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1.
Eye (Lond) ; 32(2): 163, 2018 02.
Article in English | MEDLINE | ID: mdl-29417938
2.
Eye (Lond) ; 32(2): 213-221, 2018 02.
Article in English | MEDLINE | ID: mdl-29350687

ABSTRACT

For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli's principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli's equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), then the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli's effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment.


Subject(s)
Models, Theoretical , Retinal Detachment/surgery , Retinal Perforations/surgery , Rheology , Scleral Buckling/methods , Finite Element Analysis , Humans , Retinal Detachment/physiopathology , Retinal Perforations/physiopathology , Visual Acuity
3.
Eye (Lond) ; 32(2): 210-212, 2018 02.
Article in English | MEDLINE | ID: mdl-29350688

ABSTRACT

The purpose is to use laws of physics to elucidate the mechanisms behind capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of pericytes weakens capillary walls and the vessel dilates. A dilated capillary has reduced resistance to flow, therefore increased flow in that vessel and decreased in adjoining capillaries. A preferential shunt vessel is thus formed from the dilated capillary and the adjacent capillaries become non-perfused. We apply the laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead to capillary non-perfusion. These laws of physics can give a foundation for physical or mathematical models to further elucidate this field of study. The law of Laplace predicts that a weaker vessel wall will dilate, assuming constant transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de Waele relationship for viscosity predict that a dilated vessel will receive a higher portion of the fluid flow than the adjoining capillaries. Viscosity will decrease in the dilated vessel, furthering the imbalance and resulting in a patch of non-perfused capillaries next to the dilated 'preferential' shunt vessel. Physical principles support or inspire novel hypotheses to explain poorly understood phenomena in ophthalmology. This thesis of pericyte death and capillary remodelling, which was first proposed by Cogan and Kuwabara, already agrees with histological and angiographical observations in diabetic retinopathy. We have shown that it is also supported by classical laws of physics.


Subject(s)
Capillaries/physiology , Diabetic Retinopathy/physiopathology , Physics , Retinal Vessels/physiology , Humans , Microaneurysm/physiopathology , Models, Theoretical
4.
Br J Ophthalmol ; 100(5): 683-7, 2016 May.
Article in English | MEDLINE | ID: mdl-26377413

ABSTRACT

OBJECTIVE: To validate a mathematical algorithm that calculates risk of diabetic retinopathy progression in a diabetic population with UK staging (R0-3; M1) of diabetic retinopathy. To establish the utility of the algorithm to reduce screening frequency in this cohort, while maintaining safety standards. RESEARCH DESIGN AND METHODS: The cohort of 9690 diabetic individuals in England, followed for 2 years. The algorithms calculated individual risk for development of preproliferative retinopathy (R2), active proliferative retinopathy (R3A) and diabetic maculopathy (M1) based on clinical data. Screening intervals were determined such that the increase in risk of developing certain stages of retinopathy between screenings was the same for all patients and identical to mean risk in fixed annual screening. Receiver operating characteristic curves were drawn and area under the curve calculated to estimate the prediction capability. RESULTS: The algorithm predicts the occurrence of the given diabetic retinopathy stages with area under the curve =80% for patients with type II diabetes (CI 0.78 to 0.81). Of the cohort 64% is at less than 5% risk of progression to R2, R3A or M1 within 2 years. By applying a 2 year ceiling to the screening interval, patients with type II diabetes are screened on average every 20 months, which is a 40% reduction in frequency compared with annual screening. CONCLUSIONS: The algorithm reliably identifies patients at high risk of developing advanced stages of diabetic retinopathy, including preproliferative R2, active proliferative R3A and maculopathy M1. Majority of patients have less than 5% risk of progression between stages within a year and a small high-risk group is identified. Screening visit frequency and presumably costs in a diabetic retinopathy screening system can be reduced by 40% by using a 2 year ceiling. Individualised risk assessment with 2 year ceiling on screening intervals may be a pragmatic next step in diabetic retinopathy screening in UK, in that safety is maximised and cost reduced by about 40%.


Subject(s)
Diabetic Retinopathy/diagnosis , Health Care Costs , Mass Screening/economics , Algorithms , Area Under Curve , Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/economics , Disease Progression , England/epidemiology , False Positive Reactions , Female , Humans , Male , Mathematics , Predictive Value of Tests , ROC Curve , Risk Assessment , Time Factors
5.
Diabetologia ; 54(10): 2525-32, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21792613

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world.


Subject(s)
Diabetic Retinopathy/diagnosis , Mass Screening , Models, Theoretical , Risk Assessment/methods , Algorithms , Diabetic Retinopathy/epidemiology , Female , Humans , Male
6.
Br J Ophthalmol ; 93(8): 1064-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19416932

ABSTRACT

AIMS: To examine whether the addition of dorzolamide to timolol monotherapy influences oxygen saturation in the human retina. METHODS: Non-invasive spectrophotometric retinal oximetry was used to measure oxygen saturation in retinal vessels. Twenty patients with open-angle glaucoma (11) and ocular hypertension (9) were recruited. The patients were randomised into receiving timolol monotherapy or dorzolamide-timolol combination for an 8-month test period, followed by a second test period, before which the patients switched treatments. Oximetry measurements were performed at 2-month intervals during each period. Of the 20 patients, 13 followed the study protocol into the second test period, and 10 managed all study visits. RESULTS: The oxygen saturation in retinal vessels was stable within the test periods. The mean arteriolar saturation was 96 (2)% (mean (SD)) during timolol monotherapy and 97 (2)% during dorzolamide-timolol combination therapy (p = 0.17, all patients pooled, n = 13). Corresponding values in venules were 66 (5)% during timolol monotherapy and 65 (6)% during dorzolamide-timolol therapy (p = 0.13). Patients who started on dorzolamide-timolol combination showed a significant reduction in arteriolar (98 (2)% to 95 (2)%, p<0.01) and venular saturation (69 (5)% to 66 (6)%, p<0.05) when changing to timolol monotherapy. CONCLUSION: Adding dorzolamide to timolol monotherapy has a minimal effect, but going from dorzolamide-timolol combination to timolol alone lowered arteriolar and venular oxygen saturation. The retinal oxygen saturation measurements show a high degree of stability over an extended period of time. Previous studies have suggested increased retinal and optic nerve blood flow with dorzolamide. Unchanged oxygen saturation and increased blood flow would indicate increased oxygen delivery to the retina.


Subject(s)
Antihypertensive Agents/pharmacology , Ocular Hypertension/blood , Oxygen/blood , Retinal Vessels/metabolism , Sulfonamides/pharmacology , Thiophenes/pharmacology , Timolol/pharmacology , Adolescent , Adult , Aged , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Double-Blind Method , Drug Combinations , Female , Glaucoma, Open-Angle/blood , Glaucoma, Open-Angle/drug therapy , Humans , Intraocular Pressure/drug effects , Male , Middle Aged , Ocular Hypertension/drug therapy , Oximetry/methods , Sulfonamides/therapeutic use , Thiophenes/therapeutic use , Timolol/therapeutic use , Young Adult
7.
Pharmazie ; 63(3): 171-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18444504

ABSTRACT

Drug delivery to the posterior segment of the eye is important for potentially treating various disorders in retina, choroid, vitreous humor and optic nerve. Due to anatomic membrane barriers and the lacrimal drainage it can be quite challenging to obtain therapeutic drug concentrations in the posterior parts of the eye after topical drug administration. Since the membrane barriers cannot be altered with non-invasive methods invasive methods such as direct drug injection into the vitreous humor and subconjunctival, subtenons capsule or suprascleral injections are gaining popularity. However, invasive methods can cause discomfort for the patient and can also lead to complications that are even more serious than the disease being treated. Alternatively, novel ophthalmic formulations can be developed that specifically target topical drug delivery to the posterior segment of the eye. Anatomical and physiological barriers in the eye are reviewed as well as the theoretical model of passive drug diffusion from the eye surface into the eye. It is shown that enhanced drug delivery through conjunctiva/sclera to retina can be obtained by formulating lipophilic drugs as hydrophilic drug/cyclodextrin complex solutions. Optimization of the delivery system by formulating the drug as a low-viscosity aqueous drug/cyclodextrin complex suspension results in sustained high concentrations of dissolved drug in the tear fluid which further increases the targeted drug delivery to the posterior segment.


Subject(s)
Drug Delivery Systems , Eye/anatomy & histology , Ocular Physiological Phenomena , Administration, Topical , Animals , Excipients , Humans , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/metabolism
8.
Br J Ophthalmol ; 92(4): 500-4, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18369067

ABSTRACT

AIMS: To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG). METHODS: Fifteen patients with OAG were evaluated in a randomised, cross-over, double-blind study. They were treated with either brinzolamide or dorzolamide for 3 months and then crossed-over after a 4-week washout period. They were given timolol during a 4-week run-in period and during washout. The following were performed after run-in, after washout and after each treatment period: adverse events check, measurement of visual acuity, contrast sensitivity, blood pressure, heart rate, and intraocular pressure, and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry (HRF) and colour Doppler imaging (CDI). Retinal oxygenation levels were determined using a non-invasive measurement of haemoglobin oxygen saturation by digital photographic fundus oximetry. RESULTS: Both brinzolamide and dorzolamide reduced the number of zero-flow pixels in the retina as measured by HRF, suggesting an increase in retinal blood flow (-6.86 and -0.452 respectively) with brinzolamide treatment resulting in fewer zero-flow pixels than dorzolamide (-6.41) (p = 0.024). Both brinzolamide and dorzolamide increased oxygen saturation in the retina as measured by photographic retinal oximetry in the superior (0.82 (p = 0.002) and 0.87 (p = 0.005)) and inferior (0.88 (p = 0.035) and 0.82 (p = 0.002)) retinal veins. No significant changes were found in CDI measurements of the retrobulbar blood supply during either treatment. CONCLUSION: This pilot study suggests that brinzolamide and dorzolamide may increase retinal oxygen saturation in patients with OAG.


Subject(s)
Antihypertensive Agents/pharmacology , Glaucoma, Open-Angle/physiopathology , Oxygen/blood , Retinal Vessels/drug effects , Sulfonamides/pharmacology , Thiazines/pharmacology , Thiophenes/pharmacology , Aged , Blood Pressure/drug effects , Carbonic Anhydrase Inhibitors/pharmacology , Contrast Sensitivity/drug effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Intraocular Pressure/drug effects , Laser-Doppler Flowmetry , Male , Microcirculation/drug effects , Middle Aged , Pilot Projects , Retinal Vessels/physiopathology , Visual Acuity/drug effects
9.
Article in English | MEDLINE | ID: mdl-19163943

ABSTRACT

The aim of this paper is to develop an automatic method for the registration of multitemporal digital images of the fundus of the human retina. The images are acquired from the same patient at different times by a color fundus camera. The proposed approach is based on the application of global optimization techniques to previously extracted maps of curvilinear structures in the images to be registered (such structures being represented by the vessels in the human retina): in particular, a genetic algorithm is used, in order to estimate the optimum transformation between the input and the base image. The algorithm is tested on two different types of data, gray scale and color images, and for both types, images with small changes and with large changes are used. The comparison between the registered images using the implemented method and a manual one points out that the proposed algorithm provides an accurate registration. The convergence to a solution is not possible only when dealing with images taken from very different view-points.


Subject(s)
Artificial Intelligence , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Pattern Recognition, Automated/methods , Retinal Vessels/anatomy & histology , Retinoscopy/methods , Subtraction Technique , Algorithms , Colorimetry/methods , Humans , Reproducibility of Results , Sensitivity and Specificity
10.
Br J Ophthalmol ; 92(1): 126-30, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17965100

ABSTRACT

AIMS: We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO2), as indomethacin previously has demonstrated a strong decreasing effect on ONPO2. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect of dorzolamide on ONPO2. METHODS: ONPO2 was measured 0.5 mm above the optic disc in 23 domestic pigs (26-36 kg) with a polarographic oxygen-sensitive electrode. One of the following NSAIDs was administered intravenously as increasing doses or as one large dose: indomethacin, ibuprofen, diclofenac, ketoprofen, parecyclo-oxygenase-2 inhibitor and lornoxicam. Indomethacin was both tested alone and after preceding administration of the other NSAIDs. Dorzolamide was also tested after preceding administration of NSAIDs different from indomethacin. RESULTS: Indomethacin decreased ONPO2 significantly in a dose-dependent manner. None of the other NSAIDs produced any effect on the ONPO2 (p>>0.05; n = 17). No difference was found between the effect of indomethacin injected alone, and after preceding administration of the other NSAIDs. Intravenous dorzolamide (500 mg) increased ONPO2 by 32 (7)% (n = 7; p<0.001) after preceding administration of several NSAIDs different from indomethacin. CONCLUSIONS: Indomethacin decreased ONPO2, while the other NSAIDs showed no effect on ONPO2, and they did not affect the effect of indomethacin. The hypoxic effect of indomethacin must be due to another mechanism than cyclo-oxygenase inhibition. The effect of dorzolamide on ONPO2 is not related to prostaglandin production.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Indomethacin/pharmacology , Optic Nerve/blood supply , Oxygen/blood , Animals , Carbon Dioxide/blood , Dose-Response Relationship, Drug , Hydrogen-Ion Concentration/drug effects , Optic Nerve/drug effects , Partial Pressure , Sus scrofa
11.
Br J Ophthalmol ; 91(12): 1599-601, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17627978

ABSTRACT

AIMS: To evaluate the safety of every-other-year eye screening for patients with diabetes without retinopathy. METHODS: Since 1994, patients with diabetes without retinopathy in Iceland have received eye screening every other year. 296 patients with diabetes who had no diabetic retinopathy in 1994/95 were followed with biennial eye examinations until they had developed retinopathy. The 10-year experience of this approach is reviewed. RESULTS: Out of the 296 diabetic individuals, 172 did not develop diabetic retinopathy during the 10-year observation period. 96 patients developed mild non-proliferative retinopathy, six developed clinically significant diabetic macular oedema, 23 developed preproliferative retinopathy, and four developed proliferative diabetic retinopathy during the 10-year observation period. All the patients who developed macular oedema or proliferative retinopathy had already been diagnosed as having mild nonproliferative retinopathy and entered an annual screening protocol before the sight-threatening retinopathy developed. No patient had any undue delay in treatment. CONCLUSION: Every other year screening for diabetic eye disease seems to be safe and effective in diabetics without retinopathy. Such an approach will reduce the number of screening visits more than 25%. This reduces health costs and strain on resources considerably and relieves the patients with diabetes from unnecessary clinic visits and examinations.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetic Retinopathy/diagnosis , Mass Screening , Adolescent , Adult , Aged , Aged, 80 and over , Cost Control , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/physiopathology , Female , Health Care Costs , Humans , Incidence , Macular Edema/diagnosis , Macular Edema/epidemiology , Male , Middle Aged , Time Factors , Visual Acuity
13.
Acta Ophthalmol Scand ; 83(3): 333-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15948787

ABSTRACT

PURPOSE: To study time patterns in bilateral exudative age-related macular degeneration (AMD) and the pattern of drusen before and after the onset of exudative AMD. MATERIAL AND METHODS: Out of 2220 individuals in the Icelandic genetic study of AMD, 151 had bilateral exudative AMD. We searched for previous records in the Icelandic University Retina Unit. For the 65 patients with a fluorescein angiography record of both eyes, we established the time between the onset of disease in each eye. For the 53 patients with colour fundus photographs of the latter eye taken prior to the occurrence of exudative disease, we graded the drusen before and after the onset of exudative AMD in the second eye. RESULTS: The time interval between the onset of exudative AMD in the first and second eyes was 2.5 years (95% CI: 1.8-3.2; n = 65) and the median was 1.8 years. In 82% of cases the second eye was affected within 4 years. Soft drusen in the macula were found in 95% of eyes that later developed exudative disease (n = 53). Soft and hard drusen decreased in number in the central macula following the development of exudative disease. CONCLUSIONS: Bilateral exudative AMD develops within a few years in both eyes. Drusen are less visible following the onset of exudative AMD in the second eye.


Subject(s)
Macular Degeneration/etiology , Aged , Aged, 80 and over , Exudates and Transudates , Fluorescein Angiography , Functional Laterality , Humans , Macular Degeneration/diagnosis , Middle Aged , Retinal Drusen/diagnosis , Retinal Drusen/etiology , Time Factors
14.
Br J Ophthalmol ; 88(8): 1088-91, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15258031

ABSTRACT

BACKGROUND/AIMS: Prostaglandins are important in blood flow regulation. Carbon dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in the pig. METHODS: Optic nerve oxygen tension was measured in 11 pigs with a polarographic oxygen electrode. The tip of the electrode was placed 0.5 mm above the optic disc. The effects of indomethacin, CO(2) breathing (3%) before and after indomethacin treatment, and carbonic anhydrase inhibition with or without indomethacin treatment were investigated. RESULTS: Administration of 300 mg indomethacin decreased optic nerve oxygen tension significantly. Carbonic anhydrase inhibition and CO(2) breathing increased ONPO(2) significantly. After indomethacin had been given, the rise in ONPO(2) caused by CO(2) breathing and carbonic anhydrase inhibition was significantly reduced. CONCLUSION: Systemic administration of indomethacin decreases the optic nerve oxygen tension; this is probably the result of decreased blood flow through vasoconstriction of vessels in the optic nerve. Additionally, indomethacin diminishes the ONPO(2) increasing effect of CO(2) breathing and carbonic anhydrase inhibition, thus affecting the reactivity of vessels in the optic nerve.


Subject(s)
Carbon Dioxide/physiology , Carbonic Anhydrase Inhibitors/metabolism , Cyclooxygenase Inhibitors/pharmacology , Indomethacin/pharmacology , Optic Nerve/drug effects , Oxygen/metabolism , Animals , Optic Nerve/metabolism , Swine
15.
Br J Ophthalmol ; 88(2): 276-9, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14736791

ABSTRACT

BACKGROUND/AIMS: The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta blockers, has a similar effect. In addition, the effect of dorzolamide and timolol in combination was studied. METHODS: Polarographic oxygen electrodes were placed transvitreally over the optic disc in anaesthetised pigs and ONPO(2) was recorded continually. Drugs were administered intravenously either as 100 mg timolol followed by 500 mg dorzolamide (n = 5), 500 mg dorzolamide followed by 100 mg timolol (n = 5), or 100 mg timolol and 500 mg dorzolamide given simultaneously (n = 5). Arterial blood pressure, blood gasses, and heart rate were recorded. RESULTS: ONPO(2) was unaffected by administration of 100 mg timolol as an intravenous injection (n = 5). Administration of 500 mg dorzolamide by itself significantly increased ONPO(2) from 2.96 (SD 0.62) kPa to 3.69 (SD 0.88) kPa (n = 4, p = 0.035). The dorzolamide induced ONPO(2) increase was not significantly different from the ONPO(2) increases were seen when dorzolamide was administered simultaneous with (n = 5) or 35 minutes (n = 5) after 100 mg timolol. CONCLUSION: Systemic administration of timolol does not affect the optic nerve oxygen tension despite its lowering effect on the intraocular pressure. Additionally, timolol does not affect the ONPO(2) increasing effect of dorzolamide.


Subject(s)
Antihypertensive Agents/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Optic Disk/drug effects , Oxygen/blood , Sulfonamides/pharmacology , Thiophenes/pharmacology , Timolol/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Blood Pressure/drug effects , Carbon Dioxide/blood , Drug Interactions , Heart Rate/drug effects , Intraocular Pressure/drug effects , Optic Disk/blood supply , Partial Pressure , Swine
16.
Acta Ophthalmol Scand ; 79(5): 435-40, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11594975

ABSTRACT

The physiologic mechanism of photocoagulation can been seen in the following steps. The physical light energy is absorbed in the melanin of the retinal pigment epithelium. The adjacent photoreceptors are destroyed and are replaced by a glial scar and the oxygen consumption of the outer retina is reduced. Oxygen that normally diffuses from the choriocapillaris into the retina can now diffuse through the laser scars in the photoreceptor layer without being consumed in the mitochondria of the photoreceptors. This oxygen flux reaches the inner retina to relieve inner retinal hypoxia and raise the oxygen tension. As a result, the retinal arteries constrict and the bloodflow decreases. Hypoxia relief reduces production of growth factors such as VEGF and neovascularization is reduced or stopped. Vasoconstriction increases arteriolar resistance, decreases hydrostatic pressure in capillaries and venules and reduces edema formation according to Starling's law. Vitrectomy also improves retinal oxygenation by allowing oxygen and other nutrients to be transported in water currents in the vitreous cavity from well oxygenated to ischemic areas of the retina. Vitrectomy and retinal photocoagulation both improve retinal oxygenation and both reduce diabetic macular edema and retinal neovascularization.


Subject(s)
Diabetic Retinopathy/surgery , Eye/blood supply , Laser Coagulation , Oxygen/metabolism , Retinal Vessels/metabolism , Vitrectomy , Diabetic Retinopathy/complications , Diabetic Retinopathy/metabolism , Humans , Macular Edema/etiology , Macular Edema/metabolism , Macular Edema/prevention & control , Models, Biological , Retinal Neovascularization/etiology , Retinal Neovascularization/metabolism , Retinal Neovascularization/prevention & control , Retinal Vein Occlusion/etiology , Retinal Vein Occlusion/metabolism , Retinal Vein Occlusion/prevention & control , Vitreous Body/metabolism
17.
Br J Ophthalmol ; 85(6): 702-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11371492

ABSTRACT

AIM: To examine the distribution and clinical ophthalmic characteristics of pseudoexfoliation syndrome (pseudoexfoliation) and glaucoma in Icelandic families. METHODS: Icelandic families containing three or more members aged 70 or older with at least one member with pseudoexfoliation were identified. All family members over age 45 were invited to participate. Visual acuity, Goldmann applanation tonometry, gonioscopy, slit lamp examination before and after dilatation, and dilated fundus examination were performed on all available family members. Pertinent data were obtained from medical records, including ophthalmic history and a medical history of cardiovascular disease, cerebrovascular disease, systemic hypertension, and diabetes mellitus. Participants were classified according to affected status for pseudoexfoliation, glaucoma, and age related macular degeneration. RESULTS: Six families were identified who met the criteria for entry into the study. Of 94 family members who were invited to participate 82 were enrolled (87%). Of these 25 (30%) had pseudoexfoliation syndrome, 51 (62%) were unaffected, and six (7%) were suspects. At least one individual with pseudoexfoliation was identified in the second generation of every family. A parent with pseudoexfoliation was identified in all cases either by examination (4/6) or a review of ophthalmic records (2/6). In all cases the mother was the affected parent. The prevalence of glaucoma was significantly greater in the group with pseudoexfoliation (p <0.0001). Although the presence of age related macular degeneration (ARMD) was highly associated with the presence of pseudoexfoliation, the significance was lost after correction for age (p = 0.69). Although the sample size was small, no association between pseudoexfoliation affected status and cardiovascular disease, cerebrovascular disease, systemic hypertension, or diabetes mellitus was found. CONCLUSIONS: Multiple Icelandic families with pseudoexfoliation in two generations were identified. In all cases where determination was possible, transmission to the second generation was through an affected parent. In each case the affected parent was the mother. Pseudoexfoliation was strongly associated with the presence of glaucoma, but was not associated with either ARMD or systemic disease in this study. These data clearly indicate that pseudoexfoliation is a familial condition and although not conclusive, supports the hypothesis that pseudoexfoliation syndrome is genetically inherited.


Subject(s)
Exfoliation Syndrome/genetics , Genetic Predisposition to Disease , Glaucoma, Open-Angle/genetics , Aged , Aged, 80 and over , Cross-Sectional Studies , Exfoliation Syndrome/complications , Female , Glaucoma, Open-Angle/complications , Humans , Iceland , Linear Models , Logistic Models , Macular Degeneration/complications , Macular Degeneration/genetics , Male , Middle Aged , Pedigree , Sample Size , Tonometry, Ocular , Visual Acuity
18.
Int J Pharm ; 212(1): 29-40, 2001 Jan 05.
Article in English | MEDLINE | ID: mdl-11165818

ABSTRACT

The cyclodextrin solubilization of three benzodiazepines, i.e. alprazolam, midazolam and triazolam, was investigated. The cyclodextrin solubilization was enhanced through ring-opening of the benzodiazepine rings and ionization of the ring-open forms. Additional enhancement was obtained through interaction of a water-soluble polymer with the cyclodextrin complexes. The ring-opening was pH-dependent and completely reversible, the ring-open forms dominating at low pH but the ring-closed forms at physiologic pH. The ring-closed forms were rapidly regenerated upon elevation of pH. In freshly collected human serum in vitro at 37 degrees C, the half-life for the first-order rate constant for the ring-closing reaction was estimated to be less than 2 min for both alprazolam and midazolam. Midazolam (17 mg/ml) was solubilized in aqueous pH 4.3 nasal formulation containing 14% (w/v) sulfobutylether beta-cyclodextrin, 0.1% (w/v) hydroxypropyl methylcellulose, preservatives and buffer salts. Six healthy volunteers received 0.06 mg/kg midazolam intranasally and 2 mg intravenously, and blood samples were collected up to 360 min after the administration. Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3+/-5.0 ng/ml at 15+/-2 min. The elimination half-life of midazolam was 2.2+/-0.3 h and the absolute availability was 73+/-7%. All mean values+/-SEM.


Subject(s)
Anti-Anxiety Agents/administration & dosage , Cyclodextrins/administration & dosage , Midazolam/administration & dosage , Administration, Intranasal , Adult , Animals , Chemistry, Pharmaceutical , Female , Humans , Hydrogen-Ion Concentration , Male , Midazolam/pharmacokinetics , Solubility
19.
Pharmazie ; 56(12): 963-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11802661

ABSTRACT

Intranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.


Subject(s)
Cyclodextrins/chemistry , Hypnotics and Sedatives/pharmacokinetics , Midazolam/pharmacokinetics , Administration, Intranasal , Adult , Aerosols , Biological Availability , Excipients , Female , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Indicators and Reagents , Injections, Intravenous , Irritants , Male , Microscopy, Electron, Scanning , Midazolam/administration & dosage , Midazolam/adverse effects
20.
Acta Ophthalmol Scand ; 78(4): 374-85, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10990036

ABSTRACT

Diabetic eye disease remains a major cause of blindness in the world. Laser treatment for proliferative diabetic retinopathy and diabetic macular edema became available more than two decades ago. The outcome of treatment depends on the timing of laser treatment. The laser treatment is optimally delivered when high-risk characteristics have developed in proliferative retinopathy or diabetic macular edema and before this has significantly affected vision. Laser treatment is usually successful if applied during this optimal period whereas the treatment benefit falls sharply if the treatment is applied too late. In order to optimize the timing of laser treatment in diabetic eye disease screening programs have been established. The oldest screening program is 20 years old and several programs have been established during the last decade. In this paper the organisation and methods of screening programs are described including direct and photographic screening. The incidence and prevalence of blindness is much lower in populations where screening for diabetic eye disease has been established compared to diabetic populations without screening. Technical advantages may allow increased efficiency and telescreening. From a public health standpoint screening for diabetic eye disease is one of the most cost effective health procedures available. Diabetic eye disease can be prevented using existing technology and the cost involved is many times less than the cost of diabetic blindness.


Subject(s)
Blindness/diagnosis , Blindness/prevention & control , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/prevention & control , Vision Screening , Blindness/epidemiology , Blindness/etiology , Diabetes Complications , Diabetic Retinopathy/complications , Diabetic Retinopathy/epidemiology , Economics, Medical , Europe/epidemiology , Humans , Incidence , Laser Coagulation , Prevalence , Preventive Medicine/methods , Vision Screening/economics , Vision Screening/methods , Wisconsin/epidemiology
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