Dawn A. Sim

Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography

PURPOSE To investigate the association between peripheral and central ischemia in diabetic retinopathy. DESIGN Retrospective, cross-sectional. METHODS Consecutive ultra-widefield fluorescein angiography images were collected from patients with diabetes over a 12-month period. Parameters quantified include the foveal avascular zone (FAZ) area, peripheral ischemic index, peripheral leakage index, and central retinal thickness measurements, as well as visual acuity. The peripheral ischemia or leakage index was calculated as the area of capillary nonperfusion or leakage, expressed as a percentage of the total retinal area. RESULTS Forty-seven eyes of 47 patients were included. A moderate correlation was observed between the peripheral ischemia index and FAZ area (r = 0.49, P = .0001). A moderate correlation was also observed between the peripheral leakage index and FAZ area, but only in eyes that were laser naïve (r = 0.44, P = .02). A thinner retina was observed in eyes with macular ischemia (217 ± 81.8 μm vs 272 ± 36.0 μm) (P = .02), but not peripheral ischemia (258 ± 76.3 μm vs 276 ± 68.0 μm) (P = .24). The relationships between different patterns of peripheral and central macular pathology and visual acuity were evaluated in a step-wise multivariable regression model, and the variables that remained independently associated were age (r = 0.33, P = .03), FAZ area (r = 0.45, P = .02), and central retinal thickness (r = 0.38, P = .01), (R(2)-adjusted = 0.36). CONCLUSIONS Ultra-widefield fluorescein angiography provides an insight into the relationships between diabetic vascular complications in the retinal periphery and central macula. Although we observed relationships between ischemia and vascular leakage in the macula and periphery, it was only macular ischemia and retinal thinning that was independently associated with a reduced visual function.

Optical Coherence Tomography Angiography for Anterior Segment Vasculature Imaging

PURPOSE To evaluate the application of an optical coherence tomography angiography (OCTA) system adapted for the assessment of anterior segment vasculature. DESIGN Cross-sectional, observational study. PARTICIPANTS Consecutive subjects with normal eyes on slit-lamp clinical examination and patients with abnormal corneal neovascularization. METHODS All scans were performed using a commercially available AngioVue OCTA system (Optovue, Inc., Fremont, CA) using an anterior segment lens adapter and the split-spectrum amplitude decorrelation angiography algorithm. Each subject underwent scans from 4 quadrants (superior, inferior, nasal, and temporal) in each eye by 2 trained, independent operators. MAIN OUTCOME MEASURES Analysis of signal strength, image quality, and reproducibility of corneal vascular measurements was performed. RESULTS In our study of 20 normal subjects (10 men, 10 women; mean age, 25.3±7.8 years), we found good repeatability (κ coefficient, 0.76) for image quality score and good interobserver agreement for vasculature measurements (intraclass coefficient, 0.94). After optimization of the angiography scan protocol, vascular measurements within the regions of interest were compared in the superior versus inferior quadrants (mean vascular loops, 3.34±1.16 vs. 3.12 ± 0.90 [P = 0.768]; segment-to-loop ratio, 4.18±0.71 vs. 4.32±0.87 [P = 0.129]; fractal dimension [Df] value, 1.78±0.06 vs. 1.78±0.06 [P = 0.94]; vascular loop area, 25.9±14.5 vs. 25.9±10.7 × 10(-3) mm(2) [P = 0.21]) and nasal versus temporal quadrant (mean vascular loops, 2.89±0.98 vs. 3.57±0.99 [P < 0.001]; segment-to-loop ratio, 3.94±0.69 vs. 4.55±0.78 [P = 0.897]; Df value, 1.78±0.06 vs. 1.77±0.06 [P = 0.14]; vascular loop area, 29.7±15.7 vs. 22.1±7.1 × 10(-3) mm(2) [P = 0.38]. We then used the established OCTA scanning protocol to visualize abnormal vasculature successfully in 5 patients with various corneal pathologic features, including graft-associated neovascularization, postherpetic keratitis scarring, lipid keratopathy, and limbal stem cell deficiency. CONCLUSIONS This preliminary study describes a method for acquiring OCTA images of the cornea and limbal vasculature with substantial consistency. This technique may be useful for the objective evaluation of corneal neovascularization in the future.

Repeatability and Reproducibility of Choroidal Vessel Layer Measurements in Diabetic Retinopathy Using Enhanced Depth Optical Coherence Tomography

PURPOSE To describe novel segmentation protocols for choroidal layers, Sattlers medium and Hallers large vessel layers, using enhanced depth imaging optical coherence tomography (EDI-OCT), and to examine the repeatability and reproducibility of these measurements in eyes with diabetic retinopathy. METHODS Fifty-one patients with Type 2 diabetes mellitus were imaged using custom EDI scanning protocols. Detailed segmentation was performed to quantify the retina, choroid, Hallers large, and Sattlers medium vessel layers in the total macular circle (TMC) and foveal central subfield (FCS). The coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were used as a measure of repeatability and relative reliability within graders. Reproducibility or interobserver variability was assessed using Bland-Altman plots and 95% limits of agreement (LoA). RESULTS Intragrader CR of the retina, choroid, Sattlers, and Hallers layers for thickness measurements were 19.2, 26.9, 35.2, and 29.2 μm, respectively. Intergrader 95% LoA were 27.9, 41.5, 38.6, 31.1 μm (thickness), respectively. Choroidal sublayer measurements showed good intraobserver reliability (ICC 0.78-0.98). Interobserver variability for retinal and choroidal measurements was not significantly different (P > 0.45). Measurements from the TMC showed slightly better repeatability and agreement compared with the FCS alone. Mean intergrader differences were reduced after training, and were most apparent in choroidal sublayers. CONCLUSIONS The choroidal vascular sublayers can be quantified with good reliability, repeatability, and reproducibility. Accurate quantitative assessment of these sublayers may provide new insights into the role of the choroid in visual loss in patients with diabetic retinopathy, and prove useful for future clinical trials.

Systematic Evaluation of Optical Coherence Tomography Angiography in Retinal Vein Occlusion.

PURPOSE To evaluate the clinical utility of optical coherence tomography angiography (OCTA) in patients with retinal vein occlusion (RVO), and to systematically compare OCTA images with changes seen on color fundus photography and fluorescein angiography (FA). DESIGN Reliability analysis. METHODS Eighty-one eyes of 76 patients with a history of RVO (branch, central, or hemicentral), both acute and chronic, underwent OCTA and color fundus photography. In 29 eyes, data were compared to FA imaging. Comparative and multimodal analysis of the 3 imaging procedures were performed. RESULTS We identified good agreement between FA and OCTA scans centered on the macula for capillary nonperfusion (intraclass correlation coefficient [ICC] 0.825 for the 3 × 3-mm scan and 0.891 for the 8 × 8-mm scan). Agreement for area of capillary changes (dilation, pruning, and telangiectasia) was also substantial (ICC 0.712 for the 3 × 3-mm scan and 0.787 for the 8 × 8-mm scan). For foveal avascular zone grading, agreement was good for the 3 × 3-mm scan (kappa = 1.000 for radius and kappa = 0.799 for outline) but poor for the 8 × 8-mm scan (kappa = 0.156 for radius and kappa = 0.600 for outline). The quality of the images obtained was an important issue for OCTA, as 15.1% of scans were nongradable, particularly in patients unable to maintain fixation. CONCLUSIONS OCTA is a quick, reliable, and noninvasive method to evaluate the area of capillary nonperfusion and foveal avascular zone morphology in patients with RVO. However, good fixation is a requirement for acquisition of good-quality images.

The Evaluation of Diabetic Macular Ischemia Using Optical Coherence Tomography Angiography

PURPOSE The purpose of this study was to compare optical coherence tomography (OCT) angiography to standard fluorescein angiography (FA) in the grading of diabetic macular ischemia. METHODS In our study, OCT angiography and traditional FA images were acquired from 24 diabetic patients. The level of diabetic macular ischemia in the superficial capillary plexus was graded with standard Early Treatment Diabetic Retinopathy Study (ETDRS) protocols and a comparison between conventional FA and OCT angiography was performed. The deep vascular plexus and choriocapillaris were also graded for macular ischemia. Additionally, flow indices were analyzed for all OCT angiography images. RESULTS We identified moderate agreement between diabetic macular ischemia grades for conventional FA and OCT angiography (weighted κ of 0.53 and 0.41). In addition, the intergrader agreement for the superficial, deep, and choriocapillaris scores was substantial (weighted κ of 0.65, 0.61, and 0.65, respectively). Finally, the parafoveal flow indices were shown to have a statistically significant relationship with diabetic macular ischemia grades for the superficial capillary plexus (P = 0.04) and choriocapillaris (P = 0.036), with a trend toward significance for the deep capillary plexus (P = 0.13). CONCLUSIONS We demonstrated moderate agreement between diabetic macular ischemia grading results for OCT angiography and conventional FA using standard ETDRS protocols. We also showed that OCT angiography images could be graded for diabetic macular ischemia with substantial intergrader agreement.

En face optical coherence tomography angiography for corneal neovascularisation

Background/aim Recently, there has been an increasing clinical need for objective evaluation of corneal neovascularisation, a condition which cause significant ocular morbidity. We describe the use of a rapid, non-invasive ‘en face’ optical coherence tomography angiography (OCTA) system for the assessment of corneal neovascularisation. Methods Consecutive patients with abnormal corneal neovascularisation were scanned using a commercially available AngioVue OCTA system (Optovue, Fremont, California, USA) with the split-spectrum amplitude decorrelation angiography algorithm, using an anterior segment lens adapter. Each subject had four scans in each eye by a trained operator and two independent masked assessors analysed all images. Main outcome measures were scan quality (signal strength, image quality), area of neovascularisation and repeatability of corneal vascular grade. Results We performed OCTA in 20 patients (11 men, 9 women, mean age 49.27±17.23 years) with abnormal corneal neovascularisation. The mean area of corneal neovascularisation was 0.57±0.30 mm2 with a mean neovascularisation grade of 3.5±0.2 in the OCTA scans. We found the OCTA to produce good quality images of the corneal vessels (signal strength: 36.95±13.97; image quality score 2.72±1.07) with good repeatability for assessing neovascularisation grade (κ=0.84). Conclusions In this preliminary clinical study, we describe a method for acquiring angiography images with ‘en face’ views, using an OCTA system adapted for the evaluation of corneal neovascularisation. Further studies are required to compare the scans to other invasive angiography techniques for the quantitative evaluation of abnormal corneal vessels.

Automated retinal image analysis for diabetic retinopathy in telemedicine.

There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data.

Choroidal Vascularity Index (CVI)--A Novel Optical Coherence Tomography Parameter for Monitoring Patients with Panuveitis?

Purpose To compute choroidal vascularity index (CVI) using an image binarization tool on enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans as a non-invasive optical tool to monitor progression in panuveitis and to investigate the utility of volumetric data from EDI-OCT scans using custom image analysis software. Materials and Methods In this retrospective cohort study, segmented EDI-OCT scans of both eyes in 19 patients with panuveitis were taken at baseline and at 3-month follow-up and were compared with EDI-OCT scans of normal eyes. Subfoveal choroidal area was segmented into luminal (LA) and stromal interstitial area (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to the total circumscribed subfoveal choroidal area (TCA). Results The mean choroidal thickness was 265.5±100.1μm at baseline and 278.4±102.6μm at 3 months follow up (p = 0.06). There was no statistically significant difference in TCA between study and control eyes (p = 0.08). CVI in the control group was 66.9±1.5% at baseline and 66.4±1.5% at follow up. CVI was 74.1±4.7% at baseline and 69.4±4.8% at 3 months follow up for uveitic eyes (p<0.001). The % change in CVI was 6.2 ±3.8 (4.3 to 8.0) for uveitic eyes, which was significantly higher from % change in CVI for control eyes (0.7±1.1, 0.2 to 1.3, p<0.001). Conclusion The study reports composite OCT-derived parameters and CVI as a possible novel tool in monitoring progression in panuveitis. CVI may be further validated in larger studies as a novel optical tool to quantify choroidal vascular status.

Optical coherence tomography angiography and indocyanine green angiography for corneal vascularisation

Background/Aim To describe an optical coherence tomography angiography (OCTA) system adapted for anterior segment imaging, compared with indocyanine green angiography (ICGA) in eyes with corneal vascularisation. Methods Retrospective study of subjects with corneal vascularisation secondary to microbial keratitis who had OCTA scans performed using a commercially available split-spectrum amplitude-decorrelation algorithm angiography system (AngioVue; Optovue Inc., Fremont, California, USA) and ICGA images (Spectralis; Heidelberg Engineering, Heidelberg, Germany). The agreement between OCTA and ICGA techniques in terms of area of vascularisation measured, using Bland–Altman 95% limits of agreement (LOA). Results We compared the area of corneal vascularisation in 64 scan images (eight eyes, four scans for each angiography technique). In our series, the overall mean area of vascularisation from the ICGA scans was 0.49±0.34 mm2 and OCTA scans was 0.51±0.36 mm2. We obtained substantial repeatability in terms of image quality score (κ=0.80) for all OCTA scans. The agreement between OCTA and ICGA scans was good, although ICGA measured a smaller area compared with the OCTA with a mean difference of −0.03 mm2 (95% CI −0.07 to 0.01). The LOA ranged from a lower limit of −0.27 (95% CI −0.34 to −0.19) to an upper limit of 0.20 (95% CI 0.13 to 0.28, p=0.127). Conclusions We found that rapid, non-contact OCTA adapted for the cornea was comparable with ICGA for measurement of the area of corneal vascularisation in this pilot clinical study. Further prospective studies are required to confirm if this relatively new imaging technique may be further developed to replace invasive angiography techniques for the anterior segment.

Evaluation of retinal pigment epithelium–Bruch's membrane complex thickness in dry age-related macular degeneration using optical coherence tomography

Aim To compare retinal pigment epithelium–Bruchs membrane (RPE–BM) complex thickness in patients with early and intermediate dry age-related macular degeneration (AMD) and age-matched controls using spectral domain optical coherence tomography (SD-OCT). Methods In this retrospective, cross-sectional study, 25 patients with dry AMD and 25 controls were recruited. SD-OCT scans were manually segmented by two independent investigators. Thickness values were calculated for the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Results RPE–BM thickness was significantly thicker in the dry AMD group (32.3, 30.6 and 28.4 μm for central, inner and outer subfields, respectively) compared with the normal eyes (22.7, 21.8 and 21.6 μm, respectively). RPE–BM thickness was positively correlated with age in the normal group but not in the AMD group. RPE–BM thickness in the dry AMD group was negatively correlated with visual acuity in the central and inner subfields but not in the outer. We observed good intraobserver and inter-observer reliability for both groups in all ETDRS subfields. Conclusions This study reports novel data concerning RPE–BM segmentation in dry AMD and performs a direct comparison with age-matched normal controls. Our findings confirm the electron and light microscopy derived data and also establish the value of OCT in the quantification of the RPE–BM complex.