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Clinical characteristics of exudative age-related macular degeneration in Taiwan
Taiwan Journal of Ophthalmology 2 (2012) 127e130
Contents lists available at SciVerse ScienceDirect
Taiwan Journal of Ophthalmology journal homepage: www.e-tjo.com
Original article
Clinical characteristics of exudative age-related macular degeneration in Taiwan Pao-Ju Chen a, b, San-Ni Chen a, b, * a b
Department of Ophthalmology, Changhua Christian Hospital, Changhua City, Taiwan School of Medicine, Chung Shan Medical University, Taichung, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 May 2012 Received in revised form 17 July 2012 Accepted 16 August 2012 Available online 7 December 2012
Purpose: To describe the clinical features of exudative AMD of patients in Taiwan. Methods: A retrospective case series consisting of 235 eyes in 211 patients, with a male/female ratio of 7:3, mean age 70.36 8.98 years (range 50e86), with exudative AMD, was reviewed at Changhua Christian Hospital, Taiwan. Results: Among the 211 patients, 77 (36.5%) had bilateral involvement of exudative AMD; and of the 235 eyes, 117 (49.7%) were diagnosed with idiopathic PCV, 111 (47.2%) with typical AMD, and seven eyes (2.9%) with retinal angiomatous proliferation. PCV is predominant in patients younger than 70 years (71.8%), whereas typical AMD is prevalent in patients 70 years or older (59.4%). After treatment, mean visual acuity improved in 154 eyes, as reflected in the decreasing logarithm of minimal angle of resolution (log Mar VA)dfrom 0.95 0.60 to 0.84 0.55, whereas in the other 81 eyes without treatment visual acuity deteriorateddlog Mar VA increased from 0.85 0.60 to 1.22 0.53. Conclusion: Male predominance, higher ratio of PCV, and lower ratio of retinal angiomatous proliferation are common features of exudative AMD in Taiwan. Copyright Ó 2012, The Ophthalmologic Society of Taiwan. Published by Elsevier Taiwan LLC. All rights reserved.
Keywords: exudative age-related macular generation PCV RAP typical AMD
1. Introduction Age-related macular degeneration (AMD) was once thought to be not as common in Asians as in Caucasians. However, recent reports have indicated that the prevalence rate for both early and late AMD is similar in Chinese and in Caucasians.1,2 Exudative AMD is now divided into three subgroups: typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). According to previous studies, AMD in Asians exhibits different clinical characteristics compared to that in Caucasians.3e8 The present review discusses the clinical features of exudative AMD among Taiwanese Chinese patients. 2. Materials and methods A retrospective review of patients with exudative AMD was conducted from September 2003 to February 2008 at the Department of Ophthalmology, Changhua Christian Hospitalda referral clinic of AMD in central Taiwan. The review had obtained approval from the institutional review board of Changhua Christian Hospital * Corresponding author. Department of Ophthalmology, Changhua Christian Hospital, Number 35, Nanhsiao Street, Changhua City, Taiwan. E-mail address: [email protected] (S.-N. Chen).
and was conducted in accordance with the provisions of the World Medical Association’s Declaration of Helsinki. Patients with central serous chorioretinopathy, ocular toxoplasmosis, toxocariasis, high myopia, and uveitis-associated choroidal neovascularization, as well as those with disciform scarddetected at the initial clinic examination which made subgroup classification of exudative AMD impossibledwere excluded in this review. Patients’ age, sex, and corrected decimal visual acuity were recorded. Slit lamp biomicroscopy, funduscopy with indirect ophthalmoloscope and 90 D lens, optical coherence tomography (OCT; Stratus, Carl Zeiss Meditec, Inc., Dublin, CA, USA), fluorescein angiography (FA), and indocyanine angiography (ICG) were performed in all patients. According to the findings of two independent retinal specialists (C.S. and L.C.) on fundus photography, FA, ICG, and OCT, eyes were classified into three subtypes of exudative AMD: (1) typical AMD, (2) idiopathic PCV, and (3) RAP. The two specialists were unaware of each other’s subtype classification on each patient; whenever discrepancies occurred, a third reviewer (H.J.) was required to make the final diagnosis. The diagnosis of typical AMD was based on the findings of classic or occult choroidal neovascularization as demonstrated by FA and without the angiographic characteristics of PCV in ICG. Subretinal or sub-RPE neovascularization were noted by OCT. The
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diagnosis of PCV was based on the findings of funduscopy, ICG, and OCT. Signs of funduscopy included the elevated orange lesions, hemorrhagic retinal pigment epithelial detachment (RPED)dwith or without subretinal hemorrhage, and serous RPED. Findings in OCT included single or multiple bleb and dome-shaped elevated retinal pigment epithelial (RPE) lesions, without subretinal neovascularization detected by OCT. ICG findings included polypoidal lesions, clusters of grapes polyp-like lesions, and aneurysmal dilatation of choroidal vessels. The diagnosis of RAP was based on the findings of feeding arteries and draining venules for intraretinal or subretinal neovascularization in FA and ICG, with or without RPED. Intraretinal neovascularization revealed by OCT would further augment the diagnosis of RAP. Patients were divided into three groups: (1) those treated with intravitreal bevacizumab (Genentech, Inc., South San Francisco, CA, USA) alone or in combination with other treatments if bevacizumab alone was insufficient to cause disease regression; (2) those who received such treatments as gas tamponade with SF6, intravitreal injection of triamcinolone acetonide, subtenon injection of triamcinolone acetonide, transpupillary thermotherapy, continuous wave laser therapy, or photodynamic therapy; and (3) those who were under observation only. Before 2006, all patients had received observation, laser therapy, transpupillary thermotherapy or photodynamic therapy, and intravitreal injection of triamcinolone as the major management method. Later on, most of the patients received intravitreal injections of bevacizumab as the primary therapy. Decimal visual acuity was converted to logarithm of minimal angle of resolution for paired t-test.
3. Results The demographic data of the patients are shown in Table 1. All 211 patients (148 males and 63 females) received follow-up at our clinic for 3 months to 5 years (average: 21.5 11.3 months). All patients were of Chinese ethnicity. Of the 235 eyes reviewed, 111 (in 100 patients) were classified as typical AMD, 117 (in 105 patients) as PCV, and seven (in 6 patients) as RAP. For patients with typical AMD, the mean age was 73.37 7.29 years with a male/female ratio of 3:1; those with PCV had a mean age of 67.36 9.55 years with a 2:1 sex ratio; patients with RAP had an average age of 74.25 9.18 years and a 1:1 sex ratio. For bilaterality, 11 patients with typical AMD, 12 patients with PCV, and one patient with RAP had bilateral disease of the same subtype noted during the initial and follow-up periods. At the first examination, macular scar was not categorized into any of the subtype, and was noted in 23 patients with typical AMD, 30 patients with PCV, and none among patients with RAP.
Table 2 Visual acuity change in the subtypes of patients in different treatment groups. Disease subtypes and treatment group
Initial VA
Final VA
Typical AMD (n ¼ 111) Group 1 (n ¼ 44) Group 2 (n ¼ 27) Group 3 (n ¼ 40) PCV (117) Group 1 (n ¼ 28) Group 2 (n ¼ 53) Group 3 (n ¼ 36) RAP (7) Group 1 (2) Group 3 (5)
1.13 1.09 1.02 1.01 0.80 0.81 0.89 0.67 1.05 1.00 1.07
1.03 0.76 1.10 1.47 0.81 0.68 0.84 0.95 1.78 0.84 1.96
p 0.003 0.256 0.594 0.013 0.241 0.166 0.056 0.013
AMD ¼ age-related macular degeneration; PCV ¼ polypoidal choroidal vasculopathy; RAP ¼ retinal angiomatous proliferation; VA ¼ visual acuity in logarithm of minimal angle of resolution.
In summary, 34 patients (34.0%) with typical AMD, 42 patients (40.0%) with PCV, and one patient (16.7%) with RAP (or 77 of all patients [36.5%]) had bilateral exudative AMD. For patients with unilateral disease, medium or large soft drusen was noted in the fellow eyes in 29 patients (40.8%) with typical AMD, eight eyes (11.8%) in patients with PCV, and three eyes (60%) in patients with RAP. In terms of initial visual acuity, eyes with PCV had the best mean visual acuity in log MAR (0.80) as compared to eyes with typical AMD (1.13) and RAP (1.05). As for treatment efficacy, all eyes that received treatment for exudative AMD (154 eyes) showed improvement in mean log MAR VAdfrom 0.95 0.60 to 0.84 0.55; but for those 81 eyes without treatment, the mean log MAR VA deteriorated from 0.85 0.60 to 1.22 0.53. As for response to different treatment modalities, all three subgroups of patients showed the best response to group 1 treatment (intravitreal injection of bevacizumab with or without other treatment) and less favorable response to group 2 (other treatment). Visual outcome in different treatment groups is listed in Table 2. For each age group, distribution of disease subgroup is noticeably different. Patients younger than 70 years of age had a much higher chance of having PCV (61 in 85 patients, 71.8%), and the incidence of PCV in exudative AMD dropped to 34.9% (44 in 126 patients) for patients who were 70 years or older. In contrast, typical AMD occurred only in 27.6% (23 in 85 patients) of patients under 70 years of age, and for patients 70 or older, the incidence of typical AMD increased to 59.4% (87 in 126 patients). RAP occurred only in 0.6% and 5.7% of patients younger and older than 70, respectively (Fig. 1).
Table 1 Demographic data of patients.
No. of patients (percentage) Male gender Average age (y) Bilaterality Macular scar in fellow eye at initial clinic Drusen in fellow eyes in unilateral involved patients Initial VA in logMar
All
Typical AMD
PCV
RAP
211 (100%) 70% 70.36 11.4% 26.1%
100 (47.3%) 75% 73.37 11.0% 23.0%
105 (49.7%) 67.7% 67.36 11.4% 28.6%
6 (2.9%) 50% 74.25 16.7% 0.0%
19.0%
40.8%
11.8%
60.0%
0.97
1.13
0.80
1.05
AMD ¼ age-related macular degeneration; PCV ¼ polypoidal choroidal vasculopathy; RAP ¼ retinal angiomatous proliferation; VA in logMar ¼ visual acuity in the logarithm of the minimal angle of resolution.
Fig. 1. Distribution of age-related macular degeneration (AMD) subtypes in different age groups. Polypoidal choroidal vasculopathy is predominant in patients younger than 60 years old and typical (AMD) is predominant in patients who are 70 years of age or older.
P.-J. Chen, S.-N. Chen / Taiwan Journal of Ophthalmology 2 (2012) 127e130 Table 3 Comparison of RAP from other studies of age-related macular degeneration. Author
Ethnicity
Mean age (y)
Male sex (%)
Incidence of RAP (%)
Yannuzi et al 2001 [12] Kuerzinger et al 2006 [20] Arai et al 2003 [21] Maruko et al, 2007 [6] Liu et al 2007 [3] Current study
N/A Germany Japanese Japanese Chinese Chinese
80 79 N/A 76.6 64.7 74.3
33.8 N/A N/A 30.8 85 50
10e15 9.79 1.1 4.6 4.5 2.8
N/A ¼ not available; RAP ¼ retinal angiomatous proliferation.
4. Discussion Typical AMD was used as a predominant component for identifying exudative AMD, followed by PCV or RAP.9,10 Recently, more studies have indicated that the incidence rates of PCV in exudative AMD are increasing. Proportions of the exudative AMD subtypes in those studies differ in terms of geography and time.3e7,9 Yannuzzi et al12 reported that PCV and RAP accounted for 7.84% and 10e15% of exudative AMD, respectively, in American patients. In an earlier study (2002) by Kwok et al,7 the proportion of PCV was only 9.3% in Chinese patients, whereas Liu et al3 in 2007 reported that the proportion of PCV had increased to 24.5%, and that of RAP and typical AMD accounted for 4.5% and 67.7%, respectively, among Chinese patients. As for Japanese patients, Sho et al4 reported the incidence of PCV and typical AMD to be 23% and 77%, respectively, in 2003; and according to Maruko et al,6 the proportions were 35.3% for typical AMD, 54.7% for PCV, and 4.5% for RAP. In general, the proportion of PCV is higher and RAP lower in Asians (Tables 3 and 4). In our review, we found similar trends as those in other reports for Asiansdgreater proportion of PCV (49.7%) and less incidence of RAP (2.9%). The ratio of PCV in our study is much higher than that reported in all previous studies on Chinese patients3,7 and similar to a recent report on Japanese patients.6 This is probably because of an increased tendency for the diagnosis of PCV with improved imaging techniques and greater awareness of this disease in recent years. We noted a male predominance in our study on most cases of exudative AMDd75% of all patients with typical AMD, 67.7% of patients with PCV, and 50% of patients with RAP. This is quite different from the female predominance in every subtypes, as reported on Caucasians in Western nations,9,11,12 but comparable to the results of other studies for Asians.3e8,13 Such difference in sex ratio between Oriental and Caucasian individuals is probably attributable to the difference in genotype responsible for AMD.14e18 In our series, the average age of patients with the three subtypes of exudative AMD showed a significant difference in that patients with PCV are the youngest (67.36 9.55 years), and those with RAP and typical AMD are older (74.25 9.18 and 73.37 7.29, years, respectively). Patients younger than 70 years have about
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a 72% chance of having PCV, and patients older than 70 years have more chances of having typical AMD (59.4%). Although the differences in subtype proportions among various age groups have not been well discussed in previous reports, there is a definite trend for patients with RAP to be older and patients with PCV to be younger (Tables 3 and 4). The average age of 108 patients with RAP is 80 years, as reported by Yannuzzi et al,19 compared to 79 years reported by Kuerzinger et al20 and 76.6 years by Maruko et al6 (Table 3). As for PCV, the average age is between mid and late 60s in most reports (Table 4). The age variations in subtype ratios in our case series are either due to the different presentation of the same disease at different ages or simply different diseases at different onset ages. Eyes with PCV had a better mean initial visual acuity (log MAR VA: 0.80) than those with typical AMD and RAP (log MAR VA: 1.13 and 1.05, respectively). This may be either because most patients with PCV are younger and have better basic macular function or because the neovascular tissues in typical AMD and RAP patients are often directly associated with damaged retinal tissue and may have a more rapid and destructive impact on the visual function. However, we also note that initial visual acuity in PCV patients in our review is significantly poorer than that in other reports from Japan and Korea,4e6,8 but closer to that reported on Chinese patients in Hong Kong7 (Table 4). It is not certain if the discrepancy stems from the fact that patients in Taiwan would be referred to the hospital only if they had a more severe degree of visual loss, or because the clinical symptoms of PCV are more acute and fulminant among the Chinese patients. Drusen is noted in 7.6%, 28%, and 50% in fellow eyes unilateral involved eyes of PCV, typical AMD, and RAP patients, respectively, reflecting the difference in pathophysiology and the age factors. Overall, 36.9% of our patients either had disciform scar in the fellow eye noted at the initial clinic or had the same disease noted in both eyes during the follow-up course. Such a high ratio of bilateral exudative disease in our series may be attributable to the limitation of an institutional-based study, which involves more patients having problems in their second eye and are referred to our clinic center. As for treatment, although we do not have a controlled study on the efficacy of the different treatment modalities in our series, we do notice that intravitreal injection of bevacizumab greatly improves the visual outcome in all three disease subtypes, and the improvements are statistically significant (Table 2). Intravitreal injection of bevacizumab achieves the best results when compared to other treatments. Patients with PCV and typical AMD receiving other treatments also have better visual outcome than those under observation only. In summary, male predominance, equal composition of PCV and typical AMD, and a small percentage of RAP are common features of exudative AMD among Taiwanese patients. Close follow-up of fellow eyes will be necessary because one-third of our patients have bilateral eyes involved.
Table 4 Comparison of PCV among known age-related macular degeneration studies. Author
Ethinic group
Mean age (y)
Male sex (%)
Incidence of PCV (%)
Hemorrhagic pattern (%)
Bilaterality (%)
Mean initial VA
Uyama et al 1999 [8] Sho et al 2003 [4] Maruko et al 2007 [6] Byeon et al 2008 [5] Kwok et al 2002 [4] Wen et al 2004 [13] Liu et al 2007 [3] Cackett et al 2009 [22] Current study
Japanese Japanese Japanese Koreans Chinese Chinese Chinese Chinese Chinese
65.7 68.4 72.4 64.6 65.1 68.3 65.4 68.3 67.4
69.0 63.0 77.8 78.5 68.0 73.0 73.0 62.4 67.7
N/A 23.0 54.7 24.6 9.3 22.3 24.5 N/A 49.7
34 30 N/A 48 64 83 N/A N/A 57
9.0 10.0 18.4 24.1 16.0 13.5 23.7 12.2 11.4
0.26 0.31 0.24 0.23 0.67 N/A N/A N/A 0.799
N/A ¼ not available; PCV ¼ polypoidal choroidal vasculopathy; VA ¼ visual acuity.
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Acknowledgment The authors express their special thanks to Professor Maynard Chen.
References 1. Klein R, Klein BEK, Knudtson MD, Wong TY, Cotch MF, Liu K, et al. Revalence of age-related macular degeneration in 4 racial/ethnic groups in the multi-ethnic study of atherosclerosis. Ophthalmology 2006;113:373e80. 2. Chen SJ, Cheng CY, Peng KL, Li AF, Hsu WM, Liu JH, et al. Prevalence and associated risk factor of age-related macular degeneration in an elderly Chinese population in Taiwan: the Shi-Pai eye study. Invest Ophthalmol Vis Sci 2008;49: 3126e33. 3. Liu Y, Wen F, Wang S. Subtype lesions of neovascular age-related macular degeneration in Chinese patients. Graefes Arch Clin Exp Ophthalmol 2007;245: 1441e5. 4. Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, Otsuji T, et al. Polypoidal choroidal vasculopathy: incidence, demographic features and clinical characteristics. Arch Ophthalmol 2003;121:1392e6. 5. Byeon SH, Lee SC, Oh HS, Kim SS, Koh HJ, Kwon OW. Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients. Jpn J Ophthalmol 2008;52:57e62. 6. Maruko I, Iida T, Saito M, Nagayama D, Saito K. Clinical characteristics of agerelated macular degeneration in Japan. Am J Ophthalmol 2007;144:15e22. 7. Kwok AK, Lai TY, Chan CW, Neoh EL, Lam DS. Polypoidal choroidal vasculopathy in Chinese. Br J Ophthalmol 2002;86:892e7. 8. Uyama M, Matsubara T, Fukushima I, Matsunaga H, Iwashita K, Nagai Y, et al. Idiopathic polypoidal vasculopathy in Japanese patients. Arch Ophthalmol 1999;117:1035e42. 9. Yannuzi LA, Wong DW, Sforzolini BS. Polypoidal choroidal vasculopathy and neovasculaized age-related macular degeneration. Retina 1999;117: 1503e10.
10. Cohen SY, Creuzot-Garcher C, Darmon J, Desmettre T, Korobelnik JF, Levrat F, et al. Types of choroidal neovascularisation in newly diagnosed exudative agerelated macular degeneration. Br J Ophthalmol 2007;91:1173e6. 11. Ahuja RM, Stanga PE, Vingerling JR, Reck AC, Bird AC. Polypoidal choroidal vasculopathy in exudative and haemorrhagic retinal pigment epithelial detachment. Br J Ophthalmol 2000;84:479e84. 12. Yannuzzi L, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina 2001;21:416e34. 13. Wen F, Chen C, Wu D, Li H. Polypoidal choroidal vasculopathy in Chinese patients. Graefes Arch Clin Exp Ophthalmol 2004;242:625e9. 14. Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 2006;314: 989e92. 15. Edwards AO, Ritter 3rd R, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science 2005;308:421e4. 16. Xu Y, Guan N, Xu J, Yang X, Ma K, Zhou H, et al. Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese. Mol Vis 2008;14:1373e81. 17. Kim NR, Kang JH, Kwon OW, Lee SJ, Oh JH, Chin HS. Age-related macular degeneration association between complement factor H gene polymorphisms and neovascular age-related macular degeneration in Koreans. Invest Ophthalmol Vis Sci 2008;49:2071e6. 18. Kondo N, Honda S, Ishibashi K, Tsukahara Y, Negi A. LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and in a Japanese population. Am J Ophthalmol 2007;144:608e12. 19. Yannuzzi LA, Negrao S, Iida T, Carvalho C. Retinal angiomatous proliferation in age-related macular degeneration. Retina 2001;21:416e34. 20. Kuerzinger GR, Lang GK, Lang GE. Retinal angiomatous proliferation in age-related macular degeneration. Klin Monatsbl Augenheilkd 2006;223: 691e5. 21. Arai K, Kawamura A, Yuzawa M. Retinal angiomatous proliferation in agerelated macular degeneration. Folia Ophthalmol Jpn 2003;54:513e8. 22. Cackett P, Wong D, Yeo I. A classification system of polypoidal choroidal vasculopathy. Retina 2009.
Contents lists available at SciVerse ScienceDirect
Taiwan Journal of Ophthalmology journal homepage: www.e-tjo.com
Original article
Clinical characteristics of exudative age-related macular degeneration in Taiwan Pao-Ju Chen a, b, San-Ni Chen a, b, * a b
Department of Ophthalmology, Changhua Christian Hospital, Changhua City, Taiwan School of Medicine, Chung Shan Medical University, Taichung, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 May 2012 Received in revised form 17 July 2012 Accepted 16 August 2012 Available online 7 December 2012
Purpose: To describe the clinical features of exudative AMD of patients in Taiwan. Methods: A retrospective case series consisting of 235 eyes in 211 patients, with a male/female ratio of 7:3, mean age 70.36 8.98 years (range 50e86), with exudative AMD, was reviewed at Changhua Christian Hospital, Taiwan. Results: Among the 211 patients, 77 (36.5%) had bilateral involvement of exudative AMD; and of the 235 eyes, 117 (49.7%) were diagnosed with idiopathic PCV, 111 (47.2%) with typical AMD, and seven eyes (2.9%) with retinal angiomatous proliferation. PCV is predominant in patients younger than 70 years (71.8%), whereas typical AMD is prevalent in patients 70 years or older (59.4%). After treatment, mean visual acuity improved in 154 eyes, as reflected in the decreasing logarithm of minimal angle of resolution (log Mar VA)dfrom 0.95 0.60 to 0.84 0.55, whereas in the other 81 eyes without treatment visual acuity deteriorateddlog Mar VA increased from 0.85 0.60 to 1.22 0.53. Conclusion: Male predominance, higher ratio of PCV, and lower ratio of retinal angiomatous proliferation are common features of exudative AMD in Taiwan. Copyright Ó 2012, The Ophthalmologic Society of Taiwan. Published by Elsevier Taiwan LLC. All rights reserved.
Keywords: exudative age-related macular generation PCV RAP typical AMD
1. Introduction Age-related macular degeneration (AMD) was once thought to be not as common in Asians as in Caucasians. However, recent reports have indicated that the prevalence rate for both early and late AMD is similar in Chinese and in Caucasians.1,2 Exudative AMD is now divided into three subgroups: typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). According to previous studies, AMD in Asians exhibits different clinical characteristics compared to that in Caucasians.3e8 The present review discusses the clinical features of exudative AMD among Taiwanese Chinese patients. 2. Materials and methods A retrospective review of patients with exudative AMD was conducted from September 2003 to February 2008 at the Department of Ophthalmology, Changhua Christian Hospitalda referral clinic of AMD in central Taiwan. The review had obtained approval from the institutional review board of Changhua Christian Hospital * Corresponding author. Department of Ophthalmology, Changhua Christian Hospital, Number 35, Nanhsiao Street, Changhua City, Taiwan. E-mail address: [email protected] (S.-N. Chen).
and was conducted in accordance with the provisions of the World Medical Association’s Declaration of Helsinki. Patients with central serous chorioretinopathy, ocular toxoplasmosis, toxocariasis, high myopia, and uveitis-associated choroidal neovascularization, as well as those with disciform scarddetected at the initial clinic examination which made subgroup classification of exudative AMD impossibledwere excluded in this review. Patients’ age, sex, and corrected decimal visual acuity were recorded. Slit lamp biomicroscopy, funduscopy with indirect ophthalmoloscope and 90 D lens, optical coherence tomography (OCT; Stratus, Carl Zeiss Meditec, Inc., Dublin, CA, USA), fluorescein angiography (FA), and indocyanine angiography (ICG) were performed in all patients. According to the findings of two independent retinal specialists (C.S. and L.C.) on fundus photography, FA, ICG, and OCT, eyes were classified into three subtypes of exudative AMD: (1) typical AMD, (2) idiopathic PCV, and (3) RAP. The two specialists were unaware of each other’s subtype classification on each patient; whenever discrepancies occurred, a third reviewer (H.J.) was required to make the final diagnosis. The diagnosis of typical AMD was based on the findings of classic or occult choroidal neovascularization as demonstrated by FA and without the angiographic characteristics of PCV in ICG. Subretinal or sub-RPE neovascularization were noted by OCT. The
2211-5056/$ e see front matter Copyright Ó 2012, The Ophthalmologic Society of Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.tjo.2012.10.002
128
P.-J. Chen, S.-N. Chen / Taiwan Journal of Ophthalmology 2 (2012) 127e130
diagnosis of PCV was based on the findings of funduscopy, ICG, and OCT. Signs of funduscopy included the elevated orange lesions, hemorrhagic retinal pigment epithelial detachment (RPED)dwith or without subretinal hemorrhage, and serous RPED. Findings in OCT included single or multiple bleb and dome-shaped elevated retinal pigment epithelial (RPE) lesions, without subretinal neovascularization detected by OCT. ICG findings included polypoidal lesions, clusters of grapes polyp-like lesions, and aneurysmal dilatation of choroidal vessels. The diagnosis of RAP was based on the findings of feeding arteries and draining venules for intraretinal or subretinal neovascularization in FA and ICG, with or without RPED. Intraretinal neovascularization revealed by OCT would further augment the diagnosis of RAP. Patients were divided into three groups: (1) those treated with intravitreal bevacizumab (Genentech, Inc., South San Francisco, CA, USA) alone or in combination with other treatments if bevacizumab alone was insufficient to cause disease regression; (2) those who received such treatments as gas tamponade with SF6, intravitreal injection of triamcinolone acetonide, subtenon injection of triamcinolone acetonide, transpupillary thermotherapy, continuous wave laser therapy, or photodynamic therapy; and (3) those who were under observation only. Before 2006, all patients had received observation, laser therapy, transpupillary thermotherapy or photodynamic therapy, and intravitreal injection of triamcinolone as the major management method. Later on, most of the patients received intravitreal injections of bevacizumab as the primary therapy. Decimal visual acuity was converted to logarithm of minimal angle of resolution for paired t-test.
3. Results The demographic data of the patients are shown in Table 1. All 211 patients (148 males and 63 females) received follow-up at our clinic for 3 months to 5 years (average: 21.5 11.3 months). All patients were of Chinese ethnicity. Of the 235 eyes reviewed, 111 (in 100 patients) were classified as typical AMD, 117 (in 105 patients) as PCV, and seven (in 6 patients) as RAP. For patients with typical AMD, the mean age was 73.37 7.29 years with a male/female ratio of 3:1; those with PCV had a mean age of 67.36 9.55 years with a 2:1 sex ratio; patients with RAP had an average age of 74.25 9.18 years and a 1:1 sex ratio. For bilaterality, 11 patients with typical AMD, 12 patients with PCV, and one patient with RAP had bilateral disease of the same subtype noted during the initial and follow-up periods. At the first examination, macular scar was not categorized into any of the subtype, and was noted in 23 patients with typical AMD, 30 patients with PCV, and none among patients with RAP.
Table 2 Visual acuity change in the subtypes of patients in different treatment groups. Disease subtypes and treatment group
Initial VA
Final VA
Typical AMD (n ¼ 111) Group 1 (n ¼ 44) Group 2 (n ¼ 27) Group 3 (n ¼ 40) PCV (117) Group 1 (n ¼ 28) Group 2 (n ¼ 53) Group 3 (n ¼ 36) RAP (7) Group 1 (2) Group 3 (5)
1.13 1.09 1.02 1.01 0.80 0.81 0.89 0.67 1.05 1.00 1.07
1.03 0.76 1.10 1.47 0.81 0.68 0.84 0.95 1.78 0.84 1.96
p 0.003 0.256 0.594 0.013 0.241 0.166 0.056 0.013
AMD ¼ age-related macular degeneration; PCV ¼ polypoidal choroidal vasculopathy; RAP ¼ retinal angiomatous proliferation; VA ¼ visual acuity in logarithm of minimal angle of resolution.
In summary, 34 patients (34.0%) with typical AMD, 42 patients (40.0%) with PCV, and one patient (16.7%) with RAP (or 77 of all patients [36.5%]) had bilateral exudative AMD. For patients with unilateral disease, medium or large soft drusen was noted in the fellow eyes in 29 patients (40.8%) with typical AMD, eight eyes (11.8%) in patients with PCV, and three eyes (60%) in patients with RAP. In terms of initial visual acuity, eyes with PCV had the best mean visual acuity in log MAR (0.80) as compared to eyes with typical AMD (1.13) and RAP (1.05). As for treatment efficacy, all eyes that received treatment for exudative AMD (154 eyes) showed improvement in mean log MAR VAdfrom 0.95 0.60 to 0.84 0.55; but for those 81 eyes without treatment, the mean log MAR VA deteriorated from 0.85 0.60 to 1.22 0.53. As for response to different treatment modalities, all three subgroups of patients showed the best response to group 1 treatment (intravitreal injection of bevacizumab with or without other treatment) and less favorable response to group 2 (other treatment). Visual outcome in different treatment groups is listed in Table 2. For each age group, distribution of disease subgroup is noticeably different. Patients younger than 70 years of age had a much higher chance of having PCV (61 in 85 patients, 71.8%), and the incidence of PCV in exudative AMD dropped to 34.9% (44 in 126 patients) for patients who were 70 years or older. In contrast, typical AMD occurred only in 27.6% (23 in 85 patients) of patients under 70 years of age, and for patients 70 or older, the incidence of typical AMD increased to 59.4% (87 in 126 patients). RAP occurred only in 0.6% and 5.7% of patients younger and older than 70, respectively (Fig. 1).
Table 1 Demographic data of patients.
No. of patients (percentage) Male gender Average age (y) Bilaterality Macular scar in fellow eye at initial clinic Drusen in fellow eyes in unilateral involved patients Initial VA in logMar
All
Typical AMD
PCV
RAP
211 (100%) 70% 70.36 11.4% 26.1%
100 (47.3%) 75% 73.37 11.0% 23.0%
105 (49.7%) 67.7% 67.36 11.4% 28.6%
6 (2.9%) 50% 74.25 16.7% 0.0%
19.0%
40.8%
11.8%
60.0%
0.97
1.13
0.80
1.05
AMD ¼ age-related macular degeneration; PCV ¼ polypoidal choroidal vasculopathy; RAP ¼ retinal angiomatous proliferation; VA in logMar ¼ visual acuity in the logarithm of the minimal angle of resolution.
Fig. 1. Distribution of age-related macular degeneration (AMD) subtypes in different age groups. Polypoidal choroidal vasculopathy is predominant in patients younger than 60 years old and typical (AMD) is predominant in patients who are 70 years of age or older.
P.-J. Chen, S.-N. Chen / Taiwan Journal of Ophthalmology 2 (2012) 127e130 Table 3 Comparison of RAP from other studies of age-related macular degeneration. Author
Ethnicity
Mean age (y)
Male sex (%)
Incidence of RAP (%)
Yannuzi et al 2001 [12] Kuerzinger et al 2006 [20] Arai et al 2003 [21] Maruko et al, 2007 [6] Liu et al 2007 [3] Current study
N/A Germany Japanese Japanese Chinese Chinese
80 79 N/A 76.6 64.7 74.3
33.8 N/A N/A 30.8 85 50
10e15 9.79 1.1 4.6 4.5 2.8
N/A ¼ not available; RAP ¼ retinal angiomatous proliferation.
4. Discussion Typical AMD was used as a predominant component for identifying exudative AMD, followed by PCV or RAP.9,10 Recently, more studies have indicated that the incidence rates of PCV in exudative AMD are increasing. Proportions of the exudative AMD subtypes in those studies differ in terms of geography and time.3e7,9 Yannuzzi et al12 reported that PCV and RAP accounted for 7.84% and 10e15% of exudative AMD, respectively, in American patients. In an earlier study (2002) by Kwok et al,7 the proportion of PCV was only 9.3% in Chinese patients, whereas Liu et al3 in 2007 reported that the proportion of PCV had increased to 24.5%, and that of RAP and typical AMD accounted for 4.5% and 67.7%, respectively, among Chinese patients. As for Japanese patients, Sho et al4 reported the incidence of PCV and typical AMD to be 23% and 77%, respectively, in 2003; and according to Maruko et al,6 the proportions were 35.3% for typical AMD, 54.7% for PCV, and 4.5% for RAP. In general, the proportion of PCV is higher and RAP lower in Asians (Tables 3 and 4). In our review, we found similar trends as those in other reports for Asiansdgreater proportion of PCV (49.7%) and less incidence of RAP (2.9%). The ratio of PCV in our study is much higher than that reported in all previous studies on Chinese patients3,7 and similar to a recent report on Japanese patients.6 This is probably because of an increased tendency for the diagnosis of PCV with improved imaging techniques and greater awareness of this disease in recent years. We noted a male predominance in our study on most cases of exudative AMDd75% of all patients with typical AMD, 67.7% of patients with PCV, and 50% of patients with RAP. This is quite different from the female predominance in every subtypes, as reported on Caucasians in Western nations,9,11,12 but comparable to the results of other studies for Asians.3e8,13 Such difference in sex ratio between Oriental and Caucasian individuals is probably attributable to the difference in genotype responsible for AMD.14e18 In our series, the average age of patients with the three subtypes of exudative AMD showed a significant difference in that patients with PCV are the youngest (67.36 9.55 years), and those with RAP and typical AMD are older (74.25 9.18 and 73.37 7.29, years, respectively). Patients younger than 70 years have about
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a 72% chance of having PCV, and patients older than 70 years have more chances of having typical AMD (59.4%). Although the differences in subtype proportions among various age groups have not been well discussed in previous reports, there is a definite trend for patients with RAP to be older and patients with PCV to be younger (Tables 3 and 4). The average age of 108 patients with RAP is 80 years, as reported by Yannuzzi et al,19 compared to 79 years reported by Kuerzinger et al20 and 76.6 years by Maruko et al6 (Table 3). As for PCV, the average age is between mid and late 60s in most reports (Table 4). The age variations in subtype ratios in our case series are either due to the different presentation of the same disease at different ages or simply different diseases at different onset ages. Eyes with PCV had a better mean initial visual acuity (log MAR VA: 0.80) than those with typical AMD and RAP (log MAR VA: 1.13 and 1.05, respectively). This may be either because most patients with PCV are younger and have better basic macular function or because the neovascular tissues in typical AMD and RAP patients are often directly associated with damaged retinal tissue and may have a more rapid and destructive impact on the visual function. However, we also note that initial visual acuity in PCV patients in our review is significantly poorer than that in other reports from Japan and Korea,4e6,8 but closer to that reported on Chinese patients in Hong Kong7 (Table 4). It is not certain if the discrepancy stems from the fact that patients in Taiwan would be referred to the hospital only if they had a more severe degree of visual loss, or because the clinical symptoms of PCV are more acute and fulminant among the Chinese patients. Drusen is noted in 7.6%, 28%, and 50% in fellow eyes unilateral involved eyes of PCV, typical AMD, and RAP patients, respectively, reflecting the difference in pathophysiology and the age factors. Overall, 36.9% of our patients either had disciform scar in the fellow eye noted at the initial clinic or had the same disease noted in both eyes during the follow-up course. Such a high ratio of bilateral exudative disease in our series may be attributable to the limitation of an institutional-based study, which involves more patients having problems in their second eye and are referred to our clinic center. As for treatment, although we do not have a controlled study on the efficacy of the different treatment modalities in our series, we do notice that intravitreal injection of bevacizumab greatly improves the visual outcome in all three disease subtypes, and the improvements are statistically significant (Table 2). Intravitreal injection of bevacizumab achieves the best results when compared to other treatments. Patients with PCV and typical AMD receiving other treatments also have better visual outcome than those under observation only. In summary, male predominance, equal composition of PCV and typical AMD, and a small percentage of RAP are common features of exudative AMD among Taiwanese patients. Close follow-up of fellow eyes will be necessary because one-third of our patients have bilateral eyes involved.
Table 4 Comparison of PCV among known age-related macular degeneration studies. Author
Ethinic group
Mean age (y)
Male sex (%)
Incidence of PCV (%)
Hemorrhagic pattern (%)
Bilaterality (%)
Mean initial VA
Uyama et al 1999 [8] Sho et al 2003 [4] Maruko et al 2007 [6] Byeon et al 2008 [5] Kwok et al 2002 [4] Wen et al 2004 [13] Liu et al 2007 [3] Cackett et al 2009 [22] Current study
Japanese Japanese Japanese Koreans Chinese Chinese Chinese Chinese Chinese
65.7 68.4 72.4 64.6 65.1 68.3 65.4 68.3 67.4
69.0 63.0 77.8 78.5 68.0 73.0 73.0 62.4 67.7
N/A 23.0 54.7 24.6 9.3 22.3 24.5 N/A 49.7
34 30 N/A 48 64 83 N/A N/A 57
9.0 10.0 18.4 24.1 16.0 13.5 23.7 12.2 11.4
0.26 0.31 0.24 0.23 0.67 N/A N/A N/A 0.799
N/A ¼ not available; PCV ¼ polypoidal choroidal vasculopathy; VA ¼ visual acuity.
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P.-J. Chen, S.-N. Chen / Taiwan Journal of Ophthalmology 2 (2012) 127e130
Acknowledgment The authors express their special thanks to Professor Maynard Chen.
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