6. Clark RA, Demer JL. Functional morphometry of horizontal rectus extraocular muscles during ocular duction. Invest Ophthalmol Vis Sci 2012;53(11):7375–7379. 7. Demer JL, Poukens V, Ying H, Shan X, Tian J, Zee DS. Effects of intracranial trochlear neurectomy on the structure of the primate superior oblique muscle. Invest Ophthalmol Vis Sci 2010;51(7):3485–3493.
Short-Term Changes in Choroidal Thickness After Aflibercept Therapy for Neovascular Age-Related Macular Degeneration EDITOR: I READ WITH GREAT INTEREST A RECENT ARTICLE BY
Koizumi and associates entitled ‘‘Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration.’’1 The study demonstrated a marked decrease in choroidal thickness in eyes treated with intravitreal aflibercept. Moreover, the amount of decrease after aflibercept therapy seems to be greater than the values reported after ranibizumab treatment. The authors of this study postulated that reduction in choroidal vascular permeability from fenestrated vascular walls and the narrowing of choroidal vessels may partially influence the observed change in choroidal thickness.1 Although their study provides useful information, one important piece of data is missing: changes in choroidal thickness in eyes with retinal angiomatous proliferation (RAP). It is well known that the choroid is prominently thinned in eyes with RAP.2,3 Some investigators have postulated that compromised choroidal perfusion owing to choroidal thinning may influence the development of this peculiar type of neovascularization.2 In addition, thinner choroids in RAP were found to be associated with increased risk of geographic atrophy after anti– vascular endothelial growth factor treatment.4 If marked choroidal thinning is also noted after intravitreal aflibercept therapy in RAP eyes, I suspect a possible negative influence of aflibercept on choroidal perfusion in RAP, which may already show thinned choroids. To date, little knowledge is available regarding intravitreal aflibercept treatment outcome in RAP.5,6 In addition, no previous study has reported changes in choroidal thickness following intravitreal aflibercept therapy in RAP. Fortunately, in the study by Koizumi and associates,1 indocyanine green angiography was routinely performed. Re-analysis of the indocyanine green angiography results in the typical neovascular AMD group may reveal some RAP cases. Although a relatively small number of RAP cases may not provide firm evidence regarding changes in choroidal thickness, I believe that presenting choroidal thickness data in VOL. 160, NO. 1
this cohort may provide useful information for clinicians as well as investigators who are interested in RAP. JAE HUI KIM
Seoul, South Korea THE AUTHOR HAS COMPLETED AND SUBMITTED THE ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. This work was supported by Kim’s Eye Hospital Research Center, Seoul, South Korea.
1. Koizumi H, Kano M, Yamamoto A, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration. Am J Ophthalmol 2015; 159(4):627–633. 2. Kim JH, Kim JR, Kang SW, Kim SJ, Ha HS. Thinner choroid and greater drusen extent in retinal angiomatous proliferation than in typical exudative age-related macular degeneration. Am J Ophthalmol 2013;155(4):743–749. 3. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal choroidal thickness in retinal angiomatous proliferation. Retina 2014;34(7):1316–1322. 4. Cho HJ, Yoo SG, Kim HS, et al. Risk factors for geographic atrophy after intravitreal ranibizumab injections for retinal angiomatous proliferation. Am J Ophthalmol 2015;159(2):285–292. 5. Oishi A, Tsujikawa A, Yamashiro K, et al. One-year result of aflibercept treatment on age-related macular degeneration and predictive factors for visual outcome. Am J Ophthalmol 2015;159(5):853–860.e1. 6. Tsaousis KT, Konidaris VE, Banerjee S, Empeslidis T. Intravitreal aflibercept treatment of retinal angiomatous proliferation: a pilot study and short-term efficacy. Graefes Arch Clin Exp Ophthalmol 2015;253(4):663–665.
REPLY WE WOULD LIKE TO THANK DR KIM FOR SHOWING INTEREST
in our article.1 As the author pointed out, we did not include the cases with retinal angiomatous proliferation (RAP) in our study owing to its rarity. Our study was conducted as a multicenter study with 3 university hospitals, and at each institute the eyes with RAP were treated by its own established protocol; 2 institutes applied the combined therapy of photodynamic therapy with verteporfin followed by intravitreal aflibercept injection, whereas 1 institute used aflibercept monotherapy. As a result, only 1 eye of a 76-year-old woman with RAP was treated with 3 monthly intravitreal aflibercept injections during the study period. Accordingly, we have decided not to include the patients with RAP in our study. Just as a reference, in the only 1 eye with RAP that was ultimately excluded, subfoveal choroidal thickness decreased from 158 mm to 151 mm at 1 month, 139 mm at 2 months, and 130 mm at 3 months, after 3 monthly intravitreal aflibercept injections. The percentage change in subfoveal choroidal
thickness during 3 months was 82.3%. Although the decrease in choroidal thickness may not necessarily reflect the decrease in choroidal blood flow,2 we should keep in mind the possibility of detrimental effect on the already thin choroid seen in eyes with RAP.3,4 It is not possible to draw a definite conclusion at this time, and further studies with a large number of cases are warranted. HIDEKI KOIZUMI AKIKO YAMAMOTO ICHIRO MARUKO ANNABELLE A. OKADA TOMOHIRO IIDA
Tokyo, Japan MARIKO KANO MASAAKI SAITO TETSUJU SEKIRYU
Fukushima, Japan RYO KAWASAKI
Yamagata, Japan CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINAL article for any disclosures of the authors.
1. Koizumi H, Kano M, Yamamoto A, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration. Am J Ophthalmol 2015; 159(4):627–633. 2. Sogawa K, Nagaoka T, Takahashi A, et al. Relationship between choroidal thickness and choroidal circulation in healthy young subjects. Am J Ophthalmol 2012;153(6):1129–1132. 3. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal choroidal thickness in retinal angiomatous proliferation. Retina 2014;34(7):1316–1322. 4. Kim JH, Kim JR, Kang SW, Kim SJ, Ha HS. Thinner choroid and greater drusen extent in retinal angiomatous proliferation than in typical exudative age-related macular degeneration. Am J Ophthalmol 2013;155(4):743–749.
Outbreak of Late-Onset Toxic Anterior Segment Syndrome After Implantation of One-Piece Intraocular Lenses
The authors have, therefore, recommended that companies that produce IOLs should be aware of the risk of contamination by heavy metals such as aluminum and should exercise extreme caution in manufacturing the IOLs. We thank the authors for their excellent work and would like to make some contributions with respect to heavy metal toxicity of the retina, which can be seen together with toxic anterior segment syndrome (TASS) caused by these metals. First, the authors report that none of the patients had any fundus abnormalities on the fundus examination even though vitreous opacities were found in 21.5% of the patients.1 However, it has been reported that aluminum toxicity can cause a toxic retinopathy that can be detected by an electrophysiological examination such as an electroretinogram (ERG).2,3 Also, the literature that is currently available provides little knowledge about aluminum toxicity of the retina. Therefore, it is important to determine whether aluminum toxicity could affect the retinas in patients with IOLs that had been contaminated with aluminum. Since the study by Suzuki and associates uses data collected from questionnaires that were issued directly to the 183 clinical centers where the contaminated IOLs had been used, the authors might not have been able to obtain electrophysiological findings for all the patients. However, the difference between the initial and final best-corrected visual acuities of the patients who underwent surgical treatment, which reduced the levels of aluminum in their eyes, can be compared to the values of the patients who had received only medical treatment. This might provide a proof of aluminum toxicity of the retina. If the statistical results provide a clue to the retinal toxicity, an electroretinographic examination might be required for all the patients who had only medical treatment. If the electroretinographic results for the eyes with the IOLs that had been contaminated with aluminum indicate pathologic findings in patients who had only medical treatment, these patients might be followed through ERGs to rule out ongoing retinal damage from the aluminum as well. In addition, this article also contains a minor inconsistency in terms of the patients’ genders. It states that there were 89 male patients (89 affected eyes) and 162 female patients (162 affected eyes). However, this is not what is shown in Table 1. Finally, we would like to congratulate the authors for this most interesting study and hope that our scientific contribution will provide a further contribution to the literature, especially in terms of TASS caused by heavy metals. SABAN GONUL
EDITOR: WE HAVE READ WITH GREAT INTEREST THE ARTICLE BY
BANU TURGUT OZTURK
Suzuki and associates entitled ‘‘Outbreak of Late-onset Toxic Anterior Segment Syndrome After Implantation of Onepiece Intraocular Lenses.’’1 The article describes the occurrence of late-onset ocular inflammation caused by intraocular lenses (IOLs) that had become contaminated with aluminum as a result of a damaged instrument used in the IOL factory.
THE AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. The authors indicate no funding support.
AMERICAN JOURNAL OF OPHTHALMOLOGY