ARTICLE
Changes in choroidal thickness after cataract surgery Hideharu Ohsugi, MD, PhD, Yasushi Ikuno, MD, PhD, Zaigen Ohara, MD, Hitoshi Imamura, MD, Shunsuke Nakakura, MD, PhD, Shinji Matsuba, MD, Yoshitake Kato, MD, Hitoshi Tabuchi, MD, PhD
PURPOSE: To evaluate changes in choroidal thickness before and after cataract surgery and factors affecting the changes. SETTING: Tsukazaki Hospital, Himeji, Japan. DESIGN: Prospective interventional study. METHODS: Patients having cataract surgery without other eye pathology were studied. The corrected distance visual acuity (CDVA), intraocular pressure (IOP), axial length (AL), and enhanced-depth-imaging optical coherence tomography (OCT) were measured preoperatively. The choroidal thickness was measured at 5 points (subfoveal and 1.5 mm nasal, temporal, superior, and inferior to the fovea) using the OCT device’s software. Enhanced-depth-imaging OCT and IOP measurements were obtained 3 days, 1 and 3 weeks, and 3 and 6 months postoperatively and compared with the baseline values. Stepwise analysis determined which factors (ie, age, CDVA, preoperative IOP, AL, operative time, changes in IOP) were associated with changes in choroidal thickness. RESULTS: One hundred eyes were analyzed. The postoperative IOP significantly decreased at 3 weeks, 3 months, and 6 months. The postoperative choroidal thickness significantly increased at the foveal and inferior regions throughout the follow-up; at the nasal region at 3 days, 1 week, and 6 months; at the temporal region at 1 week; and at the superior region at 6 months. These changes negatively correlated with those in IOP early after surgery. The changes in choroidal thickness later negatively correlated with the AL in all regions. CONCLUSION: Cataract surgery caused changes in choroidal thickness. The AL and changes in the IOP are critical for evaluating the changes in choroidal thickness. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2014; 40:184–191 Q 2013 ASCRS and ESCRS
The choroid, a highly vascularized structure located between the lamina fusca of the sclera and the retinal pigment epithelium (RPE), is an important tissue that supplies blood to the outer retina and is the source of many vision-threatening diseases, such as choroidal neovascularization,1 polypoidal choroidal vasculopathy,2,3 central serous chorioretinopathy,4–6 and high myopia–related chorioretinal atrophy.7–9 Therefore, studying the choroidal structures is important for understanding the pathology and mechanisms underlying these critical diseases. Spectral-domain optical coherence tomography (OCT) is a noninvasive noncontact transpupillary imaging modality used to diagnose, make treatment decisions, and monitor many retinal diseases.10,11 184
Q 2013 ASCRS and ESCRS Published by Elsevier Inc.
Similarly, obtaining choroidal thickness measurements is useful for evaluating choroidal thickening and thinning diseases. However, spectral-domain OCT has a limited ability to image the choroid due to scattering caused by the pigments in the RPE and choroidal vessels and a depth-dependent roll-off in sensitivity. A new method for visualizing the choroid, enhanced-depth-imaging OCT, has been reported.12 Enhanced-depth-imaging is an innovation of postprocessing that uses a commercially available spectral-domain OCT device. Deep choroidal images are enhanced by taking inverted images and using multiple B-scan averaging to improve the signal-tonoise ratio (SNR). Choroidal thickness is reported to be significantly related to specific pathologies. For 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2013.07.036
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
instance, the choroid is thicker in eyes with central serous chorioretinopathy than in normal eyes,13,14 and the choroid is thinner in patients with a myopic shift or axial length (AL) elongation.15–17 Choroidal thinning also is more prominent in highly myopic eyes with choroidal neovascularization.16,18 Therefore, choroidal thickness is being measured increasingly more often and is becoming an accepted procedure for clinical and research applications. On the other hand, cataract is a major cause of visual impairment in the elderly. Cataract surgery is the most common ophthalmic surgery and is performed simultaneously with glaucoma or vitreous surgery in many cases. However, according to the results in epidemiology studies, cataract surgery is associated with the onset of age-related macular degeneration (AMD).19–21 This process may be mediated via inflammatory reactions associated with the surgery,22,23 postoperative biochemical environmental changes in the eye (increased free radicals or growth factors),22,24,25 and/or increased light exposure during or after surgery.26,27 Age-related macular degeneration is a serious disease that results in central visual impairment due to neovascularization originating from the choroid. It is possible that some changes occur in the choroid as a result of cataract surgery and that they affect the development of AMD. Pierru et al.A report that cataract surgery increased the subfoveal choroidal thickness; however, to our knowledge, there have been no full-length articles reporting such changes. In this study, we evaluated changes in choroidal thickness before and after cataract surgery and assessed factors that affect these changes. PATIENTS AND METHODS This prospective clinical study comprised consecutive patients with no systemic disease or other ophthalmic disease who had cataract surgery at Tsukazaki Hospital between
Submitted: April 24, 2013. Final revision submitted: July 2, 2013. Accepted: July 7, 2013. From the Department of Ophthalmology (Ohsugi, Ohara, Imamura, Nakakura, Matsuba, Kato, Tabuchi), Tsukazaki Hospital, Himeji and the Department of Ophthalmology (Ikuno), Osaka University Graduate School of Medicine, Osaka, Japan. Kanako Oshima and Kosuke Takase, Department of Ophthalmology, Tsukazaki Hospital, provided valuable support throughout the study. Corresponding author: Hideharu Ohsugi, MD, PhD, Department of Ophthalmology, Tsukazaki Hospital, 68-1 Waku, Aboshi-ku, Himeji-City, Hyogo 671-1227, Japan. E-mail: [email protected].
185
November 20, 2010, and March 31, 2011. The research adhered to the Declaration of Helsinki, and the study was approved by the Ethics Committee, Tsukazaki Hospital. All patients provided written informed consent before the initiation of the study. The exclusion criteria were a history of intraocular surgery, retinal pathology, choroidal pathology, glaucoma, or systemic disease such as diabetes mellitus or hypertension and/or poor OCT images due to severe cataracts or unstable fixation. The exclusion criteria after cataract surgery included the development of glaucoma or cystoid macular edema, which can affect or be affected by the underlying choroidal changes. The patients were screened to meet the following inclusion criteria: cataracts with a spherical equivalent (SE) refractive error between 3.00 diopters (D) and C3.00 D, no posterior abnormalities, and clear spectral-domain OCT data using the Spectralis device (Heidelberg Engineering GmbH). This device can be used to automatically place follow-up scans in precisely the same locations.
Patient Assessment The patients had detailed ocular examinations, including assessments with an autokeratorefractometer (KR-8800, Topcon Corp.), slitlamp evaluation, dilated fundoscopy, and measurements of the corrected distance visual acuity (CDVA), intraocular pressure (IOP) (CT90A, Topcon Corp.), and AL using an interferometer (IOLMaster, Carl Zeiss Meditec AG). Measurements of OCT, AL, and IOP were obtained 1 week before cataract surgery. Optical coherence tomography and IOP measurements were also obtained 3 days, 1 and 3 weeks, and 3 and 6 months after cataract surgery. To avoid the effects of mydriatic agents or diurnal changes,28 all measurements were obtained under nonmydriatic conditions between 9 AM and 12 PM.
Surgical Technique Eyes were prepared for surgery by instilling tropicamide– phenylephrine hydrochloride 0.5% for pupil dilation and oxybuprocaine hydrochloride 0.4% for topical anesthesia. Balloon compression, which may compress the choroid and thin it, was not used. All surgeries were performed by experienced surgeons (H.O., Z.O., H.I., S.N., S.M., Y.K., H.T.) using the same technique that comprised phacoemulsification with a 2.8 mm clear corneal incision, a vacuum of 280 mm Hg, an aspiration flow rate of 40 mL/min, and a bottle height of 75 cm. The operative time was recorded in each case. Postoperatively, all patients were treated with levofloxacin hydrate 1.5% and fluorometholone 0.1% 4 times daily for 2 weeks. This was followed by nepafenac 0.1% 3 times daily for an additional 3 weeks.
Enhanced-Depth-Imaging Optical Coherence Tomography The enhanced-depth-imaging OCT device was operated by the same experienced technician. The choroid was imaged using the device with eye tracking and image-averaging systems, as previously described.12 The OCT device was pushed sufficiently close to the eye to obtain an inverted image. Each section was imaged using eye tracking, and 100 B-scans were
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
186
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Figure 1. Representative enhanced-depth-imaging OCT measurements. Six millimeter vertical (A) and horizontal (B) images that included the fovea were obtained. The green arrows denote the location of the B-scans.
Figure 2. Change in IOP over time. The asterisks indicate a statistically significant difference compared with the preoperative value (IOP Z intraocular pressure).
averaged to improve the SNR. Six-millimeter horizontal and vertical images that included the fovea were obtained. The choroidal thickness was defined as the vertical distance between the RPE and the choroidal–scleral interface. The examiners, who were blinded to the study design, manually measured the choroidal thickness at 5 points (subfoveal and 1.5 mm nasal, temporal, superior, and inferior to the fovea) using the software program included in the OCT device (Figure 1).
3 days postoperatively. No patients met the exclusion criteria after cataract surgery. The final number of patients with complete data was 100. Forty-one men and 59 women with a mean age of 72.5 years G 6.6 (SD) (range 52 to 85 years) were analyzed. Fifty right eyes and 50 left eyes were examined. Preoperatively, the mean CDVA was C0.084 G 0.19 logMAR (range 0.18 to 0.70 logMAR); the mean SE refractive error was C0.57 G 1.56 D (range 3.0 to C3.0 D); the mean AL was 23.5 G 1.1 mm (range 20.9 to 26.0 mm); the mean preoperative IOP was 13.1 G 2.6 mm Hg (range 7 to 19 mm Hg); the mean preoperative choroidal thickness was 248.5 G 82.7 mm (range 89 to 429 am) at the fovea, 192.8 G 81.2 mm (range 67 to 397 mm) nasally, 239.0 G 75.7 mm (range 91 to 475 mm) temporally, 239.0 G 86.3 mm (range 72 to 470 mm) superiorly, and 219.6 G 74.2 mm (range 78 to 392 mm) inferiorly; and the mean operative time was 659 G 186 seconds (range 377 to 1211 seconds). The postoperative IOP decreased throughout the follow-up over preoperative values, and after the Bonferroni correction was applied there was a significant difference at 3 weeks, 3 months, and 6 months (Figure 2). The postoperative choroidal thickness increased at all 5 points throughout the study period compared with preoperative values. After the Bonferroni correction was applied, the differences were significant at the foveal and inferior regions throughout the follow-up period; at the nasal region at 3 days, 1 week, and 6 months; at the temporal region at 1 week; and at the superior region at 6 months (Figures 3 to 7). Table 1 shows the results of a single regression analysis of various factors during each period, including age, CDVA, preoperative IOP, AL, operative time, and change in IOP, that affected the changes in choroidal thickness. Subsequently, a stepwise analysis
Control Study and Interexaminer Reproducibility As a control, eyes in patients who met the criteria for inclusion in this study were also examined. Two weeks later, measurements of enhanced-depth-imaging OCT and IOP were obtained again. This was done to determine whether there were differences between the 2 IOP and choroidal thickness measurements at the 5 points. To evaluate the interexaminer reproducibility of the choroidal thickness measurements, the control eyes were examined. The 2 independent examiners measured the choroidal thickness at the same 5 points. The interexaminer reproducibility values were evaluated based on the intraclass correlation coefficients (ICCs).
Statistical Analysis Statistical analyses, including a 2-way layout analysis of variance with a Bonferroni correction, a multiple stepwiseregression analysis, the paired t test, and calculation of the ICCs, were performed using a commercially available software program (JMP, version 10.0, SAS Institute, Inc.). A P value less than .05 was considered to indicate a statistically significant difference.
RESULTS Patient Demographic Data One hundred twelve preoperative cataract eyes in 112 Japanese patients were included. Of the patients, 4 opted out of the postoperative examinations and 8 were excluded postoperatively due to poor OCT images resulting from unstable fixation or corneal edema
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Figure 3. Choroidal thickness at the fovea over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
was performed to determine which factors among age, CDVA, preoperative IOP, AL, operative time, and change in IOP were most significantly associated with the changes in choroidal thickness during each period. Age, CDVA, preoperative IOP, and the operative time had no significant correlations with the changes in choroidal thickness. During some periods, changes in IOP and AL were correlated with the changes in choroidal thickness (Table 2). Control Study and Interexaminer Reproducibility Twenty eyes of 20 age-matched patients (mean age 73.5 G 7.4 years) were analyzed. Table 3 shows the results. There were no significant differences in the mean IOP and the mean choroidal thickness at each of the 5 points between the first examination and second examination. Table 4 shows the interexaminer reproducibility. The interexaminer ICCs of the choroidal thickness ranged between 0.953 mm and 0.990 mm (P!.001). Complications No serious complications (eg, vitreous loss) were observed.
Figure 5. Choroidal thickness at the temporal region over time. The asterisk indicates a statistically significant difference compared with the preoperative value.
187
Figure 4. Choroidal thickness at the nasal region over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
DISCUSSION In the present study, we determined the RPE and choroidal–scleral interface manually, as in a previous study,17 to measure the choroidal thickness so any possible errors would be taken into consideration. There were very small differences in the 2 measurements of choroidal thickness in the control group between timepoints, although the differences were not significant. Furthermore, because 2 examiners were involved in the choroidal thickness measurements, we obtained ICCs between the findings of the examiners to evaluate the reproducibility of the measurements. The ICCs were very high, comparable to those reported in earlier studies.12,17,29 Based on these results, the data reliability in the present study appears to be high. The choroid was significantly thicker in some regions or at certain timepoints after cataract surgery compared with baseline values. The postoperative increase in choroidal thickness was greatest in the inferior region, followed by the foveal and nasal regions. The increase in choroidal thickness was slight at the temporal and superior regions. It is interesting that there was an increase in choroidal thickness at the nasal and inferior regions because the choroid in the patients in this study was relatively thin in these regions. There are 2 reasons for the relative choroidal thinning observed nasally and inferiorly. One is the choroidal watershed, which isolates the choroidal
Figure 6. Choroidal thickness at the superior region over time. The asterisk indicates a statistically significant difference compared with the preoperative value.
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
188
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
be anatomically vulnerable and more susceptible to changes in IOP. The choroid may be involved in the pathogenesis of various ocular diseases. It has been suggested that cataract surgery is associated with the onset of AMD.19–21 This process might be mediated via inflammatory reactions associated with the surgery,22,23 postoperative biochemical environmental changes in the eye (increased free radicals or growth factors),22,24,25 or increased light exposure during or after surgery.26,27 The present study found that cataract surgery, which is commonly performed in ophthalmic practice, resulted in changes in choroidal thickness; thus, the fine changes in choroidal thickness might also affect the onset of AMD. Further research is needed to determine the effects of cataract surgery on choroidal thickness in patients with AMD.
Figure 7. Choroidal thickness at the inferior region over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
circulation,30 as observed on fluorescein or indocyanine green angiography. Another is the fetal choroidal fissure, which closes inferiorly at approximately 7 weeks of gestation.31 These regions can
Table 1. Single regression analysis of various factors affecting the changes in the choroidal thickness. Age Area Fovea 3 days 1 week 3 weeks 3 months 6 months Nasal 3 days 1 week 3 weeks 3 months 6 months Temporal 3 days 1 week 3 weeks 3 months 6 months Superior 3 days 1 week 3 weeks 3 months 6 months Inferior 3 days 1 week 3 weeks 3 months 6 months
Preoperative CDVA Preoperative IOP
R2
P
R2
P
b
0.11 0.34 0.47 0.39 0.33
0.009 0.05 0.07 0.05 0.03
.35 .03* .008* .03* .11
1.33 1.85 1.47 2.92 3.83
0.001 0.001 0.0005 0.002 0.003
.75 .75 .82 .65 .60
0.39 0.52 0.81 0.70 0.84
0.02 0.02 0.03 0.02 0.03
.19 .20 .08 .13 .10
0.08 0.43 0.55 0.37 0.48
0.004 0.07 0.09 0.05 0.05
.55 .009* .003* .03* .03*
1.17 6.91 7.29 0.48 3.97
0.0005 0.01 0.01 0.00006 0.002
.82 .25 .29 .94 .62
0.47 0.60 0.55 0.77 0.94
0.02 0.02 0.01 0.03 0.03
0.07 0.30 0.51 0.52 0.43
0.003 0.03 0.06 0.06 0.04
.58 .09 .02* .02* .06
2.01 7.74 5.80 0.63 1.06
0.002 0.02 0.006 0.00006 0.0002
.65 .21 .45 .94 .90
0.077 0.12 0.09 0.02 0.65
0.03 0.34 0.47 0.27 0.30
0.0007 0.05 0.08 0.02 0.02
.80 .03* .004* .14 .14
2.76 4.19 1.88 3.83 1.27
0.003 0.006 0.001 0.004 0.0003
.58 .46 .75 .55 .86
0.03 0.36 0.45 0.41 0.30
0.0006 0.04 0.05 0.03 0.02
.81 .04* .03* .07 .18
2.56 3.20 0.94 3.98 2.96
0.002 0.003 0.0002 0.002 0.001
.62 .61 .90 .62 .72
b
B
R2
P
Axial Length b
R2
P
1.56 1.20 2.35 3.65 3.86
0.05 0.01 0.04 0.10 0.09
.03* .23 .04* .001* .002*
.19 .16 .25 .82 .10
1.46 1.12 1.91 2.20 3.23
0.03 0.01 0.03 0.04 0.05
.10 .29 .11 .04* .02*
0.0006 0.0008 0.0003 0.00001 0.01
.81 .78 .87 .97 .26
1.74 2.31 3.48 5.58 4.70
0.22 0.36 0.58 0.44 0.69
0.004 0.008 0.02 0.01 0.02
.53 .37 .16 .32 .18
0.38 0.35 0.61 0.51 0.92
0.01 0.006 0.01 0.008 0.03
.30 .43 .24 .38 .11
Surgery Time b
Change in IOP
R2
P
b
0.0004 0.006 0.007 0.002 0.005
0.0001 0.01 0.01 0.0007 0.006
.92 .31 .28 .79 .45
0.76 1.97 2.46 1.95 2.10
0.08 .006* 0.19 !.0001* 0.22 !.0001* 0.13 .0002* 0.09 .003*
0.0007 0.003 0.001 0.006 0.003
0.0002 0.002 0.0004 0.01 0.001
.90 .65 .85 .31 .75
0.60 2.12 1.92 1.30 1.59
0.03 .08 0.19 !.0001* 0.12 .0003* 0.06 .01* 0.04 .04*
0.05 .02* 0.05 .03* 0.07 .008* 0.17 !.0001* 0.11 .0008*
0.003 0.007 0.01 0.002 0.007
0.005 0.01 0.02 0.0007 0.007
.49 .24 .15 .79 .40
0.49 1.73 2.12 1.00 1.69
0.03 0.12 0.12 0.02 0.05
2.51 2.17 2.43 3.52 3.61
0.09 0.05 0.06 0.10 0.08
.003* .03* .02* .001* .004*
0.003 0.01 0.01 0.004 0.01
0.004 0.03 0.06 0.003 0.02
.55 .08 .02* .57 .13
0.52 1.64 2.01 1.17 1.05
0.03 .11 0.13 .0002* 0.18 !.0001* 0.05 .02* 0.02 .13
1.86 1.30 1.86 3.78 3.56
0.04 0.01 0.02 0.07 0.06
.04* .23 .15 .007* .01*
0.008 0.01 0.007 0.003 0.008
0.02 0.04 0.01 0.001 0.009
.13 .056 .325 .71 .35
0.69 1.86 2.00 1.26 1.48
0.04 0.14 0.11 0.04 0.04
b Z b coefficient, CDVA Z corrected distance visual acuity; IOP Z intraocular pressure; P Z P value; R2 Z coefficient of determination *Statistically significant difference
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
R2
P
.10 .0003* .0004* .13 .03*
.04* .0001* .0006* .06 .06
189
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Table 2. Multiple regression analysis of factors affecting changes in choroidal thickness. Axial Length
Change in IOP P Value
Regression
Area Fovea 3 days 1 week 3 weeks 3 months 6 months Nasal 3 days 1 week 3 weeks 3 months 6 months Temporal 3 days 1 week 3 weeks 3 months 6 months Superior 3 days 1 week 3 weeks 3 months 6 months Inferior 3 days 1 week 3 weeks 3 months 6 months
Regression
P Value
R2
d d d 2.94x C 72.1 3.16x C 78.7
d d d .0059 .01096
0.76x C 2.52 1.97x C 2.92 2.46x C 0.45 1.67x C 0.13 1.70x C 1.10
.0058 !.0001 !.0001 .0011 .0137
0.075 0.185 0.221 0.199 0.148
d d d d 3.23x C 80.3
d d d d .02096
d 2.12x C 3.02 1.92x C 0.14 1.30x to 0.32 d
d !.0001 .0003 .0112 d
d 0.1947 0.124 0.064 0.053
1.74x C 43.7 d d 5.58x C 132.8 4.70x C 113.4
.0234 d d !.0001 .0008
d 1.73x C 2.53 2.12x C 0.31 d d
d .0003 .0004 d d
0.051 0.123 0.121 0.166 0.11
2.51x C 61.7 d d 3.52x C 84.4 3.61x C 87.8
.0029 d d .0011 .0036
d 1.64x C 1.78 2.01x C 0.07 d d
d .0002 !.0001 d d
0.087 0.133 0.18 0.104 0.083
d d d 3.78x C 93.3 3.56x C 89.1
d d d .0068 .0111
d 1.86x C 3.20 2.00x C 2.33 d d
d .0001 .0006 d d
d 0.142 0.114 0.072 0.064
IOP Z intraocular pressure; R2 Z coefficient of determination
As found in previous studies,32–34 the IOP deceased after cataract surgery, with a particularly significant decrease at 3 weeks and thereafter. The changes in choroidal thickness from baseline were negatively
correlated with the changes in IOP relatively early after surgery. However, the changes in choroidal thickness were not correlated over time with the IOP in many regions. Therefore, an increase in ocular
Table 3. Control study. Mean G SD Parameter IOP (mm Hg) Fovea (mm) Nasal (mm) Temporal (mm) Superior (mm) Inferior (mm)
1st Exam
2nd Exam
P Value*
13.9 G 3.2 267.7 G 99.4 208.3 G 100.6 252.5 G 87.0 264.0 G 83.7 225.3 G 86.8
14.0 G 2.8 267.0 G 97.6 209.0 G 98.8 252.1 G 87.0 264.5 G 83.0 225.2 G 85.3
.88 .43 .5 .75 .67 .92
IOP Z intraocular pressure *Paired t test
Table 4. Interexaminer reproducibility based on ICCs of the choroidal thickness of each region measured by 2 masked observers. Area Fovea Nasal Temporal Superior Inferior
ICC
P Value
0.98533 0.98973 0.95347 0.97048 0.9584
!.01 !.01 !.01 !.01 !.01
ICC Z intraclass correlation coefficient
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
190
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
perfusion pressure due to a decreased IOP, which was noted relatively early after surgery, might have increased the choroidal thickness. In the late postoperative period, the changes in choroidal thickness were not correlated with the changes in IOP in many regions; rather, the changes in choroidal thickness were negatively correlated with the AL in all regions. The longer the AL, the thinner the choroid. Future studies should address this issue in terms of high myopia. It is known that the mean subfoveal choroidal thickness is negatively correlated with age and myopic refractive error. Our previous study35 showed that the subfoveal choroidal thickness decreased by 1.4 mm for each year and by 6.2 mm for each diopter of myopia in healthy volunteers. Ho et al.36 and Nishida et al.37 showed that the subfoveal choroidal thickness decreased by 1.2 mm and 1.6 mm, respectively, for each year and by 6.2 mm and 8.1 mm, respectively, for each diopter of myopia in myopic eyes. The annual changes in choroidal thickness may have also affected the thickness for a relatively long period (3 to 6 months) after surgery. Future studies should determine how the choroidal thickness changes after glaucoma surgery, which has a great impact on IOP, more invasive vitreous surgery, and other types of procedures. Because these surgical procedures are often performed in conjunction with cataract surgery, the results in the present study focusing on cataract surgery alone may be helpful in interpreting the results obtained after concomitant surgeries. The present study has limitations. Falavarjani et al.38 argue that retinal thickness measurements can be affected by cataract type and severity. The choroidal thickness might also be affected by cataract. However, Falavarjani et al. used time-domain OCT, whereas we used the spectral-domain OCT in the present study. Furthermore, because obtaining accurate images was prioritized, poor OCT images due to severe cataracts were excluded from the analysis. Based on these points, we consider that the influence of the cataract on the measurement of the choroidal thickness was small. The small sample might be insufficient to evaluate the changes in choroidal thickness. In the present study, the lines of the RPE and choroidal–scleral interface were determined manually. However, because cross-sectional imaging is insufficient in eyes with very thick choroids, the reproducibility of the manual tracing method used here may be low. To this end, improvements in OCT performance, or if possible in algorithm development to automatically detect the choroidal–scleral interface, are desirable. The general picture may not be reflected because the measurements were obtained at 5 points only; that is, the fovea and the nasal, temporal, superior, and inferior regions
1.5 mm from the fovea. We are planning to perform a more detailed 3-dimensional analysis of the choroid to obtain additional information. WHAT WAS KNOWN It has been suggested that cataract surgery is associated with the onset of AMD, which is a serious disease that results in central visual impairment due to neovascularization originating from the choroid. WHAT THIS PAPER ADDS Cataract surgery increased choroidal thickness, and the changes in choroidal thickness negatively correlated with the AL in the late postoperative period. The fine changes in choroidal thickness after cataract surgery may affect the onset of AMD, and these effects may differ depending on the AL.
REFERENCES 1. Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol 2004; 137:496–503 2. Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004; 49:25–37 3. Gomi F, Tano Y. Polypoidal choroidal vasculopathy and treatments. Curr Opin Ophthalmol 2008; 19:208–212 4. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol 1967; 63:587–615 5. Spaide RF, Hall L, Haas A, Campeas L, Yannuzzi LA, Fisher YL, Guyer DR, Slakter JS, Sorenson JA, Orlock DA. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina 1996; 16:203–213 6. Iida T, Kishi S, Hagimura N, Shimizu K. Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy. Retina 1999; 19:508–512 7. Duke-Elder S, Abrams D. Pathological myopia. In: Duke-Elder S, ed, System of Ophthalmology. Volume 5. Ophthalmic Optics and Refraction. London, UK, Henry Kimpton, 1970; 300–362 8. Ohno H. [Electron microscopic studies of myopic retinochoroidal atrophies 1. Choroidal changes]. [Japanese]. Nippon Ganka Kiyo 1983; 43:1244–1253 9. Matsuo N, Okabe S, Hasegawa E, Okamoto S. [Report of research committee on chorioretinal degenerations]. [In Japanese]. Tokyo, Japan, The Ministry of Health and Welfare of Japan, 1978 10. Schuman JS, Hee MR, Arya AV, Pedut-Kloizman T, Puliafito CA, Fujimoto JG, Swanson EA. Optical coherence tomography: a new tool for glaucoma diagnosis. Curr Opin Ophthalmol 1995; 6:89–95 11. Jaffe GJ, Caprioli J. Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol 2004; 137:156–169 12. Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146:496–500 13. Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina 2009; 29:1469–1473
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
14. Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology 2010; 117:1792–1799 15. Ikuno Y, Tano Y. Retinal and choroidal biometry in highly myopic eyes with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2009; 50:3876–3880. Available at: http:// www.iovs.org/content/50/8/3876.full.pdf. Accessed July 30, 2013 16. Fujiwara T, Imamura Y, Margolis R, Slakter JS, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol 2009; 148:445–450 17. Ohsugi H, Ikuno Y, Oshima K, Tabuchi H. 3-D choroidal thickness maps from EDI-OCT in highly myopic eyes. Optom Vis Sci 2013; 90:599–606 18. Ikuno Y, Jo Y, Hamasaki T, Tano Y. Ocular risk factors for choroidal neovascularization in pathologic myopia. Invest Ophthalmol Vis Sci 2010; 51:3721–3725. Available at: http://www. iovs.org/content/51/7/3721.full.pdf. Accessed July 30, 2013 19. Klein R, Klein BE, Wong TY, Tomany SC, Cruickshanks KJ. The association of cataract and cataract surgery with the long-term incidence of age-related maculopathy; the Beaver Dam Eye Study. Arch Ophthalmol 2002; 120:1551–1558. Available at: http://archopht.jamanetwork.com/data/Journals/OPHTH/6842/ EEB20011.pdf. Accessed July 30, 2013 20. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD. Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies. Am J Ophthalmol 2003; 135:849–856 21. Cugati S, Mitchell P, Rochtchina E, Tan AG, Smith W, Wang JJ. Cataract surgery and the10-year incidence of age-related maculopathy; the Blue Mountains Eye Study. Ophthalmology 2006; 113:2020–2025 22. van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, Pameyer JH, de Jong PT. Increased prevalence of disciform macular degeneration after cataract extraction with implantation of an intraocular lens. Br J Ophthalmol 1994; 78:441–445. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC504819/ pdf/brjopthal00030-0019.pdf. Accessed July 30, 2013 23. Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002; 134:411–431 24. Pollack A, Marcovich A, Bukelman A, Oliver M. Age-related macular degeneration after extracapsular cataract extraction with intraocular lens implantation. Ophthalmology 1996; 103:1546–1554 25. Penfold PL, Provis JM, Billson FA. Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis. Graefes Arch Clin Exp Ophthalmol 1987; 225:70–76 26. Mainster MA, Ham WT, Delori FC. Potential retinal hazards: instrument and environmental light sources. Ophthalmology 1983; 90:927–931; discussion by T Lawwill, 931–932 27. Libre PE. Intraoperative light toxicity: a possible explanation for the association between cataract surgery and age-related macular degeneration [letter]. Am J Ophthalmol 2003; 136:961 28. Usui S, Ikuno Y, Akiba M, Maruko I, Sekiryu T, Nishida K, Iida T. Circadian changes in subfoveal choroidal thickness and the relationship with circulatory factors in healthy subjects. Invest
29.
30.
31. 32.
33.
34.
35.
36.
37.
38.
191
Ophthalmol Vis Sci 2012; 53:2300–2307. Available at: http:// www.iovs.org/content/53/4/2300.full.pdf. Accessed July 30, 2013 Ikuno Y, Maruko I, Yasuno Y, Miura M, Sekiryu T, Nishida K, Iida T. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52:5536–5540. Available at: http://www.iovs.org/content/52/8/ 5536.full.pdf. Accessed July 30, 2013 Hayreh SS. In vivo circulation and its watershed zones. Eye 1990; 4:273–289. Available at: http://www.nature.com/eye/journal/v4/ n2/pdf/eye199039a.pdf. Accessed Juy 30, 2013 Oyster CW. The Human Eye; Structure and Function. Sunderland, MA, Sinauer Associates, 1999; 57–75 Jahn CE. Reduced intraocular pressure after phacoemulsification and posterior chamber intraocular lens implantation. J Cataract Refract Surg 1997; 23:1260–1264 Hayashi K, Hayashi H, Nakao F, Hayashi F. Changes in anterior chamber angle width and depth after intraocular lens implantation in eyes with glaucoma. Ophthalmology 2000; 107:698–703 Mansberger SL, Gordon MO, Jampel H, Bhorade A, Brandt JD, Wilson B, Kass MA; for the Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology 2012; 119:1826–1831 Ikuno Y, Kawaguchi K, Nouchi T, Yasuno Y. Choroidal thickness in healthy Japanese subjects. Invest Ophthalmol Vis Sci 2010; 51:2173–2176. Available at: http://www.iovs.org/content/51/4/ 2173.full.pdf. Accessed July 30, 2013 Ho M, Liu DT, Chan VC, Lam DS. Choroidal thickness measurement in myopic eyes by enhanced depth optical coherence tomography. Ophthalmology 2013 May 15 [Epub ahead of print] Nishida Y, Fujiwara T, Imamura Y, Lima LH, Kurosaka D, Spaide RF. Choroidal thickness and visual acuity in highly myopic eyes. Retina 2012; 32:1229–1236 Falavarjani KG, Modarres M, Nikeghbali A. OCT and cataract [letter]. Ophthalmology 2010; 117:849; reply by Y Takamura, E Kubo, Y Akagi, 849–850
OTHER CITED MATERIAL A. Pierru A, Baillif-Gostoli S, Gastaud P, “Measurement of Subfoveal Choroidal Thickness Before and After Cataract Surgery Using Enhanced Depth Imaging Optical Coherence Tomography,” presented at the congress of the European Association for Vision and Eye Research, Nice, France, October 2012. Abstract available in Acta Ophthalmol 2012; 90(suppl 249). Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.17553768.2012.4726.x/abstract. Accessed July 30, 2013
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
First author: Hideharu Ohsugi, MD, PhD Department of Ophthalmology, Tsukazaki Hospital, Himeji, Japan
Changes in choroidal thickness after cataract surgery Hideharu Ohsugi, MD, PhD, Yasushi Ikuno, MD, PhD, Zaigen Ohara, MD, Hitoshi Imamura, MD, Shunsuke Nakakura, MD, PhD, Shinji Matsuba, MD, Yoshitake Kato, MD, Hitoshi Tabuchi, MD, PhD
PURPOSE: To evaluate changes in choroidal thickness before and after cataract surgery and factors affecting the changes. SETTING: Tsukazaki Hospital, Himeji, Japan. DESIGN: Prospective interventional study. METHODS: Patients having cataract surgery without other eye pathology were studied. The corrected distance visual acuity (CDVA), intraocular pressure (IOP), axial length (AL), and enhanced-depth-imaging optical coherence tomography (OCT) were measured preoperatively. The choroidal thickness was measured at 5 points (subfoveal and 1.5 mm nasal, temporal, superior, and inferior to the fovea) using the OCT device’s software. Enhanced-depth-imaging OCT and IOP measurements were obtained 3 days, 1 and 3 weeks, and 3 and 6 months postoperatively and compared with the baseline values. Stepwise analysis determined which factors (ie, age, CDVA, preoperative IOP, AL, operative time, changes in IOP) were associated with changes in choroidal thickness. RESULTS: One hundred eyes were analyzed. The postoperative IOP significantly decreased at 3 weeks, 3 months, and 6 months. The postoperative choroidal thickness significantly increased at the foveal and inferior regions throughout the follow-up; at the nasal region at 3 days, 1 week, and 6 months; at the temporal region at 1 week; and at the superior region at 6 months. These changes negatively correlated with those in IOP early after surgery. The changes in choroidal thickness later negatively correlated with the AL in all regions. CONCLUSION: Cataract surgery caused changes in choroidal thickness. The AL and changes in the IOP are critical for evaluating the changes in choroidal thickness. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2014; 40:184–191 Q 2013 ASCRS and ESCRS
The choroid, a highly vascularized structure located between the lamina fusca of the sclera and the retinal pigment epithelium (RPE), is an important tissue that supplies blood to the outer retina and is the source of many vision-threatening diseases, such as choroidal neovascularization,1 polypoidal choroidal vasculopathy,2,3 central serous chorioretinopathy,4–6 and high myopia–related chorioretinal atrophy.7–9 Therefore, studying the choroidal structures is important for understanding the pathology and mechanisms underlying these critical diseases. Spectral-domain optical coherence tomography (OCT) is a noninvasive noncontact transpupillary imaging modality used to diagnose, make treatment decisions, and monitor many retinal diseases.10,11 184
Q 2013 ASCRS and ESCRS Published by Elsevier Inc.
Similarly, obtaining choroidal thickness measurements is useful for evaluating choroidal thickening and thinning diseases. However, spectral-domain OCT has a limited ability to image the choroid due to scattering caused by the pigments in the RPE and choroidal vessels and a depth-dependent roll-off in sensitivity. A new method for visualizing the choroid, enhanced-depth-imaging OCT, has been reported.12 Enhanced-depth-imaging is an innovation of postprocessing that uses a commercially available spectral-domain OCT device. Deep choroidal images are enhanced by taking inverted images and using multiple B-scan averaging to improve the signal-tonoise ratio (SNR). Choroidal thickness is reported to be significantly related to specific pathologies. For 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2013.07.036
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
instance, the choroid is thicker in eyes with central serous chorioretinopathy than in normal eyes,13,14 and the choroid is thinner in patients with a myopic shift or axial length (AL) elongation.15–17 Choroidal thinning also is more prominent in highly myopic eyes with choroidal neovascularization.16,18 Therefore, choroidal thickness is being measured increasingly more often and is becoming an accepted procedure for clinical and research applications. On the other hand, cataract is a major cause of visual impairment in the elderly. Cataract surgery is the most common ophthalmic surgery and is performed simultaneously with glaucoma or vitreous surgery in many cases. However, according to the results in epidemiology studies, cataract surgery is associated with the onset of age-related macular degeneration (AMD).19–21 This process may be mediated via inflammatory reactions associated with the surgery,22,23 postoperative biochemical environmental changes in the eye (increased free radicals or growth factors),22,24,25 and/or increased light exposure during or after surgery.26,27 Age-related macular degeneration is a serious disease that results in central visual impairment due to neovascularization originating from the choroid. It is possible that some changes occur in the choroid as a result of cataract surgery and that they affect the development of AMD. Pierru et al.A report that cataract surgery increased the subfoveal choroidal thickness; however, to our knowledge, there have been no full-length articles reporting such changes. In this study, we evaluated changes in choroidal thickness before and after cataract surgery and assessed factors that affect these changes. PATIENTS AND METHODS This prospective clinical study comprised consecutive patients with no systemic disease or other ophthalmic disease who had cataract surgery at Tsukazaki Hospital between
Submitted: April 24, 2013. Final revision submitted: July 2, 2013. Accepted: July 7, 2013. From the Department of Ophthalmology (Ohsugi, Ohara, Imamura, Nakakura, Matsuba, Kato, Tabuchi), Tsukazaki Hospital, Himeji and the Department of Ophthalmology (Ikuno), Osaka University Graduate School of Medicine, Osaka, Japan. Kanako Oshima and Kosuke Takase, Department of Ophthalmology, Tsukazaki Hospital, provided valuable support throughout the study. Corresponding author: Hideharu Ohsugi, MD, PhD, Department of Ophthalmology, Tsukazaki Hospital, 68-1 Waku, Aboshi-ku, Himeji-City, Hyogo 671-1227, Japan. E-mail: [email protected].
185
November 20, 2010, and March 31, 2011. The research adhered to the Declaration of Helsinki, and the study was approved by the Ethics Committee, Tsukazaki Hospital. All patients provided written informed consent before the initiation of the study. The exclusion criteria were a history of intraocular surgery, retinal pathology, choroidal pathology, glaucoma, or systemic disease such as diabetes mellitus or hypertension and/or poor OCT images due to severe cataracts or unstable fixation. The exclusion criteria after cataract surgery included the development of glaucoma or cystoid macular edema, which can affect or be affected by the underlying choroidal changes. The patients were screened to meet the following inclusion criteria: cataracts with a spherical equivalent (SE) refractive error between 3.00 diopters (D) and C3.00 D, no posterior abnormalities, and clear spectral-domain OCT data using the Spectralis device (Heidelberg Engineering GmbH). This device can be used to automatically place follow-up scans in precisely the same locations.
Patient Assessment The patients had detailed ocular examinations, including assessments with an autokeratorefractometer (KR-8800, Topcon Corp.), slitlamp evaluation, dilated fundoscopy, and measurements of the corrected distance visual acuity (CDVA), intraocular pressure (IOP) (CT90A, Topcon Corp.), and AL using an interferometer (IOLMaster, Carl Zeiss Meditec AG). Measurements of OCT, AL, and IOP were obtained 1 week before cataract surgery. Optical coherence tomography and IOP measurements were also obtained 3 days, 1 and 3 weeks, and 3 and 6 months after cataract surgery. To avoid the effects of mydriatic agents or diurnal changes,28 all measurements were obtained under nonmydriatic conditions between 9 AM and 12 PM.
Surgical Technique Eyes were prepared for surgery by instilling tropicamide– phenylephrine hydrochloride 0.5% for pupil dilation and oxybuprocaine hydrochloride 0.4% for topical anesthesia. Balloon compression, which may compress the choroid and thin it, was not used. All surgeries were performed by experienced surgeons (H.O., Z.O., H.I., S.N., S.M., Y.K., H.T.) using the same technique that comprised phacoemulsification with a 2.8 mm clear corneal incision, a vacuum of 280 mm Hg, an aspiration flow rate of 40 mL/min, and a bottle height of 75 cm. The operative time was recorded in each case. Postoperatively, all patients were treated with levofloxacin hydrate 1.5% and fluorometholone 0.1% 4 times daily for 2 weeks. This was followed by nepafenac 0.1% 3 times daily for an additional 3 weeks.
Enhanced-Depth-Imaging Optical Coherence Tomography The enhanced-depth-imaging OCT device was operated by the same experienced technician. The choroid was imaged using the device with eye tracking and image-averaging systems, as previously described.12 The OCT device was pushed sufficiently close to the eye to obtain an inverted image. Each section was imaged using eye tracking, and 100 B-scans were
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
186
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Figure 1. Representative enhanced-depth-imaging OCT measurements. Six millimeter vertical (A) and horizontal (B) images that included the fovea were obtained. The green arrows denote the location of the B-scans.
Figure 2. Change in IOP over time. The asterisks indicate a statistically significant difference compared with the preoperative value (IOP Z intraocular pressure).
averaged to improve the SNR. Six-millimeter horizontal and vertical images that included the fovea were obtained. The choroidal thickness was defined as the vertical distance between the RPE and the choroidal–scleral interface. The examiners, who were blinded to the study design, manually measured the choroidal thickness at 5 points (subfoveal and 1.5 mm nasal, temporal, superior, and inferior to the fovea) using the software program included in the OCT device (Figure 1).
3 days postoperatively. No patients met the exclusion criteria after cataract surgery. The final number of patients with complete data was 100. Forty-one men and 59 women with a mean age of 72.5 years G 6.6 (SD) (range 52 to 85 years) were analyzed. Fifty right eyes and 50 left eyes were examined. Preoperatively, the mean CDVA was C0.084 G 0.19 logMAR (range 0.18 to 0.70 logMAR); the mean SE refractive error was C0.57 G 1.56 D (range 3.0 to C3.0 D); the mean AL was 23.5 G 1.1 mm (range 20.9 to 26.0 mm); the mean preoperative IOP was 13.1 G 2.6 mm Hg (range 7 to 19 mm Hg); the mean preoperative choroidal thickness was 248.5 G 82.7 mm (range 89 to 429 am) at the fovea, 192.8 G 81.2 mm (range 67 to 397 mm) nasally, 239.0 G 75.7 mm (range 91 to 475 mm) temporally, 239.0 G 86.3 mm (range 72 to 470 mm) superiorly, and 219.6 G 74.2 mm (range 78 to 392 mm) inferiorly; and the mean operative time was 659 G 186 seconds (range 377 to 1211 seconds). The postoperative IOP decreased throughout the follow-up over preoperative values, and after the Bonferroni correction was applied there was a significant difference at 3 weeks, 3 months, and 6 months (Figure 2). The postoperative choroidal thickness increased at all 5 points throughout the study period compared with preoperative values. After the Bonferroni correction was applied, the differences were significant at the foveal and inferior regions throughout the follow-up period; at the nasal region at 3 days, 1 week, and 6 months; at the temporal region at 1 week; and at the superior region at 6 months (Figures 3 to 7). Table 1 shows the results of a single regression analysis of various factors during each period, including age, CDVA, preoperative IOP, AL, operative time, and change in IOP, that affected the changes in choroidal thickness. Subsequently, a stepwise analysis
Control Study and Interexaminer Reproducibility As a control, eyes in patients who met the criteria for inclusion in this study were also examined. Two weeks later, measurements of enhanced-depth-imaging OCT and IOP were obtained again. This was done to determine whether there were differences between the 2 IOP and choroidal thickness measurements at the 5 points. To evaluate the interexaminer reproducibility of the choroidal thickness measurements, the control eyes were examined. The 2 independent examiners measured the choroidal thickness at the same 5 points. The interexaminer reproducibility values were evaluated based on the intraclass correlation coefficients (ICCs).
Statistical Analysis Statistical analyses, including a 2-way layout analysis of variance with a Bonferroni correction, a multiple stepwiseregression analysis, the paired t test, and calculation of the ICCs, were performed using a commercially available software program (JMP, version 10.0, SAS Institute, Inc.). A P value less than .05 was considered to indicate a statistically significant difference.
RESULTS Patient Demographic Data One hundred twelve preoperative cataract eyes in 112 Japanese patients were included. Of the patients, 4 opted out of the postoperative examinations and 8 were excluded postoperatively due to poor OCT images resulting from unstable fixation or corneal edema
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Figure 3. Choroidal thickness at the fovea over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
was performed to determine which factors among age, CDVA, preoperative IOP, AL, operative time, and change in IOP were most significantly associated with the changes in choroidal thickness during each period. Age, CDVA, preoperative IOP, and the operative time had no significant correlations with the changes in choroidal thickness. During some periods, changes in IOP and AL were correlated with the changes in choroidal thickness (Table 2). Control Study and Interexaminer Reproducibility Twenty eyes of 20 age-matched patients (mean age 73.5 G 7.4 years) were analyzed. Table 3 shows the results. There were no significant differences in the mean IOP and the mean choroidal thickness at each of the 5 points between the first examination and second examination. Table 4 shows the interexaminer reproducibility. The interexaminer ICCs of the choroidal thickness ranged between 0.953 mm and 0.990 mm (P!.001). Complications No serious complications (eg, vitreous loss) were observed.
Figure 5. Choroidal thickness at the temporal region over time. The asterisk indicates a statistically significant difference compared with the preoperative value.
187
Figure 4. Choroidal thickness at the nasal region over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
DISCUSSION In the present study, we determined the RPE and choroidal–scleral interface manually, as in a previous study,17 to measure the choroidal thickness so any possible errors would be taken into consideration. There were very small differences in the 2 measurements of choroidal thickness in the control group between timepoints, although the differences were not significant. Furthermore, because 2 examiners were involved in the choroidal thickness measurements, we obtained ICCs between the findings of the examiners to evaluate the reproducibility of the measurements. The ICCs were very high, comparable to those reported in earlier studies.12,17,29 Based on these results, the data reliability in the present study appears to be high. The choroid was significantly thicker in some regions or at certain timepoints after cataract surgery compared with baseline values. The postoperative increase in choroidal thickness was greatest in the inferior region, followed by the foveal and nasal regions. The increase in choroidal thickness was slight at the temporal and superior regions. It is interesting that there was an increase in choroidal thickness at the nasal and inferior regions because the choroid in the patients in this study was relatively thin in these regions. There are 2 reasons for the relative choroidal thinning observed nasally and inferiorly. One is the choroidal watershed, which isolates the choroidal
Figure 6. Choroidal thickness at the superior region over time. The asterisk indicates a statistically significant difference compared with the preoperative value.
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
188
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
be anatomically vulnerable and more susceptible to changes in IOP. The choroid may be involved in the pathogenesis of various ocular diseases. It has been suggested that cataract surgery is associated with the onset of AMD.19–21 This process might be mediated via inflammatory reactions associated with the surgery,22,23 postoperative biochemical environmental changes in the eye (increased free radicals or growth factors),22,24,25 or increased light exposure during or after surgery.26,27 The present study found that cataract surgery, which is commonly performed in ophthalmic practice, resulted in changes in choroidal thickness; thus, the fine changes in choroidal thickness might also affect the onset of AMD. Further research is needed to determine the effects of cataract surgery on choroidal thickness in patients with AMD.
Figure 7. Choroidal thickness at the inferior region over time. The asterisks indicate a statistically significant difference compared with the preoperative value.
circulation,30 as observed on fluorescein or indocyanine green angiography. Another is the fetal choroidal fissure, which closes inferiorly at approximately 7 weeks of gestation.31 These regions can
Table 1. Single regression analysis of various factors affecting the changes in the choroidal thickness. Age Area Fovea 3 days 1 week 3 weeks 3 months 6 months Nasal 3 days 1 week 3 weeks 3 months 6 months Temporal 3 days 1 week 3 weeks 3 months 6 months Superior 3 days 1 week 3 weeks 3 months 6 months Inferior 3 days 1 week 3 weeks 3 months 6 months
Preoperative CDVA Preoperative IOP
R2
P
R2
P
b
0.11 0.34 0.47 0.39 0.33
0.009 0.05 0.07 0.05 0.03
.35 .03* .008* .03* .11
1.33 1.85 1.47 2.92 3.83
0.001 0.001 0.0005 0.002 0.003
.75 .75 .82 .65 .60
0.39 0.52 0.81 0.70 0.84
0.02 0.02 0.03 0.02 0.03
.19 .20 .08 .13 .10
0.08 0.43 0.55 0.37 0.48
0.004 0.07 0.09 0.05 0.05
.55 .009* .003* .03* .03*
1.17 6.91 7.29 0.48 3.97
0.0005 0.01 0.01 0.00006 0.002
.82 .25 .29 .94 .62
0.47 0.60 0.55 0.77 0.94
0.02 0.02 0.01 0.03 0.03
0.07 0.30 0.51 0.52 0.43
0.003 0.03 0.06 0.06 0.04
.58 .09 .02* .02* .06
2.01 7.74 5.80 0.63 1.06
0.002 0.02 0.006 0.00006 0.0002
.65 .21 .45 .94 .90
0.077 0.12 0.09 0.02 0.65
0.03 0.34 0.47 0.27 0.30
0.0007 0.05 0.08 0.02 0.02
.80 .03* .004* .14 .14
2.76 4.19 1.88 3.83 1.27
0.003 0.006 0.001 0.004 0.0003
.58 .46 .75 .55 .86
0.03 0.36 0.45 0.41 0.30
0.0006 0.04 0.05 0.03 0.02
.81 .04* .03* .07 .18
2.56 3.20 0.94 3.98 2.96
0.002 0.003 0.0002 0.002 0.001
.62 .61 .90 .62 .72
b
B
R2
P
Axial Length b
R2
P
1.56 1.20 2.35 3.65 3.86
0.05 0.01 0.04 0.10 0.09
.03* .23 .04* .001* .002*
.19 .16 .25 .82 .10
1.46 1.12 1.91 2.20 3.23
0.03 0.01 0.03 0.04 0.05
.10 .29 .11 .04* .02*
0.0006 0.0008 0.0003 0.00001 0.01
.81 .78 .87 .97 .26
1.74 2.31 3.48 5.58 4.70
0.22 0.36 0.58 0.44 0.69
0.004 0.008 0.02 0.01 0.02
.53 .37 .16 .32 .18
0.38 0.35 0.61 0.51 0.92
0.01 0.006 0.01 0.008 0.03
.30 .43 .24 .38 .11
Surgery Time b
Change in IOP
R2
P
b
0.0004 0.006 0.007 0.002 0.005
0.0001 0.01 0.01 0.0007 0.006
.92 .31 .28 .79 .45
0.76 1.97 2.46 1.95 2.10
0.08 .006* 0.19 !.0001* 0.22 !.0001* 0.13 .0002* 0.09 .003*
0.0007 0.003 0.001 0.006 0.003
0.0002 0.002 0.0004 0.01 0.001
.90 .65 .85 .31 .75
0.60 2.12 1.92 1.30 1.59
0.03 .08 0.19 !.0001* 0.12 .0003* 0.06 .01* 0.04 .04*
0.05 .02* 0.05 .03* 0.07 .008* 0.17 !.0001* 0.11 .0008*
0.003 0.007 0.01 0.002 0.007
0.005 0.01 0.02 0.0007 0.007
.49 .24 .15 .79 .40
0.49 1.73 2.12 1.00 1.69
0.03 0.12 0.12 0.02 0.05
2.51 2.17 2.43 3.52 3.61
0.09 0.05 0.06 0.10 0.08
.003* .03* .02* .001* .004*
0.003 0.01 0.01 0.004 0.01
0.004 0.03 0.06 0.003 0.02
.55 .08 .02* .57 .13
0.52 1.64 2.01 1.17 1.05
0.03 .11 0.13 .0002* 0.18 !.0001* 0.05 .02* 0.02 .13
1.86 1.30 1.86 3.78 3.56
0.04 0.01 0.02 0.07 0.06
.04* .23 .15 .007* .01*
0.008 0.01 0.007 0.003 0.008
0.02 0.04 0.01 0.001 0.009
.13 .056 .325 .71 .35
0.69 1.86 2.00 1.26 1.48
0.04 0.14 0.11 0.04 0.04
b Z b coefficient, CDVA Z corrected distance visual acuity; IOP Z intraocular pressure; P Z P value; R2 Z coefficient of determination *Statistically significant difference
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
R2
P
.10 .0003* .0004* .13 .03*
.04* .0001* .0006* .06 .06
189
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
Table 2. Multiple regression analysis of factors affecting changes in choroidal thickness. Axial Length
Change in IOP P Value
Regression
Area Fovea 3 days 1 week 3 weeks 3 months 6 months Nasal 3 days 1 week 3 weeks 3 months 6 months Temporal 3 days 1 week 3 weeks 3 months 6 months Superior 3 days 1 week 3 weeks 3 months 6 months Inferior 3 days 1 week 3 weeks 3 months 6 months
Regression
P Value
R2
d d d 2.94x C 72.1 3.16x C 78.7
d d d .0059 .01096
0.76x C 2.52 1.97x C 2.92 2.46x C 0.45 1.67x C 0.13 1.70x C 1.10
.0058 !.0001 !.0001 .0011 .0137
0.075 0.185 0.221 0.199 0.148
d d d d 3.23x C 80.3
d d d d .02096
d 2.12x C 3.02 1.92x C 0.14 1.30x to 0.32 d
d !.0001 .0003 .0112 d
d 0.1947 0.124 0.064 0.053
1.74x C 43.7 d d 5.58x C 132.8 4.70x C 113.4
.0234 d d !.0001 .0008
d 1.73x C 2.53 2.12x C 0.31 d d
d .0003 .0004 d d
0.051 0.123 0.121 0.166 0.11
2.51x C 61.7 d d 3.52x C 84.4 3.61x C 87.8
.0029 d d .0011 .0036
d 1.64x C 1.78 2.01x C 0.07 d d
d .0002 !.0001 d d
0.087 0.133 0.18 0.104 0.083
d d d 3.78x C 93.3 3.56x C 89.1
d d d .0068 .0111
d 1.86x C 3.20 2.00x C 2.33 d d
d .0001 .0006 d d
d 0.142 0.114 0.072 0.064
IOP Z intraocular pressure; R2 Z coefficient of determination
As found in previous studies,32–34 the IOP deceased after cataract surgery, with a particularly significant decrease at 3 weeks and thereafter. The changes in choroidal thickness from baseline were negatively
correlated with the changes in IOP relatively early after surgery. However, the changes in choroidal thickness were not correlated over time with the IOP in many regions. Therefore, an increase in ocular
Table 3. Control study. Mean G SD Parameter IOP (mm Hg) Fovea (mm) Nasal (mm) Temporal (mm) Superior (mm) Inferior (mm)
1st Exam
2nd Exam
P Value*
13.9 G 3.2 267.7 G 99.4 208.3 G 100.6 252.5 G 87.0 264.0 G 83.7 225.3 G 86.8
14.0 G 2.8 267.0 G 97.6 209.0 G 98.8 252.1 G 87.0 264.5 G 83.0 225.2 G 85.3
.88 .43 .5 .75 .67 .92
IOP Z intraocular pressure *Paired t test
Table 4. Interexaminer reproducibility based on ICCs of the choroidal thickness of each region measured by 2 masked observers. Area Fovea Nasal Temporal Superior Inferior
ICC
P Value
0.98533 0.98973 0.95347 0.97048 0.9584
!.01 !.01 !.01 !.01 !.01
ICC Z intraclass correlation coefficient
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
190
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
perfusion pressure due to a decreased IOP, which was noted relatively early after surgery, might have increased the choroidal thickness. In the late postoperative period, the changes in choroidal thickness were not correlated with the changes in IOP in many regions; rather, the changes in choroidal thickness were negatively correlated with the AL in all regions. The longer the AL, the thinner the choroid. Future studies should address this issue in terms of high myopia. It is known that the mean subfoveal choroidal thickness is negatively correlated with age and myopic refractive error. Our previous study35 showed that the subfoveal choroidal thickness decreased by 1.4 mm for each year and by 6.2 mm for each diopter of myopia in healthy volunteers. Ho et al.36 and Nishida et al.37 showed that the subfoveal choroidal thickness decreased by 1.2 mm and 1.6 mm, respectively, for each year and by 6.2 mm and 8.1 mm, respectively, for each diopter of myopia in myopic eyes. The annual changes in choroidal thickness may have also affected the thickness for a relatively long period (3 to 6 months) after surgery. Future studies should determine how the choroidal thickness changes after glaucoma surgery, which has a great impact on IOP, more invasive vitreous surgery, and other types of procedures. Because these surgical procedures are often performed in conjunction with cataract surgery, the results in the present study focusing on cataract surgery alone may be helpful in interpreting the results obtained after concomitant surgeries. The present study has limitations. Falavarjani et al.38 argue that retinal thickness measurements can be affected by cataract type and severity. The choroidal thickness might also be affected by cataract. However, Falavarjani et al. used time-domain OCT, whereas we used the spectral-domain OCT in the present study. Furthermore, because obtaining accurate images was prioritized, poor OCT images due to severe cataracts were excluded from the analysis. Based on these points, we consider that the influence of the cataract on the measurement of the choroidal thickness was small. The small sample might be insufficient to evaluate the changes in choroidal thickness. In the present study, the lines of the RPE and choroidal–scleral interface were determined manually. However, because cross-sectional imaging is insufficient in eyes with very thick choroids, the reproducibility of the manual tracing method used here may be low. To this end, improvements in OCT performance, or if possible in algorithm development to automatically detect the choroidal–scleral interface, are desirable. The general picture may not be reflected because the measurements were obtained at 5 points only; that is, the fovea and the nasal, temporal, superior, and inferior regions
1.5 mm from the fovea. We are planning to perform a more detailed 3-dimensional analysis of the choroid to obtain additional information. WHAT WAS KNOWN It has been suggested that cataract surgery is associated with the onset of AMD, which is a serious disease that results in central visual impairment due to neovascularization originating from the choroid. WHAT THIS PAPER ADDS Cataract surgery increased choroidal thickness, and the changes in choroidal thickness negatively correlated with the AL in the late postoperative period. The fine changes in choroidal thickness after cataract surgery may affect the onset of AMD, and these effects may differ depending on the AL.
REFERENCES 1. Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol 2004; 137:496–503 2. Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004; 49:25–37 3. Gomi F, Tano Y. Polypoidal choroidal vasculopathy and treatments. Curr Opin Ophthalmol 2008; 19:208–212 4. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol 1967; 63:587–615 5. Spaide RF, Hall L, Haas A, Campeas L, Yannuzzi LA, Fisher YL, Guyer DR, Slakter JS, Sorenson JA, Orlock DA. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina 1996; 16:203–213 6. Iida T, Kishi S, Hagimura N, Shimizu K. Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy. Retina 1999; 19:508–512 7. Duke-Elder S, Abrams D. Pathological myopia. In: Duke-Elder S, ed, System of Ophthalmology. Volume 5. Ophthalmic Optics and Refraction. London, UK, Henry Kimpton, 1970; 300–362 8. Ohno H. [Electron microscopic studies of myopic retinochoroidal atrophies 1. Choroidal changes]. [Japanese]. Nippon Ganka Kiyo 1983; 43:1244–1253 9. Matsuo N, Okabe S, Hasegawa E, Okamoto S. [Report of research committee on chorioretinal degenerations]. [In Japanese]. Tokyo, Japan, The Ministry of Health and Welfare of Japan, 1978 10. Schuman JS, Hee MR, Arya AV, Pedut-Kloizman T, Puliafito CA, Fujimoto JG, Swanson EA. Optical coherence tomography: a new tool for glaucoma diagnosis. Curr Opin Ophthalmol 1995; 6:89–95 11. Jaffe GJ, Caprioli J. Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol 2004; 137:156–169 12. Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146:496–500 13. Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina 2009; 29:1469–1473
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
CHANGES IN CHOROIDAL THICKNESS AFTER CATARACT SURGERY
14. Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology 2010; 117:1792–1799 15. Ikuno Y, Tano Y. Retinal and choroidal biometry in highly myopic eyes with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2009; 50:3876–3880. Available at: http:// www.iovs.org/content/50/8/3876.full.pdf. Accessed July 30, 2013 16. Fujiwara T, Imamura Y, Margolis R, Slakter JS, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol 2009; 148:445–450 17. Ohsugi H, Ikuno Y, Oshima K, Tabuchi H. 3-D choroidal thickness maps from EDI-OCT in highly myopic eyes. Optom Vis Sci 2013; 90:599–606 18. Ikuno Y, Jo Y, Hamasaki T, Tano Y. Ocular risk factors for choroidal neovascularization in pathologic myopia. Invest Ophthalmol Vis Sci 2010; 51:3721–3725. Available at: http://www. iovs.org/content/51/7/3721.full.pdf. Accessed July 30, 2013 19. Klein R, Klein BE, Wong TY, Tomany SC, Cruickshanks KJ. The association of cataract and cataract surgery with the long-term incidence of age-related maculopathy; the Beaver Dam Eye Study. Arch Ophthalmol 2002; 120:1551–1558. Available at: http://archopht.jamanetwork.com/data/Journals/OPHTH/6842/ EEB20011.pdf. Accessed July 30, 2013 20. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD. Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies. Am J Ophthalmol 2003; 135:849–856 21. Cugati S, Mitchell P, Rochtchina E, Tan AG, Smith W, Wang JJ. Cataract surgery and the10-year incidence of age-related maculopathy; the Blue Mountains Eye Study. Ophthalmology 2006; 113:2020–2025 22. van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, Pameyer JH, de Jong PT. Increased prevalence of disciform macular degeneration after cataract extraction with implantation of an intraocular lens. Br J Ophthalmol 1994; 78:441–445. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC504819/ pdf/brjopthal00030-0019.pdf. Accessed July 30, 2013 23. Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002; 134:411–431 24. Pollack A, Marcovich A, Bukelman A, Oliver M. Age-related macular degeneration after extracapsular cataract extraction with intraocular lens implantation. Ophthalmology 1996; 103:1546–1554 25. Penfold PL, Provis JM, Billson FA. Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis. Graefes Arch Clin Exp Ophthalmol 1987; 225:70–76 26. Mainster MA, Ham WT, Delori FC. Potential retinal hazards: instrument and environmental light sources. Ophthalmology 1983; 90:927–931; discussion by T Lawwill, 931–932 27. Libre PE. Intraoperative light toxicity: a possible explanation for the association between cataract surgery and age-related macular degeneration [letter]. Am J Ophthalmol 2003; 136:961 28. Usui S, Ikuno Y, Akiba M, Maruko I, Sekiryu T, Nishida K, Iida T. Circadian changes in subfoveal choroidal thickness and the relationship with circulatory factors in healthy subjects. Invest
29.
30.
31. 32.
33.
34.
35.
36.
37.
38.
191
Ophthalmol Vis Sci 2012; 53:2300–2307. Available at: http:// www.iovs.org/content/53/4/2300.full.pdf. Accessed July 30, 2013 Ikuno Y, Maruko I, Yasuno Y, Miura M, Sekiryu T, Nishida K, Iida T. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52:5536–5540. Available at: http://www.iovs.org/content/52/8/ 5536.full.pdf. Accessed July 30, 2013 Hayreh SS. In vivo circulation and its watershed zones. Eye 1990; 4:273–289. Available at: http://www.nature.com/eye/journal/v4/ n2/pdf/eye199039a.pdf. Accessed Juy 30, 2013 Oyster CW. The Human Eye; Structure and Function. Sunderland, MA, Sinauer Associates, 1999; 57–75 Jahn CE. Reduced intraocular pressure after phacoemulsification and posterior chamber intraocular lens implantation. J Cataract Refract Surg 1997; 23:1260–1264 Hayashi K, Hayashi H, Nakao F, Hayashi F. Changes in anterior chamber angle width and depth after intraocular lens implantation in eyes with glaucoma. Ophthalmology 2000; 107:698–703 Mansberger SL, Gordon MO, Jampel H, Bhorade A, Brandt JD, Wilson B, Kass MA; for the Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology 2012; 119:1826–1831 Ikuno Y, Kawaguchi K, Nouchi T, Yasuno Y. Choroidal thickness in healthy Japanese subjects. Invest Ophthalmol Vis Sci 2010; 51:2173–2176. Available at: http://www.iovs.org/content/51/4/ 2173.full.pdf. Accessed July 30, 2013 Ho M, Liu DT, Chan VC, Lam DS. Choroidal thickness measurement in myopic eyes by enhanced depth optical coherence tomography. Ophthalmology 2013 May 15 [Epub ahead of print] Nishida Y, Fujiwara T, Imamura Y, Lima LH, Kurosaka D, Spaide RF. Choroidal thickness and visual acuity in highly myopic eyes. Retina 2012; 32:1229–1236 Falavarjani KG, Modarres M, Nikeghbali A. OCT and cataract [letter]. Ophthalmology 2010; 117:849; reply by Y Takamura, E Kubo, Y Akagi, 849–850
OTHER CITED MATERIAL A. Pierru A, Baillif-Gostoli S, Gastaud P, “Measurement of Subfoveal Choroidal Thickness Before and After Cataract Surgery Using Enhanced Depth Imaging Optical Coherence Tomography,” presented at the congress of the European Association for Vision and Eye Research, Nice, France, October 2012. Abstract available in Acta Ophthalmol 2012; 90(suppl 249). Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.17553768.2012.4726.x/abstract. Accessed July 30, 2013
J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014
First author: Hideharu Ohsugi, MD, PhD Department of Ophthalmology, Tsukazaki Hospital, Himeji, Japan
