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ABSTRACT: BACKGROUND: To evaluate the indication, visual outcome, and complication rate after implantation of a posterior iris-claw aphakic intraocular lens (IOL) during penetrating keratoplasty. METHODS: This retrospective study comprised 23 eyes (23 patients) without adequate capsule support undergoing posterior iris-claw aphakic IOL implantation (Verisyse™/Artisan®) during penetrating keratoplasty between 2005 and 2010. Mean follow-up was 18 months (range from 12 to 37 months). RESULTS: The IOLs were inserted during an IOL exchange in 17 eyes and as a secondary procedure in six aphakic eyes. Pseudophakic bullous keratopathy with corneal scar after anterior chamber intraocular lens (ACIOL) was the main indication for penetrating keratoplasty in 16 eyes (69.6 %). The final corrected distance visual acuity (CDVA) in logMAR (mean 1.0 ± 0.46) improved significantly (p < 0.05) compared to the preoperative CDVA (mean 1.8 ± 0.73). Twenty eyes (86.9 %) had a final visual acuity in logMAR better than the pre-operative CDVA. The mean postoperative IOP 16.3 mmHg ± 4.0 was not significantly (p > 0.05) higher compared to the preoperative IOP 15.6 mmHg ± 5.1. Complications included slight temporary pupil ovalization in three eyes (13.0 %) and iris-claw IOL sublocation in three eyes (13.0 %); all IOLs could be easily repositioned. Cystoid macular edema occured in one eye (4.3 %) 8 weeks after primary surgery. All grafts remained clear without any sign of graft rejection. CONCLUSIONS: Retropupillar iris-claw IOL during penetrating keratoplasty provides good visual outcomes with a favorable complication rate, and can be used for a wide range of indications in eyes without adequate capsule support.
Albrecht von Graæes Archiv für Ophthalmologie 12/2012; · 2.17 Impact Factor
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ABSTRACT: BACKGROUND: Intraocular pressure (IOP) elevation is a common problem in penetrating keratoplasty (PK), and possibly leads to graft failure. IOP elevation and secondary glaucoma may also be present after Descemet`s stripping endothelial keratoplasty (DSEK). This retrospective study analyzes the risk factors for IOP elevation and the functional outcome in those patients with post-DSEK glaucoma. METHODS: A retrospective analysis of case records of 72 DSEKs between 2007 and 2010 was performed. A total of 59 operated eyes were included. The assessment included the pre-operative history of corneal disease and glaucoma. Furthermore, the response to antiglaucoma treatment, the graft failure, the IOP, and visual acuity development were evaluated. RESULTS: The incidence of IOP elevation was 28.8 % and of post-DSEK glaucoma 11.9 %. Steroid-induced IOP elevation was the most frequent cause, with an incidence of 18.6 %. Patients with pre-existing glaucoma showed a significantly higher risk of developing IOP elevation, steroid-induced glaucoma and post-DSEK glaucoma (p = 0.006, p = 0.023, p = 0.009). In all cases, IOP elevation was treated effectively by tapering down steroid medication and initiating or increasing antiglaucoma medication. Visual acuity after 6 and 12 months improved significantly in cases with and without pre-existing glaucoma (p < 0.0001). After 24 months, clear grafts were achieved in 53 eyes (89.9 %). There was no significant difference in graft failure rates between cases with or without pre-existing glaucoma (p = 0.581) and with or without post-DSEK glaucoma (p = 0.306). CONCLUSIONS: IOP elevation after DSEK shows a high incidence. Pre-existing glaucoma increased the risk of developing IOP elevation and post-DSEK glaucoma. Although steroid-induced IOP elevation was the most frequent cause and could be treated effectively by tapering down steroid medication; there are other reasons why post-DSEK glaucoma developed. Management by medical treatment results in good visual acuity and graft survival.
Albrecht von Graæes Archiv für Ophthalmologie 11/2012; · 2.17 Impact Factor
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ABSTRACT: PURPOSE: To evaluate the indications, visual outcomes, and complication rate after implantation of a posterior chamber iris-claw aphakic intraocular lens (IOL). SETTING: Department of Ophthalmology, University Medicine Charité Berlin, Berlin, Germany. DESIGN: Retrospective case series. METHODS: Eyes without adequate capsule support had posterior chamber iris-claw aphakic IOL implantation (Verisyse/Artisan) between 2005 and 2010. RESULTS: The study comprised 137 eyes (126 patients). The mean follow-up was 5 months (range 1 to 48 months). The IOLs were inserted during primary lens surgery in 10 eyes (7.3%), during an IOL exchange procedure for dislocated posterior chamber IOLs in 95 eyes (69.4%), and as a secondary procedure in 32 aphakic eyes (23.3%). The final mean corrected distance visual acuity (CDVA) (0.38 ± 0.31 [SD] logMAR) was significantly better than preoperatively (0.65 ± 0.58 logMAR) (P < .05). In 128 eyes (93.4%), postoperative refractive errors were within ±2.00 diopters (D) of emmetropia. Complications included slight temporary pupil ovalization in 34 eyes (24.8%), cystoid macular edema in 12 eyes (8.7%), hyphema in 3 eyes (2.1%), early postoperative hypotony in 7 eyes (5.1%) and elevated intraocular pressure in 6 eyes (4.3%), chronic uveitis in 1 eye (0.7%), toxic anterior segment syndrome in 1 eye (0.7%), and endophthalmitis in 1 eye (0.7%). Iris-claw IOL disenclavation occurred in 12 eyes (8.7%); all IOLs could be easily repositioned. CONCLUSION: The retropupillary iris-claw IOL provided good visual outcomes with a favorable complication rate and can be used for a wide range of indications in eyes without adequate capsule support. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
Journal of cataract and refractive surgery 10/2012; · 2.75 Impact Factor
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ABSTRACT: Background: Large full-thickness eyelid defects are conventionally reconstructed by either a Hughes flap or Cutler-Beard bridge flap. Since the structure of the eyelid and its components are necessary for the tear film production and stability, we investigated the outcome after eyelid reconstruction focusing on dry eye symptoms using a new thermographic device, the TG-1000. Methods: Seventeen eyes of patients formerly treated with Hughes flaps (n = 16) and a Cutler-Beard bridge flap (n = 1) were compared to untreated healthy eyes (n = 17) regarding the functional and aesthetic outcome. The follow-up ranged from 3 to 63 months (mean 24.88 ± 17.86). Results: There was no significant difference in Schirmer's test, break-up time and ocular surface temperature (p > 0.05) between patients after full-thickness eyelid reconstruction and a control group. Eleven patients had minor postoperative complications such as notching of the lid margin (11/17), epiphora (1/17), superficial punctate keratitis (6/17), trichiasis (2/17) and a mild tendency to eversion of the lid margin (6/17). More than 75% of the patients rated their postoperative aesthetic outcome as good or even excellent. Conclusion: The new TG-1000 device is a simple and quick tool for screening of dry eye. This study shows that tarsoconjunctival grafts offer good aesthetic and functional outcome with sufficient tear film composition and stability.
Ophthalmic Research 08/2012; 48(4):192-8. · 1.56 Impact Factor
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ABSTRACT: INTRODUCTION: Glaucoma is a leading cause for graft failure. This retrospective study analyzes the risk factors, graft status, and treatment modalities in patients with post-penetrating keratoplasty glaucoma. METHODS: A retrospective analysis of case records of 1,848 penetrating keratoplasties carried out between 2000 and 2005 was performed. A total of 160 patients (160 eyes) with post-penetrating keratoplasty glaucoma were included; 112 cases were primary grafts, 48 repeated grafts. The assessment included the pre-operative history of corneal disease and glaucoma, the lens status, and the anesthesiological techniques. Furthermore, the response to anti-glaucoma treatment, graft failure, and endothelial cell loss was evaluated. RESULTS: The incidence of post-penetrating keratoplasty glaucoma was 8.7 % (160/1,848). Preoperative glaucoma was the most important risk factor (62/160). Half of the patients (81 patients) responded to medical therapy (51 %) and the other half of patients (79 patients) to surgical therapy (49 %); of the latter, filtering surgery were performed in 16 %, cyclodestructive procedures in 66 % and both in 16 %. One patient received a glaucoma implant and cyclodestructive procedures (1 %). After 24 months, clear grafts were achieved in 94 eyes (59 %). Visual acuity after 24 months of 20/200 (logMAR 1.0) or better was achieved in 77 eyes (46 %) and of 20/50 (logMAR 0.4) in 33 eyes (21 %). CONCLUSIONS: Careful and ongoing observation of IOP, especially in the first year after PK, is recommended for patients after penetrating keratoplasty and prompt treatment of IOP elevation when indicated. Early filtering surgery with a better outcome than other surgery procedures should be preferred if medical treatment is not sufficient. Despite anti-glaucoma therapy, good visual outcome can remain beyond expectations despite a clear graft. While there is a potential option for graft exchange, damage to the optic nerve from end-stage glaucoma leads immutably to visual loss.
Albrecht von Graæes Archiv für Ophthalmologie 05/2012; · 2.17 Impact Factor
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ABSTRACT: HintergrundDie diabetische Retinopathie zählt zu den häufigsten Ursachen eines Visusverlustes im mittleren Erwachsenenalter. Lasertherapie
und chirurgische Intervention können die Komplikation retinaler Ischämie (retinale Neovaskularisation, Rubeosis iridis) nur
zum Teil aufhalten. In vielen Fällen z.B. von diabetischem Makulaödem oder ischämischer Makulopathie bleiben die therapeutischen
Möglichkeiten unbefriedigend. Ein besseres Verständnis der pathophysiologischen Vorgänge könnte zur Entwicklung neuer therapeutischer
Strategien beitragen.
Aktuelle AnsätzeDie Übersicht analysiert den Wissensstand zu molekularen und zellulären Mechanismen der diabetischen Retinopathie. Hierbei
wird auf folgende Punkte eingegangen: 1. Humorale Faktoren, die die Gefäßveränderungen bei der diabetischen Retinopathie vermitteln
(IGF, bFGF, VEGF). 2. Interaktion auf zellulärer Ebene (Perizyten — Endothel — Leukozyten). 3. Folgeerscheinungen und pathophysiologische
Auswirkungen der Hyperglykämie bei der diabetischen Retinopathie (AGE’s, Insulin). 4. Therapeutische Ansatzpunkte und ungelöste
Probleme.
DatenbankenMedLine, Science Citation Index, American Medical Association (JAMA)
SchlussfolgerungDer molekulare Hintergrund vieler klinischer Phänomene ist zwar noch nicht abschließend geklärt. Dennoch lassen gegenwärtig
bereitsin vivo Untersuchungen eine spezifische und ursächliche Therapie möglich erscheinen.
BackgroundDiabetic retinopathy is among the leading cause of visual deterioration in middle aged patients in the western world. Laser
treatment and surgical approaches can help to prevent worsening of the disease, but the effect on ischemic or edematous diabetic
maculopathy is limited. A better understanding of the pathophysiological mechanisms, including the role of growth factors
as well as cellular interactions in diabetes, could lead to new therapeutic approaches.
Current hypothesisMolecular and cellular mechanisms of diabetic retinopathy are reviewed, focussing on the following issues:
1.
Factors responsible for the development of vascular changes. Growth factors IGF, bFGF and VEGF are reviewed with respect to
their angiogenic properties and their responsibility for diabetic changes.
2.
Cellular mechanisms involved in developing vascular changes. Pericyte-endothelial interaction as well as endothelial — leukocyte
interaction and their consequences are discussed.
3.
The molecular targets and mechanisms of hyperglycemia. Hyperglycemia leads to glycosylation of proteins and accumulation of
advanced glycation end products with subsequent increase in growth factor expression.
4.
Possibilities of treatment and their applicability to diabetic retinopathy are discussed.
Data basesMedLine, Science Citation Index, American Medical Association (JAMA)
ConclusionThe progress in delineating the molecular basis of diabetic retinopathy could result in new and more specific therapeutic
targets.
Spektrum der Augenheilkunde 04/2012; 14(5):268-282. · 0.26 Impact Factor
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ABSTRACT: Recurrence of herpetic keratitis and immune reactions is the major cause of graft failures after penetrating keratoplasty as a consequence of herpes simplex keratitis. No treatment regimen is yet considered a standard of care. This retrospective study analyzes the effectiveness of combined systemic acyclovir and immunosuppressive therapy with cyclosporine A (CSA) or mycophenolate mofetil (MMF) after high-risk keratoplasty in herpetic keratitis.
A total of 87 high-risk keratoplasties treated with postoperative combined systemic acyclovir and immunosuppressive therapy with CSA or MMF were analyzed retrospectively according to the therapeutic regimen, the degree of preoperative corneal vascularization, and tissue matching of the graft. Endpoints included immunological graft rejection, recurrence of the herpetic keratitis, graft failure, and visual acuity.
There was an overall trend toward an improvement of visual acuity. Graft failure occurred in 13.1%, in all cases after termination of immunosuppression with MMF or CSA. In 4 of 11 cases, immune reactions caused graft failure. Patients with 3 to 4 quadrants of corneal vascularization showed significantly higher rates of graft rejection than patients with 1 to 2 quadrants vascularized or avascular corneas. Herpetic recurrence occurred in 31.8% and caused 18.2% of graft failure. In 7 of 23 cases, graft rejection was induced by herpetic recurrence.
Graft survival rate and functional outcome after postoperative antiviral and immunosuppressive treatment in cases of penetrating keratoplasties after herpetic keratitis are comparable with results of normal-risk keratoplasties, despite existing high risks for immune rejections or herpetic recurrences.
Cornea 12/2011; 30(12):1398-405. · 1.73 Impact Factor
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ABSTRACT: In the follow-up of retinal vein occlusions, a patient's subjective change in vision frequently cannot be confirmed by objective measurements. Furthermore, contradictory results of OCT and distance visual acuity give the impression that current routine diagnostic tests might not be satisfying for patients with retinal vein occlusions. This prospective case series analyses the value of microperimetry as a routine diagnostic test in the follow-up of patients with retinal vein occlusions during therapy.
In a prospective case series, we tested microperimetry as a functional measure in comparison to distance visual acuity, reading ability, and OCT, on 13 patients treated for central or branch retinal vein occlusions. Treatment consisted of intravitreal bevacizumab injections combined with panretinal laser coagulation in cases of peripheral ischemia. If macular edema persisted, bevacizumab injection was repeated, or instead of this intravitreal triamcinolone or focal laser coagulation was applicated. Follow-up ranged from 6-14 months. An interim analysis was performed for the 6-month follow-up.
In the branch retinal vein occlusion group, the average of the retinal thickness measured by OCT was 502.22 μm (±SD 217.75 μm) at baseline and changed to 396.38 ± 154.38 at the 6-month follow-up (p = 0.121). Mean distance visual acuity stayed similar to the study entrance with 0.41 ± 0.34 at the 6-month follow-up (p = 0.944) Mean reading ability improved to 0.51 ± 0.52 at the 6-month follow-up but was not statistically significant (p = 0.435). The mean light sensitivity of microperimetry improved from baseline to the 6-month follow-up: the 40-points group improved from 8.62 ± 5.69 dB to 10.98 ± 5.42 (p = 0.060) and the 8-points group from 6.27 dB to 9.6 dB (p = 0.07) but missed statistical significance. The sector group showed in contrast to this an improvement from 6.02 ± 5.71 dB to 9 ± 6.07 dB (p = 0.025), which was statistically significant. Changes in the central vein occlusion group were not statistically significant but changes for both groups together showed statistical significance.
In the present case series, microperimetry was more convenient to detect, even the subtle functional changes during the disease course of branch retinal vein occlusions than distance and reading visual acuity. This indicates that microperimetry could be a possible valuable tool in the follow-up of branch retinal vein occlusions.
Albrecht von Graæes Archiv für Ophthalmologie 08/2011; 250(2):175-83. · 2.17 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Acta ophthalmologica 04/2011; 89(6):e483-9. · 2.44 Impact Factor
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ABSTRACT: Chronic graft-versus-host disease (cGvHD) is a major concomitant phenomenon in recipients of allogeneic hematopoietic stem cell transplantations, affecting multiple organ systems including the eye. Ocular structures, such as lacrimal gland, conjunctiva, and eyelids with meibomian glands, are frequently involved with clinical features ranging from dry eyes and common inflammatory conjunctival disease to severe complications like corneal ulcerations or even perforations. We present 2 patients with complicated courses of ocular cGvHD. In both cases, keratoconjunctivitis sicca refractory to systemic immunosuppressive therapy and to conventional topical treatment resulted in progressive binocular corneal melting and finally repeated perforations. According to our 2 cases and to the current pathophysiological understanding, we discuss possible strategies for the treatment and prevention of ocular cGvHD complications.
Cornea 01/2011; 30(1):107-13. · 1.73 Impact Factor
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ABSTRACT: Purpose. Tumor necrosis factor (TNF)-α contributes to inflammation-associated angiogenesis, and TNF-α receptor 1b is selectively expressed on immuno-competent and endothelial cells. This study investigated the role of TNF-α receptor 1b in the recruitment of circulating inflammatory cells and the development of choroidal neovascularization (CNV). Methods. Lethally irradiated Tnfrsf1b(-/-) mice and their wild-type (WT) controls were transplanted with whole adult bone marrow (BM) cells, competent for both TNF-α receptors 1a and 1b (gfp(+) labeled), as well as with BM cells deficient for TNF-α receptor 1b. One month after transplantation CNV was induced by laser damage of Bruch's membrane. Pathologic angiogenesis was estimated qualitatively and quantitatively by histology on choroidal flatmounts and paraffin cross sections. Macrophage invasion was investigated by immunochemistry. Results. One month after transplantation the reconstitution rate measured by FACS analysis was >80% in gfp(+)-chimeric mice. Two weeks after laser injury reduced gfp(+)-cell invasion to the laser scars and decreased pathologic angiogenesis were observed in Tnfrsf1b(-/-) versus WT recipients. Approximately 70% of the invaded gfp(+) cells were labeled with macrophage marker F4/80. Transplantation of TNF-α receptor 1b-deficient BM cells in WT recipients reduced the CNV lesion compared with WT and Tnfrsf1b(-/-) recipients that received TNF-α receptor-competent BM cells. Transplantation of receptor 1b-deficient cells to Tnfrsf1b(-/-) recipients further reduced the degree of CNV formation. Conclusions. Signals through TNF-α receptor 1b expressed on BM -derived inflammatory cells mediate an increased inflammatory cell invasion and enhanced angiogenic response after laser-induced rupture of Bruch's membrane.
Investigative ophthalmology & visual science 12/2010; 52(9):6101-8. · 3.43 Impact Factor
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ABSTRACT: RPE cells are a major player in various diseases of the retina and choroid. Proliferating RPE cells are thought to be an initiating factor in proliferative vitreoretinopathy (PVR); the aging RPE cells are important in age-related macular degeneration (AMD). Early passages of cultured human retinal pigment epithelial cells were used as a model system to identify differentially expressed genes in proliferating retinal pigment epithelial (RPE) cells.
A differential expression analysis (DEmRNA-PCR) was used to find differentially expressed mRNA in early passages of cultured human RPE cells. The detected mRNAs were identified by sequencing. Their differential expression was verified by semi-quantitative RT-PCR. The expression of the identified protein in vitro and its presence in surgically removed epiretinal membranes was demonstrated by western blotting and immunocytochemical analysis.
DEmRNA-PCR detected a decreased expression of a band at approximately 530 bp in human RPE cells of passage 3 (P3) compared to P0. This band was identified as part of the human complement regulatory factor H, a cofactor to complement factor I. The mRNA expression of both regulatory proteins of the complement system was confirmed in freshly prepared human RPE cells and in cultured cells from P0 to P8. The protein expression was verified in cultured RPE cells. The expression of both proteins in surgically removed epiretinal membranes was demonstrated by immunohistochemistry.
The identification of the differential expression of the regulatory factors H and I of the complement system in cultured RPE cells by a technique without any prerequisites demonstrates and confirms the importance of these factors in RPE cells. In addition to its known role in age-related macular degeneration, the presence of these complement factors in epiretinal membranes may also indicate a role of the complement system in proliferative retinopathy.
Albrecht von Graæes Archiv für Ophthalmologie 04/2010; 248(8):1145-53. · 2.17 Impact Factor
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ABSTRACT: Microglia cells have been associated with immunologic defense and repair. The course of retinal disease after lethal irradiation for bone marrow depletion and substitution was evaluated with respect to macrophage and microglial involvement.
Lethal irradiation in C57BL/6 mice was conducted with a low-voltage radiation unit. The animals were randomized to shielded or unshielded radiation and subsequently received transplants of GFP+ bone marrow cells (beta-actin promoter). The GFP transformation rate was analyzed by flow cytometry. GFP+ cells in the retina were examined for co-localization with macrophage and dendritic cell markers at various time points between 1 and 7 months after irradiation. Clodronate liposomes were used to investigate the fate of migrated and residential microglia cells. Pathologic angiogenesis was investigated in laser-induced choroidal neovascularization (CNV) after unshielded and shielded irradiation.
Flow cytometry revealed average transformation rates of 78.2% in unshielded and 64.1% in shielded group. Four weeks after transplantation, perfused flat mounts were virtually free of extravasal GFP+ cells in both groups, whereas 4 months after irradiation, cluster cell infiltrations, preferentially in the peripheral retina, became apparent exclusively in the unshielded group. Cell morphology ranged from oval, to a few extensions, to dendritiform with long-branched extensions. Clodronate treatment resulted in a reduction of GFP+ cells in the retinal tissue when applied 3 months after unshielded irradiation. Although GFP+ cells accumulated in the choroidal scar after laser treatment, in both the shielded and unshielded groups, GFP+ cells in the overlying retina were restricted to the unshielded group.
Approximately 3 months after lethal full-body irradiation including the eye, bone marrow-derived leukocytes exhibit a wound-healing reaction, and unlike physiological turnover, infiltrate the retina and form microglial cells.
Investigative ophthalmology & visual science 04/2010; 51(9):4831-9. · 3.43 Impact Factor
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ABSTRACT: Tumor necrosis factor alpha (TNF)-alpha contributes to inflammation-associated angiogenesis. This study investigates the role of TNF-alpha receptors 1a and 1b in the development of choroidal neovascularization (CNV).
CNV was induced in Tnfrsf1a(-/-) and Tnfrsf1b(-/-) mice with C57Bl6/J background and their wild-type (WT) (C57Bl/6J) controls by laser damage to the Bruch's membrane. TNF-alpha expression in RPE/choroid was determined by Western blot analysis. Pathologic angiogenesis was estimated qualitatively and quantitatively by fluorescein angiography and histology on choroidal flat mounts and paraffin cross-sections. Inflammatory cell invasion was investigated by clodronic acid depletion of circulating macrophages and immunochemistry, and the apoptotic activity was investigated by TUNEL assay and by caspase-3 and caspase-8 expression. Receptor 1b-specific Bmx/Etk kinase was detected by immunochemistry.
TNF-alpha levels were elevated after laser treatment. Severe CNV lesions and increased macrophage invasion were observed in Tnfrsf1a(-/-) compared with WT and Tnfrsf1b(-/-) mice. Increased immunoreactivity for Bmx/Etk kinase corresponded to the severity of CNV formation. Reduced pathologic angiogenesis and macrophage invasion in Tnfrsf1b(-/-) mice (vs. WT and Tnfrsf1a(-/-)) was accompanied by enhanced endothelial cell apoptosis and by caspase-3 and caspase-8 activation.
Receptor 1b promotes the recruitment of inflammatory cells to the site of injury and exacerbated pathologic angiogenesis probably by way of the Bmx/Etk-kinase-dependent pathway in the absence of receptor 1a. On the other hand, receptor 1a-dependent apoptosis in the absence of receptor 1b leads to reduced inflammatory response and CNV lesions after laser treatment. This demonstrates the potential for specific targeting of TNF-alpha receptors for future therapies of inflammation-associated choroidal neovascularization.
Investigative ophthalmology & visual science 03/2010; 51(8):3874-83. · 3.43 Impact Factor
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ABSTRACT: Impaired glutamatergic activity and synaptic dysfunction contributing to excitotoxicity and neuronal degeneration has been observed in the diabetic retina. Here we analyzed the expression changes and trafficking abnormalities of the AMPA glutamate receptor 2 subunit (GluR2) and its regulators protein kinase Calpha (PKCalpha) and PKC-interacting protein 1 (PICK1) in the rat retina during the early phases of streptozotocin-(STZ-) induced diabetes. Diabetes was induced in Long Evans rats by injection of STZ. Two and six weeks after induction of diabetes, immunohistochemistry and in situ hybridization were performed on retinal paraffin sections to investigate the expression and localization of GluR2 and its regulators PKCalpha and PICK1. The cellular distribution and trafficking of these proteins in retinae were also investigated by subcellular fractionation and western blotting. While no significant changes were observed for GluR2 transcripts, we observed a strong increase in GluR2 immunoreactivity, predominantly in the ganglion cell layer (GCL) and the inner plexiform layer (IPL), as early as two weeks of diabetes. GluR2/3 immunoreactivity was further increased from the GCL to OPL after 6 weeks of diabetes. Increased expression of a phosphorylated non-synaptic population of GluR2 was detected in the GCL, the IPL and in distinct photoreceptor cells within the outer nuclear layer (ONL) of diabetic animals. Further, the PICK1 retinal distribution was unchanged two and six weeks after onset of diabetes and in both control and diabetic rat retinae the PKCalpha immunoreactivity remained the same. However, phosphorylated PKCalpha immunoreactivity was increased in diabetic retina as compared to control and peaked after 6 weeks of diabetes. Activated PKCalpha was almost completely lost in all membrane fractions and primarily recovered in the cytosolic fraction. These results are consistent with PKCalpha being re-localized in the diabetic retina. The observations indicate a diabetes-dependent increase in the activation of PKCalpha and a disturbed GluR2 regulation by altered internalization and recycling.
Experimental Eye Research 10/2009; 90(2):244-53. · 3.26 Impact Factor
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ABSTRACT: ICAM-1 has been identified as a mediator of inflammatory and VEGF-dependent corneal neovascularization. Furthermore, ICAM-1 has been demonstrated to be involved in leukocyte-mediated endothelial injury in diabetic retinopathy. Here we investigated the role of ICAM-1 in retinal vaso-obliteration and vascularization. ICAM-1 deficient mice as well as their respective wild-type controls were exposed to 75% oxygen from postnatal day 7 to day 12. Retinal vascularization was investigated after lectin labeling of endothelial cells on day 14, 17, and 20 in flat mount preparations. Retinal mRNA expression of VEGF, Angiopoietin 1 and 2 as well as PDGFbeta was examined at day 14 and 20 by Real Time RT-PCR. ICAM-1(-/-) mice and their respective wild-type controls demonstrated similar retinal development and vascularization under normoxic conditions. Similarly, after oxygen challenge, the vascular area, the avascularized area as well as the area of neovascular tufts did not differ between ICAM-1(-/-) and the respective wild-type mice although the mRNA expression of VEGF, ang-1, ang-2, and PDGFbeta differed clearly. This study demonstrates that lack of ICAM-1 leads to an altered expression of angiogenic factors that in combination may neutralize each other and do not alter retinal development and angiogenesis in oxygen-induced retinopathy.
Experimental Eye Research 06/2009; 89(4):503-10. · 3.26 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the area of the retina that has the highest visual acuity. It can progress to geographic atrophy or choroidal neovascularization.
Selective literature review.
The authors discuss the results of therapeutic trials and the treatment recommendations of the ophthalmological societies. Mechanism-targeted treatments and improved modes of administration offer the potential for improved therapy.
With the advent of the antivascular endothelial growth factor (anti-VEGF) therapy, the prognosis of choroidal neovascularization has changed dramatically. Visual acuity can actually be improved, but, in most cases, the improvement can only be sustained with repeated intravitreal injections.
06/2009; 106(18):312-7. · 2.92 Impact Factor
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ABSTRACT: The pathophysiology of diabetic retinopathy involves leukocyte adhesion to retinal vasculature, early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell death. We investigated the involvement of tumor necrosis factor alpha (TNF-alpha) in diabetes-related histopathological changes in two relevant rodent models.
In short-term studies, Long-Evans rats with streptozotocin-induced diabetes were treated with or without the TNF-alpha inhibitor, etanercept. For long-term studies, tumor necrosis factor receptor I (TNF-RI)-deficient mice and TNF-RII-deficient mice, as well as C57/Bl6 wild-type mice, were fed 30% galactose for up to 20 months. The retinal histopathological alterations of hypergalactosemia were analyzed in trypsin digest preparations. Endothelial cell injury and apoptosis in rat retinas were evaluated by propidium iodide, TUNEL, CytoDeath staining, and DNA fragmentation ELISA. Caspase 3 and 8 activity was evaluated by immunoblotting and quantitative enzymatic activity assay.
Etanercept suppressed caspase activation, retinal cell injury, and apoptosis in short-term diabetic rats. Pericyte and endothelial cell loss were also reduced in long-term hypergalactosemic mice. Long-term studies demonstrated that pericyte loss and endothelial cell loss were reduced in comparison to wild-type diabetic controls.
Our study identifies an important role for TNF-alpha in the pathogenesis of signature diabetic retinopathy pathologies and demonstrates that etanercept can inhibit retinal cell death and long-term complication of diabetes. Taken together, our results suggest that etanercept could prove beneficial in preventing both early and late vascular diabetic complications.
Molecular vision 02/2009; 15:1418-28. · 2.20 Impact Factor
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ABSTRACT: The aim of the study was to compare the efficacy of perfluorobutylpentane (F4H5) and perfluorohexyloctane (F6H8) in dissolving silicone oil from the surface of silicone intraocular lenses (IOL).
Droplets of stained silicone oil were applied to an object slide either lying flat or tilted by 30 degrees . Mixing with H(2)O, F4H5 or F6H8 was documented by a digital camera. Droplets of silicone oil were applied to silicone lenses and washed off by repeated rinsing with F4H5 or F6H8. The silicone lenses of 11 patients with silicone oil remnants on the posterior IOL surface were rinsed intraoperatively with F4H5 during removal surgery.
Only F4H5 was able to mix with silicone oil and to remove it form the surface of a glass object slides. Rinsing with 25 mul F4H5 reduced the amount of silicone oil 1000 mPas or 5000 mPas attached on a silicone lens to 15% and 28%, respectively. A hanging droplet of silicone oil 5000 beneath a silicone lens was completely removed from below by F4H5. In all patients sufficient IOL cleaning was possible using F4H5. There was no significant postoperative inflammation in the vitreous or anterior chamber.
Polydimethylsiloxanes dissolve effectively in F4H5 due to its lipophilic chemical structure. A much smaller volume of F4H5 than F6H8 is able to remove silicone oil from silicone lenses completely. Intraocular use of F4H5 is safe, and initial clinical data underlines its effectiveness as a cleaning agent after contact of silicone lenses with silicone oil.
The British journal of ophthalmology 09/2008; 92(11):1522-7. · 2.92 Impact Factor
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ABSTRACT: To investigate the role of TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in the mouse.
Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice by making four separate choroidal bums in each eye. Animals were treated 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept, 5 microg/h, group 1, n = 12), chimeric monoclonal antibody (infliximab, 5 microg/h, group 2, n = 12) for 7 days by intraperitoneally implanted osmotic pumps. PBS was used as control (group 3, n = 12). The left eyes were removed for histopathologic examination and the right eyes were removed for flatmounts immunohistochemistry immediately after fluorescein angiography. In mice treated with medications 3 days before laser injury, left eyes were collected at 1 or 2 weeks after laser injury. In mice treated with medications 3 days after laser injury, left eyes were collected at 10 days after laser injury. CNV responses were compared by flatmount analysis of CNV-related fluorescence area and by determination of fluorescein angiographic leakage. The level of protein expression of TNF-alpha was semiquantitatively evaluated by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment.
Western blotting demonstrated that TNF-alpha was highly expressed in choroidal and RPE cells of wild type mice 1 week after laser treatment as compared to the control mice without laser treatment. Etanercept and infliximab administrated 3 days before laser-damage significantly reduced CNV size and pathological fluorescein leakage in comparison to the control group one and two weeks after laser injury. Only etanercept administered 3 days after laser injury still significantly reduced the development of CNV lesions. Histopathological examination confirmed that CNV lesions in treated mice had smaller diameter and thinner center as compared to the control animals.
Anti-TNF-alpha treatment reduces the size and leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age related macular degeneration.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 04/2008; 44(3):200-6.
