Evaluation of Preretinal Neovascularization in Proliferative Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To describe a method for visualizing preretinal neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA) and report the findings in the surrounding vasculature. PATIENTS AND METHODS: Patients with PDR diagnosed on clinical examination who received OCTA scans using the RTVue XR Avanti (Optovue, Fremont, CA) were evaluated. To visualize preretinal neovascularization, OCT angiograms were segmented to project vasculature above the internal limiting membrane (ILM). OCT angiograms were segmented between the ILM and Bruch's membrane to show adjacent retinal vasculature. RESULTS: Thirteen eyes were determined to have preretinal neovascularization in the posterior pole based on OCTA. One OCT angiogram was not of sufficient quality and thus was eliminated from further study. Eleven eyes (92%) had neovascularization adjacent to retinal capillary nonperfusion and six (50%) were adjacent to intraretinal microvascular abnormalities (IRMAs). CONCLUSION: OCTA provided high-resolution, depth-resolved blood flow information, allowing for visualization of preretinal neovascularization, IRMA, and adjacent capillary nonperfusion.

Optical Coherence Tomography Angiography for Detecting Choroidal Neovascularization Secondary to Choroidal Osteoma.

Choroidal osteoma is an ossifying tumor that is found predominantly in the peripapillary and macular areas. It typically affects otherwise healthy females. Vision loss may occur secondary to the development of choroidal neovascularization (CNV). Fluorescein angiography (FA) remains the gold standard for diagnosing CNV; however, the use of optical coherence tomography angiography (OCTA) as an adjunct to FA is growing. In this report, a 16-year-old female with a large, unilateral peripapillary choroidal osteoma presented with blurred vision. Exam revealed scattered intraretinal hemorrhage, but FA was unable to detect CNV overlying the tumor. OCTA detected abnormal flow in the outer retina corresponding to a type 2 CNV. Following intravitreal anti-vascular endothelial growth factor therapy, the CNV regressed, the hemorrhage resolved, and there was less fluid. OCTA may be helpful in detecting CNV noninvasively in eyes in which FA is equivocal, such as those with choroidal osteoma.

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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL ARTERY OCCLUSION.

PURPOSE: To describe the retinal microvasculature of the eyes with nonarteritic retinal artery occlusion (RAO) based on optical coherence tomography angiography. METHODS: Cross-sectional, prospective, observational study performed from September 2014 through February 2015. En face projection of optical coherence tomography angiography images centered at the macula and optic disk of the eyes presenting with RAO were acquired using the RTVue XR Avanti with AngioVue software. Qualitative analysis of the morphology of the superficial and deep retinal capillary plexuses, and radial peripapillary capillaries was performed. Retinal vasculature images using optical coherence tomography angiography were correlated with fluorescein angiography images. RESULTS: Seven patients (seven eyes) were enrolled in the study, including three eyes with central RAO and four eyes with branch RAO. Distinct differences in the distribution of zones of decreased vascular perfusion between the superficial and deep retinal capillary plexus corresponding to areas of delayed dye perfusion on fluorescein angiography were demonstrated in 6 of 7 (86.5%) eyes. CONCLUSION: This small series suggests that optical coherence tomography angiography imaging can accurately discern retinal capillary plexuses at different levels in the eyes with RAO and may be sensitive for more precisely characterizing the extent of macular ischemia and monitoring vascular flow changes during the course of the disease.

DETECTION OF MICROVASCULAR CHANGES IN EYES OF PATIENTS WITH DIABETES BUT NOT CLINICAL DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. METHODS: Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. RESULTS: Foveal avascular zone size measured 0.348 mm² (0.1085-0.671) in diabetic eyes and 0.288 mm² (0.07-0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. CONCLUSION: Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made.

Outer Retinal Changes Preceding Secondary Macular Hole Formation Years After Vitreomacular Traction Release Demonstrated on Spectral-Domain OCT.

This report describes changes documented on spectral-domain optical coherence tomography (SD-OCT) in the right eye of a 58-year-old woman who eventually developed a secondary full-thickness macular hole (FTMH). She had a history of vitreomacular traction (VMT) that had resolved spontaneously with a complete posterior vitreous detachment. Despite VMT resolution, a hyperreflective band from the internal to the external limiting membrane and evidence of photoreceptor disruption persisted on SD-OCT for 2 years, at which point an FTMH developed. Despite VMT release, the unexpected FTMH coupled with the preceding outer retinal changes suggest persistent secondary damage to Müller cells as a potential factor.

RETINAL AND CHOROIDAL VASCULATURE IN BIRDSHOT CHORIORETINOPATHY ANALYZED USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe retinal and choroidal vascular changes in eyes with birdshot chorioretinopathy using optical coherence tomography angiography. METHODS: Patients underwent imaging using the AngioVue prototype software of the RTVue XR spectral domain optical coherence tomography device (Optovue, Inc) between September and December 2014. Two trained patients evaluated the optical coherence tomography angiography images for changes in the retinal and choroidal vasculature in the posterior pole. RESULTS: Four of eight eyes (50%) had birdshot lesions in the posterior pole as demonstrated on fundus photography. All of these eyes demonstrated the areas of decreased choroidal blood flow below the disrupted retinal pigment epithelium. Larger choroidal vessels bordered the birdshot lesions. All eyes analyzed showed retinal thinning, telangiectatic vessels, and an increased intercapillary space. Capillary dilatations and loops were each seen in 7 of 8 eyes (88%). CONCLUSION: Optical coherence tomography angiography provides precise microvascular detail of the retinal vasculature and choriocapillaris that allows for the noninvasive visualization of the birdshot lesions and changes in the inner retina. The optical coherence tomography angiography images delineated widespread retinal vascular findings not previously described in the literature. In the future, optical coherence tomography angiography could be a useful tool to evaluate the natural history of birdshot chorioretinopathy, its progression, and the effect of treatment in these patients.

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.

Spectral-domain optical coherence tomography angiography of choroidal neovascularization.

PURPOSE: To describe the characteristics as well as the sensitivity and specificity of detection of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) using spectral-domain optical coherence tomography. DESIGN: Observational, retrospective study. PARTICIPANTS: Seventy-two eyes of 61 subjects (48 eyes of 43 subjects with CNV, 24 eyes of 18 subjects without CNV). METHODS: Patients imaged using the prototype AngioVue OCTA system (Optovue, Inc, Fremont, CA) between August 2014 and October 2014 at New England Eye Center were assessed. Patients in whom CNV was identified on OCTA were evaluated to define characteristics of CNV on OCTA: size using greatest linear dimension (small, <1 mm; medium, 1-2 mm; large, >2 mm), appearance (well-circumscribed, poorly circumscribed), and presence of subretinal and intraretinal fluid. Concurrently, an overlapping second cohort of patients who underwent same-day OCTA and fluorescein angiography (FA) for suspected CNV was evaluated to estimate sensitivity and specificity of OCTA in detecting CNV using FA as ground truth. MAIN OUTCOME MEASURES: Choroidal neovascularization appearance, CNV size, and presence of subretinal and intraretinal fluid. RESULTS: In 48 eyes, CNV was visualized on OCTA. Thirty-one eyes had CNV associated with neovascular age-related macular degeneration. Size of CNV was small in 23% (7/31), medium in 42% (13/31), and large in 35% (11/31). Poorly circumscribed vessels, subretinal fluid, and intraretinal fluid each were seen in 71% (22/31). Seven eyes had CNV associated with central serous chorioretinopathy. Size of CNV was small in 71% (5/7) and large in 29% (2/7). Seventy-one percent (5/7) had well-circumscribed vessels, 86% (6/7) had subretinal fluid, and 14% (1/7) had intraretinal fluid. Thirty eyes with OCTA and same-day FA were evaluated to determine sensitivity and specificity of CNV detection on OCTA. Sensitivity was 50% (4/8) and specificity was 91% (20/22). CONCLUSIONS: Using OCTA allows the clinician to visualize CNV noninvasively and may provide a method for identifying and guiding treatment of CNV. The specificity of CNV detection on OCTA compared with FA seems to be high. Future studies with larger sample sizes are needed to elaborate better on the sensitivity and specificity of CNV detection and to illustrate clinical usefulness.

Comparison of acetazolamide, brimonidine, and anterior chamber paracentesis for ocular hypertension control after initial intravitreal bevacizumab injection: a randomized clinical trial.

PURPOSE: To evaluate the effects of oral acetazolamide (ACZ), anterior chamber paracentesis (ACP), or topical brimonidine tartrate (BT) to reduce intraocular pressure (IOP) elevation after intravitreal bevacizumab injection (IVBI). PATIENTS AND METHODS: A total of 56 patients scheduled for IVBI (1.5 mg/0.06 mL) were randomly assigned to a pretreatment with ACZ (14 eyes), BT (14 eyes), as well as an immediately after ACP (14 eyes), or no treatment (control group-CG) (14 eyes). IOP was measured 90 minutes before injection (baseline), just before injection, and at 3, 10, 20, and 30 minutes after the procedure. RESULTS: IOP was increased at 3 minutes after injection in CG, 20.9±2.1 (mean±SE intraindividual change in mm Hg); BT, 15.5±2.3; ACZ, 13.7±1.7; but not in ACP, 0.3±1.2 (P<0.0001). At 30 minutes after injections, IOP difference to baseline was not significantly different in groups BT, 0.0±0.7; ACZ, -3.2±0.8; and ACP, -2.5±3.9, but was kept higher in the CG, 4.0±4.3 (P<0.0001). CONCLUSIONS: ACP prevents IOP elevation after IVBI, whereas ACZ and BT caused a faster return to baseline than untreated nonglaucomatous eyes. Further studies with larger number of subjects, including glaucomatous patients, and the use of other topical glaucoma medications are warranted to establish a standard recommendation.

Vitreous pharmacokinetics and retinal safety of intravitreal preserved versus non-preserved triamcinolone acetonide in rabbit eyes.

PURPOSE: To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina. METHODS: A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4 mg/0.1 ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4 mg/0.1 ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy. RESULTS: Median intravitreal concentrations of TA-BA (µg/ml) were 1903.1, 1213.0, 857.8, 442.0, 248.6 at 3, 7, 14, 21 and 28 days after injection. Intravitreal concentrations of TA-PF (µg/ml) were 1032.9, 570.1, 516.6, 347.9, 102.8 at 3, 7, 14, 21 and 28 days after injection. The median intravitreal triamcinolone concentration was significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection (p < 0.05). There was no significant difference between the two groups in median triamcinolone concentration at the other time points evaluated. There was no evidence of toxic effects on the retina in either group based on ERG or histological analyses. CONCLUSIONS: Following a single intravitreal injection, the median concentration of triamcinolone acetonide is significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection. No toxic reactions in the retina were observed in either group.

Intravitreal injection versus sub-Tenon's infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial.

PURPOSE: To compare the effectiveness of posterior sub-Tenon's infusion (STi) and intravitreal injection (IVI) of triamcinolone acetonide (TA) for treatment of refractory diffuse diabetic macular edema. METHODS: Thirty-six phakic diabetic patients with refractory diffuse diabetic macular edema were prospectively enrolled. Patients randomly received either 40 mg STi or 4 mg IVI of TA. Comprehensive ophthalmic evaluation was performed at baseline and 1, 2, 4, 8 +/- 1, 12 +/- 2 and 24 +/- 2 weeks after treatment. Macular morphologic changes detected by optical coherence tomography and visual acuity, intraocular pressure, and lens status were evaluated. RESULTS: Twenty-eight patients (28 eyes) completed the 24-week study. Central macular thickness was significantly reduced in the IVI group when compared with the STi group at 2, 4, 8, 12, and 24 weeks after treatment (P < 0.01). Mean visual acuities (in logarithm of the minimum angle of resolution [logMAR]) at week-4, -8, and -12 follow-up examinations were significantly higher in the IVI group (0.74, 0.75, and 0.82, respectively) when compared with the STi group (0.88, 0.88, and 0.90, respectively; P < 0.01). A significant change from baseline in mean intraocular pressure (mm Hg) was seen at weeks 4 (+/-3.21) and 8 (+/-3.35) in STi the group (P < 0.01), and at week 8 (+/-2.78) in the IVI group (P < 0.05). No patient had cataract progression during the study. CONCLUSIONS: Although the number of patients and length of follow-up in this preliminary study were limited, the changes in central macular thickness and visual acuity observed after treatment suggest that IVI TA may be more effective than STi for the management of refractory diffuse diabetic macular edema. Further studies are needed to confirm these preliminary findings.