January 2005
Volume 46, Issue 1
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Retina  |   January 2005
Assessment of Central Visual Function in Stargardt’s Disease/Fundus Flavimaculatus with Ultrahigh-Resolution Optical Coherence Tomography
Author Affiliations
  • Erdem Ergun
    From the Department of Ophthalmology, General Hospital of Vienna, Vienna, Austria;
  • Boris Hermann
    Department of Medical Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria; and
  • Matthias Wirtitsch
    From the Department of Ophthalmology, General Hospital of Vienna, Vienna, Austria;
  • Angelika Unterhuber
    Department of Medical Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria; and
  • Tony H. Ko
    Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Harald Sattmann
    Department of Medical Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria; and
  • Christoph Scholda
    From the Department of Ophthalmology, General Hospital of Vienna, Vienna, Austria;
  • James G. Fujimoto
    Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Michael Stur
    From the Department of Ophthalmology, General Hospital of Vienna, Vienna, Austria;
  • Wolfgang Drexler
    Department of Medical Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria; and
Investigative Ophthalmology & Visual Science January 2005, Vol.46, 310-316. doi:10.1167/iovs.04-0212
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      Erdem Ergun, Boris Hermann, Matthias Wirtitsch, Angelika Unterhuber, Tony H. Ko, Harald Sattmann, Christoph Scholda, James G. Fujimoto, Michael Stur, Wolfgang Drexler; Assessment of Central Visual Function in Stargardt’s Disease/Fundus Flavimaculatus with Ultrahigh-Resolution Optical Coherence Tomography. Invest. Ophthalmol. Vis. Sci. 2005;46(1):310-316. doi: 10.1167/iovs.04-0212.

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      © 2016 Association for Research in Vision and Ophthalmology.

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Abstract

purpose. To assess photoreceptor morphology in patients with Stargardt’s disease and fundus flavimaculatus using ultrahigh-resolution optical coherence tomography (UHR-OCT) and correlate it with visual acuity (VA).

methods. This was a prospective observational case series. Fourteen patients with Stargardt’s disease (nine women, five men; average age, 39 years; range, 27–53) were examined. A clinically viable UHR-OCT system employing a new, compact titanium sapphire laser was used, enabling a 3-μm axial resolution in the retina. All patients received a full ophthalmic examination, including fluorescein angiography. Outcome was judged by central transverse photoreceptor loss, central foveal thickness, VA, central atrophy according to fluorescein angiography, and fundus autofluorescence.

results. UHR-OCT was capable of visualizing and quantifying regions of central transverse photoreceptor (PR) loss. All Stargardt patients with central atrophy had a complete loss of the central photoreceptor layer in the foveal region (mean transverse photoreceptor loss, 4390 ± 2270 μm; range, 530–9240 μm). Patients without clinically evident central atrophy had an intact photoreceptor layer centrally, but had small, focal parafoveal defects. A correlation was detected between VA and transverse PR loss (Spearman ρ = −0.60, P = 0.03), which was confirmed on logistic regression analysis (R 2 = 0.49, P = 0.0001). Central foveal thickness was reduced in patients with Stargardt’s disease (85 ± 40 μm; range, 58–280 μm). The correlation was statistically significant with VA (Spearman ρ = 0.43, P = 0.04), but not with transverse PR loss (Spearman ρ = −0.23, P ≫ 0.05). Linear regression analysis showed a statistically significant association of central foveal thickness with VA (R 2 = 0.51, P = 0.0001), but not with transverse PR loss (P ≫ 0.05). The extent of atrophy seen in fluorescein angiography correlated with VA and transverse PR loss (Spearman ρ = −0.51, P = 0.007; Spearman ρ = 0.77, P = 0.0001). Similar correlations were found with the maximum transverse diameter of fundus autofluorescence (Spearman ρ= −0.72, P = 0.008; Spearman ρ = 0.77, P = 0.003).

conclusions. Ultrahigh-resolution OCT demonstrates excellent visualization of intraretinal morphology and enables quantification of the photoreceptor layer. Thus, for the first time, an in vivo visualization and quantification of transverse, central photoreceptor loss and correlation with visual function is possible. Lower VA corresponds to a greater transverse photoreceptor loss, which also correlates with the extent of changes seen in fluorescein angiography and in fundus autofluorescence. Furthermore, reduced retinal thickness (i.e., atrophy of retinal layers) does not correlate with the transverse extent of PR loss. Thus, it seems that although there may be progressive atrophy of intraretinal layers, an intact photoreceptor layer leads to better VA. UHR-OCT may present a viable alternative to the assessment of central visual function, due to the easy, objective, and noninvasive data acquisition. Therefore, UHR-OCT could be of future use in judging patients’ prognoses in Stargardt’s disease.

Stargardt’s disease and fundus flavimaculatus are variants of the same hereditary disease that affects the retinal pigment epithelium (RPE) and photoreceptor layer. 1 2 3 4 Because the faulty gene involved has a central role in photoreceptor function, these diseases manifest themselves clinically in the retina. The general course of Stargardt’s disease and fundus flavimaculatus is a slow loss of central vision, resulting in central atrophy and thus loss of central visual function. 5 6 7 8 9 10 Loss of visual acuity (VA) depends on the patients’ age at first presentation of disease. The likelihood of severe visual loss is considerably less in older patients. 5 6 Some have noted a more pernicious course of fundus flavimaculatus. 7  
It is generally accepted that mutations in the photoreceptors lead to Stargardt’s disease/fundus flavimaculatus, in addition to a pathologic RPE. Thus, from a clinical viewpoint, one of the most important clinical aspects of the disease, besides the RPE, is the assessment of photoreceptor function as a parameter of the patient’s central visual function. The latter is particularly important in performing everyday tasks, such as reading and writing, independently. As in age-related macular degeneration, the handicap of these functions can have a significant effect on quality of life. 11 Also, it is an indirect indicator of the patient’s prognosis. 
Fundus autofluorescence is generally accepted as the most effective method for ascertaining Stargardt’s disease—in particular, the extent of the condition. 12 13 14 Conventional studies with fluorescein angiography, visual field, and ERG have been performed and can provide additional useful information. 15 16 17 18 19 As for other imaging techniques, microperimetry 20 and OCT have been used in various macular dystrophies. 21 22 23 24  
Ultrahigh-resolution optical coherence tomography (UHR-OCT) is a recent development of the well-established OCT technology. It is noted for its superior axial resolution (3 μm) over standard-resolution (10–15 μm) OCT technology. 25 26 27 Although some macular dystrophies have been examined with conventional OCT, 21 22 23 24 to our knowledge, there have been no studies published investigating patients with Stargardt’s disease. The purpose of this study was to examine whether UHR-OCT can visualize and quantify transverse photoreceptor loss, in particular focal loss, and compare this with the patient’s VA. It is already known that OCT images correlate well with histologic cross sections of the retina in animal experiments. 25 26 27 28  
Methods
Fourteen patients (nine women, five men; average age, 39 ± 8 years; range, 27–53) with Stargardt’s disease participated in the study. In all cases, the disease had been diagnosed within the past 3 years at the Medical Retina Department of the Medical University of Vienna’s Department of Ophthalmology, and was confirmed with electroretinography (to rule out other potential dystrophies). One patient had had laser treatment for choroidal neovascularization in her left eye 3 years ago. This eye was therefore not included in the study. All the investigations followed the tenets of the Declaration of Helsinki, and written informed consent was obtained from all subjects in the study after the nature and possible consequences of the study had been explained. The ethics committee of the Vienna University School of Medicine approved the study. 
All patients had a full ophthalmic examination, including best-corrected Snellen VA, biomicroscopy, applanation tonometry, and fundoscopy. Furthermore, for fundus autofluorescence, a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph [HRA]; Heidelberg Engineering GmBH, Heidelberg, Germany) was used. An argon blue laser (488 nm) was used to excite lipofuscin, and macular autofluorescence was detected in a spectrum above 500 nm. The maximum transverse diameters of the autofluorescent area were measured with HRA standard software. 
Digital fluorescein angiograms were performed in all patients. The maximum transverse diameter of atrophy seen on fluorescein angiography was calculated. This was performed with a scale that was obtained with a Gullstrand-type model eye with laser-etched scale of concentric half circles in the center of an artificial fundus. 29 The innermost half-circle had a true diameter of 4 mm. Thus, having measured the value of this innermost half-circle on the computer screen (the 4-mm diameter had a value of 10 mm on the screen), we calculated the maximum transverse amount of atrophy. 
Standard resolution, commercially available ophthalmic OCT systems use superluminescent diodes emitting light with 20- to 30-nm bandwidths centered at 830 nm, resulting in a 10- to 15-μm axial image resolution. In the present study, a recently developed, compact, cost-effective (i.e., two to three times cheaper than other commercially available comparable lasers), titanium-sapphire laser (Femtolasers Produktions GmbH, Vienna, Austria), with up to a 176-nm bandwidth at an 800-nm center wavelength was used for imaging. 30 This UHR-OCT system is based on a commercially available OCT system (OCT 1) that was provided by Carl Zeiss Meditec, Inc. (Dublin, CA). 25  
For this study, the retinal exposure must account for the ultrabroad bandwidth light generated by the laser. The ANSI standards for retinal exposure account for wavelength, exposure duration, and multiple exposures of the same spot of the retina. Because the laser source generates femtosecond pulses, the laser output was coupled into a 100-m-long optic fiber, which was used to provide dispersive stretching of the pulse duration to hundreds of picoseconds. This reduces the peak pulse intensities by several orders of magnitude; and, since the laser operates at an 80-MHz repetition rate, the output can be treated as continuous wave. OCT imaging was performed with axial scan rates between 125 and 250 Hz. Assuming 30 consecutive scans at a 125-Hz scanning rate (the slowest rate used in this study) as a conservative limit, a maximum permissible exposure of 1 mW (for a 700-nm center wavelength) and 1.54 mW (for an 800-nm center wavelength) was calculated, using the ANSI standard. 31 OCT imaging was performed using up to 800 μW incident optical power in the scanning OCT beam, well below the ANSI exposure limits. All the UHR-OCT tomograms in the present study were acquired in a similar manner, with ∼3-μm axial and 15- to 20-μm transverse resolution and consisted of 600 transverse and approximately 3000 axial pixels, covering an area determined by the pathology of approximately 1 to 2 mm in depth and approximately 6 to 8 mm in the transverse direction. 
UHR-OCT scans were performed with a set grid of B-scans covering the whole foveal region. The cross section with minimal retinal thickness was assumed as the central UHR-OCT scan so that scan acquisition was independent of patients’ fixation. The assumption that the minimal retinal thickness is at the fovea may introduce a slight error in patients with Stargardt’s disease, because atrophy of the macula may not affect all areas equally. Central foveal thickness was obtained by measurement of the amount of pixels in depth and multiplying it with 1.38 μm/pixel (i.e., the spacing of depth-sampling points), assuming a group refractive index of the human retina of 1.4 for conversion of optical to geometric thicknesses. 25 26 27 28 The extent of transverse photoreceptor loss in the UHR-OCT images was measured in each patient on the same horizontal scan through the center of the fovea that was used for central foveal thickness measurements, employing a freeware medical imaging software program created at the University of Geneva (OSIRIS, ver. 4.18; available at www.idoimaging.com). 32 The transverse extent of PR loss was measured manually. The system calculated the number of pixels, which then had to be normalized, since transverse UHR-OCT scanning pattern sizes varied among the different patients. These normalized pixel values were multiplied by the transverse pixel spacing of 10 μm (6-mm transverse OCT scans with 600 A-scans), to obtain the absolute transverse extent of photoreceptor loss (Table 1)
Statistical calculations were performed on computer (SPSS for Windows, ver. 11.5.0; SPSS Sciences, Chicago, IL). The Spearman ρ rank correlation test and a logistic regression analysis of covariance (ANCOVA) was used to assess the influence of photoreceptor loss on VA. Of the 14 patients, 10 had central atrophy, and the results of these patients were correlated with VA, transverse photoreceptor loss, and maximum transverse diameter of autofluorescence. All probabilities are results of two-tailed tests. The chosen level of statistical significance was P ≤ 0.05. 
Results
The median VA was Snellen 0.4 (20/50; range, 0.05–1.25 [20/400–20/15]) for the right and 0.4 (20/50; range, 0.02–1.25 [20/1000–20/15]) for the left eye. Table 1shows VAs, the amount of transverse PR loss, and central foveal thickness in each patient examined. The mean transverse PR loss was 4390 ± 2270 μm (range, 530–9240). 
Angiographically, 4 patients had hyperfluorescent pisciform lesions (flecks) without central atrophy. Ten patients had a central atrophy of various sizes or bull’s-eye lesions and flecks. The choroid remained dark in all patients with Stargardt disease, as seen in fluorescein angiography (Figs. 1 2) . The mean extent of transverse atrophy seen on fluorescein angiography was 2985 ± 1097 μm (median, 2800; range, 1100–4600). As for autofluorescence, the mean transverse diameter was 2118 ± 1708 μm (median, 2285). 
UHR-OCT showed an excellent visualization of all major intraretinal layers—in particular, of the inner and outer segments of the photoreceptor layer—and thus, the extent of transverse photoreceptor loss. Figure 1Cdepicts a horizontal, cross-sectional, foveal UHR-OCT tomogram of the right eye of a 32-year-old patient with Stargardt’s disease. Figures 1A and 1Bindicate the location of the performed scan on the corresponding color fundus photograph and fluorescein angiogram. UHR-OCT revealed a large central transverse defect in the photoreceptor layer (defined by red arrows) and a general atrophy of all intraretinal layers. Figures 1D and 1Eshow two-fold enlarged views of the interface of the intact and impaired photoreceptor layer, clearly depicting the discontinuation of the signal bands corresponding to the inner (IS PR) and outer (OS PR) photoreceptor segments. The mean transverse defect in this case was 4320 μm, Snellen VA of 0.4 (20/50). Central foveal thickness was measured by UHR-OCT at 69 μm. 
Figure 2Cshows a horizontal, cross-sectional UHR-OCT tomogram of the left eye of a 33-year-old patient with Stargardt’s disease. Figures 2A and 2Bindicate the location of the performed scan on a color fundus photograph and fluorescein angiogram. Figures 2D and 2Eshow enlarged views of the interface of the intact and impaired photoreceptor layers. UHR-OCT clearly visualized significant atrophy of the intraretinal layers (comparable to Figure 1C ), with a central foveal thickness of 38 μm. The transverse PR loss was more pronounced (4940 μm), however, and the corresponding VA was worse (0.2 [20/100]). 
Patients without central atrophy had an intact central PR layer, but had parafoveal defects. Figure 3Cdepicts a horizontal, cross-sectional UHR-OCT tomogram of the right eye of a 42-year-old patient. Figures 3A and 3Bindicate the location of the performed scan on a color fundus photograph and fluorescein angiogram. UHR-OCT visualizes intact intraretinal layers, and a corresponding central foveal thickness of 242 μm, with 1.0 (20/20) VA. Parafoveally, UHR-OCT reveals two areas with focal transverse PR losses (Fig. 3C , defined by arrows). Figures 3D and 3Eshow enlarged views of areas of focal transverse photoreceptor layer loss. The total transverse PR loss was 1280 μm. The corresponding angiogram showed typical pisciform lesions corresponding to fundus flavimaculatus (Fig. 3B)
Statistically, a correlation was seen between VA and transverse photoreceptor loss in patients with Stargardt’s disease (Spearman ρ = −0.60, P = 0.03). A linear regression model for VA and photoreceptor loss showed a highly significant result (R 2 = 0.49, P = 0.0001; Fig. 4 ). There was also a statistically significant correlation between VA and the amount of atrophy seen in fluorescein angiography (Spearman ρ = −0.51, P = 0.007) as well as with the transverse diameter of fundus autofluorescence (Spearman ρ = −0.72, P = 0.008). 
The mean central foveal thickness was markedly reduced (85 ± 40 μm) in patients with Stargardt’s disease. Central foveal thickness did not correlate with transverse PR loss (Spearman ρ = −0.23, P ≫ 0.05) but did correlate with VA (Spearman ρ = 0.43, P = 0.04). Linear regression analysis, however, showed a statistically significant association between central foveal thickness and VA (R 2 = 0.51, P = 0.0001). There were no correlations with the amount of atrophy or with the extent of fundus autofluorescence (P ≫ 0.05); but, on linear regression, there was a statistically significant association (R 2 = 0.32, P = 0.005; R 2 = 0.37, P = 0.05). 
Transverse photoreceptor loss correlated highly with central atrophy on fluorescein angiography (Spearman ρ = 0.77, P = 0.0001) and with the extent of fundus autofluorescence (Spearman ρ = 0.77, P = 0.003). 
Discussion
This study demonstrates, for the first time, in vivo visualization and quantification of the photoreceptor layer and correlationof transverse PR loss with VA. using UHR-OCT. Thus, this represents a novel approach in the assessment of central visual function. 
The amount of PR loss correlated negatively with the patients’ VAs. It did not, however, correlate with foveal thickness. In our opinion, this implies that, even with severe intraretinal layer atrophy, VA could be relatively well preserved with an intact photoreceptor layer. Possibly, the lack of correlation is also the result of Stargardt’s disease patients who have clinically end-stage disease and thus very little foveal thickness (which has a finite value—i.e., can only be reduced to an absolute minimum), but still large defects in the PR layer. However, there is a significant correlation of PR loss with the extent of fundus autofluorescence and atrophy on fluorescein angiography, which would confirm the intimate relation between pigment epithelial and photoreceptor changes. 
Among the macular dystrophies, Stargardt’s disease, first described in 1909 by Karl Stargardt, 1 is considered to be the most common. Some investigators believe that it makes up to 7% of all macular dystrophies. 33 Generally, patients have a slow loss of VA that usually bottoms out at 20/200, although the amount of visual loss depends on the initial time of presentation of the patient. 6 8 Although it is morphologically different, it is generally accepted that fundus flavimaculatus, first described by Franchescetti 2 and Stargardt’s disease have a joint genetic background. Stargardt’s disease is generally autosomal recessive and is caused by changes within the ABCA4 gene. 34 This gene is found in both cone and rod outer segments, and acts as a flippase enzyme for N-retinylidene phosphatidylethanolamine (N-RPE), which acts as a precursor for A2E. This in turn is a precursor of lipofuscin. The ABCA4 gene is highly polymorphic and occurs in both recessive and dominant forms. 35 Not all sequence changes necessarily lead to the disease, but various phenotypes are possible, and clinical expression varies. 32 35 36  
UHR-OCT offers a novel, noninvasive approach to visualizing and quantifying the photoreceptor layer objectively in real time. Image acquisition is quick and causes no discomfort to the patient, which represents an important clinical advantage. Furthermore, the advantage of the UHR-OCT system, in comparison to conventional OCT systems, is its superior axial resolution of 3 μm, in comparison to commercially available OCT systems with 10 μm (StratusOCT; Carl Zeiss Meditec). The quality of the imaging is comparable to conventional histopathology. 26 27 28 Obviously, from a pathophysiological viewpoint, a more detailed assessment of the RPE would be very relevant in treating this disease; however, this requires a further increase in axial resolution not available now. 
In conclusion, UHR-OCT allows quantitative in vivo assessment of the photoreceptor layer in patients with Stargardt’s disease and correlates it with VA. UHR-OCT can also be of use in elucidating the health of the photoreceptor layer in Stargardt’s disease, based on the extent of transverse PR loss, particularly in those cases where central atrophy is absent. This is of particular relevance, because as seen in this study, changes in autofluorescence (i.e., RPE changes) do not necessarily reflect on photoreceptor health immediately. Therefore, in the future, UHR-OCT could provide important, adjunct diagnostic information to assess the prognosis of a patient with Stargardt’s disease. 
 
Table 1.
 
Visual acuity, Transverse Photoreceptor Loss, and Central Foveal Thickness in Patients with Stargardt’s Disease/Fundus Flavimaculatus
Table 1.
 
Visual acuity, Transverse Photoreceptor Loss, and Central Foveal Thickness in Patients with Stargardt’s Disease/Fundus Flavimaculatus
Patient Sex Age (yr) Visual Acuity Transverse PR Loss (μm) Central Foveal Thickness (μm)
RE LE RE LE RE LE
MA M 32 20/50 20/50 4320 4710 69 41
CB F 33 20/100 20/100 5300 4940 62 38
DD M 53 20/400 20/100 6060 8550 135 91
BF F 47 20/20 20/1000 530 NP 280 NP*
JH M 44 20/25 20/20 2310 3200 158 192
SK F 42 20/100 20/50 5650 5490 63 78
AK F 31 20/15 20/15 1020 1700 248 234
SP F 29 20/22 20/33 4110 3900 114 93
EP F 28 20/200 20/100 2900 6300 58 49
RR M 41 20/200 20/20 4380 3440 62 70
ER F 42 20/20 20/20 1280 1070 242 262
RS M 50 20/100 20/40 5320 8400 97 107
PS F 27 20/22 20/25 4420 4090 77 72
RW F 46 20/28 20/125 5980 9240 72 96
Figure 1.
 
Patient with Stargardt’s disease. (A) Color fundus photograph; (B) late-phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) show interface of the intact and impaired photoreceptor layer area (red arrows). Transverse PR loss was 4320 μm resulting in 0.4 (20/50) VA. ONL: outer nuclear layer; ELM: external limiting membrane; IS PR: inner segment, photoreceptor layer; OS PR: outer segment, photoreceptor layer; RPE: retinal pigment epithelium. Central foveal thickness was 69 μm.
Figure 1.
 
Patient with Stargardt’s disease. (A) Color fundus photograph; (B) late-phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) show interface of the intact and impaired photoreceptor layer area (red arrows). Transverse PR loss was 4320 μm resulting in 0.4 (20/50) VA. ONL: outer nuclear layer; ELM: external limiting membrane; IS PR: inner segment, photoreceptor layer; OS PR: outer segment, photoreceptor layer; RPE: retinal pigment epithelium. Central foveal thickness was 69 μm.
Figure 2.
 
Patient with Stargardt’s disease. The description of the panels is as in Figure 1 . Transverse PR loss was 4940 μm, resulting in 0.2 (20/100) VA. Central foveal thickness was 38 μm. Abbreviations are as in Figure 1 .
Figure 2.
 
Patient with Stargardt’s disease. The description of the panels is as in Figure 1 . Transverse PR loss was 4940 μm, resulting in 0.2 (20/100) VA. Central foveal thickness was 38 μm. Abbreviations are as in Figure 1 .
Figure 3.
 
Patient with Stargardt’s disease without central atrophy: (A) color fundus photograph; (B) late–phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) showing areas of focal transverse photoreceptor layer loss (red arrows). Total transverse PR loss was 1280 μm, resulting in 1.0 (20/20) VA. Abbreviations as in Figure 1 . Central foveal thickness was 242 μm.
Figure 3.
 
Patient with Stargardt’s disease without central atrophy: (A) color fundus photograph; (B) late–phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) showing areas of focal transverse photoreceptor layer loss (red arrows). Total transverse PR loss was 1280 μm, resulting in 1.0 (20/20) VA. Abbreviations as in Figure 1 . Central foveal thickness was 242 μm.
Figure 4.
 
Linear regression graph with 95% confidence intervals between VA and transverse PR loss.
Figure 4.
 
Linear regression graph with 95% confidence intervals between VA and transverse PR loss.
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Figure 1.
 
Patient with Stargardt’s disease. (A) Color fundus photograph; (B) late-phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) show interface of the intact and impaired photoreceptor layer area (red arrows). Transverse PR loss was 4320 μm resulting in 0.4 (20/50) VA. ONL: outer nuclear layer; ELM: external limiting membrane; IS PR: inner segment, photoreceptor layer; OS PR: outer segment, photoreceptor layer; RPE: retinal pigment epithelium. Central foveal thickness was 69 μm.
Figure 1.
 
Patient with Stargardt’s disease. (A) Color fundus photograph; (B) late-phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) show interface of the intact and impaired photoreceptor layer area (red arrows). Transverse PR loss was 4320 μm resulting in 0.4 (20/50) VA. ONL: outer nuclear layer; ELM: external limiting membrane; IS PR: inner segment, photoreceptor layer; OS PR: outer segment, photoreceptor layer; RPE: retinal pigment epithelium. Central foveal thickness was 69 μm.
Figure 2.
 
Patient with Stargardt’s disease. The description of the panels is as in Figure 1 . Transverse PR loss was 4940 μm, resulting in 0.2 (20/100) VA. Central foveal thickness was 38 μm. Abbreviations are as in Figure 1 .
Figure 2.
 
Patient with Stargardt’s disease. The description of the panels is as in Figure 1 . Transverse PR loss was 4940 μm, resulting in 0.2 (20/100) VA. Central foveal thickness was 38 μm. Abbreviations are as in Figure 1 .
Figure 3.
 
Patient with Stargardt’s disease without central atrophy: (A) color fundus photograph; (B) late–phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) showing areas of focal transverse photoreceptor layer loss (red arrows). Total transverse PR loss was 1280 μm, resulting in 1.0 (20/20) VA. Abbreviations as in Figure 1 . Central foveal thickness was 242 μm.
Figure 3.
 
Patient with Stargardt’s disease without central atrophy: (A) color fundus photograph; (B) late–phase fluorescein angiogram indicating UHR-OCT scan direction (arrow); (C) UHR-OCT image; (D, E) two-fold magnification of framed part of (C) showing areas of focal transverse photoreceptor layer loss (red arrows). Total transverse PR loss was 1280 μm, resulting in 1.0 (20/20) VA. Abbreviations as in Figure 1 . Central foveal thickness was 242 μm.
Figure 4.
 
Linear regression graph with 95% confidence intervals between VA and transverse PR loss.
Figure 4.
 
Linear regression graph with 95% confidence intervals between VA and transverse PR loss.
Table 1.
 
Visual acuity, Transverse Photoreceptor Loss, and Central Foveal Thickness in Patients with Stargardt’s Disease/Fundus Flavimaculatus
Table 1.
 
Visual acuity, Transverse Photoreceptor Loss, and Central Foveal Thickness in Patients with Stargardt’s Disease/Fundus Flavimaculatus
Patient Sex Age (yr) Visual Acuity Transverse PR Loss (μm) Central Foveal Thickness (μm)
RE LE RE LE RE LE
MA M 32 20/50 20/50 4320 4710 69 41
CB F 33 20/100 20/100 5300 4940 62 38
DD M 53 20/400 20/100 6060 8550 135 91
BF F 47 20/20 20/1000 530 NP 280 NP*
JH M 44 20/25 20/20 2310 3200 158 192
SK F 42 20/100 20/50 5650 5490 63 78
AK F 31 20/15 20/15 1020 1700 248 234
SP F 29 20/22 20/33 4110 3900 114 93
EP F 28 20/200 20/100 2900 6300 58 49
RR M 41 20/200 20/20 4380 3440 62 70
ER F 42 20/20 20/20 1280 1070 242 262
RS M 50 20/100 20/40 5320 8400 97 107
PS F 27 20/22 20/25 4420 4090 77 72
RW F 46 20/28 20/125 5980 9240 72 96
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