Therapy In Ophthalmology Research Articles

Mesenchymal stem cell therapy in veterinary ophthalmology: clinical evidence and prospects.

Mesenchymal stem cell (MSC) therapy presents a promising strategy for treating various ocular conditions in veterinary medicine. This review explores the therapeutic potential of MSCs in managing corneal ulcers, immune-mediated keratitis, chronic superficial keratitis, keratoconjunctivitis sicca, retinal degeneration, and ocular burns in feline, equine, and canine patients. Studies have demonstrated the immunomodulatory and regenerative properties of MSCs, highlighting their ability to mitigate inflammation and promote tissue regeneration. Experimental studies have shown the potential of MSC therapy in reducing corneal opacity and vascularization, indicating significant therapeutic advantages. Delivery methods play a crucial role in optimizing the therapeutic efficacy of MSCs in ocular diseases. Various delivery methods, such as intravitreal injection, subconjunctival injection, topical administration, and scaffold-mediated delivery, are being explored to optimize MSC delivery to the target ocular tissues. Clinical trials have shown significant improvements in clinical signs following MSC therapy, underscoring its efficacy in treating ocular diseases. Additionally, tissue engineering approaches incorporating MSCs, growth factors, and scaffolds offer innovative strategies for corneal regeneration and tissue repair. Despite challenges such as standardization of protocols and long-term safety assessment, ongoing research endeavours seek to unlock the full therapeutic potential of MSC therapy in ocular diseases. Future prospects in MSC therapy involve exploring scaffold and hydrogel-based approaches and cell-free therapies leveraging the bioactive molecules released by MSCs. Continued research and development efforts are essential to unlock the full therapeutic potential of MSCs and realize their transformative impact on ocular diseases in veterinary patients.

The effect of intravitreal antiangiogenic diabetic macular edema treatment on the corneal endothelium cell count

BACKGROUND: Antiangiogenic treatment of diabetic macular edema is a first-line therapy in modern ophthalmology. Novel antiangiogenic drugs are increasingly being developed to improve treatment results and solve certain issues. However, owing to the advent of new drugs, more questions arise about their effect on the patient’s retina and other structures of the eye, such as the cornea. AIM: The study aimed to investigate the effect of intravitreal administration of the anti-VEGF drug brolucizumab on the corneal endothelium in patients with diabetic macular edema. METHODS: 106 patients (106 eyes) were included in the prospective study: 31 men and 75 women. The main group consisted of 56 patients (56 eyes) were included in the prospective study: 14 men and 42 women with different stages of diabetic retinopathy with diabetic macular edema, the average age of patients was 62.2±8.4 years. The average number of endothelial cells per 1 mm2 in these patients before the loading dose of brolucizumab was 2378.9±393.3 cl/mm2. The control group included 50 patients (50 eyes) without diabetes who did not receive intravitreal injections or any other surgical interventions on the examined eye for 1 year. All patients underwent endothelial microscopy using the Tomey EM-4000 endothelial microscope (REN 2017/6294), estimated: CD (the number of endothelial cells per 1 mm2); CCT (the central thickness of the cornea, microns); CV (the coefficient of variation, %); 6A (the proportion of hexagonal cells, %). All study participants received intravitreal injections of brolucizumab in a volume of 0.05 ml (5 injections with an interval of 6 weeks). RESULTS: In the main group before intravitreal injections, the indices of the central corneal thickness and the number of endothelial cells per 1 mm2 were 549.7±30.1 microns and 2378.9±393.3 cells/mm2, respectively. After a course of antiangiogenic diabetic macular edema therapy, the central thickness of the cornea was 548.2±30.6 microns, and the number of endothelial cells per 1 mm2 was 2382.3±424.9 cells/mm2. The indicators CV (coefficient of variability, %) and 6A (proportion of hexagonal cells, %) before the start of intravitreal injections were 36.9±5% and 46.8±6.3%, respectively, after the introduction of the loading dose drugs, the average values were 37.9±4.3% and 45.8±6.3%. Changes in all indicators were not static significant. CONCLUSION: The use of brolucizumab as therapy in patients with diabetic macular edema did not cause a negative effect on the cornea, there were no statistically significant changes in the central thickness of the cornea, the number of endothelial cells per 1 mm2, the coefficient of variation and the proportion of hexagonal cells.

Adverse events associated with chimeric antigen receptor T-cell therapy in ophthalmology: a narrative review.

Chimeric antigen receptors are synthetically produced receptors engineered to engage with target cells with high specificity. These cells are created by inserting an artificial T-cell receptor into an immunoglobulin's antigen-binding region, allowing the cells to combine and target specific antigens. The use of chimeric antigen receptor (CAR) T-cell therapy has been a remarkable achievement in the field of immunotherapy, particularly in the treatment of ophthalmic tumors like retinoblastoma and uveal melanoma. However, there are some documented side effects, such as cytokine release syndrome (CRS) and immunological effector cell-associated neurotoxicity syndrome (ICANS). Additionally, ocular side effects such as blurred vision, vision impairment, and intraocular infections are also concerning and require further evaluation. This review highlights the advances made in chimeric antigen receptor (CAR) immunotherapy, including its structure and manufacture, as well as relevant clinical discoveries and associated adverse effects. By identifying the gaps in current research, this analysis provides insights into potential strategies and solutions for addressing some of the most severe side effects.

Methods, Therapeutic Applications, and Effects of Low-Level Laser Therapy in Ophthalmology

Methods, Therapeutic Applications, and Effects of Low-Level Laser Therapy in Ophthalmology

Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

“Dirty Dry Eye”– A waste volume analysis from topical therapy in keratoconjunctivitis sicca

PurposeThe healthcare system is responsible for around 5% of CO2 emissions globally and in Germany. So far, there are no data on the amount of waste from dry eye disease (DED) therapy in ophthalmology. The aim of this project was to evaluate the amount and type of waste from single- and multi-dose units (SDU/MDU) generated by eyedrops used to treat DED in Germany.MethodsThe net waste weight (outer/inner packaging, instruction leaflet, empty container) from factory-sealed products was determined using a precision scale. Based on prescription data from PharMaAnalyst, a database of medical prescriptions from over 70 million patients in Germany, the total annual waste volume for 2016–2021 and the net weight of a 30-day treatment were calculated.ResultsThe total annual waste volume increased significantly (p < 0.0001) from 7.13 tons in 2016 to 20.64 tons in 2021. A 30-day treatment with MDUs (without/with filter) results in a significantly lower mean waste volume (paper: SDU 24.3 ± 18.7 g; MDU 4.8 ± 1.7 g/8.8 g ± 1.7 g; SDU/MDU p = 0.0003, with filter p = 0.0034; plastic: SDU 35.0 ± 4.0, MDU 6.6 ± 0.7 g/ 15.1 g ± 5.8 g, SDU/MDU p < 0.0001, with filter p < 0.0001).ConclusionPrescription-based treatment of DED in Germany causes an increasing and substantial waste volume. The use of SDUs is considerably more resource-intensive than MDUs. Due to the large and rising number of patients suffering from DED improvements in packaging could considerably reduce the CO2 footprint of DED treatment.

The next‐generation therapies in ophthalmology for blindness worldwide

AbstractWith the rapid and groundbreaking development in 21st century medicine on a global scale, new possibilities have emerged for addressing eye diseases, that can be blindness, and that conventional pharmaceuticals and surgical interventions have not hitherto been able to adequately treat. Gene enhancement/supplementation, gene editing, and stem cell therapies have now emerged as key subdisciplines. Here we discuss the current state and prospects of regenerative therapy in the field of ophthalmology, with a primary focus on diseases affecting the cornea, retina, and optic nerve. Our review summarizes the latest advances, challenges, and opportunities in these fields, as well as the potential applications and limitations of different strategies. The review also highlights the importance of interdisciplinary and collaborative innovation models for achieving breakthroughs in therapeutic development for sight‐loss diseases worldwide.

Update on gene therapies in pediatric ophthalmology

Rare eye diseases encompass a broad spectrum of genetic anomalies with or without additional extraocular manifestations. Genetic eye disorders in pediatric patients often lead to severe visual impairments. Therefore, a challenge of gene therapy is to provide better vision to these affected children. In recent years, inherited retinal diseases, inherited optic neuropathies, and corneal dystrophies have dominated discussions to establish gene and cell replacement therapies for these diseases. Gene therapy involves the transfer of genetic material to remove, replace, repair, or introduce a gene, or to overexpress a protein, whose activity would have a therapeutic impact. For the majority of anterior segment diseases, these studies are still emerging at a preclinical stage; however, for inherited retinal disorders, translation has been reached, leading to the introduction of the first gene therapies into clinical practice. In the past decade, the first gene therapy for biallelic RPE65-mediated inherited retinal dystrophy has been developed and the FDA and EMA both approved ocular gene therapy. Other promising approaches by intravitreal injection have been investigated such as in CEP290-Leber congenital amaurosis. Various techniques of gene therapies include gene supplementation, CRISPR-based genome editing, as well as RNA modulation and optogenetics. Optogenetic therapies deliver light-activated ion channels to surviving retinal cell types in order to restore photosensitivity. Beyond retinal function, ataluren, a nonsense mutation suppression therapy, enables ribosomal read-through of mRNA containing premature termination codons, resulting in the production of a full-length protein. An ophthalmic formulation was recently evaluated with the aim of repairing corneal damage, pending new clinical studies. However, various congenital disorders exhibit severe developmental defects or cell loss at birth, limiting the potential for viral gene therapy. Therefore mutation-independent strategies seem promising for maintaining the survival of photoreceptors or for restoring visual function. Restoring vision in children with gene therapy continues to be a challenge in ophthalmology. © 2023 Published by Elsevier Masson SAS on behalf of French Society of Pediatrics.

Progress and prospects of gene therapy in ophthalmology from 2000 to 2022: A bibliometric analysis

BackgroundGene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. MethodsA total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. ResultsThe annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. ConclusionThis study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

Gene therapies in pediatric ophthalmology.

Genetic pediatric eye disease frequently leads to severe vision impairment or blindness. Voretigene neparvovec is the first approved gene therapy for an inherited retinal dystrophy (IRD). Voretigene neparvovec has been shown to be well tolerated and safe, with encouraging results in terms of efficacy, mainly when administered early in childhood. While we assisted at the first gene therapy available in clinical practice for an IRD, some questions remain unanswered, especially when gene therapy is delivered in young children. We review here the most recent reports and promising ongoing studies concerning various approaches on gene therapy in pediatric ophthalmology.

Deep learning segmentation of the tear fluid reservoir under the sclera lens in optical coherence tomography images.

The tear fluid reservoir (TFR) under the sclera lens is a unique characteristic providing optical neutralization of any aberrations from corneal irregularities. Anterior segment optical coherence tomography (AS-OCT) has become an important imaging modality for sclera lens fitting and visual rehabilitation therapy in both optometry and ophthalmology. Herein, we aimed to investigate whether deep learning can be used to segment the TFR from healthy and keratoconus eyes, with irregular corneal surfaces, in OCT images. Using AS-OCT, a dataset of 31850 images from 52 healthy and 46 keratoconus eyes, during sclera lens wear, was obtained and labeled with our previously developed algorithm of semi-automatic segmentation. A custom-improved U-shape network architecture with a full-range multi-scale feature-enhanced module (FMFE-Unet) was designed and trained. A hybrid loss function was designed to focus training on the TFR, to tackle the class imbalance problem. The experiments on our database showed an IoU, precision, specificity, and recall of 0.9426, 0.9678, 0.9965, and 0.9731, respectively. Furthermore, FMFE-Unet was found to outperform the other two state-of-the-art methods and ablation models, suggesting its strength in segmenting the TFR under the sclera lens depicted on OCT images. The application of deep learning for TFR segmentation in OCT images provides a powerful tool to assess changes in the dynamic tear film under the sclera lens, improving the efficiency and accuracy of lens fitting, and thus supporting the promotion of sclera lenses in clinical practice.

Models and Algorithms for the Refinement of Therapeutic Approaches for Retinal Diseases.

We are developing a Virtual Eye for in silico therapies to accelerate research and drug development. In this paper, we present a model for drug distribution in the vitreous body that enables personalized therapy in ophthalmology. The standard treatment for age-related macular degeneration is anti-vascular endothelial growth factor (VEGF) drugs administered by repeated injections. The treatment is risky, unpopular with patients, and some of them are unresponsive with no alternative treatment. Much attention is paid to the efficacy of these drugs, and many efforts are being made to improve them. We are designing a mathematical model and performing long-term three-dimensional Finite Element simulations for drug distribution in the human eye to gain new insights in the underlying processes using computational experiments. The underlying model consists of a time-dependent convection-diffusion equation for the drug coupled with a steady-state Darcy equation describing the flow of aqueous humor through the vitreous medium. The influence of collagen fibers in the vitreous on drug distribution is included by anisotropic diffusion and the gravity via an additional transport term. The resulting coupled model was solved in a decoupled way: first the Darcy equation with mixed finite elements, then the convection-diffusion equation with trilinear Lagrange elements. Krylov subspace methods are used to solve the resulting algebraic system. To cope with the large time steps resulting from the simulations over 30 days (operation time of 1 anti-VEGF injection), we apply the strong A-stable fractional step theta scheme. Using this strategy, we compute a good approximation to the solution that converges quadratically in both time and space. The developed simulations were used for the therapy optimization, for which specific output functionals are evaluated. We show that the effect of gravity on drug distribution is negligible, that the optimal pair of injection angles is (50∘,50∘), that larger angles can result in 38% less drug at the macula, and that in the best case only 40% of the drug reaches the macula while the rest escapes, e.g., through the retina, that by using heavier drug molecules, more of the drug concentration reaches the macula in an average of 30 days. As a refined therapy, we have found that for longer-acting drugs, the injection should be made in the center of the vitreous, and for more intensive initial treatment, the drug should be injected even closer to the macula. In this way, we can perform accurate and efficient treatment testing, calculate the optimal injection position, perform drug comparison, and quantify the effectiveness of the therapy using the developed functionals. We describe the first steps towards virtual exploration and improvement of therapy for retinal diseases such as age-related macular degeneration.

Advances and prospects of platelet-rich plasma therapy in veterinary ophthalmology.

In the recent decades, there has been a significant uptick on the use of platelet-rich plasma (PRP) as a better alternative for ophthalmologic therapies in pathologies, primarily of the ocular surface. PRP is a class of liquid platelet concentrate containing a supra-physiological concentration of platelets in a relatively small amount of plasma. Its potential to heal various tissues has piqued interest in its therapeutic application as a biomaterial in regenerative medicine. It is currently a popular therapeutic agent in plastic surgery, cardiothoracic surgery, reconstructive surgery, and even oral and maxillofacial surgery. Based on the data from in vitro and in vivo studies, it can be concluded that PRP possesses adequate therapeutic potential in ocular pathologies, especially those involving cornea. In addition, the high concentrations of growth factors (TGF-β, VEGF, EGF) present in the PRP accelerate the healing of the corneal epithelium. PRP has great therapeutic prospects in veterinary ophthalmology as a regenerative therapeutic modality. However, several variables are yet to be defined and standardized that can directly affect the efficacy of PRP application in different ophthalmic conditions. There is a shortage of research on the use of PRP in ocular surface defects compared to the number of studies and reports on the use of autologous and allogeneic serum eye drops. Therefore, a data-driven approach is required to generate consensus/guidelines for the preparation, characterization, and therapeutic use of PRP in veterinary ophthalmology. This review aims to inform readers of the latest research on PRP, including its preparation methods, physiological and biochemical properties, clinical applications in veterinary ophthalmology, and their safety and efficacy.

Novel drug delivery systems for the treatment of glaucoma

AbstractGlaucoma is a group of chronic irreversible neuropathies in which a progressive death of retinal ganglion cells (RGC) and a glaucomatous optic disc neuropathy occurs leading to an irreversible visual field alteration. Intraocular pressure (IOP) increase is a major risk factor strongly associated with the onset and progression of the disease although a non IOP‐dependent neurodegeneration also occurs. Taking all this into account, the glaucoma therapy is based on two different targets: lowering the IOP and neuroprotection.The treatment of choice in patients with high IOP values is topical administration of hypotensive active agents on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the antiglaucomatous drugs applied topically, make it necessary daily instillations, which are associated, in many cases, with the appearance of surface eye alterations and dry eye disease (DED). For these reasons, the development of therapeutic platforms able to increase the bioavailability of the drug while being soft with the ocular surface is getting special attention. Novel formulations involve pharmaceutical systems such as liposomes, nanoemulsions and microemulsions including also compounds with protective activity on the corneal surface (osmoprotective, antioxidants and/or bioadhesive polymers)(1–3).It is well known that therapies lowering IOP does not address neurodegeneration. Moreover, pathophysiological studies of glaucoma have shown that even in patients presenting IOP values within the normal limits, neuronal degeneration occurs. For this reason, the use of neuroprotective therapy in the treatment of glaucoma alone or simultaneously with the therapy based on the control of IOP results of great interest. Treatments destined to lower IOP, in which the target is the anterior segment of the eye are administered topically. By the contrary, neuroprotective therapies require the administration of the drugs near to the retinal target as well as their maintenance during long term Due to the multifactorial nature of the disease there is special interest in the design of novel drug delivery systems able to include a combination of active agents in the same formulation and provide long term effects with a single administration(4).Acknowledgements: Acknowledgements‐ Grant: Fondo Europeo de Desarrollo Regional (FEDER‐CICYT), grant: FIS‐PI17/00079 and PI17/00466, Research Group UCM 920415 ‘Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal)’ and the ISCII‐FEDER RETICS (OFTARED) (RD16/0008/0004 and RD16/0008/0009)PID2020‐113281RB‐C21 funded by MCIN/AEI/ 10.13039/501100011033.References.1. López‐Cano J.J, González‐Cela‐Casamayor M.A., Andrés‐Guerrero V.,Herrero‐Vanrell R. Molina‐Martínez I.T. “Liposomes as vehicles for topical ophthalmic drug delivery and ocular surface protection”. Expert Opinion on Drug Delivery. 2021. 18(7):819–847. DOI: 10.1080/17425247.2021.1872542.2. M. Gómez‐Ballesteros; J. López‐Cano; I. Bravo‐Osuna; R. Herrero‐Vanrell; I.T. Molina‐Martínez. “Osmoprotectants in Hybrid Liposome/HPMC Systems as Potential Glaucoma Treatment”. Polymers. 2019; 11(6): 929. DOI: 10.3390/polym110609293. I Bravo‐Osuna; V Andrés‐Guerrero; P Pastoriza Abel; IT Molina‐Martínez; R Herrero‐Vanrell. Pharmaceutical microscale and nanoscale approaches for efficient treatment of ocular diseases. Drug Deliv Translational Research.2016. 6(6):686–707.DOI: 10.1007/s13346‐016‐0336‐5.4. R Herrero‐Vanrell; I. Bravo‐Osuna; V. Andrés‐Guerrero; M. Vicario‐de‐la‐Torre; I.T. Molina‐Martínez. The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies. Progress in Retinal and Eye Research. 2014. 42; 27–43. DOI: 10.1016/j.preteyeres.2014.04.002.

Novel formulations in the treatment of glaucoma

AbstractNeuroprotective therapy in glaucoma is gaining a lot of interest to be used alone or simultaneously with the control of intraocular pressure (IOP). Neuronal degeneration process occurs through different pathways. For this reason, effective neuroprotection of retinal ganglion cells (RGC) and other retinal cells in glaucoma must be performed according to different targets. Recently, there is special interest in designing treatments able to include a combination of active agents in the same formulation.Treatments destined to lower IOP, in which the target is the anterior segment of the eye are administered topically. By the contrary, neuroprotective therapies require the administration of the active substances close to the retinal tissues as well as their maintenance during long term. Since the last decades the development of intraocular drug delivery systems (IDDS) has emerged as therapeutic tools to provide therapeutic concentrations inside the eye during long term, thus reducing the number of injections. Among the controlled release devices, implants (&gt;1 mm) and microparticles (1–1000 μm), are capable of releasing the active substance during long time. Furthermore, if they are prepared with biodegradable polymers, they have the advantage of disappearing from the site of administration after releasing the drug. There are currently two biodegradable implants in the clinical practice to avoid frequent administrations. One of them is loaded with dexamethasone (Ozurdex®) for intravitreal injection and Durysta™ administered in the anterior chamber. Both devices are prepared from the biopolymers derived from the lactic and glycolic acid poly‐(lactic‐co‐glycolic) acid, named as PLGA. The final products of this biodegradable biomaterial result well tolerated and they are finally eliminated from the body.Despite the advantages of the commercialized biodegradable implants, they did not allow personalized therapy and microparticles (mainly PLGA microspheres) are under investigation as therapeutic platforms for intraocular purposes(1). One of their main advantages is that they can be administered as a suspension in the vitreous using small gauge needles (30‐32G). Another interesting advantage of microspheres is that, by being able to easily modify the amount of microparticles to be administered, they become very useful tools for personalized therapies.Microspheres allow to incorporate several drugs in the same device providing a simultaneous delivery of the active substances, resulting of special interest in multifactorial diseases(2). Furthermore, the amount of injected polymer in the co‐loaded device resulted lower compared to single‐loaded systems.Acknowledgements‐Grant: PID2020‐113281RB‐C21 funded by MCIN/AEI/ 10.13039/501100011033, Research Group UCM 920415 “Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal)” and the ISCII‐FEDER RETICS (OFTARED) (RD16/0008/0004 and RD16/0008/0009).

Fractal Light Structures for Stimulation Therapy in Ophthalmology

Fractal Light Structures for Stimulation Therapy in Ophthalmology

Availability of drugs for the treatment of cats with ocular diseases in Germany - Discrepancy between theory and reality

Only a few ophthalmologics specifically approved for cats are available on the market leading to frequent use of drugs approved for humans. In Germany, the administration, dispense or prescription of pharmaceuticals is regulated by the pharmaceuticals law ('Arzneimittelgesetz' (AMG)) as well as the regulation concerning pharmacies in veterinary practice ('Verordnung über tierärztliche Hausapotheken' (TÄHAV)). The aim of this study was to collect data concerning the occurrence and frequency of feline eye diseases and to evaluate the frequency of the necessity for extra-label drug use. Evidence-based, optimal treatment schemes were generated and reviewed with regard to their feasibility in Germany. Data from 876 cats with ocular problems of the "Small Animal Clinic", Freie Universität Berlin as well as a small animal practice in Southern Germany were evaluated (01.01.2015-31.12.2018). Subsequently, the theoretical accessibility for approved agents and/or extra-label drug use in Germany was analyzed. 1198 diagnoses were based on 925 ophthalmic examinations. The most common diseases include conjunctivitis, keratitis, uveitis, hypertensive retinopathy and glaucoma. 885/1198 (73.9 %) of these diseases required treatment, which equates to 722/925 (78.1 %) cases. For all patients, treatment would have been possible according to evidence-based data. In 225/722 (31.2 %) cases, treatment with the pertaining, specifically approved agents would have been possible. Extra-label drug use would have been necessary in 497/722 cases (68.8 %). Of the 497 cases necessitating extra-label use, pharmaceuticals approved for humans would have been available for 481 cases (96.8 %), extra-label use of other veterinary pharmaceuticals would have been possible in 28 cases (5.6 %) and in 60 cases (12.2 %) especially manufactured drugs could have been employed. In a total of 36/722 cases (5 %), optimal care would not have been possible in the context of the current regulatory framework. Based on regulations concerning therapeutic necessity, the ophthalmologic therapy of cats in Germany is possible within the regulatory framework. In the present study, 5 % of the patients could not receive optimal medical care. The closure of this gap demands additional approval of veterinary ophthalmic drugs as well as the research and development of novel active agents and veterinary pharmaceuticals.

Intra- and Inter-Slice Contrastive Learning for Point Supervised OCT Fluid Segmentation.

OCT fluid segmentation is a crucial task for diagnosis and therapy in ophthalmology. The current convolutional neural networks (CNNs) supervised by pixel-wise annotated masks achieve great success in OCT fluid segmentation. However, requiring pixel-wise masks from OCT images is time-consuming, expensive and expertise needed. This paper proposes an Intra- and inter-Slice Contrastive Learning Network (ISCLNet) for OCT fluid segmentation with only point supervision. Our ISCLNet learns visual representation by designing contrastive tasks that exploit the inherent similarity or dissimilarity from unlabeled OCT data. Specifically, we propose an intra-slice contrastive learning strategy to leverage the fluid-background similarity and the retinal layer-background dissimilarity. Moreover, we construct an inter-slice contrastive learning architecture to learn the similarity of adjacent OCT slices from one OCT volume. Finally, an end-to-end model combining intra- and inter-slice contrastive learning processes learns to segment fluid under the point supervision. The experimental results on two public OCT fluid segmentation datasets (i.e., AI Challenger and RETOUCH) demonstrate that the ISCLNet bridges the gap between fully-supervised and weakly-supervised OCT fluid segmentation and outperforms other well-known point-supervised segmentation methods.

Anti-VEGF Therapy in Ophthalmology

Angiogenesis is when the growth of new blood vessels occurs from the pre-existing vasculature, occurring in both healthy and pathological conditions.Usually, there is a balance maintained between angiogenesis regulators (angiogenesis promoting factors and angiogenesis inhibiting factors), but when this balance is lost, there is either too much or too little angiogenesis. VEGF (Vascular endothelial growth factor) and its receptor (VEGFR) are critical regulators of angiogenesis that promote it.It has been seen that it plays a significant role in the regeneration mechanism of blood vessels, inflammation of body tissues, cancer states, and wound healing. Various pathological conditions show increased VEGF activity.Nowadays, there has been increased use of anti-VEGF drugs, which target the vascular endothelial growth factor and slow down its action. The application of this therapy in ophthalmology is also becoming wider and wider. The implications of anti-VEGF dungs are cancers, rheumatological disorders, macular edema, various retinopathies, glaucoma, etc. &#x0D; Anti-VEGF treatment comprises of three main drugs, namely-Avastin, Lucentis, and Eylea. Their efficiency has been proven to be equal with varying manufacturing costs, packaging, and associated risks.These are the brand names for bevacizumab, ranibizumab, aflibercept, respectively, which have helped us achieve different milestones in treating all kinds of retinal diseases. Several other diseases like iris neovascularization, age-related macular degeneration (AMD), corneal diseases also have been treated using anti-VEGF drugs. Like all drugs, anti-VEGF drugs also have some limitations and side effects, including short half-life, systemic side effects; therefore, the development of new drugs still goes on.

Bacterial corneal ulcers in pediatric patients. Algorithms of pharmacotherapy. Part II

Part I of the article presents a review of publications highlighting current exogenous and endogenous risk factors contributing to the occurrence of bacterial corneal ulcers, laboratory diagnostic methods, clinical differential diagnostic features of bacterial corneal ulcers.&#x0D; A wide variety of objective symptoms characterizes the clinical picture of bacterial corneal ulcers. Still, objective differential diagnostic signs make it possible with a high degree of probability to assume the etiology of the disease during the first biomicroscopy and immediately begin etiotropic therapy, on the timing of which the outcome of the disease depends.&#x0D; Standard laboratory examination of patients with bacterial corneal ulcers includes the bacterioscopic and cultural examination of the contents of the conjunctival sac. However, the absence of etiotropic therapy while waiting for the results of microbiological research methods, which takes from 3 to 7 days, contributes to the rapid progression of the disease, the development of endophthalmitis, and corneal perforation, up to the loss of an eye in children. In this regard, treatment must be started immediately. Therefore, the choice of a drug is determined not only by the causative agent, proven laboratory but, first of all, based on clinical differential diagnostic signs of the disease.&#x0D; The traditional, undeniable approach to the conservative treatment of bacterial corneal ulcers is conventional etiotropic therapy using local and systemic antibacterial drugs. In addition, timely intensive specific drug therapy prevents the destruction of all layers of the cornea, and the use of metabolic drugs that improve regeneration and trophism promotes epithelialization of corneal ulcers.&#x0D; Attention should be given to the necessity and validity of the choice of antibacterial drugs for various etiological forms of bacterial corneal ulcers in children. An individual approach is a basis for effective antibiotic therapy in pediatric ophthalmology.&#x0D; The article presents an up-to-date review of publications and modern algorithms for treating bacterial corneal ulcers in children, the main causative agents of which are: Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae.