|SYMPOSIUM - DIABETIC RETINOPATHY UPDATE
|Year : 2014 | Volume
| Issue : 1 | Page : 3-18
Screening for sight-threatening diabetic retinopathy: An update
Peter Henry Scanlon1, Mohamed Dirani2, Peter van Wijngaarden2
1 Department of Ophthalmology, Gloucestershire Diabetic Retinopathy Research Group, Office Above Oakley Ward, Cheltenham General Hospital, Cheltenham, GL53 7AN; The NHS Diabetic Eye Screening Programme, Victoria Warehouse, The Docks, Gloucester, GL1 2EL, England, United Kingdom
2 Department of Ophthalmology, Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia
|Date of Web Publication||3-Mar-2015|
Prof. Peter Henry Scanlon
Gloucestershire Diabetic Retinopathy Research Group, Office above Oakley Ward, Cheltenham General Hospital, Sandford Road, Cheltenham, GL53 7AN, England
Source of Support: The research work that is undertaken
on screening intervals by PHS, including an on.going
literature review in this field, has been supported by a
grant from the Health Technology Assessment Program, Conflict of Interest: None
Aims: To review the literature on Screening for Diabetic Retinopathy. Materials and Methods: A comprehensive review of the English language literature, published from March 1980 to June 2014 using key words in Zetoc. Results: Several methods were found to achieve adequate sensitivities and specificities for diabetic retinopathy screening. Studies were compared with respect to (a) Classifications used to grade diabetic retinopathy (b) The evidence for population-based screening for diabetic retinopathy (c) Alternatives to digital photography for screening (d) Reference standards used to study the effectiveness of screening methods (e) The evidence for mydriatic versus non-mydriatic digital photography, or a combination of the two (f) The number of photographic fields captured (g) Measurement of distance visual acuity (h) Cost-effectiveness of screening for diabetic retinopathy (i) Future developments in screening for diabetic retinopathy Conclusion: Based on an assessment of available studies, the most effective DR screening strategy is the use of mydriatic or staged mydriasis with digital retinal photography. Variables between different screening strategies include whether Visual Acuity is measured and the number of fields captured.
Keywords: Diabetic retinopathy, progression, risk factors, screening
|How to cite this article:|
Scanlon PH, Dirani M, van Wijngaarden P. Screening for sight-threatening diabetic retinopathy: An update. Egypt Retina J 2014;2:3-18
| Introduction|| |
The review of the literature relating to screening for diabetic retinopathy (DR) has been on-going by the first author (PHS) since March 2000. The methodology involves a search technique for articles relating to screening or management of DR utilizing Zetoc, a co-operative venture between the British Library, Manchester Information and Associated Services and the Joint Information Systems Committee of the UK Higher Education Funding Council (http://zetoc.mimas.ac.uk), which is available to Universities. Zetoc provides access to over 29,000 journals and more than 52 million article citations and conference papers through the British Library's electronic table of contents. The database covers 1993 to the present day and is updated daily.
The following subject title keywords were used:
"Retinopathy," "digital" and "imaging" and "eye." "Digital" and "imaging" and "ophthalm," "digital" and "imaging" and "diabet," "laser" and "eye," "laser" and "ophthalm," "laser" and "diabet," "visual" and "acuity," "visual" and "impairment," "blindness" and "diabet," "diabetic" and "screening," "uptake" and "screening" and "diabet" in title, "attendance" and "screening" and "diabet," and/or "vitrectomy" and "diabet" in title. These keywords were taken from other reviews in this area and refined to be selective to the field of interest of the first author (screening or management of DR). In addition, the contents page lists of the following journals, considered as those most likely to publish articles relevant to this topic, were reviewed each month:
Acta Ophthalmologica Scandinavia, American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology, British Medical Journal, Clinical and Experimental Ophthalmology, Current Eye Research, Diabetes, Diabetes Care, Diabetes Metabolism Research and Reviews, Diabetes Research and Clinical Practice, Diabetes Technology and Therapeutics, Diabetic Medicine, Diabetologia, European Journal of Ophthalmology, Eye, Graefes Archive for Clinical and Experimental Ophthalmology, Investigative Ophthalmology and Visual Science, Journal of Diabetes and its complications, Journal of Medical Screening, Journal of the Eye, Lancet, Ophthalmic Surgery and Lasers, Ophthalmologica, Ophthalmology, Pediatric Diabetes, Retina, Survey of Ophthalmology.
Articles of interest identified with this search strategy were sourced from the local NHS Trust library or on-line from the electronic journal resource (Athens  ) accessible in the Trust library.
The following matters will be addressed in this update:
- Classifications used to grade DR
- The evidence for population-based screening for DR
- Alternatives to digital photography for screening
- Reference standards used to study the effectiveness of screening methods
- The evidence for mydriatic versus nonmydriatic digital photography, or a combination of the two
- The number of photographic fields captured
- Measurement of distance visual acuity (VA)
- Cost-effectiveness of screening for DR
- Future developments in screening for DR.
| Classifications Used to Grade Diabetic Retinopathy|| |
The Airlie House classification , was the basis for grading in the Diabetic Retinopathy Study (DRS) and the Early Treatment DRS (ETDRS). The ETDRS final Retinopathy Severity Scale  provided the first detailed classification system for retinopathy severity-based on a natural history study of untreated eyes. Seven-field stereo-photographs of 30° fields were examined to arrive at a severity grading. Since the development of the severity scale, the risk of progression of DR has generally reduced because of better control of diabetes and hypertension. , Recent data from Gloucestershire  has shown that progression from mild nonproliferative DR (NPDR) in both eyes to moderate (or more severe retinopathy) in one or both eyes occurs in approximately 18% of patients over a 4 years period and progression from mild NPDR in both eyes to referable DR (which includes two-dimensional markers of screen positive maculopathy) occurs in approximately 1 in three patients over the 4 years period. If there was no DR in either eye at baseline the rate of progression to either moderate (or more severe retinopathy) or referable retinopathy in one or both eyes is <5% over 4 years. Since the ETDRS study, different grading scales have been developed to record the progression of DR using a smaller number of fields with or without stereo-photography. ,, According to the International Classification,  developed by the American Academy of Ophthalmology in 2002, any level of retinopathy more severe than mild retinopathy (defined as the presence of microaneurysms only) warrants examination by an ophthalmologist.
The screening programs that were introduced in England,  Scotland,  Wales and Northern Ireland in 2002-2003 defined the presence of at least moderate NPDR as the threshold for referral of patients to ophthalmologists. It was considered that the presence of microaneurysms alone did not warrant assessment by an ophthalmologist given the low probability of progression from mild to sight-threatening retinopathy in the annual screening interval. The recommended referral levels for the English Screening Program  and the International Classification are shown in [Table 1]. In any population-based screening program a level of risk has to be accepted and the International Classification refers at a level of risk of <6.2% developing proliferative DR over the following 12 months. The English Classification  refers at a level of risk  of 11.3% of developing proliferative DR over the following 12 months.
Two-dimensional photographic markers for clinically significant macular edema were not well-defined in the ETDRS study, which relied on three-dimensional markers of stereo-photography or stereo-examination using contact lens biomicroscopy (CLBM).  The only publication using ETDRS data, that reports on two-dimensional markers for clinically significant macular edema, is that by Bresnick et al.  who recommended the use of hard exudate within one disc diameter of the center of the fovea as the most useful marker. The recommended referral criteria for macular edema, based on two-dimensional photographic markers, used by the English Screening Program are compared with the Early Treatment DR Classification and the International Classification in [Table 2]. The latter two rely on the presence of thickening (a three-dimensional attribute), whereas the English Screening Classification relies on two-dimensional markers, although some regions in England are introducing optical coherence tomography (OCT) assessments for those with screen positive two-dimensional markers for maculopathy. A recent study (2011)  demonstrated that when patients were referred using two-dimensional markers for diabetic maculopathy, as per the English Screening Program guidelines, there was a 42.1% chance of having no edema in the macular area on spectral domain OCT (SD-OCT). Accordingly a reliance on two-dimensional markers may result in over-referral for macular edema.
| The Evidence for Population-Based Screening for Diabetic Retinopathy|| |
Early evidence of the benefits of screening for DR have come from Iceland where Kristinsson et al.  reported in 1995 that the low prevalence of blindness in people with Type 1 and Type 2 diabetes was attributed to the screening program established in 1980. A further report  showed that the prevalence of legal blindness (WHO definition VA <6/60 in the better seeing eye) from DR in the Icelandic diabetic population dropped from 2.4% in 1980 to 0.5% in 2005 (approximately one-fifth of baseline prevalence). Similar reductions in prevalence of blindness from DR have followed the introduction of screening programs in Sweden,  Poland,  and Newcastle (UK).  The Certification Office for Sight Impairment in England and Wales has recently reported  that, for the first time in at least five decades, DR/maculopathy is no longer the leading cause of certifiable blindness among working-age adults in England and Wales. This change has in the latest figures in the year 2009-2010 compared to the previously analyzed figures in 1999-2000 been attributed to the introduction of nationwide DR screening programs in England and Wales in 2003 as well as improvements in glycemic control that were introduced over the 10 years following publication of the results of the UK Prospective Diabetes Study  in 1998 and the Diabetes Control and Complications Trial  in 1993.
| Alternatives to Digital Photography for Screening|| |
Because of the relatively low cost of retinal fundus imaging systems and the permanent record of the retinal appearance that is required for the quality assurance of grading, there is currently no realistic alternative to retinal camera-based digital imaging systems in population-based screening for DR.
Direct ophthalmoscopy is useful for ad hoc case-detection but the results are too variable between different professional groups and even in the hands of a specialist registrar in ophthalmology  the sensitivity achieved for the detection of sight-threatening retinopathy was only 65% (95% confidence interval [CI]: 51-79%).
The best designed study of slit-lamp biomicroscopy by optometrists was that of Olson et al.  and Sharp et al.,  in which all those patients seen by an optometrist were also examined by a retinal specialist and subjected to both digital and 35 mm film photography. The slit-lamp examination by optometrists, for the detection of sight-threatening retinopathy (referable), achieved a sensitivity of 73% (95% CI: 52-88%) and a specificity of 90% (95% CI: 87-93%) against the reference standard of slit-lamp examination by retinal specialists. No technical failure was reported. Using two-field imaging, manual grading of red-free digital images achieved a sensitivity of 93% (95% CI: 82-98%) and a specificity of 87% (95% CI: 84-90%). 4.4% of patients had poor quality digital photographs. While direct ophthalmoscopy or slit-lamp biomicroscopy remain the methods of choice for some, the lack of a permanent record of the retinal appearance makes it very difficult for quality assurance purposes.
Wide-field scanning laser ophthalmoscopes (WSLO) have been proposed for DR screening, but have not as yet demonstrated the same level of resolution as digital cameras. Wilson et al.  have reported results of a comparative trial of scanning laser ophthalmoscopy against digital photography with a reference standard of a medical retina specialist and a trainee ophthalmologist. The scanning laser ophthalmoscope was reported as having a sensitivity of 83.6% (95% CI: 75.1-92.1%), specificity of 89.5% (95% CI: 85.8-93.2%), and ungradable image quality of 10.8% (95% CI: 9.2-12.4%) with a kappa of 0.67 (95% CI: 0.58-0.76). However, if the ungradable images are counted as test positive, as was reported in the studies by Scanlon et al.  and Harding et al.,  this alters the results to produce a sensitivity of 84.6% (95% CI: 76.6-92.6%), specificity of 78.8% (95% CI: 74.2-83.4%) and a kappa of 0.51 (0.42-0.60) for agreement. The study also reported that images were of lower resolution than conventional digital photographs, limiting the detection of microaneurysms (identifying 79.2% vs. 95.9% P < 0.001). These images also had a longer average grading time than digital photographs (106 s vs. 94 or 64 s). Single-field photography was the quickest to grade (average 64 s/eye), followed by second-field photography (average 94 s) and WSLO (average 106 s), with P < 0.001 between all three groups.
| Reference Standards Used to Study the Effectiveness of Screening Methods|| |
There are two accepted reference standards against which the sensitivity and specificity of screening methods are compared.
- Seven-field stereo-photography is widely held as the best reference standard. One disadvantage of seven-field stereo-photography is that studies using this standard often only report results in those patients with assessable seven-field images. This can be problematic as the unassessable image rate is typically high even when highly trained photographers are used-in one report from the Wisconsin Epidemiological Study of DR  10% of images were unassessable. If seven-field stereo-photography is unassessable in 10% of patients it is possible that a screening method to which this standard is compared may also be unassessable in these same patients.
- Slit-lamp biomicroscopy by an ophthalmologist is another commonly used reference standard. Examinations by retinal specialists using CLBM compared favorably with seven-field stereo-photography for the detection of macular edema in the ETDRS study reported by Kinyoun et al.  Some studies reported that the detection of any DR by ophthalmologists using slit-lamp biomicroscopy with 90D, 78D or 60D lenses have shown have shown high levels of agreement with photography (one- or two-field) with some under-reporting. ,, Kalm et al. found the sensitivity of the photographic method (two 45° nonstereo 35 mm mydriatic fundus photography) for the right and left eye separately was 87/97% (right/left eye) for background retinopathy and 81/80% for maculopathy versus 61% and 63%, respectively, for the ophthalmologist's slit-lamp, when compared with the detection of background retinopathy by both methods combined as the reference standard.  In their study Lee et al. they found that of the 730 eyes that were gradable for retinopathy severity by both methods (one 45° field 35 mm nonmydriatic fundus photography through dilated pupils versus slit-lamp biomicroscopy with a 90D lens by one of three ophthalmologists), overall agreement between the two was 86.3% (κ =0.74).  Schachat et al. found that, in a population of 1168 (21% with a history of diabetes), the frequency of DR was 7.7% (90/1168) by clinical examination, 8.7% (102/1168) by photograph grading (two 30° mydriatic stereoscopic photographs of the disc and macula), and 6.7% (78/1168) by both methods. 
In another study,  a group of patients was assessed by clinical examination (mydriatic direct and binocular indirect ophthalmoscopy in one center and the replacement of mydriatic direct ophthalmoscopy with slit-lamp biomicroscopy using a 90D lens in a second center) against a reference standard of seven-field stereo-photography. Four levels of retinopathy severity were used: None; mild nonproliferative; moderate to severe nonproliferative; and proliferative. The examination results of 10 staff ophthalmologists (two of whom were retinal specialists) compared poorly with the photographic reference standard with a sensitivity of 0.33, a specificity of 0.99, and positive and negative likelihood ratios of 72 and 0.67. Of a total of seven cases of proliferative retinopathy identified by seven-field photography, only three cases were detected by clinical examination. However, the number of subjects that had an examination that included slit-lamp biomicroscopy was not stated, nor whether this affected the examination results. In the study by Lin et al.,  nine ophthalmologists (all board-certified), using slit-lamp biomicroscopy, performed poorly in correctly grading retinopathy severity as above or below the threshold for referral (ETDRS level >35). Agreement was poor (κ =0.40, P = 0.0001) between mydriatic ophthalmoscopy and the seven-field standard 35 mm color photographs. Sensitivity of ophthalmoscopy compared with color photography was 34%, with a specificity of 100%.
Scanlon et al.  in their study have reported that, in comparison with seven-field stereo-photography, the ophthalmologist's examination gave a sensitivity of 87.4% (CI: 83.5-91.5%), a specificity of 94.9% (91.5-98.3%) and a kappa statistic of 0.80 for agreement. In summary, these studies demonstrate significant variation in the sensitivity and specificity of clinical examination relative to seven-field stereo-photography. It is apparent that the utility of clinical examination as a reference standard is determined by a range of factors including the method of examination used and the clinical proficiency of the examiner.
| The Evidence for Mydriatic and NonMydriatic Digital Photography for Screening|| |
Studies of nonmydriatic digital photography
A strong correlation has been reported  between older age and poor quality image rate in nonmydriatic digital photography for the detection of DR. Key reasons for this are higher rates of media opacity and smaller pupil sizes in older than in younger people. This fact becomes very relevant when interpreting studies that report on the use of nonmydriatic photography in the detection of DR.
- Studies of nonmydriatic digital photographic screening for DR in under 200 patients using one of the above two recognized reference standards.
Studies by Massin et al.,  Cavallerano et al.,  Aptel et al.  and Vujosevic et al.  are summarized in [Table 3]. These studies share several features in common: They are based on small numbers of patients, with low mean ages, and they do not report CIs. Accordingly the findings of these studies are not applicable to population-based screening programs.
|Table 3: Sensitivity, specificity and poor image quality of nonmydriatic photography in detection of sight threatening or referable DR|
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- Studies of nonmydriatic digital photographic screening for DR in over 200 patients.
Relevant studies are summarized in [Table 4].
|Table 4: Sensitivity, specificity and poor image quality of mydriatic photography in detection of sight threatening or referable DR (only including studies that have more than 200 patients)|
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Relevant studies are summarized in [Table 3].
There has been longstanding disagreement amongst clinicians about ungradable image rates for nonmydriatic photography. This debate was recently informed by two studies conducted in the UK by Scanlon et al.,  reported an ungradable image rate for nonmydriatic photography of 19.7% (95% CI: 18.4-21.0%), and Murgatroyd et al.,  that reported an ungradable image rate for nonmydriatic photography of 26%. The mean age of the patients in the Scanlon et al.  study was 65 years, and in the Murgatroyd et al.  study the median age of the patients was 63.0 years (range: 17-88 years, interquartile range: 51.8-70.3 years). The Health Technology Board for Scotland used data from the Scanlon et al.  study to model their nation-wide three stage screening process. On this basis it was decided that only those patients with poor quality one-field nonmydriatic images should undergo mydriatic photography.  Experience with this screening strategy in Scotland has demonstrated that 34% of patients require pupil dilation, and the need for dilation is greater in older age groups. , This influence of age was also shown by Murray et al.  in the Aboriginal population in Australia: The percentage of episodes rated adequate or excellent in a screening program that was nonmydriatic for the first 3 years and then mydriatic for the subsequent 2 years, declined with age from 97% (1126/1164), to 83% (659/792) and 75% (266/364) for patients younger than 55 years, 55-65 years and patients older than 65 years, respectively.
Studies of mydriatic digital photography
Studies of mydriatic digital photography against reference standards of seven-field stereo-photography, and ophthalmologists using slit-lamp biomicroscopy have shown consistently good results. ,,, The study by Olson et al.  demonstrated that, in 586 patients, for the detection of sight-threatening retinopathy, manual grading of two-field red-free digital images achieved a sensitivity of 93% (95% CI: 82-98%) and a specificity of 87% (95% CI: 84-90%). The reference standard was slit-lamp biomicrocopy by retinal specialists. Digital imaging had an ungradable image rate of 4.4% of patients. The study by Scanlon et al.  demonstrated that for mydriatic digital photography, in 1549 patients, for the detection of sight-threatening retinopathy, the sensitivity was 87.8%, the specificity was 86.1% and the ungradable image rate was 3.7%. The reference standard was slit-lamp biomicrocopy by an experienced ophthalmologist whose examination technique was tested against seven-field stereo-photography in a separate study.  In the latter study,  in comparison with seven-field stereo-photography, two-field mydriatic digital photography had a sensitivity of 80.2% (75.2-85.2%), specificity of 96.2% (93.2-99.2%) with a kappa statistic of 0.73 for agreement.
| The Number of Photographic Fields Captured|| |
In 1989, Moss et al.  demonstrated that for eight retinopathy levels, the rate of agreement with seven stereoscopic fields ranges from 80% for two 30° stereo fields to 91% for four 30° stereo fields. The sensitivity of two to four photographic fields compared to seven-fields for detecting any DR varies from 87% to 95%. For the detection of PDR, sensitivity varies from 74% to 90%, and for DRS high-risk characteristics, it varies from 81% to 91%, respectively. 
As discussed previously, decisions relating to the methods used in population-based screening programs are informed by acceptable levels of risk of failing to detect sight-threatening DR (STDR), balanced against the convenience and cost-effectiveness of the screening process.
Population-based screening programs that utilize nonmydriatic photography commonly capture a single 45° field centered on the fovea of each eye. This approach is time efficient and well-accepted by patients.  For many mydriatic schemes, two 45° fields are often taken - one centered on the fovea and one on the optic disc. The advantage of this approach is that a second view of the macular area is obtained, which helps to differentiate photographic artefacts from retinopathy lesions. There are some proponents , of a third-field being taken of the temporal retina but this is unusual to perform in the larger population-based screening programs because of cost/time versus lack of added diagnostic utility.
| Measurement of Distance Visual Acuity|| |
Visual acuity is widely supported as an adjunct to screening for diabetic maculopathy, but in isolation it is not sufficiently sensitive to be a screening tool. , A study  of 197 patients with diabetes found that 35% had a Snellen VA of <6/12 in one or both eyes, and only 22% of those with reduced vision had diabetic maculopathy.
In a study of VA in 1549 randomly selected people with diabetes mellitus from a county-wide digital photographic screening program in Gloucestershire, Scanlon et al.  found that the majority of visual loss in a population with diabetes is due to causes other than DR. The sensitivity, specificity and positive and negative predictive values of using subnormal vision alone to screen for STDR in an individual eye was 33.4%, 85.9%, 18.6% and 93.0%, respectively. Important contributory causes of moderate visual loss (logMAR 0.50-0.98, Snellen 6/18 or worse but better than 6/60) and of acuity blindness (logMar >1.0, Snellen 6/60 or worse) in an individual eye were lenticular opacity and capsular opacification (49%), macular degeneration (29%), diabetic maculopathy (15%), amblyopia (10%) and other media causes including corneal opacity (13%). Best corrected VA alone is, therefore, not a reliable criterion in predicting STDR. Although widely used in screening programs, there is currently no study that supports the added utility of VA as an adjunctive measure to screening. There is often a perceived need to measure VA in order to ascertain levels of subnormal vision, sight impairment and serious sight impairment in a population.
| Cost-Effectiveness of Screening for Diabetic Retinopathy|| |
Bachmann and Nelson  summarized the health economic literature relating to retinopathy screening prior to 1996. They concluded that screening by retinal photography or optician ophthalmoscopy (chiefly direct ophthalmoscopy) may be as cost-effective as examination by a general practitioner direct ophthalmoscopy or ophthalmologist direct ophthalmoscopy. In 2000, James et al.  reported results for an organized screening program in the UK using three 45° field 35 mm retinal photography and demonstrated this to be more cost-effective than the previous system of opportunistic screening (£209 per true positive compared with £289-1996/7 prices). In 2005, Scanlon  reported that, for two 45° field digital photography and one 45° field nonmydriatic digital photography, the best estimate of cost per true positive detected was £538 (range: £493-£595) for retinal photography with dilation, £622 (£570-£682) for retinal photography without dilation and £435 (£317-£769) for opportunistic screening. The organized screening program had higher costs and higher effectiveness. The additional cost of detecting additional cases was £959 based on comparing photography with dilation and opportunistic screening. Two US studies , modeling the costs of screening and the increase in treatment associated with case-detection against the benefit of avoiding blindness, demonstrated a clear health economic benefit of screening. A review article by Stefαnsson et al.  concluded that from a public health standpoint screening for diabetic eye disease is one of the most cost-effective health procedures available and Zoega et al. reported  that there was a significant relationship between screening compliance and visual outcome in diabetes patients in the Icelandic screening program. Meadsand Hyde  reported that much of the uncertainty in any sensitivity analysis of the cost of blindness due to DR in older people is associated with the cost of residential care. The excess admission to care homes caused by poor vision due to DR is impossible to quantify at the present time. In 2010, Jones and Edwards  reported a systematic review of the economic evidence relating to DR screening. The article concluded that systematic screening for DR is cost-effective in terms of sight years preserved compared with no screening. There is, however, controversy in relation to the economic evidence on optimal screening intervals. 
| Future Developments in Screening for Diabetic Retinopathy|| |
There are three main aspects of retinopathy screening that are likely to develop in coming years:
- The introduction of a second level of screening using a combined color camera and SD-OCT for those with positive two-dimensional markers for diabetic maculopathy.  This approach is unlikely to be cost-effective as a first level screening tool in population-based screening programs in the near future in view of the significant associated equipment costs
- The optimum screening interval for low risk patients is likely to be refined. It is almost inevitable that with the current epidemic of diabetes that we will need to look closer at the optimum screening intervals for people with diabetes with a view to extending the screening interval for those at very low risk of sight-threatening retinopathy. There are three approaches that could be used determine the most appropriate screening interval for a given patient:
- Based on a previous screening result ,,
- Based on individualized risk factors 
- Based on two consecutive screening results 
- Automated analysis of retinal photographs - after 50 years of development automating the detection of retinopathy is becoming a clinical reality. It has recently been demonstrated , that computer algorithms can detect microaneurysms and some other features of DR to a high degree of accuracy. The most cost-effective method in which automated analysis may assist in retinopathy screening remains to be determined. Apart from the scientific, ethical, legal and political issues,  one of the real challenges to widespread application of these algorithms in population-based screening programs is that the current screening fundus cameras are served by digital backs from the general photographic market, which come with their own commercially sensitive compression algorithms. Algorithms from different manufacturers vary significantly and are subject to regular change. RAW images (the original images produced without any compression) from modern digital cameras are now too large to be realistically used within population-based screening programs.
| Acknowledgments|| |
The authors would like to thank the administration support at Gloucestershire Diabetic Retinopathy Research Group who makes the on-going literature review possible. The guarantor of this publication is Peter. H. Scanlon.
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[Table 1], [Table 2], [Table 3], [Table 4]
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