bluuebunny/crossref_metadata_2025 huggingface dataset:
Bloody tears: A new option for early diagnosis of endometriosis
Authors: Huseva Yuliya
Published: January 2024

Aims/Purpose: To investigate the cytological composition of tears to determine the potential diagnostic criteria of endometriosis.

Methods: Tear samples obtained from the lower fornix of the conjunctiva using a glass capillary tube were examined by microscopy in 100 people: 60 healthy women who made up the control group and 40 patients with endometriosis.

Results: The proportion of women with endometriosis, in whose tear erythrocytes were determined was significantly higher, 32.5%, compared with the control group ‐ 25.0%. In 69.2% of women with endometriosis, latent haemolacria was detected in the follicular phase of the menstrual cycle, which significantly exceeded the 30.8% of people with erythrocytes in tears detected in the luteal phase. Epitheliocytes were found in tears in 97.5% of patients with endometriosis versus 75.0% of healthy women, at the same time, in 100.0% cases, − in the follicular phase of the menstrual cycle, compared with 74.3% of healthy women in the same phase of the cycle. The proportion of women with epitheliocytes in the tear in the amount of “++” was 56.4%, which was significantly more compared to 20.0% of people from the control group with epitheliocytes in the same amount; at the same time, group accumulations of epitheliocytes were found in 15.0% of patients with endometriosis, which was significantly higher than in healthy women ‐ 8.3%. In 90.0% of cases in the group with endometriosis, glandular cuboidal epithelial cells were found in the tear, morphologically resembling endometrial cells.

Conclusions: The revealed features of the cytological composition of tears in patients with endometriosis, which differed from those in the control group, reflected certain links in its etiopathogenesis, so the study of tear parameters can be useful for predicting the prevalence of “endometrioid disease” and developing pathogenetically substantiated treatment.
Promising preclinical efficacy of intravitreally administered tafasitamab and anti‐Hu CD199 on immunocompetent murine model of primary intraocular lymphoma
Authors: Skrlova Eva , Uherkova Eva , Klimova Aneta , Malarikova Diana , Svozilkova Petra , Matous Petr , Herynek Vit , Kucera Tomas , Klener Pavel , Heissigerova Jarmila
Published: January 2024

Aims/Purpose: This project aimed to evaluate the efficacy of anti‐CD19 monoclonal antibody tafasitamab and experimental chemokine receptor blocker anti‐Hu CD199 and to study the impact of the microbiome on immunotherapy in an experimental immunocompetent murine model of primary intraocular lymphoma (PIOL).

Methods: PIOL was induced in immunocompetent mice BALB/CaNn by intravitreal injection of syngeneic lymphoma A20‐CD19 cell suspension. To eliminate intestinal microflora, 50% of the mice were pre‐treated with broad‐spectrum antibiotics (metronidazole and ciprofloxacin). On days 3 and 7, mice were treated intravitreally either with tafasitamab (20 μg) or anti‐Hu CD199 (1 μg). Following the injection mice were monitored clinically 2 times per week. The experiment was terminated at the first signs of exophthalmos or on day 30. Eyes were collected post‐mortem and histologically processed.

Results: In both treated groups the signs of PIOL were delayed in comparison to the control group. The untreated group started to show signs of PIOL on day 7. In the group treated with tafasitamab first signs of PIOL started to appear on days 10–14. In the group which received experimental anti‐Hu CD199, signs of PIOL first appeared on day 17. Development of exophthalmos was delayed as well, most significantly in the group treated with anti‐Hu CD199. So far, we did not observe statistically significant differences in PIOL behaviour and the effect of the treatment between the group with the intact microbiome and the group treated with antibiotics.

Conclusions: Results of in vivo experiments confirm the efficacy of both tafasitamab and experimental anti‐Hu CD199 administered intravitreally in immunocompetent mice with PIOL. However, experimental chemokine receptor blocker anti‐Hu CD199 shows greater potential in the intravitreal treatment of PIOL.

Financial support of this project: AZV MZ CR NU20‐03‐00253, SVV UK 260631.
Vision and eye research
Authors: Uusitalo Hannu
Published: January 2024

We are all, no matter whether we are basic scientists or ophthalmologist, whether it is question of discovering of novel cellular pathways, druggable targets, new therapeutical tools or technological innovations, protecting of our visual system, treating diseases threatening its function or replacing these functions, working for vision. Good vision is one of the key elements of good health‐related quality of life (HRQoL). It is a factor of working ability and self‐activity. It is important for individual development and education, understanding of the world. Poor vision on the other hand is related to decreased HRQoL, increased risk of accidents, increased use of healthcare services, early retirement, loss of productivity and problems for independent initiative. In this presentation I will describe the relationships of visual acuity, HRQoL, use of healthcare services, and socioeconomical cost based on data of nationwide health surveys and healthcare registers. The results clearly demonstrate the significant role of vision for individuals and societies. I hope, they further motivate us to work harder in our laboratories and clinics and hopefully also convince funding organizations and governments to understand, how by supporting our efforts, it is possible not only to increase the welfare but also save money in our societies.
Developing gene‐independent approaches for retinal dystrophies
Authors: Sahel José‐Alain
Published: January 2024

Inherited retinal dystrophies (IRDs) display remarkable genetic heterogeneity, with over 300 retinal disease genes mapped and/or identified. Profound vision loss and blindness, often from birth, is a common occurrence in these clinically heterogeneous disease conditions. The therapeutic options for IRDs are currently very limited but recent advancements in understanding mechanisms of retinal degeneration and technological progress paved the way towards development of novel therapies. Much progress has been made in moving from gene discovery to gene therapy. However, the genetic heterogeneity of IRDs represents a significant challenge for development of gene therapy.

Many studies from our group have demonstrated that the survival of cones (responsible for diurnal and high‐resolution vision) depends on the presence of rods (responsible for vision at low light levels) that secrete a diffusible trophic factor identified as rod‐derived cone viability factor (RdCVF). The discovery of RdCVF, of its receptor and mechanism of action, and the demonstration of its mutation‐independent therapeutic potential in several animal models of IRDs paved the way to the development (with the start‐up company Sparing Vision) of RdCVF neuroprotective gene therapy that entered in clinical trial in 2023.

IRDs destroy photoreceptors but leave intact and functional a significant number of inner retinal cells. Using viral vectors, light‐sensitive microbial opsins can be expressed in these remaining cells, making possible their conversion into ‘artificial photoreceptors’. Our group in Paris, together with Botond Roska (IOB, Basel) and the biotech company GenSight, demonstrated that this technology, named optogenetics, can restore vision in secondary retinal neurons which can survive years after the degeneration of photoreceptors. Our groups established the foundation for the first‐in‐man clinical trial (NCT03326336) with the photoactivatable optogene ChrimsonR (developed by Ed Boyen at MIT) delivered in the eye via adeno‐associated viral vectors and electronic goggles to intensify the light and provide adaptation. We demonstrated (Nat Med 2021) that optogenetics is a remarkably effective way to restore partial vision and provide useful vision restoration in blind people.

Gene‐independent approaches such as neuroprotection and optogenetics would allow for the treatment of a broad spectrum of retinal dystrophies, even at advanced stages of disease, giving hope for vision rescue and vision restoration to approximately 2 million people with IRDs worldwide.
Functional changes in the myopic retina compromise emmetropization
Authors: Schaeffel Frank , Swiatczak Barbara
Published: January 2024

During emmetropization, the retina analyses the focus of the image and generates appropriate biochemical signals to control choroidal thickness and scleral growth. Using commercially available optical low coherence interferometry (the Lenstar LS 900), changes in eye length in the micrometre range can be picked up already after 30 min when young human subjects watch movies that were digitally filtered. We found that the emmetropic retina can distinguish real optical positive defocus from simulated/calculated defocus. It triggered choroidal thickening in the first case, and thinning in the second. Strikingly, the myopic retina was not responsive, and the choroid became thinner in both cases. Longitudinal chromatic aberration (LCA) would be a perfect signal to tell the retina where the focal plane is. We simulated chromatic defocus in our movies. Either the red or the blue plane of the RGB format was spatially filtered to simulate chromatic defocus. When blue was ‘in focus’, eyes became longer, but when red was ‘in focus’ eyes became shorter. Again, myopic eyes did not respond, suggesting that the myopic retina no longer responded to LCA. Taken together, we found that the myopic retina had undergone functional changes such that no growth‐inhibiting signal was generated. As a consequence, eye growth would become open loop, explaining why myopia does not inhibit itself.
Corneal sensory nerve function: An overview
Authors: Gallar Juana
Published: January 2024

Somatosensory innervation of the cornea is provided by the peripheral axons of a small number of primary sensory neurons located in the ophthalmic region of the trigeminal ganglion. Corneal sensory nerve fibres are heterogeneous and may express different neurotransmitters and ion channels involved in transduction and coding of the stimuli acting on the tissue. Based on their activation by one or several types of physical and chemical stimuli, corneal nerve fibres are classified as polymodal nociceptors, mechanonociceptors and cold thermoreceptors. Impulse activity originated at corneal sensory nerves reaches second‐order neurons located at the lower brainstem, from where sensory information travels to the contralateral posterior thalamus and, then, to the brain cortex.

After processing, the activation of the different classes of corneal neurons results in different sensations that depend on the type of primary sensory neuron initially activated by the stimulus, although pain is the main sensation elicited by corneal stimulation. Sensations originated at the cornea are explored by esthesiometry, allowing to quantify the threshold, intensity and quality of the evoked sensations. Sensitivity of the ocular surface is reduced with age and altered by several pathological processes that affect sensory innervation, either ocular (such as allergic keratoconjunctivitis, infectious keratitis, eye surgery, hereditary corneal dystrophies, dry eye, etc.) or systemic diseases, such as diabetes and peripheral neuropathies.

A prominent feature of ocular nociceptors is their sensitization by the inflammatory mediators released after noxious stimulation or tissue injury, while cold thermoreceptor activity is inhibited by inflammatory substances. Both the spontaneous and the stimulus‐evoked activity increases in sensitized nociceptors, which causes sustained pain and hyperalgesia. After corneal sensory nerves damage (produced as a consequence of an ocular or systemic disease, or by accidental or surgical injury), part of sensory nerves degenerates leading to reduced sensitivity to natural stimulation in the affected area. At the same time, axons start to regenerate and to recover the ability to transduce and encode the stimulus. During this regeneration process, cold thermoreceptor and nociceptor nerves may become hyperexcitable due to changes in their expression/activity of ion channels, which give rise to dryness sensation and ocular neuropathic pain.

(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)
Changes in corneal sensory nerves activity and the protective mechanisms during ocular surface pathologies
Authors: Kovacs Illes
Published: January 2024

The prevalence of dry eye complaints due to tear production disorders is steadily increasing, mainly due to increased life expectancy and changes in lifestyle (contact lens wear, increased time spent in front of computer screens). However, the prevalence of subjective complaints and clinical symptoms of tear production disorders is variable, with only 10%–30% of the population having both subjective complaints and clinical symptoms. A number of in vivo confocal corneal microscopy (IVCM) studies have been performed to qualitatively and quantitatively examine the corneal nerve network in patients with dry eye disease in an attempt to elucidate the changes in corneal innervation and their clinical significance in the disease. Most studies have reported a decrease in nerve density, which may lead to nerve damage, followed by altered sensitivity of the regenerated nerves in patients with dry eye disease, resulting in hyperalgesia or allodynia. This presentation will summarize the role of corneal sensory nerves in the control of tear secretion in healthy eyes and the changes in some pathologies, particularly in dry eye disease. The changes in corneal sensory function in dry eye disease will be described in detail based on animal and human clinical studies. Knowledge of these changes will help to understand the contradictory relationship between objective symptoms and subjective complaints in dry eye patients.
DARC technology: Where do we stand?
Authors: Cordeiro Maria Francesca
Published: January 2024

The emergence of neuroprotection in glaucoma has emphasized the importance of new endpoints to assess disease and identify those at greatest risk of blindness. Several potential outcome measures have been advocated, including immunological, genetic, structural and functional biomarkers. The identification of in vivo apoptosis could serve as a potential biomarker of disease activity. The technology that has been developed to detect apoptosing retinal cells (DARC) is now being used to assess treatment efficacy in glaucoma, wet AMD, geographic atrophy and diabetic eye disease. It is currently used as an exploratory endpoint with future plans for its development as a clinically approved endpoint.
Scanning laser ophthalmoscopy ‐ Basic optical principles
Authors: Irsch Kristina
Published: January 2024

Scanning Laser Ophthalmoscopy (SLO) produces an ocular fundus image by moving a focused laser beam via scanning mirrors over the retina in a grid pattern and registering the reflected light from each scanned point. In confocal SLO, a pinhole is placed in front of the detector to cut off scattered or defocused light coming from outside the point of interest, which otherwise can blur the image. This results in a focused, high‐contrast image of a single tissue layer located at the focal plane. Tomographic information can be extracted by moving the plane of the pinhole. The use of various wavelengths allows for different applications, such as fluorescein angiography, indocyanine green angiography, and autofluorescence imaging. This lecture will present the basic principles of SLO, as well as discuss notable applications and variants of the technology.
Acta Ophthalmologica publication strategy
Authors: Kaarniranta Kai
Published: January 2024

Acta Ophthalmologica publishes clinical and experimental original articles, reviews, editorials, educational photo‐essays, letters to the editor and doctoral theses. Priority is given to high‐quality manuscripts that have novelty value and new aspects. Manuscripts are accepted on the condition that they have not been, and will not be published elsewhere, except for abstracts of oral presentations. All submissions are first subjected to chief editors and co‐editors for evaluation and will be then reviewed by two or more independent reviewers, editorial board members, and guest editors, if the manuscript has potential to be published in Acta Ophthalmologica. To date, acceptance rate is less than 15%. Over 2000 review invitations are annually sent out. The median time from submission to online publication is less than 200 days. On average, the editors‐in‐chief decision is given during the first 3 days after submission. In this talk review process in Acta Ophthalmologica will be thoroughly discussed.
How to perform gonioscopy and normal findings in the angle
Authors: Schmidl Doreen
Published: January 2024

Although new techniques for the assessment of the anterior chamber angle have become available recently, gonioscopy remains the gold standard. Different lenses that can be used for gonioscopy and their application will be discussed. Further, suggestions for a systematic assessment of the anterior chamber angle will be presented. Normal findings in healthy eyes will be summarized.
Pathologies of the anterior chamber angle
Authors: Vass Clemens
Published: January 2024

Gonioscopy is an indispensable part of work up in the context of glaucoma. Its value lies not only in differentiation between open angle and angle closure glaucoma. It is also providing essential clues for other specific glaucoma diagnoses, like pseudoexfoliation, pigment dispersion, neovascularization, goniodysgenesis and post‐traumatic changes. Examples will be shown.
Why Gonioscopy remains essential in the time of anterior segment OCT
Authors: Hommer Anton
Published: January 2024

Beside the examination of optic nerve head and retinal nerve fibre bundles, gonioscopy is the most important examinations we have to perform when performing structure analysis.

The differentiation of angle closure, angle closure suspect and open angle is essential not only for the correct diagnosis, but as well to draw the best therapeutic consequences out of these findings.

In addition to grading systems that help us to classify the types of glaucoma, we can find pathological changes like abnormal vessels, inflammatory induced changes, pigmentations, clefts etc. that help us to make the right diagnosis and therapy.

Nowadays As‐OCT is a big help and makes it a lot easier, but there are still essential deficits, that do not allow to replace gonioscopy by this new examination.

In the presentation we will show, what we can see in normal and pathological eyes and which findings can be seen in AS‐OCT and which ones cannot been seen.
Machine learning ‐ Basic principles
Authors: Bernardes Rui
Published: January 2024

Machine learning, a subcategory of AI, is a method of data analysis. It allows computers to learn from data and build models from which predictions can be made. It is based on algorithms trained for decisions making that automatically learn and recognize patterns from data. This lecture will explain the underlying principles of machine learning and discuss the differences between models learning features from the examples and those using handcrafted features.
Introduction to static vessel analysis
Authors: French Christian
Published: January 2024

This talk will provide you with an overview of static retinal vessel analyses. Digital photography, automated vessel segmentation and analyses have revolutionized the field of retinal vessel analyses rapidly. Retinal vessel calibre changes allow for non‐invasive study of the microcirculation in vivo. The study of the retinal microcirculation has shown its potential in cardiovascular risk assessment, allowed for observation of changes in systemic health and capture changes in physical activity. This session is aimed for those new to retinal vessel analyses using fundus images.
Towards “normative” data and “standardized” protocols
Authors: Heitmar Rebekka
Published: January 2024

This talk will provide you with an overview of commonly used measurement protocols and analyses used in the assessment of the dynamics of the superficial retinal vasculature. Over the past years and following a consensus paper in 2010 researchers have adopted a more “standardized” measurement and analysis approach. More recent data from larger cohorts has been used to create “normative” data sets. Such normative data sets can have great potential for risk stratification of patients, for example those with hypertension and cardiovascular disease.
Neuro‐vascular coupling as a potential biomarker
Authors: Garhöfer Gerhard
Published: January 2024

Neuro‐vascular coupling is a physiological key feature of neural tissues to adapt its blood flow to local metabolic demands. It has been shown that also in the human retina neurons, glia cells and blood vessels are closely coupled. As such, increased retinal neural activity, induced for example by visual stimulation, leads to an immediate increase in blood flow in the optic nerve head as well as in the retinal vasculature.

Because of its optical properties and its easy accessibility, the eye offers a unique possibility to non‐invasively investigate neuro‐vascular coupling in humans. The current talk aims to summarize how the role of neuro‐vascular coupling and its potential applications in the diagnosis and follow up in systemic and ocular diseases.
Malignant masquerade syndromes
Authors: Heissigerova Jarmila
Published: January 2024

Some malignant diseases may masquerade in the eye as uveitis. The purpose of the talk is to give an overview of the possibilities of diagnosis and treatment of the recognized malignant masquerade syndromes. Among these, the most frequent is intraocular lymphoma, but also other haematological malignancies such as leukaemia, thrombocytopenia, macroglobulinaemia or other malignancies such as melanoma or retinoblastoma, and many others, are also included. Diagnosis of masquerade syndromes should be considered in all patients with idiopathic corticosteroid‐resistant chronic uveitis. Timely diagnosis and treatment may in case of malignant masquerade syndromes improve prognosis and sometimes gain control over this potentially lethal disease.
Intraocular lymphoma
Authors: Svozilkova Petra
Published: January 2024

The course of intraocular lymphoma will be focused on the diagnosis and treatment of this sight‐ and life‐threatening disease. The clinical manifestation of vitreoretinal as well as choroidal lymphoma will be presented, and diagnostic methods of intraocular fluids and tissues will be discussed.
Medical students' learning experience with the Eyesi slit lamp simulator
Authors: Deuchler Svenja , Dail Yaser Abu , Koch Frank , Büdel Claudia , Ackermann Hanns , Flockerzi Elias , Seitz Berthold
Published: January 2024

Introduction: Simulation technology is constantly improving medical education in various fields. In ophthalmology, simulation is already successfully used to teach conservative and surgical skills. In 2022, the Eyesi slit lamp simulator was introduced for the first time, allowing students to learn various examination techniques and ocular pathologies. This study describes medical students' learning experience.

Methods: In this exploratory study, 50 medical students without previous experience with slit lamp examination were selected. Each student then had two training sessions, one with the classic slit lamp and one with the Eyesi slit lamp simulator. At the end of the training, students compared their learning experiences in the two sessions using a questionnaire.

Results: The simulator course was considered useful for learning slit lamp examinations (p = 0.05). Slit lamp simulator was particularly beneficial for learning ocular pathologies (p = 0.03), as these were constantly available and systemically presented without the need of direct contact with patients. On the other hand, examination of a healthy eye was judged to be better learned (p < 0.001) by reciprocal examination with the real slit lamp.

Conclusion: The Eyesi slit lamp simulator provides a structured and promising learning experience. Thanks to the growing library of modelled clinical cases, ocular pathologies can be learned in situations similar to everyday life without the need for patients to be present, allowing students to learn at their own pace and ask questions without being shy in front of patients.
Vitreoretinal complications of uveitis: The role of vitrectomy
Authors: Vakalis Athanasios
Published: January 2024

The scope of vitreoretinal intervention in patients with uveitis has recently expanded. Therapeutic vitrectomy is performed to address complications such as visual loss from vitreous opacities, retinal detachment, development of epiretinal membranes, hypotony and in certain cases to remove confined infective foci and assist in sustained drug delivery and diagnosis.

While a plethora of studies report favourable outcomes of PPV in the management of uveitis, the quality of data remains poor, with a paucity of standardized reporting and limited prospective data.

We will discuss our own experience and review the literature on each of the above surgical indications.
Retinal oximetry in vascular diseases
Authors: Šín Martin
Published: January 2024

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of haemoglobin. The imaging technology is non‐invasive and reproducible with remarkably low variability on test–retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic disease. The aim of this presentation is review of state of the art knowledge of us of retinal oximetry in vascular diseases and its possible clinical application.

In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment.

Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular oedema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia.

Retinal oxygen metabolism is altered in uveitis associated with VKH disease. Oxygen saturation profile is abnormal in acute uveitic phase of the disease and returns to normal in those who recover with normal fundus appearance, but not in eyes that suffer permanent anatomical damage with “sunset glow fundus” and chorioretinal atrophy. Retinal oximetry may be of value in evaluating vascular and metabolic aspects of posterior uveitis.
No dye, no glory: FFA and ICGA in uveitis
Authors: Gonzalez‐Lopez Julio J.
Published: January 2024

Uveitis is a potentially sight‐threatening condition characterized by inflammation of the uvea. Accurate diagnosis of uveitis is crucial for appropriate management and preservation of vision. The diagnosis of uveitis can be challenging due to the overlapping clinical features with other ocular diseases. In this context, imaging techniques such as fluorescein angiography (FA) and indocyanine green angiography (ICGA) have become indispensable tools in the differential diagnosis of uveitis.

FA is a widely used imaging modality in the diagnosis and management of uveitis. It involves the intravenous injection of fluorescein dye, which highlights the blood vessels of the retina and choroid. FA can reveal the presence of leakage, staining, and non‐perfusion areas in the retinal and choroidal vasculature, which are indicative of the inflammatory process in uveitis. Moreover, FA can detect complications such as occlusive vasculitis or choroidal neovascularization. FA can also be used to monitor the response to treatment and detect complications of uveitis such as cystoid macular oedema.

ICGA is another imaging modality that complements FA in the diagnosis of uveitis. ICGA involves the intravenous injection of indocyanine green dye, which better highlights the choroidal vasculature. ICGA can identify areas of choroidal hypoperfusion, which are often seen in posterior uveitis such as Vogt‐Koyanagi‐Harada disease or Birdshot retinochoroiditis. ICGA can also delineate areas of choroidal neovascularization. Furthermore, ICGA can help differentiate between active and inactive uveitis, which is crucial in determining the appropriate course of treatment.

In addition to their diagnostic value, FA and ICGA can provide valuable information on the pathogenesis of uveitis. FA and ICGA can reveal the presence of subclinical inflammation in asymptomatic patients, which can guide the early initiation of treatment and prevent irreversible damage to the retina and choroid. Additionally, FA and ICGA can identify the location and extent of inflammation in uveitis, which can help in the selection of appropriate treatment modalities such as corticosteroids, immunomodulators and biologic agents.

In conclusion, FA and ICGA are invaluable tools in the differential diagnosis and management of uveitis. These imaging modalities can provide vital information on the presence, location and extent of inflammation in uveitis, which can guide the selection of appropriate treatment modalities and prevent irreversible visual loss.
Genetic findings of inherited retinal diseases in Aōtearoa/New Zealand
Authors: Vincent Andrea
Published: January 2024

Aōtearoa/New Zealand is a small island nation at the bottom of the South Pacific, with a population of 5 million, and the largest Polynesian population in the world. 15% identify as Māori, and 7% as Pacific Peoples, and the spectrum of inherited eye disease encountered in this population varies from that seen in those identifying as NZ European. Keratoconus is more common, while primary open angle glaucoma is rare. A founder PDE6B variant has been identified causing up to 16% of autosomal recessive inherited retinal disease (IRD) in the Māori population. This genetically homogenous cohort permits a clear natural history for PDE6B IRD. Recurrent pathogenic variants, some novel, are also found in other IRD genes including SNRNP200 and PRPH2. Although many of those with inherited retinal disease remain genetically uncharacterised, research to date shows a range of novel variants in a many genes, but also allows exclusion of other variants of uncertain significance, due to their frequency in this cohort. There is a need for genetics researchers to have a cultural awareness of the population, and acknowledge the socioeconomic and health disparities which result in late presentation. Documentation of the specific genetic disease spectrum, clinical phenotypes, and a knowledge of regional ancestry and iwi (tribe), aids in simplifying the diagnostic process.
Vitreoretinal surgery in difficult cases
Authors: Pappas Georgios
Published: January 2024

In the everyday practice, we are dealing with various level of difficulty, while performing vitreoretinal cases. There are some cases which require high level of skills and experience in order to perform successful and effective surgery. Refractory or myopic macular holes, optic disk pit cases, PVR cases, advanced proliferative diabetic retinopathy cases, trauma cases and paediatric vitreoretinal cases are some examples. The purpose of the SIS is a group of very experienced vitreoretinal surgeons with high volume of cases, to provide tips and pearls in to how to perform safer surgery, with the best results, anatomically and functionally. We will also provide advise into how to use chandelier additional lighting and how to use and remove heavy silicone oil and buckles.
Managing challenging paediatric vitreoretinal disease
Authors: Salvanos Panagiotis
Published: January 2024

Purpose: Vitreoretinal diseases in the paediatric age group carry significant visual morbidity. We present current vitreoretinal techniques for restoring normal visual potential in these challenging cases.

Materials and Methods: Selected challenging paediatric vitreoretinal cases operated upon from September 2020 to September 2023 were included. Operative techniques used were analysed based on disease pathophysiology, surgical indication and timing, anatomical and visual outcomes.

Results: A total of 32 eyes from 23 patients were included. Diseases included ROP, FEVR, PFV, Coats disease, congenital cataract complications, retinal detachment from optic disc coloboma, morning glory anomaly, X‐linked retinoschisis and expulsive haemorrhage. A thorough understanding of embryological disease origins, surgical anatomy in this age group, as well as pathophysiology of the selected disease entities are essential. Surgical techniques that were found to offer advantages are presented.

Conclusions: Children's age, surgical timing and operative methods are important for visual prognosis.
Preventing retinal homocysteine dysregulation protects against retinal ganglion cell death
Authors: Tribble James R. , Rutigliani Carola , Canovai Alessio , Williams Pete A.
Published: January 2024

Glaucoma, the most common cause of irreversible blindness, is characterized by progressive dysfunction and loss of retinal ganglion cells. There are no neuroprotective therapies. Metabolic dysfunction is an emerging pathophysiological mechanism in glaucoma with widespread changes to energy homeostasis, yet little is known about non‐energy metabolism. We recently identified elevated retinal homocysteine as a strong early metabolomic signature in a rat model of glaucoma. We tested whether local elevation of homocysteine to the retina compounded glaucoma in the rat model by artificially rising homocysteine through intravitreal injection. Short‐term elevation of homocysteine (from 1 to 15 μM, as has been detected in the vitreous of diabetic retinopathy patients) either alone or in addition to glaucoma does not worsen retinal ganglion cell death, suggesting that local elevation of homocysteine does not contribute to retinal ganglion cell degeneration, but may be an indicator of wider metabolic dysfunction. Homocysteine is central to one‐carbon metabolism, an anabolic pathway with an essential role in generation of methionine and methyl donors (necessary for the epigenetic regulation of gene expression), and glutathione (antioxidant). In a mouse model of glaucoma, we identified early‐ and sustained‐dysregulation of genes involved in one‐carbon metabolism in whole retina. In retinal ganglion cells, a number of these genes change prior to detectable neurodegeneration. These pathways require vitamin B6 and B12 as essential cofactors, and folic acid (B9) and choline are essential precursors, for the metabolism of homocysteine. Genes involved in the transport and utilization of these cofactors and precursors were also significantly dysregulated in the retina, further supporting dysfunctional homocysteine metabolism. Dietary deficiency in these leads to homocysteine accumulation and are well associated with optic neuropathies. We hypothesize that local retinal deficiency in these may contribute to dysfunction in one‐carbon metabolism and impact wider retinal ganglion cell homeostasis. To test this hypothesis, we first supplemented the drinking water of mice with B6 (4.5 mg/kg), folic acid (B9) (1.5 mg/kg), cobalamin (B12) (20 μg/kg), and choline (750 mg/kg) as a prophylactic treatment 7 days prior to intravitreal homocysteine injection. We used a supraphysiological dose of homocysteine (500 μM) that causes spontaneous death of ~10% of retinal ganglion cell death after 7 days in untreated animals. Pre‐treated animals were completely protected from retinal ganglion cell death. Next, we pre‐treated rats in the same way for 7 days prior to induction of our glaucoma model. In untreated rats there was a ~ 40% loss of retinal ganglion cells after 14 days, and this was significantly mitigated in pre‐treated rats (only ~25% loss), demonstrating that these cofactors can provide moderate neuroprotection in a complex, multifactorial neurodegenerative context.
Resilience and neuroprotection: The efficacy of saffron Repron® in counteracting the progression of inherited retinal degeneration
Authors: Piano Ilaria , Corsi Francesca , Galante Alessia , Bisti Silvia , Gargini Claudia
Published: January 2024

E‐mail: ilaria.piano@unipi.it.

Retinal diseases can be induced by several factors, including genetic mutations, environmental stresses, and dysmetabolic processes. The result is a progressive loss of visual function, that can leading to total blindness. Among the diseases still orphaned of an effective therapy for slowing retinal degeneration is Retinitis Pigmentosa (RP). RP is one of the inherited retinal degenerative diseases (IRDs) whose cause is attributed to genetic mutations mainly at the level of rod‐specific genes. To date, about 150 mutations out of 60 different genes have been identified.

Several therapeutic strategies are being investigated, although the results are still mostly unsatisfactory and limited to specific diseases, particularly in the case of gene therapy, which is applicable only to specific mutations and therefore not applicable on a large scale. Most of the proposed treatments have been tested in animal models, but few have progressed to human clinical trials. An important approach is to identify targets at the level of those mechanisms that are in common in all forms of RP and that drive disease progression, such as stress‐oxidative and inflammation that all together are known as oxinflammation. Here we provide data showing that in RP natural compounds are effective in slowing down the progression of the disease mainly counteracting oxinflammation. Specifically, saffron “Repron” was proved to be effective in AMD and Stargardt patients as well as in pre‐clinical models both “in vitro” and “in vivo.” We tested this treatment in a IRD model. Preliminary obtained in an animal model of RP (rd10 mice) where saffron treatment was able to slow down even the degeneration of rod due to a genetic mutation. In this study, the treatment began in rd10 pregnant females and continued throughout the weaning phase and then in pups that had become autonomous. Functional, immunohistochemical, molecular biology and biochemical analyses were performed at multiple time points from P20 to P120. The results obtained show a protective effect of saffron on both retinal function and morphology, opening a prospect of preventive treatment for those inherited diseases whose progression is known.
Pellino‐2 and NLRP3 inflammasome activation in corneal disease
Authors: Cristea Ileana
Published: January 2024

Inflammation is a common factor in disease development of several corneal diseases. While a successful inflammatory response can clear an infection, eliminate a trigger, and repair tissue damage, it has also been shown that persistent antigenic stimulus, autoimmunity, long term exposure to irritants or a faulty inflammatory response can lead to chronic inflammation. The consequences of such chronic inflammation can be tissue damage, misdirected and incomplete wound repair, and can be accompanied by ingrowth of new blood vessels.

Well‐regulated NLRP3 inflammasome activation has been shown to have protective effects against keratitis and corneal neovascularization. In contrast, abnormal activation of the NLRP3 inflammasome has been seen in acute glaucoma, age‐related macular degeneration, uveitis and Behcet's syndrome, as well as in hereditary, monogenic diseases, such as keratitis fugax hereditaria.

A common trigger for NLRP3 inflammasome activation, upon treatment with various NLRP3 stimuli, is the efflux of cytosolic potassium (K+). We have recently shown that the E3 ubiquitin ligase Pellino‐2 changes intracellular localization following K+ efflux from immune cells and colocalizes with NLRP3 in activated macrophages, suggesting that Pellino‐2 is essential for mediating the effect of K+ efflux on NLRP3 inflammasome activation. Hyperactivation of the inflammasome has been linked to the formation of keloids as well as the development of corneal neovascularization.

Here the implications of the NLRP3 inflammasome activation in innate immune cells will be discussed, and how an overactivated inflammasome contributes to corneal disease development.
Retinal biomarkers in diabetic macular edema
Authors: Elsanabary Zeinab
Published: January 2024

Objective: To clarify the prognostic value of the biomarkers detected by multimodal imaging procedures as coloured fundus imaging, fluorescein angiography, near infra‐red imaging, fundus Autofluorescence, SD‐OCT, and OCT angiography to predict the response to therapy in different retinal diseases as diabetic macular edema.

Recently, there has been an interest in determining the prognostic value of changes on optical coherence tomography (OCT) such as foveal intraretinal cysts and edema, including size and location, presence of subretinal fluid (SRF), sub‐RPE fluid, subretinal hyper‐reflective material, intraretinal hyper‐reflective foci, photo‐receptor integrity and vitreo‐retinal interface.

OCT Angiography has added more information about the precise areas of capillary non‐perfusion, presence of collaterals or retinal/optic nerve head neovascularization, and abnormalities of the FAZ. It can also differentiate between IRMA and neovessels.

Finally, FAF has been studied recently in Diabetic Macular Edema, which may help to monitor the disease progression and response to treatment.

The speaker will present examples of multimodal imaging of different retinal biomarkers in diabetic macular edema that help in predicting the prognosis.
Corneal opacities in children
Authors: Kozeis Nikolaos
Published: January 2024

The corneal opacities in childhood could be either, congenital or acquired. The congenital could either localized/non‐systemic disease, like the congenital hereditary endothelial dystrophy, posterior polymorphous corneal dystrophy, congenital hereditary stromal dystrophy, peters anomaly, congenital anterior staphyloma, sclerocornea, cornea plana, cornea tumours, epibulbar dermoid, or related to systemic/metabolic Disorders like mucopolysaccharidoses, cystinosis, tyrosinemia, schnyder crystalline dystrophy, fetal alcohol syndrome. The acquired corneal opacities could be either traumatic, like traumatic breaks in descemet membrane, corneal blood staining, corneal keloids, or non traumatic like keratoconus, posterior corneal depression, keratoglobus, congenital or infantile glaucoma, Corneal ulcers, Familial dysautonomia (Riley‐Day syndrome), Stevens‐Johnson syndrome and toxic epidermal necrolysis. We will discuss these cases, their clinical picture, work up and management.
Corneal degenerations
Authors: Modis László
Published: January 2024

The concept of degeneration means that previously intact tissues are slowly and gradually deteriorating, often to the point where they cannot perform their function properly. As their aetiology is not uniform, their clinical manifestations are also very diverse. The same is true for corneal degenerative conditions. Corneal degeneration may involve deposition of certain substances, thinning of the tissue, vascularization, or a combination of these. What distinguishes them from corneal dystrophies is that they are not hereditary, are often unilateral, and their morphology and localization are much less regular.

Corneal degeneration may be peripheral and/or central, superficial and/or deep. It may be primary or secondary according to its origin. They can be grouped in several ways. In origin, they may be (a) age‐related, (b) may develop at the base of other corneal or eye diseases (c) may be the consequence of systemic diseases. (d) may also be caused by drugs and toxins. In many cases the aetiology is obscured. Environmental factors, ultraviolet radiation and oxidative stress are also thought to play a role.

Proper diagnosis is essential in choosing effective treatment strategy and thus achieving positive clinical results. When corneal degenerations significantly affect visual acuity, the treatment should aim relieving the primary disease before inducing further changes in the cornea.
The newest IC3D classification of corneal dystrophies
Authors: Seitz Berthold , Lisch Walter
Published: January 2024

In the year 2015, the International Committee for the Classification of Corneal Dystrophies (IC3D) incorporated new clinical, histopathologic, and genetic information into the former 2008 classification. To this end, the IC3D sighted and evaluated worldwide peer‐reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates including categories 1 to 4 and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added.

On the basis of revisiting the cellular origin of corneal dystrophies, a modified anatomic classification was proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial‐stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. The entity “Epithelial recurrent erosion dystrophies ERED” actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI‐induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel‐Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel‐Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so‐called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Anterior segment OCT has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination in order to definitively diagnose them.

This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies that more accurately classifies TGFBI dystrophies affecting multiple layers rather than being confined to one corneal layer. At this time, a 3rd edition of the IC3D classification of corneal dystrophies is under way.
Adverse effects of BAK in glaucoma medications
Authors: Tatham Andrew
Published: January 2024

Benzalkonium chloride (BAK) is a common preservative found in glaucoma medications used to increase shelf‐life, prevent bacterial contamination, and enhance ocular penetration. Its detergent properties kill microorganisms by disrupting cell membranes and causing cell lysis. Unfortunately BAK also has potentially harmful cytotoxic effects, particularly for the ocular surface, with evidence of BAK‐induced apoptosis of conjunctival and corneal epithelial cells, decreased density of conjunctival goblet cells, delayed corneal wound healing and reduced density of corneal nerved. It may also affect deeper ocular structures including the lens and trabecular meshwork, with BAK shown to cause apoptosis of human trabecular meshwork cells in culture. Clinical consequences may include increased risk of ocular surface disease, reduced adherence, and with long‐term use, reduced success of glaucoma surgery.