Intravitreal Dexamethasone in Diabetic Macular Oedema: A Way of Enhancing the Response to Anti-VEGF in Non- or Poor Responders?

BACKGROUND AND PURPOSE: The aim of this study was to describe the outcomes of a switch back to anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DME) eyes treated temporarily with a dexamethasone implant (DEXi), after an initial poor response to anti-VEGF. METHODS: The study involved a case series. RESULTS: Twenty-three eyes of 17 patients were included. All were poorly responsive to anti-VEGF and switched to a DEXi after a mean of 12 anti-VEGF injections. The mean best-corrected visual acuity (BCVA) increased from 0.25 ± 0.19 (decimals) to 0.29 ± 0.20 after switching to the DEXi (p = 0.11). BCVA remained stable (0.31 ± 0.23; p = 0.11) after switching back to anti-VEGF, one month after the last injection. The mean central macular thickness (CMT) decreased significantly from 517.0 ± 128.5 µm to 343.4 ± 118.9 µm (p < 0.001) after switching to the DEXi. In eyes receiving ≥3 anti-VEGF injections during the switch back, the CMT 1 month after the last anti-VEGF injection was significantly decreased compared to the CMT before the switch to the DEXi (mean change of - 95.55 ± 89.82 µm, p = 0.005). CONCLUSION: Switching back poorly responsive DME eyes to anti-VEGF after temporary DEXi therapy is associated with good anatomical and visual outcomes similar to those obtained with the DEXi, provided that at least 3 anti-VEGF injections are administered. The DEXi might restore retinal sensitivity to anti-VEGF.

Reproducing diabetic retinopathy features using newly developed human induced-pluripotent stem cell-derived retinal Müller glial cells.

Muller glial cells (MGCs) are responsible for the homeostatic and metabolic support of the retina. Despite the importance of MGCs in retinal disorders, reliable and accessible human cell sources to be used to model MGC-associated diseases are lacking. Although primary human MGCs (pMGCs) can be purified from post-mortem retinal tissues, the donor scarcity limits their use. To overcome this problem, we developed a protocol to generate and bank human induced pluripotent stem cell-derived MGCs (hiMGCs). Using a transcriptome analysis, we showed that the three genetically independent hiMGCs generated were homogeneous and showed phenotypic characteristics and transcriptomic profile of pMGCs. These cells expressed key MGC markers, including Vimentin, CLU, DKK3, SOX9, SOX2, S100A16, ITGB1, and CD44 and could be cultured up to passage 8. Under our culture conditions, hiMGCs and pMGCs expressed low transcript levels of RLPB1, AQP4, KCNJ1, KCJN10, and SLC1A3. Using a disease modeling approach, we showed that hiMGCs could be used to model the features of diabetic retinopathy (DR)-associated dyslipidemia. Indeed, palmitate, a major free fatty acid with elevated plasma levels in diabetic patients, induced the expression of inflammatory cytokines found in the ocular fluid of DR patients such as CXCL8 (IL-8) and ANGPTL4. Moreover, the analysis of palmitate-treated hiMGC secretome showed an upregulation of proangiogenic factors strongly related to DR, including ANG2, Endoglin, IL-1ß, CXCL8, MMP-9, PDGF-AA, and VEGF. Thus, hiMGCs could be an alternative to pMGCs and an extremely valuable tool to help to understand and model glial cell involvement in retinal disorders, including DR.

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.

IL-1ß induces rod degeneration through the disruption of retinal glutamate homeostasis.

BACKGROUND: Age-related macular degeneration is characterized by the accumulation of subretinal macrophages and the degeneration of cones, but mainly of rods. We have previously shown that Mononuclear Phagocytes-derived IL-1ß induces rod photoreceptor cell death during experimental subretinal inflammation and in retinal explants exposed to IL-1ß but the mechanism is unknown. METHODS: Retinal explants were culture in the presence of human monocytes or IL-1ß and photoreceptor cell survival was analyzed by TUNEL labeling. Glutamate concentration and transcription levels of gene involved in the homeostasis of glutamate were analyzed in cell fractions of explant cultured or not in the presence of IL-1ß. Glutamate receptor antagonists were evaluated for their ability to reduce photoreceptor cell death in the presence of IL1-ß or monocytes. RESULTS: We here show that IL-1ß does not induce death in isolated photoreceptors, suggesting an indirect effect. We demonstrate that IL-1ß leads to glutamate-induced rod photoreceptor cell death as it increases the extracellular glutamate concentrations in the retina through the inhibition of its conversion to glutamine in Müller cells, increased release from Müller cells, and diminished reuptake. The inhibition of non-NMDA receptors completely and efficiently prevented rod apoptosis in retinal explants cultured in the presence of IL-1ß or, more importantly, in vivo, in a model of subretinal inflammation. CONCLUSIONS: Our study emphasizes the importance of inflammation in the deregulation of glutamate homeostasis and provides a comprehensive mechanism of action for IL-1ß-induced rod degeneration.

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.

PREOPERATIVE FACTORS INFLUENCING VISUAL RECOVERY AFTER VITRECTOMY FOR MYOPIC FOVEOSCHISIS.

PURPOSE: To determine the preoperative factors influencing visual recovery after vitrectomy for myopic foveoschisis. METHODS: Sixty-six eyes of 65 consecutive patients operated on for myopic foveoschisis were retrospectively included. All eyes underwent a preoperative ocular examination including best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography with central foveal thickness measurement and foveal status classification: simple foveoschisis, foveal detachment, or macular hole. To study the impact of preoperative visual acuity, 4 visual acuity groups separated by quartile ranges were defined. Postoperative visits at 1, 3, or 12 months including BCVA measurement and optical coherence tomography were recorded. RESULTS: Mean refraction was -15.90 diopters, mean axial length was 30.30 mm, mean central foveal thickness was 590 µm, and mean baseline logarithm of the maximum angle of resolution visual acuity was 0.68 (Snellen equivalent of 20/96). The final BCVA improved significantly from 3 months after surgery until the last follow-up visit; the mean logarithm of the maximum angle of resolution visual acuity at last follow-up was 0.43 (Snellen equivalent of 20/54). Mean central foveal thickness decreased significantly as soon as the first postoperative month (P < 0.0001). The preoperative BCVA was the only independent factor significantly correlated with the final BCVA as opposed to the foveal status (P < 0.0001). The mean BCVA and mean visual gain at the last follow-up visit were significantly different between the four visual acuity groups (P < 0.0001 and P = 0.017, respectively). CONCLUSION: The main factor influencing the postoperative visual acuity is the preoperative visual acuity. Although the preoperative anatomical status seemed important in surgeon decision making, once normalized on visual acuity, it no longer influenced the postoperative visual acuity.

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.

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PURPOSE: To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. METHODS: This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. RESULTS: A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 µm, P = 0.10). CONCLUSION: Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study.

PURPOSE: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti-VEGF injections and to compare streptococcal with non-streptococcus-associated cases with regard to baseline characteristics and injection procedure. METHODS: Retrospective, international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. RESULTS: Eighty-three cases with 87 identified pathogens were included. Coagulase-negative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). CONCLUSION: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms.

BENEFIT OF INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY FOR VITREOMACULAR SURGERY IN HIGHLY MYOPIC EYES.

PURPOSE: To report the feasibility and information provided by intraoperative optical coherence tomography (iOCT) during vitreomacular surgery in highly myopic eyes. METHODS: Retrospective observational case series on consecutive highly myopic eyes that underwent vitreomacular surgery with iOCT for epiretinal membrane (ERM), macular hole, and myopic foveoschisis. The main outcome was the qualitative and quantitative assessment of retinal changes: detection of persistent epiretinal structures, new openings, central macular thickness, and macular hole diameters after each step of the surgical procedure. Quantitative measurements (in pixels) were manually obtained on iOCT video screen captures. RESULTS: Twenty-two eyes were included: six ERMs, 10 macular holes, and 6 with myopic foveoschisis. An unsuspected postpeeling macular opening was detected by iOCT in 2/22 eyes. Intraoperative optical coherence tomography also allowed for detecting the presence of residual fragments of the vitreous cortex in 6/12 eyes after surgically induced posterior vitreous detachment. Intraoperative optical coherence tomography detected residual fragments of the internal limiting membrane in 5/21 eyes after internal limiting membrane peeling, and residual fragments of ERM in 3/15 eyes with ERM. Quantitative analysis did not find any significant change in central macular thickness and macular hole diameters before and after ERM and internal limiting membrane peeling. CONCLUSION: In highly myopic eyes, iOCT could help assess undetected macular openings and otherwise posterior vitreous status and epiretinal structure peeling.

ACUTE PSEUDOPHAKIC CYSTOID MACULAR EDEMA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study macular capillary changes and vessel density in acute pseudophakic cystoid macular edema (PCME) before and after treatment using optical coherence tomography angiography. METHODS: Retrospective observational case-control study of seven consecutive patients (eight eyes) with PCME and eight age-matched control eyes imaged with optical coherence tomography angiography (RTVue XR Avanti; Optovue, Inc, Fremont, CA) using Projection Removal Artifacts software. Vessel density was calculated. RESULTS: The mean time to diagnosis of PCME was 2.3 ± 0.9 months after surgery. At initial examination, the superficial capillary plexus pattern was near-normal in all PCME eyes, although it was attenuated in the deep capillary plexus. The mean vessel density of the superficial capillary plexus in PCME eyes was slightly but significantly lower than in control eyes (47.8 ± 3.8% vs. 52.9 ± 4.0%, P = 0.01), the difference being greater in the deep capillary plexus (44.1 ± 7.4% vs. 54.2 ± 3.2%, P = 0.007). After resolution of the edema, the deep capillary plexus completely recovered its normal pattern and the vessel density in both plexuses was no longer different from that observed in control eyes. CONCLUSION: Macular vessel density after resolution of an acute PCME did not differ from that of normal control eyes in both the superficial capillary plexus and deep capillary plexus, unlike macular edema in retinal vaso-occlusive diseases.

Evolution of Subfoveal Detachments Secondary to Idiopathic Epiretinal Membranes after Surgery.

PURPOSE: To study the characteristics of subfoveal abnormalities secondary to idiopathic epiretinal membranes (ERM) using improved-resolution spectral-domain optical coherence tomography (SD OCT) and their evolution after surgery. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: The files of 344 patients operated on consecutively for ERM over a 2-year period in a single tertiary ophthalmologic center were reviewed. Patients with vitreomacular traction syndrome, secondary ERM, or both were excluded. METHODS: In all, 293 eyes with idiopathic ERM were included in the final analysis. Fundus photographs were reviewed to assess the presence of a yellow foveal spot, and SD OCT analysis was performed. MAIN OUTCOME MEASURES: Presence or absence of a subfoveal abnormality and its SD OCT characteristics before and after surgery at 1 month, 3 months, and at final visit; best-corrected visual acuity (BCVA) and central macular thickness at baseline, 1 month, 3 months, and at the final visit. RESULTS: Before surgery, a subfoveal detachment (SD) corresponding to the yellow deposit was present in 59 of 293 eyes (20%). No difference was found for the postoperative BCVA between the 59 eyes with SD before surgery and the 234 eyes without SD (0.253 ± 0.14 logarithm of the minimum angle of resolution [logMAR] vs. 0.262 ± 0.24 logMAR, respectively; P = 0.6). Sixty-eight percent (n = 40/59) of SD disappeared after surgery during a mean follow-up of 4.8 ± 3.2 months, most of them (62%) before month 3. Among eyes with preoperative SD, no difference was found for the postoperative BCVA between eyes with disappeared SD and those with persistent SD. CONCLUSIONS: Subfoveal detachments secondary to idiopathic ERM were observed in 20% of these eyes. They disappeared after surgery in more than two thirds of cases, usually early during postoperative course. Subfoveal detachments do not affect visual outcome and should not interfere with surgical decision making.

Ocular manifestations of autoimmune polyendocrinopathy syndrome type 1.

PURPOSE OF REVIEW: The ocular manifestations in autoimmune polyendocrinopathy syndrome type 1 (APS1) are frequent and have a poor prognosis. The phenotype of these APS1-associated ocular features have been recently characterized in molecularly confirmed patients with APS1. RECENT FINDINGS: Keratopathy and retinopathy can be severe manifestations of APS1. Heterogeneous corneal involvement can be observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. This phenotypic heterogeneity, observed even in patients with identical AIRE mutations, is suggestive of a poor genotype-phenotype correlation. Similarly, in patients with retinopathy, peripheral pigmentary changes are noted in all cases, yet with heterogeneous severity, ranging from isolated patchy atrophy of the retinal pigment epithelium to a retinitis pigmentosa-like fundus. Macular atrophy with vision loss is found in most cases. The severity of ophthalmic findings is uncorrelated to that of systemic manifestations. An autoimmune origin with specific autoantibodies directed against corneal and/or retinal autoantigens is the main mechanism believed to be responsible for the ocular manifestations of APS1. SUMMARY: Progressive keratopathy and/or retinopathy can lead to severe visual loss and pain in patients with APS1. Although no treatment has shown efficacy regarding the APS1-associated ocular manifestations, ophthalmologic examinations are recommended in these patients.

CORRELATION BETWEEN CYSTOID SPACES IN CHRONIC DIABETIC MACULAR EDEMA AND CAPILLARY NONPERFUSION DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the relationship between the location of cystoid spaces and retinal capillary nonperfusion areas in diabetic cystoid macular edema (DCME). METHODS: In this retrospective study, 24 eyes of 21 patients with chronic DCME were followed using optical coherence tomography angiography. The capillary density of the superficial capillary plexus and deep capillary plexus was measured using AngioAnalytics software in all DCME eyes and in 20 healthy controls. Diabetic cystoid macular edema improved spontaneously or after treatment in 11 eyes. RESULTS: The intraretinal cystoid spaces were surrounded by capillary-flow void areas in the superficial capillary plexus in 71% of cases and in the deep capillary plexus in 96% of cases. The deep capillary plexus had lost its regular pattern in all cases. The capillary density was decreased in both plexus (mean decrease of -23.0% in the superficial capillary plexus and -12.4% in the deep capillary plexus vs. normal). In the 11 cases with DCME resolution, the capillary did not reperfuse in areas of resolved cystoid spaces, and the capillary density did not change significantly. CONCLUSION: In chronic DCME, cystoid spaces were located within capillary dropout areas. No reperfusion occurred after DCME resolution. The impact of the severity of this nonperfusion on the risk of recurrence of DCME remains to be clarified.

POSTERIOR VITREOUS DETACHMENT IN HIGHLY MYOPIC EYES UNDERGOING VITRECTOMY.

PURPOSE: To assess the rate of complete posterior vitreous detachment (PVD) in highly myopic eyes requiring vitreoretinal surgery based on intraoperative observations. METHODS: Monocentric retrospective observational case series of consecutive highly myopic patients whose eyes underwent 25 G 3-port pars plana vitrectomy between 2009 and 2012. Patients were operated on for rhegmatogenous retinal detachment, epiretinal membrane, macular hole with retinal detachment, myopic foveoschisis, and myopic macular hole. Patient records were reviewed focusing on the intraoperative assessment of PVD which was assisted in most cases by a visualization agent. RESULTS: Ninety-six eyes of 95 patients whose mean age was 62.15 ± 12.4 years (29-95) were included. Complete PVD was observed in 52.1% of eyes. The PVD rate varied depending on the disease (P < 0.0001). It was high in retinal detachment and epiretinal membrane (85 and 74.2%, respectively) and low in myopic foveoschisis and myopic macular hole (14.3 and 10%, respectively). Complete PVD was found in 42.9% of macular hole with retinal detachment. CONCLUSION: In highly myopic eyes, the rate of complete PVD varied widely depending on the vitreoretinal disease operated on. The posterior vitreous cortex was often detached from the retina in retinal detachment and epiretinal membrane but was most often attached in myopic foveoschisis and macular hole.

CAPILLARY PLEXUS ANOMALIES IN DIABETIC RETINOPATHY ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze the foveal microvasculature in eyes with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). METHODS: In this retrospective study of 20 eyes of 14 patients with DR imaged using OCTA and FA, clinical features of DR such as microaneurysms, capillary nonperfusion areas, and intraretinal microvascular abnormalities were analyzed. RESULTS: In the superficial plexus, a rarefaction of capillaries with capillary nonperfusion areas was present in all eyes. Some of these nonperfused areas were not detected on FA and were better delimited on OCTA. Conversely, in the deep plexus, capillary nonperfusion areas were seen only in 35% (7/20) of eyes, whereas DR led to an alteration of the normal capillary vortex pattern in all eyes. Only 62% of microaneurysms visualized on FA were detected by OCTA (P = 0.02). Intraretinal microvascular abnormalities were well detected by both FA and OCTA. CONCLUSION: Optical coherence tomography angiography allowed detecting DR anomalies in both superficial and deep capillary plexus in all eyes. The ability of OCTA to detect microaneurysms was lower than that of FA although its accuracy for assessing capillary nonperfusion was better and may enable a proper grading of DR progression.

NEW INSIGHT INTO THE MACULAR DEEP VASCULAR PLEXUS IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the macular deep capillary plexus (DCP) in normal eyes using optical coherence tomography angiography. METHODS: Retrospective study including 41 consecutive normal eyes imaged using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc). Default autosegmentation of the superficial capillary plexus (SCP) and DCP, and manual adjustments of "deep settings" were used to analyze the organization of the normal macular microvascularization and to investigate in vivo the connection between these capillary networks. RESULTS: Mean age was 31 years (range, 22-55 years). The SCP and DCP had 2 different organizations, but the plexus autosegmentation was imperfect: In 68% of cases, the image of the SCP variably superimposed on the DCP, interfering with its analysis. The SCP was composed on average of 7 pairs of arterioles and venules obvious on each 3-mm × 3-mm optical coherence tomography angiography scanning area. The DCP was composed of a capillary vortex arrangement, whose centers were aligned along the course of the macular superficial venules. CONCLUSION: The SCP and DCP had two different topographic organizations. The pattern of the capillary units converging into capillary vortexes highly suggests that they drain into the superficial venules. The different structural properties of the SCP and DCP could explain the differences in flow resistance and perfusion.

Anti-vascular endothelial growth factor acts on retinal microglia/macrophage activation in a rat model of ocular inflammation.

PURPOSE: To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation. METHODS: Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment. RESULTS: Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1ß, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina. CONCLUSIONS: Microglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology.

Surgical outcomes of florid diabetic retinopathy treated with antivascular endothelial growth factor.

PURPOSE: To evaluate the effectiveness of vitreoretinal surgery combined with antivascular endothelial growth factor therapy to treat florid diabetic retinopathy, a rare and severe form of diabetic retinopathy in young patients. METHODS: Retrospective observational case series including 61 eyes of 45 patients operated on for florid diabetic retinopathy over the past 5 years, with preoperative or intraoperative intravitreal injection of bevacizumab. Cases were classified into three stages of disease severity, according to the extension of the fibrovascular membranes. Main outcome measures were mean change in visual acuity, anatomical outcome, and surgical complications. RESULTS: After a mean follow-up of 20.3 months, the mean visual acuity significantly increased from +1.7 logMAR before surgery to +0.8 logMAR after surgery (P < 0.01). The visual gain was significant in Stages I and II (P < 0.05) but not significant in Stage III. A flat retina without silicone oil was achieved in 84% of eyes. Eight eyes (13%) progressed to neovascular glaucoma and/or phthisis despite repeated surgeries. CONCLUSION: Vitrectomy combined with antivascular endothelial growth factor therapy allows both favorable visual and anatomical outcomes in this rapidly evolving disease. Prognosis remains poor in severe stages, suggesting that the earlier the surgery performed, the better is the visual prognosis.