Retinal imaging is a general term for techniques that capture three-dimensional (3D) retinal tissue as two-dimensional images. It forms an essential examination basis for diagnosis and management of diseases in ophthalmic practice.
Wide-field imaging (WFI) is defined as a technique that captures a field of view of 50 degrees or more. Ultra-wide-field imaging (UWFI), with an even wider field, can capture up to 200 degrees, as with Optos®, covering over 80% of the retinal surface area.
Conventional fundus cameras have a maximum field of view of about 60 degrees, so with straight gaze they capture only slightly beyond the macular arcades, and even with eye movements, they barely reach the equator. This severely limited imaging of the peripheral fundus.
In the early 20th century, ophthalmologists relied on film-based fundus photography and fluorescein angiography. Digital imaging became widespread in the latter half of the 20th century, and all fundus cameras have since transitioned to digital systems.
The most significant change was the introduction of Optical Coherence Tomography (OCT). Since its introduction in the 1990s, it has greatly changed the understanding, management, and treatment evaluation of many chorioretinal diseases. In recent years, wide-field and ultra-wide-field imaging have also rapidly become widespread, significantly improving the evaluation of the peripheral fundus.
QWhat is the difference between wide-field imaging and ultra-wide-field imaging?
A
By definition, a field of view of 50 degrees or more is classified as wide-field imaging (WFI). Ultra-wide-field imaging (UWFI) specifically refers to systems such as Optos® that have a field of view of up to 200 degrees, and is characterized by the ability to capture more than 80% of the retinal surface area in a single image.
QIs wide-field imaging possible without pupil dilation?
A
Non-contact UWFI systems such as Optos® and CLARUS® can capture images without pupil dilation. A major advantage is that they can image the peripheral fundus even in cases of poor dilation or in children who resist dilation.
Modern wide-field and ultra-wide-field imaging systems are broadly divided into contact and non-contact types. A comparison of major devices is shown below.
RetCam® (Clarity Medical Systems): Up to 130°. Mainly used for fundus photography in children and newborns. Performed under general anesthesia or topical anesthesia. Fundus photography and fluorescein angiography are possible (FA only with RetCam® 3). As of 2019, it is the only approved contact wide-angle fundus camera in Japan.
HRA2® + Staurenghi lens: Up to 150° on contact. Supports fluorescein and autofluorescence imaging. OCT-equipped models can simultaneously acquire angiographic findings and corresponding tomographic images.
Precautions: Avoid use after trauma or early postoperative period. In cases of suspected infectious lesions, take sufficient precautions to prevent nosocomial infection.
Non-Contact Type
Optos® (Optos PLC, UK): Uses an elliptical concave mirror to capture up to 200° (from the center of the eye). Provides pseudo-color images synthesized from green (532 nm) laser imaging of the anterior retinal pigment epithelium and red (633 nm) laser imaging of the deep fundus. Supports FA, fundus autofluorescence (green/infrared), and ICGA. Non-mydriatic imaging possible.
CLARUS® 500 (Carl Zeiss Meditec): 133° in a single image, 200° with two-image composite. Uses red, green, and blue LED light sources with a slit-scan method (partial confocal). Features true color imaging and blue, green, and infrared autofluorescence modes. Non-mydriatic imaging possible.
Perform imaging after sufficient mydriasis with Mydrin®P. Instill hydroxyethyl cellulose (Scopisol®) on the cornea, contact the 130° lens directly with the cornea, and operate with a foot switch. In children, ensure reliable eyelid opening using a lid speculum or the examiner’s fingers. Applying tape to the temporal eyelid to create a pool of Scopisol® enables stable imaging.
QHow should contact and non-contact types be used differently depending on the situation?
A
Contact-type devices (such as RetCam®) are mainly used for neonates, infants, and cases requiring movement restriction. Non-contact types (Optos®, CLARUS®) are suitable for a wide age range including adults and allow peripheral imaging without mydriasis. Non-contact types are preferred in the early postoperative period or after trauma.
A major advantage of modern WFI and UWFI systems is the ability to acquire multiple imaging modes on the same device. The main acquisition modes are listed below.
Color fundus photography: Records color information and morphological changes such as hemorrhages and hard exudates.
Fluorescein angiography (FA): Evaluates vascular permeability and blood flow using fluorescein (488 nm). Ultra-widefield FA can capture peripheral vascular lesions in a single image.
Indocyanine green angiography (ICGA): Evaluates choroidal vessels. Ultra-widefield ICGA is available on Optos® California and later models.
Fundus autofluorescence (FAF): Evaluates autofluorescent substances such as lipofuscin. Blue (BAF), green (GAF), and infrared (IRAF) wavelengths provide different information.
Red-free photography: Useful for observing the nerve fiber layer.
OCT and OCT-A: Non-invasively acquire retinal cross-sectional images and blood flow information.
Note that the fundus autofluorescence mode of the Optos® 200Tx uses a green (532 nm) laser, resulting in a different color tone compared to conventional fundus cameras. This wavelength characteristic should be considered when evaluating fundus autofluorescence. The HRA also allows simultaneous FA/ICG angiography, providing concurrent angiographic findings at the same angle and marking of corresponding sites, facilitating site comparison.
Diabetic retinopathy (DR): Ultra-widefield imaging facilitates comprehensive assessment of peripheral vascular lesions and proliferative tissue. Widefield imaging is particularly useful for documenting the overall disease burden in DR3)
Mucopolysaccharidosis (MPS) retinopathy: Combination of UWF fundus photography, fundus autofluorescence, and OCT can detect retinopathy that is difficult to identify by clinical fundus examination alone. UWF fundus photography was performed in 65 of 75 cases, and findings consistent with retinopathy were confirmed in 31 cases2)
Situations where scleral depression is contraindicated (e.g., early postoperative period)
Pediatric fundus imaging using RetCam® offers the following benefits: ① objective comparison of disease progression over time, ② detailed assessment of pathology via fluorescein angiography, ③ education for junior physicians, ④ sharing information for academic presentations and publications, ⑤ communication with pediatricians and allied health professionals, and ⑥ explanation of the condition to families. Imaging is performed under general anesthesia in the operating room (EUA) or under topical anesthesia in the outpatient setting. In children under 1 year of age, imaging can be performed with physical restraint using a bath towel, but if movement cannot be adequately controlled in older children, observation and imaging are performed under sedation with triclofos sodium (Trichloryl® syrup) or chloral hydrate (Escre® suppository).
Evidence is accumulating to support the transition from conventional 7-field (7F) photography to ultra-widefield imaging for assessing the severity of diabetic retinopathy.
The agreement between UWF-F7 grading and ETDRS 7-field severity assessment is high, with substantial agreement for severe findings: nonproliferative DR (κ=0.73; agreement 96%), proliferative DR (κ=0.74; agreement 97%), scatter photocoagulation (κ=0.97; agreement 99%), and focal photocoagulation (κ=0.71; agreement 98%)4). The main advantage of UWF imaging is the ability to visualize a large area of the retina (at least 80%), enabling identification of lesions that cannot be detected by 7-field photography alone4).
The WFI/UWFI systems have the following technical limitations.
Difficulty in quantitative assessment: When converting a spherical (retinal) surface to a planar (image) surface, the periphery is displayed significantly magnified compared to the center. Therefore, special correction methods are required for quantitative evaluation of the size and area of retinal lesions.
Artifacts: In peripheral imaging, eyelids and eyelashes that interfere with the optical path are likely to be captured. With Optos®, which has a deep depth of focus, this relatively often hinders evaluation of the periphery.
Color tone differences: Optos® and CSLO-based systems use lasers or LEDs of specific wavelengths as light sources, and the color tone of the images differs from that of conventional fundus cameras that reflect light from the retinal surface. It is possible to approximate the appearance of ophthalmoscopic findings by adjusting the color balance.
Challenges of 3D-to-2D conversion: Representing the three-dimensional retinal surface as a two-dimensional image remains a challenge.
CSLO uses a single-wavelength laser beam scanned at high speed instead of bright flash light to illuminate the fundus. A confocal aperture blocks out-of-focus reflected and scattered light, acquiring high-contrast, high-resolution images. CSLO-based systems are characterized by a deep depth of focus.
Principle of Optos®
Elliptical concave mirror method: Utilizes the property that light emitted from one of the two foci of an ellipse always passes through the other. The center of the fundus scan (virtual scan point) is placed on the pupil plane, scanning a 200-degree range of the fundus.
Two-wavelength synthesis: Uses 532 nm (green) to image mainly anterior to the retinal pigment epithelium and 633 nm (red) to image deep layers of the fundus, generating a pseudo-color composite image.
Confocal method: Because information from different depths is obtained for each wavelength due to differences in tissue penetration, the color tone differs from that of a conventional fundus camera.
Principle of CLARUS®
Slit-scan method (partial confocal): Uses red, green, and blue LED light sources with BLFI (Balanced Light Fundus Imaging) technology. The central area is imaged with confocal method, and the periphery with partial confocal method.
True color images: Information acquired at red, green, and blue wavelengths is combined to provide natural color images similar to those from a fundus camera with a white light source.
Non-mydriatic capability: Single images cover 133°, composite of two images up to 200°, and montage up to 267°.
The standard field of view of the Heidelberg Retina Angiograph (HRA) is 30°, but attachments allow imaging at 55° or 102°. It is equipped with three lasers (488 nm, 785 nm, and 817 nm), enabling observation utilizing the characteristics of each wavelength. In the multicolor system, blue, green, and near-infrared light are captured simultaneously to obtain real-time pseudo-color fundus images. Averaging processing allows clear image acquisition even in cases with media opacities.
7. Latest Research and Future Perspectives (Reports at Research Stage)
Research is progressing on portable fundus imaging devices that can be connected to smartphones.
Kim et al. (2024) conducted smartphone-based fundus imaging (SBFI) using the EYELIKE device in Vietnam (Quang Tri Province and Thai Nguyen Province) and analyzed 7,023 individuals (13,615 eyes)1). The prevalence obtained using a tele-diagnosis system was generally consistent with data from other Asian countries. They concluded that SBFI has advantages over RAAB in resource efficiency and diagnostic accuracy and can be performed by screening teams without an ophthalmologist1).
Development of automated diagnostic systems combined with AI is also progressing, and application to cost-effective eye disease screening is expected.
As a research prototype, a swept-source OCT (multi-MHz FDML OCT) with a speed of up to 6,700,000 A-scans/second has been reported. A frequency-swept light source using a vertical-cavity surface-emitting laser (VCSEL) achieves an imaging range of up to 50 mm, suggesting the possibility of imaging the entire eye—including the anterior segment, lens, vitreous, retina, choroid, and sclera—with a single OCT. Realization of 4D intraoperative OCT is also one of the future goals.
This is a method to quantify the amount of autofluorescence emitted from the RPE. In Stargardt disease, even when the fundus appears normal, massive accumulation of autofluorescent material is detected, providing new insights into the disease and a means of prognosis prediction.
Ultra-widefield indocyanine green angiography (UWF-ICGA) is expected to contribute to the elucidation of the pathophysiology of central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV). A device equipped with a fluorescein angiography filter on an adaptive optics scanning laser ophthalmoscope (AO-SLO) is also under development, which may visualize macular vascular structures at histopathological resolution and change the management of macular ischemia.
QIs it possible to take fundus photographs with a smartphone?
A
Smartphone-connected fundus photography devices such as EYELIKE have been commercialized and are used for remote screening in low- and middle-income countries 1). However, at present, the field of view is limited and cannot match dedicated ultra-widefield cameras. Improved diagnostic accuracy combined with AI is expected.
Kim J, Yoon S, Kim HYS. Prevalence of Selected Ophthalmic Diseases Using a Smartphone-Based Fundus Imaging System in Quang Tri and Thai Nguyen, Vietnam. Healthc Inform Res. 2024;30(2):162-167.
Noor A, et al. Retinopathy in Mucopolysaccharidoses: Patterns, Variance, Progression. Ophthalmology. 2024.
American Academy of Ophthalmology. Diabetic Retinopathy Preferred Practice Pattern. 2024.
December 2024 Journal Highlights. Ophthalmology. 2024. [UWF-F7 grading concordance study]
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