bluuebunny/crossref_metadata_2025 huggingface dataset:
How to best take care of young patients with glaucoma
Authors: Sacchi Matteo
Published: December 2022

Paediatric glaucoma is a potentially sight‐threatening disease and is considered the second leading cause of treatable childhood blindness. Paediatric glaucoma is a clinical entity including a wide range of conditions: primary congenital glaucoma, glaucoma secondary to ocular (e.g., aniridia, Peter's anomaly), or systemic disease (e.g., Sturge Weber) and glaucoma secondary to acquired condition (pseudophakic, traumatic, uveitic glaucoma). The treatment algorithm of childhood glaucoma is a step‐by‐step approach, often starting with surgery, as in primary congenital glaucoma cases. Medical therapy is also crucial in the management of paediatric glaucoma.

Here we discuss the approach to a child with glaucoma, from the diagnosis to the medical and surgical treatment. Efficacy and side effects of each approach will be discussed.

In the talk it is emphasized that paediatric glaucoma is one of the most challenging ocular disorder, requiring a step‐by‐step approach, several examinations, often multiple surgeries, and lifelong care and that a strong alliance between eye care staff and family is of paramount importance in this challenging but also rewarding journey.
VEGFA165‐induced persistent impairment of the retinal endothelial cells' barrier only transiently depends on the growth factor's action
Authors: Deissler Heidrun L. , Rehak Matus
Published: December 2022

Retinal endothelial cells (REC) form a stable barrier persistently disrupted by exposure to 1.2 nM VEGFA165 at least for up to 9 days. Such impairment – associated with persistently low cell index values assessed as a measure of permeability and low expression or loss of plasma membrane presence of tight‐junction protein claudin‐1 – can be completely prevented by binding VEGFA or by preventing VEGFA‐driven signal transduction. When added to REC exposed to VEGFA165 for 1 day, VEGF‐binding proteins or inhibitors of VEGF receptor 2 completely but only transiently revert these disturbances induced by the growth factor not improved by addition of a second portion of the VEGFA antagonist. This inhibition is – if ever – only partially successful after addition of the inhibitors to cells exposed to VEGFA for 3 or 6 days. VEGFA concentrations in the supernatant of VEGFA‐exposed cells decline from 0.6 nM 2 days after addition to 0.1 nM after 9 days which is below the threshold necessary to induce a barrier disturbance. Free VEGFA is also not present in the supernatant of cells exposed to the growth factor and its antagonists, and other permeability‐inducing cytokines, i.e. TNFalpha, IL‐6 or IL‐8, are also not secreted during exposure to VEGFA165 for 9 days. Taken together, disturbances of para‐ and transcellular flow can be prevented or reverted by blocking VEGFA‐driven signal transduction only early during exposure, because persistent changes no longer depend on the growth factor's action.
The impact of Müller cells on development and resolution of macular edema
Authors: Rehak Matus
Published: December 2022

Müller cells support physiological neuronal activity and the integrity of the blood‐retinal barrier. A major function of Müller cells is the fluid absorption from the retinal tissue, which is mediated by transcellular water transport coupled to currents through potassium channels. In various disorders as retinal ischemia, ocular inflammation and /or retinal detachment, it was shown that Müller cells decrease the expression of the potassium channel (Kir4.1) which leads to an impairment of the water transport across Müller cell membranes, and induces the cellular swelling. Osmotic swelling of Müller cells is also induced by oxidative stress and by inflammatory mediators. The data suggest that a disturbed fluid transport through Müller cells is (in addition to vascular leakage) a pathogenic factor contributing to the development of retinal edema. Pharmacological re‐activation of the retinal water clearance by Müller cells may be used for treatment of macular edema. Intravitreal steroids as triamcinolone acetonide prevent osmotic swelling of Müller cells and induce the release of endogenous adenosine and subsequent A1 receptor activation which results in the opening of ion channels. Apparently, steroids resolve the edema by both inhibition of vascular leakage and stimulation of retinal fluid clearance by Müller cells.
Diabetic macular edema
Authors: Grzybowski Andrzej
Published: December 2022

The main diabetic macular edema (DME) treatment options include intravitreal injections of anti‐VEGF agents and intravitreal injections of corticosteroids. In the past, macular laser photocoagulation (LP) was a standard of DME treatment, however, now it is utilized as an additional treatment. Two most important techniques of LP in patients with DME include focal photocoagulation and the grid laser. According to European Society of Retina Specialists (EURETINA) guidelines focal or grid laser should be utilized mainly for non‐center involving DME. In recent years anti‐VEGFs were found superior over typical laser treatment in DME patients. However, new tissue‐sparing technique, subthreshold micropulse laser (SML), avoids protein coagulation and prevents retinal scars, allowing retinal anatomic and functional preservation. It helps to improve or stabilize visual function and decrease macular thickness in treatment of DME.

Corticosteroids are often used as an alternative therapy for eyes with insufficient response to anti‐VEGF treatment because they act on different targets than anti‐VEGF agents leading to by inflammation reduction, decrease in the disruption of the blood‐retinal barrier, and retinal angiogenesis. The major steroids used in the treatment of DME include triamcinolone acetonide (TA), dexamethasone (DEX) and fluocinolone acetonide (FA). It is known, however, that steroids frequently increase the intraocular pressure, and are related with the risk of cataract development.
The bread and butter: Structural OCT and OCT‐A in uveitis
Authors: Burke Tomas
Published: December 2022

OCT has been transformative in the diagnosis, follow‐up and management of patient with uveitis. OCT‐Angiography (OCT‐A), as a further evolution in OCT technology, has shed new light on the pathogenesis and assessment of uveitides.

In this session, there will be a discussion of how OCT and OCT‐A are used in the diagnosis and follow‐up of uveitis; how these imaging modalities relate to each other; as well as how they relate to other modalities in the multimodal imaging sphere.
Meeting and old friend: Fundus autofluorescence in uveitis
Authors: Follonosa Alejandro
Published: December 2022

Fundus autofluorescence (FAF) represents a relatively new imaging modality that has been investigated in a variety of uveitic disease processes. FAF relies on the presence of innate fluorophores within ocular tissues, which can be induced to emit light when stimulated with specific frequencies of light.

Autofluorescence in the RPE depends on the outer segment renewal and can be affected by the RPE's ability to clear lipofuscin. Hence, an increased autofluorescence is seen with RPE dysfunction and a decreased autofluorescence is seen with loss of photoreceptors or the RPE.

Abnormal autofluorescence patterns have been described in a number of infectious and non‐infectious uveitides. Most reports of abnormal FAF in patients with uveitis belong to the spectrum of white‐dot‐syndromes. In the present course we will review the main autofluorescence abnormalities in disease like Serpiginous and Serpiginous‐like choroiditis, multifocal choroiditis, punctate inner choroiditis, multiple evanescent white dot syndrome and AZOOR. The recognition of theses abnormalities (in combination with other imaging techniques like optical coherence tomography and optical coherence tomography‐angiography) is extremely helpful for understanding their pathogenesis and monitoring the inflammatory activity.
Watching the cell: The future of imaging in uveitis
Authors: Chu Colin
Published: December 2022

Being able to image individual immune cells and their live behaviour in the retina will be critical to improving our understanding and management of patients with posterior uveitis. While we can observe cells in the anterior chamber and vitreous, this often does not always reflect retinal inflammation. Many of our measures of inflammation also are indirect, such as vascular leakage, macular oedema or deterioration in the electroretinogram. I will discuss our pre‐clinical work towards this goal, efforts across the wider field and the translational pathway forward for application to uveitis patients.
Haemorrhage due to intraocular tumours
Authors: Papastefanou Vasilios
Published: December 2022

Diffuse intraocular haemorrhage poses challenges for the clinician. These involve the multitude of clinical aetiologies and the variability in the treatment pathways or plan employed towards its treatment. A particular challenge involves its association with the presence of intraocular tumours. Haemorrhage is a rare manifestation in both pigmented and non‐pigmented tumours manifesting as an initial presentation or as part of the natural course of an untreated intraocular tumour. On some instances, the mere visibility and proper assessment of an intraocular tumour might be impeded with a challenging differential diagnosis.

In addition, haemorrhage can be baffling for the ocular oncologist as it might develop in treated tumours and in relation to radiation related events. The latter could affect tumour presentation post treatment and lead to treatment dilemmas.

This talk addresses the aetiology, pathophysiologic mechanisms, imaging and clinical features involved with the development of haemorrhage in this clinical setting taking into account the particular features of pigmented and non‐pigmented tumour paradigms.
Effect of MIGS on corneal endothelium
Authors: Gugleta Konstantin
Published: December 2022

Corneal endothelium is one the meeting points between glaucoma and corneal pathologies. Endothelial cells maintain corneal transparency by dehydrating the cornea, by pumping fluid from the corneal stroma back into the aqueous humour. Loss of these cells leads to fluid accumulation and corneal opacification. Loss of endothelial cells was indeed also observed with trabeculectomy, but it evolved in one of the major issues in the “big tube” glaucoma surgery. Rapid development of new glaucoma surgery techniques in the last decade re‐opened the question in the context of microinvasive suprachoroidal and Schlemm canal techniques. The more classic subconjunctival surgical drainage pathway has observed changes lately as well: collagen gel stent XEN and PreserFlo Microshunt were relatively recently introduced. With these still relatively new techniques, the research focus in the initial stages was placed on intraocular pressure reducing efficacy and general safety. However, in the meantime also research results also on the topic of endothelial cell density following these interventions have been published, and this talk will try to summarize the current knowledge in this area.
Post‐keratoplasty glaucoma; diagnosis and treatment
Authors: Wylegala Edward
Published: December 2022

Post‐keratoplasty glaucoma is one of the most detective complications. The increase in pressure after keratoplasty destroys the ganglion cells and damages the corneal endothelial cells. The presentation was prepared based on the author's experience with nearly three thousand corneal transplants. The incidence of post‐transplant glaucoma ranges from 10 to 50%, with an average of 35%. Difficulties and variations related to measuring intraocular pressure, visual fields, and OCT will be discussed. Finally, an overview of the options for classical and laser surgical treatment will be presented.
Stem cells versus keratoprostheses
Authors: Zarei‐Ghanavati Mehran
Published: December 2022

Routine penetrating keratoplasty will not survive well in some circumstances, including harsh ocular surface environment, stem cell deficiency and chronic ocular inflammation. Fortunately, there have been advances to restore vision in these conditions in two directions: artificial keratoplasty and limbal stem cell transplantation. The recipient eye should have an intact lid mechanism and good tear film for stem cell transplantations. There may also be a need for future lamellar or penetrating keratoplasty with a chance for graft rejection. Treatment of unilateral limbal stem cell deficiency is relatively simple with three surgical options: Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET) and Simple Limbal Epithelial Transplantation (SLET). However, most patients have bilateral diseases like Stevens‐Johnson syndrome (SJS), aniridia and mucous membrane pemphigoid (MMP). In this scenario, an allogenic source for limbal stem cells is needed.

Moreover, systemic immunosuppressive will be required to decrease the chance of rejection. Another option is Cultured Oral Mucosal Epithelial Transplantation (COMET) which usually provides less optimal visual acuity. The last option is keratoprosthesis (KPro). Many KPro devices have come and gone through, and two clear winners have emerged:

Boston Keratoprosthesis KPro type I

Osteo‐odonto‐keratoprosthesis, also known as the ‘OOKP’

OOKP is suitable for patients with severe dry eye and permanent lid damage. These patients should be excluded from any type of stem cell transplantation due to the inevitable chance of failure. However, Boston KPro type I may be considered as an alternative option for stem cell transplantation. Recent meta‐analysis for comparison of Keratolimbal Allograft (KLAL) and Boston KPro I in eyes affected by chemical burn has shown quite similar outcomes. Though, it should be mentioned that there are many limitations in included studies that make it difficult to reach an accurate conclusion. KPro has the advantages of shorter rehabilitation time and no need for systemic immunosuppression.

Nevertheless, there is more chance of complications or loss of visual potential with KPro. Corneal surgeons should, in fact, be familiar with both options of KPro and stem cell transplantation to guide their patients towards the correct choice of treatment. The learning curve of such surgical techniques is steep. An extended follow‐up time is necessary to evaluate the safety of any method.
United Kingdom OOKP outcomes
Authors: Avadhanam Venkata S.
Published: December 2022

The osteo‐odonto‐keratoprosthesis (OOKP) is the only option for sight restoration in patients with end‐stage ocular surface blindness in eyes with severe dryness and eyelid anomalies or defective blink. OOKP is performed as a multistage procedure, which involves buccal mucosal grafting over the eye, OOKP device construction and its impanation into the eye in sequential steps. A retrospective study was conducted at Sussex eye hospital, Brighton, and the long‐term outcomes of the OOKP cases are presented here. In total 64 patients were included, and 74 laminae were implanted, which included 60 tooth autografts, 11 tooth allografts and 3 tibial grafts. Stevens‐Johnson syndrome was the most common indication accounting for 43% (n = 7) of the cases. Glaucoma was the most common complication noted in 86% (n = 57) of the cases. Laminar resorption was noted in 67% of the laminae. At 10 years of follow‐up, 59% of the eyes had a vision better than 6/12 and 82% had a vision better than 6/60. Autograft laminae showed a survival probability of 91% over 18 years. In summary, OOKP provides excellent visual recovery and longevity of the device over the long term; nevertheless, it requires close monitoring and timely interventions to treat any complications.
Leading and managing a keratoprosthesis service
Authors: Liu Christopher
Published: December 2022

Keratoprostheses are last resort procedures and are inherently unstable. A multidisciplinary team needs to be in place, available 24/7/365 through a coordinator, with the team led by the main keratoprosthesis surgeon. There should be a telephone number and email address which are manned day and night year round. Attention should be paid to colocation of subspecialty team members who will have different timetables. Vitreoretinal expertise, including endoscopic vitrectomy expertise, and operating theatre time should be instantly available for infection and macular on retinal detachments. The extended team may include eye surgeons (corneal, adnexal, glaucoma, vitreoretinal), maxilla‐facial surgeons, anaesthetists, radiologists, fellows, and a coordinator supported by named nurses in theatres, ward and outpatients. Attention should be paid to make keratoprosthesis services more robust by having more than one key person for key roles to cover leave and sickness and orderly succession planning.
Glaucoma gene mutations and their association with angle dysgenesis
Authors: Gupta Viney
Published: December 2022

Angle dysgenesis is associated with developmental immaturity of the outflow pathways regulated by genes, which can only be ascertained with the help of histopathological studies. Mutations in some of the commonly associated genes with glaucoma, namely CYP1B1,FOXC1 PITX2, and TEK have been shown to be associated with developmental abnormalities in the outflow pathways in experimental studies. The severity of angle dysgenesis has been correlated on histopathology with certain CYP1B1 gene mutations in patients with Primary congenital glaucoma (PCG). Though MYOC mutations are known to be associated with Juvenile onset open angle glaucoma (JOAG) and even with PCG, no studies have shown the involvement of MYOC mutations in causing angle dysgenesis. There is only one histopathological report of a JOAG patient with MYOC Tyr453His mutation, where no apparent changes of the Trabecular meshwork(TM) or Sclemm's canal were noted though intense MYOC immune‐reactivity was observed at the TM. Histopathological studies for angle dysgenesis in human glaucomatous eyes are difficult to perform and are inherently associated with tissue handling artefacts. While grossly identifiable features of Ange dysgenesis on ASOCT (ADoA) have been described before, many subtle changes may also be present on ASOCT scans which are challenging to detect or precisely quantify by human observers.

We studied the ASOCT scans of patients with open angle glaucoma diagnosed between 10 to 40 years of age, who had undergone Whole Exome Sequencing (WES) followed by a bioinformatics analysis and were found to harbour a mutation (that was pathogenic) in a known glaucoma gens. We used Deep learning (DL) models to detect ADoA.

We detected MYOC mutations in 15 patients, 10 had CYP1B1, 2 had FOXC1 and 2 had LTBP2 mutation. Among these patients, angle dysgenesis on ASOCT was observed as predicted by the DL models, among all patients with known gene mutations. Overall, our DL Model was predictive of angle dysgenesis in 81% scans among MYOC positive patients, 89% CYP1B1 patients, 85% FOXC1 and 96% among those with LTBP2 mutation on an average.

Our findings demonstrated that different gene mutations affect different parts of the proximal outflow pathways. While CYP1B1 and LTBP2 was found to affect primarily the SC morphology, the MYOC and FOXC1 were found to be associated with morphological variations in the TM, since the SC in the latter was normally developed.
On a quest for solutions
Authors: Hemelings Ruben
Published: December 2022

A plethora of classification models, and especially convolutional neural networks (CNN), have been proposed for the detection of glaucoma from fundus images. Often trained with data from a single glaucoma clinic, they report impressive performance on internal test sets, but (I) lack in objective insights into the decision making process, and (II) rarely generalize well to external sets.

Opening the black‐box: need for explainable AI

Data‐driven, feature‐agnostic CNN models have shown to outperform classical machine learning approaches that rely on manually curated image features. But this comes at the expense of explainability, a concept introduced to delineate the insights into the decision process of the algorithm. Explainable AI is particularly relevant in the field of medicine, as regularity bodies require understandable decisions, in order to gain trust from both clinicians and patients. The largest area of research in explainable AI proposes the framework of saliency or heat maps, i.e. visualizations of image regions that are deemed the most important to the trained model. However, these techniques are facing increased scrutiny over the years, as some studies indicated that most saliency mapping methods perform no better than random baselines.

In our recent work, we used various fundus image cropping policies to investigate the salient regions for glaucoma detection. Our findings provide the first irrefutable evidence that deep learning can detect glaucoma from colour fundus image regions outside the ONH.

Generalizability and domain shifts

The ability to generalize, generalizability, to unseen data is of crucial importance in building clinically useful deep learning models. This can be defined on two levels. First, a model is deemed useful when it performs well on unseen data from the same domain as the training data. More concretely, this would mean that a model trained on glaucoma data from one glaucoma center works well on a holdout set of images from the same clinic. Next to internal testing, it is critical to have models that scale well to imaging data from external sources, such as a glaucoma clinic from a different city. This transition introduces a domain shift, an event where the data distribution changes. This shift can be as small as an undetectable different image colour histogram due to other lighting conditions at the external center.

Typically, domain shifts are more marked between ophthalmic centers. The usual suspects include the following non‐exhaustive list: change in camera manufacturer, disease prevalence, and demographic characteristics such as ethnicity and age. A tool that would be suited for glaucoma screening should be able to adapt to a much lower glaucoma prevalence, when initially trained on a data set obtained from a referral center. We demonstrate that a deep learning approach backed by regression loss seems more robust to data shifts than a traditional binary classification system for glaucoma screening from fundus images. Excellent results were obtained on 12 different data sets, with close to 150 000 images evaluated.
Visual field‐based AI in glaucoma
Authors: Schmetterer Leopold
Published: December 2022

Artificial intelligence (AI) has recently evoked tremendous excitement for research in the field of Ophthalmology and glaucoma. One of the areas where AI could come into play relates to the prediction of visual field progression. Currently linear trend‐based analysis is the most widely used method for assessing visual field progression. In the recent years a variety of deep learning based approaches have been proposed to better predict visual field progression. Techniques including archetypal analysis, Gaussian mixture model with expectation maximization and Visual Geometry Group standard deep Convolutional Neural Network (CNN) will be discussed. AI has also been used to study mapping of structure to function in glaucoma. This is of importance because it may be used to reduce the variability of visual field data. Hence it may increase our ability to study functional progression by combining perimetry and OCT data. Moreover, the structure/function relationship has been shown to be an independent risk factor for glaucoma progression.
Current status of limbal transplants for the treatment of limbal stem cell deficiencies
Authors: Barraquer Rafael I.
Published: December 2022

The possible treatments for limbal stem cell (LSC) deficiencies include a wide spectrum spanning from general support measures (medical, lubricants and plasma derivatives), resection techniques, the different options for supplying LSC (limbal transplants, expanded cell transplants, SLET, heterotopic mucosal transplants), all the way to keratoplasty and keratoprosthesis. This presentation will review the current status of limbal transplants for LSC deficiencies, including autologous and homologous kerato‐limbal and conjunctivo‐limbal grafts, with an update on the indications, techniques, results and postoperative management.
Corneal stromal regeneration
Authors: Alió Jorge L.
Published: December 2022

Corneal grafting is one of the most common forms of human tissue transplantation. The corneal stroma is responsible for many characteristics of the cornea. For these reasons, an important volume of research has been made to replicate the corneal stroma in the laboratory to find an alternative to classical corneal transplantation techniques. There is an increasing interest today in cell therapy of the corneal stroma using induced pluripotent stem cells or mesenchymal stem cells since these cells have shown to be capable of producing new collagen within the host stroma and even to improve its transparency. The first clinical experiment on corneal stroma regeneration in advanced keratoconus cases has been reported and included. Fourteen patients were randomized and enrolled into 3 experimental groups: (1) patients underwent implantation of autologous adipose‐derived adult stem cells alone, (2) patients received decellularized donor corneal stroma laminas, and (3) patients received implantation of recellularized donor laminas with adipose‐derived adult stem cells. Clinical improvement was detected with all cases in their visual, pachymetric, and topographic parameters of the operated corneas.
Intracameral injection of cross‐linking hydrogel polymer as an animal model of IOP increase
Authors: Di Pierdomenico Johnny , Henderson D. C. M. , Smith C. A. , Hooper M. L. , Chauhan B. C.
Published: December 2022

Glaucoma is a multifactorial neurodegenerative disease that leads to the progressive loss of retinal ganglion cells (RGCs) and their axons resulting in visual field damage and retinal and optic nerve head changes. Progression is generally slow but, in some patients, can lead to a ‘catastrophic’ reduction of visual function and in advanced cases may lead to blindness. Glaucoma is, in fact, the leading cause of irreversible blindness worldwide.

Finding a model of retinal ganglion cell (RGC) loss or experimental glaucoma which accurately mimics human disease has been a challenge for researchers. There have been many attempts to produce a model of studying RGC pathophysiology or death longitudinally to study pharmacological treatments or neuroprotective interventions. There are many methods, both acute and chronic, that have been used to induce retinal ganglion cell death. Some methods made a direct injury to the optic nerve which causes rapid RGC death, while others are models try to increase the IOP with mechanical damage or injection of different agents into the anterior chamber to block aqueous humour outflow.

Several models of chronic glaucoma, primarily in non‐human primates and rodents, in which IOP is elevated has been described. However, most of these animal models due to the opacification of the ocular medias as a result of the inflammation or intraocular pression increase only allow to perform a single time point for many different time ex vivo analysis of the RGCs. So, longitudinal changes in the number of RGCs in the same animal can only be performed in vivo. This is an important way to remove the between‐subject variability, but any aging effects will be compounded to those due to disease progression.

A novel glaucoma model using a cross‐linking polymer result in a consistent and sustained elevation of IOP with preservation of optical media clarity for long term.

This model is based on in situ temperature sensitive cross‐linking of a mixture of two components (hyaluronic acid functionalized with vinyl sulfone (HA‐VS) and thiol groups (HA‐SH)). When the mixture is injected into the anterior chamber, the higher temperature of aqueous humour compared to air causes the gel to solidify within the anterior chamber angle thereby blocking aqueous outflow through the trabecular meshwork and increasing the IOP. Furthermore, the hydrogel is localized to the anterior chamber angle with no noticeable media opacities, thereby allowing repeated in vivo imaging.

It has been shown that the increased IOP and the optical media clarity produced in this animal model of glaucoma allows for in vivo study with the Confocal Scanning Laser Ophthalmoscope of the density and structural loss of RGCs, as well as functional loss of RGCs with electroretinography for more than 4 weeks after the hydrogel injection.
Mitochondrial transport along RGC axons: Strategies to restore energy homeostasis and visual function
Authors: Di Polo Adriana
Published: December 2022

Deficits in mitochondria anterograde axonal transport is a common feature of neurodegenerative diseases including glaucoma. Whether aberrant expression of components in the transport machinery impinge directly on metabolic stress, neuronal death, and circuit dysfunction, is currently unknown. We used multiphoton microscope live imaging to monitor mitochondrial transport along the axons of retinal ganglion cells (RGC), the neurons that die in glaucoma. We found that high intraocular pressure, the most important risk factor to develop the disease, impairs anterograde movement of mitochondria along RGC axons leading to mitochondria depletion and energy decline. Molecular profiling of motor and adaptor proteins revealed loss of Disrupted in schizophrenia (Disc1) expression in glaucomatous RGC. Adeno‐associated virus (AAV)‐based Disc1 gene delivery rescued anterograde transport and replenished mitochondria in proximal and distal axonal segments. Delivery of a genetically encoded ATP sensor combined with longitudinal live imaging revealed that Disc1 supplementation increased ATP production in stressed neurons. Strikingly, Disc1 gene therapy promoted neuronal survival, reversed abnormal RGC calcium dynamics, and restored light‐evoked retinal responses and visual behaviour. Our study provides proof‐of‐principle that enhancing mitochondrial anterograde transport is an effective strategy to alleviate metabolic stress and glaucomatous neurodegeneration.
The role of autophagy in disease
Authors: Boya Patricia
Published: December 2022

Defective proteostasis is one of the hallmarks neurodegenerative diseases. Of the different components of the proteostasis network, we are interested in autophagy and its changes with age. We have previously shown that, out of the different autophagic pathways that co‐exist in all mammalian cells, macroautophagy is the first that declines with age in the retina, A crosstalk between macroautophagy and chaperone mediated autophagy (CMA) has been described whereby, in aged mice retinas, the decrease in macroautophagy correlates with increased CMA. Our working hypothesis is that in aged and degenerated retinal cells increase CMA to compensate for macroautophagy loss, in an attempt to maintain cell viability. Here, I will present our latest data showing how CMA upregulation can protect photoreceptor cells in retinitis pigmentosa models.
corneal sensitivity with non‐contact air jet esthesiometry compared with mechanical esthesiometry
Authors: Merayo‐Lloves Jesús , del Castillo J. M. Benitez , Montero Jesús , Delpech Salvador
Published: December 2022

Purpose: The aim of the study was to assess the safety of the measurements taken with a new non‐contact esthesiometer ‐Brill Engines esthesiometer (BEE) and to compare the sensitivity obtained with the Cochet‐Bonnet esthesiometer (CBE).

Methods: Sixty‐eight eyes of thirty six healthy volunteers were included in the study. Corneal central sensitivity was measured with the new BEE and with the CBE, with a 0.08 mm of diameter nylon monofilament. Measurement was performed according with the manufacturer instructions. BEE was mounted in the slit lamp and CBE measurement was used manually. A sub‐umbral esthesiometry strategy was performed. To assess whether the data followed a normal distribution, the Kolmogorov–Smirnov test was used. Likewise, the data obtained with the BEE were compared with those obtained with the CBE. A 95% confidence level was considered statistically significant. Measurements obtained with the CBE esthesiometer were converted to millibar for their comparison with the obtained with the BEE.

Results: Sixty‐eight eyes of thirty six consecutive healthy volunteers, 30.6% males and 69.4% females, underwent and complete the participation in the study. No adverse effected, ocular surface or corneal damage were detected and both test were well tolerated by volunteers. Correlation between both esthesiometers ICC was −0.123. (Table. 1). Bland Altman plots showed the great majority of data were inside the boundaries (2 SD).

Conclusions: A new non‐contact air jet corneal esthesiometer was tested in healthy volunteers with good tolerance, no adverse effects. It is not essential to exert so much force on the ocular surface to determine the sensitivity of a healthy cornea and, BEE is more sensitive compared with CBE. To confirm the pressure margins of BEE at each level and know the intervals in subjects with eye conditions, more studies will be conducted in the future with a more diverse population.

Brill Engines esthesiometer could be used as easy use, non‐invasive and portable alternative of the Cochet Bonnet esthesiometer.
Digital solutions for dry eye disease
Authors: de Ribot Francesc March
Published: December 2022

Purpose: Present a novel solution to screen‐induced dry eye symptoms that is cheap, easily deployable and scalable.

Methods: Device presentation. Research presentation. A previously validated questionnaire for screen‐induced dry eye symptoms was applied to participants after a 30‐minute read on a laptop while the blink rate was recorded on camera. This happens twice for each participant; once with Digital Blinking Stimuli (DiBS) on and once with DiBS off. Each participant is randomized to start with either DiBS on or off without her/his knowledge. DiBS is an innovative computer program that produces screen distortion during 100 ms every 4 s to induce participants to blink at a normal rate while looking at screens. Results from both groups were compared with a Student T‐test.

Results: The results showed a significant reduction in the eye soreness, eye strain and tearing subscores with DiBS on. Additionally, with DiBS on, a significant increase in the blink rate was observed.

Conclusions: DiBS is a promising new technology that may aid in decreasing screen‐induced dry eye symptoms while at the same time being cheap and easy to deploy.
Update on intrastromal cornea ring segment (ICRS) implantation
Authors: Monteiro Tiago
Published: December 2022

1. Describe the current phenotype classification of the disease, developed for ICRS surgical planning.

2. Describe the current indications for ICRS implantation in the surgical treatment of keratoconus.

3. Describe the advantages and indications of new ICRS optical designs like variable thickness and long arc‐length.
Choroidal thickness profile in keratoconus
Authors: Costa Joao
Published: December 2022

Changes in the choroidal thickness (CT) profile in Keratoconus (KC) patients have recently been described, however, the exact changes taking place in the choroid itself are still unclear. The more recent theories about the pathophysiology of KC hint to a possible inflammatory component, which might explain the increase in their CT profile compared to a healthy population. Serum inflammatory biomarkers seem to be associated with increased choroidal thickness, and vascular dilation seems to be the major component of choroidal thickening. The atopy can have a role in choroidal profile, although not determinant. Choroidal profile cannot be used as a progression marker of KC, able to differentiate patients needing crosslinking at a particular moment.
Genetic approach of antioxidant vitamin supplementation for glaucoma neurodegeneration
Authors: Zanon‐Moreno Vicente
Published: December 2022

Glaucoma is one of the main causes of irreversible blindness, producing 12.3% of blindness worldwide.

According to data from the American Academy of Ophthalmology, it is estimated that there are about 4.5 million people with glaucoma in the world. However, the real number should be much higher if we consider that in developed countries there are 50% of people with undiagnosed glaucoma. And in developing countries, this percentage rises to 90%.

Glaucoma is an age‐related disease. Its prevalence in the population over 40 years is around 2%. And in people over 70 years, the prevalence is between 3 and 8 times higher. Taking into account the progressive aging of the population, it is expected that the number of people affected by this disease will continue to increase in the coming years.

Among all types of glaucoma, primary open‐angle (POAG) is the most common, accounting for 60–70% of all cases. This type of glaucoma is characterized by high intraocular pressure, optic nerve atrophy and progressive visual field loss.

It is a multifactorial disease determined by both genetic and environmental factors. The cause still remains unknown. So, efforts are focused on preventing blindness through early diagnosis and hypotensive treatment, which is not always effective. Currently, neuroprotective treatment is also considered.

One of the most studied processes in relation to optic nerve degeneration in glaucoma is oxidative stress. Many studies demonstrate the association between the increase in pro‐oxidant molecules and the progression of POAG. Other studies show how nutritional supplementation with antioxidant vitamins decreases the risk of glaucoma and slows down its progression.

The genetics of glaucoma and its interaction with nutritional compounds have also been studied. Thus, it has been shown in patients with POAG that those who have a certain polymorphism of a vitamin C transporter gene have a significantly lower amount of this vitamin. The same as POAG patients carrying a specific polymorphism in a vitamin E transporter gene, who have significantly lower levels of this vitamin.

Another study has identified several microRNAs with a differential profile between POAG patients and subjects with ocular hypertension (OHT). And some of these miRNAs have these vitamin transporters as target genes (with high target scores), which might explain the lower vitamins amount present in glaucomatous patients.

All these results are extremely interesting and provide a lot of information for the identification of new genetic or molecular biomarkers that allow early diagnosis. And also, for the development of new therapies for a better control of this ocular disease, which will help preventing the glaucomatous blindness.
Role of antioxidants in glaucoma medical treatment
Authors: Garcia‐Medina Jose Javier
Published: December 2022

Glaucoma is a neurodegenerative disease characterized by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. This presentation intends to update the knowledge about oxidative stress mechanisms in relation with glaucoma and the effect of antioxidant coadjuvant therapy on this disease.
Neuroprotection in glaucoma – Myth or reality?
Authors: Cordeiro Francesca
Published: December 2022

The realization that lowering IOP is unable to prevent progressive vision loss in all glaucoma patients, has led to investigation of neuroprotection as an alternative or additional treatment option. Although confirmation of neuroprotective effects by randomized clinical trials is needed, there was a demonstration of positive non‐IOP dependent effects in the LoGTS study, although negative published results of the Memantine study. Much optimism exists for the potential of nicotinamide. Furthermore, it has been proposed as a treatment strategy in other ocular diseases, such as AMD. Neuroprotection has been advocated for many years in neurodegeneration. Indeed, the therapies that have been suggested in Alzheimer's and Parkinson's Disease are similar to those investigated in ophthalmology. This talk will review the evidence for neuroprotection and its role in glaucoma and application as a practical and future treatment strategy.
The silent beast – a case of late‐onset postoperative endophalmitis
Authors: Hernanz Ines
Published: December 2022

Late‐onset postoperative cataract surgery endophthalmitis remains a rare but sight‐threatening complication usually caused by slow‐growing pathogenic agents: bacterial or fungus. The delayed diagnosis and the potential irreversible ocular damage make this condition a challenging case for ophthalmologists.

Herein, we present a 71‐year‐old woman with late‐onset fungal endophthalmitis after cataract surgery caused by candida parapsilopsis, a rare etiologic agent. This diagnosis should be taken into consideration in every late‐onset postoperative persistent panuveitis with no response to antibiotics and partial response to topical steroids, even after negative vitreous or tap culture. White deposits on the surface of the intraocular lens or the capsule are a crucial sign. Systemic and intraocular antifungal therapy along with vitrectomy and intraocular lens removal—if necessary—are the main therapy to ensure the best visual prognosis.
Microbiota in MGD
Authors: Aragona Pasquale
Published: December 2022

MGD is characterized by significant changes in meibum quality that may lead to the changes in the existing ocular surface flora that can contribute to the inflammatory state typical of the condition. Several papers have addressed this aspect. Li and coworkers, dividing the DE group into MGD and non‐MGD patients, found that no statistically significant differences between the two groups. 67 Pseudomonas, Bacillus, Acinetobacter and Corynebacterium were the most represented, although Bacilli showed a higher relative abundance in the MGD group and could be considered typical pathogens of MGD. Watters and colleagues studied patients with several degrees of MGD, among which CL wearers were included. Meibum expression did not modify the bacterial profile. CoNS were the most prevalent organisms isolated, present in two thirds of the population studied, although their presence was not correlated to the severity of MGD. CL wearers showed an increased presence of P. acnes that was correlated to MGD severity. No differences in microbiota were observed related to the severity of anterior blepharitis or CL wear. Dong and coworkers, using 16 S rDNA sequencing, investigated the microbiome of 47 Chinese MGD patients compared with a control group of 42 sex‐ and age‐matched subjects without MGD. They found significant differences at the phyla level, with a significantly higher abundance of Firmicutes (31.7% vs. 19.7%) and Proteobacteria (27.5% vs. 14.7%), and a lower abundance of Actinobacteria (34.2% vs. 57%) in MGD vs control patients. At the genus level, the numbers of Staphylococcus (20.7% vs. 7.9%) and Sphingomonas (5.7% vs. 0.8%) were significantly higher in patients with MGD vs controls, while the numbers of Corynebacterium (20.2% vs. 46.4%) were significantly lower. The meiboscores showed a significant direct correlation with the abundance of Staphylococcus in MGD patients. They concluded that patients with MGD can have bacterial microbiota alterations in the conjunctival sac, with a potential role of Staphylococcus, Corynebacterium and Sphingomonas sp. in MGD pathophysiology. In a previous study carried out on a small group of patients with blepharitis, Lee and coworkers demonstrated that blepharitis might be associated with a change in microbial composition, namely, greater quantities of Streptophyta, Corynebacterium and Enhydrobacter species. It was suggested that cytotoxicity and inflammatory components, triggered by bacterial growth, may contribute to the pathological process of MGD. Zheng et al confirmed the changes of ocular surface flora in MGD patients showing a wide bacterial profile and positive aerobic and anaerobic culture, significantly higher in both meibomian secretion and conjunctiva of MGD patients than in controls. The ocular surface inflammatory condition occurring in MGD and blepharitis could be mediated by the induced expression of acidic mammalian chitinase (AMCase) that is considered an immune response activator and is over expressed in MGD. It can be hypothesized that changes in ocular surface microbial flora can mediate AMCase upregulation.
Device‐assisted therapies in MGD
Authors: del Castillo José Benitez
Published: December 2022

Meibomian gland dysfunction (MGD) is the most frequent cause of evaporative dry eye disease (DED). Until now, the only available treatments were as follows: warm compresses, massage, omega 3, and antibiotics. As a result, multiple devices have appeared in the marketplace designed to use heat and pressure to alleviate MG blockages, as well as to remove residue along the lid margins. The mechanism of action of Lipiflow®, Miboflo®, iLux® and Jett Plasma Lift® is thermal expression. The Lipiflow® consists of a console and a single‐use sterile device that uses sensor‐regulated heat and peristaltic motion to evacuate obstructed meibum. One section of the device goes behind the eyelids, providing the warmth; an outer section gently massages the lids against the inner section. Its effects last usually 12 months. Jett Plasma Lift also remove keratinized material from de lid margin. ILux® system is not available in Europe.

​Intense pulsed light (IPL) was originally developed for use in dermatology. Brief, powerful bursts of light at specific wavelengths (in this case, between 500 and 800 nm) cause changes in blood vessels near the surface of the skin, raise skin temperature and eliminate problematic flora on the skin and eyes, all of which may have a beneficial effect on meibomian gland dysfunction. Closing the abnormal vessels decrease inflammation and oxygen supply to meibocytes (they work in anaerobic conditions). Usually four sessions are needed. Expression with forceps and the treatment directly of the lids improve results. There are multiple platforms and not all are the same. BlephEx® produces microblepharoexfoliation. It's typically repeated at four to six‐month intervals. It is useful for anterior blepharitis. Rexon‐Eye® is an electro‐medical device for the treatment of DED. The applied electrical stimulation is based on the principle of quantum molecular resonance. Transferring energy to biological tissues in the form of high frequency oscillating electrical fields biostimulate the lachrymal and the MG. Thus, it is helpful for evaporative and aqueous‐deficient DED.

​The use of these devices reset the MG. They should be used on the glands before they atrophy. A combination of these treatments will probably work best for difficult patients. Independent clinical trials and studies comparing these devices and the new coming instruments are needed.