Interpretation of Fovea Center Morphologic Features in Optical Coherence Tomography

be adjusted after surgery, we intentionally created a suboptimal surgical outcome. We designed the LAL as a safer alternative to conventional intraocular lenses (IOL) because its adjustability allows treatment of refractive surprises after cataract surgery. The anisometropia resulting from refractive surprises can be debilitating, sometimes leading to IOL exchange or further refractive surgery.1 To test the LAL in patients, one possible trial design is to target all eyes for emmetropia and to implant a large number of eyes so that some refractive surprises occur. If the standard deviation of refractive error after IOL implantation is 0.6 diopters (D), we need to implant approximately 270 eyes to generate 5 patients with adjustments of 1.25 D or more. With our study design, we required only 14 patients to generate 5 patients with this magnitude of hyperopic refractive error. Alternatively, trying to achieve emmetropia with preoperative IOL power selection and then adjusting those with refractive surprises requires unnecessarily exposing a large number of study subjects to the potential risks of an investigational device. We believe such a trial design to be unethical. By intentionally targeting patients for residual hyperopic refractive error, we minimized the number of patients exposed to an investigational device. Before initiating the trial, we conducted considerable preclinical work in the laboratory and in animals that validated the precision with which we could correct spherical refractive errors.2 Our first patients were blind ones in whom we successfully corrected postoperative spherical refractive errors. An alternative study design suggested by Downie and associates is that we might have implanted patients at high-risk for postoperative refractive errors such as postrefractive surgery patients or those with marked hyperopia or myopia. Testing postrefractive eyes was not viable because, although our preclinical testing had indicated that our lens adjustment was aberration free, postrefractive eyes already have aberrations, and if our lens had added aberrations, we might have caused a serious visual impairment. Testing short or long eyes in a preliminary study was not viable, because our lens was available only in powers of 16 to 24 D, powers unsuitable for eyes of atypical axial length. All patients gave informed consent to participate in this research study, and the consent specifically addressed the risk of wearing spectacles after surgery and the risk of an IOL exchange. In summary, although we appreciate the ethical questions raised by Downie and associates, our clinical trials with the LAL have been designed to maximize patient safety and to minimize the number of patients exposed to an investigational device. By advocating that any new medical technology be (a priori) at least as good as those already approved for clinical use, the authors put a damper on the entire process of medical innovation for which there are well-established pathways to insure patient safety 474

AMERICAN JOURNAL

and regulatory oversight. We have followed these pathways diligently in developing and testing the LAL. ARTURO CHAYET

Tijuana, Mexico CHRISTIAN A. SANDSTEDT SHIAO H. CHANG

Pasadena, California PAUL RHEE

Lake Forest, California BARBARA TSUCHIYAMA

Pasadena, California DANIEL M. SCHWARTZ

San Francisco, California

REFERENCES

1. Jin GC, Crandall AS, Jones JJ. Intraocular lens exchange due to incorrect lens power. Ophthalmology 2007;114:417– 424. 2. Schwartz DM. Light adjustable lens. Trans Am Ophthal Soc 2003;101:417– 436.

Interpretation of Fovea Center Morphologic Features in Optical Coherence Tomography EDITOR: CONGRATULATIONS TO DR MATSUMOTO AND ASSOCI-

ates for their interesting findings concerning the central foveal thickness as a good indicator for photoreceptor cell damage (visual acuity) in central serous chorioretinopathy patients.1 They defined the term outer nuclear layer thickness to be the distance between the internal limiting membrane and external limiting membrane at the central fovea. They stated that the central fovea included a minimally reflective outer nuclear layer and a very thin and highly reflective layer of Henle.1 However, the anatomy of the central fovea is still quite controversial. Yamada reported that the inner half of the foveola was composed of an inverted cone-shaped zone of Müller cells with light cytoplasm (Müller cell cone).2 Clinical cases of foveal pseudocysts or macular holes support such histologic findings.3,4 Matsumoto and associates proposed that Henle fibers at the central fovea cannot be detected by spectraldomain optical coherence tomography (OCT) because the thickness of the fiber in the central fovea is very thin, although the Henle fiber itself is highly reflective.1 However, visibility of Henle fibers on spectral-domain OCT not only depends on the thickness, but also on the angle at which the illuminating light source hits the fibers. For example, in Figure 1, the outer border of outer plexiform layer cannot be delineated from the outer nuclear layer at the parafoveal area.1 But, in Figure 2, the Henle fibers (outer part of the outer plexiform layer) are well visualized at OF

OPHTHALMOLOGY

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the temporal parafoveal area because the angle between the Henle fibers and light source becomes more perpendicular.1 Thus, the term outer nuclear layer thickness used in their report may be histologically inappropriate and may cause confusion in OCT interpretations. SUK HO BYEON YOUNG KWANG CHU

Seoul, Korea

fovea. It seems reasonable that outer nuclear layer thickness at the central fovea represents that of almost the photoreceptor layer. As reported, retinal histologic analysis of the primate has demonstrated a scant Henle fiber layer at the central fovea,1,3 which is confirmed by spectral-domain optical coherence tomography. We agree that the different intensity of the perifoveal Henle fiber layer in Figure 2 may be the result of the angle between measurement light and the object.4 HIDETAKA MATSUMOTO TAKU SATO SHOJI KISHI

REFERENCES

1. Matsumoto H, Sato T, Kishi S. Outer nuclear layer thickness at the fovea determines visual outcomes in resolved central serous chorioretinopathy. Am J Ophthalmol 2009;148:105– 110. 2. Yamada E. Some structural features of the fovea centralis in the human retina. Arch Ophthalmol 1969;82:151–159. 3. Gass JD. Müller cell cone, an overlooked part of the anatomy of the fovea centralis: hypotheses concerning its role in the pathogenesis of macular hole and foveomacular retinoschisis. Arch Ophthalmol 1999;117:821– 823. 4. Haouchine B, Massin P, Gaudric A. Foveal pseudocyst as the first step in macular hole formation: a prospective study by optical coherence tomography. Ophthalmology 2001;108:15–22.

REPLY WE THANK DRS BYEON AND CHU FOR THEIR INTEREST IN

our article. We appreciate their comment and insights and the issue they have raised. Their comment stimulated our interest about the microstructure of the fovea. A Müller cell is a large glial cell with a columnar structure. It is located between neural elements, which consist of photoreceptors, bipolar cells, and ganglion cells. Except for the fovea, Müller cell stands as perpendicular as a neural element. However, arrangement of the neural element is different in the fovea. Almost all layers of the retina are composed of densely packed cone cells in the foveal floor. The most proximal edge of the bipolar cell layer and ganglion cell layer are at the slope of the foveal pit and measure 350 ␮m and 400 ␮m diameter, respectively.1 Thus, Müller cells run obliquely along with the neural element in the foveal slope. We believe that a Müller cell cone reflects the obliquely arranged Müller cells in the fovea. It is known that the cytoplasm of Müller cells appears light in light microscopy as well as in electron microscopy. We agree that this obliquely arranged Müller cells play a critical role in the formation of macular hole or cystoid macular edema. In optical coherence tomography, even with ultra-high resolution, the outer nuclear layer is seen as a homogeneous layer with low reflectivity, which is no different at the foveal floor and in the perifoveal area.2 Although Müller cells are present in between the photoreceptor cells, an inverted cone-shaped zone is not observed at the VOL. 148, NO. 3

Maebashi, Japan

REFERENCES

1. Fine BS, Yanoff M. The retina. Ocular histology, second edition. Hagerstown, Maryland: Harper & Row, 1979:61–127. 2. Ko TH, Fujimoto JG, Schuman JS, et al. Comparison of ultra-high- and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology 2005; 112:1922–1935. 3. Yamada E. Some structural features of the fovea centralis in the human retina. Arch Ophthalmol 1969;82:151–159. 4. Matsumoto H, Stao T, Kishi S. Outer nuclear layer thickness at the fovea determines visual outcomes in resolved central serous chorioretinopathy. Am J Ophthalmol 2009;148:105–110.

Pulse-Mode Mitomycin C Use in Pterygium Surgery EDITOR: WE READ WITH GREAT INTEREST THE ARTICLE ENTITLED

“Effect of Mitomycin C on Corneal Endothelium in Pterygium Surgery” by Bahar and associates.1 In this prospective, nonrandomized study, in the mitomycin C (MMC) group, a surgical sponge soaked with MMC 0.02% was placed on the exposed sclera for 2 minutes, with the conjunctival layer draped over the sponge. The authors reported that topical use of MMC 0.02% in pterygium surgery caused a decrease in the percentage of hexagonal corneal endothelium at 1 month. Toxic effects of MMC on corneal endothelium have been observed after photorefractive keratectomy,2 after trabeculectomy,3 and after pterygium surgery.4 In an animal study, penetration of MMC into the anterior chamber through deepihthelized cornea was directly proportional to both concentration and duration of exposure.5 We would like to discuss our technique of using MMC in pterygium surgery. To minimize the penetration of MMC into the anterior chamber, we apply a surgical sponge soaked with MMC 0.02% onto bare sclera for a total of 2 minutes, divided in 4 sessions. The length of each

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