Intraocular Lenses in Children

Ophthalmology Volume 116, Number 9, September 2009 free triamcinolone acetonide (pfTA) partially alleviated the efficacy decrease observed with bevacizumab alone.” However, we noticed some limitations in the study design and interpretation of data. The dose of bevacizumab as a monotherapy (2.5 mg/100 ml) was double that combined with pfTA. The bevacizumab injections were administered in 3 monthly intervals rather than monthly, which is standard practice. These factors (dose and administration frequency) may affect the potential for tachyphylaxis as the authors note in the discussion. Furthermore, a different number of injections were administered to each individual. It also seems that not all participants in group C completed a full year of treatment as initially planned. We agree that the possibility of tachyphylaxis is very interesting and the need for a prospective study is apparent. This should include analysis of treatment benefit (visual acuity), as well as the structural changes measurable in the macula and examine the effect of monotherapy with antivascular endothelial growth factor agents but without the potential mitigating effect of corticosteroid. KONSTANTINOS N. AVGIKOS, MD SIMON E. HORGAN, FRCS, FRCOPHTH RAMESH R. SIVARAJ, MS, DNB, FRCS KUANG HU, MA, MB, BCHIR, PHD, MRCOPHTH London, UK Reference 1. Schaal S, Kaplan HJ, Tezel TH. Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 2008;115:2199 –205.

as an internal control and eliminated the impact of bevacizumab dosing differences between groups. In other words, each repeated injection with the same drug(s) should create a similar response in the absence of tachyphylaxis. However, in the presence of bevacizumab we noticed a decrease in the response with repeated injections that was partially reduced with the addition of triamcinolone. Our study certainly was not aimed to answer whether mitigation of tachyphylaxis was due to the presence of triamcinolone or a decreased dose bevacizumab. We also did not find any difference in the number of intravitreal injections between the 2 groups that developed tachyphylaxis, i.e., bevacizumab alone and with triamcinolone. As stated in the article, all patients in our cohort had at least 3 intravitreal injections and had 1-year of treatment and follow-up. The average number of intravitreal triamcinolone injections remained relatively low (3.7⫾0.7) compared with other treatment regimens since these patients never exhibited less of a response on repeated injection than the initial response. We disagree with using visual acuity as a primary outcome measure for tachyphylaxis because of the well established disparity between functional and anatomical outcome in patients with exudative age-related macular degeneration.5 Several explanations may account for this observation but the foremost would be the subjectivity of visual acuity and the confounding effects of media opacities. Assessing tachyphylaxis requires an objective outcome measurement and optical coherence tomography is ideal for this purpose. We thank Dr. Avgikos et al for their interest in our study and giving us a chance to clarify their concerns. SHLOMIT SCHAAL, MD, PHD HENRY J. KAPLAN, MD TONGALP H. TEZEL, MD Louisville, Kentucky

Author reply Dear Editor: We thank Avgikos et al for their comments on our article. In contrast to their claim, we believe there is not an accepted “standard practice” for the intravitreal injection of bevacizumab.1 If the dosing schedule of bevacizumab was only based only on the amount of endogenous vascular endothelial growth factor (VEGF) in the ocular media, the amount injected (2.5 mg) would still remain 2-log units more than the endogenous VEGF levels after 3 months,2 and this amount would exceed the median inhibition concentration for endothelial cell proliferation and migration.3 However, previous clinical experience indicated that doses even as low as 3-log units less than traditional amounts (6.2 ␮g) can also exert anti-angiogenic activity in the retina,4 indicating that binding and neutralizing VEGF may not be the only mechanism by which bevacizumab works. Such observations may be the reason for a plethora of different intravitreal bevacizumab regimens in clinical practice.1 Our current preference is to inject the medication every 3 months to avoid any unnecessary clinical risks, as well as the increased cost and discomfort of intravitreal injections. We studied tachyphylaxis in patients that received 3 different treatment regimens for exudative macular degeneration. The biological response of each patient was gauged as a quotient of the initial response. The longitudinal comparison design of the study allowed us to use each eye itself

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References 1. Schouten JS, La Heij EC, Webers CA, et al. A systematic review on the effect of bevacizumab in exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2009;247:1–11. 2. Zhu Q, Ziemssen F, Henke-Fahle S, et al. Vitreous levels of bevacizumab and vascular endothelial growth factor-A in patients with choroidal neovascularization. Ophthalmology 2008; 115:1750 –5. 3. Wang Y, Fei D, Vanderlaan M, et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 2004;7:335– 45. 4. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113:1695. 5. Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143:566 – 83.

Intraocular Lenses in Children Dear Editor: The article entitled “Long-term results of scleral fixation of posterior chamber intraocular lenses in children” published in January 2008 in Ophthalmology is an interesting article

Letters to the Editor highlighting an important issue.1 We seek a few clarifications from the authors. The authors mention that best corrected visual acuity improved in 12 eyes (48%) by more than 1 Snellen line. It actually comes within the test-retest variability of Snellen’s chart. Again it is mentioned that mean minimum angle of resolution decreased from preoperative values of 0.67⫾0.46 to 0.42⫾0.36 at final visit with P value being 0.001. There is overlap of their 95% confidence intervals, which makes this difference less reliable (0.486 – 0.854 and 0.276 – 0.564). The most glaring finding of the paper we feel is that, there was late spontaneous dislocation in 6 eyes (24%) after 7 to 10 years and resurgery was necessary in 8 (32%) eyes. It is not clear from the article how the authors have come to a conclusion that the dislocation was due to breakage and not slippage of the polypropylene suture. One important issue we would like to highlight here is the rationale for use of polypropylene suture for scleral fixation of posterior chamber intraocular lenses. We could not find any evidence supporting its use, but still it is used widely in practice. It is well established from older studies that polypropylene undergoes biodegradation in eye,2 and very little fibrosis occurs around the haptic and suture3 making intraocular lens fixation mainly dependent upon the suture material. We feel that the choice of polypropylene needs to be seriously reconsidered for scleral fixated intraocular lenses. NIRANJAN PEHERE, MS RAMESH MURTHY, MD, FRCS Hyderabad, India References 1. Asadi R, Kheirkhah A. Long-term results of scleral fixation of posterior chamber intraocular lenses in children. Ophthalmology 2008;115:67–72. 2. Altman AJ, Gorn RA, Craft J, Albert DM. The breakdown of polypropylene in the human eye: is it clinically significant? Ann Ophthalmol 1986;18:182–5. 3. Lubniewski AJ, Holland EJ, Van Meter WS, et al. Histologic study of eyes with transsclerally sutured posterior chamber intraocular lenses. Am J Ophthalmol 1990;110:237– 43.

Author reply Dear Editor: We appreciate the comments of Pehere and Murthy regarding our article, “Long-term results of scleral fixation of posterior chamber intraocular lenses in children.”1 We totally agree that test-retest measurements of visual acuity (VA) can vary by 1 Snellen line in the pediatric age group and even in adults. Therefore, in our article an increase of best-corrected visual acuity (BCVA) by more than 1 Snellen line was considered as improvement. This was mainly chosen to facilitate comparison of our results to previous studies, which were generally on primary implants, whereas our cases were mostly secondary implantation in traumatic eyes. In addition, although there is an overlap between 95% confidence intervals for mean preoperative and postoperative values of BCVA, what made this difference significant was the improvement of BCVA in each individual patient. There is no doubt that the overall final BCVA levels were

far from normal values, which were mainly due to coexistent corneal and retinal pathologies and related amblyopia. As mentioned in our article, 6 eyes (24%) developed late spontaneous dislocation of intraocular lens (IOL) and in all of these eyes, the IOL was subsequently explanted. The presence of breakage and not slippage of the polypropylene suture was clearly seen during the explantation surgery. The same problem has also been observed in another recent study.2 In our article, we discussed the disadvantages of sclera fixation of the IOL with 10-0 polypropylene sutures in detail with lack of perihaptic fibrosis and biodegradation of suture material. In addition, the alternatives to this procedure including the use of 9-0 polypropylene or the iris-fixated IOL have been mentioned. We agree that further research is needed to find an ideal method for fixation of IOL in children without sufficient capsular support. REZA ASADI, MD AHMAD KHEIRKHAH, MD Tehran, Iran References 1. Asadi R, Kheirkhah A. Long-term results of scleral fixation of posterior chamber intraocular lenses in children. Ophthalmology 2008;115:67–72. 2. Buckley EG. Safety of transscleral-sutured intraocular lenses in children. J AAPOS 2008;12:431–9.

Diabetic Macular Edema Dear Editor: We read with great interest the article, “A randomized trial comparing intravitreal triamcinolone acetonide and focal/ grid photocoagulation for diabetic macular edema,” by the DRCR network group1 published in this journal. Over the 2-year follow-up period, the authors found focal/grid photocoagulation to be more effective than either 1 mg or 4 mg intravitreal triamcinolone for patients with diabetic macular edema. We have some comments relating to the authors’ findings. The authors’ conclusions are based on the data given in Table 4 of the article showing mean change in the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score compared among the 3 treatment groups. At 2 years, pairwise comparison showed a significantly greater positive treatment response in laser-treated eyes than those after intravitreal triamcinolone acetonide (laser vs. 1 mg triamcinolone P ⫽ 0.02; laser vs. 4 mg triamcinolone P ⫽ 0.002). However, if we look at the interquartile ranges (IQRs) of the ETDRS letter score of the 3 groups (laser: [-6, 11]; 1 mg triamcinolone [-11, 9]; 4 mg triamcinolone [-11, 11]), a significant overlap is noted, making the 3 groups comparable in terms of change in best-corrected visual acuity (BCVA). Moreover, approximately 60% of patients in any of the 3 groups had a baseline BCVA 20/63 or better. The expected change in BCVA in this group of patients is within test retest variability of ETDRS chart, hence making comparisons between the groups difficult. Furthermore, the type of diffuse diabetic macular edema and its relative distribution among the 3 groups has not been

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