bluuebunny/crossref_metadata_2025 huggingface dataset:
The cleavage of Gasdermin E is the rate limiting step in the secretion of IL‐1β in RPE cells with non‐functional cellular clearance
Authors: Ranta‐Aho Sofia , Hytti Maria , Toppila Maija , Bhattarai Niina , Kaarniranta Kai , Kauppinen Anu
Published: December 2022

Purpose: Since RPE cells has important regulatory role in retinal inflammation, we examined the secretion kinetics of proinflammatory cytokine IL‐1b.

Methods: IL‐1β production and release from IL‐1a‐primed (4 ng/ml) ARPE‐19 cells was induced by inhibiting proteasomal clearance and autophagy using MG‐132 (5 μM) and Bafilomycin A1 (BafA; 50 nM), respectively. Medium samples and cell lysates were collected from the beginning of BafA exposure and continued for 24 h in 6 h intervals. IL‐1β levels were measured using the ELISA technique. The cleavage of pore forming gasdermin E was detected using the western blot method.

Results: In the lysate samples, active IL‐1β levels were highest right after the BafA exposure. After 12 h, IL‐1β levels in lysates had fallen to only 54.6% of the maximal concentration. The cleavage of gasdermin E and the secretion of IL‐1β increased concurrently.

Conclusions: In contrast to classical immunological cells, the secretion of IL‐1β from human RPE cells is a slow process. IL‐1β is secreted trough gasdermin E pores. Our data suggest that the secretion phase is the rate limiting step.
Age‐related changes in mesopic macular light sensitivity in healthy eyes
Authors: Moreira‐Estebaranz Carolina , Remis‐Gonzalez Melisa , Cedrun‐Sanchez Juan , Puell María
Published: December 2022

Purpose: Advanced age and certain ocular pathologies are known to influence mesopic light sensitivity (MLS), but it is still unclear to what extent age can predict MLS in healthy subjects and whether there are age groups whose MLS is homogeneous. The aim was to analyse the effect of age on MLS in healthy subjects without ocular pathology.

Methods: This is an observational and cross‐sectional study in 154 healthy subjects aged between 20 and 80 years (mean 43.6 ± 17.9 years) and good visual acuity. The MLS was measured with macular integrity assessment (MAIA) microperimetry at the central 10° diameter circle. MLSs at the central subfield (1° radius) and four regions (temporal, nasal, superior, inferior) of the parafoveal ring (3°–5° radius of eccentricity) were registered. The influence of age on the total mean MLS was analysed using a polynomial regression. One‐way Anova was used to compare mean MLS in each decade of age. As a result, participants were divided into three age groups (young 20–39 years, middle‐aged 40–59, and older 60–79) based on their homogenous MLS. Comparisons of MLS across age groups were performed.

Results: The increase in age correlated with a decrease in the total mean MLS (r = −0.67; p = < 0.001). Mean total MLS decreased by 2.56 dB between the oldest and youngest age groups (p < 0.01). Means for MLS in the macular central subfield and in each region of the parafoveal ring (superior, temporal, nasal, inferior and overall) were significantly different in the three age groups (all (p < 0.001), with the highest sensitivities for the youngest group and the lowest for the elderly. There were not significant differences in mean MLS (total, central subfield and parafoveal regions) for men and women in each of the three age groups.

Conclusions: Age predicts mean macular MLS measured by microperimetry. MLS was homogeneous in the young, middle‐aged and older age groups, being higher in young subjects and decreasing significantly every two decades of age.
Resveratrol nanoparticles are neuroprotective in a model of Alzheimer's disease
Authors: Shamsher Ehtesham , Guo Li , Davis Benjamin , Luong Vy , Ravindran Nivedita , Somavarapu Satyanarayana , Cordeiro Francesca
Published: December 2022

Purpose: Alzheimer's disease (AD) is the major cause of dementia in the world with increasing evidences of the retina being affected. Since no cure exists, there is an urgent unmet need to find new treatments. Resveratrol, a natural polyphenol found in red wine, has been advocated as a potential neuroprotectant in this disease. However, resveratrol has a low solubility and bioavailability limiting its clinical translation. In this study, we assessed a novel formulation of resveratrol in vitro and in vivo in a triple transgenic Alzheimer's disease (3xTg‐AD) mouse model.

Methods: Resveratrol nanoparticles (RNs) were formulated using a thin rehydration technique. They were assessed in vitro on R28 cells against glutamate excitotoxicity and cobalt chloride induced hypoxia. Next, 3xTg‐AD mice received intranasally either RNs (n = 7) or an equivalent vehicle (n = 6) 5 days a week for 3 months. After 3 months of treatment, animals were imaged using Detection of Apoptosing Retinal Cells (DARC). DARC count was defined as the number of fluorescent spots counted by a masked investigator. After sacrifice, their brains were harvested and immunostained for amyloid‐beta (Aβ) and phosphorylated tau (pTau). Retinas were immunostained with Brn3a, a retinal ganglion cell (RGC) marker.

Results: RN formulation incorporating over 10 mg/ml resveratrol was stable over 90 days. RNs were able to protect R28 cells exposed to glutamate compared to the vehicle (IC50 25.1 ± 0.4 vs. 14.4 ± 1.0 mM, p < 0.0001) but did not show any neuroprotection against cobalt chloride compared to the vehicle (260.3 ± 16.5 vs. 200.7 ± 2 2.3 μM, p > 0.05). In vivo, DARC count was reduced with RN treatment compared to the vehicle (7.7 ± 2.1 vs. 49.1 ± 13.3, p < 0.01). However, these results did not correlate with a higher RGC density compared to the vehicle (1205 ± 203 vs. 1015 ± 100 cells/mm2, p > 0.05). Interestingly, Aβ and pTau depositions in the brain were reduced compared to the vehicle (3.6 ± 0.2 vs. 4.5 ± 0.2 Aβ score, p < 0.01 and 2.1 ± 0.5 vs. 6.6 ± 1.9 pTau score, p < 0.05). No adverse effects were seen in vivo either systemically or in the eye.

Conclusions: These promising results show that RN is non‐toxic and neuroprotective in vitro and in vivo when administered intranasally. However, DARC imaging failed to show a correlation with RGC density. Further studies are needed to confirm these results.
A systematic literature review of disease progression in RPGR‐associated X‐linked retinitis pigmentosa
Authors: Li Nan , Hashim Mahmoud , Scholl Hendrik , Lam Byron
Published: December 2022

Purpose: To assess disease progression qualitatively and quantitatively in RPGR‐associated X‐linked retinitis pigmentosa (RPGR‐XLRP).

Methods: PubMed was used to identify relevant studies (01/2000–09/2021). Search terms included RP, XLRP, history, progress, disease state, health state, and burden. Included studies focused on RPGR‐XLRP (ie, results specific to RPGR or RP studies with ≥80% of patients with RPGR variants). Endpoints of interest included changes in visual acuity (VA), visual field (VF), and ellipsoid zone width (EZW), progression to legal blindness, and patient‐reported outcomes (PROs).

Results: Of 1325 studies captured by search criteria (including those examining XLRP [n = 17], RP [127], and both XLRP and RP [6]), 11 met inclusion criteria for assessment of RPGR‐XLRP disease progression. In those with RPGR‐XLRP, data suggest progressive decline in VA, VF, and EZW. Annual changes in VA were equivocal, with two studies reporting positive or minimal change in best‐corrected VA (BCVA; +2%, −0.07%) and two studies reporting VA decline (−3.5 to −5.3%, −8.2%). Annual declines in VF, measured via Goldmann or Humphrey perimetry, were observed across studies (range, −4.5, −9.0%; n = 4 studies). EZW, measured via Heidelberg Spectralis OCT, became constricted over time (n = 5 studies); 2 studies showed an 8%–9% annual exponential rate of decline. In two studies, patients reached VA‐based legal blindness (BCVA <20/400 in the better seeing eye or <6/60) by median ages of 48 and 51.3 years; in another study, 18% reached blindness (BCVA <20/400) by age 40. PRO data in this patient population were limited.

Conclusions: Published evidence shows that those with RPGR‐XLRP experience significant progressive decline in VA, VF, and EZW, eventually resulting in blindness. There is a need for more standardized longitudinal data and expanded collection of PROs to better assess visual decline in RPGR‐XLRP.
MFSD2a, the transporter of the omega‐3 fatty acid DHA, is expressed in the neural retina
Authors: Pastor María José Ruiz , Albertos‐Arranz Henar , Sanchez Saez Xavier , Maneu Victoria , Lax Pedro , Cuenca Nicolas
Published: December 2022

Purpose: The omega‐3 fatty acid, DHA, is enriched in the outer disk and synapse membranes, and it exerts an anti‐inflammatory and anti‐apoptotic effect in the neuron cells. Animal models and patients with retinal dystrophies were reported to have reduced levels of DHA in the retina, so different nutraceuticals were designed for these patients. Nevertheless, it is still unknown how DHA is cached and distributed in the retina. MFSD2a was reported as the putative transporter of omega‐3, but its expression was only described in the endothelial cells. In this study, we assessed the expression of MFSD2a in the different cell populations of the neural retina.

Methods: The expression of MFSD2a was studied by immunofluorescence in cryostat sections of the retina from healthy human donors. Double immunolabelling with different cell markers was used to study MFSD2a expression in the different retinal cell populations. Cone arrestin was used for the identification of cone photoreceptor cells. Parvalbumin is a cell marker for all horizontal cells. The transcription factors Chx10 and Pax6 were used for the identification of bipolar and amacrine cells, respectively. KDEL, an endoplasmic retention signal peptide, was used for the visualization of ganglion cells. Müller cells and RPE are positive for CRALBP.

Results: We found that MFSD2a was expressed in the outer nuclear layer as well as in the inner segments of the photoreceptor cells. Outer segments showed weak or negative immunostaining. Immunoreactivity with anti‐MFSD2a was also detected in the inner nuclear layer. Double immunostaining with parvalbumin and the transcriptional factors Chx10 and Pax6 confirmed that all populations of horizontal, bipolar, and amacrine cells, respectively, expressed the omega‐3 transporter. Also, ganglion cells expressed MFSD2a. In the double immunolabelling with anti‐MFSD2a and anti‐CRALBP, Müller cells showed punctae of immunolabelling in the tips of the external limiting membrane. Although, RPE did not seem to express MFSD2a.

Conclusions: MFSD2a is expressed by the neural cells of the retina. Photoreceptor cells, Müller cells, and all populations of bipolar, amacrine, horizontal, and ganglion cells expressed the transporter of the omega‐3 fatty acid, DHA.
Intrastromal corneal ring segments implantation with the aid of a femtosecond laser in cases of mild to moderate keratoconus: A 3‐year study
Authors: Spanos Evangelos , Atzamoglou Spiros , Kontadakis Georgios , Kontomichos Loukas , Mpatsos Georgios , Paroikakis Eustratios , Peponis Vasileios
Published: December 2022

Purpose: To evaluate the 3‐year results of femtosecond assisted intrastromal corneal ring segments (ICRS) implantation for the treatment of mild to moderate keratoconus.

Methods: Prospective case series including 4 eyes of 4 consecutive patients with keratoconus.

Each patient was implanted with ICRSs according to the preoperative topography and refraction. The segments were implanted in intracorneal pocket created with the FS200 femtosecond laser. Planning of the operation was done based on the nomograms provided by the manufacturer. Patients' follow‐up involved visual acuity measurement, refraction control, clinical examination, corneal topography (Pentacam and Orbscan) and anterior segment OCT. The operation was performed due to patients' unsatisfying spectacle corrected visual acuity and contact lens intolerance.

Results: Preoperative average steep keratometry was reduced from 53,3D (range 50.7–55.7D) to 48.6D (range 46.9‐50D) 3 years postoperatively. Preoperative average topographic astigmatism was 5.35D (range 4.2–7.9D) while postoperative was 2.7D (range 0.7–4.3D). Refraction assessment showed reduction of the refractive astigmatism from 3.5D (range 2.0–5.0D) to 2,5D (range 0.5–3.75D) and improvement of spherical equivalent from −5.0D (range − 4.0 to −7.25D) preoperatively to −2.5D (range −1.25 to −3.25D) 3 years postoperatively. Average pre‐op spectacle corrected visual acuity was 4/10, when post‐op visual acuity assessment on Snellen scale showed average improvement by 2 lines (range from 0 to 5 lines).

Conclusions: The femtosecond assisted ICRS implantation based on the results of our study, improved all patients' visual acuity, topographic and refractive parameters 3 years postoperatively.
Choroidal vascularity index: An emerging useful metric for choroidal structure assessment in pachychoroid spectrum disease
Authors: Sassi Hela , Abid Yosra , Meriem Ouederni , Nouri Slim , Cheour Monia
Published: December 2022

Purpose: To compare choroidal vascularity index (CVI) between eyes with different entities of pachychoroid spectrum diseases (PSD) and a control group.

Methods: Eighty‐two eyes of 45 patients with PSD were included in our study. Fifteen eyes had uncomplicated pachychoroid (UCP), 27 eyes had pachychoroid pigment epitheliopathy (PPE), 32 eyes had central serous chorioretinopathy (CSC) and 8 had pachychoroid neovasculopathy (PNV). These eyes were compared to 67 eyes of 34 age‐matched healthy controls. All eyes underwent DRI‐OCT Triton Swept‐Source Optical Coherence Tomography (OCT). B‐scan images were binarized into blood vessels lumen and stroma using ImageJ software. The choroidal vascularity index (CVI) was defined as the ratio of luminal area (LA) to total choroidal area in a subfoveal region of 1500 μm width.

Results: Mean CVI in patients with PSD was 64.45 ± 2.74%. A statistically significant difference was found between the PSD patients group and the control group (p < 0.001) with a higher CVI in PSD eyes. Pairwise comparisons revealed statistically significant differences between PPE/PNV groups (p < 0.05), PPE/control groups (p < 0.001), CRSC/control groups (p < 0.05) and CRSC/PPE groups (p = 0.05). The comparison between UCP/control groups, UCP/PPE groups, UCP/CRSC groups, UCP/PNV groups, PNV/control groups and PNV/CRSC groups showed no significant difference.

Conclusions: Increased CVI may reflect choroidal vascular structure changes in eyes with PSD. These findings suggest that the CVI could be useful for evaluating choroidal vascular changes in eyes with PSD and predicting a potential progression form PPE to CRSC or PNV.
Incidence and prevalence of paediatric noninfectious uveitis in South Korea
Authors: Kim Bo Hee , Chang In Beom , Lee So Young , Oh Baek‐Lok , Hong In Hwan
Published: December 2022

Purpose: To investigate the nationwide incidence and prevalence of paediatric uveitis in South Korea according to period, age, anatomic type, and systemic associations.

Methods: This nationwide population‐based cohort study used data from the Korean National Health Insurance Service from 2002 to 2018. This study included patients with noninfectious uveitis with at least three claims of diagnostic codes of uveitis on separate days with at least once claim of prescription codes of steroid and immunosuppressive agents. All the cases were classified as anterior or non‐anterior uveitis, and the incidence and prevalence were estimated by age, sex, period, and systemic associations.

Results: A total of 10 862 616 patients over 128 688 078 person‐years were evaluated from 2005 to 2016. Overall, 5368 cases of anterior uveitis and 604 cases of non‐anterior uveitis were identified. The incidence and prevalence of paediatric noninfectious uveitis were 4.64 per 100 000 person‐years and 8.25 per 100 000 persons. Both the incidence and prevalence increased with age. Anterior uveitis accounted for 84.7% of prevalent cases (6.99 per 100 000 persons). Cases of juvenile idiopathic arthritis (JIA)‐associated uveitis accounted for 8.7% of paediatric noninfectious uveitis cases with a prevalence of 0.72 per 100 000. The proportion of systemic associations was higher and JIA‐related uveitis accounted for 11.2% of recurrent or chronic cases with a prevalence of 0.62 per 100 000.

Conclusions: This is the first population‐based study investigating the largest population of paediatric patients with uveitis in Korea. The nationwide incidence and prevalence in 2005–2016 were 4.64 per 100 000 person‐years and 8.25 per 100 000, respectively. The proportion of JIA in paediatric noninfectious uveitis was 8.7%. These population‐based study findings provide a better understanding of the public health burden and aid in the planning of health‐care strategies for paediatric patients with uveitis.
Precision and agreement of individual and simultaneous volumetric measurements with optical coherence tomography in healthy and glaucoma subjects
Authors: Venkataraman Abinaya , Hedström Johan , Al‐Soboh Loujain , Dominguez‐Vicent Alberto
Published: December 2022

Purpose: To assess the repeatability of individual and combined macula and optic disc volumetric analysis, and the agreement between both scan modes with optical coherence tomography (OCT) in glaucoma and healthy control eyes.

Methods: 27 subjects with a previous diagnosis of glaucoma were included. The control group included 34 healthy subjects older than 50 years. Volumetric measurements of the macula and optic disc were performed with a spectral domain OCT. Two different scan protocols (individual and combined) were performed in each participant, and each scan mode was repeated three times. The retinal and ganglion cell complex thickness were analysed in nine and eight sectors respectively. The peripapillary retinal nerve fibre layer (pRNFL) thickness was analysed in 12 clock sectors from the optic disc area. The repeatability limit (Rlim) and agreement analysis were performed for each sector analysis.

Results: For the retinal thickness, the differences in the Rlim between both scan modes was lower than 5 μm. The differences in the Rlim between the control and glaucoma groups were lower than 3 μm. The limits of agreement interval were lower than 20 μm for each population group. The ganglion cell complex measurements showed larger repeatability values for the combined scans for each group, and the limits of agreement intervals were lower than 13 μm. The differences in the Rlim between the control and glaucoma groups were lower than 3 μm. For the pRNFL thickness, the differences in the Rlim between both scan modes were lower than 10 μm. The control group showed lower repeatability values than the glaucoma group except on sectors 2 and 3. For both population groups, the horizontal sectors showed shorter limit of agreement intervals than the vertical sectors.

Conclusions: Similar repeatability values were obtained between both scan modes in each population group. Both scan modes cannot be used interchangeable due to the wide limits of agreement.
Effect of filters on the accommodation and colour discrimination
Authors: Dominguez‐Vicent Alberto , Venkataraman Abinaya
Published: December 2022

Purpose: To evaluate the effect of coloured filters on the accommodative response and colour discrimination in young subjects.

Methods: Two long pass filters (LED light reduction and 511 nm filter), two selective absorption filters (ML41 and emerald filter), and no filter condition were evaluated. The photorefractor PowerRef3 (PlusOptix) was used to measure the objective refraction at 3 different distances (40, 100, and 400 cm). The measurement obtained at 400 cm was used as a reference to calculate the accommodative response. The fixation target consisted of five letter length words (size corresponding to 6/12 Snellen) that were presented in black font over white background. Words changed with a frequency of 2 Hz according to the rapid serial visual presentation paradigm. The Cambridge Colour Test (Metropsis) was used to measure the discrimination threshold in a 10‐vector ellipse at a 3 m viewing distance. The measurement was repeated twice, and it was performed monocularly. In total, 20 healthy volunteers with no accommodation problems or colour blindness were included.

Results: On average, the accommodative response with no filter condition was larger compared to the measurements with filters for 40 and 100 cm. The differences were in all cases lower than 0.25D, and differences were not statistically significant (p > 0.05). For the colour discrimination thresholds, the ML41 and 511 filters showed statistically significant different values compared to the other two conditions for most of the vectors. The filter 511 had the highest impact on the colour vision, as the results resemble to a Tritan defect.

Conclusions: The accommodative response in healthy young adults was not significantly different than the no filter condition. The colour discrimination thresholds with the filter ML41 and 511 were significantly different compared to the no filter condition.
Morphological comparison of the microglial cell population between organotypic retinal cultures and axotomised retinas in vivo
Authors: Riquelme María Josefa González , Lucas‐Ruiz Fernando , Galindo‐Romero Caridad , Boia Raquel , Ambrósio António Francisco , Vidal‐Sanz Manuel , Santiago Ana Raquel , Agudo‐Barriuso Marta
Published: December 2022

Purpose: Retinal organotypic cultures (ROCs) have been used since the early 1930s as in vivo surrogates to study retinal ganglion cell (RGC) loss and neuroprotection. In this work we purposed to analyse and compare the morphological changes of microglial cells (MCs) along time in ROCs and axotomised retinas.

Methods: C57/Bl6 mice were used. For the in vitro model, retinas were dissected and cultured in supplemented medium. In the in vivo model, the left optic nerve (ONC) was crushed. In both models, retinas were analysed at 24‐h intervals for up to 7 days. MCs were then immunodetected with anti‐Iba1 antibody and then photographed in the ganglion cell layer (GCL) of the retina using a confocal microscope. Finally, their morphology was quantitatively analysed using the free Image J Fiji software.

Results: After ONC, the number of MC processes decreased significantly from day 1 to 7 compared to intact retinas. Similarly, we observed a significant decrease in the number of processes of in vitro MCs, which was significantly greater than after axotomy in vivo The total length of the processes decreased in both models up to 7 days. When studying the size of the MCs, it was observed that from 1 to 7 days MCs were bigger in vitro than in vitro and in both models than in intact retinas.

Conclusions: The morphology of MCs differs in vivo and in vitro, suggesting a differential activation.
Intravitreal panitumumab for prevention of myopic axial elongation in highly myopic adult eyes with myopic macular degeneration: Phase 1 study on safety
Authors: Jonas Jost , Gyulli M. , Holz Frank , Panda‐Jonas Songhomitra , Leisan Gilemzyanova , Khakimov Dinar Dinar A. , Mukharram Bikbov
Published: December 2022

Purpose: Recent histomorphometric and clinical studies suggested that axial myopic elongation occurs through an enlargement of Bruch's membrane (BM) in the retroequatorial and equatorial region, leading to a thinning of choroid and sclera at the posterior pole. Thickness of the retina and choriocapillaris and RPE‐density in the macular region and BM thickness in any region remain independent of axial length. The equatorial‐to‐retroequatorial BM enlargement may be caused by an epidermal growth factor (EGF)‐associated RPE activity. Experimental studies in guinea pigs and monkeys showed a reduction in axial elongation by intravitreally applied blockers of EGF family members and the EGF receptor, and an increase in axial elongation by intravitreally applied EGF family members. In a clinical study, the intraocular EGF amount correlated with longer axial length. It led to the hypothesis, that ocular axial elongation is associated with EGF, and that further axial elongation may be prevented by an EGF blockade. We examined here the safety of intravitreally applied panitumumab, an EGF receptor blocker, already in clinical systemic use in oncology for two decades.

Methods: The phase‐1 study included highly myopic adult patients with myopic macular degeneration. The eyes received one to two intravitreal injections of 0.6 mg (60 μl), 1.2 mg (120 μl) or 1.8 mg (180 μl) panitumumab.

Results: The study included 10 patients (age 57–72 years, axial length: 29.10 mm–32.67 mm). Examined at day 1, 7, and 28 and at 2 and 3 months after the injections, the injected eyes did not show any intraocular inflammation or morphologic or functional changes, assessed by retinal electroretinography, perimetry, optical coherence tomography, tonometry and visual acuity measurement.

Conclusions: The preliminary observations of these 10 patients are in agreement with a notion of an intraocular tolerability of panitumumab repeatedly injected intravitreally in doses of 0.6, 1.2 or 1.8 mg.
Neuroprotective effects of ITH‐IB6 against excitotoxicity‐induced retinal injury
Authors: Di Pierdomenico Johnny , Muñoz María Norte , Ortega Alejandro Gallego , Ruiz María Boluda , Garro Jose Manuel Bernal , Perez Maria Paz Villegas , De los Rios Cristobal , Vidal‐Sanz Manuel
Published: December 2022

Purpose: To investigate the dose/response curve, therapeutic window, length of treatment and protective effects of ITH‐IB6 on retinal ganglion cell (RGC) survival in a model of NMDA‐induced excitotoxicity.

Methods: Adult Sprague Dawley rats received in their left eye an intravitreal injection of 100 mM NMDA and were treated with subcutaneous (sc) injections of vehicle (1% DMSO in saline) or ITH‐IB6 diluted in vehicle. For the dose–response study different concentrations of ITH‐IB6 (1, 3, 10, 10, 30, or 60 mg/kg) were injected for 7 days (d). To determine the therapeutic window, ITH‐IB6 was administered 12 hours (h) before or 1, 12 or 24 h after NMDA injection. To investigate duration of treatment with optimal results, ITH‐IB6 was administered for 1, 2, 3 or 7d after NMDA. Using optimal treatment protocols obtained from the above mentioned studies, ITH‐IB6‐afforded protection was studied in vivo with OCT (before processing each animal) to examine retinal thickness, and ex vivo by quantifying surviving RGCs. Retinas were analysed 7, 14 or 21d after NDMA injection and sc ITH‐IB6.

Results: The dose–response study showed significant protection with 10 or 30 mg/kg ITH‐IB6, best protection was obtained when treatment was initiated 12 h before NMDA injection and the length of treatment study documented that sc ITH‐IB6 administration for 3d provided optimal effects. In vivo, significant retinal thickness preservation was observed in ITH‐IB6‐treated when compared to vehicle‐treated rats. Ex vivo results showed that in contrast to saline, ITH‐IB6 afforded significant protection of Brn3a + RGCs at 7, 14 and 21d, respectively, after NDMA injection.

Conclusions: sc ITH‐IB6 (30 mg/kg) administered 12 h before NMDA‐induced retinal injury for 3d, protects RGCs against excitotoxicity‐induced RGC death.
Vision loss, third and fourth nerve palsy and non‐responsive midriasis after contralateral retrobulbar anaesthesia
Authors: Artola Ines , Lillo Nuria Ramirez , Morales Manuel , Conesa Eduardo , Moriche Manuel
Published: December 2022

Purpose: The purpose of this communication is to report a case of vision loss, third, and fourth nerve palsy and midriasis after contralateral retrobulbar anaesthesia. Although contralateral vision loss has been reported after locoregional block, very little evidence has been found about contralateral extraocular movement palsy and midriasis. Mechanism is not well known, though it is believed to be a consequence of the accidental subdural/subarachnoid anaesthetic injection.

Methods: A case which took place at our hospital was selected. A retrobulbar block was performed by the service of anesthesiology in an 80‐year‐old patient prior to cataract surgery on the right eye. The block consisted of a 5 ml injection of 0.5% levobupicain and 2% lidocain (1:1) in his right eye under monitorization and sterile conditions. 10 min after the injection the patient presented bradycardia, hypotension and decreased consciousness. He was administered 0.6 mg atropine, 3 ephedrine bolus and 8 migr noradrenaline and his constants came back to normality. He was kept in observation in the recovery room. After consciousness recovery he claimed vision loss in the fellow eye.

Results: At the exploration we found complete vision loss with no light perception, ptosis, third and fourth nerve palsy and dilated and non‐responsive pupil in the left eye. Funduscopy was unremarkable. He was kept in observation and 45 min later he was reexplored: ptosis, extraocular movements and pupil size improved; 2 h later exploration was completely normal.

Conclusions: To conclude, we wanted to remember some of the possible complications of retrobulbar block and the importance of its conscious selection. Above all, we wanted to highlight this infrequent reaction on the fellow eye about which we have found very little evidence.

References

1. Krilis M, Zeldovich A, Garrick R, Goldberg I. Vision loss and partial third nerve palsy following contralateral peribulbar anaesthesia. Journal of Cataract and Refractive Surgery. 2013;39(1):132–133.

2. Antoszyk A, Buckley E. Contralateral Decreased Visual Acuity and Extraocular Muscle Palsies Following Retrobulbar Anaesthesia. Ophthalmology. 1986;93(4):462–465.
The link between anterior scleral thickness, corneal biomechanical response and ocular parameters
Authors: Giménez Neus Burguera , Ajenjo Amparo Díez , Burguera Noemi , Cobija Maria Josefa Luque , Lopez Celeste Briceno , García‐Domene Mª. Carmen , Peris‐Martínez Cristina
Published: December 2022

Purpose: to assess anterior scleral thickness (AST) across diverse scleral meridians and to evaluate the relationship with corneal biomechanical response and several ocular parameters.

Methods: This prospective non‐randomized study comprised 50 eyes of 50 patients (mean age, 29.02 ± 9.48 years). Anterior scleral thickness was measured meridionally at three scleral locations (1‐, 2‐, and 3‐mm posterior to the scleral spur) using swept‐source optical coherence tomography. A multivariate model was created to associate AST with several ocular parameters. Principal component analysis (PCA) was used to reduce linearly the dimensionality of seven biomechanical input metrics to two significant components, C1 and C2. Two multivariate analyses were performed to associate C1 and C2 with AST and ocular parameters.

Results: AST was thickest in the inferior (581 ± 52 μm) and thinnest in the superior meridian (441 ± 42 μm) when compared to all meridians (p < 0.001), and similar in the nasal (529 ± 53 μm) and temporal (511 ± 59 μm) meridians (p > 0.05). The sclera exhibited the thinnest point 2 mm posterior to the scleral spur (p < 0.001). The AST was significantly linked with axial length, central corneal thickness, and intraocular pressure (p < 0.001). The PCA showed that C1 accounts for 53.84% whereas C2 for the 16.51% of the total variance in the original variables. The C1 model was significantly associated with AST along all meridians (p < 0.001). The partial correlation was moderate in the nasal (r = −0.36, p < 0.001) and inferior (r = −0.26, p = 0.004) meridians whereas weak in the temporal (r = −0.14, p = 0.05) and superior (r = −0.15, p = 0.05) meridians.

Conclusions: The relationship between the new biomechanical component and the AST provides the first evidence of the association of AST with the corneal response parameters which should be considered in corneal response interpretation. Tissue thickness varied significantly among meridians supporting the asymmetrical expansion of the ocular globe. The AST was associated with several ocular parameters.
TCF4 trinucleotide repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy
Authors: Pettinen Inka‐Tuulevi , Immonen Annamari , Rämö Joel , Jaakkola Aino , Krootila Kari , Kaukonen Maria , Lohi Hannes , Kivelä Tero , Turunen Joni
Published: December 2022

Purpose: To study the presence and role of transcription factor 4 (TCF4) triplet repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy (FECD) which causes a progressive loss of corneal endothelial cells, resulting in loss of corneal clarity, and is the leading cause of corneal transplantations in Western countries. FECD has a heterogeneous genetic background, but the best‐known risk variant is a CTG‐repeat expansion in the TCF4 gene. An expansion of more than 40 repeats is associated with an increased risk for the disease.

Methods: One hundred and twelve Finnish patients with a clinical diagnosis of FECD treated in the Helsinki University Hospital, and 202 control individuals from the Finnish Red Cross Biobank were enrolled. The patients were examined by slit‐lamp, anterior segment photography, corneal tomography, OCT, and endothelial specular microscopy. To assess the repeat number in TCF4, short tandem repeat analysis and triplet repeat primed PCR were used.

Results: Of the 112 patients with FECD, 79 were female and 33 male. A CTG‐expansion of >40 was observed in 84% (95% confidence interval [CI], 76–90) of the patients of whom two had the expansion in both alleles. In contrast, only 3% (95% CI, 1–6) of the 202 control individuals had such an expansion, each of them in a heterozygous state. Of the patients with <40 vs. >4 0 CTG‐repeats 89% vs. 97% had transplantation surgery performed in at least one eye.

Conclusions: These results indicate that the CTG‐repeat expansion in TCF4 is a notable risk factor for FECD also in the Finnish population with >80% of the patients carrying the expansion. Further analysis will be performed to clarify the association of the expansion with the clinical and pathological features in these patients.
Role of the haematological phenotype as a predictive biomarker of retinopathy of prematurity development
Authors: Martins Mariza Fevereiro , Santos Ana Carolina , Teixeira Filipa , Rosa Rita , Barros Pedro , Parreira Ricardo , Teixeira Susana , Mota Mafalda , Monteiro Madalena , Alfaiate Mário , Silva Renato , Breda Jorge , Guimarães Hercília , Marques‐Neves Carlos , Bicho Manuel
Published: December 2022

Purpose: To evaluate haematological parameters as possible biomarkers of the development of retinopathy of prematurity (ROP).

Methods: Multicenter, observational, and prospective study of preterm infants (PTI) from eight NICU, born in Portugal with gestational age (GA) < 32 weeks or birth weight (BW) <1500 g. ROP staging performed according to the International Classification of ROP (ICROP). Sociodemographic, clinical and laboratory data were collected from the first week of life. Complete blood count (CBC) was determined according to standardized methods. According to the maximum stage of ROP, PTI were divided into four groups: without ROP, ROP stage 1 (ROP‐1), ROP stage 2 (ROP‐2) and ROP stage 3 (ROP‐3). Statistical analysis was performed with the SPSS program with significant value for p < 0.05.

Results: 455 PTI were included, GA average of 29.5 ± 2.3 weeks, BW average of 1165.7 ± 313.9 grams and 50.5% were female. In this study 37.8% of the PTI developed ROP: 20% had ROP‐1, 9.4% ROP‐2 and 8.4% ROP‐3. 4.6% of PTI received treatment: laser was performed in 12 PTI (2.6%), anti‐VEGF in 7 PTI (1.5%), anti‐VEGF and laser in 1 PTI (0.2%), and anti‐VEGF, laser, and surgery in 1 PTI (0.2%). ROP‐3 was significantly associated with lower GA (p = <0.001), BW (p < 0.001), erythrocytes (p < 0.001), haemoglobin (p < 0.001), haematocrit (p < 0.001), lymphocyte (p = 0.047) and lymphocyte to monocyte ratio (LMR) (p = 0.018) compared with the other groups. Neutrophils (p = 0.039) and neutrophil to lymphocyte ratio (NLR) (p < 0.001) were higher in ROP‐3. For PTI who did not develop ROP were observed, in relation with the other groups: higher mean corpuscular haemoglobin concentration (MCHC) (p < 0.001), platelets (p = 0.029) and plateletcrit (PCT) (p = 0.007) and lower red cell distribution width (RDW) (p = 0.015) and erythroblast (p < 0.001).

Conclusions: This study shows that the increase in neutrophils, NLR, and RDW and the decrease in lymphocytes, LMR, erythrocytes, and platelets may constitute early and low‐cost predictive biomarkers of ROP development.
GPx4 reduces laser‐induced choroidal neovascularization by inhibiting ferroptosis
Authors: Qu Sichang , Grus Franz
Published: December 2022

Purpose: To investigate the protective effects of glutathione peroxidase 4 (GPx4) in laser‐Induced age‐related macular degeneration (AMD) animal model.

Methods: In this study, Norway brown rats were used to establish a laser‐induced AMD model. To investigate the protective role of GPx4, rats received laser photocoagulation and intravitreal injection of GPx4 (25 μg/eye) or PBS on the same day. The size and vascular leakage of choroidal neovascularization (CNV) were measured on 7 and 14 days after lasing by using OCT and FA. Immunohistochemical staining of the choroidal flat mounts with CD31 were used to assess angiogenesis.

Results: Compared with PBS group, intravitreal injection of GPx4 decreased the CNV size of 0.083 ± 0.121, P = 0.07 on day 7 and 0.11 ± 0.135 (p < 0.05) on day 14. By leakage grading, the CNV lesion with pathologically significant leakage (grade 2a and 2b) was reduced in GPx4 group (2%) and increased in PBS group (25.6%) from day 7 to day 14. The immunostaining with CD31 showed smaller lesions in GPx4 group than PBS group.

Conclusions: This study showed that GPx4 inhibited CNV formation and providing a novel molecular target against ferroptosis for wet AMD treatment.
the effect of amniotic membrane proteins released by ocular inserts containing self‐healing hydrogels
Authors: Acera Arantxa , Esporrin David , Diaz Aitor , De Souza Juliana , Fernandez Mercedes , Burgos Jorge , Zabalza Javier , Pereiro Xandra , Calderon Marcelo , Dupin Damien , Vecino Elena
Published: December 2022

Purpose: Growth factors found in the amniotic membrane (AM) help accelerate epithelium regeneration in the damaged cornea or conjunctiva. This study compares the effects of hydrogels releasing the AM proteins on the proliferation, migration, and time‐to‐closure (healing) of the conjunctival epithelium.

Methods: Proteins extracted from the AM using sonication were incorporated into two hydrogels used as ocular inserts. The tested inserts materials were the self‐healing, dynamic hyaluronic‐acid hydrogel based on gold‐thiolate/disulfide exchange (Hydrogel A) and a physically cross‐linked hydrogel based on a combination between Eudragit S100 and hyaluronic acid with a reinforced matrix by polyvinyl alcohol, polyvinyl pyrrolidone and polyethylene glycol (Hydrogel B). In an in vitro experiment, a scratch was made on the human conjunctival epithelium cells (Chang Conjunctiva, Clone 1‐5c‐4) to mimic an incision wound. The cells were cultured with hydrogels for 48 hours to study the effect of these materials on epithelium repair. The samples were examined using a Zeiss Observer Z1 inverted microscope, and the results were evaluated employing the Image‐J program to obtain the cell migration rate (μm/h).

Results: Hydrogel A increased the rate of closure at 22 h (121 ± 19 μm) in comparison with Hydrogel B (394 ± 78 μm). After 46 h, the scratches in Hydrogel A and control cultures were completely closed, while the Hydrogel B samples had an unclosed area of 54 ± 4 μm.

Conclusions: Both hydrogels promoted wound healing in cultured conjunctival epithelium cells. However, a lower rate of wound closure was observed for Hydrogel B than for Hydrogel A and the control, probably because the speed of cell proliferation was slower in Hydrogel B. The wound‐healing assay showed that the Hydrogel A and B increased cell viability and significantly stimulated cell migration.
Novel biallelic AHR splice site mutation cause isolated foveal hypoplasia in Saudi patient
Authors: Almoallem Basamat
Published: December 2022

Purpose: To study the clinical and molecular findings of a nonconsanguineous Saudi family with one affected 12 years boy affected by isolated foveal hypoplasia with no signs of infantile nystagmus.

Methods: Comprehensive clinical and molecular approaches were applied including detailed ophthalmological examination followed by whole‐exome sequencing (WES).

Results: Detailed ophthalmological examination revealed bilateral isolated foveal hypoplasia with the absence of the avascular zone. Novel homozygous aryl hydrocarbon receptor (AHR) splice site mutation; NM_001621.4: c.899_908 + 15del (p. ?) was identified and segregated within the family members.

Conclusions: Our identified novel splice‐site AHR mutation supports the pathogenicity of the AHR gene and expands its phenotypic spectrum. Our study represents the first report of autosomal recessive isolated foveal hypoplasia without infantile nystagmus in the literature and the second reported AHR mutation with autosomal recessive isolated foveal hypoplasia post the original cloning paper.
Retinal vascular study using OCTA In subjects at high genetic risk of developing Alzheimer's disease
Authors: López‐Cuenca Inés , Salobrar‐Garcia Elena , Sanchez‐Puebla Lidia , Espejel Eva , Del Arco Lucia García , Lozano María Pilar Rojas , Elvira‐Hurtado Lorena , Fernández‐Albarral José A. , Salazar Juan Jose , Ramírez‐Toraño Federico , Barabash Ana , De Hoz Rosa , Ramirez Jose Manuel , Ramirez Ana Isabel
Published: December 2022

Purpose: To analyse morphological changes in retinal vascular network in 103 subjects with a high genetic risk of developing Alzheimer's Disease (AD) ((family history of AD(FH) and ApoE ɛ4 characterization (ApoE ɛ4)).

Methods: OCTA images were analysed with two imaging software programs: AngioTool and Erlangen‐Angio‐Tool (EA‐Tool). Participating subjects were classified according to HF into HF− or HF+ and ApoE ɛ4 characterization into ApoE ɛ4− or ApoE ɛ4+. Vascular density was analysed considering two vascular risk factors: hypercholesterolemia (HCL) and arterial hypertension (HBP).

Results: Taking account FH and allelic characterization, vascular changes were observed mainly in the peripapillary zone. In this zone, Angio‐Tool showed in the FH+ ApoE ɛ4− group a statistically significant higher of vessels surface area percentage compared to the FH+ ApoE ɛ4+ group. EA‐Tool showed in the C3 annulus in the FH+ ApoE ɛ4+ group, statistically significant higher vascular densities compared to the groups: (i) FH− ApoE ɛ4− in sectors H3, H4, H10, and H11; and (ii) FH+ ApoE ɛ4− in sectors H4, and H12. In participants with vascular risk factors (LCH and BPH), statistically significant changes were found especially with EA‐Tool, both in the macular area, mainly in the deep plexus, and in the peripapillary area.

Conclusions: In subjects with two genetic risk factors for the development of AD, OCTA is able to show an apparent increase in vascular density in some sectors of the retina, probably caused by the opening of arteriovenous shunts. This finding is one of the first vascular changes detectable by OCTA in this type of high‐risk subjects for the development of AD. This constitutes a promising biomarker to monitor the progression of the disease.
Therapeutic window and neuroprotection with 7,8‐Dihydroxyflavone in degenerating retinal ganglion cells after excitotoxic damage
Authors: Galindo‐Romero Caridad , Asís‐Martínez Javier , Navarro Manuel Angel Salinas , Di Pierdomenico Johnny , Muñoz María Norte , Bernal‐Garro Jose M. , Ortega Alejandro Gallego , Vidal‐Villegas Beatriz , Perez Maria Paz Villegas , Vidal‐Sanz Manuel
Published: December 2022

Purpose: To evaluate the optimal therapeutic window of 7,8‐Dihydroxyflavone (DHF), an agonist of TrkB receptor, as a neuroprotectant for degenerative retinal ganglion cells (RGCs) due to an excitotoxic damage with N‐methyl‐D‐aspartic acid (NMDA).

Methods: In adult albino Sprague–Dawley rats, NMDA (5 μl of 100 nM) was intravitreally injected into the left eye (day 0) and the animals were sacrificed after 7 days. In these animals, the treatment regimen of systemically administered DHF (5 mg/kg) was evaluated in four groups of increasing dose range (n = 8/group): a single injection of DHF (day −1), two injections (days −1 and 0), four injections (days −1, 0, 1 and 2) and seven injections (day −1 and one daily injection until processing). The number of Brn3a+RGCs was automatically quantified in whole‐mounted retinas. Once the optimal dose of DHF was stablished, the time course of Brn3a+RGCs degeneration was analysed at 3, 7 and 14 days after NMDA administration (n = 8/time‐point) and their treatment with 4 injections of DHF or vehicle (0.9% NaCl containing 1% DMSO). The number of Brn3a+RGCs in injured retinas was quantified and the spatial distribution was assessed with isodensity maps. As control, intact retinas were used.

Results: Seven days after NMDA injury, DHF treatment increases the percentage of surviving Brn3a+RGCs from 27% to 68% when retinas were treated with one injection to four injections, respectively (p < 0.05). No significant changes were found between four or seven DHF injections, indicating that the optimal treatment regimen for DHF is four injections and showing a rescue of Brn3a+RGCs over the entire retinal surface. Using this DHF dose at different time‐points after NMDA injury, DHF treatment rescues most Brn3a+RGCs degeneration at 3 days and it decreases up to 56% at 14 days.

Conclusions: DHF prevents RGC death following NMDA excitotoxic damage.
comparative analysis between early and late onset primary angle closure glaucoma
Authors: Gupta Shikha , Sapkal Shruti , Dada Tanuj , Yadav Suresh , Gupta Viney
Published: December 2022

Objective: This prospective observational pilot study aimed at comparing the aetiology and clinical profile of early onset primary angle closure glaucoma (EPACG) with late onset primary angle closure glaucoma (LPACG).

Methods: The early (18–40 year) and late (≥50 year) onset PACG patients without any surgical intervention or any other pathology (leading to secondary angle closure) were enrolled. One eye of each patient was considered for analysis. Clinico‐demographic details of the patients were noted. Anterior segment optical tomography (CASIA2, Tomey Corporation, Japan), Ultrasound biomicroscopy (Vumax, Sonomed, NY) were performed to identify the etiopathogenesis among two groups.

Results: Mean age of participants was 32.8 ± 7.8 years EPACG (n = 45) and 55.83 ± 6.7 years in the LPACG group (n = 31). Relative pupillary block (90.32%, n = 28) was the commonest mechanism of angle closure in LPACG while non pupillary block [66.67%, n = 31, pseudoplateau iris‐ 44.44% (n = 20), plateau iris‐24.44% (n = 11)] was the commonest mechanism in EPACG group. The EPACG had significantly shorter axial length (22.1 ± 1.1 vs 22.93 ± 1; p = 0.003), thinner lens (4.35 ± 0.3 vs. 4.6 ± 0.2; p = 0.01), more anterior relative lens position (0.19 ± 0.01 vs. 0.2 ± 0.01; p = 0.007), lesser anterior chamber depth (2.1 ± 0.3 vs. 2.3 ± 0.32; p = 0.01) and lesser anterior chamber area (15 ± 3.3 vs. 16.7 ± 3.4; p = 0.04) compared to LPACG. EPACG had greater lens vault (0.79 ± 0.4 vs. 0.61 ± 0.2; p = 0.01) compared to LPACG. Among the EPACG, 15.55%, (n = 7, vs. none in LPACG) had nanophthalmos. The BCVA was worse in EPACG (0.2 (range 0–2) vs. 0.6 (0–2) logMAR in LPACG) despite refractive error being more emmetropic vs LPACG.

Conclusions: Non pupillary block mechanisms are more common in EPACG as compared to LPACG. Despite thinner lens, early onset group has greater lens vault and shorter axial length contributing to greater angle crowding and present with greater visual morbidity.