bluuebunny/crossref_metadata_2025 huggingface dataset:
A new inverted meniscus IOL to improve peripheral vision
Authors: Artal Pablo
Published: December 2022

The optical quality of the images formed by the eye in the retina imposes a physical limit to our vision. For decades, the eye's optics has been mainly studied on axis, typically at the fovea where the eye has its maximum spatial resolution. However, beyond the fovea, the quality of the eye in the periphery of the retina presents special characteristics. It was discovered that the crystalline lens have a protective effect for the peripheral optics that was missed after cataract surgery when intraocular lenses were implanted. In this talk, I will revise the state of the art of this area with special emphasis in the results of my lab including the design and clinical result of a new intraocular lens with an inverted meniscus shape to improve peripheral optics in pseudophakic patients.
Customized asphericity for increased depth of focus
Authors: Yago Ines
Published: December 2022

In this presentation, I will revise the visual performance at different distances of a binocular combination of two models of a new inverted meniscus intraocular lens (IOL), Art40 and Art70 (ArtIOLs, Voptica SL, Murcia, Spain) which induce different amounts of negative spherical aberration to increase the depth of focus. This combination significantly extended the depth of focus up to at least 40 cm improving visual performance at intermediate distance in comparison with trifocal LIOs. This resulted in spectacle independence for the patients without the compromise of halos or disphotopsias.
Options and considerations for the correction of presbyopia in the absence of cataract
Authors: Reinstein Dan Z.
Published: December 2022

PRESBYOND Laser Blended Vision is a treatment option for presbyopic patients that combines micro‐anisometropia with increased depth of field through non‐linear aspheric ablation profiles. This technique substantially improves visual outcomes in comparison with the conventional monovision approach. Trials show that PRESBYOND is effective in presbyopic patients with refractive errors between +5.75 and −9.00 D, including emmetropic presbyopes. With the safety advantages of modern femtosecond LASIK, retention of functional stereo acuity, contrast sensitivity and quality of vision, the rapid bilateral surgical procedure and a recovery time of a few hours, patient satisfaction is extremely high. In patients with no visually significant cataract, performing a corneal treatment avoids the increased risks associated with intraocular surgery, particularly risks that are relatively higher in younger presbyopic patients such as retinal detachment.
Innovative approaches to measuring intraocular pressure
Authors: Royo Maria Jesús Muniesa
Published: December 2022

Although different factors have been implicated in the development and progression of glaucoma, intraocular pressure (IOP) remains the main modifiable risk factor. Goldmann applanation tonometer (GAT) considers the “gold standard” for measuring IOP. The main deficiency of GAT, however, is the static nature of its measurements and that it is dependent on corneal biomechanics, central corneal thickness as well as scleral stiffness. The single measurement of IOP for the management of glaucoma provides limited information since it does not take into account the natural fluctuation of IOP, individual ranges, IOP peaks or variations throughout the day. Although the role of IOP fluctuations in glaucoma progression is not clearly defined, there is consensus on the importance of understanding the circadian profiles of IOP in glaucoma patients. Given the limitations of GAT for the actual measurement of IOP, different tonometers have been designed with the aim of advancing in self‐tonometry as Icare HOME, or obtaining independent measurements of corneal biomechanics, as Ocular Response Analyser (ORA), Pascal dynamic contour tonometer or the Corvis ST tonometer. Research to monitor IOP is based on three different strategies: (1) self‐tonometry; (2) permanent monitoring of the IOP; and (3) the temporary monitoring of the IOP. Currently, the sensors in contact lenses allow the IOP profiles to be recorded semi‐continuously for 24 hours with a minimally invasive technique, independent of the patient's position and the activity performed, opening new perspectives in the knowledge and management of glaucoma.
Anatomical and functional results of vitrectomy and gas tamponade in macular hole treatment
Authors: Novytskyy Ihor , Tomkiv U.
Published: December 2022

Background: Idiopathic macular holes (IMH) of large sizes are still challenging for vitreoretinal surgeons. Predict factors of the treatment effectiveness are little‐known.

Purpose: To evaluate the effectiveness of large idiopathic macular holes surgery with 18% perfluoropropane (C3F8) gas tamponade.

Methods: The retrospective study, which includes 68 eyes of 68 patients diagnosed with IMH stage 3 or stage 4 (Gass classification) between January 2015 and January 2020. Among them, there were 16 men (23.5%) and 52 women (76.5%). The mean age of patients was 66.7 ± 4.3. Morphologic parameters of the macular hole (base diameter, minimum diameter) were measured and then hole form factor (HFF) was calculated. All eyes underwent 25 gauge pars plana vitrectomy, internal limiting membrane peeling, 18% C3F8 gas tamponade and postoperative face‐down positioning for two weeks. The minimum follow‐up period was 3 months and the mean follow‐up period was 19.6 ± 11.4 months. The main outcome measures were IMH closure confirmed by spectral domain optical coherence tomography at 1 month postoperatively and visual acuity at 3 months postoperatively.

Results: No intra‐ and postoperative complications were observed. The IMH were closed in 61 out of 68 eyes at one month after surgery. The anatomic closure rate was 89.7%. The mean base diameter of IMH was 1022.82 ± 292.36 μm (range: 682–2019 μm). The mean minimum diameter of IMH was 471.71 ± 138.73 (range: 258–766 μm). The mean preoperative BCDVA was 0.72 ± 0.29 logMAR and mean postoperative BCDVA at 3 months after surgery was 0.5 ± 0.33 logMAR (p = 0.063, t‐test). In 47 patients (69.1%) BCDVA improved after surgery. Mean gain in visual acuity at 3 months after operation was 0.20 ± 0.27 (ΔBCDVA, logMAR). Visual acuity worsened or remained unchanged after surgery in 21 patients (30.9%) due to postoperative vitreoretinal interface disorders (foveal thinning, retinal pigment epithelium defects, and foveal cysts). The mean HFF value was 0.77 ± 0.09. There was a statistically significant moderate positive correlation between HFF and postoperative BCDVA (r = 0.56, p = 0.03, Spearman's Rho).

Conclusion: Macular hole surgery with 18% C3F8 tamponade is effective technique and is associated with high rates of IMH closure and postoperative BCVA improvement. HFF was significantly correlated with postoperative visual outcomes in cases of large IMH.
What is the best way to treat refractory macular hole?
Authors: Ruban Andrii
Published: December 2022

Background: Despite the abundance of surgical approaches proposed for persistent full thickness macular hole (PFTMH) treatment the choice of the optimal technique remains debatable.

Purpose: to analyse the anatomical and functional outcome of surgery for persistent macular holes and to determine significant risk factors for failure of primary 25‐g vitrectomy with ILM peeling and gas tamponade for treatment of FTMH.

Patients and Methods: Thirty‐eight eyes of thirty‐seven patients with FTMH that underwent primary 25‐gauge PPV, ILM peeling and gas tamponade (GT) were recruited to this retrospective, consecutive, interventional study. Four eyes with persistent holes underwent a re‐operation and outcome‐related factors were discussed.

Results: The primary closure rate was 89.5% (34/38). In all failed to close (FTC) cases in this study we used the novel technique recently described by us previously. This manoeuvre included the combination of a subretinal‐fluid application technique with centripetal displacement of the macula and ILM flap technique (inverted pedicle ILM flap technique was used in 3 cases and free ILM flap in 1 case). Four eyes that underwent the repeated surgery obtained final closure. A hole size of >500 μm has a statistically significant effect on the primary macular hole closure (F = 0.048; φ = 0.38; p ˂ 0.05). In the Group 2 with primary unclosed holes, 75% of the eyes (3/4) had an axial length (AL) > 26 mm, while in Group 1 with primary closed holes such eyes were 12.5 times less (2/34) 5.9% (F = 0.004; φ = 0.63; р ˂ 0.01).

Conclusion: The combination of a SR‐fluid application technique with centripetal displacement of the macula and ILM flap technique for refractory FTMH provide satisfactory morphologic and functional outcomes. Elongated AL, large diameter of MH and long duration of symptoms are the risk factors for initial closure. Proper second surgery can obtain satisfactory outcomes for persistent holes.
Oculomics: The eye as a window to systemic disease
Authors: Balaskas Konstantinos
Published: December 2022

Objective: To evaluate the effect of pegcetacoplan on the area of geographic atrophy (GA) and its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, and hypertransmission).

Design: Post hoc analysis of the FILLY trial using a deep‐learning model for spectral domain optical coherence tomography (SD‐OCT) auto‐segmentation.

Setting: A multicenter trial dataset from 46 participating centres in the United States, Australia and New Zealand.

Participants: 246 patients were randomized in a 1:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM) and sham treatment (pooled) for 12 months of treatment and 6 months of therapy‐free monitoring. Only participants with Heidelberg SD‐OCT were included in longitudinal analyses (n = 197, single eye per participant).

Interventions: An auto‐segmentation model quantified the area of each SD‐OCT feature of GA at baseline and at 6, 12 and 18 months. The mean square root area change from baseline was compared across the treatment arms. This was further stratified topographically.

Main Outcome Measures: Primary efficacy endpoint was the square root transformed change in area of RPE and outer retinal atrophy (RORA) in each of the treatment arms (PM, PEOM, and pooled sham) at 12 months, with secondary end‐points including RPE‐loss, hypertransmission and PRD.

Results: Eyes treated PM showed significantly slower mean change of RORA progression at 12 and 18 months (0.151 mm and 0.277 mm, p = 0.0039; 0.251 and 0.396 mm, p = 0.039, respectively) and RPE‐loss (0.147 mm and 0.287 mm, p = 0.0008; 0.242 mm and 0.410 mm, p = 0.00809). PEOM showed significantly slower mean change of RPE‐loss compared to sham at 12 months (p = 0.0313). Intact macula was preserved in PM compared to sham at 12 and 18 months (p = 0.0095 and p = 0.044).

Conclusions and Relevance: The OCT evidence suggests pegcetacoplan slows progression of RORA overall and RPE‐loss specifically whilst protecting the remaining photoreceptors and slowing the progression of healthy retina to RORA.

Significance: This post hoc analysis of optical coherence tomography (OCT) scan data from the FILLY randomized controlled phase 2 trial showed that monthly treatment was significantly associated with a slower rate of progression of geographic atrophy as defined by OCT criteria at 12 and 18 months. Furthermore, at the level of the individual retinal layers, there was evidence that monthly pegcetacoplan not only slowed down loss of retinal pigment epithelium, but also reduced the rate of loss of intact macula and isolated photoreceptor loss (which were proposed as novel monitoring targets).
Effects of refraction on straylight
Authors: Van Den Berg Thomas J. T. P.
Published: December 2022

The effect of cataract and other media opacities on functional vision is typically assessed clinically using visual acuity. However, from both clinical and basic research, it has become evident that straylight (the functional result of light scattering in the eye) must be considered also as significant part of quality of vision. The optical basis of acuity and scatter are quite different. Acuity (and contrast sensitivity) depend on the refractile structure of the eye optics (refractive error and aberrations), whereas straylight mostly depends on the presence of light scattering particles of microscopic size. It must be noted that the first aspect is of global nature; the refractile structure concerns all light entering the pupil, whereas light scattering is of local nature, concerning only part of the light entering the pupil. The other part is under the influence of the refractile structure only. The subject of this presentation is the potential link between these two phenomena, and their functional counterparts: is visual acuity in cataract and other media opacities related to straylight? On the other hand, is straylight or its measurement under the influence of refractile errors, more in particular for myopic eyes?

Potential interdependence between acuity and straylight was addressed for normal eyes by manipulating refractive correction with plus lenses. No effect on measured straylight values was found. Also statistically, little relation between straylight and acuity exists in the normal population, in concordance with expectation from theoretical modelling. Visual acuity losses with cataract and other media opacities are not due to straylight, but caused by aberrations and micro‐aberrations. Straylight defines disability glare, and causes symptoms of glare, haloes, hazy vision etc. Overall, visual acuity and straylight are rather independent aspects of quality of vision.

For myopic eyes, literature has shown a clear interdependence (Rozema et al. IOVS 2010 pp 2795–2799). To understand this finding, straylight values were measured with the C‐Quant (Oculus Optikgeräte, GmbH, Wetzlar, Germany) in (1) near‐emmetropic eyes (n = 30) with various negative powered refractive lenses and in (2) myopic eyes (n = 30) corrected with prescribed eyeglasses and contact lenses. The straylight measurements in each group were compared in the different conditions. In the near‐emmetropic group, a significant effect (p < 0.001) of each added negative diopter was found to increase straylight values with 0.006 log‐units. In the second group, no significant correlation with type of correcting lens was found on straylight values. So, refractive correction with high minus power (contact) lenses result in subtle increase of straylight values. These changes are relatively small though.
Straylight in clinical practice
Authors: Reus Nic J.
Published: December 2022

Straylight is an optical phenomenon where light is scattered in the eye. This causes a veil of light over the retina and thereby reduces the contrast of the image projected on the retina. Clinically, it may cause disability glare where people are blinded by a sun that sits low in the sky or by headlights of upcoming cars at night. Various ocular pathologies may cause an increase in straylight in the eye. Examples are cataract, corneal dystrophies, corneal scars, vitreous opacities, and opacifications of the intraocular lens. However, patients are not always aware that their complaints are (at least partly) due to increased straylight. In addition, it is not always recognized by clinicians that patients are bothered by straylight. Furthermore, interestingly, cataract surgery may actually increase straylight in the eye when surgery is performed too early. In this presentation, I will focus on various ocular pathologies that may cause increased straylight, and how to use straylight in clinical decision making.
How straylight affects driving ability
Authors: Hershko Sarah
Published: December 2022

We investigated how an increase in straylight affects the driving capacity of young, healthy volunteers between the ages of 20 and 40 years (i.e., people without cataract) in various real‐life driving circumstances using a driving simulator. This simulator allowed us to assess driving behaviour in a controlled, repeatable environment without risk to life or property, while providing a large set of parameters (speed, brake performance, deceleration, collisions, standard deviation of the lateral lane position, (SDLP), headway distance, etc.). The simulator used a fixed‐base setup with a force‐feedback steering wheel, an instrumented dashboard, brake, and accelerator pedals and with a 135° field of view. Participants had to drive along a certain course with of 6 traffic situations (e.g., crossing pedestrian, obstacle on the way, etc…) while wearing their own spectacle correction, both in the presence of a glare source and without. Next this was repeated while wearing a Tiffen Black Pro Mist (BPM) filter in front of their eyes and a glare source. These filters approximate the optical characteristics of cataract fairly well, where BPM 1 mimics simulates early cataract (which often prompts people to stop driving at night) and BPM 2 simulates serious straylight hindrance. Straylight was measured with the van den Berg straylight meter (C‐Quant).

The results showed that increased straylight significant alters driving behaviour, such as a decrease in mean, maximum and minimum speed. The detection time and reaction time to an obstacle on the road was significantly longer with increased straylight. Consequently, straylight is an important factor in traffic safety driving conditions, causing altered driving behaviour and increasing collision risk in certain traffic situations.
Developing an AI retinal biomarker
Authors: Cordeiro Francesca
Published: December 2022

Retinal imaging technologies have advanced rapidly over the past few years, and with their development their ability to be used as endpoints and even surrogate makers of eye and brain diseases. Optical Coherence Tomography (OCT) is now a routine test offered around the world. Both hardware and software advances including fast acquisition speeds, big data from a single patient scan and algorithms (with and without AI) account for recognition of the value of OCT imaging in CNS disease. Adaptive optics and OCT angiography have been also utilized for assessment of disease. The technology that has been developed to detect apoptosing retinal cells (DARC) has completed Phase 2 trials including patients with AMD, optic neuritis, Down's dementia and glaucoma. For all neurodegenerative conditions, the unmet need is to identify early disease. This can only be possible if we are able to screen to find the earliest stages of disease. Retinal imaging provides an opportunity to do this.
Integrated assessment of temporal, structural and spatial parameters of dynamic retinal vessel behaviour in diabetes mellitus type 1
Authors: Kotliar Konstantin
Published: December 2022

Vascular risk factors contribute to the development of diabetes mellitus. Dynamic retinal vessel analysis is usually defined as non‐invasive clinical observation of the reaction of retinal vessels to a physiological stimulus. The data which is thus generated may be further analysed with respect to dynamic time‐dependent and spatial vessel behaviour. We assume that assessment of different aspects of retinal vessel dynamics highlights different peculiarities of the underlying disease and allow for specific and sensitive characterization of vascular pathology. This concept of multimodal analysis of pathologic retinal vessel behaviour was performed for the example of diabetes mellitus type 1 (DM1). 35 untreated DM1 patients with no or non‐proliferative retinopathy and 35 age and gender matched medically healthy volunteers were examined by Dynamic Vessel Analyser (DVA, IMEDOS, Jena, Germany). Different aspects of dynamic retinal vessel behaviour were evaluated. Together with the examination of retinal vessel reaction to flickering light unstimulated vessel wall behaviour and pulse wave propagation were assessed using mathematical signal analysis. Additionally differences in amplitude and frequency of spatial vessel diameter changes along the measured vessel segments were analysed to assess the microstructure of retinal vascular blood columns. Significant differences in several structural and functional parameters of retinal vessels in diabetes mellitus type 1 were found. Particularly retinal vessel dilation in response to flickering light was diminished both in arteries as well as in veins and delayed in arteries; longitudinal sections of retinal arteries in DM1 patients without retinopathy possessed more mid frequency roughness (one oscillation in ~250 ÷ 416 μm) than longitudinal sections of patients with retinopathy; both retinal venous pulsations (period <1.5 s) and vasomotions (period ≥1.5 s) showed higher rate of periodicity in DM1 than in the control group. These results might indicate alterations in vascular endothelial function, smooth musculature and retinal vessel wall rigidity in diabetes mellitus, leading to altered perfusion and vascular regulation following metabolic demand in the central microcirculation. Dynamic vessel analysis includes valuable information beyond conventional DVA evaluation of temporal vessel reaction to flicker. This allows for detailed individual characterization of vascular damage and further understanding of underlying disease pathology.
Retinal vessel analysis and models of pathomechanisms of diabetic retinopathy
Authors: Schmetterer Leopold
Published: December 2022

Diabetic retinopathy is a sight threatening complication of diabetes mellitus. The development of OCT angiography has shed new light into the vascular damage associated with the disease. Using wide‐field OCT angiography we and others have shown that OCTA provides excellent results for assessment of DR in persons with diabetes. This diagnostic performance can even be enhanced when choroidal OCT angiography are included in addition to retinal data. This highlights the importance of the choroid in the pathophysiology of diabetic retinopathy, which has received limited attention. It has also been shown that OCT angiography metrics predict progression of diabetic retinopathy. Finally, there is a long‐standing discussion of whether diabetic retinopathy is primarily a neurodegenerative or a vascular disease. Combining OCT and OCT angiography sheds new light into this relation and highlights the importance of systemic hypertension.
New genes and new phenotypes
Authors: Jurkute Neringa
Published: December 2022

Primary mitochondrial diseases together represent a major cause of inherited neurological disorders that, due to dysfunction of the mitochondrial respiratory chain, can affect many parts of body, especially high energy demand organs, such as liver, heart, kidney, muscle and the eye. As the eye is particularly vulnerable to mitochondrial dysfunction, approximately half of all the patients with confirmed mitochondrial disease will develop significant ocular involvement and the complication that patients are most afraid of is visual loss. This can arise either from a primary optic neuropathy (the most common ocular involvement), from outer retinal degeneration, or in some cases from retrochiasmal visual pathway involvement resulting in varying patterns of visual field defects. To date, inherited optic neuropathies have been linked with pathogenic variants in over 40 genes across both the mitochondrial (mtDNA) and nuclear (nDNA) genomes with maternal (mtDNA) inheritance, autosomal dominant, recessive and x‐linked inheritance observed. Inherited optic neuropathies are a significant cause of blindness in both the paediatric and adult population with an estimated prevalence of 1 in 10 000 in the UK. The prevalence is estimated low because of the difficulty in making a confirmed molecular diagnosis due to multiple factors: mutations have been identified in both genomes, a limited number of genes are included in next generation sequencing (NGS) panels, phenocopies etc. Current genetic testing strategies for inherited eye diseases fail to identify pathogenic variants in a significant proportion of cases suggesting that previously unidentified genes harbouring pathogenic variants remain to be identified. However, whole exome sequencing (WES) and particularly whole genome sequencing (WGS), and unbiased interrogation of genomic variants offers an unparalleled opportunity to detect variants in both uncharacterised genes and non‐coding regions of the genome leading to previously unknown gene‐disease associations. This presentation highlights the power of unbiased WGS to elucidate the missing heritability in mitochondrial eye diseases and reports novel gene‐disease or gene‐phenotype associations.
OPA1 trans‐splicing: A gene therapy approach to treat OPA1‐related optic neuropathies
Authors: le Dantec Yannick , Baris Olivier , Lenaers Guy
Published: December 2022

Dominant Optic Atrophy is a blinding disease related in 70% of cases to OPA1 variants. OPA1 variants are leading to haplo‐insufficiency or dominant negative effects, leading in 20% of cases to a syndromic presentation, with neurosensorial hearing loss as the most prevalent secondary symptom. Bi‐allelic OPA1 variants are also leading to the Behr syndrome, a severe polyneuropathy involving CNS and PNS symptoms.

With the objective to generate a versatile ocular gene therapy for OPA1 patients, we designed a trans‐splicing strategy as a molecular process allowing to correct all OPA1 mRNA transcripts with variants located in and downstream of the GTPase domain, while respecting the normal expression pattern of the 8 OPA1 isoforms, related to alternative splicing occurring before exon 6. Notably, this strategy can theoretically correct most of the haplo‐insufficient and dominant‐negative variants, and should not result in OPA1 over‐expression, whatever the level of the therapeutic vector expression, as the trans‐splicing process uses the endogenous OPA1 pre‐mRNAs to generate a mature‐RNA (mRNA) devoid of the pathogenic variant.

We shall present our latest results concerning the feasibility of this approach, and its possible transfer to a clinical trial.
Treatment strategies for mitochondrial optic neuropathies
Authors: Yu‐Wai‐Man Patrick
Published: December 2022

Three decades have elapsed since the first reports of human disease being directly caused by defects within the mitochondrial genome, including the identification of the m.11778G > A mitochondrial DNA (mtDNA) mutation in patients with Leber hereditary optic neuropathy (LHON). LHON causes severe bilateral visual loss among young adults with an estimated prevalence of 1 in 30 000 in the general population. Most patients carry point mutations in mtDNA with the three most common pathogenic variants being m.3460G > A (MT‐ND1), m.11778G > A (MT‐ND4) and m.14484 T > G (MT‐ND6). LHON carries a poor visual prognosis and patient management remains largely supportive. However, major advances in our understanding of the mechanisms underpinning retinal ganglion cell loss in this mitochondrial disorder are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. The eye is an ideal target organ for gene therapy given its relative ease of anatomical access, but some key issues need to be explored further, in particular, the most efficient gene delivery systems and the optimal window for therapeutic intervention in LHON.
Targeting neuroinflammation in early diabetic retinopathy
Authors: Fragiotta Serena
Published: December 2022

Neurodegeneration has been proven to represent a critical element of diabetic retinopathy (DR) pathogenesis. The neuronal involvement is subclinical, engaging in the early phases of diabetic retinopathy, and contributes to the further microvascular impairment and blood‐retinal barrier breakdown. The importance of neurodegeneration resides in the possibility of targeting neuronal apoptosis as an early intervention to slow and prevent the development of microvascular alterations visible on clinical examination. This presentation summarizes the multimodal imaging features and functional tests helpful in identifying neuronal damage in a subclinical stage before recognizing DR signs. Clinical features of neurodegeneration are crucial in identifying high‐risk patients to develop a vascular impairment and thus serve as outcome measures to understand the efficacy of supplementation. The potential approach for targeting neurodegeneration that includes topical compounds acting on different elements of the pathogenic cascade will be discussed. Further, the current evidence and clinical trials performed on humans will be examined, including the three main topical agents tested, brimonidine, somatostatin, and citicoline, with promising results.
When not to do a trabeculectomy (Trab vs tube)
Authors: Porteous Alastair
Published: December 2022

Despite the advent of modern minimally invasive glaucoma surgery techniques, trabeculectomy still remains the gold standard surgical technique for controlling the intraocular pressure in patients with uncontrolled glaucoma – achieving adequate pressure control, often in the low teens. There are, however, particular indications and subtypes of glaucoma where a trabeculectomy may not be the most appropriate first‐line surgical technique. In this presentation we will aim to discuss, using both personal experience and the latest published evidence, the factors that lead to both a higher and lower chance of surgical success. In particular we will discuss the rationale for choosing to perform tube surgery over a trabeculectomy.
Clinical outcomes in a large multi‐Centre prospective corneal transplant study
Authors: Jesper Hjortdal
Published: December 2022

The output from Work package 2 (WP2) of the VISICORT project included four deliverables:

Establishment of secure multi‐site clinical database of human corneal transplant recipients.

Report of 1‐year outcomes from multi‐site prospective biological sampling and clinical follow‐up of full thickness (FT)‐ and posterior lamellar (PL)‐CT recipients

Report of 3‐year prospective outcomes of FT‐ and PL‐CT recipients

Report of clinical factors associated with adverse immunological outcomes from FT‐ and PL‐CT within the overall transplant practice of a network of 5 leading EU centres.

In more general terms, the main mission of WP2 was to develop a cloud‐based system to collect relevant, well‐defined clinical information and track biological samples, to recruit patients from the five clinical centers, to collect biological samples and clinical data and to follow these patients clinically over several years.

The current speech focus on the clinical outcomes 928 prospectively enrolled patients followed up to 3 years.

Beyond confirming known factors associated with an adverse immunological outcome after FT‐ and PL‐CT such as the influence of primary diagnosis and type of surgery as risk factors, the clinical factors study revealed factors which needs to be explored further on. Identification of a re‐bubbling procedure (repeated injection of air to keep a PL graft in place) as an important risk factor for development of a later acute rejection episode is important as re‐bubbling is necessary in a fair large number of CT‐PL procedures (15–25%). The finding that presence of loose sutures after CT‐FT is a significant risk factor for AGR is not surprising, but further confirms that patients undergoing CT‐FT needs to be followed closely.

Concerning graft failure, it is worth to note that presence of diabetes 2 was identified as a significant risk factor for graft failure after CT‐FT. This may be due to a partially neurotrophic disease state in many patients with diabetes 2 and this has to be taken into account when deciding to perform CT‐FT and in the clinical follow‐up, which need to be meticulous.

The current clinical variables study is unique, and it would seem compelling to continue the clinical follow‐up of the recruited patients beyond the funding period for VISICORT. This would of course require new grant applications and obtaining new ethical approvals from the ethics committees at the five clinical centres.
Cerebral achromatopsia
Authors: Rauscher Franziska G. , Barbur John L. , Plant Gordon T.
Published: December 2022

Chromatic sensitivity was assessed in patients with pregeniculate and postgeniculate lesions. We examine changes in central vision along at foveal fixation and in each of the four paracentral quadrants of the visual field using the Colour Assessment and Diagnosis (CAD) test, a dynamic luminance contrast masking technique that isolates the use of Red / Green (RG) and Yellow / Blue (YB) colour signals. Because the extraction of colour signals in early visual processing involves opponent mechanisms, subjects with congenital RG loss of sensitivity exhibit symmetric increase in thresholds towards the long wavelength (“red”) and middle wavelength (“green”) regions of the spectrum locus. This is also frequently the case with acquired loss of chromatic sensitivity as a result of retinal or optic nerve disease. The findings from this study represent an exception to this rule. The patients investigated showed a marked asymmetry in colour thresholds. The study reveals how discrete, localized damage to visual pathways can cause selective loss of visual function and how the latter varies with retinal topography.

The 36 pregeniculate patients investigated exhibited impairment in both RG and YB. Loss of colour vision was symmetrical for both RG and YB discrimination. Some pregeniculate patients exhibited substantial loss of colour vision in areas where perimetric loss was largely absent. All quadrants revealed similar symmetric loss of colour sensitivity.

In 23 patients with postgeniculate lesions, patients with pre‐striate damage exhibited symmetric loss of chromatic sensitivity which affected either one or both chromatic mechanisms. Striate or extra‐striate lesions tended to exhibit general loss of colour vision within the area identified by visual field testing. More specific chromatic loss was associated with less impaired areas that were often normal on perimetric testing. Some patients with striate or extra‐striate lesions presented with asymmetric chromatic loss for one or more colour categories. When striate or extra‐striate lesions were also accompanied by underlying pre‐striate damage, chromatic sensitivity loss was always symmetric.

The findings from this study show that the loss of chromatic sensitivity in cerebral achromatopsia depends strongly on the exact location and extent of the lesion with significant variation over the visual field. The same subject can exhibit loss of chromatic sensitivity that is either RG or YB specific, but also, spatially localized, non‐opponent loss of sensitivity for primary colours.
Microbiome and autoimmunity
Authors: Kverka Miloslav
Published: December 2022

In humans, most epithelial surfaces are colonized by complex ecosystem of microorganisms called microbiota. While each of these surfaces has unique microbial colony, host–microbe interactions are necessary for our adaptation to the environment, development of many physiological processes and their constant regulation. The largest microbial community resides in the gut, where it consists mainly of diverse community of bacteria, but fungi, protozoa, archaea and viruses (mostly bacteriophages) are present as well. Disruption of gut microbiota, i.e. dysbiosis, is associated with numerous inflammatory, metabolic, cardiovascular and neoplastic diseases. This extraordinarily broad scope of effects is caused either directly, by producing bioactive metabolites, or indirectly, by shaping the cellular and humoral response in the host's cells – mainly in the gut epithelial and immune cells, which can even reach distant organs and tissues. Dysbiosis is often associated with impaired barrier function (“leaky gut”) which leads increased interactions of the microbial antigens with the immune system and to local and systemic inflammation. Thus all actions influencing gut microbiota, such as shifts in diet, administration of antibiotics or probiotics or faecal microbiota transfer, have recently emerged as attractive therapeutic or preventive interventions in medicine. Here, I will shortly describe mechanisms of their action and outline concepts that bridge the gap between microbiota and immune mechanisms.

Acknowledgement: Research is supported by Czech Academy of Sciences (Lumina Quaeruntur Program LQ200202105).
Corneal surface analysis – Topography
Authors: Langenbucher Achim
Published: December 2022

Placido topographers are widely used in ophthalmology and optometry for a measurement of corneal surface topography. With an extremely high resolution this technology could measure mean curvature and astigmatism, mapping a manual keratometer with SimK values, as well as asphericity. In addition, corneal irregularities and scars as well as (early) forms of ectatic diseases (e.g. keratoconus, keratoglobus or PMD) could be identified as long as the precorneal tear film is intact. In this talk we give an overview on the capabilities as well as the drawbacks of this imaging technique and dedicated analysis and screening indices which assist the examiner in identifying corneal surface pathologies or diseases.
Corneal curvature and thickness – Scheimpflug
Authors: Kovacs Illes
Published: December 2022

Although the Scheimpflug principle was first described over a century ago, the clinical use of Scheimpflug camera in anterior segment imaging started only a decade ago. Scheimpflug imaging has since advanced significantly and modern instruments provide comprehensive imaging and topographic data of the anterior segment using a noncontact method. It provides anterior and posterior surface topography of the cornea that is derived from true elevation measurements. Approximately 25 000 data points are used to calculate topographic corneal thickness, corneal curvature, anterior chamber angle, volume, and height. Pachymetry and topography of the entire anterior and posterior surface of the cornea from limbus to limbus are calculated and displayed. Keratoconus detection maps may be generated to assist in the classification and diagnosis of keratoconus prior to contact lens fitting or refractive surgery. Zernike wavefront representation of the anterior and posterior surface of the cornea may be calculated based on the measured height data. In this presentation the clinical applications and limitations of Scheimpflug imaging will also be discussed.
Corneal endothelium – Specular microscopy
Authors: Modis László
Published: December 2022

Corneal endothelium is a single layer of hexagonal cells covering the inner surface of the cornea and maintains the corneal deturgescence by continuous pumping of water and ions from the stroma to the aqueous humour. This mechanism is necessary to preserve the transparency of the cornea. The corneal endothelium is derived from the neural crest. Endothelial cells are arranged in a mosaic pattern of mostly hexagonal shaped cells. The cells can be characterized by different size (polymegathism) and different shape (pleomorphism). These parameters may reflect a compromised endothelial functional status.

The corneal endothelial cell layer does not capable for regeneration, a constant and age‐dependent loss of corneal cells present during lifetime. Extensive injury of corneal endothelium leads to permanent corneal swelling and bullous alterations on the corneal surface. If left untreated and in chronic cases inflammation, later on permanent scarring may occur leads to loss of corneal transparency and finally decreased vision.

Generally, a healthy cornea has about 1500–3500 endothelial cells/mm2 in the central area (age 40–75). The gold standard for the evaluation of endothelial cell density is endothelial microscopy, based on specular reflection, when light is reflected from the interfaces of materials with different indices of refraction. In addition, in vivo confocal microscope can also be used to visualize the endothelium, along with other tissue components of the cornea.

Different forms of corneal damage by inflammatory processes or by mechanical trauma following intraocular surgery can lead to additional endothelial cell loss. Evaluation and proper examination of corneal endothelium and endothelial cell density is important and has clinical relevance in aging, corneal preservation, phacoemulsification, and post‐keratoplasty corneas.
DARC
Authors: Cordeiro Francesca
Published: December 2022

Clinical trials of new treatments in glaucoma have traditionally relied on IOP as the endpoint. However, the emergence of neuroprotection in glaucoma has lead to a need for new measures of treatment efficacy. Several potential outcomes have been suggested 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) has recently moved from experimental preclinical stages to clinical trials, with Phase 2a trials including patients with glaucoma, AMD, optic neuritis, Down's dementia and glaucoma. The Phase 1 results showed that DARC has potential in glaucoma, with significantly greater levels of apoptosis in patients with increasing progression compared to stable, and Phase II results also discussed.
Advantages and pitfalls of confocal microscopy for detection of AK
Authors: Lagali Neil
Published: December 2022

Corneal infection by the diverse genotypes of the acanthamoeba parasite is becoming an increasingly common aetiology of serious cases of microbial keratitis in Europe, due in part to the growing use of contact lenses. The detection and diagnosis of acanthamoeba keratitis (AK), however, remains challenging in a clinical setting. Several diagnostic methods are typically used, including culture, clinical signs and symptoms, RTPCR, and in vivo confocal microscopy (IVCM). Only IVCM, however, is able to give a rapid and objective result that is not dependent on the location of a limited biopsy sample. Nevertheless, IVCM has both advantages and limitations for AK assessment when applied in a real‐world setting. An overview is given of the current knowledge on distinguishing features of AK when assessed by IVCM, and several challenging cases of suspected AK will be presented, along with considerations regarding how to assess characteristic features seen in IVCM images, that can either be indicative of AK infection, or conversely be features masquerading as AK‐specific findings. Finally, recommendations for the use of IVCM in the clinic for AK assessment, diagnosis and follow‐up will be given.
Acanthamoeba keratitis – Clinical signs and potential specific conservative treatment
Authors: Szentmary Nora
Published: December 2022

Acanthamoeba keratitis is a “chameleon”. It presents classically with greyish epithelial changes, perineuritis, superficial multifocal stromal infiltrates and ring infiltrate. In the presence of clinical signs, polymerase chain reaction, in vitro culture or histopathological examination have to be used to confirm the diagnosis. In vivo confocal microscopy is applied as an early non‐invasive ad‐hoc diagnostic method. Our finding emphasizes that pre‐testing the in vitro susceptibility of the AK isolate with the non‐nutrient E. coli agar plate assay against the anti‐amoebic drug intended for treatment will give valuable information on whether the drug is likely to be active on the Acanthamoeba isolate in vivo.
Genetic dissection of eye development – Lessons from Pax6
Authors: Kozmik Zbynek
Published: December 2022

A paired domain and homeodomain‐containing transcription factor Pax6 is an evolutionarily conserved regulator implicated in the eye development of both vertebrates and invertebrates. Mutations of the Pax6 gene disrupt eye development in both mammals and insects while Pax6 misexpression can lead to the formation of ectopic eyes. Genetic and expression studies have indicated that the development of vertebrate eyes is guided by a conserved gene regulatory network with Pax6 being one of the key transcription factors. To define the regulatory inputs into Pax6 gene we performed a genetic dissection of its regulatory landscape. To uncover the direct target genes of Pax6 we performed chromatin immunoprecipitation (ChIP‐seq) using mouse embryonic retina as a sample. We will present our preliminary genetic data on functional validation of Pax6‐regulated enhancers.
Retinal pigmented epithelium development from the perspective of transcription factors and cis‐regulatory elements
Authors: Gulkar‐Cohen Mazal , Messika Naama , David Ahuvit , Idelson Maria , Cohen‐Tayar Yamit , Reubinoff Benjamin , Elkon Ran , Ashery‐Padan Ruth
Published: December 2022

Normal vision depends on the retinal pigmented epithelium (RPE), a metabolic cell layer that is vital to the development and function of the adjacent retinal photoreceptors. The LIM‐homeodomain transcription factor Lhx2 is important key factor for generation of the progenitors of both RPE and retina during early stages of eye development and is also essential for the generation of different stem cells giving rise to multiple types of organs.

The purpose of this project is to understand the gene regulatory network (GRN) and the cis‐regulatory sequences bound by Lhx2/LHX2 in mouse and human in the developing and mature retinal pigment epithelium (RPE) of mammals.

The methods include functional studies in vivo using Cre/loxP and knockdown approaches in RPE derived from human embryonic stem cells (hES‐RPE). The functional studies are combined with analyses of the global molecular changes, by identifying and characterizing cis‐regulatory regions bound by the complex and the impact of the mutation on gene expression and tissue differentiation.

The results reveal essential role for Lhx2 in maintaining RPE fate in the embryonic optic cup and in differentiated hES‐RPE. Lhx2 seems to function as direct regulator of tissue specific transcription factors as well as cytoskeletal and cell adhesion genes.

Conclusions: the GRN and the cis regulatory sequences identified provide novel insight on the activity of an important developmental regulator in controlling RPE differentiation, morphology and function in mice and humans.
The eye and lymphoma: New concepts of an old acquaintance
Authors: Touhami Sara
Published: December 2022

Intraocular lymphoma (IOL) is a life‐threatening condition that results from the proliferation of malignant lymphocytic cells arising from either the central nervous system (CNS) (primary CNS lymphoma) or outside the CNS with secondary dissemination and metastasis to the eye (secondary IOL). Primary intraocular lymphoma (PIOL), also known as primary vitreoretinal lymphoma (PVRL), is a subset of PCNSL where the findings are ocular.

PVRL is particularly feared because it can manifest as non‐specific uveitis, leading to a potentially fatal diagnostic delay. Although clinical and ancillary parameters can provide valuable diagnostic clues, the only valid confirmation comes from cytological analysis and molecular studies of clonality based on vitreous and/or (sub)retinal biopsies performed during vitrectomy. Standard three‐port twenty‐five‐gauge transconjunctival vitrectomy is the usual sampling technique; however, it is important to remember that the diagnostic yield of vitreous cells depends on the way samples are harvested, transported and analysed. Even when surgical recommendations are strictly followed and analyses performed by trained pathologists, the diagnostic yield of vitrectomy is not 100%.

The objective of this course is to describe the clinical features of PVRL and its characteristics on ancillary exams in both typical and more challenging situations, and present the diagnostic procedures that are or will be available in the near future. Therapeutic management will be discussed later during this course.