bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical and functional results of vitrectomy and gas tamponade in macular hole treatment
Authors: Novytskyy Ihor , Tomkiv U. 
Published: December 2022

AbstractBackground: 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

AbstractBackground: 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

AbstractObjective: 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

AbstractThe 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

AbstractStraylight 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

AbstractWe 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

AbstractRetinal 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

AbstractVascular 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

AbstractDiabetic 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

AbstractPrimary 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

AbstractDominant 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

AbstractThree 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.