Examples of Cropped Leukocoric and Non-Leukocoric Pupils from a Set of 7377 Pictures of Patient Zero (and Control Children Who Were Photographed Alongside Patient).

<p>Each spiral contains: (i) cropped leukocoric pictures from Patient Zero (denoted Lk+/Rb+), (ii) non-leukocoric pupils from Patient Zero (Lk−/Rb+), and (iii) non-leukocoric pupils from healthy control subjects (Lk−/Rb−). <b>A</b>) Cropped leukocoric pupils that exhibit a gray scale (classic leukocoria); cropped leukocoric pupils with non-black and white appearance are also shown: <b>B</b>) yellow, i.e., “xanthocoria”; <b>C</b>) pink, i.e., “rhodocoria”; <b>D</b>) orange, i.e., “cirrocoria”. Many pupils in A–D contain specular reflections of cornea that appear as a white dot and are not indicative of disease.</p

Saturation-Value Scale for Quantifying Leukocoria in Photographs of Children with Retinoblastoma.

<p><b>A)</b> Sectioning the Saturation-Value plane of HSV color space into a useful scale for classifying pupillary reflexes in recreational photographs. In this proposed scale, leukocoria is divided into differing degrees of brightness and color concentration (1° being the brightest, least colored; 3° is the least bright and most colored); areas that likely represent a typical “red” or “black” pupillary reflex are indicated. Each data point labeled “Rb” refers to the average H, S, or V of all leukocoric images of one of nine patients; the superscript of each label refers to the patient number (beginning with zero); subscript text refers to right or left pupil. “PL” refers to Pseudo-Leukocoria from images of a healthy individual that were collected with one of three different camera phones; the subscript refers to the camera that was used to photograph the individual (see text). “NL” refers to Non-Leukocoric controls (average of right and left pupils) from healthy children (i.e., data contained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076677#pone-0076677-g005" target="_blank">Figure 5</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076677#pone-0076677-t001" target="_blank">Table 1</a>). The value “n” below each Rb, NL, and PL point refers to the number of pictures from which each average was calculated. <b>B)</b> Plot showing the average Hue of cropped pupils from panel A.</p

Longitudinal Set of Clinical Images of the Left Retina of Patient Zero Collected with Fundus Photography and Age-Matched Leukocoria in Left Pupil.

<p>The left retina contains three tumors; one large tumor at 12 o'clock, and two smaller tumors at 6 o'clock and 9 o'clock (the two smaller tumors were treated with laser photoablation therapy which resulted in tumor eradication and exposure of the sclera). The radiation symbol denotes the point in time when proton beam radiation therapy was administered to the left eye (age of patient is listed in days).</p

A Collection of ∼7,000 Digital Photographs of a Single Patient with Retinoblastoma.

<p><b>A</b>) Longitudinal frequency of photography of “Patient Zero” by parents over a three year period (i.e., from birth to 3 years old; 7377 photographs). <b>B</b>) The majority of leukocoric pictures (∼80%) were collected with this compact 7.1 megapixel Canon PowerShot SD750 camera. <b>C</b>) Digital picture of Patient Zero (i.e., child on left, exhibiting leukocoria in left eye) and a healthy playmate (i.e., child on right, exhibiting a red reflex in both eyes). <b>D</b>) Example of a digital picture of Patient Zero; right eye exhibited leukocoria, and the left eye exhibited a red reflex. Photographs in C & D were taken with Canon PowerShot SD750. Permission to include images of the healthy control child was granted by both parents.</p

Quantification of Hue and Value of right and left Leukocoric Pupils of Patient Zero and 19 Healthy Control Children.

<p><b>A</b>) Depiction of Hue as an angular quantity. <b>B</b>) Polar plots of average Hue, per pixel (angular dimension) and average Value, per pixel (radial dimension) for right eye of patient that exhibited leukocoria (red circles), and right eye from 19 healthy children (blue squares). <b>C</b>) Polar plots of average Hue, per pixel (angular dimension) and average Value, per pixel (radial dimension) for left eye of patient that exhibited leukocoria (red circles), and left eye from 19 healthy children (blue squares). <b>D</b>) Combination of data points from plots C and D.</p

Examples of “Pseudo-Leukocoria” (Bilateral or Unilateral) in a Healthy Adult without any Known Eye Disease.

<p>Upper panel: photograph collected with a Motorola Droid Razr® and “pseudo-leukocoria” which can be seen in the right eye (unilateral). Middle panel: photograph collected with a Samsung SGH-I997® and with “pseudo-leukocoria” observable in the left eye (unilateral). Lower panel: photograph collected with an Apple iPhone 4® and “pseudo-leukocoria” can be partially seen in both eyes (bilateral). As described in the text, all photographs were taken in the same low-light conditions i.e., intensity of 0.0259±0.0074 µE/m²/s.</p

Quantification of Saturation and Value of Right and Left Leukocoric Pupils of Patient Zero and 19 Healthy Control Children.

<p><b>A</b>) Digital image showing bilateral leukocoria in Patient Zero taken at the age of 199 days. <b>B</b>) Illustration of cylindrical HSV (Hue, Saturation, Value) color space. <b>C</b>) Plot of average Saturation and Value of cropped leukocoric and control pupils from right eyes of Patient Zero (red circles) and 19 control subjects (blue squares). <b>D</b>) Plot of average Saturation and Value of cropped leukocoric and control pupils from left eyes of patient (red circles) and 19 control subjects (blue squares). <b>E</b>) Saturation and Value from right and left leukocoric and control pupils (a combination of plots C and D). Images of cropped pupils are matched to enlarged data points in order to illustrate the range of Saturation and Value of leukocoric and control pupils.</p

Mean Colorimetric Properties Calculated From Images Containing Leukocoric and Healthy Control Pupils and Cropped by Two Different Researchers (Trials).

<p>Mean Colorimetric Properties Calculated From Images Containing Leukocoric and Healthy Control Pupils and Cropped by Two Different Researchers (Trials).</p

Comparison of Frequency of Leukocoria with Age of Patient Zero and Timeline of his Treatment.

<p><b>A</b>) Number of leukocoric pictures plotted as a function of age. Inset shows expansion of age 0–135 days. <b>B</b>) Daily frequency of leukocoric pictures from a set of 7377 facial pictures plotted as a function of age. Inset shows expansion of age 0–135 days. <b>C</b>) First leukocoric pictures of patient at 12, 35, and 78 days old. <b>D</b>) Comparison of monthly frequency of leukocoria with treatment of patient. E) Lateral distribution of leukocoria in 7377 photographs of Patient Zero. After the first month of life, the right eye accounted for the majority of leukocoric pupils that were observed until the right eye was enucleated.</p

Leukocoria in Children with Retinoblastoma.

<p><b>A</b>) The reflection of visible light by an intraocular Rb tumor can cause the pupil to appear white (<i>leukocoric</i>) during photography; an increase in the size of a tumor will generally increase the number of photographic angles that will produce leukocoria during recreational photography. <b>B</b>) An example of a leukocoric picture from a set of 7377 pictures of a patient (Patient Zero) with bilateral Rb. Images of Patient Zero were donated by his parents.</p