bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo pigmentation of amelanotic retinal pigment epithelium – An ex vivo model
Authors: Gupta Santosh , Lytvynchuk Lyubomyr , Ardan Taras , Studenovska Hana , Znaor Ljubo , Erceg Slaven , Stieger Knut , Motlik Jan , Petrovski Goran
Published: January 2024

Purpose: Retinal Pigment Epithelial (RPE) cells perform critical functions in the visual cycle. Their melanin pigmentation, which is organized into specialized compartments ‐ melanosomes, is highly critical for proper vision. We hereby show an ex vivo model for de novo pigmentation of RPE cells.

Methods: A chemical method to induce pigmentation in a non‐pigment model of ARPE‐19 cells was applied using L‐DOPA as a repurposed drug from the current treatment of Parkinson's disease.

Results: L‐DOPA was optimized for its toxic effect on ARPE‐19 cells along with pigmentation development. We found 1000 μM L‐DOPA to start inducing pigmentation of RPEs by Day 3, and achieve full pigmentation by Day 5. The gene expression of RPE‐specific markers (Tyrosinase, CRALBP, PEDF) was significantly higher in L‐DOPA‐treated ARPE‐19 compared to non‐treated ones. Positive expression for Tyrosinase was confirmed by ICC at both Day 3 and Day 5 of L‐DOPA treatment. Transmission electron microscopy showed the de novo melanosome formation with ultrastructural features of various stages of maturity (Stage I to IV), apical‐basal polarity, and melanosomes localization on the apical side of the RPEs in the L‐DOPA treated cells.

Conclusions: Our study showed that L‐DOPA treatment could induce de novo melanosome formation in amelanotic RPE cells.

Keywords: RPE, Melanosomes, L‐DOPA, Pigmentation.
A colour Vision Test – Comparing results between computer screens
Authors: Gomes Andreia , Linhares Joao , Alves Paulo Jorge , Monteiro José , Nascimento Sérgio
Published: January 2024

Aims/Purpose: A colour vision test was developed to run on web browser without specific hardware. It can estimate observers' colour vision thresholds, response times and eye movements with a webcam. The aim of this work was to compare the chromatic thresholds (CT) obtained for normal colour vision observers when estimated on calibrated and uncalibrated computer screens.

Methods: Four squares with random luminance noise were presented on a uniform grey background. One square was randomly selected to present a colour with a particular hue and saturation. Twenty‐six hues were tested on or near the dichromatic confusion lines. CT for each hue were estimated after a staircase procedure, and by computing the colour difference between the observers' CT and the reference white of the screen in use. The observers' task was to point and select the coloured square with the computer mouse. Two conditions were considered: a condition where the uncalibrated screen of the participants' laptop was used (L), and a condition using a screen calibrated in colour and luminance (D). The setup for D condition was equal across observers ensuring the same stimulus size and colour, observers' distance to screen and dark environment. The setup for L condition was uncontrolled but observers were guided towards providing information about pixel size, using a dark environment, disabling screen night light mode, using a laptop screen, and ensuring that screen brightness and zoom were adequate.

Results: 48 normal colour vision observers performed this test on D condition, while a subset of 45 observers repeated this test on L condition. CT were averaged across observers for both conditions. It was found that CT are comparable across different screens and correlatable with traditional colour vision tests. It was also found that hues at degrees 157°,162°,167°,179°,185° and 347° had statistical differences (p < 0.05) when comparing conditions L and D.

Conclusions: These results seem to indicate that the assumptions made to run the colour vision test on unknown computer screens with the instructions given, may be sufficient to obtain CT comparable to traditional colour vision tests, even if the test was done in non‐controlled conditions.
Assessment of functional changes in long‐standing type 1 diabetic patients without diabetic retinopathy with multifocal electroretinogram
Authors: Álvarez Marta Arias , Alonso Sofia Bielsa , Hospital Elvira Orduna , Tomas‐Grasa Cristina , Sopeña‐Pinilla Maria , Fernández‐Espinosa Guisela , Díaz‐Barreda Mª. Dolores , Mena Diego Rodríguez , Acha Javier , Pinilla Isabel
Published: January 2024

Aims/Purpose: To early evaluate local functional changes in the retina of long‐standing type 1 diabetic patients (DM1) without diabetic retinopathy (DR) through the use of multifocal electroretinogram (mfERG).

Methods: 46 eyes of 46 long‐standing DM1 patients without DR and 46 eyes of 46 healthy subjects were studied. Eyes with previous history of ocular diseases that could alter mfERG results were excluded. Participants were evaluated using mfERG with RETIscan recording system by Roland, following the standardized international guidelines of the International Society for Clinical Electrophysiology of Vision (ISCEV). The electrical density and implicit time of each first‐order response (K1) were measured and analysed in both study groups, as well as interocular differences.

Results: Mean age was 48.00 ± 9.77 years in the DM1 group and 51.69 ± 4.75 years in the control group. The average duration of diabetes was 29.19 ± 7.85 years and the mean HbA1c level was 7.33 ± 0.9%. No statistically significant differences were found between the ages of the groups. In mfERG, a statistically significant decrease in P1 response density was recorded in the R1 ring (central 0°‐2°) in the DM1 group compared to the control subjects (p = 0.029). Additionally, the R1/R2 ratio was significantly lower in diabetic patients than in the control group (p = 0.009). There was also a statistically significant increase in the implicit time of P1 in the R5 ring (central >15°) in the DM1 group compared to the control group (p = 0.027). No interocular differences were found in the DM1 group. Regarding quadrant analysis, no statistically significant differences were found in the DM1 group.

Conclusions: In patients with long‐standing DM1 without RD, mfERG enables the detection of subclinical and local findings, which indicates the presence of a pre‐existing neurodegenerative process prior to the onset of retinal lesions.
Influence of visual acuity on monocular face perception and exploration: Evidence from gaze‐contingency
Authors: Hupin Nathan , Hemptinne Coralie , Yuksel Demet
Published: January 2024

Aims/Purpose: The remarkable ability of the human brain to identify faces has traditionally been divided in the scientific literature into relative contribution of an analytical versus a holistic way of processing the visual stimuli. Although the “part‐by‐part” analysis allows identification, previous studies have proven that the ability to perceive all parts in a simultaneous fashion seems to be the key element of what makes observers experts at face identification. Here, we aim to better understand the impact of visual acuity (VA) on the holistic and analytical processing of the face.

Methods: We performed face‐matching tasks of unfamiliar faces using a gaze‐contingency approach in 12 normally sighted adults. Three viewing conditions (full view, mask effect, window effect) were simulated while VA was artificially decreased using a blur technique to obtain a linear scale of VA from LogMar 1,3 to 0,3.

Results: At the group level, response times and number of fixations in full view, mask effect and window effect remained well preserved at VA as low as LogMar 1,0. Around that level of VA, both time and number of fixations increased with decreasing VA and were higher in the mask condition than in the other conditions.

Conclusions: Facial identification performances remain well preserved at low VA. Evolution has allowed the brain to identify faces even if pathologies affecting the visual pathways strongly limit VA. This probably derives from the holistic strategy for face identification and the involvement of brain areas specialized in high level visual processing.
Electrophysiological response of myopic young adults with a novel ophthalmic lens for the control of myopia progression
Authors: Silva‐Leite Sara , Alves‐Touças Sílvia , Amorim‐de‐Sousa Ana , Fernandes Paulo , Méijome José Manuel González
Published: January 2024

Aims/Purpose: To evaluate the changes in the electrophysiological response of the retina induced by a novel perifocal ophthalmic lens designed for myopia control.

Methods: This experimental cross‐sectional study, evaluated eleven myopic participants (24.9 ± 4.5 years) with refractive errors lower than 6.00 D (spherical equivalent of −2.40 ± 1.32 D in the right eye and − 2.24 ± 1.56 D in the left eye). Refraction, best‐corrected visual acuity, and axial length were obtained at baseline. The global flash multifocal electroretinogram (gf‐mfERG) was assessed for the sensorial dominant eye with the RETI‐port/scan21 (Roland Consult, Wiesbaden, Germany). The gf‐mfERG recordings were performed with a stimulus array pattern of 61‐scaled hexagons displayed on a 19‐inch RGB monitor at a 33 cm distance (optically corrected). The retina was divided into three groups ‐ the fovea (that included concentric ring 1), the parafovea (rings 2 and 3) and the peripheral retina (rings 4 and 5). The peak‐time (in milliseconds, ms), the amplitude (in nano‐volts, nV) and the mean response density (nV/deg2) of the direct and implicit components (DC and IC, respectively) were analysed and compared between control (monofocal contact lenses) and test conditions (perifocal lenses). These lenses have an add power of +2.50 D on the temporal side, and + 2.00 D on the nasal side, intended to change the peripheral refraction.

Results: No differences were found in the DC and IC peak time between the control and test measurements, for the fovea, parafovea and peripheral retina. The mean response density of the DC was higher with the perifocal lens for the perifovea (p‐value = 0.033) and for the peripheral retina (p‐value = 0.026). For the IC, the mean response density was also higher with the perifocal lens, only for the parafovea (p‐value = 0.003).

Conclusions: Perifocal lenses for myopia control upregulate the parafoveal and peripheral retinal electrical activity.
Tryptamine psychedelics shape population receptive fields in early visual cortex in the presence of perceptual distortions
Authors: Pais Marta , Soares Carla , Teixeira Marta , Lima Gisela , Rijo Patrícia , Cabral Célia , Castelo‐Branco Miguel
Published: January 2024

Aims/Purpose: N, N‐dimethyltryptamine (DMT) is a psychedelic tryptamine associated with conspicuous visual hallucinatory phenomena and changes in perceived visual space. The neural basis of these effects remain unidentified. We asked whether changes in population receptive field properties in the primary visual cortex (V1) occur in parallel with changes in visual phenomenology.

Methods: We tested this hypothesis using magnetic resonance imaging using a placebo‐controlled design of inhaled DMT. We used a population receptive field (pRF) mapping method, which assesses neural population visual response properties and retinotopic maps in visual cortex. One‐Way Repeated Measures ANOVA was performed to determine if populations of visual neurons do reorganize along eccentricity in response to inhaled DMT. We also tested the phenomenology of visual hallucinations using the Hallucinogen Rating scale (HRS) with a focus on the visual cluster of symptoms.

Results: We show that the pRF sizes in V1 are significantly increased in peripherical field in the active condition (inhaled DMT) versus placebo (F (3, 54) = 22.6790, p‐value <0.0001). Post hoc Paired Sample T‐Tests were used to determine which pairs of bins of eccentricity were associated to significant differences. We found statistically significant differences for the peripherical bins of eccentricity (3.75 deg, 6.25 deg, 8.75 deg). These effects were accompanied by higher visual scores in Hallucinogen Rating scale (HRS) F(1,9) = 46 434, p < 0.05).

Conclusions: This evidence for fast effects of DMT resulting in increased population receptive fields is consistent with the presence of visual manifestations and may explain perceptual distortions induced by psychedelics such as field blurring and the enlargement of nearby visual space, particularly at the visual periphery.
Are there any indicative signs in colour Doppler imaging of de novo development thyroid orbitopathy after radioiodine treatment
Authors: Walasik‐Szemplińska Dorota , Kamiński Grzegorz , Sudoł‐Szopińska Iwona
Published: January 2024

Aims/Purpose: The aim of this study was to identify indicative signs in doppler flow parameters in the central retinal artery (CRA) and ophthalmic artery (OA) which might be associated with de novo development of thyroid‐associated orbitopathy in the early period after radioiodine treatment in patients with Graves disease.

Methods: 82 patients with hyperthyroidism were enrolled: 44 with Graves disease and 38 with toxic nodular goitre. In both groups, blood flow parameters in the CRA and OA were analysed before and 2 and 4 weeks after radioiodine administration. The peak systolic velocity (PSV) and end‐diastolic velocity (EDV) were evaluated, and the resistive index (RI) was calculated.

Results: There were no statistically significant differences in the PSV, EDV or RI between groups at baseline and 4 weeks after radioiodine administration. Two weeks after radioiodine administration, the RI in the CRA and EDV in the OA were significantly lower, and the EDV in the CRA was higher in patients with Graves disease than in patients with toxic nodular goitre. There was an inverse correlation between baseline thyrotropin receptor autoantibody (TRAb) levels and the difference between the RI at weeks 4 and 2 (RI3‐RI2) in the CRA and a positive correlation between the baseline anti‐thyroid peroxidase antibody concentration and RI3‐RI2 in the OA.

Conclusions: Administration of radioiodine results in more prominent features of hyperkinetic circulation. Patients with Graves disease and high TRAb titers have a lower sensitivity to radioiodine treatment. High TRAb titers suggest higher disease activity and a weaker therapeutic effect of radioiodine.

References

1. Alp M, Ozgen A, Can I, Cakar P, Gunalp I. Colour Doppler imaging of the orbital vasculature in Graves' disease with Computed tomographic correlation. Br J Ophthalmol 2000; 84: 1027–1030.

2. Chiovato L, Fiore E, Vitti P, et al. Outcome of thyroid function in Graves' patients treated with radioiodine: role of thyroidstimulating and thyrotropin‐blocking antibodies and of radioiodine‐induced thyroid damage. J Clin Endocrinol Metab 1998; 83: 40–46.

3. Kaise K, Kaise N, Yoshida K, et al. Thyrotropin receptor antibody activities significantly correlate with the outcome of radioiodine (131I) therapy for hyperthyroid Graves' disease. Endocrinol Jpn 1991; 38: 429–433.
Changes in visual function in long‐term type 1 diabetic patients without diabetic retinopathy using full‐field electroretinogram
Authors: Álvarez Marta Arias , Fernández‐Espinosa Guisela , Sopeña‐Pinilla Maria , Tomas‐Grasa Cristina , Alonso Sofia Bielsa , Boned‐Murillo Ana , Garza Inés Vicente , Mena Diego Rodríguez , Orduna Hospital Elvira , Pinilla Isabel
Published: January 2024

Aims/Purpose: To evaluate changes in retinal function in type 1 diabetic patients (DM1) without diabetic retinopathy (DR) using full‐field electroretinogram (ffERG).

Methods: Forty‐six eyes of long term DM1 patients without DR were compared to 46 eyes of healthy subjects. None of them had any ophthalmic pathology that could alter the findings. All the subjects were evaluated following the standardized international ISCEV guidelines. The amplitude and implicit time (IT) of each component of scotopic and photopic responses were evaluated, along with interocular differences.

Results: There were no age differences between groups. A significant increase in the rod response IT of the DM1 patients was observed compared to the control group (p = 0.0012). The b wave amplitude in the mixed response was statistically reduced in the DM1 group compared to the control group (p = 0.03). There was an increase in the IT of both a and b‐wave in the mixed response at the higher stimulus intensity in the DM1 compared to control (p = 0.023 and p = 0.004 respectively). b/a rate was similar in both groups. The oscillatory potentials (OPs) showed an increase in their IT (p = 0.008) and a decrease in OP2 amplitude in the DM1 group. Cone mediated b‐wave was diminished in DM1.

Conclusions: Full‐field electroretinogram enables the detection of subclinical findings in long term DM1 patients suggesting the existence of neurodegeneration prior the appearance of DR, particularly in the rod system and OPs.
Soluble epoxide hydrolase gene deletion ameliorates retinal and ophthalmic arterial senescesome
Authors: Manicam Caroline , Zare Elahe , Dejung Mario , Butter Falk , Grus Franz , Pfeiffer Norbert , Perumal Natarajan
Published: January 2024

Aims/Purpose: Neurovascular dysfunction in glaucoma is exacerbated by aging. We recently deciphered the crucial role of the cytochrome P450 (CYP) metabolic pathway in the retina (R) and ophthalmic artery (OA). Vasoactive CYP metabolites are hydrolysed by soluble epoxide hydrolase (sEH), thereby diminishing their protective effects. Hence, sEH has emerged as a novel inhibitory target. This study defined the neuro‐vasculoprotective molecular signatures of Ephx2 gene deletion (KO) that impinge senescence in the neural R and OA.

Methods: Retinae and OA were isolated from young (3–5 months) and old (12–24 months) male wild type (WT) and KO mice. Samples were pooled (n = 5 mice/group/replicate) to yield 4 biological replicates per group and subjected to label‐free mass spectrometry‐based proteomics and in‐silico bioinformatics analyses.

Results: A total of 3706 retinal and 644 OA proteins were identified. Aging profoundly affected the R and OA proteome of WT mice, as demonstrated by the differential expressions of 183 and 111 proteins, respectively. The key changes attributed to age‐related R cellular dysfunction and DNA damage were reflected in the inactivation of NAD+ (p = 9.1 × 10−4) and sirtuin (p = 6.2 × 10−3) signalling pathways. Remarkably, KO had a major influence on the regulation of R proteins involved in bioenergetics reprogramming via mitochondrial homeostasis in young mice, which was shown by the activation of oxidative phosphorylation (p = 1.3 × 10−6) and inhibition of mitochondrial dysfunction (p = 3.4 × 10−3), both of which corresponded to upstream involvement of UQCC3 (p = 7.3 × 10−7). A translation regulator, LARP1, which regulates cell proliferation and protein synthesis, was highly activated in the aged KO retina (p = 10 × 10−16) compared to aged WT (p = 3.1 × 10−5). In the OA, vascular remodelling processes observed in the aged WT mice, primarily compromised microtubule dynamics (3.6 × 10−8) and cell–cell contact (3.7 × 10−6), were significantly attenuated in the KO. Noteworthy, KO significantly mitigated proteome changes attributed to inflammatory response in the OA of both young and aged mice.

Conclusions: In gist, the Ephx2 gene deletion significantly ameliorated detrimental senescesome in ocular neurovascular tissues. The potential use of sEH inhibitors for glaucoma needs further investigation.
Influence of the postoperative restrictive methodologies and efficacy of the Baerveldt 350 implant after 12 months follow‐up
Authors: del Mar Schilt‐Catafal Maria , Arciniegas Carlos , Gutierrez‐Lemus Nathalie , Marrón Elena Ávila , Guevara‐Chavarría Osvaldo , Djavanmardi Shirin , Duch Susana
Published: January 2024

Aims/Purpose: To assess the clinical outcomes subsequent to the implantation of a Baerveldt 350 drainage device, utilizing different restrictive methodologies to prevent sudden postoperative hypotony (HT) (IOP <6 mmHg), and their subsequent impact on the incidence of a Hypertensive phase (HP).

Methods: A retrospective observational analysis of 71 consecutive eyes that had a Baerveldt 350 implanted. 50 eyes had 6 or 7/0 polyglactin tube ligation (ligature group = LG) and 21 eyes had a 3/0 polypropylene intraluminal tear cord 3/0 added to the ligation (ripcord‐ligature group = RLG), which was manually removed at the surgeon's discretion after spontaneous opening of the polyglactin. Intraocular pressure (IOP) and ocular hypotensive medication (OHM) lowering, failure rate, complete and partial success (CS and PS) and presence of HP were analysed.

Results: The mean preoperative IOP was 26.14 (11.34) mmHg with 2.98 OHM for the LG and 28 (8.76) mmHg with 3.35 OHM for the RLG (p = 0.545 and p = 0.397). At the end of the follow‐up, the mean postoperative IOP was 13.35 (3.87) mmHg for the LG and 10.81(2.66) mmHg for the RLG (p = 0.01). The mean reduction of OHM was 2.25 (1.38) for the LG and 2.81 (1.6) for the RLG (p = 0.168). HP was noted in 26 patients (37.14%), 25 of them took place in the LG (50%); however, only 1 took place in the RLG (5%) (p = 0.00023). 35% of the patients who exhibited HP achieved CS, compared to 67.7% of the patients that did not show HP (p = 0.022). The survival analysis for a 12 months follow‐up period, showed that the estimate survival time for the LG was 10.97 (±0.521), and 11.64 (±0.342) for the RLG (p = 0.216). Two predictors were identified for risk of failure and CS: age of the patient before surgery (OR 0.157; 95% CI 0.029–0.865; p = 0.033) and the presence of HP (OR 3.90; 95% CI 1.189–12.794; p = 0.025). Lastly, HT was noted in 55 patients (80.9%), 45 of them took place in the LG (81.8%); however, only 10 took place in the RLG (18.2%) (Pearson Chi‐S p = 0.000225).

Conclusions: Baerveldt 350 drainage device implantation has proven to be an effective procedure for glaucoma control. The use of the ripcord added to the absorbable ligature was associated with less risk of HP, and with better IOP results at the 12‐months follow‐up. Nevertheless, further research with larger population and larger follow‐up is needed to obtain robust results.
Anti‐cytokine antibodies attenuated neuroglial degeneration under hypoxic stress
Authors: Guan Chaoqiang , Zhang Linglin , Perumal Natarajan , Lin Hao , Francis Alfred Francis Pakkam John , Pfeiffer Norbert , Grus Franz , Manicam Caroline
Published: January 2024

Aims/Purpose: Hypoxia is a vital cause of neurodegenerative diseases such as glaucoma and retinal ischemia. We investigated the potential neuroprotective effects of anti‐cytokine antibodies against hypoxic damage.

Methods: An in vitro hypoxia model was established using cobalt chloride (CoCl2) stimulation in microglial cells (BV‐2). Immunofluorescence staining was performed to detect the expression markers of different microglial phenotypes in BV‐2. Different concentrations of CoCl2 (0–150 μM) were tested to generate dose–response curves. Following exposure to CoCl2 at an approximate IC50 of 0.1 mM, BV‐2 were treated with anti‐tumour necrosis factor‐alpha (anti‐TNF‐α) or anti‐ interleukin‐1 beta (anti‐IL‐1β) antibodies for 24 h. Cell viability was determined by MTS assay. Proteome changes in BV‐2 were analysed with the mass spectrometry‐based proteomics approach.

Results: Immunocytochemistry revealed the expression of M1 marker consisting CD68 and M2 marker CD206 in the BV‐2 cells. Hypoxia induced by mimetic CoCl2 led to a concentration‐dependent viability impairment in BV‐2 and cells treated with 0.1 mM CoCl2 for 24 h showed decreased viability of ~46%‐ 50%. Interestingly, the application of anti‐TNF‐α (2ug/ml) and anti‐IL‐1β (4ug/ml) antibodies significantly improved the BV‐2 cell viability to 80% (p < 0.0001) and 76% (p < 0.0001), respectively. Proteomics and bioinformatics analyses of the differentially expressed proteins revealed that CoCl2 induced proteome alterations involved in mitochondrial dysfunction signalling pathway (p = 1.10 × 10−3), which were eliminated by the treatment with both anti‐TNF‐α and anti‐IL‐1β. Besides, CoCl2‐induced activation of endoplasmic reticulum (ER) stress response (p = 3.33 × 10−9) was alleviated by anti‐IL‐1β and anti‐TNF‐α treatment (p = 1.7 × 10−7 and p = 8.82 × 10−7, respectively). Particularly, anti‐TNF‐α antibody significantly downregulated proteins involved in apoptosis (p = 1.58 × 10−10). Anti‐IL‐1β induced Nrf2‐mediated antioxidant response and exerts protection against oxidative stress (p = 1.00 × 10−6).

Conclusions: Antibodies targeting cytokines provide neuroprotective effects on microglial cells from hypoxic stress. These findings demonstrated the potential use of anti‐cytokines in the treatment of neurodegenerative diseases.
Intraocular pressure and its determinants in a very old population. The ural very old study
Authors: Jonas Jost , Mukharram Bikbov , Gyulli M. , Iakupova Ellina , Panda‐Jonas Songhomitra , Tuliakova Azaliia , Fakhretdinova Albina , Iulia A.
Published: January 2024

Aims/Purpose: To assess the distribution of intraocular pressure (IOP) and its determinants in a very old population.

Methods: The population‐based Ural Very Old Study (UVOS) was performed in a rural and urban region of Bashkortostan/Russia and consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85+ years. As part of a series of medical and ophthalmological examinations, we measured IOP by non‐contact tonometry.

Results: The study included 1042 (68.3%) individuals with available IOP readings (mean age:88.1 ± 2.7 years). After excluding individuals with anti‐glaucomatous therapy, mean IOP was 14.5 ± 5.1 mmHg (median:14 mmHg; 95%CI:8,25) with a right‐sided skewed distribution. In multivariable analysis, higher IOP was associated (correlation coefficient r:0.38) with female sex (beta:0.13; p = 0.002), thinner central cornea thickness (beta:0.23; p < 0.001), higher systolic blood pressure (beta:0.13; p = 0.006), higher estimated cerebrospinal fluid pressure (CSFP) (beta:0.11; p = 0.04), longer axial length (beta:0.09; p = 0.02), and status after cataract surgery (beta:‐0.17; p < 0.001). In that model, the IOP measurements increased by 0.02 mmHg (95%CI:0.01,0.03) for each increase in systolic blood pressure by 1 mmHg, by 0.11 mmHg (95%CI:0.004,0.22) for each increase in estimated CSFP by 1 mmHg, by 0.2 mmHg (95%CI:0.1,0.3) for each central corneal thickness increase by 10 μm, and by 0.31 mmHg (95%CI:0.05,0.59) for each axial length increase by 1 mm. It decreased by 1.13 mmHg (95%CI:0.54,1.72) with cataract surgery.

Conclusions: In this study population aged 85 + years, corneal thickness‐adjusted IOP‐readings increased with higher blood pressure and estimated CSFP and longer axial length, and it decreased with cataract surgery.
Outstanding partnership in neuroinflammation. Highlighting open‐angle glaucoma diagnosis and therapy
Authors: Villanueva Carolina Garcia , Andrés‐Blasco Irene , Gallego‐Martínez Alex , Zanón‐Moreno Vicente , Vila‐Arteaga Jorge , Feijoo Julian Garcia , Pinazo‐Duran Maria Dolores
Published: January 2024

Aims/Purpose: Despite significant advances in neuroprotection strategies, patients are still at high risk for glaucoma neurodegeneration (GND), in which neuroinflammation (NINF) is exceedingly implicated. It has recently been shown that in the acute phase, NINF cascades lead to apoptosis, meanwhile in later stages a wide variety of signalling pathways act trying to repair existing damage. Also, NINF affects adult neurogenesis (NG), that, in turns, remains an unknown field to be explored in GND.

Methods: A total of 135 participants of both sexes, aged 35–80 years, were selected and classified into: open‐angle glaucoma (OAG) patients (n = 70) and healthy controls (CG; n = 65). Demographics, clinical and molecular data were registered. Tears were collected from the inferior meniscus and frozen at −80°C until processing by the multiplex system (human cytokine panel) to determine the cytokine/chemokine levels. Data were processed by using the IBM SPSS 25.0 program.

Results: Mean age of the participants was 62 ± 14 years (68% were aged over 60 years). Gender distribution was 38% males/62% females. Tears from patients with OAG showed differential expression profile of the assayed cytokines/chemokines, as compared to the CG. Specifically, the granulocyte‐macrophage colony stimulating factor (GM‐CSF; p < 0.001), interferon‐γ (IFN‐γ; p < 0.001), tumour necrosis factor alpha (TNFa); and interleukin (IL) ‐4 and − 10 (p < 0.05) revealed significantly higher levels in the OAG patients versus the CG.

Conclusions: Liberation of anti‐ and pro‐inflammatory cytokines with a broad range of functions in adult NG, as the aforementioned factors: the GM‐CSF, INFg, TNFa, IL‐4 and IL‐10, can be fully considered when managing GND and visual outcomes.
Association between functional parameter and structural, and vascular parameters in advanced glaucoma
Authors: Özalp Onur , Atay Kubra , Ozer Taylan Can , Bilgec Mustafa Deger , Atalay Eray
Published: January 2024

Aims/Purpose: We aimed to evaluate the function‐vasculature, and function–structure relationships in advanced glaucoma patients.

Methods: This cross‐sectional study included 29 eyes of 24 advanced glaucoma patients. Advanced glaucoma was classified as visual fields (VFs) with a mean deviation (MD) below ‐12 dB according to Hodapp‐Parrish‐Anderson classification system. The structural parameters, cup/disc area ratio, cup/disc vertical ratio, cup/disc horizontal ratio, rim area, disc area, cup volume, retinal nerve fibre layer thickness, macular ganglion cell complex (GCC) thickness, were measured using optical coherence tomography (OCT, Optovue, Fremont, CA). The vessel density of superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), outer retina (OR), and choriocapillaris (CC) were analysed by optical coherence tomography angiography (OCTA, DRI OCT Triton Plus, Topcon, Tokyo, Japan). For all layers, the average vessel density of the area between 1 mm and 3 mm diameter circles was calculated, assuming the 1 mm diameter area centered on the fovea as the central region. Relationships between 10–2 VF MD values, and structural and vascular parameters were assessed by Pearson's correlation coefficients. p < 0.05 was considered statistically significant.

Results: The mean ± SD age of all patients was 61.9 ± 15.8 years and 75% were male. For structural parameters, there was a positive correlation between the MD and GCC thickness values (p = 0.001, r = 0.617), while none of the parameters of the optic disc were related to the MD value. There were significant positive correlations with the vessel densities of the SRCP and CC layers (p = 0.001, r = 0.593 and p = 0.002, r = 0.541, respectively).

Conclusions: Decreased vessel densities of the SRCP and CC were significantly associated with severity of visual field damage. This study showed that OCTA can be a promising method in daily use for monitoring advanced glaucoma.
Analysis of the impact of different schemes of preparation to trabeculectomy on the healing markers using in vitro model of the Tenon fibroblast cultures isolated directly from the patient
Authors: Kosior‐Jarecka Ewa , Piłat Joanna , Przekora Agata , Wróbel‐Dudzińska Dominika , Żarnowski Tomasz
Published: January 2024

Aims/Purpose: The aim of the study was to assess the influence of different regimes of patient's preparation before trabeculectomy on the markers of healing process in Tenon's fibroblast cultures.

Methods: The studied group consisted of 66 patients with open angle glaucoma undergoing primary trabeculectomy. The patients were divided into 5 groups with different regimes of preparation before the surgery based on application or withdrawal of topical antiglaucoma medications and steroids. During trabeculectomy the samples of Tenon's capsule were obtained. Tenon fibroblasts were isolated directly from the explants to test their proliferation ability and the level of released healing markers. Following factors typical of healing process were evaluated using commercially available ELISA kits: IL 1‐β, IL‐6, IL‐8, VEGF‐A, TGF‐ β1 and MMP‐9.

Results: Concentrations of IL‐1β, IL‐6 and TGF‐ β1 were significantly higher in the group obtaining antiglaucoma drops. Additionally, in this group the fibroblasts revealed the highest proliferation potential, indicating the active healing process. The levels of IL‐8, VEGF‐A and MMP‐9 were similar between the groups.

Conclusions: Our study shows that for the best conjunctival anti‐inflammatory control, the most influential factor is the withdrawal of antiglaucoma medications.
Transcriptomic analyses reveal the molecular mechanisms underlying the ocular surface damage in treated glaucoma patients
Authors: Irigoyen Cristina , Montañes Javier Moreno , Carnero Elena , Naveiras Miguel , de la Puente Miriam , de la Viesca Maria Fraga , Zamora Jorge Gonzalez
Published: January 2024

Aims/Purpose: Topical glaucoma drugs have a high prevalence of ocular surface disease (OSD), affecting to its compliance. The clinical signs of OSD are very similar to those observed in patients with dry eye syndrome; however, the mechanisms mediating the onset of symptoms are unknown. The purpose of this study is to identify conjunctival transcriptomic changes in patients treated with topical medication and patients with dry eye and compare them to healthy controls.

Methods: Impression cytology was performed, and samples were selected for RNA sequencing; 33 patients treated for glaucoma, 9 with dry eye and 14 healthy controls. After a quality check, the reads were aligned, and gene expression was quantified by counting exonic regions. Ingenuity Pathway Analysis identified the routes and biologic processes associated with transcriptomic changes.

Results: In treated patients, up‐regulation of immune‐related genes represented the 79% of the altered pathways. In dry eye samples, immune system and inflammation represented 39% of the altered routes; increased expression of genes related to mitochondrial metabolism and oxidative stress represented 16% and decreased expression of genes involved in maintaining conjunctival integrity and cell differentiation represented 15%.

Conclusions: According to our results, an exacerbation of the immune system is observed in patients with glaucoma treatment as the main pathway involved in ocular surface damage. However, in the case of patients with dry eye, the damage is the result of multiple pathways. Knowledge of the mechanisms involved in ocular surface damage is essential in the search for effective treatments for these patients.
Panuveitis and palpable purpura in a patient with interstitial Pasteurella multocida pneumonia
Authors: Murgia Carlo , Carbini Andrea , Satta Aurora , Dore Stefano , Pinna Antonio
Published: January 2024

Aims/Purpose: We describe a case of panuveitis and palpable purpura in a patient with Pasteurella multocida pneumonia.

Methods: A 75‐year‐old pseudophakic woman with type‐2 diabetes and chronic obstructive pulmonary disease complained of lower limb palpable purpura and right vision loss of five‐day duration. On admission, right visual acuity was hand motion. Slit‐lamp examination disclosed severe conjunctival and perikeratic reaction, corneal oedema, 3‐mm hypopyon with heavy fibrin accumulation and blood clots, and synechiae to the IOL.

Results: Chest computed tomography revealed interstitial pneumonia. Sputum culture yielded P. multocida. Amoxicillin/clavulanic tablets (1gx3/daily) and topical and systemic steroids were given. Later on, fluorescein angiography showed multiple areas of choroiditis bilaterally. With the above‐mentioned therapy, there was full recovery of the skin, lung, and eye lesions.

Conclusions: This report emphasizes that P. multocida infection should be considered in patients with intraocular inflammation, palpable purpura, and interstitial pneumonia. A multidisciplinary approach is necessary for a correct diagnosis and management.
Assessment of tear derived extracellular vesicles as a minimally source of novel biomarkers for subconjunctival glaucoma surgery
Authors: Viñas‐Palau Clara , Sanroque‐Muñoz Marta , García Jéssica Botella , El Jarroudi Rachid Bouchikh , Loscos‐Arenas Jordi , Borras‐Serres Francesc Enric
Published: January 2024

Aims/purpose: Glaucoma is a highly prevalent pathology causing avoidable blindness. Topical treatments used to stabilize intraocular pressure (IOP) may produce several side effects including inflammatory reactions. Patients who fail to control IOP or suffer significant side effects undergo subconjunctival glaucoma surgery (SGS). Estimations point to 30–40% of these patients will develop local scarring and fibrosis, which are the main complications of SGS. Thus, predicting the surgical outcome and starting preemptively fibrosis treatment are crucial. The aim of this study was to determine whether tears, and specifically tear‐derived extracellular vesicles (L‐EVs), can be used as liquid biopsy source, as a previous step for identifying new biomarkers for SGS outcome.

Methods: Tear samples were obtained from patients (no surgical treatment, n = 11) by Schirmer's test. L‐EVs were enriched by size‐exclusion chromatography. Protein quantification was measured by microBCA assay and miRNA extraction (both from whole tear and L‐EVs) was performed using commercial kits.

Results: Whole tear samples displayed variable miRNA and protein concentrations among patients (range 222.0–1388.1 ng miRNAs and 5.6–27.2 μg protein). Levels of miRNA and protein were also highly variable but considerably reduced in L‐EVS (0.14–46.78 ng miRNAs and 0.5–4.2 μg protein). Yet, in most patients, both types of samples (whole tears and L‐EVs) rendered sufficient quantity of protein and miRNA to perform proteomic and transcriptomic analysis.

Conclusions: Concentration of miRNAs and Protein in tears and L‐EVs is highly variable among patients. As expected by their higher enrichment, miRNA and protein concentrations in L‐EVs are reduced compared to whole tears, yet quantities may be still enough to perform mic analyses. This higher purification of L‐EVS may help identifying specific biomarkers related to SGS outcome in a minimally invasive manner.
Mapping of fundus photography to 3D imaging for ocular radiotherapy
Authors: Haasjes Corne , Pors Lennart , Beenakker Jan‐Willem
Published: January 2024

Aims/Purpose: Ocular Proton Therapy (OPT) is one of the main treatments for uveal melanoma. Full inclusion of fundus images in the treatment planning is currently hindered by the refraction of the eye's optical elements. In this study we developed and evaluated a method to correct for these effects, with the final aim of enabling an OPT‐planning which spares more of the healthy retina.

Methods: A paraxial method to correct for the scaling fundus photographs of the central retina was developed using ray transform matrices. This method was subsequently extended to the full retina using ray tracing simulations in Zemax OpticStudio through the ZOSPy library [1]. These methods were evaluated in 33 eyes in which the corneal topography, lens location, thickness and curvature, and retinal shape were personalized. The resulting scaling of the fundus images was finally compared with the method currently used in OPT planning (EYEPLAN).

Results: For the central retina the magnification relative to the average eye ranged from 0.79 to 1.50 and was approximately inversely proportional to the eye's spherical equivalent. For the peripheral retina, a nodal point‐based mapping provided no systematic errors and the least variation between subjects (up to 2.5 degrees at 70degrees eccentricity). This method proved a significant improvement compared to the currently used method which had a systematic error of approximately 21 degrees as it incorrectly modelled the refractive effect of the eye's optics.

Conclusions: Using the nodal point as a reference point, fundus images can be accurately mapped to 3D imaging, enabling the inclusion of optical information in OPT planning.

References

1. van Vught, Haasjes, Beenakker. ZOSPy a toolbox for optical simulations. github.com/MREYE‐LUMC/ZOSPy.
The anatomy of the anterior interface revisited
Authors: Tassignon Marie‐José
Published: January 2024

With the advent of the intraoperative OCT in 2015, the anterior interface could be visualized during cataract surgery. This technology allowed better understanding of the anterior interface that was considered for so many years as being virtual. Based on the intraoperative OCT device, we were able to describe a new type of congenital cataract based on a dysgenesis of the anterior interface which we called AVLID: anterior vitreo‐lenticular interface dysgenesis. This type of congenital cataract is responsible for about one third of the newborn cataract in developed countries. It also allowed us to observe that the anterior interface was not large enough to accommodate the bag‐in‐the‐lens in some eyes with childhood cataract. We then developed a new capsule stretching technique to enlarge the anterior interface per operatively. In addition, we observed the presence of anterior vitreous detachment (AVD) in adults starting from 45 years on. We found an incidence of 60% AVD in adult eyes and were able to study the consequences on accommodation of AVD. The anterior interface was given the name of Berger, an Austrian anatomist from Graz (1887). However, the most important structure of the anterior interface is the ligament of Wieger. Wieger was an ophthalmologist and described the hyaloidal‐capsular ligament in his thesis which he defended in Strassbourg (1884). It is this ligament that influences accommodation and as a result the name of Wieger should be recognized as such.
Retinal circuit disassembly, plasticity, and repair in glaucoma
Authors: Ou Yvonne
Published: January 2024

Precise connections between synaptic partners are shaped during development to ensure proper neural circuit function, but how these connections are disassembled and rearranged after injury is less well understood. In glaucoma, a neurodegenerative disease of the optic nerve, the ganglion cell is injured but very little is known about how the presynaptic circuitry is perturbed. Furthermore, the ability to diagnose and treat glaucoma at an optimal stage before irreversible retinal ganglion cell loss occurs requires a comprehensive understanding of inner retina circuit disassembly and plasticity. This lecture will provide insights into retinal circuit disassembly and plasticity, the role of microglia in synapse disassembly and the opportunities for retinal repair of inner retinal circuitry in glaucoma. These findings expand knowledge of how adult neural circuits react and rearrange in the face of injury and permit.

The design of novel psychophysics testing paradigms and retinal ganglion cell regeneration or neuroprotection strategies.
Mitochondria and vision – a life in mitochondria always on the move
Authors: Votruba Marcela
Published: January 2024

Mitochondrial disease is among the most common form of inherited neurological disorder, with a minimum prevalence of 1:5000 and few if any effective treatments or cures. Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, in order to maintain their shape, distribution and size. Mitochondrial dysfunction is seen in numerous diseases, including rare primary genetic mitochondrial diseases, many affecting the eye and vision and various common degenerative disorders. Mitochondrial dysfunction is implicated in the ageing process and also contributes to ischaemic cardiac disease and cancer. Mitochondrial dysfunction has been well documented in neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, glaucoma and age‐related macular degeneration. Consequently, it is now becoming a major target for new therapeutic development. To date, however, there have been few if any successes. The problems faced in addressing mitochondrial dysfunction range from identifying suitable targets to lack of methods that reliably transfect mitochondria. There may be huge potential in taking an advanced therapy medicinal products (ATMPs) approach, developing medicines for human use that are based on genes, tissues or cells. A novel approach in the literature is the transplantation of fully functional mitochondria directly into defective cells. Could this be the more generic solution that would address the diverse range of mitochondrial defects in disease?
Corneal nerves and wound healing: No gain without pain
Authors: Ferrari Giulio
Published: January 2024

Corneal nerves and wound healing: no gain without pain?

Corneal nerves are instrumental to the maintenance of corneal integrity. Their role in promoting epithelial cell migration and proliferation has been extensively described. Recently, the impact of corneal innervation on the limbal stem cell niche is starting to merge. Specifically, nerve‐derived factors orchestrate a complex biological response which involves the generation of pain, immune activation and stem cell interaction. On the other hand, epithelial and leukocyte cells have an impact on corneal nerves through secretion of soluble factors and, possibly, mechanical interaction. While the generation of pain is inevitably associated with wound healing, and its suppression generally impairs this process, excessive inflammation can perpetuate pain and negatively impact on corneal integrity. We will discuss the benefits, and shortcomings, of this nerve‐controlled process and review the potential therapeutic opportunities opened by recent findings in the field.
Machine learning applied to brain imaging data
Authors: Castelo‐Branco Miguel
Published: January 2024

Multivariate data‐driven analysis may identify subtle anomalies in retinal and brain structure in the absence of visible pathology. The modelling of healthy ageing critically requires methodology that can detect subtle changes in this process and that can also be applied to pathological conditions. In the last few years multiple machine learning models have been proposed that learn age patterns from magnetic resonance images.

In recent years, classification approaches using imaging data have shown that multimodal classification methods may perform better than the use of a single imaging modality for the diagnosis of neurodegenerative conditions of the eye and the brain. The currently used clinical approach often emphasizes the use of qualitative structural, molecular and/or functional imaging data for clinical diagnosis. Based on the hypothesis that classification of isolated imaging modalities is not predictive of their respective value in combined approaches, we investigate the potential of multimodal quantitative integration approaches in neurodevelopmental and neurodegenerative conditions. We also review imaging evidence based on machine learning reflecting critical interactions between ageing, systemic disorders (diabetes) and neurodegenerative diseases.
Machine learning applied to OCT data from human and mouse models of disease
Authors: Bernardes Rui
Published: January 2024

Optical Coherence Tomography (OCT) is now widely adopted in clinical practice in ophthalmology and neurology, with the retina being the primary target. While its first use was restricted to fundamentally assessing changes in the retina structure from the health status, OCT became increasingly useful in anticipating disease onset, progression, and response to therapy. With the increasing role of the eye as a window into the brain, the ability of OCT to gather information on optical properties of the imaged tissue and subtle changes of these, new approaches are required to make essential information on the status of the central nervous system (CNS) visible and useful out of OCT data. Texture analysis, texture analysis biomarkers, and machine learning approaches applied to computed fundus images from OCT data will be discussed and demonstrated to be helpful in human and animal models of Alzheimer's disease studies.