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  • 1. Anjos, Rita
    et al.
    Vieira, Luisa
    Costa, Livio
    Vicente, André
    Ophthalmology Department, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; Serviço de Oftalmologia, Hospital de Santo António dos Capuchos, Lisbon, Portugal.
    Santos, Arnaldo
    Alves, Nuno
    Amado, Duarte
    Ferreira, Joana
    Cunha, João Paulo
    Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study2016In: Neuro-ophthalmology (Aeolus Press. 1980), ISSN 0165-8107, E-ISSN 1744-506X, Vol. 40, no 1, p. 8-15Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.

  • 2.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.

    Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.

    Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.

    Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.

  • 3.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Rodriguez Garcia, Maria Angels
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren Hochhard, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sarcomere remodelling and gene expression profile changes following strabismus surgery2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose : To investigate the extent and time axis of sarcomere remodeling and of gene expression profile changes following resection surgery in an animal model of strabismus surgery.

    Methods : The right superior rectus (SR) of 16 adult New Zealand white rabbits was resected 4 mm and reattached to the sclera, with ethical permission and following the animal care directives. The superior rectus muscle of 4 rabbits was collected 1, 2, 4 and 6 weeks after surgery. The SR of 4 control rabbits was also collected. The muscles were divided into two pieces longitudinally and one half was directly frozen for RNA extraction and the other half was stretched, fixed in 2% paraformaldehyde and frozen after sucrose cryoprotection. Serial longitudinal sections were processed for immunohistochemistry with antibodies against desmin. For each muscle section, the area comprising exclusively longitudinally sectioned myofibers was evaluated and the number of dividing sarcomeres present within that area was determined. RNA sequencing was performed with Illumina HiSeq 2500.

    Results : One week after surgery, the number of sarcomere divisions was 86.5/mm2 (range 30.9-152.7), after two weeks 72.0/ mm2 (42.5-95.9), after 4 weeks 95.7/ mm2 (37.4-161.3). After 6 weeks the number of sarcomere divisions (26.8/ mm2, 9.2-60.7) was similar to that of the control samples (26.0/ mm2, 6.0-66.9). RNA sequencing revealed up to 198 differentially expressed genes and further bioinformatics analysis is ongoing. Preliminary data indicate that the most significantly altered biological processes are those involved in extracellular matrix organization and inflammation, along with regulation of response and production of growth factors involved in muscle repair and regeneration.

    Conclusions : Signs of sarcomerogenesis were present during the first 4 weeks after resection of the superior rectus, suggesting that sarcomerogenesis plays a role in surgical failure due to recovery of muscle length. We suggest that medical approaches to limit this mechanism may be a desirable complementary therapy to strabismus surgery in the future.

  • 4. McLoon, Linda K.
    et al.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Fitzpatrick, Krysta R.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 1, p. 322-329Article in journal (Refereed)
    Abstract [en]

    Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.

    Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.

    Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.

    Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.

  • 5. Melancia, Diana
    et al.
    Vicente, André
    Cunha, João Paulo
    Abegão Pinto, Luís
    Ferreira, Joana
    Diabetic choroidopathy: a review of the current literature2016In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 254, no 8, p. 1453-1461Article in journal (Refereed)
    Abstract [en]

    Diabetic retinopathy is an increasingly prevalent disease, and a leading contributor to the burden of all-cause blindness worldwide. In addition to retinal changes, choroidal abnormalities are common in patients with diabetes. The first studies concerning this vascular structure were based on histologic, indocyanine angiography and laser Doppler flowmetry techniques, but the development of new optical coherence tomography (OCT) technologies and imaging software for enhanced depth imaging (EDI)-OCT in recent years has made it possible to provide more detailed images of the choroidal anatomy and topography.In diabetic patients, several choroidal changes have been described in the literature throughout the years; the recent focus is choroidal thickness, which is significantly different from that in healthy patients. However, understanding choroidal manifestations of diabetic eye disease remains a real challenge, and this gap is hindering efforts towards better defining choroidal evaluation as a predictive factor for disease evolution and treatment response.This review aims to summarize the recent literature concerning changes in choroidal structure in diabetic patients, the relationship to diabetic retinal disease progression, and finally, the current and potential application of the measurement of variations in choroidal thickness for patient management.

  • 6.
    Rodríguez, Maria Angels
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren Hochhard, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Gene expression profile of extraocular muscles following resection strabismus surgery2019In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 182, p. 182-193Article in journal (Refereed)
    Abstract [en]

    This paper aims to identify key biological processes triggered by resection surgery in the extraocular muscles (EOMs) of a rabbit model of strabismus surgery by studying changes in gene expression. Resection surgery was performed in the superior rectus of 16 rabbits and a group of non-operated rabbits served as control. Muscle samples were collected from groups of four animals 1, 2, 4 and 6 weeks after surgery and processed for RNA-sequencing and immunohistochemistry. We identified a total of 164; 136; 64 and 12 differentially expressed genes 1, 2, 4 and 6 weeks after surgery. Gene Ontology enrichment analysis revealed that differentially expressed genes were involved in biological pathways related to metabolism, response to stimulus mainly related with regulation of immune response, cell cycle and extracellular matrix. A complementary pathway analysis and network analysis performed with Ingenuity Pathway Analysis tool corroborated and completed these findings. Collagen I, fibronectin and versican, evaluated by immunofluorescence, showed that changes at the gene expression level resulted in variation at the protein level. Tenascin-C staining in resected muscles demonstrated the formation of new tendon and myotendinous junctions. These data provide new insights about the biological response of the EOMs to resection surgery and may form the basis for future strategies to improve the outcome of strabismus surgery.

  • 7.
    Słoniecka, Marta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Cell signaling pathways in human mutant PAX6 corneal cells: an in vitro model for aniridia-related keratopathyManuscript (preprint) (Other academic)
  • 8. Tavares Ferreira, Joana
    et al.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Proença, Rita
    Santos, Bruno O
    Cunha, João P
    Alves, Marta
    Papoila, Ana L
    Abegão Pinto, Luís
    Choroidal thickness in diabetic patients without diabetic retinopathy2018In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 38, no 4, p. 795-804Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude.

    METHODS: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 μm apart in 4 directions-nasal, temporal, superior, and inferior). Linear regression models were used.

    RESULTS: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16-24.27 μm). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 μm and 11.6 μm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients' CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure.

    CONCLUSION: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.

  • 9.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aniridia-related keratopathy: structural changes, signaling pathways and clinical aspects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood.

    The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia.

    Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR.

    All ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed in the pannus of all ARK corneas and the changes observed in decentered and centered transplants were analogous. Furthermore, ARK corneas presented analogous signaling pathways changes in the subepithelial pannus and epithelium, with decreased detection of Notch1 signaling pathway and increased presence of the Notch1 inhibitors Numb and Dlk1. Increased detection of Wnt/beta-catenin (enhanced presence of Wnt5a, Wnt7a and beta-catenin), SHH (detection of GLI1 and HES1) and mTOR (identification of mTOR and rpS6) signaling pathways were found in the subepithelial pannus and epithelium of all ARK corneas, when compared to normal controls. In the mutant PAX6 corneal cells, the signaling pathway changes encountered were similar to those found in the ARK patients. The cell signaling pathway dissimilarities encountered in ARK corneas were similar to the pattern found in human fetal corneas with the exception of Notch1.

    The analogous pathological features of all ARK cases and the similarity in pathway alterations found in all ARK corneas irrespective of being naïve or previously submitted to distinct surgical procedures involving transplantation of limbal stem cells or not, and mutant PAX6 corneal cells, advocates an important role for host specific factors in the pathophysiology of ARK. Moreover, the similar pattern found between fetal human corneas and ARK corneas indicates a less differentiated host milieu in ARK. The present results provide the basis for further studies investigating the possibility of modulating these pathways in order to delay or avoid ARK.

  • 10.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, B.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vivinex (c) toric lenses refractive results after cataract surgery, preliminary study including 50 eyes2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, p. 135-135Article in journal (Other academic)
  • 11.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Altered Signaling Pathways in Aniridia-Related Keratopathy2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 13, p. 5531-5541Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To study the Notch1, Wnt/beta-catenin, sonic hedgehog (SHH), and mammalian target of rapamycin (mTOR) cell signaling pathways in naive and surgically treated corneas of aniridia cases with advanced aniridia-related keratopathy (ARK).

    METHODS. Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation, and two adult healthy control corneas were processed for immunohistochemistry in this descriptive study. Antibodies specific against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta-catenin), SHH (glioma-associated oncogene homolog [Gli1]; Hes1), and mTOR (mTOR1; ribosomal protein S6 [rpS6]) signaling pathways were used as well as antibodies against PAX6 and keratin 13 (Krt13).

    RESULTS. All ARK corneas presented signs of conjunctivalization and analogous signaling pathway changes in the subepithelial pannus and epithelium, with decreased detection of the Notch1 signaling pathway and an increased presence of the Notch1 inhibitors Numb and Dlk1. Increased detections of Wnt/beta-catenin (enhanced presence of Wnt5a, Wnt7a, and beta-catenin), SHH (detection of Gli1 and Hes1), and mTOR (identification of mTOR and rpS6) signaling pathways were found in the subepithelial pannus and epithelium of all ARK corneas, when compared with normal controls.

    CONCLUSIONS. The similarity in pathway alterations found in all ARK corneas, irrespective of limbal stem cell transplantation, further supports the discussion on the role of host-specific factors and limbal stem cell deficiency in ARK.

  • 12.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stenevi, Ulf
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aniridia-related keratopathy: structural changes in naïve and transplanted corneal buttons2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198822Article in journal (Refereed)
    Abstract [en]

    Background: To study structural changes in naive and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK).

    Methods and findings: Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry. Antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor alpha 11 integrin and laminin alpha 3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, alpha-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68) were used. Naive ARK, KLAL ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed by the presence of caveolin-1 and collagen IV in the pannus of all ARK aniridia corneas. The changes observed in decentered and centered transplants were analogous.

    Conclusions: Given the similar pathological features of all cases, conditions inherent to the host seem to play an important role on the pathophysiology of the ARK in the long run.

  • 13.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aniridia-related Keratopathy Relevant Cell Signaling Pathways in Human Fetal CorneasManuscript (preprint) (Other academic)
  • 14.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Faculty of Medicine, Visual Sciences Study Center, Lisbon University, Lisbon, Portugal.
    Pedrosa Domellöf, Fátima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Exophiala phaeomuriformis keratitis in a subarctic climate region: a case report2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, p. 425-428Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report a case of Exophiala phaeomuriformis mycotic keratitis in a patient from a subarctic climate region. Dematiaceous fungi (black yeasts) have been gaining importance as corneal keratitis and ulcer causative agents in certain regions, but no cases have been described in Scandinavia.

    METHODS: Case report of a patient with a persistent corneal erosion that eventually presented a brown-pigmented infiltrate. The patient had a history of several months of topical therapy comprising medication for glaucoma, corticosteroids and antibiotics. A therapeutic contact lens was used, and amniotic membrane transplantation was performed before the development of the pigmented infiltrate.

    RESULTS: Exophiala phaeomuriformis was identified on the microbiological cultures from the surgically obtained infiltrate scrapes. The patient responded to topical amphotericin and fluconazole, the erosion was cured and a stromal scar subsided. During follow-up, sequential slit-lamp images and anterior segment optical coherence tomography (OCT) scans were obtained.

    CONCLUSION: This is the first described case of keratitis caused by E. phaeomuriformis in a subarctic region, the first in Europe and, to our knowledge, the second reported case in the literature. It is important to remember that superficial corneal brown-pigmented infiltrates should raise the suspicion of an unusual fungal infection even in this climate. This is particularly important in patients with ocular surface disease treated with steroids and antibiotics for a long time.

  • 15.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Visual Sciences Study Center, Faculty of Medicine, Lisbon University.
    Prud'homme, Sylvie
    Ferreira, Joana
    Abegão Pinto, Luís
    Stalmans, Ingeborg
    Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)2017In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 57, no 4, p. 201-207Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years.

    METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered.

    RESULTS: We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, n = 105) involved a new drug, and the remainder (33.5%, n = 53) tested fixed drug associations. The bulk of the trials (n = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (n = 15), carbonic anhydrase inhibitors (n = 14), β-blockers (n = 7), angiostatic steroids (n = 6), α2-adrenergic agonists (n = 4), 5-HT2A receptor agonists (n = 4), and NMDA receptor antagonists (n = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial.

    CONCLUSION: Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.

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