bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I investigate acquired megaloblastic anemia
Authors: Torrez Mary , Chabot‐Richards Devon , Babu Daniel , Lockhart Evelyn , Foucar Kathryn 
Published: January 2022

AbstractIn this review of megaloblastic anemia (MA), an overview of vitamin B12 and folate body requirements, biochemical pathways, and laboratory testing strategies will be provided. However, the focus of this review is the classic and unique features of MA in blood and bone marrow. Acquired MA is a benign disorder for many, but can be detrimental for some. The clinical presentation can vary considerably, and the spectrum of symptoms and signs is diverse and quite broad. Prompt recognition and therapy are critical to prevent potential irreversible damage and clinical sequelae, especially in patients with vitamin B12 deficiency. A delay in diagnosis of vitamin B12 deficiency can result in significant neurologic sequelae that may not fully resolve with treatment, including in neonates and young infants. The blood and bone marrow features in MA can closely mimic thrombocytopenic purpura, myelodysplasia, and other myeloid neoplasms. Both pancytopenia and normal MCV at presentation are common in MA and raise unique challenges for the diagnostician. Partially treated MA is also a significant diagnostic “trap”. MA is highly responsive to treatment, and patients tend to improve rapidly upon treatment initiation. However, the broad range of clinical and hematologic features makes the rapid, successful diagnosis of MA a unique challenge for the hematopathologist. Even in the era of state‐of‐the‐art laboratory testing, a high suspicion is required.
Hydroquinone increases risk for retinal pigment epithelial (RPE) cell degeneration
Authors: Bhattarai Niina , Hytti Maria , Mysore Yashavanthi , Kaarniranta Kai , Kauppinen Anu 
Published: January 2022

AbstractPurposeCigarette smoke increases the risk for age‐related macular degeneration (AMD) e.g. through oxidative stress and mitochondrial damage in human retinal pigment epithelial (RPE) cells. Vascular endothelial growth factor (VEGF) promotes choroidal neovascularization in wet AMD, for which anti‐VEGF injections are used as therapy. Since VEGF is important for the RPE cell functionality and integrity, too low VEGF levels increase the risk for RPE cell degeneration. Pigment epithelium‐derived factor (PEDF) improves mitochondrial activity and reduces neovascularization. The aim of the present study was to examine the effects of the cigarette smoke component hydroquinone on the VEGF and PEDF levels in RPE cells.MethodsIL‐1α‐primed ARPE‐19 cells were exposed to hydroquinone (10 μM, 50 μM, 200 μM; 18 h, 1 h or 15 min). Enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of intracellular VEGF as well as secreted VEGF and PEDF. The 2′,7′‐dichlorofluorescin diacetate (DCFDA) probe was used to detect ROS production. Lactate dehydrogenase (LDH) and intracellular ATP were measured using commercial kits, and total protein concentrations using a protocol based on the Bradford method.ResultsHydroquinone reduced the levels of both intra‐ and extracellular VEGF. In addition, the release of PEDF as well as the ratio between VEGF and PEDF were reduced at all used concentrations. ROS production increased at 50 μM hydroquinone, and the cell membrane was compromised at 200 μM hydroquinone after 15 min exposure. ATP levels were reduced from the 50 μM hydroquinone concentration upwards and total protein levels at all concentrations, already without cytotoxicity.ConclusionsAccording to our present data, hydroquinone favors anti‐angiogenic conditions but predisposes to the RPE cell degeneration, impaired mitochondrial function, and reduced protein synthesis in human RPE cells.
Retinal ganglion cells derived from retinal organoids – a contemporary model to study neurodegenerative retinal diseases
Authors: Saruhanian Sarkis , Kolko Miriam , Freude Kristine 
Published: January 2022

AbstractPurposeNeurodegenerative retinal diseases are a significant course for blindness. Diseases such as glaucoma, which is the leading course of irreversible blindness in the world, and other inner retinal conditions such as inherited mitochondrial neuropathies are poorly understood. The treatment options for these diseases are often limited and insufficient to prevent blindness. Common for most of these diseases is the loss of the retinal ganglion cells (RGC).MethodsTo elucidate the underlying pathological and protective pathways in these inner retinal diseases, respectively, we aim to assess retinal organoids generated from patient‐specific induced pluripotent stem cells (iPSC) and their controls. We have previously established the method of extracting RGCs from our retinal organoids via magnetic‐activated cell sorting (MACS).ResultsThe subsequent characterization of these RGCs was performed using cell‐specific markers such as CD90, BRN3a and RBPMS via qPCR and immunocytochemistry. Electron microscopy was used to investigate the intracellular organelle conditions of the RGCs. Future experiments are aimed at respiratory capacity analysis, metabolomics, transcriptomics and proteomics of RGCs extracted via MACS from retinal organoids derived from patient iPSCs in hopes of identifying the differences and possibly cellular mechanisms contributing to neurodegenerative retinal diseases in patients compared to healthy controls.ConclusionsThis could potentially lead to further understanding of disease mechanisms in patients with inner retinal diseases. In addition, this could establish a diseases model to test new treatment options such as neuroprotective drugs.
Development of desiccated stromal lenticules and study of their integration in vivo
Authors: Vautier Anais , Chaventré Fanny , Lefevre Sabine , Toubeau David , Arnoult Christophe , Albou‐Ganem Catherine , Gabison Eric , Bourges Jean Louis , Boyer Olivier , Muraine Marc 
Published: January 2022

AbstractPurposeSMILE (Small Incision Lenticule Extraction) surgery consists in removing a stromal lenticule of a known refractive power. Usually eliminated, it could be advantageously offered on demand for refractive or therapeutic purposes. The aim is to develop desiccation of SMILE lenticules as a long‐term preservation technique and evaluate their quality in vitro and in vivo.MethodsLenticules were collected after SMILE procedures in patients. Lenticules were desiccated under a specific protocol. Histological and electron microscopic analysis were performed. Six rabbit eyes were grafted with an inlay technique which consisted in inserting a desiccated lenticule inside a stromal pocket. Rabbits were sacrificed at different times between 6 and 24 weeks. Their corneas were analysed with optical coherence tomography (OCT), histology and immunofluorescence.ResultsUnder microscopic analyses of desiccated lenticules, we found a preserved stromal architecture after rehydration. We noticed a decellularization of the lenticules after desiccation (shown by both DAPI and haematoxylin eosin staining). All rabbits’ corneas remained clear after grafting. No rejection occurred without any immunosuppressive treatment. With OCT, we noted the lenticular implantation was regular with no decrease in lenticule thickness. On histological analysis, we found no inflammatory infiltration around lenticules. No nuclear material was visible in histology at week 12 inside lenticules. This absence of recolonization with host cells at week 12 was confirmed with DAPI. Analyses at 4 and 6 months are in progress.ConclusionsIn rabbit corneas, we observed a favourable integration of human desiccated SMILE lenticules at this time. We still must investigate the refractive issue of this lenticular implantation. If we obtain favourable results, we could set up a clinical trial with the use of desiccated SMILE lenticules to treat hyperopia or keratoconus.
Temperature and heat flux density of the eye surface in healthy individuals with different subfoveal thickness of the choroid
Authors: Anatychuk Lukyan , Pasyechnikova Nataliya , Naumenko Volodymyr , Kobylianskyi Roman , Zadorozhnyy Oleg 
Published: January 2022

AbstractPurposeTo study the temperature and heat flux (HF) density of the ocular surface of healthy individuals depending on the thickness of the choroid.MethodsThis pilot study included 22 healthy individuals (44 eyes). The age of the studied healthy individuals ranged from 18 to 86 years. In all cases, measurement of temperature and HF density were performed on the outer surface of the cornea of both eyes. A thermoelectric device was used to measure epibulbar temperature and HF density. Optical coherence tomography was performed to determine the subfoveal thickness of the choroid.ResultsMean room temperature during examination sessions was 21.5 ± 0.8°C. In addition, mean temperature of the external ocular surface and mean HF density from the human eye were 34.7 ± 0.7°C and 7.5 ± 1.2 mW/cm2, respectively. The thickness of the choroid in healthy individuals averaged 307 ± 37 μm. There was a positive correlation between the thickness of the choroid with the heat flux density of the eye (r = 0.6; p = 0.000) in contrast to the temperature of the cornea (r = 0.2; p = 0.1).ConclusionsIn healthy people, the density of the heat flux of the eye on the surface of the cornea depends on the subfoveal thickness of the choroid, in contrast to the temperature of the outer surface of the eye.
Clinical outcomes and satisfaction of autologous serum tears treatment for ocular surface diseases
Authors: Aguilar‐Valdez Itzel , De La Parra‐Colin Paola , Luna‐Briceño Jesús 
Published: January 2022

AbstractPurposeTo evaluate clinical outcomes and patient‐reported satisfaction of autologous serum tears for ocular surface diseases.MethodsWe retrospectively analyzed the clinical charts of 40 patients that were treated with 20% autologous serum tears for at least 3 months. We retrieved data for the Ocular Surface Disease Index (OSDI) questionnaire, fluorescein staining, corrected distance visual acuity (CDVA), and evidence of epithelial defects or corneal ulcers. We compared data from the initial visit to 3 months after autologous serum tears prescription. Concurrently with the study, we obtained patient‐reported satisfaction with the Treatment Satisfaction Questionnaire for Medication (TSQM).ResultsThe mean age was 59.3 (SD 15.2), 70% were female; 60% had aqueous deficient or mixed dry eye disease, 20% had neurotrophic keratopathy, and 20% had a persistent epithelial defect of different etiologies. OSDI improved from 32.7 ± 18.1 to 9.1 ± 7.7 (p < 0.001). At baseline, 92.5% of patients had a grade 2 score or higher in the Oxford staining score, whereas after treatment, 32.5% had a grade 2 score or higher (p < 0.001). The median of CDVA was 0.5 (0.2, 0.8) at baseline and 0.3 (0.2, 0.6) after treatment (p = 0.006). At baseline, 25% of patients had an epithelial defect or aseptic corneal ulcer, all resolved after treatment. The mean TSQM were 89.3 for global satisfaction, 84.8 for efficacy, and 68.5 for the convenience. No side effects were reported.ConclusionsAutologous serum tears improved the signs and symptoms of ocular surface diseases. Patients showed a high degree of satisfaction with the treatment.
Elevated intraocular pressure‐induced interlamellar keratitis in a patient with LASIK surgery 14 years ago
Authors: Arias Pablo Cisneros , El Bakkali Ismael Bakkali , Puyuelo Javier Ascaso , Muro Enrique Minguez , Moscarda Eva Nuñez , de Rivas Marta Orejudo , Pérez‐Rivasés Guillermo , Murillo Ana Boned , Barreda Maria Dolores Díaz 
Published: January 2022

AbstractPurposeTo describe a case of interlamellar keratitis induced by elevated intraocular pressure (IOP) in a patient with a history of LASIK surgery and the importance of having a strong diagnostic suspicion for establishing adequate treatment.MethodsIntraocular pressure‐induced interlamellar keratitis is one of the potential complications of LASIK refractive surgery. The cases described generally occur a few months after surgery although there are some cases that have been described several years after surgery, usually in a context of uveitis and corticosteroid treatment or silent glaucoma. We present a case of 43‐year‐old woman who came to the emergency room with visual acuity (VA) impairment in the left eye in the setting of elevated intraocular pressure‐induced interlamellar keratitis secondary to the intravitreal corticosteroid implant in her left eye due to a diabetic retinopathy. She underwent LASIK surgery 14 years ago.ResultsThe treatment was based on lowering the intraocular pressure. Oral acetazolamide and topical timolol, bimatoprost and brinzolamide were used. The patient recovered her baseline VA and the IOP were properly controlled posteriorly.ConclusionsThis case shows the importance of considering this diagnosis in patients with corneal haze, elevated intraocular pressure and a history of LASIK surgery to establish an adequate treatment. A full recovery is expected.Bibliography1. Galal A, Artola A, Belda J, (2006) Interface corneal edema secondary to steroid‐induced elevation of intraocular pressure simulating diffuse lamellar keratitis. Journal of refractive surgery.2. Lee V, Sulewski M, Zaidi A (2010) Elevated Intraocular Pressure–Induced Interlamellar Stromal Keratitis Occurring 9 Years After Laser In Situ Keratomileusis. Corneal Journal.3. Lyle W, Jin G, Jin Y (2003) Interface fluid after laser in situ keratomileusis. Journal of refractive surgery.4. Tourtas T, Kopsachilis N, Meiller R, et al. (2010). Pressure‐Induced Interlamellar Stromal Keratitis After Laser In Situ Keratomileusis. Corneal Journal.
Use of the corneal bioreactor to evaluate the anti‐edema effect and the ulcer healing rate between two commercial hyperosmotic eye drops: ODM5 and Muro 128
Authors: Peyret Benjamin , Crouzet Emmanuel , Chauchat Laure , Dumollard Jean Marc , Thuret Gilles , Gain Philippe 
Published: January 2022

AbstractPurposeThe corneal bioreactor (BR) in our laboratory, with an intraocular pressure (IOP) of 21 mmHg and the renewal of the culture medium, allows to maintain the homeostasis of the 3 layers of the cornea. We showed that an IOP reduced to 10 mmHg allowed to simulate a corneal edema (760 ± 57 µm) with a healthy epithelium.AimTo compare 2 hyperosmolar eye drops in the evolution of corneal deturgescence and epithelial ulcer healing: ODM5 composed mainly of NaCl 5% and hyaluronic acid (Horus Pharma, Saint‐Laurent‐du‐Var, France) and Muro 128 composed mainly of NaCl 5% and various excipients (Bausch+Lomb, Bridgewater, NJ)MethodsBeforehand, 3 pairs of human corneas were preserved for 2 weeks in the BR filled with CorneaMax (Eurobio, France), with a pressure maintained at 10 mmHg. A central epithelial ulcer of 6.64 ± 0.04 mm in diameter was made (D0). Each cornea received a drop of Muro 128 or ODM5 four times a day. Corneal central volume measurement (Casia 1, Tomey) was performed daily at the beginning and end of the day. Ulcer healing was monitored daily by fluorescein labelling and quantified by image analysis (Fiji) taken with a macroscope. At D14, the corneas were removed and fixed for immunostaining of E‐Cad (cell architecture), Zo‐1 (tight junctions), MUC16 (mucins), K3K12 (cell maturity) and for histology (Saffron Eosin Hemathein).ResultsMean daily volume loss was comparable: 2.43 ± 1.55 mm3 with ODM5 vs. 2.18 ± 1.71 mm3 with Muro 128 (p = 0.698 3). Corneal ulcers in all 3 pairs healed at D4, D5, D5 with ODM5 vs. D5, D13, and 1 cornea never healed with Muro 128. In IHC and histology, the epithelium was of better quality with ODM5.ConclusionsThe efficacy of the 2 eye drops is comparable. Epithelial preservation is partly better with ODM5, possibly related to the presence of hyaluronic acid.
Surgically induced, pharmacologically mediated endothelial corneal proliferation
Authors: Tanev Ivan , Kirkova Radina 
Published: January 2022

AbstractPurposeThe aim of our study is to evaluate the possibility for pharmaceutically mediated endothelial corneal proliferation in patients with corneal dystrophies.MethodsIt’s a cohort prospective study. We perform full ophthalmic examination /best corrected visual acuity for distance and near, tonometry, biomicroscopy, ophthalmoscopy, endothelial cell count/. We divide our patients with corneal endothelial dystrophies into two groups for therapeutic options: Group A and Group B. Patients from group A recieved only pharmaceutical product – a Rho‐kinase inhibitor to stimulate the proliferation of corneal endothelial cells. In Group B stripping of Descemet membrane is performed, in combination with a Rho‐kinase inhibitor.ResultsAll data from our study were statistically analyzed.ConclusionsSurgically induced pharmaceutically mediated corneal endothelial profileration showed promising results.
Study of corneal backscatter by Scheimpflug imaging in patients with keratoconus treated with corneal Cross‐linking
Authors: Moscarda Eva Josefina Núñez , Boned‐Murillo Ana , Díaz‐Barreda Mª Dolores , El Bakkali Ismael Bakkali , Rivasés Guillermo Pérez , Cisneros Pablo , deRivas Marta Orejudo , Del Buey Sayas María Ángeles , Pascual Paula Casas 
Published: January 2022

AbstractPurposeTo compare corneal densitometry obtained using Pentacam HR in the eyes of patients with keratoconus treated with corneal collagen cross‐linking (CXL) versus the eyes of healthy controls.MethodsAn observational case‐control study was carried out on 18 eyes of 15 patients with keratoconus treated with CXL (classical therapy), and 30 eyes of 15 healthy controls, in which ocular pathology had previously been ruled out. All patients underwent a Scheimpflug corneal tomography with Pentacam HR. For the analysis, the backscattering of light is measured in the anterior (120 µm) central and posterior (60 µm) corneal layers.ResultsThe group of patients treated with CXL therapy were 11 men and 4 women, the mean age was 28.06 years (range 17–44 years). In the CXL group the mean light scattering in the previous layer was 24.35 ± 1.074 (C: 21.6 ± 0.68 p > 0.05); central layer 14.68 ± 0.53 (C: 14.48 ± 0.41 p <0.05); posterior layer 10.75 ± 0.35 (C: 11.04 ± 0.36 p < 0.05) and full thickness 16.6 ± 0.62 (C: 15.71 ± 0.44 p < 0.05).ConclusionsThere are statistically significant differences in the densitometry values of the anterior layer of patients with keratoconus treated with CXL compared to healthy controls. We did not find statistically significant differences for the central, posterior and total variables.
Measurement of electroretinogram responses in OPA1‐associated autosomal dominant optic atrophy using a handheld device
Authors: Rufus‐Toye Remi , Jurkute Neringa , Leo Shaun , Mahroo Omar , Yu‐Wai‐Man Patrick 
Published: January 2022

AbstractPurposeAutosomal dominant optic atrophy (ADOA) associated with OPA1 variants is the most common inherited optic neuropathy in the population. The utility of the Ganzfeld electroretinogram (ERG) in evaluating ADOA has not been extensively investigated. In this study, we explored the potential of using a handheld ERG device (RETeval®) to measure ERG responses in a cohort of patients with ADOA carrying pathogenic OPA1 mutations.MethodsThe Ganzfeld photopic ERG was recorded in 15 individuals with OPA1‐associated ADOA in response to series of flashes (200, automatically adjusted in intensity to pupil diameter) using the RETeval® handheld ERG device and skin electrodes. Two to three series were obtained from each eye. The recordings were analysed for noise and drift manually. Both visual acuity measurements, and optical coherence tomography ganglion cell layer (GCL) and retina nerve fibre layer (RNFL) thicknesses were recorded to explore correlation with ERG parameters.ResultsThere was a significant correlation between LogMAR visual acuity and both the a‐wave (ρ = ‐0.60, p = 0.02, n = 15) and b‐wave (ρ = ‐0.54, p = 0.04, n = 15) peak times. As a‐wave and b‐wave peak time correlated with age, a multiple linear regression analysis was performed to exclude age as a confounder. With respect to the a‐wave analysis, the coefficients for visual acuity and age were ‐0.66 (p = 0.019) and 0.015 (p = 0.14), respectively. With respect to b‐wave analysis, the coefficients for visual acuity and age were ‐1.32 (p = 0.017) and 0.028 (p = 0.16), respectively. There was no significant correlation between a‐wave and b‐wave peak times with the OCT structural parameters that were analysed.ConclusionsIn patients with OPA1‐associated ADOA, a‐wave and b‐wave peak times correlated negatively with LogMAR visual acuity, independent of the effects of age. The pathophysiological relevance of these findings requires further investigation in a larger patient cohort.
The physicochemical properties of preserved and preservative‐free latanoprost eye drops and their impact on human conjunctival goblet cells
Authors: Müllertz Olivia , Nagstrup Anne , Mouhammad Zaynab Ahmad , Freiberg Josefine Clement , Nagymihaly Richard , Jacobsen Jette , Larsen Susan , Bair Jeffrey , Utheim Tor Paaske , Dartt Darlene , Heegaard Steffen , Petrovski Goran , Kolko Miriam 
Published: January 2022

AbstractPurposeTo investigate the impact on human conjunctival goblet cell (GC) survival and mucin release for benzalkonium chloride (BAK) preserved and preservative‐free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.MethodsGC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin release was evaluated through mucin‐specific immunostaining. pH‐value, osmolality, drop mass and surface tension for all LT eye drops were measured.ResultsAfter application with PF‐LT for 30 minutes (min), the GC survival was maintained (p = 0.7043), while all BAK‐LT eye drops reduced survival to approximately 70% (p<0.0001). Following application with PF‐LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK‐LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH of the BAK‐LT and PF‐LT eye drops were 6.0‐6.9 and 6.8, respectively. The osmolality was 258‐288 mOsm/kg for the BAK‐LT eye drops and 276 for PF‐LT eye drop. The mean drop mass was 26‐31 mg for the BAK‐LT eye drops and 30mg for PF‐LT. The surface tension was lower for all BAK‐LT eye drops (31.1‐32.1 mN/m) compared to PF‐LT (42 mN/m).ConclusionsPF‐LT compared to various branded and generic LT preparations containing BAK should be used to improve goblet cell tolerability and ocular surface health.