Participants

Participants in this study included 11 eyes from 11 idiopathic macular telangiectasia type 1 patients (10 men and 1 woman; mean age: 60.4 years, range: 45-78 years), and 14 eyes from 7 idiopathic macular telangiectasia type 2 patients (3 men and 4 women; mean age: 66.7 years, range: 58-75 years). All individuals were recruited after they visited the Kyoto University Hospital (Kyoto, Japan) between September 4, 2008 and April 26, 2012, and none displayed any other macular abnormality or inherited color blindness. We also examined 10 eyes of 10 healthy volunteers (5 men and 5 women; mean age: 62.9 years, range: 36-69 years) with no eye diseases. Specific exclusion criteria for eyes with idiopathic macular telangiectasia included neovascular maculopathy (ie, age-related macular degeneration, polypoidal choroidal vasculopathy, retinal angiomatous proliferation, idiopathic choroidal neovascularization, angioid streaks), pathologic myopia, other causes of secondary macular telangiectasia (ie, retinal vein occlusion and radiation retinopathy), diabetic retinopathy, and any history or signs of retinal surgery, including laser treatment. We used the criteria proposed by Yannuzzi and associates to perform diagnosis and classification of idiopathic macular telangiectasia using slit-lamp biomicroscopy findings, fundus photographs, and fluorescein angiography (FA) findings. We excluded patients with diabetes from the diagnosis of idiopathic macular telangiectasia type 1.

All patients and volunteers in this study underwent a comprehensive ophthalmologic examination, including measurements of best-corrected visual acuity (BCVA) and intraocular pressure, axial length assessed using an IOL Master (Carl Zeiss Meditec, Dublin, California, USA), indirect ophthalmoscopy, slit-lamp fundus observation with a Goldmann 3-mirror contact lens, color fundus photography, SD-OCT, and AO-SLO. All patients with idiopathic macular telangiectasia also underwent simultaneous FA and indocyanine green angiography (IA), confocal blue reflectance imaging, infrared reflectance (IR) imaging, and fundus-monitoring microperimetry (MP). FA, IA, confocal blue reflectance, and IR images were acquired using a confocal SLO (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). Confocal blue reflectance images were obtained using a 488-nm light stimulus, whereas IR images were obtained using an 820-nm light stimulus. Each study participant underwent all examinations within the same week.

The Adaptive Optics Scanning Laser Ophthalmoscopy System

The AO-SLO system used here was a simplified version designed and constructed in our laboratory based on previous reports detailing the usefulness of incorporating a wide-field SLO with an AO-SLO. The AO-SLO system is confocal, enabling creation of high-contrast “en-face” images in any plane; these images show individual cone photoreceptor cells. The system is composed of 4 primary optical subsystems: the AO subsystem, which includes the wavefront sensor and the spatial light modulator; the high-resolution confocal SLO imaging subsystem; the wide-field imaging subsystem; and the pupil observation subsystem, which facilitates the initial alignment of the subject’s pupil with respect to the optical axis of the AO-SLO system through adjustment of the chin rest position. The wavefront sensor measures aberrations in the whole eye, and the spatial light modulator compensates for these aberrations. Further details of our AO-SLO system are described in the Supplemental Material (available at AJO.com ).

Adaptive Optics Scanning Laser Ophthalmoscopy Imaging of Cone Mosaic Features

The AO-SLO images were obtained to cover a 3 × 3-mm-square area around the fovea. AO-SLO imaging was performed by shifting the focus from the retinal nerve fiber layer to the retinal pigment epithelium, then recording images that showed the cone mosaic. Offline, a montage of AO-SLO images was created by selecting the area of interest and generating each image to be included in the montage from a single frame, without averaging. Comparisons between AO-SLO images and wide-field images for the same eye were used to ensure that each image corresponded to the area of interest. The montage of AO-SLO images was used for the registration with images of other imaging modalities by matching the shape of the vessels.

We next applied the automated cone labeling process of Li and Roorda, which uses an algorithm implemented in MATLAB (Mathworks Inc, Natick, Massachusetts, USA) and a function from the MATLAB Image Processing Toolbox. We manually corrected the results of automated cone labeling on any images for which the algorithm failed to identify the cones, as follows: an experienced observer who was masked to the classification and other clinical findings examined each image after automated cone labeling; the observer manually labeled the areas where cones were visible but had not been identified, then entered this area into the computer software.

We selected areas without shadows of vascular components, and estimated cone density in areas 0.5 mm and 1.0 mm from the center of the fovea by instructing the computer software program to divide the number of cones in each area by the size of the area ( Figure 1 ). These distances from the center of the fovea were selected because the system does not always clearly show individual cones within the central fovea (a limitation that has been reported for similar systems ) but does clearly show cones >0.2 mm from the center. The center of the fovea, defined here as the center of the foveal avascular zone, was determined from the montage of AO-SLO images. To obtain accurate lengths of scans, we corrected the magnification effect in each eye using the adjusted axial length method devised by Bennett and associates.

Cone labeling and cone density measurement. (Top row) Cone images 0.5 mm temporal from the center of the fovea. Left, normal eye; middle, idiopathic macular telangiectasia type 1; right, idiopathic macular telangiectasia type 2. (Second row) Cone labeling results of each image. The cone densities are 30 156, 12 343, and 7031 cones/mm ² in the normal eye (left), type 1 eye (middle), and type 2 eye (right), respectively. (Third row) Cone images 1.0 mm temporal from the center of the fovea. Left, normal eye; middle, idiopathic macular telangiectasia type 1; right, idiopathic macular telangiectasia type 2. (Bottom row) Cone labeling results of each image. The cone densities are 17 500, 6875, and 4062 cones/mm ² in the normal eye (left), type 1 eye (middle), and type 2 eye (right), respectively. The field of view of each image is 80 × 80 μm.

To quantify the extent of the leakage area in FA images (within areas scanned by AO-SLO) and the dark regions in AO-SLO images, each image was examined by 2 independent experienced observers (S.O. and K.T.) who used an image processing software (Image J) available from the National Institutes of Health (Bethesda, Maryland, USA) to manually identify any region of abnormality and to measure their respective areas. The area in each eye was taken as the mean of the areas measured by the 2 observers.

Spectral-domain Optical Coherence Tomography Evaluation of Photoreceptor Layer Features

SD-OCT examinations were performed in all eyes using a Spectralis HRA+OCT (Heidelberg Engineering). Horizontal and vertical line scans through the center of the fovea were obtained at a 30-degree angle, after which we performed 12 radial scans centered on the fovea. We then obtained volume scans (19 horizontal B-scans at 15 × 20 degrees; the distance between each B-scan was 237 μm). At each location of interest on the retina, 50 SD-OCT images were acquired and averaged to reduce speckle noise.

We manually marked each area of interest (ie, the area with intraretinal cystoid spaces in type 1 and retinal lamellar cavities in type 2) by drawing a line in each B-scan image taken by volume scan, then projecting it onto the IR image ( Figure 2 ). Each projected image was then merged into 1 en-face image; thus, the SD-OCT images were registered with images obtained by other imaging modalities ( Figures 3-6 ).

Areas of interest graded with spectral-domain optical coherence tomography. The spectral-domain optical coherence tomography imaging protocol comprises 19 B-scans per volume scan of 15 × 20 degrees; each scan was averaged with 50 frames per B-scan. Areas of interest were manually marked (ie, areas with intraretinal cystoid spaces in idiopathic macular telangiectasia type 1 [Top], and inner and outer lamellar cavities in type 2 [Bottom]) by drawing a line in each B-scan image and projecting it onto the infrared image. Each projection image was merged into 1 en-face image.

Idiopathic macular telangiectasia type 1 using multimodal imaging. Images of the left eye of a 59-year-old man with type 1 idiopathic macular telangiectasia and a Snellen equivalent best-corrected visual acuity (BCVA) of 20/15. (Top row, left) Fundus photograph showing microaneurysms, cystoid macular edema, and hard exudates. (Top row, middle) Early-phase fluorescein angiography (FA) image showing telangiectasia and microaneurysms. (Top row, right) Late-phase FA image showing late leakage, with green arrows indicating the directions of the scans producing the images in third row and bottom row, and a white box indicating the size of the double-headed arrows in third row and bottom row. Leakage is observed superior, inferior, and temporal to the fovea. (Second row, left) Confocal blue reflectance image showing no abnormal reflectance. (Second row, middle) Infrared reflectance image showing areas of interest graded in spectral-domain optical coherence tomography (SD-OCT). Intraretinal cystoid spaces are indicated in red. (Second row, right) Fundus-related microperimetry (MP) image showing a parafoveal scotoma temporal and inferior to the fovea. (Third row and Bottom row) SD-OCT images. (Third row) Horizontal line scan through the center of the fovea, taken in the direction of the horizontal arrow in top row, right, revealing intraretinal cystoid spaces (red arrowheads) and disruptions of the cone outer segment tip (COST) line (blue arrowheads). The line representing the junction between the inner and outer photoreceptor segments (IS/OS) between the blue arrows is also irregular in the temporal side of the fovea. (Bottom row) A vertical line scan through the center of the fovea, in the direction of the vertical arrow in top row, right, demonstrating an intraretinal cystoid space (red arrowhead). RPE: retinal pigment epithelium.

Idiopathic macular telangiectasia type 1 using adaptive optics scanning laser ophthalmoscopy (AO-SLO). AO-SLO images of the area indicated by white box in the image in Figure 3 , top row, right. (Top, left) AO-SLO showing scattered patchy dark regions (yellow arrows). Dark regions are seen mainly temporal to the fovea, where there is IS/OS irregularity (third row of Figure 3 ) and decreased retinal sensitivity (second row, right, of Figure 3 ). The areas where these features appear are included in the fluorescein angiography leakage area (Bottom, left). Additionally, dark regions are mostly included in the area with intraretinal cystoid spaces (second row, middle, of Figure 3 ). The white asterisk indicates the fixation point. Red asterisks indicate shadows of microaneurysms. (Middle and Right) High-magnification views of the areas outlined by the white boxes (a-d) in top left panel.

Idiopathic macular telangiectasia type 2 using multimodal imaging. Images of the right eye of a 59-year-old man with type 2 idiopathic macular telangiectasia and a Snellen equivalent best-corrected visual acuity (BCVA) of 20/32. All panels correspond to those shown in Figure 2 . (Top row, left) Fundus photograph demonstrating dilated and blunted vessels, as well as graying of the macula. (Top row, middle) Early-phase fluorescein angiography (FA) image showing a network of retinal telangiectasis. (Top row, right) Late-phase FA image showing late leakage, with green arrows indicating the directions of the scans producing the images in third row and bottom row, and a white box indicating the size of the double-headed arrows in third row and bottom row. Leakage is observed temporal to the fovea. (Second row, left) Confocal blue reflectance image demonstrating a ring-like area of increased parafoveal reflectance (arrow). (Second row, middle) Infrared reflectance image showing areas of interest graded in spectral-domain optical coherence tomography (SD-OCT). Areas with inner and outer lamellar cavities are indicated in red. (Second row, right) Microperimetry (MP) image showing a parafoveal scotoma predominantly temporal to the fovea. (Third row and Bottom row) SD-OCT images. (Third row) Horizontal line scan through the center of the fovea, taken in the direction of the horizontal arrow in image in top row, right, showing inner and outer lamellar cavities (red arrowheads). The cone outer segment tip (COST) and inner and outer photoreceptor segments (IS/OS) are disrupted temporal to the center of the fovea (between the blue arrowheads). (Bottom row) Vertical line scan through the center of the fovea, taken in the direction of the vertical arrow in top row, right, demonstrating inner lamellar cavities (red arrowheads) and the irregularity of the COST and IS/OS in the fovea (between the blue arrowheads). RPE: retinal pigment epithelium.

Idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO). AO-SLO images of the area indicated by white box in Figure 5 , top row, right. (Top, left) AO-SLO images showing oval patchy dark regions (yellow arrows) surrounded by small dark patches. Dark regions are seen in all areas around the fovea, corresponding to the area of IS/OS disruption (third row and bottom row of Figure 5 ) and the area of decreased retinal sensitivity (second row, right, of Figure 5 ). The areas wherein these features appear on various images are smaller than the area of increased reflectance in the confocal blue reflectance image (second row, left, of Figure 5 ). Note that small patchy dark regions are observed even nasal to the fovea where no leakage is seen on FA (Bottom, left). Dark regions are seen in a wider area of the inner and outer lamellar cavities (second row, middle, of Figure 5 ). The asterisk indicates the fixation point. (Middle-left, Middle-right, and Right) High-magnification views of the areas outlined by the white boxes (a-f) in top left panel.

Microperimetry: Retinal Sensitivity Measurements

We used fundus-monitoring MP (MP-1; NIDEK, Padova, Italy) to measure retinal sensitivity. The MP-1 software can be set to automatically track fundus movements and evaluate every acquired frame for shifts in the directions of the x- and y-axes of the fundus with respect to a reference image obtained by an infrared camera at the beginning of the examination.

We used a 4-2-staircase strategy with Goldmann size III stimulus against a white background with illumination of 1.27 cd/m ² to examine 55 stimulus locations covering the central 20 degrees. The differential luminance, defined as the difference between stimulus and background luminance, was 127 cd/m ² at 0 dB stimulation; the maximum stimulus attenuation was 20 dB. The duration of the stimulus was 200 ms.

Statistical Analyses

BCVA measured using the Landolt chart was expressed as the Snellen equivalent or the logarithm of minimal angle of resolution (logMAR). We used Tukey-Kramer tests to evaluate differences in patient age, refractive error, and cone density for eyes with and without idiopathic macular telangiectasia. Student t tests were used to compare logMAR visual acuity between type 1 and type 2 and to evaluate the relationships between cone density and tomographic or angiographic changes. For interobserver measurements, 2-way mixed, average-measure intraclass correlation coefficients (ICC [3, K]) were obtained. We calculated the Pearson product moment correlation coefficient to determine associations between mean cone density and both logMAR visual acuity and retinal sensitivity. All statistical evaluations were performed in SPSS v.17 (SPSS Inc, Chicago, Illinois, USA). Significance was defined as P < .05.