| 1. |
- Barth, Henrik, et al.
(författare)
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A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute
- 2016
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 254:4, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Barth, Henrik, et al.
(författare)
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A new model for in vitro testing of vitreous substitute candidates
- 2014
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - Hedidelberg, Germany : Springer. - 0721-832X .- 1435-702X. ; 252:10, s. 1581-1592
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Barth, Henrik, et al.
(författare)
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A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades
- 2021
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 46:3, s. 373-379
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop a treatment model of rhegmatogenous retinal detachment (RRD) in which the effects of various vitreous tamponades can be explored.METHODS: In a primary session, detachment was produced in the right eye of 24 rabbits using vitrectomy, posterior vitreous detachment, retinal break induction, and subretinal injection of viscoelastic solution. The following day, detachments were treated in 16 eyes using SF6 (n = 8) or Healaflow® (HF, a cross-linked hyaluronic acid hydrogel, n = 8) tamponade. Animals were followed for 1 month and thereafter examined macroscopically and morphologically in hematoxylin and eosin-stained sections.RESULTS: Retinal detachment (RD) was successfully treated using repeated surgery. Two HF eyes developed progressive vitritis and were excluded from further evaluation. Enlargement of the initial retinal rupture with concomitant RD was seen in 4/8 SF6 eyes, while all 6 HF eyes displayed an attached retina. Attached areas showed a normal retinal morphology except for in 1 HF eye with extensive degeneration.CONCLUSIONS: The RRD repeat vitrectomy model offers a possibility to explore the efficacy and complications of novel potential vitreous tamponades. Gel-based Healaflow® displays excellent anatomic reattachment, however, vitritis and retinal degeneration in some cases warrants further investigation.
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| 5. |
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| 6. |
- Barth, Henrik, et al.
(författare)
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Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model
- 2019
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 257:4, s. 769-783
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Bäckman, Anders, et al.
(författare)
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The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light
- 2014
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Ingår i: Acta Ophthalmologica. - Hoboken, USA : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 92:7, s. 656-661
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Carlsson, Jan-Olof, et al.
(författare)
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Retinal surgery quality indicators for uncomplicated primary rhegmatogenous retinal detachment without a national registry
- 2022
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Ingår i: Acta Ophthalmologica. - : Wiley-Blackwell Publishing Inc.. - 1755-375X .- 1755-3768. ; 100:8, s. e1589-e1594
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The objective of this study was to evaluate the possibility of analysing quality indicators for uncomplicated primary rhegmatogenous retinal detachment in a hospital department of ophthalmology without the support of a national registry or need to collect data from referring ophthalmological centres.METHODS: In 2014, we operated 231 consecutive eyes with uncomplicated retinal detachment. Our quality indicators were primary anatomical success, final anatomical success and postoperative endophthalmitis. We reviewed medical records in our university surgical department retrospectively and compared them with medical records from the regional hospitals that had referred most of the operated patients and done their own postoperative examination. Our hypothesis was that any retinal re-detachment and/or serious postoperative complication would be reported back.RESULTS: The medical records at the surgical department revealed primary anatomic success for 91.3% of eyes and final anatomical success of 99.6%. The data from the regional hospitals confirmed that our hypothesis was correct. All patients with adverse outcomes were referred back for reoperation. Patients who were not referred again had an attached retina and showed no signs of endophthalmitis.CONCLUSION: Our hypothesis that data in the surgical department's medical records would closely reflect those in referring hospitals was borne out. This supports, under current conditions, an effective strategy for analysing chosen quality indicators without relying on a national registry or reviewing records from regional hospitals.
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| 9. |
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| 10. |
- Crafoord, Sven, 1950-, et al.
(författare)
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Cellular migration into neural retina following implantation of melanin granules in the subretinal space
- 2000
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 238:8, s. 682-689
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Tidskriftsartikel (refereegranskat)abstract
- Background: In some retinal diseases and following transplantation of retinal pigment epithelium (RPE), melanin granules are liberated to the subretinal space. Our aim was to investigate the cellular response to implanted extracellular melanin. Methods: After pars plana vitrectomy, 17 albino rabbits received a suspension of melanin granules in the subretinal space. Postoperative examination included ophthalmoscopy, color fundus photography, histology using monoclonal antibodies identifying RPE cells (AE1/3), macrophages (RAM 11), B-lymphocytes (CD20) and T-lymphocytes (CD45), and electron microscopy. The follow-up time was 2 weeks, 4 weeks and 6 months. Results: On fundus photographs, the layer of melanin showed focal attenuation with lighter areas at 6 months. Melanin granules were phagocytosed by RPE cells and macrophages at 2 weeks, as identified by monoclonal antibodies. In areas where an abundance of melanin was present, multilayers of macrophages were seen associated with considerable photoreceptor damage. Pigment-laden cells invaded the neural retina. The cellular infiltration of the retina was focal, and when it involved the outer nuclear layer the photoreceptor damage was severe. Electron microscopy demonstrated the presence of melanosomes intracellularly in Müller glia. The process of phagocytosis and removal of melanin granules from the subretinal space was slow and not completed at 6 months. Conclusion: Our experiments show that implantation of melanin granules in the subretinal space of albino rabbits may induce a considerable phagocytic cellular response featuring the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was associated with focal photoreceptor damage.
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