- •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
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Fig. 4.7 (a) Fluorescein angiography of the posterior pole, showing few microaneurysms and hemorrhages. The clinical features of this single image could erroneously lead to the diagnosis of mild NPDR. (b) Interestingly, the FA of the periphery shows extensive areas of retinal nonperfusion and amputation of the retinal vessels predominantly located in the temporal areas where a point hyper-fluorescence related to early NVE is detectable (arrow)
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Fig. 4.8 (a) NVEs located on the nasal and inferior quadrants, associated to sectorial peripheral ischemia and breakdown of the blood-retinal barrier in a patient with long-lasting type I diabetes and poor metabolic control. (b) Spontaneous regression of new vessels, after wide improvement of the glucose control (This image was published on Bandello et al. [18], Copyright Elsevier)
4.2Diagnostic Tools
4.2.1Fluorescein Angiography
Fluorescein angiography (FA) enables the identification of the retinal areas of nonperfusion and of the neovascularization (Fig. 4.7). Even if the “high-risk” characteristics of PDR were primarily defined by biomicroscopy and did not require further examination, FA is currently a validated diagnostic tool for the diagnosis and management of PDR (Fig. 4.8). Retinal new vessels (NVs) are clearly visible on FA examination. In fact, different from normal retinal vascularization, which is constituted by
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Fig. 4.9 Color (a) and red-free (b) fundus photographs showing NVE (arrow) on the superior temporal vascular arcade, several hemorrhages, and cotton wool spots. (c–e) The angiographic pattern of active new vessels: fluorescein leakage is beginning on early frames (c), then is widely increasing on intermediate frames (d), and then is showing a pronounced leakage on late phases (e). Localized areas of retinal non-perfusion are clearly visible temporally to the macula (arrowhead)
intact astrocytes, in pathological new vessels, reactive glial cells are the key structural elements, which lead to reduced endothelial cell tight junctions maintenance and abundant fluorescein dye leaking [19]. Thus, NVs show profuse leakiness characteristics, clearly visible from the early angiograms and widely increasing on later frames, different from IRMAs, which do not reveal any sign of leakage (Fig. 4.9).
4.2.2Fundus Photography
Fundus photography is an invaluable tool for the management and follow-up of diabetic patients, even in case of PDR. The seven fields technique or the stereo fundus photography can be used to monitor the progression of the PDR.
4.2.3Ultrasonography
Ultrasonography (US) is a valuable tool to assess the intraocular pathology when biomicroscopy is seriously limited by media opacity, such as in case of extensive vitreous hemorrhage. The frequency widely used in ophthalmology is included
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between a range of 8 and 10 MHz. The use of ultrasound is essential in monitoring many ocular diseases, including vitreous and preretinal hemorrhage, retinal detachment and fibrovascular proliferation, and in the planning of surgical intervention [20]. In case of vitreous hemorrhage, US should be performed to exclude any other comorbidity, such as retinal tear or detachment.
Vitreous hemorrhage has the typical appearance of mobile, diffuse opacity in the vitreous cavity, with minimal reflectivity.
Fibrovascular membranes may undergo a fibrous contraction, resulting in tangential tractions between the retina and vitreous or splitting of the cortical vitreous [21, 22].
Tractional retinal detachment could be clearly identified with US as a hyperreflective membrane, adherent to the posterior hyaloid, immobile on kinetic examination. Tractional retinal detachment can assume the typical “tent-like” appearance, characterized by a concave elevation of the retina with a central vitreoretinal adherence, or a “table-top” shape, where the area of adherence is larger. Usually retinal detachment maintained a tight adhesion to the optic nerve and is visible even if the gain is widely reduced [23, 24].
4.2.4Optical Coherence Tomography
Optical coherence tomography (OCT) has a limited role in the diagnosis and progression of PDR, while biomicroscopy, FA, and US are the more common in the clinical practice. Nevertheless, a better clinical understanding of the retinal morphology has been provided by recent Spectral Domain OCT (SD-OCT), which can correlate at the same time with FA examination. In a recent paper, the SD-OCT appearance of NVD and NVE has been described [9]. NVD on SD-OCT appears as a hyperreflective line protruding from the optic disk in case of vitreous detachment or sitting over it in case of posterior hyaloid adherence. NVE is noted as homogenous hyperreflective loops arising from the retinal surface. IRMAs appear as intraretinal lesions, providing a disorganization of the inner retinal layers that do not project into the vitreous, but at least may protrude through the internal limiting membrane.
OCT has reached an increasing diagnostic role in the management of vitreoretinal abnormalities, especially when the macula is involved. OCT enables the clear identification of taut and thickened posterior hyaloid and its pathological adherences to the macula and evaluates the tractions secondary to the fibrosis and shrinking of the neovascular complexes [25]. In case of tractional retinal detachment, OCT can assess the possible macular involvement and the possible presence of vitreomacular adherences [26].
OCT is a valuable instrument in the evaluation of the retinal thickness, especially in case of visual impairment following PRP procedure, identifying cystoid macular
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Fig. 4.10 (a) Fluorescein angiography of the posterior pole, clearly showing a localized hyperfluorescence from leakage phenomenon, related to the presence of NVE (arrow) located above the inferior temporal vascular arcade, as well as intraretinal microvascular abnormalities (arrowhead), diffuse macular edema secondary to the breakdown of the blood-retinal barrier, and multiple areas of retinal non-perfusion. (b) FA revealing in the periphery hypo-fluorescent confluent areas of retinal ischemia, more evident in the nasal sector, and the presence of new vessels (arrow). (c) Infrared image of the posterior pole, showing the precise location of the OCT scan. (d) OCT scan of the macula area, slightly above to the fovea, showing macular edema and increased retinal thickness, associated to presence of intraretinal cysts
edema and serous retinal detachment [27] (Fig. 4.10). The OCT assessment is also widely performed for the analysis of macular morphology after surgical intervention for the advanced form of PDR [28].
The recent analysis of the retinal nerve fiber layer (RNFL) thickness has enabled the collection of several valuable evidences, not only in the management of glaucoma, but also in other diseases, including PDR. In a recent work, peripapillary RNFL thickness increased at 6 months after PRP, while a significant decrease was noted at 24 months after PRP [29]. The authors concluded that PRP, in addition to the natural history of DR, could lead to a significant RNFL thickness loss.
Choroidal thickness (CT) measurement is another useful tool for evaluation of the retinal disease provided by recent SD-OCT instruments. In type 1 diabetes, including PDR, a choroidal thinning has been detected compared to healthy subjects, suggesting an involvement of choroid in the pathogenesis and progression of
