Advantages of the Utilization of Wide-Field OCT and Wide-Field OCT Angiography in Clinical Practice.

Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the peripheral retina. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation of these procedures in clinical practice and refers to them as traditional and ultra-wide-field fluorescein angiography (UWF-FA). A PUBMED search was performed using the terms WF-OCT OR WF-OCTA OR UWF-FA AND the specific clinical entity, and another search for diabetic retinopathy (DR), retinal vein occlusion (RVO), Coats disease, peripheral retinal telangiectasia, peripheral retinal degeneration, lattice degeneration, and posterior vitreous detachment. The analysis only included the studies in which the analyzed field of view for the OCT or OCTA exam was larger than 55 degrees. The evaluation of the extracted studies indicates that WF imaging with OCT and OCTA provides substantial information on retinal disorders involving the peripheral retina. Vascular diseases, such as DR or RVO, can be reliably evaluated using WF-OCTA with results superior to standard-field fluorescein angiography. Nevertheless, UWF-FA provides a larger field of view and still has advantages over WF-OCTA concerning the evaluation of areas of non-perfusion and peripheral neovascularization. Detailed information on the vascular morphology of peripheral changes should be obtained via WF-OCTA and not angiographic examinations. WF-OCT can serve as a valuable tool for the detection and evaluation of vitreoretinal traction, posterior vitreous detachment, and peripheral retinal degeneration, and guide therapeutic decisions on a patient's eligibility for surgical procedures.

Wide-Field Fluorescein Angiography in Patients with Idiopathic Acute Anterior Uveitis.

PURPOSE: To elucidate whether wide-field fluorescein angiography (WFFA) can yield additional information in patients with newly diagnosed idiopathic acute anterior uveitis (AAU). METHODS: The WFFA was performed in patients with idiopathic AAU, and the findings were analyzed according to the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Forty-four eyes of 30 patients (22 eyes of 13 patients in the pediatric group and 22 eyes of 17 patients in the adult group) were studied. The mean age was 12.41 ± 3.92 (range, 5-18) years in the pediatric group and 42.36 ± 32.07 (range, 24-68) years in the adult group. Thirteen eyes (59%) of pediatric patients and 12 eyes (54%) of adult patients showed some evidence of posterior segment activity on the WFFA (p = .764).     Systemic treatment was administered in 53.8% of the pediatric and 5.9% of adult patients, depending on the disease severity. CONCLUSION: Pediatric patients with idiopathic AAU may have subtle posterior segment manifestations more than adult patients, and posterior segment findings may affect the treatment preferences of physicians.

Topographic distribution of retinal neovascularization in proliferative diabetic retinopathy using ultra-wide field angiography.

Purpose: To analyze the topographic distribution of neovascularization (NV) and capillary nonperfusion (CNP) using ultra-wide field fluorescein angiography (UWFFA) in patients with proliferative diabetic retinopathy (PDR). Methods: This was a prospective, single-center, observational study in which all patients who presented between March 2019 and December 2020 and satisfied the inclusion criteria were recruited. In our study, patients with treatment-naïve PDR without any fibrovascular proliferation underwent UWFFA. The images were analyzed qualitatively for the topographic distribution of NV and the CNP area was quantified. The number of lesions picked by UWFFA was compared with 7 standard field (7SF) image using overlay of 7SF. The main outcome measure was characteristics of neovascularization, such as the number, location, and area of CNP, measured using UWFFA, which was considered with 95% confidence intervals (CI). Results: Two hundred and fifty-three eyes of 187 patients with a mean age of 56.03 ± 8 years were included. Mean neovascularization elsewhere (NVE) was 2.91 ± 3.43. Maximum NVEs were seen in the superotemporal (ST; 0.9 ± 1.13) quadrant, followed by the inferotemporal (IT; 0.7 ± 1.08), inferonasal (IN; 0.66 ± 1.02) and superonasal (SN; 0.66 ± 1.01) quadrants. Maximum CNP area was seen in the SN (13.75 ± 8.83 disc diameter square [DD2]) quadrant, followed by the IN (13.48 ± 8.59 DD2), IT (11.34 ± 8.37 DD2), and ST (11.3 ± 8.34 DD2) quadrants. Mean CNP area was maximum in patients with only neovascularization of disc (NVD; 64.99 ± 41.47 DD2), followed by both NVD and NVE (61.37 ± 35.61 DD2), and was minimum in patients with only NVE (36.44 ± 22.03 DD2). Eighty-one (32%) eyes out of 253 had NVE and 189 (75%) out of 253 had CNP area outside 7SF (overlay) of Early Treatment Diabetic Retinopathy Study (ETDRS). Conclusion: Diabetic NV lesions and CNP areas are distributed asymmetrically throughout the retina and are not restricted to the posterior pole. Compared to conventional 7SF imaging, UWFFA reveals significantly more retinal vascular pathology in patients with PDR.

Peripheral and central retinal vascular changes in asymptomatic family members of patients with familial exudative vitreoretinopathy.

PURPOSE: To evaluate the peripheral vascular changes and effects of these on macular microvasculature in asymptomatic family members of familial exudative vitreoretinopathy (FEVR) patients. METHODS: This is a retrospective study including 61 eyes of asymptomatic family members of FEVR patients. Retinal abnormalities were assessed via ultra-widefield fluorescein angiography (UWF-FA) and optical coherence tomography angiography (OCTA). The eyes were grouped into 3: the first group comprised of eyes with normal findings on UWF-FA; the second group comprised of eyes with abnormal findings on UWF-FA but without any retinal ischemia; and the third group involved eyes with retinal ischemia or neovascularization. RESULTS: Best corrected visual acuity (BCVA) was 20/20 in all eyes. Forty eyes (65.6%) had abnormalities on UWF-FA. The most common feature was peripheral vascular looping, increased tortuosity, and anastomosis (63.9%). ODM/ODD ratio was higher in group 3 compared to groups 1 and 2. Deep foveal VD was lower in group 1 compared to groups 2 and 3. The mean FAZ area and perimeter were smaller in groups 2 and 3 compared to group 1. CONCLUSION: Even asymptomatic family members of FEVR patients may have significant peripheral retinal vascular abnormalities which may be associated with smaller optic disc, macular ectopia, and macular microvascular changes.

Tubulointerstitial Nephritis and Uveitis Syndrome in the United Arab Emirates.

PURPOSE: To report the first series of tubulointerstitial nephritis (TINU) syndrome from the Middle East. METHODS: We retrospectively included patients with elevated urine beta-2 microglobulin, and a diagnosis of TINU based on anterior uveitis with or without posterior involvement. Multimodal imaging, duration of follow-up, local and systemic treatment used were recorded. RESULTS: 24 eyes of 12 patients (8 male, mean age 20.3 years) met the criteria for TINU. The most common posterior segment clinical finding was optic nerve head edema (41.7%), while on fluorescein angiography 58.3% and 75% of eyes had peripheral vascular and optic disc leakage, respectively. The mean follow-up was 2.5 years and all patients required immunomodulatory treatment. CONCLUSIONS: Middle Eastern patients with TINU seem to have a male predominance, a bimodal distribution in terms of age, and present with ocular involvement first. Multimodal imaging is paramount in detecting subclinical inflammation and tailoring immunomodulatory treatment.

An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of ß transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45-65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.

How to Achieve Near-Normal Visual Acuity with Bevacizumab in Diabetic Macular Edema Patients.

Patients suffering from diabetic retinopathy (DR) and diabetic macular edema (DME) are inherently interested in achieving normal or near-normal visual acuity. The study aimed to investigate factors influencing the visual acuity achieved by DME patients after bevacizumab (IVB) treatment. 98 patients (98 eyes) diagnosed with DR and DME underwent IVB treatment (9 injections/12 months). Patients were diagnosed and monitored using swept-source optical coherence tomography (SS-OCT), ultra-wide-field fluorescein angiography (UWFFA) and Early Treatment Diabetic Retinopathy Study (ETDRS) chart testing. We assessed macular central subfield thickness (CST), non-proliferative diabetic retinopathy (NPDR) indicators and best-corrected visual acuity (BCVA). After the treatment, patients were divided into BCVA≤75 and BCVA>75 groups. The IVB therapy increased the number of ETDRS letters read by about 9 and 8 in the BCVA≤75 and the BCVA>75 group, respectively. Before and after treatment, the BCVA>75 group had lower CST than the BCVA≤75 group. The treatment reduced macular CST by 177 µm in the BCVA≤75 group and only by 93 µm in the BCVA>75 group. Total non-perfusion area (NPA) decreased in both BCVA score groups after IVB therapy. Normal or near-normal vision can be achieved with IVB treatment, provided it starts when visual acuity is not significantly reduced yet. The ophthalmic screening of DR patients should also target those with relatively high visual acuity.

Evaluation and Comparison of Choroidal Thickness in Patients with Behçet Disease with versus without Ocular Involvement.

PURPOSE: To assess the subfoveal choroidal thickness (SFCT) in patients with Behçet disease (BD) and compare the SFCT in patients with and without ocular BD (OBD) and between patients with active and quiescent phases of the Behçet's posterior uveitis. METHODS: This prospective cross-sectional study was conducted on patients with BD (n = 51) between October 2016 and October 2018. Complete ocular examinations including slit lamp biomicroscopy and fundus examination with dilated pupils were performed for all patients. The SFCT values were compared between patients with and without OBD. Enhanced depth imaging optical coherence tomography (EDI-OCT) was done to measure the SFCT, and wide field fundus fluorescein angiography (WF-FAG) was performed to evaluate the ocular involvement and determine the active or quiescent phases of the Behçet's posterior uveitis. The correlation between the changes of SFCT and the WF-FAG scores was assessed. RESULTS: One hundred and two eyes of 51 patients with BD, aged 29 to 52 years were studied. Of these, 23 patients were male. The mean age ± standard deviation in patients with OBD and patients without ocular involvement was 38.71 ± 7.8 and 36.22 ± 10.59 years (P = 0.259) respectively. The mean SFCT in patients with OBD was significantly greater than in patients without OBD (364.17 ± 93.34 vs 320.43 ± 56.70 µm; P = 0.008). The difference of mean SFCT between the active compared to quiescent phase was not statistically significant when only WF-FAG criteria were considered for activity (368.12 ± 104.591 vs 354.57 ± 58.701 µm, P = 0.579). However, when the disease activity was considered based on both WF-FAG and ocular exam findings, SFCT in the active group was higher than the inactive group (393.04 ± 94.88 vs 351.65 ± 58.63 µm, P = 0.060). This difference did not reach statistical significance, but it was clinically relevant. CONCLUSION: Choroidal thickness was significantly increased in BD patients with ocular involvement; therefore, EDI-OCT could be a noninvasive test for evaluation of ocular involvement in patients with BD. The increased SFCT was not an indicative of activity in OBD; however, it could predict possible ocular involvement throughout the disease course.

Fluorescein Angiography Scoring System Using Ultra-Wide-Field Fluorescein Angiography Versus Standard Fluorescein Angiography in Patients with Sarcoid Uveitis.

Purpose: To compare standard fluorescein angiography (FA) and ultra-wide-field (UWF) FA in evaluating sarcoid uveitis activity using the scoring system adopted by the Angiography Scoring for Uveitis Working Group (ASUWG).Methods: Standard and UWF FA images of 36 eyes with sarcoid uveitis were acquired on the same day. Three graders independently graded 72 FA images using the ASUWG scoring system. We evaluated inter-observer variability using the intra-class correlation coefficient (ICC) and compared scores of each angiographic sign.Results: The ICC was 0.77 for standard FA and 0.87 for UWF FA, with respective total scores of 12.0 and 14.6. UWF FA had higher scores than standard FA for optic disc hyperfluorescence, posterior retinal vascular staining and/or leakage, and peripheral capillary leakage.Conclusions: The scores for UWF FA had a higher ICC than those for standard FA in evaluating sarcoid uveitis. Peripheral capillary leakage scores were particularly high for UWF FA.

Wide-field optical coherence tomography angiography for the detection of proliferative diabetic retinopathy.

PURPOSE: To compare the ability of wide-field optical coherence tomography angiography (WF-OCTA) to that of ultra-wide field fluorescein angiography (UWF-FA) and ultra-wide-field color fundus photography (UWF-CP) to detect retinal neovascularization (NV) in eyes with proliferative diabetic retinopathy (PDR). METHODS: In this cross-sectional study, naïve patients with active PDR underwent UWF-FA and UWF-CP using the Optos 200Tx and WF-OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000. NV was defined on OCTA when the co-registered B-scan with flow overlay of the vitreoretinal interface (VRI) segmentation showed extraretinal proliferation. Three masked readers examined the UWF-FA, UWF-CP, and WF-OCTA independently for the presence of NV. Statistical analysis was performed to compare the diagnostic accuracy of the 3 wide-field imaging modalities using OCT B-scan as the reference standard. RESULTS: In 82 eyes with PDR, neovascularization of the disc (NVD) was detected in 13 eyes by UWF-CP, 35 eyes with UWF-FA, and 37 eyes with OCTA using the VRI slab. Upon review of the 2500 OCT B-scans with superimposed flow overlay of each eye, NVD was confirmed in 37 eyes. The sensitivity and specificity of NVD detection were 35.1% and 97.8%, respectively for UWF-CP; 94.6% and 100%, respectively, for UWF-FA; and 100% and 100% for WF-OCTA. One hundred ninety-six foci of neovascularization elsewhere (NVE) were identified with the OCT B-scan with superimposed flow overlay. UWF-CP analysis was able to detect 62 foci of NVE of the 196 confirmed by B-scan (31.6% detection rate). An additional 11 foci of NVE seen on UWF-CP were not confirmed by B-Scan (15% false positive rate). There were 182 foci of NVE identified by UWF-FA (detection rate 91.3%), while WF-OCTA detected 196 retinal NVEs (detection rate 100%). The rate of false positives for both UWF-FA and WF-OCTA was low (< 2%). CONCLUSION: WF-OCTA can identify NV that is not evident in UWF-CP and represents a faster and safer alternative to UWF-FA for surveillance of PDR with comparable diagnostic accuracy.

Automated measurement of leakage on wide-field angiography in the assessment of retinal vasculitis.

Automated analysis of leakage on fluorescein angiography is a measurable and clinically applicable endpoint that can be used to follow patients with posterior uveitis. A number of studies have analyzed the use of automated analysis of leakage on fluorescein angiography and are reviewed in this article.

Peripheral retinal avascularity and capillary leakage in central serous chorioretinopathy.

PURPOSE: To report a novel finding of peripheral retinal avascularity (PRA) and peripheral capillary leakage (PCL) on wide-field fluorescein angiography (WFA) in non-dependent quadrants, in eyes with bilateral chronic central serous chorioretinopathy (CSCR). METHODS: Forty six patients with bilateral CSCR were studied. Four patients had PRA and PCL, and 42 patients did not. The demographic profile, clinical findings, and imaging characteristics of the two groups were compared. RESULTS: There was no significant difference between those patients with and without PRA and PCL with respect to the demographic profile, clinical findings, and imaging characteristics. Laser photocoagulation to extrafoveal points of leakage seen on fluorescein angiography (FA) was sufficient to cause complete resolution of CSCR in these 4 patients. PRA areas were not treated. CONCLUSION: The PRA and PCL in CSCR are novel findings, which have not been previously described.

Peripheral Microvascular Abnormalities Detected by Wide-Field Fluorescein Angiography in Eyes with Branch Retinal Vein Occlusion.

PURPOSE: To evaluate the location of microvascular abnormalities using wide-field fluorescein angiography (WFFA) and investigate the impact on visual outcome in eyes with branch retinal vein occlusion (BRVO). METHODS: Forty eyes of 39 patients (24 males and 15 females with an average age of 71 years) were retrospectively reviewed. One patient had BRVO bilaterally. WFFA was performed in all patients to evaluate perfusion status and detect microvascular abnormalities. The WFFA images were divided into 3 zones: zone 1, posterior pole; zone 2, mid-periphery; zone 3, far periphery, in order to document the presence of microvascular abnormalities. Scatter retinal photocoagulation (PC) was performed for retinal neovascularization (NV) and/or widespread nonperfused areas (NPAs). RESULTS: The incidence of microvascular abnormalities in zone 3 was significantly (p < 0.0001) less than in zones 1 and 2. The presence of larger NPAs in zone 1, but not in zone 3, was associated with the incidence of NV and vitreous hemorrhage. The presence of peripheral lesions and the application of PC did not affect the visual outcome. CONCLUSION: The presence of peripheral abnormalities or scatter PC for NPAs did not affect the visual outcome in eyes with BRVO.

Extension of peripheral nonperfusion in eyes with retinal vein occlusion during intravitreal dexamethasone treatment.

BACKGROUND: To evaluate the change in peripheral perfusion status in patients with retinal vein occlusion (RVO) during dexamethasone treatment. METHODS: Thirty-five eyes of patients with macular oedema due to either branch or central retinal vein occlusion were included. At baseline, patients were treated with an intravitreal dexamethasone implant (Ozurdex® ) and followed until month 6. Wide-field angiographies were classified as ischaemic and nonischaemic. Peripheral nonperfusion (PNP) was determined manually by calculating the percentage of nonperfusion area in relation to the total visible retina (ischaemic index). RESULTS: Thirteen eyes showed evidence of >10 disc area of PNP at baseline and were graded as ischaemic RVO. In nonischaemic eyes, the mean area of PNP was 0.3% at baseline, 0.6% after 1 month, 0.6% after 3 months and 0.6% after 6 months, respectively (p > 0.05). In ischaemic RVO, the ischaemic index was calculated to be 18% at baseline. One month after treatment, mean area of PNP was 16% and after 3 months was 19% (p = 0.8; p = 0.6). After retreatment, total PNP area was 18% (month 6; p = 0.9). During treatment, best-corrected visual acuity (BCVA) increased and central retinal thickness (CRT) decreased from baseline to final follow-up with no differences between nonischaemic/ischaemic RVO. A significant negative correlation between the total area of PNP and visual acuity was identified (r = -0.6; p = 0.04). CONCLUSION: Using 200° wide-field fluorescein angiography, the ischaemic index was shown to remain stable during dexamethasone treatment. This finding was consistent in ischaemic as well as in nonischaemic conditions.

Inter-observer Variability in Scoring Ultra-wide-field Fluorescein Angiography in Patients with Behçet Retinal Vasculitis.

PURPOSE: To test inter-observer agreement in applying the scoring system of the Angiography Scoring of Uveitis Working Group (ASUWG) to ultra-wide-field fluorescein angiograms (UWFA) obtained from patients with Behçet retinal vasculitis. METHODS: Both standard FA and UWFA images were obtained from 21 patients with retinal vasculitis associated with Behçet disease. Three graders independently graded 21 series of standard FA and 21 series of UWFA images. Spearman rank correlation and the intra-class correlation coefficient (ICC) were used to analyze the correlations. RESULTS: Total scores of all angiographic signs observed in both UWFA and standard FA images were significantly correlated between each pair of graders and among the three graders (ICC of standard FA = 0.874, p<0.001; ICC of UWFA = 0.928, p<0.001). CONCLUSIONS: The ASUWG scoring system is a reliable method of scoring UWFA images with regard to judging the activity of retinal vasculitis in ocular Behçet disease.

Role of Ultra-Wide Field Imaging in the Management of Tubercular Posterior Uveitis.

PURPOSE: To assess the utility of ultra-wide field (UWF) versus conventional fundus imaging in the management of tubercular (TB) posterior uveitis. METHODS: Twenty-two consecutive patients (33 eyes) diagnosed with TB posterior uveitis in a tertiary care center who underwent UWF fundus photography and fluorescein angiography (FA) between July 2014 and March 2015 were included. Complete clinical and imaging records of the patients were retrospectively reviewed. A circle simulating the central 75-degree field was drawn on UWF pseudocolor and fluorescein angiography images. Findings within the circle were compared with the information yielded by the complete image and its impact on patient management was noted. RESULTS: The clinical manifestations of posterior tubercular uveitis included retinal vasculitis (17 eyes), multifocal serpiginoid choroiditis (13 eyes), choroidal granulomas (2 eyes) and intermediate uveitis (1 eye). UWF imaging revealed additional capillary non-perfusion areas, neovascularization, active vasculitis, and peripheral choroiditis lesions in 30/33 eyes (90.9%), which influenced treatment decision in 15 eyes (45.5%). CONCLUSIONS: UWF imaging is useful in the detection of peripheral pathologies in tubercular posterior uveitis that may influence management decisions, such as addition of immunosuppressive therapy or scatter laser photocoagulation.

Simplified correction of ischemic index in diabetic retinopathy evaluated by ultra-widefield fluorescein angiography.

PURPOSE: To develop a novel, simplified method for correcting the ischemic index of nonperfused areas in diabetic retinopathy (DR). METHODS: We performed a retrospective review of 103 eyes with naive DR that underwent ultra-widefield angiography (UWFA) over a year. UWFAs were graded according to the quantity of retinal non-perfusion, and uncorrected ischemic index (UII) and corrected ischemic index (CII) were calculated using a simplified, novel method. RESULTS: The average differences between UII and CII in the non-proliferative DR group and the proliferative DR group were 0.7 ± 0.9% in the <25% CII group, 3.0 ± 0.9% in the 25% to 49.9% CII group, and 3.6 ± 0.6% in the >50% CII group, respectively. A CII >25% was critical for determining DR progression (p < 0.001). CONCLUSIONS: Distortion created by UWFA needs to be corrected because the difference between UII and CII in DR increases with the ischemic index.