Claudine E. Pang

Epiretinal proliferation seen in association with lamellar macular holes: a distinct clinical entity.

Purpose: To describe the prevalence and imaging characteristics of a distinct entity of epiretinal proliferation seen predominantly in association with lamellar macular holes (LMH), termed lamellar hole–associated epiretinal proliferation (LHEP). Methods: Retrospective observational case review of 2,030 eyes of 1,104 patients with diagnoses including LMH, full-thickness macular hole, and epiretinal membrane (ERM) imaged with spectral domain optical coherence tomography (SD-OCT) from 2008 to 2013. Lamellar hole–associated epiretinal proliferation, defined on SD-OCT imaging as an epiretinal material of homogenous medium reflectivity, was identified and its features were qualitatively compared against conventional ERM using the SD-OCT data. Results: Lamellar hole–associated epiretinal proliferation was found in 68 of 2,030 eyes (3.3%), of which 88.2% had LMH and 11.8% had full-thickness macular hole. Lamellar hole–associated epiretinal proliferation was found in 60 of 197 eyes (30.5%) with LMH and 8 of 99 eyes (8.0%) with full-thickness macular hole. Lamellar hole–associated epiretinal proliferation was not seen in 1,734 eyes with ERM, which had no inner retinal defects detectable on SD-OCT. Lamellar hole–associated epiretinal proliferation appeared as a substantial material of homogenous medium reflectivity on the epiretinal surface that demonstrated contiguity with the middle retinal layers and conformed to the adjacent retinal anatomy. Of the eyes with LHEP and LMH, 98% had splitting of the retina in the region of Henles fiber layer in the area immediately around the partial thickness hole, whereas 88% had visible connecting tissue from the base of the lamellar hole to the proliferating epiretinal tissue. In contrast to ERM, LHEP did not induce tractional effects such as distortion or edema of the underlying normal retinal tissue. Morphologic stability was demonstrated in 97% of eyes containing LHEP in serial eye-tracked SD-OCT images for up to 63 months of retrospective follow-up. Conclusion: Spectral domain optical coherence tomography imaging showed that a subset of patients with LMH had an epiretinal proliferation with medium reflectivity and no evidence of contractile properties that was contiguous with layers of the mid-retina. This phenotype differs from conventionally described ERMs in appearance and induced changes of the underlying retina. Given these distinct anatomical relationships, the presence of LHEP could affect surgical outcomes.

The Premacular Bursa's Shape Revealed In Vivo by Swept-Source Optical Coherence Tomography

OBJECTIVE To resolve the controversy surrounding the shape and relationship of posterior vitreous spaces by characterizing the connections between the premacular bursa, the area of Martegiani, and Cloquets canal. DESIGN Comprehensive posterior vitreous maps were created using swept-source optical coherence tomography (SS OCT) in a cross-sectional study. PARTICIPANTS The posterior vitreous of 102 eyes of 51 volunteers 21 to 54 years of age without ocular pathologic features was imaged using SS OCT. METHODS The DRI OCT-1 Atlantis 3D SS OCT (Topcon Medical Systems, Oakland, NJ) was used to acquire scans of the posterior vitreous over an 18×18-mm area. MAIN OUTCOME MEASURES Posterior vitreous spaces and their relationships were identified. RESULTS The premacular bursa was identified in all 102 eyes and was found to extend superiorly beyond our scanning ability at a variable angle. No discernible superior borders could be identified. Instead, a connection of the bursa with the preoptic area of Martegiani or its extension, Cloquets canal, was found in 101 of 102 eyes. This connection occurred at a variable distance from the optic nerve, where it formed a flat and broad superior channel. The skyward direction of this channel was found to be gravity dependent in all 14 eyes of the 7 subjects examined in various head positions. Although SS OCT was able to identify vitreous degeneration, the above changes were present in 28 eyes even without any discernible vitreous degeneration. CONCLUSIONS The premacular bursa, also called the posterior precortical vitreous pocket, was found to continue superiorly beyond the posterior pole without a detectable border. The bursa fused broadly with the extension of the preoptic area of Martegiani, namely Cloquets canal, or the hyaloidal tract of Eisner. These findings suggest that there is a direct anteroposterior connection between the retrolental and premacular and preoptic spaces already existent in the eyes of young adults before the occurrence of vitreous degeneration. This observation may have important implications with respect to the movement of intrinsic and extrinsic mediators between the anterior and posterior segments.

Comparing Functional And Morphologic Characteristics Of Lamellar Macular Holes With And Without Lamellar Hole-associated Epiretinal Proliferation

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.

Multimodal imaging findings in retinal deep capillary ischemia.

Purposes: To evaluate the multimodal imaging findings in retinal deep capillary ischemia (DCI). Methods: This was a retrospective review of 5 eyes of 4 patients with sudden onset of paracentral scotomas caused by DCI. Multimodal imaging techniques, including color and red-free photographs, near-infrared reflectance, fluorescein angiography, and spectral-domain optical coherence tomography, were performed in all eyes, and the findings were correlated with microperimetry in two eyes. Imaging findings in DCI were compared with those of a cotton wool spot caused by superficial capillary ischemia (SCI). Results: Unlike SCI, the imaging findings in DCI were subtler during both the acute and chronic phase, but specific optical coherence tomographic findings could readily differentiate these entities. Acute SCI showed inner retinal whitening, edema, and increased reflectivity, whereas acute DCI showed increased reflectivity of middle retinal layers. Chronic DCI showed retinal thinning with middle layer atrophy, whereas chronic SCI showed inner layer atrophy. In one patient, microperimetry showed a paracentral dense scotoma that corresponded well to the optical coherence tomographic findings. Conclusion: Deep capillary ischemia may represent a nonspecific finding of retinal ischemia and produces characteristic changes within the middle retinal layers, analogous to a deep cotton wool spot, but with distinct features differing from the superficial cotton wool spot which is seen in SCI. Among the various multimodal imaging techniques, optical coherence tomography seemed to be the most sensitive and specific technique in detecting DCI in both the acute and chronic phases.

The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals

PURPOSE To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. RESULTS Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. CONCLUSIONS Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin.

Ultra-Widefield Imaging With Autofluorescence and Indocyanine Green Angiography in Central Serous Chorioretinopathy

PURPOSE To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). DESIGN Retrospective observational case series. METHODS In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). RESULTS In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. CONCLUSIONS Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease.

Swept-Source Optical Coherence Tomography Features of Choroidal Nevi

PURPOSE To investigate the morphologic characteristics of choroidal nevi using swept-source optical coherence tomography and compare this with enhanced-depth optical coherence tomography. DESIGN Retrospective observational case series. METHODS One choroidal nevus each from 30 eyes of 30 patients was included and received imaging with swept-source OCT (SS-OCT) and enhanced-depth imaging OCT (EDI-OCT). For SS-OCT, a scan acquisition protocol was used involving 12 mm horizontal and vertical scans in the posterior fundus. The main outcome measures were morphologic features of choroidal nevi obtained with SS-OCT imaging. These features were compared to images obtained with EDI-OCT. A 2-tailed Fisher exact test was the statistical method used. RESULTS SS-OCT allowed for an appreciation of intralesional details: Of the 30 nevi imaged, intralesional vessels were apparent in 30 (100%), intralesional cavities in 6 (20%), intralesional granularity in 14 (47%), abnormal choriocapillaris in 25 (83%), and abnormal choriocapillaris confined to the tumor apex in 17 (58%). Distended bordering vessels were identified in 22 nevi (73%) and were significantly associated with the presence of previous or persistent subretinal fluid. Intrinsic hyperreflectivity with hyporeflective shadowing was significantly (P = .05) more apparent in 14 of 21 melanotic nevi (67%) compared with 2 of 9 amelanotic nevi (22%). Visualization of the complete nevus-scleral interface was significantly (P = .02) more apparent in 7 of 9 amelanotic nevi (78%) compared with 6 of 21 melanotic nevi (29%), and was not significantly related to tumor thickness (measured by ultrasound) or to tumor configuration. Tumor diameter (but not tumor height) was statistically significantly associated with secondary retinal changes (P = .05) and configuration (P = .01). EDI-OCT was equivalent at determining secondary retinal changes (P = .29), the presence of distended bordering vessels (P = 1), visualization of the nevus-scleral interface (P = .6), and hyporeflective gradation at the nevus-scleral interface (P = .33). However, in melanotic lesions, SS-OCT was significantly superior at visualizing intralesional vessels (P = .0002), intralesional granularity (P = .0005), and abnormal choriocapillaris (P = .0001). CONCLUSION Imaging of choroidal nevi with SS-OCT enables visualization of intralesional details such as vessels (present in 100% of tumors imaged), cavities, and granularity. For melanotic lesions, SS-OCT is significantly better at depicting certain intralesional characteristics compared to EDI-OCT. Distended bordering vessels were recognized in over two thirds of the nevi imaged and were significantly associated with previous or persistent subretinal fluid.

Feasibility And Clinical Utility Of Ultra-widefield Indocyanine Green Angiography

Purpose: To evaluate the feasibility and clinical utility of a novel noncontact scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiographic system. Methods: Ultra-widefield indocyanine green angiographic images were captured using a modified Optos P200Tx that produced high-resolution images of the choroidal vasculature with up to a 200° field. Ultra-widefield indocyanine green angiography was performed on patients with a variety of retinal conditions to assess utility of this imaging technique for diagnostic purposes and disease treatment monitoring. Results: Ultra-widefield indocyanine green angiography was performed on 138 eyes of 69 patients. Mean age was 58 ± 16.9 years (range, 24–85 years). The most common ocular pathologies imaged included central serous chorioretinopathy (24 eyes), uveitis (various subtypes, 16 eyes), age-related macular degeneration (12 eyes), and polypoidal choroidal vasculopathy (4 eyes). In all eyes evaluated with ultra-widefield indocyanine green angiography, high-resolution images of choroidal and retinal circulation were obtained with sufficient detail out to 200° of the fundus. Conclusion: In this series of 138 eyes, scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiography was clinically practical and provided detailed images of both the central and peripheral choroidal circulation. Future studies are needed to refine the clinical value of this imaging modality and the significance of peripheral choroidal vascular changes in the diagnosis, monitoring, and treatment of ocular diseases.

ASSOCIATION BETWEEN NEEDLE SIZE, POSTINJECTION REFLUX, AND INTRAOCULAR PRESSURE SPIKES AFTER INTRAVITREAL INJECTIONS.

Purpose: To compare the effect of 30-gauge versus 32-gauge needle size on postinjection reflux and immediate postinjection intraocular pressure (IOPimmed_post) spikes in eyes injected with anti-vascular endothelial growth factor agents. Methods: This was a prospective interventional case series of 65 eyes of 54 consecutive patients in a clinical practice setting who received intravitreal anti-vascular endothelial growth factor therapy. All eyes had preinjection IOP, IOPimmed_post, postinjection reflux, and axial lengths recorded. Results: There was a higher incidence of postinjection reflux in eyes injected with 30-gauge (53%) compared with those injected with 32-gauge (13%, P = 0.0007). Among 34 eyes injected with 30-gauge, 16 eyes without appreciable postinjection reflux had mean IOPimmed_post of 44.3 ± 7.48 mmHg and mean IOPimmed_post elevation of 29.6 ± 2.10 mmHg, which was significantly higher than the 18 eyes with reflux (mean IOPimmed_post of 18.8 ± 7.15 mmHg and mean IOPimmed_post elevation of 4.5 ± 1.74 mmHg, P < 0.0001). Among 31 eyes injected with 32-gauge, 27 eyes without appreciable postinjection reflux had mean IOPimmed_post of 44.4 ± 10.82 mmHg and mean IOPimmed_post elevation of 29.5 ± 1.99 mmHg, which was significantly higher than the 4 eyes with reflux (mean IOPimmed_post of 21.3 ± 8.54 mmHg and mean IOPimmed_post elevation of 9.5 ± 4.05 mmHg, P < 0.001). The differences in reflux and IOP between the two groups were unrelated to axial lengths (P = 0.451). Conclusion: Eyes receiving injections with 32-gauge needles had a lower incidence of postinjection reflux and higher mean IOP immediately after injection.

Adaptive optics imaging of cone mosaic abnormalities in acute macular neuroretinopathy.

BACKGROUND AND OBJECTIVE To assess the cone photoreceptor mosaic in acute macular neuroretinopathy (AMN) using adaptive optics (AO) imaging. PATIENTS AND METHODS Four patients with AMN were evaluated retrospectively by near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO), spectral-domain optical coherence tomography (SD-OCT), and a flood-illuminated retinal AO camera. Microperimetry was performed in one patient. RESULTS The cone photoreceptor density was decreased at the level of the AMN lesions. The cone mosaic disruption appeared heterogeneous and more widespread than the lesion detected in the IR-SLO and SD-OCT images. The areas of cone loss correlated with SD-OCT and microperimetry. After resolution of the AMN lesion on IR-SLO, there was incomplete recovery of the cone photoreceptor mosaic. CONCLUSION Cone photoreceptor damage and reconstitution were documented in vivo at the cellular level in AMN using AO imaging. AO imaging appeared more sensitive than combined IR-SLO and SD-OCT to detect and follow photoreceptor damage in patients with AMN.