- Email: [email protected]
Corneal biomechanical properties and intraocular pressure measurement in Marfan patients
ARTICLE
Corneal biomechanical properties and intraocular pressure measurement in Marfan patients Necip Kara, MD, Ercument Bozkurt, MD, Okkes Baz, MD, Hasan Altinkaynak, MD, Huseyin Dundar, MD, Kemal Yuksel, MD, Ahmet Taylan Yazici, MD, Ahmet Demirok, MD, Sukru Candan, MD
PURPOSE: To compare the biomechanical properties of the cornea and intraocular pressure (IOP) between patients with Marfan syndrome and age-matched controls. SETTING: Departments of Ophthalmology and Genetics, Bakirkoy Maternity and Children Diseases Hospital, and Beyoglu Eye Education and Research Hospital, Istanbul, Turkey. DESIGN: Cross-sectional study. METHODS: This study comprised patients with Marfan syndrome (study group) and healthy individuals (control group). The study group was subdivided into patients with ectopia lentis and patients without ectopia lentis. In the right eye of each patient, the corneal hysteresis (CH), corneal resistance factor (CRF), Goldman-correlated IOP, and corneal-compensated IOP were recorded. RESULTS: Overall, the mean CH, CRF, Goldman-correlated IOP, and corneal-compensated IOP were not significantly different between the study group and the control group. The mean CH was 9.9 mm Hg G 1.2 (SD) in study eyes with ectopia lentis and 11.2 G 1.5 mm Hg in study eyes without ectopia lentis (PZ.016); the mean CRF was 8.2 G 1.8 mm Hg and 11.3 G 1.9 mm Hg, respectively (P<.001). The mean Goldman-correlated IOP was 11.7 G 2.7 mm Hg in study eyes with ectopia lentis and 16.2 G 4.3 in study eyes without ectopia lentis (PZ.003); the mean corneal-compensated IOP was 13.5 G 4.1 mm Hg and 15.6 G 3.8 mm Hg, respectively (PZ.07). CONCLUSION: The CH, CRF, and Goldman-correlated IOP were significantly lower in the Marfan syndrome eyes with ectopia lentis than in the Marfan syndrome eyes without ectopia lentis. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2012; 38:309–314 Q 2011 ASCRS and ESCRS
Marfan syndrome is a rare inherited connective tissue disorder transmitted as an autosomal dominant trait. The estimated incidence varies from 1:5000 to 1:50 000 according to different studies.1–4 The abnormality in Marfan patients involves defects in the protein fibrillin-1 (FBN1) on chromosome 15, a structural component of microfibrils that is an important part of the connective tissue, such as basement membranes and elastic tissues. Marfan syndrome is characterized by skeletal, cardiovascular, pulmonary, skin, and ocular involvements. The major ocular finding of Marfan syndrome is ectopia lentis. Approximately 60% of patients have lens dislocation.5 The lens dislocation is usually superior and temporal. This may present at birth or develop during childhood or adolescence. Other ocular involvements include a flat cornea, increased Q 2011 ASCRS and ESCRS Published by Elsevier Inc.
axial length (AL), cataract, hypoplastic iris, or hypoplastic ciliary muscle that causes decreased miosis; axial myopia; amblyopia; glaucoma; and retinal detachment.3,6,7 Corneal biomechanical evaluation may be helpful in the long-term monitoring of glaucoma. It can help avoid misinterpretation of intraocular pressure (IOP), be used in preoperative screening of refractive surgery candidates, and help differentiate between healthy corneas and abnormal corneas.8,9 A relatively new tool for in vivo assessment of corneal biomechanics is the Ocular Response Analyzer (Reichert, Inc). The biomechanical analyzer can measure IOP, corneal hysteresis (CH), and the corneal resistance factor (CRF). Corneal hysteresis is related to the viscoelastic behavior of the corneal tissue and is calculated as the difference between the 2 pressure 0886-3350/$ - see front matter doi:10.1016/j.jcrs.2011.08.036
309
310
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
values at 2 applanation measurements. The CRF is an indicator of the elastic properties of the cornea and is calculated as a linear function of the 2 pressures associated with the 2 applanation processes.10 The aim of the study was to evaluate the biomechanical properties of the cornea using the Ocular Response Analyzer in Marfan patients with and without lens dislocation. PATIENTS AND METHODS Study Population and Design This prospective cross-sectional comparative study was performed at the Ophthalmology, Cardiology, and Genetic Departments, Istanbul Bakirkoy Maternity and Children Diseases Hospital, and Istanbul Beyoglu Eye Education and Research Hospital. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee. All participants received oral and written information about the study and provided written informed consent. For participants younger than 18 years, a parent provided written informed consent. The participants were divided into 2 groups: cases with Marfan syndrome (study group) and normal cases (control group). Marfan patients were recruited in cooperation with the Departments of Cardiology and Clinical Genetics, Bakirkoy Maternity and Children Diseases Hospital, Istanbul, Turkey. The patients were defined as having Marfan syndrome based on clinical features (eg, 2 major diagnostic criteria), genetic confirmation (FBN1 mutation), or both. Also, the study group was divided into 2 subgroups according to the presence of ectopia lentis. The control group comprised individuals without Marfan syndrome who were matched with patients in the study group in mean age and spherical refraction. Those in the control group were recruited from the hospital staff and their families. Patients with a history of ocular surgery, ocular inflammatory disease, or glaucoma were excluded from the study.
Study Measurements Each clinical examination consisted of corrected distance visual acuity (CDVA) using a Snellen chart and the manifest refraction, biomicroscopy of the anterior segment, and a dilated fundus evaluation. The right eye of each participant was used in the study. Study participants had central corneal thickness (CCT) measurements with a DGH-550 ultrasound pachymeter (DGH Technology, Inc.), AL measurements with the Submitted: April 21, 2011. Final revision submitted: July 6, 2011. Accepted: August 18, 2011. From the Department of Ophthalmology (Kara) and Department of Genetics (Candan), Bakirkoy Maternity and Children Diseases Hospital, and Beyoglu Eye Education and Research Hospital (Bozkurt, Baz, Altinkaynak, Dundar, Yuksel, Yazici, Demirok), Istanbul, Turkey. Corresponding author: Necip Kara, Kartaltepe Mh. Akin Sk. Akin Apt. No:8/14 Bakirkoy/Istanbul, Turkey. E-mail: dr.necipkara@ gmail.com.
IOLMaster biometer (Carl Zeiss Meditech AG), and biomechanical measurements with the Ocular Response Analyzer. Three biomechanical measurements were performed in all subjects by an experienced clinician. Three good-quality measurements (symmetric, well-defined inward and outward applanation spike heights) were obtained for each eye, and the mean value of each parameter was used in the analysis. The clinician was masked to who was in the study group and who was in the control group. Analysis of the process resulted in 2 parameters of the biomechanical properties of the cornea; that is, CH and CRF. The analysis also yielded a Goldmann-correlated IOP value, which corresponds to that measured with the Goldmann applanation tonometer, and a corneal-compensated IOP value, which is thought to be little affected by corneal properties.10 The other measurements, including AL and CCT measurements, were performed by another experienced technician.
Statistical Analysis All statistical tests were performed using SPSS software (version 16, SPSS, Inc.). Snellen visual acuity measurements were converted to logMAR notation for statistical analysis. The normality of the data was confirmed using the Kolmogorov-Smirnov test (PO.05). One-way analysis of variance was used to compare variables between groups. The Pearson correlation was used to examine the relationships between the measured variables. A P value less than 0.05 was considered significant.
RESULTS Table 1 shows the baseline characteristics in the study group, the 2 study subgroups, and the control group. The mean age (PZ.11), spherical refraction (PZ.18), mean CCT (PZ0.23), and mean AL (PZ.18) did not differ significantly between the study group and the control group. There was a statistically significant difference in the spherical refraction (PZ.01), mean logMAR CDVA (PZ.021), mean CCT (PZ.04), and the mean AL (PZ.001) between the 2 study subgroups (eyes with ectopia lentis and eyes without ectopia lentis). Biomechanical Parameters Table 2 shows the results of the between-group comparison of CH and CRF. The mean CH and CRF values were not statistically significantly different between the study group and the control group. However, there was a significant difference in the mean CH and CRF values between the 2 study subgroups (PZ.016 and P!.001, respectively). Table 3 shows the results of the comparison of CH and CRF between study eyes with ectopia lentis and control eyes; there was a statistically significant difference in the mean CH and CRF values between study eyes with ectopia lentis and control eyes (PZ.02 and P!.001, respectively). A correlation analysis between CH–CRF values and CCT–AL values found that in the study group, the CH and CRF values were significantly associated with
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
311
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
Table 1. Patient demographics and characteristics. Study Group Parameter Eyes (n) Sex Female Male Age (y) Mean G SD Range Sphere (D) Mean G SD Range CDVA (logMAR) Mean G SD Range CCT (mm) Mean G SD Range AL (mm) Mean G SD Range
Study Group
Control Group
P Value*
Ectopia Lentis (C)
Ectopia Lentis ( )
P Value*
38
38
d
17
21
d
17 21
17 21
d
8 9
9 12
.50
18.7 G 7.8 8, 31
21.2 G 5.3 10, 30
.11
21.2 G 6.5 14, 29
17.2 G 8.2 8, 31
.16
2.0 G 2.7 6.00, C4.25
1.3 G 1.9 6.25, C1.50
.18
3.8 G 2.2 6.00, C0.50
1.1 G 2.5 5.50, C4.25
.01
0.07 G 0.11 0.0, 0.4
0.01 G 0.04 0.0, 0.22
.007
0.11 G 0.15 0.0, 0.4
0.04 G 0.06 0.0, 0.22
.021
564 G 40 498, 635
577 G 39 490, 663
.23
538 G 32 502, 573
575 G 39 498, 635
.04
24.0 G 1.9 21.0, 27.3
23.4 G 1.0 21.8, 26.3
.18
26.0 G 1.3 24.8, 27.3
23.1 G 1.5 21.0, 25.8
.001
AL Z axial Length; CCT Z central corneal thickness; CDVA Z corrected distance visual acuity *One-way analysis of variance
CCT (r Z 0.470, PZ.018, and r Z 0.440, PZ.024, respectively). The AL was also significantly associated with the CH and CRF values (r Z 0.410, PZ.022, and r Z 0.600, PZ.002, respectively). In the control group, the CH value was not significantly associated with CCT or AL (r Z 0.294, PZ.073, and r Z 0.164, PZ.331, respectively). Also, the CRF value
was not significantly associated with AL (r Z 0.001, PZ.95), whereas the CRF was significantly correlated with CCT (r Z 0.432, PZ.007). Intraocular Pressure Table 2 also shows the IOP values measured with the biomechanical analyzer. Overall, the mean
Table 2. Study parameters. Study Group Parameter CH (mm Hg) Mean G SD Range CRF (mm Hg) Mean G SD Range IOPcc (mm Hg) Mean G SD Range IOPg (mm Hg) Mean G SD Range
Study Group
Control Group
P Value*
Ectopia Lentis (C)
Ectopia Lentis ( )
P Value*
10.8 G 1.5 8.6, 14.8
11.1 G 1.2 8.3, 13.1
0.30
9.9 G 1.2 8.6, 11.7
11.2 G 1.5 8.7, 14.8
.016
10.2 G 2.4 5.3, 15.2
11.0 G 1.3 9.2, 14.2
.07
8.2 G 1.8 5.3, 10.8
11.3 G 1.9 8.0, 15.2
!.001
14.4 G 4.1 6.7, 23.7
15.1 G 3.2 9.1, 22.8
.43
13.5 G 4.1 9.3, 19.5
15.6 G 3.8 9.2, 23.7
.07
14.5 G 4.3 6.4, 25.4
15.5 G 3.2 10.0, 23.0
.31
11.7 G 2.7 6.4, 14.7
16.2 G 4.3 9.6, 25.5
.003
CH Z corneal hysteresis; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure *One-way analysis of variance
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
312
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
Table 3. Comparison of biomechanical measurements between the study subgroup with ectopia lentis and the control group.
Parameter CH (mm Hg) Mean G SD Range CRF (mm Hg) Mean G SD Range IOPcc (mm Hg) Mean G SD Range IOPg (mm Hg) Mean G SD Range
Study Group with Ectopia Lentis
Control Group
9.9 G 1.2 8.6, 11.7
11.1 G 1.2 8.3, 13.1
.020
8.2 G 1.8 5.3, 10.8
11.0 G 1.3 9.2, 14.2
!.001
13.5 G 4.1 9.3, 19.5
15.1 G 3.2 9.1, 22.8
.14
11.7 G 2.7 6.4, 14.7
15.5 G 3.2 10, 23
.002
P Value*
CH Z corneal hysteresis; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmanncorrelated intraocular pressure *One-way analysis of variance
Goldman-correlated IOP and corneal-compensated IOP were not statistically significantly different between the study group and the control group (PZ.31 and PZ.43, respectively). Also, despite a significant difference in the mean Goldmann-correlated IOP value (PZ.003) between the study eyes with ectopia lentis and the study eyes without ectopia lentis, there was no statistically significant difference in the mean corneal-compensated IOP (PZ.07). DISCUSSION The corneal stroma constitutes 90% of the total thickness of the cornea and is a highly organized arrangement of collagen fibrils; it is responsible for the cornea’s mechanical and refractive properties.11 Although the factors that maintain the corneal shape are not well understood, biophysical factors contribute to the rigidity and elasticity of the cornea.12 It has been suggested that the specific architecture of the anterior 100 to 120 mm of the corneal stroma is responsible for the stability of the corneal shape.13 Corneal involvement has been described in autoimmune connective tissue disorders (eg, scleroderma, rheumatoid arthritis, and systemic lupus erythematosus) and heritable connective tissue disorders (eg, Ehlers-Danlos syndrome, Marfan syndrome, and Weill-Marchesani syndrome).4,14–20 Marfan syndrome is a pleiotropic autosomal dominant disorder caused by mutations in FBN1. Fibrillin is widely distributed throughout ocular tissues such as the cornea stroma and zonular fibers.21–23
In vivo confocal microscopy of corneas of patients with Marfan syndrome shows corneal thinning, an alteration in the stroma, and an opaque stromal matrix.2,24 Ectopia lentis is a major diagnostic criterion for Marfan syndrome. Although the exact mechanism leading to zonular stretching remains uncertain, a pathogenic effect of degraded fibrillin fragments has been suggested.25–27 Previously, corneal characteristics in Marfan syndrome have been assessed using corneal topographic maps, in vivo confocal microscopy, and CCT measurements.16,24 In the current study, we measured the biomechanical parameters of CH, CRF, Goldmanncorrelated IOP, and corneal-compensated IOP using the Ocular Response Analyzer; the results were compared between patients with Marfan syndrome (study group) and age-matched healthy individuals (control group). To our knowledge, our study is the first to determine the in vivo biomechanical properties of the cornea in patients with Marfan syndrome. This study generated new results. First, corneal biomechanical parameters, such as CH and CRF, were not significantly different between the study group and the control group. However, the CH and CRF values were significantly lower in Marfan syndrome eyes with ectopia lentis than in Marfan syndrome eyes without ectopia lentis. Second, the Goldmanncorrelated IOP and corneal-compensated IOP values did not differ significantly between the study group and the control group. We found no difference in the corneal-compensated IOP values between the eyes of patients with Marfan syndrome with ectopia lentis and the eyes of patients with Marfan syndrome without ectopia lentis, whereas the Goldmann-correlated IOP was significantly lower in the eyes with ectopia lentis. Third, there was no significant difference in AL or CCT between the study group and the control group, although study eyes with ectopia lentis had a significantly higher AL value and a significantly thinner CCT value than eyes without ectopia lentis. Corneal biomechanical properties, including CH and CRF, are important in corneal refractive surgery; IOP measurement; and the development, progression, and diagnosis of ocular diseases, such as keratoconus and glaucoma.8,9 Two earlier studies assessed the biomechanical properties of the cornea measured with the Ocular Response Analyzer in patients with connective tissue disorders. First, Prata et al.14 found that patients with rheumatoid arthritis had lower CH values and lower IOP values than age-matched controls. Second, Emre et al.15 evaluated the corneal biomechanical properties in patients with scleroderma; the mean CRF values were higher in the scleroderma group than in a control group of age-matched healthy subjects.
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
In our study, eyes with Marfan syndrome and ectopia lentis had lower CH and CRF values than eyes with the syndrome but without ectopia lentis. These outcomes might be associated with several mechanisms. First, eyes with defects that affect zonular stability may also have defects in the connective corneal tissue, causing a decrease in corneal biomechanical parameters. Distribution of fibrillin has been found in diseased corneas and zonular fibers.21–23 Thus, morphologic and biomechanical abnormalities resulting from mutations in FBN1 may produce the same diseases of the cornea and dislocation of the lens. Second, a longer AL in eyes with Marfan syndrome and ectopia lentis might contribute to the lower CH and CRF values. An increased AL is a minor criterion for Marfan disease diagnosis.24 A longer AL has been associated with lower biomechanical parameters of the cornea.28,29 In the Marfan syndrome group, we found a significant negative correlation between AL and CH–CRF values. Another possible factor for lower biomechanical values in cases of Marfan syndrome with ectopia lentis may be a thinner cornea. In previous studies,2,16 Marfan syndrome–affected corneas were significantly thinner than healthy human corneas. Also, a lower CCT value has been highly associated with ectopia lentis in patients with Marfan syndrome.2,16 Several studies11,28,30,31 found a positive significant correlation between the CCT and corneal biomechanical parameters. In our study, a positive correlation was found between CCT and CH–CRF values in the Marfan syndrome group. Accurate measurement of IOP is a basic parameter of every ophthalmologic examination. It was recently shown that corneal biomechanical properties have a greater effect on IOP measurement error in applanation tonometry than corneal thickness or curvature.32 The literature suggests that the corneal biomechanics are important and help with the assessment of accurate IOP.32,33 In our study, the measurements taken with the biomechanical analyzer showed that eyes with Marfan syndrome with ectopia lentis had significantly lower Goldmann-correlated IOP values than eyes with Marfan syndrome without ectopia lentis; however, the corneal-compensated IOP value was not significantly different between the 2 subgroups. The lower Goldmann-correlated IOP values in eyes with Marfan syndrome and ectopia lentis may be associated with decreased corneal biomechanical properties (viscoelasticity and elasticity). These results show that Ocular Response Analyzer measurements may help obtain correct IOP measurements in corneas affected by connective tissue disorders, such as Marfan syndrome. In summary, our data indicate that the eyes in patients with Marfan syndrome and ectopia lentis
313
have lower biomechanical parameter values, including CH and CRF. Moreover, Goldmann-correlated IOP could give erroneously lower IOP values in these patients. Thus, corneal-compensated IOP measured with the Ocular Response Analyzer should be taken into account when determining the accurate IOP value in patients with Marfan syndrome with ectopia lentis. REFERENCES roud G, Boileau C. Marfan syndrome in the third 1. Collod-Be millennium. Eur J Hum Genet 2002; 10:673–681. Available at: http://www.nature.com/ejhg/journal/v10/n11/pdf/5200876a.pdf. Accessed August 30, 2011 2. Sultan G, Baudouin C, Auzerie O, De Saint Jean M, Goldschild M, Pisella P-J; the Marfan Study Group. Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis. Invest Ophthalmol Vis Sci 2002; 43:1757–1764. Available at: http://www.iovs.org/content/43/6/1757.full.pdf. Accessed August 30, 2011 3. Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366:1965–1976. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC1513064/pdf/nihms-10620.pdf. Accessed August 30, 2011 4. Ammash NM, Sundt TM, Connolly HM. Marfan’s syndromed diagnosis and management. Curr Prob Cardiol 2008; 33:7–39 5. Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 1981; 79:684–733. Available at: http://www. pubmedcentral.nih.gov/picrender.fcgi?artidZ1312201&blobtypeZ pdf. Accessed August 30, 2011 6. Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, Opitz JM, Pope FM, Pyeritz RE, Rimoin DL, Sillence D, Spranger JW, Thompson E, Tsipouras P, Viljoen D, Winship I, Young I, Reynolds JF. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet 1988; 29:581–594 7. De Paepe A, Devereux RB, Dietz HC, Hennekam RCM, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet Am 1996; 62:417–426 8. Glass DH, Roberts CJ, Litsky AS, Weber PA. A viscoelastic biomechanical model of the cornea describing the effect of viscosity and elasticity on hysteresis. Invest Ophthalmol Vis Sci 2008; 49:3919–3926. Available at: http://www.iovs.org/cgi/ reprint/49/9/3919. Accessed August 30, 2011 rautret J, Garra C, Maurice-Tison S, 9. Touboul D, Roberts C, Ke Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622 10. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005; 31:156–162 11. Shah S, Laiquzzaman M, Cunliffe I, Mantry S. The use of the Reichert ocular response analyzer to establish the relationship between ocular hysteresis, corneal resistance factor and central corneal thickness in normal eyes. Cont Lens Anterior Eye 2006; 29:257–262 €llhas MO, Schroeder B, Grobherr M, 12. Hager A, Loge K, Fu Wiegand W. Changes in corneal hysteresis after clear corneal cataract surgery. Am J Ophthalmol 2007; 144:341–346 €ller LJ, Pels E, Vrensen GFJM. The specific architecture 13. Mu of the anterior stroma accounts for the maintenance of corneal curvature. Br J Ophthalmol 2001; 85:437–443. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1723934/pdf/ v085p00437.pdf. Accessed August 31, 2011
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
314
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
14. Prata TS, Sousa AK, Garcia Filho CAA, Doi LM, Paranhos A Jr. Assessment of corneal biomechanical properties and intraocular pressure in patients with rheumatoid arthritis [letter]. Can J Ophthalmol 2009; 44:602. Available at: http://download. journals.elsevierhealth.com/pdfs/journals/0008-4182/PIIS000 8418209801294.pdf. Accessed August 31, 2011 € Ates‚ H, C‚inar E, Inceo _ lu O, lu N, Yargucu F, 15. Emre S, Kayıkc‚iog g Pırıldar T, Oksel F. Corneal hysteresis, corneal resistance factor, and intraocular pressure measurement in patients with scleroderma using the Reichert ocular response analyzer. Cornea 2010; 29:628–631 € m C. Corneal 16. Konradsen TR, Koivula A, Kugelberg M, Zetterstro curvature, pachymetry, and endothelial cell density in Marfan syndrome. Acta Ophthalmol (Oxf) 2010 Sep 9; [Epub ahead of print] 17. Heur M, Costin B, Crowe S, Grimm RA, Moran R, Svensson LG, Traboulsi EI. The value of keratometry and central corneal thickness measurements in the clinical diagnosis of Marfan syndrome. Am J Ophthalmol 2008; 145:997–1001 18. Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristics in patients with Weill-Marchesani syndrome. J Cataract Refract Surg 2009; 35:1026–1032 19. Patel SJ, Lundy DC. Ocular manifestations of autoimmune disease. Am Fam Physician 2002; 66:991–998. Available at: http://www.aafp.org/afp/2002/0915/p991.pdf. Accessed September 1, 2011 20. Pesudovs K. Orbscan mapping in Ehlers-Danlos syndrome. J Cataract Refract Surg 2004; 30:1795–1798. Available at: http://www.pesudovs.com/konrad/Docs/Orbscan.pdf. Accessed September 1, 2011 21. Wheatley HM, Traboulsi EI, Flowers BE, Maumenee IH, Azar D, Pyeritz RE, Whittum-Hudson JA. Immunohistochemical localization of fibrillin in human ocular tissues; relevance to the Marfan syndrome. Arch Ophthalmol 1995; 113:103–109 22. Streeten BW, Licari PA, Marucci AA, Dougherty RM. Immunohistochemical comparison of ocular zonules and the microfibrils of elastic tissue. Invest Ophthalmol Vis Sci 1981; 21:130–135. Available at: http://www.iovs.org/content/21/1/130.full.pdf. Accessed September 1, 2011 23. Ashworth JL, Kielty CM, McLeod D. Fibrillin and the eye. Br J Ophthalmol 2000; 84:1312–1313. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1723284/pdf/v084p01312. pdf. Accessed September 1, 2011 24. Iordanidou V, Sultan G, Boileau C, Raphael M, Baudouin C; the Marfan Study Group. In vivo corneal confocal microscopy in Marfan syndrome. Cornea 2007; 26:787–792
€chinger HP, €ller PK, Ba 25. Reinhardt DP, Ono RN, Notbohm H, Mu Sakai LY. Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis; a potential disease-causing mechanism in Marfan syndrome. J Biol Chem 2000; 275:12339–12345. Available at: http://hwmaint.jbc.org/ cgi/reprint/275/16/12339. Accessed September 1, 2011 26. Nemet AY, Assia EI, Apple DJ, Barequet IS. Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol 2006; 51:561–575 27. Sachdev N, Wakefield D, Coroneo MT. Lens dislocation in Marfan syndrome and UV-B light exposure [letter]. Arch Ophthalmol 2003; 121:585 28. Narayanaswamy A, Chung RS, Wu R-Y, Park J, Wong W-L, Saw S-M, Wong TY, Aung T. Determinants of corneal biomechanical properties in an adult Chinese population. Ophthalmology 2011; 118:1253–1259 29. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006; 141:868–875 30. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008; 246:1491–1494 31. Leite MT, Alencar LM, Gore C, Weinreb RN, Sample PA, Zangwill LM, Medeiros FA. Comparison of corneal biomechanical properties between healthy blacks and whites using the Ocular Response Analyzer. Am J Ophthalmol 2010; 150: 163–168 32. Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement; quantitative analysis. J Cataract Refract Surg 2005; 31:146–155 33. Harada Y, Naoi N. Corneal elasticity as a measure of intra-ocular pressure: a controlled clinical examination. Kobe J Med Sci 2004; 50:141–152. Available at: http://www.med.kobe-u.ac.jp/ journal/contents/50/141.pdf. Accessed September 1, 2011
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
First author: Necip Kara, MD Department of Ophthalmology, Bakirkoy Maternity and Children Diseases Hospital, Istanbul, Turkey
Corneal biomechanical properties and intraocular pressure measurement in Marfan patients Necip Kara, MD, Ercument Bozkurt, MD, Okkes Baz, MD, Hasan Altinkaynak, MD, Huseyin Dundar, MD, Kemal Yuksel, MD, Ahmet Taylan Yazici, MD, Ahmet Demirok, MD, Sukru Candan, MD
PURPOSE: To compare the biomechanical properties of the cornea and intraocular pressure (IOP) between patients with Marfan syndrome and age-matched controls. SETTING: Departments of Ophthalmology and Genetics, Bakirkoy Maternity and Children Diseases Hospital, and Beyoglu Eye Education and Research Hospital, Istanbul, Turkey. DESIGN: Cross-sectional study. METHODS: This study comprised patients with Marfan syndrome (study group) and healthy individuals (control group). The study group was subdivided into patients with ectopia lentis and patients without ectopia lentis. In the right eye of each patient, the corneal hysteresis (CH), corneal resistance factor (CRF), Goldman-correlated IOP, and corneal-compensated IOP were recorded. RESULTS: Overall, the mean CH, CRF, Goldman-correlated IOP, and corneal-compensated IOP were not significantly different between the study group and the control group. The mean CH was 9.9 mm Hg G 1.2 (SD) in study eyes with ectopia lentis and 11.2 G 1.5 mm Hg in study eyes without ectopia lentis (PZ.016); the mean CRF was 8.2 G 1.8 mm Hg and 11.3 G 1.9 mm Hg, respectively (P<.001). The mean Goldman-correlated IOP was 11.7 G 2.7 mm Hg in study eyes with ectopia lentis and 16.2 G 4.3 in study eyes without ectopia lentis (PZ.003); the mean corneal-compensated IOP was 13.5 G 4.1 mm Hg and 15.6 G 3.8 mm Hg, respectively (PZ.07). CONCLUSION: The CH, CRF, and Goldman-correlated IOP were significantly lower in the Marfan syndrome eyes with ectopia lentis than in the Marfan syndrome eyes without ectopia lentis. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2012; 38:309–314 Q 2011 ASCRS and ESCRS
Marfan syndrome is a rare inherited connective tissue disorder transmitted as an autosomal dominant trait. The estimated incidence varies from 1:5000 to 1:50 000 according to different studies.1–4 The abnormality in Marfan patients involves defects in the protein fibrillin-1 (FBN1) on chromosome 15, a structural component of microfibrils that is an important part of the connective tissue, such as basement membranes and elastic tissues. Marfan syndrome is characterized by skeletal, cardiovascular, pulmonary, skin, and ocular involvements. The major ocular finding of Marfan syndrome is ectopia lentis. Approximately 60% of patients have lens dislocation.5 The lens dislocation is usually superior and temporal. This may present at birth or develop during childhood or adolescence. Other ocular involvements include a flat cornea, increased Q 2011 ASCRS and ESCRS Published by Elsevier Inc.
axial length (AL), cataract, hypoplastic iris, or hypoplastic ciliary muscle that causes decreased miosis; axial myopia; amblyopia; glaucoma; and retinal detachment.3,6,7 Corneal biomechanical evaluation may be helpful in the long-term monitoring of glaucoma. It can help avoid misinterpretation of intraocular pressure (IOP), be used in preoperative screening of refractive surgery candidates, and help differentiate between healthy corneas and abnormal corneas.8,9 A relatively new tool for in vivo assessment of corneal biomechanics is the Ocular Response Analyzer (Reichert, Inc). The biomechanical analyzer can measure IOP, corneal hysteresis (CH), and the corneal resistance factor (CRF). Corneal hysteresis is related to the viscoelastic behavior of the corneal tissue and is calculated as the difference between the 2 pressure 0886-3350/$ - see front matter doi:10.1016/j.jcrs.2011.08.036
309
310
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
values at 2 applanation measurements. The CRF is an indicator of the elastic properties of the cornea and is calculated as a linear function of the 2 pressures associated with the 2 applanation processes.10 The aim of the study was to evaluate the biomechanical properties of the cornea using the Ocular Response Analyzer in Marfan patients with and without lens dislocation. PATIENTS AND METHODS Study Population and Design This prospective cross-sectional comparative study was performed at the Ophthalmology, Cardiology, and Genetic Departments, Istanbul Bakirkoy Maternity and Children Diseases Hospital, and Istanbul Beyoglu Eye Education and Research Hospital. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee. All participants received oral and written information about the study and provided written informed consent. For participants younger than 18 years, a parent provided written informed consent. The participants were divided into 2 groups: cases with Marfan syndrome (study group) and normal cases (control group). Marfan patients were recruited in cooperation with the Departments of Cardiology and Clinical Genetics, Bakirkoy Maternity and Children Diseases Hospital, Istanbul, Turkey. The patients were defined as having Marfan syndrome based on clinical features (eg, 2 major diagnostic criteria), genetic confirmation (FBN1 mutation), or both. Also, the study group was divided into 2 subgroups according to the presence of ectopia lentis. The control group comprised individuals without Marfan syndrome who were matched with patients in the study group in mean age and spherical refraction. Those in the control group were recruited from the hospital staff and their families. Patients with a history of ocular surgery, ocular inflammatory disease, or glaucoma were excluded from the study.
Study Measurements Each clinical examination consisted of corrected distance visual acuity (CDVA) using a Snellen chart and the manifest refraction, biomicroscopy of the anterior segment, and a dilated fundus evaluation. The right eye of each participant was used in the study. Study participants had central corneal thickness (CCT) measurements with a DGH-550 ultrasound pachymeter (DGH Technology, Inc.), AL measurements with the Submitted: April 21, 2011. Final revision submitted: July 6, 2011. Accepted: August 18, 2011. From the Department of Ophthalmology (Kara) and Department of Genetics (Candan), Bakirkoy Maternity and Children Diseases Hospital, and Beyoglu Eye Education and Research Hospital (Bozkurt, Baz, Altinkaynak, Dundar, Yuksel, Yazici, Demirok), Istanbul, Turkey. Corresponding author: Necip Kara, Kartaltepe Mh. Akin Sk. Akin Apt. No:8/14 Bakirkoy/Istanbul, Turkey. E-mail: dr.necipkara@ gmail.com.
IOLMaster biometer (Carl Zeiss Meditech AG), and biomechanical measurements with the Ocular Response Analyzer. Three biomechanical measurements were performed in all subjects by an experienced clinician. Three good-quality measurements (symmetric, well-defined inward and outward applanation spike heights) were obtained for each eye, and the mean value of each parameter was used in the analysis. The clinician was masked to who was in the study group and who was in the control group. Analysis of the process resulted in 2 parameters of the biomechanical properties of the cornea; that is, CH and CRF. The analysis also yielded a Goldmann-correlated IOP value, which corresponds to that measured with the Goldmann applanation tonometer, and a corneal-compensated IOP value, which is thought to be little affected by corneal properties.10 The other measurements, including AL and CCT measurements, were performed by another experienced technician.
Statistical Analysis All statistical tests were performed using SPSS software (version 16, SPSS, Inc.). Snellen visual acuity measurements were converted to logMAR notation for statistical analysis. The normality of the data was confirmed using the Kolmogorov-Smirnov test (PO.05). One-way analysis of variance was used to compare variables between groups. The Pearson correlation was used to examine the relationships between the measured variables. A P value less than 0.05 was considered significant.
RESULTS Table 1 shows the baseline characteristics in the study group, the 2 study subgroups, and the control group. The mean age (PZ.11), spherical refraction (PZ.18), mean CCT (PZ0.23), and mean AL (PZ.18) did not differ significantly between the study group and the control group. There was a statistically significant difference in the spherical refraction (PZ.01), mean logMAR CDVA (PZ.021), mean CCT (PZ.04), and the mean AL (PZ.001) between the 2 study subgroups (eyes with ectopia lentis and eyes without ectopia lentis). Biomechanical Parameters Table 2 shows the results of the between-group comparison of CH and CRF. The mean CH and CRF values were not statistically significantly different between the study group and the control group. However, there was a significant difference in the mean CH and CRF values between the 2 study subgroups (PZ.016 and P!.001, respectively). Table 3 shows the results of the comparison of CH and CRF between study eyes with ectopia lentis and control eyes; there was a statistically significant difference in the mean CH and CRF values between study eyes with ectopia lentis and control eyes (PZ.02 and P!.001, respectively). A correlation analysis between CH–CRF values and CCT–AL values found that in the study group, the CH and CRF values were significantly associated with
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
311
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
Table 1. Patient demographics and characteristics. Study Group Parameter Eyes (n) Sex Female Male Age (y) Mean G SD Range Sphere (D) Mean G SD Range CDVA (logMAR) Mean G SD Range CCT (mm) Mean G SD Range AL (mm) Mean G SD Range
Study Group
Control Group
P Value*
Ectopia Lentis (C)
Ectopia Lentis ( )
P Value*
38
38
d
17
21
d
17 21
17 21
d
8 9
9 12
.50
18.7 G 7.8 8, 31
21.2 G 5.3 10, 30
.11
21.2 G 6.5 14, 29
17.2 G 8.2 8, 31
.16
2.0 G 2.7 6.00, C4.25
1.3 G 1.9 6.25, C1.50
.18
3.8 G 2.2 6.00, C0.50
1.1 G 2.5 5.50, C4.25
.01
0.07 G 0.11 0.0, 0.4
0.01 G 0.04 0.0, 0.22
.007
0.11 G 0.15 0.0, 0.4
0.04 G 0.06 0.0, 0.22
.021
564 G 40 498, 635
577 G 39 490, 663
.23
538 G 32 502, 573
575 G 39 498, 635
.04
24.0 G 1.9 21.0, 27.3
23.4 G 1.0 21.8, 26.3
.18
26.0 G 1.3 24.8, 27.3
23.1 G 1.5 21.0, 25.8
.001
AL Z axial Length; CCT Z central corneal thickness; CDVA Z corrected distance visual acuity *One-way analysis of variance
CCT (r Z 0.470, PZ.018, and r Z 0.440, PZ.024, respectively). The AL was also significantly associated with the CH and CRF values (r Z 0.410, PZ.022, and r Z 0.600, PZ.002, respectively). In the control group, the CH value was not significantly associated with CCT or AL (r Z 0.294, PZ.073, and r Z 0.164, PZ.331, respectively). Also, the CRF value
was not significantly associated with AL (r Z 0.001, PZ.95), whereas the CRF was significantly correlated with CCT (r Z 0.432, PZ.007). Intraocular Pressure Table 2 also shows the IOP values measured with the biomechanical analyzer. Overall, the mean
Table 2. Study parameters. Study Group Parameter CH (mm Hg) Mean G SD Range CRF (mm Hg) Mean G SD Range IOPcc (mm Hg) Mean G SD Range IOPg (mm Hg) Mean G SD Range
Study Group
Control Group
P Value*
Ectopia Lentis (C)
Ectopia Lentis ( )
P Value*
10.8 G 1.5 8.6, 14.8
11.1 G 1.2 8.3, 13.1
0.30
9.9 G 1.2 8.6, 11.7
11.2 G 1.5 8.7, 14.8
.016
10.2 G 2.4 5.3, 15.2
11.0 G 1.3 9.2, 14.2
.07
8.2 G 1.8 5.3, 10.8
11.3 G 1.9 8.0, 15.2
!.001
14.4 G 4.1 6.7, 23.7
15.1 G 3.2 9.1, 22.8
.43
13.5 G 4.1 9.3, 19.5
15.6 G 3.8 9.2, 23.7
.07
14.5 G 4.3 6.4, 25.4
15.5 G 3.2 10.0, 23.0
.31
11.7 G 2.7 6.4, 14.7
16.2 G 4.3 9.6, 25.5
.003
CH Z corneal hysteresis; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure *One-way analysis of variance
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
312
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
Table 3. Comparison of biomechanical measurements between the study subgroup with ectopia lentis and the control group.
Parameter CH (mm Hg) Mean G SD Range CRF (mm Hg) Mean G SD Range IOPcc (mm Hg) Mean G SD Range IOPg (mm Hg) Mean G SD Range
Study Group with Ectopia Lentis
Control Group
9.9 G 1.2 8.6, 11.7
11.1 G 1.2 8.3, 13.1
.020
8.2 G 1.8 5.3, 10.8
11.0 G 1.3 9.2, 14.2
!.001
13.5 G 4.1 9.3, 19.5
15.1 G 3.2 9.1, 22.8
.14
11.7 G 2.7 6.4, 14.7
15.5 G 3.2 10, 23
.002
P Value*
CH Z corneal hysteresis; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmanncorrelated intraocular pressure *One-way analysis of variance
Goldman-correlated IOP and corneal-compensated IOP were not statistically significantly different between the study group and the control group (PZ.31 and PZ.43, respectively). Also, despite a significant difference in the mean Goldmann-correlated IOP value (PZ.003) between the study eyes with ectopia lentis and the study eyes without ectopia lentis, there was no statistically significant difference in the mean corneal-compensated IOP (PZ.07). DISCUSSION The corneal stroma constitutes 90% of the total thickness of the cornea and is a highly organized arrangement of collagen fibrils; it is responsible for the cornea’s mechanical and refractive properties.11 Although the factors that maintain the corneal shape are not well understood, biophysical factors contribute to the rigidity and elasticity of the cornea.12 It has been suggested that the specific architecture of the anterior 100 to 120 mm of the corneal stroma is responsible for the stability of the corneal shape.13 Corneal involvement has been described in autoimmune connective tissue disorders (eg, scleroderma, rheumatoid arthritis, and systemic lupus erythematosus) and heritable connective tissue disorders (eg, Ehlers-Danlos syndrome, Marfan syndrome, and Weill-Marchesani syndrome).4,14–20 Marfan syndrome is a pleiotropic autosomal dominant disorder caused by mutations in FBN1. Fibrillin is widely distributed throughout ocular tissues such as the cornea stroma and zonular fibers.21–23
In vivo confocal microscopy of corneas of patients with Marfan syndrome shows corneal thinning, an alteration in the stroma, and an opaque stromal matrix.2,24 Ectopia lentis is a major diagnostic criterion for Marfan syndrome. Although the exact mechanism leading to zonular stretching remains uncertain, a pathogenic effect of degraded fibrillin fragments has been suggested.25–27 Previously, corneal characteristics in Marfan syndrome have been assessed using corneal topographic maps, in vivo confocal microscopy, and CCT measurements.16,24 In the current study, we measured the biomechanical parameters of CH, CRF, Goldmanncorrelated IOP, and corneal-compensated IOP using the Ocular Response Analyzer; the results were compared between patients with Marfan syndrome (study group) and age-matched healthy individuals (control group). To our knowledge, our study is the first to determine the in vivo biomechanical properties of the cornea in patients with Marfan syndrome. This study generated new results. First, corneal biomechanical parameters, such as CH and CRF, were not significantly different between the study group and the control group. However, the CH and CRF values were significantly lower in Marfan syndrome eyes with ectopia lentis than in Marfan syndrome eyes without ectopia lentis. Second, the Goldmanncorrelated IOP and corneal-compensated IOP values did not differ significantly between the study group and the control group. We found no difference in the corneal-compensated IOP values between the eyes of patients with Marfan syndrome with ectopia lentis and the eyes of patients with Marfan syndrome without ectopia lentis, whereas the Goldmann-correlated IOP was significantly lower in the eyes with ectopia lentis. Third, there was no significant difference in AL or CCT between the study group and the control group, although study eyes with ectopia lentis had a significantly higher AL value and a significantly thinner CCT value than eyes without ectopia lentis. Corneal biomechanical properties, including CH and CRF, are important in corneal refractive surgery; IOP measurement; and the development, progression, and diagnosis of ocular diseases, such as keratoconus and glaucoma.8,9 Two earlier studies assessed the biomechanical properties of the cornea measured with the Ocular Response Analyzer in patients with connective tissue disorders. First, Prata et al.14 found that patients with rheumatoid arthritis had lower CH values and lower IOP values than age-matched controls. Second, Emre et al.15 evaluated the corneal biomechanical properties in patients with scleroderma; the mean CRF values were higher in the scleroderma group than in a control group of age-matched healthy subjects.
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
In our study, eyes with Marfan syndrome and ectopia lentis had lower CH and CRF values than eyes with the syndrome but without ectopia lentis. These outcomes might be associated with several mechanisms. First, eyes with defects that affect zonular stability may also have defects in the connective corneal tissue, causing a decrease in corneal biomechanical parameters. Distribution of fibrillin has been found in diseased corneas and zonular fibers.21–23 Thus, morphologic and biomechanical abnormalities resulting from mutations in FBN1 may produce the same diseases of the cornea and dislocation of the lens. Second, a longer AL in eyes with Marfan syndrome and ectopia lentis might contribute to the lower CH and CRF values. An increased AL is a minor criterion for Marfan disease diagnosis.24 A longer AL has been associated with lower biomechanical parameters of the cornea.28,29 In the Marfan syndrome group, we found a significant negative correlation between AL and CH–CRF values. Another possible factor for lower biomechanical values in cases of Marfan syndrome with ectopia lentis may be a thinner cornea. In previous studies,2,16 Marfan syndrome–affected corneas were significantly thinner than healthy human corneas. Also, a lower CCT value has been highly associated with ectopia lentis in patients with Marfan syndrome.2,16 Several studies11,28,30,31 found a positive significant correlation between the CCT and corneal biomechanical parameters. In our study, a positive correlation was found between CCT and CH–CRF values in the Marfan syndrome group. Accurate measurement of IOP is a basic parameter of every ophthalmologic examination. It was recently shown that corneal biomechanical properties have a greater effect on IOP measurement error in applanation tonometry than corneal thickness or curvature.32 The literature suggests that the corneal biomechanics are important and help with the assessment of accurate IOP.32,33 In our study, the measurements taken with the biomechanical analyzer showed that eyes with Marfan syndrome with ectopia lentis had significantly lower Goldmann-correlated IOP values than eyes with Marfan syndrome without ectopia lentis; however, the corneal-compensated IOP value was not significantly different between the 2 subgroups. The lower Goldmann-correlated IOP values in eyes with Marfan syndrome and ectopia lentis may be associated with decreased corneal biomechanical properties (viscoelasticity and elasticity). These results show that Ocular Response Analyzer measurements may help obtain correct IOP measurements in corneas affected by connective tissue disorders, such as Marfan syndrome. In summary, our data indicate that the eyes in patients with Marfan syndrome and ectopia lentis
313
have lower biomechanical parameter values, including CH and CRF. Moreover, Goldmann-correlated IOP could give erroneously lower IOP values in these patients. Thus, corneal-compensated IOP measured with the Ocular Response Analyzer should be taken into account when determining the accurate IOP value in patients with Marfan syndrome with ectopia lentis. REFERENCES roud G, Boileau C. Marfan syndrome in the third 1. Collod-Be millennium. Eur J Hum Genet 2002; 10:673–681. Available at: http://www.nature.com/ejhg/journal/v10/n11/pdf/5200876a.pdf. Accessed August 30, 2011 2. Sultan G, Baudouin C, Auzerie O, De Saint Jean M, Goldschild M, Pisella P-J; the Marfan Study Group. Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis. Invest Ophthalmol Vis Sci 2002; 43:1757–1764. Available at: http://www.iovs.org/content/43/6/1757.full.pdf. Accessed August 30, 2011 3. Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366:1965–1976. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC1513064/pdf/nihms-10620.pdf. Accessed August 30, 2011 4. Ammash NM, Sundt TM, Connolly HM. Marfan’s syndromed diagnosis and management. Curr Prob Cardiol 2008; 33:7–39 5. Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 1981; 79:684–733. Available at: http://www. pubmedcentral.nih.gov/picrender.fcgi?artidZ1312201&blobtypeZ pdf. Accessed August 30, 2011 6. Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, Opitz JM, Pope FM, Pyeritz RE, Rimoin DL, Sillence D, Spranger JW, Thompson E, Tsipouras P, Viljoen D, Winship I, Young I, Reynolds JF. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet 1988; 29:581–594 7. De Paepe A, Devereux RB, Dietz HC, Hennekam RCM, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet Am 1996; 62:417–426 8. Glass DH, Roberts CJ, Litsky AS, Weber PA. A viscoelastic biomechanical model of the cornea describing the effect of viscosity and elasticity on hysteresis. Invest Ophthalmol Vis Sci 2008; 49:3919–3926. Available at: http://www.iovs.org/cgi/ reprint/49/9/3919. Accessed August 30, 2011 rautret J, Garra C, Maurice-Tison S, 9. Touboul D, Roberts C, Ke Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622 10. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005; 31:156–162 11. Shah S, Laiquzzaman M, Cunliffe I, Mantry S. The use of the Reichert ocular response analyzer to establish the relationship between ocular hysteresis, corneal resistance factor and central corneal thickness in normal eyes. Cont Lens Anterior Eye 2006; 29:257–262 €llhas MO, Schroeder B, Grobherr M, 12. Hager A, Loge K, Fu Wiegand W. Changes in corneal hysteresis after clear corneal cataract surgery. Am J Ophthalmol 2007; 144:341–346 €ller LJ, Pels E, Vrensen GFJM. The specific architecture 13. Mu of the anterior stroma accounts for the maintenance of corneal curvature. Br J Ophthalmol 2001; 85:437–443. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1723934/pdf/ v085p00437.pdf. Accessed August 31, 2011
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
314
CORNEAL BIOMECHANICAL PARAMETERS IN MARFAN SYNDROME
14. Prata TS, Sousa AK, Garcia Filho CAA, Doi LM, Paranhos A Jr. Assessment of corneal biomechanical properties and intraocular pressure in patients with rheumatoid arthritis [letter]. Can J Ophthalmol 2009; 44:602. Available at: http://download. journals.elsevierhealth.com/pdfs/journals/0008-4182/PIIS000 8418209801294.pdf. Accessed August 31, 2011 € Ates‚ H, C‚inar E, Inceo _ lu O, lu N, Yargucu F, 15. Emre S, Kayıkc‚iog g Pırıldar T, Oksel F. Corneal hysteresis, corneal resistance factor, and intraocular pressure measurement in patients with scleroderma using the Reichert ocular response analyzer. Cornea 2010; 29:628–631 € m C. Corneal 16. Konradsen TR, Koivula A, Kugelberg M, Zetterstro curvature, pachymetry, and endothelial cell density in Marfan syndrome. Acta Ophthalmol (Oxf) 2010 Sep 9; [Epub ahead of print] 17. Heur M, Costin B, Crowe S, Grimm RA, Moran R, Svensson LG, Traboulsi EI. The value of keratometry and central corneal thickness measurements in the clinical diagnosis of Marfan syndrome. Am J Ophthalmol 2008; 145:997–1001 18. Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristics in patients with Weill-Marchesani syndrome. J Cataract Refract Surg 2009; 35:1026–1032 19. Patel SJ, Lundy DC. Ocular manifestations of autoimmune disease. Am Fam Physician 2002; 66:991–998. Available at: http://www.aafp.org/afp/2002/0915/p991.pdf. Accessed September 1, 2011 20. Pesudovs K. Orbscan mapping in Ehlers-Danlos syndrome. J Cataract Refract Surg 2004; 30:1795–1798. Available at: http://www.pesudovs.com/konrad/Docs/Orbscan.pdf. Accessed September 1, 2011 21. Wheatley HM, Traboulsi EI, Flowers BE, Maumenee IH, Azar D, Pyeritz RE, Whittum-Hudson JA. Immunohistochemical localization of fibrillin in human ocular tissues; relevance to the Marfan syndrome. Arch Ophthalmol 1995; 113:103–109 22. Streeten BW, Licari PA, Marucci AA, Dougherty RM. Immunohistochemical comparison of ocular zonules and the microfibrils of elastic tissue. Invest Ophthalmol Vis Sci 1981; 21:130–135. Available at: http://www.iovs.org/content/21/1/130.full.pdf. Accessed September 1, 2011 23. Ashworth JL, Kielty CM, McLeod D. Fibrillin and the eye. Br J Ophthalmol 2000; 84:1312–1313. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1723284/pdf/v084p01312. pdf. Accessed September 1, 2011 24. Iordanidou V, Sultan G, Boileau C, Raphael M, Baudouin C; the Marfan Study Group. In vivo corneal confocal microscopy in Marfan syndrome. Cornea 2007; 26:787–792
€chinger HP, €ller PK, Ba 25. Reinhardt DP, Ono RN, Notbohm H, Mu Sakai LY. Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis; a potential disease-causing mechanism in Marfan syndrome. J Biol Chem 2000; 275:12339–12345. Available at: http://hwmaint.jbc.org/ cgi/reprint/275/16/12339. Accessed September 1, 2011 26. Nemet AY, Assia EI, Apple DJ, Barequet IS. Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol 2006; 51:561–575 27. Sachdev N, Wakefield D, Coroneo MT. Lens dislocation in Marfan syndrome and UV-B light exposure [letter]. Arch Ophthalmol 2003; 121:585 28. Narayanaswamy A, Chung RS, Wu R-Y, Park J, Wong W-L, Saw S-M, Wong TY, Aung T. Determinants of corneal biomechanical properties in an adult Chinese population. Ophthalmology 2011; 118:1253–1259 29. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006; 141:868–875 30. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008; 246:1491–1494 31. Leite MT, Alencar LM, Gore C, Weinreb RN, Sample PA, Zangwill LM, Medeiros FA. Comparison of corneal biomechanical properties between healthy blacks and whites using the Ocular Response Analyzer. Am J Ophthalmol 2010; 150: 163–168 32. Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement; quantitative analysis. J Cataract Refract Surg 2005; 31:146–155 33. Harada Y, Naoi N. Corneal elasticity as a measure of intra-ocular pressure: a controlled clinical examination. Kobe J Med Sci 2004; 50:141–152. Available at: http://www.med.kobe-u.ac.jp/ journal/contents/50/141.pdf. Accessed September 1, 2011
J CATARACT REFRACT SURG - VOL 38, FEBRUARY 2012
First author: Necip Kara, MD Department of Ophthalmology, Bakirkoy Maternity and Children Diseases Hospital, Istanbul, Turkey