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Izumi Yoshida,1,2 Hikari Taniguchi,1 Masashi Sakamoto,1 Takatoshi Maeno1 1Sakura Medical Center, Toho University, Chiba, Japan; 2Toho-Kamagaya Hospital, Kamagaya-shi, Chiba, 273-0132, JapanCorrespondence: Izumi YoshidaSakura Medical Center, Toho University, Sakura-shi, Chiba, 285-8741, JapanTel +81-43-462-8811Fax +81-43-462-8835Email izumi.yoshida@med.toho-u.ac.jpPurpose: To investigate the association between the inclusion of components identified on images in target spots of photodynamic therapy (PDT) and exudate relapse in eyes with age-related macular degeneration (AMD).Methods: Forty-one eyes (39 patients) with polypoidal choroidal vasculopathy (PCV) and 32 eyes (31 patients) with typical AMD (tAMD) who underwent PDT were retrospectively investigated. Each component identified on fluorescein (FA) or indocyanine angiography (IA), optical coherence tomography (OCT), or color photography was graded as not depicted, covered with a margin ≥ 500 μm or < 500 μm, and protruding. Associations between these grades and the dry rate (proportion of subjects with continuous absence of exudate over following 12-month period) and the relapse index (2 × number of injections administered + accumulation of exudate for 12 months post-PDT) were investigated.Results: In PCV, the association between worse coverage and decreasing dry rates for feeder vessels and polyps approached statistical significance. With coverage margins ≥ 500 μm, dry rate tended to be greater than with coverage margins < 500 μm for feeder vessels, classic lesions, and occult lesions on FA. In the tAMD group, coverage with margins ≥ 500 μm tended to yield a higher dry rate than coverage with margins < 500 μm for CNV on IA. Coverage with margins ≥ 500 μm for occult and classic lesions on FA yielded no dry subjects, and all subjects with classic lesions or staining had recurrence (P = 0.009 and 0.050). Worse coverage and worse dry rate in PCV and worse relapse index in tAMD were related to pigment epithelial detachment on OCT (P = 0.040 and 0.006).Conclusion: Polyps in PCV and pigment epithelial detachment (PED) in tAMD were verified as appropriate targets, corresponding to the existing guidelines, and feeder vessels, classic lesion, occult lesion, and PED in PCV and CNV on IA in tAMD were suggested as further targets. OCT was superior to FA for evaluating PED.Keywords: photodynamic therapy, age-related macular degeneration, spot size, angiography

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

Purpose: To evaluate the risk factors for acute atherothrombotic events in patients with exudative age-related macular degeneration (AMD) without a history of coronary artery disease or stroke. Methods: Two hundred fifty-nine patents with exudative AMD were evaluated for carotid atherosclerosis, peripheral arterial disease, and chronic kidney disease (CKD). Results: A mean intima-media thickness of ≥1.0 mm was found in 28.2% of patients; 8.9% of patients had severe carotid artery stenosis. The prevalence rates of severe atherosclerosis with a plaque score >10, peripheral arterial disease, and CKD were 16.6, 5.4, and 32%, respectively. Diabetes mellitus and AMD affecting eyes bilaterally were identified as risk factors for abnormal carotid artery thickening, and age and body mass index were identified as risk factors for CKD. Conclusion: The current study confirmed that potentially 30% of patients with exudative AMD without a history of coronary artery disease or stroke have a high risk of acute atherothrombotic events.

Aim To clarify whether the cardio-ankle vascular index (CAVI) independently contributes to the development of exudative age-related macular degeneration (AMD) compared with carotid arteriosclerosis parameters and other risk factors. Methods Eighty-eight consecutive patients with exudative AMD were enrolled. A control group (40 age-matched men, 65 years of age or older) was also evaluated, and the parameters were compared between the two groups. A logistic regression analysis was used to determine independent factors for the diagnosis of AMD. In addition, simple linear and multiple regression analyses were used to determine the relationships between the CAVI and other parameters. Results The carotid intima-media thickness and plaque scores in the AMD group did not differ significantly from those observed in the control group. The CAVI in the AMD group was significantly (p=0.01) higher than that observed in the control group. A logistic regression analysis showed that the CAVI (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.26-7.20; p=0.007) and the use of lipid-lowering drugs (OR, 0.29; 95% CI, 0.10-0.86; p=0.03) independently contributed to the diagnosis of AMD. Age, the high-sensitivity C-reactive protein level and the incidence of exudative AMD each independently contributed to the CAVI. Conclusions The CAVI is more significantly associated with exudative AMD than carotid atherosclerosis parameters. The overall arterial stiffness is correlated with the pathogenesis of exudative AMD. The CAVI is a useful marker of exudative AMD in elderly patients with arteriosclerosis risk factors.

To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD).Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection.In the ranibizumab group, the mean plasma VEGF levels were 245.7 ± 233.4 pg/ml before the injection, 246.6 ± 304.8 pg/ml after 1 day, 217.8 ± 212.9 pg/ml after 1 week, and 260.0 ± 290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0 ± 170.3 pg/ml before the intravitreal injection and 8.2 ± 12.9 pg/ml after 1 day, 9.1 ± 9.1 pg/ml after 1 week, and 41.9 ± 41.4 pg/ml after 1 month (p 0.0001, vs before injection).Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.