bluuebunny/crossref_metadata_2025 huggingface dataset:
Upcoming implications of the DECODE VRL study for the diagnostics of PVRL
Authors: Kakkassery Vinodh
Published: December 2022

Aim of this talk is to give insight into the impact of registry in primary vitreoretinal lymphoma (PRVL) care in Germany. Further, the talk will give information on the recently started nationwide multi‐center prospective DECODE VRL study in Germany. The DECODE VRL has the approach to implement and clinically validate a standardized, innovative molecular diagnostics for PRVL by using previously new recognized biomarkers like MYD88 (Bonzheim et al., Blood 2015) and miRNA 92, 19b and 21 (Kakkassery et al., Blood 2017). Both projects will contribute to a better care of PVRL in the future.
15 years of PVRL‐experience of Prague uveitis Centre
Authors: Heissigerova Jarmila , Klimova Aneta , Brichova Michaela , Rihova Eva , Svozilkova Petra
Published: December 2022

Intravitreal lymphoma is a malignant masquerade syndrome which is crucial to identify among uveitis patients because of its life‐threatening nature.

A total of 35 immunocompetent patients, 15 men and 20 women, were observed with vitreoretinal lymphoma in the Centre for Diagnosis and Treatment of Uveitis in Prague between the years 2003 to 2019. Primary vitreoretinal lymphoma (PVRL) was diagnosed in 15 patients, 6 patients from this group did not show any CNS involvement nor had an intraocular relapse during the observation period. The clinical manifestation of lymphoma in our patients was usually the vitreous haze, sometimes accompanied by retinal lesions and anterior chamber cells with or without keratic precipitates. In our observation, the diagnosis was determined by cytology or/and flow cytometry from vitreous analysis in all patients with exception of 4 patients with clinically highly suspicious finding of vitreous. Beside the vitritis, retinal infiltration was present in 3 of these 4 patients. From this group of 4 patients, the diagnosis was confirmed from brain biopsy in 3 patients and lung biopsy in 1 patient. The vitreous analysis was negative for lymphoma in 2 patients and in 2 patients' vitreous analysis was not performed. Over the years, the sensitivity of VRL detection from vitreous sample became very high, in our observation 94%.

All patients diagnosed with VRL by vitreous analysis were sent to haemato‐oncologist work‐up. Treatment was decided by the consensus of a haemato‐oncologist and an ophthalmologist according to the clinical manifestation. Combination of intravitreal and systemic chemotherapy is recommended in many reports. There has been a decline in ocular and brain radiotherapy in recent years because of the unpredictable and irreversible nature of its side effects. Autologous stem cell transplantation (ASCT) following systemic chemotherapy was indicated in 3 patients. The relapse of lymphoma was observed in 13 patients, first relapse was after 11–120 months (median 32 months).

Supported by research project AZV MZ CR NU20‐03‐00253.
Alternatives for corneal stroma replacement
Authors: Ahearne Mark
Published: December 2022

Corneal blindness affects millions worldwide. The global shortage of donor corneas suitable for transplantation has led to the development of biomaterial‐based alternatives. The unique composition and structure of the corneal stroma are a significant challenge to replicate using conventional biomaterials and material fabrication techniques. One approach to overcome this problem is to decellularize the corneal stroma taken for animals, as these have similar structural properties and composition to native human stroma. This talk will provide an overview of the work done by our group in developing different decellularization approaches that can be used to fabricate corneal stromal constructs. A number of different decellularization techniques have been examined and their effectiveness at removing cells and cellular components while still maintaining the stromal extracellular matrix has been evaluated. New methods to recellularize the decellularized corneal stromal constructs have been explored. The development of decellularized corneal hydrogels and their advantages and limitations, shall all be discussed.
Artificial cornea: Myth or reality?
Authors: Lagali Neil
Published: December 2022

Since the first human corneal transplantation was performed by Eduard Zirm over 110 years ago, the paradigm of using human donor corneas for treating blinding corneal disease has remained largely unchanged. Intense research efforts, however, have been undertaken during the past decades, to engineer an alternative to the human cornea to meet the large global demand for this specialized donor tissue. The various artificial, or engineered corneas that have reached preclinical and in several cases clinical testing during the past years will be presented, along with the advantages and limitations of each technology. Various technologies use either cell‐free or cell‐loaded tissues, de‐cellularized or re‐cellularized human or animal tissues, and aim to replace various layers of the cornea or in certain cases, the entire cornea. For the most prevalent indications for corneal transplantation, however, human donor tissue remains the method of choice due to the unparalleled visual outcomes. Nevertheless, newer emerging treatment methods and alternatives to donor cornea transplantation are being reported, that can potentially ease the global demand for donor tissue and tissue banking in the future. Here we present these developments and provide the latest update on the most promising engineered corneal replacements tested in the clinic.
Bacterial keratitis – Challenges with changing microbial resistance
Authors: Modis László
Published: December 2022

About 90% of corneal infections are bacterial in origin. The most common pathogens are Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Pseudomonas aeruginosa. The two main causes of bacterial keratitis are contact lens usage and corneal injury.

Patients typically complain of pain, sensitivity to light, blurred vision, tearing and yellowish purulent discharge. Clinical signs of bacterial keratitis include epithelial defect, ulceration in addition, stromal oedema and infiltrates with indistinct margins are present. Purulent material may appear in the anterior chamber.

Most cases can be successfully treated with empiric therapy. If the pathogen is not known, moxifloxacin or cefazolin with tobramycin or gentamycin recommended as primary treatment. For severe keratitis eye drops should be applied both day and night for the first 48 hours. If the causative agent and its susceptibility are available from the microbiological sample and/or from smear, the topical treatment should be adjusted accordingly. If no improvement in the clinical picture seen after 48 hours with topical treatment, repeat sampling for microbiological culture recommended. In case of further progression, keratectomy with histological evaluation of the specimen is necessary. Corticosteroids may be considered after 48 hours when the infective organism is identified, and the keratitis is responding to therapy.

In addition to antimicrobial treatment pupillary dilation advised to immobilize the iris and ciliary body. Cycloplegia may also decrease pain as well as synechia formation. In therapy resistant cases crosslinking may be an additional option if herpetic origin can be excluded.

If the clinical picture does not improve, it is important to reassess the differential diagnosis of the keratitis caused by herpetic, fungal and Acanthamoeba infection.

In cases of non‐healing and rapidly progressive corneal inflammation or ulceration, therapeutic corneal transplantation is recommended. However, surgery has a better prognosis in the non‐inflammatory period when the eye is quiet.
The chameleon of herpetic keratitis
Authors: Seitz Berthold
Published: December 2022

In Europe, herpes simplex virus type I (HSV) is a common cause of keratitis. The disease may be well treated if the ophthalmologist is aware of the various types of clinical expressions of this typical unilateral chameleon, and treatment is adjusted accordingly. Types of expression include 1. epithelial keratitis (dendritica/ geographica), 2. stromal keratitis (necrotizing “ulcer” “vs. non‐necrotizing = interstitial keratitis”), 3. endotheliitis (= “disciform keratitis”), 4. so‐called “metaherpetic keratitis” (= neurotrophic keratopathy), 5. (vascularized) corneal scars. In the acute phase, concomitant ocular hypertension should be treated predominantly without surgery (no prostaglandin analoga!). After keratoplasty and in case of severe recurrences of herpetic keratitis, systemic acyclovir application (2 × 400 mg/day) for at least 1 year is indispensable! In 1.5% of corneal excisions during keratoplasty, HSV PCR is positive without clinical suspicion of herpetic keratitis. This may be one reason for primary or secondary graft failure and needs adequate treatment.
Imaging and check‐up for evolutive myopia
Authors: Bremond‐Gignac Dominique
Published: December 2022

Myopia is the most common ocular pathology with a major recent increasing in Asia and all over the world. This refractive anomaly has usually an onset during infancy. However, myopia is not only a refractive pathology but it may also lead to retinal complications. When myopia is diagnosed, a complete check‐up should be performed including VA, refraction under cycloplegia, orthoptic check‐up, optical axial length, fundus and if possible ultra‐wide field fundus and macular OCT. These examinations lead to propose the best‐adapted system for myopia control. The follow‐up of myopia include systematically VA, Refraction under cycloplegia and optical axial length. Practical cases will be described for a better understanding of myopia evolution in children.
Pathophysiology of intraocular haemorrhage: Role of iron in cell death
Authors: Picard Emilie , Youale Jenny , Daruich‐Matet Alejandra , Behar‐Cohen Francine
Published: December 2022

Retinal haemorrhages are present in several retinal pathologies, such as exudative AMD, diabetic retinopathy, or myopic degeneration. As a consequence of erythrocytes lysis following haemorrhage, haemoglobin (Hb) is released into the extracellular space, and heme is degraded into iron, which becomes under a free (unbound) form. While iron is essential for retinal functions, labile free iron enhances Fenton reaction and therefore leads to oxidative stress. Cones are the most sensitive retinal cells to iron excess and local accumulation of iron rapidly induces photoreceptors and retinal pigment epithelium cells death. A local retinal homeostasis of iron exists to equilibrate iron level in retinal cells, but a deficiency of iron‐related proteins causes iron accumulation and retinal degeneration. Heme‐binding proteins, hemopexin and haptoglobin, and their receptors, as well as heme transporters were also found expressed in retinal cells suggesting their roles in retinal iron regulation. As therapeutic strategy, chemical chelators used to control iron accumulation in systemic iron overload diseases, have demonstrated efficiency to protects the retina in various models of retinal degenerations. Our team uses transferrin (TF), the iron transporter protein, to reduce iron overload and therefore preserve visual function. Control of iron impairment in retinal tissues may be a therapeutic strategy during haemorrhages.
Maturation of stem cell derived retinal organoid cells following subretinal transplantation
Authors: Singh Mandeep S.
Published: December 2022

Retinal cell therapy is envisioned as a treatment modality to repair the retina and improve vision in people with degenerative or hereditary retinopathies. In pursuit of this goal, transplantation of ES/iPS‐derived photoreceptor precursor cells is being developed as a treatment to replace lost photoreceptor cells. Several studies have shown that photoreceptor precursors can mature and incorporate into the recipient retina following transplantation in the subretinal space. However, knowledge regarding the identity and distribution of transplanted cells is incomplete, and furthermore, how closely the transplanted photoreceptors resemble normal photoreceptors in an intact wild‐type retina is unclear. In addition, a key gap in knowledge pertains to how the recipient retina regulates the maturation, fate specification, and migration of transplanted donor cells. This talk will describe how the subretinal space in the degenerative recipient eye promotes the maturation of transplanted rod and cone photoreceptor cells. In addition, observations of graft‐derived cells that migrate into the recipient retina, including some that travel long distances away from the graft, are presented. These findings highlight that in vitro human micro‐organogenesis can produce complex organoids with unusual and unexpected ectopic components that do not typically comprise the normal organ, and thus can profoundly influence therapeutic studies that use those organoids. These findings demonstrate the importance of the extracellular microenvironment in determining cell identity and behaviour in human organoids being developed for treatment purposes.
Retinal structure: From Cajal drawings to present morphological techniques
Authors: Cuenca Nicolás
Published: December 2022

The scientist Santiago Ramón y Cajal and his work on the organization of the nervous system and the Neuronal Theory are widely known. However, his studies and contributions on the structure of the retina remain almost forgotten. La rétine des vertébrés, appearing in the journal La Cellule (1892), is a masterpiece of scientific literature, frequently cited in scientific articles even today. In this presentation we want to highlight his work on the neuroanatomy of the retina as well as his excellent descriptions and artistic drawings of its cells. Santiago Ramón y Cajal published his first studies of the retina using the Golgi technique in 1888. Cajal describes in detail the histology and anatomy of the retina of the various types of vertebrates. His studies of the structural organization of the retina, as well as the almost prophetic predictions he made about its functions, have become the basis of retinal neuroanatomy, neurophysiology, and neuropathology. The descriptions made by the scientist on the types of retinal cells in different species and on the way in which these cells are interconnected are the most outstanding and complete that have been carried out. The new techniques of confocal microscopy and immunocytochemistry allow us to morphologically identify the various cell types as well as the synaptic connections between them and ratify the ideas proposals by Cajal.
Biomechanical effect of intracorneal ring segment implantation
Authors: Hamon Loïc , Pfahl Luisa J. , Flockerzi Elias , Berger Tim , Langenbucher Achim , Seitz Berthold , Daas Loay
Published: December 2022

Background: Previous studies have reported significant differences in corneal biomechanics between keratoconic and healthy corneas. Corvis ST® (CST – OCULUS, Wetzlar, Germany) and Ocular Response Analyser® (ORA – Reichelt Inc., Depew, NY, USA) are two single central air‐puff tonometers and are commonly used to analyse the corneal biomechanics. Implantation of intracorneal ring segments (ICRS) using a femtosecond laser represents a reliable surgical option to widen the spectrum of the stage‐related therapy of keratoconus for selected patients. Our purpose was to analyse the change in corneal biomechanical properties after ICRS implantation in keratectasia.

Methods: This retrospective monocentric study included 118 patient eyes that underwent femtosecond laser‐assisted ICRS implantation (INTACS SK®, Addition Technology Inc., Des Plaines, IL, USA) for keratectasia. Biomechanical analysis was performed using both ORA, with determination of Corneal resistance factor (CRF), Corneal hysteresis (CH) and Keratoconus Match Index (KMI), as well as by CST with determination of stiffness parameter A1 (SP‐A1), Ambrosio's related thickness to the horizontal profile (Arth), integrated radius (IR), deformation amplitude‐ratio (DA‐ratio) as well as Corvis Biomechanical Index (CBI) and Tomographical Biomechanical Index (TBI). Data collection was performed preoperatively and after 6 months postoperatively for ORA and CST and additionally after 1 and 2 years for ORA.

Results: The CRF decreased significantly postoperatively (5.8 ± 1.7 mmHg) compared to preoperatively (6.8 ± 3.7 mmHg; p < 0.001), and increased again during follow‐up (6.2 ± 1.9 mmHg; p = 0.001), without regaining preoperative values. CH and KMI did not change significantly. SP‐A1, IR and DA‐ratio increased significantly after ICRS implantation (p < 0.001). Arth decreased significantly from 190 ± 88 to 157 ± 108. However, there was no significant postoperative change for CBI and TBI.

Conclusions: Corneal biomechanical properties showed inconsistent changes after ICRS implantation. The classical corneal biomechanical parameters (using single central air‐puff tonometers) do not seem to be suitable for follow‐up after ICRS implantation.
Laser vision correction in glaucoma; myths and reality
Authors: Patsoura Elisabeth
Published: December 2022

Laser vision correction has been a well‐established, rapidly developing, safe and widely used technique for refractive error correction. Nevertheless, there are several drawbacks for its use in specific groups of patients. A classic contraindication has been patients with glaucoma. These include those with diagnosed glaucoma and even glaucoma suspects. The main concern remains the evaluation of the intraocular pressure (IOP) after refractive surgery. Newer technology has been helpful in achieving accurate IOP measurements bypassing to an extend the biomechanical changes and thinning of the cornea induced by laser correction. Use of conversion factors may well be applied. Perioperative care of these patients has also been an issue as corticosteroids drops are used, sometimes for a prolonged period of time potentially causing a rise in IOP. Choosing between superficial techniques and LASIK, the former inducing high intraocular pressure during flap dissection is also a question to be answered. In addition, following up those patients to assess possible glaucoma progression can be challenging. Thorough preoperative assessment is mandatory with functional and anatomical testing of the optic nerve. This is especially important so new glaucoma disease is not missed especially in high myopes. Last but not least patients on glaucoma treatment usually have a compromised ocular surface due to the long‐term effects of topical drops. This fact has to be taken into consideration when deciding to proceed or not with laser refractive surgery. In conclusion the glaucoma patient and the glaucoma suspect are challenging patients regarding the potential laser vision correction. Several factors need to be considered in order to make the correct decision. So, myths andreality are analysed that either defeat or support the argument that under the laser vision correction can be safely performed in carefully selected glaucoma eyes.
Update on Boston KPro1
Authors: Hannush Sadeer
Published: December 2022

Since the introduction of the last major iteration of the Boston Type I keratoprosthesis in 2002, it has undergone several improvements, including the development of a titanium back plate in two sizes, a click‐on version, and the recently introduced Lucia. The Lucia is currently available in one aphakic power with a blue or brown back plate that incorporates radial slit apertures to both allow aqueous nutrition of the carrier donor cornea and simulate the natural iris. Moreover, the Lucia can be produced at low cost, making it more accessible to those in need around the world.
Update on tibial bone keratoprosthesis
Authors: de la Paz Maria
Published: December 2022

Osteo‐odontokeratoprosthesis (OOKP) is the gold standard for end stage cicatricial disease of the ocular surface to restore sight in patients with corneal blindness. The use of tibial bone is an option in cases of edentulia or when patient refuses to sacrifice a tooth. The surgery consists in retrieving a disc of the tibial bone and inserting an optical cylinder in the center, much like in OOKP surgery using a canine tooth.

A review of 113 patients who underwent tibial bone keratoprosthesis (Tibia KPro) at a single center performed by a single surgeon showed prosthesis retention rate of 69% at 5 years and 54% at 10 years. BCVA better than or equal to decimal 0.05 at 5 years was 33% and 19% at 10 years. Patients with chemical burn had better prosthesis retention as well as visual acuity results compared to autoimmune cases. Complications found postoperatively were keratoprosthesis extrusion, glaucoma, retinal detachment, buccal mucosa necrosis, retroprosthetic membrane, etc.

The anatomical results in the long‐term are comparable to OOKP (67% prosthesis retention at 10 years). However, the visual acuity results with OOKP at 10 years was better at 49% (for BCVA better than or equal to decimal 0.05) than patients with Tibia KPro. Moreover, there were more complications in Tibia KPro than in OOKP such as mucous membrane necrosis and retroprosthetic membrane formation.

At present, in vitro studies are being undertaken to produce substitutes for OOKP skirts using biomimetic bone‐like composites.
What has COVID taught us about glaucoma management?
Authors: Normando Eduardo
Published: December 2022

Since the spread of coronavirus pandemic caused by the SARS‐CoV‐2 virus, several measures were implemented worldwide to try to stop the pandemic and minimize its impact on healthcare.

Ophthalmologists are one of the most exposed specialists to airborne particles due to their close proximity to patients' faces during the examination.

Therefore during the pandemic, all non‐essential procedures and appointments were cancelled or postponed, and new approaches to virtual clinics were explored.

This presentation will discuss the impact of Covid related delayed care in patients with glaucoma and how the implementation of virtual and diagnostic clinics had on reducing long waiting list and streamlining patient's care .
Future approaches to glaucoma management
Authors: Cordeiro Francesca
Published: December 2022

There have been several advances in glaucoma management over the past few years. This talk will include coverage of medical changes such as neuroprotective strategies and sustained release medications, and diagnostic advances including artificial intelligence applications, the water drinking test, DARC, visual field analysis and tear fluid assessment. Finally, home monitoring possibilities in glaucoma including self‐tonometry and visual field testing will be discussed.
Development of co‐encapsulating bevacizumab and dexamethasone liposomes with cell penetrating peptide surface functionalisation for posterior eye drug delivery
Authors: Farooq Umer , Fitzhenry Laurence , O'Reilly Niall , Behl Gautam , Ahmed Zubair , Gasco Paolo , Singh Thakur Raghu Raj , Mcloughlin Peter
Published: December 2022

Background: Intravitreal injections to the eye are the standard treatment for wet age‐related macular degeneration (AMD) but are associated with several drawbacks. Intravitreal injections not only cause structural damage but the invasive procedure also causes discomfort and pain, resulting in decreased patient adherence to the therapy. Our work aims to develop a topical liposomal formulation, functionalised with a cell penetrating peptide (CPP) that has the potential to reach the posterior segment of the eye and inhibit neovascularisation and inflammation, which are the hallmarks of wet AMD and Diabetic Retinopathy. The proposed formulation will offer non‐invasive administration (topical) with decreased dosing frequency (owing to its sustained release action), facilitating increased patient compliance.

Methods: The liposomes were prepared by the thin film hydration method, followed by the extrusion of obtained multilamellar vesicles into single unilamellar vesicles. The formulations were characterized for their size, PDI and % encapsulation efficiency (%EE). Initially, a Design of Experiments approach was adopted to optimize the encapsulation efficiency of dexamethasone in liposomes, with the amounts of DPPC, cholesterol and dexamethasone being the factors and the size, PDI and %EE as the responses. HPLC was used to quantify the amount of encapsulated dexamethasone. Bevacizumab was then co‐loaded with optimized dexamethasone liposome formulation and bicinchoninic acid (BCA) assay was used to quantify the amount of encapsulated bevacizumab in the liposomes.

Results: Liposomes with an average size of 137 ± 3 nm, PDI of 0.07 ± 0.03 and a zeta potential of −3.09 ± 0.42 were synthesized. Dexamethasone encapsulation efficiency was improved from initially observed value of 13.01 ± 0.06 to the optimized value of 52.8 ± 2.5. This optimized formulation has a %EE 5.8 time greater than the previously reported values for DPPC‐dexamethasone liposomes (1). Bevacizumab was successfully co‐encapsulated into the liposomes along with dexamethasone. Bevacizumab demonstrated %EE of 91.3 ± 4.07 in the dual encapsulated liposomes, whereas %EE of dexamethasone was 75.1 ± 4.4.

Further studies: The liposome formulation will be functionalised with the CPP and characterized for drug release, transport through ocular layers, cytotoxicity, anti‐angiogenesis and anti‐inflammatory activities using in vitro, ex vivo and in vivo models.

References

1. Bhardwaj U, Burgess DJ. Physicochemical properties of extruded and non‐extruded liposomes containing the hydrophobic drug dexamethasone. Int J Pharm. 2010;388(1–2):181–9.

This project is funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie Actions (grant agreement – No 813440).
Deep learning model to identify angle dysgenesis on ASOCT images
Authors: Dhakonia Shweta Birla
Published: December 2022

Anterior segment spectral domain–optical coherence tomography (ASOCT) is 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. The anatomical variability of the drainage angle, TM and SC morphology makes it difficult to distinguish normal from abnormal. Therefore, the interpretation of ASOCT images requires expertise and a deep understanding of the complexity involved in the developmental anomalies of the outflow pathways. While the ASOCT scans can successfully capture the gross changes, they may fail to identify angle dysgenesis in cases where altered extracellular matrix anomalies are subtle enough to get unnoticed by the human eyes of an expert. Deep learning (DL) has demonstrated convincing results and potential in classifying ophthalmic diseases. The integration of high‐resolution ASOCT images trained DL algorithms can further enhance the translational potential of DL‐based classification for angle dysgenesis. Apart from the gross changes in the iridocorneal angle region, the perturbations in TM layers due to associated gene mutations are also captured on ASOCT scans and may be identified by DL algorithms. We have developed DL models, which can identify obscure features of angle dysgenesis in ASOCT scans (ADoA) and validated its performance in eyes with primary open angle glaucoma. Eight hundred ASOCT B‐scans were included, and each image was cropped to extract the iridio‐corneal angle (ICA) area and a TM area to form two datasets. Finally, the total number of images after augmentations in each dataset increased to 8160, divided into training and testing sets for model building. To avoid overfitting, incorporate variability and increase the size of the datasets, 23 different types of augmentation techniques were performed on each image using the CloDSA tool, a freely available package.

Three deep learning models were developed for a consensus‐based outcome to identify ADoA objectively. The models performed well on the internal as well as external validation datasets. The model performance on the multiple independent datasets highlights the translational relevance of image‐based diagnostic alternatives in clinical settings, as it has the potential to be deployed for screening patients and their family members for detection of angle dysgenesis in vivo.
The ABC of AI
Authors: Stalmans Ingeborg
Published: December 2022

Artificial Intelligence (AI) is a booming field, and is extensively present in our daily life. But at the same time AI is often perceived a mysterious and therefore even threatening. A better understanding of the principles of AI may unveil the mysteries of this technology and allow to reveal its potential to aid our lives, and in particular facilitate and move forward the medical field. In this presentation, the principles of AI, the different methods as well as the applications in various field (going from daily life to application in ophthalmology) will be discussed.
Promises and hazards of artificial intelligence
Authors: Grzybowski Andrzej
Published: December 2022

Artificial intelligence (AI)‐based technologies employing deep‐learning (DL) approaches have proven effective in supporting decisions in many medical specialties, including radiology, cardiology, oncology, dermatology, ophthalmology, and others. For example, AI/DL algorithms have been shown to reduce waiting times, improve medication adherence, customize insulin dosages, and help interpret magnetic resonance images. The number of AI life‐science papers listed in PubMed increased from 596 in 2010 to 12 422 in 2019. The number of papers on the use of AI in the field of ophthalmology also has increased dramatically. Moreover, human cognitive capacity to effectively manage information is often exceeded by the quantity of data generated, and unlike humans, who have bad days and emotions, and who get tired, with subsequent decreases in performance and accuracy, AI works 24/7 without vacations or complaints. AI/DL algorithms have been used to detect diseases based on image analysis, with fundus photos and optical coherence tomography (OCT) scans analysed for retinal diseases, chest radiographs assessed for lung diseases, and skin photos analysed for skin disorders. Retinal photos have also been used to identify risk factors related to cardiovascular disorders, including blood pressure, smoking, and body mass index.

One of many challenges in the field of AI is determining what constitutes evidence of impact and benefit for AI medical devices and who should assess the evidence. The majority of AI studies are conducted in experimental conditions and based on preselected data. They might provide inadequate insight into the use of AI applications in heterogeneous, real‐world care settings. One of the potential hazards of the clinical use of algorithms identified was the risk of applying an algorithm trained on a particular demographic group to a population that differs in factors such as ethnicity, age, and sex. Moreover, many studies of algorithms developed with AI have excluded low‐quality images, treating them as ungradable images, and patients with comorbid eye diseases, making them less reflective of real‐world conditions. The future development of ophthalmology depends on better and possibly unlimited access to the medical data stored within electronic health records. However, this access cannot be allowed to compromise of privacy of this very sensitive data. There is a need for effective regulations that will set a balance between individual protection and the common good.

A recent report from the National Academy of Medicine highlights some important challenges in the further development of AI applications in health care. The authors advocate the use of openly accessible, standardized, population‐representative data; addressing explicit and implicit biases related to AI; developing and deploying appropriate training and educational programs for health workers to support health‐care AI; and balancing innovation and safety through the use of regulation and legislation to promote trust.
How to make glaucoma screening cost‐effective?
Authors: Abegão Pinto Luis
Published: December 2022

Glaucoma screening has not been recommended as part of any Scientific Society Guideline, due mostly to low prevalence in overall population, high cost and a high rate of false positives.

Hospital‐based healthcare systems, based on within‐department referrals present a new opportunity for screening. A human‐lead secondary screening has thus been implemented in CHLUN, Lisbon Portugal since 2019, with positive results.

A retrospective review of 12‐month sample was conducted. Patient charts were reviewed through a retinography‐based AI. Comparison of the human‐based model (which used ancillary examinations, including OCT, Perimetry, Retinography and Paquimetry) and the AI‐assisted diagnosis was done in terms of diagnosis and associated direct and indirect costs.

Based on this single site results, AI‐based analysis of retinographies can prove to be tool for ophthalmologists considering referral for a Glaucoma Clinic.
Mesenchimal stem cells for ocular surface disease
Authors: Calonge Margarita
Published: December 2022

Corneal damage due to different circumstances such as chemical injuries, cicatrizing immune‐based keratoconjunctivitis, severe dry eye disease (graft vs host disease mainly), sequelae of infections, repeated ocular surgeries or congenital disorders (such as congenital aniridia) affects the integrity of the corneal epithelium, being an important cause of visual impairment and blindness that affects millions of people worldwide Mesenchymal stem cells (MSC) and its derivatives represent a readily available, non‐immunogenic source of stem cell that has a great amount of regenerative and anti‐inflammatory properties. For these reasons, MSC have emerged as very attractive candidates for cell‐based therapies in numerous and diverse clinical applications including the treatment of ocular surface diseases such as limbal stem cell deficiency, dry eye disease, or even as a potential therapy to improve corneal allograft survival. Although part of the current preclinical evidence has already been successfully translated into the clinical evidence field, work must continue to overcome all the scientific and the technical challenges that still need to be solved. This presentation summarizes the main preclinical and clinical evidence that encouragingly supports MSC‐based therapies as safe and effective treatments for the regeneration of the ocular surface.
Micellar solutions of Pluronic F127 for ocular drug delivery
Authors: Klahan Butsabarat , O'Reilly Niall , Chauhan Anuj , Sigurdsson Hakon Hrafn , Mering Satu , Fitzhenry Laurence
Published: December 2022

The goal of this research was to prepare drug‐encapsulated polymeric micelles for delivery to the posterior segment of the eye. Solutions of surface active PF127 at the critical micellar concentration (CMC) were prepared in deionized water (DI water) and phosphate buffer (PBS). The CMC of PF127 solution in DI water and PBS solution were found to 0.21 ± 0.04 and 0.16 ± 0.05% (w/v), respectively. In addition, the micellization of the PF127 was observed around 25 and 21°C in DI water and PBS solution, respectively by DSC analysis. The hydrodynamic diameter of the PF127 micelles were found to range between 3 and 4 nm with polydispersity indices ranging between 0.35 ± 0.22 and 0.96 ± 1.52.

Curcumin (CUR), a natural dietary compound having an anti‐VEGF properties, was successfully loaded into PF127 copolymers by the thin‐film hydration method. The CUR‐loaded PF127 micelles were confirmed by several characterization techniques including DLS and HPLC. A detailed study of the effect of experimental conditions on both the particle size and drug encapsulation efficiency (%EE) of the CUR micelles was also carried out. CUR‐loaded PF127 micelles with small particle sizes (around 15 nm, PDI = 0.19 ± 0.13) and %EE around 10% were observed at high centrifugation speed. Also, increasing the copolymer‐to‐drug ratio resulted in higher %EE (>90%). Additionally, the CUR‐loaded PF127 micelles were easy to reconstitute in water by manual shaking after lyophilization. These results suggest that PF127 micelles are a promising carrier for delivery of CUR to the eye. Future work will study in more detail about the physicochemical properties and the ability of these micelles to transport CUR across ocular barriers in ex vivo and in vivo trials.
ex vivo model of spontaneous neuroretinal degeneration for evaluating neuroprotection
Authors: Fernandez‐Bueno Ivàn
Published: December 2022

Ex vivo neuroretina models are considered adequate tools for improving the knowledge of retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, immunohistochemistry, electrophysiology and molecular biology techniques can be applied over retinal explant cultures.

Although several cell culture‐based techniques have been developed to investigate retinal function, such as retinal cells primary cultures, co‐cultures with retinal pigment epithelium (RPE) cells, or 3D aggregates cultures, ex vivo models provide a better alternative to animal experimentation and are inexpensive and easy to develop. Limitations of these ex vivo systems include the absence of choroidal and retinal blood flow, the lack of vitreous and RPE, and the axotomy of the ganglion cells, which considerably limit the evaluation of the inner retina modifications. However, these limitations are also critical for the retina to degenerate spontaneously and progressively as the culture progresses.

Neuroretina culture systems began to develop in the 1920 s, using chicken embryos' retinas and posteriorly mammalian retinas. In 1954, Trowell developed the membrane culture method, in which the retina was placed with the vitreous surface in contact with a supporting porous membrane and maintained at an air‐medium interface. In 1989, Caffé et al. cultured the neuroretina with the photoreceptors layer facing downward over porous membrane, the technique that is currently considered the gold standard. Since then, ex vivo mammal neuroretina cultures from rats, mice, hamsters, guinea pigs, rabbits, cats, dogs, pigs, cows or primate, have been used to describe the differentiation processes of post‐natal retinas; to provide valuable insights into retinal diseases processes; to test potential therapeutic substances; to examine the role of growth factors over retinal cells' dynamics; to assess nanostructured scaffolds and their potential cytotoxicity, and to evaluate potential advanced therapies.

Although mammal neuroretina is an excellent alternative to the dependency on post‐mortem human eyes, ex vivo human neuroretina cultures have also been characterized. They have improved the current knowledge about photoreceptors, ganglion cells, glial cells and microglia dynamics. Furthermore, human tissues are theoretically better suited for translational research than animal cells and perhaps even animal models, which exponentially increases the usefulness of the neuroretina cultures, and the extrapolation of the results obtained, marking a promising future for the screening and evaluation of potential neuroprotectors.
An overview of functional, psychophysical and structural techniques to study murid models in vision science
Authors: Navarro Santiago Milla
Published: December 2022

The retina is a highly specialized tissue, made up of various cell types that are structured and organized to form a complex neural network. However, the retina is also highly susceptible to various types of pathophysiological alterations, which can lead to the loss of the different cellular elements and thus to the loss of a large part of the retina's visual functions.

Over time, different types of behavioural, functional or electrophysiological tests have been developed that have allowed us to study the different visual capacities of the retina in murine models of retinal neurodegeneration, without the need to sacrifice the animals or induce serious damage from invasive recording.

Behavioural testing has proven to be a powerful tool for the study of alterations in retinal visual pathways. These techniques allow a simple but effective analysis of the visual capabilities of experimental animal models with retinal degenerative processes. Physiological aspects such as light sensitivity or the degree of visual acuity of these animal models can be quickly and effectively analysed by applying different types of tests such as the Light/Dark Transition Test or the Optomotor Test, respectively. Likewise, behavioural techniques also allow us to study other biological aspects such as the circadian activity of the animal models, which would allow us to study alterations that also affect the retinal pathways that do not participate in the image formation process. In addition, the simplicity of some of these tests allows the combination of several parameters that allow us to simultaneously study several visual abilities equally.

Likewise, other non‐invasive functional tests, such as the Pupillary Light Reflex study, allow us to determine the degree to which retinal neurodegenerative disorders affect other closely related signalling pathways, such as the afferent and efferent pathways responsible for the pupillary reflex.

Finally, electroretinographic recording techniques are an invaluable tool for studying the functionality of the various retinal cell populations. By applying specific light stimuli, it is possible to record the specific response of certain cellular elements, studying how various pathophysiological alterations of the retina affect its functionality. Variations of these techniques have even made it possible to study the activity of cells in the primary visual cortex.

With the development of new fields of study, such as optopharmacology, the knowledge and correct choice of visual characterization techniques is essential to study the efficacy of these new ophthalmological approaches.
Development of a new vitreous tamponade for the treatment of rhegmatogenous retinal detachment
Authors: Valldeperas Xavier
Published: December 2022

We are developing a new endotamponade for the management of rhegmatogenous retinal detachment (RD). It will be reabsorbable and its efficacy will not be dependent on head posture, being equally effective for superior and inferior RD. This solution will be totally biocompatible and it will not need major changes in the usual pars plana vitrectomy surgical process.
VCN‐01: from the preclinic to a phase I trial for refractory retinoblastoma patients
Authors: Catala Jaume
Published: December 2022

Why do we propose an oncolytic adenovirus for the treatment of retinoblastoma?

Physiopathology:

Conventional chemotherapy‐independent

Highly selective RB1 route (only infects E2F‐1‐high cells)

Convenient local administration & low systemic spread

Clinical availability of a GMP‐grade virus already evaluated by the AEMPS (Spanish Drug Agency)

Security data available from adult treatment of refractory solid tumours

Clinical translation to EudraCT: 2016–001060‐11

VCN‐01 is active for the treatment of chemo‐resistant retinoblastoma

The distribution of the infective virus is restricted to the eye in mice and rabbits

VCN‐01 intravitreal injection is both feasible and safe in rabbits

Phase I Safety and Activity trial of the Oncolitic Adenovirus VCN‐01 for Patients With Refractory Retinoblastoma

Single Site,

Open Label With Dose Escalation

To evaluate safety and Activity of intravitreal VCN‐01in Patients With Refractory Retinoblastoma

Inclusion criteria

Unilateral somatic mutation RBL

Germinal mutation RBL active in only one eye (fellow eye non‐affected or enucleated)

Rellapsed or refractory to systemic, intra‐arterial or intra‐vitreal chemotherapy

Age: 1–12 yo

Exclusion criteria

Indication for immediate enucleation of the affected eye:

glaucoma

rubeosis iridis

anterior chamber disease

Conclusion.

Phase I trial EudraCT: 2016–001060‐11 to include Patients with Reactivated or refractory RBL.
value of the retina in the diagnosis of Alzheimer's disease
Authors: Salobrar‐Garcia Elena
Published: December 2022

Vision, which is a process that requires the involvement of a large number of neurons, is often impaired during Alzheimer's disease (AD). Over the past few decades, research has shown that several visual functions and structures are compromised during AD and can also be used to differentiate affected individuals from those who show normal aging. Retina is a projection from the central nervous system and shares many features with the brain. Classically, the damage in AD was thought to be restricted mainly to the brain. However, in the last years it has been demonstrated in retinas of AD human postmortem specimens, the presence of Aβ plaques and pTau deposition, being more abundant in the superior region of the retina matching with greater neuronal degeneration. Also, it has been suggested that Aβ plaques in the retina may anticipate those in the brain. In addition, recently it has also been possible to observe in vivo Aβ plaques in human retinas, with imaging techniques and ingesting curcumin as a marker of Aβ deposits. Recently, using in vivo hyperspectral imaging techniques in the retina, it has been reported that Aβ load in the brain can be predicted. These findings provide histopathological evidence that the visual system may be altered much earlier in the AD disease process than previously thought, and thus support the use of visual biomarkers in the early detection of the disease. Current in vivo imaging techniques such as OCT are allowing ophthalmologists to detect and quantify data consistent with the histopathological findings described in the retinas of AD patients. In early AD, OCT has demonstrated a thickening of the macular region and a subsequent thinning of the peripapillary area of the retina in more advanced stages of the disease. New analytic methods have shown in AD patients that thinned regions are interspersed with thickened ones in all retinal layers, except inner nuclear and outer segments. This causes roughness to appear on retinal layer thickness maps, finding that Fractal Dimension (FD) of retinal layers is greater in the AD patients, being roughness of retinal layers, assessed by the FD of their thickness maps, a possible early retinal biomarker of AD.

In the other hand, recent data suggest the vascular involvement of the retina in AD patients. Vascular changes in the retina are thought to share similar pathogenic mechanisms with cerebral vasculature. OCT and OCT angiography (OCTA) has demonstrated a thinning of the choroidal thickness in early AD and decrease of the foveal avascular zone in patients with moderate AD.

All these observations support the value of the retina as a biomarker of AD that will allow us, with the development of new research, to discover new retinal biomarkers that will help us to improve the diagnosis and follow‐up of this growing pathology.