- •Foreword
- •Preface
- •Contents
- •Contributors
- •Acronyms
- •1.1 Introduction
- •1.2 Epidemiology
- •1.3 Risk Factors
- •1.3.1 Duration of Diabetes Mellitus
- •1.3.2 Glycemic Control
- •1.3.3 Hypertension
- •1.3.4 Ethnic Differences
- •1.3.5 Obesity
- •1.3.6 Socioeconomic Status
- •1.3.7 Other Risk Factors
- •1.4 Pathophysiology
- •Conclusion
- •References
- •2: Non-proliferative Diabetic Retinopathy
- •2.1 Clinical Overview
- •2.1.1 Clinical Findings
- •2.1.2 Classification of NPDR
- •2.1.3 Atypical Forms of NPDR
- •2.2 Diagnostic Tools
- •2.2.1 Telemedicine
- •2.2.2 Fundus Photography
- •2.2.3 Fluorescein Angiography
- •2.2.4 Ultrasonography
- •2.2.5 Optical Coherence Tomography
- •2.2.6 Adaptive Optics Scanning Laser Ophthalmoscope
- •2.2.7 Multifocal Electroretinogram
- •2.2.8 Pattern Visual Evoked Potentials
- •2.2.9 Other Diagnostic Tools
- •2.3 Present Therapies
- •2.3.1 Primary Interventions
- •2.3.1.1 Glycemic Control
- •2.3.1.2 Blood Pressure Control
- •2.3.1.3 Lipid-Lowering Therapy
- •2.3.2 Secondary Interventions
- •2.3.2.1 Protein Kinase C Inhibitors
- •2.4 Evolving Algorithms
- •2.4.1 Screening
- •2.4.2 Laser Photocoagulation
- •2.5 New Frontiers
- •References
- •3: Diabetic Macular Edema
- •3.1 Clinical Overview
- •3.1.1 Clinical Findings
- •3.1.2 Biomicroscopic Classification of DME
- •3.2 Diagnostic Tools
- •3.2.1 Fluorescein Angiography
- •3.2.2 Optical Coherence Tomography
- •3.2.3 Fundus Photography
- •3.2.4 Microperimetry
- •3.2.5 Multifocal Electroretinogram
- •3.2.6 Other Imaging Under Investigation
- •3.3 Present Therapies
- •3.3.1 Laser Photocoagulation
- •3.3.2 Intravitreal Pharmacotherapies
- •3.3.2.1 Intravitreal Steroids
- •3.3.2.2 Intravitreal Anti-VEGF
- •3.3.3 Pars Plana Vitrectomy
- •3.4 Evolving Algorithms
- •3.4.1 Therapeutic Algorithms
- •3.4.2 Factors Associated with Favorable Response to the Therapy
- •3.4.3 Treatment of DME Associated with Macular Ischemia
- •3.5 New Frontiers
- •References
- •4: Proliferative Diabetic Retinopathy
- •4.1 Clinical Overview
- •4.1.1 Clinical Findings
- •4.1.2 Classification of PDR
- •4.2 Diagnostic Tools
- •4.2.1 Fluorescein Angiography
- •4.2.2 Fundus Photography
- •4.2.3 Ultrasonography
- •4.2.4 Optical Coherence Tomography
- •4.2.5 Perimetry
- •4.2.6 Further Diagnostic Tools
- •4.3 Present Therapies
- •4.3.1 Panretinal Laser Photocoagulation
- •4.3.2 Intravitreal Injections
- •4.3.2.1 Intravitreal Steroids
- •4.3.2.2 Intravitreal Anti-VEGF Agents
- •4.4 Evolving Algorithms
- •4.5 New Frontiers
- •References
- •5.1 Introduction
- •5.2 Pathophysiology
- •5.3 Neovascular Glaucoma
- •5.4 Tractional Retinal Detachment
- •5.5 Treatment
- •5.5.1 Panretinal Laser Photocoagulation
- •5.5.2 Pars Plana Vitrectomy and Endophotocoagulation
- •5.5.4 Silicone Oil Tamponade
- •5.5.4.1 Viscodissection
- •Conclusion
- •References
2 Non-proliferative Diabetic Retinopathy |
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Fig. 2.12 FA photographs show a reduction in the BRB (blood-retinal barrier) breakdown in a case of diffuse edematous capillaropathy before (a) and 1 month (b) after IVR (Ranibizumab); a better glycometabolic control is mandatory to reduce the risk of retinal lesions’ recurrence and progression. The OCT scans before (c) and after (d) the IV treatment show normal macular profile
The treatment of DP and EC consists primarily in prevention, such as obtaining a proper glycemic control and avoiding any rapid glycemic drop. Typically, DP and EC are self-limiting diseases, with spontaneous resolution, and thus, no specific treatment is required. Intravitreal triamcinolone acetonide and periocular betamethasone injections revealed an improvement in visual acuity and optic disk swelling, due to their anti-edema and angiostatic effects [32, 33]. Intravitreal injections of bevacizumab (IVB) have been performed in the treatment of DP and EC associated with macular edema, revealing a visual regain [34, 35] (Fig. 2.12).
2.2Diagnostic Tools
Typically, in the NPDR, dilated fundus examination is sufficient by itself to diagnose the different degrees of the disease and their progression to more severe forms. Patients should undergo routinely evaluations, in order to obtain an early identification and prompt management of DR, according to the degree of the retinopathy. Nevertheless, telemedicine, fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), and ultrasound imaging are important diagnostic tools commonly used in the everyday clinical practice.
2.2.1Telemedicine
Screening programs resulted to be a cost-effective solution to reduce the risk of blindness in the working age [36]. Telemedicine has been recently worldwide
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introduced for the screening of DR, especially to increase the access to health care, to give timely evaluation for DR, and to reduce the health costs [37]. In addition these new technologies could also maximize the cooperation between ophthalmologists and other health-care specialists, such as diabetologists or pediatricians. Mydriatic and non-mydriatic fundus cameras have been developed for the integration of a multidisciplinary care team that could help the diabetic patient in the management of this dramatic disease. The use of non-mydriatic retinal camera has the advantage to work with undilated pupils, using infrared light. This kind of examination is certainly more comfortable for the patient. Different types of retinal digital cameras have progressively been introduced in non-ophthalmological settings and routinely performed by non-eye-care professionals [38, 39]. Even if some cameras need qualified photographers to take the images, new non-mydriatic instruments have been developed that could also be performed by inexperienced technicians. The data are analyzed by a grading center or in some cases by qualified ophthalmologists, to enable the detection of the early signs of DR and also to standardize the classification of the gravity of the DR. In case of findings of DR, the patient is promptly referred for a complete ophthalmological evaluation, including dilated fundus examination. Several studies confirmed that telemedicine showed a good sensitivity and specificity and is currently considered as a preferred screening method [40]. Nevertheless, physicians should keep in mind that telemedicine is not a substitute for a complete ophthalmological examination. In addition a specialized personnel is required to analyze the results and, in some cases, to perform the screening examination.
2.2.2Fundus Photography
Fundus photography has been routinely performed since 1976 in multicenter clinical trials to record the occurrence and the progression of the DR and to classify the different degrees of the disease using a standardized method [41]. The new technologies associated with the use of digital photographs, instead of the previous film images, played an important role both in the clinical activity and in the research field. Color fundus photographs could be achieved using the stereoscopic and non-stereoscopic technique and through different wide-angle fields (such as 30° or 60° fields). Classically, standard protocols are performed adopting the seven-field technique, which allowed a visualization of the periphery of about 75° fields. To obtain wide-field imaging, new digital cameras have been introduced that allowed an ultra wide-angle (200°) images of the retina with a single photograph [42].
The natural course of the DR at all stages could be monitored and compared at the next visits, especially in the early NPDR form, where no treatment is required, but only a closer follow-up and a proper systemic control is needed (Figs. 2.13 and 2.14).
2 Non-proliferative Diabetic Retinopathy |
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Fig. 2.13 Color photos of severe NPDR (or pre-proliferative DR) characterized by several widespread hemorrhages inside and outside the major vascular arcades, cotton wool spots (black arrows) at the posterior pole (a) and in the periphery (b) where vessels appear with increased caliber, and deviousness (white arrow) due to flow slowdown (venous beading)
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Fig. 2.14 A case of severe NPDR. At baseline the color photo (a) shows several cotton wool spots all around the optic disk (black arrows), suggesting an acute infarction of the retinal tissue, and in the FA image (b), the hypofluorescent areas are due to the diffuse impairment of perfusion. After few months (c), the lesions regress (black arrow), leaving retinal ischemia biomicroscopically detectable by the presence in the nasal sector of an obliterated major vessel which appears white for the hyalinization (white arrow)
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Fig. 2.15 Red-free image (a), early (b) and late FA phases (c, d) in NPDR. Some microaneurysms are located around the perifoveal vascular arcade; they are hyperfluorescent in the early phase and responsible of fluorescein leakage in the late phases. The areas of leakage correspond to the presence of intraretinal fluid that amount to an initial cystoid macular edema (white arrow). The patient refers initial visual impairment and metamorphopsia
2.2.3Fluorescein Angiography
Fluorescein angiography (FA) is a well-known diagnostic tool in the management of DR, which allows the identification and follow-up of the area of retinal nonperfusion and neovascularization and the abnormal vascular permeability (Figs. 2.15 and 2.16).
•In mild and moderate NPDR, FA examination is usually not necessary, because dilated fundus photography is considered the standard of care. Nevertheless, if performed, FA could easily detect a greater number of microaneurysms compared to biomicroscopy and color fundus photographs [43] (Fig. 2.17). As shown by the Diabetes Control and Complications Trial (DCCT) Research Group, FA is not indicated for the detection and management of the earliest changes in DR compared to the fundus photographs [44].
•In case of severe NPDR, FA could document the altered caliber of the vessels, the presence of IRMA, and the onset of the peripheral ischemia (Fig. 2.18), and it could be useful in the identification and follow-up, toward the progression to the vision-threatening PDR. Even if the Early Treatment Diabetic Retinopathy Study Research Group showed that severe NPDR has an increased risk to
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Fig. 2.16 NPDR with cotton wool spots in red-free image (a) (black arrows) and retinal non-per- fusion in the nasal sector which remains hypofluorescent in all FA phases (b, c) (white arrow)
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Fig. 2.17 (a) Initial DR with few microaneurysms (black arrows) and a small hemorrhage (white arrow) at the posterior pole documented by red-free image. FA image (b) shows hypofluorescence due to mask effect of the hemorrhage and hyperfluorescence corresponding to the ectasic vessels. Panretinal FA (c) does not detect further lesions. The FA examination in the absence of more lesions at dilated biomicroscopic exam should be avoided and reserved to more severe stages of DR. (d) SD-OCT vertical scan shows hyporeflective shadow cones that correspond to the retinal vessels
