Faculty Bibliography

Purpose Safety and efficacy of ocriplasmin to treat symptomatic vitreomacular adhesion (VMA), was established in phase 3 clinical trials using time-domain optical coherence tomography (TDOCT) to assess retinal anatomy. Using spectral domain optical coherence tomography (SDOCT) allows observation and measurement of subtle retinal changes and enables more accurate monitoring of disease progression and response to therapy. A Phase 4 study was designed to retrospectively review and further characterize anatomic and symptomatic changes, using SD-OCT, following treatment of VMA with JETREA (ocriplasmin). Methods The Phase 4 OZONE study will include 200 patients from ~30 US sites. Anatomic and symptomatic changes over 6-months in patients treated with ocriplasmin for VMA and imaged with SD-OCT. Images will be masked and uploaded to a Central Reading Center (CRC) for review and analysis. The primary endpoint is the proportion of patients with ellipsoid zone disruption by Day 21 post-ocriplasmin injection, which was not present at baseline. Secondary endpoints include: incidence, time to onset and/or resolution of ellipsoid zone disruption, subretinal fluid development, VMA status, macular hole changes, vitrectomy, visual acuity changes from baseline and adverse drug reactions (Table 1). Results As of 11/12/14, preliminary data from 52 patients at 11 clinics were available. Preliminary data on baseline characteristics include: mean age: 71 years; gender: 61.5% female; baseline lens status in study eye: phakic= 67%, pseudophakic= 33%, and aphakic=0%; baseline visual acuity in study eye (Snellen) 20/40 or better=29%, 20/50-20/80=52%, and 20/100 or worse= 17%, 10/200= 2%; injection position: supine=83%, sitting=2%, sitting at 45degree=12%. Conclusions The OZONE study utilizing SD-OCT in post-ocriplasmin patients will further characterize anatomic and symptomatic changes post-ocriplasmin. Data from the full population and image analysis will be available

Purpose To determine the rate of neovascularization (NV) in eyes with acquired vitelliform lesion (AVL) during and following vitelliform collapse. To correlate the optical coherence tomography (OCT) and histopathological characteristics of these neovascular membranes. Methods Retrospective cohort analysis of 112 patients with AVL. Patients that demonstrated evidence of vitelliform collapse, defined as a temporal reduction in the size of subretinal vitelliform material clinically, using OCT and fundus autofluorescence imaging, were included for further analysis. Clinical and OCT characteristics of neovascular membranes were determined. A correlation between OCT and histopathological characteristics of an eye that was clinically diagnosed as non-neovascular but demonstrated a type 1 membrane on post mortem examination was also performed. Results Twenty-six patients (16 males and 10 females) demonstrated evidence of vitelliform collapse, and 7 (26.9%) of these developed NV. 5 of these patients were diagnosed with NV following acute subretinal hemorrhage or exudation. Mean age of patients was 81.1 +/- 11.6 years, and mean period of follow up was 9.0 +/- 4.2 years. All neovascular membranes were type 1. Persistent OCT findings prior to the development of NV included: (1) Irregular elevation of the retinal pigment epithelium (RPE) layer at the site of NV. (2) Separation of the RPE layer and Bruch's membrane (BrM) by a hyporeflective material containing punctate hyper-reflectivity (figure 1). Three patients had fluorescein angiography (FA) within 6 months preceding the diagnosis of neovascular disease that did not demonstrate leakage. Histopathologic examination demonstrated a fibrovascular scar and thick basal laminar deposit (BlamD) under the fovea with hemorrhage between the scar and BrM. These lesions correlated with the split RPE-BrM band on OCT images acquired 8 months before the patient's death (figure 2). Conclusions The rate of Type 1 NV during and following vitelliform collapse in AVLs is significant. In this subgroup of patients, neovascular membranes appear to remain dormant in the anatomic space between BrM and BLamD before the clinical signs of NV, including exudation and hemorrhage, become manifest. Interval review of these patients is therefore indicated as is a prospective study of this topic

PURPOSE:: To investigate the association between the type of neovascularization (NV) and the clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration. METHODS:: Eighty-three patients with treatment-naive, unilateral, neovascular age-related macular degeneration were retrospectively analyzed. Neovascular lesions were classified using both fluorescein angiography and optical coherence tomography as Type 1 (subretinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed NV. The associations between NV lesion type and baseline clinical and imaging characteristics of the fellow eye, including central geographic atrophy, noncentral geographic atrophy, pigmentary changes, soft drusen, cuticular drusen, reticular pseudodrusen, and subfoveal choroidal thickness, were examined. Subfoveal choroidal thickness was defined as thin if thickness was <120 mum. RESULTS:: In the fellow eyes of patients with treatment-naive, unilateral, neovascular age-related macular degeneration, Type 3 NV had an increased adjusted odds ratio of reticular pseudodrusen (15.361, P < 0.001) and thin subfoveal choroidal thickness (21.537, P < 0.001) as well as a tendency toward an increased adjusted odds ratio of central geographic atrophy (4.775, P = 0.028). Fellow eyes of patients with Type 1 NV showed a decreased adjusted odds ratio of reticular pseudodrusen (0.233, P = 0.007) and thin subfoveal choroidal thickness (0.080, P = 0.005). CONCLUSION:: In patients with unilateral, neovascular age-related macular degeneration, certain nonneovascular features of the fellow eye correlate with the NV lesion composition based on type, as anatomically classified utilizing both fluorescein angiography and optical coherence tomography. Patients with Type 3 NV were more likely to have reticular pseudodrusen and/or thin subfoveal choroidal thickness in the fellow eye compared with those with Type 1 NV. Patients with Type 3 NV also showed a trend toward increased central geographic atrophy in the fellow eye.

PURPOSE: To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. METHODS: Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at pre-defined locations. RPE cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. RESULTS: In 13 GA eyes (449 locations), Shedding, Sloughed, and Dissociated morphologies were abundant; 22.2% of atrophic locations had Dissociated RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had Entombed RPE; Sloughed, Dissociated, and Bilaminar morphologies were abundant. Of abnormal RPE, CNV and GA both have ~35% Sloughed/Intraretinal, with more Intraretinal in CNV (9.5% vs 1.8%). Shedding cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. CONCLUSION: RPE morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are Dissociated and Sloughed cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping studies.

IntroductionThe characteristics of type 3 neovascularization (NV), also known as retinal angiomatous proliferation, have been well described clinically, as well as with fluorescein angiography (FA), indocyanine green angiography, and optical coherence tomography (OCT). OCT angiography (OCT-A) is a novel and non-invasive technique for imaging retinal microvasculature by detecting changes, with respect to time, in reflectivity related to blood flow.MethodIn this case series, we describe two patients who presented with type 3 NV and underwent clinical examination and multimodal imaging, including OCT-A.ResultsIn the first patient, OCT-A demonstrated flow within two separate lesions in the same eye, one of which was only weakly detected by FA. In the second patient, sequential OCT-A demonstrated a reduction in intralesional flow following intravitreal therapy.ConclusionsOCT-A may have a role in the early diagnosis of type 3 NV and in assessing the response to treatment. Further studies are needed to determine sensitivity and specificity.

BACKGROUND AND OBJECTIVE: To investigate the clinical course and outcomes of patients with vitreomacular traction (VMT) managed initially by observation. PATIENTS AND METHODS: This noncomparative case series included patients with a diagnosis of VMT based on clinical symptoms and findings on spectral-domain optical coherence tomography (SD-OCT) between 2005 and 2014. VMT was documented using a standardized grading system based on the degree of distortion of the foveal contour. Data were collected at five retina clinics using standardized collection forms. Visual acuity, changes in SD-OCT findings, and timing of the release of VMT as seen on SD-OCT were recorded. RESULTS: The study included 230 eyes of 185 patients. Mean age was 72.5 years, and mean follow-up was 32 months. At baseline, VMT grading was grade 1 in 92 eyes (40%), grade 2 in 118 eyes (51.3%), and grade 3 in 20 eyes (8.7%). By last follow-up, spontaneous release of VMT occurred in 73 eyes (31.7%). Spontaneous release of VMT occurred at a mean of 18 months (median: 10.9 months) after initial visit. Mean logMAR best corrected visual acuity (BCVA) was 0.28 (20/55) (range: 20/20 to 20/400) at baseline and 0.25 (20/51) (range: 20/20 to 20/400) at last follow-up. Pars plana vitrectomy was performed in 10 eyes (4.1%) for macular hole (six eyes) and increased VMT (four eyes); BCVA was at least 20/40 in eight of the 10 eyes at last follow-up. CONCLUSION: Patients with VMT generally had a favorable clinical course when managed initially by observation. Spontaneous release of VMT occurred in approximately one-third of patients. At last follow-up, pars plana vitrectomy was performed in fewer than 5% of patients. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:571-576.].

PURPOSE:: To compare the functional and morphologic characteristics and evolution of lamellar macular holes (LMHs) with and without lamellar hole-associated epiretinal proliferation (LHEP). METHODS:: This was a retrospective observational case review of 145 eyes of 136 patients with LMH seen in a vitreoretinal clinical practice, and the eyes were subdivided into 2 groups based on the presence or absence of LHEP. Main outcome measures were logarithm of minimal angle of resolution (logMAR) visual acuity and morphologic characteristics as seen with spectral domain optical coherence tomography over retrospective follow-up. RESULTS:: In 62 eyes (42.7%), LHEP was detected, while 83 eyes (57.3%) had the presence of epiretinal membrane without LHEP. The mean logMAR visual acuity in eyes with LHEP was 0.51 (20/65 Snellen equivalent), which was significantly poorer than that in the eyes without LHEP at 0.33 (20/43 Snellen equivalent, P = 0.002). Multivariate analysis showed that the presence of LHEP was significantly associated with larger LMH diameter at the middle retinal level (P = 0.01) and thinner retinal thickness at the base of the LMH (P < 0.001). A higher proportion of eyes with LHEP (88%) had ellipsoid disruption compared with eyes without LHEP (24%, P = 0.001). Over the mean retrospective follow-up of 26 months, 5% of eyes with LHEP had functional decline of 0.3 logMAR visual acuity compared with 4% of eyes without LHEP (P = 0.99), whereas 18% of eyes with LHEP had morphologic progression compared with 13% of eyes without LHEP (P = 0.49). CONCLUSION:: Eyes with LMH and LHEP were associated with poorer visual acuity, larger LMH diameters, thinner retinal thickness, and higher incidence of ellipsoid disruption compared with eyes without LHEP, suggesting a process involving more severe retinal tissue loss and injury. Both LMH with and without LHEP seemed to be stable configurations over time.