Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial.

AIMS: To determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582). METHODS: Details of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy. RESULTS: No adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye. CONCLUSION: The results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

Identification of Postoperative Foveal Displacement after Macular Surgery for Idiopathic Epiretinal Membrane.

Introduction: To analyze foveal displacement after macular surgery for idiopathic epiretinal membrane (iERM). Methods: Twenty-eight patients who underwent macular surgery for symptomatic iERM in one eye by one physician were included in this retrospective study. Spectral domain optical coherence tomography (SD-OCT) volume scans were acquired with a Spectralis OCT device (Heidelberg Spectralis). Using the follow-up view mode, the displacement of the fovea was classified and measured according to its postoperative location in the horizontal and/or vertical plane. Results: One day after surgery, 86% of eyes (24/28) showed foveal displacement. Vertical displacement occurred in a superior direction in 50% eyes, and in an inferior direction in 36% of the eyes. The postoperative mean foveal displacement on the vertical plane was 99 ± 82 µm (range, 0-300). Horizontal displacement occurred in a nasal direction in 21%, and temporally in 21%. The postoperative mean foveal displacement on the horizontal plane was 35 ± 45 µm (range, 0-123). One year after the macular surgery 69% of the eyes showed still a foveal dislocation. Discussion: Most of the eyes with iERM showed a foveal dislocation after the macular surgery. Our findings emphasize the necessity to carefully study of the OCT images in such eyes after the surgery as the manually determined postoperative foveal position may be in a different vertical or horizontal plane than the machine-generated pre- and postoperative overlay for the foveal position. Our findings may thus be helpful for surgeons to avoid misinterpretation when evaluating OCT images pre- and postoperatively.

Clinical Phenotype and Course of PDE6A-Associated Retinitis Pigmentosa Disease, Characterized in Preparation for a Gene Supplementation Trial.

Importance: Treatment trials require sound knowledge on the natural course of disease. Objective: To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. Design, Setting, and Participants: This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. Exposures: Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. Main Outcomes and Measures: Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). Results: Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). Conclusions and Relevance: Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.

Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial.

Importance: Achromatopsia linked to variations in the CNGA3 gene is associated with day blindness, poor visual acuity, photophobia, and involuntary eye movements owing to lack of cone photoreceptor function. No treatment is currently available. Objective: To assess safety and vision outcomes of supplemental gene therapy with adeno-associated virus (AAV) encoding CNGA3 (AAV8.CNGA3) in patients with CNGA3-linked achromatopsia. Design, Setting, and Participants: This open-label, exploratory nonrandomized controlled trial tested safety and vision outcomes of gene therapy vector AAV8.CNGA3 administered by subretinal injection at a single center. Nine patients (3 per dose group) with a clinical diagnosis of achromatopsia and confirmed biallelic disease-linked variants in CNGA3 were enrolled between November 5, 2015, and September 22, 2016. Data analysis was performed from June 6, 2017, to March 12, 2018. Intervention: Patients received a single unilateral injection of 1.0 × 1010, 5.0 × 1010, or 1.0 × 1011 total vector genomes of AAV8.CNGA3 and were followed up for a period of 12 months (November 11, 2015, to October 10, 2017). Main Outcomes and Measures: Safety as the primary end point was assessed by clinical examination of ocular inflammation. Systemic safety was assessed by vital signs, routine clinical chemistry testing, and full and differential blood cell counts. Secondary outcomes were change in visual function from baseline in terms of spatial and temporal resolution and chromatic, luminance, and contrast sensitivity throughout a period of 12 months after treatment. Results: Nine patients (mean [SD] age, 39.6 [11.9] years; age range, 24-59 years; 8 [89%] male) were included in the study. Baseline visual acuity letter score (approximate Snellen equivalent) ranged from 34 (20/200) to 49 (20/100), whereas baseline contrast sensitivity log scores ranged from 0.1 to 0.9. All 9 patients underwent surgery and subretinal injection of AAV8.CNGA3 without complications. No substantial safety problems were observed during the 12-month follow-up period. Despite the congenital deprivation of cone photoreceptor-mediated vision in achromatopsia, all 9 treated eyes demonstrated some level of improvement in secondary end points regarding cone function, including mean change in visual acuity of 2.9 letters (95% CI, 1.65-4.13; P = .006, 2-sided t test paired samples). Contrast sensitivity improved by a mean of 0.33 log (95% CI, 0.14-0.51 log; P = .003, 2-sided t test paired samples). Conclusions and Relevance: Subretinal gene therapy with AAV8.CNGA3 was not associated with substantial safety problems and was associated with cone photoreceptor activation in adult patients, as reflected by visual acuity and contrast sensitivity gains. Trial Registration: ClinicalTrials.gov Identifier: NCT02610582.

Rebound Phenomenon after Intravitreal Injection of Triamcinolone Acetonide for Macular Edema.

INTRODUCTION: The aim of this article was to report on a rebound phenomenon after intravitreal triamcinolone acetonide (IVTA) injection for macular edema secondary to diabetic retinopathy (DR) and central or branch retinal vein occlusion (CRVO/BRVO). METHODS: The data were analyzed retrospectively. Complete ophthalmic examinations, including spectral domain optical coherence tomography, were performed before and 2 months after IVTA injection. The incidence of a rebound phenomenon was defined as an increase in central retinal thickness of >10% from baseline at 2 months after IVTA injection. RESULTS: This retrospective study included 211 consecutive patients (268 eyes). One hundred ninety (71.2%), 39 (14.6%), and 39 (14.6%) eyes had macular edema (ME) due to DR, CRVO, and BRVO. In total, 9.7% of the eyes showed a rebound phenomenon (DR: 9.5%, CRVO: 5.2%, BRVO: 15.4%). The mean number of prior injections of vascular endothelial growth factor inhibitor or corticosteroid agent was statistically significantly higher in the rebound group (6.8 vs. 5.3) than in the nonrebound group (p = 0.01). CONCLUSION: Our study shows that 9.7% of the eyes with ME secondary to DR and RVO developed a rebound phenomenon following IVTA injection, limiting its therapeutic effect. We found an increased number of prior intravitreal pharmacotherapy to be a risk factor for a rebound phenomenon.

CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA.

PURPOSE: Choroideremia (CHM) is a rare inherited retinal degeneration resulting from mutation of the CHM gene, which results in absence of functional Rab escort protein 1 (REP1). We evaluated retinal gene therapy with an adeno-associated virus vector that used to deliver a functional version of the CHM gene (AAV2-REP1). METHODS: THOR (NCT02671539) is a Phase 2, open-label, single-center, randomized study. Six male patients (51-60 years) with CHM received AAV2-REP1, by a single 0.1-mL subretinal injection of 10 genome particles during vitrectomy. Twelve-month data are reported. RESULTS: In study eyes, 4 patients experienced minor changes in best-corrected visual acuity (-4 to +1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); one gained 17 letters and another lost 14 letters. Control eyes had changes of -2 to +4 letters. In 5/6 patients, improvements in mean (95% confidence intervals) retinal sensitivity (2.3 [4.0] dB), peak retinal sensitivity (2.8 [3.5] dB), and gaze fixation area (-36.1 [66.9] deg) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure. CONCLUSION: Gene therapy with AAV2-REP1 can maintain, and in some cases, improve, visual acuity in CHM. Longer term follow-up is required to establish whether these benefits are maintained.

Efficacy and Safety of Retinal Gene Therapy Using Adeno-Associated Virus Vector for Patients With Choroideremia: A Randomized Clinical Trial.

IMPORTANCE: Choroideremia (CHM) is a rare, degenerative, genetic retinal disorder resulting from mutation of the CHM gene, leading to an absence of functional ras-associated binding escort protein 1 (REP1). There is currently no approved treatment for CHM. OBJECTIVE: To assess the safety and efficacy of retinal gene therapy with an adeno-associated virus vector (AAV2) designed to deliver a functional version of the CHM gene (AAV2-REP1) for treatment of patients with choroideremia. DESIGN, SETTING, AND PARTICIPANTS: Tübingen Choroideremia Gene Therapy (THOR) was a single-center, phase 2, open-label randomized clinical trial. Data were collected from January 11, 2016, to February 26, 2018. Twenty-four-month data are reported for 6 men with a molecularly confirmed diagnosis of CHM. Intention-to-treat analysis was used. INTERVENTIONS: Patients received AAV2-REP1 by a single, 0.1-mL subretinal injection of 1011 genome particles during vitrectomy into 1 eye randomly assigned to receive treatment. MAIN OUTCOMES AND MEASURES: Primary end point was change in best-corrected visual acuity (BCVA) on the Early Treatment Diabetic Retinopathy Study chart from baseline to month 24 in the treated eye vs the control eye. Secondary end points included microperimetry variables, change in fundus autofluorescence, and spectral-domain optical coherence tomographic evaluations from baseline to month 24 in the treated eye vs the control eye. RESULTS: On enrollment, the mean (SD) age of the 6 men included in the study was 54.9 (4.1) years. The mean (SD) BCVA score was 60.3 (13.4) (approximately 20/63 Snellen equivalent) in the study eyes and 69.3 (20.6) (approximately 20/40 Snellen equivalent) in the control eyes. At 24 months, the BCVA change was 3.7 (7.5) in the treated eyes and 0.0 (5.1) in the control eyes (difference, 3.7; 95% CI, -7.2 to 14.5; P = .43). Mean change in retinal sensitivity was 10.3 (5.5) dB in the treated eyes and 9.7 (4.9) dB in the control eyes (difference, 0.6; 95% CI, -10.2 to 11.4; P = .74). A total of 28 adverse events were reported; all were consistent with the surgical procedure (eg, conjunctival hyperemia, foreign body sensation), and none were regarded as severe. CONCLUSIONS AND RELEVANCE: Among 6 participants, gene therapy with AAV2-REP1 was associated with maintenance or improvement of visual acuity, although no significant difference was found from control eyes. All safety issues were associated with the surgical procedure and none were judged severe. Continued investigations could more precisely define the efficacy and safety of gene therapy with AAV2-REP1 in CHM. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02671539.

Development of Methodology and Study Protocol: Safety and Efficacy of a Single Subretinal Injection of rAAV.hCNGA3 in Patients with CNGA3-Linked Achromatopsia Investigated in an Exploratory Dose-Escalation Trial.

Achromatopsia is an autosomal recessively inherited congenital defect characterized by a lack of cone photoreceptor function, leading to severely impaired vision. In this clinical study, achromatopsia patients were treated with a single subretinal injection of rAAV.hCNGA3 to restore cone function. The focus of this trial was on the safety of the treatment. After surgery, patients were monitored in eight extensive visits during the first year, followed by a 4-year follow-up period with annual visits. For essential complementation of the standard ophthalmological and systemic examinations, disease-specific methods were developed to assess the safety, efficacy, and patient-reported outcomes in this trial.

Optical Coherence Tomography in Patients With the Subretinal Implant Retina Implant Alpha IMS.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess changes in retinal structure and thickness after subretinal implantation of the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany). PATIENTS AND METHODS: Spectral-domain optical coherence tomography (SD-OCT) imaging was performed to assess the structure and thickness of the retina anterior to the microphotodiode array preoperatively, within 6 weeks and 6 months ± 1 month after implantation. Thickness measurements were performed using the distance tool of the built-in software. Three thickness measurements were performed in each of the four quadrants of the retina on the microchip within 6 weeks and 6 months ± 1 month after implantation. RESULTS: The mean ± standard deviation change in retinal thickness from within 6 weeks to 6 months ± 1 month after implantation in all four quadrants combined was 24 µm ± 68 µm. None of the tested variables (location, time, or their interaction) had a statistically significant effect on the mean retinal thickness (P = .961, P = .131, and P = .182, respectively; n = 19). CONCLUSION: The authors report on qualitative and quantitative findings in retinal structure in 27 patients after subretinal implantation of the Retina Implant Alpha IMS using OCT technology. No significant changes of retinal thickness could be observed in a period of 6 months after surgery. With more patients receiving subretinal implants and with advanced OCT technology, the data set will be extended to study possible changes in retinal structure in finer detail. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:993-999.].

Retinal Capillary Network and Foveal Avascular Zone in Eyes with Vein Occlusion and Fellow Eyes Analyzed With Optical Coherence Tomography Angiography.

PURPOSE: To evaluate the perifoveolar retinal capillary network at different depths and to quantify the foveal avascular zone (FAZ) in eyes with retinal vein occlusion (RVO) compared with their fellow eyes and healthy controls using spectral-domain optical coherence tomography angiography (SD-OCTA). METHODS: We prospectively recruited 23 patients with RVO including 15 eyes with central RVO (CRVO) and 8 eyes with branch RVO (BRVO), their fellow eyes, and 8 age-matched healthy controls (8 eyes) for imaging on prototype OCTA software within RTVue-XR Avanti. The 3 × 3 mm and 6 × 6 mm en face angiograms of superficial and deep retinal capillary plexuses were segmented. Perifoveolar retinal capillary network was analyzed and FAZ was quantified. RESULTS: Decrease in vascular perfusion at the deep plexus was observed in all eyes with CRVO (8/8, 100%) and BRVO (6/6, 100%) without cystoid macular edema, and in 8 of 15 (53%) and 2 of 8 (25%) of the fellow eyes, respectively. Vascular tortuosity was observed in 13 of 15 (87%) CRVO and 5 of 8 (63%) BRVO eyes. Collaterals were seen in 10 of 15 (67%) CRVO and 5 of 8 (63%) BRVO eyes. Mean FAZ area was larger in eyes with RVO than their fellow eyes (1.13 ± 0.25 mm2 versus 0.58 ± 0.28 mm2; P = 0.007) and controls (1.13 ± 0.25 mm2 versus 0.30 ± 0.09 mm2; P < 0.0001), and in fellow eyes of RVO patients when compared to controls (0.58 ± 0.28 mm2 versus 0.30 ± 0.09 mm2; P = 0.01). CONCLUSIONS: Spectral-domain OCTA reveals abnormalities at different levels of perifoveolar retinal capillary network and is able to quantify the FAZ in RVO. Longitudinal studies may be considered to evaluate the clinical utility of OCTA in RVO and other retinal vascular diseases.

Predictors of Macular Atrophy Detected by Fundus Autofluorescence in Patients With Neovascular Age-Related Macular Degeneration After Long-Term Ranibizumab Treatment.

BACKGROUND AND OBJECTIVE: To study the relationship between baseline morphologic characteristics of the choroidal neovascular (CNV) lesion and long-term development of macular atrophy in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA). PATIENTS AND METHODS: Certified graders evaluated baseline and 7-year follow-up (SEVEN-UP study) images of 41 eyes from the MARINA/ANCHOR and HORIZON trials. Using GRADOR software and stepwise linear regression, graders correlated lesion characteristics on fluorescein angiography (FA) at both visits with areas of definite decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) imaging at the SEVEN-UP visit. RESULTS: Three of 41 eyes (7.3%) had macular atrophy on FA at baseline (mean ± standard deviation [SD] size: 0.29 mm(2) ± 1.50 mm(2)), 29 (70.7%) at SEVEN-UP (mean ± standard deviation [SD] area: 7.42 mm(2) ± 7.97 mm(2)). On FAF imaging at the SEVEN-UP visit, all 41 eyes (100%) had DDAF (mean ± SD size: 10.29 mm(2) ± 8.07 mm(2)). Variables significantly associated with area of DDAF at the SEVEN-UP visit were the area of leaking CNV lesion components (coefficient: 0.953; P < .001), the area of other lesion components (coefficient: 1.094; P = .038), and the area of retinal pigment epithelial (RPE) atrophy (coefficient: 1.334; P = .040) on baseline FA imaging. CONCLUSION: The area of DDAF at more than 7 years after initiation of ranibizumab therapy was 35% larger than the original CNV lesion. The baseline area of leaking CNV and other components of the CNV lesion and the baseline area of RPE atrophy were important predictors of the area of definite decreased autofluorescence, presumably corresponding to areas of photoreceptor and RPE loss. The findings from this study may guide hypothesis generation for future AMD trials.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography. METHODS: Optical coherence tomography angiography cube scans (3 mm × 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images. RESULTS: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 (± 0.07) mm. CONCLUSION: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography.

SUBRETINAL NEOVASCULARIZATION IN MACULAR TELANGIECTASIA TYPE 2: OPTICAL COHERENCE TOMOGRAPHIC ANGIOGRAPHY AND TREATMENT RESPONSE.

PURPOSE: To report the optical coherence tomographic angiography findings and response to treatment in a case of macular telangiectasia Type 2 with subretinal neovascularization. METHODS: Case report. RESULTS: A 64-year-old man with macular telangiectasia Type 2 developed subretinal neovascularization, which was imaged on optical coherence tomographic angiography. He was treated with intravitreal aflibercept, and there was a remarkable reduction of flow in the subretinal neovascular network on optical coherence tomographic angiography. CONCLUSION: Optical coherence tomographic angiography provides detailed information on the retinal microvasculature and subretinal neovascularization in macular telangiectasia Type 2. It can be used to assess response to treatment.

EN FACE OPTICAL COHERENCE TOMOGRAPHY OF MACULAR MICROCYSTS DUE TO OPTIC NEUROPATHY FROM NEUROMYELITIS OPTICA.

PURPOSE: To describe the multimodal imaging, including en face optical coherence tomography (OCT) and OCT angiography, findings of a case of macular microcysts associated with neuromyelitis optica. METHODS: Findings on clinical examination, color fundus photography, fluorescein angiography, fundus autofluorescence, visual fields, and OCT including en face OCT and OCT angiography are presented. RESULTS: A 12-year-old African American boy presented with bilateral optic atrophy from neuromyelitis optica. Clinical examination was notable for bilateral optic nerve head pallor. Visual fields of both eyes showed generalized depression. Fluorescein angiography and fundus autofluorescence were unremarkable. Spectral domain OCT B-scan images showed characteristic paracentral, hyporeflective, microcystic lesions in the inner nuclear layer of both eyes, and en face OCT images demonstrated a corresponding pattern of large paracentral cysts radiating peripherally into smaller diffuse cysts. Optical coherence tomographic angiography of the superficial and deep retinal capillary plexuses was unremarkable. CONCLUSION: Macular microcysts have been associated with various forms of optic atrophy, including neuromyelitis optica. Spectral domain and en face OCT imaging of the microcysts demonstrated a very characteristic pattern. Normal fluorescein and OCT angiography suggest that nonvascular causes, such as Müller cell degeneration, might contribute to the etiologic mechanism.

Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration.

PURPOSE: To analyze type 1 neovascular membranes in age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography, to correlate morphologic characteristics with imaging and clinical criteria, and to analyze structural features of type 1 neovascularization sequentially after anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Prospective interventional case series. METHODS: Macular OCT angiography images were acquired using the RTVue XR Avanti with AngioVue. Distinct morphologic patterns and quantifiable features of the neovascular membranes were studied on en face projection images at baseline and follow-up. RESULTS: Thirty-three eyes of 25 patients were included. In 75% of the eyes, a highly organized vascular complex could be identified. A large main central vessel trunk/feeder vessel could be seen in 72% of these eyes, with vessels radiating in a branching pattern either in all directions from the center of the lesion ("medusa" pattern), or from one side of the lesion ("seafan" pattern). Of the 18 eyes with follow-up OCT angiography, the lesion area and vessel density remained unchanged, even after anti-vascular endothelial growth factor (VEGF) therapy, indicating a more mature longstanding neovascular complex resistant to anti-VEGF therapy. CONCLUSIONS: OCT angiography provides a unique opportunity to study the morphology of occult type 1 neovascular membranes in AMD and allows precise structural and vascular assessment noninvasively. We identified a large mature neovascular complex in approximately 75% of eyes, typically consisting of a feeder vessel and large branching vessels resistant to anti-VEGF therapy. OCT angiography may better guide evaluation and treatment of neovascular AMD, and may contribute to the development of improved therapies.

Imaging areas of retinal nonperfusion in ischemic branch retinal vein occlusion with swept-source OCT microangiography.

The authors present the case of a patient with a history of ischemic branch vein occlusion and multimodal imaging of the retinal vasculature by fluorescein angiography (FA) and ultrahigh-speed swept-source optical coherence tomography (SS-OCT) microangiography (SS-OCT laser prototype; 1,050 nm, 100,000 A-scans/second). Multiple images across the macula were acquired (3 × 3 mm cubes in clusters of four repeated B-scans). En face images of the vasculature were generated by implementing an intensity differentiation algorithm. The retinal vasculature as well areas of nonperfusion could be identified precisely at multiple retinal levels. Ultrahigh-speed SS-OCT microangiography provides noninvasive, three-dimensional, high-resolution images of the retinal vasculature including the capillaries.