Analysis of Peripapillary Atrophy Using Spectral Domain Optical Coherence Tomography Citation

Objective—To study retinal morphological changes around the optic disc in patients with peripapillary atrophy (PPA) with high-resolution spectral domain optical coherence tomography (SD OCT). Design—Cross-sectional, retrospective analysis Participants—One hundred and three eyes of 73 patients with PPA and 21 eyes of 12 normal patients seen at the New England Eye Center, Tufts Medical Center between January 2007 and August 2009. Methods—SD OCT images taken through the region of PPA were quantitatively and qualitatively analyzed. Inclusion criteria included eyes with at least 300 μm of temporal PPA as detected on color fundus photographs. The study population was divided into subgroups according to the following clinical diagnoses: glaucoma (n=13), age-related macular degeneration (n=11), high myopia (n=11), glaucoma and high myopia (n=3), and optic neuropathy (n=11). Fifty-four patients were classified with other diagnoses. Using OCT software, retinal thickness and retinal nerve fiber layer thickness (RNFL) were both manually measured perpendicular to the internal limiting membrane and retinal pigment epithelium (RPE) 300 μm temporal to the optic disc, within the region of peripapillary atrophy. Qualitative analysis for morphological changes in the atrophic area was also performed. Main outcome measures—Qualitative assessment and quantitative measures of retinal and retinal nerve fiber layer thickness in PPA. Results—The study group was categorized by 6 characteristics demonstrated in the area of PPA by SD OCT: RPE loss with accompanying photoreceptor loss, RPE disruption, RNFL thickening with plaque-like formation, intraretinal cystic changes, inner and outer retinal thinning, and abnormal retinal sloping. Statistical analysis of measurements revealed a statistically significant difference in the total retinal thickness between normal eyes and eyes with PPA (p = 0.0005), with Corresponding Author/Reprints Jay S. Duker, MD, Department of Ophthalmology, Chairman, Tufts Medical Center, 800 Washington St., Box #450, Boston, MA 02111, Tel: 617-636-4677, Fax: 617-636-4866, [email protected]. Conflict of Interest Authors with financial/conflicting interests are listed after references. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Ophthalmology. Author manuscript; available in PMC 2012 March 1. Published in final edited form as: Ophthalmology. 2011 March ; 118(3): 531–536. doi:10.1016/j.ophtha.2010.07.013. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript normals 15% thicker than the PPA group; however, the RNFL thickness was not significantly different between the normal and PPA group (p = 0.05). Conclusion—Eyes with peripapillary atrophy manifest characteristic retinal changes that can be described via SD OCT. Peripapillary atrophy (PPA) is a clinical finding associated with chorioretinal thinning and disruption of the retinal pigment epithelium (RPE) in the area surrounding the optic disc. It is non-specific and can occur in both benign and pathologic conditions, including glaucoma 1 and high myopia 2. The normal cross-sectional anatomic structure of the peripapillary region of the eye is arranged with all the retinal cell layers organized in a parallel fashion, ending at the edge of the optic disc, with the topmost retinal nerve fiber layer increasing in thickness before diving into the disc. This normal architecture is disrupted with the development of peripapillary atrophy. Classification of peripapillary atrophy into two zones was first proposed by Jonas, et al 3: zone beta, a central zone of chorioretinal atrophy with visible large choroidal vessels and sclera, and zone alpha, a more peripheral area of irregular hypoand hyperpigmentation, with both types often present side by side in the same eye 3. Histological investigations of peripapillary atrophy describe changes in beta zone atrophy as a complete loss of retinal pigment epithelium cells and photoreceptors, and thinning of the choroid in combination with an almost complete collapse of the choriocapillaris. Alpha zone atrophy has been described as having structural irregularities in the retinal pigment epithelium cells 3–7. Optical coherence tomography (OCT) can perform noninvasive, real time imaging of the retina and anterior eye 8–10. OCT is a technology that provides high-resolution measurements and cross-sectional imaging of the retina and retinal nerve fiber layer (RNFL). The technology is analogous to ultrasound B-mode imaging, measuring the echo time delay of back-reflected light rather than sound from structures at different longitudinal distances8–10. Successive axial scans at different transverse points are used to generate cross-sectional images. The axial resolution in OCT imaging is inversely proportional to the bandwidth of the light source. Spectral domain (SD) OCT devices utilize an interferometer with a spectrometer and a high speed camera to measure echoes of light in the Fourier domain. Standard commercial OCT instruments use a superluminescent diode light source at a near infrared wavelength of 820 nm with a bandwidth of 50 nm, achieving 5–8 μm axial resolution in tissue. Usually a nonspecific finding, PPA has also been closely correlated with glaucoma and high myopia. However, the way that the peripapillary region is affected in these diseases is not well understood. Closer examination of PPA in vivo using SD OCT was of interest to gain a better understanding of the changes occurring in this region. Although the clinical and histological findings in peripapillary atrophy have been described, the OCT correlate of peripapillary atrophy has not been assessed in detail. Therefore, the purpose of this study is to examine OCT changes in the region of peripapillary atrophy. Patients and Methods A retrospective review of 103 eyes (73 patients) with peripapillary atrophy was undertaken. Each patient underwent complete ophthalmic examination and Cirrus HD-OCT (software version 4.0, Carl Zeiss Meditec, Inc., Dublin, CA, USA) imaging in the ophthalmology department of the New England Eye Center, Tufts Medical Center, Boston, Massachusetts between January 2007 and August 2009. Examination included best corrected visual acuity, slit-lamp examination, fundus biomicroscopy, fundus photography, and OCT examination. Manjunath et al. Page 2 Ophthalmology. Author manuscript; available in PMC 2012 March 1. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript This study protocol was approved by the Institutional Review Board (IRB)/Ethics Committee of the Tufts Medical Center and is adherent to the tenets of the Declaration of Helsinki. Inclusion for the study required the presence at least 300 μm of clinically apparent temporal peripapillary atrophy visible on fundus imaging. Both eyes were included if they met the criteria for atrophy. Five line raster scans at a ± 7 degree angle from the horizontal through the center of the fovea and the optic nerve were analyzed. A 5-line raster scan consists of 5 horizontal lines, each 6 mm long and spaced 0.25 mm apart. Each high definition line is comprised of 4096 A-scans, with a transverse resolution of ~15–20 μm. The raster scan closest to the fovea was selected for measurements. Only good quality images with an intensity of 6 out of 10 or greater were used in this study. Cirrus HD-OCT software provides a measurement tool to draw straight lines. One observer (VM) manually measured two parameters on the raster images: (1) total retinal thickness, which was measured from the internal limiting membrane to Bruch membrane, and (2) RNFL thickness which was also measured perpendicular to the retinal pigment epithelium. All measurements were performed 300 μm temporal to the edge of the RPE, which this study defined as the edge of the optic disc.11 Bruch’s membrane may be seen extending further than the RPE in histological studies12, however SD OCT does not allow for that level of cellular resolution. Automated RNFL thickness measurements generated along a standard 3.4 mm circle centered on the optic disc were not utilized in this study as the measured area of thickness would have been beyond the region of PPA in most cases. In addition to linear thickness measurements, angle measurements were performed on the OCT images to measure the angle between the RPE and the vertical edge of the disc in both normal eyes and those with PPA. Cirrus software does not provide a tool for angle measurements, therefore the images were exported to publicly available research analysis software ImageJ (National Institutes of Health, USA, http://rsbweb.nih.gov/ij/, accessed December 20, 2009). The vertical to horizontal aspect ratio is distorted in OCT images to facilitate better visualization of retinal details and measurements of distance or angle must account for this. Accordingly, before angles were measured using ImageJ software, the scale was set by measuring a horizontal line of a known length, the pixel aspect ratio was altered to 1/3 to account for the difference in horizontal to vertical ratio, and the units were changed to micrometers. All angle measurements were verified for accuracy by drawing a right angle triangle using the Cirrus line tool and calculating the angle using trigonometry. All measurements were also performed on 21 eyes of 12 normal patients lacking PPA for comparison. The images were analyzed for morphological changes in the retina in the area of peripapillary atrophy. When the area of atrophy on the Cirrus generated en face fundus image was measured using Cirrus software, the same distance could be measured on the corresponding OCT image, confirming that the area of observed morphological changes were in the same location on both the fundus image and OCT scan. Retinal thickness and retinal nerve fiber layer thickness measurements were compared between the normal and PPA groups using the Student t-test with statistical significance defined as a P value of less than 0.05. Manjunath et al. Page 3 Ophthalmology. Author manuscript; available in PMC 2012 March 1. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript