Ultra-widefield Fluorescein Angiography Images Research Articles

Precise Measurement of Retinal Vascular Bed Area and Density on Ultra-wide Fluorescein Angiography in Normal Subjects

To characterize and quantify the total retinal vascular bed area (RVBA) and vascular density (VD) in normal eyes using stereographically corrected ultra-wide-field (UWF) fluorescein angiography (FA). Cross-sectional study. Fifty-nine eyes of 31 normal subjects with no evidence of ocular disease underwent FA using the Optos 200Tx (Optos plc, Dunfermline, United Kingdom). Central and peripheral-steered FA images were montaged and stereographically projected. The early-phase FA was used to extract the retinal vasculature as a binary mask. Two independent, masked reading center-certified graders delineated the peripheral edge of the total retinal area (TRA) on a middle-phase frame. The RVBA and TRA were computed automatically in mm2 using software provided by the manufacturer. The VD was calculated by dividing RVBA by TRA. The mean RVBA was 42.3 ± 14.8mm2 for the entire retina, with no difference between male and female subjects (P= .439) or between right and left eyes (P= .407). The mean VD was 4.3% ± 1.4% for the entire retina, with no difference based on sex (P= .629) or laterality (P= .426). A negative correlation was observed between age and both RVBA and VD (RVBA: R=-0.6, P < .001; VD: R=-0.52, P < .001). Pairwise comparisons showed that subjects aged >65 years had smaller RVBA and VD than those younger than 50 years for the entire retina and in all quadrants. RVBA and VD can be extracted from UWF FA images using automated processing techniques and may provide a reliable alternative to measures such as nonperfusion area.

Correlation of Ultra-Widefield Fluorescein Angiography and OCT Angiography in Sickle Cell Retinopathy

To determine whether the degree of peripheral nonperfusion seen on ultra-widefield (UWF) fluorescein angiography (FA) correlates with measures of macular vascular flow as seen on OCT angiography (OCTA) in sickle cell retinopathy. Prospective, observational study. Patients with sickle cell disease undergoing an eye examination at an urban, tertiary medical center. All patients underwent dilated fundus examination as well as UWF FA and macular OCTA imaging on the same day. The peripheral nonperfusion seen on UWF FA was measured to calculate an ischemic index (visualized nonperfusion/total visualized retinal area× 100%), and OCTA measurements of macular vessel density were recorded. The degree of peripheral nonperfusion and vessel density were then correlated. Correlation between ischemic index as seen on UWF FA and macular vessel density on OCTA. Thirty-six eyes from 19 patients (10 women, 9 men) with a mean age of 30.8 years were included. Sickle genotypes included 14 patients with SS (73.7%), 4 with SC (21.1%), and 1 with β-thalassemia (5.2%). Average ischemic index was 4.4% for all eyes and was found to be higher in patients with sickle SC (8.0%) than in those with sickle SS (3.2%; P= 0.01). Ischemic index also was higher in those with proliferative sickle cell retinopathy (9.3%) than in those without (2.8%; P < 0.01). Ischemic index on UWF FA showed a statistically significant correlation (P < 0.05) with vessel density on OCTA in the temporal subfield of the superficial capillary plexus and in all subfields of the deep capillary plexus. Peripheral nonperfusion seen on UWF FA is greater in those with sickle SC disease and proliferative retinopathy and is correlated with macular vessel density on OCTA, especially the deep retinal plexus.

Distribution of Nonperfusion Area on Ultra-widefield Fluorescein Angiography in Eyes With Diabetic Macular Edema: DAVE Study

To explore the distribution of nonperfusion area (NPA) in eyes with diabetic macular edema (DME) and its relationship with the severity of DME. Prospective, observational case series. Forty eyes of 29 patients with treatment-naïve DME who participated in the DAVE study (NCT01552408) were included. Ultra-widefield fluorescein angiography images were sent to the Doheny Image Reading Center, where they were montaged and corrected using stereographic projection to adjust for peripheral distortion. Two experienced, independent/masked certified graders manually segmented the NPA and the total visible retinal area (TRA), and computed the NPA and TRA in square millimeters (mm2). The ischemic index (ISI) was calculated. The distributions of NPA and ISI within different retinal zones were correlated with the severity of DME. In 40 eyes with treatment-naïve DME (mean age, 55.8 years) visual acuity (VA) (mean 59.6 EDTRS letters) was correlated with central macular thickness (CMT) (mean 536.9μm, R=-0.418, P= .008) and macular volume (MV) (mean 11.9mm3, R=-0.449, P= .004). The NPA and ISI among the different retinal zones were significantly different (NPA: P < .001; ISI: P= .005). The NPA and ISI in the midperiphery were negatively associated with CMT (NPA: P= .04; ISI: P= .02). However, the global NPA and ISI for the entire retina were not associated with CMT or MV (P > .05). In eyes with DME, the ISI increases with increasing distance from the fovea. The severity of DME does not appear to correlate with global NPA and ISI.

Peripheral Findings and Retinal Vascular Leakage on Ultra-Widefield Fluorescein Angiography in Patients with Uveitis

To compare ultra-widefield fluorescein angiography (UWFFA) with simulated conventional fluorescein angiography (FA) to evaluate peripheral pathology and leakage and correlate with clinical activity in patients with uveitis. Retrospective chart review. All uveitis patients initially evaluated with UWFFA (Optos 200Tx) between May 2012 and December 2013 were included in this study, including follow-up visits through August2014. Uveitis status was deemed as having active or inactive inflammation based on clinical examination. Changes to therapy, influence on management, and clinical diagnosis were also noted. UWFFA images were compared with simulated 50-degree FA images to evaluate for peripheral lesions, and leakage location was also graded. Imaging characteristics were then correlated with clinical information. Correlation of leakage on UWFFA with clinical inflammation. An initial set of 243 uveitis patients and a total of 1008 eye images were reviewed. When UWFFA was compared with a simulated 50-degree FA image, UWFFA added additional information regarding the presence of peripheral vascular leakage in 25%, peripheral nonperfusion in 14%, peripheral lesions in 6.6%, and peripheral neovascularization in 3.9% of patients. A total of 600 eye images exhibited fluorescein leakage, of which 21% displayed central leakage only, 11% had central and peripheral leakage, 31% had peripheral leakage only, and 37% had diffuse vascular leakage. Based on peripheral findings on widefield angiography, the treatment was changed in 69 patients (28%). Corresponding eye examinations were reviewed for each imaging session, and of 600 eye images with vascular leakage, 567 eye images were also clinically active, which was 95% sensitive as a surrogate indicator of clinical inflammation. Anterior chamber cell and vitreous haze also significantly correlated with leakage on widefield angiography. Retinal vascular leakage on UWFFA reveals increased pathology and leakage compared with conventional angiography, which can influence management, and accurately identifies and correlates with active inflammation in patients with uveitis. A more objective measure of inflammation in the form of leakage exhibited on UWFFA may help standardize treatment and care of patients with uveitis.

Automated quantitative characterisation of retinal vascular leakage and microaneurysms in ultra-widefield fluorescein angiography

Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality used to characterise pathology in the retinal vasculature such as microaneurysms (MAs) and vascular leakage. Despite its potential value for diagnosis...

Clinical Outcome of Retinal Vasculitis and Predictors for Prognosis of Ischemic Retinal Vasculitis

To determine factors affecting the visual outcome in eyes with retinal vasculitis and the rate of neovascularization relapse in ischemic vasculitis. Retrospective cohort study. We reviewed 1169 uveitis patients from Moorfields Eye Hospital, London, UK. Retinal vasculitis was observed in 236 eyes (121 ischemic, 115 nonischemic) that were compared with a control group (1022 eyes) with no retinal vasculitis. Ultra-widefield fluorescein angiography images were obtained in 63 eyes with ischemic vasculitis to quantify area of nonperfusion measured as ischemic index. The risk of vision loss was significantly more in the retinal vasculitis compared with the non-vasculitis group (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.24-2.25, P= .001). Retinal vasculitis had twice the risk of macular edema compared to the non-vasculitis group. Macular ischemia increased the risk of vision loss in vasculitis eyes by 4.4 times. The use of systemic prednisolone in eyes with vasculitis was associated with a reduced risk of vision loss (HR 0.36, 95% CI 0.15-0.82, P= .01). Laser photocoagulation was administered in 75 eyes (62.0%), out of which 29 (38.1%) had new vessel relapse and required additional laser treatment. The median ischemic index was 25.8% (interquartile range 10.2%-46%). Ischemia involving ≥2 quadrants was associated with increased risk of new vessel formation (HR 2.7, 95% CI 1.3-5.5, P= .003). Retinal vasculitis is associated with an increased risk of vision loss, mainly secondary to macular ischemia, and has a higher risk of macular edema compared to eyes with no vasculitis. Ischemia involving ≥2 quadrants is a risk factor for new vesselformation.

Improve our understanding of ocular fundus diseases with ultra-wide-field fluorescein angiography

Ultra-wide-field fluorescein angiography (UWFA) can obtain very wide retinal images (up to 200° ), and is a very helpful tool to detect peripheral retinal lesions which cannot be found by other imaging methods. Analyzing the characteristics of the UWFA images may improve our understanding, treatment outcomes and management strategies of ocular fundus diseases. However this technology is still in its premature stage, there is still a lot of work to be done to improve its clinical application and study the characteristics and clinical meanings of these peripheral retinal lesions. Key words: Retinal diseases/diagnosis; Fluorescein angiography; Diagnostic techniques, ophthalmological; Editorial

Comparative analysis of ultra-wide-field fluorescein angiography and early treatment diabetic retinopathy study 7 standard field photography in diabetic retinopathy

Objective To observe the ocular fundus features and consistency of classification of diabetic retinopathy (DR) by ultra-wide-field fluorescein angiography (UWFA) and the simulated early treatment diabetic retinopathy study (ETDRS) 7 standard field (7SF) imaging. Methods This is a retrospective clinical description study. Ninety-six eyes of 55 DR patients were included. The ages ranged from 25 to 73 years, with a mean age of (41.34±15.07) years. UWFA examination (British Optos 200Tx imaging system) using the protocol for obtaining 7SF images as described in the ETDRS, 7 circular regions with a range of 30 degrees are spliced as 7SF templates to determine the observation range. This template was then overlaid on the UWFA image to identify the potential viewable area of 7SF. And the visualized area of the retina, retinal non-perfusion (NP) area, retinal neovascularization (NV) area, and pan-retinal photocoagulation (PRP) area of UWFA and 7SF were quantified by a retinal specialist. Results UWFA imaging and 7SF imaging have a high degree of consistency in judging DR classification (kappa=0.851, P=0.000). The retinal visual area, NP area, NV area and PRP area of the UWFA imaging were 3.16, 3.38, 2.22 and 3.15 times more comparing with the simulated 7SF imaging (t=213.430, 45.013, 22.644, 142.665; P=0.000, 0.000, 0.003, 0.000). The lesions of 8 eyes were found outside the range of simulated 7SF imaging, including peripheral NP in 5 eyes, NV areas in 3 eyes, respectively. Conclusion UWFA imaging and simulated 7SF imaging are consistent to judge DR classification, but UWFA can find more peripheral retinal lesions. Key words: Diabetic retinopathy/diagnosis; Fluorescein angiography; Tomography, optical coherence

Application of ultra-wide-field fluorescein angiography and 7 standard field in retinal vein occlusion

Objective To observe the angiographic features of patients with retinal vein occlusion (RVO) by ultra-wide-field fluorescein angiography (UWFA) and compare with the conventional 7 standard field (7SF) imaging. Methods This is a retrospective clinical description study. Fifty-eight eyes of 56 RVO patients were included. There were 25 males (26 eyes) and 31 females (32 eyes). The age ranged from 25 to 69 years, with a mean age of (48.12±18.56) years. The course of disease was from 2 days to 25 months, with a mean course of (12.78±11.35) months. Thirty eyes were diagnosed with central RVO (51.72%), 26 eyes were diagnosed with branch RVO (44.83%) and 2 eyes were diagnosed with hemicentral RVO (3.45%). Retinal laser photocoagulation was performed in 11 eyes (18.97%). All patients received examinations of UWFA (British Optomap 200Tx imaging system) and optical coherence tomography (OCT). Using the protocol for obtaining 7SF images as described in the Early Treatment Diabetic Retinopathy Study, 7 circular regions with a range of 30 degrees were combined as the 7SF template to determine the observation area. This template was then overlaid on the UWFA image to identify the potential viewable area of 7SF. The visualized retinal area, retinal non-perfusion area, retinal neovascularization area, and laser spot area of UWFA and 7SF were quantified by a retinal specialist. In addition, the OCT images of the affected eye were observed and analyzed to confirm the existence of macular edema. Correlation analysis was done between retinal non-perfusion, retinal neovascularization and macular edema detected by UWFA. Results The results of UWFA and 7SF examination were the same. Compared with 7SF, UWFA showed 3.53 times more retinal visual area, 3.31 times more non-perfusion area, 1.94 times more neovascularization area, and 3.59 times more laser spots (t=72.13, 4.69, 1.76, 5.78; P=0.000, 0.005, 0.102, 0.000). Lesions of 11 eyes (18.97%) were found outside the range of 7SF images. By UWFA, non-perfusion area correlated with neovascularization and macular edema (χ2=12.13, 4.82; P=0.000, 0.028; C=0.42, 0.28). Non-perfusion area anterior to the equator have significantly correlations with macular edema (χ2=6.32, P=0.012, C=0.31), but non-perfusion posterior to the globe equator have no relevance with macular edema (χ2=2.88, P=0.090, C=0.22). Conclusions UWFA can detect more peripheral retinal lesions than 7SF images. By UWFA, non-perfusion area has correlation with neovascularization and macular edema. Key words: Retinal vein occlusion/diagnosis; Fluorescein angiography; Tomography, optical coherence

Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections.

PurposeThe aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy.MethodsThis study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders.ResultsTwelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation.ConclusionIn patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA.

Case Series of Pediatric Sickle Retinopathy By Sensitive Clinical Imaging Technologies Suggests Frequent Early Pathology

Introduction: Sickle cell retinopathy (SCR) reflects disease-related vascular injury. Previous studies of pediatric SCR using standard imaging approaches reported retinopathy in <15% of children (Estepp JH, Br J Haematol 161:402;2013). Sensitive clinical retinal imaging modalities of ultra-widefield fluorescein angiography (UWFA), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCT-A) may better characterize early retinal changes in pediatric SCR. Fluorescein angiography detects retinopathy through dynamic visualization of retinal blood flow. UWFA captures up to twice as much retinal area as conventional fluorescein angiography and is more sensitive in identifying peripheral vascular changes in SCR (Friberg TR, Ophthalmic Surg Lasers Imaging 39:304;2008). SD- OCT and OCT-A utilize reflected light to produce detailed cross-sectional images of the retina and allow visualization of blood flow in retinal layers. To our knowledge, this is the first case series using these technologies in pediatric SCR. Methods: A consecutive series of children with sickle cell disease (SCD) of any phenotype, ages 10-19 years, accepting enrollment are described. Examinations including acuity, standard slit-lamp examination (biomicroscopy), UWFA, SD- OCT and OCT-A were performed according to standard acquisition protocols. Testing is non-invasive except fluorescein angiography, which requires a small volume of intravenous dye.Results: Eight children (mean age 16.3 years; 5 HbSS, 2 HbSC,1 HbS-Beta thalassemia0) were evaluated. Three were on hydroxyurea therapy, 1 on chronic transfusion, 1 on both and 3 on no therapy. No patient had vision disturbance at the time of examination. Biomicroscopic examination revealed sunburst lesions in the mid-peripheral retina in 3 patients and subtle vascular changes in the far periphery of all patients. In contrast, UWFA detected extensive capillary non- perfusion of the peripheral retina with abnormal vascular loops (Goldberg Stage I) in all 8 patients; 3 patients had peripheral arteriovenous anastomoses (Goldberg Stage II) that were undetectable by biomicroscopy. No patient had Goldberg Stages III-V. SD-OCT demonstrated thinning of the temporal macula in 2 patients, and OCT-A of both patients revealed flow voids in both the superficial and deep retinal capillary plexus in the area of thinned retina. Both the SD- OCT and OCT-A abnormalities were undetectable with standard biomicroscopy.Conclusions: All 8 children with SCD in this case series demonstrated evidence of SCR using the combination of standard biomicroscopy, UWFA, SD-OCT, and OCT-A imaging. Findings from these sensitive imaging modalities suggest that pediatric SCR is more prevalent than previously suspected. Additional patients and age-equivalent controls will be included in this report to validate the specificity of findings to SCD. Larger cross-sectional and prospective analyses using sensitive retina imaging are needed to confirm our findings and identify their significance for detecting pathology. If confirmed, these approaches may enhance early screening for patients at risk of vision-threatening consequences of SCR.Supported by the Irving Institute CTSA at CUMC and by 2T35HL007616 (DP). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CORRELATION OF MULTIMODAL IMAGING IN SICKLE CELL RETINOPATHY.

To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was Sβ thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and Sβ thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.

Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography

To assess whether the presence of peripheral nonperfusion on ultrawide field (UWF) fluorescein angiography (FA) is associated with diabetic retinopathy (DR) severity and the presence of predominantly peripheral lesions (PPLs). Single-site, cross-sectional, retrospective study. Sixty-eight eyes of 37 diabetic subjects with or without DR and no history of prior panretinal laser photocoagulation. Both 200° UWF images and UWF FA images were acquired at the same visit. Early Treatment Diabetic Retinopathy Study (ETDRS) templates were overlaid digitally based on disc and macula location onto stereographically projected UWF images. Images were evaluated for the presence of PPLs, defined as more than 50% of the graded lesion located outside the ETDRS field in each of the 5 extended fields. The UWF-FA images were evaluated by 2 masked, independent graders for extent of retinal nonperfusion area (NPA) and nonperfusion index (NPI; nonperfused/total gradable area). Association of NPA and NPI with DR severity and presence of PPLs. Distribution of DR severity was as follows: no DR, 8.8% eyes; mild nonproliferative DR (NPDR), 17.6%; moderate NPDR, 32.4%; severe NPDR, 17.6%; proliferative DR (PDR), 19.1%; and high-risk PDR, 4.4%; with PPL present in 61.8%. There was strong intragrader (r = 0.95) and intergrader (r = 0.86) agreement for NPA. Presence of PPLs was associated with increased NPA (191.8 mm(2) vs. 306.1 mm(2); P = 0.0019) and NPI (0.25 vs. 0.43; P = 0.0003). These relationships remained significant after adjusting for DR severity and diabetes duration. In eyes without PDR (n = 52), increasing NPA and NPI was associated with worsening DR (NPA, P = 0.001; NPI, P = 0.0003). NPA and NPI were not associated with clinically significant macular edema (NPA, P = 0.99; NPI, P = 0.67), nor correlated with visual acuity (NPA, r = 0.14, P = 0.23; NPI, r = 0.24, P = 0.05). Following a standardized protocol, the evaluation of UWF FA for NPA and NPI is reproducible. Both parameters are correlated highly with the presence of PPLs and DR severity. Given that the presence and extent of PPLs have been associated with increased risks of DR progression, the clinical identification of PPLs may reflect closely the extent of nonperfusion and ischemia, thus accounting for the increased risk of progression.

Reliability of Ischemic Index Grading in Common Retinal Vascular Diseases.

Retinal nonperfusion is closely associated with vision-threatening complications such as neovascularization and macular edema. The purpose of this study is to investigate the reliability of a calculated ischemic index (ISI) by means of intergrader and intragrader agreement on ultrawide-field fluorescein angiography (UWFFA) in common retinal vascular diseases. Eight trained graders evaluated 15 UWFFA images provided digitally and re-graded on a different day. They included five eyes with diabetic retinopathy (DR), five with branch retinal vein occlusion (BRVO), and five with central retinal vein occlusion (CRVO). To assess intergrader and intragrader agreement and variability among different diseases, the replicate inter- and intragrader standard deviations (SDs) and coefficients of variation (CVs) were calculated. Mean ISI was 46% for images of DR, 26% for images of BRVO, and 61.3% for images of CRVO. Combined intragrader and intergrader replicate SDs were 17.8% for DR, 3.8% for BRVO and 13.0% for CRVO. Combined intragrader and intergrader replicate coefficients of variation were 38.6% (percent of mean ISI) for DR, 14.7% for BRVO, and 21.2% for CRVO. Intergrader and intragrader variability was high when assessing DR. This may be due to the chronic nature of DR progression, which can lead to patchy areas of ischemia. Intergrader and intragrader variability was better for CRVO and best for BRVO. This may be due to the acute or subacute nature of retinal vein occlusions.

Patterns of Peripheral Retinal and Central Macula Ischemia in Diabetic Retinopathy as Evaluated by Ultra-widefield Fluorescein Angiography

To investigate the association between peripheral and central ischemia in diabetic retinopathy. Retrospective, cross-sectional. 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. 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). 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.

Role of ultra-widefield fluorescein angiography in the management of uveitis

ObjectiveTo discuss and illustrate the role of ultra-widefield fluorescein angiography (UWFFA) in the diagnosis and management of peripheral retinal vasculitis. DesignRetrospective case series. ParticipantsFour consecutive patients in whom UWFFA showed far peripheral vasculitis were included. All patients were seen between May 2011 and May 2012 at the Doheny Eye Institute. MethodsConventional fluorescein angiogram (FA) images or areas determined by the Early Treatment of Diabetic Retinopathy Study Group protocol for imaging the posterior pole and peripheral retina were superimposed on the UWFFA images. The ability to detect the extent and severity of vasculitis and vascular occlusion using both conventional FA and UWFFA was compared by 2 investigators, and any discrepancies were adjudicated by a third investigator. ResultsIn none of the cases was the full extent of vasculitis and capillary occlusion visible in the fields normally portrayed by conventional FA. In contrast, capillary nonperfusion and peripheral vasculitis were detectable by UWFFA in all cases. In 2 cases, the posterior extent of vasculitis could have been detected by conventional FA. ConclusionsDetection and depiction of the extent and severity of peripheral vascular changes are enhanced with UWFFA, aiding in the management of vasculitis in the retinal periphery.

Characterization of Ischemic Index Using Ultra-widefield Fluorescein Angiography in Patients With Focal and Diffuse Recalcitrant Diabetic Macular Edema

To explore the association of angiographic nonperfusion in focal and diffuse recalcitrant diabetic macular edema (DME) in diabetic retinopathy (DR). A retrospective, observational case series of patients with the diagnosis of recalcitrant DME for at least 2 years placed into 1 of 4 cohorts based on the degree of DR. A total of 148 eyes of 76 patients met theinclusion criteria at 1 academic institution. Ultra-widefield fluorescein angiography (FA) images and spectral-domain optical coherence tomography (SDOCT) images were obtained on all patients. Ultra-widefield FA images were graded for quantity of nonperfusion, which was used to calculate ischemic index. Main outcome measures were mean ischemic index, mean change in central macular thickness (CMT), and mean number of macular photocoagulation treatments over the 2-year study period. The mean ischemic index was 47% (SD 25%; range 0%-99%). The mean ischemic index of eyes within Cohorts 1, 2, 3, and 4 was 0%, 34% (range 16%-51%), 53% (range 32%-89%), and 65% (range 47%-99%), respectively. The mean percentage decrease in CMT in Cohorts 1, 2, 3, and 4 were 25.2%, 19.1%, 11.6%, and 7.2%, respectively. The mean number of macular photocoagulation treatments in Cohorts 1, 2, 3, and 4 was 2.3, 4.8, 5.3, and 5.7, respectively. Eyes with larger areas of retinal nonperfusion and greater severity of DR were found to have the most recalcitrant DME, as evidenced by a greater number of macular photocoagulation treatments and less reduction in SD OCT CMT compared with eyes without retinal nonperfusion. Areas of untreated retinal nonperfusion may generate biochemical mediators that promote ischemia and recalcitrant DME.

Comparison of ultra-widefield fluorescein angiography with the Heidelberg Spectralis&amp;reg; noncontact ultra-widefield module versus the Optos&amp;reg; Optomap&amp;reg;

PurposeTo compare ultra-widefield fluorescein angiography imaging using the Optos® Optomap® and the Heidelberg Spectralis® noncontact ultra-widefield module.MethodsFive patients (ten eyes) underwent ultra-widefield fluorescein angiography using the Optos® panoramic P200Tx imaging system and the noncontact ultra-widefield module in the Heidelberg Spectralis® HRA+OCT system. The images were obtained as a single, nonsteered shot centered on the macula. The area of imaged retina was outlined and quantified using Adobe® Photoshop® C5 software. The total area and area within each of four visualized quadrants was calculated and compared between the two imaging modalities. Three masked reviewers also evaluated each quadrant per eye (40 total quadrants) to determine which modality imaged the retinal vasculature most peripherally.ResultsOptos® imaging captured a total retinal area averaging 151,362 pixels, ranging from 116,998 to 205,833 pixels, while the area captured using the Heidelberg Spectralis® was 101,786 pixels, ranging from 73,424 to 116,319 (P = 0.0002). The average area per individual quadrant imaged by Optos® versus the Heidelberg Spectralis® superiorly was 32,373 vs 32,789 pixels, respectively (P = 0.91), inferiorly was 24,665 vs 26,117 pixels, respectively (P = 0.71), temporally was 47,948 vs 20,645 pixels, respectively (P = 0.0001), and nasally was 46,374 vs 22,234 pixels, respectively (P = 0.0001). The Heidelberg Spectralis® was able to image the superior and inferior retinal vasculature to a more distal point than was the Optos®, in nine of ten eyes (18 of 20 quadrants). The Optos® was able to image the nasal and temporal retinal vasculature to a more distal point than was the Heidelberg Spectralis®, in ten of ten eyes (20 of 20 quadrants).ConclusionThe ultra-widefield fluorescein angiography obtained with the Optos® and Heidelberg Spectralis® ultra-widefield imaging systems are both excellent modalities that provide views of the peripheral retina. On a single nonsteered image, the Optos® Optomap® covered a significantly larger total retinal surface area, with greater image variability, than did the Heidelberg Spectralis® ultra-widefield module. The Optos® captured an appreciably wider view of the retina temporally and nasally, albeit with peripheral distortion, while the ultra-widefield Heidelberg Spectralis® module was able to image the superior and inferior retinal vasculature more peripherally. The clinical significance of these findings as well as the area imaged on steered montaged images remains to be determined.

ULTRA–WIDE-FIELD ANGIOGRAPHY IMPROVES THE DETECTION AND CLASSIFICATION OF DIABETIC RETINOPATHY

To evaluate patients with diabetic retinopathy using ultra-wide-field fluorescein angiography and to compare the visualized retinal pathology with that seen on an overly of conventional 7 standard field (7SF) imaging. Two hundred and eighteen eyes of 118 diabetic patients who underwent diagnostic fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. The visualized area of the retina, retinal nonperfusion, retinal neovascularization, and panretinal photocoagulation were quantified by two independent masked graders. The respective areas identified on the ultra-wide-field fluorescein angiography image were compared with an overly of a modified 7SF image as outlined in the Early Treatment Diabetic Retinopathy Study. Ultra-wide-field fluorescein angiograms imaging, on average, demonstrated 3.2 times more total retinal surface area than 7SF. When compared with 7SF, ultra-wide-field fluorescein angiography showed 3.9 times more nonperfusion (P < 0.001), 1.9 times more neovascularization (P = 0.036), and 3.8 times more panretinal photocoagulation (P < 0.001). In 22 eyes (10%), ultra-wide-field fluorescein angiography demonstrated retinal pathology (including nonperfusion and neovascularization) not evident in an 7SF overly. Compared with conventional 7SF imaging, ultra-wide-field fluorescein angiography reveals significantly more retinal vascular pathology in patients with diabetic retinopathy. Improved retinal visualization may alter the classification of diabetic retinopathy and may therefore influence follow-up and treatment of these patients.