bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term efficacy of idebenone in patients with Leber hereditary optic neuropathy in the LEROS study: Analysing change in visual acuity according to causative mutation and disease phase
Authors: Yu‐Wai‐Man Patrick , Carelli Valerio , Llòria Xavier , Tomasso Livia , Klopstock Thomas
Published: January 2024

Aims/Purpose: Leber hereditary optic neuropathy (LHON) is a mitochondrial disease resulting in severe vision loss. The causative mitochondrial DNA (mtDNA) mutation impacts disease progression and prognosis. In LEROS, a Phase IV, open‐label interventional study (Clinicaltrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment (IDE) were compared to those of an external Natural History (NH) cohort. Here, we compare VA change from baseline to Month 24 according to primary mtDNA mutation and disease stage.

Methods: Eyes of patients with LHON and either a m.G11778A, m.T14484C or m.G3460A, mtDNA mutation were stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 but ≤5 years). Data from 181 patients were compared to retrospective data from the NH cohort (N = 372), matched by time since symptom onset at baseline. We compare the difference in least squares‐mean VA change, or delta VA, from baseline to Month 24 in IDE versus NH eyes (a negative value favours IDE).

Results: In treated subacute/dynamic m.G11778A eyes (n = 60 IDE), delta VA was −0.32 logMAR (p = 0.002) versus the NH cohort (n = 47). In chronic m.G11778A eyes, delta VA was −0.11 logMAR (n = 82 IDE vs n = 51 NH; p = 0.043). In subacute/dynamic m.T14484C eyes, delta VA was +0.20 logMAR (n = 35 IDE vs n = 10 NH; p = 0.285). In chronic m.T14484C eyes, delta VA was −0.52 logMAR (n = 11 IDE vs n = 18 NH; p < 0.001). In subacute/dynamic m.G3460A eyes, delta VA was +0.53 logMAR (n = 26 IDE vs n = 18 NH; p = 0.001). In chronic m.G3460A eyes, delta VA was −0.13 logMAR (n = 23 IDE vs n = 24 NH; p = 0.162).

Conclusions: Idebenone improved VA in a large proportion of eyes; this benefit manifested to varying degrees depending on disease stage and mtDNA mutation. m.G11778A eyes saw a consistent benefit regardless of disease stage. m.T14484C and m.G3460A results should be interpreted with caution in some cases due to the relatively low number of eyes; further study is warranted.
Optic nerve head dimension as biomarker in Leber hereditary optic neuropathy
Authors: Battista Marco , Carbonelli Michele , Coutinho Catarina P. , Oakley Jonathan , Cascavilla Maria Lucia , Galzignato Alice , Lari Giorgio , Amore Giulia , La Morgia Chiara , Bandello Francesco , Carelli Valerio , Barboni Piero
Published: January 2024

Aims/Purpose: To study the optic nerve head (ONH) dimension in symptomatic and asymptomatic patients with Leber hereditary optic neuropathy (LHON) and to correlate ONH parameters with genotype and clinical phenotype.

Methods: Seventy‐eight affected patients, 175 asymptomatic carriers, and 29 age‐matched healthy controls were enrolled in the study. All patients underwent ONH optical coherence tomography (OCT) measurements by DRI OCT Triton (Topcon, Japan) and were analysed with the Orion custom software (Volexeron, CA, USA). The following parameters were obtained for each eye: disc area, horizontal and vertical diameter; retinal nerve fibre layer (RNFL) and ONH volume. For the comparison of the different parameters the ANOVA with Bonferroni post‐hoc test was performed.

Results: LHON‐affected patients appeared to have smaller ONH size parameters compared to control cases, but only the vertical disc diameter of patients with mutations 11 778 and 14 484 were statistically significant. Also, carrier patients with the mutation 11 778 presented a statistical significantly smaller vertical disc diameter compared to controls, instead 14 484 carriers presented a bigger diameter. ONH volume of all affected patients was significantly smaller. Moreover, asymptomatic 11 778 carriers older than 35 years were significantly smaller. Linear regression sustained the relationship between age, volume, and RNFL, unlike between age and disc area.

Conclusions: This study exposed the differences of ONH size in LHON‐affected and ‐carrier patients with different mutations: smaller disc in 11 778 affected and unaffected patients and larger disc in 14 484 carriers. A strong correlation was found between ONH volume both in affected patients and carriers older than 35 years old. These results highlight the importance of the 3D ONH structure as a potential biomarker to support clinicians in the characterization of symptomatic LHON patients and possibly at‐risk mutation carriers with different genetic mutations and clinical course.
Choroidal thickness as a biomarker for axial length change
Authors: Biba Matilda , Lingham Gareth , Acquah Emmanuel Kobia , Loughman James , Flitcroft Daniel
Published: January 2024

Aims/Purpose: Assessing axial eye growth is a key component in myopia management; however, access to biometry is limited in primary eye care settings. This study evaluated choroidal thickness, compared to spherical equivalent refraction, as a potential biomarker of axial elongation.

Methods: The Myopia Outcome Study of Atropine in Children (MOSAIC) is a double‐blind, randomized controlled trial of 0.01% atropine eye drops. Irish myopic participants aged 6–16 years used either 0.01% atropine or placebo eye drops nightly for 2 years. Spherical equivalent refraction (SER) was measured by cycloplegic autorefraction, axial length (AL) by partial coherence interferometry and choroidal thickness (ChT) by Swept Source‐OCT. The respective 12‐month changes in both eyes were included in mixed linear regression analysis, while controlling for treatment group and within‐subject correlation. ROC analysis was conducted to assess the ability of ChT and/or SER to identify eyes in the top 25% (fast progressors) of AL change.

Results: Of the 250 participants enrolled in MOSAIC (mean age 11.8 years, 62% female), 217 (87%) completed the 12‐month visit. Mean 12‐month change in AL, ChT and SER were 0.268 ± 0.19 mm, −3.62 ± 33.3 um and −0.437 ± 0.346 DS respectively. Analysis revealed a significant association between change in ChT and AL (−0.01 ± 0.002 mm per 10 μm; p < 0.001) and change in SER and AL (−0.28 ± 0.02 mm per 1D; p < 0.001). When both SER and ChT were combined in a single model, a 1D myopic change in SER and a 10um decrease in ChT were associated with a 0.27 mm (p < 0.001) and 0.007 mm increase in AL (p = 0.002), respectively. ROC analysis revealed that change in ChT was a stronger predictor of fast AL progression (AUC = 0.77) compared to SER change (AUC = 0.72), with the combined model performing better than either variable alone (AUC = 0.80).

Conclusions: ChT change was significantly associated with AL change over 12 months and better than SER alone at identifying fast AL progressors, with a combined SER and ChT model achieving the best results.
Retinal ganglion cells in a mouse model of Alzheimer's disease: A temporal study
Authors: Sanchez‐Puebla Lidia , Gómez‐Moreno Mar , Matamoros José A. , Fernández‐Albarral José A. , de Hoz Rosa , Salazar Juan Jose , Salobrar‐Garcia Elena , López‐Cuenca Inés , Nieto‐Vaquero Carmen , Cuartero María Isabel , Ramírez Ana I. , Ramirez Jose Manuel
Published: January 2024

Aims/Purpose: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by the progressive loss of neurons and their synapses in the brain. Similar alterations have been observed in the retina even before they manifest in the brain. The retina has been proposed as a readily accessible biomarker for AD. In a previous work utilizing a murine model of AD (APPNL‐F/NL‐F), changes in retinal thickness, as measured by optical coherence tomography (OCT), were observed at 15 and 17 months. The objective of this study was to quantitatively assess the population of retinal ganglion cells (RGCs) in this same AD murine model over a specified time period and compare it with wild‐type (WT) mice.

Methods: To quantitatively assess the population of retinal ganglion cells we used two study groups: the APPNL‐F/NL‐F model throughout the time period of (6, 9, 12, 17, and 20 months) and compared with wild‐type (WT) mice age matched (n = 30 in both groups). The quantification of retinal ganglion cells (RGCs) was conducted using immunohistochemical analysis with the Brn3a marker. This analysis was performed using a semi‐automatic algorithm implemented in the MatLab environment, which was developed by the Ramón Castroviejo Institute for Ophthalmic Research. For the analysis, the entire retina was considered and segmented into the peripapillary, intermediate, and peripheral zones.

Results: A statistically significant decresase (p < 0.05) in the population of Brn3a + cells was observed in the APPNL‐F/NL‐F group compared to the WT group. This decreased was found in the total retina at 12 months, in the peripapillary zone at 9, 12, and 20 months, and in the intermediate zone at 12 months of the study.

Conclusions: The APPNL‐F/NL‐F mouse model exhibits RGCs loss at 9, 12, and 20 months, mirroring the patterns observed in human cases. These findings suggest that the model holds promise for investigating and studying mechanisms related to RGC degeneration in Alzheimer's disease.
Gradient myopic defocus causes scleral tissue reinforcement and structural scleral remodelling
Authors: Hileeto Denise , Gillis Thomas , Irving Elizabeth
Published: January 2024

Aims/Purpose: To determine histological effects of lens induced refractive change on scleral remodelling in chicks.

Methods: 18 Ross‐Ross chicks were raised for 14 days on a 14 hr light/10 hr dark cycle. 6 chicks were allowed to develop normally. 6 chicks wore conventional ‐10D lenses for the full 14 days. 6 chicks wore conventional ‐10D lenses for the first 7 days and myopia progression control (MPC) lenses or the next 7 days. MPC lenses had a central power of ‐10D and a gradient power rise at pupil edge (+ 2.75D). Birds were euthanized after 14 days and eyes were routinely processed for histopathological evaluation. Whole mount H&E‐stained tissue sections were microscopically analysed using bright field microscopy.

Results: All lens treated birds developed significant myopia as expected Total scleral thickness was significantly reduced in the group wearing conventional ‐10 lenses (p < 0.05), but remained comparable to the normal control group for the MPC lenses treated birds. New appositional growth of the cartilaginous sclera was observed in all MPC lenses treated eyes and only in those eyes. The thickness of the cartilaginous component of the sclera was 135 ± 6, 153 ± 5, 125 ± 8 μm for conventional myopic, MPC lenses treated, and control birds respectively. There was a significant increase in the cartilaginous scleral thickness in the MPC lenses treated birds compared to the other two groups (p < 0.03), but not between the conventional ‐10D lens treated and control birds (p > 0.05).

Conclusions: It is possible to induce appositional growth in hyaline cartilage in the chick sclera. In our study, this has only been achieved by using MPC lenses to reverse previously induced experimental myopia with conventional minus lenses. Our finding suggests that gradient decrease in peripheral lens power and the resulting differential level of defocus it causes could be a potential trigger of scleral reinforcement through stimulation of cartilage growth in the chick sclera.
A systems biology approach to understand retinal ciliopathies
Authors: Liu Xiaonan , Pacwa Anna , Bugara Klaudia , Machna Bartosz , Rodak Piotr , Machowicz Joanna , Lewin‐Kowalik Joanna , Smedowski Adrian
Published: January 2024

Aims/Purpose: Many of the described ciliopathies display multi‐organ developmental phenotypes, including retina. A variety of proteins encoded by genes associated with retinal ciliopathies are present in the connecting cilium of the retina, which is essential for photoreceptor function. Owing to the complicated genetic networks of ciliopathies, it is more difficult to characterize ciliopathies than other rare diseases, and only a handful of exact genotype–phenotype correlations have been established. The scientific aim of this study was to unravel the protein‐level mechanisms of retinal ciliopathies using system and molecular biology techniques.

Methods: Due to the network of protein interactions, the effect of a ciliopathy mutation is not limited to a single gene product. Instead, it impacts the interacting partners and, as a result, can have an effect on the activity of a whole subnetwork. To analyse this, we selected 46 genes that have been previously associated with non‐syndromic and multi‐syndromic retinal ciliopathies and applied proximity labeling‐based method (UltraID) coupled with mass spectrometry (MS) approach for systematic analysis of retinal ciliopathy proteomes.

Results: Bioinformatic analysis of the comprehensive dataset reveals 3772 high confidence interactions and among them 179 interactions (4.7%) were previously reported for the retinal ciliopathy protein. We further conducted a subcellular localization analysis on the interacting proteins. There are 232 unique prey proteins (13.6%) with annotated subcellular localization or tissue distribution in photoreceptor, cilium, retina, or eye, indicating our PPI data are retinal ciliopathy context specific.

Conclusions: Protein–protein interaction (PPI)‐based analyses, rather than focusing on specific genes or loci implicated in retinal ciliopathies, highlight connections that are most affected by the disease state, thereby facilitating the discovery of higher‐order relationships within the genetic architecture of ciliopathies.
A colour vision test assisted by neural networks
Authors: Monteiro José , Alves Paulo , Gomes Andreia , Nascimento Sérgio , Linhares João
Published: January 2024

Aims/Purpose: Traditional computerized colour vision tests resort to the magnitude of chromatic thresholds to determine the quality of the colour vision of an observer. The limits of perceived colours are tested against a background that will be conspicuous to normal colour vision observers, but inconspicuous to colour vision deficient (CVD) observers. The purpose of this work was to implement a Neural Network capable of performing independent and automatic classification of the colour vision of an observer, using as inputs the sRGB chromaticity coordinates, response times, and eye movements obtained using a colour vision test on a computer screen calibrated in colour and luminance (Display++).

Methods: Chromatic discrimination limits were estimated using a staircase procedure that tested colour vision close to the dichromatic confusion lines. Only the last 8 responses were considered in the analysis. 50 normal colour vision observers and 8 CVD observers performed the test on Display++. CVD participants were diagnosed using the results of the anomaloscope and the CAD colour vision tests. A Sequential Neural Network was implemented with a dense structure (256–128–64‐16‐1 nodes), with relu and sigmoid activation functions, dropout commands to prevent overfitting, the Adam optimizer, and the binary crossentropy loss function. The performance of the neural network was estimated by computing its accuracy, where variables are related to the results obtained after training the Neural Network and inspecting the test results. The database was divided into a training/test following different splitting strategies: T1 observers' responses considering sRGB coordinates, response times, and eye movements. T2 observers' responses considering only sRGB coordinates.

Results: The averages and standard deviations of the estimated accuracy for five consecutive trials with a random division between training/test for conditions T1 and T2 was 91% ± 7% and 93% ± 5% respectively. It was found that the implemented neural network had an accuracy of more than 90% across all conditions.

Conclusions: The accuracies found across conditions considered seem to indicate that the implemented Neural Network can analyse and classify the colour vision of human observers, with an accuracy greater than 90% of success.
Study of peripheral blur in retinal electrical activity
Authors: Queiros António , Nevado Ana , Pereira‐da‐Mota Ana Filipa , Amorim‐de‐Sousa Ana , Fernandes Paulo
Published: January 2024

Aims/Purpose: The aim of this study was to evaluate changes in peripheral refraction by the use of a contact lens to control the progression of myopia. In addition, the response of electrophysiological activity in different areas of the retina with and without contact lens was also determined.

Methods: We recruited 7 myopic individuals (23.71 ± 5.41 years) with refraction up to −4.50D (spherical equivalent), without eye pathologies and surgeries. Visual acuity was recorded, high and low contrast, with the updated refraction and with the Misight 1 Day contact lens. Peripheral refraction measurements were obtained using an open‐field autorefractometer. Multifocal electrophysiology measurements were performed binocularly with and without contact lens, with dilated pupil. Topography and aberrometry values were also recorded.

Results: lens, peripheral refractions become significantly more myopic. The change in peripheral refraction induced at 30° Nasal is −0.66D. High Contrast Visual Acuity was always superior to Low Contrast VA in both conditions. The Misight 1 Day contact lens manifests a different behaviour along the anterior surface of the cornea. LC induces a significant increase in high‐order aberrations, especially in comatic aberrations, which increase three times their initial value.

Conclusions: Regarding the electrophysiological response of the retina, with the use of the LC Misight 1 Day, it presented a greater implicit time and amplitude of the P1 component, in the superior temporal retina, these differences being statistically significant. The implicit time of the P2 component increased in the temporal retina and in the retinal area delimited by Rings 3, 4 and 5.
Healthy aging does not alter centre surround orientation effects in foveal intraocular and interocular contrast suppression
Authors: Pitchaimuthu Kabilan , Nguyen Bao , McKendrick Allison
Published: January 2024

Aims/Purpose: Healthy aging alters how the perceived contrast of a pattern is influenced by its surround. Neural mechanisms underlying this aging effect can be disentangled by manipulating stimulus orientation, duration, and by using dichoptic viewing. Here, we tested whether intraocular and interocular center surround contrast suppression demonstrate distinct effects of surround orientation, and if so, whether they are altered by healthy aging.

Methods: We measured the perceived contrast of a circular, vertically oriented sine grating (0.67° diameter, 20% contrast) alone and in the presence of annular sinusoidal surround (6° diameter, 40% contrast) in 18 younger (19–32 years) and 18 older adults (61–78 years). Factors explored were: intraocular versus interocular viewing, parallel versus orthogonal surround orientation, and 40 ms versus 200 ms stimulus duration. Surround orientation effect (SOE) was calculated as 1‐ (contrast suppression by orthogonal surround/ contrast suppression by parallel surround). SOE was 0 if contrast suppression was equal between both surround orientations, and the value increased if parallel surround produced stronger suppression than orthogonal surround.

Results: The interocular SOE was not influenced by stimulus duration, whereas, intraocular SOE was stronger at 40 ms compared to 200 ms (viewing condition x stimulus duration: F(1,34) = 24.38, p < 0.01). Older and younger adults showed similar SOE under all test conditions (main effect of age: F(1,34) = 0.02, p = 0.89). Age did not affect how stimulus duration influenced intraocular and interocular SOE (age x viewing condition x stimulus duration: F(1,34) = 0.41, p = 0.52).

Conclusions: Our results suggest that centre surround orientation effects on intraocular and interocular contrast suppression is dependent on stimulus duration and this relationship is unaltered by healthy aging.
Analysis of the relation between facial asymmetry and users' preference between standard versus customized inset progressive addition lenses
Authors: Espinilla Oscar Garcia , Pavón Irene Sánchez , Herranz Raúl Martín
Published: January 2024

Aims/Purpose: User adaptation to progressive addition lenses (PALs) wear requires accurate facial measurements, mainly naso or interpupillary distances, usually measured with a frame ruler. But facial asymmetries are usually ignored. Measurement of foveal fixation axis (FFA) ‐the line linking directly the fixation point and the fovea‐ allows precise facial asymmetry assessment. This study aimed to compare users' preference between standard versus customized inset PALs in patients with and without facial asymmetry according to their FFA measurement.

Methods: A crossed, double blind, randomized study was conducted. Participants were classified according to previous experience with PALs (neophytes, PALs users, dropout, and uncomfortable PALs users) and with (>1.0 mm) or without (≤1.0 mm) facial asymmetry. After a complete eye test, two different PALs (LifeStyle 3i, Hoya) were prescribed in a randomized and masked order (2.5 mm standard inset and FFA customized inset PALs). PAL users' preference between both lenses was collected (subjective opinion) after 30 days of wear. Statistical analysis was performed using SPSS 26 (Chicago, USA). ANOVA was used to compare different groups and Chi‐square was used to analyse the frequency of choice of both PALs.

Results: 71 participants (37 women and 34 men) were included. 49 with FFA asymmetry; 56% of them (95%CI 42–71%) preferred customized inset lens (Figure 1) (p = 0.05), in dropout group 67% (95%CI 33–100%). No differences (p > 0.05) in clinical parameters were found between patients with or without FFA asymmetry.

Conclusions: Participants with FFA asymmetry preferred customized inset lens, especially dropout patients. Facial asymmetry could be a relevant factor in PALs adaptation and FFA measurement could improve users' satisfaction with customized PALs in patients with facial asymmetry.

FIGURE 1 (Left). PALs choice according to the patients' facial asymmetry. (Right). PALs choice according to the patients previous use of PALs.

image

FIGURE 1 (Left). PALs choice according to the patients' facial asymmetry. (Right). PALs choice according to the patients previous use of PALs.
Neurovascular coupling reflex from contralateral stimulation: System setup
Authors: Jordão João , Quental Hugo , Morgado Miguel , Figueira João , Castro‐Farías Daniela , DeBuc Delia Cabrera , Castelo‐Branco Miguel , Paques Michel , Bernardes Rui
Published: January 2024

Aims/Purpose: Neurovascular coupling (NVC) is the blood flow modulation in response to stimuli and has been extensively studied in the brain. Concerning the human retina, this behaviour has been only measured in the ipsilateral eye, where stimuli and observed effects involve the same eye. This work aims to set up the hardware to assess NVC in the contralateral eye and demonstrate its feasibility in edifying human retina‐retina or cortico‐retinal connections.

Methods: Adaptive optics (AO) is a cutting‐edge technology in retinal fundus imaging, offering exceptional spatial resolution. The NVC effect was successfully assessed using the RTX1, an AO retinal camera capable of ipsilateral stimulation. The possible effects of contralateral stimulation can be readily assessed by providing RTX1 with an external flickering device. Furthermore, connecting the thread between previous fMRI results and photic stimulation in the ipsi‐ and contralateral retina can offer valuable information on uncharted interocular or brain‐retina neural pathways and lead to cost‐effective and non‐invasive biomarkers for neurodegenerative diseases or early brain vasculature impairment diagnosis.

Results: Even though further optimization of flicker‐related parameters is necessary to investigate the contralateral NVC response, preliminary tests showed the successful integration of a fully operational contralateral stimulation prototype with the RTX1. The entire procedure has been documented, and all components have been thoroughly evaluated.

Conclusions: These preliminary assessments precede a clinical study involving patients with type 1 Diabetes Mellitus and a control group of healthy individuals. It follows previous fMRI studies that showed impaired NVC in type 2 diabetic patients by measuring the BOLD (Blood Oxygen Level‐Dependent) response using block and event‐related optical stimuli. A comparative analysis of the findings aims to demonstrate the potential role of neurovascular uncoupling in the early pathogenesis of diabetic retinopathy.
The effects of post‐saccadic oscillations on visual processing time
Authors: Llapashtica Emsal , Barbur John
Published: January 2024

Aims/Purpose: Saccadic eye movements enable us to search for a target of interest in a crowded scene, or in the case of goal‐directed saccades, to bring the peripheral target to the fovea. Visual information is processed quickly at the end of each saccade, yet precise measurements of the times involved remain controversial. This research investigates the time needed to process visual information at the end of each saccade.

Methods: A new psychophysical test makes it possible to measure eye movement response latencies and visual processing times. When the test is used in conjunction with an eye tracker, each component that makes up the ‘integrated saccade latency’ (ISL) time, from the onset of the peripheral stimulus to the correct interpretation of the information carried by the stimulus, can be measured and the discrete components delineated. We measured ISL times in six subjects in response to Landolt ring optotypes of varying contrast presented peripherally at an eccentricity of 8° and also at the point of regard (0°).

Results: We show that the time required to process and encode the stimulus attribute of interest at the end of a saccade is longer than that needed to carry out the same task in the absence of an eye movement. Depending on the stimulus contrast, these time durations ranged between 101–120 ms (15%) and 34–48 ms (75%) when eye movements were involved and 57–35 (15%) and less than 25 ms (75%) in the absence of eye movements.

Conclusions: The extended visual processing times measured when saccades are involved may be the result of transient loss of spatial resolution caused by eyeball instability during post‐saccadic oscillations. These results explain why stimuli of high luminance contrast yield best performance in visual tasks when eye movements are involved.

Acknowledgements: We acknowledge the UK Civil Aviation Authority for their support.
ZOSPy, a python package for ray tracing simulations
Authors: van Vught Luc , Haasjes Corné , Beenakker Jan‐Willem
Published: January 2024

Aims/Purpose: Ray tracing simulations with optical models of the eye are used for a wide range of applications, such as designing intra‐ocular lenses. These simulations are often performed in OpticStudio (Ansys/Zemax), a piece of software with powerful analytical tools. However, OpticStudio largely relies on manual user interaction, limiting its ability to analyse a large number of eyes. While OpticStudio has an Application Programming Interface (the ZOS‐API) that allows for automation, using this API requires in‐depth programming knowledge. Thus, we developed ZOSPy, an open source library that provides an accessible interface to the ZOS‐API which allows users to directly focus on the optical modelling and analyses.

Methods: ZOSPy is a python‐based wrapper around the official ZOS‐API, which provides full access to the API and enables full control of OpticStudio. In addition, we facilitated the usage of the API by simplifying initiation of the API connection, adding functions that fully wrap analyses and including auto‐completion in Python. Finally, it provides unit‐tests that enable validation of different OpticStudio versions.

Results: ZOSPy has been used to facilitate ray tracing in several studies. One study used ZOSPy to assess the relation between the anatomy and Negative Dysphotopsia. by determining retinal illumination profiles and [1] In another study, ZOSPy was used to show that the extent of an intra‐ocular tumour can be erroneously overestimated by transillumination during surgery [2].

Conclusions: ZOSPy allows users to omit complex coding and directly focus on optical modelling and analyses, which reduces the threshold for using ray tracing simulation in (ophthalmic) research.

References

1. van Vught, et al. Effect of anatomical differences and intraocular lens design on negative dysphotopsia. JCRS.

2. Jaarsma‐Coes, et al. Comparison of Magnetic Resonance Imaging‐Based and Conventional Measurements for Proton Beam Therapy of Uveal Melanoma. Ophthalmol Retina. 2023.
Comparing the effect of benzalkonium chloride‐preserved, polyquad‐preserved, and preservative‐free prostaglandin analogue eye drops on cultured human conjunctival goblet cells
Authors: Nagstrup Anne , Freiberg Josefine , Hansen Pernille May , Boix‐Lemonche Gerard , Utheim Tor Paaske , Dartt Darlene , Petrovski Goran , Heegaard Steffen , Kolko Miriam
Published: January 2024

Aims/Purpose: To investigate the effect of benzalkonium chloride (BAK)‐preserved latanoprost and bimatoprost, polyquad (PQ)‐preserved travoprost, and preservative‐free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK‐preserved and PF latanoprost on the cytokine secretion from GC.

Methods: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)‐6 and IL‐8 from GC.

Results: BAK‐preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK‐preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK‐preserved bimatoprost by 45% (p = 0.006), PQ‐preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK‐preserved latanoprost caused an increase in the secretion of pro‐inflammatory IL‐6 and IL‐8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not.

Conclusions: BAK‐preserved PGA eye drops were more cytotoxic to GCs than PQ‐preserved and PF PGA eye drops. BAK‐preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ‐preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK‐preserved PGA eye drops.
Factors associated with retinal nerve fibre layer stability after glaucoma surgery
Authors: Eun Park Sung
Published: January 2024

Aims/Purpose: The first objective of the present study was to investigate whether retinal nerve fibre layer (RNFL) deterioration exists after successful glaucoma surgery, and how long it lasts. The second objective was to identify the factors associated with RNFL thickness stability after surgery.

Methods: A retrospective observational study was conducted. A total of 128 eyes of 108 patients who received one successful glaucoma surgery including trabeculectomy and Ahmed valve implantation, and had been followed up with cirrus optical coherence tomography (cOCT) were examined. We defined intraocular pressure (IOP) reduction as the difference between peak IOP before surgery and IOP at the first cOCT examination after surgery. RNFL thickness reduction greater than −5.03 μm/year immediately after surgery, but remained below −5.03 μm/year in two or more consecutive examinations was defined as a ‘maintenance after progression group’ (group1). Also, the other group was defined as a ‘maintenance group’ (group 2), RNFL thickness reduction less than −5.03 μm/year.

Results: There was no significant difference between two groups in sex, age, diagnosis, and operation. However, preoperative IOP was statistically significantly higher in group 2 than in group 1 (p = 0.039). There was no significant difference between group 1 and 2 in the duration of IOP elevation before surgery (p = 0.998). The preoperative RNFL thickness tended to be thicker in group 2 than in group 1, but it was not statistically significant. The average duration of progression in group 2 was 23.9 months. Factors containing age, sex, operation, diagnosis, preoperative IOP, preoperative IOP rise duration, and pretreatment RNFL thickness were less relevant with postoperative RNFL thickness reduction stabilization.

Conclusions: In conclusion, the factor that showed a significant difference between the ‘maintenance after progression group’ (group 1) and the ‘maintenance group’ (group 2) was preoperative IOP.

References

Kim WJ, Kim KN, Sung JY, Kim JY, Kim CS. Relationship between preoperative high intraocular pressure and retinal nerve fibre layer thinning after glaucoma surgery. Sci Rep‐Uk 2019, 9.
Evolution of the morphology of filtering blebs through anterior segment OCT, one, three and six months after Preserflo Microshunt implant and its correlation with intraocular pressure
Authors: Prades Gemma Ortega , Pérez‐Torregrosa Vicente‐Tomás , Gallén Leyre Sanz , Parot Álvaro‐Andrés Ojeda , Pérez Prudencia Rochina , Samper Antonio Miguel Duch
Published: January 2024

Aims/Purpose: Study the evolution of the morphology of filtering blebs through AS‐OCT, one, three and six months after Preserflo implant and its correlation with IOP.

Methods: Prospective observational study of 16 eyes with cataract and glaucoma, poorly controlled with maximum medical treatment and mean IOP of 23.6 mmHg, which underwent combined surgery with Preserflo and 0.04% MMC. The patients underwent measurement of IOP and AS‐OCT of conjunctival bleb one, three and six months after surgery. Bleb morphology is classified following the Leanzhofer classification as uniform or multiform (multilayer and/or multicystic). The presence of an episcleral aqueous lake in the distal part of the device is also studied.

Results: Of the 16 patients studied, all completed the quarterly check‐up and 9 the six‐monthly check‐up. Of the total number of patients, 9 presented multiform multilayered bleb and 7 multiform multilayered with superficial cysts in the 1st and 3rd month. Of the 9 who completed the study up to the 6th month, 4 maintained their multilayered morphology, and of the remaining 5, who both in the 1st and 3rd month presented a multilayered morphology with superficial cysts, we observed a slight flattening of the bleb. The mean IOP in the 1st month was 12.5 mmHg, 12.6 in the 3rd month and 13.4 in the 6th month. Episcleral lake was observed in 9 cases, which remained present throughout the study.

Conclusions: SA‐OCT is useful for monitoring conjunctival blebs after Preserflo implantation. Despite the slight thinning after the sixth month of the multiform multilayered blebs with superficial cysts, IOP remains stable. Therefore, the presence of multiform blebs and a maintained episcleral lake seem to be related to good hypotensive control.

References

1. Lenzhofer M, Strohmaier C, Hohensinn M, Hitzl W, Sperl P, Gerner M, Steiner V, Moussa S, Krall E, Reitsamer HA. Longitudinal bleb morphology in anterior segment OCT after minimally invasive transscleral ab interno Glaucoma Gel Microstent implantation. Acta Ophthalmol 2019 Mar; 97(2): e231‐e237.
Potential neuroprotective effects of anti‐cytokine antibodies against lipopolysaccharide‐induced microglial inflammation
Authors: Zhang Linglin , Perumal Natarajan , Guan Chaoqiang , Francis Alfred Francis Pakkam John , Pfeiffer Norbert , Grus Franz H. , Manicam Caroline
Published: January 2024

Aims/Purpose: Microglia‐mediated neuroinflammation is involved in many neurodegenerative diseases, including glaucoma and diabetic retinopathy. This study examined the effects of anti‐cytokine antibodies on LPS‐induced inflammatory response of microglial cells, and explored the underlying molecular mechanisms by proteomic analysis.

Methods: A lipopolysaccharide (LPS)‐induced neuroinflammation model was established in murine BV‐2 microglial cells in vitro. The expression of microglial cell markers (CD68 and CD206) were detected by immunocytochemistry. BV‐2 was stimulated with LPS (1 μg/mL) with or without anti‐tumour necrosis factor‐alpha (anti‐TNF‐α, 2 μg /ml) or anti‐interleukin‐1 beta (anti‐IL‐1β, 4 μg /ml) for 24 h. LPS‐induced inflammation level was analysed using the Griess assay to determine nitric oxide (NO) concentration. Proteome alterations were characterized employing the mass spectrometry‐based proteomics and bioinformatics analyses.

Results: Immunocytochemistry confirmed the expression of microglial markers in BV‐2 cells. LPS stimulation induced excessive activation of BV‐2, with significant increase in NO generation (p < 0.0001). Anti‐IL‐1β significantly attenuated 34% of the LPS‐induced NO generation (p < 0.0001). Interestingly, anti‐TNF‐α showed a stronger anti‐inflammatory effect by reducing 57% of LPS‐induced NO generation (p < 0.0001). Bioinformatics analyses revealed that differentially expressed proteins involved in inflammation (p = 3.8 × 10−5) and apoptotic (p = 3.2 × 10−11) signalling pathways were significantly activated by LPS. Particularly, LPS‐mediated upregulation of STAT1 (p = 8.6 × 10−6) was restored by anti‐IL‐1β and anti‐TNF‐α (p = 3.1 × 10−4 and p = 2.7 × 10−3, respectively). Anti‐IL‐1β induced proteome alterations involved in anti‐inflammatory signalling pathways and promote glial cell polarization towards neuroprotective M2 phenotype (p = 5.3 × 10−6), while anti‐TNF‐α treatment significantly regulated proteins involved in immune response of macrophages (p = 2.7 × 10−8).

Conclusions: In summary, anti‐TNF‐α and anti‐IL‐1β antibodies alleviated LPS‐induced neuroinflammation and altered proteins involved in neuroprotective pathways. Hence, anti‐cytokine antibodies have therapeutic potential as neuroprotective agents.
ZEISS VISULAS green SLT in primary open‐angle glaucoma and ocular hypertension: 6 month follow up in a real‐world setting
Authors: Sacchi Matteo , Tomaselli Davide , Calzi Gaia Li , Monsellato Gianluca , Brancato Cinzia , Nucci Paolo
Published: January 2024

Aims/Purpose: The aim of this study is to report preliminary data of efficacy and safety of ZEISS VISULAS® green Selective Laser Trabeculoplasty (SLT) in primary open‐angle glaucoma (POAG) and ocular hypertension (OHT) in a real‐life clinical setting.

Methods: We prospectively collected data of 34 treated eyes in 17 patients during 2022. Patients followed a regular clinical management in our center (San Giuseppe Hospital, University Eye Clinic, IRCCS Multimedica, Milan, Italy). Follow up was of 6 months. Inclusion criteria were adult patients, diagnosis of POAG or OHT. Exclusion criteria were previous laser trabeculoplasty (LT), filtration surgery, and cyclophotocoagulation procedures. Main outcome was ≥20% intraocular pressure (IOP) reduction at 6 months. All the procedures were performed by two doctors (CB, DT). Adverse events were recorded.

Results: We included 34 eyes of 17 patients. Mean age was 67.4 ± 11.5 years. Patients were 88.2% Caucasian, 47.1% females, with a diagnosis of OHT (64.7%), mild POAG (29.4%), or moderate POAG (5.9%). The mean IOP was significantly decreased from baseline to 6 months (21.5 ± 2.1 vs 18.0 ± 2.6 mmHg, p < 0.05). Primary outcome (≥ 20% IOP reduction at 6 months) was reached in 52.9% cases. There was no significant increase in glaucoma medical therapy at 6 months (1.1 ± 1.0 vs 1.4 ± 1.0 medication per eye, p = 0.23). No patient received a second SLT treatment or underwent filtration surgery or cyclophotocoagulation procedures during the follow‐up. No major ocular or systemic side effects were found. The most common adverse event was ocular discomfort in 10 cases (29.4%), always mild and transient. SLT treatment was performed with an average of 100.2 ± 6.7 spots, 27.4 ± 4.7 μJ energy, and a 360° distribution for 32 of 34 eyes (2 eyes treated at 270°).

Conclusions: We reported the preliminary short‐term data of efficacy and safety of ZEISS VISULAS® green SLT treatment in POAG and OHT. To the best of our knowledge, this is the first report of ZEISS VISULAS® green SLT in a real‐life clinical setting. This technology has been shown to be effective and safe in lowering IOP at 6 months after the treatment. Limits of this study were the small sample size and the short follow‐up time.
Combined non‐penetrating deep sclerectomy with phacoemulsification versus non‐penetrating deep sclerectomy alone
Authors: López Carmen Miquel , Abellán Maria Victoria Navarro , de los Reyes Retamero Sánchez María , González Luis Eloy Pérez , Olivares Javier Hernández
Published: January 2024

Aims/Purpose: To compare the intraocular pressure after two surgical techniques: combined non‐penetrating deep sclerectomy with phacoemulsification (Phaco‐NPDS) and non‐penetrating deep sclerectomy (NPDS) alone.

Methods: It is a retrospective study including thirty‐two patients with primary open angle glaucoma (POAG) or pseudoexfoliative glaucoma (PXG) who were not controlled with medication. They were assigned to Phaco‐NPDS (twenty‐two eyes) or NPDS (twenty eyes). Complications in surgery were noted and also, they were followed up after the surgery and intraocular pressure (IOP) was measured at one day, a month, six months and a year after the surgery. Moreover, best corrected visual acuity (BCVA) and the number of the anti‐glaucoma medications at the end of the postoperative medication was measured.

Results: Mean IOP in the Phaco‐NPDS group decreased from 24.55 ± 5.8 mmHg to 17.31 ± 2.1 mmHg and in the NPDS group from 26.05 ± 4.1 to 15.6 ± 2.3 mmHg one day after surgery. The decreases of IOP in the postoperative period were statistically significant in both groups (p < 0.05). There was no significant IOP difference between Phaco‐NPDS and NPDS patients postoperatively (p > 0.05). The mean number of glaucoma medications decreased from 3.31 ± 1.4 to 0.68 ± 0.2 and from 3.2 ± 1.3 to 0.3 ± 0.5 in the Phaco‐NPDS and NPDS groups, respectively. The decreases in the mean number of the anti‐glaucoma medications at the end of the postoperative, 24‐month follow‐up period were found to be statistically significant for both Phaco‐NPDS and NPDS groups (p < 0.05). Mean BCVA increased significantly in both groups. However, the visual outcome was significantly better for the Phaco‐NPDS group (p < 0.05).

Conclusions: Phaco‐NPDS surgery achieved excellent IOP control, while also providing immediate visual recovery. The success rate was similar to that of the NPDS procedure alone. It is advisable to consider Phaco‐NPDS as a primary surgery for patients with coexisting cataract and open angle glaucoma, including PXG.
A novel effect of plasma rich in growth factors in the small leucine‐rich proteoglycans regulation in trabecular meshwork
Authors: del Olmo Aguado Susana , Cueto Carla Martin , Cueto Andrés Fernández‐Vega , Uña Ignacio Rodriguez , de Pablo Herranz Nagore , Calvo Pedro Pablo Rodriguez , Fernández Luis Quirós , Merayo‐Lloves Jesús
Published: January 2024

Aims/Purpose: To analyse the effect of plasma rich in growth factors (PRGF) on the activity of small leucine‐rich proteoglycans (SRLPs) involved in extracellular matrix regulation in a trabecular meshwork fibrosis in vitro model.

Methods: Trabecular meshwork cells were obtained from cadaveric donors in collaboration with the Blood and Tissue Centre of the Principality of Asturias (CEImPA2022.359). The cells were exposed to TGFβ2, which induces the expression of fibrosis markers. After 24 h in the presence of TGFβ2, the cells were treated with PRGF or human serum (control group) for 7 days. After the treatment period, samples were processed for immunocytochemistry or gene expression analysis by qPCR. Immunocytochemical techniques were used to examine the markers α‐sma, collagen I and collagen IV markers. The gene expression analysis included the genes lumican (LUM), decorin (DCN), biglycan (BGN) and fibromodulin (FMOD).

Results: The induction of fibrosis in trabecular meshwork cells, characterized by an increase in extracellular matrix components such as α‐sma, collagen I and collagen IV, led to an increase in the expression of several SRLPs analysed, such as lumican, decorin, biglycan and fibromodulin. Treatment with PRGF for 7 days significantly reduced the expression of lumican, decorin and biglycan. In contrast, fibromodulin expression levels were slightly increased in the PRGF‐treated group.

Conclusions: SRLPs play an important role in the regulation of the extracellular matrix in several ocular tissues. In glaucoma, altered expression of SRLPs such as lumican, decorin and biglycan leads to a glaucomatous phenotype in animal models. Changes in the expression of SRLPs have also been reported in the aqueous humour of glaucoma patients. PRGF treatment regulates the expression of SRLPs, as well as the expression and deposition of other fibrotic markers, and may promote aqueous humour flow and intraocular pressure control.
Differential response of macular and disc capillaries in response to the orthostatic hypotension test
Authors: Pappelis Konstantinos , Jansonius Nomdo
Published: January 2024

Aims/Purpose: To investigate the effect of the orthostatic hypotension test on the macular and disc capillaries, in subjects with different blood pressure (BP) status.

Methods: We prospectively recruited ophthalmologically healthy subjects (age 50–65) from a large‐scale population‐based Dutch cohort. We allocated participants to four groups: low BP, normal BP, treated high BP, and untreated high BP. We obtained two 6x6 mm macular and two 6x6 mm disc OCTA scans of the superficial capillaries. After lying for 5 min, participants stood up for 3 min, following which third scans were obtained from both regions. We quantified vessel density (VD) using customized software. We used linear mixed models to compare VD among groups before and after the orthostatic hypotension test.

Results: We included 98 eyes from 98 subjects for the macular scans and 95 for the disc scans. Parafoveal VD was similar between groups (p = 0.65) and increased following the orthostatic hypotension test (40.4%, 40.6% pre‐test and 40.7% post‐test; p = 0.002). Post hoc analysis revealed that this difference was only significant between the first and third scan (p = 0.001). Peripapillary VD remained unchanged pre‐ and post‐test (p = 0.61), but differed between groups (low BP: 44.0%, normal BP: 45.0%, treated high BP: 44.1%, untreated high BP: 44.5%; p = 0.022). Post hoc analysis revealed that these differences were significant between normotensives and subjects with low BP (p = 0.028) and borderline between normotensives and subjects with treated high BP (p = 0.072).

Conclusions: We observed an autoregulatory response of macular, but not disc, capillaries, following BP drop due to the orthostatic hypotension test.