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  • 1.
    Barth, Henrik
    et al.
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Andréasson, Sten
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    Ghosh, Fredrik
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute2016Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 254, nr 4, s. 697-703Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute.

    Methods: A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry.

    Results: Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay).

    Conclusions: Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.

  • 2.
    Barth, Henrik
    et al.
    Department of Ophthalmology, Lund University, BMC D10,, Lund, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Ophthalmology, Faculty of Medicine and Health, Örebro University Hospital, Orebro, Sweden.
    Arnér, Karin
    Department of Ophthalmology, Lund University, BMC D10, Lund, Sweden.
    Ghosh, Fredrik
    Department of Ophthalmology, Lund University, BMC D10, Lund, Sweden.
    Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model2019Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 257, nr 4, s. 769-783Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To investigate the inflammatory response of current and future potential vitreous substitutes in an experimental in vivo vitrectomy model.

    METHODS: Twenty-five gauge pars plana vitrectomy was performed in the right eye of 60 pigmented rabbits, with subsequent injection of 0.5-1.0 ml of Healaflow® (cross-linked hyaluronic acid, n = 12), Bio-Alcamid® (polyalkylimide, n = 8), silicone oil (n = 12), or balanced saline solution (BSS, n = 28). Postoperative clinical evaluation was performed; and the rabbits were sacrificed at 1 day, 1 week, or 1 month. The eyecups were then examined macroscopically; the retinas sectioned and stained with hematoxylin and eosin (Htx), and immunohistochemically labeled for glial fibrillary acidic protein (GFAP), CD45, galectin-3, CD68, and CD20. Unoperated left eyes from treated animals as well as eyes from untreated animals were used as controls.

    RESULTS: Vitrectomy without major complications was achieved in 46/60 eyes. The remaining 14 eyes were analyzed separately. One eye developed endophthalmitis after 1 week and was excluded. Eyes treated with Healaflow®, silicone oil, and BSS had a comparable appearance macroscopically and in Htx-stained sections, whereas Bio-Alcamid®-injected eyes exhibited increased macroscopic inflammation and severely affected retinas. GFAP upregulation was present in all treatment groups, most prominent in eyes treated with Bio-Alcamid® and silicone oil. Upregulation of CD45 and CD68 in the inner retina and vitreous space was most prominent with Bio-Alcamid® treatment, and these eyes together with their silicone oil-treated counterparts also displayed a stronger upregulation of CD20-labeled cells compared with remaining groups. General upregulation of galectin-3, mainly in the inner retina, was found in all groups. In eyes with perioperative complications, labeling of CD45, CD68, and especially GFAP was comparably high.

    CONCLUSIONS: We here describe differences in the postsurgery inflammatory profiles of existing and potential vitreous substitutes. Bio-Alcamid® and silicone oil display severe signs of gliosis and inflammation, whereas Healaflow® elicits minimal reactions comparable with BSS, highlighting its potential application as a vitreous substitute in a future clinical setting.

  • 3.
    Barth, Henrik
    et al.
    Lund University Hospital, Department of Ophthalmology, Lund, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Ophthalmology.
    Ghosh, Fredrik K.
    Lund University Hospital, Department of Ophthalmology, Lund, Sweden.
    Developing a retinal detachment model for in vivo testing of vitreous substitutes with repeated pars plana vitrectomy2018Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9, artikkel-id 5941Artikkel i tidsskrift (Annet vitenskapelig)
  • 4.
    Barth, Henrik
    et al.
    Department of Ophthalmology, Lund University, Lund, Sweden .
    Crafoord, Sven
    Örebro universitet, Institutionen för läkarutbildning. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    O'Shea, Timothy M.
    Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Pritchard, Christopher D.
    Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Langer, Robert
    Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Ghosh, Fredrik
    Department of Ophthalmology, Lund University, Lund, Sweden .
    A new model for in vitro testing of vitreous substitute candidates2014Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 252, nr 10, s. 1581-1592Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To describe a new model for in vitro assessment of novel vitreous substitute candidates.

    Methods: The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid (R)), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow (R)). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL.

    Results: Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid (R)-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow (R)-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow (R) and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid (R)-exposed retinas showed sparse labeling of GFAP.

    Conclusions: Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid (R) had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow (R) shows protection from culture-induced trauma indicating favorable biocompatibility.

  • 5.
    Bäckman, Anders
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Makdoumi, Karim
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden; Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Mortensen, Jes
    Department of Ophthalmology, Ryhov County Hospital, Jönköping, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light2014Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, nr 7, s. 656-661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model.

    Methods: Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007-0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60min of UVA exposure (irradiance 30 and 3mW/cm(2)). Standard settings of UVA were compared with high-power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model.

    Results: Bacterial eradication (%) was increased after 60 compared with 30min of UVA exposure for concentrations of 0.03-0.07% but not for 0.09% riboflavin. There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80% to 50% (p=0.01). A correlation could be calculated for the amount of riboflavin at 60min of UVA and the ability to kill bacteria (p=0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High-power UVA method was less potent in microbial elimination, eradicating only 60% of bacteria after 6min versus 97-99% after 60min in the low-power setting, compared with respective controls (p=0.02).

    Conclusions: In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross-linking settings. Further studies are needed to evaluate the clinical relevance of these findings.

  • 6.
    Crafoord, Sven
    Örebro universitet, Hälsoakademin.
    Do vitreoretinal patients benefit from the use of small-gauge instruments?2008Inngår i: Acta Ophthalmologica, ISSN 1755-3768, Vol. 86, nr 2, s. 120-121Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Crafoord, Sven
    et al.
    Departments of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Andreasson, Sten
    Departments of Ophthalmology, University of Lund, Lund, Sweden.
    Ghosh, Fredrik
    Departments of Ophthalmology, University of Lund, Lund, Sweden.
    Experimental vitreous tamponade using polyalkylimide hydrogel2011Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 249, nr 8, s. 1167-74Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To evaluate polyalkylimide as a possible vitreous tamponading agent.

    METHODS: A 20-gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkylimide (Bio-Alcamid) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy.

    RESULTS: The viscoelastic hydrogel was successfully injected, and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod- and cone-derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus, while the peripheral part appeared intact.

    CONCLUSION: Polyalkylimide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.

  • 8.
    Crafoord, Sven
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Ghosh, Fredrik
    Department of Ophthalmology, Skåne University Hospital, Lund, Sweden; Lund University, Lund, Sweden.
    Sebag, Jerry
    VMR Institute for Vitreous Macula Retina, Huntington Beach CA, USA; Doheny Eye Institute, Los Angeles CA, USA.
    Vitreous biochemistry and artificial vitreous2014Inngår i: Vitreous: in Health and Disease / [ed] Jerry Sebag MD, FACS, FRCOphth, FARVO, New York, USA: Springer, 2014, 1, s. 81-92Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 9.
    Crafoord, Sven
    et al.
    Örebro universitet, Hälsoakademin.
    Karlsson, Niklas
    la Cour, Morten
    Sheathotomy in complicated cases of branch retinal vein occlusion2008Inngår i: Acta Ophthalmologica, ISSN 1755-3768, Vol. 86, nr 2, s. 146-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To report the clinical experience and results of using a microsurgical technique to decompress the arteriovenous connection in complicated branch retinal vein occlusion (BRVO) combined with haemorrhage, oedema and ischaemia.

    Methods: We carried out a retrospective, non-randomized, interventional case study of the surgical sheathotomy decompression procedure. We enrolled 12 patients (seven women, five men; median age 64 years) with BRVO and decreased visual acuity (VA) caused by haemorrhage, oedema and ischaemia. The mean duration of thrombosis was 7 months (2–15 months). The patients were examined for pre- and postoperative best corrected VA (BCVA), intraocular pressure (IOP) and fundus photography. Ten patients were examined with fluorescein angiography and eight with ocular coherence tomography (OCT). Postoperative progression of cataract was recorded, as were other complications. The mean follow-up time was 20 months (8–39 months).

    Results: Best corrected VA had improved in nine patients, was unchanged in one patient and had deteriorated in two patients at the last follow-up. Noted complications were venous haemorrhage at surgery in five patients, retinal detachment in one patient and progression of cataract in four patients.

    Conclusions: Microsurgical treatment with sheathotomy of BRVO is a technically feasible procedure with few complications. Postoperative increased reperfusion could explain the resolution of macular haemorrhage, oedema and ischaemia, and may improve visual function in patients with this common vascular eye disease.

  • 10.
    Joussen, Antonia M
    et al.
    Department of Ophthalmology, Charité, University Medicine, Berlin, Germany.
    Rizzo, Stanislao
    U.O.Chirurgia Oftalmica, Azienda Ospedaliero, Universitaria Pisana, Pisa, Italy.
    Kirchhof, Bernd
    Department of Vitreoretinal Surgery, University of Cologne, Cologne, Germany.
    Schrage, Norbert
    Augenklinik Kön-Merheim, Cologne, Germany.
    Li, Xiaoxin
    Beijing University, Beijing, China.
    Lente, Christina
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Hilgers, Ralf-Dieter
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Crafoord, Sven
    Örebro universitet, Institutionen för läkarutbildning.
    Heavy silicone oil versus standard silicone oil in as vitreous tamponade in inferior PVR (HSO Study): interim analysis2011Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, nr 6, s. e483-e489Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The Heavy Silicone Oil versus Standard Silicone Oil Study (HSO study) is designed to answer the question whether a heavier-than-water tamponade improves the prognosis of eyes with proliferative vitreoretinopathy (PVR) of the lower retina.

    METHODS: The HSO Study is a multicentre, randomized, prospective, controlled clinical trial stratified by surgeon comparing two endotamponades within a two-arm parallel-group design. Patients with inferiorly and posteriorly located PVR grade C-A6 were randomized to either HSO or standard silicone oil as a tamponading agent. The main end-point criteria are complete retinal attachment at 12 months and change in visual acuity (VA) 12 months postoperatively compared to the preoperative VA.

    RESULTS: Forty-six patients treated with HSO were compared to 47 patients treated with standard silicone oil. There was no difference among the groups regarding baseline data. Three patients in the HSO and five patients in the standard silicone oil group fulfilled intraoperative exclusion criteria. There was no significant difference between both groups regarding anatomical success. Neither noninferiority nor superiority was shown with regard to final acuity.

    CONCLUSIONS: The HSO Study is the first randomized prospective clinical trial to compare heavy and standard silicone oil in patients with PVR of the lower retina. The intermediate results failed to demonstrate superiority of a heavy tamponade.

  • 11.
    Landström, Fredrik J
    et al.
    Department of Otolaryngology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Christer O. S.
    Department of Otolaryngology, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för läkarutbildning. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Reizenstein, Johan A.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Adamsson, Gun-Britt M.
    Department of Head and Neck Oncology Center, Örebro University Hospital, Örebro, Sweden.
    Löfgren, Lennart A.
    Department of Head and Neck Oncology Center, Örebro University Hospital, Örebro, Sweden.
    Electroporation therapy of skin cancer in the head and neck area.2010Inngår i: Dermatologic Surgery, ISSN 1076-0512, E-ISSN 1524-4725, Vol. 36, nr 8, s. 1245-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent.

    OBJECTIVE: To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin.

    MATERIALS AND METHODS: Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow-up period was 24 months and included biopsies after 8 weeks.

    RESULTS: In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow-up period

    CONCLUSION: Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer.

  • 12.
    Makdoumi, Karim
    et al.
    Örebro universitet, Hälsoakademin.
    Bäckman, Anders
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Crafoord, Sven
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Response to: Bactericidal effect of photo-activated riboflavin using UVA2010Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 248, nr 5, s. 757-758Artikkel i tidsskrift (Fagfellevurdert)
  • 13.
    Makdoumi, Karim
    et al.
    Örebro universitet, Hälsoakademin.
    Bäckman, Anders
    Mortensen, Jes
    Crafoord, Sven
    Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA)2010Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 248, nr 2, s. 207-212Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: To evaluate the antibacterial efficacy of photo-activated riboflavin using Ultraviolet A (UVA) on three bacterial strains commonly detected in keratitis. METHODS: Three bacterial strains (Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa) were cultured on blood/hematin-agar plates and dispersed in PBS. Dispersion was done of 10 microl of bacterial stock-solutions in 90 microl of RPMI, where different riboflavin molarities had been added, to achieve a bacterial concentration of 1-4 x 10 (4)/ml. Riboflavin end molarities before illumination were 0, 100, 200, 300 and 400 microM. Each solution had a negative control. The solutions were illuminated with UVA (365 nm) for 30 minutes (5.4 J/cm(2)) and then continued for a total time of 60 minutes (10.8 J/cm(2)). A count of CFU was conducted after incubation and results compared. RESULTS: In all tested strains, a slight decrease of bacteria was seen when exposed to UV for 30 minutes. A doubling of the UV dose showed a marked decrease of bacterial count in all bacteria tested. The combination of UV and riboflavin showed a more extensive reduction of CFU, confirming an interaction effect between UV and riboflavin. CONCLUSION: Riboflavin photo-activation using UVA (365 nm) can achieve an extensive eradication of bacteria, and the combination is more potent in reducing bacterial number than UV alone.

  • 14.
    Makdoumi, Karim
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Ophthalmology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Bäckman, Anders
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Clinical Research Centre, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Mortensen, Jes
    Dept. Ophthalmology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Magnuson, Anders
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Clinical Epidemiology and Biostatistic Unit, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba Castellanii2013Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 251, nr 2, s. 509-514Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose To investigate whether ultraviolet light (UVA) at 365 nm can inhibit/eliminate Acanthamoeba growth and if riboflavin would potentiate such an association.

    Method: Acanthamoeba castellanii in a fluid medium with a concentration of approximately 1.7 x 10(4) protozoa/ml were prepared with (0.01 %) and without riboflavin. Exposure of UVA (dose 5.475 J/cm(2)) took place twice, with each illumination period followed by culturing of 10 mu l in peptone yeast-extract glucose (PYG) medium for 7 days. Every suspension prepared had a non-exposed control solution. Determination of Acanthamoeba was conducted daily, by count in Burker chamber days 4 through 7 after exposure. Statistical analysis was done by repeated-measurement ANOVA and post-hoc analysis for unpaired samples.

    Results: The exposure of ultraviolet light resulted in an inhibited growth of Acanthamoeba compared to the non-exposed solutions, with a statistically significant reduction over time (p = 0.0003). The addition of riboflavin did not amplify the effect, and there were no tendencies for an interaction effect between UVA and riboflavin. The antiprotozoal effect of the UVA wavelength, utilized in CXL, is solely mediated by ultraviolet light, and riboflavin does not seem to amplify the antimicrobial efficacy.

  • 15.
    Makdoumi, Karim
    et al.
    Örebro universitet, Hälsoakademin. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Vasoproliferative retinal tumours in a Swedish population2011Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, nr 1, s. 91-94Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To describe the clinical appearance and the visual outcome of a cohort of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed and treated between 2002 and 2007 at the University Hospital of Orebro.

    Methods: Nine patients with diagnosed VPRTs were included in a retrospective study. The mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received cryotherapy; six eyes were also treated with photocoagulation. One patient was treated with intravitreal injections of ranibizumab (Lucentis((R))) and another was referred for brachytherapy. Because of persisting macular oedema, one eye was treated with intravitreal injection of triamcinolon.

    Results: Of the treated eyes, one had anterior uveitis, six had macular oedema at baseline and four had an exudative retinal detachment at the time of diagnosis. Seven eyes underwent vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21 (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two out of four patients with retinal detachment were successfully treated surgically.

    Conclusion: VPRTs are benign intraretinal changes. Several complications are associated with this condition. All patients in this study had symptom-giving tumours and six patients (six eyes) already had profound macular oedema at presentation. In these cases, when complications have already developed, the final visual prognosis is poor, thereby making it important to detect these tumours early. The patient who received anti-vascular endothelial growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct regression in exudations during the follow-up time. However, no increase in visual acuity was seen. At latest examination a peripheral exudative retinal detachment was still observed. Whether anti-VEGF treatment is effective, as either an alternative or complementary therapy, must be established in the future.

  • 16.
    Makdoumi, Karim
    et al.
    Örebro universitet, Hälsoakademin.
    Mortensen, Jes
    Crafoord, Sven
    Infectious keratitis treated with corneal crosslinking2010Inngår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 29, nr 12, s. 1353-1358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To describe 7 eyes with severe infectious keratitis treated using collagen crosslinking (CXL) with riboflavin. Materials and Methods: Seven eyes of 6 patients with severe infectious keratitis were treated with corneal crosslinking. Three patients were contact lens users. Symptom duration before CXL ranged between 0 and 7 days. Corneal melting was present in all cases. Photodocumentation of the keratitis was carried out and repeated at follow-up. All but 1 patient received topical antibiotic treatment in addition to the CXL treatment. CXL was conducted according to the standardized protocol for keratoconus. Results: In all but 1 eye, patients experienced improvement in symptoms within 24 hours. Two patients reported no symptoms whatsoever at this time. Corneal melting was arrested and complete epithelialization was achieved in all cases. In the 2 eyes with hypopyon, this regressed completely within 2 days after the CXL. Follow-up ranged between 1 and 6 months. Discussion: Our experience based on the above and other cases suggest that CXL could be an effective tool in battling difficult cases of infectious keratitis. This treatment could present many advantages but will need further investigation.

  • 17.
    Makdoumi, Karim
    et al.
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Mortensen, Jes
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden; Department of Ophthalmology, Ryhov County Hospital, Jönköping, Sweden.
    Sorkhabi, Omid
    Department of Ophthalmology, Ryhov County Hospital, Jönköping, Sweden.
    Malmvall, Bo-Eric
    Department of Infectious Medicine, Futurum, the Academy of Health, Ryhov County Hospital, Jönköping, Sweden; Department of Infectious Medicine, Institution of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study2012Inngår i: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 250, nr 1, s. 95-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis.

    Methods: A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643).

    Results: All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant.

    Conclusions: This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.

  • 18.
    Makdoumi, Karim
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden; Faculty of Medicine and Health Department of Biomedicine, Örebro University, Örebro, Sweden.
    Crafoord, Sven
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Ophthalmology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Levels of beta-trace protein in optic disc pit with macular detachment2017Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, nr 8, s. 815-819Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: To report beta-trace protein (βTP) levels in the subretinal fluid (SRF) of four patients with a macular detachment associated with optic disc pit (ODP).

    METHODS: Four patients with a serous retinal detachment involving the macula was operated by pars plana vitrectomy (PPV) with C2 F6 gas tamponade and peeling of internal limiting membrane (ILM). Patients with a follow-up period exceeding one year postoperatively were included in the study. The SRF was drained using a fine cannula without laser photocoagulation, and the samples were analysed using particle-enhancing nephelometry. The levels of βTP were compared to 20 routine cerebrospinal fluid (CSF) samples.

    RESULTS: In four of the five samples from SRF had relatively low βTP levels, with a mean concentration of 6.6 mg/l (range 2.0 to 23.1 mg/l) compared to 16.0 mg/l (range 6.3-26.8 mg/l) in CSF. The only SRF sample within the range corresponding to normal CSF was the first sample from patient 4, and the analysis of the renewed aspirate during the second operation was 2.8 mg/l. Postoperatively, the regression of SRF was slow, but regression of SRF in the foveal region took place in all cases; however, visual acuity (VA) was improved in only half of the patients.

    CONCLUSION: The results from the analysed SRF regarding βTP concentration in these patients indicate that the SRF in ODP is not identical to CSF, as the concentrations of βTP differ.

  • 19.
    Pritchard, Christopher D.
    et al.
    Massachusetts Institute of Technology, Cambridge MA, USA.
    Crafoord, Sven
    Örebro University Hospital, Örebro, Sweden.
    Andréasson, Sten
    Lund University Hospital, Lund, Sweden.
    Arnér, Karin M.
    Lund University Hospital, Lund, Sweden.
    O'Shea, Timothy M
    Massachusetts Institute of Technology, Cambridge MA, USA.
    Langer, Robert
    Massachusetts Institute of Technology, Cambridge MA, USA.
    Ghosh, Fredrik K.
    Lund University, Lund, Sweden.
    Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in an experimental vitrectomy model in rabbits2011Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, nr 3, s. 936-943Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to employ an experimental protocol for in vivo evaluation of sols of 5 wt.% poly(ethylene glycol) (PEG) in phosphate-buffered saline as artificial vitreous substitutes. A 20 gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of eight pigmented rabbits. Approximately 1 ml of the viscoelastic PEG sols was then injected into the vitreous space of six eyes. PEG with an average molecular weight of 300,000 and 400,000 g mol(-1) was used in two and four eyes, respectively. Two eyes received balanced salt solution and served as controls. Full-field electroretinography was carried out and intra-ocular pressure (IOP, palpation) measured pre- and post-operatively at regular intervals up to 41 days. The rabbits were killed and the eyes examined by retinal photography, gross macroscopic examination and histology. The viscoelastic sols were successfully injected and remained translucent throughout the post-operative period, with some inferior formation of precipitates. None of the eyes displayed IOP elevation post-operatively, but in three of the PEG sol injected eyes transient hypotony was noted. One eye sustained retinal detachment during surgery and another two in the post-operative period. ERG recordings confirmed preservation of retinal function in three out of four eyes injected with 400,000 g mol(-1) PEG. Histological examination revealed up-regulation of glial acidic fibrillary protein in Müller cells in PEG sol injected eyes, but normal overall morphology in eyes with attached retinas. The viscosity of the sol was not retained throughout the post-operative period, indicating the demand for polymer cross-linking to increase residence time. The results provide promising preliminary results on the use of PEG hydrogels as a vitreous substitute.

  • 20.
    Schulz-Key, Steffen
    et al.
    Department of Ophthalmology, Uppsala University Hospital, Uppsala, Sweden.
    Carlsson, Jan-Olof
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Longterm follow-up of pars plana vitrectomy for vitreous floaters: complications, outcomes and patient satisfaction.2011Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, nr 2, s. 159-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Floaters caused by degenerative or postoperative changes in the vitreous can interfere with all aspects of visual functioning. The aim of this study is to report the longterm outcome of pars plana vitrectomy (PPV) for persistent vitreous opacities.

    METHODS: In a retrospective, non-randomized, interventional case study we reviewed all cases of vitreous floaters that were vitrectomized at our department between 1997 and 2006. Patient complaints and satisfaction were assessed by a questionnaire administered at the end of follow-up.

    RESULTS: Seventy-three consecutive cases were included (61 patients). Mean Snellen best corrected visual acuity (BCVA) before surgery was 0.81. Overall, 85% of patients complained of severe or very severe difficulty caused by floaters. A total of 42% of eyes were pseudophakic, four of which were operated with combined PPV and phacoemulsification. Mean follow-up time was 37 months. Of the phakic eyes, 60% were operated for cataract during follow-up. One retinal detachment (RD) occurred immediately postoperatively (1.3%) and another four eyes developed RD during longterm follow-up 24-44 months after PPV (5.5% of cases). Postoperative BCVA remained mostly unchanged. Overall, 88% of patients were satisfied with the results of the operation.

    CONCLUSIONS: Some patients make considerable complaints as a result of vitreous opacities and their distress does not correlate with visual acuity. Vitrectomy is a safe and effective procedure with which to help these patients. Patients should be informed about the risk of cataract progression, unexpected inflammatory reaction and an increased risk for RD several years after PPV (5.5%).

  • 21.
    Slidsborg, Carina
    et al.
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Lyng Forman, Julie
    Departmant of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
    Fielder, Alistair R.
    Department of Optometry and Visual Science, City University, London, UK .
    Crafoord, Sven
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Baggesen, Kirsten
    Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark .
    Bangsgaard, Regitze
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Callo Fledelius, Hans
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Greisen, Gorm
    Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    La Cour, Morten
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Experts do not agree when to treat retinopathy of prematurity based on plus disease2012Inngår i: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 96, nr 4, s. 549-553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To investigate inter-reader agreement on five severity levels of central vascular changes (none, mild, moderate, severe pre-plus disease, plus disease) and aggressive posterior retinopathy of prematurity (ROP), and to see whether an unintended shift in indication for treatment occurred.

    Methods: Four international ROP readers participated. Before the grading of the photographs, the readers were informed that a high proportion of advanced ROP cases were included. In total, 243 photographs/948 quadrants were available from 136 infants. As a standard series of photographs was available, grading was performed under optimised conditions.

    Results: The four readers agreed on the quadrant scores of only 70 (7.38%) of the 948 quadrants-that is, on 1, 5, 15, 4 and 45 quadrants for scores 0, 1, 2, 3 and 4, respectively. The mean scores differed systematically between the readers (permutation test, p<0.0001). Agreement on presence of aggressive posterior ROP from all four readers was not obtained for any of the photographs. Readers scored plus disease in at least two quadrants in 95.5% of the eyes for which treatment was indicated. All four readers agreed on the scoring of indication for treatment for 195 eyes (80.2%); however, treatment was only recommended in 18 (7.4%) eyes. One reader was found to differ systematically from the others in indicating treatment (Rasch analysis; p=0.0001). Finally, a significant shift in indication for treatment occurred between birth period 2000-2002 and 2003-2006 (Mann-Whitney rank sum test, p<0.001).

    Conclusions: Inter-reader agreement on central vascular changes is poor, especially when based on more than two rating categories. The subjective nature of diagnosing such vascular changes possibly resulted in earlier treatment of preterm infants in Denmark over the entire study period (1997-2006). The recent increased incidence of treated infants in Denmark is, at least in part, explained by a significant shift in indication for treatment.

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