A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transpla... more A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transplantation surgery from a 6 or 12 o'clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro-inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy. Retrospective analysis of a prospective cohort of 246 patients with exudative age-related macular degeneration treated with an RPE-choroid graft transplantation and a lighter-than-water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two-tailed Fisher's exact test was used for statistical analysis. Thirty-nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p=0.8). Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.
To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genoty... more To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR). A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples. BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers fro...
We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid... more We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid graft with direct blood flow detection by experimental phase-resolved Doppler optical coherence tomography (PRD-OCT). Seven patients with age-related macular degeneration underwent an RPE-choroid graft translocation in a prospective institutional cohort study. Spectral domain optical coherence tomography (SD-OCT) was used to measure the revascularization stage. With PRD-OCT the presence of flow was imaged postoperatively. The PRD-OCT confirmed flow in three patients when SD-OCT indicated the afferent vessel ingrowth stage, and in all seven patients when the SD-OCT indicated the efferent vessel ingrowth stage. The PRD-OCT study was able to detect the presence of blood flow in a free RPE-choroid graft. The PRD-OCT findings directly confirmed the revascularization that was otherwise based on the more circumstantial evidence provided by SD-OCT images and angiography. The use of both techniques to monitor the revascularization process in a free graft in patients are an interesting example of replacing more invasive by noninvasive techniques. There is potential future use of PRD-OCT for the visualization of vascularization patterns in other pathologies.
The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized b... more The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized by vascular growth and leakage in the retina. Two new drugs, pegaptanib and ranibizumab, have been shown to improve vision or slow the progression of AMD. Both drugs inhibit the action of vascular endothelial growth factor--pegaptanib as an oligonucleotide and ranibizumab as a monoclonal antibody--thereby decreasing angiogenesis in the eye. Adverse effects are associated with the intravitreal administration of both drugs and include increased intraocular pressure, local bleeding, and infection.
To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analys... more To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analysis of genotypic data and relevant clinical characteristics. The validation series consisted of data from 546 patients operated on from primary rhegmatogenous retinal detachment (RRD) coming from centres in the Netherlands, Portugal, Spain and the UK. Temporal and geographical validation was performed. The discrimination capability of each model was analysed and compared with the original series, using a receiver operating curve. Then, clinical variables were combined in order to improve the predictive capability. A risk reclassification analysis was performed with and without each one of the variables. Reclassification of patients was compared and models were readjusted in the original series. Readjusted models were further validated. One of the models showed good predictability in the temporal sample as well as in the original series (area under the curve (AUC) original=0.7352; AUC temp...
To evaluate the effectiveness of 6 months treatment with ibopamine eye drops in raising the intra... more To evaluate the effectiveness of 6 months treatment with ibopamine eye drops in raising the intraocular pressure in patients with therapy-resistant hypotony after vitreoretinal surgery for proliferative vitreoretinopathy secondary to rhegmatogenous retinal detachment or penetrating trauma. A 2% ibopamine eye drop was topically administered 3 times daily during 24 weeks. Seventeen patients were included. Nine patients were able to continue their treatment up to 24 weeks; their mean intraocular pressure increase was 2.11 mmHg (SE, 0.56; 95% confidence interval, 0.96 to 3.23; P < 0.0005) in comparison with baseline values. Eight patients stopped using ibopamine before 24 weeks because of complains of follicular conjunctivitis or irritation without clinically observable conjunctivitis. In these patients a comparable increase in intraocular pressure was observed up to treatment discontinuation. This study confirms that the use of topical ibopamine may result in a sustained increase in intraocular pressure of >2 mmHg in the majority of patients, but was only well tolerated in half of them. There may only be a few patients, however, who will clinically benefit from this rise in intraocular pressure. A better formulation or method of administration would be needed.
The encircling band used in conventional retinal detachment surgery creates a circular indentatio... more The encircling band used in conventional retinal detachment surgery creates a circular indentation of the eye and thus may increase the anterior-posterior axial length. The myopia induced by encircling elements in retinal detachment surgery varies between 0 and 3 D. In a series of 25 patients, the average change in refraction after surgery was -2.25 D. To achieve early visual rehabilitation, patients were fitted with extended-wear soft contact lenses 7 to 10 days after surgery. The patients were followed for up to 6 months and contact lenses were exchanged according to changes in refraction. Visual rehabilitation using extended-wear lenses was immediate and excellent. The contact lenses were tolerated well. Two patients developed a minor corneal infiltrate under the soft lens and were withdrawn from the study.
During eye surgery translocating a graft of retinal tissue without damaging the vulnerable top la... more During eye surgery translocating a graft of retinal tissue without damaging the vulnerable top layer is highly problematic using the currently available instruments. This study presents indirect Heat Induced Attachment and Detachment (HIAD) as a new concept for single side attachment of tissue to, and detachment from a heated metal wire. A small-scale prototype was built, having a 50 mum molybdenum wire that could be heated via an electric current. Tests (n = 60) were performed on submerged chicken meat to study the attachment and detachment properties of the prototype at different electric signal lengths. A 9V signal was applied to the prototype, with amplifier input signal lengths varying from 0.6-1.5 ms. Voltages and currents were sampled at 250 kHz to obtain energies. Both attachment and detachment occurred with 98% and 90% certainty, respectively, supplying 41 and 110 mJ of energy to the prototype in 0.7 and 1.5 ms. The attachment strength was estimated at 0.2 mN. Visible damage appeared to be approximately 0.005 mm(2). The concept of indirect heating of the instrument-tissue interface proved to be effective as the prototype could induce attachment and detachment of tissue. Indirect HIAD may be applicable in many different surgical applications.
To evaluate the presence of collagen types I to VII, IX, XI, and XVIII at the posterior pole, the... more To evaluate the presence of collagen types I to VII, IX, XI, and XVIII at the posterior pole, the equator and the pre-equatorial area in human donor eyes, since collagens are important macromolecules that contribute to vitreoretinal adhesion at the vitreoretinal interface. Freshly isolated human retinectomy samples from the equator were used for reverse transcription-polymerase chain reaction to detect mRNA of the above-mentioned collagens. In addition, human donor eyes and equatorial retinectomy samples were embedded in paraffin, stained with antibodies against the collagens and evaluated by light microscopy (LM). Retinectomy samples expressed mRNA of all tested collagen types. By LM, vitreous cortex was positive for collagen types II, V, IX, and XI. In all three regions within the donor eyes and in the retinectomy samples, the internal limiting membrane (ILM) showed types IV, VI, and XVIII; the retinal vasculature was positive for types I to VI and XVIII in most specimens; and the retinal layers showed condensed spots of type VII. In addition, type VII increased in density and in distribution over the retinal layers toward the posterior pole. Staining patterns of collagen types I to V, IX, XI, and XVIII confirmed previous observations. Important new findings include the presence of type VI in the ILM and type VII in several layers of the retina. Both collagens can anchor matrix components, and type VI could be involved in vitreoretinal attachment. Furthermore, the presence of collagen mRNA in human retinectomy samples may be an indication of postnatal collagen production by retinal cells.
To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)... more To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)-choroid graft. This prospective cohort study used spectral domain-optical coherence tomography (SD-OCT) after RPE-choroid graft surgery in 12 patients. This SD-OCT was combined with fluorescein angiography (FA) and indocyanine green angiography (ICGA) in 5 patients. SD-OCT revealed that vessel diameter, number of vessels, and graft thickness increased in 10 of 12 patients, starting between 3 and 10 days after surgery. A subsequent decrease in thickness was found in all 10 patients, beginning as early as 8 days after surgery. Initially, the graft vessels were optically clearer than the underlying choroidal recipient vessels. Between 8 and 30 days after surgery, the optically clear vessels became gray, similar to the recipient choroid. FA and ICGA revealed perfusion in 4 of 5 patients between postoperative days 6 and 15. Between postoperative days 12 and 60, the entire choroidal structure of the graft was visible on ICGA. CONCLUSIONS; These data suggest that enlargement of vessel diameter, increase in the number of choroidal vessels, and graft thickening visualized by SD-OCT correspond with the ingrowth of afferent vessels, as demonstrated by ICGA. The subsequent establishment of efferent vessels results in flow, imaged as a change in color of the graft's vessels from optically clear to gray, graft thinning on SD-OCT, and complete revascularization on ICGA. SD-OCT, a noninvasive examination, can be used to demonstrate early graft perfusion in patients (trialregister.nl/trialreg/admin/rctview.asp number, NTR1768).
Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (... more Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis.
To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cat... more To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non-typeable Pseudomonas spp. These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time.
Journal of biochemical and molecular toxicology, Jan 9, 2015
Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory d... more Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory drugs, but side effects include retinopathy and vision loss. The objective of this study was to examine the effect of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro. Permeability of ARPE-19 cell monolayers was determined using Fluorescein isothiocyanate (FITC)-labeled dextran. The influence of CQ and HCQ on cell death and the expression tight junction molecules was examined. CQ and HCQ significantly increased ARPE-19 monolayer permeability after 3 and 18 h, respectively, and enhanced mRNA levels for claudin-1 and occludin. Cytotoxicity was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE barrier permeability in vitro, independent of cytotoxicity or loss of zonula occludens-1, claudin-1, and occludin expression. Our findings suggest that CQ/HCQ-induced permeability of the RPE layer may contribute to blood-retinal barr...
A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transpla... more A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transplantation surgery from a 6 or 12 o'clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro-inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy. Retrospective analysis of a prospective cohort of 246 patients with exudative age-related macular degeneration treated with an RPE-choroid graft transplantation and a lighter-than-water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two-tailed Fisher's exact test was used for statistical analysis. Thirty-nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p=0.8). Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.
To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genoty... more To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR). A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples. BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers fro...
We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid... more We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid graft with direct blood flow detection by experimental phase-resolved Doppler optical coherence tomography (PRD-OCT). Seven patients with age-related macular degeneration underwent an RPE-choroid graft translocation in a prospective institutional cohort study. Spectral domain optical coherence tomography (SD-OCT) was used to measure the revascularization stage. With PRD-OCT the presence of flow was imaged postoperatively. The PRD-OCT confirmed flow in three patients when SD-OCT indicated the afferent vessel ingrowth stage, and in all seven patients when the SD-OCT indicated the efferent vessel ingrowth stage. The PRD-OCT study was able to detect the presence of blood flow in a free RPE-choroid graft. The PRD-OCT findings directly confirmed the revascularization that was otherwise based on the more circumstantial evidence provided by SD-OCT images and angiography. The use of both techniques to monitor the revascularization process in a free graft in patients are an interesting example of replacing more invasive by noninvasive techniques. There is potential future use of PRD-OCT for the visualization of vascularization patterns in other pathologies.
The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized b... more The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized by vascular growth and leakage in the retina. Two new drugs, pegaptanib and ranibizumab, have been shown to improve vision or slow the progression of AMD. Both drugs inhibit the action of vascular endothelial growth factor--pegaptanib as an oligonucleotide and ranibizumab as a monoclonal antibody--thereby decreasing angiogenesis in the eye. Adverse effects are associated with the intravitreal administration of both drugs and include increased intraocular pressure, local bleeding, and infection.
To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analys... more To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analysis of genotypic data and relevant clinical characteristics. The validation series consisted of data from 546 patients operated on from primary rhegmatogenous retinal detachment (RRD) coming from centres in the Netherlands, Portugal, Spain and the UK. Temporal and geographical validation was performed. The discrimination capability of each model was analysed and compared with the original series, using a receiver operating curve. Then, clinical variables were combined in order to improve the predictive capability. A risk reclassification analysis was performed with and without each one of the variables. Reclassification of patients was compared and models were readjusted in the original series. Readjusted models were further validated. One of the models showed good predictability in the temporal sample as well as in the original series (area under the curve (AUC) original=0.7352; AUC temp...
To evaluate the effectiveness of 6 months treatment with ibopamine eye drops in raising the intra... more To evaluate the effectiveness of 6 months treatment with ibopamine eye drops in raising the intraocular pressure in patients with therapy-resistant hypotony after vitreoretinal surgery for proliferative vitreoretinopathy secondary to rhegmatogenous retinal detachment or penetrating trauma. A 2% ibopamine eye drop was topically administered 3 times daily during 24 weeks. Seventeen patients were included. Nine patients were able to continue their treatment up to 24 weeks; their mean intraocular pressure increase was 2.11 mmHg (SE, 0.56; 95% confidence interval, 0.96 to 3.23; P < 0.0005) in comparison with baseline values. Eight patients stopped using ibopamine before 24 weeks because of complains of follicular conjunctivitis or irritation without clinically observable conjunctivitis. In these patients a comparable increase in intraocular pressure was observed up to treatment discontinuation. This study confirms that the use of topical ibopamine may result in a sustained increase in intraocular pressure of >2 mmHg in the majority of patients, but was only well tolerated in half of them. There may only be a few patients, however, who will clinically benefit from this rise in intraocular pressure. A better formulation or method of administration would be needed.
The encircling band used in conventional retinal detachment surgery creates a circular indentatio... more The encircling band used in conventional retinal detachment surgery creates a circular indentation of the eye and thus may increase the anterior-posterior axial length. The myopia induced by encircling elements in retinal detachment surgery varies between 0 and 3 D. In a series of 25 patients, the average change in refraction after surgery was -2.25 D. To achieve early visual rehabilitation, patients were fitted with extended-wear soft contact lenses 7 to 10 days after surgery. The patients were followed for up to 6 months and contact lenses were exchanged according to changes in refraction. Visual rehabilitation using extended-wear lenses was immediate and excellent. The contact lenses were tolerated well. Two patients developed a minor corneal infiltrate under the soft lens and were withdrawn from the study.
During eye surgery translocating a graft of retinal tissue without damaging the vulnerable top la... more During eye surgery translocating a graft of retinal tissue without damaging the vulnerable top layer is highly problematic using the currently available instruments. This study presents indirect Heat Induced Attachment and Detachment (HIAD) as a new concept for single side attachment of tissue to, and detachment from a heated metal wire. A small-scale prototype was built, having a 50 mum molybdenum wire that could be heated via an electric current. Tests (n = 60) were performed on submerged chicken meat to study the attachment and detachment properties of the prototype at different electric signal lengths. A 9V signal was applied to the prototype, with amplifier input signal lengths varying from 0.6-1.5 ms. Voltages and currents were sampled at 250 kHz to obtain energies. Both attachment and detachment occurred with 98% and 90% certainty, respectively, supplying 41 and 110 mJ of energy to the prototype in 0.7 and 1.5 ms. The attachment strength was estimated at 0.2 mN. Visible damage appeared to be approximately 0.005 mm(2). The concept of indirect heating of the instrument-tissue interface proved to be effective as the prototype could induce attachment and detachment of tissue. Indirect HIAD may be applicable in many different surgical applications.
To evaluate the presence of collagen types I to VII, IX, XI, and XVIII at the posterior pole, the... more To evaluate the presence of collagen types I to VII, IX, XI, and XVIII at the posterior pole, the equator and the pre-equatorial area in human donor eyes, since collagens are important macromolecules that contribute to vitreoretinal adhesion at the vitreoretinal interface. Freshly isolated human retinectomy samples from the equator were used for reverse transcription-polymerase chain reaction to detect mRNA of the above-mentioned collagens. In addition, human donor eyes and equatorial retinectomy samples were embedded in paraffin, stained with antibodies against the collagens and evaluated by light microscopy (LM). Retinectomy samples expressed mRNA of all tested collagen types. By LM, vitreous cortex was positive for collagen types II, V, IX, and XI. In all three regions within the donor eyes and in the retinectomy samples, the internal limiting membrane (ILM) showed types IV, VI, and XVIII; the retinal vasculature was positive for types I to VI and XVIII in most specimens; and the retinal layers showed condensed spots of type VII. In addition, type VII increased in density and in distribution over the retinal layers toward the posterior pole. Staining patterns of collagen types I to V, IX, XI, and XVIII confirmed previous observations. Important new findings include the presence of type VI in the ILM and type VII in several layers of the retina. Both collagens can anchor matrix components, and type VI could be involved in vitreoretinal attachment. Furthermore, the presence of collagen mRNA in human retinectomy samples may be an indication of postnatal collagen production by retinal cells.
To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)... more To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)-choroid graft. This prospective cohort study used spectral domain-optical coherence tomography (SD-OCT) after RPE-choroid graft surgery in 12 patients. This SD-OCT was combined with fluorescein angiography (FA) and indocyanine green angiography (ICGA) in 5 patients. SD-OCT revealed that vessel diameter, number of vessels, and graft thickness increased in 10 of 12 patients, starting between 3 and 10 days after surgery. A subsequent decrease in thickness was found in all 10 patients, beginning as early as 8 days after surgery. Initially, the graft vessels were optically clearer than the underlying choroidal recipient vessels. Between 8 and 30 days after surgery, the optically clear vessels became gray, similar to the recipient choroid. FA and ICGA revealed perfusion in 4 of 5 patients between postoperative days 6 and 15. Between postoperative days 12 and 60, the entire choroidal structure of the graft was visible on ICGA. CONCLUSIONS; These data suggest that enlargement of vessel diameter, increase in the number of choroidal vessels, and graft thickening visualized by SD-OCT correspond with the ingrowth of afferent vessels, as demonstrated by ICGA. The subsequent establishment of efferent vessels results in flow, imaged as a change in color of the graft's vessels from optically clear to gray, graft thinning on SD-OCT, and complete revascularization on ICGA. SD-OCT, a noninvasive examination, can be used to demonstrate early graft perfusion in patients (trialregister.nl/trialreg/admin/rctview.asp number, NTR1768).
Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (... more Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis.
To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cat... more To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non-typeable Pseudomonas spp. These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time.
Journal of biochemical and molecular toxicology, Jan 9, 2015
Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory d... more Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory drugs, but side effects include retinopathy and vision loss. The objective of this study was to examine the effect of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro. Permeability of ARPE-19 cell monolayers was determined using Fluorescein isothiocyanate (FITC)-labeled dextran. The influence of CQ and HCQ on cell death and the expression tight junction molecules was examined. CQ and HCQ significantly increased ARPE-19 monolayer permeability after 3 and 18 h, respectively, and enhanced mRNA levels for claudin-1 and occludin. Cytotoxicity was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE barrier permeability in vitro, independent of cytotoxicity or loss of zonula occludens-1, claudin-1, and occludin expression. Our findings suggest that CQ/HCQ-induced permeability of the RPE layer may contribute to blood-retinal barr...
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Papers by Jan van Meurs