Ultra-widefield Fundus Fluorescein Angiography Research Articles

An Update on Noninfectious Retinal Vasculitis.

Retinal vasculitis (RV) signifies the inflammation of various retinal vessels. Noninfectious RV differs from infectious RV with regard to its pathogenesis and treatment. It can have varied clinical presentations and may be associated with systemic vasculitic diseases. Noninfectious RV can be caused due to type-III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. Noninfectious RV is primarily classified on the basis of the type of retinal vessels involved. It can be further classified as an occlusive or nonocclusive. RV can be a major association of systemic diseases like Behcet's disease, sarcoidosis and systemic lupus erythematosus. Newer modalities, like ultra-widefield fundus fluorescein angiography, can help in the management of RV. Effective treatment of noninfectious RV requires anti-inflammatory and immunosuppressive therapy. The patients may require treatment with high-dose corticosteroids and biological agents. Anti-vascular endothelial growth factor injections and laser photocoagulation may be indicated to treat the occlusive disease. Prompt treatment may prevent complications like vitreous hemorrhage, neovascular glaucoma, and tractional retinal detachment. The treatment more often requires a multidisciplinary approach. This review provides a comprehensive update on the various causes of noninfectious RV, including both systemic and isolated ocular conditions. It also details various complications and management strategies for this condition.

RELATIONSHIP BETWEEN RETINAL HEMORRHAGE ON GREEN AND RED CHANNELS OF ULTRA-WIDEFIELD FUNDUS IMAGES AND RETINAL PERFUSION IN ACUTE BRANCH RETINAL VEIN OCCLUSION.

To explore the relationship between retinal hemorrhage in the green and red channels on ultra-widefield fundus images and the nonperfusion area (NPA) on ultra-widefield fundus fluorescein angiography in patients with acute branch retinal vein occlusion (BRVO). This was a retrospective cross-sectional study with 96 patients, including 46 with ischemic BRVO and 50 with nonischemic BRVO. Correlation analysis between green channel hemorrhage (GCH), red channel hemorrhage (RCH), and NPA was performed. Panretina was divided into posterior and peripheral areas. Ischemic BRVO showed significantly higher GCH% and RCH% than nonischemic BRVO in the peripheral regions (both P < 0.001), whereas no significant differences were observed in the panretinal and posterior areas (all P > 0.05). Significant correlations were found between NPA% in the panretinal and peripheral areas and the corresponding GCH% and RCH% (all P < 0.01). However, no significant correlation was observed between posterior NPA% and posterior GCH% or RCH% (both P > 0.05). In addition, peripheral GCH% and RCH% were related to panretinal NPA% (r = 0.506, P < 0.001; r = 0.558, P < 0.001). Retinal hemorrhage on ultra-widefield fundus image was significantly associated with NPA, providing insights for assessing retinal perfusion status in acute BRVO patients.

Evaluation of Inflammation in the Peripheral Multiple Sclerosis Retina Using Ultra-Widefield Optical Coherence Tomography: A Pilot Study.

Reports of fundus fluorescein angiography (FFA) in active multiple sclerosis (MS) have shown peripheral perivenous sheathing. We sought to assess the feasibility of ultra-widefield (UWF) FFA and optical coherence tomography (OCT) in assessing the peripheral retina in MS. Participants with MS and healthy controls underwent bilateral UWF fundus photography and FFA. Swept-source OCTs were captured centrally, peripherally, and to delineate any abnormalities visualized. We recruited five people with relapsing remitting MS, with a mean age of 36.9 (± 9.9), mean disease duration of 11 years (± 6.3), and a median expanded disability status score of 0.75 (0 to 2.5). In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. A pilot study using UWF-FFA and peripheral OCT to examine the retina in MS suggests that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:586-588.].

New approaches in the detection and management of diabetic retinopathy in the near future

Diabetes mellitus (DM), a group of metabolic diseases characterized by hyperglycemia, is a major public health problem worldwide. In recent years, the incidence and prevalence of DM has been increasing as a global epidemic. Diabetic retinopathy (DR) is the most common complication of DM and remains the major cause of preventable blindness among working-age people in most developed countries and it has a significant socioeconomic impact and source of morbidity. DR, which has long been recognized as a microvascular disease, has been demonstrated by laboratory and clinical evidence that inflammation and retinal neurodegeneration may also contribute to diabetic retinal damage in the early stages of DR. New diagnostic and treatment modalities in DR management is promising. Further elucidation of the underlying molecular mechanisms may provide new medical approaches for the development of novel therapeutic modalities. Nowadays, novel diagnostic devices such as ultrawide field fundus fluorescein angiography, optic coherence tomography angiography and adaptive optics retinal imaging have improved the detection of DR earlier, faster and more accurately. Subthreshold micropulse laser and other laser photocoagulation applications may be an alternative to conventional retinal photocoagulation with lower complications for DR treatment. In recent years, artificial intelligence, machine learning, and deep learning based diagnosis and treatment applications are developing. In addition, in recent years, unmanned automated-based diagnostic and treatment methods and newly developed intravitreal drugs and implants can offer more diagnostic and treatment options with promising results. This review provides an overview of novel diagnostic and treatment approaches for preventing the progression of diabetic retinopathy.

Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield fluorescein angiography for the evaluation of lesions in retinal vein occlusion

BackgroundTo compare widefield swept-source optical coherence tomography angiography (SS-OCTA) with ultra-widefield fundus fluorescein angiography (UWF-FA) for detecting retinal vein occlusion (RVO) lesions.MethodsThirty-four eyes of 32 patients with treatment-naïve RVO were enrolled at Peking University People’s Hospital from September 2021 to March 2022. Patients were imaged with a UWF-FA (200°) and a widefield SS-OCTA using 24 × 20 mm scan single capture. Quantitative assessments of RVO lesions such as foveal avascular zone (FAZ) area and perimeter, non-perfusion areas (NPA), number of microaneurysms (MAs), capillary changes and collateral vessels were performed.ResultsThe measurement of FAZ area and perimeter were comparable between SS-OCTA and UWF-FA (0.373 (range, 0.277–0.48) mm2 vs. 0.370 (range, 0.277–0.48) mm2, P = 0.818 and 2.480 (range, 2.011–2.998) vs. 2.330 (range, 2.027–2.807) mm, P = 0.536, respectively). Intraclass correlation coefficients (ICCs) of FAZ area and perimeter between SS-OCTA and UWF-FA was high (0.999, [0.997–0.999] and 0.996 [0.991–0.996], respectively), suggesting good agreement. The mean NPA area was larger on SS-OCTA than that on UWF-FA (89.977 ± 78.805 mm2vs. 87.944 ± 77.444 mm2, P = 0.037). The ICC of NPA area was also high (0.999, [0.999–1.000]). The median of total MA count was less on SS-OCTA than on UWF-FA (7 (range, 0–19) vs.12 (range, 0–23), P < 0.001). Agreement in detecting MAs between SS-OCTA and UWF-FA was found to be good (ICC = 0.920, [0.555–0.974]).The total capillary changes and collateral vessels count were less on UWF-FA than SS-OCTA (11 ± 9 vs 6 ± 7, P < 0.001 and 4 (range, 0–6) vs 0 (range, 0–0), P < 0.001, respectively). Agreement in detecting capillary changes and collateral vessels between OCTA and UWF-FA was found to be fair (ICC = 0.733, [0.081–0.905] and 0.564, [0.039–0.805], respectively).ConclusionCompared with UWF-FA, widefield SS-OCTA was found comparable or even superior in detecting FAZ, NPA, capillary changes and collateral vessels except MAs in RVO. Widefield SS-OCTA may offer a more efficient alternative to FA for diagnosis and monitoring RVO.

The evaluation of the efficacy of adalimumab in refractory non-infectious uveitis with ultra-widefield fundus fluorescein angiography.

To investigate the efficacy of adalimumab in the cases with refractory non-infectious uveitis and evaluate retinal vascular leakage changes on ultra-widefield fundus fluorescein angiography. Twenty-three patients with refractory uveitis were included in study. Forty-four eyes of 23 patients with non-infectious uveitiswere evaluated. Clinically active inflammation was present in 19 eyes (43.18%), while 25 (56.8%) were inactive. The mean drug burden was a 9.91 ± 3.78 (5-21) in baseline, 7.3 ± 4.25 at third and 8.0 ± 4.71 at sixth month (p = 0.022). The mean choroidal thickness was 256.65 ± 43.63μm in baseline, 240.49 ± 36.73μm at third and 224.81 ± 34.91μm at sixth month (p ≤ 0.05). In terms of leakage extend, leakage was initially present in a mean of 2.95 ± 4.55 clock hours, 2.41 ± 3.91 at third and 1.76 ± 3.44 at sixth month (p < 0.001). Adalimumab was found to be effective in establishing inflammation control by reducing drug burden, controlling retinal vascular leakage and choroidal inflammation in refractory uveitis.

Ultra-Widefield Fundus Fluorescein Angiography Findings in Patients with Fuchs' Uveitis Syndrome.

Background:The aim of this study was to evaluate ultra-widefield (UWF) fundus fluorescein angiography (FFA) findings in patients with Fuchs’ uveitis syndrome (FUS).Materials and Methods:This cross-sectional study was conducted in patients with FUS. All the patients underwent a complete ophthalmologic examination, and FFA was carried out with Optos UWF retinal imaging. Standard FFA and image acquisition consisted of early phase (15–45 s) images, and late-phase (5–10 min) images were also obtained for both eyes.Results:Forty eyes from twenty unilateral FUS patients, including 11 females (55%), who had a mean age of 38.50 ± 6.97 years, were enrolled. Eighty-five percent of the FUS eyes had optic disc hyperfluorescence (ODH) in the FFA. A significant relationship was observed between ODH and iris heterochromia (P = 0.004). ODH was seen in all the patients with iris heterochromia (n = 16). Peripheral vascular leakage (PVL), capillary nonperfusion, chorioretinal scar, and vascular sheathing were observed in 3, 3, 2, and 8 of the patients’ eyes, respectively.Conclusion:UWF FFA imaging seemed to be mandatory for evaluating the prognosis of the FUS patients, and another investigation may require to be conducted to evaluate the effect of antivascular endothelial growth factor agents for the management of PVL in these patients.

Application of iris angiography combined with ultra-wide-field fundus fluorescein angiography in diabetic retinopathy

Objective: To explore the application and value of iris angiography combined with ultra-wide-field fundus fluorescein angiography (UWFA) in diabetic retinopathy (DR). Methods: This was a cross-sectional study. From May 2016 to December 2019, 60 consecutive DR patients (120 eyes) including 30 patients (60 eyes) with severe non-proliferative DR (NPDR) and proliferative DR (PDR), respectively, who underwent iris angiography combined with UWFA in Tianjin Medical University Eye Hospital were enrolled in the study. There were 25 males and 35 females, with an average age of (53.5±10.7) years. All of the patients underwent ophthalmologic examination including visual acuity, intraocular pressure, slit-lamp microscopy, slit-lamp funduscopy, ultra-wide-field fundus photography, and iris angiography combined with UWFA. Iris angiography included iris fluorescein angiography (IFA) and iris indocyanine green angiography. The onset time of the iris vascular fluorescein leakage was recorded, and the circumference range of the pupil margin fluorescein leakage was measured by a self-developed software. Wilcoxon rank sum test was used to compare and analyze the difference in the onset time and the range of the iris vascular fluorescein leakage between the severe NPDR and PDR groups. Results: IFA showed that the onset time of the iris vascular fluorescein leakage was 31.00 (25.75, 34.00) s and 27.00 (21.75, 29.50) s in the severe NPDR group and the PDR group, respectively. The difference between two groups was statistically significant (Z=-2.13, P=0.033). The range of the iris vascular fluorescein leakage was 20.00(10.75, 75.00)° and 135.00(60.00, 182.50)° in the severe NPDR group and the PDR group, respectively. There was significant difference between two groups (Z=-4.23, P<0.001). Neovascularization of the iris was not found in all patients with PDR by slit-lamp microscope examination, but was found in 8 eyes by IFA and iris indocyanine green angiography. UWFA findings demonstrated that there was no strong fluorescence in retinal neovascularization elsewhere and/or neovascularization of the optic disc in severe NPDR patients. However, that could be seen in all PDR patients. Among them, 10 eyes had terminally petaloid or focal fluorescein leakage in macular area. Conclusions: Iris angiography combined with UWFA and quantitative analysis method could not only accurately assess the degree of fundus lesions, but also obtain more accurate and comprehensive iris vascular information, which provided help for comprehensive and personalized treatment of DR. (Chin J Ophthalmol, 2021, 57: 916-921).

Application of iris fluorescein angiography in diabetic iridopathy and retinopathy in brown iris.

This study aimed to evaluate the relationship between diabetic iridopathy (DI) and diabetic retinopathy (DR) and distinguish iris neovascular and physiological leakage using iris fluorescein angiography (IFA). A total of 210 subjects were prospectively recruited in this study. Sixty normal subjects were divided equally into three groups (<40 years old, 40-59 years old, and 60-79 years old). One hundred fifty patients with diabetic mellitus (DM) were divided equally into five groups (no retinopathy, mild non proliferative DR (mildnPDR), moderate nPDR, severe nPDR, and PDR group). Normal subjects underwent IFA. Patients with DR underwent both IFA and ultrawide field fundus fluorescein angiography (uwFFA) at the same time. The leakage time and area were recorded and compared with each group. Fluorescein leakage occurred at the pupillary edge of patients that were 40-59 and 60-79 years old but not in those <40 years old. In the PDR group, the leakage time was earlier and the leakage area was larger than nPDR and patients with no retinopathy (p = 0.039 and p = 0.005, respectively). However, the leakage time and area were not significantly different between patients with no retinopathy and nPDR (p > 0.05). IFA examination can only assist in estimating the fundus severity of PDR patients, whereas the fundus changes of patients with no retinopathy and nPDR were not related to DI changes.Trial registration No.: ChiCTR1800018003.The date of registration: Aug 26th, 2018.

Ultra-widefield fundus fluorescein angiography findings in patients with ankylosing spondylitis experiencing uveitis.

To evaluate ultra-widefield fundus fluorescein angiography (FFA) findings in cases of ankylosing spondylitis (AS)-associated uveitis. Forty-five eyes of 23 AS patients followed up with a diagnosis of uveitis were included. Sixteen (69.6%) men and seven (30.4%) women with a mean age of 46.26 ± 10.87 years were included in the study. Retinal vascular leakage was observed in 19 (42.2%) eyes at FFA, diffuse in six (13.3%) and peripheral in 13 (28.9%) eyes. Active anterior uveitis attack was present in seven (36.8%) eyes with vascular leakage at FFA, while no active uveitis findings were present in 12 (63.15%) eyes. No statistical relation was determined between peripheral and diffuse leakage and active uveitis (p = 0.195). No significant association was also determined between both diffuse and peripheral leakage and visual acuity (p = 0.066). We observed widespread retinal vascular leakage at UWF angiography in AS patients (in eyes undergoing active uveitis attacks and inactive eyes).

Randomised trial of wide-field guided PRP for diabetic macular oedema treated with ranibizumab

BackgroundDiabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections.MethodPatients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year.ResultsThere were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33).ConclusionThe addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

Ultra-widefield fundus fluorescein angiography in pediatric retinal vascular diseases.

Purpose:To describe the utility of RetCam ultra-wide-field fundus fluorescein angiography in pediatric retinal vascular diseases.Methods:A retrospective chart review was carried out in 43 eyes of 22 pediatric patients who were diagnosed or suspected to have a retinal vascular disease. Fluorescein angiography was carried out using the 130 degree lens of RetCam 3. Fluorescein angiography guided treatment (laser/cryotherapy) was carried out wherever required.Results:Diseases studied included - coats disease, familial exudative vitreoretinopathy, retinopathy of prematurity, congenital retinal folds, double optic nerve head, persistent fetal vasculature and incontinentia pigmenti. RetCam assisted fluorescein angiography was helpful in establishing a diagnosis in 4 patients (18%), in decision making regarding treatment in 18 patients (82%), in deciding need for retreatment in 5 patients (23%), helped in staging of disease in 5 patients (23%) and in detecting clinically subtle findings in 6 patients (27%).Conclusion:RetCam assisted FFA is extremely useful to document peripheral retinal vascular pathologies in pediatric patients and helps to take crucial therapeutic and retreatment decisions.

Evaluation of rhegmatogenous retinal detachments using Optos ultrawide field fundus fluorescein angiography and comparison with ETDRS 7 field overlay

PurposeTo evaluate the ultrawide field fundus fluorescein angiography (UWFA) characteristics of rhegmatogenous retinal detachments (RRDs) and compare the findings with an early treatment diabetic retinopathy study (ETDRS) 7 field (ETDRS7F) overlay. MethodsUWFA (Optos, PLC, Dunfermline, UK) was performed in 10 eyes with macula-off RRDs in 9 patients. The findings of UWFA were compared with that of an overlay of standard ETDRS7F. ResultsVascular dilation, tortuosity of vessels, and blockage of choroidal fluorescence were noted in all eyes in both UWFA and ETDRS7F overlay. Other findings in UWFA and ETDRS7F included peripheral perivascular staining (10 versus 4 eyes), peripheral capillary nonperfusion (CNP) (9 eyes compared to none), vascular loop formation (7 eyes versus none), optic disc hyperfluorescence (5 eyes in both), petaloid leak at macula (2 eyes in both), and neovascularization elsewhere (3 eyes versus none). ConclusionsPeripheral perivascular staining and leak, CNP, and vascular tortuosity are common UWFA features of RRDs. Standard ETDRS7F missed peripheral CNP, peripheral vascular loops, and peripheral retinal new vessels in all eyes compared to UWFA in the current study.

Ultra-widefield fundus fluorescein angiography in the diagnosis and management of retinal vasculitis.

PurposeTo quantify the additional information provided by ultra-widefield fluorescein angiography, compared with 7-field standard imaging, in patients with retinal vasculitis (RV).Patients and methodsRetrospective case series of 106 patients.ResultsRetinal vascular pathology was identified by UWF FFA, but not by standard ETDRS 7-field area, in 62 patients (58.5%) and in 79 eyes (43.4%). The pathology included active RV (47 eyes, 25.8% of eyes); retinal ischaemia, or infarction (53 eyes, 29.1%); and retinal neovascularization (7 eyes, 3.8%). A change to management was made in 36 patients (34%). Of these, 21 (20% of all patients undergoing angiography) were made after the identification of retinal vascular pathology, which was found only on UWF FFA, outside the ETDRS area.ConclusionUltra-widefield fluorescein angiography has clear advantages over standard multi-field imaging. It is currently the standard method of assessment for RV in this centre.

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results.

Heidelberg Spectralis Ultra-Widefield Fundus Fluorescein Angiography in Infants

To describe the intraoperative use of the Heidelberg Spectralis for ultra-widefield fundus fluorescein angiography in infants. Retrospective observational case series. A modified Heidelberg Spectralis was used to perform ultra-widefield fundus fluorescein angiography in infants undergoing an examination under general anesthesia for a range of retinal vasculopathies. Peripheral angiographic findings, angiographic image acquisition time, and any complications were reviewed. A total of 22 eyes of 11 infants underwent intraoperative ultra-widefield fundus fluorescein angiography using the modified Heidelberg Spectralis. Ultra-widefield fundus fluorescein angiography was successfully performed in all infants and permitted capture of the posterior pole as well as the peripheral retina in a single shot centered on the macula. Peripheral retinal pathologies captured include neovascularization, capillary nonperfusion, and skip areas from previous laser treatment. Capturing of angiographic images took a mean time of 7.09 minutes. Image artifact from condensation of the ultra-widefield lens was noted during imaging of 1 infant. The modified Heidelberg Spectralis is an effective and reliable imaging tool for performing ultra-widefield fundus fluorescein angiography in infants. It is capable of capturing wide-angle images of high quality. The technique has advantages as an alternative to RetCam fluorescein angiography in infants undergoing an examination under general anesthesia.

Current concepts in diabetic retinopathy.

For the past several decades, tremendous efforts have been made to decrease the complications of diabetes, including diabetic retinopathy. New diagnostic modalities like ultrawide field fundus fluorescein angiography and spectral domain optical coherence tomography has allowed more accurate diagnosis of early diabetic retinopathy and diabetic macular edema. Antivascular endothelial growth factors are now extensively used to treat diabetic retinopathy and macular edema with promising results. There remains uncertainty over the long term effects and the socioeconomic costs of these agents.