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Ultra-widefield Imaging Technology

Dr. Simon Chen | 27 May 2013

This course expired on 30 November 2013.

Multi-modal ultra-widefield imaging (UWFI) technology is playing an increasing role in diagnosing, treating, managing and understanding retinal diseases that involve the peripheral retina. The Optos imaging device is one of the most widely used UWFI devices, and the focus of this month’s CPD article.

Peripheral retinal pathology such as retinal tears, retinal detachments, choroidal tumours, and retinal vasculitis among others, is an important cause of sight threatening disease and increasingly recognised as playing an important role in common eye conditions including diabetic retinopathy. Consequently, assessment of the peripheral retina should form part of any comprehensive eye examination.

The term ultra-widefield imaging (UWFI) can be applied to technology that captures retinal images with a field of view greater than 100°. Traditional fundus cameras used in routine optometric practice typically image a field of view ranging from 20° to 50°, enabling visualisation of the posterior pole including the macula and optic disc. Imaging of the mid-peripheral retina with traditional fundus cameras is possible by making multiple photographic sweeps of the peripheral retina. However, this process requires an experienced photographer, is time consuming, uncomfortable and inconvenient for the patient because of the multiple camera flash exposures, requirement to hold the eye in extreme positions of gaze and the need for pharmacological mydriasis to obtain clear peripheral retinal images.

Multiple peripheral retinal images can be combined to form a single overview image using montage software but this is time consuming and abnormalities occurring at the boundaries of the overlapping images may be obscured. Even in well-dilated, cooperative patients, the view of the peripheral retina is limited using traditional fundus cameras and peripheral retinal pathology can be missed. These logistic barriers are sufficient to deter the majority of clinicians from routinely imaging the peripheral retina with traditional fundus cameras.

UWFI allows quick, convenient simultaneous imaging of the posterior pole and peripheral retina in a single image and can document pathology not recordable with traditional fundus cameras (Figure 1).Patients tend to prefer UWFI over conventional photography because of speed and comfort.1

Commercially available UWFI devices include the Optos imaging device (Optos, Scotland), Retcam (Clarity Medical Systems, USA), Ocular Staurenghi 230 SLO Retina Lens (Ocular Instruments, USA) and Heidelberg Spectralis ultra-widefield module (Heidelberg, Germany). The Optos device is the most widely used UWFI device in optometric practice.

Ultra-widefield Technology and Imaging Modes

The Optos imaging device combines a scanning laser ophthalmoscope (SLO) with an ellipsoid mirror to produce non-mydriatic ultra-widefield images with a field of view up to 200° in a single image, covering approximately 80 per cent of the retinal surface. The instrument takes one image in approximately 0.3 seconds thus minimising motion artefacts. Total scanning time, including patient positioning, takes approximately three to five minutes, requiring less operator experience and patient co-operation than imaging with traditional fundus cameras.

Figure 1. Ultra-widefield pseudo-colour image showing 360-degree choroidal detachments secondary to ocular hypotony.

SLO technology incorporates the principles of confocal laser scanning microscopy and a low power laser passed through the pupil to sweep across the retina, enabling high resolution retinal image capture. An advantage of SLO imaging over conventional fundus photography using white light is the ability to acquire images through small pupils (2mm diameter or larger) because the scanning laser beam occupies only a small portion of the pupil. Because the laser illuminates a very small point on the retina at any moment, the illumination level required for image acquisition is a factor of 200 lower than with a fundus camera, avoiding the need to use a bright flash. SLO images are less susceptible to image degradation by media opacities than conventional photography and the wavelength of the illuminating light can be selected, enabling additional imaging modes such as fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA).

The ability of the Optos device to image the peripheral retina is based upon the optics of an ellipsoid mirror, which has two focal points. The eye is positioned so that one of the mirror’s focal points is behind the iris plane while the scanning laser beams are directed through the second focal point, enabling wide scanning angles.2

Figure 2. Branch retinal vein occlusion with laser scars and superior choroidal nevus. Left: Pseudo-colour image. Centre: Green laser image highlighting superficial retinal collateral vessels. Right: Red laser image highlighting a choroidal nevus.

Ultra-widefield pseudo-colour and monochromatic imaging

The Optos device scans the retina with a red (633nm) and green laser (523nm). The images produced are pseudo-colour images because blue light is absent. The images created by each laser wavelength can be viewed separately to enable selective viewing of pathology at different anatomical levels. The red laser penetrates the deeper layers of the retina and choroid, highlighting choroidal pathology such as choroidal nevi, whereas the green laser does not penetrate as deeply and provides better images of the superficial layers of the retina and retinal vessels (Figure 2).3

Ultra-widefield fundus autofluorescence

FAF imaging is a technique used to assess the health and function of the retinal pigment epithelium (RPE) and neurosensory retina. Conventional FAF cameras focus on the posterior pole but recent Optos units enable ultra-widefield FAF imaging using a green laser (532nm) for excitation.4 This has provided new insights into the pathophysiology of conditions such as retinal dystrophies.

FAF is based on the principle that fluorophores are excited by light of a certain wavelength and, in turn, emit a characteristic light spectrum. In the retina, the majority of the FAF signal arises from the fluorophore lipofuscin in the RPE.5 In diseased cells, lipofuscin accumulates as a result of oxidative breakdown of fatty acids, retinoids, and proteins, causing increased FAF and possible impending cellular damage.

When the cells eventually die these areas appear dark on FAF imaging. FAF images can be likened to a metabolic map of the RPE with characteristic FAF abnormalities described in numerous diseases, including inherited retinal dystrophies, central serous chorioretinopathy, macular telangiectasia, hydroxychloroquine toxicity and age related macular degeneration (AMD) (Figure 3).6-10 Areas of abnormal FAF are often more easily visible, more extensive and may occur before the development of ophthalmoscopically visible lesions.

Figure 3. Ultra-widefield fundus autofluorescence image showing characteristic descending tracts of hyper and hypo-autofluorescence due to chronic central serous chorioretinopathy.

Ultra-widefield fluorescein angiography

The addition of a blue laser (488nm) in some Optos units enables the acquisition of ultra-widefield fluorescein angiography (UWFA) images, which are particularly useful in eyes with retinal vascular disease such as diabetic retinopathy or retinal vein occlusion, as well as posterior segment inflammatory conditions such as retinal vasculitis.

Traditional FFA employs standard fundus cameras which capture approximately 45° of the retina in one image. Although mosaic creation software can combine multiple peripheral images into a single image, the images are not captured simultaneously and must be combined from different time points making assessment of retinal vascular blood flow imprecise. The ability to assess the macula and peripheral retinal vascular flow simultaneously with UWFA in a single image provides a more comprehensive overview of the retinal vasculature and has brought with it a new understanding of the role that peripheral retinal pathology plays, particularly in retinal vascular conditions such as diabetic retinopathy.11

Clinical Applications of UWFI in Specific Eye Conditions

UWFI is increasingly being used in clinical practice to assess, monitor and guide the management of a wide variety of retinal disorders. Research into the utility of these new technologies in conditions such as retinal detachment, choroidal dystrophies and AMD is ongoing.

A summary of clinical applications of UWFI in specific eye conditions is presented below.

Diabetic retinopathy

The role of UWFI in screening and monitoring of diabetic retinopathy
The current gold standard for detecting and classifying diabetic retinopathy and other retinal vascular disorders is the seven standard field protocol (7SF) developed by the Early Treatment of Diabetic Retinopathy Study (ETDRS) research group. This combines seven 30° fundus images, three centred horizontally across the macula and four around the optic nerve, to image approximately 70 per cent of the retina.12 UWFI enables up to 200° of the retina to be efficiently imaged and provides potential advantages for the routine screening of diabetic retinopathy.

A recent study comparing non-mydriatic UWFI, conventional dilated fundus photography using the 7SF ETDRS standard, and dilated clinical examination by a retinal specialist in detecting and classifying diabetic retinopathy in 103 diabetic patients, reported a 99 per cent sensitivity and 100 per cent specificity for UWFI in detecting diabetic retinopathy diagnosed on ETDRS photographs.13 The same study also showed a reduced sensitivity of 73 per cent for UWFI in detecting proliferative diabetic retinopathy compared to ETDRS photographs, emphasising the superior ability of conventional fundus cameras to identify subtle retinal neovascularisation.

The reduced sensitivity in identifying proliferative diabetic retinopathy was attributed to suboptimal non-mydriatic UWFI image quality. The acquisition of non-mydriatic ultra-widefield images was performed in less than half the time required to obtain dilated ETDRS photographs, even excluding the time needed for dilation.

UWFA may play a role in enabling Mearlier and more precise detection and treatment strategies for diabetic macular edema and proliferative diabetic retinopathy. When compared to conventional fluorescein angiography using the 7SF ETDRS standard, UWFA has been shown to demonstrate more than double the amount of retinal pathology, such as non-perfusion and neovascularisation. UWFA demonstrated areas of retinal neovascularisation and non-perfusion that would have been missed by 7SF in approximately 10 per cent of eyes in one study.14

The role of UWFI in the treatment of diabetic retinopathy

Retinal ischaemia stimulates the production of vascular endothelial growth factor (VEGF) leading to disruption of the blood-retinal barrier and retinal vascular leakage.15 This causes diabetic macular edema, the leading cause of diabetes associated visual loss. Anti-VEGF drugs such as bevacizumab (Avastin), ranibizumab (Lucentis) and aflibercept (Eylea) are of proven efficacy in the treatment of diabetic macular edema.16 VEGF also stimulates the growth of retinal new vessels, which are the hallmark feature of proliferative diabetic retinopathy.

Retinal ischaemia is identified with FFA. Recent studies using UWFA to detect and quantify peripheral retinal ischaemia have shown that peripheral areas of retinal ischaemia correlate with diabetic macular edema and patients with more extensive retinal ischaemia are more likely to develop diabetic macular edema (Figure 4).17 The clinical implications of UWFA detection of peripheral retinal ischaemia in diabetic patients may include a need for closer monitoring and earlier follow-up than patients without retinal ischaemia.

Figure 4. Diabetic macular edema. Left: Pseudo-colour image showing diabetic macular edema with hard exudates. Right: Ultra-widefield fluorescein angiogram showing extensive macular vascular leakage and peripheral retinal ischaemia.

The ability to identify peripheral retinal ischaemia with UWFA has led to recent interest in a new treatment strategy termed "targeted retinal photocoagulation" (TRP) which may have benefits in treating diabetic macular edema and proliferative diabetic retinopathy.18 The conventional treatment for proliferative diabetic retinopathy is panretinal photocoagulation (PRP) which involves treating the peripheral retina diffusely with laser photocoagulation to ablate areas of both ischaemic and non-ischaemic retina. In contrast, TRP limits laser treatment to only the areas of retinal ischaemia identified by UWFA, aiming to spare well-perfused "normal" retina from laser-induced scarring to minimise the side effects of PRP.

The Diabetic Retinopathy Study reported that PRP was associated with a reduction in visual acuity in 10 per cent of patients and a constriction of visual fields in 5 per cent.19 PRP may also exacerbate diabetic macular edema and cause poor night vision.

In patients with chronic diabetic macular edema, it has been hypothesised that TRP to treat areas of peripheral ischaemia may reduce VEGF production and prevent or reduce the severity of diabetic macular edema, potentially reducing the need for macular laser treatment or the number and frequency of anti-VEGF injections needed. The results of prospective studies in this area are awaited.

Retinal vein occlusion

Central retinal vein occlusions (CRVO) and branch retinal vein occlusions (BRVO) are classified as ischaemic or non-ischaemic depending upon the degree of retinal ischaemia present, traditionally assessed with standard FFA.

Using UWFA, the extent of peripheral retinal ischaemia in patients with retinal vein occlusion can be better assessed and visualised than with conventional FFA (Figure 5). The extent of retinal ischaemia has been shown to be associated with macular oedema and retinal neovascularisation.20

Figure 5. Central retinal vein occlusion. Left. Pseudo-colour image. Right: Ultra-widefield fluorescein angiogram.

Current treatments for macular oedema associated with retinal vein occlusion focus on macular laser treatment or intravitreal therapy using anti-VEGF agents or steroids. As previously described with diabetic macular edema, it has been hypothesised that TRP to ablate localised areas of peripheral retinal ischaemia in patients with retinal vein occlusions may reduce VEGF production and potentially reduce the incidence of sight threatening retinal neovascularisation and macular oedema, possibly leading to a reduced need for intravitreal anti-VEGF therapy. However, early studies have not shown a significant benefit of TRP in the treatment of CRVO.21

Age-related macular degeneration

UWFI with FAF has identified numerous abnormalities in the peripheral retina of patients with age related macular degeneration (AMD). Peripheral FAF abnormalities have been found in approximately 69 per cent of eyes with AMD compared to 18 per cent of eyes without AMD.22 Different peripheral FAF patterns often correlate with specific abnormalities visible with UWFI e.g. granular FAF with peripheral drusen, nummular FAF with cobblestone degeneration, and mottled FAF with RPE depigmentation (Figure 6). The FAF changes are typically symmetrical between both eyes. Abnormal peripheral FAF occurs more frequently in the neovascular (wet) form of AMD compared with the non-neovascular (dry) form.

Figure 6. Age related macular degeneration. Left: Pseudo-colour image. Right: Ultra-widefield FAF image showing central localised hypo-FAF, temporal granular hyper-FAF, and nasal nummular hypo-FAF patterns. FAF = fundus autofluorescence.

Patterns of macular FAF abnormalities, particularly those in the junctional zone surrounding areas of geographic atrophy, are of prognostic importance, in some cases identifying a subset of eyes at a higher risk for progression.10 FAF provides a tool for monitoring the evolution of geographic atrophy secondary to AMD and is useful for both clinical trials and clinical practice.

It remains to be determined if non-neovascular AMD eyes with abnormal peripheral FAF patterns are at a higher risk for converting to neovascular AMD. UWFI with FAF data is being collected in the Age-Related Eye Diseases Study 2 and will help to evaluate the prognostic significance of these peripheral retinal abnormalities.

Uveitis

Retinal vasculitis and other forms of posterior uveitis are often associated with peripheral retinal vascular changes. FFA is able to detect and highlight retinal vessel inflammation and leakage that can be difficult to detect on biomicroscopic inspection of the retina.

UWFI and UWFA can reveal signs of uveitis disease activity not detected on traditional fundus imaging or FFA. This has been shown to provide additional clinically important information that frequently alters management decisions in the treatment of retinal vasculitis, including conditions such as pan-uveitis, ocular sarcoidosis, intermediate uveitis and Behcet’s disease.23

Choroidal nevi and melanomas

Traditional fundus photography of peripheral pigmented choroidal lesions such as choroidal nevus or choroidal melanoma often yields suboptimal images, particularly for large or peripheral lesions, making it difficult to localise lesions and to take comparable serial photographs for monitoring. UWFI usually enables the entire lesion to be captured in a single image, allowing a greater appreciation of the overall lesion topography and location relative to other anatomical landmarks, such as the optic disc and retinal vessels (Figure 7). This is particularly helpful in monitoring lesions for potential growth over time.

Figure 7. Pseudo-colour image showing a halo nevus of the choroid.

When attempting to differentiate a benign pigmented choroidal nevus from a choroidal melanoma, it has been shown that comparison of the UWFI red and green laser image characteristics of the lesion can improve diagnostic accuracy, when combined with assessment of clinical risk factors for growth of a choroidal melanoma.24 Choroidal melanomas typically appear dark on red laser images and bright on the green laser images.

UWFI with FAF may help to identify choroidal tumours with orange pigment, which is indicative of lipofuscin, and is a recognised risk factor for growth of malignant melanomas.25

Inherited retinal and choroidal dystrophies

FAF imaging in patients with inherited retinal dystrophies often demonstrates abnormalities in the macula, which may assist in diagnosis and are visualised with conventional FAF cameras or UWFI based FAF systems. Parafoveal rings of increased FAF are a non-specific manifestation of retinal dysfunction that can occur in numerous retinal dystrophies including retinitis pigmentosa, Leber congenital amaurosis, cone dystrophy and X-linked retinoschisis (Figure 8).6 Choroidal dystrophies such as gyrate atrophy and choroideraemia typically lead to early FAF changes in the peripheral retina. These changes may also be identified in asymptomatic carriers, potentially aiding in their identification.26

Figure 8. Retinitis pigmentosa. Left: Pseudo-colour image. Right: Ultra-widefield autofluorescence image showing parafoveal ring of increased autofluorescence and peripheral areas of hypo autofluorescence.

Retinal tears and retinal detachment

UWFI can be useful to document peripheral retinal tears and retinal detachment for the purposes of patient education, monitoring and medicolegal documentation (Figure 9). Retinal tears located in the anterior retina, particularly in the superior and inferior retina, cannot always be visualised with UWFI using the Optos unit, thus it is cannot replace dilated binocular indirect ophthalmoscopy with scleral indentation to identify retinal tears in patients presenting with flashing lights or floaters.27

Figure 9. Pseudo-colour image showing an inferior bullous retinal detachment.

Intraocular gas injected during surgical repair of a retinal detachment can make post-operative viewing of the retina difficult due to the low refractive index of gas. UWFI can be useful in post-operative monitoring due to its ability to image the retina through a gas bubble (Figure 10).

Figure 10. Pseudo-colour image showing an eye following retinal detachment surgery with an intraocular gas bubble.

Other conditions

UWFI may detect peripheral pathology that is missed with conventional fundus photography using the 7SF ETDRS standard. UWFI has been reported to enable earlier detection of peripheral retinal pathology in conditions including sickle cell retinopathy and Coats disease.28-29 UWFI using the Optos unit has even been used to obtain retinal images in babies with retinopathy of prematurity.30

Limitations

Notable limitations of UWFI with the Optos unit include:

  1. UWFI cannot image the anterior retina or ora serrata, so anteriorly located pathology, including retinal tears and retinal dialyses may be missed, particularly if located in the superior or inferior retina. It is for this reason that optometrists should understand that UWFI cannot replace binocular indirect ophthalmoscopy combined with scleral indentation as the gold standard for the detection of peripheral retinal tears and anterior retinal pathology.
  2. There is a learning curve involved in image acquisition and image quality is operator dependent.
  3. Artefacts commonly arise from the eyelids, cataracts, vitreous opacities, intraocular lenses and lens capsule (Figure 11).
  4. Colour representation is different from traditional camera systems, which use white light illumination. This is due to the use of red and green lasers, without blue light, to illuminate the retina during image acquisition.
  5. Peripheral distortion of retinal images occurs due to the limitations of having to represent a three-dimensional image in two dimensions. Lesions located peripherally appear larger than posteriorly located lesions, making measurement of peripheral retinal lesion dimensions inaccurate.


Figure 11. Pseudo-colour image demonstrating image artefacts caused by the eyelid, eye lashes, floaters and reflections from an intraocular lens.

Conclusions

Multi-modal ultra-widefield imaging technology is playing an increasing role in the diagnosis, treatment, monitoring and understanding of retinal diseases that involve the peripheral retina.

Although ultra-widefield imaging cannot replace stereoscopic biomicroscopic clinical examination of the retina, its use to document findings in the peripheral retina can assist practitioners in patient education, diagnosis, monitoring and sharing of clinical information with colleagues and represents a significant advance in imaging technology.

Dr. Simon Chen is a retinal specialist and surgeon with expertise in intravitreal anti-VEGF therapy and vitreoretinal surgery. He is an investigator for numerous international clinical trials of novel treatments for retinal disease.

Dr. Chen trained at the teaching hospitals of the Universities of Oxford and Cambridge, UK and completed advanced surgical fellowships at the Oxford Eye Hospital and Lions Eye Institute. He practices at Vision Eye Institute in Bondi Junction, Drummoyne, Chatswood and Hurstville, NSW.

Note: Images used in this CPD module were cropped and adjusted to optimise brightness, contrast, exposure, and colour balance.

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References

1. Ultra-wide-field imaging for cytomegalovirus retinitis. Mudvari SS, Virasch VV, Singa RM, et al. Ophthalmic Surg Lasers Imaging. 2010 May-Jun;41(3):311-5.

2. Non-mydriatic panoramic fundus imaging using a non-contact scanning laser-based system. Friberg TR, Pandya A, Eller AW. Ophthalmic Surg Lasers Imaging. 2003 Nov-Dec;34(6):488-97.

3. Digital imaging in differential diagnosis of small choroidal melanoma. Saari JM, Kivelä T, Summanen P, et al. Graefes Arch Clin Exp Ophthalmol. 2006 Dec;244(12):1581-90.

4. Panoramic autofluorescence: highlighting retinal pathology. Slotnick S, Sherman J. Optom Vis Sci. 2012 May;89(5):E575-84.

5. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Delori FC, Dorey CK, Staurenghi G, et al. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):718-29.

6. Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update. Robson AG, Michaelides M, Saihan Z, et al. Doc Ophthalmol. 2008 Mar;116(2):79-89.

7. Fundus autofluorescence and central serous chorioretinopathy. Spaide RF, Klancnik JM Jr. Ophthalmology. 2005 May;112(5):825-33.

8. Fundus autofluorescence in type 2 idiopathic macular telangiectasia: correlation with optical coherence tomography and microperimetry. Wong WT, Forooghian F, Majumdar Z, et al. Am J Ophthalmol. 2009 Oct;148(4):573-83.

9. Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine. Kellner U, Renner AB, Tillack H. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3531-8.

10. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al; FAM-Study Group. Am J Ophthalmol. 2007 Mar;143(3):463-72.

11. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Wessel MM, Nair N, Aaker GD, et al. Br J Ophthalmol. 2012 May;96(5):694-8.

12. Diabetic retinopathy study. Report Number 6. Design, methods, and baseline results. Report Number 7. A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci. 1981 Jul;21(1 Pt 2):1-226.

13. Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7-field 35-mm photography and retinal specialist examination for evaluation of diabetic retinopathy. Silva PS, Cavallerano JD, Sun JK, et al. Am J Ophthalmol. 2

' The Optos imaging device is one of the most widely used UWFI devices '