Regulation of subfoveal choroidal blood flow in age-related macular degeneration.

PURPOSE: To assess the capability of the subfoveal choroidal circulation to regulate its blood flow in response to an acute increase in ocular perfusion pressure in the eyes of healthy elderly persons or of subjects with neovascular age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment distribution changes (group 2), and 23 subjects with subfoveal classic neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%, 20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean +/- 95% confidence interval). In groups 1 and 2, the increase in PPm did not induce significant changes in the mean values of the different LDF parameters. In group 3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant correlations were found between age and the changes of each of the LDF parameters and of PPm at the end of squatting for the young and elderly healthy groups. CONCLUSIONS: In response to an acute, moderate increase in PPm induced by isometric exercise, subfoveal choroidal blood flow behaves similarly in young and elderly healthy persons and is not significantly different from its value at rest. In contrast, in patients with neovascular AMD, this flow increases, indicating altered regulation in response to the increase in PPm.

Adaptive optics for ophthalmic applications using a pyramid wavefront sensor.

A new adaptive optics system for the eye using a pyramid wavefront sensor interfaced in closed-loop with a piezoelectric deformable mirror is presented. Sensing parameters such as CCD integration time, pupil sampling and beam steering amplitude are tested on the bench and in vivo on several volunteers to optimize real-time optical correction. The system allows closed-loop operation at a frame rate of 55 Hz and reduces ocular aberration up to lambda/5 residual RMS over a 6 mm pupil. Aberration correction and mirror control stability clearly increase when smaller beam steering amplitudes synonymous of higher wavefront sensing sensitivity are used. This result suggests that using pyramid wavefront sensors can improve the performance of adaptive-optics system for ophthalmic applications.

Linearity of the pyramid wavefront sensor.

The pyramid wavefront sensor is very similar to the Fourier knife-edge test, but employs dynamic modulation to quantify the phase derivative. For circular modulation, we compare approximate geometrical optics calculations, more exact diffraction calculations, and experimental results. We show that both the sinusoidal and the approximate linear relationship between wavefront derivative and wavefront sensor response can be derived rigorously from diffraction theory. We also show that geometrical, diffraction and experimental results are very similar, and conclude that the approximate geometrical predictions can be used in place of the more complex diffraction results.

Light-induced retinal vascular damage by Pd-porphyrin luminescent oxygen probes.

PURPOSE: The phosphorescence lifetime of certain metalloporphyrins dissolved in a physiological medium provides an optical signature for local oxygen concentration (pO(2)). This effect is used for measuring physiological pO(2) levels in various tissues. However, the phosphorescence quenching of certain metalloporphyrin triplet states by oxygen also creates singlet oxygen, which is highly reactive and capable of inducing tissue damage. In the current study, the Pd-meso-tetra(4-carboxyphenyl) porphyrin dye (PdTCPP) was simultaneously used as an oxygen sensor and a photosensitizer. Phototoxicity was assessed in the eye fundus and correlated with tissue oxygenation, drug-light dose, and severity of tissue damage. METHODS: The kinetics of photochemical oxygen depletion during PdTCPP excitation was measured in vivo on the optic disc of piglets by phosphorescence lifetime imaging. Blood-retinal barrier breakdown and tissue damage were assessed by confocal and electron microscopy. RESULTS: For a retinal irradiance of 5 mW/cm(2) at 532 nm and an injected PdTCPP dose of 20 mg/kg, the mean phosphorescence lifetime measured at the optic disc increased from 100 to 600 micros within 8 minutes of continuous illumination. This corresponds to a decrease of pO(2) from 25 to 0 mm Hg, induced by a light dose of only 2.4 J/cm(2). An exposure time of 6 minutes (1.8 J/cm(2)) generated an increase in phosphorescence lifetime from 100 to 400 micros, corresponding to a decrease in pO(2) from 25 to 4 mm Hg. This caused edema in all retinal layers, whereas irradiation of 2 minutes (0.6 J/cm(2)) damaged blood vessels and induced edema in the inner nuclear layer only. Heavy redistribution of occludin occurred after a 30-minute exposure time (9 J/cm(2)). CONCLUSIONS: PdTCPP is potentially phototoxic under certain experimental conditions and can induce damage in peripapillary retina and optic nerve head after light exposure. The severity of tissue damage correlates with the phosphorescence measurements.

Blood pO2 and blood flow at the optic disc.

A fundus camera-based phosphorometer to noninvasively and quasicontinuously measure the blood partial pressure of oxygen (pO(2,blood)) in the microvasculature of the pig optic nerve using the principle of the phosphorescence quenching by O(2) is described. A porphyrin dye is injected into the venous circulation and the decay of its phosphorescence emission is detected locally in the eye, after excitation with a flash of light. Combined with blood flow measurements by means of a laser Doppler flowmeter mounted on the phosphorometer, we demonstrate the capability of the instrument to determine the time course of optic nerve blood flow and pO(2,blood) in response to various physiological stimuli, such as hyperoxia and hypercapnia. This instrument appears to be a useful tool for the investigation of the oxygenation of the optic nerve.

MEMS for enhanced optical diagnostics in endoscopy.

Endoluminal microscopy and spectroscopy could significantly improve the efficiency of clinical endoscopic examination by allowing in-situ detection, staging and grading of potentially cancerous lesions. Indeed, high-end optical microscopy techniques such as confocal, coherence-gated and single-/multi-photon microscopy today deliver optical histology information and spectrally/spatially resolved measurements of tissue reflectance allow grading and staging of precancerous/cancerous lesions. Owing to the brisk development of MEMS technologies, miniaturization requirements satisfying the dimension requirements for endoscope integration have been met within the last decade and the present paper will report on the current and future development of MEMS-based endoscopes for optical diagnosis.

Effect of isovolumic hemodilution on oxygen delivery to the optic nerve head.

BACKGROUND: To investigate the effect of isovolumic hemodilution on the tissue oxygenation of the optic nerve head (ONH). MATERIAL AND METHODS: In 9 miniature pigs (6 - 12 kg), hemodilution was performed by replacing 100 - 140 ml of blood by an equivalent volume of 6 % hydroxyethyl starch in saline. The blood flow parameters in the ONH microcirculation, namely velocity (BVel), volume (BVol) and flow (BF), were measured by laser Doppler flowmetry. Microelectrodes placed at approximately 50 micrometer from the disk surface and the phosphorescence quenching technique were used to measure pO 2 in the vitreous (pO 2 (vitr)) and in the ONH capillary blood (pO 2 (blood)), respectively. Arterial blood pressure, hematocrit (Hct) and gas content were documented. RESULTS: In all animals, hemodilution reduced Hct by 30 +/- 6 %. All the flow parameters increased markedly. Simultaneously, pO 2 (blood) (baseline: 31 +/- 3 mm Hg) dropped to approximately 75 % of its initial value, while pO 2 (vitr) (baseline: 26 +/- 8 mm Hg) increased by 15 +/- 8 %. CONCLUSIONS: Hemodilution leads to an increase of pO 2 (vitr) reflecting a similar rise of the ONH tissue pO 2. This effect results from an enhanced blood perfusion of the ONH, which over-compensates the decrease of the blood O 2 content.

Effect of isometric exercise on choroidal blood flow in type I diabetic patients.

BACKGROUND: In healthy subjects, choroidal blood flow is regulated when the mean ocular perfusion pressure increases. Since capillary vascular beds are altered in diabetic patients, the regulation of choroidal blood flow could be affected by this pathology. PATIENTS AND METHODS: 10 type I diabetic patients without retinopathy (DNR group) and 7 type I diabetic patients with retinopathy (DR group) participated in the study. In NDR and DR groups, choroidal blood flow was measured while patients raised their mean arterial blood pressure by squatting. The results were compared to those of a previous study in normals. Pupillometry was performed at rest on the two diabetic groups and on seven normals during a modification of illumination (white/black screen transition). RESULTS: In the NDR and DR groups, mean ocular perfusion pressure raised by 61 and 50 % during squatting, respectively. Consecutively, choroidal blood flow did not change in NDR as in normals, but increased linearly in DR patients. The white/black screen transition produced an increase of the pupil diameter of 52 and 49 % in normals and NDR patients, respectively, while it increased by only 16 % in the DR patients. CONCLUSIONS: As already shown in healthy subjects, choroidal blood flow is regulated in NDR patients when the ocular perfusion pressure increases. In DR patients, the absence of this control could be due to a failure of the autonomic nervous system, as suggested by pupillometry results.