Retinal oximetry with a prototype handheld oximeter during hyperoxia.

PURPOSE: Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during isocapnic hyperoxia. A comparison is made between the handheld oximeter and the Oxymap T1. METHODS: Thirteen young healthy subjects with a mean age of 25 ± 2 years were recruited at the Leiden University Medical Center. Retinal oximetry images were acquired during normoxia and during isocapnic hyperoxia for both the prototype oximeter and the OxymapT1. Isocapnic hyperoxia was induced with the dynamic end-tidal forcing technique. For both oximeters, the oxygen saturation and vessel width were measured with Oxymap Analyzer software. The hyperoxic state was verified with blood gas analysis. RESULTS: The mean oxygen saturation measured with the handheld oximeter in arterioles was 91.3% ± 3.9% during normoxia and 94.6% ± 3.9% during hyperoxia (p = 0.001). Oxygen saturation in venules was 56.3% ± 9.8% during normoxia and 82.2 ± 7.4% during hyperoxia (p < 0.001). For the Oxymap T1, the mean oxygen saturation for arterioles was 94.0% ± 2.6% during normoxia and 95.4%±3.2% during hyperoxia (p = 0.004). For the venules, the oxygen saturation was during normoxia 58.9%±3.2% and 84.3 ± 4.0% during hyperoxia (p < 0.001). CONCLUSION: The handheld retinal oximeter is sensitive to the changes in inhaled oxygen concentration. A small increase in oxygen saturation was measured in the arterioles and a larger increase in the venules. The handheld oximeter gives similar values as the 'gold standard' Oxymap T1 oximeter.

Automatic fundus image quality assessment on a continuous scale.

Fundus photography is commonly used for screening, diagnosis, and monitoring of various diseases affecting the eye. In addition, it has shown promise in the diagnosis of brain diseases and evaluation of cardiovascular risk factors. Good image quality is important if diagnosis is to be accurate and timely. Here, we propose a method that automatically grades image quality on a continuous scale which is more flexible than binary quality classification. The method utilizes random forest regression models trained on image features discovered automatically by combining basic image filters using simulated annealing as well as features extracted with the discrete Fourier transform. The method was developed and tested on images from two different fundus camera models. The quality of those images was rated on a continuous scale from 0.0 to 1.0 by five experts. In addition, the method was tested on DRIMDB, a publicly available dataset with binary quality ratings. On the DRIMDB dataset the method achieves an accuracy of 0.981, sensitivity of 0.993 and specificity of 0.958 which is consistent with the state of the art. When evaluating image quality on a continuous scale the method outperforms human raters.

Fundus imaging in newborn children with wide-field scanning laser ophthalmoscope.

PURPOSE: Current fundus imaging in newborn babies requires mydriatics, eye specula and corneal contact. We propose that a scanning laser ophthalmoscope (SLO) allows ultra wide-field imaging with reduced stress for the child. METHODS: This prospective observational single centre study was conducted in Landspítali, University Hospital, Reykjavik, Iceland. In this study, a noncontact wide-field SLO (Optomap 200Tx) was used to image the retina in healthy full-term newborns without the use of mydriatics or eye specula. The child was held by one of the parents, while one of the researchers supported the child's head in front of the SLO camera for alignment and opened the eye with either a finger or a cotton tip. RESULTS: Fifty-nine participants were recruited (34 females). The mean age was 16 days, and the mean gestational age was 40 ± 1 weeks at the time of imaging. Ultra-wide-field (200°) images were obtained of 44 participants. Twenty-seven participants (61%) had at least one ultra wide-field image with the optic disc and vessel segments in all quadrants of the fundus visible and in focus. No retinal pathology was found in the participants with the exception of one participant with small retinal haemorrhages. CONCLUSION: Scanning laser ophthalmoscope (SLO) ultra-wide-field fundus imaging is feasible in healthy full-term newborns without corneal contact, eye speculum or mydriatics. This approach could be an improvement for retinal imaging in newborn infants. Eye movement of the infant, whether asleep or awake, influenced which part of the fundus was captured, but focus and image quality were generally good.

Retinal vessel oxygen saturation and vessel diameter in retinitis pigmentosa.

PURPOSE: To assess retinal vessel oxygen saturation and retinal vessel diameter in retinitis pigmentosa. METHODS: A retinal oximeter (Oxymap ehf., Reykjavik, Iceland) was used to measure retinal vessel oxygen saturation and vessel diameter in ten patients with retinitis pigmentosa (RP) (mean age 49 years, range 23-71 years). Results were compared with age- and gender-matched healthy individuals. All patients had advanced stage of the disease with visual fields restricted to the macular region. RESULTS: Oxygen saturation in retinal venules was 58.0 ± 6.2% in patients with RP and 53.4 ± 4.8% in healthy subjects (p = 0.017). Oxygen saturation in retinal arterioles was not significantly different between groups (p = 0.65). The mean diameter of retinal arterioles was 8.9 ± 1.6 pixels in patients with RP and 11.4 ± 1.2 in healthy controls (p < 0.0001). The corresponding diameters for venules were 10.1 ± 1.2 (RP) and 15.3 ± 1.7 (healthy, p < 0.0001). CONCLUSIONS: Increased venous saturation and decreased retinal vessel diameter suggest decreased oxygen delivery from the retinal circulation in retinitis pigmentosa. This is probably secondary to tissue atrophy and reduced oxygen consumption.

γ-Cyclodextrin nanoparticle eye drops with dorzolamide: effect on intraocular pressure in man.

PURPOSE: To test a new drug delivery platform with dorzolamide γ-cyclodextrin (γCD) nanoparticle eye drops for intraocular pressure (IOP) control and safety and compare with Trusopt.(®) METHODS: Self-aggregating γCD nanoparticle eye drops containing 3% dorzolamide were given once a day (QD) and compared with Trusopt given three times a day (TID) in a prospective randomized single masked crossover trial over 24 h. Seventeen subjects with IOP over 18 mmHg were recruited. IOP was measured with an Icare Tonometer Pro.(®) RESULTS: There was no statistically significant difference in the IOP lowering effect of dorzolamide nanoparticle eye drops QD and Trusopt TID. At peak (4 h), the IOP reduction from baseline was 3.8±2.6 mmHg (18%, P<0.05) in the nanoparticle eye drop group and 3.1±3.7 mmHg in the Trusopt group (14%, P<0.05, P=0.97 between groups). At trough (24 h), the IOP reduction was 1.4±2.8 mmHg (6%, P>0.05) in nanoparticle eye drop group and 1.5±2.0 mmHg (7%, P>0.05) in the Trusopt group (P=0.23 between groups). Burning sensation measured on the visual analogue scale (1-100) was less from the nanoparticle eye drops (12±15) than from the Trusopt (37±30), (P=0.0038). Visual acuity and conjunctival hyperemia did not differ between the two groups. CONCLUSIONS: Dorzolamide cyclodextrin nanoparticle eye drops QD lower IOP and the effect seems comparable to Trusopt given TID. The nanoparticle eye drops are well tolerated and seem to have a better safety profile than Trusopt.

The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy.

PURPOSE: Diabetic retinopathy is characterized by morphological lesions in the retina secondary to disturbances in retinal blood flow which may influence the supply of oxygen to the retinal metabolism. Using retinal oximetry, it has been shown that the oxygen saturation is increased in retinal arterioles and venules from diabetic patients with retinopathy, but oxygenation before the development of retinopathy and possible differences in retinal oxygenation between diabetic maculopathy and proliferative diabetic retinopathy patients have not been evaluated. METHODS: One-hundred and fifty-six consecutive patients referred for specialist evaluation of diabetic retinopathy, and eighty normal control persons were subjected to retinal oximetry of the larger retinal arterioles and venules. The diabetic patients were allocated to one of four groups with severity of retinopathy ranging from no retinopathy to vision-threatening retinopathy, and the oxygen saturation in arterioles and venules was compared between these groups. RESULTS: Increasing severity of retinal changes from no retinopathy to diabetic maculopathy was accompanied with increasing oxygen saturation in retinal venules and decreasing oxygen extraction, whereas proliferative diabetic retinopathy showed increased oxygen saturation in both retinal arterioles and venules to result in a normal oxygen extraction. CONCLUSION: Prospective observational and interventional studies are needed to show whether changes in retinal oxygen saturation precede or follow the development of diabetic retinopathy. Additionally, studies of regional variations in haemodynamic parameters in patients with vision-threatening diabetic retinopathy might improve the understanding of the pathophysiology of diabetic retinopathy. This is a precondition for improving the prevention and treatment of the disease.

Spectrophotometric retinal oximetry in pigs.

PURPOSE: To assess the validity of spectrophotometric retinal oximetry by comparison to blood gas analysis and intravitreal measurements of partial pressure of oxygen (pO(2)). METHODS: Female domestic pigs were used for all experiments (n = 8). Oxygen fraction in inspired air was changed using a mixture of room air, pure oxygen, and pure nitrogen, ranging from 5% to 100% oxygen. Femoral arterial blood gas analysis and retinal oximetry were performed at each level of inspiratory oxygen fraction. Retinal oximetry was performed using a commercial instrument, the Oxymap Retinal Oximeter T1. The device simultaneously acquires images at two wavelengths (570 nm and 600 nm), and specialized software automatically detects retinal blood vessels. In three pigs, invasive pO(2) measurements were performed after the initial noninvasive measurements. RESULTS: Comparison of femoral arterial oxygen saturation and the optical density ratio over retinal arteries revealed an approximately linear relationship (R(2) = 0.74, P = 3.4 × 10(-9)). In order to test the validity of applying the arterial calibration to veins, we compared noninvasive oximetry measurements to invasive pO2 measurements in three pigs. This relationship was approximately linear (R(2) = 0.45, P = 0.04). CONCLUSIONS: Noninvasive spectrophotometric oximetry is sensitive to changes in oxygen saturation in pigs and correlated with intravitreal pO(2) measurements and with femoral artery pO(2). Pigs present a higher intraindividual variability in retinal oxygen saturation and a lower overall saturation than do humans. The difference between porcine and human eyes makes direct comparisons of measurements difficult.

Regulation of retinal blood flow in health and disease.

Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.