Research Article: Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan

Date Published: February 28, 2019

Publisher: Public Library of Science

Author(s): Tsutomu Yasukawa, Ryusaburo Mori, Miki Sawa, Ari Shinojima, Chikako Hara, Tetsuju Sekiryu, Yuji Oshima, Masaaki Saito, Yukinori Sugano, Aki Kato, Masayuki Ashikari, Yoshio Hirano, Hitomi Asato, Mayumi Nakamura, Kiyoshi Matsuno, Noriyuki Kuno, Erika Kimura, Takeshi Nishiyama, Mitsuko Yuzawa, Tatsuro Ishibashi, Yuichiro Ogura, Tomohiro Iida, Fumi Gomi, Yuhua Zhang.


Abnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.

Sixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as “within,” “close,” and “distant,” based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.

In Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF. In Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

Partial Text

Age-related macular degeneration (AMD) is a progressive retinal degenerative disease and a common cause of blindness and visual disability in elderly patients in developed countries [1]. There are two advanced types of AMD: non-neovascular and neovascular. The former is characterized by retinal pigment epithelium (RPE) death and underlying choriocapillaris loss leading to geographic atrophy (GA) with or without quiescent choroidal neovascularization (CNV), and the latter by exudation from CNV. In late AMD, both types induce cone photoreceptor death, resulting in severe central visual loss. Photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) therapy are currently the standard treatments for neovascular AMD [2–7]. Anti-VEGF therapy effectively sustains or improves the visual acuity (VA) in most patients with neovascular AMD. However, repeated injections are required in many cases and are associated with high cost and possible ocular and systemic complications [8–12]. Because no satisfactory treatment exists for GA, it is important to prevent progression to late AMD. Understanding the clinical features of the earlier stages of AMD and the fellow eyes of those with unilateral neovascular AMD might be essential to develop a new prophylaxis for AMD.

The Japanese Fundus Autofluorescence and Microperimetry in Early Age-Related Maculopathy (JFAM) Study was conducted between December 2006 and July 2009 at five university hospitals in Japan. The study adhered to the tenets of the Declaration of Helsinki. The institutional ethics committees at Nagoya City University Graduate School of Medical Sciences, Nihon University School of Medicine, Osaka University Graduate School of Medicine, Fukushima Medical University School of Medicine, and Kyushu University Graduate School of Medical Sciences reviewed and approved the study protocol. Patients provided written informed consent before entry into the study.

It is generally difficult to assess progression of clinical findings such as drusen and pigment changes in eyes with early-to-intermediate AMD, while the incidence of AMD definitely increases with age [7,13,14]. The Age-Related Eye Disease Study (AREDS) Research Group created the AMD categories based on abnormal findings seen on color fundus photographs. Category 4, the most severe condition, is characterized by unilateral CNV or GA and in the fellow eye the VA is 20/32 or better [35]. Another study reported that the probability of progression to bilateral advanced AMD was 24.4% at 2 years in eyes with category 4, which was much higher than other categories [36]. However, in Japanese populations, the prevalence of late AMD is slightly lower than in Caucasians [7,13,24–28,35,36]. Moreover, PCV is predominant and unilateral in many cases, while the prevalence rates of RAP and GA, which often affect both eyes, are much lower [28–32]. Because an aim of the current study was to identify eyes with a potential for transition of unilateral neovascular AMD to bilateral neovascular AMD, we enrolled patients without neovascular AMD but abnormal FAF in one eye and neovascular AMD in the other eye. In the current study, six (9.1%) eyes progressed to neovascular AMD during the 12-month follow-up, which might be comparable to the results of the AREDS study. Five of the six eyes were evaluated by fundus photography. All five eyes had soft drusen and four eyes had hyperpigmentation (Table 4).

The patchy pattern of abnormal FAF predominates in Japanese populations as in Caucasian populations. In contrast, the reticular pattern was seen much less frequently in Japanese patients, which is consistent with the low rate of atrophic AMD in Japan. Abnormal FAF might be a valuable finding as are drusen and pigment changes in eyes with early-to-intermediate AMD and eyes with a fellow eye with late AMD. Microperimetry might be useful to assess macular function in these eyes, predict the progression to advanced stages of AMD, and assess the efficacy of possible prophylactic treatments in future studies.




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