bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel melanin‐binding carbonic anhydrase II inhibitor for long‐acting topical glaucoma treatment
Authors: Valtari Annika , Kalinin Stanislav , Jäntti Janika , Stenberg Katja , Vellonen Kati‐Sisko , Toropainen Elisa , Ruponen Marika , Urtti Arto 
Published: January 2024

Aims/Purpose: We are developing new eye drop treatment for glaucoma with dosing frequency once a week by utilizing drug binding to ocular melanin. Carbonic anhydrase (CA) II enzyme inhibitors decrease intraocular pressure (IOP) and thus halt the progression of retinal damage by reducing the secretion of aqueous humour in the ciliary body. Since ciliary body is a melanin‐rich tissue, we hypothesize that long‐lasting CAII inhibition and IOP‐lowering effect may be achieved due to gradual drug release from melanin‐bound drug depot.Methods: Melanin binding affinity for about 30 novel CAII inhibitors was studied with microscale thermophoresis, and three structurally rather similar and equipotent molecules with different melanin binding properties were selected for in vivo efficacy studies. IOP‐lowering effect of these new molecules was studied with albino and pigmented rabbits with iCare® PRO rebound tonometer. For pharmacokinetic studies, the high melanin binding new CAI (molecule 184) was labelled with tritium, and the study was conducted with albino and pigmented rats with conventional methods. Bound drug was analysed from iris‐ciliary body pellet and unbound fraction from supernatants.Results: Melanin‐binding affinity of new CAII inhibitors varies from low or non‐binders (Kd > 650 μM) to high melanin binders (Kd < 65 μM). In vivo efficacy results show that the molecules decrease IOP in both albino and pigmented eyes at the level comparable with dorzolamide (Trusopt®). In pigmented eyes, melanin binding prolongs the effect of compound 184 even up to 2 weeks after single eye drop. In the pharmacokinetic rat study, molecule 184 shows remarkably prolonged tissue binding and high iris‐ciliary body exposure in pigmented eyes.Conclusions: After topical administration IOP‐lowering effect of high melanin‐binding CA II inhibitor is significantly prolonged in pigmented eyes.
Sitagliptin, an anti‐diabetic drug, inhibits the pro‐inflammatory microglia reactivity via dipeptidyl peptidase‐4 (DPP4)
Authors: Léger Hélène , Leote Cristiana , Bufano Lucia , Boia Raquel , Santiago Ana Raquel , Fernandes Rosa , Ambrósio António Francisco 
Published: January 2024

Aims/Purpose: Diabetic retinopathy is characterized by a chronic low‐grade retinal neuroinflammation triggered by diabetes and mediated, at least in part, by microglial cells. We previously showed that sitagliptin, an oral drug for type 2 diabetes, developed to inhibit dipeptidyl peptidase 4 (DPP4) and increase insulin release, can prevent retinal neuroinflammation in diabetic rat models and the LPS‐induced morphological changes of microglial cells in retinal organotypic cultures. However, the mechanisms underlying these effects are not clarified. We hypothesize that sitagliptin is able to directly inhibit microglia reactivity via Dpp4.Methods: BV‐2 microglia cell line was exposed to a non‐toxic dose of lipopolysaccharide (LPS, 0.1 μg/mL) in the presence or absence of 200 μM sitagliptin. The expression of Dpp4, iNOS, IL‐1 beta and TNF were assessed by Western Blot and/or RT‐qPCR. The BV‐2 phagocytic efficiency was assessed using fluorescent microbeads. The metabolic activity and proliferation of BV‐2 cells were assessed by resazurin assay and Edu staining, respectively. Dpp4 deletion in BV‐2 cells was generated using Crispr‐cas9 method.Results: Sitagliptin inhibited the LPS‐induced increase in protein levels of iNOS, IL‐1 beta and TNF to 39.9 ± 6.3%, 47.2 ± 8.1% and 34.0 ± 7.2%, respectively, comparing to LPS. Sitagliptin reduced the LPS‐induced increase in phagocytic efficiency by approximately 40%. Sitagliptin did not affect the metabolism and proliferation of BV‐2. BV‐2 cells express Dpp4. Dpp4 deletion does not affect the LPS‐induced phagocytosis but abrogated the effect of sitagliptin on the reduction of BV‐2 phagocytic efficiency (approx. 320% as in LPS).Conclusions: Sitagliptin exerts direct anti‐inflammatory effects on microglia, mediated by DPP4. These results suggest that sitagliptin can potentially be used in retinal pathologies characterized by microglia‐mediated neuroinflammation.Support.FCT‐Portugal: PEst UID/NEU/04539/2013, UIDB/04539/2020 and UIDP/04539/2020 and PTDC/NEU‐OSD/1113/2012. COMPETE‐FEDER.
The outcome of cataract surgery in paediatric uveitis
Authors: Mtalai Naoual , Ghizlane Daghouj , Chahir Roukaya , Loubna Elmaaloum , Bouchra Allali , Asmaa Elkettani 
Published: January 2024

Aims/Purpose: Cataract is a frequent complication of chronic uveitis. It can be a consequence of intraocular inflammation or the use of corticosteroids. In children, uveitic cataract is a source of amblyopia, hence the interest in surgery. Our work aims to study the therapeutic particularities, the peri and post‐operative complications and the visual and functional results of these cataracts.Methods: We performed a retrospective study of 14 patients (18 eyes) with uveitis; involving children under 15 years of age; who underwent cataract surgery between January 2011 and November 2022.Results: The average age of the operated children was 9.5 years (4–14 years) with a female predominance of 70%. Uveitis was bilateral in 8 children. The aetiology of the uveitis was found in 9 patients. It was juvenile idiopathic arthritis (JIA) in 6 cases, ocular toxoplasmosis in 1 case, tuberculosis in 1 case and Eales disease in 1 case. The aetiology of the uveitis was not found in 5 patients. The initial visual acuity varied between light perception and 2/10. Total white cataract was found in 44% of cases, posterior subcapsular in 39% of cases, anterior subcapsular in 5.5% of cases and corticonuclear and posterior subcapsular in 11% of cases. Phacoemulsification was performed with implantation in the lens bag in 17 eyes, only 1 patient in our series was not implanted. Post‐operative visual acuity was greater than 7/10 in 68% of cases, between 7/10 and 3/10 in 16% of cases and less than 3/10 in 16% of patients. Post‐operative complications were dominated by the inflammatory reaction of the anterior segment, which was controlled by corticosteroid treatment in 40% of cases, macular oedema occurred in 2 patients in our series post‐operatively and Elsching's beads in 6 eyes (34%). Immunosuppressive treatment was maintained in 75% of cases.Conclusions: Cataract surgery in uveitic children requires careful management to ensure successful outcomes. The control of peri‐operative inflammation in the surgery of paediatric uveitic cataracts is the key to obtaining good visual outcomes and preventing amblyopia.ReferencesAlAmeer AM, Al Shamrani M. Outcome of cataract surgery in pediatric uveitis (experience at King Khalid Eye Hospital). Oman J Ophthalmol. 2022 Mar 2;15(1):43–48.
Analysis of the effects of FineVision Micro F and AcySof IQ PanOptix intraocular lenses on visual quality under different lighting condition
Authors: Haddi Inas Baoud Ould , Cervantes Dayan Flores , Ramírez Emilio Dorronzoro , Sánchez Vanesa Blázquez , Arias Cristina Bonnin 
Published: January 2024

Aims/Purpose: To analyse the effect of the design of FineVision Micro F and AcrySof IQ PanOptix trifocal intraocular lenses on the visual quality of patients under photopic and mesopic illumination conditions.Methods: Observational, prospective, cross‐sectional study. The study was conducted at the Hospital Universitario Sanitas la Moraleja in Madrid. The study followed the principles of the Declaration of Helsinki. The sample included 16 patients who underwent cataract or lensectomy surgery, with bilateral implantation of one of the two intraocular lenses (IOLs) under study: 20 eyes with FineVision Micro F implant and 12 eyes with AcrySof IQ PanOptix. After 30 days after surgery, an assessment of photopic and mesopic, monocular and binocular visual acuity (VA) was performed for three distances: far (4 m), intermediate (66 cm) and near (40 cm) with the ETDRS test. A p‐value <0.05 was considered a criterion for statistical significance.Results: Visual acuity analysis showed significant differences between FineVision Micro F and AcrySof IQ PanOptix lenses, under photopic conditions, for intermediate distance (p‐value 0.014) with means of 0.04 ± 0.05 and 0.11 ± 0.11, respectively and near distance (p‐value 0.001), with means of 0.05 ± 0.06 and 0.12 ± 0.06, respectively. On the other hand, in mesopic conditions, statistically significant differences (p‐value 0.032) were observed in close distance, with means of 0.43 ± 0.3 and 0.52 ± 0.2, respectively.Conclusions: Both FineVision Micro F and AcrySof IQ PanOptix IOL designs provide optimal VA at far distances in both photopic and mesopic illumination conditions. The FineVision Micro F IOL provides better intermediate and near VA in photopic conditions and near distance in mesopic conditions than the AcrySof IQ PanOptix IOL, and this difference is clinically significant.
Prospective clinical study of a new intraocular lens with extended depth of focus: ISOPURE, 1 year follow‐up
Authors: Bradly Dounia , Dany Salik , Elie Motulsky 
Published: January 2024

Aims/Purpose: Monofocal lenses are currently the most frequently implanted intraocular lenses (IOL). New implants with enhanced depth of focus (EDOF) could improve intermediate and near visions with uncompromised far visual acuity and limited dysphotopsia. The objective of this study is to compare Group 1 – a bilateral implantation of an EDOF IOL‐ Isopure® versus Group 2 – a bilateral monofocal IOL – Micropure® – (BVI, Belgium).Methods: Eligible patients with bilateral cataracts were randomly assigned to two groups. Monocular, binocular, corrected, uncorrected, near, intermediate and far visions were measured before, 1 month and 1 year after surgery using ETDRS charts. A pre‐ and post‐operative questionnaire was realized to assess the impact of their vision on daily routine.Results: One year after the surgery near median visions were respectively 0.22 ± 0.18 and 0.44 ± 0.10 LogMar (p‐value = 0.0515) while intermediate visions were −0.02 ± 0.12 and 0.14 ± 0.07 LogMar (p‐value = 0.0595). No significant difference was demonstrated in the binocular distance visual acuities, respectively −0.09 ± 0.14 and −0.12 ± 0.15 (p‐value = 1.00). The study revealed no significant difference regarding sensitivity of contrast and the defocus curve had a larger curve plate of good visual acuity in the Isopure® group. The questionnaire's analysis showed no significant difference between the groups.Conclusions: Although no significant difference was demonstrated, this study suggests that with a larger patient sample, the Isopure® implant may provide better near and intermediate visual activity, since our p‐values are close to 0.05, with the same distance vision and no deterioration of the contrast sensitivity. This implant provides a daily visual comfort and the patients reported a better satisfaction, fewer dysphotopsias, less difficulties with daily activities and less dependence on their glasses.
Evaluation of pan‐epithelial viability in the whole porcine lens
Authors: Poinard Sylvain , Coulomb Louise , Cortez Oliver Dorado , Thomas Justin , He Zhiguo , Perrache Chantal , Ganeau Alice , Forest Fabien , Mascarelli Frederic , Gain Philippe , Thuret Gilles 
Published: January 2024

Purpose: The lens has a monolayer of epithelial cells on its anterior surface that contributes to its homeostasis. A quantification of the viability of these cells is essential to evaluate the safety of new therapies targeting the lens (cataract, presbyopia). The observation of this whole tissue is made difficult by its optical properties (transparency and refraction) and only simplified models have been used until now to measure epithelial viability (primary cell cultures or partial surgical specimens).Aims: To develop a method to quantify the viability of epithelial cells on whole ex vivo lenses.Methods: Ten fresh pairs of 6‐month‐old porcine lens were retrieved from local slaughterhouse. For each pair, one lens was randomly selected to undergo a localized lesion and the other lens remained intact. The lesion was made on the anterior surface with a steel hexagonal rod (to make the mark easily identifiable) previously immersed in liquid nitrogen for one minute. Both lenses were incubated for 1 h at 20°C in a HEC mixture. Images were acquired with a macroscope and analysed with ImageJ. Calcein‐AM and Ethidium images were used to calculate the area covered by living epithelial cells. Hoescht images allowed to count cell nuclei per unit area. Viable epithelial cell density (vECD) was defined as the number of viable cells per unit area. The lenses were immersed (isotonic saline) inside a black container during the measurements to minimize reflections and refractive phenomena or drying of the samples.Results: The vECD median on the ten pairs was 2840 cells/mm2 [10th‐90th percentiles = 2479–3494] for cryo‐applied lenses versus 3364 cells/mm2 [2919–3739] for healthy lenses (p = 0.002).Conclusions: The triple HEC staining adapted to the whole lens provides an unrivalled measure of pan‐epithelial viability without the need for a tedious capsule dissection step that destroys the lens architecture. Other studies will be necessary to determine its ability to discriminate small variations or type of mortality.
A novel approach for measurement of retinal oxygen extraction based on laser speckle flowgraphy and retinal oximetry
Authors: Pai Viktoria , Lindner Theresa , Janku Patrick , Pylypenko Liudmyla , Hommer Anton , Schmetterer Leopold , Schmidl Doreen , Garhöfer Gerhard 
Published: January 2024

Aims/Purpose: Several ocular diseases lead to a reduction in retinal oxygen metabolism. However, measurement of retinal oxygen extraction is mostly based on time‐consuming and custom‐built devices. Hence, the aim of this study is to assess retinal oxygen extraction based on measurement of retinal blood flow with the commercially available laser‐speckle flowgraphy (LSFG) and measurement of retinal oxygen saturation with the commercially available retinal oximetry.Methods: Ten young healthy subjects participated in the present study. Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic disc at the same position. The corrected arterial (co2, CRA) and venous (co2, CRV) oxygen content was estimated from the parameters evaluated and the difference between these two determined parameters (co2, DIFF) was assessed. Retinal oxygen extraction was calculated using mean vessel flow rate (MV) and cO2, DIFF. To validate the novel approach, baseline measurement and measurement during inhalation of 100% oxygen were performed, as retinal oxygen extraction is known to decrease during hyperoxia.Results: MV significantly decreased during 100% oxygen breathing (−23 ± 10%, p < 0.001). While cO2, CRA only slightly increased by 1 ± 2% (p = 0.093), cO2, CRV increased by 9 ± 14% (p = 0.050). Consequently, cO2, DIFF decreased by 10 ± 20% (p = 0.087). This led to a pronounced decrease in retinal oxygen extraction by −31 ± 18% during hyperoxia (p < 0.001).Conclusions: During breathing of 100% oxygen a significant decrease in TRBF and retinal oxygen extraction was assessed. The decrease in retinal oxygen extraction during hyperoxia is consistent with findings in literature and is physiologically expected. Therefore, the novel approach for measurement of retinal oxygen extraction appears to be feasible. Larger studies in patient cohorts using this method should be conducted in the future.
Catapol might protect against retinal ischaemia by anti‐oxidation, anti‐ischaemia, Wnt pathway inhibition and VEGF downregulation
Authors: Chao Howard Wen‐Haur , Chao Hsiao‐Ming 
Published: January 2024

Aims/Purpose: Retinal ischaemic disorders, including retinal vascular occlusion, age‐related macular degeneration and glaucoma, pose a threat to vision. This study examines the potential protective effects of catalpol against retinal ischaemia.Methods: RGC‐5 cells were cultured in DMEM with 10% FBS, penicillin (100 U/mL) and streptomycin (100 mg/mL) at 37°C. Cell viability was assessed using the MTT assay. H2O2 (1 mM)/OGD induced oxidative stress and ischaemic‐like injury. Catalpol or vehicle was administered 15 min before the insult. Retinal ischaemia was induced in Wistar rat eyes by increasing intraocular pressure to 120 mmHg for 60 min, followed by reperfusion. Intravitreous injections of catalpol (0.5 or 0.25 mM), WNT inhibitor Dkk1 (1 μg/4 μL), anti‐VEGF lucentis (20 μg/2 μL), or anti‐VEGF eyelea (80 μg/4 μL) were given 1 day before or after retinal ischaemia. Effects were evaluated using electrophysiology, histopathology, immunohistochemistry, fluorogold retrograde labeling, and Western blotting.Results: H2O2 (1 mM)/OGD significantly (p < 0.001) reduced RGC‐5 cell viability by inducing reactive oxygen species and ischaemic‐like insult. Pretreatment with catalpol (0.5 mM) dose‐dependently attenuated this oxidative/ischaemic‐like effect (p < 0.05), suggesting its antioxidative properties. Pre‐ischaemic treatment with catalpol (0.5 and 0.25 mM) dose‐dependently and significantly (p < 0.05; 0.5 mM) mitigated ischaemia‐induced reductions in ERG b‐wave amplitude and RGC cell number. Compared to eyes treated with DKK1, lucentis, or eyelea, catalpol appeared to protect against retinal ischaemia by downregulating WNT and VEGF expression (downstream).Conclusions: Catalpol may provide protection against retinal ischaemia through antioxidation and anti‐ischaemic mechanisms by downregulating the upstream WNT pathway and downstream VEGF concentration.References1. Chao, et al. Ferulic acid, but not tetramethylpyrazine, significantly attenuates retinal ischaemia/reperfusion‐induced alterations by acting as a hydroxyl radical scavenger. J. Ocul. Pharm. Ther. 24:461–472, 2008.2. Liu, et al. Baicalein significantly protects hRPE cells against H2O2‐induced oxidative stress by scavenging ROS and down‐regulating the expression of MMP9 and VEGF. J. Ocul. Pharm. Ther. 26:421–429, 2010.
Comparative effect of intravitreal faricimab versus aflibercept in a patient with diabetic macular oedema
Authors: Montero‐Moreno Javier , Diez‐Montero Cecilia , Sanchis‐Merino Maria Eugenia , Hernandez‐Fernandez Rosario , Cañibano‐Perez Elisabeth 
Published: January 2024

Aims/Purpose: To report the changes in diabetic macular oedema (DME) and visual acuity (VA) in a single patient with bilateral DME treated with intravitreal 2 mg aflibercept (AFL) and 6 mg faricimab (FAR) in the context of a randomized clinical trial during 44 weeks.Methods: Interventional case report within a clinical trial.Results: A 57‐year‐old female patient entered a clinical trial to test the efficacy of FAR for DME. DME was present in both eyes. The left eye (LE) was randomized to masked treatment (which resulted to be 6 consecutive intravitreal FAR every 4 weeks followed by FAR every 8 weeks, totalling 8 injections). The RE received open label treatment with monthly AFL at baseline; and then every 4 weeks after Week 16, until Week 44, totalling 8 injections). Baseline best corrected VA was RE 50 letters and LE 64 letters; at Week 24, RE 46 and LE 62; and at Week 44, RE 46 and LE 76. Optical coherence tomography (OCT) revealed a progressive reduction of central macular thickness (CMT) as well as hard exudates and disorganization of retinal layers in both eyes. Angio OCT showed a progression of non‐perfused macular areas in both eyes; the anti‐vascular endothelial growth factor effect of the treatment induced a reduction in the severity of diabetic retinopathy in both eyes demonstrated by fluorescein angiography and colour fundus imaging.Conclusions: Our results show that treatment with AFL and FAR in the eyes of the same patient may cause a similar reduction in CMT, even though a better visual outcome was observed in the eye treaded by FAR.
Acute zonal occult outer retinopathy as a luetic ocular manifestation
Authors: Sanchez Manuel Morales , Ortega Mª Mar Esteban , Lozano Carmen Isabel García , Hernandez Eduardo Conesa , Artola Ines , Pernas Sergio 
Published: January 2024

Aims/Purpose: Based on a clinical case seen in our setting, the purpose of this communication is to describe a case of ocular syphilis with an uncommon initial manifestation as well as its clinical and imaging features, diagnosis, treatment and evolution.Methods: We selected a case seen at the University Hospital Infanta Sofía in 2023. A 54‐year‐old male with Acquired Inmune Deficiency Syndrome (AIDS) under antiretroviral (ARV) treatment, diagnosed with cataract, who 1 month after surgery presented a paradoxical worsening of baseline visual acuity (VA) bilaterally accompanied by nyctalopia.Results: During the exam, we found VA from right eye (RE) of 0.03 and from left eye (LE) of 0.03. Fundus examination showed a bilateral central vitreous organization. Macular OCT from both eyes showed preserved foveal profile with pachychoroid associated with patchy absence of external limiting membrane, evident focal loss of ellipsoid zone and cysts in outer layers of the RE. Campimetry with practically abolished fields, neuroimaging study, complete serology including antirecoverin antibodies, and vitreous sample for microbiology were performed. From this study, it was found that the patient had a positive luetic seroconversion within a maximum period of five years. With these data, we oriented the differential diagnosis of the described retinopathy towards an infectious or toxic aetiology due to ARV drugs as the most probable causes. The patient was treated with intravenous penicillin with great improvement of vision and nyctalopia.Conclusions: Ocular syphilis is the great simulator par excellence and although infrequent, it can debut with atypical forms of uveitis.References1. Lima BR, Mandelcorn ED, Bakshi N, Nussenblatt RB, Sen HN. Syphilitic outer retinopathy. Ocul Immunol Inflamm 2014; 22: 4–8.2. Dutta Majumder P, Chen EJ, Shah J, Ching Wen Ho D, Biswas J, See Yin L, et al. Ocular syphilis: an update. Ocular Immunology and Inflammation 2017; 1–9.3. Roe RH, Jumper JM, Galino V, et al. Retinal pigment epitheliopathy macular telangectasias, and intraretinal crystal deposits in HIV‐positive patients receivingritonavir. Retina 2011; 31: 559–565.