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Morten la Cour

Publications and source records attributed to Morten la Cour.

At least 19 recordsLinked to original sources
PubMed2007

Surgical induction of choroidal neovascularization in a porcine model.

PURPOSE: To develop a reproducible surgical technique for the induction of choroidal neovascularization (CNV) in the subretinal space of porcine eyes and to analyse the resulting CNV clinically and histologically. METHODS: Two different modifications of a surgical technique previously described were compared with the original method. In ten porcine eyes retinal pigment epithelial (RPE) cells were removed using a silicone tipped cannula, in ten porcine eyes Bruch's membrane was perforated once with a retinal perforator without prior RPE removal and in ten eyes RPE removal was followed by a single perforation of Bruch's membrane. Fifteen of the eyes, five from each group, were enucleated 30 minutes after surgery, while the remaining eyes were enucleated after 14 days. Prior to enucleation, at day 14, fundus photographs and fluorescein angiograms were obtained. Eyes were examined by light microscopy and by immunohistochemical staining. In addition to these 30 eyes, two eyes underwent surgery with the purpose of subsequent scanning electron microscopic (SEM) examination. RESULTS: In eyes enucleated immediately after surgery neuroretinas overlying the induced lesions were intact without apparent atrophy of cells regardless of the surgical technique applied. The process of RPE removal was found to induce breaks in Bruch's membrane and both the size and the number of breaks varied between eyes. CNV membranes were identified in 15 of 15 eyes enucleated after 14 days. CNV membranes induced by perforation of Bruch's membrane without prior RPE removal were significantly thicker than membranes from eyes undergoing both RPE removal and Bruch's perforation (p = 0.03) and also thicker than membranes from eyes with only RPE-removal (p < 0.01). CNV membranes from eyes with perforation of Bruch's membrane without prior RPE removal had a higher cellular content and were more richly vascularized and also exhibited the highest propensity to leak in fluorescense angiograms. CONCLUSION: All three surgical techniques were capable of inducing CNV, but the one applying perforation of Bruch's membrane without RPE removal was easier to reproduce and involved fewer variables than the techniques utilizing RPE removal. The presence of RPE cells seems to affect both the morphology and cellular composition of induced CNV.

Animals↗
PubMed2007

Subretinal posterior pole injury induces selective proliferation of RPE cells in the periphery in in vivo studies in pigs.

PURPOSE: To study topographical differences in porcine retinal pigment epithelial (RPE) cell proliferation (1) in vivo, after experimental central surgical subretinal injury, and (2) in vitro. METHODS: Domestic pigs underwent either experimental RPE debridement (n = 5), subretinal amniotic membrane transplantation (n= 4), or both (n= 1) in the left eye. RPE cell proliferation was assayed by injection of the thymidine analogue 5-bromodeoxyuridine (5-BrdU) at postoperative day 0 and 1. RPE cells in S-phase were identified by their incorporation of 5-BrdU, as detected by immunohistochemistry. The in vitro proliferation of primary RPE isolates from the peripheral and central retina was assayed by a colorimetric assay and by [(3)H]thymidine incorporation. RESULTS: After subretinal surgery, in vivo incorporation of 5-BrdU was seen in peripheral RPE cells in 8 of 10 surgically treated eyes, but never in central RPE cells. This observation was true of both types of experimental surgery performed. In vitro, RPE isolates from the pre-equatorial region consistently yielded higher cell densities than did RPE cell isolates from more central parts of the epithelium. This was apparent through the three first passages of porcine RPE cells in culture. After 1 and 4 days in culture, pre-equatorial RPE cells had incorporated significantly more [(3)H]thymidine than had the more central RPE cells. CONCLUSIONS: Experimental subretinal surgical injury of the RPE below the central retina is followed within 48 hours by a peripheral, but not a central, proliferation of RPE cells. In vitro, peripheral RPE cells have a higher proliferative capacity than do central RPE cells.

Amnion↗
PubMed2006

An isotonic preparation of 1 mg/ml indocyanine green is not toxic to hyperconfluent ARPE19 cells, even after prolonged exposure.

PURPOSE: To investigate the in vitro toxicity of indocyanine green and infracyanine green (ICG) to cultured ARPE19 cells, in particular with respect to the concentration and time dependence of this toxicity. METHODS: ARPE19 cells were grown for at least 1 week past confluence (hyperconfluent cells) before being subjected to challenge with ICG. Cell survival was tested with the MTT assay. RESULTS: When applied in isotonic solutions, ICG in all concentrations (below 5 mg/ml) and at all exposure times tested (2 mins-2 hours) was found not to affect the survival of ARPE19 cells. ARPE19 cultures older than 30 days were more resistant to a 5 mg/ml hypotonic ICG solution than younger cultures. CONCLUSION: When toxicity of ICG was tested in hyperconfluent ARPE19 cultures, these cells were found to be more resistant to the dye than has been previously reported for more immature ARPE19 cells.

Cell Line↗
PubMed2006

Optic nerve pH and PO2: the effects of carbonic anhydrase inhibition, and metabolic and respiratory acidosis.

PURPOSE: Earlier studies have demonstrated that carbonic anhydrase inhibitors (CAIs) increase optic nerve oxygen tension (ONPO(2)) in pigs. We hypothesized that the mechanism of this effect was either a CO(2) increase or a pH decrease in tissue and blood. To test this hypothesis we investigated and compared how optic nerve pH (ONpH) and ONPO(2) are affected by: (1) carbonic anhydrase inhibition; (2) respiratory acidosis, and (3) metabolic acidosis. We measured ONpH with a glass pH electrode and ONPO(2) with a polarographic oxygen electrode. One of the electrodes was placed in the vitreous cavity 0.5 mm over the optic nerve in the eyes of domestic pigs. METHODS: We measured ONpH during carbonic anhydrase inhibition and ONpH or ONPO(2) during NH(4)Cl-induced metabolic acidosis and during CO(2) breathing (respiratory acidosis). RESULTS: Baseline ONpH was 0.12 +/- 0.06 lower than arterial pH (mean +/- SD, n = 10, p < 0.001). Optic nerve pH decreased with arterial pH during carbonic anhydrase inhibition, metabolic and respiratory acidosis. Optic nerve oxygen tension was not affected by metabolic acidosis but increased during CO(2) breathing, as it has been shown to do during carbonic anhydrase inhibition. CONCLUSIONS: There is a close correlation between arterial blood pH and intraocular pH. Isolated ONpH changes do not affect ONPO(2), thus the ONPO(2) increase seen with carbonic anhydrase inhibition is probably not only due to pH changes in the blood and optic nerve. Accumulation of CO(2), either alone or in combination with a pH change, is likely to cause the ONPO(2) increase, but a direct vascular effect should also be considered.

Acidosis, Respiratory↗
PubMed2006

Longterm incidence of rhegmatogenous retinal detachment and survival in a defined population undergoing standardized phacoemulsification surgery.

PURPOSE: To determine the longterm risk of pseudophakic retinal detachment (PRD) in a defined population undergoing standardized phacoemulsification surgery at a single centre. DESIGN: We carried out a register-based, retrospective, consecutive, uncontrolled study. All 6352 eyes that underwent cataract surgery at our institution during the years 1996-1998 were included in the study. The main outcome measure was the incidence of surgery for PRD. METHODS: Cataract-operated eyes were identified by a search in the local hospital registry. Eyes that subsequently underwent surgery for PRD were identified by a search in the Danish Patients Registry (LPR). Follow-up ended by 31 December 2003. Eyes in patients who died before that date were censored. RESULTS: The 8-year cumulated incidence of PRD after phacoemulsification was 0.93 per eye (95% CI 0.65-1.33). This is 8.77 (95% CI 7.12-10.72) times higher than expected in eyes that do not undergo cataract surgery. The incidence rate for retinal detachment was significantly higher in pseudophakic eyes than in the background population for at least 6 years after surgery. Patient mortality was slightly increased for men, but no different for women from that of the background population. CONCLUSION: For eyes undergoing phacoemulsification surgery, the cumulated incidence of PRD continues to increase for at least 8 years after surgery. Comparison of the cumulated incidence of PRD between different studies requires equal lengths of follow-up.

Adolescent↗
PubMed2005

[Treatment of neovascular age-related macular degeneration with intravitreal vascular endothelial growth factor inhibitor--secondary publication].

Subfoveal neovascularization is the most frequent cause of severe visual loss in patients with age-related macular degeneration (AMD). Pharmacologic inhibition of vascular endothelial growth factor (VEGF) is a new principle of treatment of this condition. The effects of intravitreal pegaptanib administered every sixth week for 48 weeks in three different dosages were examined in a prospective, double-masked, randomised trial against subconjunctival sham injection with change in visual acuity as the outcome parameter in 1,186 patients with subfoveal neovacularization in AMD. 70% of the patients treated with pegaptanib avoided moderate visual loss, compared to only 55% of the control group (p < 0.001 for 0.3 mg pegaptanib versus the control group, p < 0.001 for 1.0 mg and p = 0,03 for 3.0 mg). The improved visual prognosis was detectable beginning six weeks after the first injection (p < 0.002). Adverse events included endophthalmitis (1.3% of patients), traumatic lens damage (0.7%), retinal detachment (0.6%) and severe visual loss in one patient (0.1%). Intravitreal pegaptanib improves the visual prognosis in neovascular AMD. The long-term effect and safety of the treatment are not known.

Aged↗
PubMed2005

Correlation between clinical and histological features in a pig model of choroidal neovascularization.

PURPOSE: To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features. METHODS: CNV was induced by surgical removal of the retinal pigment epithelium (RPE) and perforation of Bruch's membrane in four pig eyes. In addition, two eyes had an amniotic membrane implanted in the subretinal space. Retinal landmarks such as arterioles, crossing of vessels and the optic nerve were used to obtain an exact mapping of histological findings on colour fundus photographs (FPs) and fluorescein angiograms (FAs). We analysed the appearance on the FPs and FAs of the following histological features: CNV, hypo/hyperpigmented RPE, and pathological changes to the retina and choroid. RESULTS: CNV was found in all eyes and correlated to areas with late staining but no leakage in the FAs. Areas of hypopigmented RPE were identified and corresponded to window defects in the FAs. Where fibrovascular tissue was covered with hyperpigmented RPE, blocked fluorescence was found on the FAs. The implanted amniotic membrane showed staining but no leakage in the FAs. CONCLUSION: In a pig model of surgically induced CNV, histological mapping was used to make clinicopathological correlations of the following lesion components: CNV, window defects, blocked fluorescence. Our findings give a more solid foundation for interpretation of fluorescein angiograms in pig models.

Amnion↗
PubMed2005

Age-related maculopathy: a risk indicator for poorer survival in women: the Copenhagen City Eye Study.

PURPOSE: To examine patient survival in age-related maculopathy in a 14-year follow-up study. DESIGN: Population-based 14-year cohort study. PARTICIPANTS: Nine hundred forty-six residents, aged 60 to 80 years, living in the Osterbro district of Copenhagen, Denmark, participated in the first examination conducted from 1986 to 1988. These participants were followed until death or until May 1, 2002, whichever came first. METHODS: Participants underwent an extensive ophthalmologic examination at Rigshospitalet, the National University Hospital of Copenhagen. Standardized protocols for physical examination, blood samples, and data from the National Central Person Register, the National Death Register, and the National Patient Register were used. MAIN OUTCOME MEASURES: Mortality and age-related maculopathy. RESULTS: By May 1, 2002, 60.9% (577 of 946) of the participants of the baseline study cohort had died. The adjusted 14-year cumulative mortality hazard ratio for subjects with early and late age-related maculopathy at baseline was 1.26 (95% confidence interval [CI], 1.06-1.51). We identified a strong correlation between mortality and age-related maculopathy among women (relative risk, 1.59; 95% CI, 1.23-2.07) but not among men. CONCLUSIONS: When adjusting for survival-related factors, age-related maculopathy is a significant risk indicator for poorer survival in women and may be a marker of underlying serious systemic factors or aging processes specific to women.

Aged↗
PubMed2005

14-year incidence, progression, and visual morbidity of age-related maculopathy: the Copenhagen City Eye Study.

PURPOSE: To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss. DESIGN: Population-based cohort study. PARTICIPANTS: Nine hundred forty-six residents (age range, 60-80 years) of Copenhagen participated in the study from 1986 through 1988. Excluding participants who had died since baseline, 359 persons (97.3% of survivors) were reexamined from 2000 through 2002. METHODS: Participants underwent extensive ophthalmologic examinations. Age-related maculopathy lesions were determined by grading color fundus photographs from the examinations using a modified Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence of drusen type and size, pigmentary abnormalities, pure geographic atrophy, exudative ARM, visual impairment, and blindness. RESULTS: The 14-year incidences of early and late ARM were 31.5% and 14.8%, respectively. Individuals 75 to 80 years of age at baseline had significantly (P< or =0.05) higher 14-year incidences of the following lesions than those aged 60 to 64 years: medium or large drusen (> or =125 microm; 34.2% vs. 12.8%, respectively), soft drusen (45.2% vs. 21.4%), pigmentary abnormalities (31.4% vs. 17.0%), pure geographic atrophy (17.4% vs. 1.0%), and exudative ARM (23.3% vs. 5.7%). Severe drusen type, large drusen, and retinal pigmentary abnormalities at baseline were important predictors of incident late ARM. The 14-year incidences of visual impairment (<20/40 but >20/200) or legal blindness from late ARM were 6.0% and 3.4%, respectively. Late ARM caused 35.7% of all visual impairment and 66.7% of all blindness. CONCLUSIONS: There is a high incidence of ARM lesions in this elderly white population. Severe drusen type and size or a combination of drusen and pigmentary abnormalities significantly increases the risk of developing late ARM, the most frequent cause of legal blindness in this population.

Aged↗
PubMed2005

Pharmacokinetics of intravitreal 5-fluorouracil prodrugs in silicone oil: experimental studies in pigs.

PURPOSE: To examine the in vivo pharmacokinetics of intravitreal 5-Fluorouracil (5-FU) following tamponade with 5-FU prodrug silicone oil formulations. METHOD: Two different alkoxycarbonyl 5-FU prodrugs denoted C12 and C18 were synthesized and formulated as silicone oil suspensions. A total of 26 pigs underwent conventional three-port lens-sparing pars plana vitrectomy. Approximately 1.6 ml of the prodrug-silicone oil formulation was placed in the vitreous cavity. Operated eyes were enucleated between 20 min and 168 hours postoperatively, and analysed for their content of free 5-FU by high performance liquid chromatography. RESULTS: With the C12 prodrug silicone oil formulation, the concentration of free 5-FU in the vitreous water phase 1 hour after surgery was 3.30 +/- 1.62 microg/ml. After 4 hours this concentration had declined to 1 microg/ml. With the C18 prodrug, the concentration of free vitreal 5-FU never reached 1 microg/ml during the 7 days these experiments lasted. A mathematical model is presented that can explain the measured data if the clearance of 5-FU from the vitreous water phase follows first order kinetics with a half-life of 20 min. CONCLUSION: These experiments, and the model analysis, suggest that the elimination half-life of 5-FU in the vitreous cavity of a vitrectomized, silicone oil-filled eye is very fast. The model analysis indicates that an alkoxycarbonyl 5-FU prodrug with a specific release rate constant of 10.7 microg/square root h cm(2) can maintain an intravitreal 5-FU concentration above 1 microg/ml for 5 days in the porcine eye.

Animals↗
PubMed2005

Risk factors for age-related maculopathy in a 14-year follow-up study: the Copenhagen City Eye Study.

PURPOSE: To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM). DESIGN: Population-based cohort study. PARTICIPANTS: At baseline, 946 volunteers participated in the study during 1986--88. These subjects were between 60 and 80 years of age and lived in the Østerbro district of Copenhagen. Excluding participants who had died since baseline, 359 subjects (97.3% of survivors) were re-examined 14 years later, during 2000--2002. A total of 31.8% (301/946) of the original material was included in the risk factor analyses. METHODS: Participants underwent an ophthalmological examination at Rigshospitalet, the National University Hospital of Copenhagen. Similar standardized protocols for physical examination were used at the baseline and follow-up examinations. Age-related maculopathy lesions were determined by the same grader grading colour fundus photographs from both examinations using a modification of the Wisconsin Age-related Maculopathy Grading System protocol. RESULTS: Of the 359 participants, 94 had incident early ARM and 52 had incident late ARM at follow-up in either eye. In logistic regression, the risk factors for early ARM or worse were as follows: cataract (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.2-6.2); family history of ARM (OR 4.5, 95% CI 1.3--15.5), and alcohol consumption >250 g/week (OR 4.6, 95% CI 1.1-19.2). High levels of apolipoprotein B (>100 mg/l) decreased the risk of development of early ARM or worse (OR 0.4, 95% CI 0.2-0.8), while high levels of apolipoprotein A1 (>or= 150 mg/l) increased the risk of late ARM (OR 2.5, 95% CI 1.2-5.3). Advanced age at baseline was also associated with the incidence of late ARM (OR 2.0, 95% CI 1.4-2.9). CONCLUSIONS: These findings indicate a direct correlation between age, cataract, family history, alcohol consumption, the apolipoproteins A1 and B and the 14-year incidence of ARM.

Age Distribution↗
PubMed2005

Nordic research in ophthalmology.

Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.

Animals↗
PubMed2005

A new animal model of choroidal neovascularization.

PURPOSE: The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig. METHODS: A total of 26 Danish landrace pigs was used. A sample of 22 eyes in 12 pigs underwent retinal photocoagulation with a xenon lamp, six eyes in four pigs underwent retinal photocoagulation with a diode laser, and mechanical rupture of Bruch's membrane (BM) was induced in 12 pigs following surgical debridement of the retinal pigment epithelium without damage to the neuroretina. RESULTS: All 12 pigs (100%) in the group with mechanical rupture of BM developed CNV. The induced membranes were morphologically similar to CNV membranes in humans. Induced CNV was found in 13 of 22 (54%) xenon lamp-treated animals and in five of six (83%) diode laser-treated animals. The CNV in these groups was small and the morphology of the induced lesions was dominated by retinal gliosis and retinal neovascularization, probably due to a marked destruction of the neuroretina. CONCLUSIONS: Surgical debridement of the retinal pigment epithelium followed by mechanical rupture of BM is a reproducible method of producing CNV in the domestic pig, whereas photocoagulation gives rise to glially derived subretinal fibrovascular membranes and primarily retinal neovascularization.

Animals↗
PubMed2005

Clinical characteristics of subretinal deposits in central serous chorioretinopathy.

PURPOSE: To describe abnormal subretinal material in central serous chorioretinopathy (CSC). DESIGN: Retrospective observational case series. PARTICIPANTS: 168 consecutive patients (336 eyes) with a definite diagnosis of serous foveal detachment attributable to CSC in one or both eyes, on one or more occasions. METHODS: Review of all cases seen during a six-year period. Grading of the amount of subretinal material at presentation as absent, questionable, mild, moderate or severe. RESULTS: Of 168 patients with CSC, 133 (79%) were men and 35 (21%) women. The median age was 45.2 years (range 22-70 yrs). The median duration of symptoms was 2 months (range 0.1-144 months). Subretinal material was found in the symptomatic eye or, in bilateral cases, in the eye that had most recently become symptomatic in 138 patients and in increasing amounts with increasing duration of symptoms (p < 0.001) but unrelated to age or sex. A substantial fraction of the material was shown by optical coherence tomography to be attached to the photoreceptor outer segments of the detached retina. CONCLUSIONS: Increasing amounts of subretinal material are found with increasing duration of symptoms in eyes with CSC. This suggests that early granular deposits may be composed of fragments of photoreceptor outer segments that accumulate when the phagocytosis photoreceptor outer segment material is disrupted by the serous detachment of the retina. Other possible origins that cannot be excluded include plasma proteins excluding from the choriocapillaris, inflammatory debris, and lipid exudate originating from occult choroidal neovascularization secondary to CSC.

Adult↗
PubMed2004

Optic nerve oxygenation.

The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen tension. Lowering the intraocular pressure tends to increase the optic nerve oxygen tension, even though this effect may be masked by the autoregulation when the optic nerve oxygen tension and perfusion pressure is in the normal range. Carbonic anhydrase inhibitors increase the optic nerve oxygen tension through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by the cyclo-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical trials and needed to test this hypotheses.

Animals↗
PubMed2004

Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels.

BACKGROUND: Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain and probably also in the optic nerve and retina. Additionally they elevate the oxygen tension in the optic nerve in the pig. We propose that they also raise the oxygen tension in the retina. We studied the oxygen tension in the pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied. METHODS: A polarographic oxygen electrode was placed transvitreally immediately over the retina or the optic disc in anaesthetised pigs. The oxygen tension was recorded continually and 500 mg dorzolamide was injected intravenously. Retinal vessel diameters were analysed from monochromatic fundus photographs taken before and after injection of dorzolamide. RESULTS: Baseline retinal oxygen tension (RPO2) was 3.34+/-0.50 kPa (mean +/- SD, n=6) and baseline optic nerve oxygen tension (ONPO2) was 3.63+/-1.00 kPa. RPO2 was increased by 0.36+/-0.11 kPa (n=6, P=0.025) and ONPO2 by 0.73+/-0.34 kPa (n=6, P=0.003) 30 min after dorzolamide administration. The retinal arterioles was significantly dilated by 13+/-7% (n=5, P=0.016) and the retinal venules by 12+/-8% (n=5, P=0.030) 30 min after injection of dorzolamide. CONCLUSION: Retinal and optic nerve oxygen tension increased with systemic administration of dorzolamide. The retinal vessels dilated, probably causing increased blood flow inducing the observed increase in RPO2. The increased oxygenation of retina by CAI may offer therapeutic possibilities in ischaemic diseases of the retina and optic nerve.

Animals↗