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Age-related macular degeneration (AMD) is a clinical diagnosis based on characteristic macular findings in individuals over 50 years old. Age is one of the most important diagnostic criteria for AMD. The Beaver Dam Eye Study compared the 5-year incidence and progression of AMD in people aged 75 years or older to the group of people in 43–54 years. The incidence of developing large drusen (125–249 μm) was 8.3 times higher in the former group. The same trend was observed in other pathological changes in these two age groups as the following: larger drusen (>250 μm), 32 times; soft indistinct drusen, 9 times; pigmentary changes, 14.3 times higher, respectively. Because of the much more increased incidences of macular degenerative lesions with age, the AMD-like signs in younger persons may prompt us for the workup of a differential diagnosis of AMD.
In addition to age, the history of other risk factors including ethnic specificity, smoking, hypertension, dietary factors, and aspirin is sensible to be considered in the diagnostic workup for AMD. , A recent meta-analyses and literature review on the global prevalence of AMD revealed that, among the population age ranging 45–85 years, the global prevalence of any type of AMD was approximately 8.7%. If AMD is categorized into early and late stages, the prevalence of early AMD was 8.0% and that of late AMD was 0.4%. To analyze the impact of ethnic differences on the prevalence of AMD, it was noticed that early AMD was more common in individuals of European ancestry (8.8%) than in Asians (6.8%). Whereas the prevalence of the late stage of AMD did not differ significantly between Europeans (0.59%) and Asians (0.56%). Among individuals of African ancestry, the prevalence of any AMD was the lowest. A recent study on AMD-associated visual impairment among Europeans, an encouraged report showed that the prevalence of blindness and visual impairment among European patients with AMD is on the decrease. It is likely to be contributed by improved diagnostic procedures, that is, earlier diagnosis of late AMD and the earlier introduction of anti-VEGF therapy.
In some previous studies, it was believed that women are at increased risk of developing AMD, particularly those women who have a longer life span. However, after age effects were excluded, the analysis of recent studies showed that sex was not markedly associated with the prevalence of AMD. Numerous epidemiology studies addressed the relationship between cigarette smoking and AMD. There is reasonably consistent evidence that smoking cigarettes results in an increased risk of the disease. Based on the summary of these studies, the odds ratio was ∼2.0, meaning that smoking roughly doubles the risk of AMD. High dietary fat intake theoretically may increase the risk of developing AMD. The elevated levels of cholesterol due to high dietary fat may have an adverse impact on choroidal circulation. The exceeded fat deposition in Bruch’s membrane may affect transport functions of retinal pigment epithelium (RPE). However, the dietary factors as biochemical markers for AMD have not been consistently proven. Based on meta-analyses and systematic reviews, an association between other risk factors and AMD was calculated. Some case-controlled studies did identify a significant association between hypertension and late AMD. Aspirin may increase the risk of neovascular AMD, though the evidence is limited. Other factors such as cataract surgery, blue iris, and exposure to sunlight are suspected, but their influence remains uncertain. ,
In terms of the risk factors for age-related macular degeneration, age and genetic make-up are the most important risk factors identified to date. Over the next decade, more novel genes that are involved in the development of AMD might be identified and validated. The question that whether antioxidant vitamin and mineral supplementation prevents or delays the development of the disease will be answered as the results of large ongoing trials become available. Other risk factors such as alcohol consumption, estrogen replacement, and lifetime light exposure require further study. Studies with large numbers of late-stage disease are needed to provide the power to investigate moderate risks. , In summary, obtaining the history and risk factors of each individual is essential for clinicians to start the diagnostic process and establish communication with patients.
Drusen are the hallmark of AMD. However, few small drusen alone without pigmentary changes, based on the classification of AMD, are considered as normalcy. Meanwhile, in the study of geographic atrophy evolution, even when typical drusen is absent, diffuse mottling of small pigment clumps or microreticular pattern of small lines in aged eyes are still evidence of early AMD. Therefore, both drusen (>medium drusen) and pigmentary changes are required as diagnostic criteria of early AMD. Drusen are rare before the age of 40, but are common by the sixth decade. Drusen are extracellular deposits located between the RPE and Bruch’s membrane. The distribution is highly variable. Drusen may be confined to the macula, and may encircle it around the macular periphery. They may also be seen in the midperipheral or peripheral area. The size of drusen, the composition of drusen, and the pigmentary abnormalities are also highly variable. Therefore, the examination of drusen and drusen-associated progression of macular changes require multimodal imaging studies. In this section, the clinical features of various drusen examined by multimodal imaging techniques are referred to Chapter 4, Table 4.1.
Using color fundus photography (CFP) obtains equivalent information as that of biomicroscopic examination. CFP illustrates different subtypes of macular drusen (e.g., medium and large, hard and soft, and scattered and confluent) and drusen location, number, and area of involvement. CFP is a sensitive imaging technique showing pigmentary abnormalities, for example, various patterns of hyper- and hypo-pigmentation, indicating loss of RPE. As areas indicated by black dashed boxes in Fig. 5.1A and B middle, the sharply delineated area of hypopigmentation with choroidal vessels are typical geographic atrophy (GA). The GA lesions typically gradually expand and encroach upon the fovea. At this point, central visual functions deteriorate significantly.
However, there are limitations of CFP, including variability of pigmentation and drusen appearance, lack of depth resolution of fundus, and lack of detailed quantitative information. , In spite of these limitations and the emergence of newer imaging modalities, CFP remains applicable in routine clinic and large clinical trials. It must be realized that the application of CFP in future studies is necessary because it allows for comparisons with earlier studies regarding AMD classification criteria Chapter 3, Table 3.1) and for validation of the newer techniques.
Fundus autofluorescence (FAF) is a specific modality for the evaluation of GA because it provides high-contrast retinal images detecting RPE atrophy. Atrophic areas represent decreased autofluorescence (hypoautofluorescence) due to the loss of the RPE cells. Because of the demarcation between areas of RPE loss and neighboring areas of relatively intact photoreceptors and RPE, semiautomated quantification of atrophic areas by FAF is applicable. As a result, FAF has been used as a morphologic marker for the progression of GA in clinical studies. FAF imaging technique that employs a confocal scanning laser ophthalmoscope with a blue light excitation wavelength filter (488 nm) and an emission filter of 500–521 nm is currently the most commonly used method for FAF. However, FAF imaging is susceptible to media opacities, thus it is difficult to observe the fovea with macular pigment that absorbs blue light. Meanwhile, the blue light causes patient discomfort. The following FAF photographs of six patients are excellent examples that quantitatively monitoring the progression of GA. In a literature review, the median of GA progression monitored by FAF is ∼1.78 mm 2 /year ( Fig. 5.2 ).
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