Angiotensin AT(1) receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodilatation in normotensive diabetic rats.

AIMS/HYPOTHESIS: The renin angiotensin system is emerging as a potential therapeutic target for diabetic retinopathy. This study examines the effects of angiotensin-converting-enzyme inhibition by captopril and angiotensin AT(1) receptor antagonism using candesartan-cilexetil on retinal blood flow and acetylcholine-stimulated vasodilatation in normotensive diabetic rats. METHODS: Non-diabetic or streptozotocin-induced diabetic rats were treated for 2 weeks with captopril (100 mg/kg/day) or candesartan cilexetil (2 mg/kg/day). Retinal haemodynamics were measured using video fluorescein angiography. Effects of exogenous acetylcholine on retinal haemodynamics were examined following intravitreal injection. Total retinal diacylglycerol was labelled using diacylglycerol kinase, separated by thin-layer chromatography, and quantified using autoradiography. RESULTS: Diabetic rats had prolonged retinal mean circulation time and decreased retinal blood flow compared with non-diabetic rats. Treatment of diabetic rats with either captopril or candesartan blocked the development of these blood flow abnormalities. Intravitreal injection of acetylcholine (10(-5) mol/l) in non-diabetic rats increased retinal blood flow by 53.9+/-22.0% relative to baseline whereas this response to acetylcholine was blunted in diabetic rats (4.4+/-19.6%, p<0.001). Candesartan treatment of diabetic rats restored the acetylcholine-stimulated retinal blood flow response to 60.0+/-18.7% compared with a 56.2+20.1% response in candesartan-treated non-diabetic rats. Total retinal diacylglycerol levels were increased in diabetic rats (3.75+/-0.98 nmol/mg, p<0.05) compared with non-diabetic rats (2.13+/-0.25 nmol/mg) and candesartan-treatment of diabetic rats normalized diacylglycerol levels (2.10+/-0.25 nmol/mg, p<0.05). CONCLUSION/INTERPRETATION: This report provides evidence that angiotensin-converting enzyme inhibition and AT(1) receptor antagonism ameliorates retinal haemodynamic dysfunctions in normotensive diabetic rats.

Comparison of the effectiveness of 4 anti-inflammatory drops in relieving photophobia after pupil dilation.

PURPOSE: To compare the relative effectiveness of diclofenac, flurbiprofen, ketorolac, and prednisolone acetate in relieving photophobia after pupil dilation for fundus examination. SETTING: Eye, Ear, Nose, and Throat Hospital, New Orleans, Louisiana, USA. METHODS: This prospective, blind, placebo-controlled study comprised 105 patients randomly assigned to 1 of 10 treatment groups. Five minutes after instillation of dilating drops, each patient received drops of different test medications in the right and left eyes. Light sensitivity and pupil measurement tests were performed over 2 hours after the pharmacological mydriasis. After photostimulation, patients were asked to rate their photosensitivity on numerical and analog scales and to indicate a filter value required to alleviate right-induced discomfort. Test results were analyzed to detect differences among the pain levels associated with each treatment. RESULTS: There were no significant differences between the placebo and any active treatment drug at any time during the study. CONCLUSION: These findings suggest that mediators other than prostaglandins may have a role in photosensitivity or that increased postmydriatic photosensitivity is a result of higher light levels entering the eye through the dilated pupil.

Fluorescent microsphere imaging: a particle-tracking approach to the hemodynamic assessment of the retina and choroid.

BACKGROUND AND OBJECTIVES: Quantitative assessment of choriocapillaris circulation has proven difficult. Although the fluorescent vesicle system provides a means of quantifying the retinal circulation, the attempts at imaging fluorescent liposomes in the choroidal microcirculation have been largely unsuccessful. The authors introduce a new tool, fluorescent microsphere imaging, and examine its utility for evaluating the hemodynamics of the retina and choroidal microcirculation. The usefulness of fluorescent microsphere imaging is demonstrated through the examination of the retinal and choroidal circulations of three rhesus monkeys. MATERIALS AND METHODS: Fluorescent microsphere imaging uses polystyrene latex microspheres that incorporate one or more dyes. These microspheres are injected intravenously into an animal and are excited in the eye through the resident lasers of a scanning laser ophthalmoscope. The excited particles are detected by the ophthalmoscope, and its output is then digitized directly or recorded on a videocassette recorder for subsequent image analysis. Multiple-dye microspheres use the principle of resonance energy transfer for the activation of the final dye in a non-radiative cascade. These microspheres enable the investigator to tailor the excitation and emission spectra of the particles for the investigation of different ocular tissues. RESULTS: Using 488/515 microspheres (excitation and emission peaks at 488 nm and 515 nm, respectively), the authors captured images of particles circulating in the perimacular retinal circulation. Shifting excitation and emission spectra toward the red and infrared enabled the imaging of blood flow in progressively deeper tissue. Using 633/825 microspheres, the authors recorded and tracked particles in the microcirculation of the choroid. CONCLUSION: The authors' findings suggest that fluorescent microsphere imaging provides images useful for studying the retinal circulation and for evaluating previously inaccessible choroidal hemodynamics.