Faculty Bibliography

PURPOSE/OBJECTIVE:To characterize relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization (MNV) and visual responses to ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS:This was a post hoc analysis of the phase 3 HARBOR trial of ranibizumab in nAMD. Analyses included ranibizumab-treated eyes with baseline multimodal imaging data; baseline MNV; subretinal and/or intraretinal fluid at screening, baseline, or week 1; and spectral-domain optical coherence tomography images through month 24 (n = 700). Mean best-corrected visual acuity (BCVA) over time and mean BCVA change at months 12 and 24 were compared between eyes with type 1, type 2/mixed type 1 and 2 (type 2/M), and any type 3 MNV at baseline. RESULTS:At baseline, 263 (37.6%), 287 (41.0%), and 150 (21.4%) eyes had type 1, type 2/M, and any type 3 lesions, respectively. Type 1 eyes had the best mean BCVA at baseline (59.0 [95% CI: 57.7-60.3] letters) and month 24 (67.7 [65.8-69.6] letters), whereas type 2/M eyes had the worst (50.0 [48.6-51.4] letters and 60.8 [58.7-62.9] letters, respectively). Mean BCVA gains at month 24 were most pronounced for type 2/M eyes (10.8 [8.9-12.7] letters) and similar for type 1 (8.7 [6.9-10.5] letters) and any type 3 eyes (8.3 [6.3-10.3] letters). CONCLUSION/CONCLUSIONS:Differences in BCVA outcomes between CONAN lesion type subgroups support the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT00891735. Date of registration: April 29, 2009.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging (MMI) features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with macular neovascularization (MNV). DESIGN/METHODS:Retrospective, observational case series. METHODS:Fourteen eyes (14 patients, 7 male) were imaged with spectral-domain optical coherence tomography (OCT), and either fluorescein angiography or OCT angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity (BCVA) assessments. RESULTS:Mean age was 75±13 (range: 45-96) years, with mean follow-up duration of 27±21 (range: 1-56) months. Neovascular age-related macular degeneration (nAMD) was found in 71% (10/14) eyes. Type 2 MNV lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved following intravitreal anti-VEGF therapy in all eyes. Baseline BCVA improved from LogMar 0.84±0.32 (Snellen equivalent 20/138) to LogMar 0.48±0.31 (Snellen equivalent 20/60) at last follow-up, with treatment of the MNV. CONCLUSIONS:Type 2 MNV and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal anti-VEGF therapy results in rapid resolution of BDs and visual improvement in most eyes.

PURPOSE/OBJECTIVE:To describe the differential response of two distinct inflammatory signs occurring in eyes with punctate inner choroidopathy (PIC). METHODS:Retrospective, observational case series utilizing multimodal imaging (MMI). RESULTS:Four eyes of 4 myopic female patients (mean age 35 years, range 31-42) presenting with retinal manifestations of PIC. All study eyes had 2 distinct signs of active disease: 1) acute focal hyperreflective lesions splitting the retinal pigment epithelium/Bruch's membrane (RPE/BrM) complex on optical coherence tomography (OCT) which appeared hypoautofluorescent on fundus autofluorescence (FAF), and 2) more diffuse areas of outer retinal disruption (ORD) limited to the ellipsoid zone and interdigitation zone on OCT and corresponding to hyperautofluorescence on FAF. All patients were treated with oral prednisone and demonstrated prompt regression of the RPE/BrM complex lesions with a concurrent, paradoxical centrifugal expansion of ORD. The ORD eventually resolved in all eyes (mean time 6 weeks, range 4-10 weeks). CONCLUSIONS:In patients with PIC, two distinct inflammatory signs observed with MMI display a differential response to systemic corticosteroids. Whereas focal inflammatory lesions splitting the RPE/BrM complex appear to respond rapidly, the more diffuse, transient ORD shows little response. This difference in treatment response may reflect different immunological phenomena with independent natural history.

PURPOSE/OBJECTIVE:To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN/METHODS:Multicenter retrospective observational case series. PARTICIPANTS/METHODS:Sixty-three patients with SIC in 1 eye. METHODS:Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES/METHODS:Standardized grading of imaging features. RESULTS:Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS:In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Objective: To explore the applicability of an ambulatory inertial sensor (G-walk) to characterize gait function during the Timed Up and Go (TUG) Test under three different conditions.
Background(s): In Parkinson's disease (PD), the current lack of both reliable and feasible biomarkers of gait function and mobility limits the objective characterization of motor ability, clinical progression, and responsiveness to treatments. Current assessments of motor function rely on a clinicians' subjective judgement and/or the patient's self-reported questionnaires, which are not sensitive in capturing subtle changes over time and restrict comparability across raters. Ambulatory inertial sensors allow for non-invasive, wireless transmission of accurate quantitative data and therefore, may represent a useful tool in ambulatory settings. Design/Methods: Nineteen (19) PD patients (H&Y <4) and 10 agematched controls (CTRL) were consecutively enrolled to undergo inertial TUG (iTUG) testing under three experimental conditions: normal walking (iTUGnorm), dual task walking (iTUGcog), and at maximum speed (iTUGfast). The time needed to complete each test was sub-divided into six distinct phases quantified by the sensor: sitto- stand (1), forward gait (2), mid-turn (3), return gait (4), end-turn (5) and stand-to-sit (6). Other assessments included UDPRS Part III, MoCA, depression, fatigue, Benton and Rey-Osterrieth visual tests.
Result(s): A total of nineteen PD patients and ten CTRLs completed all assessments. PD patients were divided into mild (H&Y=2, n=12) and moderate (H&Y=3, n=7) disease severity. One-way-ANOVA and correlation analysis were performed. Different patterns of kinematic performance were observed (figure 1.A and 1.B). In PD, iTUG correlations were found with cognitive function, visual performance and motor severity, while in CTRLs there was only a correlation with motor performance only. iTUGfast performance seemed more sensitive experimental condition when PD was stratify by severity (figure 1.B).
Conclusion(s): iTUG assessed by an ambulatory inertial sensor is a quick, sensitive and feasible tool for objective measurements of functional mobility in PD. Utilizing validate tests for mobility and gait under different stress conditions can provide distinct information of gait function and mobility. Future longitudinal studies are warranted to better characterize the sensitivity to disease progression and the potential for monitoring and optimizing therapeutic interventions in this patient population. (Figure Presented)

PURPOSE/OBJECTIVE:Macular perivenous retinal whitening results from hypoperfusion-induced ischemia of the middle retina that can occur in central retinal vein occlusion (CRVO). We describe an unusual case of recurrent CRVO with macular perivenous retinal whitening and retino-ciliary venous sparing in the setting of 2 prothrombotic diseases, antiphospholipid syndrome and Type II cryoglobulinemia. METHODS:A 50-year-old man presented with intermittent loss of vision in his right eye related to a recurrent CRVO. Color photography, optical coherence tomography, and fluorescein angiography were performed and compared with those obtained during a previous CRVO that occurred 6 years earlier in the same eye. RESULTS:On presentation, visual acuity was hand motion in the right eye, 20/30 in the left eye. Funduscopic examination of the right eye showed vascular tortuosity, scattered retinal hemorrhages, and retinal whitening in the macula. Optical coherence tomography showed hyperreflectivity of the middle layers of the retina that correlated with the areas of retinal whitening. A discrete area of retinal sparing was noted in the superonasal macula that, on fluorescein angiography, corresponded to the distribution of a single retino-ciliary vein. A review of retinal imaging obtained during the patient's previous CRVO showed similar but more subtle findings of retino-ciliary sparing. Laboratory testing revealed antiphospholipid syndrome and Type II cryoglobulinemia. As the patient's CRVO progressed and subsequently stabilized after treatment in the following months, this area of venous sparing remained the only functional, nonischemic retinal tissue in his macula. Presumably, this vein possessed privileged and uncompromised blood flow by circumventing the occluded venous circulation. CONCLUSION/CONCLUSIONS:Macular perivenous retinal whitening should be considered in the differential diagnosis of retinal whitening and occurs in CRVO secondary to hypoperfusion-induced middle retinal ischemia. To our knowledge, this case represents the first description of retino-ciliary venous sparing of the retina in CRVO.

PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow. METHODS: This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti-vascular endothelial growth factor therapy. RESULTS: Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti-vascular endothelial growth factor therapy (all tested variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.

PURPOSE/OBJECTIVE:To determine the long-term effect of internal limiting membrane with associated epiretinal membrane (ERM) peeling versus single peeling alone in terms of best-corrected visual acuity and anatomical outcomes on spectral-domain optical coherence tomography. METHODS:This retrospective comparative cohort study of patients who had follow-up of >1 year and underwent surgery for ERM by a single surgeon (S.C.) from January 1, 2008 to December 31, 2012 compared cases in which the internal limiting membrane was stained with brilliant blue G to facilitate double peeling (n = 42) and single peeling (n = 43) of the ERM alone for up to 3 years of follow-up. For continuous variables, an independent two-tailed t-test was performed. For binary variables, the Fisher's exact test was performed. Statistical significance was defined as P < 0.05. RESULTS:Eighty-five of 142 patients fit the inclusion criteria. At the last follow-up, the single-peeling group were more likely to have ERM remaining in the central fovea postoperatively (P = 0.0020, becoming significant by postoperative Year 1, P = 0.022) and less likely to develop inner retinal dimpling (P = 0.000, becoming significant by postoperative Month 3, P = 0.015). At 3 years, central foveal thickness had decreased in the single-peeling group by -136.9 µm and by -84.1 μm in the double-peeling group, which was not significantly different (P = 0.08). Mean best-corrected visual acuity improved in both the groups at all time points. There was no statistically significant difference between the 2 groups at 3 years (P = 0.44; single-peeling group, 0.32 ± 0.42, Snellen 20/42; double-peeling group, 0.23 ± 0.27, Snellen 20/34). CONCLUSION/CONCLUSIONS:Brilliant blue G-assisted internal limiting membrane peeling for ERM results in a more thorough removal of residual ERM around the paracentral fovea. However, there is no difference in long-term best-corrected visual acuity at 3 years and a greater likelihood of inner retinal dimpling.