bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating single‐cell and spatial transcriptomics delineates spatial gene expression patterns and molecular signatures of various tissues in mouse eyes
Authors: Ouyang Shuai
Published: January 2025

Aims/Purpose: The eye is a highly organized structure composed of well‐defined anatomical area with coordinated but distinct‐functional roles. This study aimed to elucidate spatial gene expression patterns and molecular signatures in different ocular tissues.

Methods: We performed spatial transcriptomics sequencing on normal mouse eye samples and integrated single‐cell transcriptomics and spatial transcriptomics for comprehensive bioinformatics analysis of eye. Findings regarding the discovery of several ligand‐receptor pairs and gene expression patterns were validated by in situ sequencing and immunofluorescence experiments.

Results: Firstly, we revealed the spatial gene expression patterns of ocular tissues and identified core spatial regulons of various tissues within the eye. Based on spatial transcriptomics analysis, we uncovered that the central retina prominently mediates synaptic signaling and ion channel transmission functions while the peripheral retina has significant visual reception and oxidative phosphorylation functions. In addition, this undertaking characterized critical neurotransmitters and spatial ligand‐receptor pairs action modes of distinct cell types within the retina, which might contribute to the maintenance of retinal electrical signal transmission. Furthermore, we simulated the spatial differentiation trajectories of lens and corneal cells, and delineated the spatial location dependent changes in gene expression profiles. Subsequently, we identified several novel spatial region‐specific regulators in lens and cell type‐specific regulators in cornea. Finally, we unveiled an ocular spatial organizational communication signaling system that dependent on candidate long‐distance inter‐tissue signaling molecule communication.

Conclusions: This undertaking is likely to aid forthcoming studies on the mechanisms of eye development, differentiation, regeneration and disease occurrence. Our dataset also serves as a scientific resource for atlas, but will also be useful in screening for molecular targets of eye lesions occurring in specific spatial locations, which will greatly improve our understanding of the mechanisms underlying the maintenance of ocular homeostasis in health and disease.
A low dose bimatoprost 0.01% & timolol 0.1% eye gel compared to bimatoprost 0.03% & timolol 0.5% eye drops: A phase III randomized study
Authors: Stalmans Ingeborg , Cordeiro M. Francesca
Published: January 2025

Aims/Purpose: To compare the efficacy and safety of preservative‐free (PF) fixed combination, bimatoprost 0.01%/timolol 0.1% eye gel (BTFC eye gel) with bimatoprost 0.03%/timolol 0.5% eye drops (BTFC eye drops) in patients with open‐angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: Phase III, international, multicentre, randomised, 2 parallel groups, investigator‐masked, 3‐month treatment duration study. Patients with OHT or OAG, insufficiently controlled with a first‐line monotherapy, and requiring a dual therapy, were randomized to receive either PF BTFC eye gel (bimatoprost 0.01%/timolol 0.1%) or PF BTFC eye drops (bimatoprost 0.03%/timolol 0.5%), once daily for 12 weeks. The primary efficacy endpoint was the change from baseline (Day 1) to Week 12 in IOP at 08:00, in the study eye. Noninferiority was based on a predetermined criteria (upper 95% confidence interval margin of 1.5 mmHg at Week 12 at 08:00). Further efficacy and safety endpoints were assessed as secondary outcomes.

Results: The mean change from baseline to Week 12 in IOP at 08:00 was −10.96 ± 3.43 mmHg for BTFC eye gel and −11.14 ± 3.56 mmHg for BTFC eye drops. Noninferiority of T4030 was demonstrated, based on the predetermined criteria. IOP‐lowering efficacy was also similar between treatment groups at Week 6 (08:00; 10:00; 16:00) and Week 12 (10:00; 16:00). The safety profile was similar between T4030 and Ganfort; however, more patients withdrew from the study due to a treatment‐related adverse event (AE) with BTFC eye drops (8 patients [21 AEs]), compared to BTFC eye gel (no patients). Global tolerance was considered as satisfactory/very satisfactory by the investigator for more patients in the T4030 (96.4%) versus Ganfort (91.6%) at Week 6, with a statistically significant between group difference (p = 0.020).

Conclusions: A low dose PF bimatoprost 0.01%/timolol 0.1% eye gel can be considered as a safe and effective tool in the therapeutic management of glaucoma and OHT.
Differential profile of mirnas in aqueous humour: A new potential epigenetic mechanism for pseudoexfoliation glaucoma
Authors: Villanueva Carolina Garcia , Andrés‐Blasco Irene , Martucci A. , Lopez J. F. Ramos , Moreno Vicente Zanon , Montero M. Gonzalez , Nucci C. , Durán Maria Dolores Pinazo , Feijoo Julian Garcia
Published: January 2025

Aims/Purpose: Pseudoexfoliation glaucoma (PEG), is the most prevalent of the secondary glaucomas, characterized by the accumulation of fibrillar extracellular material in the anterior eye chamber. The miRNAs are regulators of gene expression, as epigenetic effectors. Our aim is to identify candidate miRNAs that may be involved in PEG physiopathology.

Methods: A collaborative, longitudinal, prospective, case‐control study was set up in 120 participants, of both sexes, that were classified as: PEG patients (n = 60) and healthy individuals (CG n = 60). Sociodemographic and opththalmologic data were recorded. Aqueous humor was collected at the onset of glaucoma surgery, labelled and stored at. ‐80° until processing. Total ARN was obtained, and expression and quantitation of the miRNAs ‐122‐5p, ‐146a‐5p and ‐320a‐3p, were assayed by real time quantitative polimerase chain reaction (RT qPCR) in both study groups. Databases DIANA TOOLS, miRDB, TargetScanHuman 7.2 were used to connect the target genes with its biological functions. Data were processed by IBM SPSS 28.0 statistical program.

Results: Mean age was 73 ± 11 years. Gender distribution was 32 % men/68 % women. Mean intraocular pressure was 17 mmHg in the right eye (RE) and 19 mmHg in the left eye (LE). Mean retinal nerve fiber layer thickness was 73 μm in RE and 71 μm in LE. MiRNAs ‐122‐5p (p = 0.02),146a‐5p (p = 0.02) and ‐320a‐3p (p = 0.04) showed a significantly higher expression in the aqueous humor of PEG versus CG.

Conclusions: miRNAs ‐122‐5p, ‐146a‐5p and ‐320a‐3p are involved in PEG pathogenesis, epigenetically affecting the expression of target genes and protein translation, by means of their biological functions, in relation to extracellular matrix, metalloproteinases, glutamate, and the signaling pathways MAPK and RhoA/ROCK. We may suggest to investigate new biological therapies on the basis of the above miRNAs in PEG patients.
Identification of diagnostic and prognostic biomarkers in dry eye disease in primary open‐angle glaucoma: A cross‐sectional case‐control study
Authors: Sáez Sara Mora , Andrés‐Blasco Irene , Cerdà‐Ibáñez Marta , Peris‐Martínez Cristina , Durán Maria Dolores Pinazo
Published: January 2025

Aims/Purpose: To integrate clinical and molecular data that allow us to identify diagnostic and prognostic biomarkers of dry eye disease (DED) in primary open‐angle glaucoma (POAG).

Methods: A cross‐sectional case‐control study consisting of 182 participants of both sexes, was done. Volunteers were classified into 4 groups: healthy controls (CG; n = 50), DED group (n = 42), POAG group (PG; n = 44), and DED+POAG (n = 46). All participants underwent a complete and systematic medical history, filled out the questionnaires, and were subjected to ophthalmologic examination. Reflex tear samples were collected and subsequently processed using enzyme‐linked immunosorbent assay (ELISA) to quantify the levels of interleukins (IL) ‐1β and ‐18. Statistical analysis was performed with the SPSS 28.0 program.

Results: Mean age of the study participants was 60+15 years, with a total of 56 males (31%) and 126 females (69%). The use of preservative‐containing eye drops was observed in 13% of the POAG patients, and 21% of the DED+POAG group. Clinical data [Schirmer test, tear break‐up time (TBUT), tear meniscus height (TMH) measured by optical coherence tomography (OCT)], and the tear expression of IL‐1β and IL‐18 were significantly different between groups. According to the ocular surface disease index (OSDI) questionnaire, dry eyes were more severe (OSDI=42) and the IL‐1β and IL‐18 tear levels were significantly higher in 37% of the DED+POAG patients.

Conclusions: We suggest that assessment of TMH, OSDI, and the tear expression of IL‐1β and IL‐18 can be potential biomarkers for identifying patients at risk of DED in the POAG subgroup undergoing treatment with antihypertensive eye drops.
Neurovascular coupling response: A follow‐up study
Authors: Jordão João , Rodrigues Sérgio , Domingues Joana , Serranho Pedro , Guimarães Pedro , Bernardes Rui
Published: January 2025

Aims/Purpose: This work aims to assess the consistency of the neurovascular coupling (NVC) response of a healthy subject group at two visits 5 months apart.

Methods: Fundus images (4x4 degrees) of the macular region (3 baseline acquisitions and 3 acquisitions each preceded by flicker stimulation) of 13 healthy adults (one eye each, age (m+/‐sd): 33.08+/‐11.4 yrs.) were acquired with the rtx1 AO camera (ImagineEyes, Orsay, France). The rtx1 was configured for a 20 second, 15Hz, and 4 μW.cm^(‐2) flicker stimulation over a 29x20 degrees area of the imaged eye fundus. Acquisitions for each subject were repeated 159+/‐17 (m+/‐sd) days later.

The lumen of retinal arterioles within the macular region was determined using custom‐developed software for the automatic segmentation of lumen‐wall interfaces. An experienced technician visually assessed all segmentations to reject subpar results. Lumen diameters were calculated from the distance between the lumen‐wall interfaces as measured perpendicular to the vessel axis along a vessel segment. NVC responses were calculated per eye as the relative difference (%) of the lumen diameter after stimulation to the respective baseline.

Results: A total of 22 out of 156 images (14%) were rejected and excluded from further analysis. NVC responses ranged from 0.21% to 8.28% (3.36+/‐2.75 % (m+/‐sd)) for the first visit and from ‐0.24% to 9.13% (3.03+/‐2.54 %) for the follow‐up. Response differences between time points ranged from ‐6.15% (8.28% to 2.13%) to 4.21% (0.98% to 5.19%), with an average (sd) of 0.34(3.03) % for the group. A paired sample Wilcoxon test between time points is not statistically significant (p = 0.650), supporting that the responses are consistent between time points.

Conclusions: The obtained results show a consistent NVC response for a 5‐month interval.
Orthokeratology and myopia control: A comprehensive meta‐analysis of axial growth in children and adolescents
Authors: Queirós António , Mota‐Silva Inês , Pereira‐da‐Mota Ana Filipa
Published: January 2025

Aims/Purpose: The aim of this study was to evaluate the longitudinal effect on axial eye length in myopic children and adolescents treated with orthokeratology (OK) lenses compared to spectacles (GL), through a systematic review and meta‐analysis

Methods: We conducted a systematic search of PubMed and Google Scholar databases for randomized controlled trials and cohort studies investigated the effects of longitudinal axial length difference, using the keyword “Axial Length” AND “orthokeratology” AND “spectacles”. From the initial 91 studies, we excluded 13 review studies, 10 meta‐analysis studies, 7 systematic reviews and 37 studies that did not meet the inclusion criteria. Of the 24 selected studies, detailed information was available at 24, 18, 12, 6, 3 and 1 month, with 10, 8, 19, 17, 2 and 3 studies respectively, allowing for the comparison between 2172 eyes treated with orthokeratology and 2095 eyes with glasses.

Results: The analysis of the 24 studies (which included 59 comparisons from 1 month to 24 months) showed no statistically significant differences in initial axial length [AL(GL) = 24.39 ± 0.34 mm ; AL(OK) = 24.44 ± 0.38 mm] and initial refractive error [M(GL) = ‐2.59 ± 0.70 D ; M(OK) = ‐2.53 ± 0.44 D] between the two treatment groups (p > 0.565, independent samples t‐test) and for the evolution time intervals (p > 0.591, ANOVA). This analysis encompassed 4267 eyes with a mean age of 10.23 ± 1.21 years. Forest plot provided in an overall effect size of myopic defocus AL=‐0.16 com IC 95% ‐0.19 a ‐0.14, Z=12.71 p < 0.001. A random effects model was used considering the heterogeneity observed (I2=97%; p < 0.001, df=58). There was a greater myopia control effect at 24 months (AL=‐0.26, 95% IC ‐0.29 to ‐0.22, Z=13.71 p < 0.001; I2=0%; p = 0.95) than to treatments of less than 3 months (AL=‐0.04, 95% IC ‐0.06 to ‐0.01, Z=2.60 p = <0.009; I2=86%; p < 0.001).

Conclusions: While the treatment at 24 months shows an homogeneous behaviour among studies, shorter follow‐up times renders a larger heterogeneity and for that reason, longer follow‐up periods should be preferred to estimate a more solid effect size. Orthokeratology treatment has been shown to be effective in myopia control progression for short or longer longitudinal treatments in children and young people with spectacles comparison.
Retinal image quality with myopia control lenses, in the synthetic accommodative wavefront model
Authors: García Maria Mechó , Fernandes Paulo , Faria‐Ribeiro Miguel Ángel
Published: January 2025

Aims/Purpose: Current myopia control contact lenses (CLs) are based on multifocality designs that affect decrease retinal image quality (RIQ). This study aimed to evaluate the changes in RIQ and accommodative response (AR) with two myopia control CLs.

Methods: 100 synthetic eyes were generated using anc accommodative wavefront model to simulate the changes in RIQ with accommodation. The synthetic eyes were “fitted”, using direct wavefront summation, with two myopia control CLs: the MiSight with +2.00D treatment zones and the Mylo with an EDOF design. Peak image quality was calculated for the naked eye and with CLs, in the relaxed state and a target vergence of 40 cm, with an entrance pupil diameter of 4.28 mm. Additionally, the AR that maximizes RIQ was calculated.

Results: The mean RIQ [ranged from 0 to 1] for the relaxed eye was 0.42 ± 0.10 without a CLs. It halved to 0.26 ± 0.05 with the Misight and reduced by threefold to 0.15 ± 0.04 with the Mylo. For 40cm the RIQ was 0.34 ± 0.09 without a CL, 0.24 ± 0.07 with the Misight and 0.19 ± 0.03 with the Mylo.

For target vergences with demands close the effective add power of the CL, the accommodative RIQ through‐focus produced a second peak prior to the maximum peak, correspondent to the focusing power of the treatment zones1, yielding a RIQ of 0.08 ± 0.03 and 0.12 ± 0.04 for the Misight and Mylo, respectively. The AR without CL was 2.33 ± 0.20 D, 1.75 ± 0.22 D and 1.75 ± 0.22 D with the Misight and the Mylo, respectively.

Conclusions: Both myopia control CLs reduced the RIQ in the relaxed and accommodated states. For 40 cm, both CLs induce a secondary peak in the RIQ through‐focus. With Mylo, the secondary peak appeared less than 0.1D from the maximum peak, possibly due to its EDOF design. The AR was reduced with both CLs 0.58 D (lag) compared to the naked eye condition. These results indicate that, both lenses impose significant limitations RIQ and AR.

References

Faria‐Ribeiro M, Amorim‐de‐Sousa A, González‐Méijome JM. Predicted accommodative response from image quality in young eyes fitted with different dual‐focus designs. Ophthalmic Physiol Opt. 2018;38(3):309‐16.
Silver bismuth sulfide quantum dot‐based bioelectronics for light‐mediated neuronal stimulation
Authors: Kaleli Humeyra Nur , Balamur Rıdvan , Kaya Tarık Safa , Önal Asım , Pehlivan Çiğdem , Sahin Afsun , Nizamoğlu Sedat , Hasanreisoğlu Murat
Published: January 2025

Aims/Purpose: Nanomaterial based bioelectronics have been effectively developed as optoelectronic bio‐interfaces for neural stimulation and can be fabricated from diverse substances to adapt to cellular environments. In this study, we employed silver bismuth sulfide (AgBiS2) quantum dot (QD)‐based neural interfaces stimulated by near‐infrared light.

Methods: Primary neuron isolation and culture on AgBiS2 QD based photovoltaic device and indium tin oxide (ITO) control device was performed. Cell viability was assessed by CTG, MTT, Live/Dead assay and LDH leakage assays. Cellular stress with light stimulation was assessed by measuring intracellular reactive oxygen species. Cell specific biomarkers, NeuN, beta‐III Tubulin and F‐actin, were examined by immunofluorescence staining to demonstrate short‐ and long‐term morphological changes and neural network improvements. Number of neuron count and neurite length measurement were analyzed to compare groups. Under light stimulation (λ = 780 nm), neural dynamics and electrophysiological activity were examined through intracellular calcium flow and patch clamp.

Results: Throughout the 14‐day culture period, neurons remained healthy and viable, preserving their characteristics and forming extensive networks with neurite outgrowth on both the device and ITO. Light stimulation was found to have no adverse effects on viability or intracellular stress levels. The device demonstrated successful photostimulation of neurons with calcium release and generating action potential under 780 nm light illumination which is validating its potential to be used as optoelectronic bio‐interfaces for neural applications.

Conclusions: Our study holds high potential for the development of QD‐based retinal prosthesis, enabling near infrared light‐controlled activation in vision related diseases.

Funding Information: This study was funded by the European Union (ERC, MESHOPTO, 101045289).

References

Balamur R, Oh JT, Karatum O, Wang Y, Onal A, Kaleli HN, Pehlivan C, Şahin A, Hasanreisoglu M, Konstantatos G, Nizamoglu S. Capacitive and Efficient Near‐Infrared Stimulation of Neurons via an Ultrathin AgBiS2 Nanocrystal Layer. ACS Applied Materials & Interfaces. 2024 May 29
Evaluation of the conjunctival bacterial flora in the New Zealand white rabbit
Authors: Cejudo Raquel Maroto , Encalada Denisse Michelle Espinosa , Rodriguez Oscar Esparcia , Gómez‐Juarez Sango Mónica , Pretel Fernando Andrés , Valenciano Carlos Cava
Published: January 2025

Aims/Purpose: We aimed to characterize the normal bacterial flora of conjunctiva and eye lids of the white New Zealand rabbit.

Methods: Twelve rabbits (Twenty‐four eyes) were employed. Before sampling, an ophthalmological examination of the ocular surface was performed to exclude the presence of any lesions.

Microbiological sampling by sterile swabs was performed on the superior and inferior conjunctival fornix. Samples were placed in eSwab 1 mL transport medium (eSwab® – Copan's Liquid Amies Elution Swab) and submitted for culture. They were cultured on blood agar, chocolate agar and sabouraud agar. Species identification was carried out by mass spectrophotometry (MALDI‐TOF, BioMèrieux®) and/or conventional techniques. They were seeded in triplicate and the quantification of the germs was expressed in terms of CFU/mL.

Results: Seven different species were observed. The most frequent was Moraxella cuniculi (705 ± 1129 CFU/mL), followed by Corynebacterium spp (71.43 ± 267.3 CFU/mL) and coagulase negative Staphylococcus (5 ± 10.92 CFU/mL). Other less frequently species observed were Staphylococcus aureus, Streptococcus viridans, Tsukamurella spp and Bacillus spp.

Statistical analysis showed a significant statistical difference between M. cuniculli and the other species observed. (Krussal Wallis p < 0.001).

Conclusions: M. cuniculi was the species with the highest CFU/mL in the conjunctival flora of the rabbit.
Evaluating brolucizumab in neovascular AMD: Clinical outcomes from a tertiary care eye hospital
Authors: López‐Cuenca Inés , Fabozzi Lorenzo , Younis Saad , Sen Sagnik , Palmieri Filomena
Published: January 2025

Aims/Purpose: To present real‐world clinical data on the effectiveness of brolucizumab in managing neovascular age‐related macular degeneration (nAMD), either as primary therapy or as switch therapy, in a tertiary care eye hospital in London.

Methods: This research involved 37 eyes diagnosed with nAMD, all of which received intravitreal injections of brolucizumab. The main metrics assessed were changes in best corrected visual acuity (BCVA) and central retinal thickness (CRT) by optical coherence tomography (OCT), as well as the incidence of serious ocular adverse events. Additional evaluations included intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci (HF), macular atrophy, and retinal pigment epithelial tears. The patients are classified into: patients not previously treated (Naïve) and patients treated with other anti‐VEGF agents.

Results: The average BCVA for all patients after treatment was 0.47 ± 0.33 LogMAR, compared to a baseline of 0.50 ± 0.28 LogMAR (p = 0.372). Treatment‐naïve patients showed a non‐significant improvement in BCVA (p = 0.116). Both treatment‐naïve patients and the entire cohort exhibited a statistically significant reduction in mean CRT following the injections. Most patients showed enhancements in OCT findings, notably in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes developed ocular adverse events, specifically intraocular inflammation.

Conclusions: While brolucizumab did not lead to a significant improvement in BCVA, it effectively reduced CRT in both the overall study group and in treatment‐naïve nAMD patients. The study identified intraocular inflammation as a noteworthy adverse event related to brolucizumab. Therefore, careful patient selection, education, and diligent monitoring of inflammation are essential for those receiving this therapy.
Actual lens position of three intraocular lenses in highly myopic eyes: an ultrasound biomicroscopy‐based study
Authors: Qi Jiao , Zhu Xiangjia
Published: January 2025

Aims/Purpose: To evaluate the actual lens positions (ALPs) of three intraocular lenses (IOLs) in highly myopic eyes and to identify relevant factors using ultrasound biomicroscopy (UBM).

Methods: Ninety‐three highly myopic eyes (93 patients) that underwent uneventful cataract surgery were included: 36 eyes were implanted with Zeiss 409MP IOLs, 27 with Rayner 920H IOLs, and 30 with HumanOptics MCX11 IOLs. The prediction error (PE), ALP determined by UBM, and the factors associated with ALP at 3 months after surgery were evaluated.

Results: The eyes in the MCX11 IOL group had a more hyperopic PE (0.67 ± 0.45 diopters [D]) and greater ALP (4.86 ± 0.39 mm) than those in the 409MP and 920H IOL groups at 3 months after surgery (PE: −0.25 ± 0.54 and −0.16 ± 0.65 D, respectively; ALP: 4.34 ± 0.26 and 4.14 ± 0.32 mm, respectively). The MCX11 IOLs showed more backward bending deformation after surgery than 409MP and 920H IOLs. The radius of curvature of the IOL was negatively correlated with ALP (r=−0.532, p = 0.002) in the MCX11 IOL group, but not in the other two groups. Multivariate analysis showed that MCX11 IOLs were more prone to bending in highly myopic eyes with a smaller anterior capsular opening (β=0.236, p = 0.023) and lower implanted power (β=0.542, p = 0.001).

Conclusions: In highly myopic eyes, IOLs with good capsular support show less backward bending, which result in a more stable lens position and refractive status postoperatively. Severe capsular contraction and low implanted power are risk factors for bending of certain IOLs.
Preclinical evaluation on the biocompatibility and biosafety of a new foldable brown‐diaphragm intraocular lens: an in vitro and in vivo study
Authors: Zhang Keke , Zhang Shaohua , He Wenwen , Lu Yi , Zhu Xiangjia
Published: January 2025

Aims/Purpose: A new foldable brown‐diaphragm intraocular lens (IOL) was preclinically evaluated in vitro and in vivo by comparing its biocompatibility and biosafety with those of a commercially available IOL.

Methods: The new brown‐diaphragm IOL is made of hydrophobic acrylic material, with incorporating a transparent optical zone and surrounding brown diaphragm. Cellular experiments evaluating lens epithelial cell morphology, adhesion, and migration were conducted to exclude cytotoxic effects. Twelve New Zealand rabbits had the new brown‐diaphragm IOL implanted in one eye and another 12 had a commercially available foldable IOL implanted, followed by slit‐lamp evaluations, corneal endothelial cells density measurement and aqueous humor analysis to identify any dye leakage from the brown‐diaphragm IOL. Haematoxylin and eosin staining of ocular tissue and scanning electron microscopy (SEM) of the IOL surface were performed after 12‐week observation.

Results: In vivo experiments showed there were no statistically significant differences between the two groups in terms of postoperative inflammation and capsular biocompatibility. There were no significant changes in corneal endothelial cell density between before and after surgery in either group. LC‐MS/MS analysis showed that the target dye was not detected in aqueous humor samples. Histopathology of ocular sections and SEM imaging of IOL surfaces showed similar changes in both groups.

Conclusions: The newly‐invented brown‐diaphragm IOL showed good biocompatibility and biosafety. Combined with its foldability and peripheral shading, it could be a new choice for patients with iris defects.
The importance of adequate preparation of the ocular surface before biometry in reducing refractive errors in patients undergoing cataract surgery
Authors: Biela Katarzyna , Winiarczyk Mateusz , Mackiewicz Jerzy
Published: January 2025

Aims/Purpose: To evaluate the impact of dry eye disease (DED) on refractive errors in patients after cataract surgery.

Methods: Fifty patients undergoing cataract surgery were studied. Two study groups and a control group were distinguished. The first study group (group A, n = 22, 44%) were patients with preoperatively diagnosed DED who received appropriate treatment (eyelid margin hygiene and moisturizing the ocular surface). The second study group (group B, n = 14, 28%) were patients in whom such treatment was also implemented, despite the lack of a diagnosis of DED. The remaining patients (n = 14, 28%) were the control group (Group C). Biometric measurements with calculation of intraocular lens (IOL) power were performed twice in all of them (before and after treatment of DED). Refraction and refractive errors were evaluated one month after surgery.

Results: Significant improvement in best corrected visual acuity (BCVA) was obtained in all groups after surgical treatment. In both study groups, a significant reduction in the mean absolute error (MAE) after the treatment was achieved – in study group A, the MAE was 0.37 ± 0.30 D vs 0.24 ± 0.33 D, p = 0.003. In study group B, MAE was 0.29 ± 0.26 D vs 0.23 ± 0.23 D, p = 0.017. The control group showed no difference in MAE (0.27 ± 0.18D vs 0.33 ± 0.21 D, p = 0.322). In study group A, there was a significant reduction in the percentage of MAE in the ± 0.25 D range (36.36% vs 77.27%, p = 0.016). The results are comparable with previous publications.

Conclusions: Diagnosis and treatment of dry eye syndrome before cataract surgery is an important factor in reducing refractive errors after surgery. The use of lubricating drops and eyelid margin hygiene before biometry can be considered for all patients undergoing cataract surgery.
Carlevale intraocular lens refractive predictability: A retrospective analysis
Authors: Dias Bruno Guerreiro , Matos Diogo Bernardo , Marques‐Neves Carlos , Faria Mun Yueh , Ferreira Nuno Pinto
Published: January 2025

Aims/Purpose: The purpose of this study was to evaluate the refractive predictability of the sutureless scleral fixation Carlevale intraocular lens (IOL) for the correction of aphakia in the absence of capsular support.

Methods: Retrospective cohort study. Consecutive patients implanted with Carlevale IOL between February 2020 and February 2024, with a minimum follow‐up of 3 months, were included. Exclusion criteria included use of toric IOLs and absence of postoperative refraction due to a severely limited visual acuity or lack of cooperation. The clinical data were acquired from the patients' records. Primary outcome was the postoperative spherical equivalent deviation (PSED) in relation to the preoperative refractive target. Secondary outcomes included the best corrected visual acuity (BCVA), surgically induced astigmatism (SIA), and postoperative complications.

Results: A total of 44 eyes were implanted with the Carlevale IOL in the study period. Of these, 30 met the inclusion criteria and were included in the statistical analysis. The mean follow‐up time was 18.3 ± 11.7 months, and the mean age at the time of surgery was 70.93 ± 16.28 years. The most common surgical indications were aphakia after complicated cataract surgery (40%, n = 12), IOL dislocation (33.3%, n = 10), and aphakia after trauma (20%, n = 6). The PSED was ‐0.62 ± 1.51 diopters, with no statistically significant difference between surgical indication groups (p = 0.606). BCVA showed a statistically significant increase from 1.52 ± 0.88 to 0.42 ± 0.41 logMAR (p < 0.001). The trauma group had worse BCVA results (p = 0.013). The SIA was 1.14 ± 1.93 diopters. Regarding postoperative complications, the most common were transient ocular hypertension (20%), bleeding (hyphema or hemovitreous; 13.3%), and cystoid macular edema (6.6%).

Conclusions: The Carlevale IOL is a valuable option in our arsenal for managing aphakic eyes with no capsular support. It appears to provide acceptable predictability in refractive outcomes, with low astigmatism and few associated complications.
Clinical impact of intraocular lens tilt and decentration on visual outcome in patients undergoing cataract surgery
Authors: Rodríguez Laura Moreno , Tielas Lourdes Salgueiro , Sánchez‐Lozano Azahara , García‐Onrubia Luis , Velarde‐Rodríguez Gonzalo , Faria‐Ribeiro Miguel Ángel , Alejandre‐Alba Nicolás
Published: January 2025

Aims/Purpose: To study the association between best corrected visual acuity (BCVA) and tilt and decentration of Clareon intraocular lenses (IOL) (CNA0T0). Additionally, to evaluate the best corrected visual acuity for intermediate distance (BCVA‐ID), the kappa angle represented as the distance of the Mu chord (CMu), the white‐to‐white distance (WTW), axial length (AL), and capsulorhexis characteristics.

Methods: A cross‐sectional study was conducted including both eyes of a total of 111 patients. BCVA and BCVA‐ID (60cm) were expressed in LogMAR. Photographs were taken to assess the circularity, area, and principal radii of the capsulorhexis. The tilt and decentration of the IOL, as well as the WTW distance, were measured with anterior segment OCT (CASIA II). AL and CMu were evaluated with the IOL Master 700 biometer.

Results: The median monocular and binocular BCVA were 0.00 [IQR 0.05] and ‐0.02 [0.1], respectively, while the median BCVA‐ID was 0.6 [0.06] and 0.49 [0.06]. The median IOL tilt was 5.30 [1.50], with a decentration of 0.23 [0.17]. The median WTW distance was 11.82 [0.53], the median CMu was 0.35 [0.21], and the capsulorhexis circularity was 93.7 [6] %.

In the correlation analysis, no significant association was observed between IOL tilt and BCVA (r = 0.03 p = 0.63); however, there was a significant association with BCVA‐ID (r = ‐0.16 p = 0.01). None of the other variables showed correlation, except for IOL tilt and CMu (r = 0.20 p < 0.001) and AL (r = ‐0.35 p < 0.001).

Conclusions: IOL tilt is not correlated with best corrected visual acuity for distance, although it is correlated with intermediate distance visual acuity. The measured values of tilt and decentration are low, suggesting good postoperative stability of the intraocular lens.

Study partially supported by an Investigator Initiated Trial Grant from Alcon (#78232309).
The use of the smart eye camera device for cataract screening in the endocrine and ophthalmology clinics in a general hospital in Jordan
Authors: Khalil Mohammed , Abu‐Ismail Luai , Imran Mohammed Abu , Khemlani Rohan , Nakayama Shintaro , Nishimura Hiroki , Shimizu Eisuke
Published: January 2025

Aims/Purpose: To asses the usefuleness of the Smart Eye Camera (SEC) slit light device by OUI Inc. in comparing the prevalence of cataract in diabetic and non‐diabetic patients in an outpatient setting in a general hospital in Jordan. The study aims also to delineate risk factors for the development of cataract in diabetic patients.

Methods: 207 patients (414 eyes) were examined using the SEC device which captures videos of the anterior segment similar to a slit lamp exam. After completion of data collection, web‐saved videos were reviewed and grades of cataract or each eye were recorded using a modified LOCS III (lens opacity classification system). The assigned observer recorded nuclear, cortical and posterior subcapsular grades for each eye from 0 to 5.

Results: Mean age was 55 (range 40‐85). After exclusion of 19 pseudophakic eyes and 3 low quality images, 204 patients (392 eyes, 198 right (OD) and 194 OS (left) eyes) were analyzed. Nuclear cataract was found in 114 eyes (29%), cortical cataract in 104 eyes (27%) and posterior subcapsuar in 77 eyes (20%). Overall, odds ratio for developing cataract in diabetes in this study population was 1.606, with a p‐value of 0.09. Also the relative risk of developing cataract in diabetes was 1.123. A second and third observer independently evaluated the SEC videos and recorded their findings. Interobserver agreement kappa value was fair to moderate especially for nuclear cataract. Posterior subcapsular cataract was difficult to assess with no means of retroillumination on the device. Additionally, we looked into possible assosiations between DM control, comorbidities and medciations used by diabetic patients and the development of cataract, especially hypertension, thyroid disease and hyperlipidemia. All diabetic patients were type 2 with 34.2% having a Hba1c > 7.5

Conclusions: The Smart Eye Camera is a small, fast and accurate tool for the diagnosis and grading of cataract in the outpatient setting and would be very helpful on a national scale for cataract screening, especially in the rural areas and in clinical trials. Moreover, cataract tends to be more common in diabetic patients in Jordan probably through multifactorial mechanisms.

References

Evaluation of Nuclear Cataract with Smartphone‐Attachable Slit‐Lamp Device by Hiroyuki Yazu et al in Diagnostics 2020, 10, 576
Impact of time to idebenone initiation on visual acuity in leber hereditary optic neuropathy: Post hoc analysis of the leros study
Authors: Carelli Valerio , Yu‐Wai‐Man Patrick , Llòria Xavier , Silva Magda Joana , Klopstock Thomas
Published: January 2025

Aims/Purpose: It is not yet established whether time of idebenone treatment initiation from symptom onset (Ti) impacts the clinical outcome of patients with Leber hereditary optic neuropathy (LHON). LEROS, a Phase IV, open‐label, international, natural‐history controlled study (NCT02774005), assessed the long‐term efficacy of idebenone in the treatment of LHON.1 In this post‐hoc analysis of LEROS study data, we report visual acuity (VA) endpoints by Ti.

Methods: VA endpoints at last visit were assessed as previously described, in idebenone‐treated eyes from the LEROS study with an observation time of 12–24 months (m) and a m.11778G > A mitochondrial DNA mutation.1 In this post‐hoc analysis, eyes were stratified by Ti. No statistical comparisons were performed.

Results: Median [range, n] age at baseline was similar regardless of Ti (0–3m: 32.2y [12.6–49.6, 10]; 3–6m: 36.2y [12.6–62.5, 21]; 6–9m: 37.4y [12.6–64.5, 20]; 9–12m: 33.0y [19.5–49.6, 19]; 12–24m: 32.4y [12.1–60.2, 44]; > 24m: 34.7y [12.4–62.4, 61]). VA endpoints at last visit were also similar regardless of Ti; however, minor differences were observed. Eyes that were 3–6m from symptom onset at treatment initiation had the best median [interquartile range (IQR)] VA at last visit (0–3m: 1.27 [0.40–1.68]; 3–6m: 1.22 [0.30–1.80]; 6–9m: 1.40 [1.02–1.56]; 9–12m: 1.52 [0.98–1.60]; 12–24m: 1.39 [0.58–1.74]; > 24m: 1.32 [0.90–1.62]) and the best median [IQR] VA change from last visit to baseline (0–3m: 0.08 [‐0.20–0.62]; 3–6m: ‐0.20 [‐0.46–0.10]; 6–9m: ‐0.11 [‐0.19–0.00]; 9–12m: ‐0.10 [‐0.48– ‐0.04]; 12–24m: ‐0.09 [‐0.47–0.00]; > 24m: ‐0.06 [‐0.18–0.00]).

Conclusions: LEROS study data provides important insights into the impact of time of treatment initiation on VA outcome. However, given the small number of eyes and large variation in the data, caution must be taken in interpreting these results.

References

1. Yu‐Wai‐Man P et al. Cell Rep Med. 2024;5:101437.
Visual acuity outcomes by causative mutation in the natural history of leber hereditary optic neuropathy: Analysis of historical data from case record survey‐2 (CRS‐2)
Authors: Yu‐Wai‐Man Patrick , van Everdingen Judith , Leroy Bart , Krawczynski Maciej , Lamperti Costanza , Carelli Valerio , Llòria Xavier , Klopstock Thomas
Published: January 2025

Aims/Purpose: The clinical progression of Leber hereditary optic neuropathy (LHON) is influenced by the causative mitochondrial DNA (mtDNA) mutation. The Case Record Survey‐2 (CRS‐2; NCT02796274) aimed to establish the natural history of LHON in idebenone‐naïve patients. Here, we report the 12‐ and 24‐month clinical outcomes by mutation.

Methods: Data were extracted from case records (20 sites, 7 European countries) meeting the criteria: aged ≥12 y, m.11778G > A, m.3460G > A or m.14484T > C mtDNA mutation, onset of symptoms (OoS) after 1999, ≥2 visual acuity assessments (VAA) within 5y of OoS. Baseline (BL) was the first VAA after OoS; subacute/dynamic (S/D) and chronic eyes were ≤1 or > 1 y from OoS at BL, respectively. Spontaneous clinically relevant recovery, stabilisation and worsening (sCRR, sCRS and sCRW, respectively) were calculated as previously described.1 Eyes eligible for analysis had a VAA 12±3 or 24±3 months from BL.

Results: Eligible eyes included 96 S/D and 11 chronic eyes for the 12‐month analysis and 44 S/D and 2 chronic eyes for the 24‐month analysis.

At 12 months, rates of sCRR, sCRS and sCRW in overall S/D eyes were: 13% (12/96), 26% (11/42) and 66% (50/76), respectively. By mutation, these rates were: m.11778G > A: 9% (6/68), 23% (7/30), 70% (37/53); m.3460G > A: 0% (0/16), 29% (2/7), 82% (9/11); and m.14484T > C: 50% (6/12), 40% (2/5), 33% (4/12), respectively. There were few chronic eyes, with overall rates of 18% (2/11), 100% (2/2) and 67% (4/6), respectively.

At 24 months, rates of sCRR, sCRS and sCRW in overall S/D eyes were: 27% (12/44), 46% (10/22) and 46% (16/35), respectively. By mutation, these rates were: m.11778G > A: 11% (3/27), 33% (5/15), 57% (13/23); m.3460G > A: 50% (7/14), 67% (4/6), 33% (3/9); and m.14484T > C: 67% (2/3), 100% (1/1), 0% (0/3), respectively.

Conclusions: The CRS‐2 study offers important insights into the impact of causative mutation on the natural history of LHON.

References

1. Yu‐Wai‐Man P, et al. Cell Rep Med. 2024;5:101437.
Myopi‐X spectacle lenses vs atropine 0.01% for myopia control: Turkish study
Authors: Akagun Nilay , Altiparmak Emrah
Published: January 2025

Abstract: The global surge in myopia poses significant health and economic challenges due to associated complications. Current myopia management strategies include atropine eye drops, orthokeratology, special design contact lenses, and myopia‐control spectacle lenses. The Miyopi‐X (Novax®) spectacle lens is a novel peripheral defocus progressive addition lens designed to mitigate myopia progression. This study aims to assess the efficacy of Miyopi‐X spectacle lenses compared to single vision lenses (SV) and atropine 0.01% eye drops in myopia management.

Methods: A retrospective study was conducted on patients aged 5–18 years. Clinical records of patients using Myopi‐X lenses, SV lenses, and those receiving atropine 0.01% eye drop treatment between September 1, 2022, and September 30, 2023, were reviewed. Primary outcome measures included cycloplegic spherical equivalent refraction (SE) and axial length (AL) measured at baseline and 12 months.

Results: The study included 92 patients: 41 in the Myopi‐X group, 25 in the SV group, and 26 in the atropine group. At 12 months, both Myopi‐X and atropine 0.01% groups exhibited significantly less SE progression than SV lenses (p < 0.001). No significant difference in SE change was observed between Myopi‐X and atropine 0.01% (p: 0.90). Similarly, both Myopi‐X and atropine 0.01% groups showed significantly less AL progression than SV lenses at 12 months (p < 0.001). However, pairwise comparisons revealed a significant difference in AL change between Myopi‐X and atropine 0.01% groups (p: 0.02), with atropine 0.01% demonstrating better control over axial elongation compared to Myopi‐X lenses.

Conclusions: Miyopi‐X lenses and atropine 0.01% are effective in slowing myopic axial elongation. This study represents the first of its kind conducted on Turkish myopic children/adolescents.

References

Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, et al. Low‐Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double‐Blinded, Placebo‐Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control. Ophthalmology. 2019;126:113‐124.

Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123:1036‐42.
Biodistribution of alpha‐lipoic acid in beta‐cyclodextrins: Analyzing ex vivo delivery to the posterior segment of the eye
Authors: Ta Phuong Linh , Just Lucia Bernat , Alambiaga‐Caravaca Adrián , Alarma Vicente Rodilla , Castellano Alicia López , Morell Francisco Bosch
Published: January 2025

Aims/Purpose: α‐lipoic acid (ALA), a natural antioxidant, has shown significant value in delaying retinal damage progression. The purpose of this study was to quantify the amount of α‐lipoic acid in β‐ cyclodextrins (ALA‐βCD) complexation in various ocular tissues, especially in the posterior segment of the eye and the neuroretina, after administration from solution and ocular inserts containing the drug.

Methods: ALA‐βCD was dissolved in phosphate saline solution (PBS) to obtain a 1 mg/mL solution. Inserts containing 1 mg/mL ALA‐βCD were prepared using eye‐compatible polymers: polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and hyaluronic acid (HA).

Porcine eyes were obtained from an abattoir shortly after sacrifice and they were cleaned and placed on a Franz diffusion cell. The solution (250 μl) was administered every 2h and washed after 5 min with PBS. The inserts were placed in contact with either the cornea or the sclera. Both experiments were carried out for 8h at 37°C with humidity control. The eyes were then washed with PBS and stored at ‐80°C for 12 h wrapped in parafilm to maintain their morphology. The frozen eyes were surgically dissected to separate the different eye structures. The ALA from various structures/tissues was extracted by soaking them in acetonitrile: water solution (80:20, v/v) for 12h under constant stirring. The samples were then filtered, and the concentration of ALA determined by a validated HPLC method.

Results: ALA was detected in all ocular tissues. The higher content of ALA found in the inserts was due to its longer contact time than the solution, and it increased bioadhesibility allowed greater biodistribution of ALA in the ocular tissues. Up to 1.5 % of ALA in the inserts reached the neuroretina, the target tissue for the treatment of retinopathies.

Conclusions: The data show that in ex vivo, ALA can diffuse from the cornea and the sclera, reaching the posterior segment of the eye, and particularly the neuroretina. This data proves the way to carry out in vivo studies to assess the potential of topically administered ALA in protecting the eye from retinopathies.

References

Alambiaga‐Caravaca AM, et al. Biodistribution of progesterone in the eye after topical ocular administration via drops or inserts. Int Jour of Pharma. 2023 Jan;630:122453.
Long‐term results of unilateral or bilateral injection of lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy
Authors: Biousse Valérie , Yu‐Wai‐Man Patrick , Newman Nancy , Subramanian Prem , Moster Mark , Wang An‐Guor , Donahue Sean , Leroy Bart , Carelli Valerio , Vignal‐Clermont Catherine , Sadun Alfredo , Sergott Robert , Fernández Gema Rebolleda , Chwalisz Bart , Banik Rudrani , Taiel Magali , Sahel José‐Alain
Published: January 2025

Aims/Purpose: To evaluate the efficacy and safety of intravitreal lenadogene nolparvovec gene therapy (LNGT) in patients with Leber hereditary optic neuropathy due to the m.11778G > A MT‐ND4 mutation for up to 5 years after administration.

Methods: REFLECT is a randomized, double‐masked, placebo‐controlled phase 3 study. The first‐affected eye received LNGT; the other eye was randomly injected with LNGT or placebo. RESTORE is the 5‐year follow‐up study of the two phase 3 studies RESCUE and REVERSE, in which patients received an injection of LNGT in one eye and a sham injection in the other eye. REFLECT interim data at 4 years after LNGT and RESTORE final data at 5 years are presented.

Results: In REFLECT, 48 patients were treated bilaterally and 50 unilaterally. The mean (standard deviation [SD ]) improvement in best‐corrected visual acuity (BCVA) from nadir to 4 years was ‐0.40 (0.32) (+20 ETDRS letters) and ‐0.34 (0.31) (+17 letters) LogMAR in the first and second‐affected eyes of bilaterally treated patients, and ‐0.38 (0.41) (+19 letters) and ‐0.27 (0.32) (+14 letters) LogMAR in the first and second‐affected eyes of unilaterally treated patients. Better BCVA improvement and higher responder rates were observed in patients treated bilaterally. In RESTORE, 62 unilaterally treated patients completed the study. At 5 years, mean (SD) change in BCVA from nadir was ‐0.44 (0.46) LogMAR (+22 ETDRS letters) for LNGT‐treated eyes and ‐0.39 (0.36) LogMAR (+20 ETDRS letters) for sham‐treated eyes. Overall, LNGT safety was favorable in REFLECT and RESTORE.

Conclusions: The persistence of the LNGT effect and the favorable safety profile were confirmed 4 years after a unilateral or bilateral injection in REFLECT and 5 years after a unilateral injection in RESTORE. Bilateral LNGT provided additional benefit compared to unilateral LNGT.