Faculty Bibliography

PURPOSE: To describe a new set of findings in eyes with pseudoxanthoma elasticum, specifically large defects in Bruch membrane. METHODS: Retrospective review of the optical coherence tomography image obtained with the Heidelberg Spectralis of the posterior pole of patients with pseudoxanthoma elasticum. Large dehiscences in Bruch membrane were defined as any defect in Bruch membrane greater than 250 microm in diameter that was not contiguous with a visible angioid streak. RESULTS: There were 28 eyes of 14 patients, with a mean age of 53.6 years; 10 were female. Large dehiscences in Bruch membrane were seen in nine eyes of six patients, and all were within peripapillary atrophy manifested by loss of the choroid and retinal pigment epithelium. The edges of Bruch membrane showed an abrupt termination in the optical coherence tomography images, and often with an upturned edge surrounding the region devoid of Bruch membrane. The mean refractive error of the patients was -2.1 diopters (D) in the right eye and -2.5 D in the left. CONCLUSION: Pseudoxanthoma elasticum shares peripapillary atrophy and large dehiscences of Bruch membrane with pathologic myopia. Although theories of pathologic myopia involve stresses from ocular expansion, those of pseudoxanthoma elasticum typically do not. The Bruch membrane defect in pseudoxanthoma elasticum may be related to fragility secondary to abnormal calcification and to the surrounding abiotrophy of surrounding affected tissues of the posterior pole of the eye.

PURPOSE: To investigate the interactions among multimodal imaging findings and multimodal vision testing in neovascular age-related macular degeneration. METHODS: Patients enrolled in a prospective study of neovascular age-related macular degeneration with at least 3 previous intravitreal anti-vascular endothelial growth factor injections. Each patient underwent multimodal fundus imaging including spectral domain optical coherence tomography and fundus autofluorescence, and multimodal vision testing, including visual acuity, contrast sensitivity, reading speed, and microperimetry. RESULTS: There were 73 eyes of 49 consecutive patients enrolled. Generalized estimating equations' modelling showed that the significant independent predictors of visual acuity were the area of confluent hypoautofluorescence and involvement of the foveal center with either granular or confluent hypoautofluorescence (P < 0.001). Contrast sensitivity was negatively correlated with the area of confluent hypoautofluorescence (P < 0.001), involvement of the foveal center with granular hypoautofluorescence (P = 0.017), and subfoveal choroidal thickness (P = 0.042). The only significant predictor of reading speed was the size of confluent hypoautofluorescence (P < 0.001). The size of the defect in the ellipsoid zone (P < 0.001) and the presence of intraretinal fluid (P = 0.045) were correlated with microperimetry score. CONCLUSION: Confluent absence of autofluorescence was a highly significant predictor of vision testing and serves as an easy parameter to obtain in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate eyes with refractile drusen using clinical imaging and to identify candidate histologic correlates of refractile drusen. METHODS: Refractile drusen were defined as drusenoid material containing small refractile spherules. Retrospective analysis of color, autofluorescence, and spectral domain optical coherence tomography images of eyes with refractile drusen was performed to characterize the morphology and topography of these lesions. Macular sections from donor eyes were processed with a von Kossa stain for calcium phosphate and viewed by light microscopy. Punches of retinal pigment epithelium-choroid from donors with geographic atrophy were prepared for transmission electron microscopy. RESULTS: Fundus findings of 14 eyes of 10 patients with age-related macular degeneration (age, 82.9 +/- 5.6 years) were evaluated. A generalized loss of autofluorescence signal over refractile drusen appeared to spread over a larger area than each druse, for drusen located centrally. By color fundus photography, refractile drusen showed corresponding depigmentation around drusen that were located in the center of the macula. Optical coherence tomography imaging of refractile drusen showed hyperreflective dots. In the histologic specimens, drusen contained many small spherules rich in calcium phosphate. Ultrastructural examination of the spherules showed complex assemblies consisting of concentric shells containing thin layers of calcium. CONCLUSION: Refractile drusen appear to be a stage of drusen regression marked by loss of retinal pigment epithelium, thus contributing to the development of geographic atrophy. Calcium-containing spherules appear to account for the glistening appearance.

PURPOSE: To examine the colocalization error between the infrared reflectance (IR) scanning laser ophthalmoscope (SLO) and spectral domain optical coherence tomography (SD-OCT) images of the Heidelberg Spectralis. METHODS: The IR and corresponding horizontal raster SD-OCT images were compared in 10 healthy volunteers examined with 3 Heidelberg Spectralis + OCT instruments. The center points of retinal vessels selected by random uniform sampling in scanning laser ophthalmoscope-IR images were compared with colocalizing points in corresponding SD-OCT images by two masked readers. The error of colocalization was measured in the SD-OCT image. The point positions were recorded using Cartesian coordinates measured in microns. The error of colocalization was evaluated using a fixed-effects generalized least squares regression model with location and instrument as predictor variables. RESULTS: A total of 1,617 points in the IR and SD-OCT images were analyzed, and the mean error of colocalization was 42.2 +/- 32.4 mum. The Heidelberg Spectralis instrument used was not a significant predictor of colocalization error (P = 0.15). The colocalization errors were negatively correlated with x-coordinate position (P < 0.001). CONCLUSION: There is a mean colocalization error between the IR and SD-OCT images produced by the Heidelberg Spectralis that is on the scale of many features being evaluated in the fundus. The variability in these measurements means the confidence interval for the exact colocalization is much larger. Because of the magnitude and variability of the error, the colocalization feature of the Heidelberg Spectralis should be used as a rough guide, not an absolute determinant.

PURPOSE:: To demonstrate the evolution and treatment response of Type 3 neovascularization using spectral domain optical coherence tomography. METHODS:: We retrospectively analyzed 40 eyes treated with intravitreal anti-vascular endothelial growth factor therapy for Type 3 neovascularization over a variable follow-up period. RESULTS:: In 17 eyes, spectral domain optical coherence tomography captured the development of Type 3 neovascularization from punctate hyperreflective foci that preceded any outer retinal defect. The more mature Type 3 lesions were associated with outer retinal disruption and adjacent cystoid macular edema. In addition, 37 of 40 Type 3 lesions (93%) were associated with an underlying pigment epithelial detachment, of which 26 (70%) were drusenoid, 6 (16%) serous, and 5 (14%) mixed. Type 3 vessels appeared to leak fluid into the pigment epithelial detachment cavity, creating serous pigment epithelial detachments as large as 925 mum in maximal height. Treatment with anti-vascular endothelial growth factor agents led to prompt involution of the lesion and resorption of the intraretinal and subretinal pigment epithelium fluid after one or two injections (median = 1). CONCLUSION:: In some eyes with age-related macular degeneration, the earliest sign of Type 3 neovascularization is punctate hyperreflective foci above the external limiting membrane. The mature Type 3 lesions and associated serous pigment epithelial detachments are highly responsive to anti-vascular endothelial growth factor therapy.

Two eyes with neovascular age-related macular degeneration and a suboptimal response to intravitreal ranibizumab and bevacizumab developed tears after being switched to intravitreal aflibercept, a drug with enhanced binding characteristics to vascular endothelial growth factor. Both eyes had sub-retinal pigment epithelium (RPE) choroidal neovascularization adherent to the back surface of the RPE in the fibrovascular RPE detachment that showed increased contracture of the fibrovascular tissue following the use of aflibercept. The driving force to develop the tears may be related to the recently described angiofibrotic switch, which is governed by the ration of connective tissue growth factor to vascular endothelial growth factor. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:87-90.].

PURPOSE:: The aim of this study was to characterize peau d'orange and angioid streaks, characteristic findings in eyes of patients with pseudoxanthoma elasticum, by examining fundus photography and optical coherence tomography imaging. METHODS:: Color photographs were evaluated directly as were the component red and green channels. Optical coherence tomography images were evaluated for reflectivity pattern of the band corresponding to the retinal pigment epithelium-Bruch membrane complex. RESULTS:: Eighteen eyes of 9 patients with a mean age of 48.7 years (range, 31-61 years) were examined; 7 of them were women. Color photographs showed areas of yellowish opacification that obscured visualization of the underlying choroid. At the outer edges of this confluent area, opacification were nonconfluent changes with similar appearance and these regions were typical peau d'orange. Angioid streaks occurred within and extended up to the outer border of the confluent opacification. Underlying choroidal details could be seen through the regions of peau d'orange and through the gaps in angioid streaks. The red channel image showed increased reflectivity from the confluent deposit and improved visualization of the choroidal vasculature, except where the confluent opacification was located. Optical coherence tomography imaging showed increased reflectivity from the outer border of the retinal pigment epithelium-Bruch membrane complex. CONCLUSION:: The findings suggest that the confluent region is the relevant lesion, not the subconfluent zone known as peau d'orange. Imaging characteristics of the confluent area of opacity are consistent with diffuse infiltration with calcium, a chief histologic abnormality of pseudoxanthoma elasticum. The name coquille d'oeuf was suggested for the confluent area of opacity as a consequence.

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.