A Rapid and Affordable Eye Diagnostic Camera Shivam Shah1, Nitish Thakor1 1 Department of Biomedical Engineering, Johns Hopkins University 3400 North Charles Street Baltimore, MD 21210 Abstract— Corneal disease is the second leading cause of blindness in the developing world. Over 314 million people are visually impaired and nearly 90% live in the developing world. Better diagnosis of corneal disease would decrease the number of blindness cases. Fluorescein sodium is often used to diagnose dry eye, corneal abrasions, corneal ulcers, and other afflictions. A diagnostic eye camera that could take naked and fluorescent images of the cornea would improve diagnostics in the developing world. A web camera with a USB 1.0 interface was adapted for fluorescent imaging. Blue LEDs covered in an additional blue-light filter and a yellow band-pass filter were used to provide optimal imaging. The resultant device has the ability to image any part of the human body, and fluorescently image the eye. The device can be bulk manufactured for approximately $10.88 and disseminated in the developing world with fluorescein sodium dye strips. Initial results show that the images provided by this device can be used accurately to diagnose many corneal diseases and some other ocular diseases as well. I. INTRODUCTION The cornea is the eye’s outermost layer and has three primary functions. With the eye lids, the cornea helps protect the rest of the eye from germs, dust, and other harmful objects. The cornea also controls and focuses the light coming into the eye, and contributes to 65-75% of the eye’s total focusing power. Additionally, the cornea filters out some of the damaging ultraviolet light present in sunlight [1]. The World Health Organization defines blindness as visual acuity of 3/60 or less [2]. About 45 million people in the world are blind and 314 million are visually impaired. Over 87% of the world’s visually impaired live in developing countries and 85% of visually impaired cases are preventable [3]. Corneal disease is second only to cataracts as a major cause of blindness [3]. Medical conditions involving the cornea include numerous disorders, infections, and diseases. Many of these can be diagnosed with the aid of the camera described here. layers of corneal tissue include the epithelium, Bowman’s layer, stroma, Descemet’s membrane, and the endothelium. The epithelium is the outermost layer and functions to block the passage of foreign material into the eye and provides a smooth surface that absorbs oxygen and cell nutrients from tears. Thousands of tiny nerve endings are present in this layer making the cornea extremely sensitive to pain. Epithelial cells anchor to the basement membrane part of the epithelium [4]. Below the basement membrane is Bowman’s layer, a transparent piece of tissue. Injuries involving this collagen rich layer can lead to significant scar tissue formation and potential vision loss. The stroma lies behind Bowman’s layer and accounts for 90% of the cornea’s thickness. Water and collagen account for 94% of the stroma layer. Descement’s membrane is a strong layer of collagen behind the stroma that is regenerated easily after injury [4]. The endothelium is the innermost layer of the cornea and functions to pump excess fluid that drains from the inside of the eye, out of the stroma. Without this pumping mechanism, the stroma would become hazy and opaque. If injured, endothelial cells are lost forever. Corneal edema and blindness can occur if too many endothelial cells die making a corneal transplant the only available treatment option [4]. II. STRUCTURE OF THE CORNEA Corneal tissue is arranged in five layers and contains no blood vessels, a rare characteristic in tissue. The absence of blood vessels allows the cornea to remain clear and able to refract light properly. The aqueous humor held in the anterior chamber directly posterior to the cornea provides nourishment (Fig. 1). The five Figure 1: Structure of the Human Eye [4] III. CORNEAL AFFLICTIONS Corneal infections can arise when a foreign object penetrates the tissue from, for example, a poke to the eye. Bacteria or fungi from a dirty contact lens can also pass into the cornea. These infections called keratitis can reduce visual clarity, produce corneal discharge, erode the corneal, and lead to the formation of scars, a cause of vision impairment [5]. Another chronic affliction is dry eye, in which the eye does not produce enough quality tears to keep the surface lubricated. The uncomfortable feeling and increased risk of infection make dry eye extremely unfavorable. Treatment of dry eye ranges from artificial tears to a surgical procedure preventing the drainage of tears [5]. Corneal dystrophy occurs when one or more parts of the cornea lose transparency. Over twenty such dystrophies have been identified, with each affecting the eye in a related but slightly different manner. Some lead to vision impairment, while others lead to severe pain episodes. Most of the dystrophies identified are inherited, occur gradually, and originate in one of the five corneal layers before spreading to others [5]. Keratoconus is the most common corneal dystrophy in the United States affecting one in every 2000 Americans. This disorder involves the progressive thinning of the cornea starting with the middle, resulting in a bulge. The abnormal curvature changes the refractive properties of the cornea requiring vision correction or special treatment with contact lenses. In most cases the cornea heals without any lingering effects, but in 10-20% of the cases corneal scars form, preventing the wearing of contact lenses [5]. Other afflictions include lattice dystrophy, map-dotfingerprint dystrophy, pterygium, ocular herpes, and even shingles. Corneal afflictions can be diagnosed in different ways including the use of a camera to image the external eye and simple field tests for visual impairment [5]. IV. CASE STUDY I: FIELD TESTS Nearly 90% of the visually impaired live in developing countries that lack the necessary equipment to properly diagnose levels of impairment and type of disease [6]. The issue is further complicated by the fact that on average there is one ophthalmologist per million of people living in Africa [6]. A screening test should require little training to administer or interpret, utilize easily transportable materials, and not be culturespecific or dependent on literacy. Screening helps determine those who need further treatment, but also helps correct for those with a visual impairment who were falsely classified as blind. The screening kit developed in a study by Keefe et al. consists of a visual acuity test card, a pinhole mask to determine refractive errors, and two manuals describing how to use the kit and interpret the results [7]. The field tests are completed to screen for normal or low vision and not to determine the distance visual acuity accurately. Figure 2 shows an example of a near vision test card. The letter E was used in four different orientations as it was believed to be a relatively easy symbol to describe. Only three different sizes of the letter were used instead of the standard six sizes for simplicity. Distance vision was tested by asking the observer to identify the smallest sized symbols at a distance of six meters. If 3 of the 4 orientations were described correctly, then the patient had normal vision. If not, the person was asked to identify the largest symbols and if 3 of the 4 orientations were classified correctly, the patient had low vision. Regardless, of the outcome of this initial test the patient was asked to identify the symbols through a pinhole. If vision was improved with the pinhole, a significant refractive error may be present. If vision was classified as low vision and did not improve using the pinhole, then a serious ocular disease could be present. Appropriate referrals should be made with screening results. The test card can be rotated to prevent memorized responses. Further information about the test protocol can be found on page 526 of the original published article [8]. Figure 2: Near vision test card [7] Qualitative feedback from users of this test has been positive. The test card and testing protocol were found easy to use and understand. Results from the screening test were also compared quantitatively with the Snellen test. The Snellen test is the six optotype test commonly used by almost all optometrists outside the developing world [7]. A study involving 123 subjects was performed at the Royal Victorian Eye and Ear Hospital and 85% were determined to have the same result for distance visual acuity in both tests. 93% were determined to be in the same visual acuity category – normal, low vision, blind. The specificity was found to be 96% (115/119) and details can be found in Figure 3. The simple test kit described above contains all of the tools to determine whether a person has normal vision, should be referred for refractive error correction, or referred for treatment of an ocular disease [9]. The overall cost of the device is primarily determined by printing test cards and transportation costs. No price was explicitly given, but the screening test kit is expected to be distributed for less than $1 per kit. Figure 4: Virtual Perimetry (VIP) Set-Up [11] Figure 3: Test results from comparison study involving described design and Snellen test on 123 patients [7]. The field test described above helps determine who needs refractive error correction, but does not sufficiently identify ocular disease. The patient is referred to an eye specialist if low vision does not improve with the aid of a pinhole. An ocular disease is assumed to be the cause, but no specific information about ocular disease can be provided by the test. V. CASE STUDY II: VIP - VIRTUAL PERIMETRY Researchers at Tel Aviv University in Israel have recently developed goggles called Virtual Perimetry that simplify eye exams and provide more accurate results. The goggles prevent the need for a large bulky machine. Traditionally, patients have been asked to sit with their chin resting on a ledge and focus their eyes on a center target. Visual stimuli are provided around the periphery, and the patient is asked to press a button when the stimulus is seen. This test helps determine the health of the retina and optic nerve. Results can be used to uncover glaucoma and conditions like optic neuritis. The elderly who benefit most from routine eye examinations sometimes have difficulty sitting in the correct position and often compensate by pressing the button even when the stimulus is not actually observed. The goggles can be worn by the patient anywhere including in the hospital as long as there is a computer hook-up (Fig. 4). These cost-effective goggles instantly study a patient’s reflex to an applied visual stimulus. Pricing for this device was undetermined, but the target market is hospitals and optometrist’s starting a private practice [10]. The device might be priced above $100, which would make it unaffordable for the developing world. The user of the device must be trained. The goggles test for refractive error and losses in peripheral vision, but do not specifically test for an ocular disease. VI. CASE STUDY III: PERFECT SIGHT A student group at MIT has identified the need to find a cheaper and more efficient way to diagnose patients with refractive error. No diagnosis of visual impairment or improper diagnosis of visual impairment was found to lead to a productivity loss of 89-133 billion USD, which exceeds the annual Gross Domestic Product (GDP) of 46 out of 52 African countries [12]. The device consists of a retrofitted cell phone, audio feedback, controls, and a cheap optical piece (Fig 5). The user is asked to look at the optical piece and complete some tasks, and the cell phone application calculates the refractive power needed for myopia, hyperopia, astigmatism, and presbyopia. Figure 5: Perfect Sight – The optical piece is attached to the cell phone. Tasks on the cell phone are completed with audio feedback and controls. The prescription is determined by the cell phone application [12]. The device costs only $1 and is significantly cheaper than traditional lenses (priced over $100) used by optometrists to determine refractive error. The patient’s information can be entered into the cell phone providing electronic storage. The device is also expected to be safer than some optometric tests completed to determine refractive error as no lasers or cycloplegic drugs are used. The easy transportation and manufacturing of the overall device make it highly scalable. The current prototype was evaluated and reached a resolution of 0.22 diopters with the cell phone camera and 0.16 diopters with a higher resolution camera. Doctors prescribe refractive correction in 0.25 diopter increments. With 16 subjects, the average absolute error was determined to be 0.5 diopters with a standard deviation of 0.2 diopters for both cylindrical (astigmatism) and spherical (myopia, hyperopia). A comparison between estimated and actual values is shown in Fig. 6. The device is still in the prototype stage and needs to reduce the average optical error below 0.25 diopters before widespread dissemination is possible [13]. Unlike the devices described in the case studies, the eye diagnostic camera provides information that can be directly used to diagnose ocular disease. The camera rapidly obtains images of the naked eye and an eye stained with fluorescein sodium. The cost of the camera is minimized to make it affordable for health care personnel in the developing world. VIII. MATERIALS A complementary metal oxide semi-conductor (CMOS) camera was purchased from www.epathchina.com. The ¼” inch camera uses a USB 1.0 interface to connect to any desktop or portable computer. The camera is rated at 15 frames per second with a resolution of 800x600 pixels. The computer must have a processing speed greater than 133MHz, a 32 MB or larger video RAM, and an available USB port. Two super bright blue LEDs were purchased from www.sparkfun.com. Each LED is rated at 4,000 mcd. The forward voltage is 3.4 volts with a maximum current of 20 mA. Additional circuit elements including a 9V battery, wires, switch, and resistors were obtained from the Johns Hopkins University’s BME Instrumentation supply. A 545/30 bandpass filter was borrowed from Dr. Thakor’s laboratory. The bandpass filter passes light between the wavelength of 530-560 nm. A Dichrofilm sampler was obtained from www.rosco.com. A primary blue lightweight plastic color filter was used to coat the LEDs. IX. DESIGN Figure 6: Evaluation of Perfect Sight resolution [13]. VII. CLINICAL NEED As the previous case studies have identified, there is a large clinical need for devices that help with eye diagnosis. Nearly 314 million people are visually impaired, but 87% of visual impaired cases are preventable [14]. Corneal disease is the second only to cataracts in causing blindness. Due to the lack of optometrists in the developing world, eye diagnosis needs to be simplified. Eye specialists can use electronic images of the outer eye to diagnose most corneal diseases. Fluorescein sodium is used in some ophthalmic tests to determine damage to the corneal epithelium. This protein fluorescent dye binds directly to the basal membrane of the corneal epithelium. The basal membrane can only be accessed by the protein dye if there is damage to the outer layer of cells in the epithelium. The test is often used to find dry eye patches, abrasions, ulcers, etc [15]. The goal of this project was to adapt a web camera with a USB interface for eye diagnostic testing of the cornea. A simple external image of the eye without any adaptation also has significant use in the developing world. Thus, the option to use this device as a simple imaging camera was maintained. The second use of this device is fluorescent imaging of the cornea with the use of fluorescein sodium. Fluorescein sodium dye is usually applied to the patient’s eye with the aid of a sterile strip. In 1981, Grossman found that the dye is best excited with blue light with a wavelength around 450nm as opposed to ultraviolet radiation as previously believed [16]. After excitation, the dye fluoresces in the yellow/green region of the visible light spectrum at a wavelength around 540nm [16]. Adapting the web camera to eye diagnostics requires blue light and a yellow filter (Fig.7). Camera spectra provided in Figure 9. The primary assumption is that the blue light LEDs purchased do not produce any light in the 700-740nm range, a range of light which the used filter also passes through. Figure 7: Schematic of how fluorescein photography works. A light source covered with a blue filter excites the fluorophore. Both blue light and yellow light are reflected towards the camera. A yellow barrier filter passes only the fluorescent light to the camera [17]. For the blue excitation light, two LEDs were placed in a circuit as shown in Figure 8. The forward voltage of the LEDs was 3.4 volts (VL) and the voltage source (Vs) was 9 volts. The guiding formula was: RT (Vs VL ) / IL The circuit contained a 360 ohm resistor so the current through the LEDs was about 15.5 mA, which was below the 20mA maximum. A toggle switch was placed between the nine volt battery and resistor. Figure 8: Schematic of the circuit used in this device. Once the switch is closed, the voltage drop across the resistor creates a current of 15.5mA that turns the blue LEDs on. Although blue light LEDs were used with a peak transmission of light at a wavelength of 468 nm, a dichroic primary blue filter was used to filter out any additional light with a wavelength above 500nm. Fluorescent imaging is optimal when the excitation light source has no overlap with the emitted fluorescence. The wavelength of any light from the light source must be below the wavelength of the emitted light [17]. The Rosco color filter that was used has a transmission Figure 9: Transmission spectra for the primary blue filter used in this device [18]. The yellow light filter transmission spectra could not be obtained, but this filter passes light between 530-560 nm. Optimal fluorescence is obtained with the use of these filters as the excitation light is around 450nm and the yellow filter passes light with wavelength of 540nm, the expected wavelength of the emitted light. The purchased web camera needed to be removed from a plastic clip and placed into a rapid prototyped adapter. The adapting device included a grip and a head with a removable back piece. The pieces were designed using a Pro/ENGINEER and SolidWorks, and printed using a rapid prototyping machine. The adapter and dimensions can be seen in Figure 10. The grip was cylindrical with a height of 4.5 in. and internal radius of 0.6 in. The wall thickness of the grip and the head were 0.15 in. The primary box in the head of the device had overall dimensions of 2.55 x 2.33 x 1.90 in. The head also included a protruding rectangular box with dimensions of 1.475 x 1.15 x 0.60 in. Two holes for the filter and camera head with radii of 0.488 and 0.438 in., respectively, were placed in both aforementioned boxes in the head of the device. More dimensions can be seen in the figure provided. Figure 10: 3D views and dimensions of camera adapter. X. RESULTS The working device is depicted in Figure 11. Figure 11: The top figure show a frontal view of the device, the middle figure shows a side view, and the bottom figure shows a back view of the device. Images were taken of the eye without the yellow filter on the camera lens and with the yellow filter (Fig. 12). There was no fluorescent staining in the first round of images. The effect of the yellow filter was tested. The images with the filter appear to be significantly darker because less yellow light was reflected from the eye. The next set of images was of a paper dyed with fluorescein sodium (Fig.13). The images were taken to show that the darkness of the bottom image in Figure 12 is eliminated when a fluorescent image is present. This validates that the emitted light is in the yellow region passed by the filter. Figure 12: The first figure is of a healthy eye without the filter, and the second figure is of a healthy eye with the yellow filter. Figure 13: The left figure is of the fluorescently dyed paper imaged without a yellow filter, and the right figure is the same dyed paper imaged with the yellow filter. Another round of images was taken of a healthy eye dyed with fluorescein sodium. The first image was taken with the yellow filter to catch the time sensitive fluorescence and the second image was taken without the yellow filter. The images shown in Figure 14 confirm that the eye is healthy. No fluorescein sodium molecules bound to the basal membrane beneath the corneal epithelium. This means that no cells in the corneal epithelium were damaged, exposing the basal membrane to the surface. roughly $10,000, and a used one can be purchased online for around $3,000. An eye specialist can use this large, bulky instrument to observe the anterior segment of the patient’s eye which includes the cornea. The instrument can be adapted for use with fluorescent imaging. Heine also has a handheld slit-lamp biomicroscope (model HSL 150) that can be purchased for $750 and adapted for use in fluorescent imaging [20]. The cost breakdown for building the prototype device and bulk manufacturing the device are shown in Figure 15. Circuit elements include resistors, wires, solder, electrical tape etc. The cost of the device for dissemination is expected to be $11.88. Only one device is needed to serve a community in the developing world. Conservatively, 50 families in one community can benefit from one device. Assuming that families in Africa live on the equivalent of a $0.50 per day, the community of 50 families survives on $25 per day [12]. Hence, this device is affordable as it is less than half of what a community survives on daily. Figure 14: The first image is of a stained healthy eye with a yellow filter and dark due to the absence of corneal damage. The second image is of a stained healthy eye without the yellow filter. XI. SAFETY The LEDs that are utilized in this device are bright, but not harmful if the device is used properly. The maximum permissible exposure (MPE) to the eye was determined to be 2.92J/cm2 [19]. The power generated by one LED is the current multiplied by the voltage or 0.016 A*3.4 V= 0.0544 W. The total power of both LEDs is 0.1088 W. Assuming that the area of the eye is 2 cm2, the LEDs provide 0.0544 W/cm2 [19]. Dividing the MPE of 2.92 J/cm2 by 0.0544 W/cm2 gives the maximum exposure time of the device – 53s. Therefore, the device should not be used to image the eye for a continuous span longer than 53s. However, images of the eye can easily be obtained in this time period, and the patient can be exposed to the LEDs for cumulatively more than 53s if the exposure is discontinuous. Figure 15: Cost breakdown for prototype and bulk manufacturing this device. The cost per device decreases with bulk manufacturing primarily because supplies are cheaper when purchased in bulk. XII. COST EFFECTIVENESS XIII. ADVANTAGES The ophthalmic test using fluorescein sodium is usually completed with a camera already purchased for viewing the eye. A new slit-lamp biomicroscope costs The described device provides medical personnel in the developing world the ability to screen corneal diseases in a high-throughput manner. The device allows for images to be saved to a computer to be evaluated by an eye specialist later if none is present at the time. Saved images provide a record of a patient’s development of or recovery from an ocular disease. The device is cost-effective and requires little training to use. The ability to remove the yellow filter allows the camera to be used for any imaging of the body including wounds and skin moles. Tracking the healing process of a wound and diagnosing skin cancer better would decrease the great health divide between the developing world and countries like the United States, Russia, and United Kingdom. XIV. FUTURE CONSIDERATIONS More testing of the device should be completed to understand its limitations as a diagnostic eye camera. The differences between images of diseases eyes taken by adapted slit lamp biomicroscopes and the eye diagnostic camera described here need to be compared in a clinical study (Fig.16). Most limitations are expected to arise from the image quality provided by the purchased web camera. However, if this device is found satisfactory by three clinicians at the Wilmer Eye Institute, the device can be deemed ready for dissemination in the developing world. Fluorescein sodium strips or drops must also be disseminated with the device. Fluorescein sodium strips cost approximately $0.20 per strip. These strips are better suited for the developing world because they require less training and cannot apply a harmful dose to the eye. Figure 16: The corneal abrasion is visible due to staining and imaging with fluorescein sodium [21]. XV. ACKNOWLEDGEMENTS Kartikeya Murari, Heather Benz, and Chris Browne helped in the making of this device. The funding for the prototype and laboratory space was provided by Dr. Nitish Thakor and the Department of Biomedical Engineering at Johns Hopkins University. XVI. REFERENCES [1] [2] [3] [4] “Facts about the Cornea and Corneal Disease.” National Eye Institute (2010). “The prevention of blindness: report of a WHO Study Group.” World Health Organization (1973):10-11. “Visual impairment and blindness.” World Health Organization (2009). Ibid. 1. [5] [6] Ibid. 1. Foster A, Johnson G. “Blindness in the developing world.” British Journal of Ophthalmology 77 (1993):398-399. [7] Keefe JE, et al. “A simplified screening test for identifying people with low vision in developing countries.” Bulletin of the World Health Organization 74(5) (1996):525-532. [8] Ibid. 7. [9] Ibid. 7. [10] “New goggles take hassle out of eye test.” Indo-Asian News Service August 9, 2008. [11] Ibid. 10. [12] “Perfect Sight – Increasing global accessibility to diagnostic services for eye care.” MIT Media Lab (2010). [13] Ibid. 12. [14] Ibid. 3. [15] Williams R. “The Sodium Fluorescein Technique.” Medical and Science Photography (2002). [16] Grossman J. “A simple technique for fluorescein photography.” Plastic and Reconstructive Surgery 67(2) (1981):257-258. [17] Ibid. 15. [18] “Color filter technical data spreadsheet” access: http://www.rosco.com/us/filters/permacolor.asp [19] Calkins JE. “Retinal light exposures from ophthalmoscopes, slit lamps and overhead surgical lamps.” [20] Heine HSL 150 Hand-Held Slit Lamp - www.heine.com [21] Sowka J, et al. Handbook of Ocular Disease Management Jobson. Publishing LLC. (2001).