence or dysgenesis of the SC is expected to be associated with a poor outflow facility.We evaluated the response of Selective laser trabeculoplasty (SLT) and correlated the visibility of SC on ASOCT in eyes with JOAG. This is because we had previously observed that only 40% of patients diagnosed with JOAG respond to SLT. In this study, we observed that detection of SC on ASOCT among patients undergoing SLT, (even without having evident angle dysgenesis on gonioscopy) was a significant predictor deciding the response to SLT. Success of SLT was defined as a reduction of IOP by 20% or more from pre‐laser value at 6‐months follow‐up without any further IOP‐lowering medication or surgery. A successful reduction in IOP at six‐month follow‐up was correlated with the extent of angle dysgenesis on ASOCT (ADoA).We observed that presence of SC was associated with 8.3 times greater chances of success of SLT than its absence. Also if the presence of SC was detected in >50% ASOCT scans in one eye, it was associated with 21.4 times greater chances of SLT success (p = 0.009). Hence in vivo imaging of the angle is a non‐invasive method of detecting angle dysgenesis, in the absence of an apparent goniodysgenesis. It may help in selecting potential candidates for SLT (or other angle based surgeries) by predicting possible outcome and thus providing more realistic expectations when advising patients, regarding the likelihood of success /failure of their treatment.
In vivo identification of angle dysgenesis
Authors: Mahalingam Kathikeyan 
Published: December 2022

AbstractAnterior segment Spectral domain–optical coherence tomography (SD‐OCT) is being increasingly used in glaucoma patients, primarily to investigate the anterior chamber angle and visualize the trabecular meshwork (TM) and Schlemm's canal (SC) in vivo. With the advent of angle surgery for glaucoma much interest has been generated in the aqueous outflow pathways. Our studies have shown that in vivo imaging of anterior chamber angle with ASOCT can been used to detect gross features of angle dysgenesis in primary congenital glaucoma (PCG), juvenile onset open angle glaucoma (JOAG) and adult onset primary open angle glaucoma (POAG), which has been described either as an absence of SC and/or the presence of abnormal tissue or a hyper‐reflective membrane within angle recess. This membrane is similar to what Barkan had described in PCG and was later described to be an angle cicatrization that portends a poorer success with goniotomy. Absence of development of SC was also shown by Hollander et al to be associated with a severe form of goniodysgenesis while its presence was seen in less severe goniodysgenesis on histopathological studies involving PCG. In fact, angle dysgenesis on ASOCT (ADoA), can be observed even in eyes with gonioscopically normal appearing angles. It is known that gonioscopy provides only a superficial representation of the histopathological anomalies affecting the angle. The presence of a thick compact tissue in the TM samples of Juvenile glaucoma patients has been observed, irrespective of whether they had an apparent goniodysgenesis or not. Hence, what appears to be morphologically normal angle on gonioscopy may harbour dysgenesis of the TM or even the SC. Primary congenital glaucoma, JOAG and adult onset POAG form a spectrum in terms of severity of angle dysgenesis. While most of the PCG eyes have features of ADoA, the same are present in 40% of JOAG eyes and in up to 35% of adult onset POAG. The size of the SC has also shown to be decreased in patients with adult‐onset open angle glaucoma based on in vivo OCT studies. We also present interesting observations of angle dysgenesis in fellow eyes of children with unilateral PCG.
Ocular surgical use of autologous platelet‐rich plasma
Authors: Rodriguez Alejandra E. 
Published: December 2022

AbstractEye platelet‐rich plasma (E‐PRP) concentrates platelets in a small volume of plasma which contains a high concentration of important growth factors and cell adhesion molecules. These cell adhesion molecules and growth factors occupy a major role in wound healing and enhance the physiological procedure at the site of the injury or the surgery. Platelet‐rich plasma in the form obtained in ophthalmology, E‐PRP, is a reliable and effective surgical coadjuvant to promote corneal wound healing in severe corneal ulcers and corneal perforations and may be associated with other ocular surface reconstruction procedures.Actually, platelet‐rich plasma (E‐PRP) offers new surgical perspectives in many fields of medicine helping in wound healing, it represents a greater similarity to the natural healing process as a composite of multiple growth factors, is safe due to its autologous nature and has both mitogenic and chemotactic properties. E‐PRP functions as a drug delivery system and a tissue sealant.The α‐granules within these platelets liberate platelet‐derived growth factors, platelet‐derived growth factor BB (PDGF‐BB), transforming growth factor β1 (TGF‐β1), epidermal growth factor (EGF), and vascular endothelial growth factor A (VEGF‐A) which have an important anti‐inflammatory action. It has many ocular surface applications such as in dry eye, dormant corneal ulcers, and it is also used surgically as a sutured clot of autologous fibrin membrane in big neurotrophic corneal ulcers or imminent/already perforated eyes.There are new uses of E‐PRP such as the intracameral application of E‐PRP for different purposes or injection into the lacrimal glands. All of them with the aim of improving the functionality of damaged eye tissue.
A novel approach of increasing bioavailability of drug molecules to the posterior ocular segment through topical administration using penetration enhancing agents
Authors: Thareja Abhinav , Leigh Thomas , Hakkarainen Jenni J. , Alvarez‐Lorenzo Carmen , Hughes Helen , Fernandez‐Trillo Francisco , Blanch Richard J. , Ahmed Zubair 
Published: December 2022

AbstractA major cause of blindness worldwide is disease and damage in the posterior ocular segment. Due to poor penetration of therapeutic molecules, topical eye drops tend to be the least effective. We demonstrate a potential approach of penetration enhancement in topical drug formulations for such diseases using three penetration enhancing agents (PEAs) — an in‐house synthesized novel helical polymer and two commonly used cell penetrating peptides (CPPs), TAT and Penetratin, to enable increased penetration of the most commonly used anti‐inflammatory drug, dexamethasone sodium phosphate (DSP). A rapid and cost‐effective ex‐vivo screening model of excised porcine cornea and sclera is used to assay trans‐corneal/scleral penetration of the three PEAs and results quantified using UV & fluorescence spectroscopy for PEAs and by high performance liquid chromatography (HPLC) for DSP. All three PEAs effectively cross both the cornea and sclera individually. A significant enhancement of DSP trans‐corneal/scleral permeation after topical application with PEAs is observed. ZO‐1 immunostaining of the tight junctions in corneal epithelium demonstrated intact tight junctions and transepithelial electrical resistance (TEER) measurements of the corneal epithelium before and 60 minutes after application show very negligible to no difference, thus proving no damage has been done to the integrity of corneal barrier and barrier function. Finally, in‐vitro cytotoxicity of PEAs was determined using MTT assays in ARPE‐19 and HCE‐2 cells, whilst immunostaining with β‐III tubulin was used in assays involving adult rat primary retinal neurons. None of the PEAs exhibit any trace of cytotoxicity. We conclude that CPPs are able to increases the efficiency of drug delivery through the cornea and improve the chances of drug delivery to the posterior ocular segment.
Restoring vision in blind patients: From optogenetic to sonogenetic therapies
Authors: Picaud Serge 
Published: December 2022

AbstractVisual restoration is certainly the greatest challenge for brain‐machine interfaces with the high pixel number and high refreshing rate. In the recent year, we brought retinal prostheses and optogenetic therapy up to successful clinical trials. Optogenetics relies on the expression of a microbial opsin in residual neurons by gene therapy. These strategies can provide some vision in blind patients with diseases of photoreceptors such as retinal dystrophies or age‐related macular degeneration. They can reintroduce some information in at the retinal level by activating residual neurons after the loss of photoreceptors. For patients with optic nerve atrophy as in glaucoma and diabetic retinopathy, visual restoration requires the direct activation of the visual cortex. However, cortical prostheses have shown efficacy for limited periods of time and limited pixel numbers.In the present project, we are investigating a novel approach to restore vision at the cortical level with sonogenetic therapy. This approach relies on expressing an ultrasound‐sensitive ionic channel in cortical neurons to imprint images at this level by ultrasound stimulations.The Mscl ionic channel fused to the tdTomato reporter gene was expressed in the visual cortex of rats following a cortical AAV injection. The channel expression was indicated by the red fluorescence of tdTomato. Recording with penetrating electrodes indicated responses to cortical ultrasound stimulation with a high temporal resolution but a shorter latency than natural visual responses. In the absence of AAV injection, the visual cortex was not responsive to ultrasounds. Moving the ultrasound stimulator moved the activated area as indicated by Ecog electrode array recording. Finally, mice having learned to associate a flash of light to a water delivery responded similarly to an ultrasound cortical stimulation if the MscL protein was expressed in their cortex.These results indicate that the MscL channel induces an ultrasound sensitivity of cortical neurons generating a cortical activations with a spatiotemporal resolution suitable for vision restoration and perceived as phosphenes. Further studies will have to demonstrate true vision of forms by this sonogenetic approach prior to a clinical translation.
Immunomodulation for retinal degenerations
Authors: Langmann Thomas 
Published: December 2022

AbstractThis talk highlights the role of key immune pathways in the pathophysiology of major retinal degenerative diseases including age‐related macular degeneration. We will first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced immune reaction involving responses of local microglia and recruited macrophages. Presenting these innate immune cells as targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, intracellular regulators involved in the activation of microglia and more general modifiers of their inflammatory response and migration. We briefly summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years.
Neuroprotective effects of intraocular bone marrow‐derived mononuclear cell transplants in inherited retinal degenerations
Authors: Di Pierdomenico Johnny , Ayuso Diego Garcia , Sanz Manuel Vidal , Perez Maria Paz Villegas 
Published: December 2022

AbstractInherited retinal degenerations are diseases characterized by photoreceptor loss secondary to genetic defects. At present, only a minority are susceptible of genetic treatment and therefore are a frequent cause of blindness in infancy and adulthood.Retinitis Pigmentosa (RP) is the most frequent inherited retinal degeneration. This disease has a prevalence of around 1 in 4000 individuals and is caused by mutations in more than 300 genes. RP is characterized by progressive loss of photoreceptors, rods and then cones that may die secondarily to rod loss.The rats P23H and Royal college of Surgeon (RCS) are two well characterized animal models of RP because they bear genetic defects observed in RP patients. The P23H rat suffers an autosomal dominant mutation of the rhodopsin gene that causes protein misfolding and endoplasmic reticulum stress in rods, which die first followed by cones. The RCS rat has a mutation of MERTK gene, that impedes the normal photoreceptor outer segment phagocytosis by RPE cells thus causing simultaneous rod and cone degeneration.Therapies for inherited photoreceptor degeneration aim to prevent or delay death of the photoreceptors, or in specific circumstances try to replace them.The Bone marrow derived‐mononuclear cells (BM‐MNCs) are a mononuclear CD34+ subpopulation of bone marrow‐derived cells that can be separated from the other cellular fractions of the bone marrow aspirate using a Ficoll density gradient‐based protocol. The BM‐MNCs is a mixture of specific bone marrow cell subtypes in which is possible to find cells: Lin+, Lin−, CD34+, c‐Kit+, CD133+ or Sca‐1+ HSCs, endothelial precursor cells, and Mesenchymal Stem Cells.BM‐MNCs transplantation has shown promising results in different animal models of neuronal degeneration, including inherited photoreceptor degenerations.In our studies we have performed a syngeneic intravitreal or subretinal transplantation of BM‐MNCs in a P23H‐1 and RCS rats, and we have documented that both increase photoreceptor survival. They also improve the morphology of the photoreceptors outer segment, decrease synaptic degeneration in the outer plexiform layer and reduce glial fibrillary acidic protein (GFAP) expression in Müller cells. However, the transplanted cells did not penetrate the retina, only survived for up to 15 days, and did not modify microglial cell activation and migration or the electroretinographic responses. Their beneficial effects are maybe due to a paracrine trophic effect achieved through release of neurotrophic, anti‐angiogenic and/or immunomodulatory factors.In conclusion, the intra ocular transplantation BM‐MNCs shows photoreceptor neuroprotective actions in inherited retinal degenerations. These cells may have the potential to slow down photoreceptor loss, and therefore could be indicated for treatment of the early stages of photoreceptor degenerations.
Pharmacological strategies in retinal dystrophies
Authors: Maneu Victoria 
Published: December 2022

AbstractThe therapeutic options for a patient affected by a retinal degenerative disease are discouraging. Despite several clinical trials show promising results, we still need to go a long way until the arrival to the clinics of therapies that could partially restore the retinal functionality, as optogenetics, or stem cell transplant, or, even better, that cure the disease by targeting its aetiology, as gene therapy. Until these therapies reach clinical success, targeting key factors in the degenerative process could temporarily slow its progression. Although there are many different retinal degenerative diseases, with different aetiology and clinical evolution, the degenerative process is always accompanied by common biochemical and molecular factors, it does not matter if the degeneration has a genetic cause, as it happens in inherited retinal dystrophies as retinitis pigmentosa, Leber congenital amaurosis or Stargardt disease; or if it is a multifactorial disease as age‐related macular degeneration; or if it is secondary to other pathologies, as diabetic retinopathy. The high metabolic rate of the retinal cells, their continuous exposition to high oxygen levels and light‐induced stress are key factors in the development of the degenerative process. When retinal cells start to die, activated glial cells secrete proinflammatory cytokines, chemokines and trophic factors that worsen the degenerative process. Thus, trying to reduce the oxidative stress and inflammation that are always present in the degenerating tissue seems a good approach to be tried. Moreover, considering the great number of mediators involved in the degenerative process, a widest approach combining therapies with antioxidant, anti‐inflammatory and antiapoptotic molecules, as well as neurotrophic factors could slow the progression of the disease and preserve the visual capacity for a certain time. Moreover, even when the vision has been completely lost, the neuroprotection could improve other non‐visual functions, like the control of circadian rhythms and pupil contraction and could also influence the patient's memory and mood. It is also relevant to note that this therapy can keep a healthy tissue and provide an adequate environment of healthy cells that will help to the clinical success of other techniques as cell transplant or optogenetic approaches, which could hardly be successful in a damaged tissue surrounded by dying cells.Supported by: Spanish Ministry of Science and Innovation (MICINN‐FEDER PID2019‐106230RB‐I00) Generalitat Valenciana (PROMETEO/2021/024).