Choroidal biomarkers.

A structurally and functionally intact choroid tissue is vitally important for the retina function. Although central retinal artery is responsible to supply the inner retina, choroidal vein network is responsible for the remaining one-third of the external part. Abnormal choroidal blood flow leads to photoreceptor dysfunction and photoreceptor death in the retina, and the choroid has vital roles in the pathophysiology of many diseases such as central serous chorioretinopathy, age-related macular degeneration, pathologic myopia, Vogt-Koyanagi-Harada disease. Biomarkers of choroidal diseases can be identified in various imaging modalities that visualize the choroid. Indocyanine green angiography enables the visualization of choroid veins under the retinal pigment epithelium and choroidal blood flow. New insights into a precise structural and functional analysis of the choroid have been possible, thanks to recent progress in retinal imaging based on enhanced depth imaging (EDI) and swept-source optical coherence tomography (SS-OCT) technologies. Long-wavelength SS-OCT enables the choroid and the choroid-sclera interface to be imaged at greater depth and to quantify choroidal thickness profiles throughout a volume scan, thus exposing the morphology of intermediate and large choroidal vessels. Finally, OCT angiography allows a dye-free evaluation of the blood flow in the choriocapillaris and in the choroid. We hereby review different imaging findings of choroidal diseases that can be used as biomarkers of activity and response to the treatment.

Towards Non-Invasive Extraction and Determination of Blood Glucose Levels.

Diabetes is a condition where the body is incapable of proper utilization of glucose and one that, if not properly managed, can lead to critical illness. Glucose monitoring and decision support is vital in avoiding potential adverse health effects. Current methods mainly involve invasive blood extraction for the purposes of blood glucose level notification, yet such methods rely on active user participation and subjective interpretation of the result. This paper reviews existing research in methods of extraction and monitoring of glucose levels. The purpose of this paper is to examine blood glucose extraction methods in addition to indicators of blood glucose level, toward development of an innovative, non-invasive extraction technology. Decision support methods are also analyzed toward customized, automated, and intelligent diabetic management.

Spectral-domain optical coherence tomography as an indicator of fluorescein angiography leakage from choroidal neovascularization.

PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) findings that predict angiographic leakage in choroidal neovascularization (CNV). METHODS: SD-OCT and fluorescein angiography (FA) images of 93 eyes of 93 patients were retrospectively analyzed. All patients were previously treated with anti-vascular endothelial growth factor agents for CNV from age-related macular degeneration. FA images were analyzed to assess the presence of leakage. SD-OCT images were analyzed to identify the overall presence of fluid, as well as specific patterns of fluid presentation, including intraretinal cystic spaces (ICS), retinal pigment epithelium detachment (PED), and neurosensory detachment (NSD). The presence of ultrastructural features such as intraretinal hyperreflective flecks and the inherent reflectivity and boundary definition of the subretinal material were evaluated. Both the association and the sensitivity, specificity, and both positive and negative predictive values of SD-OCT findings compared with FA leakage were calculated. RESULTS: A statistically significant association between SD-OCT findings and FA leakage was found for eyes that displayed fluid, NSD, intraretinal flecks, and low reflectivity or undefined boundaries from subretinal material, and not for PED or ICS. Sensitivity and specificity for SD-OCT findings were, respectively: 94% and 27% for fluid; 68% and 88% for NSD; 81% and 83% for intraretinal flecks; 63% and 92% for undefined boundaries of subretinal material; and 94% and 87% for low reflectivity from subretinal material. CONCLUSIONS: The evidence of fluid on SD-OCT is sensitive but nonspecific in identifying FA leaky CNV. The assessment of neurosensory detachment as well as other ultrastructural elements may increase the specificity of analysis.

Displayed reflectivity of choroidal neovascular membranes by optical coherence tomography correlates with presence of leakage by fluorescein angiography.

PURPOSE: To evaluate and correlate the displayed optical reflectivity of choroidal neovascularization (CNV) subretinal material on spectral-domain optical coherence tomography with the presence of dye leakage on fluorescein angiography (FA). METHODS: Thirty-nine eyes of 39 patients with a diagnosis of predominantly classic CNV from age-related macular degeneration underwent simultaneous spectral-domain optical coherence tomography and FA imaging. Eight patients had a newly diagnosed untreated CNV. Thirty-one patients had already been treated with anti-vascular endothelial growth factor agents. In 18 of these eyes, CNV lesions showed persistent leakage on FA. In 13 eyes, CNV lesions did not show leakage by FA. Subretinal CNV material boundaries visualized on spectral-domain optical coherence tomography B-scans were manually traced, and optical reflectivity was calculated using the mean grayscale value. To account for variable image brightness, the retinal pigment epithelial reflectivity was measured. The absolute difference between CNV material and retinal pigment epithelial reflectivity (ΔREF) from the three groups (newly diagnosed CNV, previously treated CNV showing FA leakage, and previously treated CNV not showing FA leakage) was compared. RESULTS: In untreated lesions, ΔREF was significantly higher compared with previously treated, but still leaky CNV (P < 0.0001). Lesions showing FA leakage had significantly higher ΔREF compared with those that did not display leakage (P < 0.0001). CONCLUSION: The displayed reflectivity of subretinal CNV material in spectral-domain optical coherence tomography appears to be an important parameter that can provide information regarding the FA leakage status.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

PURPOSE: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. METHODS: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 microm) versus noncentral location of errors were studied. RESULTS: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P < or = 0.005) except the Optovue RTvue-100 (P = 0.165). CONCLUSION: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Bimodal spatial distribution of macular pigment: evidence of a gender relationship.

The spatial distribution of the optical density of the human macular pigment measured by two-wavelength autofluorescence imaging exhibits in over half of the subjects an annulus of higher density superimposed on a central exponential-like distribution. This annulus is located at about 0.7 degrees from the fovea. Women have broader distributions than men, and they are more likely to exhibit this bimodal distribution. Maxwell's spot reported by subjects matches the measured distribution of their pigment. Evidence that the shape of the foveal depression may be gender related leads us to hypothesize that differences in macular pigment distribution are related to anatomical differences in the shape of the foveal depression.

Subthreshold infrared footprinting with indocyanine green for localizing low-intensity infrared photocoagulation.

A novel technique for localizing subthreshold infrared (810 nm) laser treatment and its use in three patients is described. Two patients were treated for choroidal neovascularization with transpupillary thermotherapy or focal subthreshold photocoagulation, and the third patient was treated with grid laser photocoagulation for diabetic macular edema using the 810-nm laser after undergoing indocyanine green angiography for diagnostic purposes. Postoperative indocyanine green images, obtained without reinjection of indocyanine green, revealed areas of hypofluorescence that corresponded to the laser treatment spots. This technique, named subthreshold infrared footprinting, can precisely localize subthreshold infrared laser photocoagulation sites and is potentially useful for evaluating treatment postoperatively and planning additional therapy if necessary.