bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objective measurement of accommodation in patients with an accommodating intraocular lens compared to phakic, presbyopic, and pseudophakic eyes
Authors: Eppig Timo , Seer Manuel , Müller Violetta , Schütz Saskia , Rombach Michiel , van Lawick Willem 
Published: January 2025

Aims/Purpose: The restoration of accommodation after cataract surgery remains to be one of the biggest challenges in ophthalmology. Numerous concepts for restoration of accommodation have failed due to a lack of objective accommodation measurement. The purpose of this study was to demonstrate the dynamic pseudophakic accommodation in patients with an accommodative AIOL by means of an objective accommodation measurement and to compare the data with a young phakic, a presbyopic and a monofocal pseudophakic person.Methods: We included 3 patients in the study who had a Lumina AIOL implanted in both eyes. All patients had completed at least the 6 month follow‐up. In addition, we included both eyes of 3 comparative persons with different status of the lens (phakic, presbyopic and pseudophakic). We used a binocular open‐field videorefractor (PowerRef 3, Plusoptix GmbH, Germany) to measure the change of refraction, pupil diameter and ocular convergence while patients were asked to focus on an ETDRS chart. The ETDRS chart was then continuously moved from 6m distance to 33 cm distance while the patients were asked to focus on a single letter. The resulting curves were then compared to demonstrate the objective change in refraction.Results: The data exhibit a continuous change of binocular refraction which follows the pupil constriction and decrease of pupil distance (convergence) in the young phakic person and the AIOL patients. The maximum accommodative change was up to 2.5 D in the AIOL patients and up to 3 D in the young phakic person for a stimulus distance of 33 cm. The presbyopic patient and the monofocal pseudophakic patient showed pupil constriction and convergence but the accommodative range was less pronounced with a maximum change of 1 D.Conclusions: The PowerRef 3 allows for an objective proof of pseudophakic accommodation in patients with an AIOL. AIOL eyes show defined change of refractive power that can be maintained constant for the time of fixation to a near target compared to presbyopic and monofocal pseudophakic eyes that show only little modulation, which can be attributed to pseudo‐accommodative effects.
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‐analysisMethods: 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.
Efficacy of orthokeratology on peripheral refraction in youth: A comprehensive meta‐analysis
Authors: Queirós António , Silva‐Pinheiro Inês , Fernandes Paulo 
Published: January 2025

Aims/Purpose: This study aims to determine the impact of orthokeratology lenses on relative peripheral defocus (RPD) in children and adolescents through a systematic review and meta‐analysis.Methods: A thorough literature search was conducted using PubMed and Web‐of‐Science databases, focusing on randomized controlled trials (RCTs) and cohort studies investigating the effects of orthokeratology on peripheral refraction. The search employed the keywords "peripheral refraction" AND "orthokeratology." The inclusion criteria required studies to report spherical equivalent (M) peripheral refraction at 25° and/or 30°, including standard deviation or standard error of the mean, and present data graphically or in tables for horizontal meridian measurements before and after orthokeratology treatment. Relative peripheral refraction (RPR) was computed. From an initial pool of 133 studies, 124 were excluded for various reasons, resulting in a final sample of 9 studies. Four studies included data up to 12 months, while five provided data for less than three months, allowing separate analyses before pooling for an overall effect.Results: The 9 studies included 3 RCTs and 6 cohort studies with 239 participants aged 6 to 30 years. The pre‐treatment refractive error was M = ‐2.48 ± 0.29D, with follow‐up periods ranging from 14 days to 1 year. All studies indicated a myopic shift at 30° Nasal (‐2.13 ± 1.05 D) and 30° Temporal (‐2.40 ± 0.47 D), averaging ‐2.27 ± 0.83D. The meta‐analysis yielded an overall myopic defocus effect size of M = ‐2.29 (95% CI ‐1.94 to ‐2.64, Z = 12.84, p < 0.001) using a random effects model due to observed heterogeneity (I2 = 63%; p < 0.001). Myopic blur induction was greater at 1 year (M = ‐2.64, 95% CI ‐2.42 to ‐2.85, Z = 24.52, p < 0.001; I2 = 0%; p = 0.84) compared to treatments under 3 months (M = ‐1.98, 95% CI ‐1.94 to ‐2.64, Z = 7.37, p < 0.001; I2 = 63%; p < 0.001).Conclusions: The results suggest a more consistent effect with longer treatment durations, highlighting the necessity for extended follow‐up periods to achieve a reliable effect size estimate. Orthokeratology effectively induces myopic defocus at 30° eccentricity in children and adolescents over both short and long‐term treatments.
Closed‐perfusion transretinal erg (tERG) on mouse and human retinas
Authors: Saeid Sama , Pitkänen Marja , Ilonen Emma , L'Ecuyer Zia , Niskanen Jukka , Tenhu Heikki , Vinberg Frans , Koskelainen Ari 
Published: January 2025

Aims: The isolated mouse and postmortem human retina can serve as a sensitive biosensor for preclinical drug testing. To facilitate testing with minimal amounts of potential drug molecules or nanostructures, we developed a closed‐perfusion tERG setup. The major challenge with small perfusate volumes was the healthiness and stability of the retina in prolonged experiments.Methods: We conducted ex vivo tERG experiments using WT C57BL/6J and Gnat1‐/‐ mouse, and human donor retinas (Lion's Eye Bank, Utah). The isolated mouse or punches of human retinas were embedded in a specimen holder and the retina was perfused with a constant flow (5‐6 ml/min) from photoreceptor side, circulated with a peristaltic pump. Added Penicillin‐Streptomycin to prevent bacterial growth. 50 μM BaCl2 inhibited the K+ currents in Müller glial cells, and 20 μΜ D, L‐2‐amino‐4‐phosphonobutyric acid was added to isolate the rod component. Stimulated the dark‐adapted retina with 530 nm full‐field flashes. The electrical connection through the perfusate from the peristaltic pump to the specimen holder was cut off with burettes that also attenuated the pulsation from the pump. The stimulus and recording devices were remotely controlled by an automatic setup implemented with LabVIEW software.Results: The minimum perfusate needed in our closed perfusate circulation was 50 ml. Pen‐Strep was indispensable for long recordings. With mice, rod responses were stable for more than 24 hours and rod and cone bipolar cell responses for up to 12 hours. Rod responses from human donor tissue were stable up to 12 hours. We used our setup to test the zwitterionic polymer poly (sulfobetaine methacrylate), serving as a promising material for thermoresponsive nanostructures, for possible harmful effects on mouse rod and bipolar cell functioning. No effects on rod and bipolar cell responses were observed.Conclusions: Our method enables long, stable tERG recordings with closed perfusion on mouse and human retinas, allowing fast preclinical drug efficacy and biocompatibility testing with tiny amounts of drug molecules, materials, or nanostructures. Sulfobetaine as monomer or linear polymer did not harm rod, ON‐bipolar, or synapse functioning, suggesting the material can safely be used for constructing thermoresponsive nanostructures for drug delivery.
A new light‐adaptive lens improves contrast sensitivity when transitioning from bright to dark environments
Authors: Duarte‐Toledo Raul , Mompean Juan , Paniagua‐Diaz Alba , Lakhchaf Nacer , Kobia‐Acquah Emmanuel , Artal Pablo , Barrau Coralie 
Published: January 2025

Aims/Purpose: Light‐adaptive lenses, known as photochromic, adjust dynamically light intake. We recently evaluated the effect of a new ultra‐responsive light‐adaptive lens on contrast sensitivity recovery during fade back compared to the older photochromic generation, showing that faster fadeback speed improves contrast sensitivity. However, data was lacking in varying light, specifically when moving from bright to dark environments, and in comparison to a static clear lens. This study assessed dynamic contrast sensitivity changes with the new light‐adaptive lens after exposure to a transient bright light, compared to the older photochromic lens and to a static clear lens.Methods: Ten healthy subjects (28.7 ± 3.4 years, spherical equivalent ‐1.8 ± 1.8 D, astigmatism < 1D) were trained to control contrast of a sinusoidal grating (24 cycles/degree) at 3 m. Three lenses were used in a double‐blind cross‐over design; a clear lens, a photochromic TO2, and a new light‐adaptive TO1, twice as fast as TO2 in returning to clear state. Subjects were exposed to a bright light (8000 lux) for 30 seconds, then transitioned to darkness where contrast sensitivity was measured dynamically for 100 seconds. Recovery times for first contrast perception and 90% contrast sensitivity were recorded for each lens, tested three times. MANOVA with Tukey tests were performed.Results: TO1 recovered 90% contrast sensitivity 35% faster than clear lens (p < 0.01) and 23% faster than TO2 (p < 0.01). Initial contrast perception recovery was 55% faster with TO1 compared to clear lens (p < 0.001).Conclusions: The new light‐adaptive lens TO1 significantly improves visual performance in dynamic light conditions compared to the older photochromic lens TO2 and the static clear lens. This performance enhancement reduces light stress and improves visual function under normal viewing conditions.
Retinal vessel flicker light responsitiviness and its relation to analysis protocols, static and metabolic data in healthy subjects
Authors: Artemiev Dmitri , Todorova Margarita 
Published: January 2025

Aims/Purpose: To assess agreement between different analysis protocols for determination of retinal vessel dilation response to flicker light (FL) and its relation to static‐ and metabolic parameters of retinal vessels in healthy subjects.Methods: 24 right eyes of 24 healthy controls (mean age: 35.87 ± SD 14.20 years), who underwent dynamic‐ and static retinal diameter‐ and oxygen saturation measurements on Retinal Vessel Analyser were included (RVA, Imedos, Jena, Germany). Using repeated video analyses, responses to FL were measured within the superior‐temporal (ST) area. Taking the length and the location into account, the FL data were evaluated in 3 groups: length < 1 optic disc (OD) (group 1); length > 1OD: close to the OD (group 2) and within the VesselMap area (group 3).For comparability, the static‐ (CRA, CRV, AVR) and oxygen saturation parameters (A‐V SO2, V‐SO2, A‐V SO2) were calculated in the ST peripapillary area using the VesselMap tool of RVA and were evaluated in relation to the corresponding dynamic ones (group 3).Results: In all groups, vascular FL response of arteries was less pronounced compared to venules (p = 0.023). Event thought, FL responses (mean ± SD: FL‐A; FL‐V, %) in group 1 to be more pronounced (mean 3.36 ± 2.31; 4.42 ± 1.69) compared to those in groups 2 (mean: 2.97 ± 2.40; 4.08 ± 1.55) and 3 (2.84 ± 2.29; 4.21 ± 2.03) they did not reach statistically significant values (p > 0.44).The mean flicker response of venules showed negative correlations to the corresponding static‐ and metabolic parameters: CRV (r = ‐0.489; p = 0.015) and V‐SO2 (r = ‐0.375; p = 0.001).Conclusions: Our study confirms, that flicker light response, even showing slight difference about its length and location, allows agreeable measurements. However, even in healthy subjects, the effect of the static‐ and metabolic retinal vessel measurements on retinal venular flicker response should be taken in consideration.
Influence of lighting conditions on visual acuity with two intraocular lens designs
Authors: Haddi Inas Baoud Ould , Cervantes Dayan Flores , Ramírez Emilio Dorronzoro , Sánchez Vanesa Blázquez , Arias Cristina Bonnin 
Published: January 2025

Purpose: To compare the visual outcomes under different lighting conditions of two intraocular lens designs (Tecnis® Eyhance™ and PhysiOL® IsoPure 123™).Methods: This was an observational, prospective, cross‐sectional study conducted in accordance with the principles of the Helsinki Declaration. All surgeries were performed by the same experienced surgeon (E.D.R) at Hospital Universitario Sanitas La Moraleja in Madrid. The sample included 40 patients who underwent cataract surgery or lens extraction, with bilateral implantation of one of the three intraocular lenses (IOLs) under study: 20 patients with Eyhance™ IOL and 20 patients with IsoPure 123™ IOL. Patients were evaluated 30 days after surgery. During this visit, binocular visual acuity (VA) was assessed under photopic ( ≥ 85 cd/m2) and mesopic ( ≤ 5 cd/m2) conditions for three distances: distance (4 meters), intermediate (66 cm), and near (40 cm) using a logMAR scale with the ETDRS test. A significance level of p < 0.05 was considered statistically significant.Results: The analysis of photopic VA did not reveal statistically significant differences for distance vision; the values were (‐0.10 ± 0.08) and (‐0.06 ± 0.07) for Eyhance™, IsoPure 123™ respectively. For intermediate distance, the values were (0.10 ± 0.06) and (0.09 ± 0.08) for Eyhance™ and IsoPure 123™, respectively. Regarding near vision under photopic conditions, the values were (0.07 ± 0.07), (0.07 ± 0.06) for Eyhance™, IsoPure 123™ respectively. In terms of mesopic conditions, no statistically significant differences were found for distance vision, with values of (0.06 ± 0.09) and (0.07 ± 0.08) for Eyhance™ and IsoPure 123™, respectively. For intermediate distance under mesopic conditions, no significant differences were observed, with values of (0.38 ± 0.10) and (0.43 ± 0.11) for Eyhance™ and IsoPure 123™,respectively. For near vision under mesopic conditions, the values were (0.38 ± 0.11) and (0.39 ± 0.11) for Eyhance™ and IsoPure 123™, respectively.Conclusions: Both Eyhance™ and IsoPure 123™ intraocular lens designs provide similar VA for all distances under both photopic and mesopic lighting conditions. Therefore, both lenses are an excellent option for distance and intermediate vision.
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.
Ocular post‐mortem analyses with histopathological and molecular assessments in leber hereditary optic neuropathy following AAV2 gene therapy
Authors: Carelli Valerio , Newman Nancy , Caporali Leonardo , Ross‐Cisneros Fred , Boschetti Elisa , Biousse Valérie , DuBois Lindreth , Liu Henry , Ancian Philippe , Taiel Magali , Sadun Alfredo 
Published: January 2025

Aims/Purpose: To perform post‐mortem ocular analyses in two patients with Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A MT‐ND4 mutation who received lenadogene nolparvovec (AAV2‐ND4) gene therapy.Methods: Two patients with MT‐ND4 LHON received an intravitreal injection of lenadogene nolparvovec in one eye and a sham injection in the other during the RESCUE study. Post‐mortem histopathological and molecular (ddPCR) analyses were performed on laser‐captured retinal and optic nerve samples.Results: Within 2 months of gene therapy, both participants developed intraocular inflammation in the treated eye; both events resolved within months. Patient 1 died of acute alcohol toxicity and patient 2 of cardiac arrest. Patient 1 had severe optic atrophy and loss of retinal ganglion cells (RGCs), while patient 2 was a much milder case of LHON, with consistent preservation of RGCs and optic nerve axons, being only the temporal fibers lost. In patient 1, an angiocentric lymphocytic chronic inflammation was noted in the optic nerve head and temporal retina. No persistent inflammation was seen in patient 2. AAV2‐ND4 distribution in the treated eye was asymmetric in both patients, more prevalent in temporal RGCs. A much lower level of AAV2‐ND4 was detected in the retina of the untreated eye in both cases. Finally, mtDNA copy number was upregulated in both eyes of patient 2, possibly reflecting better preservation of RGCs and axons.Conclusions: This is the first postmortem study of human eyes injected unilaterally with AAV2‐based gene therapy. Gene transfection of RGCs was successful in both eyes despite unilateral administration. AAV2‐ND4 transfer seems to be facilitated by axonal preservation and may be confirmed, and further characterized by analysis of the eyes, nerves, optic chiasm and optic tracts from patient 2.
Exploratory and comprehensive description of an italian cohort of patients affected by leber hereditary optic neuropathy carrying the pathogenic variants m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1
Authors: Romagnoli Martina , Carbonelli Michele , Amore Giulia , Fiorini Claudio , Zenesini Corrado , D'Agati Pietro , Tropeano Concetta Valentina , Cascavilla Maria Lucia , Barboni Piero , Caporali Leonardo , Carelli Valerio , La Morgia Chiara 
Published: January 2025

Aims/Purpose: This is an observational study to track the disease course of patients affected by Leber Hereditary Optic Neuropathy (LHON), regularly attending the neurophthalmological clinic of the IRCCS ISNB (Bologna).Methods: To satisfy inclusion criteria, subjects needed a confirmed genetic diagnosis for 2 of the 3 primary LHON mutations (m.11778G > A/MT‐ND4; m.3460G > A/MT‐ND1). There was no restriction on age, and patients could have received idebenone or any other treatment.Results: 397 subjects from 137 families were enrolled, 196 symptomatic (49%; male: 79%), 201 asymptomatic (51%; male: 40%). Of these, 66 (17%; symptomatic: 55%) carried the m.3460G > A/MT‐ND1 variant, 331 (83%; symptomatic: 48%) the m.11778G > A/MT‐ND4, with a ratio of affected male: female of 2: 1 for the first, and 4: 1 for the m.11778G > A/MT‐ND4 carriers.Of the 196 symptomatic patients, 37 had LHON childhood onset and 3 had unilateral LHON.106 patients (54%) were treated with idebenone and/or lenadogene nolparvovec.For both mutations the distribution of age at onset is multimodal, and different between males and females. LHON females showed later age at onset (post‐menopausal peak) in the m.11778G > A/MT‐ND4 subgroup, while the m.3460G > A/MT‐ND1 density plot showed a peak in the fertile young age.Then, visual acuities of both eyes were collected from 1252 outpatient visits. The resulted best‐fitted LOWESS curve depicting the evolution of BCVA over time did not show a difference between m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1 symptomatic patients.Conclusions: We highlight the highest penetrance in females of the m.3460G > A/MT‐ND1 variant, for which females had an age of onset more similar to males at difference with the m.11778G > A/MT‐ND4 for which females had a delayed peak of onset, after menopause. Clinically, the two variants seem to behave similarly. This “real world” study is a precious tool to define genotype/phenotype relationships and highlight the most appropriate subpopulations for clinical trials.