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Evaluation of the anterior chamber angle in keratoconus and normal subjects
Contact Lens & Anterior Eye 38 (2015) 277–282
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Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Evaluation of the anterior chamber angle in keratoconus and normal subjects ˜ c , J.P.G. Bergmanson b , R.L. Brautaset a,∗ M. Nilsson a , W. Miller b , A. Cervino a b c
Unit of Optometry, Department of Clinical Neuroscience, Karolinska Institutet, Box 8056, 104 20 Stockholm, Sweden TERTC, University of Houston, College of Optometry, Houston, TX 77204-2020, USA University of Valencia, Valencia, Spain
a r t i c l e
i n f o
Article history: Received 10 July 2014 Received in revised form 5 March 2015 Accepted 6 March 2015 Keywords: Keratoconus Anterior chamber angle VisanteTM OCT OrbscanTM II Apical protrusion
a b s t r a c t Purpose: To evaluate the anterior chamber angle in keratoconus eyes by use of the VisanteTM OCT and OrbscanTM II. Methods: Anterior chamber angle was measured with the VisanteTM OCT and OrbscanTM II in 52 subjects, 26 KC subjects and 26 age and control subjects. Results: When comparing the nasal and temporal angles obtained with the two techniques no correlation was found (R2 always below 0.01) in either the control subjects or in the KC subjects. Despite this, there was an overall statistically significant difference in mean anterior chamber angles (p < 0.001) between VisanteTM OCT and OrbscanTM II. There was no statistical difference (p > 0.05) between nasal and temporal anterior chamber angles when comparing controls and KC subjects with either of the two instruments. In general, the VisanteTM OCT gave a smaller estimate of the anterior chamber angle. Conclusion: The values from the VisanteTM OCT and OrbscanTM II cannot be interchanged since the difference in measurement of the anterior chamber angle was significantly different between the two instruments. © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Little is known about the relationship between anterior chamber angles in normal patients and those patients who have keratoconus. The anterior chamber angle evaluation is an important diagnostic step to identify those patients with shallow angles who are at risk for angle-closure glaucoma [1,2]. It is also helpful to identify those patients prone to developing angle-closure as a result of pupillary dilation [3]. In assessing the chamber angle, the depth of the anterior chamber is measured as the distance from the posterior corneal surface to the anterior surface of the crystalline lens—this measurement is often referred to as the anterior chamber depth. However, clinically, it is the iridio-corneal angle that is estimated and this measurement is commonly graded using van Herrick’s technique or by performing gonioscopy [4]. The accurate assessment of the iridio-corneal angle measurement is intended to determine who is at risk for angle closure during dilation, an important step in performing a comprehensive assessment of the retina, especially in eyes that are, more prone to peripheral retinal and posterior segment disease such as highly
∗ Corresponding author. Tel.: +46 0 8 1232 3840; fax: +46 0 8 672 3846. E-mail address: [email protected] (R.L. Brautaset).
myopic patients. It has been reported that posterior segment disease is as common in patients with keratoconus (KC) as in the normal population [5]. Patients with KC may in some instances exhibit a greater level of posterior segment disease. A report by Cohen and Myers [6] found that patients with KC are more prone to develop glaucomatous optic neuropathy. A dilated pupil is necessary in order to fully binocularly evaluate the retina and optic nerve of keratoconic patients using a binocular indirect ophthalmoscope or indirect lenses with biomicroscopy. Current clinical measurements to evaluate the anterior chamber angle may be affected by the ectasia found in KC patients. Thus the biomicroscopic evaluation of the anterior chamber angle using the van Herrick’s technique may yield an unreliable grade assessment in KC patients due to corneal ectasia. In addition, gonioscopy may be challenging and potentially traumatic to the fragile KC corneal surface. Vigorous eye rubbing is associated with KC [7–9] and this could potentially be a risky activity in eyes with narrow angles. The possibility for angle closure as a result of excessive eye rubbing thereby compressing the anterior chamber has been previously reported [10] and is most likely to happen in individuals with shallow angles. Recently it was established in vivo and histopathologically that the cornea peripheral to Fleischer ring is also affected by KC [11,12]. This research has, as a consequence, suggested that KC is a pancorneal pathology and not a disease restricted to the region of
http://dx.doi.org/10.1016/j.clae.2015.03.004 1367-0484/© 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
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Table 1 Demographic data over the study group. KC—keratoconus, SD—standard deviation, D—diopters. Peripheral corneal thickness measured in the 7–10 mm range.
Number of subjects Age (mean, years ± 1SD) Spherical equivalent (D) Visual acuity (log MAR) Minimal corneal thickness Visante (m ± 1SD) Minimal corneal thickness Orbscan (m ± 1SD) Minimum peripheral corneal thickness Visante (m ± 1SD)
KC Patients
Controls
26 (48 eyes) 38.7 ± 13.2 −8.80 0.33 427.79 ± 66.75
26 (52 eyes) 36.9 ± 13.8 −2.90 0.03 524.38 ± 30.58
415.66 ± 77.01
534.58 ± 49.24
505.58 ± 62.90
565.08 ± 36.40
the cone itself. It follows that peripheral structural alterations and changes in the corneal curvature may modify its relative relationship to the uvea. The corneal ectasia, as one would expect and as is well documented [13–15] will demonstrate an anterior chamber depth that increases with KC. However, this finding does not describe the changes that may occur in the peripheral regions of the cornea in KC. The data from Emre et al. [16] suggests that the anterior chamber angle may become narrower with increasing degree of KC. Based on the recent histopathological and reported anterior chamber angle findings, this study intended to explore potential alteration in the angle formed between the peripheral cornea and the uvea in patients with KC. 2. Methods 2.1. Subjects Fifty-two subjects, 26 KC subjects with a mean age of 38.7 years (±13.2) and 26 control subjects, with a mean age of 36.9 years (±13.8) were recruited for this study from the University Eye Institute, University of Houston College of Optometry, and Houston, Texas, USA. For demographic details see Table 1. This study was part of a study focused to detail characteristics of KC [12].
with the Orbscan topographer [20]. Biomicroscopy was performed using a Haag Streit (BQ900) biomicroscope and the same investigator judged all subjects. The KC grading and distribution of clinical findings can be seen in Table 2. All contact lens wearers, except scleral lens wearers, were included in both groups since this was assumed not to affect the anterior chamber angle.
2.3. Instrumentation and angle measurements The OrbscanTM II (at the time of purchase distributed by Bausch & Lomb Surgical, Orbtek Inc, Salt Lake City, Utah, USA) is a scanning optical slit topography imaging system that uses slit-beam images (entire corneal surface, 11 mm) to derive a three-dimensional anterior segment topography. The device is said to require clear reflections from epithelial and endothelial corneal surfaces and homogeneous composition of the optical media to obtain precise measurements [21,22]. The system measures over 9000 data points using 20 slits from the temporal and nasal position. The instrument provides information about the cornea, iris, and lens. Also incorporated in the Orbscan is a corneal angle estimate tool. This tool has been found to be capable of detecting significant differences in the numeric gonioscopy measurements according to Shaffers classification [23]. The VisanteTM OCT (Carl Zeiss Meditec, Inc, Dublin, CA, USA) is an anterior segment optical coherence tomography (ASOCT) that obtains high-resolution, real-time, cross-sectional images of the cornea and anterior chamber [24–26]. The axial and transverse resolution is 18 and 60 m, respectively, which use an infrared light source (1310 nm) to produce the cross-sectional images. It is also equipped with an angular calliper, which is useful in estimating the anterior chamber angle. With the Orbscan the angles between the cornea and the iris along the 0◦ and 180◦ axis (nasal and temporal) were estimated. This was done by the using the corneal angle estimation tool with which the clinician subjectively identifies the apex of the anterior chamber angle and aligns a line tangential to the posterior surface of the cornea and the anterior surface of the iris. Using the Visante OCT the anterior chamber angle is calculated objectively using the angle calliper tool and displayed on the screen. As with the Orbscan, only the angles along the 0 and 180 meridians were assessed.
2.2. Inclusion To be included, a KC subject must manifest one or more of the following clinical signs: posterior stress lines (Vogt striae), Fleischer ring, external sign (Munson sign) together with a topography positive for KC (central corneal power superior to 48.7D, and an inferior superior asymmetry above 1.9 [17–19]). Exclusion criteria included: any previous ocular surgery, the use of any systemic or ocular medications and any chronic disorder that can affect the eye, currently being pregnant or a nursing mother, and participating in an ophthalmologic drug or device research study within 30 days prior to entering the present study. Biomicroscopic examination and topographic measurements were used to confirm or deny the presence of KC. The degree of KC was graded based on the CLEK grading scale using the greatest corneal curvature as determined
2.4. Statistical analysis Only the nasal and temporal angles from both instruments were used for comparison. All statistics were performed using InStatTM (GraphPad) and OriginTM (Origin Lab) statistical software. The anterior chamber angle measurements were analysed by use One-Way ANOVA with post hoc tests. A regression analyze (linear correlation) was used to evaluate the relation between angles from the different techniques. Bland and Altman [27] plots were used for assessment of the level of agreement. This research followed the tenants of the Declaration of Helsinki, was in accord with the Health Insurance Portability and Accountability Act of 1996, and was approved by the Committee for the
Table 2 KC grading and distribution of clinical findings. K-value—keratometry value, D—dioptres. Eye
Sim K-value (Orbscan) Cyl (D)
OD −5.27 OS −4.77 Biomicroscopic findings Prominant nerve fibres OD 20 OS 19
CLEK ◦
Axis ( )
Max K (D)
Min K (D)
Category 1/2/3
129.25 60.65
52.58 51.18
47.28 49.80
2/7/15 4/12/9
Fleischer ring 7 8
Vogt striae 23 24
Munson sign 3 0
Anterior corneal scarring 5 4
Posterior corneal scarring 9 12
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Table 3 Anterior chamber angle measured with Orbscan and Visante OCT. The table shows mean anterior angle (in degrees) and one standard deviation. KC—keratoconus patients, Control—control subjects, Diff—difference. Orbscan
Temporal Nasal
Visante
KC
Control
Diff
39.43 ± 4.30 44.48 ± 4.65
38.98 ± 3.43 43.32 ± 3.43
Table 4 Statistical comparison and correlation (R2 ) of anterior chamber angles with Orbscan and Visante OCT in control subjects and KC subjects. KC—keratoconus patients, Control—control subjects. p-Value
Correlation (R2 )
7.25
<0.001
0.0113
13.57
<0.001
0.0375
3.24
>0.05
0.0298
9.27
<0.001
0.0762
Mean difference Orbscan vs Visante Temporal Control Orbscan vs Temporal Control Visante Nasal Control Orbscan vs Nasal Control Visante Temporal KC Orbscan vs Temporal KC Visante Nasal KC Orbscan vs Nasal KC Visante Controls vs KC Temporal Control Orbscan vs Temporal KC Orbscan Nasal Control Orbscan vs Nasal KC Orbscan Temporal Control Visante vs Temporal KC Visante Nasal Control Visante vs Nasal KC Visante
−0.82
>0.05
−1.39
>0.05
−4.83
>0.05
−5.69
>0.05
Protection of Human Subjects of the University of Houston. Written informed consent was obtained from all KC and control subjects. 3. Results Mean values (±1SD) of the temporal and nasal anterior chamber angle measured with the Orbscan and Visante OCT for both KC subjects and controls can be seen in Table 3. The results showed that there was no statistical difference between nasal and temporal anterior chamber angles when comparing controls and KC subjects with either of the two instruments. However, the Visante OCT always gave a narrower estimate of the anterior chamber angle (Table 4). When comparing the two instruments, a statistically significant difference was found in the anterior chamber angle of controls when measured with the Orbscan and Visante for both nasal and temporal angles. This statistical difference was observed in only the nasal angle of KC subjects (Table 4). The average difference between the two instruments was 12.01◦ (±9.28) and 6.46◦ (±9.23) for the nasal and temporal anterior chamber angles, respectively, in the control subjects, and 9.57◦ (±12.09) and 1.51◦ (±11.85), respectively, for the nasal and temporal angles in the KC subjects. There was no correlation between the two instruments (Table 4). No correlation could be found between the anterior chamber angle and other parameters measured in KC patients presented in Tables 1 and 2, i.e., minimum central and peripheral corneal thickness, Sim K-value and CLEK category. In Fig. 1a–d Bland and Altman plots compare the measurement of temporal and nasal angles for the two techniques in both control and KC subjects. The values obtained were spread across the plots and there is no obvious relationship between values and the
0.45 1.16
KC
Control
Diff
37.92 ± 11.54 36.74 ± 10.35
32.52 ± 9.34 31.31 ± 9.42
5.40 5.43
differences, however, there is a trend indicating that Orbscan overestimates small angles whereas Visante OCT underestimates wide angles. 4. Discussion Keratoconus is defined as a bilateral, non-inflammatory progressive ectatic corneal disease characterized by localized apical protrusion and thinning, irregular astigmatism, and scarring in the cornea [28–31]. With KC patients angle estimates using the traditional von Herick’s technique may not provide accurate assessment and gonioscopy may provoke undesired corneal trauma and discomfort. The latter is especially the case with the KC diseased corneal structure where the epithelial adhesion apparatus is greatly affected [11]. An evaluation of the anterior chamber angle in KC subjects is most frequently screened during biomicroscopy using van Herick’s technique. However, this technique may induce errors since the anterior chamber depth may be influenced by localized apical protrusion and thinning which would increase the measured depth thus giving a false impression of the angle [13–15]. In cases of suspected narrow angles, the measurement can be more accurately determined using gonioscopy, which is a more invasive procedure for the ocular surface. Although invasive, clinicians may prefer gonioscopy due to the ability to indent the tissue in order to differentiate angle closure due to apposition or synechiae. Two other alternatives for angle assessment are utilized in the present study; Orbscan Topographer and OCT, both of which do not have the above mentioned limitations. The average anterior chamber angles recorded in this study with Orbscan and Visante, for both KC and controls are similar (about 37.0◦ ± 7) to that found in control subjects in previously published studies [16,32,33]. We have to conclude that the angular relationship between the outer coat and uvea has not changed in KC. In addition, no correlation could be found between the depth of the anterior chamber angle and the degree of KC. This is, however, not in agreement with the findings of Emre et al. [16] who found that the anterior chamber angle was decreased in patients with severe KC. This may be partially explained by the different technologies used to assess the anterior chamber angle. Emre et al. [16] used the Pentacam topographer (Scheimpflug imaging system) to measure various anterior chamber biometrics. These differences in instrumentation were evident even within this current study when comparing the Visante OCT to the Orbscan topographer. The present data used the same way of grading the degree of KC as Emre and coworkers [16] (i.e., k-values), however, the larger number of KC eyes included by Emre et al. may also explain the narrower anterior chamber angle in severe cases of KC found in their study as compared to the present data. It was recently demonstrated that the peripheral cornea was affected by this disease [11,12]. However, both these studies found the peripheral cornea was affected to a lesser degree than the tissue within the Fleischer ring; presumably these peripheral changes were not sufficient to alter the geometry of the angle. Orbscan devices have also previously been shown to provide accurate and reproducible results of ocular structures when compared to ultrasound, optical pachymetry, Scheimpflug imaging and the IOLMaster [22,34–39]. Measurements of anterior
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Orbscan-Visante (deg)
a
Temporal Angle: Orbscan vs. Visante in Control Subjects 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,3372x + 54,267 R² = 0,5922
15
20
25
30
35
40
45
50
55
(Orbscan+Visante)/2 (deg)
Nasal Angle: Orbscan vs. Visante in Control Subjects
Orbscan-Visante (deg)
b
50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,2358x + 58,125 R² = 0,5323
15
20
25
30
35
40
45
50
55
50
55
(Orbscan+Visante)/2 (deg)
Orbscan-Visante (deg)
c
Temporal Angle: Orbscan vs. Visante in KC Subjects 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,4083x + 55,978 R² = 0,5749
15
20
25
30
35
40
45
(Orbscan+Visante)/2 (deg) Fig. 1. (a–d) Bland and Altman plots comparing the level of agreement between the two instruments and in control subjects (plots (a) and (b), temporal and nasal angles, respectively) and KC subjects (plots (c) and (d), temporal and nasal angles, respectively). Solid lines represent the mean difference and dotted lines represent ±2 SD. There is good spread of values across the plots, and there is no obvious relationship between the mean values and differences.
chamber angles with the Orbscan have been found not to be affected by refractive status [40], which is in line with the results of this study since all estimations of anterior chamber angle were possible in all subjects with KC. Applications of anterior segment OCT (ASOCT), e.g., Visante OCT, have been well described in the field of glaucoma/anterior segment surgery [41–45] as well as in corneal surgery where it is useful for determining both diagnostic [46,47] and therapeutic procedures [25,48,49]. For corneal central thickness and anterior chamber depth there are indications that it is repeatable but not interchangeable with other techniques [50].
Aurich et al. [51] has shown that anterior segment OCT is a reliable method to assess important parameters for diagnosis and therapeutic outcomes of patients with keratoconus. The use of OCT techniques for corneal biometric evaluation has also become more common and is likely to be used alongside or substituted for more traditional measurements based on, for example, ultrasound and Orbscan techniques. The Orbscan requires a clear reflection from the epithelial and endothelial surfaces as well as a homogeneous composition of the optical media to obtain precise measurements [21,32]. No difficulty was observed making the measurements in the current study with the Orbscan in KC subjects, which is in line
M. Nilsson et al. / Contact Lens & Anterior Eye 38 (2015) 277–282
with the findings of Aurich et al. [51]. However, with the Orbscan corneal angle estimation tool, the clinician subjectively identifies the apex of the anterior chamber angle and aligns a line tangential to the posterior surface of the cornea and the anterior surface of the iris. To overcome any inter-observer variations, the same experienced observer for all subjects included in this study performed this determination. However, this subjective definition of the apex and the tangential lines may remain as a possible cause for some of the variations in the results and thus make it difficult to compare with the automatic measurements made by the Visante OCT. A comparison of the Orbscan and Visante OCT anterior chamber angles showed no statistical difference in either controls or KC subjects. In addition, there was no correlation between the two instruments. Looking at the Bland Altman plots it can be observed that even though the mean difference could be considered as acceptable in all situations tested, the spread of these differences and trendlines show that the Orbscan yielded higher values for narrow angles while the opposite occurs for larger angles, with a difference in some cases exceeding 30◦ between the two methods. This trend occurred in a similar fashion when measuring both KC and control eyes, and both temporal and nasal angles, as observed from the slope of the trendlines obtained in Fig. 1a–d. The differences between the two instruments might not be clinically significant, but the lack of correlation between the two instruments and the spread of difference values across the Bland and Altman plots, imply that the two techniques should not be interchanged. Despite KC being a progressive, pancorneal, ectatic disease characterized by corneal thinning and apical protrusion with consequent chamber distortion, we conclude that these changes the temporal and nasal angular anatomy of the anterior chamber do not lead to a difference between the anterior chamber angles in normals and KC patients. This conclusion did not vary with the technology utilized. Acknowledgements This manuscript was produced without compensation from government or private enterprise. TERTC has over the last year, received support for studies sponsored by: Alcon Foundation, Bausch + Lomb, Contamac, CooperVision, and the NEI T35 EY07088 grant. References [1] Lowe RF. Time-amplitude ultrasonography for ocular biometry. Am J Ophthalmol 1968;66:913–8. [2] Congdon NG, Youlin Q, Quigley H, Hung PT, Wang TH, Ho TC, et al. Biometry and primary angle-closure glaucoma among Chinese, white, and black populations. Ophthalmology 1997;104:1489–95. [3] Barrett BT, McGraw PV, Murray LA, Murgatroyd P. Anterior chamber depth measurement in clinical practice. Optom Vis Sci 1996;73:482–6. [4] Van Herick W, Shaffer RN, Schwartz A. Estimation of width of angle of anterior chamber. Incidence and significance of the narrow angle. Am J Ophthalmol 1969;68:626–9. [5] Eandi CM, Del Priore LV, Bertelli E, Ober MD, Yannuzzi LA. Central serous chorioretinopathy in patients with keratoconus. Retina 2008;28:94–6. [6] Cohen EJ, Myers JS. Keratoconus and normal-tension glaucoma: a study of the possible association with abnormal biomechanical properties as measured by corneal hysteresis. Cornea 2010;29:955–70. [7] Karseras AG, Ruben M. Aetiology of keratoconus. Br J Ophthalmol 1976;60:522–5. [8] McMonnies CW. Abnormal rubbing and keratectasia. Eye Contact Lens 2007;33:265–71. [9] McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea 2009;28:607–15. [10] Hussin HM, Majid MA. Angle closure glaucoma and lens subluxation secondary to eye rubbing in a patient with mycosis fungoides. Ann Ophthalmol 2009;41:109–11. [11] Mathew J, Goosey J, Bergmanson J. Quantified Histopathology of the Keratoconic Cornea. Optom Vis Sci 2011;88(8):988–97. [12] Brautaset RL, Nilsson M, Leach N, Tukler JH, Miller WL, Bergmanson J. Central and peripheral corneal thinning in keratoconus. Cornea 2013;32:257–61.
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Evaluation of the anterior chamber angle in keratoconus and normal subjects ˜ c , J.P.G. Bergmanson b , R.L. Brautaset a,∗ M. Nilsson a , W. Miller b , A. Cervino a b c
Unit of Optometry, Department of Clinical Neuroscience, Karolinska Institutet, Box 8056, 104 20 Stockholm, Sweden TERTC, University of Houston, College of Optometry, Houston, TX 77204-2020, USA University of Valencia, Valencia, Spain
a r t i c l e
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Article history: Received 10 July 2014 Received in revised form 5 March 2015 Accepted 6 March 2015 Keywords: Keratoconus Anterior chamber angle VisanteTM OCT OrbscanTM II Apical protrusion
a b s t r a c t Purpose: To evaluate the anterior chamber angle in keratoconus eyes by use of the VisanteTM OCT and OrbscanTM II. Methods: Anterior chamber angle was measured with the VisanteTM OCT and OrbscanTM II in 52 subjects, 26 KC subjects and 26 age and control subjects. Results: When comparing the nasal and temporal angles obtained with the two techniques no correlation was found (R2 always below 0.01) in either the control subjects or in the KC subjects. Despite this, there was an overall statistically significant difference in mean anterior chamber angles (p < 0.001) between VisanteTM OCT and OrbscanTM II. There was no statistical difference (p > 0.05) between nasal and temporal anterior chamber angles when comparing controls and KC subjects with either of the two instruments. In general, the VisanteTM OCT gave a smaller estimate of the anterior chamber angle. Conclusion: The values from the VisanteTM OCT and OrbscanTM II cannot be interchanged since the difference in measurement of the anterior chamber angle was significantly different between the two instruments. © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Little is known about the relationship between anterior chamber angles in normal patients and those patients who have keratoconus. The anterior chamber angle evaluation is an important diagnostic step to identify those patients with shallow angles who are at risk for angle-closure glaucoma [1,2]. It is also helpful to identify those patients prone to developing angle-closure as a result of pupillary dilation [3]. In assessing the chamber angle, the depth of the anterior chamber is measured as the distance from the posterior corneal surface to the anterior surface of the crystalline lens—this measurement is often referred to as the anterior chamber depth. However, clinically, it is the iridio-corneal angle that is estimated and this measurement is commonly graded using van Herrick’s technique or by performing gonioscopy [4]. The accurate assessment of the iridio-corneal angle measurement is intended to determine who is at risk for angle closure during dilation, an important step in performing a comprehensive assessment of the retina, especially in eyes that are, more prone to peripheral retinal and posterior segment disease such as highly
∗ Corresponding author. Tel.: +46 0 8 1232 3840; fax: +46 0 8 672 3846. E-mail address: [email protected] (R.L. Brautaset).
myopic patients. It has been reported that posterior segment disease is as common in patients with keratoconus (KC) as in the normal population [5]. Patients with KC may in some instances exhibit a greater level of posterior segment disease. A report by Cohen and Myers [6] found that patients with KC are more prone to develop glaucomatous optic neuropathy. A dilated pupil is necessary in order to fully binocularly evaluate the retina and optic nerve of keratoconic patients using a binocular indirect ophthalmoscope or indirect lenses with biomicroscopy. Current clinical measurements to evaluate the anterior chamber angle may be affected by the ectasia found in KC patients. Thus the biomicroscopic evaluation of the anterior chamber angle using the van Herrick’s technique may yield an unreliable grade assessment in KC patients due to corneal ectasia. In addition, gonioscopy may be challenging and potentially traumatic to the fragile KC corneal surface. Vigorous eye rubbing is associated with KC [7–9] and this could potentially be a risky activity in eyes with narrow angles. The possibility for angle closure as a result of excessive eye rubbing thereby compressing the anterior chamber has been previously reported [10] and is most likely to happen in individuals with shallow angles. Recently it was established in vivo and histopathologically that the cornea peripheral to Fleischer ring is also affected by KC [11,12]. This research has, as a consequence, suggested that KC is a pancorneal pathology and not a disease restricted to the region of
http://dx.doi.org/10.1016/j.clae.2015.03.004 1367-0484/© 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
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Table 1 Demographic data over the study group. KC—keratoconus, SD—standard deviation, D—diopters. Peripheral corneal thickness measured in the 7–10 mm range.
Number of subjects Age (mean, years ± 1SD) Spherical equivalent (D) Visual acuity (log MAR) Minimal corneal thickness Visante (m ± 1SD) Minimal corneal thickness Orbscan (m ± 1SD) Minimum peripheral corneal thickness Visante (m ± 1SD)
KC Patients
Controls
26 (48 eyes) 38.7 ± 13.2 −8.80 0.33 427.79 ± 66.75
26 (52 eyes) 36.9 ± 13.8 −2.90 0.03 524.38 ± 30.58
415.66 ± 77.01
534.58 ± 49.24
505.58 ± 62.90
565.08 ± 36.40
the cone itself. It follows that peripheral structural alterations and changes in the corneal curvature may modify its relative relationship to the uvea. The corneal ectasia, as one would expect and as is well documented [13–15] will demonstrate an anterior chamber depth that increases with KC. However, this finding does not describe the changes that may occur in the peripheral regions of the cornea in KC. The data from Emre et al. [16] suggests that the anterior chamber angle may become narrower with increasing degree of KC. Based on the recent histopathological and reported anterior chamber angle findings, this study intended to explore potential alteration in the angle formed between the peripheral cornea and the uvea in patients with KC. 2. Methods 2.1. Subjects Fifty-two subjects, 26 KC subjects with a mean age of 38.7 years (±13.2) and 26 control subjects, with a mean age of 36.9 years (±13.8) were recruited for this study from the University Eye Institute, University of Houston College of Optometry, and Houston, Texas, USA. For demographic details see Table 1. This study was part of a study focused to detail characteristics of KC [12].
with the Orbscan topographer [20]. Biomicroscopy was performed using a Haag Streit (BQ900) biomicroscope and the same investigator judged all subjects. The KC grading and distribution of clinical findings can be seen in Table 2. All contact lens wearers, except scleral lens wearers, were included in both groups since this was assumed not to affect the anterior chamber angle.
2.3. Instrumentation and angle measurements The OrbscanTM II (at the time of purchase distributed by Bausch & Lomb Surgical, Orbtek Inc, Salt Lake City, Utah, USA) is a scanning optical slit topography imaging system that uses slit-beam images (entire corneal surface, 11 mm) to derive a three-dimensional anterior segment topography. The device is said to require clear reflections from epithelial and endothelial corneal surfaces and homogeneous composition of the optical media to obtain precise measurements [21,22]. The system measures over 9000 data points using 20 slits from the temporal and nasal position. The instrument provides information about the cornea, iris, and lens. Also incorporated in the Orbscan is a corneal angle estimate tool. This tool has been found to be capable of detecting significant differences in the numeric gonioscopy measurements according to Shaffers classification [23]. The VisanteTM OCT (Carl Zeiss Meditec, Inc, Dublin, CA, USA) is an anterior segment optical coherence tomography (ASOCT) that obtains high-resolution, real-time, cross-sectional images of the cornea and anterior chamber [24–26]. The axial and transverse resolution is 18 and 60 m, respectively, which use an infrared light source (1310 nm) to produce the cross-sectional images. It is also equipped with an angular calliper, which is useful in estimating the anterior chamber angle. With the Orbscan the angles between the cornea and the iris along the 0◦ and 180◦ axis (nasal and temporal) were estimated. This was done by the using the corneal angle estimation tool with which the clinician subjectively identifies the apex of the anterior chamber angle and aligns a line tangential to the posterior surface of the cornea and the anterior surface of the iris. Using the Visante OCT the anterior chamber angle is calculated objectively using the angle calliper tool and displayed on the screen. As with the Orbscan, only the angles along the 0 and 180 meridians were assessed.
2.2. Inclusion To be included, a KC subject must manifest one or more of the following clinical signs: posterior stress lines (Vogt striae), Fleischer ring, external sign (Munson sign) together with a topography positive for KC (central corneal power superior to 48.7D, and an inferior superior asymmetry above 1.9 [17–19]). Exclusion criteria included: any previous ocular surgery, the use of any systemic or ocular medications and any chronic disorder that can affect the eye, currently being pregnant or a nursing mother, and participating in an ophthalmologic drug or device research study within 30 days prior to entering the present study. Biomicroscopic examination and topographic measurements were used to confirm or deny the presence of KC. The degree of KC was graded based on the CLEK grading scale using the greatest corneal curvature as determined
2.4. Statistical analysis Only the nasal and temporal angles from both instruments were used for comparison. All statistics were performed using InStatTM (GraphPad) and OriginTM (Origin Lab) statistical software. The anterior chamber angle measurements were analysed by use One-Way ANOVA with post hoc tests. A regression analyze (linear correlation) was used to evaluate the relation between angles from the different techniques. Bland and Altman [27] plots were used for assessment of the level of agreement. This research followed the tenants of the Declaration of Helsinki, was in accord with the Health Insurance Portability and Accountability Act of 1996, and was approved by the Committee for the
Table 2 KC grading and distribution of clinical findings. K-value—keratometry value, D—dioptres. Eye
Sim K-value (Orbscan) Cyl (D)
OD −5.27 OS −4.77 Biomicroscopic findings Prominant nerve fibres OD 20 OS 19
CLEK ◦
Axis ( )
Max K (D)
Min K (D)
Category 1/2/3
129.25 60.65
52.58 51.18
47.28 49.80
2/7/15 4/12/9
Fleischer ring 7 8
Vogt striae 23 24
Munson sign 3 0
Anterior corneal scarring 5 4
Posterior corneal scarring 9 12
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Table 3 Anterior chamber angle measured with Orbscan and Visante OCT. The table shows mean anterior angle (in degrees) and one standard deviation. KC—keratoconus patients, Control—control subjects, Diff—difference. Orbscan
Temporal Nasal
Visante
KC
Control
Diff
39.43 ± 4.30 44.48 ± 4.65
38.98 ± 3.43 43.32 ± 3.43
Table 4 Statistical comparison and correlation (R2 ) of anterior chamber angles with Orbscan and Visante OCT in control subjects and KC subjects. KC—keratoconus patients, Control—control subjects. p-Value
Correlation (R2 )
7.25
<0.001
0.0113
13.57
<0.001
0.0375
3.24
>0.05
0.0298
9.27
<0.001
0.0762
Mean difference Orbscan vs Visante Temporal Control Orbscan vs Temporal Control Visante Nasal Control Orbscan vs Nasal Control Visante Temporal KC Orbscan vs Temporal KC Visante Nasal KC Orbscan vs Nasal KC Visante Controls vs KC Temporal Control Orbscan vs Temporal KC Orbscan Nasal Control Orbscan vs Nasal KC Orbscan Temporal Control Visante vs Temporal KC Visante Nasal Control Visante vs Nasal KC Visante
−0.82
>0.05
−1.39
>0.05
−4.83
>0.05
−5.69
>0.05
Protection of Human Subjects of the University of Houston. Written informed consent was obtained from all KC and control subjects. 3. Results Mean values (±1SD) of the temporal and nasal anterior chamber angle measured with the Orbscan and Visante OCT for both KC subjects and controls can be seen in Table 3. The results showed that there was no statistical difference between nasal and temporal anterior chamber angles when comparing controls and KC subjects with either of the two instruments. However, the Visante OCT always gave a narrower estimate of the anterior chamber angle (Table 4). When comparing the two instruments, a statistically significant difference was found in the anterior chamber angle of controls when measured with the Orbscan and Visante for both nasal and temporal angles. This statistical difference was observed in only the nasal angle of KC subjects (Table 4). The average difference between the two instruments was 12.01◦ (±9.28) and 6.46◦ (±9.23) for the nasal and temporal anterior chamber angles, respectively, in the control subjects, and 9.57◦ (±12.09) and 1.51◦ (±11.85), respectively, for the nasal and temporal angles in the KC subjects. There was no correlation between the two instruments (Table 4). No correlation could be found between the anterior chamber angle and other parameters measured in KC patients presented in Tables 1 and 2, i.e., minimum central and peripheral corneal thickness, Sim K-value and CLEK category. In Fig. 1a–d Bland and Altman plots compare the measurement of temporal and nasal angles for the two techniques in both control and KC subjects. The values obtained were spread across the plots and there is no obvious relationship between values and the
0.45 1.16
KC
Control
Diff
37.92 ± 11.54 36.74 ± 10.35
32.52 ± 9.34 31.31 ± 9.42
5.40 5.43
differences, however, there is a trend indicating that Orbscan overestimates small angles whereas Visante OCT underestimates wide angles. 4. Discussion Keratoconus is defined as a bilateral, non-inflammatory progressive ectatic corneal disease characterized by localized apical protrusion and thinning, irregular astigmatism, and scarring in the cornea [28–31]. With KC patients angle estimates using the traditional von Herick’s technique may not provide accurate assessment and gonioscopy may provoke undesired corneal trauma and discomfort. The latter is especially the case with the KC diseased corneal structure where the epithelial adhesion apparatus is greatly affected [11]. An evaluation of the anterior chamber angle in KC subjects is most frequently screened during biomicroscopy using van Herick’s technique. However, this technique may induce errors since the anterior chamber depth may be influenced by localized apical protrusion and thinning which would increase the measured depth thus giving a false impression of the angle [13–15]. In cases of suspected narrow angles, the measurement can be more accurately determined using gonioscopy, which is a more invasive procedure for the ocular surface. Although invasive, clinicians may prefer gonioscopy due to the ability to indent the tissue in order to differentiate angle closure due to apposition or synechiae. Two other alternatives for angle assessment are utilized in the present study; Orbscan Topographer and OCT, both of which do not have the above mentioned limitations. The average anterior chamber angles recorded in this study with Orbscan and Visante, for both KC and controls are similar (about 37.0◦ ± 7) to that found in control subjects in previously published studies [16,32,33]. We have to conclude that the angular relationship between the outer coat and uvea has not changed in KC. In addition, no correlation could be found between the depth of the anterior chamber angle and the degree of KC. This is, however, not in agreement with the findings of Emre et al. [16] who found that the anterior chamber angle was decreased in patients with severe KC. This may be partially explained by the different technologies used to assess the anterior chamber angle. Emre et al. [16] used the Pentacam topographer (Scheimpflug imaging system) to measure various anterior chamber biometrics. These differences in instrumentation were evident even within this current study when comparing the Visante OCT to the Orbscan topographer. The present data used the same way of grading the degree of KC as Emre and coworkers [16] (i.e., k-values), however, the larger number of KC eyes included by Emre et al. may also explain the narrower anterior chamber angle in severe cases of KC found in their study as compared to the present data. It was recently demonstrated that the peripheral cornea was affected by this disease [11,12]. However, both these studies found the peripheral cornea was affected to a lesser degree than the tissue within the Fleischer ring; presumably these peripheral changes were not sufficient to alter the geometry of the angle. Orbscan devices have also previously been shown to provide accurate and reproducible results of ocular structures when compared to ultrasound, optical pachymetry, Scheimpflug imaging and the IOLMaster [22,34–39]. Measurements of anterior
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Orbscan-Visante (deg)
a
Temporal Angle: Orbscan vs. Visante in Control Subjects 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,3372x + 54,267 R² = 0,5922
15
20
25
30
35
40
45
50
55
(Orbscan+Visante)/2 (deg)
Nasal Angle: Orbscan vs. Visante in Control Subjects
Orbscan-Visante (deg)
b
50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,2358x + 58,125 R² = 0,5323
15
20
25
30
35
40
45
50
55
50
55
(Orbscan+Visante)/2 (deg)
Orbscan-Visante (deg)
c
Temporal Angle: Orbscan vs. Visante in KC Subjects 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25
y = -1,4083x + 55,978 R² = 0,5749
15
20
25
30
35
40
45
(Orbscan+Visante)/2 (deg) Fig. 1. (a–d) Bland and Altman plots comparing the level of agreement between the two instruments and in control subjects (plots (a) and (b), temporal and nasal angles, respectively) and KC subjects (plots (c) and (d), temporal and nasal angles, respectively). Solid lines represent the mean difference and dotted lines represent ±2 SD. There is good spread of values across the plots, and there is no obvious relationship between the mean values and differences.
chamber angles with the Orbscan have been found not to be affected by refractive status [40], which is in line with the results of this study since all estimations of anterior chamber angle were possible in all subjects with KC. Applications of anterior segment OCT (ASOCT), e.g., Visante OCT, have been well described in the field of glaucoma/anterior segment surgery [41–45] as well as in corneal surgery where it is useful for determining both diagnostic [46,47] and therapeutic procedures [25,48,49]. For corneal central thickness and anterior chamber depth there are indications that it is repeatable but not interchangeable with other techniques [50].
Aurich et al. [51] has shown that anterior segment OCT is a reliable method to assess important parameters for diagnosis and therapeutic outcomes of patients with keratoconus. The use of OCT techniques for corneal biometric evaluation has also become more common and is likely to be used alongside or substituted for more traditional measurements based on, for example, ultrasound and Orbscan techniques. The Orbscan requires a clear reflection from the epithelial and endothelial surfaces as well as a homogeneous composition of the optical media to obtain precise measurements [21,32]. No difficulty was observed making the measurements in the current study with the Orbscan in KC subjects, which is in line
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with the findings of Aurich et al. [51]. However, with the Orbscan corneal angle estimation tool, the clinician subjectively identifies the apex of the anterior chamber angle and aligns a line tangential to the posterior surface of the cornea and the anterior surface of the iris. To overcome any inter-observer variations, the same experienced observer for all subjects included in this study performed this determination. However, this subjective definition of the apex and the tangential lines may remain as a possible cause for some of the variations in the results and thus make it difficult to compare with the automatic measurements made by the Visante OCT. A comparison of the Orbscan and Visante OCT anterior chamber angles showed no statistical difference in either controls or KC subjects. In addition, there was no correlation between the two instruments. Looking at the Bland Altman plots it can be observed that even though the mean difference could be considered as acceptable in all situations tested, the spread of these differences and trendlines show that the Orbscan yielded higher values for narrow angles while the opposite occurs for larger angles, with a difference in some cases exceeding 30◦ between the two methods. This trend occurred in a similar fashion when measuring both KC and control eyes, and both temporal and nasal angles, as observed from the slope of the trendlines obtained in Fig. 1a–d. The differences between the two instruments might not be clinically significant, but the lack of correlation between the two instruments and the spread of difference values across the Bland and Altman plots, imply that the two techniques should not be interchanged. Despite KC being a progressive, pancorneal, ectatic disease characterized by corneal thinning and apical protrusion with consequent chamber distortion, we conclude that these changes the temporal and nasal angular anatomy of the anterior chamber do not lead to a difference between the anterior chamber angles in normals and KC patients. This conclusion did not vary with the technology utilized. Acknowledgements This manuscript was produced without compensation from government or private enterprise. TERTC has over the last year, received support for studies sponsored by: Alcon Foundation, Bausch + Lomb, Contamac, CooperVision, and the NEI T35 EY07088 grant. References [1] Lowe RF. Time-amplitude ultrasonography for ocular biometry. Am J Ophthalmol 1968;66:913–8. [2] Congdon NG, Youlin Q, Quigley H, Hung PT, Wang TH, Ho TC, et al. Biometry and primary angle-closure glaucoma among Chinese, white, and black populations. Ophthalmology 1997;104:1489–95. [3] Barrett BT, McGraw PV, Murray LA, Murgatroyd P. Anterior chamber depth measurement in clinical practice. Optom Vis Sci 1996;73:482–6. [4] Van Herick W, Shaffer RN, Schwartz A. Estimation of width of angle of anterior chamber. Incidence and significance of the narrow angle. Am J Ophthalmol 1969;68:626–9. [5] Eandi CM, Del Priore LV, Bertelli E, Ober MD, Yannuzzi LA. Central serous chorioretinopathy in patients with keratoconus. Retina 2008;28:94–6. [6] Cohen EJ, Myers JS. Keratoconus and normal-tension glaucoma: a study of the possible association with abnormal biomechanical properties as measured by corneal hysteresis. Cornea 2010;29:955–70. [7] Karseras AG, Ruben M. Aetiology of keratoconus. Br J Ophthalmol 1976;60:522–5. [8] McMonnies CW. Abnormal rubbing and keratectasia. Eye Contact Lens 2007;33:265–71. [9] McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea 2009;28:607–15. [10] Hussin HM, Majid MA. Angle closure glaucoma and lens subluxation secondary to eye rubbing in a patient with mycosis fungoides. Ann Ophthalmol 2009;41:109–11. [11] Mathew J, Goosey J, Bergmanson J. Quantified Histopathology of the Keratoconic Cornea. Optom Vis Sci 2011;88(8):988–97. [12] Brautaset RL, Nilsson M, Leach N, Tukler JH, Miller WL, Bergmanson J. Central and peripheral corneal thinning in keratoconus. Cornea 2013;32:257–61.
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