Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma, as Measured with Swept Source Optical Coherence Tomography

Abstract

Purpose: To investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon).

Methods: This retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 μm), centered on the circular Bruch's membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24-2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman's rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela's method.

Results: We found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 μm, PPG: 248 ± 13 μm, OAG: 233 ± 20 μm). Multiple regression analysis showed that MD (β = 0.29, P = 0.013), vertical C/D ratio (β = -0.25, P = 0.020) and tissue MBR (β = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 μm) than the non-GE patients (243.6 ± 19.5 μm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients.

Conclusion: Cupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.

Fig 1. Distribution of the correlation between local and overall lamina cribrosa (LC) thickness in a grid superimposed on the LC.

(A) The numbers in the grid cells represent Spearman’s rank correlation coefficient. The cells highlighted in gray had a higher correlation coefficient. (B) The numbers in the grid cells represent the P value. The cells highlighted in gray were significantly correlated (P value < 0.05). (C) Map showing the position of 4 areas of high correlation, comprising 4, 12, 16, and 36 grid cells, respectively.

Fig 2. Simplified software technique for measuring lamina cribrosa (LC) thickness in a 4 x 4 grid.

(A) 4 x 4 grid superimposed on an en-face image of the LC, showing the position of the B-scan images below. (B-E) Horizontal cross-sectional B-scan images, with orange dots indicating the anterior and posterior borders of the LC. Average LC thickness was defined as the average thickness in the 16 grid cells.

Fig 3. B-scan and en-face images.

(A) B-scan image. The dotted lines (B-G) indicate the position of the en-face images below. (B) Upper area of the lamina cribrosa (LC). (C) Upper border of the LC. (D, E) Centerline of the LC. (F) Lower border of the LC. (G) Lower area of the LC.

Fig 4. Difference in the association between average lamina cribrosa thickness (avgLCT) and HFA MD in glaucoma patients with generalized enlargement (GE)-type discs and non-GE discs.

(A) Representative appearance of a GE disc. (B) Comparison of avgLCT in patients with non-GE and GE discs.

Fig 5. The correlation between measurements of lamina cribrosa thickness (LCT) made with the original and simplified versions of the software.

Scatter plot graph showing the correlation of LCT measurements made with the original and simplified versions of the software. Note: the correlation coefficient between LCT measurements made with the original and simplified versions was 0.71 (P < 0.001).

Fig 6. AvgLCT measurements made with the simplified version of the software.

(A) Bar graph indicating LC thickness in patients with different stages of glaucoma (normal: n = 22, PPG: n = 28, OAG: n = 100). Note: there were significant differences between these groups (Kruskal-Wallis test followed by Steel-Dwass test). *: P < 0.01. (B) ROC curve. The area under the ROC curve was 0.91, with a cutoff value of 246.3 μm.

Fig 7. Association between glaucoma parameters and average thickness of the LC (AvgLCT).

(A) MD (B) cpRNFLT (C) vertical C/D ratio (D) tissue MBR.