RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration.

Purpose: A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls. Methods: The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. Results: The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799-19,554] pg/mL vs. 5435 [3420-9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls. Conclusions: We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients. Translational Relevance: The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

Closure of Full-Thickness Macular Holes Associated with Macular Edema with Medical Therapy.

PURPOSE: The purpose of this study was to report the closure of macular hole without surgery in 7 cases using medical therapies. METHODS: The retrospective review of 7 cases of full-thickness macular holes, which closed after medical therapy without surgery. RESULTS: Seven eyes of 7 patients developed full-thickness macular holes, which initially closed on medical therapy without surgery. Six patients were kept on maintenance therapy; 1 recurred and 5 did not develop recurrence. One patient was taken off of maintenance therapy and later developed recurrent macular hole requiring macular hole surgery. CONCLUSIONS: Medical therapy to decrease macular edema may facilitate macular hole closure and should be considered, especially for small macular holes with significant edema. Reopening of macular holes may occur after stopping topical maintenance therapy for macular edema, which occurred at 10 weeks and 9 months after maintenance therapy was discontinued or markedly tapered.

DYNAMIC ECHOGRAPHY OF VARIX OF THE VORTEX VEIN AMPULLA.

PURPOSE: To describe four cases of varix of the vortex vein ampulla imaged with dynamic echography. METHODS: Observational case series of four patients with varix of the vortex vein ampulla diagnosed with ocular examination maneuvers such as digital pressure or Valsalva. Dynamic echography was used to confirm the diagnosis. RESULTS: Dynamic echography can quickly and noninvasively show the varix of the vortex vein ampulla disappear with external pressure, or engorge with a Valsalva maneuver or altered gaze directions. CONCLUSION: Dynamic echography is very helpful in the establishment of the diagnosis of varix of the vortex vein ampulla and differentiating this benign condition from other retinal or choroidal abnormalities.

Automated quantitative OCTA measurements of uveal melanoma-treated eyes with and without radiation retinopathy after I-125 plaque therapy and of nonirradiated fellow eyes.

OBJECTIVES: To determine if commercial OCTA measurements can provide quantitative biomarkers for detection of radiation retinopathy (RR) s/p I-125 plaque brachytherapy in patients with uveal melanoma. METHODS: Retrospective review of 6 × 6 mm OCTA images of nonirradiated fellow eyes (group 1, 28 eyes), eyes without RR (group 2, 22 eyes), eyes with RR (group 3, 13 eyes). We used automated AngioVue AngioAnalytics OCTA software determinations of FAZ size, perimeter size, and 27 capillary density measurements (nine regions of each segmentation: full-thickness retina, superficial plexus, deep plexus). RESULTS: Average time since irradiation was 1.9 years in group 2, and 3.7 years in group 3. FAZ size was 1.2 mm in group 3 compared with 0.2 mm in group 1 and 0.3 mm in group 2 (both p < 0.001). Capillary density was statistically significantly reduced in group 3 compared with group 1 in all 27 regions. Group 2 had significantly decreased superficial plexus capillary density compared with group 1 in three regions. Group 3 had significantly reduced capillary density compared with group 2 in 6/27 (22%) regions. Linear regression showed a change in whole-scan density of -1.5 per year after irradiation in the full-thickness retina segmentation (p = 0.008). CONCLUSION: Quantitative OCTA may aid in early detection of RR.

Simulating vascular leakage on optical coherence tomography angiography using an overlay technique with corresponding thickness maps.

BACKGROUND: To demonstrate a technique for using optical coherence tomography angiography (OCTA) to simulate leakage in eyes with diabetic macular oedema and determine the sensitivity and positive predictive value of detecting leaking microvasculature on OCTA using fluorescein angiography (FA) as the comparative norm. METHODS: 6×6 mm OCT angiograms were overlaid with the corresponding OCT thickness maps. Microvascular abnormalities on the OCT angiogram underlying areas of thickening on the OCT thickness map were assumed to be leaking. Two independent readers blindly read the OCTA overlay images then the FA images cropped to the same approximate region to delineate areas of leaking microvasculature. The results were compared to determine the sensitivity and positive predictive value of OCTA for detection of leaking vessels. RESULTS: 28 eyes of 19 diabetic patients were included. Each eye demonstrated an average of seven leaking microvascular abnormalities on the OCTA images and 22 leaking abnormalities on the FA images. Sensitivity of leaking microvasculature detection by OCTA was 26.1% and positive predictive value was 68.4%. The correlation coefficient of the two readers' detection of leaking microvasculature was 0.605 for OCTA reads compared with 0.916 for FA. CONCLUSION: OCTA as a whole can be used to simulate leakage, but currently, sensitivity of the technique is low. Further understanding of the OCTA technology may yield novel means of detecting retinal pathology.

Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma.

PURPOSE: To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. DESIGN: Multicenter, retrospective case series and literature review. PARTICIPANTS: Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). METHODS: The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. MAIN OUTCOME MEASURES: Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). RESULTS: In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. CONCLUSIONS: Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

SENSITIVITY AND SPECIFICITY OF DETECTING POLYPOIDAL CHOROIDAL VASCULOPATHY WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis with structural en face optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Retrospective review of the medical records of eyes diagnosed with PCV by indocyanine green angiography with review of diagnostic testing with structural en face OCT and OCTA by a trained reader. Structural en face OCT, cross-sectional OCT angiograms alone, and OCTA in its entirety were reviewed blinded to the findings of indocyanine green angiography and each other to determine if they could demonstrate the PCV complex. Sensitivity and specificity of PCV diagnosis was determined for each imaging technique using indocyanine green angiography as the ground truth. RESULTS: Sensitivity and specificity of structural en face OCT were 30.0% and 85.7%, of OCT angiograms alone were 26.8% and 96.8%, and of the entire OCTA were 43.9% and 87.1%, respectively. Sensitivity and specificity were improved for OCT angiograms and OCTA when looking at images taken within 1 month of PCV diagnosis. CONCLUSION: Sensitivity of detecting PCV was low using structural en face OCT and OCTA but specificity was high. Indocyanine green angiography remains the gold standard for PCV detection.

Spectral-Domain Optical Coherence Tomography Angiography for the Diagnosis and Evaluation of Polypoidal Choroidal Vasculopathy.

PURPOSE: To compare the diagnostic ability of optical coherence tomography angiography (OCTA) with indocyanine green angiography (ICGA) in polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective review of 47 eyes with PCV imaged with ICGA and OCTA. For each eye, it was determined which imaging modality better delineated the PCV complex. The presence of a branching vascular network (BVN) and polyp(s) were noted. RESULTS: PCV was better visualized with ICGA in 21 eyes (44.7%) and with OCTA in 9 eyes (19.2%). The results were comparable in 17 eyes (36.2%). Of the 44 eyes with BVN on ICGA, 41 eyes (93.2%) also showed BVN on OCTA. Of the 28 eyes with polyp(s) on ICGA, 22 eyes (78.6%) also showed polyp(s) on OCTA. Polyps were high-flow lesions or faint low-flow dilations on OCTA. CONCLUSION: OCTA readily detects BVNs and can detect most polyps, but in many cases ICGA is better able to detect the PCV complex.

Optical coherence tomography angiography artifacts in retinal pigment epithelial detachment.

OBJECTIVE: To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED). DESIGN: Retrospective review. METHODS: Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as "decorrelation tails." RESULTS: OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the "decorrelation tails" artifact, which caused the RPED to appear as a bright ring on the segmented OCTA. CONCLUSIONS: OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.

Visualization of changes in the foveal avascular zone in both observed and treated diabetic macular edema using optical coherence tomography angiography.

BACKGROUND: Central vision loss in diabetic retinopathy is commonly related to diabetic macular edema (DME). The objective of this study was to describe changes between consecutive visits on optical coherence tomography angiography (OCTA) of the foveal avascular zone (FAZ) in eyes with DME. METHODS: 20 eyes from 14 patients with DME were imaged on 2 successive clinic visits separated by at least 1 month. The mean interval between visits was 3.2 months. The only intervention used was intravitreal anti-VEGF in 11 eyes; the others were observed over time without treatment. Two different readers measured FAZ area using a pseudo-automated tool in comparison to a manual tracing tool. Qualitative changes in the appearance of the vasculature surrounding the FAZ were also recorded. The retinal capillary plexus was segmented into deep and superficial plexuses, and FAZ measurements were done on the superficial, deep, and summated plexuses. RESULTS: Pseudo-automated and manual measurements of FAZ area decreased significantly (p < 0.05) between visits in the deep, superficial, and summated plexuses. Qualitative analysis of vasculature surrounding the FAZ showed that most of the vascular changes (65%) over time were visible in the deep plexus, compared to 30 and 20% in the superficial and summated plexuses, respectively. CONCLUSIONS: The most significant differences in FAZ size over time were in the summated plexus (p < 0.001), while changes in FAZ appearance were most prominent in the deep plexus. Absolute decrease in FAZ size over visits was largest in the deep plexus. Our results demonstrate that OCTA can effectively be used to measure FAZ area in patients with DME, visualize qualitative changes in retinal vasculature, and visualize the segmentation levels at which these changes can be best appreciated. However, larger studies are needed to evaluate the reproducibility of manual and pseudo-automated measuring techniques.

Characteristics and racial variations of polypoidal choroidal vasculopathy in tertiary centers in the United States and United Kingdom.

PURPOSE: To evaluate the characteristics and racial variations amongst patients with polypoidal choroidal vasculopathy (PCV) in the United States and the United Kingdom. METHODS: Fundus photos and indocyanine green angiography images were evaluated in a multicenter retrospective study to establish the diagnosis of PCV. Visual acuity (VA) was recorded in ETDRS letter count. RESULTS: Eighty eyes of 71 PCV patients (average age of 69.4 ± 10.4 years) were included in the analysis. Of the total 71 subjects, 46 (65%) were women, 33 (46.5%) were Blacks, 16 (22.5%) were Whites, 19 (26.8%) were Asians and 3 (4.2%) belonged to other races. The Black subgroup had vision gain of 3.5 letters. The White and Asian subgroups had vision loss of 13.1 and 3.5 letters, respectively. There was female predominance in Blacks (67%), Whites (69%), and Asians (58%). PCV was found to be a bilateral disease in 14 patients (20%). There was significant decrease of 7 letters with every decade increase in age (p = 0.005). Final VA was worse in males when compared to females (p = 0.042), and worse in Whites when compared to Blacks (p = 0.005). For every 10 letters worse in initial VA upon diagnosis with PCV, the final VA was worse by 6 letters (p < 0.001). The location of the polypoidal lesion within the macula was associated with significant decrease of 14 letters in BCVA (p = 0.02). The length of follow up was significantly associated with worse visual outcome (p = 0.012). Final VA had no significant correlation with the lens status, or the different treatment modalities. CONCLUSIONS: Based on our cohort from tertiary centers in the United States and United Kingdom, PCV is a bilateral disease in one-fifth of patients. It features a variable female predominance based on ethnicity. Increased age, worse vision upon initial presentation, longer follow up and macular location of the polyp were associated with worse visual outcome.

En Face Doppler Optical Coherence Tomography Measurement of Total Retinal Blood Flow in Diabetic Retinopathy and Diabetic Macular Edema.

IMPORTANCE: Alterations in ocular blood flow play an important role in the pathogenesis and progression of diabetic retinopathy (DR). However, the measurement of retinal blood flow in clinical studies has been challenging. En face Doppler optical coherence tomography (OCT) provides an effective method for measuring total retinal blood flow (TRBF) in the clinic. OBJECTIVE: To investigate TRBF in eyes with DR of varying severity, with or without diabetic macular edema (DME), using en face Doppler OCT. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted from May 23, 2014, to January 11, 2016, which analyzed 41 eyes with DR from 31 diabetic patients, 20 eyes without DR from 11 diabetic patients, and 16 eyes from 12 healthy age-matched controls, all at the New England Eye Center in Boston, Massachusetts. MAIN OUTCOMES AND MEASURES: Participants were imaged with a high-speed, swept-source OCT prototype at 1050-nm wavelength using repeated en face Doppler OCT raster scans, comprising 600 × 80 axial scans and covering a 1.5 × 2-mm2 area centered at the optic disc. The TRBF was automatically calculated using custom Matlab software. RESULTS: This study included 41 eyes with DR from 31 diabetic patients (mean [SD] age, 62.8 [13.4] years; 12 were female patients), 20 eyes without DR from 11 diabetic patients (mean [SD] age, 58.8 [10.1] years; 5 were female patients), and 16 eyes from 12 healthy age-matched controls (mean [SD] age, 57.9 [8.1] years; 8 were female participants). The mean (SD) TRBF was 28.0 (8.5) µL/min in the eyes with DME, 48.8 (13.4) µL/min in the eyes with DR but without DME, 40.1 (7.7) µL/min in the diabetic eyes without retinopathy, and 44.4 (8.3) µL/min in age-matched healthy eyes. A difference in TRBF between the eyes with DME that were treated and the eyes with DME that were not treated was not identified. The TRBF was consistently low in the eyes with DME regardless of DR severity. The eyes with moderate nonproliferative DR but without DME exhibited a wide range of TRBF from 31.1 to 75.0 µL/min, with the distribution being highly skewed. CONCLUSIONS AND RELEVANCE: High-speed en face Doppler OCT can measure TRBF in healthy and diabetic eyes. Diabetic eyes with DME exhibited lower TRBF than healthy eyes (P ≤ .001). Further longitudinal studies of TRBF in eyes with DR would be helpful to determine whether reduced TRBF is a risk factor for DME.

ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY.

PURPOSE: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. METHODS: The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. RESULTS: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. CONCLUSION: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization.

PURPOSE: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS: A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). CONCLUSIONS: En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV.

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.

Optical Coherence Tomography Angiography Findings in Coats' Disease.

BACKGROUND AND OBJECTIVE: To describe optical coherence tomography angiography (OCTA) findings in patients with unilateral Coats' disease. PATIENTS AND METHODS: Retrospective, observational case series of four patients with unilateral Coats' disease who underwent bilateral OCTA imaging. RESULTS: Bilateral macular OCTA findings of eight eyes are described. An abnormal foveal avascular zone (FAZ) with inner retinal vessels traversing the avascular zone in the superficial capillary plexus was visible on OCTA in the affected eye of all four patients. A similarly abnormal FAZ was noted on OCTA in the clinically normal fellow eye in two of the four patients (50%). CONCLUSION: OCTA may demonstrate an abnormal foveal avascular zone in both the affected eye and the clinically unaffected fellow eye, suggesting widespread pathology of the retinal vasculature in Coats' disease. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:632-635.].