bluuebunny/crossref_metadata_2025 huggingface dataset:
Does retinal microglia respond to peripheral nervous system injury?
Authors: Avilés‐Trigueros Marcelino
Published: January 2024

The nervous system is the principal integration and coordination centre of the organism receiving, processing and transmitting information to produce a response that regulates and maintains homeostasis. In the central nervous system (CNS), homeostasis is regulated by haemato‐neuronal barriers that prevent free entry to immune system cells, although there is increasing evidence that neuro‐immunological interactions during injury, inflammation and chronic peripheral disease may contribute to the establishment and development of chronic neurodegenerative pathologies at the CNS level.

Inflammation plays a significant role in the resolution and sequelae of CNS damage. In recent years, special attention has been dedicated to the role and phenotype of phagocytic cells acting in the CNS and, in particular, to the study of which macrophage subpopulations contribute to excessive or detrimental inflammation or, on the contrary, to beneficial repair or resolution of the lesion.

All this raises the question of how local peripheral neuroimmunological interaction induces an inflammatory response in the CNS and how this can be better understood. The study of this phenomenon in the retina is of particular interest, as the retina does not receive neural afferents from other areas of the CNS.

The use of experimental models of peripheral lesions of the peripheral nervous system, such as sciatic nerve trauma, or inflammatory lesions, such as the induction of a peripheral arthritic joint process, aims to investigate the time course of the response in the CNS to local peripheral inflammation in the retina of adult mice. The results reveal qualitative and quantitative cellular changes compatible with microglial activation processes in the retina, but no significant changes occur in its neuronal population. The presence and activation of haematic mononuclear‐phagocytic cells of myelopoietic origin are also observed in the retina, where they differentiate into microglia.

In the absence of local retinal injury, we postulate that the detected neuroinflammatory reaction may be due to a preventive CNS defence reaction favouring neuroprotection since microglial cells derived from the haematic monocyte/macrophage cell population may consider within the M2 macrophage subtype, characterized by their ability to suppress proinflammatory immune responses and promote the expression of neuroprotective and repair genes.

On the other hand, we must consider that activation of the mononuclear phagocytic system in the retina caused by a peripheral inflammatory process could potentially be detrimental to patients with neurodegenerative retinal diseases or contribute to their development.
Microglial changes in the retina and optic nerve of Parkinson's disease patients
Authors: Sáez Xavier Sánchez
Published: January 2024

xsanchez@ua.es

Patients that suffer from Parkinson disease (PD) also display non‐motor alterations. Among these non‐motor symptoms, there is clinical evidence of visual dysfunction in the pathology. Here, we will describe that there is retinal degeneration in these patients observed as a loss of retinal dopaminergic amacrine cells and intrinsically photosensitive retinal ganglion cells. Also, we describe in the ganglion cell layer the accumulation of phosphorylated alpha‐synuclein in axons and dendrites and the presence of Lewy bodies. Moreover, there is a degeneration of starburst amacrine cells, which are involved in motion direction selectivity. All these pathogenic processes are accompanied with an activation of microglia, which contribute to the retinal and optic nerve neurodegeneration providing a neuroinflammatory environment. By immunohistochemistry and bioinformatic analysis we have found that retinal and optic nerve microglia show morphological and protein expression profile changes in these patients. Taken together, these results demonstrate that in PD, microglia have a key role in the response to the retinal neurodegeneration.
Clinical validation of an adaptive optics visual simulator (VAO), a new instrument for the clinic
Authors: Hervella Lucía , Villegas Eloy A. , Robles Consuelo , Prieto Pedro M. , Artal Pablo
Published: January 2024

Purpose: To validate in the clinic the Adaptive Optics Visual Simulator VAO (Voptica SL, Murcia, Spain).

Setting: Laboratory of Clinical Optics, University of Murcia, Spain.

Methods: Adaptive optics visual simulators have been widely used in research laboratories for various applications within the visual sciences, however, their use in clinical practice has been limited. Recently, an Adaptive Optics Visual Simulator (VAO, Voptica S.L) has been commercially introduced as a medical device for clinical use. VAO combines optical measurements and visual testing within the same compact instrument. It incorporates a Hartmann‐Shack wave‐front sensor to measure objective refraction and aberrations, together with a spatial light modulator capable of correcting or inducing any optical profile while performing visual testing. In seventy‐six eyes from 38 subjects, subjective refraction (SR) was measured using VAO and trial frame as a gold standard (GS). The agreement of spherical equivalent (M) and cross cylinders (J0 and J45) between SR with VAO and with the GS was estimated using different statistic parameters: 95% confidence limits (CL), Student's t‐test or Wilcoxon Rank Sum and Pearson correlation coefficient (r).

Results: There was a strong correlation (r ranged between 0.88 and 0.99) for subjective refraction (M, J0, J45) between GS and VAO and there were not statistically significant differences (p > 0.05). The 95% CL of M, J0 and J45 were ±0.58, ±0.14 and ±0.14 D respectively. In addition to the subjective refraction, the visual acuity was also validated comparing BCVA values from GS with those from VAO, a high correlation (ρ = 0.73) was found for BCVA between both methods. Individual differences in BCVA between both methods were around or below 1 line since 95% CI was ±0.10 LogMAR.

Conclusions: Our findings suggest that VAO, the new instrument for vision analysis based on adaptive optics, provides measurements that are comparable to those of the gold standard technique in healthy eyes with 73.7% of the spherical equivalent (M) differences between them within ±0.25 D and 68.4% for BCVA within ±0.05 LogMAR. Thus, subjective refraction found with VAO can be used for prescribing, as a baseline to simulate any optical profile and to customize the selection of the ablation and the IOL design in refractive surgery.
Remote assessment of visual acuity during video consultations
Authors: Galindo‐Romero Caridad , López‐López José A. , Meroño‐Gutiérrez Marta , Bryce Elle , Edwards Lydia , Hagerty Eilidh , McDonald Kirsty , García‐Ayuso Diego , Di Pierdomenico Johnny , Cameron Lorraine , Wallace Claudine , Valiente‐Soriano Francisco J.
Published: January 2024

Purpose: To assess the reliability and repeatability of visual acuity (VA) measurement obtained remotely via electronic devices using the Optonet Vision Unit (OVU), a web‐based digital eye care software used in eye care practitioner's consultations.

Methods: A total of 78 adult participants (20–54 years of age) were recruited, 36 from Glasgow Caledonian University (Scotland, UK) and 42 from the University of Murcia (Spain). Each participant underwent a monocular VA test and retest (TRT, right eye) using three different VA charts, two of them performed in the practitioner's consultation: the Early Treatment Diabetic Retinopathy Study (ETDRS) chart as the gold‐standard VA test and the OVU computerized VA chart (Optonet Ltd©, UK) designed according to the ETDRS format; and one remote VA measurement obtained in another room using OVU. Prior to the remote VA measurement, each participant set up the video‐consultation version of the OVU software on a screen through directions provided by the examiner from another room via a Zoom call (Zoom Video Communications©, Inc., CA, USA). Small adjustments could be made by the examiner using the information that the electronic device used by the participant transmitted to the online software to which it was connected. Participants were asked to stand about 4 meters from the screen and instructed to read the letters presented. The order of VA acquisition was randomized for each participant. VA scores were recorded in logMAR, and data were analysed with SPSS. The duration of the video consultation was timed from the moment the Zoom call link was sent to the participant until the VA measurement was completed.

Results: The mean ± standard deviation (SD) of VA measured was −0.006 ± 0.14 logMAR with the ETDRS chart, −0.07 ± 0.15 logMAR with OVU and –0.05 ± 0.16 logMAR with remote OVU. TRT variability (range comprising 95% differences) showed a good agreement in ETDRS chart (mean difference ± 0.0077 logMAR, 95% CI: −0.014 to 0.06); OVU (mean difference ± 0.0028 logMAR, 95% CI: −0.012 to 0.10); and remote OVU (mean difference ± 0.0024 logMAR, 95% CI: −0.012 to 0.08). The duration of the remote VA assessment was 6.68 ± 2.21 min.

Conclusion: This study demonstrates the potential of OVU charts for clinical and teleconsultation uses, which may be useful for VA measurement in remotely based patients.
New technologies for eye care practitioners
Authors: Martín‐González Santiago , Portela‐Camino Juan A.
Published: January 2024

Keywords: orthoptics, optometry, visual rehabilitation, visual therapy.

In the 1920s, Mary Maddox opened a vision rehabilitation center in London, being considered the first orthoptist (an unknown profession in Spain, whose competences fall on Optics‐Optometry). Her father, Ernest E. Maddox, an ophthalmologist, had developed various instruments to investigate binocular vision. The new discipline seeks to improve the binocular state of the patient, affected by symptomatic tropias or phorias, through exercises that train eye movements, ductions, versions, vergences, fixations and saccades. Amblyopia, on the other hand, is still treated by occlusion of the fellow eye, following practices that began in the 18th century (George L. de Buffon).

During the 20th century, orthoptic specialists used different instruments, which have survived to this day, for the diagnosis and treatment of deviations. Perhaps the most advanced of them is the synoptophore, capable of determining objective and subjective deviations, the presence of normal or abnormal correspondences, and the presence of suppression scotoma. The synoptophore is also used in rehabilitation, together with the aperture rule, vectograms or the Brock string. However, in the case of tropias and during the 20th century, orthoptic therapy occupies a very marginal place compared to the surgical solution. The Hubel and Wiesel experiments in the 60s and 70s were interpreted restrictively, rooting concepts such as the so‐called critical period, which discouraged any attempt to treat amblyopia beyond occlusion, particularly in adulthood.

However, research carried out from the second half of the 20th century to nowadays provides evidence of the usefulness of vision rehabilitation in the treatment of strabismus and non‐strabismus visual dysfunctions, and in the recovery of amblyopia in adulthood. Basic research led by Dennis M. Levi of the University of California at Berkeley and Robert F. Hess of McGill University, as well as clinical research by the Paediatric Eye Disease Investigator Group, PEDIG, are good examples.

New technologies based on computers are currently renewing and revitalizing orthoptic practice, both in diagnosis and treatment. Eye‐trackers combined or not with Virtual Reality allow (a) to record eye movements accurately and objectively, and to identify visual behaviour and deficits, and (b) to train those movements, providing positive feedback to the patient. Screens have evolved from conventional models, later 3D and finally Virtual Reality, allowing dynamic exercises and avoiding other limitations, such as postural ones. Software algorithms adapt the difficulty of the exercises to patient's performance, record therapy compliance, and store the results in the cloud for remote control of home therapy. In addition, gamification techniques allow increasing the patient's motivation and adherence to treatment. These improvements are essential in perceptual learning, the paradigm of the new visual rehabilitation model.
Update of treatment for myopia
Authors: Bremond‐Gignac Dominique
Published: January 2024

The use of myopia control devices is essential due to increased frequency of myopic children. Different solutions can be proposed in evolutive forms. Ocular check‐up and discussion with parents and their child allowed to adapt the best system to control myopia evolution. Optical correction are based on defocus system to control myopia. Defocus glasses with different systems (DIMS, HALT, …), defocus soft contact lenses with systems (dual concentric ring, EDOF), and orthokeratology are proposed. Atropine low dose is also a very effective treatment when duration is at least 2 years. Different systems to treat myopia must be customized to children and parents needs.
AI in ophthalmology: From invisible to visible
Authors: He Mingguang
Published: January 2024

The emergence of artificial intelligence offers great potential to revolutionize practice pattern in highly image driven specialties of medicine, including Ophthalmology. In the 2 years, our research team has been collecting pairwise images, such as full colour fundus photograph (FCFP) and fundus fluorescein angiogram (FFA), on the same patients. Based on these images and Generative Adversarial Network (GAN), we developed algorithm that can “generate” FFA‐style of images based on traditional FCFP. With this technology, we can “visualize” the microaneurysm, retinal ischemia, retinal neovascularization from FCFP much better than ever before. In this lecture, we will summarize the progression on this “generative AI” work including the accuracy, challenges and opportunities.
TFOS lifestyle report: Effects of environmental conditions on the ocular surface
Authors: Villani Edoardo ,   the Environmental Conditions Subcommittee of the TFOS Lifestyle Workshop
Published: January 2024

This presentation summarizes the findings of the Environmental Conditions Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease” (www.tearfilm.org). The tear film and the ocular surface morphofunctional unit are directly exposed to the surrounding environment. Environmental factors with potential, probable or well‐established impact on the ocular surface health include: climate factors (temperature, humidity, windspeed, altitude, dew point, ultraviolet light), outdoor and indoor pollutants (gases, particulate matter, and airborne pollutants) and allergens. These factors interact each other in complex and concurrent ways, contributing to different specific ocular surface diseases, including dry eye, ocular allergies, conjunctival and corneal degenerative conditions, injuries, and neoplastic diseases. Age and sex, race/ethnicity, geographical area, and seasonality are some of the key elements playing a relevant role in environmental factors‐related ocular surface diseases.

Throughout an extensive narrative review process, this report evaluated in detail the evidence about each of those environmental conditions and the associated ocular surface diseases. Distinct environmental conditions may increase risk and/or aggravate certain conditions and may contribute to specific diseases. Indeed, a systematic review, conducted to investigate the association between outdoor pollution and dry eye signs and symptoms, found evidence supporting the risk factor role of air pollution (from NO2 and CO, but not from PM10) and soil pollution (from chromium).
TFOS lifestyle report: Effects of contact lenses on the ocular surface and adnexa
Authors: Filipe Helena Prior ,   the Contact Lenses Subcommittee of the TFOS Lifestyle Workshop
Published: January 2024

This presentation summarizes the evidence‐based findings of the Contact Lens Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease” (www.tearfilm.org).

Several risk factors can increase the potential for complications associated with contact lens wear, such as ignoring appropriate contact lens care, disregarding an ocular or systemic disease (especially if associated with an unhealthy ocular surface), reduced clinical surveillance and the simultaneous use of excessive alcohol, tobacco, or recreational drugs. The recent pandemic has introduced novel challenges to the wear of contact lenses, including mask associated dry eye, discomfort and fatigue with digital devices, accidental exposure to hand sanitizers and a decreased duration of contact lens wear. Adverse environments for lens wearers, such as pollution, dust, smoke, and sport or work accidents determining ocular trauma, can represent challenges for the use of contact lens, though protective in some cases. To ensure the best outcomes for contact lens wearers in adverse situations, prescription choice should consider several factors, including night driving, sports, wear at high altitude, military application, and outer space environments.

This presentation synthetises the lifestyle‐related choices made by both clinicians and contact lens wearers, and underlines that, if appropriately undertaken, these can positively impact contact lens wearers quality of life. A systematic review and meta‐analysis highlight the need to better understand the influence of lifestyle factors on contact lens dropout.
Effect of the transplantation type on the neuroprotective properties of mesenchymal stromal cells
Authors: Norte‐Muñoz María , García‐Bernal David , Gallego‐Ortega Alejandro , Lucas‐Ruiz Fernando , Vidal‐Sanz Manuel , Barriuso Marta Agudo
Published: January 2024

Many preclinical studies using adult Mesenchymal Stromal Cells (MSCs) for neurodegenerative diseases show promising results. However, there is a lack of concordance between the extensive research on MSC neuroprotection and clinical translation as evidenced by the few clinical trials currently using this strategy. A major discordance between animal models and patients is the type of transplant. Commonly, human cells are tested in animal models but this is a xenotransplant. As a rule, though, patients are either treated with autologous (syngeneic) or allogeneic cells. However, the crosstalk between the grafted cells and the host tissue is something that, despite its importance, is not being systematically investigated. We will show here that the therapeutic outcome, host homeostasis and immune response to intravitreal administered bone‐marrow MSCs radically changes depending on the type of transplantation. As expected, xenografts are the more damaging, followed by allografts with or without immunosuppression. Syngrafts are not completely innocuous, but they do not alter neuronal functionality, making them the safest and the best ones to neuroprotect and to induce axonal regeneration. In conclusion, the transplantation modality should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.
Laser/MIGS in myopic glaucoma
Authors: Gugleta Konstantin
Published: January 2024

Myopic glaucoma represents a therapeutic challenge, especially if due to the lack of adequate pharmacological pressure control surgery becomes necessary. Issues such as thin sclera and an increased risk of choroidal haemorrhage postoperatively make it difficult to offer an “one size fits all” solution. The standard method of trabeculectomy is burdened with additional risks, in comparisons to non‐myopic glaucomatous eyes. MIGS, such as XEN, and implants such as PreserFlo, have opened new more standardized avenues for filtering procedures, but still carry an increased risk of complications. Several years ago a modification of cyclodestructive procedure, micropulse transcleral laser therapy, has been introduced and since then used for the intermediate levels of intraocular pressure reduction. When faced with operative risks mentioned above, this laser method, combined with continued application of pharmacological therapy, can achieve reasonable levels of intraocular pressure reduction with an, in comparison to alternative methods, unprecedented levels of safety.
Refractive surgery in myopic glaucoma, good or bad?
Authors: Bron Alain
Published: January 2024

Most often, it is said and written that glaucoma is a contraindication to refractive surgery. The main argument is that modifying the corneal shape or the corneal thickness will impact intraocular pressure (IOP) measurements. This is indeed a poor argument since IOP by far, does not resume glaucoma diagnosis and care. In this presentation I will try to defend refractive surgery in selected glaucoma patients with an open‐minded and reasonable approach.
The effect of physical exercise on myopia progression
Authors: Carpena‐Torres Carlos
Published: January 2024

The increasing incidence of myopia in the coming decades supposes a scientific and public health challenge to reduce the negative impact of this chronic condition in society worldwide. Faced with this situation, it becomes clear it is necessary to control myopia progression as early as possible through the usual optical and pharmacological therapies. Still, there is also a need to discover new adjuvant treatments to be incorporated into clinical practice, including the regular practice of physical exercise as a possible strategy to decelerate eye growth and, therefore, myopia development. During the last decade, different cohort and cross‐sectional studies associated higher physical activity and increasing time outdoors with reduced risk of myopia development. However, due to the design of these studies and the multifactorial factors influencing axial growth of the eye, it would not be possible to establish a clear effect of physical exercise on controlling myopia progression. The current talk will discuss the most representative works in the field, focusing on their levels of evidence, and will explore future lines of research to answer whether physical activity can really help to reduce myopia progression and which ocular mechanisms could be implicated.
LHON spectrum disorder: Phenotype and genes
Authors: Barboni Piero
Published: January 2024

Leber hereditary optic neuropathy (LHON) is an inherited optic neuropathy primarily affecting young male with subacute bilateral visual loss. Clinically it is characterized by central scotoma, discromatopsia, and usually permanent central visual loss.

This disease has a typical optic disc appearance at fundus examination of pseudoedema and microangiopathy which characterize the asymptomatic and subacute phases of the disease. Optic disc atrophy follows in the chronic phase.

When the disease manifests, the preferential involvement of papillomacular fibres and macular retinal ganglion cell (RGC) damage are evident. These clinical features combined with the ophthalmoscopic pattern create the framework that make the disease unique.

Primary point mutations of mitochondrial DNA (mtDNA) have been described as the genetic cause of the disease in about 90% of cases. Recently, new autosomal recessive DNA mutations have been reported in patients affected by subacute visual loss associated with a clinical picture resembling LHON.

We herein describe the phenotype of 6 patients in which whole‐exome sequencing identified variants in the MECR gene in 2 probands of the same pedigree, in the NDUFAF4 gene in one patient, and mutation in the nuclear gene DNAJC30 in 3 patients. The 3 male probands with DNAJC30 mutation presented the typical LHON clinical picture with subacute loss of vision at an adult age in 2 cases and at a childhood age in one case. The pattern of visual loss with central scotoma and discromatopsia was associated with pseudoedema and microangiopathy at fundus appearance. Optical coherence tomography (OCT) analysis showed in both acute and asymptomatic family members the swelling of fibres while in the dynamic and chronic stages a progressive thinning of fibres. Visual recovery was detected in the younger patient and, partially, in one of adult patient.

The 3 other patients carrying the MECR and NDUFAF4 gene variants showed a particular course of the disease characterized by a childhood onset of visual loss followed by a recurrence of visual loss at an adult age. The childhood onset was insidious in one case and subacute in the other 2 cases (about 6 years of age).

OCT analysis demonstrated in the insidious case the temporal thinning of fibres and the macular RGC atrophy followed by swelling of fibres during the recurrence.

In the differential diagnosis of inherited optic neuropathies with clinical presentation resembling LHON we should take into consideration the recessive form with mutations in the DNAJC30 gene which appears to overlap the mtDNA LHON disease. Moreover, clinical patterns resembling LHON with recurrence of visual loss represent another form of LHON with unique clinical presentation associated with variants in the MECR and the NDUFAF4 genes. These new clinical and genetic patterns enlarge the spectrum of LHON disease.
Pharmacogenetic basis of glaucoma
Authors: Milla Elena
Published: January 2024

Personalized medical treatment is becoming more important in the current therapeutic scenario in order to gain greater efficiency and reduce adverse drug reactions. A few decades ago, pharmacogenetic studies entered the therapeutic field of glaucoma. Our group performed a study whose aim was the analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta‐blockers (BB) and prostaglandin analogues (PGA). It was a prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single‐nucleotide polymorphisms were genotyped by real‐time PCR assays: prostaglandin‐F2α receptor (rs3766355, rs3753380); cytochrome‐P450 2D6 (rs16947, rs769258); and beta‐2‐adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP) and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). 0.57 (41%) eyes were under 3 or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. Mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg respectively. Significant differences in tIOP were found in heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) (p = 0.031). MD values presented significant differences between wildtype rs3766355 (−2 ± 2.2 dB), HT (−3.87 ± 4 dB) and HM carriers (−9.37 ± 9.51 dB) (p = 0.009). Significant differences were also observed between MD in wildtype rs3753380 (−6.1 ± 8.67 dB), HT (−9.02 ± 8.63 dB), and HM carriers (−9.51 ± 7.44 dB) (p = 0.017). In conclusion, patients carrying the variant rs3766355 in HM or HT presented clinically significant higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, the more alleles affected, the worse the MD value meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.
The effect of glaucoma surgical procedures on the corneal endothelium
Authors: Georgoudis Panagiotis
Published: January 2024

All types of surgery in the anterior chamber can cause damage to the corneal endothelial cells and result in reduction of the endothelial cell density. This is the case for glaucoma procedure as well.

During this presentation, we will review the available evidence of the effect of trabeculetomy, glaucoma drainage devices (tubes) and MIGs, on the health of the corneal endothelium, in the short and long term.
Keratopathy in Pseudoexfoliation syndrome
Authors: Kandarakis Stylianos
Published: January 2024

Pseudoexfoliation Syndrome (PEX) engenders a distinctive ocular condition known as PEX‐associated keratopathy. This secondary corneal disorder arises from the abnormal accumulation of pseudoexfoliative material on the corneal endothelium, compromising its structural integrity and functional properties. Histopathologically, PEX deposits lead to alterations in endothelial cell morphology, with attendant changes in cell density and pleomorphism. These pathological shifts culminate in compromised pump function, disrupting the delicate balance of corneal hydration and leading to decreased transparency. Clinically, PEX‐associated keratopathy manifests as corneal guttae, a distinctive pattern of focal excrescences seen on specular microscopy. These endothelial excrescences contribute to diminished visual acuity and increased susceptibility to corneal decompensation. Furthermore, PEX‐associated keratopathy presents a unique set of challenges in the context of corneal surgery, necessitating meticulous preoperative evaluation and specialized surgical approaches. Thus, a nuanced understanding of the intricate relationship between PEX and its associated keratopathy is essential for optimizing the management and visual outcomes of individuals afflicted by this complex ocular syndrome.
Size of the foveal blue scotoma related to the shape of the foveal pit but not to macular pigment
Authors: Schaeffel Frank
Published: January 2024

Co‐authors: Yun Chen and Weizhong Lan.

The central fovea is known to lack S‐cones. A nice psychophysical demonstration was introduced by Magnussen et al, Vision Res 2001. If the computer screen is sinusoidally modulated in brightness at about 1 Hz and is viewed through a blue filter that transmits below 480 nm, the “foveal blue scotoma” becomes visible as a small irregular black spot that follows fixation. It is highly variable among subjects. We studied the possible reasons ‐ foveal shape or macular pigment distribution. We found that the steeper the foveal slopes and the narrower the foveal pit, the larger the foveal blue scotoma. We found no correlation with macular pigment distribution or Maxwell's spot. Therefore, the foveal blue scotoma appears to be a consequence of the lack of S‐cones in the foveal center. Unlike the foveal blue scotoma, Maxwell's spot is based on macular pigment as previously proposed.
Molecular mechanisms that cause cell death in LHON
Authors: Sadun Alfredo
Published: January 2024

Mitochondrial impairments, caused by mtDNA mutations, lead to RGC death and optic atrophy causing blindness in LHON. It was once thought that this was a disease of impaired bioenergetics. More recent thinking, considering the tempo of damage, studies in cybrids and a faithful mouse genetic model of LHON, has led to the realization that the problem is more that of the pathological generation of Reactive Oxygen Species (ROS). For example, synaptosome analysis from the brains of LHON mice show normal levels of ATP, but the blockage of Complex I activity was associated with very high levels of ROS. We hypothesized that the mtDNA mutation, specifically for 3460 in ND1, changed the atomic structures around COQ10 such that ROS were generated. In order to test that hypothesis, we conducted a series of experiments with statistical ensembles, built with Monte Carlo and Boltzmann sampling for simulations in computational chemistry. We began with the single amino acid mutation in ND1 of Complex I that switches hydrophobic alanine to hydrophilic threonine, at the entry of the Coenzyme Q10 binding channel. We explicated the mechanistic consequences of this mutation, using the tools of Molecular Dynamics and Free Energy Perturbation simulations. We showed that the mutant remained capable of binding Coenzyme Q10. Indeed, the mutated channel was even more proficient than the wild type in reducing ubiquinone to ubiquinol due to the closer average proximity of the Coenzyme Q10 headgroup to the chain of iron–sulfur clusters, from which it received electrons via quantum mechanical tunnelling. However, the mutation kinetically hindered the exit of the reduced (ubiquinol) form of Q10 from the ND1 channel, slowing the passage of its headgroup due to unfavourable electrostatics. This effect lead to overproduction of ROS via re‐oxidation of Coenzyme Q10 as electrons were sent back up the Iron–sulfur cluster chain, where the ROS production occurs. Another line of studies has shown that ROS lead to the death of RGCs affecting the smallest axons first. In those areas of the optic nerve in which larger axons are preponderate, the ROS are absorbed by the larger axons and little more happens. However, there is a dearth of large axons inferior temporally where the papillomacular bundle enters the optic nerve. Then, the ROS begins a reiterative and vicious cycle of cell death and the production of more ROS. This explains both the very peculiar spatial and temporal features of the optic neuropathy in LHON.
Clinical outcome of organ‐cultured preloaded DMEK compared to standard DMEK ‐ A single center study
Authors: Rickmann Annekatrin , Wahl Silke , Szurman Peter
Published: January 2024

The use of ready‐to‐use grafts from specialized eye banks might provide a number of benefits, including graft quality control, assured availability at a certain operation time, a decreased likelihood of case cancellation, and a shorter and less sophisticated DMEK surgery, with a resulting lower risk of graft damage. However, it is critical to thoroughly establish the clinical safety of employing these preloaded tissues. Especially since most of the studies were prepared and stored under hypothermic conditions. There are only a few studies on preprepared tissues in organ culture, which are partly controversial.

In this prospective study we included patients who received DMEK surgery at the Knappschaft Eye Clinic Sulzbach between 05/2021–12/2022. Patients received either a preloaded DMEK (pDMEK), prepared 5 days before surgery in the eye bank, or a conventional, directly before surgery, surgeon‐prepared DMEK (sDMEK).

The preliminary data shows that preloaded DMEK is a safe procedure, but there is a trend towards more frequent rebubbling in the pDMEK group and a statistically non‐significant lower postoperative endothelial cell count compared to the sDMEK group. However, visual acuity and corneal thickness reduction were similar in both groups.
Usefulness of eye tracking systems in multiple sclerosis
Authors: Guantay Carla Daniela
Published: January 2024

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by inflammation and neurodegeneration. It represents the leading cause of nontraumatic disability in young adults in many places around the world.

Currently, for the objective quantification of the damage of the visual pathway swept‐source OCT (SS‐OCT) is considered the most appropriate technique. Additionally, during the course of the disease multiple neurological deficiencies can appear, including eye motility disorders.

Patients may develop various ocular motor disorders (OMDs) affecting visual function and significantly increasing disability. These alterations involve visual function and may decrease quality of life perceived by patients because they affect, among other functions, reading capability.

OMDs, can be analysed by several recording systems, although they have not been incorporated into the practice routine clinic due to its complexity, high costs and also because the value of these alterations is probably not known.

It is possible that an accurate examination of motility eye, may have a substantial impact on the diagnosis and management of those patients. OMDs has been suggested as potential biomarker of early neurological deterioration and its evaluation could contribute to obtaining progression and response to treatments, facilitating translational development of so‐called precision medicine.

Eye trackers are state‐of‐the‐art tools that can obtain valuable information of OMDs in neurological degenerations. In MS, oculomotor alterations as saccadic dysmetria, saccadic intrusions, nystagmus, fixational deficits, smooth pursuit impairment, skew deviation, optokinetic and vestibulo‐ocular reflex impairments, may go unnoticed because systematic examination of the oculomotor systems do not use routinely these techniques.

As mentioned, objective recordings of eye movements through eye‐tracking systems are not currently performed widely, despite that they have been described as an important adjunct in diagnosis, documentation, and management of different neurologic conditions.

In addition, eye tracking is also a capable method to investigate the relationship between behaviour and neural mechanisms. Eye motion recordings provide a measure of functional preservation of the nervous system, which should be recognized to be of significant importance in assessing a disease in which disability is manifested by disruption of normal neuronal functions.

In fact, it has been described that eye tracking tasks (especially saccadic tasks) are often used as an adjunct to traditional scales for cognitive assessment. In addition, eye tracking data confirmed that MS is characterized by attention deficits.

In conclusion, there is a growing interest in the use of eye tracking systems as biomarkers for MS. Specifically in this work we have analysed a large series MS patients to detect if any of the anomalies that patients refer to, such as reading difficulties, are related to disorders of the ocular motor systems.
Use of OCT in the search for biomarkers in neurodegenerative diseases
Authors: Salobrar‐Garcia Elena
Published: January 2024

Over the last 10 years, research has increasingly demonstrated that the retina, a tissue in the central nervous system that grows from the brain, is affected by various pathological processes in patients with neurodegenerative diseases.

Some of the changes widely detected in these diseases are abnormal deposition of different proteins in the retinal and choroid layers, retinal glial changes, neuronal death as well as changes in the vision of these patients.

OCT provides high‐resolution two‐dimensional cross‐sectional imaging and three‐dimensional volumetric measurements, making it particularly useful for analysing retinal structural abnormalities consistent with disease pathogenesis. This tool can help us to measure hallmark signs and structural‐functional biomarkers in the accessible retina to assess risk, disease progression, and therapeutic efficacy in patients with neurodegenerative diseases.

In this SIS, we will review the findings found in the retina by OCT and Optical coherence tomography angiography (OCT‐A) in different neurodegenerative diseases and the use of new machine learning techniques in the search for a guide to be used in clinical practice, to assess risk, disease progression, and therapeutic efficacy in patients with neurodegenerative diseases.
Gut microbiome in ocular health and disease
Authors: Scuderi Gianluca
Published: January 2024

The term microbiome defines a complex ecosystem of microbial species colonizing our body, including their genome and the environment in which they live. Recent studies support the existence of a gut‐retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age‐related macular disorders. Understanding the role of the microbiome in ocular disorders may be crucial in driving the disease prevention and treatment approach. The presentation aims to offer an overview of the importance of the gut microbiome in relation to ocular health. More in detail, the gut microbiome will be characterized in terms of composition and functions. The role of gut microbiome dysbiosis will be discussed to understand the clinical and prognostic implications in the development or progression of retinal diseases.
Omics approaches for assessing nutrition and ocular health in the modern era
Authors: Andrés‐Blasco Irene
Published: January 2024

The relation of nutrition, omics sciences and ocular health has become increasingly prominent. The advent of genomics, proteomics, and metabolomics offers profound insights into how individual dietary components impact our genetic expression and overall health. Personalized nutrition, informed by omics data, enables dietary recommendations to optimize vision and prevent ocular diseases. Modern diets, often rich in processed foods, have shown correlations with increasing incidences of vision problems. In contrast, diets emphasizing antioxidants and specific micronutrients have demonstrated potential protective effects on the eyes. By understanding individual genetic predispositions, omics sciences pave the way for preventive measures, ensuring better ocular health and reducing the prevalence of conditions like macular degeneration. The future promises even more precise dietary interventions to improve eye health based on individual genetic profiles.
Immunotherapy induced uveitis
Authors: Makhoul Dorine
Published: January 2024

Uveitis can affect all layers of the eye and may be due to various etiologies: autoimmune, infectious, iatrogenic or masquerade syndrome. Recently, a new iatrogenic uveitis entity has been associated with cancer immunotherapy (CIT).

Immune checkpoint inhibitors and targeted therapies including BRAF and MEK inhibitors are increasingly used for treatment of metastatic malignancies. There is currently 10 immune checkpoint inhibitors (ICPIs) targeting one of three ligands, leading to T‐cell activation for attack against malignant cells. These ligands include cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4, ipilimumab), programmed death protein 1 (PD‐1, pembrolizumab, nivolumab), and programmed death ligand‐1 (PD‐L1, atezolizumab, avelumab, durvalumab).

ICPIs overcome T‐cell inhibition and increases the activity of immune system and the loss of immune homeostasis, which can lead to autoimmune/inflammatory side effects, termed immune‐related adverse events (IRAEs). IRAEs can include ophthalmic manifestations as uveitis, which can very between anterior uveitis, intermediate uveitis, and panuveitis, but also some cases of ocular surface disorders, optic neuropathy and orbitopathy.

The aim of my presentation is therefore to describe ICPI‐induced ocular IRAEs, more specifically the uveitis, detailing the anatomical specificities, potential risk factors, workup, and the management through an adapted treatment, and outcome, in relation to the outcome of the underlying tumour.
Anti‐microbial drugs induced uveitis
Authors: Heissigerova Jarmila
Published: January 2024

Anti‐microbial drugs are in rare cases recognized as inducers of intraocular inflammation, including occlusive vasculitis. The purpose of this talk to give overview of clinical features and of possibilities of treatment of these diseases.
IOL calculation in complex cases
Authors: Langenbucher Achim
Published: January 2024

Ocular biometry is a routine procedure before cataract surgery with intraocular lens implantation. In most cases optical biometry is used which is known to be highly reliable. However, there are cases where standard IOL power calculation fails and achieved refraction deviates significantly from formula predicted refraction. Especially in patients with a history of refractive surgery or after corneal grafting or pterygium removal calculation of an appropriate lens might be challenging. The purpose of this talk is to show which clinical cases in general have a high risk for inappropriate prediction of the refractive outcome. Different calculation concepts are discussed which could help to overcome refractive surprises. At the end, some challenging clinical examples are presented and discussed.
Combined cataract and vitreoretinal surgery
Authors: Modis László
Published: January 2024

Combined cataract surgery and vitrectomy is a surgical technique used to address both cataract and vitreoretinal disorders. With the advances in surgical tools, simultaneous removal of cataract associated with vitreoretinal disorders is gaining popularity. This technique offers several advantages over separate surgeries, including reduced surgical time and anaesthesia exposure, as well as quicker visual rehabilitation. However, the optimal timing and approach for combined cataract surgery and vitrectomy remain controversial.

Indications for combined cataract surgery and vitrectomy include various vitreoretinal conditions, such as retinal detachment, diabetic retinopathy, macular holes, and epiretinal membranes. The timing of surgery depends on the severity of the cataract and the vitreoretinal pathology, as well as the surgeon's preference. The most common surgical techniques include phacoemulsification with posterior chamber intraocular lens implantation, followed by pars plana vitrectomy. The filling of the vitreous cavity is possible with several types of tamponades, such as different gases, but in extreme cases even with silicone oil. After gas tamponade, proper positioning of the patient is of great importance.

Complications associated with combined cataract surgery and vitrectomy include posterior capsule rupture, intraocular lens dislocation, postoperative inflammation, and intraocular pressure elevation. However, the overall complication rate is low, and the visual outcomes are generally favourable.

In conclusion, combined cataract surgery and vitrectomy is a useful technique for managing various vitreoretinal conditions. Proper patient selection, careful surgical planning, and close postoperative monitoring are critical for achieving optimal outcomes.
TFOS lifestyle report: Effects of nutrition on the ocular surface and adnexa
Authors: Versura Piera ,   the Nutrition Subcommittee of the TFOS Lifestyle Workshop
Published: January 2024

This presentation summarizes the findings of the Nutrition Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease” (www.tearfilm.org). It is now recognized that unhealthy nutrition habits, which include either under and over eating, can impair our daily wellbeing and contribute to the risk of developing several diseases. Nutrients are substances required by the body to perform its basic functions, and must be obtained from our diet. They are broadly classified into three groups: macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals), and water. In the report each element of nutrition and its known impact on the ocular surface is discussed on the basis of scientific evidence. Vitamin deficiencies, such as vitamin A and C, have been consistently associated with ocular surface impairment, but links with other systemic nutritional deficiencies are far less established, and just hypothesized at present. The influence of factors such as age, sex, ethnicity, socioeconomical issues on nutrition, and the modulation of the gut microbiome to improve ocular surface disease are also explored. Certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body, thus leading to deficiencies of micro‐ and macro‐nutrients that are important in maintaining ocular surface health.

Among supplements, the omega‐3 and omega‐6 polyunsaturated fatty acids are the most extensively studied dietary supplements in ocular surface disease, with numerous randomized controlled trials, systematic reviews and meta‐analyses, mostly in patients with dry eye disease, and showing low to moderate certainty evidence for a reduction in either symptoms and signs.

An overarching issue identified in the report is the relative paucity of high‐quality evidence in explaining the role of nutrition in ocular surface health and disease. Eye doctors are advised to consider the evidence prior to providing nutritional recommendations to patients with respect to treatment for an ocular surface disease.