Is There a Nonperfusion Threshold on OCT Angiography Associated With New Vessels Detected on Ultra-Wide-Field Imaging in Diabetic Retinopathy?

Purpose: To determine whether the nonperfusion index (NPI) measured on widefield (WF) optical coherence tomography angiography (OCTA) could be used as an alternative method for the diagnosis of proliferative diabetic retinopathy (PDR) and to study the relationship between the NPI and the location of new vessels (NV) in eyes with PDR. Methods: Fifty-one treatment-naïve eyes with either severe nonproliferative DR (NPDR) or PDR were imaged using ultra-wide-field imaging and wide-field OCTA. Results: The NPI was significantly higher in eyes with PDR (18.94% vs. 7.51%; P < 0.01). Using the NPI on the whole image to assess PDR status, the area under the curve was 0.770, but the area under the curve increased when the NPI of the most peripheral circle was used (area under the curve of 0.792). Four eyes with PDR (17%) had NV outside the OCTA image field, and their mean NPI (6.15 %) did not differ from that measured in severe NPDR eyes (7.51%; P = 0.67) and was lower than in other eyes with PDR (21.49%; P = 0.023). The presence of NV in a sector was associated with a higher NPI in the same sector (29.2% vs. 6.0%; P < 10-15). Conclusions: Although the NPI was significantly higher in eyes with PDR compared with severe NPDR eyes, its measurement on the whole wide-field OCTA image was not sensitive enough to replace the detection of NV for the diagnosis of PDR. Translational Relevance: Because the presence of new vessels was related to the local nonperfusion index in the same sector, the assessment of nonperfusion outside the optical coherence tomography angiography field is important in diabetic retinopathy.

Retinal capillary and choriocapillaris assessment using a beam modifier optical coherence tomography angiography module to increase lateral optical resolution.

PURPOSE: To assess a new optical coherence tomography angiography (OCTA) technology and its contribution to retinal vascularization and choriocapillaris (CC) exploration. METHODS: A new module, named "Beam expander" (BE), which increases the lateral resolution of OCTA, was used in combination with a prototype software in the PLEX® Elite 9000 Swept-Source OCT instrument (ZEISS, Dublin, CA). This prospective study involved 22 healthy subjects imaged with and without BE. Qualitative analysis of superficial capillary plexus (SCP), deep capillary complex (DCC) retinal and CC angiograms were performed. Perfusion density (PD), vessel density (VD), and foveal avascular zone (FAZ) measurements were also compared. RESULTS: Qualitative analysis of single SCP and DCC retinal angiograms acquired with BE showed significantly better vessel sharpness (respectively, p = 0.0002, and p<0.0001), and greater peripheral image quality (p = 0.028 and p = 0.007) compared to standard OCTA images. Mean VD of whole retina single scans was significantly higher for BE angiograms compared to classic angiograms (28.16 ±1.29 mm-1 and 23.36 ±0.92 mm-1, respectively, p<0.0001). Repeatability of VD, PD and FAZ raw size were found to be similar between the two methods (intraclass correlation coefficient: 0.671, 0.604 and 0.994 with BE versus 0.764, 0.638 and 0.990 without BE). CC image quality was found to be significantly superior with BE, and flow deficits were more visible in all BE scans compared to standard scans. CONCLUSIONS: An increase in lateral resolution of the OCT beam resulted in higher quality of retinal and choriocapillaris OCTA images in healthy subjects. These results provide significant insights into the future OCTA imaging enhancements.

Two-Year Outcome of Aflibercept Intravitreal Injection in Vitrectomized Eyes with Diabetic Macular Edema.

Purpose: To evaluate the efficacy of intravitreal aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at two years. Methods: This is a prospective, non-comparative, multicenter observational study including diabetic patients with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Participants were managed at clinicians' discretion using Treat and Extend or Observe and Plan regimen during the second year. Visual acuity, OCT findings and number of IAI were assessed at two years. Results: Available data for 28 eyes with DME previously vitrectomized treated with aflibercept intravitreal injection during at least 2 years were collected. Visual gain was +5.4 letters (p = 0.01), and central macular thickness decreased significantly -62µm, p < 0.001) at 2 years. Resolution of macular edema allowing discontinuation of aflibercept was observed in 7 eyes (15%). Mean number of injections was 14.6, and mean interval injection was 6.4 weeks for 2 years. Conclusion: These results suggest that IAI is beneficial in vitrectomized eyes leading to improvement of visual and anatomical outcome which was maintained for 2 years.

Retinal Sensitivity Correlates With the Superficial Vessel Density and Inner Layer Thickness in Diabetic Retinopathy.

Purpose: The purpose of this paper was to present our study on the relationship between the parafoveal sensitivity measured using microperimetry and the vessel density (VD) assessed by optical coherence tomography-angiography (OCT-A) in eyes with diabetic retinopathy (DR). Methods: The observational case series was conducted in a tertiary ophthalmology center. Eyes with DR and without macular edema were consecutively included. All eyes underwent microperimetry and OCT-A. The correlation between the regional retinal sensitivity and the corresponding local capillary changes and structural alterations seen on OCT-A was assessed in each retinal quadrant. Results: Thirty-seven eyes of 21 patients were included. The mean retinal sensitivity was 28.7 ± 2 decibel (dB). The mean parafoveal VD was 43.2 ± 4.2% in the superficial capillary plexus (SCP) and 48.1 ± 3.3% in the deep capillary complex (DCC). In the multivariate linear regression model, the mean retinal sensitivity was positively correlated with the VD in the SCP in the parafoveal ring (P = 0.01) and with the inner nuclear layer (INL) thickness (P = 0.01). The qualitative analysis of each quadrant showed the presence of areas of capillary dropout with a normal sensitivity. Conversely, all areas of decreased sensitivity (<25 dB) were associated with a decreased VD in the SCP and the DCC. Conclusions: The parafoveal sensitivity positively correlated with the VD in the SCP in DR eyes. Areas with a low retinal sensitivity were always co-located with a loss of capillaries in the SCP and the DCC despite preserved outer retinal layers.

Impact of image averaging on vessel detection using optical coherence tomography angiography in eyes with macular oedema and in healthy eyes.

PURPOSE: To assess the repeatability of multiple automatic vessel density (VD) measurements and the effect of image averaging on vessel detection by optical coherence tomography angiography (OCTA). METHODS: An observational study was conducted in a series of healthy volunteers and patients with macular oedema. Five sequential OCTA images were acquired for each eye using the OptoVue HD device. The effect of the averaging of the 5 acquisitions on vessel detection was analysed quantitatively using a pixel-by-pixel automated analysis. In addition, two independent retina experts qualitatively assessed the change in vessel detection in averaged images segmented in 9 boxes and compared to the first non-averaged image. RESULTS: The automatic VD measurement in OCTA images showed a good repeatability with an overall mean intra-class correlation coefficient (ICC) of 0.924. The mean ICC was higher in healthy eyes compared to eyes with macular oedema (0.877 versus 0.960; p < 0.001) and in the superficial vascular plexus versus the deep vascular complex (0.967 versus 0.888; p = 0.001). The quantitative analysis of the effect of the averaging showed that averaged images had a mean gain of 790.4 pixels/box, located around or completing interruptions in the vessel walls, and a mean loss of 727.2 pixels/box. The qualitative analysis of the averaged images showed that 99.6% of boxes in the averaged images had a gain in vessel detection (i.e., vessels detected in the averaged image but not in the non-averaged image). The loss of pixels was due to a reduction in background noise and motion artifacts in all cases and no case of loss of vessel detection was observed. CONCLUSION: The automatic VD measurement using the OptoVue HD device showed a good repeatability in 5 acquisitions in a row setting. Averaging images increased vessel detection, and in about a third of boxes, decreased the background noise, both in healthy eyes and, in a greater proportion, in eyes with macular oedema.

Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR) and its risk factors in adult type 1 diabetes (T1D) patients METHODS: In this cross-sectional study, all T1D patients followed in the University Center for Diabetes and its Complications of Lariboisière Hospital (Paris, France) between January 2017 and February 2019 were included. Ophthalmologic and systemic data were collected from electronic records. The association between DR (and each grade) and associated factors were estimated by univariate and multivariate analyses using logistic regression models. RESULTS: A total of 1464 patients (46.2% of women, mean age: 42.2 ± 15.8 years) were included. The mean hemoglobin A1c (HbA1c) was 7.8 ± 1.7% and the mean diabetes duration was 20.5 ± 13.5 years. DR prevalence was 50.1% (47.4-52.6) and the prevalence of mild, moderate, and severe non-proliferative DR and proliferative DR was 19.1%, 9.4%, 3.9%, and 17.6%, respectively. DR was significantly associated with male gender, an older age, former and current smoking status, a higher BMI, the presence of nephropathy and neuropathy, higher HBA1c, and longer diabetes duration. Patients with HbA1c > 10% had an adjusted odds ratio (OR) of 3.25 (1.77-6.01) of having DR compared to patients with HbA1c < 6.5%. Patients with a diabetes duration > 30 years had an adjusted OR of 24.87 (14.82-42.67) higher of having DR compared to patients with a diabetes duration < 10 years. CONCLUSION: In this study, 50.1% of adult T1D patients had DR and 17.6% had proliferative DR. Diabetes duration and HbA1c were major risk factors.

ETOILE: Real-World Evidence of 24 Months of Ranibizumab 0.5 mg in Patients with Visual Impairment Due to Diabetic Macular Edema.

PURPOSE: To evaluate the real-world effectiveness of intravitreal ranibizumab 0.5 mg (Lucentis) in improving visual acuity (VA) in adults with decreased VA due to diabetic macular edema (DME). PATIENTS AND METHODS: Real-world prospective observational 24-month study. Ranibizumab-naïve patients (n=116) were enrolled, treated and followed up according to investigators' usual procedures. Outcomes included change from baseline to month 24 in best-corrected VA (BCVA; primary outcome), central retinal thickness (CRT), treatment exposure and safety. RESULTS: Overall, 62.9% of patients completed the study per protocol, 68.6% completed the induction phase (first three injections one month apart). On average, patients had 12.5 ophthalmologist visits and 5.74 injections in year 1, decreasing to 4.6 visits and 1.94 injections in year 2. Mean baseline BCVA was 58.4 letters, mean gain at M24 was +6.08 letters (95% CI: 2.95, 9.21). Gains were higher for patients who completed induction, and for patients who did not switch treatment. Mean CRT improved by 149.17 µm at M24. There were no new safety signals. BCVA variation of ≥6 letters by M3 was predictive of BCVA gains at M24 (p=0.007), as was hypertension medication at baseline (p=0.022). CONCLUSION: Real-world ranibizumab treatment improved VA in DME patients, despite fewer injections than recommended.

One-Year Outcome of Aflibercept Intravitreal Injection in Vitrectomized Eyes with Diabetic Macular Edema.

AIM: To evaluate the efficacy of intravitreal Aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at one year. METHODS: This is a prospective, non-comparative, multicenter observational study including diabetic patients whose HbA1c is < 9%, with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy since at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Visual acuity, OCT findings and number of IAI were assessed at 6 months and one year. RESULTS: Forty-six eyes were included. Indications for vitrectomy were epiretinal membrane (58.7%), intravitreal hemorrhage (26.1%), and vitreomacular traction (8.7%), retinal detachment (4.3%), and other cause (4.3%). Median duration of macular edema was 3 years. Median interval between vitrectomy and first visit was 9 months. Thirty eyes were non-naïve and received previously thermal laser (44.3%), intravitreal injection of triamcinolone (26.7%), of ranibizumab (70%), of dexamethasone implant (36.7%), or bevacizumab (6.7%). Data was available for 35 eyes at 1 year. Visual gain was significant, +6 letters (p <0.001) and central subfield thickness (CST) decreased significantly (-108µm, p < 0.001) at 1 year. Mean number of injections was 9.3 and mean interval injection was 5.8 weeks. CONCLUSION: These results suggest that IAI may be beneficial in vitrectomized eyes with refractory DME which require frequent injections to obtain visual and anatomical improvement. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, registration Number NCT02874859.

Ten-year incidence and assessment of safe screening intervals for diabetic retinopathy: the OPHDIAT study.

BACKGROUND: To estimate the 10-year incidence of referable diabetic retinopathy (DR) in a French population with type 1 and 2 diabetes mellitus (DM). A secondary objective was the assessment of safe screening intervals in patients with diabetes without retinopathy. METHODS: Observational, prospective and multicentric study between June 2004 and September 2017 based on a regional screening programme for DR in the Paris region. The incidence of referable DR in patients without retinopathy at baseline was calculated by the Turnbull survival estimator. A safe screening interval was defined as a 95% probability of remaining without referable DR. RESULTS: Among the 25 745 participants with type 1 (n=6086) or type 2 (n=19 659) DM, the 10-year cumulative incidence of referable DR was 19.10% (95% CI 17.21% to 21.14%) and 17.03% (15.78% to 18.35%), median (IQR) follow-up=3.33 (4.24) years. The safe screening interval for patients without DR at the first examination for type 1 and 2 DM was 2.2 (95% CI 2.0 to 2.4) and 3.0 (2.9 to 3.1) years, respectively. In a subgroup of low-risk patients with type 2 DM, the safe screening interval was 4.2 (3.8 to 4.6) years. CONCLUSIONS: These data suggest that in Paris area, a 2-year, 3-year and 4-year screening interval was considered safe for type 1 DM, type 2 DM and for low-risk patients with type 2 DM, respectively, without DR at the first examination. While these data might be used to support the consideration of extending screening intervals, a randomised clinical trial would be suitable to confirm the safety for patients with DM.

Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography.

Optical coherence tomography angiography is evolving towards wider fields of view. As single widefield acquisitions have a lower resolution, preventing an accurate segmentation of vascular plexuses in the periphery, we examined the retinal vascularisation from the macula to the periphery in all retinal quadrants, using 3 × 3-mm volume scans, to obtain montages with sufficient image resolution up to 11 mm from the foveal centre. Images were qualitatively and quantitatively analysed, using C- and B-scan approaches to calculate the capillary density (CD) and the interplexus distance (IPD). Three vascular plexuses (i.e., superficial vascular plexus: SVP, intermediate capillary plexus: ICP, and deep capillary plexus: DCP) were observed up to the mid-periphery in all sectors. The CD of the SVP decreased from about 5 mm of eccentricity, along with ganglion cell density decrease. The CD of the ICP progressively decreased from the fovea towards the periphery, along with the retinal thinning and then vanished from 8 to 9 mm of eccentricity, becoming undetectable beyond. This ICP disappearance resulted in an increased IPD between the SVP and the DCP in an area known to be frequently affected by capillary drop-out in diabetic retinopathy. The DCP only showed a slightly decreased CD towards the retinal periphery.

RAPID MACULAR CAPILLARY LOSS IN PATIENTS WITH UNCONTROLLED TYPE 1 DIABETES.

PURPOSE: To analyze the evolution of macular vessel density (VD) over 1 year, during early worsening of diabetic retinopathy, in patients with uncontrolled Type 1 diabetes (T1D). METHODS: Retrospective study of 12 eyes of 9 patients with T1D with early worsening of diabetic retinopathy imaged with optical coherence tomography angiography. The following data were collected at the time of pan retinal photocoagulation initiation and after 6 and 12 months: vessel density within three retinal plexuses-superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus; foveal avascular zone area, acircularity index, and flow density (FD)-300; central macular thickness; and HbA1c levels. RESULTS: A history of rapid reduction in blood glucose was found in seven of nine cases. Vessel density was significantly decreased at 12 months in all plexuses: from 44.68 ± 4.75 to 40.23 ± 7.13 in the superficial vascular plexus (P = 0.008), from 42.72 ± 4.86 to 37.12 ± 8.64 in the intermediate capillary plexus (P = 0.03), and from 22.68 ± 3.93 to 19.66 ± 4.92 in the deep capillary plexus (P = 0.004). Intermediate capillary plexus and deep capillary plexus changes were strongly correlated (r = 0.86, P < 0.001) and were significant as early as 6 months. The mean foveal avascular zone area increased (P = 0.05) and the FD-300 decreased (P = 0.03). No significant change in acircularity index, central macular thickness, and visual acuity were observed over time. CONCLUSION: Early worsening of diabetic retinopathy induces a rapid macular capillary dropout mainly affecting the intermediate capillary plexus and deep capillary plexus.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti-Vascular Endothelial Growth Factor.

PURPOSE: To assess change in retinal nonperfusion (NP) after anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) using 2 different imaging modalities: swept-source widefield (SS-WF) OCT angiography (OCTA) and ultra-widefield (UWF) fluorescein angiography (FA). DESIGN: Observational case series. PARTICIPANTS: Ten eyes of 9 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) initiating 3 monthly anti-VEGF intravitreal injections for DME. METHODS: All eyes were imaged with UWF color fundus photographs (CFPs), UWF FA, and SS-WF OCTA at baseline (M0) and 1 month after the third anti-VEGF injection (M3). All images were aligned and divided into 16 boxes for analysis of NP areas by 2 blinded retina specialists. MAIN OUTCOME MEASURES: The number of discrepancies between SS-WF OCTA and UWF FA regarding the detection of NP areas and small vessels passing through NP areas; assessment of DR severity on UWF CFP; and change in each NP area between M0 and M3: number of boxes/eye with presence of at least 1 NP area, number of arterioles or venules that disappeared or reappeared, and number of NP areas in which capillaries disappeared or reappeared. RESULTS: The diabetic retinopathy (DR) severity score improved by at least 1 stage in 8 of 10 eyes, with a significant decrease in the mean number of microaneurysms and retinal hemorrhages on UWF CFP at M3 versus M0 (n = 40±28 vs. 121±57; P = 0.0020) and regression of fundus neovascularization when present. All NP areas detected on FA were seen on SS-WF OCTA, but additional NP areas were detected on SS-WF OCTA at M0 in 29% (46/160) of boxes. No reperfusion of arterioles or venules was observed at M3 on FA or SS-WF OCTA. Retinal capillaries were only visible on OCTA, and no reperfusion in NP areas was observed even when a reduction in dark areas was visible on FA. CONCLUSIONS: No reperfusion of vessels or capillary network was detected in NP areas using 2 imaging techniques, UWF FA and SS-WF OCTA, in eyes with DR after 3 anti-VEGF injections. The detection rate of NP areas was higher with SS-WF OCTA than with UWF FA.

Reduced vessel density in the superficial and deep plexuses in diabetic retinopathy is associated with structural changes in corresponding retinal layers.

PURPOSE: To explore the relationships between vessel density (VD) in the retinal vascular plexuses with the thickness and structural changes of their corresponding retinal layers in patients with diabetic retinopathy (DR). METHODS: Retrospective analysis of 17 eyes of 17 Type 1 diabetes (T1D) patients with severe non-proliferative or proliferative DR and no current or past macular edema. Seventeen age- and sex-matched healthy subjects were included as controls. Using optical coherence tomography (OCT) and OCT-angiography (OCTA), VD was measured in the superficial vascular plexus (SVP) and deep vascular complex (DVC) that includes the intermediate (ICP) and deep capillary plexuses (DCP), and compared to the retinal thickness (RT) of the inner (from the inner limiting membrane to the inner plexiform layer) and intermediate (inner nuclear and outer plexiform layer) retinal layers. The correlation between the inner and intermediate RT and the VD of the corresponding vascular networks (SVP and DVC, respectively) was assessed. All OCT and OCTA examinations were performed using the RTVue XR Avanti (Optovue, Fremont, CA). RESULTS: The inner RT and VD in all plexuses were significantly reduced in T1D patients compared to healthy subjects. The capillary drop-out patterns were polygonal and well-defined in the SVP while the ICP and DCP showed a more diffuse capillary rarefaction and a VD that varied in the same proportion. The inner RT significantly correlated with VD in the SVP (r = 0.71 in healthy subjects and r = 0.62 in T1D patients, p <0.01). The intermediate RT did not significantly correlate with VD in the DVC. CONCLUSIONS: In T1D subjects, OCTA allowed observing different capillary drop-out patterns in the SVP and in the ICP-DCP, with different structural changes in the corresponding retinal layers, suggesting that they should be considered as distinct anatomical and functional entities.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY CAN IMPROVE DIABETIC RETINOPATHY SCORE WITHOUT CHANGE IN RETINAL PERFUSION.

PURPOSE: To compare the changes in retinal perfusion on ultra-wide-field fluorescein angiography with the changes in diabetic retinopathy lesions observed on ultra-wide-field fundus color photographs after 3 monthly anti-vascular endothelial growth factor injections. METHODS: Retrospective interventional cohort study analyzing the files of 14 patients with DR (18 eyes). UWF color photos and FA were analyzed at baseline (M0) and 1 month after the third anti-VEGF injection (M3). The main outcomes included the count of the number of red dots (microaneurysms, hemorrhages) and assessment of DR severity score (DRSS); the analysis of non-perfusion areas and disappearance or reappearance of arterioles or venules in the non-perfusion areas on FA. RESULTS: Eighteen eyes of 14 diabetic patients, with mean age of 63 ± 5 years, were included. The DRSS score improved by at least one stage in 11/18 (61%) eyes. The mean number of red dots significantly decreased at M3 (n = 80 ± 85) compared with M0 (n = 139 ± 130) (P < 0.0001). No reperfusion of arterioles or venules was observed in or around nonperfusion areas. CONCLUSION: After anti-vascular endothelial growth factor injections, the improvement in the DRSS score based on color fundus photographs can occur without retinal reperfusion on ultra-wide-field fluorescein angiography.

OPTICAL COHERENCE TOMOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND DIAGNOSIS OF CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the sensitivity and specificity of different retinal imaging combinations for the diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: Patients aged 50 years or older referred for suspicious recent-onset CNV related to age-related macular degeneration were prospectively included for 6 months. Data recorded included color fundus photographs (CFPs), spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) images. Five retina specialists randomly interpreted SD-OCT combined with CFP, and then FA combined with CFP. The reference diagnosis of CNV was based on the agreement of two readers in the interpretation of the SD-OCT + FA + CFP combination. RESULTS: One hundred and forty-eight patients (148 eyes) were included. For the diagnosis of CNV, the sensitivity of both SD-OCT + CFP and FA + CFP was of 90.9%. Type 2 CNV was diagnosed in 98% to 100% of cases with SD-OCT + CFP or FA + CFP, whereas Type 1 CNV was diagnosed in 82.9% of cases with SD-OCT + CFP and 81.6% with FA + CFP. CONCLUSION: When used as a first diagnostic test, SD-OCT combined with CFP had sensitivity and specificity similar to those of FA combined with CFP, for the diagnosis of CNV in age-related macular degeneration. This shows the increasingly important role of SD-OCT as a first-line test in the diagnosis of CNV.

VESSEL DENSITY OF SUPERFICIAL, INTERMEDIATE, AND DEEP CAPILLARY PLEXUSES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To provide values of retinal vessel density (VD) in the three retinal capillary plexuses, foveal avascular zone (FAZ) area, and retinal layer thickness in a cohort of healthy subjects. METHODS: The optical coherence tomography angiography maps of 148 eyes of 84 healthy subjects, aged 22 to 76 years, were analyzed for measuring VD of the retinal capillary plexuses, using the Optovue device comprising a projection artifact removal algorithm. Foveal avascular zone metrics were measured, and the relationship between optical coherence tomography angiography findings and age, sex, and image quality was studied. RESULTS: The deep capillary plexus showed the lowest VD (31.6% ± 4.4%) in all macular areas and age groups compared with the superficial vascular plexus (47.8% ± 2.8%) and intermediate capillary plexus (45.4% ± 4.2%). The mean VD decreased by 0.06%, 0.06%, and 0.08% per year, respectively, in the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus. Mean FAZ area, FAZ acircularity index, and capillary density in a 300-µm area around the FAZ were 0.25 ± 0.1 mm, 1.1 ± 0.05, and 50.8 ± 3.4%, respectively. The yearly increase in FAZ area was 0.003 mm (P < 0.001). CONCLUSION: The deep capillary plexus, a single monoplanar capillary plexus located in the outer plexiform layer, has the lowest VD, a significant finding that might be used to evaluate retinal vascular diseases. Vascular density decreased with age in the three capillary plexuses.

Central retinal thickness following panretinal photocoagulation using a multispot semi-automated pattern-scanning laser to treat ischaemic diabetic retinopathy: Treatment in one session compared with four monthly sessions.

PURPOSE: To compare central retinal thickness (CRT) after panretinal photocoagulation (PRP) with a multispot semi-automated PAttern-SCAnning Laser (PASCAL) in one session (SS-PRP) versus four monthly sessions (MS-PRP) in diabetic retinopathy. METHODS: Multicentre, prospective, randomized, single-blinded, controlled trial evaluating the noninferiority of SS-PRP versus MS-PRP for CRT measured with macular spectral-domain optical coherence tomography (SD-OCT), with a 9-month follow-up in patients presenting severe nonproliferative diabetic retinopathy (DR) or mild proliferative DR without macular oedema (ME) at baseline. RESULTS: Ninety-seven eyes of 97 participants with a mean age of 57.0 ± 14.2 years were included. The mean change of CRT from baseline to 9 months was not statistically different in SS-PRP or in MS-PRP: +16.9 ± 28.3 µm versus +24.7 ± 31.8 µm, respectively (p = 0.224). The variation in mean best-corrected visual acuity (BCVA) from baseline to 9 months was similar in both groups: -1.1 ± 6.5 letters versus -0.6 ± 6.2 letters (p = 0.684). The number of patients with stabilization of DR was not statistically different between the two groups. No severe complication was recorded in either group. CONCLUSION: This study showed the noninferiority of PRP performed in one session versus four monthly sessions with a PASCAL concerning central retinal thickness for treating mild proliferative or severe nonproliferative DR without ME at baseline.

Optical Coherence Tomography Angiography of Familial Retinal Arteriolar Tortuosity.

BACKGROUND AND OBJECTIVE: To analyze the location of familial retinal arterial tortuosity (fRAT) in the three-dimensional structure of retinal capillaries. PATIENTS AND METHODS: Retrospective observational study. Twelve eyes of six patients (two of whom were brothers) were imaged by optical coherence tomography angiography (OCTA). The data from their ocular and systemic examinations were recorded. RESULTS: OCTA imaging clearly showed increased tortuosity of second- and third-order retinal arteries in all cases, visible in the superficial vascular plexus (SVP) up to the arteriole termination in the capillaries. No change was visible in the deep capillary plexus (DCP). CONCLUSIONS: OCTA shows that fRAT affects all the course of the arterioles up to the capillaries in the SVP. The DCP does not show arteriolar tortuosity because it does not contain arterioles. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:397-401.].

Association Between Vessel Density and Visual Acuity in Patients With Diabetic Retinopathy and Poorly Controlled Type 1 Diabetes.

Importance: Capillary dropout is a hallmark of diabetic retinopathy, but its role in visual loss remains unclear. Objective: To examine how macular vessel density is correlated with visual acuity (VA) in patients younger than 40 years who have type 1 diabetes without macular edema but who have diabetic retinopathy requiring panretinal photocoagulation. Design, Settings, and Participants: Retrospective cohort study of VA and optical coherence tomography angiography data collected from consecutive patients during a single visit to Lariboisière Hospital, a tertiary referral center in Paris, France. The cohort included 22 eyes of 22 patients with type 1 diabetes without macular edema but with bilateral rapidly progressive diabetic retinopathy that was treated with panretinal photocoagulation between August 15, 2015, and December 30, 2016. Eyes were classified into 2 groups by VA: normal (logMAR, 0; Snellen equivalent, 20/20) and decreased (logMAR, >0; Snellen equivalent, <20/20). The control group included 12 eyes from age-matched healthy participants with normal vision. Main Outcomes and Measures: Visual acuity and mean vessel density in 4 retinal vascular plexuses: the superficial vascular plexus and the deep capillary complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Results: Of the 22 participants, 11 (50%) were men, mean (SD) age was 30 (6) years, and mean (SD) hemoglobin A1c level was 8.9% (1.6%). Of the 22 eyes with diabetic retinopathy, 13 (59%) had normal VA and 9 (41%) had decreased VA (mean [SD]: logMAR, 0.12 [0.04]; Snellen equivalent, 20/25). Mean [SE] vessel density was lower for eyes with diabetic retinopathy and normal VA compared with the control group in the superficial vascular plexus (44.1% [0.9%] vs 49.1% [0.9%]; difference, -5.0% [1.3%]; 95% CI, -7.5% to -2.4%; P < .001), in the deep capillary complex (44.3% [1.2%] vs 50.6% [1.3%]; difference, -6.3% [1.8%]; 95% CI, -9.9% to -2.7%; P = .001), in the intermediate capillary plexus (43.8% [1.2%] vs 49.3% [1.2%]; difference, -5.5% [1.7%]; 95% CI, -9.0% to -2.0%; P = .003), and in the deep capillary plexus (24.5% [1.0%] vs 30.5% [1.0%]; difference, -6.1% [1.4%]; 95% CI, -8.9% to -3.2%; P < .001). Mean vessel density was lower in eyes with diabetic retinopathy and decreased VA compared with eyes with diabetic retinopathy and normal VA; the mean (SE) loss was more pronounced in the deep capillary complex (34.6% [1.5%] vs 44.3% [1.2%]; difference, -9.6% [1.9%]; 95% CI, -13.6% to -5.7%; P < .001), especially in the deep capillary plexus (15.2% [1.2%] vs 24.5% [1.0%]; difference, -9.3% [1.5%]; 95% CI, -12.4% to -6.1%; P < .001), than in the superficial vascular plexus (39.6% [1.1%] vs 44.1% [0.9%]; difference, -4.5% [1.4%]; 95% CI, -7.3% to -1.7%; P = .002). Conclusions and Relevance: These data suggest that in patients with type 1 diabetes without macular edema but with severe nonproliferative or proliferative diabetic retinopathy, decreased VA may be associated with the degree of capillary loss in the deep capillary complex.