Does optic nerve head(ONH) remodeling precedes retinal nerve fiber layer(RNFL) thinning in glaucoma patients?

Abstract

 

Purpose

 

Glaucoma is characterized by progressive loss of retinal ganglion cells and remodeling of the ONH. Animal studies show that optic disc surface height change measured by CSLO precedes RNFL thinning measured by OCT in experimental glaucoma. However, long-term clinical data corroborating this observation is lacking. In this prospective study, we followed 146 eyes of 90 glaucoma patients followed for at least 4 years to determine the sequence of ONH and RNFL changes.

 

Methods

 

Eyes were imaged by CSLO (HRT) and SD-OCT (Cirrus HD-OCT) at 4-month intervals for measurement of ONH surface topology and RNFL thickness, respectively. Only images meeting the quality criteria (signal strength ≥8 for OCT; SD≤30µm for HRT) in the same visits were included for analysis. RNFL progression was defined when there were more than 20 pixels coded in red in the RNFL thickness change map analyzed by the Guided Progression Analysis(i.e. consecutive thickness changes greater than the test-retest variability). ONH progression was analyzed with reference to Topographic Change Analysis based on two criteria (less conservative: total clusters inside ONH ≥0.1% of the disc area with a mean depth change of ≥20µm; more conservative: total clusters inside ONH ≥2% of disc area with ≥100µm mean depth change).

 

Results

 

The mean follow-up duration was 64.5 months (range: 48.3-76.6 months). FIG 1 shows the Venn diagrams of progression detection using different criteria. 26 and 10 eyes had progression evident in both CSLO and OCT at the final visit, with 17 (65.4%) and 7 eyes (70%) had optic disc surface height depression before RNFL thinning, using the less and more conservative criteria, respectively. Only 6 (23.1%) and 2 (20%) eyes had RNFL thinning detected before ONH surface depression. The agreement between OCT and CSLO progression was poor in both criteria (kappa: 0.074-0.096).

 

Conclusions

 

ONH surface depression occurred prior to RNFL thinning in most glaucoma patients. ONH remodeling may be an early sign for therapeutic intervention before irreversible loss of neuronal tissues in glaucoma.

 

 

Fig 1 Venn diagrams showing the number of eyes and patients with progression detected by OCT and CSLO using the less and more conservative criteria.

 

 

Fig 2 Serial RNFL thickness maps (A), RNFL thickness change maps (B), ONH surface topology maps (C), ONH significance maps (D) of a glaucomatous eye followed for 59.4 months.

 

Keywords: 550 imaging/image analysis: clinical