Influence of Corneal Opacity on Intraocular Pressure Assessment in Patients with Lysosomal Storage Diseases

Abstract

Aims: To investigate an influence of mucopolysaccharidosis (MPS)- and Morbus Fabry-associated corneal opacities on intraocular pressure (IOP) measurements and to evaluate the concordance of the different tonometry methods.

Methods: 25 MPS patients with or without corneal clouding, 25 Fabry patients with cornea verticillata ≥ grade 2 and 25 healthy age matched controls were prospectively included into this study. Outcome measures: Goldmann applanation tonometry (GAT); palpatory assessment of IOP; Goldmann-correlated intraocular pressure (IOPg), corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH) assessed by Ocular Response Analyzer (ORA); central corneal thickness (CCT) and density assessed with Pentacam. Statistical analysis was performed using linear mixed effect models and Spearman correlation coefficients. The concordance between tonometry methods was assessed using Bland-Altman analysis.

Results: There was no relevant difference between study groups regarding median GAT, IOPg, IOPcc and CCT measurements. The limits of agreement between GAT and IOPcc/IOPg/palpatory IOP in MPS were: [-11.7 to 12.1mmHg], [-8.6 to 15.5 mmHg] and [- 5.4 to 10.1 mmHg] respectively. Limits of agreement were less wide in healthy subjects and Fabry patients. Palpatory IOP was higher in MPS than in healthy controls and Fabry patients. Corneal opacity correlated more strongly with GAT, IOPg, CH, CRF, CCT and corneal density in MPS (r = 0.4, 0.5, 0.5, 0.7, 0.6, 0.6 respectively) than in Fabry patients (r = 0.3, 0.2, -0.03, 0.1, 0.3, -0.2 respectively). In contrast, IOPcc revealed less correlation with corneal opacity than GAT in MPS (r = 0.2 vs. 0.4).

Conclusions: ORA and GAT render less comparable IOP-values in patients suffering from MPS-associated corneal opacity in comparison to Fabry and healthy controls. The IOP seems to be overestimated in opaque MPS-affected corneas. GAT, IOPg and biomechanical parameters of the cornea correlate more strongly with the corneal clouding than IOPcc in MPS patients.

Trial registration: ClinicalTrials.gov NCT01695161.

Conflict of interest statement

Prof. Susanne Pitz was supported by Genzyme (US) and Shire. The funds were used for the acquisition of the Ocular Response Analyzer. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Consort 2010 flow diagram.

Fig 2. Opaque corneal clouding of grade 4 in patient suffering from MPS I.

Fig 3. Cornea verticillata grade 3 in patient suffering from Morbus Fabry.

A bilateral, whorl-like pattern of powdery, white, yellow or brown corneal deposits.

Fig 4. Association of GAT, IOPcc, IOPg, CH, CRF, CCT and density with diagnostic group and the grade of the corneal clouding.

Estimated means and 95% confidence intervals are shown.

Fig 5. Association between Goldmann applanation tonometry (GAT), corneal compensated IOP (IOPcc), Goldmann correlated IOP (IOPg), corneal hysteresis (CH), corneal resistance factor (CRF) central corneal thickness (CCT), corneal density and the grade of corneal clouding in all experimental groups.

Estimated means and 95% confidence intervals are shown.

Fig 6. Bland-Altmann Plot for agreement between Goldmann applanation tonometry (GAT) and corneal-compensated IOP (IOPcc).

Fig 7. Bland-Altmann Plot for agreement between Goldmann applanation tonometry (GAT) and Goldmann-correlated IOP (IOPg).

Fig 8. Bland-Altmann Plot for agreement between Goldmann applanation tonometry (GAT) and palpatory assessed IOP (palp IOP).

Fig 9. Goldmann applanation tonometry (GAT), corneal compensated IOP (IOPcc), Goldmann-correlated IOP (IOPg), corneal resistance factor (CRF), central corneal thickness (CCT) and corneal hysteresis (CH) in MPS type IV, VI and healthy controls in the right (OD) and the left (OS) eyes.