Abstract
Purpose.:
To study factors associated with choroidal thickness (CT) and to compare CT in angle closure (AC), open angle (OA), and normal eyes.
Methods.:
Forty controls, 106 OA, and 79 AC subjects underwent measurements of posterior CT by spectral domain-optical coherence tomography, and of intraocular pressure (IOP), blood pressure, axial length (AL), and central corneal thickness (CCT).
Results.:
CT was significantly greater in AC than in OA and normal eyes (HSD test, P ≤ 0.05), but there was no significant difference between OA and normal CT; mean CT was 234, 235, and 318 μm in the normal, OA, and AC groups, respectively. With multivariable analysis among all participants, thinner CT was associated with older age, longer AL, higher IOP, and thicker CCT (all P ≤ 0.03, R 2 = 0.45). Adjusting for other relevant variables, the AC group had a significantly greater CT than either the normal or the OA group (P = 0.003 and 0.03, respectively). In multivariable analysis including only OA and AC patients, neither cup-to-disc ratio nor visual field mean deviation were significantly associated with CT. Multivariable analysis for CT among normal eyes found longer AL to be associated with thinner CT (P = 0.04).
Conclusions.:
AC eyes had significantly thicker CT than OA and normal eyes, even after adjusting for the shorter AL in AC eyes, supporting hypotheses that choroidal expansion contributes to the development of AC disease. Age, AL, CCT, and IOP were also significantly associated with CT, while severity of glaucoma damage was not.
The examination protocol was conducted in a seated position. BP measurements were obtained using an automatic blood pressure cuff (Datascope Corp., Paramus, NJ: median of 3 measurements), followed by measurement of IOP (average of 2 measurements) using a tonometer (Icare; Icare Finland Oy, Espoo, Finland). AL (median of 3 measurements); anterior chamber depth (ACD: average of 2 measurements); and keratometry (average of 2 measurements) were then measured using a biometer (IOLMaster 500; Carl Zeiss Meditec, Dublin, CA). Scans of the macular region were obtained using SD-OCT equipment (Spectralis; Heidelberg Instruments, Inc., Heidelberg, Germany).
The SD-OCT images were obtained utilizing enhanced depth imaging, which allows better visualization of the choroidal-scleral interface (CSI) than standard retinal SD-OCT images. The macular region was scanned using a single 30° linear scan centered on the fovea. Several scans were obtained, and the image with the best visualization of the border between the choroid and sclera, the CSI, was chosen.
Keratometry readings and the most recent refraction were entered into an integrated patient database software (Heidelberg Eye Explorer; Heidelberg Engineering, Heidelberg, Germany) to estimate optical magnification and, therefore, to allow for more accurate comparisons across individuals. We have previously shown that failure to correct for these variables significantly impacts thickness estimation.
9
Demographic data as well as clinical measurements were tabulated for all participants and by diagnostic group. For outcomes for which two or three repeat measurements were available (e.g., BP or AL), the median was used for analysis. The significance of differences among diagnostic groups was determined using the χ2 test for categorical variables, analysis of variance for normally distributed variables, and the Kruskal-Wallis test for continuous variables that were not normally distributed. Pairwise comparisons among diagnostic groups were made by partitioning the χ2 statistic for categorical variables and using Tukey's studentized range (HSD) test for continuous variables; rank statistics were analyzed in the case of continuous variables that were not normally distributed.
Univariate linear regression analysis was used to identify participant characteristics that were associated with CT. Three multivariable linear models of CT were constructed: one for all participants, one for OA and AC participants only, and one for normal participants. Independent variables for each model were chosen using the backward selection method with the criterion for staying in the model set at a probability value of 0.10. A variable included in a multivariable model was considered to be statistically significant only if the P value was 0.05 or less. Estimated coefficients and the associated variances and covariances from the multivariable model were used to make pairwise comparisons of the adjusted mean CTs for the diagnostic groups. All analyses were performed using data analysis software (SAS 9.2; SAS Institute, Cary, NC).
In this prospective study of 225 participants, including 40 normals, AC diagnosis was associated with a thicker choroid while older age, longer AL, higher IOP, and thicker CCT were associated with a thinner choroid. Several other investigations of factors associated with CT have also determined that older persons and eyes with longer AL or myopic refraction have a thinner choroid.
9–13 Our present results confirm most of the features associated with CT from our previous report, where AC diagnosis was associated with greater CT and older age, longer AL, and thicker CCT were associated with thinner CT.
9 To our knowledge, there are no other publications evaluating CT among OA, AC, and normal persons.
AC eyes had a thicker choroid when compared with OA and normal eyes, even after adjusting for the shorter AL in AC eyes. Furthermore, in a recent study comparing the response of OA and AC eyes in the water-drinking test (WDT),
17 we found that 30 minutes after rapidly drinking 1 L of water, there was a significantly greater increase in CT and in IOP in AC than in OA eyes. This greater increase in CT in AC eyes occurred despite the increase in IOP in these eyes, which would be expected to cause thinning of the choroid, all other factors being equal.
17 This suggests that in addition to having a significantly thicker choroid at baseline, AC eyes have a greater tendency to dynamic change in CT than do OA eyes.
17
The significantly greater baseline CT and the greater tendency to choroidal expansion in AC eyes may be related to the development of AC disease.
30–32 For example, choroidal expansion participates in secondary AC after central retinal vein occlusion or after scleral buckling procedures.
33 Recent UBM studies of AC eyes show abnormal separations between the choroid and sclera, an observation consistent with the idea that choroidal expansion contributes to the development of AC.
34–35 Clinical observations also suggest that intra- and postoperative choroidal expansion is more common in extreme cases of AC disease, such as nanophthalmos. We hypothesize that choroidal expansion contributes to the process of AC by the following sequence of events. The intraocular volume increase coincident with choroidal expansion causes an immediate increase in IOP.
30–32 As a result of this IOP increase, trabecular aqueous outflow would likely increase in order to restore IOP toward normal.
30–32 A posterior to anterior pressure differential would result as fluid left the anterior chamber, and aqueous volume in the anterior chamber would decrease.
30–32 The lens would then move forward, narrowing the iris-lens channel and intensifying resistance to aqueous movement through the pupil (pupillary block).
30–32 Using Navier-Stokes equations of fluid dynamics, we have previously demonstrated that in the AC eye, even an anterior lens movement of a few μm could result in an increased transiris pressure differential,
36 leading the iris to bow forward to make contact with the meshwork. Thus, in the predisposed eye with a baseline narrow angle, dynamic expansion of the choroid would contribute to a greater chance for symptomatic or asymptomatic AC.
30–32
In our previous report, we also found that the combination of lower BP or higher IOP, expressed as lower diastolic PP, was associated with a thinner choroid.
9 In the present expanded group of eyes, higher IOP was associated with thinner CT, while PP was not a significant variable. Polska et al. have shown that human choroidal blood flow is maintained in the face of changes in ocular PP, including both mean arterial pressure and IOP.
37,38 This autoregulation seems more efficient with changes in blood pressure than with changes in IOP.
37,38 Prior work in animals had also demonstrated that the autoregulatory capacity of choroidal blood flow was less effective with changes in IOP compared with changes in BP.
39 Although our finding is from a cross-sectional comparison, it is compatible with these studies, since less effective autoregulation would allow greater changes in choroidal blood volume and CT with changes in IOP than with changes in BP. It is logical that higher IOP would reduce choroidal blood volume and CT. Consistent with this hypothesis, although AC eyes had an expansion of the choroid during the WDT, those eyes with greater IOP increase had less choroidal expansion.
17
Interestingly, CCT, which has been linked to several aspects of ocular anatomy and physiology, including a greater risk of OAG,
40 was also found to be inversely associated with CT in the multivariable model in all patients (
Table 4). However, when AL and ACD were excluded from the list of factors being considered for the multivariable model, CCT was no longer associated significantly with CT (
Table 5). We speculate that the association of CCT with CT may somehow be related to AL and ACD. Further research is needed to clarify the relationships among these factors.
Among the 40 normal subjects in our study, we found that longer AL was the only factor significantly associated with thinner CT, while the association between older age and thinner CT was of borderline significance. Several groups have reported thinner CT with older age in normals,
11,25,41,42 while at least two groups have found an association between thinner CT and longer AL or myopic refractive error.
11,43 It is interesting that other factors found to be associated with CT in our multivariable analysis among all patients (
Table 4), such as CCT and IOP, were not found to be associated with CT among normals considered alone. It is possible that a larger sample of normals would allow detection of associations between CT and these other factors. However, it is also possible that these features are inherently related to OA or AC glaucoma.
Our data do not support the idea that glaucoma damage is associated with a thinner choroid, as had been suggested by prior histological studies.
22–24 First, no significant difference in CT was found between normals and the OA group or between the POAGS and POAG groups. Furthermore, neither visual field MD nor CDR was found to be associated with CT in the multivariable analysis among glaucoma patients (
Table 6). Several other studies have found no association between glaucoma damage and CT as measured by SD-OCT.
25–28 It is important for studies that evaluate relationships between CT and disease states to account for the important variables that may confound such assessments, such as age, AL, CCT, BP, and IOP.
The limitations of our study include the possibility that the glaucoma patients at a referral center may differ from a population-based sample of individuals with glaucoma. However, we have no reason to believe that they are unrepresentative. Second, we measured the choroid in the posterior 6 mm of the eye. It is possible that other areas of the choroid might have different thicknesses, though at present the ability of commercial SD-OCT instruments to measure the peripheral choroid is limited. We were not able to obtain ideal images of the choroid in 12% of the macular scans. The visualization of the CSI will undoubtedly improve with further developments in technology.
In summary, we found that factors that were significantly associated with a thinner choroid were older age, longer AL, higher IOP, and thicker CCT. AC subjects had a thicker choroid than OA and normal subjects, even after adjusting for the shorter AL in AC eyes. This observation supports hypotheses suggesting that choroidal expansion is a contributing factor to the development of AC disease. Finally, we found that CT is not related to the degree of glaucoma injury.