Intraocular Pressure and Corneal Biomechanical Properties in Patients with Myotonic Dystrophy

Intraocular Pressure and Corneal Biomechanical Properties in Patients with Myotonic Dystrophy

Intraocular Pressure and Corneal Biomechanical Properties in Patients with Myotonic Dystrophy Nicola Rosa, MD,1,2 Michele Lanza, MD,1,2 Maria Borrelli...

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Intraocular Pressure and Corneal Biomechanical Properties in Patients with Myotonic Dystrophy Nicola Rosa, MD,1,2 Michele Lanza, MD,1,2 Maria Borrelli, MD,1 Alberto Palladino, MD,3 M. Grazia Di Gregorio, MD,3 Luisa Politano, MD3 Purpose: To compare intraocular pressure (IOP) between patients with myotonic dystrophy (DM1) and normal subjects, taking into account corneal characteristics. To determine whether lower IOP measurements in patients with DM1 are due to thinner corneas. Design: Comparative case series. Participants: Fifty-three eyes of patients with DM1 and 53 eyes of normal age- and sex-matched subjects. Methods: Corneal biomechanical properties and corneal compensated intraocular pressure (IOPcc) measured with the Ocular Response Analyzer (Reichert Inc., Depew, NY), central corneal thickness measured with the Oculus Pentacam (Oculus, Wetzlar, Germany), and IOP were evaluated in patients with DM1 and compared with age- and sex-matched healthy subjects. Main Outcome Measurements: Goldmann applanation tonometry, central corneal thickness, corneal hysteresis (CH), corneal resistance factor (CRF), and IOPcc. Results: Compared with the healthy subjects, patients with DM1 showed lower IOP (12.4⫾3.6 mm Hg vs. 14.9⫾3.4 mmHg) (P⬍0.01) and IOPcc (12.7⫾4.5 vs. 15.9⫾3.5) (P⬍0.01), and thicker cornea (575.9⫾35.02 ␮m vs. 556.3⫾33.2 ␮m) (P⬍0.01), but no significant changes in CH (P ⫽ 0.03) and CRF (P ⫽ 0.37). Conclusions: Lower IOP in patients with DM1 is not related to differences in central corneal thickness or corneal biomechanical properties. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:231–234 © 2009 by the American Academy of Ophthalmology.

Myotonic dystrophy (DM1) is the most common inherited muscle disease in adults, affecting approximately 1 in 8000 people. DM1 is caused by an expanded (CTG)n repeat (from 37 to several thousands) within the noncoding 3’ untranslated region of the DM1 protein kinase gene on chromosome 19p35. It is inherited with an autosomal dominant pattern1–3 and characterized by myotonia, muscular wasting, frontal baldness, testicular atrophy, and ocular abnormalities, including cataract, ptosis, exposure keratitis, pigmentary abnormalities, abnormal electroretinograms, abnormal dark adaptation, and weakness of the orbicularis ocular muscles.4 It has been reported that patients with DM1 can show ocular hypotony.5–7 Previous studies have suggested that the hypotony in patients with DM1 could be related to an increased facility of outflow or a decreased aqueous secretion; however, the pathophysiologic mechanism responsible for low intraocular pressure (IOP) remains unclear.8 –13 It is also well known that the corneal characteristics influence Goldmann applanation tonometry readings.14 –23 The objective of our study was to determine whether differences in corneal characteristics (i.e., corneal thickness) could account for differences in IOP between a group of patients with DM1 and a group of normal sex- and agematched control subjects. © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.

Patients and Methods A total of 53 eyes of 53 patients (27 male and 26 female) affected by DM1, who belonged to 40 unrelated families (maximum 3 patients from the same family) followed at the Cardiomyology and Medical Genetics of Second University Medical School, were consecutively enrolled in this study. The diagnosis was based on family history, typical muscle findings, and electromyography, and confirmed by genetic analysis. The control group consisted of 53 eyes (53 healthy subjects) age and sex matched. The age range was between 19 and 67 years (mean 39.2⫾13.6 years). None of the patients involved in the study used topical medications or medications known to alter aqueous humor flow or IOP, or reported previous eye surgery or contact lenses. An informed consent, according to the guidelines of the Declaration of Helsinki, was obtained from each patient. Institutional review board approval was obtained. All patients underwent a complete ophthalmic examination, including measurement of the IOP by a Goldmann applanation tonometer, an examination by the Ocular Response Analyzer (Reichert Inc., Depew, NY) to measure corneal hysteresis (CH), corneal resistant factor (CRF), and corneal compensated intraocular pressure (IOPcc), and a corneal tomography performed by an Oculus Pentacam (Oculus, Wetzlar, Germany) to measure the central corneal thickness. The Ocular Response Analyzer, similar to a noncontact tonometer, uses a metered collimated air pulse to applanate the cornea in the central 3.0 mm diameter and an infrared electro-optical system ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2008.09.001

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Ophthalmology Volume 116, Number 2, February 2009 Table 1. Characteristics of Normal and Myotonic Patients

CCT IOP IOPcc CH CRF

Normal Mean ⴞ SD (min; max)

DM1 Mean ⴞ SD (min; max)

P Value

556.4⫾33.2 ␮m (485; 643) 14.9⫾3.4 mmHg (8; 24) 15.9⫾3.5 mmHg (9; 24.5) 10.3⫾1.4 mmHg (6.9; 14) 10.3⫾1.7 mmHg (5.8; 13.5)

575.9⫾35.02 ␮m (518; 661) 12.4⫾3.6 mmHg (5; 20) 12.7⫾4.5 mmHg (7.03; 32.1) 10.78⫾1.9 mmHg (3.9; 15.7) 10.03⫾1.86 mmHg (6; 14.1)

⬍0.01 ⬍0.01 ⬍0.01 0.03 0.37

CCT ⫽ central corneal thickness; IOP ⫽ intraocular pressure; IOPcc ⫽ corneal compensated intraocular pressure; CH ⫽ corneal hysteresis; CRF ⫽ corneal resistant factor. Mean ⫾ SD and minimum and maximum of values obtained in normal and myotonic patients (DM1) for all the evaluated parameters. Significance of differences (P value).

to record inward and outward applanation events. The 2 applanations take place within approximately 20 ms. The difference between the inward and outward motion applanation pressures is called CH and is defined as the difference in pressure between peak l and peak 2. This device is also able to provide another value: CRF that is the result of large-scale clinical data analysis and that is derived from specific combinations of the inward and outward applanation values using proprietary algorithms and is defined as a linear function of the 2 peaks24,25; IOPcc is obtained from the difference between the 2 applanation pressures using the formula P2-kP1, where P1 and P2 are the first and second applanation pressures, respectively, and k is a constant. Because the difference between P1 and P2 is related to the corneal biomechanical properties, the value of IOPcc is supposed to represent a measure of IOP that is free of the corneal influence.18 The differences observed in the 2 groups of patients were evaluated with the paired Student t test.

Results The obtained results are summarized in Table 1. Comparison of the patients’ characteristics in the 2 groups showed a significant dif-

ference in central corneal thickness (P⬍0.001) and IOP (P⬍0.001) (Figs 1 and 2). The 2 parameters that measure the biomechanical properties of the cornea, CH and CRF, were within normal limits for both groups, and no significant difference was found between the 2 groups (CH: P ⫽ 0.11; CRF: P ⫽ 0.37). The lack of influence of the corneal characteristics on the IOP measurements was confirmed by the significant difference in IOPcc (P⬍0.001), which is a pressure measurement that should be less affected by corneal properties than other methods of tonometry because it compensates for the biomechanical properties of the cornea and not just for its thickness.18

Discussion Our study shows that IOP is significantly lower in myotonic patients compared with a group of normal subjects. This phenomenon cannot be ascribed to different corneal characteristics that could alter the applanation tonometry readings. Myotonic patients show a corneal thickness higher

Figure 1. Histogram showing the intraocular pressure (IOP) distribution in normal subjects and myotonic dystrophy patients (DM1).

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Figure 2. Histogram showing the central corneal thickness (CCT) distribution in normal subjects and myotonic dystrophy patients (DM1).

than in the control group, and in this case higher and not lower values with Goldmann applanation tonometry will be expected. On the basis of this finding, our study supports the hypothesis that the lower IOP we observed in DM1 could be caused by an increased outflow or a decreased aqueous production. Thicker corneas in myotonic patients could be caused by stromal lamellar thickening or increased stromal hydration. Further studies comparing the central corneal thickness between different kinds of myotonic patients are necessary to establish whether this finding is a main feature of DM1 or is present in other myotonic syndromes and to clarify the reason.

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7. Kuhn E, Piesbergen HJ. Hypotension des Bulbus und Katarakt bei myotonischer Dystrophie [in German]. Klin Monatsbl Augenheilkd Augenarztl Fortbild 1957;130:329 –35. 8. Burian HM, Burns CA. Ocular changes in myotonic dystrophy. Trans Am Ophthalmol Soc 1966;64:250 –73. 9. Ginsberg J, Hamblet J, Menefee M. Ocular abnormality in myotonic dystrophy. Ann Ophthalmol 1978;10:1021– 8. 10. Nappi G, Savoldi F, Sandrini G, Poloni M. Tonographic evaluation of intraocular pressure in myotonic dystrophy. Boll Soc Ital Biol Sper 1978;54:180 –3. 11. Manschot WA. Histological findings in a case of dystrophia myotonica. Ophthalmologica 1968;155:294 – 6. 12. Burns CA. Ocular histopathology of myotonic dystrophy: a clinicopathologic case report. Am J Ophthalmol 1969;68: 416 –22. 13. Houber JP, Babel J. Uveo-retinal lesions in myotonic dystrophy: histological study [in French]. Ann Ocul (Paris) 1970;203:1067–76. 14. Whitacre MM, Stein R. Sources of error with use of Goldmann–type tonometers. Surv Ophthalmol 1993;38:1– 30. 15. Broman AT, Congdon NG, Bandeen-Roche K, Quigley HA. Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure. J Glaucoma 2007;16:581– 8. 16. Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol 2000;44:367– 408. 17. Saleh TA, Adams M, McDermott B, et al. Effects of central corneal thickness and corneal curvature on the intraocular pressure measurement by Goldmann applanation tonometer and ocular blood flow pneumatonometer. Clin Experiment Ophthalmol 2006;34:516 –20. 18. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the Ocular Response Analyzer. J Glaucoma 2006;15:364 –70.

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Ophthalmology Volume 116, Number 2, February 2009 19. Tonnu PA, Ho T, Newson T, et al. The influence of central corneal thickness and age on intraocular pressure measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann applanation tonometry. Br J Ophthalmol 2005; 89:851– 4. 20. Martinez-de-la-Casa JM, Garcia-Feijoo J, Fernandez-Vidal A, et al. Ocular Response Analyzer versus Goldmann applanation tonometry for intraocular pressure measurements. Invest Ophthalmol Vis Sci 2006;47:4410 – 4. 21. Francis BA, Hsieh A, Lai MY, et al. Effects of corneal thickness, corneal curvature, and intraocular pressure level on Goldmann applanation tonometry and dynamic contour tonometry. Ophthalmology 2007;114:20 – 6.

22. Hager A, Schroeder B, Sadeghi M, et al. The influence of corneal hysteresis and corneal resistance factor on the measurement of intraocular pressure [in German]. Ophthalmologe 2007;104:484 –9. 23. Kohlhaas M, Boehm AG, Spoerl E, et al. Effect of central corneal thickness, corneal curvature, and axial length on applanation tonometry. Arch Ophthalmol 2006;124:471– 6. 24. Luce DA. Determining in vivo biomechanical properties of the cornea with an Ocular Response Analyzer. J Cataract Refract Surg 2005;31:156 – 62. 25. Touboul D, Roberts C, Kérautret J, et al. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008;34:616 –22.

Footnotes and Financial Disclosures Originally received: April 15, 2008. Final revision: September 3, 2008. Accepted: September 3, 2008. Available online: November 18, 2008.

Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2008-470.

1

Centro Grandi Apparecchiature, 2nd University of Naples, Naples, Italy.

2

Eye Department, 2nd University of Naples, Naples, Italy.

3

Department of Experimental Medicine, Cardiomyology and Medical Genetics, 2nd University of Naples, Naples, Italy.

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Correspondence: Nicola Rosa, MD, Centro Grandi Apparecchiature, 2nd University of Naples Via De Crecchio 16, 80100 Napoli, Italy. E-mail: nicola.rosa@ unina2.it.