Cornea. 2019 May;38(5):595-599.

Measurement of Corneal Biomechanical Properties in Diabetes Mellitus Using the Ocular Response Analyzer and the Corvis ST.

Lisa Ramm, MD; Robert Herber; Eberhard Spoerl, PhD; Lutz E. Pillunat, MD; Naim Terai, MD

Department of Ophthalmology, University Hospital Dresden, Fetscherstr. 74, 01307 Dresden, Germany

Corresponding author:

Lisa Ramm, MD

Department of Ophthalmology

University Hospital Carl Gustav Carus, TU Dresden

Fetscherstr. 74

01307 Dresden, Germany

Tel.: +49 351 458 3381

Fax: +49 351 458 4335





Hyperglycemia in diabetes mellitus (DM) might induce changes in corneal biomechanics. Therefore, biomechanical properties of the cornea were measured using the ocular response analyzer and the Corvis ST.


In the study, 35 eyes of 35 diabetic patients were included. After an ophthalmological examination, measurements with the ocular response analyzer and the Corvis ST were taken. Additionally, biometry and corneal topography were performed and HbA1c values were collected. Results were compared to an age-, pachymetry- and intraocular pressure-matched group of 35 healthy subjects.


Mean age (67.6 ± 10.3; 64.1 ± 8.3 years), intraocular pressure (13.4 ± 2.9; 12.8 ± 2.8 mm Hg), and central corneal thickness (556.4 ± 31.7; 548.6 ± 32.9 μm) were not significantly different between the groups (P > 0.05). In DM, the corneal hysteresis (CH) and the corneal resistance factor (CRF) were increased (CH: 10.8 ± 2 vs. 9.4 ± 1.6, P = 0.002; CRF: 10.6 ± 2.1 vs. 9.6 ± 1.5, P = 0.022). Also, most dynamic corneal response parameters showed significant differences. Beside others, A1 and A2 deflection amplitudes were increased (P < 0.001) and highest concavity and A2 time were extended (P < 0.001 and 0.007) in DM. According to current HbA1c value, DM was classified as controlled (≤7%) and poorly controlled (>7%) and significant biomechanical differences were measured between both groups.


In DM, significant changes in corneal biomechanical properties were detectable. In patients, CH and CRF were increased and most dynamic corneal response parameters were different compared to healthy subjects.

PMID: 30681520



Corneal biomechanics might be changed in diabetes mellitus

Diabetes mellitus (DM) causes different systemic changes in the human body, including architecture and pathophysiology of the corneal tissue [1]. There also is increasing evidence that DM affects corneal biomechanics. The key factor, hyperglycemia, leads to an increase in protein glycosylation and to the formation of advanced glycosylation end products (AGEs). Apart from direct tissue-toxic effects, AGEs might exert direct structural changes in the corneal stroma by enhancing the degree of collagen crosslinks, resulting in changes in the biomechanical behavior of the corneal tissue [1-3]. This pathophysiologic step may be the reason for inaccuracies and misinterpretations of intraocular pressure (IOP) readings in some patients with DM [1-3]. Goldmann applanation tonometry is considered as the gold standard for IOP measurement. However, uncertainties result from different factors, such as corneal thickness, curvature or rigidity [4-7]. For this reason, different new tonometers, accounting for biomechanical properties of the cornea, are available at present. The Reichert Ocular Response Analyzer (ORA, Reichert Technologies, Depew, NY, USA) and the Dynamic Scheimpflug Analyzer Corvis ST (CST, Oculus, Wetzlar, Germany) are two of the most recognized non-contact tonometers, which were designed to account for corneal biomechanical properties.


Measurement of corneal biomechanical properties in diabetes mellitus

In a prospective, cross-sectional study, 70 eyes of 35 patients with DM and 35 healthy subjects were included. Participants with any prior corneal diseases, contact lens usage, previous ocular surgeries, systemic connective tissue diseases or glaucoma were excluded. To provide comparability of the results, healthy subjects were randomly selected from a group of 96 healthy volunteers (group matching) according to age, central corneal thickness (CCT) and IOP.

After a complete ophthalmological examination, ocular biometry (IOL Master, Carl Zeiss Meditec., Oberkochen, Germany) and corneal topography (Pentacam, Oculus, Wetzlar, Germany) were performed to exclude any further corneal alteration. In DM patients HbA1c values were collected to define two groups: a well controlled (HbA1c ≤ 7 %) and a poorly controlled (HbA1c > 7 %) DM group.

Corneal biomechanical properties were measured using the ORA and the CST. Details have been described elsewhere [8-11]. Briefly, a rapid jet of air induces a corneal applanation. The airflow forces the cornea to move inwards with increasing intensity until it reaches a concave state. Afterwards, the intensity of the air jet decreases and the cornea returns to its natural shape according to its inherent elasticity.

The ORA uses an infrared beam to measure the corneal deformation. Depending on corneal biomechanical properties, the acting pressure necessary to achieve defined corneal deformation states differs. The device calculates the Corneal Hysteresis (CH) and the Corneal Resistance Factor (CRF) from these pressure values [8, 9, 11]. The CST monitors the corneal applanation process using a high-speed Scheimpflug camera, which creates a two dimensional cross-sectional image of the moving cornea. Subsequently, the device calculates dynamic corneal response (DCR) parameters to describe the corneal biomechanical behavior during the introduced applanation process [8, 10].


The Corneal Hysteresis and the Corneal Resistance Factor are increased in patients with diabetes mellitus

In DM, CH and CRF, as measured by the ORA, were statistically significantly increased (CH: 10.8 ± 2 vs. 9.4 ± 1.6; P = 0.002 and CRF: 10.6 ± 2.1 vs. 9.6 ± 1.5; P = 0.022). Furthermore, a non-significant rise in CH and CRF in poorly controlled DM compared to patients with HbA1c value ≤ 7 % was detected (CH: 10.9 ± 1.6 vs. 10.5 ± 2.2 mmHg, P = 0.446; CRF: 11 ± 1.8 vs. 10.3 ± 2.2 mmHg, P = 0.425). These results are in agreement with most of the earlier ORA studies in patients with DM [2, 12, 13]. The CH is an indicator for the viscous damping capacity of the cornea, while the CRF represents the global corneal resistance against deformation [2, 11-13]. Accordingly, the current results showed an increased corneal viscosity in DM. The reason might be a change in ground substance of the cornea, as discussed before [2, 3, 12, 13]. Chronic hyperglycemia in DM presumably induces the formation of AGEs by non-enzymatic glycosylation, leading to an accumulation of AGEs in different cell types and within the laminin of basal membranes [14]. Furthermore, corneal proteoglycans and glycosaminoglycans might be glycosylated in DM [12, 13, 15]. Earlier studies showed an age-dependent CH decrease as a consequence of the reduction of matrix components with increasing age [16, 17]. The higher viscous properties of the cornea in DM might be the result of a reduction of this age-dependent reduction of matrix components caused by glycation of proteoglycans and glycosaminoglycans [13, 18]. Furthermore, AGEs might induce a higher crosslinking of corneal collagen fibrils and proteoglycans [2, 12, 19-21], which additionally leads to higher corneal resistance against deformation. Moreover, corneal epithelial and endothelial cells could also be responsible for changes in biomechanics in DM. A dysfunction of these cells might alter the corneal hydration control, leading to corneal swelling and edema [1, 12]. Accordingly, higher CCT values have been reported in diabetic patients [2, 13, 22].



Figure 1: Corneal Hysteresis (CH) and Corneal Resistance Factor (CRF) measured by Ocular Response Analyzer in healthy subjects and patients with diabetes mellitus (CH P = 0.002; CRF P = 0.022)


Dynamic corneal response parameters measured by Corvis ST are altered in diabetic patients

To the best of our knowledge, this is one of the first studies using the CST to investigate corneal biomechanics in DM [3]. The device provides different DCR parameters to describe corneal biomechanical properties. Most of these indices showed differences between healthy subjects and patients with DM. Among others, time of highest concavity (HC Time, 16.02 ± 0.47 vs. 17.26 ± 0.47 ms, P < 0.001) and 2nd applanation time (A2 Time, 21.54 ± 0.46 vs. 21.87 ± 0.47 ms, P = 0.007) were significantly increased in DM. In agreement with ORA results, the additional time needed to achieve defined points during corneal applanation process could indicate a higher corneal viscosity. On the other hand, applanation amplitudes A1 (A1 deflection amplitude, 0.1 ± 0.01 vs. 0.11 ± 0.01 mm, P < 0.001) and A2 (A2 deflection amplitude, 0.11 ± 0.01 vs. 0.13 ± 0.01 mm, P < 0.001) were significantly higher in patients with DM. Accordingly, comparing the two DM groups, A1 deflection amplitude (0.111 ± 0.008 vs. 0.106 ± 0.007 mm, P = 0.047) and A1 deformation amplitude (0.148 ± 0.01 vs. 0.139 ± 0.138 mm, P = 0.006) were significantly higher in poorly controlled compared to well controlled patients. This finding contradicts the assumption of a higher corneal stiffness in DM, as a decrease in amplitudes would be expected [10, 23, 24]. A possible explanation might be that the elastic component of corneal behavior is unchanged in DM while its inertia is increased. This could cause a later stop of the corneal movement if it is introduced once during the deformation process. Two further DCR parameters, the integrated radius (7.628 ± 1.075 vs. 8.416 ± 0.995 1/mm, P = 0.048) and the deflection amplitude ratio max (DA ratio max at 1 mm: 1.542 ± 0.049 vs. 1.585 ± 0.053, P = 0.028; at 2 mm: 4.05 ± 0.391 vs. 4.487 ± 0.516, P = 0.03) were smaller in uncontrolled compared to well controlled patients. The integrated radius is the amount of the corneal concave state over the time between applanation 1 and applanation 2 [10, 25]. DA ratio max is a parameter which describes the ratio between the central deformation and the average of peripheral deformation determined at 1 mm and 2 mm from the apex [25]. A higher corneal stiffness is accompanied by a decrease of the integrated radius and the DA ratio max [26]. Therefore, a higher integrated radius and DA ratio max in uncontrolled DM might indicate a reduced corneal flexibility. This could again be the result of increased corneal viscosity in DM.



Figure 2: A1 and A2 deflection amplitude, highest concavity (HC) and A2 time measured by Corvis ST in healthy subjects and diabetes mellitus patients (A1 defl. amp. P <0.001, A2 defl. amp. P < 0.001, HC time P < 0.001, A2 time P = 0.007)


In conclusion, in patients with DM, changes in corneal biomechanical properties were detectable using ORA and CST. These changes might be of importance in clinical practices as they may influence IOP measurement and refractive procedures, and may accompany corneal diseases in patients with DM. However, the underlying pathophysiologic mechanisms should be elucidated in further studies.




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