May 12, 2011 - High-resolution spectral-domain optical coherence tomography (SD OCT) .... between photoreceptor layer thickness and best-corrected visual.
The Functional Significance of Foveal Abnormalities in Albinism Measured Using Spectral-Domain Optical Coherence Tomography Sarim Mohammad, BSc,1,* Irene Gottlob, MD,1,* Anil Kumar, MRCOphth,1 Mervyn Thomas, BSc,1 Christopher Degg, PhD,2 Viral Sheth, BMedSci,1 Frank Antony Proudlock, PhD1 Purpose: The relationship between foveal abnormalities in albinism and best-corrected visual acuity (BCVA) is unclear. High-resolution spectral-domain optical coherence tomography (SD OCT) was used to quantify foveal retinal layer thicknesses and to assess the functional significance of foveal morphologic features in patients with albinism. Design: Cross-sectional study. Participants: Forty-seven patients with albinism and 20 healthy control volunteers were recruited to the study. Methods: Using high-resolution SD OCT, 7⫻7⫻2-mm volumetric scans of the fovea were acquired (3-m axial resolution). The B scan nearest the center of the fovea was identified using signs of foveal development. The thickness of each retinal layer at the fovea and foveal pit depth were quantified manually using ImageJ software and were compared with BCVA. Main Outcome Measures: Total retinal thickness, foveal pit depth, photoreceptor layer thickness, and processing layer thickness in relation to BCVA. Results: Total photoreceptor layer thickness at the fovea was correlated highly to BCVA (P ⫽ 0.0008; r ⫽ – 0.501). Of the photoreceptor layers, the outer segment length was correlated most strongly to BCVA (P⬍0.0001; r ⫽ – 0.641). In contrast, there was no significant correlation between either total retinal thickness or pit depth and BCVA (P⬎0.05). This was because of an inverse correlation between total photoreceptor layer thickness and total processing layer thickness (P⬍0.0001; r ⫽ – 0.696). Conclusions: Neither the total retinal thickness nor the pit depth are reliable indicators of visual deficit, because patients with similar overall retinal thickness had widely varying foveal morphologic features. In albinism, the size of the photoreceptor outer segment was found to be the strongest predictor of BCVA. These results suggest that detailed SD OCT images of photoreceptor anatomic features provide a useful tool in assessing the visual potential in patients with albinism. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:1645–1652 © 2011 by the American Academy of Ophthalmology.
Albinism is a group of congenital disorders in melanin biosynthesis that affects approximately 1 in 4000 people in the United Kingdom.1 The condition can be divided broadly into 2 categories, oculocutaneous albinism and ocular albinism. In oculocutaneous albinism, there is a reduction or absence of melanin in the hair, skin, and eyes, whereas in ocular albinism, the melanin deficiency is limited mainly to the eyes.2 The ocular manifestations associated with albinism include reduced or absent foveal pit, nystagmus, iris transillumination, macular transparency, strabismus, refractive errors, and optic nerve misrouting. High-resolution imaging of the retina using optical coherence tomography (OCT), now available in many ophthalmology services, provides the capability of generating high-quality, reproducible, objective measurements of foveal morphologic features. However, contro© 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
versy exists over whether there is any clinical value to the retinal abnormalities measured using OCT, such as absent or diminished foveal depression, continuation of the inner retinal layers, and lack of specialization of foveal photoreceptors. Harvey et al3 found a weak inverse correlation (r ⫽ – 0.21) between total retinal thickness and visual acuity, although only 11 volunteers were included in this study. Marmor et al4 characterized the foveal pit as visually insignificant, suggesting that photoreceptor specialization at the fovea, which can take place without the formation of a foveal pit, is the most important determinant of vision. However, this study was based on 4 subjects, of whom only 2 were suspected as having albinism. The same conclusion was reached by McAllister et al5 on observation of 6 patients with albinism. ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2011.01.037
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Seo et al6 suggested that apart from anatomic anomalies, ocular hypopigmentation also plays a part in the poor vision seen in albinism. They developed a grading system that took into account both of these factors and identified 4 key OCT abnormalities in the fovea of patients with albinism, namely absent foveal depression, foveal hyporeflectivity, choroidal transillumination, and the appearance of a double hyperreflective layer at the junction of the retina and the choroid (which they termed the tram-tract sign). They concluded that this grading system had greater predictive value of visual function compared with grading systems based on iris transillumination and macular transparency. However, the sample size (n ⫽ 13) was too small to draw any statistically significant conclusions. In addition, Chong et al7 suggested that some of the features on which Seo et al based their grading system, such as the tram-tract sign and hyporeflectivity of the photoreceptor layers, might have been the result of the low resolution of images from time-domain (TD) OCT. Apart from lower resolution, TD OCT also has a slower scan acquisition time, making it prone to motion artifacts in patients with eye-movement disorders. Based on their observations in 12 volunteers, Chong et al suggested that an alternative grading system using higher-resolution OCT should be devised. This should incorporate the absence of central foveal depression, persistence of ganglion and plexiform retinal layers, persistence of the nerve fiber layer, and a very prominent image of the entire choroid as key features. Previous studies investigating OCT and albinism used relatively small sample sizes and were unable to show a conclusive relationship between retinal morphologic features and visual acuity. The present study used spectraldomain (SD) OCT with an axial resolution of 3 m and a B-scan acquisition time of 23 ms to compare foveal abnormalities in a group of 47 volunteers with albinism. Cone outer segment length was correlated strongly to visual acuity. Also, the thickness of photoreceptor layers was correlated inversely to the size of the remaining retinal layers, reducing the significance of overall macular thickness as a useful clinical measure.
The diagnosis was based on patients showing all 3 signs of visual evoked potential asymmetry, diminished foveal reflex on clinical fundus examination, and iris transillumination. Visual evoked potential testing was carried out in accordance with International Society for Clinical Electrophysiology of Vision standards. Although not included as diagnostic criteria, all patients included in the study exhibited nystagmus (range, 0.6 –14.5° amplitude) on eye movement recordings (250 Hz; EyeLink pupil tracker, SR Research, Osgoode, Canada). In a number of patients, the nystagmus was of low amplitude (27.5% of the patients included had nystagmus of ⬍2° amplitude). Twenty healthy control volunteers (age range, 23– 48 years; mean age, 36.7 years) with no known ophthalmic or neurologic disease were recruited from within the ophthalmology departments at the University of Leicester and the University Hospitals of Leicester NHS Trust. Snellen acuity charts were used to test uniocular and binocular BCVA, and results were converted to logarithm of minimum angle of resolution (logMAR) for the purposes of statistical analysis.
Scan Acquisition A high-resolution SD OCT device (SOCT Copernicus HR; OPTOPOL Technology S.A., Zawiercie, Poland), with a theoretical axial resolution of 3 m and a transverse resolution of 12 to 18 m in tissue, was used to obtain 3-dimensional cross-sectional images of the macula of both eyes in all the volunteers. Each 3-dimensional scan consisted of 75 B scans, with each B scan being 7 mm wide and 2 mm deep and containing 750 A scans with a distance of 0.09 mm between successive B scans. The acquisition time for each B scan was 23 ms, with the result that motion artifact caused by the nystagmus was minimal (e.g., during the slow phase of a typical jerk nystagmus of 5° and 3.5 Hz, the average motion artifact is 1.25% of scan width). B scans acquired during nystagmus quick phases were identified from discontinuities in the alignment of the retinal vasculature between successive B scans and were excluded from the analysis. High-quality macular scans of both eyes were obtained in 44 of the 47 albinism patients. In 3 pediatric patients, we were able to image only 1 eye because of poor cooperation. In one of the patients with good scans bilaterally, the left eye had to be excluded because of a detachment of the retinal pigment epithelium (RPE) in the foveal region. All 20 control volunteers provided highquality scans.
Image Analysis
Patients and Methods Patients Twenty-eight male and 19 female albinism patients (age range, 7–54 years; mean age, 26.8 years) were recruited from pediatric and adult neuro-ophthalmology clinics at the Leicester Royal Infirmary between September 2009 and April 2010. Before inclusion in the study, informed consent was sought from each participant after explaining the nature and consequences of the study. For volunteers younger than 18 years, consent was obtained from parents or guardians as well as assent being obtained from the children. The study was conducted in keeping with the Declaration of Helsinki protocols and was approved by the local research and ethics committee. The sample size was based on pilot data from the number of patients with albinism required to show a correlation between photoreceptor layer thickness and best-corrected visual acuity (BCVA) at a significance level of P ⫽ 0.01 (power, 90%; r ⫽ 0.5; ⫽ – 0.0037; ␦X ⫽ 29.2 m).
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The images were inspected visually, and the fovea was identified based on signs of foveal development such as the presence of a rudimentary pit, thinning of the inner retinal layers, doming of the outer nuclear layer, and lengthening of the photoreceptor outer segments (Fig 1). The most robust sign for the identification of the fovea in patients with albinism was thickening of the outer segment layer (OSL). Although this often was not as localized, as in control volunteers, all patients with albinism displayed some thickening, permitting the center of the thickening to be used as a marker. B scans were flattened along the RPE using the manufacturer’s software to minimize any inaccuracies in the measurement of layer thickness. The thickness of each layer was measured using ImageJ (National Institutes of Health, Bethesda, MD; available at: http://rsbweb.nih.gov/ij/; accessed March 17, 2010) by manually identifying each layer at the fovea. Pit depth was estimated from the difference between the retinal thickness at the fovea and the mean of retinal thicknesses at 1 mm nasal and temporal to the fovea.
Mohammad et al 䡠 Predicting VA in Albinism Using SD OCT
Figure 1. Optical coherence tomography images showing signs of foveal development. A, Rudimentary foveal pit. B, Outer nuclear layer (ONL) thickening. C, Increased outer segment (OS) length. BCVA ⫽ bestcorrected visual acuity.
The retinal layers were subdivided into processing layers and photoreceptor layers, where the processing layers consisted of the nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer; whereas the photoreceptor layers consisted of the outer nuclear layer (ONL), the inner segment, and the OSL. The RPE was considered separately from the 2 aforementioned groups. In 43 patients, measurements from both eyes were available, and these were averaged, whereas in the remaining 4 patients, data from just 1 eye were used. The thickness of retinal layers in the 2 groups was compared using the Mann–Whitney U test. The total retinal thickness (sum of all photoreceptor and processing layers), foveal pit depth, the total thickness of the photoreceptor layers, and the total thickness of the processing layers were correlated with visual acuity using Spearman’s rank correlation. Statistical analyses were carried out using SPSS software version 16.0 (SPSS, Inc., Chicago, IL).
In comparison, all the eyes in the control group had a welldeveloped foveal pit, showed thickening of the outer nuclear layer, and had a complete discontinuation of the nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer. The outer plexiform layer was the only processing layer found in the control group, although this was significantly thicker in the patients with albinism (P ⫽ 6.06⫻10–9). Of the photoreceptor layers, the OSL was the only significantly thinner layer in the patients with albinism (P ⫽ 3.12⫻10–9) as compared with controls. There were no significant differences in the thickness of the ONL, inner segment, and RPE between the 2 groups (P⬎0.05). Figure 3 summarizes the thickness of each of the retinal layers in the albinism and control groups, illustrating the area of analysis on representative examples. In the patients with albinism, the thicknesses of all the processing layers were correlated positively with each other, as were the thicknesses of all the photoreceptor layers (P⬍0.05). However, there was strong inverse correlation between the total thickness of the photoreceptor and processing layers (r ⫽ 0.690; P ⫽ 1.03⫻10–7), as illustrated in Figure 4. Figure 5 displays the contribution of each of the retinal layers to the overall macular thickness, with the volunteers organized in descending order according to the thickness of photoreceptor layers. The figure clearly demonstrates that despite having a similar overall foveal thickness, patients with albinism may have vastly different foveal morphologic features. Albinism patients on left of the figure show photoreceptor morphologic features that are closest to normal, although retinal thicknesses are among some of the thickest in the group. Neither total retinal thickness (r ⫽ – 0.232; P ⫽ 0.144) nor pit depth (r ⫽ – 0.245; P ⫽ 0.122) were correlated significantly to BCVA (Fig 6). In contrast, both total processing layer thickness (r ⫽ 0.364; P ⫽ 0.019) and total photoreceptor layer thickness (r ⫽ – 0.501; P ⫽ 8.36⫻10– 4) were correlated to BCVA. The correlation was much stronger for the total photoreceptor layer
Results For patients with albinism, BCVA ranged from 0.18 to 1.0 logMAR (mean, 0.57 logMAR), with a peak in frequency between 0.5 and 0.6 logMAR. Figure 2 illustrates the distribution of visual acuities seen in the albinism group. All controls had a BCVA of better than 0.0 logMAR. The foveal retina was thicker in the albinism group (total thickness, 309⫾24.0 m) compared with the control group (total thickness, 206⫾15.0 m; P ⫽ 5.19⫻10–10. Visual inspection of the OCT scans revealed that although none of the patients with albinism had a fully developed foveal pit, 17 displayed a rudimentary foveal depression. The nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer continued through the fovea in all patients with albinism.
Figure 2. Bar graph showing the distribution of best-corrected visual acuity in patients with albinism. The visual acuity is provided in logarithm of minimal angle of resolution (logMAR) units.
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Discussion Using a large sample size, the results of this study provide quantitative evidence for the functional significance of foveal photoreceptors in the retina of patients with albinism. Photoreceptor outer segment length was found to be the strongest predictor of visual acuity. In contrast, there was no significant relationship between either total retinal thickness or foveal pit depth and visual acuity. This lack of correlation was the result of the relationship between the total thickness of photoreceptor layers and the total thickness of processing layers, where increasing total thickness of photoreceptor layers was associated with decreasing total thickness of processing layers. This meant that the degree of deviation away from normal foveal morphologic features was not related to overall retinal thickness. Given that the most obvious abnormalities on a cursory viewing of OCT images from patients with albinism are the absent or diminished foveal pit and retinal thickening, it would be easy to assume that these features are be associated with poor visual function. Although one previous study suggested no relationship between foveal thickness and visual acuity,8 Harvey et al3 found a weak inverse correlation (r ⫽ – 0.21). However, both of these studies used a small number of patients (n ⫽ 13 and n ⫽ 11, respectively). The present findings agree with the correlation coefficient reported by Harvey et al: the current study also finds a weak negative correlation (r ⫽ – 0.23). Harvey et al speculated that such weak correlation is possibly the result of the difficulty they had in imaging the macula with a TD OCT
Figure 3. A, Comparison of typical optical coherence tomography (OCT) scans from albino and control patients. The inset on the right illustrates the various retinal layers. GCL ⫽ ganglion cell layer; INL ⫽ inner nuclear layer; IPL ⫽ inner plexiform layer; IS ⫽ inner segment; NFL ⫽ nerve fibre layer; ONL ⫽ outer nuclear layer; OPL ⫽ outer plexiform layer; OS ⫽ outer segment; RPE ⫽ retinal pigment epithelium. B, Bar graph illustrating the mean thickness of each retinal layer at the fovea in both the albino and control groups. The error bars indicate the standard deviation (SD). Apart from the outer plexiform layer, no other processing layers were present in the control group. The outer segment length was significantly smaller in the albino group.
thickness, and also total photoreceptor layer thickness increased with improving visual acuity (i.e., lower logMAR scores), whereas total processing layer thickness decreased with improving visual acuity. When considering photoreceptor layers individually, both foveal OSL thickness (r ⫽ – 0.641; P ⫽ 6.31⫻10– 6) and ONL
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Figure 4. Plot of total photoreceptor layer thickness against processing layer thickness at the fovea for 47 patients with albinism. Data from both eyes was averaged where available.
Mohammad et al 䡠 Predicting VA in Albinism Using SD OCT
Figure 5. Bar chart illustrating the contribution of processing layers (red colors) and photoreceptor layers (blue colors) to overall retinal thickness. Each bar represents an individual patient or control subject. The data from both eyes was averaged except in four patients with albinism where data from only one eye was available. The patients are organized in descending order of photoreceptor layer thickness. The albinism patients are on the left and the controls are on the right. GCL ⫽ ganglion cell layer; INL ⫽ inner nuclear layer; IPL ⫽ inner plexiform layer; IS ⫽ inner segment; NFL ⫽ nerve fibre layer; ONL ⫽ outer nuclear layer; OPL ⫽ outer plexiform layer; OS ⫽ outer segment; RPE ⫽ retinal pigment epithelium.
device used in their study, which has a long scan acquisition time, giving rise to motion artifact in patients with nystagmus.3 However, this study provides conclusive evidence that total macular thickness is not a good predictor of visual acuity using a higher-resolution SD OCT device with a faster scan acquisition time and a larger patient group. The present findings agree with those of Chong et al7 regarding the Seo et al grading system; however, Chong et al did not comment on the importance of photoreceptor specialization in their proposed grading system. During foveal development, cone cells undergo extensive morphogenesis.9 At fetal week 11, the cone photoreceptors are cuboidal, changing to a thin, elongated shape in the adult.10 This facilitates centripetal migration of peripheral cones, and the density of cone cells at the fovea increases from 11 200/mm2 at fetal week 11 to approximately 200 000/mm2 in the adult eye.11–13 According to Marmor et al,4 the fine spatial vision provided by the fovea is dependent on both postnatal lengthening and spatial packing of
cones in this region, but they claim that the foveal pit plays little part in providing good vision. The correlation of visual acuity with both OSL (an indicator of postnatal cone lengthening) and ONL (an indicator of spatial packing of cones) observed in the current study, together with the poor correlation between the foveal pit size and visual acuity, provides strong evidence that their suggestions are accurate. The authors agree with the recommendation from McAllister et al5 that while assessing the fovea in patients with albinism, rather than using qualitative terms such as foveal hypoplasia and fovea plana, a more quantitative approach needs to be taken. Because the OSL was found to be the strongest predictor of visual acuity, this is considered to be the most important measurable indicator of functional vision currently available from OCT recordings. The present results show that foveal thickness is higher in patients with albinism compared with controls. Macular thickness in patients with albinism has been quantified previously by 5 groups as 219 m (n ⫽ 13),6 233 m (n ⫽
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Figure 6. Scatterplots showing the comparison of binocular best-corrected visual acuity (BCVA) with (A) the total thickness of the foveal retina, (B) foveal pit depth, (C) processing layer thickness, (D) photoreceptor layer thickness, (E) outer nuclear layer thickness, and (F) outer segment length at the fovea. In 43 patients with albinism from whom data from both eyes was available, this was averaged, whereas in the remaining 4 patients, data from 1 eye was used. The visual acuity is provided in logarithm of minimal angle of resolution (logMAR) units. OS ⫽ outer segment.
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Mohammad et al 䡠 Predicting VA in Albinism Using SD OCT 11),3 240.4 m (n ⫽ 10),14 247 m (n ⫽ 13),8 and 300 m (n ⫽ 1).15 In the current study, the albinism group had a mean retinal thickness of 309 m (standard deviation, 24.0 m), which is at the higher end of the range quoted in previous studies. This may be because TD OCT has a longer acquisition time, leading to greater movement artifact, which would bias successful recordings from patients with less severe nystagmus. Also, comparison of SD OCT and TD OCT in the past has shown that TD OCT devices reported smaller measurements of retinal thickness compared with SD OCT devices.16 –18 The mean foveal thickness of 206 m (standard deviation, 15.8) in the control group is comparable with that of previous SD OCT studies of the normal fovea.16 –18 During embryonic development, the processing layers migrate centrifugally to form the foveal pit.19 However, there is a lack of consensus in previous literature regarding the relationship between foveal pit formation and photoreceptor specialization. Springer20 proposed that photoreceptor specialization cannot occur without a foveal pit. In contrast, Marmor et al4 and McAllister et al5 both found that individuals without a foveal pit can exhibit significant cone specialization. The current study found a negative correlation between the size of the photoreceptor layers and the thickness of processing layers, indicating that a relationship between foveal pit formation and photoreceptor specialization does exist. The pattern of visual acuities seen in the albinism group is similar to what has been described previously in studies that contain a large cohort of individuals with albinism.21,22 Although some studies have reported the presence of a significant percentage of albinism patients without nystagmus, the diagnosis is not confirmed in these studies using either visual evoked potential asymmetry or genetic testing.4,5,23 It is possible that a few of these studies may favor the inclusion of patients with minimal nystagmus to improve the quality of OCT recordings.3–5 The use of eye movement recordings confirmed the presence of nystagmus in all of the current patients, in accordance with the findings of Summers,22 who found 39 of 40 albinism patients to exhibit nystagmus. The current study found that nystagmus oscillations in excess of 10° amplitude did not prevent successful capture of high-quality OCT images because of the rapid acquisition of single B scans. In summary, this study provides quantitative evidence of the functional significance of OCT recordings in albinism. In particular, the photoreceptor layers, especially the OSL, are correlated strongly to visual acuity. Because nystagmus associated with albinism also leads to deterioration in vision because of motion blur, these findings indicate that OCT has a clinical use in recognizing patients who have potential for visual improvement as a result of treatments to reduce nystagmus intensity, such as pharmacologic interventions.24,25 With the rapid development of OCT technology, it is likely that high-resolution hand-held OCT devices soon will be available clinically. These may allow the visualization of photoreceptor morphologic features in neonates, possibly enabling us to assess the future potential for vision and the need for early intervention.
References 1. Sarvananthan N, Surendran M, Roberts EO, et al. The prevalence of nystagmus: the Leicestershire nystagmus survey. Invest Ophthalmol Vis Sci 2009;50:5201– 6. 2. Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis [serial online] 2007;2:43. Available at: http://www.ojrd.com/content/pdf/1750-11722-43.pdf. Accessed January 7, 2011. 3. Harvey PS, King RA, Summers CG. Spectrum of foveal development in albinism detected with optical coherence tomography. J AAPOS 2006;10:237– 42. 4. Marmor MF, Choi SS, Zawadzki RJ, Werner JS. Visual insignificance of the foveal pit: reassessment of foveal hypoplasia as fovea plana. Arch Ophthalmol 2008;126:907–13. 5. McAllister JT, Dubis AM, Tait DM, et al. Arrested development: high-resolution imaging of foveal morphology in albinism. Vision Res 2010;50:810 –7. 6. Seo JH, Yu YS, Kim JH, et al. Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism. Ophthalmology 2007;114:1547–51. 7. Chong GT, Farsiu S, Freedman SF, et al. Abnormal foveal morphology in ocular albinism imaged with spectral-domain optical coherence tomography. Arch Ophthalmol 2009;127:37– 44. 8. Holmstrom G, Eriksson U, Hellgren K, Larsson E. Optical coherence tomography is helpful in the diagnosis of foveal hypoplasia. Acta Ophthalmol 2010;88:439 – 42. 9. Bumsted K, Hendrickson A. Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea. J Comp Neurol 1999;403:502–16. 10. Hendrickson AE. Primate foveal development: a microcosm of current questions in neurobiology. Invest Ophthalmol Vis Sci 1994;35:3129 –33. 11. Curcio CA, Allen KA, Sloan KR, et al. Distribution and morphology of human cone photoreceptors stained with antiblue opsin. J Comp Neurol 1991;312:610 –24. 12. Yuodelis C, Hendrickson A. A qualitative and quantitative analysis of the human fovea during development. Vision Res 1986;26:847–55. 13. Diaz-Araya C, Provis JM. Evidence of photoreceptor migration during early foveal development: a quantitative analysis of human fetal retinae. Vis Neurosci 1992;8:505–14. 14. Izquierdo NJ, Emanuelli A, Izquierdo JC, et al. Foveal thickness and macular volume in patients with oculocutaneous albinism. Retina 2007;27:1227–30. 15. Meyer CH, Lapolice DJ, Freedman SF. Foveal hypoplasia in oculocutaneous albinism demonstrated by optical coherence tomography. Am J Ophthalmol 2002;133:409 –10. 16. Leung CK, Cheung CY, Weinreb RN, et al. Comparison of macular thickness measurements between time domain and spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2008;49:4893–7. 17. Grover S, Murthy RK, Brar VS, Chalam KV. Comparison of retinal thickness in normal eyes using Stratus and Spectralis optical coherence tomography. Invest Ophthalmol Vis Sci 2010;51:2644 –7. 18. Carpineto P, Nubile M, Toto L, et al. Correlation in foveal thickness measurements between spectral-domain and timedomain optical coherence tomography in normal individuals. Eye (Lond) 2010;24:251– 8. 19. Hendrickson AE, Yuodelis C. The morphological development of the human fovea. Ophthalmology 1984;91:603–12. 20. Springer AD. New role for the primate fovea: a retinal excavation determines photoreceptor deployment and shape. Vis Neurosci 1999;16:629 –36.
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21. Anderson J, Lavoie J, Merrill K, et al. Efficacy of spectacles in persons with albinism. J AAPOS 2004;8:515–20. 22. Summers CG. Vision in albinism. Trans Am Ophthalmol Soc 1996;94:1095–155. 23. Wolf AB, Rubin SE, Kodsi SR. Comparison of clinical findings in pediatric patients with albinism and different amplitudes of nystagmus. J AAPOS 2005;9:363– 8.
24. Bagheri A, Aletaha M, Abrishami M. The effect of horizontal rectus muscle surgery on clinical and eye movement recording indices in infantile nystagmus syndrome. Strabismus 2010;18: 58 – 64. 25. McLean R, Proudlock F, Thomas S, et al. Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin. Ann Neurol 2007;61:130 – 8.
Footnotes and Financial Disclosures Originally received: September 16, 2010. Final revision: January 11, 2011. Accepted: January 11, 2011. Available online: May 12, 2011.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2010-1276.
1
Ophthalmology Group, University of Leicester, Leicester, United Kingdom.
2
Medical Physics Department, Leicester Royal Infirmary, Leicester, United Kingdom. *Mr. Mohammad and Dr. Gottlob contributed equally as the senior authors of this article.
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Supported by the Wolfson Foundation, London, UK, and the Ulverscroft Foundation, Leister, UK. The sponsor or funding organization had no role in the design or conduct of this research. Correspondence: Frank Antony Proudlock, PhD, Ophthalmology Group, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, P.O. Box 65, Leicester LE2 7LX, United Kingdom.