bluuebunny/crossref_metadata_2025 huggingface dataset:
characterization of retinal ganglion cells subtypes in the rat retina
Authors: Ruzafa Noelia , Villegas Patricia , Prieto Laura , Pereiro Xandra , Vecino Elena
Published: December 2022

Purpose: Retinal ganglion cells (RGCs) are a heterogeneous population of neurons that propagates visual information to the brain. Glaucoma is a disease characterized by the selective death of RGCs, which induce a progressive and irreversible loss of vision. In glaucoma, not all RGCs subtypes are affected equally; however, a rigorous characterization has not been fully described. Thus, the aim of this work is to fully characterize and quantify different RGCs subtypes at different localizations in rat retinas.

Methods: RGCs were labelled by immunochemistry in control rat whole‐mount retinas. Images were captured using the optic disc as a reference for the different retinal zones. RGCs were labelled with an antibody against RBPMS that is considered the 100% of RGCs, and co‐labelled with subtype‐specific antibodies against: CART, Islet1/2, TBR2, SPP1. After quantification, the percentage of RGCs of each subtype were calculated in relation to the total RBPMS positive cells.

Results: In the rat retina, the density of RGCs was 1853/mm2 in centre, 2041/mm2 in middle‐centre, 1760/mm2 in middle‐periphery and 916/mm2 in periphery. CART was expressed in 31.2% of the RGCs from the centre, in 32.1% from the middle‐centre, in 33.3% from the middle‐periphery and in 27.8% from the periphery of the retina. Islet1/2 was expressed in 72.4% of the central RGCs, in 79.3% from the middle‐central RGCs, in 77.8% from the middle‐peripheral RGCs and in 72.4% from the peripheral RGCs of the retina. TBR2 was expressed in 11.4% of the RGCs from the centre, in 13.3% from the middle‐centre, in 12.8% from the middle‐periphery and in 16.1% from the periphery of the retina. SPP1 slightly marked the soma of almost 100% of total RGCs.

Conclusions: There is a characteristic pattern for each RGCs subtype in the rat retina. Therefore, we will compare these results with the same analysis in a rat glaucoma model allowing us to elucidate which RGCs subtypes are most susceptible.

Supported by ELKARTEK (KK‐2019/00086), MINECO‐Retos (PID2019‐111139RB‐I00) and PIBA (2020_1_0026).
The stiffness of the substrate affects Müller cell survival, morphology and reactivity
Authors: Prieto Laura , Pereiro Xandra , Villegas Patricia , Ruzafa Noelia , Vecino Elena
Published: December 2022

Purpose: Müller cells (MCs), the main glial cell type of the retina, are key to retinal homeostasis, metabolism, neuronal support and signalling. They have been shown to be mechanosensitive and thus respond to mechanical cues such as changes in the extracellular matrix (ECM) stiffness. These alterations are related with different retinal diseases, where MCs intermediate filaments polymerization is enhanced by the stress forces generated by the environment. In this study, we have analysed how different substrate stiffness affects MCs survival and behaviour in vitro.

Methods: Primary cultures of rat MCs were performed on acrylamide gels of 1, 10, 100 and 200 kPa, and on a glass‐slip as control. All culture dishes were treated with poly‐L‐Lysine and laminin. MCs were labelled by immunocytochemistry with antibodies against vimentin for morphology, Ki67 for proliferation, GFAP for reactivity, and with antibodies against pressure receptors Piezo1 and TRPV4. Positive‐labelled cells were counted and cell area was measured with ImageJ.

Results: Survival is severely reduced on softer gels (1 kPa 5.19 ± 1.64%), while on stiffer gels, mainly 200 kPa, it more closely resembles control conditions (66.33 ± 27.22%). MCs grown on softer gels exhibit a round shape and reduced cell area compared to control (1 kPa 8.79 ± 0.10%; 10 kPa 17.15 ± 0.89%), while those grown on stiffer gels show a fusiform shape and a more similar area to the control ones (100 kPa 28.59 ± 0.67%; 200 kPa 47.27 ± 4.39%). More MCs grown on softer gels become reactive as shown by the increased expression of GFAP. However, cell proliferation does not seem to be affected by substrate stiffness.

Conclusions: MCs do not thrive in softer substrates as shown by their reduced survival, cell area, round morphology and increased reactivity. This suggests that the stiffness of the substrate in vitro, and in consequence the ECM stiffness, is determinant for MCs behaviour.

Funding: ELKARTEK (KK‐2019/00086), MINECO‐Retos (PID2019‐111139RB‐I00) and PIBA (2020_1_0026).
Retinal tissue oxygenation differs between eye fundus regions, but not with age, sex, and intraocular pressure in non‐human primates
Authors: Akitegetse Cléophace , Poirier Jasmine , Lapointe Nicolas , Hamel Éric , Desroches Joannie , Dargis Natasha , Palmour Roberta , Ptito Maurice , Bouchard Jean‐François
Published: December 2022

Purpose: Oxygen plays a central role in multiple physiological and pathophysiological processes, and retinal oxygen supply has been found to be an important factor in many ocular diseases. Animal models are often used to study the pathophysiological mechanisms of diseases, especially non‐human primates (NHP) due to their great similarities with humans. Few data are available on the quantification of oxygen in the retina of NHP. The objectives of the study were to establish NHP tissue oxygen saturation (StO2) normative values in different eye fundus regions, compare StO2 in these regions and analyse how StO2 correlates to age, sex and intraocular pressure (IOP).

Methods: 44 vervet monkeys (28 males/16 females, 5–28 years old) were included in the study. IOP was measured in both eyes with an ocular tonometer. StO2 was measured in both eyes using the Zilia Ocular oximeter in the temporal (tONH) and nasal (nONH) optic nerve head, the peripapillary region (pPL) and the perifovea (pFV). T‐tests were used to compare between regions (paired), between both eyes (paired) and between sexes (independent). Kendall's tau was used to assess the correlation between StO2 and age, as well as that between StO2 and IOP.

Results: Mean StO2 was 55.7% ± 4.3% in the tONH, 55.0% ± 3.9% in the nONH, 63.9% ± 7.3% in the pPL and 74.2% ± 3.4% in the pFV. No significant difference in StO2 was observed between the left and the right eyes, just as no significant difference was observed between tONH and nONH. The StO2 was lower in tONH and nONH than in pPL (p = 0.0226 and 0.0060, respectively). No correlation was found between StO2 and age, StO2 and sex, or StO2 and IOP.

Conclusions: StO2 in the retinal tissue of NHP has been assessed for the first time. Regional variations similar to previous human studies were observed. The results of this study show the applicability of the Zilia Ocular on NHP and provide normative values that can serve as a basis for future studies.
Acute bilateral glaucoma related to uveal effusion syndrome associated with topiramate
Authors: López Carmen Miquel , Perea Juan Antonio Sánchez , Menargues Manuel Almarcha , Abellán Maria Victoria Navarro , Molina Celia Gómez
Published: December 2022

Purpose: Drugs mostly sulfa‐related compounds, have produced uveal effusions, forward rotation of the iris‐lens diaphragm, transient myopia, and secondary angle closure. It has been recently encountered one case in which uveal effusions have occurred after administration of topiramate, a new anticonvulsant medication.

Methods: A 54‐year‐old woman was seen in our emergency department with severe headaches, progressively blurry vision and photophobia in both eyes starting that morning. On examination, her visual acuity was hand movement in both eyes. Central corneal edema was observed, narrow chamber and anterior lens‐iris complex displacement with an unreactive middle pupil in both eyes. The funduscopic examination was difficult to assess due to the media opacity. Intraocular pressure measured with an applanation tonometer was 45 mm of mercury (mmHg) in the right eye and 50 mmHg in the left eye. Her medications included topiramate which she had started 2 weeks prior to initial examination due to headaches followed by neurology.

Results: Topiramate‐induced angle closure has even been described as an idiosyncratic reaction in patients with normal depth of anterior chamber. The drug causes a prostaglandins increasement that trigger ciliary body edema at the local level but without acting at the systemic level. Ultrasound biomicroscopy shows the presence of a ciliochoroidal effusion syndrome, edema and the ciliary body anterolateral rotation, with zonular relaxation, changes that lead to iris‐lens diaphragm anterior displacement and, as a consequence, narrowing of the responsible anterior chamber with an acute glaucoma crisis.

Conclusions: Topiramate is a sulfamate monosaccharide and belongs to a new generation of antiepileptic drugs, widely prescribed throughout the world as treatment of generalized tonic–clonic seizures and partial seizures. Prophylaxis of migraine, bipolar disorder, depression and neuropathic pain are other recent indications of its use. Bilateral acute glaucoma due to uveal effusion syndrome should be considered as an infrequent complication of topiramate use.

References.

1. Prithvi S. Sankar, MD; Louis R. Pasquale et al. Uveal Effusion and Secondary Angle‐Closure Glaucoma Associated With Topiramate Use. Arch Ophthalmol. 2001;119(8):1210–1211.
What are the parameters associated with the structural damage differences in open‐angle glaucoma?
Authors: Park Sung Eun
Published: December 2022

Purpose: To analyse which parameters affect retinal nerve fibre layer (RNFL)‐dominant defects rather than ganglion cell‐inner plexiform layer (GCIPL)‐dominant defects in open angle glaucoma patients.

Methods: A prospective observational study with a total of 58 eyes from 33 patients with open angle glaucoma was conducted. We divided them into two groups; patients with RNFL‐dominant defects (Group 1) and GCIPL‐dominant defects (Group 2), and compared glaucomatous parameters between the two groups.

Results: Higher pre‐treatment IOP (p = 0.012), mean IOP (p = 0.037), and younger age (p = 0.049) were significantly more associated with group 1. When adjusting mean IOP, age, LCCI, and MVD, only pre‐treatment IOP (p = 0.014) was significantly associated with group 1. When adjusting pretreatment IOP, age, LCCI, and MVD, higher mean IOP (p = 0.008) and greater LCCI (p = 0.035) were significantly associated with group 1.

Conclusions: RNFL‐dominant loss group is more deeply associated pre‐treatment and mean IOP, and LCCI than GCIPL‐dominant loss group. The higher pre‐treatment and mean IOP, and greater LCCI, the higher the probability of RNFL‐dominant defect.

References

1. Thylefors B, Negrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ.1995;73:115–121.

2. O'Neill EC, Mackey DA, Connell PP, Hewitt AW, Danesh‐Meyer HV, Crowston JG. The optic nerve head in hereditary.
Amfenac together with simvastatin reduces IL‐8 and MCP‐1 and increases VEGF release from ARPE‐19 cells upon inflammatory conditions
Authors: Bhattarai Niina , Hytti Maria , Kolari Onni , Nisula Hilkka , Loukovaara Sirpa , Kauppinen Anu
Published: December 2022

Purpose: Rhegmatogenous retinal detachment (RRD) is a sight‐threatening condition with the separation of the neurosensory retina from the retinal pigment epithelium (RPE). Clinical data have associated statin medication with lower risk of re‐vitrectomy in patients operated for RRD. We have previously shown statins to have anti‐inflammatory properties in lipopolysaccharide (LPS)‐treated RPE cells. The purpose of the present study was to examine whether the nonsteroidal anti‐inflammatory drug (NSAID) amfenac could complement the anti‐inflammatory effect of simvastatin in human RPE cells under pathophysiological conditions induced by IL‐1a. In addition to inflammatory markers, we studied the effects of amfenac and simvastatin on growth factors regulating blood vessel formation.

Methods: ARPE‐19 cells were pre‐treated with 0.1 μM amfenac and 5 μM simvastatin for 24 h after which 10 pg/ml of IL‐1α was added for 24 h. Enzyme‐linked immunosorbent assay (ELISA) was used to measure secretion of cytokines (IL‐8, MCP‐1), vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF). Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay.

Results: Amfenac and simvastatin were well tolerated upon inflammatory conditions. Both medicines alone and together reduced IL‐1a‐activated IL‐8 release. Simvastatin significantly reduced also the release of MCP‐1. The effect of amfenac alone was not significant but together with simvastatin, significant reduction in MCP‐1 levels was still reached. IL‐1a with the DMSO solvent increased release of PEDF and VEGF compared to DMSO group. Exposure of IL‐1α‐treated cells to amfenac and simvastatin together increased VEGF levels with no changes in the PEDF.

Conclusions: Amfenac and simvastatin showed potential to reduce inflammation in the retina upon retinal detachment. Increased VEGF levels may have neuroprotective effects by improving connections between RPE cells and photoreceptors.
Accelerated maturation of ARPE‐19 cells for the translational assessment of gene therapy
Authors: Locri Filippo , Bernd Jonathan , Plastino Flavia , Kvanta Anders , Andre Helder
Published: December 2022

Purpose: Retinal pigment epithelium (RPE) modulates the exchange of metabolite products to and from the retina, and are paramount to maintain retinal function. The human RPE cell‐line ARPE‐19 is commercially available and widely used as an alternative to primary RPE. However, these cells undergo epithelial‐mesenchymal transition (EMT) losing many features of primary RPE such as polarity, pigmentation, and expression of RPE signature markers. We aimed to determine whether a combination of RPE‐specific laminin (LN) coating and media supplementation with nicotinamide (NAM) could improve ARPE‐19 expression of genes and proteins, along with morphological phenotype resembling mature RPE to improve assessment of RPE‐specific gene therapy strategies.

Methods: ARPE‐19 cells were propagated on tissue culture plastic with or without NAM supplementation and/or coated with human recombinant LN‐521. Cell morphology was evaluated by phase microscopy. RPE maturation was performed by immunocytochemistry and gene expression by qPCR. Viral transduction experiments with adeno associated virus (AAV)1 or AAV2, VMD2‐driven GFP, were assessed at 2‐ and 4‐weeks post‐plating in the different culturing condition with low multiplicity of infection.

Results: The combination of LN‐521 coating with NAM supplementation promoted cytoskeletal and tight junction proteins reorganization, and expression of differentiation markers such as VMD2, RPE65 and PDGFRB. In addition, the combination reduced the expression of the EMT markers, TNFα and TGF‐β1; and NCAM1, an immature phenotype RPE marker. Both AAV1‐ and AAV2‐VMD2‐GFP expression was detected from 2‐weeks and improved at 4‐weeks post‐plating.

Conclusions: Our study demonstrates that the combination of NAM with LN‐521 accelerated the kinetics of expression of mature RPE signature genes, reduced expression of EMT genes, accompanied with improved epithelial cell morphology and cytoskeletal organization, bringing the dedifferentiated ARPE‐19 closer to their in vivo phenotype. Moreover, viral‐mediated RPE‐specific gene expression demonstrates the amenability of the combinatorial cultures for translational assessment of RPE gene therapies.
Vascular parameters after vitrectomy for rhegmatogenous retinal detachment, an optical coherence tomography angiography study
Authors: Bontzos George , Smoustopoulos George , Gkizis Ilias , Kontou Evgenia , Garnavou‐Xirou Christina , Xirou Stamatia‐Tina
Published: December 2022

Purpose: To analyse vascular changes such as the postoperative foveal avascular zone (FAZ) area, the superficial vessel density (sVD) and deep vessel density (dVD) and their correlation with functional (best‐corrected visual acuity, metamorphopsia) and anatomical outcomes (foveal macular thickness, FMT) after surgery for rhegmatogenous retinal detachment (RRD) repair.

Methods: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas or silicone oil tamponade and a minimum 6 months follow‐up, were re‐examined. For patients where silicone oil was applied, measures were taken after its removal. Foveal avascular zone (FAZ) area, sVD, dVD and FAZ area were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. Moreover, anatomical association was tested between areas of reported metamorphopsias and vascular changes in the corresponding area.

Results: Twenty‐one patients with macula‐on and 24 with macula‐off RRD were included in the study. In both groups, no significant difference in macular thickness and FAZ area was found compared to fellow eyes. In macula‐on RRD eyes, a lower total dVD (p < 0.05) was detected; FAZ area was not related to FMT, and the postoperative BCVA was correlated with total DVD (p < 0.05) or FAZ area. In macula‐off RRD eyes, sDV (p = 0.012), and dVD (p = 0.05 and p < 0.05, respectively) were observed when compared to fellow eyes. The prevalence of metamorphopsia in macula‐on group was 42.86% (9/21), whereas in macula ‐off this number increased to 62.5% (15/24). For both of these groups, we found significant association between sDV and presence of metamorphopsia but only in the inferior paramacular area (p = 0.01).

Conclusions: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; BCVA was related to vessel density but not FAZ area. Metamorphopsias were also related to lower vessel density inferiorly of the macula.
Ocular biometric dimensions according to gender. Are they different?
Authors: Vilaplana‐Mora J. M. , Hernández Irene Gil , Hernandis José‐Miguel Hervás , Alarcón‐Correcher F. , Montero Ana López , Vidal‐Oliver L. , Duch‐Samper Antonio M.
Published: December 2022

Purpose: To analyse ocular biometric parameters in men and women in a population of cataract surgery candidates and determine whether statistically significant differences exist.

Methods: A cross‐sectional study of 5034 eyes of 2671 patients was performed. Biometric parameters of the eyes were measured by Zeiss IOLMaster 700. The axial length (AL), mean anterior radio (aR), mean posterior radio (pR), central corneal thickness (CCT), anterior chamber depth (ACD) (epithelium to lens), lens thickness (LT), and White to White corneal diameter (W2W) were evaluated. These data represent normative biometric values for the Valencian population.

Results: The mean age in the male group was 73 ± 9.6 years, the mean age in the female group was 73.8 ± 8.3 years. The male/female ratio was 0.84. The male–female difference, with a 95% confidence interval (CI) in AL, ACD, and LT were 0.65 mm [0.57; 0.73] (p < 0.01), 0.17 mm [0.14; 0.2] (p < 0.01), and 0.031 mm [0.005; 0.5] (p < 0.05), respectively. Differences (95% CI) in W2W and CCT were 0.18 mm [0.15; 0.20] (p < 0.01), and 4.89 μm [2.55; 7.23] (p < 0.01). Differences (95% CI) in aR and pR were 0.137 mm [0.12; 0.153] (p < 0.01) and 0.122 mm [0.106; 0.139] (p < 0.01). All biometric eye parameters (AL, aR, pR, CCT, ACD, LT, W2W) measured, were lower in females than in males, with a statistically significant difference.

Conclusions: Statistically significant differences between genders were found in all the biometric parameters evaluated. In our population, women's eyes are smaller than men's in all biometric parameters that shape them. Gender must be taken into account in the biometric evaluation of the eye. These results may be relevant in intraocular lens power calculation and in the evaluation of refractive error.
Secretory autophagy is increased in 5xFAD mice
Authors: Ruuth Johanna , Tamminen Toni , Toropainen Elisa , Koskela Ali , Korhonen Paula , Tanila Heikki , Malm Tarja , Kaarniranta Kai
Published: December 2022

Purpose: Chronic oxidative stress, disturbed proteostasis and increased protein aggregation are key hallmarks in Alzheimer's disease and age‐related macular degeneration pathology. In this study, we assessed the protein aggregation and secretory autophagy related biomarker changes in 5xFAD mice model expressing abundant levels of human beta‐amyloid (Aβ42).

Methods: The eyes of 6‐ and 12‐month‐old WT (n = 5) and 5xFAD (n = 5) were examined by immunomicroscopy. The paraffin sections were immunostained with the key regulators of secretory autophagy HMGB1, Aβ42, IL‐1β, and ferritin as well as protein aggregation markers ubiquitin protein and SQSTM1/p62.

Results: Immunohistochemistry analysis revealed that ubiquitin protein conjugates and Aβ42 were increased in 6 and 12 months old 5xFAD mice. SQSTM1/p62 was decreased in 12 months old 5xFAD mice. In 12‐month‐old time point, they located basolateral side of the retinal pigment epithelial (RPE) cells but also in extracellular space. Concurrently, secretory autophagy markers were elevated in the RPE and extracellular space between RPE and Bruch's membrane.

Conclusions: Secretary autophagy may be a novel regulator in drusen biogenesis. 5xFAD mouse is a good model to study protein aggregation and secretory autophagy mechanism in response to degenerative retina processes.
Multimodal imaging features in chorioretinitis sclopetaria
Authors: Ferchichi Molka , Maamouri Rym , Nouri Slim , Sassi Hela , Cheour Monia
Published: December 2022

Purpose: To describe the multimodal imaging findings in a case of chorioretinitis sclopetaria (CS).

Methods: Single case report.

Results: A 26‐year‐old male reported a history of ocular injury to the right eye (OD) in childhood caused by a palm tree branch after which he underwent cataract surgery. On examination, his best‐corrected visual acuity was light perception in OD. Anterior segment examination revealed the presence of an anterior chamber intraocular lens. Intraocular pressure was within the normal range. Dilated funduscopy showed an area of bare sclera in the inferonasal quadrant adjacent to a white fibroglial proliferation that extended to the nasal and temporal periphery consistent with CS. A large area of chorioretinal atrophy involving the macular region with a nasal demarcation line and scattered hyperpigmented patches was also noted. The left eye examination was unremarkable. Fundus autofluorescence showed hypoautofluorescence of the scar tissue and in the posterior pole. Swept‐source optical coherence tomography scans confirmed the rupture of the choroid underneath a full‐thickness hyperreflectivity in the inferonasal quadrant and revealed disruptions in the macular RPE and outer retinal layers.

Conclusions: CS is caused by a shock wave from a high‐velocity projectile resulting in the tearing of the choroid, retinal pigment epithelium (RPE), and neurosensory retina which later induces fibrous scarring, RPE hyperplasia, and photoreceptor loss. Multimodal imaging findings of CS are consistent with these features.
Patient‐reported outcomes measurements in dry eye patients after 84 days of daily treatment with a preservative‐free combination containing sodium hyaluronate and trehalose: The TEARS study
Authors: Mateo‐Otobia Antonio , Chassany Olivier , Duracinsky Martin
Published: December 2022

Purpose: Dry eye disease (DED) is characterized by ocular discomfort and visual disturbance that can impact quality of life. This study evaluated, after 84 days of daily use, the improvement of ocular surface disease (OSD) and various Patient‐Reported Outcomes Measurements (PROM) in patients with DED receiving a preservative‐free combination containing sodium hyaluronate and trehalose (SH‐THL, Thealoz® Duo, Laboratoires Théa).

Methods: This is a multicenter, non‐interventional survey in 312 adult subjects with DED. Clinical tests and Ocular Surface Disease Index (OSDI®) were performed at baseline and Day 84. Dry Eye Questionnaire (DEQ‐5) was done at baseline, 28 days and 84 days, as well as other PROM related to satisfaction, eye drop, comfort and impact on life's activities. SH‐THL was to be instilled when needed.

Results: 82.4% were women, the mean age was 57.9 ± 15.2 years. At baseline (BL), the overall OSDI was 41.7 ± 20.6 (60.3% of patients had a severe score, i.e. between 33–100) and significantly improved after 84 days to 27.3 ± 19.8 (34.5% of patients with a severe score). Similarly, the DEQ‐5 score significantly improved at 28‐day and 84‐day visits (p < 0.001 compared to BL). Patient satisfaction with treatment significantly improved at all visits (p < 0.001 compared to BL). 72.3% preferred SH‐THL to their previous treatment after 84 days. There was a statistically significant difference in the overall scores of the impact on patient's life and the eye drop questionnaires, at all visits: 80.3% agreed on “My current drops make my eyes comfortable” at Day 84; 38.6% reported No Impact on working on a computer and 68.1% reported No Impact on sleeping at Day 84.

Conclusions: The OSDI mean improvement of −14.4 points over time was higher than the minimal important difference reported in literature. Eye drops containing SH‐THL improved significantly after 84 days the Patient‐Reported Outcomes Measurements on satisfaction, eye drop, comfort and impact on life's activities in Dry Eye patients in a real‐world setting.
The role and clinical significance of intraoperative optical coherence tomography for cataract surgery
Authors: Öztek Melisa , Reyna Erick Carlos , Binder Susanne , Stieger Knut , Lytvnchuk Lyubomyr
Published: December 2022

Purpose: to evaluate the clinical significance of intraoperative spectral domain optical coherence tomography (iOCT) in cataract surgery with implantation of different types of intraocular lenses (IOL).

Methods: In this retrospective observational study, the iOCT image data of 151 cataract cases with different types of implanted IOLs were analysed. For intraoperative imaging a Rescan® 700 was used and the following image criteria were traced: standard surgical steps, IOL optic position, IOL haptic position. Patient eyes were divided into: group 1: n = 101 eyes with lens‐in‐bag (LIB); group 2: n = 15 eyes with bag‐in‐the‐lens IOL (BIL); group 3: 5 eyes with iris‐claw IOL (ICL); group 4: 15 eyes with intrascleral fixated 3‐piece IOL (3‐IOL); group 5: 15 eyes with intrascleral fixated Carlevale IOL (C‐IOL). The data were post‐processed and evaluated statistically.

Results: iOCT enabled an additional control of subsequent surgical steps in all studied cases: LIB: the completeness of hydrodissection and hydrodelineation, condition of hydrated paracentesis (in 11% of cases ‐ an incomplete adaptation of paracentesis); BIL: separation of anterior hyaloid and correct implantation of capsular edges into the IOL; ICL: thickness of the iris fold between IOL claws; 3‐IOL/C‐IOL: the position of optic with regard to the iris and position of the haptic in the intrascleral space.

Conclusions: The application of iOCT assisted cataract surgery with different IOLs generates useful live data that potentially reduce the risks of intra‐ and postoperative complications (posterior capsule rupture, hypotony, etc.). It can confirm the correct positioning of alternative IOL types intraoperatively, which is crucial to facilitate an optimal IOL performance. The use of iOCT shall be considered during learning process in cataract surgery.
A novel tool to study bipolar cell responses in glaucoma
Authors: Ortega Alejandro Gallego , Siga Yukihiro , Villafranca‐Baughman Deborah , Quintero Heberto , Vidal‐Sanz Manuel , Di Polo Adriana
Published: December 2022

Purpose: Retinal ganglion cell death has been well studied in glaucoma, however how the calcium (Ca2+) dynamics in living inner retinal neurons alter to ocular hypertensive stress is poorly understood. Here we characterized a novel adeno‐associated virus (AAV) mediated Ca2+ sensor to investigate light‐evoked Ca2+ responses in bipolar cells with two‐photon laser scanning microscopy (TPLSM).

Methods: To visualize ON bipolar cell specific Ca2+ expression, we bioinformatically designed a serotype 2 AAV vector carrying GCaMP6f, a Ca2+indicator, under human MiniPromoter: Ple265 (PCP2, 986 bp, AAV.Ple265.GCaMP). The AAV.Ple265.GCaMP6 was administered intravitreal to adult mice (2 μl/eye). Two and 4 weeks later (n = 3 mice/group), eyes were collected, and retinal cross sections (16 μm) were prepared for immunohistochemistry using the following primary antibodies: GFP to visualize GCaMP6f, and bipolar cell‐specific markers PCP2 or PKCa. Furthermore, we monitored real time light‐evoked Ca2+ responses in bipolar cell terminals at 4 weeks after the injection and amplitude (ΔF/F0) was calculated.

Results: At 2 weeks after the viral injection, GCaMP6f was clearly visualized in bipolar cells, but its expression was limited to the cell body and dendritic trees. Four weeks post‐injection, GCaMP6f expression was abundantly detected in many bipolar cell bodies, dendrites, axons, and axonal terminals. TPLSM allowed visualization of bipolar cell‐specific GCaMP6f expression in axonal terminals in vivo, and light‐evoked sustained ON‐responses were recorded in terminal microdomains (average intensity = 1.25 ΔF/F0).

Conclusions: Our study reveals that the AAV.Ple265.GCaMP is a powerful tool to monitor ON bipolar cell specific light‐evoked Ca2+ responses in bipolar cells, and can be potentially used for studies aimed at understanding the response of these neurons to glaucomatous damage.
Tlr4 gene deletion accelerates retinal degeneration in rd10 and P23H/+ murine models of retinitis pigmentosa
Authors: González Mateo Pazo , Cruz Alonso Sánchez , de la Rosa Cano Enrique J. , De La Villa Pedro , Sánchez Catalina Hernández
Published: December 2022

Purpose: The photoreceptor degeneration associated to retinitis pigmentosa (RP) is caused by a wide variety of genetic mutations, which greatly complicates the development of a universal effective treatment. As a process independent of the causative mutation, the inflammatory response resulting from neuronal death could represent a potential candidate for a general treatment for RP. In this context, we studied the role of TLR4, one of the main mediators of innate immunity, on the retinal degenerative process in two murine models of RP.

Methods: rd10 and P23H/+ mice were used to evaluate the consequences of Tlr4 haploinsufficiency and complete deletion on retinal degeneration. Visual function was evaluated by electroretinographic recordings and optomotor test and retinal cytoarchitecture by immunohistology. The myeloid cell population (main mediators of the innate immune response) reactivity was studied by immunohistology and flow cytometry. Gene expression was assessed by RT‐quantitative PCR.

Results: We found that Tlr4 expression was significantly increased in the retina of both RP models. To assess the effect of Tlr4 deletion in PR progression first we confirmed that abrogation of Tlr4 expression did not impair visual function in wild‐type animals. However, Tlr4 deficiency accelerated RP progression in both rd10 and P23H/+ mice. Deletion of a single Tlr4 allele reduced the retinal electroretinographic response and photoreceptor survival in both RP models. Moreover, complete abrogation of Tlr4 further exacerbates this phenotype. These results were confirmed by assessing visual acuity by optomotor test in P23H/+ mice. Microglia analysis showed higher proportion of phagocytic microglia and lower of homeostatic microglia in the photoreceptor layers upon Tlr4 total deletion.

Conclusions: The TLR4 receptor exerts a neuroprotective effect on the retinal neurodegenerative process in RP, thus suggesting a potential therapeutic target for the disease.
Characterization of rotational symmetry and noise in multifocal contact lens power maps
Authors: Raso Alicia López , Alonso Jose Manuel Lopez , Alcocer Javier Ruiz , Prieto Elena Durán , Martínez Mercedes Burgos , Goodenough Neil
Published: December 2022

Purpose: Spherical multifocal contact lenses are typically designed with a rotationally symmetrical power profile. Imperfections in the raw material, manufacturing and measurement process can break this symmetry, altering the intended lens design. The purpose of this work is to develop a method to separate the intended symmetric design profile from the asymmetries and to give the spatial distribution of the measurement noise uncertainty in diopters.

Methods: NIMO TR1504 (Lambda‐X) version V.2.13.2 has been used to measure the local power map of various multifocal contact lenses. From the map, a set of radial power profiles is obtained for different angles (0°, 180°), (0°, 360°). A symmetrical lens should show a constant radial profile for different angles, while asymmetries manifest as differences in the set of radial power profiles. They are analysed using a Principal Components Method (PCA) implemented in MATLAB.

Results: The method displays a map of the symmetric radial profile of the lens, another map of the deviations with spatial structure indicating the angles where the deviations are stronger (rotational asymmetries), and noise with three separated components (spatially random variations). Asymmetries of the order of 0.17D (with maximums of 0.4D), and random noise values of 0.12D were found in some lenses.

Conclusions: The characterization of multifocal contact lens prescription is important in visual optics. The prescription perceived by the patient depends on the distribution of the radial power profile on the pupil. That is the reason why asymmetries and imperfections estimation is important. The method developed in this work allows to calculate a diopter equivalent number for them.
Retinal vascular abnormalities in a patient with an overgrowth syndrome
Authors: Romero Miriam Montserrat Sancho , Maeso Alicia Traveset , Camps Anna Serret , Mier Felipe Costales , Carmona Fernando Paredes
Published: December 2022

Purpose: To present a case report of unilateral vascular abnormalities on the retina of a patient with an overgrowth syndrome.

Methods: A 26‐year‐old male who presents hemihypertrophy, hemimegaloencephaly, cutaneous haemangiomas and intellectual disability who underwent a complete ophthalmological examination. A detailed retinal imaging was performed as well as a fluorescein angiography (FA) and optical coherence tomography (OCT).

Results: Fundus examination of the right eye revealed retinal vascular tortuosity while on the left eye there was fibrovascular proliferative tissue with new vessels from the optic nerve to retinal temporal vessel arcades and an area of chorioretinal atrophy in the superior‐temporal sector. FA illustrated diffuse retinal vascular leakage around temporal arcades which was more evident in late‐phase fluorescein angiograms, but no ischemic areas were found. An extrafoveal epiretinal membrane was seen by OCT on the left eye. As his visual acuity was adequate (20/20 vision in both eyes), initially a conservative management was considered, with visits every 6 months.

Conclusions: Patients with an overgrowth syndrome can present different ocular abnormalities as optic nerve hypoplasia, strabismus, and high myopia but it is not frequent to find retinal vascular abnormalities. These patients would require a strict follow‐up by an ophthalmologist. This case also led us to think of the importance of a multidisciplinary work and how useful is to have a genetic testing and a differential diagnosis from all types of overgrowth disorders associated with ocular manifestations.
Incomitant strabismus as a form of presentation of neurolymphymatosis
Authors: Hernández Irene Gil , Nicolas Javier Garulo , Belda Raul Martinez , Del Rio Noemi Ruiz , Duch‐Samper Antonio M.
Published: December 2022

Purpose: To report a case of Neurolymphomatosis to raise awareness of this condition. Neurolymphomatosis (NL) is the invasion of cranial nerves or roots by malignant cells from a non‐Hodgkin lymphoma (NHL).

Methods: A 74 years old female, with known large B cell lymphoma treated 2 years prior with R‐CHOP chemotherapy, consulted our department for diplopia and blurred vision in left eye (OS). The clinical exploration evidenced a decrease of visual acuity (VA) on OS associated with hyporeactive pupil and signs of granulomatous panuveitis with inferior subretinal infiltrates. On her right eye (OD), she had a limitation of adduction, supraduction and underduction. A magnetic resonance imaging (MRI) was performed, which found a mandibular mass. Its pathological study confirmed a recurrence of haematological disease and a new line of treatment with chemotherapy was established.

Results: 2 weeks later, resolution of the strabismus and reabsorption of the retinal infiltrates were observed. The final VA of the patient was 0.8.

Conclusions: Contrast MRI is the most specific and sensitive non‐invasive imaging technique, as the path of the infiltrated nerves will capture gadolinium. PET‐CT with FDG‐18 can help locate possible biopsy areas. The Gold Standard diagnostic technique is the biopsy of the affected nerves, but can only be performed in 50% of cases. Clinical information from the ophthalmological examination can be a support to guide the diagnosis.

References.

1. Baehring JM, Batchelor TT. Diagnosis and management on neurolymphomatosis. Cancer J. 2012;18(5):463–8.

2. Sahin H, Mete A, Pehlivan M. Neurolynphomatosis in non‐Hodgkin lymphoma with cranial multineuritis. Medicine. 2018;97:15.
ATN grading system in a dome‐shaped macula and ridge shaped macula high lymyopic cohort
Authors: Garcia‐Zamora Maria , Flores‐Moreno Ignacio , Ruiz‐Medrano Jorge , Puertas Mariluz , Almazan‐Alonso Elena , Vega‐Gonzalez Rocio , Gonzalez‐Buendia Lucia , Ruiz‐Moreno Jose M.
Published: December 2022

Purpose: The purpose of this study was to analyse the ATN grading in highly myopic patients with dome‐shaped macula (DSM) and ridge‐shaped macula (RSM).

Methods: This was a cross‐sectional, noninterventional study. 57 eyes of 38 different patients were included. They were classified as DSM or RSM based on the number of radial scans affected on the swept‐source optical coherence tomography (SS‐OCT) (12 = DSM; 12 = RSM). All patients underwent a complete ophthalmological examination in addition to SS‐OCT. They were graded using the ATN system for myopic maculopathy by 2 masked retina specialists that assessed the atrophic (A), tractional (T), and neovascular (N) components. As complementary measurements, age, axial length (AL) and best corrected visual acuity (BCVA) were collected. Height and orientation of the macular bulge and the presence of Bruch's membrane defects, scleral perforating vessels and staphyloma were recorded.

Results: Out of total 57 eyes, 13 eyes (22.8%) were classified as DSM. Regarding the atrophic component (A), there were statistically significant differences between groups, with DSM group showing a greater stage of atrophy (predominantly stage A3 in 69.2% of the sample) compared to the RSM group (predominantly stage A2 in 61.3% of the sample) (p < 0.05). As for the tractional (T) and neovascular (N) components, there were no significant differences between groups. The presence of Bruch's membrane defects was more frequently seen in DSM (p < 0.05).

Conclusions: DSM group showed more Bruch's membrane defects and a greater stage of the atrophy component, based on the ATN grading system, compared with RSM group. As Bruch's membrane may have biomechanical properties in terms of strength, the defects found around the macula, added to the major atrophic component, may be a cause of a local relaxation that induce a central bulge forming the dome.
Validation of postnatal growth and retinopathy of prematurity (G‐ROP) criteria for retinopathy of prematurity in a Spanish tertiary care hospital with an advanced neonatal intensive care unit
Authors: Picazo Carlos Cauto , Camps Isabel Pascual , Pérez Lorena Azorín , Ruiz Marta Solaz , García Laura Fernández , Martínez Ester Torres , Seller Amparo Ortiz , Palacios Inmaculada Almor , Hernández Ana Rodrigo , González Honorio Barranco , Gregori Enrique España
Published: December 2022

Purpose: Validation of the new Postnatal Growth and Retinopathy of Prematurity (G‐ROP) criteria for screening of retinopathy of prematurity (ROP) in a Spanish tertiary care hospital with an advanced neonatal intensive care unit.

Methods: Retrospective cohort study that includes premature infants with current ROP screening criteria (less than or equal to 32 weeks of gestational age and/or less than or equal to 1500 g of birth weight) born between January 2017 and December 2021 in a tertiary care hospital with an advanced neonatal intensive care unit. The compliance with the G‐ROP criteria was assessed for each patient, including: gestational age <28 weeks, birth weight <1051 g, weight gain <120 g during 10–19 days postnatal age, <180 g during 20–29 days, <170 g during 30–39 days or hydrocephalus. The objective was to determine specificity, sensitivity and reduction of patients examined with these new criteria.

Results: Of 483 patients included (203 female and 280 male), the new G‐ROP criteria predicted 100% of cases of type 1 ROP (treatment‐requiring ROP) (15 of 15 cases) (Sensitivity 100%, Specificity 37.68%). Applying these criteria, there would be a reduction of 34.36% (166 patients) in infants requiring examination.

Conclusions: This study observes that the new G‐ROP screening criteria may suppose an increase of sensitivity and specificity with a reduction of the number of infants requiring screening. However, other studies with a larger population would be necessary to verify the results.
Comparative study of lipid profile influence on foveal avascular central zone
Authors: Aoun Safa Ben , Sassi Hela , Fekih Khawla , Nouri Slim , Mzoughi Khadija , Cheour Monia
Published: December 2022

Purpose: To evaluate the influence of lipid profile on foveal avascular central zone (ACZ) using Swept Source Optical Coherence Tomography Angiography (SS‐OCT A).

Methods: A cross‐sectional, comparative study including 30 eyes of 15 volunteers with no history of ocular disease or surgery was conducted in the department of ophthalmology of Habib Thameur University Hospital, Tunis. SS‐OCT A imaging was performed using the DRI‐OCT Triton (Topcon, Japan). The macula was imaged using 3 × 3 mm scans, and superficial retinal OCT angiograms were extracted and analysed. Foveal ACZ was characterized by its perimeter, its area, its circularity, the aspect ratio (AR), the roundness index (Round), the solidity and the Feret's diameter (Feret). Patients with dyslipemia were compared to a control group using the Mann–Whitney U‐test and the degree of correlation between two variables was expressed as the Spearman's correlation coefficient.

Results: Eleven males and four females were included in the study. Sixteen eyes of eight patients (53.3%) with dyslipemia were compared to fourteen eyes of 7 healthy controls (46.7%). Mean age was 53.33 ± 9.73 years. Mean total ACZ measurements were: Perimeter (2.63 ± 0.53), Area (3.98 ± 1.49), Circularity (7.07 ± 0.97), AR (1.23 ± 0.23), Round (8.32 ± 1.18), Solidity (8.86 ± 0.41) and Feret (6.53 ± 3.24). Comparative study revealed that ACZ area was higher in the dyslipemia group than in the control group (4.64 vs. 3.31, p = 0.02). There was no significant difference between the two groups in the other measurements of ACZ.

Conclusions: Dyslipemia causes enlargement of the foveal avascular central zone without affecting its form. These results suggest that dyslipemia may affect foveal vascular structure potentially through chronic ischemia mechanisms.
Topical sevoflurane ocular toxicity: in vivo study
Authors: Encalada Denisse Michelle Espinosa , Cejudo Raquel Maroto , Valenciano Carlos Cava , Sango Mónica Gómez‐Juarez , Vidal Victoria Adámoli , Pretel Fernando Andrés
Published: December 2022

Purpose: To determine sevoflurane (SF) ocular toxicity in an animal model and compare the results with the changes induced by common ocular substances: Povidone Iodine 5% (PI) and salt solution (SS).

Methods: Twelve rats (24 eyes) and 3 rabbits (6 eyes) where included. Eyes were randomized, receiving a single 0,1 ml dose of SF, PI or SS. After instillation, eyes were evaluated using Draize test at different time frames. A histopathological (HP) study was also performed.

Results: Keratitis was the only finding identified in the animals. In rats, it was observed in 16/24 eyes (8 in SS, 4 in SF and 4 in PI group). Only the keratitis observed after SS and PI instillation showed statistically significant differences, with a higher incidence in PI group (p = 0.012). Similar results were observed in rabbits: keratitis was present in 5/6 eyes (3 in SF and 2 in BSS group), but no significant differences were observed in any group at any time of study. The risk ratio (=1) did not show a higher risk of keratitis with any substance. In HP study, only mild inflammatory changes were observed.

Conclusions: Topical administration of SF has shown to be safe for the eye surface of animal model.

References

Recent findings suggest sevoflurane role as an analgesic, antiseptic and wound‐healing agent. Nevertheless, previous to study these effects on the eye, it is necessary to perform and toxicological test. This is the first study performed in vivo to evaluate sevoflurane ocular toxicity.
The use of preservative‐free hydrocortisone in the postoperative treatment regimen after trans‐PRK
Authors: Sakellaris Dimitris , Panagiotis Garitsis , Zachos Zachariadis , Balidis Miltos
Published: December 2022

Purpose: The purpose of this study was to exhibit the advantages of preservative‐free hydrocortisone in the postoperative treatment regimen of transepithelial photorefractive keratectomy (Trans‐PRK) for the promotion of epithelization and minimalization of early haze appearance.

Methods: In this prospective, randomized controlled study, 40 patients who had undergone trans‐PRK were divided into two equal groups, the first group received hydrocortisone (Softacort®, Laboratoires Thea) 2 drops 4 times daily for 7 days and the control group received no complementary medication. Both groups were given: artificial tears 2 drops hourly for 7 days, then administered every 2 h for 21 days and tapered till 3 months post‐operation, antibiotic drops (quinolone) 4 times daily and autologous serum hourly for 7 days, and a bandage contact lens till complete epithelization of the surgical wound. Patients were monitored daily to determine the time of a complete epithelization and then on day 15 and 30 to assess any signs of early‐onset haze and visual acuity. Scheimpflug topography and anterior segment OCT were performed on day 15 and 30 as well as IOP tonometry.

Results: The results showed a significant decrease in recovery days in patients treated with hydrocortisone compared to the control group (p < 0.0006) which was associated with a higher rate of early‐onset haze. Both groups had satisfactory visual acuity and no significant differences in their IOP were observed.

Conclusions: In conclusion, the use of hydrocortisone sodium phosphate drops (Softacort®) has been shown to be efficient in corneal epithelization and haze management and safe in patients after trans‐PRK.