bluuebunny/crossref_metadata_2025 huggingface dataset:
Choroidal quantitative features in high myopia: Characteristics and association with neovascular and atrophic complications
Authors: Arrigo Alessandro , Aragona Emanuela , Parodi Maurizio B. , Bandello Francesco
Published: January 2024

Aims/Purpose: To investigate the quantitative choroidal features associated with the presence of MNV or atrophy in high myopia.

Methods: The study was designed as a retrospective, case series with 2‐year follow‐up. Optical coherence tomography (OCT) images were used to measure choroidal thickness (CT) and to assess the presence and subtype of dome‐shaped macula (DSM). In DSM eyes we also calculated the presence and type of choroidal deepening (CD). The eyes were categorized as Subgroup 1 (high myopia without complications), Subgroup 2 (high myopia complicated by macular neovascularization (MNV)) and Subgroup 3 (high myopia complicated by macular or posterior pole atrophy). The main outcome measures were the detection of significant CT cutoffs associated with the three subgroups of eyes and the clinical impact of DSM and CD subtypes.

Results: Our study cohort (190 eyes (190 patients) affected by high myopia) was categorized as Subgroup 1 (66 eyes), Subgroup 2 (72 eyes) and Subgroup 3 (52 eyes). The mean axial length was 31.74 ± 2.01 mm (−13.0D ± 2.0D). Baseline CT values allowed to separate the subgroups with myopic‐related complications (AUC 0.85; standard error 0.04; confidence interval 0.78–0.92; p < 0.05). DSM was distributed as follows: Subgroup 1 (39%), Subgroup 2 (44%) and Subgroup 3 (29%). In Subgroup 1, vertical DSM was the most frequent (54%), with CD absence characterizing the 46% of cases. Round DSM was the most represented subtype in Subgroup 2 (49%), with 55% of sub‐dome CD subtypes; in these cases, MNV resulted always localized in the fovea. Subgroup 3 equally showed horizontal or vertical DSM (53% and 47%, respectively), with 80% of cases showing peri‐dome CD.

Conclusions: Choroidal quantitative assessment can categorize three high myopia subgroups. MNV subgroup is characterized by intermediate choroidal thinning and higher prevalence of round DSM with sub‐dome CD. DSM subtypes may have a role in predicting myopic complications and MNV localization.
Greater reduction in hyperreflective foci with faricimab compared to aflibercept in patients with diabetic macular oedema
Authors: von Schulthess Esther , Maunz Andreas , Chakravarthy Usha , Holekamp Nancy , Singh Rishi , Patel Katie , Bachmeier Isabel , Yu Siqing , Gibson Kara , Willis Jeffrey , Glittenberg Carl , Fauser Sascha
Published: January 2024

Aims/Purpose: In diabetic macular oedema (DME), hyperreflective foci (HRF) may be a biomarker for disease severity and progression. This post hoc analysis aimed to test if faricimab, a dual‐action therapeutic inhibiting both vascular endothelial growth factor (VEGF)‐A and angiopoietin‐2 (Ang‐2), yields improved resolution of retinal HRF in DME compared to aflibercept.

Methods: Phase 3 YOSEMITE/RHINE (NCT03622580/NCT03622593) spectral‐domain optical coherence tomography (SD‐OCT) volumes from 1527 DME patients were automatically segmented using a deep learning‐based HRF model trained with manually‐annotated B‐scans from phase 2 BOULEVARD (NCT02699450). Bright objects ≤50 μm in diameter were classified as retinal HRF. HRF volumes were assessed within the 1‐ and 3‐mm diameter Early Treatment Diabetic Retinopathy Study (ETDRS) rings, separated into inner and outer retina. Treatment groups were compared using a Mixed Model for Repeated Measures.

Results: In the inner retina at 1 mm diameter, adjusted mean HRF volumes reduced more markedly from baseline to week 48 for faricimab every 8 weeks (Q8W; −118.29 pL) and faricimab treat&extend (T&E; −130.05 pL) than aflibercept Q8W (−58.67 pL; p = 0.0006 and p < 0.0001, for comparison of each faricimab arm vs aflibercept, averaged across all visits, respectively). In the inner retina at 3‐mm diameter, reductions from baseline to week 48 were − 406.76 pL (faricimab Q8W), −533.01 pL (faricimab T&E) and − 397.67 pL (aflibercept Q8W; p = 0.0142 and p = 0.0034, for comparison to aflibercept averaged across all visits, respectively). Similar, statistically significant results were obtained for the outer retina.

Conclusions: Significantly greater retinal HRF volume reductions were observed with faricimab compared to aflibercept. Our findings of better resolution of the pathological manifestations of DME with faricimab support the therapeutic potential of dual Ang‐2/VEGF‐A inhibition.
Influence of different fluid types on the development of fibrosis and atrophy in patients with nAMD
Authors: Weigert Guenther , Deak Gabor , Michl Martin , Reiter Gregor , Boryshchuk Daniela , Frommlet Florian , Sacu Stefan , Gerendas Bianca , Schmidt‐Erfurth Ursula
Published: January 2024

Aims/Purpose: Subretinal fibrosis and macular atrophy often associated with vision loss are regularly seen in patients with long‐term neovascular age‐related macular degeneration (nAMD). Apart from the influence of fluid distribution on visual acuity its effect on the development of fibrotic and atrophic alterations could give important insight for better understanding the pathogenesis of end‐stages and might influence treatment decisions. Hence, we investigated the influence of fluid distribution on fibrosis and atrophy using AI‐supported fluid quantification.

Methods: Sub‐ and intra‐retinal fluid (SRF and IRF) and pigment epithelium detachment (PED) were quantified on optical coherence tomography (OCT) volumetric scans using the Vienna Fluid Monitor, Version 2 (RetInSight, Vienna, Austria) at all timepoints until the appearance of atrophy or fibrosis evaluated by the Vienna Reading Center (VRC). In total, 569 treatment naïve nAMD patients were included in the analysis. A disease activity‐dependent treat&extend‐based anti‐VEGF treatment regimen was used. A logistic regression model for fibrosis/atrophy was created.

Results: Fluid distribution and dynamics showed a significant influence on the development of fibrosis/atrophy. If the standard deviation of IRF increased by 1 unit (100 nL; p = 0.006) odds to develop fibrosis increased by 4.4. Hence, patients with little IRF at baseline that increased rapidly during the following visits were likely to develop fibrosis. However, atrophy did not seem to be influenced by IRF significantly, whereas PED and SRF showed a significant influence on the development of MA.

Conclusions: Automated assessment of fluid type and volume using artificial intelligence allows an objective and precise assessment of the activity of IRF, SRF and PED and therefore its influence on the development of fibrosis or atrophy. AI‐based fluid monitoring offers guidance to improve anatomical and visual outcomes in the long‐term management of nAMD in clinical routine.
The effect of zinc on the stiffness of chicken lenses
Authors: Gorla Shilpa , Choh Vivian
Published: January 2024

Aims/Purpose: Aquaporins are specialized water channels. A volume change through permeable aquaporins may be necessary for the lens' ability to change shape during accommodation1. This study aimed to determine the effects of zinc2, an agonist that increases aquaporin 0 (AQP0) permeability in oocytes, on the biomechanics of chicken lenses.

Methods: White Leghorn chickens (Gallus gallus domesticus, N = 6) were sacrificed at 14 days of age. Both eyes were enucleated and lenses were dissected in Tyrode's solution (TS). One lens from each bird was treated with zinc chloride (80 μg/mL in TS for 15 min, at room temperature; RT), while the other lens (control lens) was incubated in TS (15 min, RT). Lenses were compressed (CellScale Micro Tester G2) to test their biomechanical integrity. For each lens, force‐compression data were generated by the MicroTester G2 software (ver. 1.0.0.1) and fit to a three‐parameter exponential curve with the equation y = y0 + aebx; the unitless b‐coefficient of the exponential equation was used to assess stiffness as it describes how rapidly the force increases as the compression distance increases. B‐coefficients from each curve were extracted and the effects of zinc treated versus control lenses were analysed using a paired t‐test.

Results: The b‐coefficient value for zinc‐treated lenses averaged to 4.2 ± 0.8 while the mean value for control lenses was significantly (p = 0.01) lower at 3.2 ± 0.5, indicating that zinc‐treated lenses were stiffer.

Conclusions: The compression data show a zinc‐associated increase in lens stiffness. AQP0 typically plays a role in allowing water to enter, but not exit, the lens, therefore zinc may have led to an increase in water content, resulting in stiffer lenses. However, water permeability was not measured in this study, therefore the AQP0‐associated mechanism of lens stiffening cannot be confirmed. Further study is needed to determine zinc's action on the biomechanics of the lens.

References

1. Gerometta R, Candia OA. A decrease in the permeability of aquaporin zero as a possible cause for presbyopia. Medical Hypotheses. 2016 Jan 1;86:132–4.

2. Németh‐Cahalan KL, Kalman K, Froger A, Hall JE. Zinc modulation of water permeability reveals that aquaporin 0 functions as a cooperative tetramer. The Journal of general physiology. 2007 Nov;130(5):457–64.
Investigation of changes in socio‐demographic and clinical factors related to quality of life in patients undergoing phacoemulsification
Authors: Kontou Evgenia , Smoustopoulos Georgios , Bontzos George , Papadopoulos Alexandros , Sgouros Panagiotis , Xirou Tina
Published: January 2024

Aims/Purpose: This study investigates and evaluates the socio‐demographic and clinical factors related to health‐related quality of life (HRQoL) for patients who underwent cataract surgery, using phacoemulsification.

Methods: A prospective cohort study, was carried out at the General Hospital ‘Korgialenio‐ Benakio’, from December 2020 to February 2021. In total, 82 patients were recruited, 48 men and 34 women and their age ranged between 40 and 89 years old. Demographic data and full medical history were recorded for every patient. In addition, their everyday habits and way of life were reported. Best‐corrected visual acuity was measured before and after the operation. All operations were performed by the same surgeon without any reported complications during or after the operation. All patients filled out three HRQoL questionnaires (EQ‐5D, SF‐36 and VFQ‐25), before the operation and 1 month after surgery. The results pre‐ and post‐operatively were collected and the important socio‐demographic and clinical factors were evaluated using the relevant HRQoL questionnaire utility scale.

Results: Visual acuity improved in all patients following the operation. There was a statistically significant improvement in the general health of the sample (p < 0.01), recorded across all questionnaires (EQ‐5D, SF‐36 and VFQ‐25). A similar improvement was revealed in responses related to mental well‐being (p < 0.01). Factors affecting HRQoL scales of cataract surgery candidates were found to be age, marital status, educational level, metabolic disease, cardiovascular disease, mobility issues, mental well‐being and almost all factors related to ophthalmic disorders.

Conclusions: The improved visual acuity achieved by cataract surgery using phacoemulsification leads to significant improvement in post‐operative HRQoL of patients. The findings regarding the important factors related to these HRQoL improvements should be evaluated by physicians before considering any surgical intervention.
Comparison of quality of life with two trifocal intraocular lenses under different lighting conditions
Authors: Haddi Inas Baoud Ould , Cervantes Dayan Flores , Ramírez Emilio Dorronzoro , Sánchez Vanesa Blázquez , Arias Cristina Bonnin
Published: January 2024

Aims/Purpose: To evaluate the effect of two types of trifocal intraocular lenses on the visual quality of patients undergoing cataract surgery by assessing contrast sensitivity, halo perception and subjective visual satisfaction under photopic and mesopic lighting conditions.

Methods: Observational, prospective, cross‐sectional study. The study was conducted at the Hospital Universitario Sanitas la Moraleja in Madrid. The study followed the principles of the Declaration of Helsinki. The sample included 16 cataract or lensectomy patients with bilateral implantation of one of the two intraocular lenses (IOL) under study: 20 eyes implanted with FineVision and 12 eyes implanted with PanOptix. After 30 days after surgery, contrast sensitivity was measured with the CSV‐1000 test (2.5 metres) for four spatial frequencies (3, 6, 12 and 18 c/g), halo perception was assessed with the Halo.V.1 software and finally quality of life was assessed with the VF‐14 questionnaire. A p‐value < 0.05 was considered a criterion for statistical significance.

Results: Analysis of contrast sensitivity under photopic conditions showed significant differences greater for the FineVision lens of 0.15 log units at 3 c/g and 12 c/g frequencies between the two lenses under photopic illumination conditions (p‐value 0.034). However, there were no statistically significant differences in mesopic illumination conditions. Furthermore, there was no statistically significant difference when purchasing the perception of halos, with a p‐value (0.149). On the other hand, patients' subjective perception of quality of life scored worse in night vision (p‐value 0.023) and near vision (p‐value 0.046) when comparing the PanOptix lens and the FineVision.

Conclusions: The FineVision IOL lens provides better contrast sensitivity in photopic illumination conditions than the PanOptix. However, in mesopic conditions, both IOL designs provide similar contrast sensitivity values for the far distance. On the other hand, although the lenses did not show statistically significant differences in halo perception, the FineVision shows better vision satisfaction results during night driving than the PanOptix.
Changes in visual acuity and quality of life following lens surgery in Alport syndrome
Authors: Golahmadi Aida Kafai , Clarke Kirsty , Bloch Edward , Shalchi Zaid , Shunmugam Manoharan , Storey Helen , Flinter Frances , Mohamed Moin , Mahroo Omar
Published: January 2024

Aims/Purpose: Alport syndrome can have ocular features, including anterior lenticonus, which affects vision and quality of life. We explored visual acuities and vision‐related quality of life, as quantified using the National Eye Institute 25 item Visual Functioning Questionnaire (VFQ‐25), in a cohort of patients before and after lens exchange surgery.

Methods: Patients with genetically confirmed Alport syndrome were recruited for an ocular phenotyping study, and completed the NEI‐VFQ25 (a validated visual function questionnaire, yielding a total score out of 100). Patients with lenticonus were offered lens exchange surgery. Best recorded visual acuities before and after surgery were collated, and converted to logMAR for analysis. Changes in quality of life were ascertained by comparing scores obtained before, and some time after, surgery.

Results: Five patients (10 eyes) underwent lens exchange surgery for lenticonus. All were male; mean (SD) age at first eye surgery was 43 (8.5) years. For right eyes, mean (SD) pre‐ and post‐operative logMAR visual acuities were 0.31 (0.28) and 0.05 (0.10), respectively. For left eyes, these were 0.23 (0.11) and 0.02 (0.10), respectively. Median pre‐op acuities were 0.30 and 0.18 for right and left eyes, respectively; median post‐operative acuities were 0.03 and 0.00, respectively. Median improvements were 0.2 and 0.18 for right and left eyes, respectively. Taking all eyes together, the improvement seen following surgery was significant (p = 0.001). Four of the five patients completed the VFQ25 before and after surgery. Initial and final mean (SD) scores were 68.5 (13.7) and 94.1 (4.9), respectively, with a significant difference seen (p < 0.05).

Conclusions: Objective improvement in best‐recorded visual acuity was seen in this cohort of patients. Anterior lenticonus was shown to have an adverse effect of vision‐specific quality of life, with improvement demonstrated following lens exchange surgery.
Tolerability of silica microparticle gels as drug delivery vehicles
Authors: Poluianova Aleksandra , Robciuc Alexandra , Moilanen Jukka , Kaarniranta Kai , Leino Lasse , Pollari Ville , Dargelas Frederic , Reay Marcus
Published: January 2024

Aims/Purpose: Over the past decades, polymeric particles have become widespread in the field of drug delivery. Silica microparticles (SiMPs) are biodegradable—silicic acid being the main degradation product—and can release medication sustainably for a long period of time. Our aim was to determine the effects of soluble silicic acid on in vitro models of human epithelial cells.

Methods: HCE‐2 and ARPE‐19 cells were exposed to serial dilutions of silicic acid produced by dissolving silica hydrogel in PBS, and cell viability was assessed after 24, 48 and 72 h of incubation. Cell viability data were provided by AlamarBlue assay, while membrane integrity was analysed through LDH release. For more information on the silicic acid impact on cellular stress, we assayed biochemical markers, such as IL‐6, IL‐8, MCP‐1, Caspase‐3 and Hsp‐70, using specific ELISAs.

Results: AlamarBlue assay did not show any statistical differences in survival rate between the control group and maximum 30 μg/mL silicic acid in all timepoints in ARPE‐19 cells (24 h 95.42 ± 4.81%, 48 h 87.55 ± 6.48% and 72 h 97.64 ± 6.38%) and HCE‐2 cells (24 h 97.38 ± 5.97%, 48 h 100.81 ± 8.32% and 72 h 101.73 ± 2.62%). Additionally, we did not detect any toxic changes in LDH release test in ARPE‐19 cells in 24, 48 and 72 h time points (30 μg/mL silicic acid: 24 h 9.0 ± 11.5%, 48 h 10.4 ± 13.4% and 72 h 13.8 ± 16.6%). The LDH release data in treated (max. 30 μg/mL) HCE‐2 cells were comparable to control cells. Assessed inflammatory markers mostly were similar as well when comparing control and treatment groups, although IL‐6, MCP‐1, Caspase‐3 and Hsp‐70 showed increased values with time.

Conclusions: Our results do not show major cytotoxicity of silicic acid on the two different epithelial cell lines, nor did not induce stress or inflammatory markers. Therefore, these findings support the use of our novel SiMPs as drug delivery vehicles in the treatment of ophthalmic diseases.
Taurine influences the phagocytic function of retinal pigment epithelium cells in healthy and dystrophic animals
Authors: Vacas Ana Martínez , Valiente‐Soriano Francisco Javier , Vidal‐Sanz Manuel , Perez Maria Paz Villegas , García‐Ayuso Diego
Published: January 2024

Aims/Purpose: To investigate the influence of taurine on the phagocytic function of the retinal pigment epithelium (RPE) in normal and dystrophic rats.

Methods: Normal albino Sprague–Dawley (SD) and pigmented dystrophic Royal College of Surgeons (RCS‐p+) rats that suffer an inherited photoreceptor degeneration due to RPE phagocytosis impairment were used for the study. Taurine depletion was induced in SD rats (n = 8) by providing β‐alanine in drinking water (3%) from postnatal day 21 (P21). Taurine supplementation was administered to RCS‐p+ rats (n = 8) in drinking water (0.2 M) from P21. Untreated RCSp+ (n = 8) and SD (n = 8) rats served as control groups. Rats were processed at P81 (SD) and at P45 (RCS) and received an intravitreal injection (IV) of. 1.5 μL of Fluorogold (FG, 3%) diluted in saline 24 h before processing. The RPE was dissected, flat‐mounted and immunodetected with anti‐S opsin antibodies to label the RPE phagosomes which were quantified using ImageJ and size criteria.

Results: The mean numbers (± SD) of phagosomes per RPE whole mount was 414 ± 118 in control SD rats, 1034 ± 528 in taurine‐depleted SD rats 88 ± 12 in untreated RCS and 119 ± 9 in taurine‐treated RCS rats. The numbers of phagosomes were significantly higher in SD rats than in RCS‐p+ rats (t‐test, p < 0.0001) documenting the impaired phagocytic function of RCS‐p+ rats. In SD rats, the number of phagosomes were significantly higher in taurine‐depleted rats evidencing that taurine depletion decreases the RPE phagocytic capacity (t‐test, p < 0.0059). Finally, in RCSp+ rats, the numbers of phagosomes were significantly higher in taurine‐treated than in non‐treated RCS rats (t‐test, p < 0.0001) indicating that taurine supplementation ameliorates the phagocytic capacity of the RPE cells in RCS‐p+ rats.

Conclusions: Taurine influences the phagocytic capacity of the RPE cells in normal rats and in dystrophic RCS‐p+ rats.
High‐intensity physical activity seems to be associated to a higher basal parasympathetic activity and to a reduced OSDI score in young adults
Authors: Blanco María Serramito , Torres Carlos Carpena , Carracedo Gonzalo , Aracil‐Marco Adolfo
Published: January 2024

Aims/Purpose: To identify if the habitual practice of physical activity is associated to the basal parasympathetic activity and to dry eye disease‐related symptoms.

Methods: Eleven adults (82% women; age: 30.7 ± 4.9 years; BMI 22.2 ± 1.9 kg m−2) responded the Ocular Surface Disease Index (OSDI), the Dry‐Eye 5 (DEQ5) and the International Physical Activity (IPAQ) questionnaires. Subsequently: a) the inferior tear meniscus height (ITMH) and the automated non‐invasive break‐up time (NIBUT) of both eyes; b) the heart rate variability (Polar H10 chest band; Kubios HRV software) and, simultaneously, the Schirmer test; and, c) the tear film break‐up time (BUT) were measured. Correlational analyses were performed among the measured variables.

Results: The total weekly physical activity was of 3420 ± 3302 metabolic equivalents (MET) min−1 week−1, with a weekly high‐intensity physical activity (HIPA) of 567 ± 661 MET min−1 week−1. The OSDI score was 14.1 ± 8.3, the DEQ5 score was 7.2 ± 4.8, the ITMH was 229.3 ± 40.7 (OD) and 252.7 ± 51.2 (OS) μm, the NIBUT was 8.5 ± 5.7 (OD) and 8.8 ± 6.1 (OS) s, and the BUT was 9.7 ± 4.1 (OD) and 8.3 ± 3.9 (OS) s. Two surrogates of the parasympathetic activity (the PNS index, and the root‐squared mean of successive standard deviations, RMSSD) showed values of 0.762 ± 1.899 and 60.1 ± 37.8 ms, respectively. The HIPA showed a direct correlation with the parasympathetic activity surrogates (r = 0.784, p = 0.004, PNS index; r = 0.737, p = 0.009, RMSSD). Similarly, the HIPA showed an inverse correlation with the OSDI (r = −0.759, p = 0.006) and the DEQ5 (r = −587, p = 0.07). No other correlations were found, neither among the HIPA nor among the parasympathetic surrogates with the ITMH, the NIBUT, the BUT or the Schirmer test.

Conclusions: These preliminary results suggest that in young subjects HIPA seems to be associated to an increased basal parasympathetic activity and to a reduced perception of dry‐eye symptomatology.
Antioxidant insights of wild olive (acebuche) oil ophthalmic nanoemulsions against arterial hypertension
Authors: Santana‐Garrido Álvaro , Durán‐Lobato Matilde , Mate Alfonso , Martín‐Banderas Lucía , Vázquez Carmen María
Published: January 2024

Aims/Purpose: Many systemic and ocular disturbances are closely related to oxidative stress, including hypertensive eye diseases. In this context, the oral administration of wild olive oil, also known as acebuche (ACE) oil (Olea europaea var. sylvestris), proved to modulate local production of reactive oxygen species (ROS) by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase1. Here we aimed to develop an ophthalmic formulation based on ACE oil as a localized therapy against oxidative damage associated with arterial hypertension (AH).

Methods: Nanoemulsions (NEs) of ACE oil were successfully produced, characterized, and evaluated in vivo in terms of efficacy. The antioxidant properties of these NEs were tested in mice with AH induced via administration of Nω‐nitro‐L‐arginine‐methyl‐ester (L‐NAME), which underwent intravitreal or topical ophthalmic treatment with ACE oil NEs. At the end of the treatments, a histological analysis of the cornea and retina was performed together with an evaluation of the activity/expression of NADPH oxidase in these ocular tissues.

Results: Adequate ophthalmic formulations were designed to present the features for ophthalmic administration, including a nanometre size (below 200 nm), moderate negative ZP, adequate osmolality and pH, among others. Histological analysis indicated that NEs reduced hypertension‐dependent morphological alterations in the cornea and retina. Furthermore, the evaluation of the activity and expression of NADPH oxidase suggest a noticeable antioxidant effect of NEs through downregulation of NOX1, NOX2 and NOX4 isoforms and counteracting excess ROS production in the hypertensive eye.

Conclusions: Topical administration, via intravitreal or drop instillation, of an ophthalmic formulation based on ACE oil NEs might show promise against ocular pathologies related to AH. Interestingly, this therapeutical approach provided better outcomes compared to long‐term dietary administration of the oil, both in terms of cumulative dose and treatment time required.

References

1. Santana‐Garrido Á et al. Antioxidants. 2020. DOI: https://doi.org/10.3390/antiox9090885
Study of the single or combined action of three different neuroprotection strategies in an acute hypertension model in mice
Authors: Valiente‐Soriano Francisco Javier , Ortega Alejandro Gallego , Muñoz María Norte , Rios Cristobal De Los , Agudo‐Barriuso Marta , Vidal‐Sanz Manuel
Published: January 2024

Aims/Purpose: To study the neuroprotective effects of a TrkB receptor activator (DHF), a calcium channel blocker that prevents Ca2+ toxic influx (ITH12657) and/or a P2X7 receptor blocker (ITH15004) administered alone or in combination in an animal model of acute ocular hypertension (AOHT).

Methods: Pigmented adult mice (C57BL/6 strain) were separated into 9 experimental groups (n = 8 per group), 7 received intraperitoneal injections of the neuroprotective drugs alone or in combination, 1 received saline as the vehicle group and 1 was naïve. AOHT was performed by connecting the anterior chamber of the left eye to a bottle of saline at a height of 130 cm achieving an intraocular pressure of 97 mmHg for 60 min. Longitudinally in vivo analysis of the pSTR amplitude and the inner retinal thickness was measured by electroretinogram and SD‐OCT, respectively; and ex vivo analysis of the retinal ganglion cell population was identified immunohistochemically by Brn3a at 7 after AOHT in all experimental groups.

Results: The neuroprotectant treatment administered alone had a beneficial effect on the pSTR wave response amplitude (50–60% amplitude response) compared to vehicles (⁓25% amplitude response), which increased in all treatment combinations (⁓75%) except for ITH12657+ ITH15004 at 7 days after AOHT. Similar results were obtained in the inner retinal thickness, with the combined treatments producing a better retinal response after 7 days of AOHT, particularly for DHF + ITH15004 and DHF + ITH12657 + ITH15004 which showed no difference compared to control thicknesses. Regarding the RGC population, all treatments had a neuroprotective effect (⁓70% population survival at 7 days) compared to vehicles (⁓40%) which was not increased by their combination.

Conclusions: The single or combined action of three different neuroprotective strategies results in functional and morphological protection of the retina 7 days after AOHT.
Two different visual stimuli that cause axial eye shortening and choroidal thickening have no additive effect
Authors: Ingrassia Lea , Swiatczak Barbara , Schaeffel Frank
Published: January 2024

Aims/Purpose: Previous studies identified two visual stimuli that can make the human eye shorter and potentially inhibit myopia: [1] watching digitally filtered movies that kept the red channel in focus but were low pass filtered in the blue and [2] reading text with inverted contrast. We have tested whether the two mechanisms may be additive, perhaps causing even more inhibition of eye growth.

Methods: Fifteen emmetropic (average refraction: −0.6 ± 0.7 D) and fifteen myopic (average refraction: −3.7 ± 1.8 D, range −6 to −1.5D) young subjects (average age: 26 ± 4 years) read text from a large screen (65″) in a dark room at 2 m distance. Text with inverted contrast (bright letters on dark background) was digitally filtered in real time by custom‐developed software written in Visual C++ to present the red channel of the RGB colour format unfiltered while green and blue were blurred (red in focus) accordingly to the human longitudinal chromatic aberration function. Changes in axial length before and after 30 min of reading were measured using low coherence interferometry with auto positioning system (Lenstar LS‐900).

Results: Unexpectedly, in emmetropes, significant eye elongation was found after 30 min of reading text with inverted contrast, combined with the red in focus filter (+5.7 ± 15.3 μm). As previously found, unfiltered text with inverted contrast made eyes shorter (−7.9 ± 14.7 μm, p < 0.05). Strikingly, no such changes were observed in myopic eyes, neither with the red in focus filter, nor when text with inverted contrast remained unfiltered.

Conclusions: In emmetropes, the two stimuli had no additive effects but rather cancelled each other out. There may be a simple explanation: the red in focus filter made the text very blurry in the blue channel. Apparently, this removed the spatial information that is needed by the retina to detect defocus in the blue. Therefore, our finding supports the view that the emmetropic retina needs some spatial information in the blue to generate eye growth inhibiting signals—and they were lost in myopes.

References

1. Swiatczak B, Schaeffel F. (2022). Myopia: why the retina stops inhibiting eye growth. Sci Rep.

2. Swiatczak B, Schaeffel F. (2022). Transient Eye Shortening During Reading Text With Inverted Contrast: Effects of Refractive Error and Letter Size. Transl Vis Sci Technol.
Retinal vessel analysis in vascular occlusions of the eye
Authors: Schätzel Jana , Eichhorn Jakob , Stachs Oliver , Fuchsluger Thomas
Published: January 2024

Aims/Purpose: This cohort study investigates how the static and dynamic vessel parameters differ in patients with vascular occlusions and if there are any variations between the different types of vessel occlusion.

Methods: Patients with the diagnosis of branch retinal artery obstruction BRAO, central retinal artery obstruction CRAO, branch retinal vein obstruction BRVO, central retinal vein obstruction CRVO, anterior ischaemic optic neuropathy AION and any combination of these Combo were included in our study. During their inpatient stay for cardiovascular diagnostics all patients were examined via static and dynamic vessel analysis (IMEDOS Health GmbH, Jena) to obtain the arteriovenous ratio (AVR), the central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE) and the flicker light induced dilation of the retinal arteries (FLA) and veins (FLV). The vessel density was determined via OCT angiography (Heidelberg Engineering GmbH, Heidelberg).

Results: 34 patients (70% male; 30% female; mean age 69.6 ± 11.3 years) with 9 (26.5%) CRVO, 8 (23.5%) AION, 5 (14.7%) BRAO and 4 (11.8%) CRAO, BRVO and Combo each have been included. The best visual acuity (BCVA) of the diseased eye differed significantly between the groups (AION 0.41 ± 0.61, CRAO 2.40 ± 0.20, BRAO 0.16 ± 0.05, CRVO 0.81 ± 0.86, BRVO 0.18 ± 0.10, Combo 1.53 ± 0.68; p < 0.001) whereas the BCVA of the healthy eyes were comparable. The CRVE showed a significant difference between the groups CRAO – CRVO (p = 0.008), CRAO – Combo (p < 0.001) and BRAO–Combo (p = 0.026). The FLV of the diseased eye was significantly higher in patients with AION than in the CRAO group (p = 0.049). The parameters of the static vessel analysis of the healthy eyes were comparable.

Conclusions: Preliminary analysis shows significant differences of individual parameters of the retinal vessel analysis between different types of vascular occlusion. The diagnostic and research benefit for the individual patient remains to be further evaluated.
Association between chromatic sensitivity and peripapillary retinal nerve fibre layer thickness in healthy eyes
Authors: Pérez‐Carrasco M° Jesús , Carballo‐Álvarez Jesús , Puell María
Published: January 2024

Purpose: Knowledge of the retinal structure—chromatic sensitivity relationship of healthy eyes would be important for early detection of retinal neuropathies such as glaucoma. This study investigated the association between colour vision thresholds and the thicknesses of the retina in healthy young eyes.

Methods: Measurements were made in 56 healthy eyes of 56 young subjects of mean age 25 ± 2.4 years (range 20–31 years), and distance visual acuity ≤0.1 logMAR. Chromatic sensitivity was measured using the Color Assessment and Diagnosis (CAD) test. The macular thicknesses of the central fovea, parafovea, and macular ganglion cell complex (mGCC), and the thickness of the peripapillary retinal nerve fibre layer (pRNFL) were measured by spectral‐domain optical coherence tomography (SD‐OCT). Relationships between red‐green (RG) and yellow‐blue (YB) thresholds and the retinal thicknesses were examined through Spearman correlation.

Results: Significant correlations were detected between pRNFL thickness, in the inferior hemisphere, and the RG and YB‐thresholds (r = −0.30, p = 0.03 and r = −0.31, p = 0.02; respectively). Decreased pRNFL thickness correlated with worse colour thresholds. No significant correlations were found between macular thicknesses and colour thresholds.

Conclusions: Greater inferior pRNFL thickness was related to better chromatic sensitivity in healthy eyes of young subjects.
Incidence of choroidal neovascularisation in the fellow eye in neovascular age‐related macular degeneration patients and its correlation with type of drusen
Authors: Xirou Tina , Bontzos Georgios , Smoustopoulos Georgios , Georgopoulos Efstathios , Aikaterini Nikiforou , Xirou Christina Garnavou , Kabanarou Stamatina
Published: January 2024

Aims/Purpose: To study the incidence of choroidal neovascularization (CNV) in the fellow eye of patients with neovascular age‐related macular degeneration (nAMD) and its association with the presence and type of drusen.

Methods: This is a retrospective study reviewing patient records' between 2018 and 2022. Forty‐four patients with newly‐diagnosed unilateral nAMD were included. All patients have been followed up for at least 4 years. The presence and type of drusen (soft, hard, pachydrusen/PED) were documented. The risk of developing nAMD in the fellow eye was estimated depending on age, gender, type of drusen, choroidal thickness and other factors.

Results: The presence of soft drusen, pachydrusen/PED and hard drusen was documented in 46.4%, 25.3% and 18.9% of patients, respectively. The risk of developing CNV in fellow eye, overall, was 20.7%. In particular, the risk in any drusen group was significantly increased in comparison with the group without drusen (vs. 3.5%, p < 0.01 < 0.01, < 0.01). According to the multivariate Cox regression analysis, age (HR, 1.053; p = 0.03) and drusen type (p = 0.01) were the main risk factors. In comparison with the group without drusen, pachydrusen (HR = 18.46; p = 0.01) and soft drusen (HR = 2.41; p = 0.28) demonstrated an increased risk.

Conclusions: In patients with unilateral nAMD, the incidence of developing CNV in the fellow eye is increased and depends on the type of drusen. Pachydrusen/PED was the main risk factors but soft and hard drusen increase this risk as well but to a lesser degree.
Immunohistochemical characterization of pluripotency of an iPSC line derived from a patient with cone‐rod dystrophy related to a mutation in the PROM1 gene
Authors: Hernández‐Rodríguez Leticia , Puertas‐Neyra Kevin , García‐Ferrer Yenisey , De la Fuente Miguel , Coco Rosa , Fernandez‐Bueno Ivan
Published: January 2024

Purpose: PROM1 gene encodes the protein Prominin‐1 which plays a critical role in the morphogenesis of photoreceptors outer segments. The c.1354dupT mutation in PROM1 causes a premature stop codon and it has been related with different inherited retinal diseases (IRD) phenotypes. The aim of this study was to demonstrate the expression of key pluripotency genes by studying protein transcription factors and surface markers on the iPSC line [DCB]‐FiPSC1‐Ep5F‐2.

Methods: Our group generated the iPSC line [DCB]‐FiPSC1‐Ep5F‐2 from a patient with Cone‐rod dystrophy (CRD) related to the mutation c.1354dupT in the PROM1 gene. iPSC was grown on matrigel coated 15 μ‐slide 8‐well culture plates and fixed with 10% formalin solution. Plates were washed with Tris Buffered Saline and blocked (0.3%Triton X‐100 and 3%Donkey serum) for 60 min. Then, different combinations of primary antibodies related to pluripotency (OCT4, SSEA3, SOX2, SSEA4, TRA1‐60, NANOG and TRA1‐81) were incubated at 4°C overnight. Afterwards, species‐specific secondary antibodies were conjugated and immunostaining with DAPI was used. Finally, the samples were evaluated by confocal microscopy.

Results: Immunofluorescence analysis of the iPSC line [DCB]‐FiPSC1‐Ep5F‐2 revealed the expression of the common embryonic stem cell markers such as the transcription factors OCT4, NANOG and SOX2, and the surface markers SSEA3, TRA‐1‐81, SSEA4 and TRA‐1‐60. Transcriptional markers stain cell nuclei, while surface markers stain cell membranes showing that iPSCs have the potential for pluripotency and multilineage differentiation.

Conclusions: Although molecular characterization is necessary to completely elucidate iPSC pluripotency and bank this line in an international depository, the [DCB]‐FiPSC1‐Ep5F‐2 patient derived iPSC line could be useful as a disease model for the development of personalized therapies.
Retinal haemorrhage after cardiopulmonary resuscitation of a patient
Authors: Kontou Evgenia , Sgouros Panagiotis , Smoustopoulos Georgios , Papadopoulos Alexandros , Bontzos George , Garnavou‐Xirou Christina , Xirou Tina
Published: January 2024

Aims/Purpose: We present a rare case of a patient who presented with bilateral retinal haemorrhage after cardiopulmonary resuscitation (CPR).

Methods: A 37‐year‐old man, with a medical history of allergic bronchial asthma and a BMI >35, was referred to our emergency department from the cardiology clinic. He complained of sudden, painless, monocular visual acuity reduction after cardiac arrest and CPR because of an acute myocardial infarction (right coronary). He underwent a complete ophthalmic examination, as well as multimodal imaging and he was under close monitoring for the following months.

Results: In his initial ophthalmic examination, best corrected visual acuity was 0.1 in his right eye and 1.0 in his left eye (Snellen's chart). Intraocular pressure was 14 mmHg and 15 mmHg in his right and left eye, respectively. Dilated fundus examination showed bilaterally scattered sub‐retinal, intraretinal and pre‐retinal haemorrhages in the posterior pole, with involvement of the right fovea. After the resolution of the haemorrhages, a fluoroangiography was performed which revealed delayed central retinal vein filling in the right eye. 2 months later, during follow‐up examination, visual acuity in the right eye was 0.7 and in the left eye 1.0. The haemorrhages have been absorbed bilaterally, leaving in the right eye a sub‐foveal photoreceptor and RPE disruption.

Conclusions: Retinal haemorrhages can be observed after CPR. According to the literature, there have been reports of retinal haemorrhages in infants after CPR. Meanwhile, there is only one published case of an adult with associated comorbidities with this clinical presentation. The underlying pathophysiology of this clinical entity is still unclear, although a potential relationship between the increase in central venous pressure during CPR, and sequential retinal venous stasis is suspected.
Swept source optical coherence tomography and optical coherence tomography angiography in central serous chorioretinopathy
Authors: hager Ben amor , Namsia Walid , Yasmine Walha , Arije Jouini , Eya Essassi , Sana Khochtali , Moncef Khairallah
Published: January 2024

Aims/Purpose: To describe swept source optical coherence tomography (SS‐OCT) and SS‐OCT angiography (SS‐OCT‐A) findings in central serous chorioretinopathy (CSCR).

Methods: A retrospective study including 20 patients (22eyes) with acute CSCR, 31 patients (44eyes) with chronic CSCR, 35 uneffected fellow eyes and 50 healthy subjects (50 eyes). SS‐OCT was performed for all eyes with quantitative and qualitative analysis. SS‐OCT‐A was practiced for 17 eyes of the acute group, 38 eyes of the chronic group, 29 uneffected fellow eye and all the healthy subjects with quantitative and qualitative assessment.

Results: The SS‐OCT revealed a serous retinal detachment in 100% of eyes with acute CRSC and 69% of eyes with chronic CSCR. The Pigment epithelial detachment was present in 9 eyes in the acute group and in 5 eyes in the chronic group. Outer nuclear layer thickness was lower in the chronic group compared to the acute group and the fellow eyes. Three eyes with acute CSCR and 11 eyes with chronic CSCR had alterations in the ellipsoid zone. The interdigitating zone was thickened and regular, granular, defective and atrophic. Macular oedema and hypereflective membrane were only present in chronic CSCR. Other abnormalities were present in both groups such as fibrin, hyperreflective dots and pigment epithelial irregularities. Subfoveal choroidal thickness and Haller's layer thickness were significantly higher in the acute CSCR, chronic CSCR and the fellow eyes than in the control group. The SS‐OCT‐A showed vascular abnormalities and vascular rarefications in superficial (SCP) and deep (DCP) capillary plexus. The vascular densities (VD) of SCP and DCP in chronic CSCR were lower than those in the acute group, fellow eyes and the control group. We objected in the two groups (acute and chronic) hypointense areas, pattern hyperintense and hypointense and a hyperintense neovascular membrane, the later was only found in the chronic CSCR. The VD of choriocapillaris in acute and chronic CSCR were lower compared to fellow eyes and the control group.

Conclusions: SS‐OCT shows structural retinal and choroidal changes during the acute and chronic phase of CSCR. The qualitative and quantitative vascular changes attested by SS‐OCT‐A affect not only the choriocapillaris but also the retinal capillary plexuses.
Hyperreflectivity of the outer portion of the outer nuclear layer seen on optical coherence tomography in some cases of NR2E3‐associated retinopathy
Authors: Fong Sammi Wing Fai , Arno Gavin , Webster Andrew R. , Michaelides Michel , Mahroo Omar
Published: January 2024

Aims/Purpose: Bi‐allelic variants in NR2E3 are associated with Enhanced S‐cone Syndrome. Several features have been described on optical coherence tomography (OCT) including schisis, outer nuclear layer (ONL) thickening and ellipsoid zone thickening in some patients. We have observed that in some individuals, the outer portion of the ONL appears hyperreflective compared with the inner portion. We investigated the prevalence of this sign in our genetically confirmed patient cohort.

Methods: The electronic genetic database of Moorfields Eye Hospital was searched for patients with molecularly confirmed autosomal recessive NR2E3‐retinopathy. Patients who had undergone macular OCT (Spectralis, Heidelberg Engineering) were included. The horizontal foveal scan from the right eye (at the first visit for which OCT was available) was examined. The presence or absence of the specific sign was noted, together with presence of other features including schisis, atrophy or scarring.

Results: 33 patients from 29 unrelated families were included (mean (SD) age, 29 (17) years; range from 5 to 59 years). Of these, 7 (21%) showed some hyperreflectivity in the outer ONL. The mean (SD) age of these individuals was 18 (12) years. The mean (SD) age of the rest of the cohort was 32 (17) years. The difference was not quite statistically significant (p = 0.052). After exclusion of those with schisis, atrophy or scarring (n = 14), the proportion with the hyperreflectivity sign was 37% (7 of 19 patients). The difference in ages reached significance (p = 0.024).

Conclusions: A significant proportion of patients (21–37%) with autosomal recessive NR2E3‐retinopathy show this sign. One limitation of this study is that the prominence of the sign is dependent upon the type of scan performed (more distinct on single line scans with greater averaging than on regular volume scans). Patients with the sign were younger on average, suggesting it may be more prevalent in earlier stages.
Vitreous haemorrhage revealing haemophilia C
Authors: Jallouli Aida , Maamouri Rim , Belhedi Mariem , Lazzem Wiem , Chouaieb Sonia , Cheour Monia
Published: January 2024

Aims/Purpose: To report a rare case of vitreous haemorrhage revealing factor XI deficiency in 83‐year‐old man.

Results: A 83‐year‐old man presented with 6 months history of painless visual loss in the right eye (OD). There was no prior ophthalmic history, trauma or unusual bleeding tendency. Ophthalmic examination showed a best corrected visual acuity limited to hand motion in OD and 20/40 in the left eye (OS). Slit examination revealed the presence of bilateral grade 3 nuclear cataract. Fundus examination was unremarkable in OS but could not be visualized in OD. B scan ultrasonography revealed vitreous haemorrhage without retinal detachment. Etiological assessment revealed prolonged activated partial thromboplastin time. Further investigations revealed the presence of a hereditary coagulopathy, namely, haemophilia C or factor XI deficiency (factor XI level < 1%). The patient underwent successful cataract extraction and pars plana vitrectomy with silicone oil tamponade without prophylactic treatment. Peri‐operative fundus examination revealed superior branch retinal vein occlusion. Partial visual recovery was noted. No bleeding events were observed during follow‐up.

Conclusions: Factor XI deficiency is a rare disorder. Haemorrhagic symptoms are variable since there is no correlation between haemorrhagic risk and factor level. In severely affected patients, cataract extraction and vitrectomy can be performed safely without prophylactic treatment.
Dopamine and motion perception: Unveiling retinal connections in Parkinson's disease
Authors: Paleo Víctor , Bellón Sofía , Moratalla Rosario , De La Villa Pedro , Alcacer Cristina
Published: January 2024

Aims/Purpose: Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons, which occurs not only in the pars compacta of the sustantia nigra of the midbrain, but also in the retina, where dopaminergic amacrine cells (DAC) have been well characterized. Indeed, parkinsonian patients display visual impairments in early stages of the disease, including motion perception deterioration. Retinal cells responsible of motion perception are the directional selective ganglion cells (DSGC) which receive inhibitory synapses from starburst amacrine cells (SAC). Consequences of DAC degeneration in PD on the functionality of SAC and DSGC is unknown. In this work, we studied the functional connections between DAC and SAC in order to understand the pathophysiological mechanisms that determine the visual dysfunction in PD patients.

Methods: Using immunohistochemistry and confocal imaging, we studied the retinal connections between DAC and SAC in wild‐type mice. To determine the type of Dopamine (DA) receptor expressed by SAC, we used transgenic mice whose cells expressing D1 or D2 receptors also express fluorescent markers. Intravitreal injections of 6‐OHDA were performed in a series of animals, followed by immunohistochemistry and optokinetic test.

Results: We observed that DAC and SAC have direct synaptic contacts, and that the SAC located in the OFF sublamina of the inner plexiform layer express D2 receptors (D2R) but not D1 receptors. Moreover, depletion of DA in the 6‐OHDA injected mice induced a significant reduction of motion perception.

Conclusions: This study shows for the first time in mice that the amacrine retinal cells responsible for perceiving directional selective moving stimuli express D2R. These findings provide new ways of detecting visual impairments in preclinical models of retinal DA degeneration.