Br J Ophthalmol 96:806-810 doi:10.1136/bjophthalmol-2011-300557
  • Clinical science
  • Original article

Corneal biomechanical properties and intraocular pressure measurement in patients with nanophthalmos

  1. Omer Faruk Yilmaz1
  1. 1Beyoglu Eye Research and Training Hospital, Istanbul, Turkey
  2. 2Kanuni Sultan Suleyman Education and Research Hospital, Department of Ophthalmology, Istanbul, Turkey
  1. Correspondence to Necip Kara, Kartaltepe Mh, Akın Sk, Akın Apt No:8/14, Bakırköy, Istanbul 34001, Turkey; dr.necipkara{at}
  1. Contributors Conception and design, or analysis and interpretation of data: CA, NK and OB; drafting the article or revising it critically for important intellectual content: CA, NK and BS; and final approval of the version to be published: CA, BS, AD and OFY.

  • Accepted 12 February 2012
  • Published Online First 7 March 2012


Aims To compare the biomechanical properties of the cornea and intraocular pressure (IOP) between patients with nanophthalmos and age-matched controls.

Methods In this prospective, cross-sectional and comparative study, 27 eyes of 27 healthy individuals (control group) and 27 eyes of 27 patients with nanophthalmos (study group) were enrolled. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure (IOPcc) and Goldmann correlated intraocular pressure (IOPg) were recorded for the right eye of each participant using Reichert Ocular Response Analyser measurements. Also, all participants in this study underwent a standardised ocular examination including IOP measurement with Goldmann applanation tonometry (IOPGAT), central corneal thickness and axial length (AL) assessments.

Results Mean CH in the nanophthalmic eyes and in the control eyes were 13.3±2.4 mm Hg and 11.6±1.7 mm Hg, respectively (p=0.003); mean CRF values in the nanophthalmic and the control eyes were 13.2±1.8 mm Hg and 11.4±1.9 mm Hg, respectively (p=0.001). Mean IOPGAT was 15.2±3.3 mm Hg in the nanophthalmic eyes and 13.4±2.7 mm Hg in the control group (p=0.031); mean IOPg values for the nanophthalmic and the control groups were 17.1±5.3 mm Hg and 14.7±3.5 mm Hg, respectively (p=0.042). Mean IOPcc values in the nanophthalmic and the control group were 13.6±6.1 mm Hg and 14.8±3.2 mm Hg, respectively (p=0.365).

Conclusion The CH, CRF, IOPg and IOPGAT were significantly higher in the nanophthalmic eyes, whereas no significant differences in IOPcc were observed. These findings may be taken into account when measuring IOP values in patients with nanophthalmos.


Nanophthalmos is a rare congenital disorder of the eye in which both the anterior and posterior segments are abnormally small with no ocular or systemic abnormalities.1 2 Clinical features of nanophthalmos include a short axial length (AL), a thickened sclera, hyperopia, narrow palpebral fissure, shallow anterior chamber, high incidence of angle-closure glaucoma, uveal effusion and high lens to eye volume ratio.3–5

The corneal changes associated with nanophthalmos include microcornea, irregular corneal astigmatism, steepening, corneal opacities and corneal vascularisation.6–8 Nanophthalmos is often associated with angle-closure glaucoma because of the short AL of the eye in this condition. Once glaucoma is diagnosed, accurate intraocular pressure (IOP) measurements are very important to ensure IOP goals.

Corneal biomechanical evaluation may be helpful for the avoidance of a misinterpretation of the IOP and the differentiation of healthy corneas from abnormal corneas.9–11 The Ocular Response Analyser (ORA) for in vivo evaluation of corneal biomechanical parameters was recently introduced by Reichert (Reichert Ophthalmic Instruments, Buffalo, New York, USA). The ORA measures corneal biomechanical parameters and IOP using a non-contact rapid air pulse. The air pulse causes the cornea to move inward, through applanation (inward applanation), and into slight concavity. With the decreasing force of the air pulse, the cornea moves through a second applanation (outward applanation) while returning from concavity to its normal convex curvature. This equipment measures the IOP, corneal hysteresis (CH) and corneal resistance factor (CRF). CH is calculated as the difference between the two pressure values at two applanation processes and is a measure of the viscous damping of the cornea. The CRF is calculated as a linear function of the two pressures associated with the two applanation processes and is a measure directly related to the viscous and elastic resistance inherent to the cornea.12 The aim of the study was to investigate the biomechanical parameters of the cornea and IOP measurement in patients with nanophthalmos.


This prospective, cross-sectional and comparative study was performed at the 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 each participant provided written informed consent. A written informed consent was provided by parents for participants younger than 18 years old.

The participants were divided into two groups: participants with nanophthalmos (study group) and participants with normal cases (control group). The control group was comprised of individuals without nanophthalmos and they were matched with patients in the study group according to mean age and gender.

The study included the patients with nanophthalmos whose diagnosis was based on a shorter than average AL (<20.5 mm), a shallow anterior chamber (<3.0 mm), and moderate to severe hyperopia (>+3.5 D). All participants had symmetrically cupped optic discs (<0.3) without any neuroretinal rim abnormality such as peripapillary haemorrhage, notch or focal thinning. Patients suffering from diabetes, taking cortisone either systemically or topically or any other topical medication, and who had a history of previous ocular surgery or eye trauma, contact lens use, dry eye or corneal abnormalities which may affect measurement of IOP were excluded.

Each clinical examination included best-corrected visual acuity using a Snellen chart and the manifest refraction, IOP measurement by Goldmann applanation tonometry (IOPGAT), ORA analysis, biomicroscopy of the anterior segment and dilated fundus examination as a last step of examination.

For all study participants, central corneal thickness (CCT) measurements were taken with ultrasound pachymetry (DGH-550, DGH Technology Inc., Exton, Pennsylvania, USA), and AL measurements were taken with the IOL Master (Carl Zeiss Meditech, AG, Jena, Germany); moreover, ORA measurements (Reichert Ophthalmic Instruments, Buffalo, New York, USA) were also taken.

All ORA measurements were obtained using the same calibrated instrument by the same masked technician. Briefly, each patient was seated and asked to fixate on a target light and the measurement was taken. A non-contact probe scanned the central corneal area and released an air puff. For each patient, three measurements of good quality with minimal variability were obtained; the reading with best signal value was used for statistical evaluation. Analysis of the process resulted in the identification of two parameters of the biomechanical properties of the cornea, that is, CH and CRF. The analysis also resulted in the corneal compensated IOP (IOPcc) value and a Goldmann correlated IOP (IOPg) value corresponding to the Goldmann applanation tonometer. The other measurements including the AL and CCT were also performed by an experienced technician.

All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) V.16. The normality of the data was confirmed using the Shapiro–Wilk test (p>0.05). A t test was used to compare variables between groups. An ANOVA test was used to compare more than two means. Once a significant difference was found between the means, the Bonferroni test was used for differences. Pearson's correlation was used to examine the relationships among the measured variables. A p value of less than 0.05 was considered significant.


This study included 27 healthy subjects and 27 patients with nanophthalmos. The demographic and clinical characteristics of the two groups of subjects are shown in table 1. No statistically significant differences were observed between the two groups in terms of age and gender distributions.

Table 1

The demographic and clinical characteristics of patients

Significant differences were observed in the mean best-corrected visual acuity (p<0.001), spherical refraction (p<0.001), mean CCT (p<0.001) and mean AL (<0.001) for the patients with and without nanophthalmos (table 1).

Table 2 shows the results of the comparison of CH and CRF between the two groups. The mean CH value was 13.3±2.4 mm Hg in the nanophthalmic group and 11.6±1.7 mm Hg in the control group (p=0.003). The mean CRF values in the nanophthalmic and the control group were 13.2±1.8 mm Hg and 11.4±1.9 mm Hg, respectively (p=0.001).

Table 2

Biomechanical parameters of nanophthalmic and control groups

Table 3 summarises the IOP values measured with the ORA (IOPcc and IOPg) and Goldmann applanation tonometer (IOPGAT) in two groups. The mean IOPGAT value was 15.2±3.3 mm Hg for the nanophthalmic group and 13.4±2.7 mm Hg for the control group (p=0.031). The mean IOPg value was 17.1±5.3 mm Hg for the nanophthalmic group and 14.7±3.5 mm Hg for the control group (p=0.042). The mean IOPcc values in the nanophthalmic and the control group were 13.6±6.1 mm Hg and 14.8±3.2 mm Hg, respectively (p=0.365). We also made a comparison of IOP measurements (IOPGAT, IOPg and IOPcc) within groups. In the nanophthalmic eyes, IOPcc was significantly lower than IOPg (p<0.001) and IOPGAT (p=0.046). In the control group, there was no significant differences between the IOP measurements (p>0.05).

Table 3

Intraocular pressure of nanophthalmic and control groups

The correlation analysis was performed for CCT, AL, spherical refraction, CH-CRF, IOPg, IOPGAT and IOPcc values. The CH values were significantly associated with CCT, spherical refraction, AL and IOPcc values (r=0.340, p=0.008; r=0.416, p=0.001; r=−0.385, p=0.003; and r=−0.651, p<0.001, respectively) (figure 1A–D), but no significant correlation was found with IOPg and IOPGAT. The CRF values were significantly associated with CCT, spherical refraction, IOPg, IOPGAT and AL (r=0.691, p<0.001; r=0.534, p<0.001; r=0.447, p<0.001; and r=0.347, p=0.011; and r=−0.461, p<0.001, respectively) (figure 2A–E), but no significant correlation was found with IOPcc.

Figure 1

Corneal hysteresis (CH) was positively correlated with central corneal thickness (CCT) (A; r=0.340, p=0.008) and spherical refraction (B; r=0.416, p=0.001) while CH showed a negative correlation with axial length (AL) (C; r=−0.385, p=0.003) and corneal compensated intraocular pressure (IOPcc) (D; r=−0.651, p≤0.001).

Figure 2

Corneal resistance factor (CRF) was positively correlated with central corneal thickness (CCT) (A; r=0.691, p<0.001), spherical refraction (B; r=0.534, p<0.001), Goldmann correlated intraocular pressure (IOPg) (C; r=0.447, p<0.001) and intraocular pressure measured with Goldmann applanation tonometry (IOPGAT) (D; r=0.347, p=0.011) while CRF showed a negative correlation with axial length (AL) (E; −0.461, p<0.001).


Nanophthalmos is a special subtype of microphthalmia and is characterised by a smaller eye than normal eye with no systemic findings or other developmental defects that are present in other cases of microphthalmos.13–15

Although the exact mechanism of nanophthalmos is still not known, several possible hypotheses have been offered to explain it.16–18 First, one possible explanation is the developmental arrest of the globe after the closure of the embryonic fissure.19 However, this theory does not explain all the ocular findings. Another theory was reported by Ryan and colleagues.15 They suggested that a smaller-than-normal optic vesicle growing from the forebrain at an early stage may be the cause of the reduced size of the eye. Also, scleral thickening of nanophthalmic eyes could be explained by the development of a normal amount of scleral cells surrounding a smaller optic vesicle, thereby resulting in a proportionately denser population of cells.4 15 19

Clinical features of nanophthalmic eyes include a narrow palpebral fissure, very short AL, high hyperopia, small cornea, shallow anterior chamber, thickened choroid and sclera, high lens to eye volume ratio, and angle-closure glaucoma.3 19 20 Also, posterior segment changes including macular hypoplasia, retinal pigment epithelium changes, uveal effusion, retinal detachment, retinal cyst, macular hypoplasia, retinoschisis, papillomacular folds, ‘drusen-like’ deposits and pigmentary retinopathy have been described.4 15 19 21–24

Few reports in the literature describe the corneal findings of patients with nanophthalmos. Although the most described features is the small corneal diameter, other features, that is, irregular corneal astigmatism, very steep or flat curvature, corneal opacities and corneal vascularisation have been reported.6–8

In this study, we investigated the corneal biomechanical properties as measured with ORA and the IOP measurements of these patients. To our knowledge, this is the first study to investigate these properties. We found that the patients with nanophthalmos had significantly higher CH and CRF values when compared with age matched controls. This result may be associated with several possible mechanisms. In our study, the mean AL was significantly lower in the nanophthalmic group as compared with the control group and a significant negative correlation was also found between CH and AL. A significant negative correlation has been reported between the AL and biomechanical parameters of the cornea.25 26 A possible factor for higher biomechanical values in the nanophthalmic eyes may be the greater corneal thickness found in the eyes of these patients. In many previous studies, a positive significant correlation has been observed between the CCT and corneal biomechanical parameters.25 27–29 In our study, the CCT values were significantly higher in patients with nanophthalmos as compared with the age matched controls, and a significant positive correlation between CH and CCT was also found. Second, the nanophthalmic corneal stroma may have some unknown properties that result in higher corneal biomechanical properties. Although some current studies have described histological anomalies of the scleral collagen in nanophthalmic eyes, no histological or ultrastructural investigations have been conducted on nanophthalmic corneas.30–33 Further studies are required to elucidate this hypothesis. Higher CH values in nanophthalmos eyes reflect the higher viscous resistance which represent ocular resistance due to the combined effect of corneal thickness and ocular rigidity. However, higher CRF values show the higher viscous and elastic resistance which is an indicator of the overall ‘resistance’ of the cornea.

Reliable measurement of IOP is an important parameter in ophthalmic examinations, for the diagnosis and the monitoring of glaucoma, and also in clinical investigations. The measurement of IOP in patients with different corneas is problematic due to the effect of corneal thickness and other biomechanical properties on the measurement techniques.34 Indeed, corneal biomechanical properties have a greater effect on IOP measurement error than corneal thickness or curvature in applanation tonometry.35 Also, Narayanaswamy et al found CH to be lower in glaucomatous eyes compared with control eyes.36 The literature suggests that corneal biomechanics are important and help with the assessment of the accuracy of IOP.35 37 In this study, the ORA measurements showed that the nanophthalmic eyes had significantly higher IOPg and IOPGAT values than the healthy eyes. However, the IOPcc value of the nanophthalmic eyes was not significantly different from that of the healthy eyes. The higher IOPg and IOPGAT values of nanophthalmic eyes may be associated with the increased biomechanical properties of the cornea. In nanophthalmic eyes, IOPcc which is less affected by corneal biomechanical properties was significantly lower than IOPg and IOPGAT which are more affected corneal physical properties. In healthy eyes, there were no significant differences among the IOPGAT, IOPcc and IOPg. These results show that IOPcc measured by ORA may be important when trying to correct IOP measurements which are important for the diagnosis and monitoring of glaucoma for the corneas of nanophthalmic eyes.

The present study has certain limitations. Although IOPcc values measured by ORA were found as similar in nanophthalmic and normal eyes in the current study, future studies including IOP measurements obtained by direct cannulation of anterior chamber and determining the ‘true’ IOP by direct measurement are required for the accuracy of our assumption. Also, our IOP measurements with Goldmann applanation were done only with the prism at 180°. Most clinician measures the IOP with Goldmann applanation tonometer at 180° and 90° and average them.

In summary, our study indicates that patients with nanophthalmos have higher biomechanical parameters including CH and CRF. Furthermore, IOPg and IOPGAT are influenced by corneal properties and could thus contribute to erroneously high IOP values in these patients. Thus, IOPcc measured with ORA may be taken into consideration when attempting to determine the accurate IOP value in patients with nanophthalmos.


  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was approved by Beyoglu Eye Education and Research Hospital Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.