- Email: [email protected]
Accommodation Measured with Optical Coherence Tomography in Patients with Marfan's Syndrome
Accommodation Measured with Optical Coherence Tomography in Patients with Marfan’s Syndrome Tiina Rysä Konradsen, MD,1,2 Annemari Koivula, MD, PhD,1,2 Maria Kugelberg, MD, PhD,1,2 Charlotta Zetterström, MD, PhD3 Purpose: To evaluate accommodation in patients with Marfan’s syndrome using optical coherence tomography (OCT). Design: Clinical case-control study. Participants and Controls: The study included 31 eyes of 31 patients with Marfan’s syndrome and 31 eyes of 31 unaffected controls. Subgroups of eyes of patients with Marfan’s syndrome with and without a subluxated lens also were compared. Methods: The changes in the anterior segment during accommodation and cycloplegia were studied with OCT. Main Outcome Measures: Accommodative power, anterior chamber depth (ACD), lens thickness, and pupil diameter. Results: No difference in accommodative power or ACD were found between the groups (P⬎0.05). The lens was thicker in the presence of Marfan’s syndrome (P ⫽ 0.017 at baseline; P ⫽ 0.043 during accommodation; P ⫽ 0.046 during dilatation). The baseline pupil diameter was smaller in patients with Marfan’s syndrome (P ⫽ 0.01), decreased less during accommodation (P ⫽ 0.02), and increased more during dilatation compared with controls (P⬍0.01). No difference was found in these variables between the subgroups of eyes of patients with Marfan’s syndrome with and without a subluxated lens (P⬎0.05). Conclusions: The results of this study suggested that even though the pupil and crystalline lens are affected in patients with Marfan’s syndrome, these patients have the same ability to accommodate as normal subjects. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2009;116:1343–1348 © 2009 by the American Academy of Ophthalmology.
Marfan’s syndrome, the most common genetic connective tissue disorder, causes symptoms in virtually all organ systems. Typical symptoms include tall stature, arachnodactyly (spiderlike fingers and toes), aortic dilatation, scoliosis, and hernias. The estimated incidence of this syndrome is about 2 to 3 per 100,000 births; there is no gender, racial, or ethnic predilection.1,2 Many affected individuals have a mutation in chromosome 15, encoding for the matrix protein fibrillin-1, which is an important part of the connective tissue. However, this does not include all individuals with the syndrome, and, therefore, genetic testing alone is not sufficiently specific to establish a diagnosis. The diagnosis is based on a combination of typical symptoms, a family history of Marfan’s syndrome, and genetic testing, according to the Ghent criteria.3 Dislocation of the crystalline lens is a major criterion for Marfan’s syndrome, and it has been reported to occur in about 60% of patients with Marfan’s syndrome.4 Other known ocular features in Marfan’s syndrome, which are minor criteria for diagnosing the syndrome, are increased axial length, abnormally flat corneas, and a hypoplastic iris causing decreased miosis. The question arises regarding dislocation of the crystalline lens and the consequent ability to accommodate, but © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
there are few devices to measure this in clinical practice. A relatively new device to study the anterior segment in real time is anterior segment optical coherence tomography (OCT). It has been used for ⬎10 years in refractive surgery5–7 and for diagnosis of angle-closure glaucoma.8 Baikoff et al9 studied accommodation in a normal population using Visante OCT (Carl Zeiss, Jena, Germany) and concluded that it is a user-friendly instrument for imaging the anterior segment. It has also been shown to have good repeatability and reproducibility.10,11 However, to the best of our knowledge, the ocular changes in Marfan’s syndrome including accommodation have not been studied previously with Visante OCT. The aim of this study was to determine the changes in the anterior segment during accommodation and after administration of cyclopegic drops in patients with Marfan’s syndrome using Visante OCT.
Methods Subjects Patients were recruited in cooperation with the Departments of Cardiology and Clinical Genetics at the Karolinska University ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.01.023
1343
Ophthalmology Volume 116, Number 7, July 2009 Hospital, Stockholm, Sweden. These departments have records on most known patients diagnosed with Marfan’s syndrome in the region of Stockholm (population 1.9 million in 2007). A total of 100 letters including information about the study were sent to possible candidates, who were asked to contact the research group if they were willing to participate. Family members with a diagnosis of Marfan’s syndrome also were invited to participate. A second reminder letter was sent if the patients did not respond. All patients had a diagnosis of Marfan’s syndrome based on the Ghent criteria.3 The study was approved by the local ethics committee. All patients were provided with written and oral information about the study, and written informed consent was provided by each patient. For patients ⬍18 years of age, written informed consent was provided by a parent. The more myopic eye of each patient was included in the study. The inclusion criteria were age ⱖ12 years and a best-corrected logarithm of the minimum angle of resolution visual acuity of ⫹0.3 or better to enable focusing on the fixation point in the Visante OCT. The exclusion criterion was a previous intraocular or corneal surgery. Fifty-six individuals were examined for participate in the study, and 31 of these met the inclusion criteria. Individuals who did not have Marfan’s syndrome served as the control group and they were matched with patients in the study group for mean age and spherical refraction. Controls were recruited from among the hospital staff and their families. As in the study group, the more myopic eye of each control subject was included. The exclusion criteria were the same as for the patients.
Design and Methods of Measurement This clinical case-control study was carried out at St. Erik’s Eye Hospital in Stockholm, Sweden. All measurements were performed from January to December 2007. Before the assessment with Visante OCT, the manifest refraction and best-corrected visual acuity were measured. Visual acuity was tested with the Early Treatment of Diabetic Retinopathy Study (logarithm of the minimum angle of resolution) chart. The anterior segment was scanned with Visante OCT at baseline and during accommodation and dilatation (Fig 1). All assessments were carried out by an ophthalmic nurse who was specially trained in the use of the device, and the images were analyzed by an ophthalmologist. At baseline, the manifest refraction was used during scanning with the Visante OCT. Two images of the anterior segment in the
Figure 2. Superonasal dislocation of the crystalline lens in Marfan’s syndrome.
unaccommodated state were assessed: The first was focused on the anterior chamber and the second was focused on the crystalline lens. Quadruple image sections were assessed to obtain crosssectional images at 0, 45, 90, and 135 degrees. These 2 series of images then were assessed during maximal accommodation and dilatation. Accommodation is stimulated with Visante OCT by defocusing the visual object inside the device and gradually adding negative power in front of the patient’s eye as long as the patient still has a clear image of the object. After the accommodative measurements, a combination drop of 0.75% cyclopentolate and 2.5% phenylephrine was used for dilatation. As we determined in preliminary testing, the difference in the anterior chamber depth (ACD) in the 4 cross-sections was minimal; only measurement in the horizontal axis was included. The pupil diameter and lens thickness, however, varied more in the 4 cross-sections, and, therefore, the mean value of each variable in the 4 cross-sections was analyzed. The ACD, pupil diameter, and lens thickness were measured in millimeters. The lens thickness was measured at the thickest point of the lens. The accommodative power was measured as the difference in diopters (D) between the spherical equivalent during accommodation and at baseline. The primary study outcomes were the accommodative power in the patients compared with the controls and the ACD, pupil diameter, and lens thickness at baseline and during accommodation and dilatation. To determine if lens subluxation affects the results, the subgroups of patients with and without subluxation also were compared. Subluxation of the crystalline lens was determined by visible dislocation or iridophacodonesis on slit-lamp examination or by astigmatism of ⱖ1 D at a site other than the cornea (Fig 2).
Statistical Analysis
Figure 1. Visante optical coherence tomography (OCT) is a noncontact, high-resolution tomographic device used for in vivo imaging and measurement of ocular structures in the anterior segment. It provides crosssectional images of the anterior segment, using 1310-nm light waves. An OCT image of the anterior segment of a 19-year-old man with Marfan’s syndrome (refraction, ⫺1.75 ⫺1.75 ⫻ 90) at baseline.
1344
Before starting the study, we estimated the lowest clinically relevant differences and the size of each group to show those differences. For accommodation, we estimated that a difference of 1.5 D (with ␣ ⫽ 0.05 and  ⫽ 0.2) between the Marfan eyes and the controls eyes would require about 30 patients in each group. Further, according to our calculations, a difference between the groups in the change in the ACD from the nonaccommodative state to accommodation of 0.1 mm (with ␣ ⫽ 0.05 and  ⫽ 0.2) would require 26 patients in each group. Statistical analyses were performed using the Student t test. P⬍0.05 was considered significant.
Konradsen et al 䡠 Accommodation Measured with OCT in Marfan’s Syndrome Table 1. Baseline Data from Patients and Controls
Patients, n Gender Male Female Age, yrs* Spherical refraction* (D)
No. Gender Male Female Age, yrs* Spherical refraction* (D)
Marfan’s Syndrome
Controls
31
31
15 16 35.4 (12.7–63.8) ⫺3.3 (⫺17.5 to ⫹1.5)
13 18 34.1 (11.9–61.6) ⫺2.3 (⫺10.3 to ⫹2.5)
0.74 0.30
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
P
15
16
10 5 35.1 (13.3–63.8) ⫺3.6 (⫺115 to ⫺0.75)
5 11 35.6 (12.7–63.3) ⫺3.0 (⫺17.5 to ⫹1.5)
P
0.92 0.67
*Age and spherical refraction are expressed as the mean (range).
Results
between the eyes of the patients with Marfan’s syndrome with and without a subluxated lens (Table 2).
Age and Refraction Of the 56 individuals who contacted us, 31 patients with Marfan’s syndrome (15 men, 16 women) met the inclusion criteria; 31 unaffected individuals (13 men, 18 women) served as the control group. The ages and spherical refractions of the 2 groups did not differ significantly (Table 1). The eyes of the patients with Marfan’s syndrome then were divided into subgroups—those with and without a subluxated lens—and those groups also did not differ in age or spherical refraction (Table 1).
Accommodative Power The accommodative power was the change in the refractive power (spherical equivalent) between baseline and maximal accommodation. In Marfan’s syndrome the mean (⫾ standard deviation [SD]) spherical equivalent was ⫺3.5⫾4.0 D at baseline and ⫺10.1⫾5.0 D during full accommodation, with a total accommodative power of ⫺6.6⫾2.2 D. In the control group, the mean spherical equivalent changed from ⫺2.6⫾3.2 D at baseline to ⫺9.4⫾4.0 D during full accommodation, with an accommodative power of ⫺6.8⫾2.3 D. There was no difference between the groups (Table 2). There was also no difference
Anterior Chamber Depth In the eyes of patients with Marfan’s syndrome, the ACD decreased from 2.92⫾0.35 mm (mean ⫾ SD) at baseline to 2.83⫾0.32 mm during accommodation (P⬍0.01) and increased to 3.05⫾0.39 mm during dilatation (P⬍0.01). In the control group, the measurements were 3.05⫾0.35 mm at baseline, 2.93⫾0.32 mm during accommodation (P⬍0.01), and 3.17⫾0.34 mm during dilatation (P⬍0.01). There was no significant difference between the groups (Table 3). There was also no difference in the ACD between the eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 3).
Lens Thickness In the eyes of patients with Marfan’s syndrome, the lens was thicker at all time points, changing from 4.27⫾0.56 mm at baseline to 4.39⫾0.49 mm during accommodation (P⬍0.01) and 4.19⫾0.58 mm during dilatation (P⬍0.01). The respective values for the control group were 3.97⫾0.38 mm, 4.18⫾0.30 mm (P⬍0.01), and 3.94⫾0.38 mm (P⬎0.05; Table 4). All differences between the groups were significant (P ⫽ 0.017 at baseline; P ⫽
Table 2. Spherical Equivalent at Baseline and during Accommodation, and Accomodative Power Spherical Equivalent (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Accomodative power
⫺3.5⫾4.0 ⫺10.1⫾5.0 ⫺6.6⫾2.2
⫺2.6⫾3.2 ⫺9.4⫾4.0 ⫺6.8⫾2.3
⫺0.96 (⫺2.82 to 0.89) ⫺0.71 (⫺3.03 to 1.60) 0.25 (⫺0.89 to 1.39)
0.30 0.54 0.66
Spherical Equivalent (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Accomodative power
⫺3.6⫾3.2 ⫺10.5⫾4.2 ⫺6.6⫾2.2
⫺3.0⫾5.0 ⫺9.7⫾5.8 ⫺6.5⫾2.2
⫺0.65 (⫺3.76 to 2.47) ⫺0.80 (⫺4.5 to 2.97) ⫺0.13 (⫺1.75 to 1.49)
0.67 0.67 0.87
CI ⫽ confidence interval for difference of mean values.
1345
Ophthalmology Volume 116, Number 7, July 2009 Table 3. Anterior Chamber Depth (ACD) in Patients and Controls and from the Eyes with Marfan’s Syndrome with and without a Subluxated Lens ACD, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation
2.92⫾0.35 2.83⫾0.32 3.05⫾0.36
3.05⫾0.35 2.93⫾0.32 3.17⫾0.34
⫺0.12 (⫺0.30 to 0.05) ⫺0.10 (⫺0.27 to 0.06) ⫺0.12 (⫺0.31 to 0.06)
0.17 0.21 0.18
ACD, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation
2.93⫾0.40 2.84⫾0.37 3.04⫾0.46
2.91⫾0.31 2.83⫾0.28 3.05⫾0.32
0.02 (⫺0.24 to 0.28) 0.005 (⫺0.24 to 0.25) ⫺0.02 (⫺0.31 to 0.27)
0.87 0.25 0.27
CI ⫽ confidence interval for difference of mean values.
0.043 during accommodation; P ⫽ 0.046 during dilatation). However, no difference in lens thickness was found between the subgroups of eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 4).
Pupil Diameter In the eyes of patients with Marfan’s syndrome, the mean pupil diameters varied from 4.53⫾1.30 mm at baseline, decreased to 3.70⫾1.17 mm during accommodation (P⬍0.01), and increased to 7.12⫾0.96 mm during dilatation (P⬍0.01). In the control group, the values were 5.27⫾0.99 mm at baseline, 3.93⫾0.92 mm during accommodation (P⬍0.01), and 6.90⫾0.84 mm during dilatation (P⬍0.01). The pupil size in the eyes of patients with Marfan’s syndrome at baseline was significantly smaller (P ⫽ 0.01). In the eyes of patients with Marfan’s syndrome, the pupil size decreased less during accommodation (P ⫽ 0.02) and increased more during dilatation compared with controls (P⬍0.01; Table 5). However, there was no difference in pupil diameter between the subgroups of the eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 5).
Discussion Lens subluxation is a well known feature of Marfan’s syndrome. However, little is known about accommodation in
Marfan’s syndrome. Maumenee4 used Prince’s rule and a letter target with 11 patients with Marfan’s syndrome and found that accommodation was normal for age. In the current study, we evaluated accommodation in a larger group of patients with Marfan’s syndrome and compared the results with controls matched for age and spherical refraction. To the best of our knowledge, anterior segment OCT has not been used previously in studies of Marfan’s syndrome, and therefore no comparison with previous results was possible. Baikoff et al9 used OCT to study accommodation in a normal population. Those investigators reported the same forward movement of the anterior lens surface and pupil contraction during accommodation as in the current study. Those authors also analyzed variations in these variables owing to age and grade of ametropia, which we did not, making a comparison of the results of the 2 studies difficult. In addition, eyes with a phakic refractive lens have been studied with Visante OCT, and significant forward movement of the anterior lens surface occurred during accommodation.6 Marfan’s syndrome is a relatively rare condition, and many of these patients have undergone ocular surgery. Despite this, we were able to include 31 patients in the study who were well matched with the controls for age and refraction. Only 1 person performed all assessments in a
Table 4. Lens Thickness in Patients an Controls, and from Eyes with Marfan’s Syndrome with and without a Subluxated Lens Lens Thickness, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation
4.27⫾0.56 4.39⫾0.49 4.19⫾0.58
3.97⫾0.38 4.18⫾0.30 3.94⫾0.38
0.30 (0.06 to 0.54) 0.21 (0.007 to 0.42) 0.25 (0.004 to 0.50)
0.017* 0.043* 0.046*
Lens Thickness, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation
4.39⫾0.67 4.49⫾0.57 4.30⫾0.70
4.17⫾0.43 4.30⫾0.40 4.09⫾0.42
0.22 (⫺0.19 to 0.62) 0.19 (⫺0.17 to 0.55) 0.21 (⫺0.21 to 0.63)
0.29 0.29 0.32
CI ⫽ confidence interval for difference of mean values. *Significant difference.
1346
Konradsen et al 䡠 Accommodation Measured with OCT in Marfan’s Syndrome Table 5. Pupil Diameter in Patients and Controls, and from Eyes with Marfan’s Syndrome with and without a Subluxated Lens Pupil Diameter, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation Difference baseline accommodation Difference from baseline dilatation
4.53⫾1.30 3.70⫾1.17 7.12⫾0.96 ⫺0.83⫾0.65 2.59⫾1.04
5.27⫾0.99 3.93⫾0.92 6.90⫾0.84 ⫺1.34⫾1.02 1.63⫾0.80
⫺0.74 (⫺1.32 to ⫺0.15) ⫺0.22 (⫺0.76 to 0.31) 0.23 (⫺0.23 to 0.69) 0.51 (0.08 to 0.95) 0.96 (0.49 to 1.44)
0.01* 0.40 0.33 0.02* 0.0001*
Pupil Diameter, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation Difference from baseline accommodation Difference from baseline dilatation
4.49⫾1.43 3.58⫾1.25 7.11⫾1.09 ⫺0.91⫾0.71
4.57⫾1.20 3.82⫾1.11 7.13⫾0.85 ⫺0.74⫾0.59
⫺0.07 (⫺1.04 to 0.89) ⫺0.25 (⫺1.11 to 0.62) ⫺0.02 (⫺0.73 to 0.70) ⫺0.17 (⫺0.65 to 0.31)
0.88 0.57 0.97 0.47
2.62⫾1.20
2.56⫾0.92
0.06 (⫺0.72 to 0.84)
0.88
CI ⫽ confidence interval for difference of mean values. *Significant difference.
standardized manner, which minimized the risk of a random error. Nevertheless, the current study had some limitations, one of which was the imprecise determination of the exact endpoint of accommodation with OCT. It has been reported that OCT used to measure subjective accommodation might overestimate the true objective accommodation.12 The subjective minus-lens-to-blur method also was shown to induce accommodation, even in pseudophakic eyes.13 These facts, together with instrumental myopia14 that causes increased accommodation when the subject is aware of the short distance to the visual object, might have contributed to higher values of accommodation than if accommodation were measured with an objective method that eliminated these artefacts. However, all participants in this study were given the same instructions, and the assessments were standardized, which should have minimized the risk of the results being caused by error. Previous histopathologic studies15,16 have shown that there are both quantitative and qualitative abnormalities in the zonules in patients with Marfan’s syndrome. Pavlin et al17 also reported that ultrasound biomicroscopy shows increased lenticular sphericity in areas of zonular abnormality. In that study, using OCT, the crystalline lens was thicker in patients with Marfan’s syndrome compared with controls. In light of the histopathologic studies, this may be explained by the abnormality in the zonular fibers leading to decreased traction on the lens, thus increasing the lens thickness. This increase in baseline lens thickness in the eyes of patients with Marfan’s syndrome might indicate a partially accommodated state, adding lenticular myopia to manifest refraction, in addition to axial myopia. In clinical practice, lenticular myopia may lead to false calculation of intraocular lens power, as reported by Siganos et al.18 In the current study, lens thickness did not differ with and without visible subluxation, which indicates possible subclinical changes in the zonules of many patients with Marfan’s syndrome, before these changes become visible during slit-
lamp examination. Nevertheless, it seems that the zonules that remain function in a manner that is similar to those in normal eyes. This assumption is supported by the fact that the changes owing to accommodation in ACD, lens thickness, and accommodative power did not differ between groups with and without subluxation. According to Schachar et al,19 –21 accommodation results from increased tension in the equatorial zonules that flatten the lens equator and decreased tension in the anterior and posterior zonules, causing steepening of the anterior and posterior lens surfaces. In many studies of accommodation, the lenses were stable and did not move forward during accommodation.21–23 Because the iris blocks the light waves of OCT, the lens equator is invisible with this device. The same mechanisms of accommodation still may apply for Marfan’s syndrome if the zonules are defective equally in the equator as well as anterior and posterior to the equator, as previous histopathologic studies have implied.15,16 In Marfan’s syndrome, the lens is typically subluxated superonasally, opposite to the gravitational effect. How this affects the behavior of the crystalline lens and the zonules in accommodation should be studied further. One ocular diagnostic criterion for Marfan’s syndrome is iris hypoplasia, which causes decreased miosis.1 In the current study, the change in the mean pupil diameter from baseline to accommodation was smaller in patients with Marfan’s syndrome than in the controls. However, whether this is due to a smaller pupil size at baseline or an actual decrease in miosis is unclear. The change in pupil diameter from baseline to dilatation was greater in patients with Marfan’s syndrome than in controls, which indicates that the iris in patients with Marfan’s syndrome may be more susceptible to pharmacologic agents. We saw no difference in the pupillary function between the eyes of patients with Marfan’s syndrome with and without lens subluxation, which suggests that the changes in pupillary function are
1347
Ophthalmology Volume 116, Number 7, July 2009 characteristic of Marfan’s syndrome independent of lens subluxation. In summary, the results of the current study suggested that even though the pupil and crystalline lens are affected in Marfan’s syndrome, these patients can accommodate the same as normal patients. The observed changes seem to be connected to Marfan’s syndrome itself rather than subluxation of the crystalline lens.
References 1. Judge DP, Dietz HC. Marfan’s’s syndrome. Lancet 2005;366: 1965–76. 2. Ammash NM, Sundt TM, Connolly HM. Marfan’s syndromediagnosis and management. Curr Probl Cardiol 2008;33:7–39. 3. De Paepe A, Devereux RB, Dietz HC, et al. Revised diagnostic criteria for the Marfan’s syndrome. Am J Med Genet 1996;62:417–26. 4. Maumenee IH. The eye in the Marfan’s syndrome. Trans Am Ophthalmol Soc 1981;79:684 –733. 5. Lai MM, Tang M, Andrade EM, et al. Optical coherence tomography to assess intrastromal corneal ring segment depth in keratoconic eyes. J Cataract Refract Surg 2006;32:1860 –5. 6. Koivula A, Kugelberg M. Optical coherence tomography of the anterior segment in eyes with phakic refractive lenses. Ophthalmology 2007;114:2031–7. 7. Baikoff G, Bourgeon G, Jodai HJ, et al. Pigment dispersion and Artisan phakic intraocular lenses: crystalline lens rise as a safety criterion. J Cataract Refract Surg 2005;31:674 – 80. 8. Nolan WP, See JL, Chew PT, et al. Detection of primary angle closure using anterior segment optical coherence tomography in Asian eyes. Ophthalmology 2007;114:33–9. 9. Baikoff G, Lutun E, Ferraz C, Wei J. Static and dynamic analysis of the anterior segment with optical coherence tomography. J Cataract Refract Surg 2004;30:1843–50. 10. Muscat S, McKay N, Parks S, et al. Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography. Invest Ophthalmol Vis Sci 2002;43: 1791–5.
11. Fine IH, Hoffman RS, Packer M. Profile of clear corneal cataract incisions demonstrated by ocular coherence tomography. J Cataract Refract Surg 2007;33:94 –7. 12. Richdale K, Bullimore MA, Zadnik K. Lens thickness with age and accommodation by optical coherence tomography. Ophthalmic Physiol Opt 2008;28:441–7. 13. Nemeth G, Tsorbatzoglou A, Vamosi P, et al. A comparison of accommodation amplitudes in pseudophakic eyes measured with three different methods. Eye 2008;22:65–9. 14. Kotulak JC, Morse SE, Wiley RW. The effect of knowledge of object distance on accommodation during instrument viewing. Perception 1994;23:671–9. 15. Traboulsi EI, Whittum-Hudson JA, Mir SH, Maumenee IH. Microfibril abnormalities of the lens capsule in patients with Marfan’s syndrome and ectopia lentis. Ophthalmic Genet 2000;21:9 –15. 16. Mir S, Wheatley HM, Hussels IE, et al. A comparative histologic study of the fibrillin microfibrillar system in the lens capsule of normal subjects and subjects with Marfan’s syndrome. Invest Ophthalmol Vis Sci 1998;39:84 –93. 17. Pavlin CJ, Buys YM, Pathmanathan T. Imaging zonular abnormalities using ultrasound biomicroscopy. Arch Ophthalmol 1998;116:854 –7. 18. Siganos DS, Siganos CS, Popescu CN, Margaritis VN. Clear lens extraction and intraocular lens implantation in Marfan’s’s syndrome. J Cataract Refract Surg 2000;26:781– 4. 19. Schachar RA. Qualitative effect of zonular tension on freshly extracted intact human crystalline lenses: implications for the mechanism of accommodation. Invest Ophthalmol Vis Sci 2004;45:2691–5. 20. Schachar RA, Tello C, Cudmore DP, et al. In vivo increase of the human lens equatorial diameter during accommodation. Am J Physiol 1996;271:R670 – 6. 21. Schachar RA. The mechanism of accommodation and presbyopia. Int Ophthalmol Clin 2006;46:39 – 61. 22. Schachar RA, Davila C, Pierscionek BK, et al. The effect of human in vivo accommodation on crystalline lens stability. Br J Ophthalmol 2007;91:790 –3. 23. Schachar RA, Cudmore DP. The effect of gravity on the amplitude of accommodation. Ann Ophthalmol 1994;26: 65–70.
Footnotes and Financial Disclosures Originally received: September 11, 2008. Final revision: January 14, 2009. Accepted: January 20, 2009. Available online: May 8, 2009.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Manuscript no. 2008-1091.
1
Anterior Segment Department, St. Erik’s Eye Hospital, Stockholm, Sweden. 2
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. 3
Department of Ophthalmology, University of Oslo, Oslo, Norway.
1348
Financial support was provided through the regional agreement on medical training and clinical research between Stockholm county council and the Karolinska Institute. Correspondence: Tiina Rysä Konradsen, MD, St. Erik’s Eye Hospital, S-11282 Stockholm, Sweden. E-mail: [email protected].
Marfan’s syndrome, the most common genetic connective tissue disorder, causes symptoms in virtually all organ systems. Typical symptoms include tall stature, arachnodactyly (spiderlike fingers and toes), aortic dilatation, scoliosis, and hernias. The estimated incidence of this syndrome is about 2 to 3 per 100,000 births; there is no gender, racial, or ethnic predilection.1,2 Many affected individuals have a mutation in chromosome 15, encoding for the matrix protein fibrillin-1, which is an important part of the connective tissue. However, this does not include all individuals with the syndrome, and, therefore, genetic testing alone is not sufficiently specific to establish a diagnosis. The diagnosis is based on a combination of typical symptoms, a family history of Marfan’s syndrome, and genetic testing, according to the Ghent criteria.3 Dislocation of the crystalline lens is a major criterion for Marfan’s syndrome, and it has been reported to occur in about 60% of patients with Marfan’s syndrome.4 Other known ocular features in Marfan’s syndrome, which are minor criteria for diagnosing the syndrome, are increased axial length, abnormally flat corneas, and a hypoplastic iris causing decreased miosis. The question arises regarding dislocation of the crystalline lens and the consequent ability to accommodate, but © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
there are few devices to measure this in clinical practice. A relatively new device to study the anterior segment in real time is anterior segment optical coherence tomography (OCT). It has been used for ⬎10 years in refractive surgery5–7 and for diagnosis of angle-closure glaucoma.8 Baikoff et al9 studied accommodation in a normal population using Visante OCT (Carl Zeiss, Jena, Germany) and concluded that it is a user-friendly instrument for imaging the anterior segment. It has also been shown to have good repeatability and reproducibility.10,11 However, to the best of our knowledge, the ocular changes in Marfan’s syndrome including accommodation have not been studied previously with Visante OCT. The aim of this study was to determine the changes in the anterior segment during accommodation and after administration of cyclopegic drops in patients with Marfan’s syndrome using Visante OCT.
Methods Subjects Patients were recruited in cooperation with the Departments of Cardiology and Clinical Genetics at the Karolinska University ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.01.023
1343
Ophthalmology Volume 116, Number 7, July 2009 Hospital, Stockholm, Sweden. These departments have records on most known patients diagnosed with Marfan’s syndrome in the region of Stockholm (population 1.9 million in 2007). A total of 100 letters including information about the study were sent to possible candidates, who were asked to contact the research group if they were willing to participate. Family members with a diagnosis of Marfan’s syndrome also were invited to participate. A second reminder letter was sent if the patients did not respond. All patients had a diagnosis of Marfan’s syndrome based on the Ghent criteria.3 The study was approved by the local ethics committee. All patients were provided with written and oral information about the study, and written informed consent was provided by each patient. For patients ⬍18 years of age, written informed consent was provided by a parent. The more myopic eye of each patient was included in the study. The inclusion criteria were age ⱖ12 years and a best-corrected logarithm of the minimum angle of resolution visual acuity of ⫹0.3 or better to enable focusing on the fixation point in the Visante OCT. The exclusion criterion was a previous intraocular or corneal surgery. Fifty-six individuals were examined for participate in the study, and 31 of these met the inclusion criteria. Individuals who did not have Marfan’s syndrome served as the control group and they were matched with patients in the study group for mean age and spherical refraction. Controls were recruited from among the hospital staff and their families. As in the study group, the more myopic eye of each control subject was included. The exclusion criteria were the same as for the patients.
Design and Methods of Measurement This clinical case-control study was carried out at St. Erik’s Eye Hospital in Stockholm, Sweden. All measurements were performed from January to December 2007. Before the assessment with Visante OCT, the manifest refraction and best-corrected visual acuity were measured. Visual acuity was tested with the Early Treatment of Diabetic Retinopathy Study (logarithm of the minimum angle of resolution) chart. The anterior segment was scanned with Visante OCT at baseline and during accommodation and dilatation (Fig 1). All assessments were carried out by an ophthalmic nurse who was specially trained in the use of the device, and the images were analyzed by an ophthalmologist. At baseline, the manifest refraction was used during scanning with the Visante OCT. Two images of the anterior segment in the
Figure 2. Superonasal dislocation of the crystalline lens in Marfan’s syndrome.
unaccommodated state were assessed: The first was focused on the anterior chamber and the second was focused on the crystalline lens. Quadruple image sections were assessed to obtain crosssectional images at 0, 45, 90, and 135 degrees. These 2 series of images then were assessed during maximal accommodation and dilatation. Accommodation is stimulated with Visante OCT by defocusing the visual object inside the device and gradually adding negative power in front of the patient’s eye as long as the patient still has a clear image of the object. After the accommodative measurements, a combination drop of 0.75% cyclopentolate and 2.5% phenylephrine was used for dilatation. As we determined in preliminary testing, the difference in the anterior chamber depth (ACD) in the 4 cross-sections was minimal; only measurement in the horizontal axis was included. The pupil diameter and lens thickness, however, varied more in the 4 cross-sections, and, therefore, the mean value of each variable in the 4 cross-sections was analyzed. The ACD, pupil diameter, and lens thickness were measured in millimeters. The lens thickness was measured at the thickest point of the lens. The accommodative power was measured as the difference in diopters (D) between the spherical equivalent during accommodation and at baseline. The primary study outcomes were the accommodative power in the patients compared with the controls and the ACD, pupil diameter, and lens thickness at baseline and during accommodation and dilatation. To determine if lens subluxation affects the results, the subgroups of patients with and without subluxation also were compared. Subluxation of the crystalline lens was determined by visible dislocation or iridophacodonesis on slit-lamp examination or by astigmatism of ⱖ1 D at a site other than the cornea (Fig 2).
Statistical Analysis
Figure 1. Visante optical coherence tomography (OCT) is a noncontact, high-resolution tomographic device used for in vivo imaging and measurement of ocular structures in the anterior segment. It provides crosssectional images of the anterior segment, using 1310-nm light waves. An OCT image of the anterior segment of a 19-year-old man with Marfan’s syndrome (refraction, ⫺1.75 ⫺1.75 ⫻ 90) at baseline.
1344
Before starting the study, we estimated the lowest clinically relevant differences and the size of each group to show those differences. For accommodation, we estimated that a difference of 1.5 D (with ␣ ⫽ 0.05 and  ⫽ 0.2) between the Marfan eyes and the controls eyes would require about 30 patients in each group. Further, according to our calculations, a difference between the groups in the change in the ACD from the nonaccommodative state to accommodation of 0.1 mm (with ␣ ⫽ 0.05 and  ⫽ 0.2) would require 26 patients in each group. Statistical analyses were performed using the Student t test. P⬍0.05 was considered significant.
Konradsen et al 䡠 Accommodation Measured with OCT in Marfan’s Syndrome Table 1. Baseline Data from Patients and Controls
Patients, n Gender Male Female Age, yrs* Spherical refraction* (D)
No. Gender Male Female Age, yrs* Spherical refraction* (D)
Marfan’s Syndrome
Controls
31
31
15 16 35.4 (12.7–63.8) ⫺3.3 (⫺17.5 to ⫹1.5)
13 18 34.1 (11.9–61.6) ⫺2.3 (⫺10.3 to ⫹2.5)
0.74 0.30
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
P
15
16
10 5 35.1 (13.3–63.8) ⫺3.6 (⫺115 to ⫺0.75)
5 11 35.6 (12.7–63.3) ⫺3.0 (⫺17.5 to ⫹1.5)
P
0.92 0.67
*Age and spherical refraction are expressed as the mean (range).
Results
between the eyes of the patients with Marfan’s syndrome with and without a subluxated lens (Table 2).
Age and Refraction Of the 56 individuals who contacted us, 31 patients with Marfan’s syndrome (15 men, 16 women) met the inclusion criteria; 31 unaffected individuals (13 men, 18 women) served as the control group. The ages and spherical refractions of the 2 groups did not differ significantly (Table 1). The eyes of the patients with Marfan’s syndrome then were divided into subgroups—those with and without a subluxated lens—and those groups also did not differ in age or spherical refraction (Table 1).
Accommodative Power The accommodative power was the change in the refractive power (spherical equivalent) between baseline and maximal accommodation. In Marfan’s syndrome the mean (⫾ standard deviation [SD]) spherical equivalent was ⫺3.5⫾4.0 D at baseline and ⫺10.1⫾5.0 D during full accommodation, with a total accommodative power of ⫺6.6⫾2.2 D. In the control group, the mean spherical equivalent changed from ⫺2.6⫾3.2 D at baseline to ⫺9.4⫾4.0 D during full accommodation, with an accommodative power of ⫺6.8⫾2.3 D. There was no difference between the groups (Table 2). There was also no difference
Anterior Chamber Depth In the eyes of patients with Marfan’s syndrome, the ACD decreased from 2.92⫾0.35 mm (mean ⫾ SD) at baseline to 2.83⫾0.32 mm during accommodation (P⬍0.01) and increased to 3.05⫾0.39 mm during dilatation (P⬍0.01). In the control group, the measurements were 3.05⫾0.35 mm at baseline, 2.93⫾0.32 mm during accommodation (P⬍0.01), and 3.17⫾0.34 mm during dilatation (P⬍0.01). There was no significant difference between the groups (Table 3). There was also no difference in the ACD between the eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 3).
Lens Thickness In the eyes of patients with Marfan’s syndrome, the lens was thicker at all time points, changing from 4.27⫾0.56 mm at baseline to 4.39⫾0.49 mm during accommodation (P⬍0.01) and 4.19⫾0.58 mm during dilatation (P⬍0.01). The respective values for the control group were 3.97⫾0.38 mm, 4.18⫾0.30 mm (P⬍0.01), and 3.94⫾0.38 mm (P⬎0.05; Table 4). All differences between the groups were significant (P ⫽ 0.017 at baseline; P ⫽
Table 2. Spherical Equivalent at Baseline and during Accommodation, and Accomodative Power Spherical Equivalent (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Accomodative power
⫺3.5⫾4.0 ⫺10.1⫾5.0 ⫺6.6⫾2.2
⫺2.6⫾3.2 ⫺9.4⫾4.0 ⫺6.8⫾2.3
⫺0.96 (⫺2.82 to 0.89) ⫺0.71 (⫺3.03 to 1.60) 0.25 (⫺0.89 to 1.39)
0.30 0.54 0.66
Spherical Equivalent (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Accomodative power
⫺3.6⫾3.2 ⫺10.5⫾4.2 ⫺6.6⫾2.2
⫺3.0⫾5.0 ⫺9.7⫾5.8 ⫺6.5⫾2.2
⫺0.65 (⫺3.76 to 2.47) ⫺0.80 (⫺4.5 to 2.97) ⫺0.13 (⫺1.75 to 1.49)
0.67 0.67 0.87
CI ⫽ confidence interval for difference of mean values.
1345
Ophthalmology Volume 116, Number 7, July 2009 Table 3. Anterior Chamber Depth (ACD) in Patients and Controls and from the Eyes with Marfan’s Syndrome with and without a Subluxated Lens ACD, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation
2.92⫾0.35 2.83⫾0.32 3.05⫾0.36
3.05⫾0.35 2.93⫾0.32 3.17⫾0.34
⫺0.12 (⫺0.30 to 0.05) ⫺0.10 (⫺0.27 to 0.06) ⫺0.12 (⫺0.31 to 0.06)
0.17 0.21 0.18
ACD, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation
2.93⫾0.40 2.84⫾0.37 3.04⫾0.46
2.91⫾0.31 2.83⫾0.28 3.05⫾0.32
0.02 (⫺0.24 to 0.28) 0.005 (⫺0.24 to 0.25) ⫺0.02 (⫺0.31 to 0.27)
0.87 0.25 0.27
CI ⫽ confidence interval for difference of mean values.
0.043 during accommodation; P ⫽ 0.046 during dilatation). However, no difference in lens thickness was found between the subgroups of eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 4).
Pupil Diameter In the eyes of patients with Marfan’s syndrome, the mean pupil diameters varied from 4.53⫾1.30 mm at baseline, decreased to 3.70⫾1.17 mm during accommodation (P⬍0.01), and increased to 7.12⫾0.96 mm during dilatation (P⬍0.01). In the control group, the values were 5.27⫾0.99 mm at baseline, 3.93⫾0.92 mm during accommodation (P⬍0.01), and 6.90⫾0.84 mm during dilatation (P⬍0.01). The pupil size in the eyes of patients with Marfan’s syndrome at baseline was significantly smaller (P ⫽ 0.01). In the eyes of patients with Marfan’s syndrome, the pupil size decreased less during accommodation (P ⫽ 0.02) and increased more during dilatation compared with controls (P⬍0.01; Table 5). However, there was no difference in pupil diameter between the subgroups of the eyes of patients with Marfan’s syndrome with and without a subluxated lens (Table 5).
Discussion Lens subluxation is a well known feature of Marfan’s syndrome. However, little is known about accommodation in
Marfan’s syndrome. Maumenee4 used Prince’s rule and a letter target with 11 patients with Marfan’s syndrome and found that accommodation was normal for age. In the current study, we evaluated accommodation in a larger group of patients with Marfan’s syndrome and compared the results with controls matched for age and spherical refraction. To the best of our knowledge, anterior segment OCT has not been used previously in studies of Marfan’s syndrome, and therefore no comparison with previous results was possible. Baikoff et al9 used OCT to study accommodation in a normal population. Those investigators reported the same forward movement of the anterior lens surface and pupil contraction during accommodation as in the current study. Those authors also analyzed variations in these variables owing to age and grade of ametropia, which we did not, making a comparison of the results of the 2 studies difficult. In addition, eyes with a phakic refractive lens have been studied with Visante OCT, and significant forward movement of the anterior lens surface occurred during accommodation.6 Marfan’s syndrome is a relatively rare condition, and many of these patients have undergone ocular surgery. Despite this, we were able to include 31 patients in the study who were well matched with the controls for age and refraction. Only 1 person performed all assessments in a
Table 4. Lens Thickness in Patients an Controls, and from Eyes with Marfan’s Syndrome with and without a Subluxated Lens Lens Thickness, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation
4.27⫾0.56 4.39⫾0.49 4.19⫾0.58
3.97⫾0.38 4.18⫾0.30 3.94⫾0.38
0.30 (0.06 to 0.54) 0.21 (0.007 to 0.42) 0.25 (0.004 to 0.50)
0.017* 0.043* 0.046*
Lens Thickness, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation
4.39⫾0.67 4.49⫾0.57 4.30⫾0.70
4.17⫾0.43 4.30⫾0.40 4.09⫾0.42
0.22 (⫺0.19 to 0.62) 0.19 (⫺0.17 to 0.55) 0.21 (⫺0.21 to 0.63)
0.29 0.29 0.32
CI ⫽ confidence interval for difference of mean values. *Significant difference.
1346
Konradsen et al 䡠 Accommodation Measured with OCT in Marfan’s Syndrome Table 5. Pupil Diameter in Patients and Controls, and from Eyes with Marfan’s Syndrome with and without a Subluxated Lens Pupil Diameter, mm (mean ⴞ SD)
Marfan’s Syndrome
Control
Difference (95% CI)
P
Baseline Accommodation Dilatation Difference baseline accommodation Difference from baseline dilatation
4.53⫾1.30 3.70⫾1.17 7.12⫾0.96 ⫺0.83⫾0.65 2.59⫾1.04
5.27⫾0.99 3.93⫾0.92 6.90⫾0.84 ⫺1.34⫾1.02 1.63⫾0.80
⫺0.74 (⫺1.32 to ⫺0.15) ⫺0.22 (⫺0.76 to 0.31) 0.23 (⫺0.23 to 0.69) 0.51 (0.08 to 0.95) 0.96 (0.49 to 1.44)
0.01* 0.40 0.33 0.02* 0.0001*
Pupil Diameter, mm (mean ⴞ SD)
Marfan’s Syndrome with Subluxated Lens
Marfan’s Syndrome without Subluxated Lens
Difference (95% CI)
P
Baseline Accommodation Dilatation Difference from baseline accommodation Difference from baseline dilatation
4.49⫾1.43 3.58⫾1.25 7.11⫾1.09 ⫺0.91⫾0.71
4.57⫾1.20 3.82⫾1.11 7.13⫾0.85 ⫺0.74⫾0.59
⫺0.07 (⫺1.04 to 0.89) ⫺0.25 (⫺1.11 to 0.62) ⫺0.02 (⫺0.73 to 0.70) ⫺0.17 (⫺0.65 to 0.31)
0.88 0.57 0.97 0.47
2.62⫾1.20
2.56⫾0.92
0.06 (⫺0.72 to 0.84)
0.88
CI ⫽ confidence interval for difference of mean values. *Significant difference.
standardized manner, which minimized the risk of a random error. Nevertheless, the current study had some limitations, one of which was the imprecise determination of the exact endpoint of accommodation with OCT. It has been reported that OCT used to measure subjective accommodation might overestimate the true objective accommodation.12 The subjective minus-lens-to-blur method also was shown to induce accommodation, even in pseudophakic eyes.13 These facts, together with instrumental myopia14 that causes increased accommodation when the subject is aware of the short distance to the visual object, might have contributed to higher values of accommodation than if accommodation were measured with an objective method that eliminated these artefacts. However, all participants in this study were given the same instructions, and the assessments were standardized, which should have minimized the risk of the results being caused by error. Previous histopathologic studies15,16 have shown that there are both quantitative and qualitative abnormalities in the zonules in patients with Marfan’s syndrome. Pavlin et al17 also reported that ultrasound biomicroscopy shows increased lenticular sphericity in areas of zonular abnormality. In that study, using OCT, the crystalline lens was thicker in patients with Marfan’s syndrome compared with controls. In light of the histopathologic studies, this may be explained by the abnormality in the zonular fibers leading to decreased traction on the lens, thus increasing the lens thickness. This increase in baseline lens thickness in the eyes of patients with Marfan’s syndrome might indicate a partially accommodated state, adding lenticular myopia to manifest refraction, in addition to axial myopia. In clinical practice, lenticular myopia may lead to false calculation of intraocular lens power, as reported by Siganos et al.18 In the current study, lens thickness did not differ with and without visible subluxation, which indicates possible subclinical changes in the zonules of many patients with Marfan’s syndrome, before these changes become visible during slit-
lamp examination. Nevertheless, it seems that the zonules that remain function in a manner that is similar to those in normal eyes. This assumption is supported by the fact that the changes owing to accommodation in ACD, lens thickness, and accommodative power did not differ between groups with and without subluxation. According to Schachar et al,19 –21 accommodation results from increased tension in the equatorial zonules that flatten the lens equator and decreased tension in the anterior and posterior zonules, causing steepening of the anterior and posterior lens surfaces. In many studies of accommodation, the lenses were stable and did not move forward during accommodation.21–23 Because the iris blocks the light waves of OCT, the lens equator is invisible with this device. The same mechanisms of accommodation still may apply for Marfan’s syndrome if the zonules are defective equally in the equator as well as anterior and posterior to the equator, as previous histopathologic studies have implied.15,16 In Marfan’s syndrome, the lens is typically subluxated superonasally, opposite to the gravitational effect. How this affects the behavior of the crystalline lens and the zonules in accommodation should be studied further. One ocular diagnostic criterion for Marfan’s syndrome is iris hypoplasia, which causes decreased miosis.1 In the current study, the change in the mean pupil diameter from baseline to accommodation was smaller in patients with Marfan’s syndrome than in the controls. However, whether this is due to a smaller pupil size at baseline or an actual decrease in miosis is unclear. The change in pupil diameter from baseline to dilatation was greater in patients with Marfan’s syndrome than in controls, which indicates that the iris in patients with Marfan’s syndrome may be more susceptible to pharmacologic agents. We saw no difference in the pupillary function between the eyes of patients with Marfan’s syndrome with and without lens subluxation, which suggests that the changes in pupillary function are
1347
Ophthalmology Volume 116, Number 7, July 2009 characteristic of Marfan’s syndrome independent of lens subluxation. In summary, the results of the current study suggested that even though the pupil and crystalline lens are affected in Marfan’s syndrome, these patients can accommodate the same as normal patients. The observed changes seem to be connected to Marfan’s syndrome itself rather than subluxation of the crystalline lens.
References 1. Judge DP, Dietz HC. Marfan’s’s syndrome. Lancet 2005;366: 1965–76. 2. Ammash NM, Sundt TM, Connolly HM. Marfan’s syndromediagnosis and management. Curr Probl Cardiol 2008;33:7–39. 3. De Paepe A, Devereux RB, Dietz HC, et al. Revised diagnostic criteria for the Marfan’s syndrome. Am J Med Genet 1996;62:417–26. 4. Maumenee IH. The eye in the Marfan’s syndrome. Trans Am Ophthalmol Soc 1981;79:684 –733. 5. Lai MM, Tang M, Andrade EM, et al. Optical coherence tomography to assess intrastromal corneal ring segment depth in keratoconic eyes. J Cataract Refract Surg 2006;32:1860 –5. 6. Koivula A, Kugelberg M. Optical coherence tomography of the anterior segment in eyes with phakic refractive lenses. Ophthalmology 2007;114:2031–7. 7. Baikoff G, Bourgeon G, Jodai HJ, et al. Pigment dispersion and Artisan phakic intraocular lenses: crystalline lens rise as a safety criterion. J Cataract Refract Surg 2005;31:674 – 80. 8. Nolan WP, See JL, Chew PT, et al. Detection of primary angle closure using anterior segment optical coherence tomography in Asian eyes. Ophthalmology 2007;114:33–9. 9. Baikoff G, Lutun E, Ferraz C, Wei J. Static and dynamic analysis of the anterior segment with optical coherence tomography. J Cataract Refract Surg 2004;30:1843–50. 10. Muscat S, McKay N, Parks S, et al. Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography. Invest Ophthalmol Vis Sci 2002;43: 1791–5.
11. Fine IH, Hoffman RS, Packer M. Profile of clear corneal cataract incisions demonstrated by ocular coherence tomography. J Cataract Refract Surg 2007;33:94 –7. 12. Richdale K, Bullimore MA, Zadnik K. Lens thickness with age and accommodation by optical coherence tomography. Ophthalmic Physiol Opt 2008;28:441–7. 13. Nemeth G, Tsorbatzoglou A, Vamosi P, et al. A comparison of accommodation amplitudes in pseudophakic eyes measured with three different methods. Eye 2008;22:65–9. 14. Kotulak JC, Morse SE, Wiley RW. The effect of knowledge of object distance on accommodation during instrument viewing. Perception 1994;23:671–9. 15. Traboulsi EI, Whittum-Hudson JA, Mir SH, Maumenee IH. Microfibril abnormalities of the lens capsule in patients with Marfan’s syndrome and ectopia lentis. Ophthalmic Genet 2000;21:9 –15. 16. Mir S, Wheatley HM, Hussels IE, et al. A comparative histologic study of the fibrillin microfibrillar system in the lens capsule of normal subjects and subjects with Marfan’s syndrome. Invest Ophthalmol Vis Sci 1998;39:84 –93. 17. Pavlin CJ, Buys YM, Pathmanathan T. Imaging zonular abnormalities using ultrasound biomicroscopy. Arch Ophthalmol 1998;116:854 –7. 18. Siganos DS, Siganos CS, Popescu CN, Margaritis VN. Clear lens extraction and intraocular lens implantation in Marfan’s’s syndrome. J Cataract Refract Surg 2000;26:781– 4. 19. Schachar RA. Qualitative effect of zonular tension on freshly extracted intact human crystalline lenses: implications for the mechanism of accommodation. Invest Ophthalmol Vis Sci 2004;45:2691–5. 20. Schachar RA, Tello C, Cudmore DP, et al. In vivo increase of the human lens equatorial diameter during accommodation. Am J Physiol 1996;271:R670 – 6. 21. Schachar RA. The mechanism of accommodation and presbyopia. Int Ophthalmol Clin 2006;46:39 – 61. 22. Schachar RA, Davila C, Pierscionek BK, et al. The effect of human in vivo accommodation on crystalline lens stability. Br J Ophthalmol 2007;91:790 –3. 23. Schachar RA, Cudmore DP. The effect of gravity on the amplitude of accommodation. Ann Ophthalmol 1994;26: 65–70.
Footnotes and Financial Disclosures Originally received: September 11, 2008. Final revision: January 14, 2009. Accepted: January 20, 2009. Available online: May 8, 2009.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Manuscript no. 2008-1091.
1
Anterior Segment Department, St. Erik’s Eye Hospital, Stockholm, Sweden. 2
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. 3
Department of Ophthalmology, University of Oslo, Oslo, Norway.
1348
Financial support was provided through the regional agreement on medical training and clinical research between Stockholm county council and the Karolinska Institute. Correspondence: Tiina Rysä Konradsen, MD, St. Erik’s Eye Hospital, S-11282 Stockholm, Sweden. E-mail: [email protected].