- •Diabetic Retinopathy
- •Preface
- •Acknowledgments
- •Contents
- •Contributors
- •Pathophysiology of Diabetic Retinopathy
- •1.1 Retinal Anatomy
- •1.1.1 History
- •1.1.2 Anatomy
- •1.1.3 Microanatomy of the Retina Neurons
- •1.1.4 Intercellular Spaces
- •1.1.5 Internal Limiting Membrane
- •1.1.6 Circulation
- •1.1.7 Arteries
- •1.1.8 Veins
- •1.1.9 Capillaries
- •1.2 Hemodynamics, Macular Edema, and Starling’s Law
- •1.3 Biochemical Basis for Diabetic Retinopathy
- •1.3.1 Increased Polyol Pathway Flux
- •1.3.2 Advanced Glycation End Products (AGEs)
- •1.3.3 Activation of Protein Kinase C (PKC)
- •1.3.4 Increased Hexosamine Pathway Flux
- •1.4 Macular Edema
- •1.5 Development of Proliferative Diabetic Retinopathy
- •1.6 Summary of Key Points
- •1.7 Future Directions
- •References
- •Genetics and Diabetic Retinopathy
- •2.1 Background for Clinical Genetics
- •2.2 The Role of Polymorphisms in Genetic Studies
- •2.3 Types of Genetic Study Design
- •2.4 Studies of the Genetics of Diabetic Retinopathy
- •2.4.1 Clinical Studies
- •2.4.2 Molecular Genetic Studies
- •2.4.3 EPO Promoter
- •2.4.4 Aldose Reductase Gene
- •2.4.5 VEGF Gene
- •2.5 Genes in or Near the HLA Locus
- •2.6 Receptor for Advanced Glycation End Products (RAGE) Genes
- •2.7 Endothelial NOS2 and NOS3 Genes
- •2.9 Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 1 Gene (SLC2A1)
- •2.11 Potential Value of Identifying Genetic Associations with Diabetic Retinopathy
- •2.12 Summary of Key Points
- •2.13 Future Directions
- •Glossary
- •References
- •Epidemiology of Diabetic Retinopathy
- •3.1 Introduction and Definitions
- •3.2 Epidemiology of Diabetes Mellitus
- •3.3 Factors Influencing the Prevalence of Diabetes Mellitus
- •3.4 Epidemiology of Diabetic Retinopathy
- •3.5 Diabetes and Visual Loss
- •3.6 Prevalence and Incidence of Diabetic Retinopathy
- •3.7 By Diabetes Type
- •3.8 By Insulin Use
- •3.10 By Duration of Diabetes Mellitus
- •3.11 By Ethnicity
- •3.12 Gender
- •3.13 Age at Onset of Diabetes
- •3.14 Socioeconomic Status and Educational Level
- •3.15 Family History of Diabetes
- •3.16 Changes Over Time
- •3.17 Epidemiology of Diabetic Macular Edema (DME)
- •3.18 Epidemiology of Proliferative Diabetic Retinopathy (PDR)
- •3.19 Socioeconomic Impact of Diabetes
- •3.20 Socioeconomic Impact of Diabetic Retinopathy
- •3.21 Summary of Key Points
- •3.22 Future Directions
- •References
- •Systemic and Ocular Factors Influencing Diabetic Retinopathy
- •4.1 Introduction
- •4.2 Systemic Factors
- •4.2.1 Glycemic Control
- •4.2.1.1 Type 1 Diabetes Mellitus
- •4.2.1.2 Type 2 Diabetes Mellitus
- •4.2.1.3 Rapidity of Improvement in Glycemic Control
- •4.2.2 Glycemic Variability
- •4.2.3 Insulin Use in Type 2 Diabetes
- •4.2.5 Blood Pressure
- •4.2.6 Serum Lipids
- •4.2.7 Anemia
- •4.2.8 Nephropathy
- •4.2.9 Pregnancy
- •4.2.10 Other Systemic Factors
- •4.2.11 Influence on Visual Loss
- •4.3 Effects of Systemic Drugs
- •4.3.1 Diuretics
- •4.3.3 Aldose Reductase Inhibitors
- •4.3.4 Drugs That Target Platelets
- •4.3.5 Statins
- •4.3.6 Protein Kinase C Inhibitors
- •4.3.7 Thiazolidinediones (Glitazones)
- •4.3.8 Miscellaneous Drugs
- •4.4 Ocular Factors Influencing Diabetic Retinopathy
- •4.6 Economic Consequences
- •4.7 Summary of Key Points
- •4.8 Future Directions
- •References
- •Defining Diabetic Retinopathy Severity
- •5.1 Summary of Key Points
- •5.2 Future Directions
- •5.3 Practice Exercises
- •References
- •6.1 Optical Coherence Tomography (OCT)
- •6.2 Heidelberg Retinal Tomograph (HRT)
- •6.3 Retinal Thickness Analyzer (RTA)
- •6.4 Microperimetry
- •6.5 Color Fundus Photography
- •6.6 Fluorescein Angiography
- •6.7 Ultrasonography
- •6.8 Multifocal ERG
- •6.9 Miscellaneous Modalities
- •6.10 Summary of Key Points
- •6.11 Future Directions
- •6.12 Practice Exercises
- •References
- •Diabetic Macular Edema
- •7.1 Epidemiology and Risk Factors
- •7.2 Pathophysiology and Pathoanatomy
- •7.2.1 Anatomy
- •7.3 Physiology
- •7.4 Clinical Definitions
- •7.5 Focal and Diffuse Diabetic Macular Edema
- •7.6 Subclinical Diabetic Macular Edema
- •7.7 Refractory Diabetic Macular Edema
- •7.8 Regressed Diabetic Macular Edema
- •7.9 Recurrent Diabetic Macular Edema
- •7.10 Methods of Detection of Diabetic Macular Edema
- •7.11 Case Report 1
- •7.12 Case Report 2
- •7.13 Other Ancillary Studies in Diabetic Macular Edema
- •7.14 Natural History
- •7.15 Treatments
- •7.15.1 Metabolic Control and Effects of Drugs
- •7.16 Focal/Grid Laser Photocoagulation
- •7.16.1 ETDRS Treatment of CSME
- •7.17 Evolution in Focal/Grid Laser Treatment Since the ETDRS
- •7.18 Macular Thickness Outcomes After Focal/Grid Photocoagulation
- •7.19 Resolution of Lipid Exudates After Focal/Grid Laser Photocoagulation
- •7.20 Inconsistency in Defining Refractory Diabetic Macular Edema
- •7.21 Alternative Forms of Laser Treatment for Diabetic Macular Edema
- •7.22 Peribulbar Triamcinolone Injection
- •7.23 Intravitreal Triamcinolone Injection
- •7.24 Intravitreal Dexamethasone Delivery System
- •7.27 Combined Intravitreal and Peribulbar Triamcinolone and Focal Laser Therapy
- •7.28 Vitrectomy
- •7.29 Supplemental Oxygen and Hyperbaric Oxygenation
- •7.30 Resection of Subfoveal Hard Exudates
- •7.31 Subclinical Diabetic Macular Edema
- •7.32 Cases with Simultaneous Indications for Focal and Scatter Laser Photocoagulation
- •7.34 Factors Influencing Treatment of Diabetic Macular Edema
- •7.35 Sequence of Therapy
- •7.36 Interaction of Cataract Surgery and Diabetic Macular Edema
- •7.37 Summary of Key Points
- •7.38 Future Directions
- •References
- •Diabetic Macular Ischemia
- •8.1 Introduction
- •8.2 Pathogenesis, Anatomy, and Physiology
- •8.3 Natural History
- •8.4 Clinical Evaluation
- •8.5 Clinical Significance of Diabetic Macular Ischemia
- •8.6 Controversies and Conundrums
- •8.7 Summary of Key Points
- •8.8 Future Directions
- •References
- •Treatment of Proliferative Diabetic Retinopathy
- •9.1 Introduction
- •9.2 Laser Photocoagulation
- •9.2.1 Indications
- •9.2.2 PRP Technique
- •9.2.3 Complications
- •9.2.4 Outcome
- •9.3 Intraocular Pharmacological Therapy
- •9.4 Vitreoretinal Surgery
- •9.4.1 Indications
- •9.4.2 Preoperative Management
- •9.4.3 Instrumentation
- •9.4.4 Techniques
- •9.4.5 Postoperative Management
- •9.4.6 Complications
- •9.4.7 General Outcome
- •9.5 Follow-Up Considerations in PDR
- •9.6.1 Cataract and PDR
- •9.6.2 Dense Vitreous Hemorrhage and Untreated PDR
- •9.6.3 Untreated PDR with Diabetic Macular Edema
- •9.6.4 PDR with Severe Fibrovascular Proliferation/Traction Retinal Detachment
- •9.6.5 PDR with Neovascular Glaucoma
- •9.6.6 Conditions Altering the Clinical Course of PDR
- •9.7 Summary of Key Points
- •9.8 Future Directions
- •References
- •Cataract Surgery and Diabetic Retinopathy
- •10.1 Scope of the Problem of Diabetic Retinopathy Concomitant with Surgical Cataract
- •10.2 Visual Outcomes After Cataract Surgery in Patients with Diabetic Retinopathy
- •10.3 Postoperative Course and Special Considerations After Cataract Surgery in Patients with Diabetic Retinopathy
- •10.4 The Influence of Cataract Surgery on Diabetic Retinopathy
- •10.5 The Role of Ancillary Testing in Managing Cataract Surgery in Eyes with Diabetic Retinopathy
- •10.6 Candidate Risk and Protective Factors for Diabetic Macular Edema Induction or Exacerbation Following Cataract Surgery and Suggested Management Actions
- •10.7 The Problem of Adherence to Preferred Practice Guidelines
- •10.8 Management of the Diabetic Eye Without Macular Edema About to Undergo Cataract Surgery
- •10.9 Treatment of Diabetic Macular Edema Detected Before Cataract Surgery When the Macular View Is Clear
- •10.10 Management When Cataract Sufficient to Obscure the Macular View and DME Coexist or When Refractory DME and Cataract Coexist
- •10.11 Patients with Simultaneous Indications for Panretinal Photocoagulation and Cataract Surgery
- •10.12 Management of Cataract in Patients with Diabetic Retinopathy Undergoing Vitrectomy
- •10.13 Influence of Vitrectomy Surgery on Cataract Formation
- •10.15 Postoperative Endophthalmitis in Patients with Diabetic Retinopathy
- •10.16 Summary of Key Points
- •10.17 Future Directions
- •References
- •The Relationship of Diabetic Retinopathy and Glaucoma
- •11.1 Interaction of Diabetes and Glaucoma
- •11.2 Iris and Angle Neovascularization Pathoanatomy and Pathophysiology
- •11.3 Epidemiology
- •11.4 Clinical Detection
- •11.5 Classification
- •11.6 Risk Factors for Iris Neovascularization
- •11.7 Entry Site Neovascularization After Pars Plana Vitrectomy
- •11.8 Anterior Hyaloidal Fibrovascular Proliferation
- •11.9 Treatments for Iris Neovascularization
- •11.10 Modifiers of Behavior of Iris Neovascularization
- •11.11 Management of Neovascular Glaucoma
- •11.12 Summary of Key Points
- •11.13 Future Directions
- •References
- •The Cornea in Diabetes Mellitus
- •12.1 Introduction
- •12.2 Pathophysiology
- •12.3 Anatomy and Morphological Changes
- •12.4 Clinical Manifestations
- •12.5 Ocular Surgery
- •12.6 Treatment of Corneal Disease in Diabetes Mellitus
- •12.7 Conclusion
- •12.8 Summary of Key Points
- •12.9 Future Directions
- •References
- •Optic Nerve Disease in Diabetes Mellitus
- •13.1 Relevant Normal Optic Nerve Anatomy and Physiology
- •13.2 The Effect of Diabetes on the Optic Nerve
- •13.3 Nonarteritic Anterior Ischemic Optic Neuropathy and Diabetes
- •13.4 Diabetic Papillopathy
- •13.5 Disk Edema Associated with Vitreous Traction
- •13.6 Superior Segmental Optic Hypoplasia (Topless Optic Disk Syndrome)
- •13.7 Wolfram Syndrome
- •13.8 Summary of Key Points
- •13.9 Future Directions
- •References
- •Screening for Diabetic Retinopathy
- •14.1 Introduction
- •14.2 Who Does Not Need to Be Screened
- •14.5 Screening with Dilated Ophthalmoscopy by Ophthalmic Technicians or Optometrists
- •14.6 Screening with Dilated Ophthalmoscopy by Ophthalmologists
- •14.7 Screening with Dilated Ophthalmoscopy by Retina Specialists
- •14.8 Photographic Screening
- •14.9 Nonmydriatic Photography
- •14.10 Mydriatic Photography
- •14.11 Risk Factors for Ungradable Photographs
- •14.12 Number of Photographic Fields
- •14.13 Criteria for Referral
- •14.14 Obstacles to the Use of Teleophthalmic Screening Methods
- •14.15 Combination Methods of Screening
- •14.16 Case Yield Rates
- •14.17 Compliance with Recommendation to Be Seen by an Ophthalmologist
- •14.18 Intravenous Fluorescein Angiography and Oral Fluorescein Angioscopy
- •14.19 Automated Fundus Image Interpretation
- •14.20 Subgroups Needing Enhanced Screening Efforts
- •14.21 Screening in Pregnancy
- •14.22 Economic Considerations
- •14.23 Comparisons of the Screening Methods
- •14.24 Accountability of Screening Programs
- •14.25 Summary of Key Points
- •14.26 Future Directions
- •References
- •Practical Concerns with Ethical Dimensions in the Management of Diabetic Retinopathy
- •15.1 Incorporating Ancillary Testing in the Management of Patients with Diabetic Retinopathy
- •15.2.1 Case 1
- •15.2.2 Case 2
- •15.4 Working in a Managed Care Environment (Capitation)
- •15.5 Interactions with Medical Industry
- •15.7 Comanagement of Patients
- •15.9 Summary of Key Points
- •15.10 Future Directions
- •References
- •Clinical Examples in Managing Diabetic Retinopathy
- •16.1.1 Discussion
- •16.2 Case 2: Bilateral Proliferative Diabetic Retinopathy with Acute Vitreous Hemorrhage in One Eye and a Chronic Traction Retinal Detachment in the Other Eye
- •16.2.1 Discussion
- •16.2.2 Opinion 1
- •16.2.3 Opinion 2
- •16.2.4 Opinion 3
- •16.3 Case 3: Sight Threatening Diabetic Retinopathy in a Patient with Concomitant Medical and Socioeconomic Problems
- •16.3.1 Discussion
- •16.4 Case 4: Asymptomatic Retinal Detachment Following Vitrectomy in a Patient Who Has Had Panretinal Laser Photocoagulation
- •16.4.1 Discussion
- •16.5 Case 5: Management of Progressive Vitreous Hemorrhage Following Scatter Photocoagulation for Proliferative Diabetic Retinopathy
- •16.5.1 Discussion
- •16.6.1 Discussion
- •16.7 Case 7: Proliferative Diabetic Retinopathy with Macular Traction and Ischemia
- •16.7.1 Discussion
- •16.8 Case 8: What Is Maximal Focal/Grid Laser Photocoagulation for Diabetic Macular Edema?
- •16.8.1 Definition of the Problem
- •16.8.2 Discussion
- •16.9 Case 9: What Independent Information Does Macular Perfusion Add to Patient Management in Diabetic Retinopathy?
- •16.9.1 Discussion
- •16.10 Case 10: Macular Edema Following Panretinal Photocoagulation for Proliferative Diabetic Retinopathy
- •16.10.1 Discussion
- •16.11 Case 11: Diabetic Macular Edema with a Subfoveal Scar
- •16.11.1 Discussion
- •16.12.1 Definition of the Problem
- •16.12.2 Discussion
- •16.13.1 Definition of the Problem
- •16.13.2 Discussion
- •16.14 Case 14: How Is Diabetic Macular Ischemia Related to Visual Acuity?
- •16.14.1 Definition of the Problem
- •16.14.2 Discussion
- •References
- •Subject Index
14 Screening for Diabetic Retinopathy |
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Table 14.1 Definition of Chance-Corrected Agreement (Kappa) |
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Gold standard method |
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Test |
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With this framework,
sensitivity ¼ A=ðA þ CÞ
specificity ¼ D=ðB þ DÞ
kappa ¼ ½observed agreement expected agreement&=½1 expected agreement&;
where observed agreement ¼ ðA þ DÞ=ðA þ B þ C þ DÞ and expected agreement ¼ ðA þ BÞðA þ CÞ=ðA þ B þ C þ DÞ2
þðC þ DÞðB þ DÞ=ðA þ B þ C þ DÞ2:
Sensitivity and specificity do not depend on prevalence of the condition in the population, but kappa does. As the prevalence decreases, kappa decreases for any given values of the sensitivity and specificity.60
14.8 Photographic Screening
The gold standard for photographically detecting DR is seven-field stereoscopic fundus photography covering 65–75 degrees of the fundus. This method is costly, not liked by patients because of its higher flash intensity than digital imaging and need for more photographs, and impractical for screening
purposes; it is used in research protocols rather than clinical care.3,5,28,29,36 There are many strate-
gies for photoscreening, making comparison of different techniques difficult. Several of the strategies that have undergone pilot trials follow:
1.Mydriatic fundus photography with various
numbers of fields (2, 3, 5, 6) and various degrees captured per field (30, 45, 60).36,61,9,24,28,42,48
2.Nonmydriatic 45 degree fundus photography with various numbers of fields (1, 2, 4).3,21,61,62,63,64,11
3.Staged screening comprised of stage single-field nonmydriatic photography followed by singlefield mydriatic photography for ungradable images with stage 1 efforts followed by slitlamp biomicroscopy by an ophthalmologist for ungradable images with stage 1 and 2 efforts.
4.Single-field nonmydriatic fundus photography for patients < 50 years old and single-field mydriatic fundus photography for patients 50 years old.
5.For type 2 diabetics, three-field 45 degree nonmydriatic fundus photographs with dilation as needed to obtain satisfactory image quality. For
type 1 diabetics, five-field 45-degree mydriatic fundus photographs.26
An understanding of the trade-offs incurred by different strategies compared to seven-field imaging is helpful in choosing a preferred method of photoscreening. Underascertainment of DR by methodologies using fewer than seven fields has been estimated to range from 5 to 15%.65 Using TIFF and JPEG compressed images, digital images are associated with 86–92% and 72–74% sensitivity, respectively, compared to using color slides.36 Approximately 27% of cases of PDR and 8–15% of all DR lesions occur outside the area photographed with single-field 45 degree nonmydriatic photography.39 Over time and after weighing these relative drawbacks, the trend has been toward single-image screening methods (Table 14.2). Adding more fields adds to the cost, increases the probability of poor quality images and
374
Table 14.2 Performance characteristics of two single-image photographic screening methods
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NPDR |
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PDR |
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Referable DR |
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Technique |
Sensitivity (%) |
Specificity (%) |
Sensitivity (%) |
Specificity (%) |
Sensitivity (%) |
Specificity (%) |
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Single-field |
6156, 96.729 |
92.9,29 8256 |
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92.029 |
97.6,29 10056 |
38,69 61,47 77,61 |
85,47 86,5 93,71 |
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nonmydriatic |
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78,5 89,21 85,70 |
95,61 95,69 |
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45 degree |
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85,71 96,56 |
97,21 97,70 |
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Single-field |
97.529 |
93.329 |
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96.629 |
10029 |
81,61 84.472 |
79.2,72 9261 |
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mydriatic 45 |
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degree |
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The definitions of referable retinopathy, the reference standard technique, the rates of ungradable photographs, the rates of referable retinopathy, whether eyes or patients are used in calculation of referral rates, and whether the ungradable photographs are included in the referable category vary among studies, and therefore comparison of sensitivities and specificities must be guarded. Some studies had a mixture of nonmydriatic and mydriatic photographs taken. For purposes of classification, they are put into the group for which most of the photographs were taken. NPDR = nonproliferative diabetic retinopathy. PDR = proliferative diabetic retinopathy. DR = diabetic retinopathy.
leads to extra referrals for ophthalmic examination without sufficient compensatory improvement in case finding.66
The settings for screening have varied, but include university diabetes clinics, private practice offices, hospital endocrinology clinics, nursing homes, com-
munity health clinics, and mobile units in vans.3,21,36,42,66–68 Methods of notifying the target
population that screening will occur may be important.27 In some models multimedia advertisement of screening is used, whereas in others there is no advertising, but only routine use of a modality in the course
of diabetic, nonophthalmic care.11 The assessment of screening techniques may need to take into account the social environment. A successful screening approach in an urban environment with tertiary care medical centers may differ from the approach adapted to a rural environment with few eye care professionals.24 Screening for certain subgroups of the population, while a laudable goal, has proven impractical. For example, in nursing homes, the relatively high proportion of subjects who are unable to cooperate or undergo treatment even if amenable disease is discovered has rendered the cost per case too high.42
Different Definitions of Diabetic Retinopathy Severity in Screening Studies
Defining severity of DR is challenging, and many different sets of definitions have been established (see Chapter 5). The ETDRS definitions are difficult for any but professional graders to employ. Predictably, definitions designed for clinical use are simpler, as are those designed for screening purposes. One example of definitions of severity for screening purposes by nonophthalmologists follows (Table 14.3).
Table 14.3 Simplified classification of diabetic retinopathy
Stage |
Retinal pathology |
1Mild nonproliferative (occasional microaneurysms and/or hemorrhages and/or exudates)
2Moderate nonproliferative (intraretinal hemorrhages and/or cotton wool spots and/or venous anomalies
in one to three quadrants)
3Severe nonproliferative (intraretinal hemorrhages and/or cotton wool spots and/or venous anomalies in
all quadrants)
4Proliferative noncomplicated (new vessels on disk or retina)
5Proliferative complicated (tractional retinal detachment, preretinal, or vitreous hemorrhage)
Maculopathy |
Presence of hard exudates within 1 disk diameter of the foveola |
Treated |
Presence of photocoagulation scars anywhere (sectoral, panretinal, focal, grid) |
Reproduced with permission from Deb-Joarder24
14 Screening for Diabetic Retinopathy |
375 |
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Even simpler classifications are in use. Kuo and colleagues have a four level system: no retinopathy, background retinopathy, pre-proliferative retinopathy, and proliferative or post-photocoa- gulation retinopathy.3 Comparison of screening outcomes among studies using different systems is fraught with uncertainty.
Technical and practical issues arise in photographic screening. Because the photographs are taken by ancillary staff in a general clinic, training is important in recognizing unusable images and repeating photography until a usable image can be obtained. With training, such staff perform as well as ophthalmic photographers in producing gradable images.36 Staff must be trained on the importance of physiologic mydriasis in a darkened room, and feedback on photographic quality is necessary to reduce the number of artifacts that degrade image quality. Photography of the second eye may need to be delayed for a time after the first eye photograph to allow for spontaneous redilation. It seems to be necessary to photograph both eyes and not one. A strategy of photographing only one eye results in a 9% rate of false negatives.62 Although DR is usually
a symmetric condition, it is asymmetric often enough that both eyes need to be screened.62,73
Many have worried that nonstereoscopic photographic screening methods will miss DME, yet the presence of hard lipid exudates within 1 disk diameter of the center of the macula is >90% sensitive in detecting DME, and lipid can be sensitively detected with nonstereoscopic fundus photography.36 Moreover, most of the cases of DME without lipid exudates are recommended for referral based on other screening criteria.36
Film-based photographic screening methods are now a chapter in history, not a viable method.68 Digital methods allow for the possibility of machine-based interpretation, teleophthalmic interpretation, and more rapid turnaround in interpretation compared to film-based systems.5 Who should interpret the digital fundus images remains controversial, but it appears that nonophthalmologists can perform well. With 40 h of training by an ophthalmologist, grading of fundus photographs by endocrinologists matched the gold standard results of consensus gradings by two experienced ophthalmologists in detecting DR.24 Various systems have
used technicians, opticians, nurse practitioners, internists, and optometrists for grading.9,47,74
14.9 Nonmydriatic Photography
The reported rates of ungradable images using a nonmydriatic camera range from 4 to 34%.11,21,30,68,75
These cameras are easy to use; training to a reasonable standard of proficiency can be attained within 1 h. Level of training in ophthalmic photography does not seem to influence image quality much, a favorable attribute for consideration in screening programs.76 Higher rates of ungradable images lead to higher rates of referral for dilated eye examinations by eye care professionals because of doubt by the photography graders regarding adequacy of the image to exclude the risk of missing referable retinopathy. This is seen by different subgroups in the care team as a positive or a negative. Where numbers of professionals are high relative to the proportion of patients to be seen, a higher rate of referral is seen as a positive. Where numbers of professionals are low relative to the number of patients to be seen, a higher rate of referral is seen as a negative and has led to adoption of mydriatic screening over nonmydriatic screening as a response.24 In Singapore, where national photographic screening for DR by trained family practitioners using a 45 degree fundus photograph obtained with a nonmydriatic camera has been in place since the early 1990s, only 38% of the patients referred actually had DR, reflecting a much poorer specificity for the technique in practice than under idealized study conditions.77 Similarly, in Gloucestershire, UK, the actual percentages of patients referred based on screening who, in fact, had no DR on actual clinical examination varied from 47.8 to 56.7% over the first 4 years of implementing a systematic screening program.78 It is recognized that most screening tests perform less well in real-world settings than in
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D.J. Browning |
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settings based on a study design.55 In a study from Colorado, USA, family physicians reading nonmydriatic 45 degree fundus photographs failed to refer 10.2% of patients deemed needing a referral to an ophthalmologist by a secondary image grader who was an ophthalmologist.21 Nonmydriatic photography often requires placing the patient in a darkened room for a time and has been found to lengthen the screening process compared to a mydriatic screening procedure.24 There are metrics of fundus image quality other than percentage of ungradable images, such as grades of image quality and ability to detect referable DR, and all such metrics are beneficially influenced by mydriasis and negatively influenced by nonmydriasis.24 The perils of nonmydriatic fundus photography missing sight-threatening peripheral neovascular fronds have been documented, but despite admonitions that general practitioners become better direct ophthalmoscopists, the statistical evidence favors nonmydriatic photography over nonmydriatic ophthalmoscopy for detecting referable retinopathy.30
14.10 Mydriatic Photography
There are several objections raised whenever mydriatic methods of screening are considered. The first is that narrow angle glaucoma attacks may be triggered. The risk is low and has been estimated to be 1 in 7,000 examinations or lower.47,79 The second is that patients will object and refuse screening under these conditions. When mild mydriatic agents such as tropicamide 1% are used and only a single dose is given, patient acceptance has been high.24 The ability to drive after mydriasis is a third objection, particularly in those over 55 years of age. Somewhat counterintuitively, pharmacologic dilation has been reported to speed screening for DR compared to nonmydriatic screening.24 The choice of the mydriatic used may be important. Patient acceptance of moderate mydriasis achieved with tropicamide 1% was reported to be good.24 Mydriatic screening methods are particularly useful in older patients with more miotic pupils. Mydriatic photography as a backup when nonmydriatic photography gives poor images can reduce the rate of ungradable images to <1%.21
14.11Risk Factors for Ungradable Photographs
In nonmydriatic photoscreening, increasing the number of fields imaged above two increases the number of cases deemed to have poor quality sets of images requiring referral.66 The rate of ungradable photo-
graphs decreases if mydriatic photoscreening is used rather than nonmydriatic photoscreening.24,61,75 In 12
studies using nonmydriatic photography, the median
and the range of ungradable photographs were 18.3%
and 4.0–42.3%, respectively.24,75,61,5,68,11,21,47,63,71,64
By comparison, among six studies using mydriatic photography, the median and the range of ungradable
photographs were 3.7% and <1–5%, respectively.24,75,61,21,47,9 Increasing age is associated with
an increasing rate of ungradable photographs whether by nonmydriatic or mydriatic photographic technique, because of both an increasing effect of
cataract and a decreasing pupillary diameter alone or after pharmacologic mydriasis.5,24,61,71,75 There is
a floor for the percentage of ungradable photographs. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), in which mydriasis and professional ophthalmic photographers were used in a population-based study, 1.5% of participants had ungradable photographs.17
14.12 Number of Photographic Fields
Whether a greater number of photographic fields are associated with a higher rate of detection of referable retinopathy at a reasonable price of more time, expense, and increased patient dissatisfaction with bright flashes is controversial.28 Some studies suggest that more fields increase the rates of referable retinopathy. Others suggest that no clinically important gains are made by this provision.61 The trend in the literature seems to be that single-field photography predominates based on adequate performance and simplicity.
14.13 Criteria for Referral
The criteria for referral for a complete, dilated eye examination by an ophthalmologist are not identical across studies. All screening methodologies
