0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Choroidal Hyperreflective Foci in Stargardt Disease Shown by Spectral-Domain Optical Coherence Tomography Imaging Correlation With Disease Severity FREE

Niloofar Piri, MD1; Brooke L. W. Nesmith, MD, JD1; Shlomit Schaal, MD, PhD1
[+] Author Affiliations
1Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky
JAMA Ophthalmol. 2015;133(4):398-405. doi:10.1001/jamaophthalmol.2014.5604.
Text Size: A A A
Published online

Importance  The presence of choroidal hyperreflective foci in Stargardt disease is, to our knowledge, a potentially new finding. Evaluation of these foci may aid in better understanding of the disease process.

Objectives  To report the presence of choroidal hyperreflective foci in spectral-domain optical coherence tomography (SD-OCT) images from eyes with Stargardt disease and investigate the relationship between the number of hyperreflective foci and disease severity.

Design, Setting, and Participants  Twenty-six eyes of 13 patients with a clinical diagnosis of Stargardt disease were evaluated in a retrospective case series. Patient data were collected between January 1, 2009, and August 31, 2014.

Main Outcomes and Measures  The number of choroidal hyperreflective foci in Stargardt disease as well as correlation with visual acuity, central macular thickness (CMT), and disease duration were the main outcomes. A total of 707 macular SD-OCT scans of 13 patients with Stargardt disease were reviewed and evaluated for the presence and number of retinal/choroidal hyperreflective foci, central macular thickness, visual acuity, and disease duration. Enhanced depth imaging with OCT (EDI-OCT) scans available for 2 patients were compared with SD-OCT scans. A PubMed/Google search was performed to identify SD-OCT images in Stargardt disease; these findings were reviewed for the presence of choroidal hyperreflective foci.

Results  The mean (SD) numbers of hyperreflective foci in each retinal/choroidal layer in decreasing frequency were as follows: Bruch membrane/retinal pigment epithelial (RPE) complex, 78.22 (24.39); choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina, 16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87). The number of hyperreflective foci in the Bruch membrane/RPE complex increased exponentially with decreasing CMT (R2 = 0.99; P = .008). The number of hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer increased proportionally with decreasing visual acuity (R2 = 0.97, R2 = 0.95, and R2 = 0.99, respectively; and P = .007, P = .006, and P = .008, respectively). Direct correlation existed between the number of hyperreflective foci in the choriocapillaris and the Sattler layer and disease duration (R2 = 0.98 and R2 = 0.99, respectively; and P = .006 and P =.009, respectively). In the 10 studies on Stargardt disease, choroidal hyperreflective foci were present in 51 of 54 SD-OCT images (94%).

Conclusions and Relevance  Based on the findings of the present study, choroidal hyperreflective foci in Stargardt disease, prominent at the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer, correlate with disease severity in terms of retinal atrophy, decline in vision, and disease duration. Further studies are necessary to assess whether these findings are unique to Stargardt disease.

Figures in this Article

In 1909, Karl Stargardt, a German ophthalmologist, first described a rapidly progressive macular dystrophy of juvenile onset with poor visual outcome.1 He noted the presence of yellowish-white deposits called retinal flecks, which have become the hallmark feature in Stargardt disease. Stargardt disease is an autosomal recessive retinal degeneration caused by a mutation in the ABCA4 gene, which encodes the retina-specific adenosine triphosphate–binding cassette transporter.2 A defect in this transporter, which is located in the rim of photoreceptor discs, results in accumulation of the toxic all-trans-retinal and its derivative, resulting in the death of retinal pigment epithelial cells (RPEs) and their overlying cone and rod photoreceptors.2,3

Fundus flavimaculatus, a variant of Stargardt disease, was first described by Franceschetti, a European ophthalmologist, in 1962.4 Fundus flavimaculatus tends to be of later onset than Stargardt disease, and its presentation is predominantly one of retinal flecks. In the present study, the term Stargardt disease is used for both entities.

The exact location of the characteristic flecks seen in Stargardt disease, as well as their chemical composition, was controversial for many years.4 In 1967, mucopolysaccharide deposits (hyaluronic acid) were identified in retinal cells.5 In 1980, light and electron microscopy were used to demonstrate massive accumulation of lipofuscin in the RPE cells of patients with Stargardt disease.3 Better understanding of the location of these flecks came about with the introduction of optical coherence tomography (OCT) imaging.

With OCT imaging, a diagnostic modality that has transformed the vitreoretinal field for more than a decade, evaluation of high-resolution cross-sectional images of the retinal layers in patients with Stargardt disease is possible. Correlation of imaging studies to the histology of retinal tissues in vivo can be accomplished with OCT.6,7 The introduction of spectral-domain OCT (SD-OCT) with axial resolution as low as 7 μm further advanced the high-resolution imaging of different layers of both the retina and choroid.

In 2006, Querques et al8 analyzed retinal flecks in patients with Stargardt disease using time-domain OCT (Stratus OCT; axial resolution, 8-10 µm).The investigators defined 2 types of hyperreflective foci: type 1, located in the inner wall of the RPE layer, and type 2, located in the outer nuclear layer and clearly separated from the RPE. The investigators presumed that the 2 types of retinal hyperreflective foci reflect different stages of the same disorder. The authors hypothesized that type 2 hyperreflective deposits could be the residual of type 1 deposits, which would be consistent with progressive degradation of the flecks in the fundus from a well-defined lesion to residual material.

In 2010, retinal flecks in Stargardt disease were evaluated9 using SD-OCT (axial resolution of 7 µm, faster, and with fewer motion artifacts) and demonstrated 5 different stages of evolution of the hyperreflective foci, which were shown to occur between the Bruch membrane/RPE complex and the outer nuclear layer.

After observing the presence of choroidal hyperreflective foci on SD-OCT in a patient with Stargardt disease, we initiated the present study. To our knowledge, this is the first study to describe the presence of choroidal hyperreflective foci in SD-OCT macular sections in patients with Stargardt disease. This study also demonstrates the correlation between the presence of hyperreflective foci in Stargardt disease with retinal thickness, visual acuity, and disease duration.

This retrospective study was approved and monitored by the institutional review board of the University of Louisville with waiver of informed consent. Patients with the diagnosis of Stargardt disease were identified through the billing office at Kentucky Lions Eye Center, University of Louisville, between January 1, 2009, and August 31, 2014, by retrieval of the International Classification of Diseases, Ninth Revision, code for sensory retinal dystrophy (362.75). Medical records were then reviewed for the clinical diagnosis of Stargardt disease. Twenty-six eyes of 13 patients were included in this study. Data collected included age at presentation, duration of disease, sex, best-corrected visual acuity (BCVA), central macular thickness (CMT), color fundus photos, fundus autofluorescence images, fluorescein angiography (Heidelberg Retina Angiograph, HRA 2; Heidelberg Engineering), and 18 to 37 macular SD-OCT sections (OCT; Heidelberg Engineering). All OCT cuts were reviewed carefully for the presence and character of retinal and choroidal hyperreflective foci, defined as round or oval hyperreflective areas 10 to 50 μm in diameter. A total of 707 macular SD-OCT scans of 13 patients with Stargardt disease were included in this study. Two observers (N.P. and B.L.W.N.) independently quantified hyperreflective foci according to this definition by counting, on a high-magnification SD-OCT section of the central macula crossing through the fovea (Figure 1), the number of hyperreflective foci in the retinal and choroidal layers as follows: inner retinal layers (between the internal limiting membrane and external limiting membrane), outer retinal layers (between the external limiting membrane and RPE including the external limiting membrane, myoid zone, ellipsoid zone, and interdigitating zone), Bruch membrane/RPE complex, choriocapillaris, Sattler layer of the choroid, and Haller layer of the choroid. Before independently quantifying the hyperreflective foci, we agreed on the identification of each layer in the SD-OCT sections.10,11 The interobserver agreement on the number of hyperreflective foci in every layer was subsequently measured and κ statistical analysis was performed. Enhanced depth imaging-OCT (EDI-OCT) scans, available for only 2 patients, were compared with the corresponding SD-OCT scans to ascertain whether there was a difference in visualization of the choroid and in the number of hyperreflective foci.

Place holder to copy figure label and caption
Figure 1.
Spectral-Domain Optical Coherence Tomography (SD-OCT) of the Retina

Prevalence of hyperreflective foci in the different layers of the retina and choroid. In the fundus photograph (left), the green box demonstrates the total area that was scanned; green arrow, the section of the scan shown in the SD-OCT image (right). RPE indicates retinal pigment epithelial.

Graphic Jump Location

A comprehensive literature search was performed in PubMed and Google for articles from January 1, 2009, through August 31, 2014, using the search terms Stargardt disease, retinal dystrophy, and optical coherence tomography. Articles including high-quality SD-OCT images with all retinal and choroidal layers visible were then reviewed independently to assess the presence or absence (without quantification) of choroidal hyperreflective foci.

Statistical analysis was carried out using SPSS software, version 19.0 (SPSS Inc). The data were categorized in groups according to the retinal or choroidal layer that was analyzed. Correlation was sought between the number of hyperreflective foci in different layers and BCVA, disease duration, and CMT. Multivariate analysis was performed using 1-way analysis of variance.

Demographic findings of the 13 patients are presented in the Table. Mean (SD) age at diagnosis was 35 (19.7) years (range, 9-49 years). Of 13 patients, 7 (54%) were male and 6 (46%) were female. Mean BCVA was 0.67 (0.44) , with an approximate Snellen equivalent of 20/100 (6.5 lines) (logMAR range, 0-1.5; Snellen equivalent, 20/600-20/20). The mean duration of disease was 9 (10) years (range, 1-28 years).

Table Graphic Jump LocationTable.  Demographic Characteristics of the Study Population

For each patient, 18 to 37 SD-OCT cuts were reviewed. Evaluation of the SD-OCT images demonstrated not only retinal hyperreflective foci but also multiple hyperreflective deposits in different layers of the choroid in all patients (Figure 2). The hyperreflective foci in the choroidal layers were adjacent to the vascular borders; none were found within the vessels. The hyperreflective foci in the Bruch membrane/RPE complex were primarily round; however, in deeper layers, they also appeared to be oval.

Place holder to copy figure label and caption
Figure 2.
Clinical Images of 5 Patients With Stargardt Disease

Note the increased number of choroidal hyperreflective foci with increased disease severity. In the fundus photographs, the green boxes and horizontal green lines demonstrate the total area that was scanned; the highlighted horizontal green lines and green arrows demonstrate the section of the scan shown in the spectral-domain optical coherence tomography images.

Graphic Jump Location

There was a high degree of interobserver agreement on the number of hyperreflective foci in the different layers in this study (eTable 1 in the Supplement). The highest degree was in the outer retina, the Bruch membrane/RPE complex, and the choriocapillaris (>90% observed agreement). Agreement was less than 90% in the Sattler and Haller layers, possibly because decreased signal intensity in the deeper layers caused more discrepancy between the 2 observers.

The mean number of hyperreflective foci measured in the central cuts crossing through the fovea in the retinal and choroidal layers differed between the layers (P = .03) and, in decreasing frequency, were as follows: Bruch membrane/RPE complex, 78.22 (24.39); choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina, 16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87).

Figure 3A shows the number of hyperreflective foci in the different layers of the retina and choroid as a correlation of CMT. There was no correlation between the mean number of hyperreflective foci in the inner retina (0.95 [1.58]; P = .29), the outer retina (16.64 [6.96]; P = .38), choriocapillaris (25.77 [17.57]; P = .29), Sattler layer (18.59 [12.89]; P = .08), or Haller layer (0.73 [0.87]; P = .18) and CMT. The mean number of hyperreflective foci in the Bruch membrane/RPE complex (78.22 [24.39]) increased exponentially with decreasing retinal thickness according to the following formula: number of hyperreflective foci = 88 − 40 • (1 − exp [0.03 • CMT]); R2 = 0.99; P = .008).

Place holder to copy figure label and caption
Figure 3.
Mean Number of Hyperreflective Foci in Different Layers of the Retina

A, The number of hyperreflective foci increased in the Bruch membrane/retinal pigment epithelial (RPE) complex with decreasing central macular thickness. B, The number of hyperreflective foci increased in the choriocapillaris, the Bruch membrane/RPE complex, and the Sattler layer with decreasing vision. C, The number of hyperreflective foci increased in the choriocapillaris and Sattler layer with disease duration. Lines across the graphs indicate correlation; limit lines, SD.

Graphic Jump Location

Figure 3B shows the number of hyperreflective foci in the different layers of the retina and choroid as a correlation of BCVA. There was no correlation between the number of hyperreflective foci in the outer retina, inner retina, or Haller layer with BCVA (P = .06).

The mean number of hyperreflective foci in the Bruch membrane/RPE complex increased proportionally with decreasing visual acuity according to the following formula: number of hyperreflective foci = 171 + 3 • (logMAR)3; R2 = 0.97; P = .007.

The mean number of hyperreflective foci in the choriocapillaris increased proportionally with decreasing visual acuity according to the following formula: number of hyperreflective foci = 21 + 3 • (logMAR)2; R2 = 0.95; P = .006.

The mean number of hyperreflective foci in the Sattler layer increased proportionally with decreasing visual acuity according to the following formula: number of hyperreflective foci = 24 − 1 • (logMAR)3; R2 = 0.99; P = .008.

Figure 3C shows the number of hyperreflective foci in the different layers of the retina and choroid as a correlation of duration of the disease. There was no correlation between the number of hyperreflective foci in the outer retina, inner retina, Bruch membrane/RPE complex, or Haller layer with the duration of the disease (P = .07).

The mean number of hyperreflective foci in the choriocapillaris increased proportionally with disease duration according to the following formula: number of hyperreflective foci = 15 + 2 • (years)3; R2 = 0.98; P = .006.

The mean number of hyperreflective foci in the Sattler layer increased proportionally with disease duration according to the following formula: number of hyperreflective foci = 10 + 3 • (years)3; R2 = 0.99; P = .009.

Figure 4 shows EDI-OCT and SD-OCT scans of the same foveal cut for 2 patients. There was no difference in the visualization of the choroid or the number of hyperreflective foci between the 2 imaging methods. Enhanced depth imaging–OCT demonstrated a mean of 4.5 (4.5) (range, 1- 8) more hyperreflective foci than were demonstrated by the SD-OCT.

Place holder to copy figure label and caption
Figure 4.
Comparison of Spectral-Domain Optical Coherence Tomography (SD-OCT) Images With Enhanced Depth Imaging (EDI)–OCT Images in 2 Patients

No difference in hyperreflective foci was found between observations with the use of SD-OCT (top OCT image) and EDI-OCT (bottom) in patients 1 and 10. In the fundus photographs (left), green boxes demonstrate the total area that was scanned; green arrows, the section of the scan shown in the OCT images (right).

Graphic Jump Location

The literature review identified 47 studies with high-quality SD-OCT images.2,9,1256 In the 10 studies on Stargardt disease,2,9,1219 choroidal hyperreflective foci were present in 51 of 54 (94%) SD-OCT images. The remaining 37 studies2056 discussed other retinal dystrophies, in which 16 of 195 (0.08%) SD-OCT scans demonstrated the presence of choroidal hyperreflective foci (eTable 2 in the Supplement). The hyperreflective foci in these studies were of the same shape and size as those in the present study. The number of hyperreflective foci was not quantified.

Spectral-domain OCT has contributed substantially to our understanding of the disease process of various vitreoretinal disorders. In the case of Stargardt disease, which is characterized by the clinical appearance of yellow flecks throughout the fundus, SD-OCT enables the identification of the location and distribution of hyperreflective foci within the retinal and choroidal layers. The flecks seen clinically in Stargardt disease were previously shown8,9 to occur between the Bruch membrane/RPE complex and the outer nuclear layer. The present study clearly demonstrates that hyperreflective foci are not only present in the retinal layers of patients with Stargardt disease but are more prevalent in the choroidal layers, specifically in the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer.

The choroidal hyperreflective foci seen on SD-OCT imaging in the present study were identified in the choroidal layers of all patients. Using polarization-sensitive OCT, Ritter et al57 described increased depolarizing material in the choroid of patients with Stargardt disease, which may be related to the findings in the present study. The present study also shows that, in contrast to previous beliefs, the hyperreflective foci are not confined to the outer retina; they can also be seen in the more superficial retinal layers. In the choroid of patients with RPE atrophy, such as age-related macular degeneration with geographic atrophy, similar hyperreflective foci were not found.

In this study, we identified an inverse correlation between the number of hyperreflective foci in the Bruch membrane/RPE complex and CMT as well as an inverse correlation between the number of hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer and BCVA. In addition, the number of hyperreflective foci increased in the choriocapillaris and Sattler layer with increasing duration of disease. This latter finding may reflect a downward migration from the outer retina with time. Furthermore, as apparent in Figure 2, the hyperreflective foci in the choroidal layers increase as vision declines.

The reason for the presence of hyperreflective foci in the choroid is uncertain. The present understanding of the underlying pathologic mechanism in Stargardt disease is concentrated in the outer retinal layers. The adenosine triphosphate–binding cassette transporter protein that is defective in Stargardt disease is present in the outer segments of photoreceptors, specifically in the rim of the photoreceptor discs.3 Thus, one would expect to see an accumulation of these hyperreflective foci, or lipofuscin deposits, in the outer retinal layers. The presence of hyperreflective foci mainly in choroidal layers, as well as in superficial retinal layers, might suggest migration of the lipofuscin deposits from the outer retina toward both the inner retina and choroid, possibly following a degradation process. The significance of this migratory process in either disease progression or its relationship to visual outcome is yet to be determined. This discussion of underlying mechanisms is contingent upon the demonstration that the hyperreflective foci are composed of lipofuscin deposits and are unique to Stargardt disease, which was not demonstrated in this study and presents an area for further investigation. No attempt to pursue information on the clinical correlates of the hyperreflective foci seen using OCT was made in this study. Therefore, the possibility of a correlation between OCT findings and those noted in color fundus photographs, fluorescein angiography, or fundus autofluorescence images from the same eye should be investigated. In the absence of such correlation analysis, no direct conclusion regarding the origin, nature, and significance of the choroidal lesions can be drawn.

The small number of cases available for evaluation owing to the rarity of the disease is one limitation of our study. Further limitations include the lack of serial OCTs to monitor possible changes in the hyperreflective foci over time, including changes in the number and position of the foci in the retina and choroid. In addition, dark adaptation or microperimetry was not available in this study population; thus, only correlations between BCVA and CMT could be made with disease severity. The use of SD-OCT scans instead of EDI-OCT scans, which would arguably allow for better visualization of the choroidal layers, may also be a limitation; however, EDI-OCT scans were available for 2 patients in this cohort and were compared with each other (Figure 4). When SD-OCT and EDI-OCT were compared on the same cuts, it was apparent that choroidal hyperreflective foci were visible to the same degree in both imaging techniques in these 2 patients. This visibility may be secondary to the atrophy of retinal layers in Stargardt disease. Indeed, the CMT of both patients who underwent EDI-OCT imaging was less than 200 µm. Thus, there is better penetration of infrared wavelength to deeper choroidal layers and better visualization of choroidal layers in the absence of enhanced depth imaging. Chun et al58 recently described choroidal atrophic changes with infrared scanning laser ophthalmoscopic imaging, demonstrating that both retinal and choroidal atrophy allow better visualization of deeper layers even without EDI-OCT. We assume that if EDI-OCT imaging were available for all our patients, the results would not differ substantially.

To our knowledge, this study demonstrated for the first time that the characteristic hyperreflective foci clinically observed in the fundus of patients with Stargardt disease are present not only in the outer retinal layers, as previously noted, but also in the choroid. These hyperreflective foci correlate with disease severity in terms of degree of retinal atrophy and visual acuity as well as disease duration. Studies using serial, longitudinal SD-OCT and EDI-OCT will aid in better understanding of the disease process in Stargardt disease.

Submitted for Publication: September 9, 2014; final revision received November 13, 2014; accepted November 17, 2014.

Corresponding Author: Shlomit Schaal, MD, PhD, Department of Ophthalmology and Visual Sciences, University of Louisville, 301 E Muhammad Ali Blvd, Louisville, KY 40202 (s.schaal@louisville.edu).

Published Online: January 15, 2015. doi:10.1001/jamaophthalmol.2014.5604.

Author Contributions: Drs Piri and Schaal had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Piri, Schaal.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Piri, Schaal.

Statistical analysis: Piri, Schaal.

Administrative, technical, or material support: Schaal.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: The work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This study was presented, in part, at the Annual Meeting of the Retina Society; September 13, 2014; Philadelphia, Pennsylvania.

Haji Abdollahi  S, Hirose  T.  Stargardt-fundus flavimaculatus: recent advancements and treatment. Semin Ophthalmol. 2013;28(5-6):372-376.
PubMed   |  Link to Article
Westeneng-van Haaften  SC, Boon  CJ, Cremers  FP, Hoefsloot  LH, den Hollander  AI, Hoyng  CB.  Clinical and genetic characteristics of late-onset Stargardt’s disease. Ophthalmology. 2012;119(6):1199-1210.
PubMed   |  Link to Article
Eagle  RC  Jr, Lucier  AC, Bernardino  VB  Jr, Yanoff  M.  Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology. 1980;87(12):1189-1200.
PubMed   |  Link to Article
Lois  N, Holder  GE, Bunce  C, Fitzke  FW, Bird  AC.  Phenotypic subtypes of Stargardt macular dystrophy–fundus flavimaculatus. Arch Ophthalmol. 2001;119(3):359-369.
PubMed   |  Link to Article
Klien  BA, Krill  AE.  Fundus flavimaculatus: clinical, functional and histopathologic observations. Am J Ophthalmol. 1967;64(1):3-23.
PubMed   |  Link to Article
Huang  D, Swanson  EA, Lin  CP,  et al.  Optical coherence tomography. Science. 1991;254(5035):1178-1181.
PubMed   |  Link to Article
Baumal  CR.  Clinical applications of optical coherence tomography. Curr Opin Ophthalmol. 1999;10(3):182-188.
PubMed   |  Link to Article
Querques  G, Leveziel  N, Benhamou  N, Voigt  M, Soubrane  G, Souied  EH.  Analysis of retinal flecks in fundus flavimaculatus using optical coherence tomography. Br J Ophthalmol. 2006;90(9):1157-1162.
PubMed   |  Link to Article
Voigt  M, Querques  G, Atmani  K,  et al.  Analysis of retinal flecks in fundus flavimaculatus using high-definition spectral-domain optical coherence tomography. Am J Ophthalmol. 2010;150(3):330-337.
PubMed   |  Link to Article
Michalewska  Z, Michalewski  J, Nawrocki  J.  New OCT technologies take imaging deeper and wider. Retin Physician. 2013;10(3):42-48.
Staurenghi  G, Sadda  S, Chakravarthy  U, Spaide  RF; International Nomenclature for Optical Coherence Tomography (IN•OCT) Panel.  Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus. Ophthalmology. 2014;121(8):1572-1578.
PubMed   |  Link to Article
Gomes  NL, Greenstein  VC, Carlson  JN,  et al.  A comparison of fundus autofluorescence and retinal structure in patients with Stargardt disease. Invest Ophthalmol Vis Sci. 2009;50(8):3953-3959.
PubMed   |  Link to Article
Verdina  T, Tsang  SH, Greenstein  VC,  et al.  Functional analysis of retinal flecks in Stargardt disease [published online July 30, 2012]. J Clin Exp Ophthalmol. doi:10.4172/2155-9570.1000233.
PubMed
Nakao  T, Tsujikawa  M, Sawa  M, Gomi  F, Nishida  K.  Foveal sparing in patients with Japanese Stargardt’s disease and good visual acuity. Jpn J Ophthalmol. 2012;56(6):584-588.
PubMed   |  Link to Article
Burke  TR, Yzer  S, Zernant  J, Smith  RT, Tsang  SH, Allikmets  R.  Abnormality in the external limiting membrane in early Stargardt disease. Ophthalmic Genet. 2013;34(1-2):75-77.
PubMed   |  Link to Article
Fujinami  K, Sergouniotis  PI, Davidson  AE,  et al.  The clinical effect of homozygous ABCA4 alleles in 18 patients. Ophthalmology. 2013;120(11):2324-2331.
PubMed   |  Link to Article
Lee  W, Nõupuu  K, Oll  M,  et al.  The external limiting membrane in early-onset Stargardt disease. Invest Ophthalmol Vis Sci. 2014;55(10):6139-6149.
PubMed   |  Link to Article
Sisk  RA, Leng  T.  Multimodal imaging and multifocal electroretinography demonstrate autosomal recessive Stargardt disease may present like occult macular dystrophy. Retina. 2014;34(8):1567-1575.
PubMed   |  Link to Article
Salvatore  S, Fishman  GA, McAnany  JJ, Genead  MA.  Association of dark-adapted visual function with retinal structural changes in patients with Stargardt disease. Retina. 2014;34(5):989-995.
PubMed   |  Link to Article
Lim  JI, Tan  O, Fawzi  AA, Hopkins  JJ, Gil-Flamer  JH, Huang  D.  A pilot study of Fourier-domain optical coherence tomography of retinal dystrophy patients. Am J Ophthalmol. 2008;146(3):417-426.
PubMed   |  Link to Article
Aleman  TS, Soumittra  N, Cideciyan  AV,  et al.  CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy. Invest Ophthalmol Vis Sci. 2009;50(12):5944-5954.
PubMed   |  Link to Article
Wang  NK, Chou  CL, Lima  LH,  et al.  Fundus autofluorescence in cone dystrophy. Doc Ophthalmol. 2009;119(2):141-144.
PubMed   |  Link to Article
Thiadens  AA, den Hollander  AI, Roosing  S,  et al.  Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet. 2009;85(2):240-247.
PubMed   |  Link to Article
Audo  I, Friedrich  A, Mohand-Saïd  S,  et al.  An unusual retinal phenotype associated with a novel mutation in RHOArch Ophthalmol. 2010;128(8):1036-1045.
PubMed   |  Link to Article
Burstedt  MS, Golovleva  I.  Central retinal findings in Bothnia dystrophy caused by RLBP1 sequence variation. Arch Ophthalmol. 2010;128(8):989-995.
PubMed   |  Link to Article
Michaelides  M, Gaillard  MC, Escher  P,  et al.  The PROM1 mutation p.R373C causes an autosomal dominant bull’s eye maculopathy associated with rod, rod-cone, and macular dystrophy. Invest Ophthalmol Vis Sci. 2010;51(9):4771-4780.
PubMed   |  Link to Article
Littink  KW, Koenekoop  RK, van den Born  LI,  et al.  Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations. Invest Ophthalmol Vis Sci. 2010;51(11):5943-5951.
PubMed   |  Link to Article
Mackay  DS, Henderson  RH, Sergouniotis  PI,  et al.  Novel mutations in MERTK associated with childhood onset rod-cone dystrophy. Mol Vis. 2010;16:369-377.
PubMed
Park  SJ, Woo  SJ, Park  KH, Hwang  JM, Chung  H.  Morphologic photoreceptor abnormality in occult macular dystrophy on spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2010;51(7):3673-3679.
PubMed   |  Link to Article
Yeoh  J, Rahman  W, Chen  F,  et al.  Choroidal imaging in inherited retinal disease using the technique of enhanced depth imaging optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2010;248(12):1719-1728.
PubMed   |  Link to Article
Ferrara  DC, Costa  RA, Tsang  S, Calucci  D, Jorge  R, Freund  KB.  Multimodal fundus imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;248(10):1377-1386.
PubMed   |  Link to Article
Duncan  JL, Talcott  KE, Ratnam  K,  et al.  Cone structure in retinal degeneration associated with mutations in the peripherin/RDS gene. Invest Ophthalmol Vis Sci. 2011;52(3):1557-1566.
PubMed   |  Link to Article
Kitaguchi  Y, Kusaka  S, Yamaguchi  T, Mihashi  T, Fujikado  T.  Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy. Clin Ophthalmol. 2011;5:345-351.
PubMed   |  Link to Article
Lacassagne  E, Dhuez  A, Rigaudière  F,  et al.  Phenotypic variability in a French family with a novel mutation in the BEST1 gene causing multifocal best vitelliform macular dystrophy. Mol Vis. 2011;17:309-322.
PubMed
Henderson  RH, Mackay  DS, Li  Z,  et al.  Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1Br J Ophthalmol. 2011;95(6):811-817.
PubMed   |  Link to Article
Zhao  L, Grob  S, Corey  R,  et al.  A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy. Eye (Lond). 2012;26(6):866-871.
PubMed   |  Link to Article
Sergouniotis  PI, Holder  GE, Robson  AG, Michaelides  M, Webster  AR, Moore  AT.  High-resolution optical coherence tomography imaging in KCNV2 retinopathy. Br J Ophthalmol. 2012;96(2):213-217.
PubMed   |  Link to Article
Preising  MN, Hausotter-Will  N, Solbach  MC, Friedburg  C, Rüschendorf  F, Lorenz  B.  Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy. Invest Ophthalmol Vis Sci. 2012;53(7):3463-3472.
PubMed   |  Link to Article
Dev Borman  A, Ocaka  LA, Mackay  DS,  et al.  Early onset retinal dystrophy due to mutations in LRAT: molecular analysis and detailed phenotypic study. Invest Ophthalmol Vis Sci. 2012;53(7):3927-3938.
PubMed   |  Link to Article
Thiadens  AA, Slingerland  NW, Florijn  RJ, Visser  GH, Riemslag  FC, Klaver  CC.  Cone-rod dystrophy can be a manifestation of Danon disease. Graefes Arch Clin Exp Ophthalmol. 2012;250(5):769-774.
PubMed   |  Link to Article
Adhi  M, Duker  JS.  Optical coherence tomography—current and future applications. Curr Opin Ophthalmol. 2013;24(3):213-221.
PubMed   |  Link to Article
Esteves  F, Dolz-Marco  R, Hernández-Martínez  P, Díaz-Llopis  M, Gallego-Pinazo  R.  Pattern dystrophy of the macula in a case of Steinert disease. Case Rep Ophthalmol. 2013;4(3):129-133.
PubMed   |  Link to Article
Zerbib  J, Querques  G, Massamba  N,  et al.  Reticular pattern dystrophy of the retina: a spectral-domain optical coherence tomography analysis. Am J Ophthalmol. 2013;156(6):1228-1237.
PubMed   |  Link to Article
Birch  DG, Locke  KG, Wen  Y, Locke  KI, Hoffman  DR, Hood  DC.  Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa. JAMA Ophthalmol. 2013;131(9):1143-1150.
PubMed   |  Link to Article
de Laat  P, Smeitink  JA, Janssen  MC, Keunen  JE, Boon  CJ.  Mitochondrial retinal dystrophy associated with the m.3243A>G mutation. Ophthalmology. 2013;120(12):2684-2696.
PubMed   |  Link to Article
Pach  J, Kohl  S, Gekeler  F, Zobor  D.  Identification of a novel mutation in the PRCD gene causing autosomal recessive retinitis pigmentosa in a Turkish family. Mol Vis. 2013;19:1350-1355.
PubMed
Ahn  SJ, Cho  SI, Ahn  J, Park  SS, Park  KH, Woo  SJ.  Clinical and genetic characteristics of Korean occult macular dystrophy patients. Invest Ophthalmol Vis Sci. 2013;54(7):4856-4863.
PubMed   |  Link to Article
Acton  JH, Greenberg  JP, Greenstein  VC,  et al.  Evaluation of multimodal imaging in carriers of X-linked retinitis pigmentosa. Exp Eye Res. 2013;113:41-48.
PubMed   |  Link to Article
Gliem  M, Zaeytijd  JD, Finger  RP, Holz  FG, Leroy  BP, Charbel Issa  P.  An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet. 2013;4:14.
PubMed   |  Link to Article
Baek  J, Lee  HK, Kim  US.  Spectral domain optical coherence tomography findings in bilateral peripheral cone dystrophy. Doc Ophthalmol. 2013;126(3):247-251.
PubMed   |  Link to Article
Xu  H, Ying  L, Lin  P, Wu  J.  Optical coherence tomography for multifocal vitelliform macular dystrophy. Optom Vis Sci. 2013;90(1):94-99.
PubMed   |  Link to Article
Cho  SC, Woo  SJ, Park  KH, Hwang  JM.  Morphologic characteristics of the outer retina in cone dystrophy on spectral-domain optical coherence tomography. Korean J Ophthalmol. 2013;27(1):19-27.
PubMed   |  Link to Article
Ba-Abbad  R, Sergouniotis  PI, Plagnol  V,  et al.  Clinical characteristics of early retinal disease due to CDHR1 mutation. Mol Vis. 2013;19:2250-2259.
PubMed
Zhao  X, Ren  Y, Zhang  X, Chen  C, Dong  B, Li  Y.  A novel GUCY2D mutation in a Chinese family with dominant cone dystrophy. Mol Vis. 2013;19:1039-1046.
PubMed
van Huet  RA, Estrada-Cuzcano  A, Banin  E,  et al.  Clinical characteristics of rod and cone photoreceptor dystrophies in patients with mutations in the C8orf37 gene. Invest Ophthalmol Vis Sci. 2013;54(7):4683-4690.
PubMed   |  Link to Article
Yzer  S, Barbazetto  I, Allikmets  R,  et al.  Expanded clinical spectrum of enhanced S-cone syndrome. JAMA Ophthalmol. 2013;131(10):1324-1330.
PubMed   |  Link to Article
Ritter  M, Zotter  S, Schmidt  WM,  et al; Macula Study Group Vienna.  Characterization of Stargardt disease using polarization-sensitive optical coherence tomography and fundus autofluorescence imaging. Invest Ophthalmol Vis Sci. 2013;54(9):6416-6425.
PubMed   |  Link to Article
Chun  R, Fishman  GA, Collison  FT, Stone  EM, Zernant  J, Allikmets  R.  The value of retinal imaging with infrared scanning laser ophthalmoscopy in patients with Stargardt disease. Retina. 2014;34(7):1391-1399.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Spectral-Domain Optical Coherence Tomography (SD-OCT) of the Retina

Prevalence of hyperreflective foci in the different layers of the retina and choroid. In the fundus photograph (left), the green box demonstrates the total area that was scanned; green arrow, the section of the scan shown in the SD-OCT image (right). RPE indicates retinal pigment epithelial.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Comparison of Spectral-Domain Optical Coherence Tomography (SD-OCT) Images With Enhanced Depth Imaging (EDI)–OCT Images in 2 Patients

No difference in hyperreflective foci was found between observations with the use of SD-OCT (top OCT image) and EDI-OCT (bottom) in patients 1 and 10. In the fundus photographs (left), green boxes demonstrate the total area that was scanned; green arrows, the section of the scan shown in the OCT images (right).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Mean Number of Hyperreflective Foci in Different Layers of the Retina

A, The number of hyperreflective foci increased in the Bruch membrane/retinal pigment epithelial (RPE) complex with decreasing central macular thickness. B, The number of hyperreflective foci increased in the choriocapillaris, the Bruch membrane/RPE complex, and the Sattler layer with decreasing vision. C, The number of hyperreflective foci increased in the choriocapillaris and Sattler layer with disease duration. Lines across the graphs indicate correlation; limit lines, SD.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Clinical Images of 5 Patients With Stargardt Disease

Note the increased number of choroidal hyperreflective foci with increased disease severity. In the fundus photographs, the green boxes and horizontal green lines demonstrate the total area that was scanned; the highlighted horizontal green lines and green arrows demonstrate the section of the scan shown in the spectral-domain optical coherence tomography images.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Demographic Characteristics of the Study Population

References

Haji Abdollahi  S, Hirose  T.  Stargardt-fundus flavimaculatus: recent advancements and treatment. Semin Ophthalmol. 2013;28(5-6):372-376.
PubMed   |  Link to Article
Westeneng-van Haaften  SC, Boon  CJ, Cremers  FP, Hoefsloot  LH, den Hollander  AI, Hoyng  CB.  Clinical and genetic characteristics of late-onset Stargardt’s disease. Ophthalmology. 2012;119(6):1199-1210.
PubMed   |  Link to Article
Eagle  RC  Jr, Lucier  AC, Bernardino  VB  Jr, Yanoff  M.  Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology. 1980;87(12):1189-1200.
PubMed   |  Link to Article
Lois  N, Holder  GE, Bunce  C, Fitzke  FW, Bird  AC.  Phenotypic subtypes of Stargardt macular dystrophy–fundus flavimaculatus. Arch Ophthalmol. 2001;119(3):359-369.
PubMed   |  Link to Article
Klien  BA, Krill  AE.  Fundus flavimaculatus: clinical, functional and histopathologic observations. Am J Ophthalmol. 1967;64(1):3-23.
PubMed   |  Link to Article
Huang  D, Swanson  EA, Lin  CP,  et al.  Optical coherence tomography. Science. 1991;254(5035):1178-1181.
PubMed   |  Link to Article
Baumal  CR.  Clinical applications of optical coherence tomography. Curr Opin Ophthalmol. 1999;10(3):182-188.
PubMed   |  Link to Article
Querques  G, Leveziel  N, Benhamou  N, Voigt  M, Soubrane  G, Souied  EH.  Analysis of retinal flecks in fundus flavimaculatus using optical coherence tomography. Br J Ophthalmol. 2006;90(9):1157-1162.
PubMed   |  Link to Article
Voigt  M, Querques  G, Atmani  K,  et al.  Analysis of retinal flecks in fundus flavimaculatus using high-definition spectral-domain optical coherence tomography. Am J Ophthalmol. 2010;150(3):330-337.
PubMed   |  Link to Article
Michalewska  Z, Michalewski  J, Nawrocki  J.  New OCT technologies take imaging deeper and wider. Retin Physician. 2013;10(3):42-48.
Staurenghi  G, Sadda  S, Chakravarthy  U, Spaide  RF; International Nomenclature for Optical Coherence Tomography (IN•OCT) Panel.  Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus. Ophthalmology. 2014;121(8):1572-1578.
PubMed   |  Link to Article
Gomes  NL, Greenstein  VC, Carlson  JN,  et al.  A comparison of fundus autofluorescence and retinal structure in patients with Stargardt disease. Invest Ophthalmol Vis Sci. 2009;50(8):3953-3959.
PubMed   |  Link to Article
Verdina  T, Tsang  SH, Greenstein  VC,  et al.  Functional analysis of retinal flecks in Stargardt disease [published online July 30, 2012]. J Clin Exp Ophthalmol. doi:10.4172/2155-9570.1000233.
PubMed
Nakao  T, Tsujikawa  M, Sawa  M, Gomi  F, Nishida  K.  Foveal sparing in patients with Japanese Stargardt’s disease and good visual acuity. Jpn J Ophthalmol. 2012;56(6):584-588.
PubMed   |  Link to Article
Burke  TR, Yzer  S, Zernant  J, Smith  RT, Tsang  SH, Allikmets  R.  Abnormality in the external limiting membrane in early Stargardt disease. Ophthalmic Genet. 2013;34(1-2):75-77.
PubMed   |  Link to Article
Fujinami  K, Sergouniotis  PI, Davidson  AE,  et al.  The clinical effect of homozygous ABCA4 alleles in 18 patients. Ophthalmology. 2013;120(11):2324-2331.
PubMed   |  Link to Article
Lee  W, Nõupuu  K, Oll  M,  et al.  The external limiting membrane in early-onset Stargardt disease. Invest Ophthalmol Vis Sci. 2014;55(10):6139-6149.
PubMed   |  Link to Article
Sisk  RA, Leng  T.  Multimodal imaging and multifocal electroretinography demonstrate autosomal recessive Stargardt disease may present like occult macular dystrophy. Retina. 2014;34(8):1567-1575.
PubMed   |  Link to Article
Salvatore  S, Fishman  GA, McAnany  JJ, Genead  MA.  Association of dark-adapted visual function with retinal structural changes in patients with Stargardt disease. Retina. 2014;34(5):989-995.
PubMed   |  Link to Article
Lim  JI, Tan  O, Fawzi  AA, Hopkins  JJ, Gil-Flamer  JH, Huang  D.  A pilot study of Fourier-domain optical coherence tomography of retinal dystrophy patients. Am J Ophthalmol. 2008;146(3):417-426.
PubMed   |  Link to Article
Aleman  TS, Soumittra  N, Cideciyan  AV,  et al.  CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy. Invest Ophthalmol Vis Sci. 2009;50(12):5944-5954.
PubMed   |  Link to Article
Wang  NK, Chou  CL, Lima  LH,  et al.  Fundus autofluorescence in cone dystrophy. Doc Ophthalmol. 2009;119(2):141-144.
PubMed   |  Link to Article
Thiadens  AA, den Hollander  AI, Roosing  S,  et al.  Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet. 2009;85(2):240-247.
PubMed   |  Link to Article
Audo  I, Friedrich  A, Mohand-Saïd  S,  et al.  An unusual retinal phenotype associated with a novel mutation in RHOArch Ophthalmol. 2010;128(8):1036-1045.
PubMed   |  Link to Article
Burstedt  MS, Golovleva  I.  Central retinal findings in Bothnia dystrophy caused by RLBP1 sequence variation. Arch Ophthalmol. 2010;128(8):989-995.
PubMed   |  Link to Article
Michaelides  M, Gaillard  MC, Escher  P,  et al.  The PROM1 mutation p.R373C causes an autosomal dominant bull’s eye maculopathy associated with rod, rod-cone, and macular dystrophy. Invest Ophthalmol Vis Sci. 2010;51(9):4771-4780.
PubMed   |  Link to Article
Littink  KW, Koenekoop  RK, van den Born  LI,  et al.  Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations. Invest Ophthalmol Vis Sci. 2010;51(11):5943-5951.
PubMed   |  Link to Article
Mackay  DS, Henderson  RH, Sergouniotis  PI,  et al.  Novel mutations in MERTK associated with childhood onset rod-cone dystrophy. Mol Vis. 2010;16:369-377.
PubMed
Park  SJ, Woo  SJ, Park  KH, Hwang  JM, Chung  H.  Morphologic photoreceptor abnormality in occult macular dystrophy on spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2010;51(7):3673-3679.
PubMed   |  Link to Article
Yeoh  J, Rahman  W, Chen  F,  et al.  Choroidal imaging in inherited retinal disease using the technique of enhanced depth imaging optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2010;248(12):1719-1728.
PubMed   |  Link to Article
Ferrara  DC, Costa  RA, Tsang  S, Calucci  D, Jorge  R, Freund  KB.  Multimodal fundus imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;248(10):1377-1386.
PubMed   |  Link to Article
Duncan  JL, Talcott  KE, Ratnam  K,  et al.  Cone structure in retinal degeneration associated with mutations in the peripherin/RDS gene. Invest Ophthalmol Vis Sci. 2011;52(3):1557-1566.
PubMed   |  Link to Article
Kitaguchi  Y, Kusaka  S, Yamaguchi  T, Mihashi  T, Fujikado  T.  Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy. Clin Ophthalmol. 2011;5:345-351.
PubMed   |  Link to Article
Lacassagne  E, Dhuez  A, Rigaudière  F,  et al.  Phenotypic variability in a French family with a novel mutation in the BEST1 gene causing multifocal best vitelliform macular dystrophy. Mol Vis. 2011;17:309-322.
PubMed
Henderson  RH, Mackay  DS, Li  Z,  et al.  Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1Br J Ophthalmol. 2011;95(6):811-817.
PubMed   |  Link to Article
Zhao  L, Grob  S, Corey  R,  et al.  A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy. Eye (Lond). 2012;26(6):866-871.
PubMed   |  Link to Article
Sergouniotis  PI, Holder  GE, Robson  AG, Michaelides  M, Webster  AR, Moore  AT.  High-resolution optical coherence tomography imaging in KCNV2 retinopathy. Br J Ophthalmol. 2012;96(2):213-217.
PubMed   |  Link to Article
Preising  MN, Hausotter-Will  N, Solbach  MC, Friedburg  C, Rüschendorf  F, Lorenz  B.  Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy. Invest Ophthalmol Vis Sci. 2012;53(7):3463-3472.
PubMed   |  Link to Article
Dev Borman  A, Ocaka  LA, Mackay  DS,  et al.  Early onset retinal dystrophy due to mutations in LRAT: molecular analysis and detailed phenotypic study. Invest Ophthalmol Vis Sci. 2012;53(7):3927-3938.
PubMed   |  Link to Article
Thiadens  AA, Slingerland  NW, Florijn  RJ, Visser  GH, Riemslag  FC, Klaver  CC.  Cone-rod dystrophy can be a manifestation of Danon disease. Graefes Arch Clin Exp Ophthalmol. 2012;250(5):769-774.
PubMed   |  Link to Article
Adhi  M, Duker  JS.  Optical coherence tomography—current and future applications. Curr Opin Ophthalmol. 2013;24(3):213-221.
PubMed   |  Link to Article
Esteves  F, Dolz-Marco  R, Hernández-Martínez  P, Díaz-Llopis  M, Gallego-Pinazo  R.  Pattern dystrophy of the macula in a case of Steinert disease. Case Rep Ophthalmol. 2013;4(3):129-133.
PubMed   |  Link to Article
Zerbib  J, Querques  G, Massamba  N,  et al.  Reticular pattern dystrophy of the retina: a spectral-domain optical coherence tomography analysis. Am J Ophthalmol. 2013;156(6):1228-1237.
PubMed   |  Link to Article
Birch  DG, Locke  KG, Wen  Y, Locke  KI, Hoffman  DR, Hood  DC.  Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa. JAMA Ophthalmol. 2013;131(9):1143-1150.
PubMed   |  Link to Article
de Laat  P, Smeitink  JA, Janssen  MC, Keunen  JE, Boon  CJ.  Mitochondrial retinal dystrophy associated with the m.3243A>G mutation. Ophthalmology. 2013;120(12):2684-2696.
PubMed   |  Link to Article
Pach  J, Kohl  S, Gekeler  F, Zobor  D.  Identification of a novel mutation in the PRCD gene causing autosomal recessive retinitis pigmentosa in a Turkish family. Mol Vis. 2013;19:1350-1355.
PubMed
Ahn  SJ, Cho  SI, Ahn  J, Park  SS, Park  KH, Woo  SJ.  Clinical and genetic characteristics of Korean occult macular dystrophy patients. Invest Ophthalmol Vis Sci. 2013;54(7):4856-4863.
PubMed   |  Link to Article
Acton  JH, Greenberg  JP, Greenstein  VC,  et al.  Evaluation of multimodal imaging in carriers of X-linked retinitis pigmentosa. Exp Eye Res. 2013;113:41-48.
PubMed   |  Link to Article
Gliem  M, Zaeytijd  JD, Finger  RP, Holz  FG, Leroy  BP, Charbel Issa  P.  An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet. 2013;4:14.
PubMed   |  Link to Article
Baek  J, Lee  HK, Kim  US.  Spectral domain optical coherence tomography findings in bilateral peripheral cone dystrophy. Doc Ophthalmol. 2013;126(3):247-251.
PubMed   |  Link to Article
Xu  H, Ying  L, Lin  P, Wu  J.  Optical coherence tomography for multifocal vitelliform macular dystrophy. Optom Vis Sci. 2013;90(1):94-99.
PubMed   |  Link to Article
Cho  SC, Woo  SJ, Park  KH, Hwang  JM.  Morphologic characteristics of the outer retina in cone dystrophy on spectral-domain optical coherence tomography. Korean J Ophthalmol. 2013;27(1):19-27.
PubMed   |  Link to Article
Ba-Abbad  R, Sergouniotis  PI, Plagnol  V,  et al.  Clinical characteristics of early retinal disease due to CDHR1 mutation. Mol Vis. 2013;19:2250-2259.
PubMed
Zhao  X, Ren  Y, Zhang  X, Chen  C, Dong  B, Li  Y.  A novel GUCY2D mutation in a Chinese family with dominant cone dystrophy. Mol Vis. 2013;19:1039-1046.
PubMed
van Huet  RA, Estrada-Cuzcano  A, Banin  E,  et al.  Clinical characteristics of rod and cone photoreceptor dystrophies in patients with mutations in the C8orf37 gene. Invest Ophthalmol Vis Sci. 2013;54(7):4683-4690.
PubMed   |  Link to Article
Yzer  S, Barbazetto  I, Allikmets  R,  et al.  Expanded clinical spectrum of enhanced S-cone syndrome. JAMA Ophthalmol. 2013;131(10):1324-1330.
PubMed   |  Link to Article
Ritter  M, Zotter  S, Schmidt  WM,  et al; Macula Study Group Vienna.  Characterization of Stargardt disease using polarization-sensitive optical coherence tomography and fundus autofluorescence imaging. Invest Ophthalmol Vis Sci. 2013;54(9):6416-6425.
PubMed   |  Link to Article
Chun  R, Fishman  GA, Collison  FT, Stone  EM, Zernant  J, Allikmets  R.  The value of retinal imaging with infrared scanning laser ophthalmoscopy in patients with Stargardt disease. Retina. 2014;34(7):1391-1399.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Supplement.

eTable 1. Mean Number of Hyperreflective Foci Counted by Two Observers Independently and the Observed Agreement in Each Layer

eTable 2. Results of Literature Search for Articles Regarding Stargardt Disease and Other Retinal Dystrophies With SD-OCT Images, Which Were Reviewed for the Presence or Absence of Choroidal Hyperreflective Foci

Supplemental Content

Some tools below are only available to our subscribers or users with an online account.

1,057 Views
1 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs