Keratoconus is an idiopathic, progressive, noninflammatory ectasia of the lower central cornea.1 It is considered to originate in the corneal epithelial basement membrane1 and it is associated with various ocular disorders, such as retinitis pigmentosa,2,3 macular coloboma,3,4 Leber's congenital amaurosis,5 retinal aplasia,4 cone-rod dystrophy,6 central serous chorioretinopathy,7 and choroidal neovascularization (CNV).8 The latter two of these involve the choroid, thereby leading researchers to speculate that the basement membrane is involved in keratoconus, and that similar alterations in basement membrane–retinal pigment epithelium (RPE) interactions can alter the integrity of the outer blood retinal barrier. Accordingly, central serous chorioretinopathy and CNV may represent dysfunction of epithelial layer, and potentially their basement membrane.
Optical coherence tomography (OCT) is a noninvasive, noncontact imaging modality for acquiring high-resolution, cross-sectional retinal scans.9 It is a valuable tool for diagnosing and managing chorioretinal disease. Imaging of deeper structures such as the choroid with this method was previously a hard modality, since light scatter and decreased resolution and sensitivity associated with increasing depth. However, new OCT-based techniques for in vivo choroidal imaging are now available.10–13
Spaide10 described a technique for enhanced depth imaging (EDI) OCT. The method involves placing an objective lens of the spectral-domain OCT (SD-OCT) device (Spectralis; Heidelberg Engineering, Heidelberg, Germany) closer to the eye, such that an inverted image can be obtained. This maneuver places the deeper structures closer to zero delay, allowing for better choroid visualization. Its eye-tracking and image-averaging technology, high-speed scanning, reduced noise, and greater macular area coverage produces high-resolution, optical, cross-sectional images of the choroid. The thickness of the choroid can be measured at various locations within the macular region.
To the best of my knowledge, variations in the choroidal thickness related to keratoconus are unreported. The current study evaluated and compared macular and peripapillary choroidal parameters, generated using SD-OCT, in patients with keratoconus to age- and sex-matched healthy participants.
Patients and Methods
Study Design and Subjects
This was a prospective, observational cross-sectional study. The study population consisted of patients with documented keratoconus, examined at the Cornea Division of the Kayseri Training and Research Hospital. Keratoconus was diagnosed by a cornea specialist, according to slit-lamp biomicroscopy findings of localized corneal thinning and ectasia. These were confirmed using corneal topography. Informed consent was obtained from all participants before study commencement. The study protocol conformed to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the University of Erciyes, Turkey.
The control group included age- and sex-matched individuals in good general and ocular health, recruited from the outpatient clinic of the Kayseri Training and Research Hospital. All controls had good visual acuity (VA) with a spherical equivalent (SE) ranging from −2.60 diopters (D) to 0.00 D, and no retinal disease. I randomly selected one eye, per participant, if both were eligible.
The inclusion criterion was best-corrected Snellen VA of greater than 20/40. Patients with glaucoma and ocular hypertension were excluded by glaucoma specialists, according to intraocular pressure less than 21 mm Hg and normal optic nerve appearance observed by conducting a nonglaucomatous, standard automated perimetry visual field examination. I excluded patients with a history of surgery, laser treatment, retinal disease, or neurological diseases that could affect the optic disc or visual field, as well as those with tilted discs, non-glaucomatous optic disc atrophy, or any significant media opacity that obscured the fundus.
I instructed contact lens wearers not to use their lenses for a minimum of 24 hours before the examination. Each study participant underwent a complete ophthalmic examination, including central corneal thickness (CCT) assessment, keratometry (K) performed using a Scheimpflug camera (Pentacam HR; Oculus GmbH, Wetzlar, Germany), axial length (AL) of the eye measured using the IOLMaster (Carl Zeiss Meditec, Dublin, CA), slit-lamp biomicroscopy, fundus examination, and gonioscopy. I measured refraction using a Tonoref II autorefractor/tonometer (Nidek, Gamagori, Japan). SE was calculated as the sum of the spherical plus half of the cylindrical error.
I used images acquired using a Heidelberg Spectralis SD-OCT imaging platform (HEYEX software 6.0; Heidelberg Engineering, Heidelberg, Germany) with an EDI program to measure choroidal thickness in patients and controls. Scans with quality scores of less than 20, or with inadequate quality as determined by unclear images of the fundus or an unclear border of the choroidea, were excluded from the analysis.
The between-groups difference in subfoveal choroidal thickness was detected using the EDI OCT technique,10 in which the SD-OCT instrument was pushed close to the eye to obtain an inverted image. Seven sections, each comprising 100 averaged scans to improve the signal-to-noise ratio, were obtained in a 5° × 30° rectangle that encompassed the macula and optic nerve. The horizontal section, passing directly through the center of the fovea, was used to measure choroidal thickness. Using the attached measuring software in the Heidelberg Spectralis OCT, I measured the choroid from the outer border of the hyperreflective line (corresponding to the RPE), to the inner scleral border. Macular measurements of choroidal thickness were performed at the subfoveal location and at 750-μm intervals, from the fovea, up to locations at 1.5 mm nasal and 1.5 mm temporal from the center of the fovea; these measurements were performed between 12 and 2 PM to avoid diurnal variations (Figure 1).
Optical coherence tomography (OCT) scans showing the macular choroidal thicknesses of a patient with keratoconus, and a control subject. (Top) Scanning laser ophthalmoscopy fundus image obtained using Spectralis (Heidelberg Engineering, Heidelberg, Germany) for eye tracking. Seven green lines indicate the location and direction of the scan pattern. The marked green line passed directly through the center of the fovea. (Bottom left) An OCT image of a 21-year-old patient with keratoconus obtained using Spectralis. Image averaging performed with the aid of eye tracking and enhanced depth imaging are used for choroidal visualization. Black lines indicate choroidal thickness measurements at the fovea, 0.75 mm and 1.5 mm temporal to the fovea, and 0.75 mm and 1.5 mm nasal to the fovea. (Bottom right) An OCT image of an 18-year-old control subject obtained using Spectralis.
The peripapillary choroidal thickness was measured using a 360°, 3.4-mm diameter peripapillary circle scan (consisting of 100 averaged scans, centered on the optic disc), which also measures the peripapillary retinal nerve fiber layer thickness. Because automated choroidal thickness measurements were not provided by the software, I manually aligned the choroidal interfaces in the peripapillary two-dimensional view. I placed the inner choroidal interface delineation on Bruch's membrane, to discriminate between the RPE and choroid. I placed the outer choroidal interface delineation between the choroid and sclera. Choroidal thickness was calculated using Heidelberg Eye Explorer software for each segment (temporal, superotemporal, superonasal, nasal, inferonasal, inferotemporal, and global; Figure 2). Before the primary analysis, I calculated interexaminer and intraexaminer intraclass correlation coefficients using 15 randomly selected images, to test the reproducibility of measurements. Foveal retinal thickness (central subfield retinal thickness) was determined automatically in all eyes.
Choroidal thickness measurement using the imaging and analysis tool of Heidelberg Engineering spectral-domain optical coherence tomography (SD-OCT). The top panel displays an image and choroidal thickness profile of a 27-year-old patient with keratoconus, and the bottom panel presents the corresponding findings of a 26-year-old control. In the left picture, the location of the peripapillary scan is exposed in an infrared image. The middle picture illustrates the peripapillary SD-OCT scan displayed with the two borderlines of the choroidea, and the right picture presents the calculated thickness for each segment of peripapillary choroidal thickness. The numbers in parentheses and colors of each segment display the standard values for the peripapillary retinal nerve fiber layer thickness, and not for the peripapillary choroidea thickness. TS = temporal superior; T = temporal; TI = temporal inferior; NS = nasal superior; N = nasal; NI = nasal inferior; G = global.
Statistical analysis was performed using SPSS version 21.0 (SPSS, Chicago, IL). The distribution of the data was evaluated using the Kolmogorov–Smirnov test. The Student's t-test was used to analyze parametric data, and the Mann–Whitney U test was used to analyze nonparametric data to compare the two groups. Group gender distributions were compared using the chi square test. To analyze the choroidal thickness profile in the macula (distance from the fovea: subfoveal, 0.75 mm temporal, 1.5 mm temporal, 0.75 mm nasal, and 1.5 mm nasal to the fovea), a generalized linear model for repeated measures (within-subject effect) was employed. A similar model was employed when the peripapillary choroidal thickness was analyzed in measured segments. Univariate and stepwise (combining forward and backward) multivariable linear regression analyses were used to explore the influencing factors for macular and peripapillary choroidal thickness.
Multivariable analysis of the possible influencing factors included age, sex, SE, AL, CCT, and K. The relationship between the mean foveal choroidal and retinal thicknesses was analyzed using the Pearson correlation coefficient. Significance was set at a P value of less than .05.
The study population consisted of 45 patients with keratoconus and 56 healthy participants, all of whom were examined between July 2016 and February 2017.
Among the 101 enrolled participants, the female/male ratios were 14 (31.1%) / 31 (68.9%) and 16 (28.6%) / 40 (71.4%) in the study and control groups, respectively. There was no significant difference in gender distribution between the control and keratoconus groups (P = .781). The mean age was 24.5 years ± 7.2 years (range: 14 years to 39 years) in patients with keratoconus and 22.5 years ± 7.4 years (range: 13 years to 38 years) in controls. There was no significant difference in age between patients with keratoconus and controls (P = 170). The mean SE was −4.33 D ± 3.41 D (range: −15.63 D to −0.50 D) in the keratoconus group and −0.69 D ± 0.72 D (range: −2.6 D to 0.00 D) in the control group (P < .001). The mean K (46.9 D ± 3.0 D vs. 43.0 D ± 1.2 D; P < .001) was significantly higher and the CCT (465.0 μm ± 33.1 μm vs. 558.5 μm ± 20.2 µm; P < .001) values were significantly lower in the keratoconus group. There was no significant difference in AL (23.8 mm ± 0.6 mm vs. 23.6 mm ± 0.7 mm; P = .24) between the groups. The differences in SE, average central K, CCT, and AL between the groups are shown in Table 1.
Analyses of Spherical Equivalent, Average Central Keratometry, Central Corneal Thickness, and Axial Length
Intraexaminer intraclass correlation coefficient values (95%confidence intervals) for foveal and global peripapillary measurements were 0.976 (0.954–0.987) and 0.974 (0.916–0.992), respectively. Interexaminer intraclass correlation coefficients for foveal and global peripapillary measurements were 0.944 (0.893–0.971) and 0.943 (0.816–0.972), respectively.
The choroid was thinner at 1.5 mm nasal to the fovea than at all extrafoveal locations, in both groups (P < .001). The choroid was thinnest nasally, thicker in the subfoveal region, and then thinner again temporally, although not as thin as the choroid proximal to the disc.
The choroid was significantly thinner at 0.75 mm temporal to the fovea than under the fovea, in the keratoconus group. This finding was not observed in the controls (427.48 ± 78.51 vs. 394.35 ± 86.39, P < .001 for the keratoconus group; 351.03 ± 99.08 vs. 348.30 ± 108.04, P = .516 for the controls). In the two groups, the lowest and highest values for macular choroidal thickness were observed at 1.5 mm nasal to the fovea, and at the subfoveal location, respectively. The variation trends of macular choroidal thickness in the keratoconus and control groups are illustrated in Figure 3.
Variation trends of macular choroidal thickness in the keratoconus and control groups. Graphs show the mean choroidal thickness measured at different locations across a horizontal section through the fovea (at 750-μm intervals from 1.5 mm nasal to 1.5 mm temporal to the fovea) in this series of keratoconus (left) and normal (right) eyes.
The mean subfoveal choroidal thickness was 351.03 μm ± 99.08 μm in the control group versus 427.48 μm ± 78.51 μm in the keratoconus group (P < .001). The choroidal thickness was significantly higher in the keratoconus group than in the control group at subfoveal and extrafoveal measurement locations (except at 1.5 mm temporal to the fovea; 394.35 μm ± 86.39 μm vs. 348.30 μm ± 108.04 μm, P = .019; 378.24 μm ± 87.13 μm vs. 320.23 μm ± 105.80 μm, P = .004; and 331.55 μm ± 82.46 μm vs. 286.16 μm ± 99.69 μm, P = .021 for the measurement locations at 0.75 mm temporal, 0.75 mm nasal, and 1.5 mm nasal to the fovea, respectively). There was no significant difference in the choroidal thickness at 1.5 mm temporal to the fovea, between the keratoconus and control groups (375.06 μm ± 93.83 μm vs. 336.82 μm ± 114.67 μm, P = .068), although a trend toward increasing thickness, for this location, was observed in the keratoconus group, compared with the control group.
AL and CCT were significantly correlated with the mean thickness of the subfoveal choroid [standardized correlation coefficient (β) = −0.297, P < .001; β = −0.352, P < .001, respectively], as well as with the choroidal thickness at 0.75 mm temporal to the fovea (β = −0.380, P < .001; β = −0.220, P = .018, respectively), at 0.75 mm nasal to the fovea (β = −0.333, P < .001; β = −0.251, P = .008, respectively), and at 1.5 mm nasal to the fovea (β = −0.268, P = .006; β = −0.192, P = .048, respectively). Other factors were not significantly correlated with the subfoveal choroidal thickness (P = .052, P = .206, P = .065, and P = .187 for age, gender, SE, and K, respectively).
The choroidal thickness at subfoveal and other extrafoveal measurement locations (except for 1.5 mm temporal to the fovea) was significantly higher in the keratoconus group than in the control group after adjusting for AL (P < .001, P = .003, P < .001, and P = .005 for subfoveal and 0.75 mm temporal, 0.75 mm nasal, and 1.5 mm nasal to the fovea locations, respectively); however, only the subfoveal choroidal thickness differed significantly between the two groups after adjusting for CCT (P = .029, P = .240, P = .075, and P = .073 for subfoveal and 0.75 mm temporal, 0.75 mm nasal, and 1.5 mm nasal to the fovea locations, respectively). Table 2 shows the mean choroidal thickness in the macula of all examined locations.
Mean Choroidal Thickness Measurements at Various Locations in the Keratoconus and Control Groups
The peripapillary choroid was thinner in the inferonasal and inferotemporal segments than in the other segments (temporal, superotemporal, superonasal, and nasal) in both groups (P < .001). The peripapillary choroid was significantly thinner in the inferonasal segment than in the inferotemporal segment in the keratoconus group (P = .018) but not in the control group (P = .480). In the two groups, the inferonasal and temporal segments exhibited the lowest and highest values, respectively, for peripapillary choroidal thickness. The variation trends of peripapillary choroidal thickness in the keratoconus and control groups are illustrated in Figure 4.
Variation trends of peripapillary choroidal thickness in the keratoconus (left) and control (right) groups. All measurements are performed at 3.46 mm from the center of the optic disc.
Differences in the mean global peripapillary choroidal thicknesses were insignificant between the keratoconus and control groups (212.39 μm ± 57.62 μm vs. 211.65 μm ± 58.91 μm, P = .951). There were no significant differences in all the other measured segment thicknesses between the two groups (225.55 μm ± 50.16 μm vs. 218.33 μm ± 68 μm, P = .551 for the temporal segment; 222.74 μm ± 50.88 μm vs. 215.05 μm ± 60.81 μm, P = .510 for the superotemporal segment; 220.41 μm ± 63.12 μm vs. 212.37 μm ± 60.31 μm, P = .526 for the superonasal segment; 211.58 μm ± 67.47 μm vs. 214.90 μm ± 58.90 μm, P = .797 for the nasal segment; 185.72 μm ± 66.32 μm vs. 196.03 μm ± 64.27 μm, P = .443 for the inferonasal segment; and 196.46 μm ± 72.41 μm vs. 198.54 μm ± 69.09 μm, P = .851 for the inferotemporal segment thicknesses). The peripapillary choroidal thicknesses at different locations in the keratoconus and control groups are shown in Table 3.
Mean Choroidal Thickness at Different Segments in the Keratoconus and Control Groups, Obtained With 360° 3.4-mm Diameter Peripapillary Circle Scans
AL was significantly correlated with the mean global thickness of the peripapillary choroid (β = −0.214, P = .037), as well as with the choroidal thickness of the temporal segment (β = −0.226, P = .027) and nasal segment (β = −0.225, P = .028). Other factors were not significantly correlated with the mean global peripapillary choroidal thickness (P = .436, P = .085, P = .377, P = .928, and P = .565 for age, gender, SE, CCT, and K, respectively).
The severity of keratoconus was graded using various Pentacam measurements, including anterior curvature, according to which K values of 43.1 D to 46.9 D were considered mild, and K greater than 50 D was severe. The difference in mean subfoveal choroidal thickness between mild and severe keratoconus (437.82 μm ± 53.4 μm vs.418.87 μm ± 113.9 μm) was not significant (P = .660). Increasing subfoveal choroidal thickness was not associated with increasing keratoconus disease severity.
The correlation between mean subfoveal choroidal thickness and global peripapillary choroidal thickness was positive, and moderately strong in the keratoconus group (R = 0.57, P < .001) and nearly perfect in the control group (R = 0.72, P < .001; Figure 5).
Correlation between the mean subfoveal choroidal thickness and global peripapillary choroidal thicknesses in the keratoconus and control groups. (Left) Scatterplot showing the subfoveal choroidal and global peripapillary thickness in this series of keratoconus eyes. The trend line is shown with 95% confidence intervals (CIs). (Right) Scatterplot showing the subfoveal choroidal and global peripapillary thickness in this series of normal eyes. The trend line is shown with 95% CIs.
The mean retinal thickness of the fovea was 271 μm ± 14.2 μm in the control group and 264.9 μm ± 20.5 μm in keratoconus group (P = .099). There was no significant correlation between mean subfoveal choroidal thickness and foveal retinal thickness in either the patients with keratoconus or the controls (R = 0.247, P = .11; R = 0.104, P = .45, respectively).
In this study, I demonstrated that choroidal thickness increases in the fovea, but not in the peripapillary area, in patients with keratoconus by using SD-OCT. To the best of my knowledge, this is the first study evaluating variations in the choroidal thickness in patients with keratoconus by using SD-OCT.
Theories regarding the pathogenesis of keratoconus are based on the related histopathological changes observed in the corneal extracellular matrix (ECM). These include fragmentation of the epithelial basement membrane, superficial linear ruptures in the Bowman's layer, and delayed fold development in Descemet's membrane.1,14 Moreover, corneas of patients with keratoconus are characterized by upregulated expression of genes encoding various enzymes linked to ECM remodeling and downregulated expression of genes encoding type-IV collagen, laminin, and fibronectin.
The above downregulated genes encode for the molecules related to cell attachment to various basement membranes throughout the body,15–17 and these molecules are also involved in the attachment of the RPE to Bruch's membrane.18,19 Alterations in the expression of genes that encode the tissue inhibitor of metalloproteinase 3 (TIMP-3) and cathepsin are also found in the corneas of patients with keratoconus.20,21TIMP-3 is involved in RPE and Bruch's membrane remodeling and plays an important role in regulating choroidal vascularization.19
The choroid is made up of blood vessels, melanocytes, fibroblasts, resident immunocompetent cells, and supporting collagenous and elastic connective tissue. Thus, choroid is a highly vascularized structure, with some connective tissues.22 Choroidal thickness is therefore likely related to choroidal vessel diameter, large choroidal vessel number, and connective tissue amount. My results indicate that choroidal thickening, involving at least the subfoveal region but not the peripapillary choroid, seems to relate to these factors in patients with keratoconus.
In this study, the choroid was thinnest nasally and became thicker in the subfoveal region, and then thinner again temporally (but not as thin as the choroid proximal to the disc). These findings were observed in both controls and in patients with keratoconus, using a Heidelberg Spectralis SD-OCT device. These findings confirm recently published results regarding choroidal thickness in the macular area of healthy subjects, obtained using different SD-OCT devices.23,24 Using inverted images obtained with Heidelberg Spectralis SD-OCT, Margolis and Spaide23 demonstrated that choroidal thickness decreases rapidly in the nasal direction, up to 3 mm from the fovea. Using a Cirrus SD-OCT device (Cirrus-HD; Carl Zeiss Meditec, Dublin, CA), Manjunath et al.24 determined that the choroid is thinner in the nasal portion of the macula, and near the optic disc, in healthy subjects. I also found that the choroid is significantly thinner at 0.75 mm temporal to the fovea than in the subfoveal location in patients with keratoconus, but this was not observed in healthy controls.
This study showed that the mean subfoveal choroidal thickness in patients with keratoconus was 427.48 μm ± 78.51 μm, whereas it was 351.03 μm ± 99.08 μm in healthy participants. Margolis and Spaide23 also used the same EDI OCT technique and reported a mean subfoveal choroidal thickness of 287 μm ±76 μm in healthy participants. However, the mean age of their participants was 50.4 years, which was unlike the value of 22.5 years (mean healthy participants) in my study. Considering that subfoveal choroidal thickness decreased by 15.6 μm with every decade of life, this may account for the difference in mean subfoveal choroidal thickness measurements between the two studies.23 Using Spectralis OCT with EDI, Tan and Cheong25 reported a mean subfoveal choroidal point thickness of 326.4 μm ± 95.2 μm in healthy participants, whose mean age was 23.0 years. This finding is in agreement with my findings, probably because the similarity in the ages of participants in both studies.
Tan and Cheong25 noted that the mean subfoveal choroidal point thickness varied significantly with AL but did not vary according to age or sex, being consistent with my results. They observed a significant association between subfoveal choroidal thickness and SE but did not evaluate CCT.
However, I identified a significant association of subfoveal choroidal thickness with CCT but not with SE. Using a three-dimensional 1,060-nm SD-OCT, Esmaeelpour et al.26 found that subfoveal choroidal thickness and AL are negatively correlated in healthy participants. My study also confirmed a significant reduction in choroidal thickness with increasing AL.
In this study, I also described the pattern of choroidal thickness in the peripapillary area in both controls and patients with keratoconus. In both the keratoconus and control groups, the inferonasal and inferotemporal segment thicknesses were significantly lower than the temporal, superotemporal, superonasal, and nasal segment thicknesses; these findings are in accordance with the recently published results of Ho et al.27 using high-definition SD-OCT. They reported a significant decrease in choroidal thickness in the inferior portion of the peripapillary area compared with all other peripapillary quadrants in healthy participants.
Huang et al.28 recently reported that, in normal participants, the inferonasal, inferior, and inferotemporal segment thicknesses were significantly lower than the temporal, superotemporal, superior, superonasal, and nasal thicknesses. This finding is consistent with my study findings. Using EDI SD-OCT, Huang et al.28 also found no statistically significant differences among the inferonasal, inferior, and inferotemporal segment thicknesses. In this study, no statistically significant differences were observed among the inferonasal and inferotemporal segment thicknesses in the controls, which is consistent with previously reported findings. However, the inferonasal segment thickness in the present study was significantly lower than the inferotemporal segment thickness in patients with keratoconus.
It is unclear why the inferior segment of the peripapillary choroid is thinner than that in the other segments. This regional difference in choroidal thickness may result from ocular development. A regional difference in ocular development may contribute to the thinner choroid found in the inferior segment because the optic fissure is located in the inferior aspect of the optic cup the last part of the globe to close.29 The prelaminar portion of the optic disc head is supplied by the peripapillary choroidal circulation. In addition, the choroid is thinner in the inferior segment.
Consequently, the inferior optic disc may be more vulnerable to changes in choroidal circulatory flow. This is supported by previous studies that have shown that glaucoma influences the superior hemifield of the optic disc more frequently and more severely than the inferior hemifield of the optic disc.30,31
My study found that the mean global peripapillary choroidal thickness in patients with keratoconus and in healthy participants was 212.39 μm ± 57.62 μm and 211.65 μm ± 58.91 μm, respectively. Huang et al.28 reported an average peripapillary choroidal thickness of 165.03 μm ± 40.37 μm in 76 healthy participants. However, the mean participant age in their study was 56.95 years, compared with a mean age of 22.5 years in my study. The differences in my findings may result from the narrow age range (13 years to 38 years) of the controls. The 13.0-μm decrease in peripapillary choroidal thickness occurs per decade of life may account for the differences in the mean peripapillary choroidal thickness measurements between the two studies.28
The differences in ethnicity or differences in patient profiles may also contribute to the disparities. Conversely, Ho et al.27 reported that the ages of their participants did not correlate with peripapillary choroidal thickness, which is also consistent with my study findings.
Huang et al.28 found that peripapillary choroidal thickness and AL were not correlated, whereas Jiang et al.32 reported that a thicker peripapillary choroid was associated with a shorter AL. In this study, I observed that peripapillary choroidal thickness and AL are negatively correlated, which is similar to findings by Jiang et al.32
Foveal retinal thickness in the macular area did not show significant differences between the patients with keratoconus and controls. This is in accordance with recently published data by Moschos et al.33 using an OCT model 3000 (Stratus OCT3; Carl Zeiss Meditec, Dublin, CA); they reported no significant differences were found in the thickness of the central fovea between controls and patients with keratoconus.
Moreover, my study found no significant correlation between the mean subfoveal choroidal thickness and foveal retinal thickness in patients with keratoconus or in controls. Manjunath et al.24 reported that the central foveal thickness of the retina was poorly correlated with the choroidal thickness in the area directly beneath the fovea. This suggested that retinal thickness may not directly relate to choroidal thickness in healthy eyes.
The correlation between the mean subfoveal choroidal thickness and global peripapillary choroidal thickness was good in the keratoconus group and almost perfect in the control group. This finding is in agreement with recently published data by Jiang et al.,32 in which a thicker global peripapillary choroid related to a thicker subfoveal choroid on univariate analyses, after adjusting for age; however, Jiang et al.32 dropped subfoveal choroidal thickness from the list of independent parameters in the multivariate analysis because of collinearity.
Vascular conditions, such as polypoidal choroidal vasculopathy (PCV), may also affect choroidal thickness variability.34 It is believed to be a subtype of neovascular age-related macular degeneration characterized with an abnormal branching network of vessels, with aneurysmal dilations. PCV should be classified based on the location of the polyps: subfoveal, juxtafoveal, extrafoveal, peripapillary, or peripheral.35 Chen et al.36 traced microstructural changes in both the retina and choroids in PCV after photodynamic therapy and stated that the imaging properties among branching network of vessels and polyps were different on OCT angiography (OCTA), probably because of both blood turbulence due to different flow trends in polyps and velocities detectable in OCTA, and they demonstrated the choroidal remodeling effect of photodynamic therapy in PCV by using an in vivo imaging approach.
Since there are choroidal thickness and vascular changes on new imaging modality OCTA in vascular situations such as PCV, there also may be macular choroidal thickness variation trends in keratoconus due to blood turbulence (different flow orientations), and subfoveal choroidal thickness may be increased. Just like in PCV, in patients with keratoconus, by using newer imaging modalities such as OCTA, which demonstrates vascular changes in addition to choroidal thickness changes, further and prospective studies can be done and this suggestion can be investigated.
My findings revealed a thicker subfoveal choroid in patients with keratoconus than in controls. Choroidal thickening, as documented in this study and when confirmed in a larger population, should prompt reconsideration of the pathophysiological role of choroidal thickness variations in the natural history of keratoconus.
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Analyses of Spherical Equivalent, Average Central Keratometry, Central Corneal Thickness, and Axial Length
|Parameters||Keratoconus Group (n = 45)||Median||Control Group (n = 56)||Median||P Value|
|Mean ± SD||Mean ± SD|
|Spherical equivalent (D)||−4.33 ± 3.41 (−15.63 to −0.50)||−3.12||−0.69 ± 0.72 (−2.6 to 0.0)||−0.5||< .001|
|Average central keratometry (D)||46.9 ± 3.0 (43.10–55.5)||46||43.0 ± 1.2 (40.6–45.8)||43.1||< .001|
|Central corneal thickness (µm)||465.0 ± 33.1 (398–517)||471||558.5 ± 20.2 (524–609)||552||< .001|
|Axial length (mm)||23.8 ± 0.6 (22.1–25.1)||23.8||23.6 ± 0.7 (22.5–25.1)||23.6||.24|
Mean Choroidal Thickness Measurements at Various Locations in the Keratoconus and Control Groups
|Location (mm)||Choroidal Thickness (µm)||P Value||Adjusted P Value|
|Keratoconus Group (n = 45)||Control Group (n = 56)|
|Mean ± SD||Mean ± SD|
|Subfoveal||427.48 ± 78.51||351.03 ± 99.08||< .001||.029|
|Temporal 0.75a||394.35 ± 86.39||348.30 ± 108.04||.019||.240|
|Temporal 1.5||375.06 ± 93.83||336.82 ± 114.67||.068||.618|
|Nasal 0.75||378.24 ± 87.13||320.23 ± 105.80||.004||.075|
|Nasal 1.5||331.55 ± 82.46||286.16 ± 99.69||.021||.073|
Mean Choroidal Thickness at Different Segments in the Keratoconus and Control Groups, Obtained With 360° 3.4-mm Diameter Peripapillary Circle Scans
|Segments||Choroidal Thickness (µm)||P Value|
|Keratoconus Group (n=45)||Control Group (n=56)|
|Mean ± SD||Mean ± SD|
|Temporal||225.55 ± 50.16||218.33 ± 68||.551|
|Superotemporal||222.74 ± 50.88||215.05 ± 60.81||.510|
|Superonasal||220.41 ± 63.12||212.37 ± 60.31||.526|
|Nasal||211.58 ± 67.47||214.90 ± 58.90||.797|
|Inferonasal||185.72 ± 66.32||196.03 ± 64.27||.443|
|Inferotemporal||196.46 ± 72.41||198.54 ± 69.09||.851|
|Global||212.39 ± 57.62||211.65 ± 58.91||.951|