bluuebunny/crossref_metadata_2025_split huggingface dataset:
rho kinase inhibitor for primary open‐angle glaucoma and ocular hypertension ‐ a Cochrane systematic review
Authors: Freiberg Josefine Clement , von Spreckelsen Alexander , Azuara‐Blanco Augusto , Kolko Miriam , Virgili Gianni 
Published: December 2022

AbstractPurpose: To compare the efficacy and safety of rho kinase inhibitor (ROKi) with placebo or other glaucoma medication in people diagnosed with open‐angle glaucoma (OAG), primary open‐angle glaucoma (POAG) or ocular hypertension (OHT).Methods: We searched CENTRAL, MEDLINE, Embase, PubMed, LILACS, ClinicalTrials and ICTRP for randomized clinical trials and controlled clinical trials with no restrictions of type, year, and publication status. Two review authors independently screened, extracted data, and evaluated risk of bias.Results: We included 17 trials (4953 participants) evaluating the efficacy and safety of marketed ROKI‐based drugs; netarsudil and ripasudil. Trial duration varied from 24 h to 12 months. The intraocular pressure (IOP) lowering effect of netarsudil may be superior to placebo (mean difference (MD) 3.11 mmHg 95% CI 2.59–3.62; low‐certainty evidence), but inferior to latanoprost (MD 0.97 mmHg 95% CI 0.67–1.27; moderate‐certainty) and timolol (MD 0.66 95% CI 0.41–0.91; low‐certainty). Combining netarsudil and latanoprost probably further reduces IOP compared with either netarsudil (MD 2.66 mmHg 95% CI 2.35–2.98; moderate‐certainty) or latanoprost (MD 1.64 mmHg 95% CI 1.11–2.16; moderate‐certainty). Combining ripasudil and timolol may probably reduce IOP compared with timolol monotherapy (MD 0.75 mmHg 95% CI 0.21–1.29; moderate‐certainty). The certainty of evidence reporting ocular adverse events (AEs) was very low or low. However, compared to timolol, netarsudil (21 additional ocular AEs per 100‐person‐months 95% CI 14–27; moderate‐certainty) and combination therapy with ripasudil/timolol (35 additional ocular AEs per 100 person‐months 95% CI 25–45; moderate‐certainty) probably lead to more ocular AEs. ROKi was not associated with any particular serious AEs.Conclusions: The current evidence suggests that in people diagnosed with OHT or (P)OAG, the hypotensive effect of netarsudil may be inferior to latanoprost and slightly inferior to timolol. Combining netarsudil and latanoprost probably further reduces IOP compared with monotherapy. However, differences are small and may not be clinically significant. Netarsudil as mono‐ or combination therapy may result in more ocular AEs, but the evidence on AEs is limited.
Retinal blood flow and oxygen saturation in patients previously infected with COVID‐19
Authors: Lindner Theresa , Hommer Nikolaus , Kallab Martin , Schlatter Andreas , Nadvornik Clemens , Janku Patrick , Kauer Victoria , Rumpf Benedikt , Haslacher Helmuth , Garhöfer Gerhard , Schmidl Doreen 
Published: December 2022

AbstractPurpose: The SARS‐CoV‐2 pandemic has affected all countries in the world and is still ongoing. Although respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. We therefore set out to investigate whether ocular vascular alterations remain after patients have recovered.Methods: Patients that had recovered from COVID‐19 infection within the last 6 months before inclusion and healthy age‐ and sex‐matched controls were recruited. Main inclusion criteria for patients were confirmed positive PCR test for SARS‐CoV‐2 in the medical history and positive testing for SARS‐CoV‐2 seroprevalence while controls had no history of COVID‐19 infection. Arteriovenous (AV) difference in oxygen saturation was calculated out of retinal arterial and venous oxygen saturation, which were measured with a commercially available Dynamic Vessel Analyser (DVA, Imedos, Germany). Retinal vessel diameters and arteriovenous ratio (AVR) were assessed using the same device. In addition, mean blur rate in the tissue area of the optic nerve head (MT) was quantified using laser speckle flowgraphy (LSFG, Nidek, Japan).Results: 29 patients that had recovered from moderate to severe COVID‐19 requiring hospitalization (mean age 35 ± 17 years) and 11 control subjects (mean age 36 ± 12 years) were included in the present study. No differences between groups regarding sex or concomitant diseases in the medical history were found. Body mass index (BMI) was significantly higher in patients that had recovered from COVID‐19 (27.5 ± 5.6 vs. 24.5 ± 2.8 m2/kg, p = 0.036). AVR as well as AV difference in oxygen saturation was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). MT in the optic nerve head also was significantly lower in patients (23.4 ± 10.1 a.u.) than in control subjects (47.3 ± 26.6 a.u., p < 0.001).Conclusions: The results of this study imply that retinal metabolism is still altered in patients after recovering from COVID‐19 infection. Longitudinal studies are required to investigate whether these changes in retinal vessels as well as optic nerve head blood flow are temporary or remain.
COVID‐19 vaccination and vision loss in three older male individuals homoplasmic for m.14484 T > C mutation in the ND6 gene
Authors: Votruba Marcela 
Published: December 2022

AbstractPurpose: To report three older male individuals, all homoplasmic for m.14484 T > C mutation in the ND6 gene, presenting onset of vision loss weeks‐months after covid vaccination. None reported a history of covid‐19 infection.Methods: All clinical data was extracted and reported here as a Case Series.Results: A 68 years old man (A) had a 3rd dose of BioNTech/Pfizer COVID‐19 vaccination on 1st Nov 2021. 10 days later his vision was 6/6 OD and 6/60 OS. By Dec 2021 VA was 6/36 OD and 6/60 OS. His nephew lost vision age of 18 years with LHON. In March 2022, visual acuities were HM OD and HM OS. In May 2022 visual acuity was HM OD, PL OS. He started on idebenone 300 mg tds.A 55 years old man (B) had a 1st dose Astra Zeneca COVID‐19 vaccination in mid Feb 2021. 12 days later, March 2021 he developed a Bell's Palsy and sensory neuropathy at the top of his legs, feet and upper arms, with difficulty walking. MRI showed enhanced optic nerves and enhanced lesions at C2. In April 2021, he lost vision in his right eye, followed by left eye in June 2021. By September 2021 vision was CF BEs. He started on idebenone 300 mg po tds. In May 2022 he was LogMAR @ 2 m 1.34 OD and MH OS.A 72 years old man (C) had his 2nd dose of BioNTech/Pfizer COVID‐19 vaccination in April 2021. In Sept 2021 he reported loss of vision in both eyes but could not date onset. He was the maternal cousin of individual B. In May 2022 vision was 3/60 OD CF OS. He started on idebenone 300 mg po tds.Conclusions: Adverse ocular events related to COVID‐19 vaccines are remarkable rare. There are >20 published case reports (~89 patients) of adverse ocular events within 28 days of COVID‐19 vaccination, with all three vaccines (Pfizer, AstraZeneca and Moderna). Reports incl. conjunctivitis, facial and abducens nerve palsy, CSR, uveitis, MEWDS, VKH, Graves' Disease, endothelial graft rejection, AAION and AZOOR. The role of vaccination in subsequent vision loss in those with underlying mitochondrial mutation is not clear.
Ocular surface assessment of preserved and preservative‐free brimonidine tartrate in glaucoma patients: A parallel‐grouped comparison trial
Authors: Kim Myungjin , Rho Seungsoo , Lee Chang Kyu , Kim Ko Eun , Shin Jonghoon , Kim Eunsol 
Published: December 2022

AbstractPurpose: To evaluate and compare the efficacy and safety of preservative‐free and preserved brimonidine tartrate 0.15% in open‐angle glaucoma and ocular hypertension.Methods: We conducted a multicenter (four institutions), randomized, investigator‐masked, parallel‐group clinical trial. A total of 60 eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open‐angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative‐free (n = 29) brimonidine groups. Enrolled eyes received three times daily monotherapy of brimonidine. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate at 12 weeks after the first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear‐film break‐up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events.Results: After 12 weeks, both preserved and preservative‐free groups showed similar amount of IOP reduction, corneal and conjunctival staining score, drug tolerance, and adherence rate. The preservative‐free group showed significantly better TBUT and higher patient satisfaction with regard to drug use and management. The reduction amount of systolic and diastolic blood pressures during 12 weeks were significantly lower in the preserved group than the preservative‐free group.Conclusions: Preservative‐free brimonidine tartrate showed comparable efficacy and safety with better corneal tear film stability and patient satisfaction compared to preserved brimonidine.
Estimation of the adherence to Mediterranean diet by Greek glaucomatous patients
Authors: Vlachogianni Ioanna , Chatzistefanou Klio , Droutsas Konstantinos , Moschos Marilita 
Published: December 2022

AbstractPurpose: An estimation of the nutritional profile of patients with primary open angle glaucoma (POAG). We focused on the evaluation of the adherence to Mediterranean diet in Greek population.Methods: An observational study was conducted to assess the adherence to the Mediterranean diet in patients who attended the General Hospital of Athens G. Gennimatas. An experienced dietitian interviewed both healthy and glaucomatous patients and filled the Med Diet Score (range 0–55). The scoring includes food groups close to Mediterranean dietary pattern like non‐refined cereals, fruits, vegetables, legumes, olive oil, fish and potatoes.Results: A total of 132 questionnaires were completed successfully by 64 healthy and 68 patients. Both groups were equally distributed for sex (50/50 males/females) and age (71.9 years ± 10). The overall adhesion to the Mediterranean diet was similar in both groups with the majority of them (around 80%) having moderate adherence. There is no difference between 2 groups for Body Mass Index (BMI), dietary supplements and salt consumption, smoking habits or comorbidities like diabetes type II and hypertension.Conclusions: There is no data concerning adherence to Mediterranean diet in Greek glaucomatous patients. This study indicated that both healthy and glaucomatous patients have moderate adherence to the Mediterranean diet.Reference1. Demosthenes B Panagiotakos et al. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev Med. 2007;44(4):335–40. doi: 10.1016/j.ypmed.2006.12.009.
clinical grade of genetically corrected RPE cells for autologous cell therapy of hereditary retinal dystrophies
Authors: Ureña‐Peralta Juan , Brymova Anna , Mayordomo Noelia Pimentel , Jendelova Pavla , Ardan Taras , Studenovska Hana , Motlik Jan , Petrovski Goran , Erceg Slaven 
Published: December 2022

AbstractPurpose: The generation of genetically corrected RPE cells from patient‐derived human induced pluripotent stem cells (hiPSCs) may provide a source for autologous therapeutically‐relevant therapy for this rare retinal dystrophy as well to create the human cellular disease models. Recently we generated a faithful RPE model from patient bearing mutation in MERTK gene and genetically corrected these cells using CRISPR/Cas9 system. For further application in humans is necessary to differentiate the hiPSC towards RPE in clinical grade conditions.Methods: The RPE cells from the genetically corrected patient‐derived hiPSC (1 and 2 alleles) as well as patient's RP‐hiPSC and control healthy hiPSC were characterized using immunocytological methods for the differentiation and polarization markers, electronic microscopy, RT‐PCR, TEER measurement, ELISA test, Western Blot and phagocytic assay.Results: All generated RPE cells exhibit typical features of RPE cells We demonstrated the reestablishment of the expression of full‐length MERTK protein as well as the reversion of lost phagocyte function of hiPSC‐RPE in vitro, which represents the first example of its kind in this field.Conclusions: The generated hiPSC‐derived RPE in clinical grade conditions display the typical characteristics of mature RPE cells re‐establishing the function of phagocytosis in genetically corrected patient‐derived RPE cells in vitro. Functional in vivo studies in animal models such as RCS rats or larger animals will confirm whether this strategy can completely restore the vision and be employed as a potential treatment for patients.
Cyclodiode vs micropulse transscleral laser treatment
Authors: Kelada Monica , Bloom Philip , Normando Eduardo Maria 
Published: December 2022

AbstractPurpose: Continuous wave transscleral cyclophotocoagulation (CW‐TSCPC), is reserved for refractory glaucoma with poor visual potential due to its complication rate, attributed to continuous energy damaging adjacent tissues. Micropulse (MP‐TSCPC), however, utilizes short energy pulses separated by ‘off’ periods, and is associated with a lower complication rate. The National Institute for Health and Care Excellence has deemed evidence surrounding MP‐TSCPC as inadequate, limiting its use to research purposes. This study aims to evaluate the efficacy and safety of MP‐TSCPC compared to CW‐TSCPC. It also aims to investigate whether glaucoma type affects treatment outcomes.Methods: This retrospective study included 86 CW‐TSCPC eyes and 188 MP‐TSCPC eyes at a London tertiary centre. Follow‐up was conducted for 24‐months. Primary outcome was overall treatment success defined as success at the last available follow‐up. Success required at least 20% IOP reduction, with the same or fewer medications, and IOP between 6–18 mmHg (complete success)/19–21 mmHg (qualified success). Secondary outcomes were retinal nerve fibre layer (RNFL) thickness progression, and visual field (VF) change. Safety outcomes were visual acuity (VA) and complication rate.Results: 24‐months success rate was 27.6% for CW‐TSCPC and 30.1% for MP‐TSCPC, p = 0.96. Average IOP was reduced by 44.8% (CW‐TSCPC) and 26.5% (MP‐TSCPC) from baseline 19.0 ± 3.0 mmHg and 19.1 ± 2.2 mmHg, respectively. Both interventions significantly reduced glaucoma medications at 24‐months (p ≤ 0.05). The proportion of patients experiencing complication(s) was significantly higher after CW‐TSCPC (32.9%) vs MP‐TSCPC (16.2%, p = 0.002). Both procedures displayed VA worsening. RNFL thickening rate was greater following CW‐TSCPC (p = 0.31). MP‐TSCPC reduced VF loss rate significantly among severe disease (p = 0.04).Conclusions: Both interventions demonstrated similar success rates, and reduced IOP and glaucoma medications. MP‐TSCPC displayed minimal complications. There was no clear association between glaucoma type and treatment outcomes. Further prospective studies, with measures of medication compliance, are required to further evaluate MP‐TSCPC efficacy and safety compared to CW‐TSCPC.
Implantation of a novel glaucoma drainage with a small lumen silicone tube in rabbits: A pilot study
Authors: Kim Myungjin , Rho Seungsoo , Han Jongchul , Kim Eunsol , Kim Hae Rang 
Published: December 2022

AbstractPurpose: To assess surgical safety and expert usability of a novel glaucoma drainage implant with a smaller lumen compared to conventional silicone tubes.Methods: The newly constructed devices have been implanted via a specially designed injector system in 4 eyes of 4 New Zealand White rabbits, and their intraocular pressure was measured on days 7, 14, 21, and 28 postoperatively. The histopathologic evaluation was done after the 1 month‐follow up period using H&E staining and Masson‐trichrome staining. For the implantation, a limbal incision without mitomycin‐C (MMC) was performed in one eye, and a fornix incision with MMC was performed in three eyes.Results: The histologic sections showed well‐tolerated tissue response in all 4 eyes. All eyes showed filtering blebs on day 28 except one eye that had a buttonhole during the implantation. IOPs were better controlled in the 2 eyes done fornix incision with MMC plus without the buttonhole than other 2 eyes (6 mmHg vs 12.5 mmHg at day 28). The device was highly visible during the procedure of operation and had the flexibility to fit the surgeon's various procedures.Conclusions: The novel glaucoma drainage implant was effective and flexible to fulfil the surgeon's need in a pilot study with rabbits.
Leber congenital amaurosis and early onset severe retinal dystrophy in the Czech Republic: Mutational spectrum and clinical findings
Authors: Vajter Marie , Kousal Bohdan , Moravikova Jana , Chylova Monika , Dudakova Lubica , Stankova Daniela , Boday Arpad , Krutilkova Vera , Liskova Petra 
Published: December 2022

AbstractPurpose: Leber congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD) is a group of ultra‐rare retinal diseases with an estimated prevalence of 1/80 000. The aim of this study was to perform a detailed clinical characterization in patients with LCA/EOSRD confirmed at the DNA level.Materials and methods: 16 patients (eight females, eight males) from 16 families underwent ocular examination in the Department of Ophthalmology, 1st Faculty of Medicine and General University Hospital in Prague between the years 2010–2021. Pathogenic variants in genes associated with LCA/EOSRD were searched using targeted gene panels, exome and/or genome sequencing. Confirmation of the presence of causal variants and segregation within the families was performed by Sanger sequencing. Next we have performed review of available clinical documentation of five additional probands examined elsewhere in the Czech Republic.Results. The mean age at the first examination was 17.8 years (range 2–42 years). The mean age of symptoms onset was 1,99 years (range 6 weeks to 5 years). In five patients, the disease was caused by biallelic mutations in the RPE65 gene, in 4 patients in the CEP290 gene and in three patients in the CRB1 gene. Biallelic mutations in the GUCY2D, LCA5, RPGRIP1 and CLN3 genes were the cause of the disease in one patient each. As for probands suffering from LCA/EOSRD and examined elsewhere two were documented carriers for pathogenic variants in the CEP290 gene, two in the CRB1 gene and one in the GUCY2D gene.Conclusions: This is the first study presenting molecular genetic and clinical characteristics of patients with LCA/EOSRD from the Czech Republic. Biallelic mutations in the CEP290 gene are the most common genetic cause of LCA/EOSRD in our patient group.This work was supported by NU20‐07‐00182; EJPRD19‐234 Solve‐RET.
ELAVL1/HuR regulates both endo‐ and exogenous neuroprotection in retinal ganglion cells
Authors: Smedowski Adrian , Pacwa Anna , Liu Xiaonan , Machowicz Joanna , Rodak Piotr , Pietrucha‐Dutczak Marita , Akhtar Saeed , Amadio Marialaura , Lewin‐Kowalik Joanna 
Published: December 2022

AbstractPurpose: To evaluate the impact of HuR gene silencing on the ratio of age‐related degeneration of Retinal Ganglion Cells (RGC), which potentially describes the efficiency of endogenous neuroprotection mechanisms, as well as to assess the exogenous neuroprotection capacity of HuR‐ silenced RGC in rat glaucoma model treated with Metallothionein.Methods: Thirty‐five eight‐week‐old male Long Evans rats were divided into two groups: experimental and control. Animals from experimental group received intravitreal injection of AAV‐shRNA‐HuR. Control group received injection of AAV‐shRNA scramble control. Animals from both groups were sacrificed in 3 different time points: 2, 4 and 6 months after injection. Both healthy and treated retinas from each animal were collected and processed as whole mounts for immunostainings and RGC count. For the second trial, animals were divided into groups and transfected with virus particles as described above. To induce chronic glaucoma model, 8 weeks after AAV injection, unilateral episcleral vein cauterization was performed. Half of animals from each group received intravitreal injection of Metallothionein (MT), the other group received PBS injection. During the experiment IOP was monitored. Both healthy and treated retinas from each animal were collected and processed as whole mounts for immunostainings and RGC count.Results: RGC count (per visual field under 20× magnification) was 310 ± 31, 296 ± 25, 189 ± 41 in experimental group and 399 ± 51, 395 ± 49, 390 ± 23 in control respectively for 2, 4 and 6 months after injection (Kaplan‐Mayer trend rank p < 0.0001). Loss of RGC in central retina was 33.7% in animals from shRNA‐MT‐treated glaucoma and 11.4% in shRNA control‐MT‐treated glaucoma (p < 0.05). In peripheral part of the retina the loss was 37.4% in animals from shRNA‐MT‐treated glaucoma and 11.5% in shRNA control‐MT‐treated glaucoma (p < 0.01).Conclusions: Silencing of hur gene enhanced age‐related loss of RGC which translates into impaired endogenous neuroprotection pathways, moreover the absence of HuR critically limits neuroprotective activity of exogenously delivered Metallothionein.
Spontaneous corneal perforation in treatment‐resistant MPO‐ANCA‐associated small vessel vasculitis
Authors: Zehnder Karin , Reinhold Aja , Gugleta Konstantin , Gatzioufas Zisis 
Published: December 2022

AbstractPurpose: Spontaneous corneal perforation is a rare complication in peripheral ulcerative keratitis (PUK). Identifying the systemic cause of PUK is essential for optimal treatment. MPO‐ANCA‐associated small vessel vasculitis is a potential cause of PUK. Being an autoimmune disorder, immunosuppressive therapy is indicated. Besides steroids, biologicals such as rituximab can be used with excellent results.Methods: In this case report, we would like to present a 83‐year‐old male patient with PUK caused by MPO‐ANCA‐positive small vessel vasculitis.Results: In this patient with PUK due to small vessel vasculitis, a spontaneous corneal perforation could not be prevented despite maximal immunosuppressive therapy. Thus, a tectonic penetrating keratoplasty à chaud was inevitable.Conclusions: Ophthalmologists should be aware of the rare complication of corneal perforation secondary to PUK caused by vasculitis.