ORIGINAL STUDY
The Impact of Lens Vault on Visual Acuity and Refractive Error: Implications for Management of Primary Angle-closure Glaucoma Monisha E. Nongpiur, MD,*w Shweta Singhal, PhD,* Stephen Stewart, MA, MBBS,z Hla M. Htoon, PhD,*w Arun K. Narayanaswamy, DO, DNB, MMED,*w Tien Y. Wong, FRCS, PhD,*wy Shamira A. Perera, BSc (Hons), FRCOphth,* and Tin Aung, FRCS, PhD*wy
Purpose: To investigate the relationship between lens vault (LV), visual acuity (VA), and refraction. Methods: This was a cross-sectional study of 2047 subjects aged 50 years and older recruited from a community polyclinic. Anterior segment optical coherence tomography was performed, and customized software was used to measure LV. VA was measured using a logarithm of minimum angle of resolution chart (logMAR chart; Lighthouse Inc.), and was classified as normal (logMAR < 0.3), mild impairment (0.3 < logMAR < 0.6), and moderate/severe impairment (logMAR > 0.6). Refraction was measured with an autorefractor machine and spherical equivalent was defined as sphere plus half cylinder. Angle closure was defined as posterior trabecular meshwork not visible for Z2 quadrants on nonindentation gonioscopy. Results: Complete data were available for 1372 subjects including 295 (21.5%) with angle closure. Angle-closure subjects were significantly older (P < 0.001), with shorter axial length (P < 0.001), shallower anterior chamber depth (P < 0.001), and greater LV (P < 0.001). There was no significant difference in VA (P = 0.12) compared with those without angle closure. After adjusting for age, sex, axial length, anterior chamber depth, and spherical equivalent, there was no significant association between LV and VA (P = 0.35) or between LV and spherical equivalent (P = 0.06). Conclusions: The magnitude of LV was not associated with VA or spherical equivalent. Lens extraction may be a consideration in eyes with angle closure with large LV in the absence of visually significant cataract. Key Words: lens vault, visual acuity, angle closure
(J Glaucoma 2016;25:e236–e240)
T
he lens plays an important role in the pathogenesis of primary angle-closure glaucoma (PACG).1–3 In addition to the thickness and position of the lens, another parameter, found to be associated with angle closure is the Received for publication July 1, 2014; accepted March 25, 2015. From the *Singapore National Eye Centre, Singapore Eye Research Institute; wDuke-NUS Graduate Medical School; yYong Loo Lin School of Medicine, National University of Singapore, Singapore; and zUniversity College London Medical School, London, UK. M.E.N. and S.S. are joint first authors. Supported by grants from National Medical Research Council, Singapore. Disclosure: The authors declare no conflict of interest. Reprints: Tin Aung, FRCS, PhD, Singapore National Eye Center, Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000264
lens vault (LV).4 The LV, imaged by anterior segment optical coherence tomography (ASOCT), is a surrogate measurement of the amount of lens that is located anterior to the plane of the anterior chamber angles. An increase in LV may worsen angle crowding in an already predisposed eye by instigating a more pronounced iris bowing through relative pupil block, and in more severe cases may also directly push the peripheral iris towards the angles.4 LV has been found to distinguish eyes with angle closure from those with open angles better than biometric parameters such as anterior chamber depth (ACD), axial length (AL), lens thickness (LT), and lens position.4 LV is the ASOCT risk factor for angle closure that is most analogous to the lens component. Although an increased LV may either represent an aged lens, an intumescent lens or subluxed lens, the targeted removal of this component converges to a lens extraction. With age, the compaction of crystallins during cataractogenesis may lead to an increase in refractive index and a yellowing of the lens itself. This is often accompanied by an increase in LT and a myopic shift related to the development of nuclear cataract.5 Studies have shown that for cases of visually significant cataract and PACG, cataract extraction results in deepening of the anterior chamber and widening of the angles, and in some cases, may lower intraocular pressure (IOP) and reduce the likelihood of progression.6,7 However, there is a lack of consensus on the role of lens extraction in eyes with PACG or primary angle closure with good visual acuity (VA). An ongoing multicentered randomized-controlled trial, the effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) is currently investigating whether early lens extraction in PACG improves patient-reported outcomes and costeffectiveness compared with standard care.8 The relationship of LV with VA or refractive error is not known, particularly in eyes with angle closure. Whereas good VA may naturally preclude cataract surgery, an increased LV may support the decision to proceed with cataract surgery even with a VA that was considered “normal” for surgical intervention. The aim of this study was to investigate the relationship between LV, VA, and refraction in subjects with angle closure.
METHODS Approval for the study was granted by the Singapore Eye Research Institute institutional review board. This study was conducted in accordance with the Declaration of
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J Glaucoma
Volume 25, Number 3, March 2016
Helsinki, and written informed consent was obtained from all subjects before enrollment. Subjects aged 50 years and older were recruited from a government-run polyclinic that provides primary health care services for residents living in the area around the clinic. Details of the study have been described previously.9 Recruited subjects did not have any ophthalmic complaints and individuals with a history of glaucoma, previous intraocular surgery, previous laser treatment, or penetrating eye injury were excluded. All subjects underwent a detailed eye examination that included an assessment of VA using a logarithm of minimum angle of resolution chart (logMAR chart; Lighthouse Inc., Long Island, NY), slit-lamp examination (model BQ 900; Haag-Streit, Bern, Switzerland), stereoscopic optic disc examination with a 78-D lens (Volk Optical Inc., Mentor, OH), and measurement of IOP with a Goldmann applanation tonometer (Haag-Streit, Koniz, Switzerland). AL and ACD were measured by IOLMaster (Carl Zeiss, Jena, Germany). Refraction was measured with an autorefractor machine (Topcon Auto K KR7100D; Topcon Corp., Tokyo, Japan). Spherical equivalent was defined as sphere plus half cylinder. Static nonindentation and dynamic indentation gonioscopy were performed using the Goldmann 2-mirror lens and Sussman 4-mirror lens, respectively. The drainage angles were assessed under the lowest level of ambient illumination that permitted a view of the angle, and high magnification ( 16). An eye was considered to have angle closure if the posterior pigmented trabecular meshwork was not visible for at least 180 degrees on nonindentation gonioscopy with the eye in the primary position. Slight tilting of the gonioscopy lens was permitted in the presence of convex iris profile. Each of the 2 mirrors of the Goldmann 2-mirror lens was inclined at an angle of 62 degrees towards the front surface. Indentation gonioscopy with a Sussman 4-mirror lens was used to establish the presence or absence of peripheral anterior synechiae (PAS).
Impact of Lens Vault on Visual Acuity and Refractive Error
FIGURE 1. Anterior segment optical coherence tomography images illustrating the measurement of lens vault as determined by the Zhongshan Angle Assessment Program.
Classification of Visual Impairment For all subjects, their logMAR VA was classified as normal vision/minimal visual impairment (logMARr0.3), mild visual impairment (0.3 < logMARr0.6), moderate/ severe (logMAR > 0.6) visual impairment. These classes are based on similar stratification used in previous studies.11,12
Statistical Analysis Statistical analyses were performed with IBM SPSS Statistics for Windows (version 21.0., Armonk, NY: IBM Corp). We examined the relationship between VA and LV, and that between spherical equivalent and LV. A multiple linear regression model was constructed with LV as the dependent variable with age, sex, VA, spherical equivalent, AL, and ACD as independent variables. The independence of variables in the linear regression model was assessed by the Durbin-Watson estimate. Variance inflation factor and tolerance were calculated to test potential multicollinearity among the independent variables. R2 (coefficient of multiple determination) was evaluated to examine the adequacy of the multiple linear regression model. A P-value of 21 mm Hg. None of the subjects had corresponding glaucomatous optic neuropathy. Table 1 shows the distribution of the various parameters among eyes with angle closure and those without angle closure. Angle-closure eyes were seen more often in older patients (P < 0.001) and had significantly shorter AL (P < 0.001), smaller ACD (P < 0.001), and greater LV (P < 0.001) but no significant differences were noted in the VA among the 2 groups (P = 0.12). The majority of subjects had normal VA/mild visual impairment (86.3% to 86.8%) in both the groups.
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J Glaucoma
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TABLE 1. Demographic and Clinical Data of the Study Subjects
Measures Age (SD) (y) Women [n (%)] Race (Chinese) [n (%)] Visual acuity [mean (SD)] (logMAR) Axial length [mean (SD)] (mm) Spherical equivalent [mean (SD)] (D) ACD [mean (SD)] (mm) Lens vault (SD) (mm) Visual acuity [n (%)] Normal vision/mild visual impairment Moderate/severe visual impairment
No Angle Closure (n = 1077) 61.8 559 949 0.37
(7.4) (51.9) (88.1) (0.22)
Angle Closure (n = 295) 64.6 193 284 0.39
P
(7.4) < 0.001 (65.4) < 0.001 (96.3) < 0.001 (0.20) 0.12
24.15 (1.37)
23.07 (0.88) < 0.001
+ 0.37 (2.78)
+ 2.04 (1.78) < 0.001
3.20 (0.33)
2.69 (0.22) < 0.001
388 (252)
775 (188)
929 (86.3)
256 (86.8)
147 (13.7)
39 (13.2)
< 0.001 0.41
Normal vision = logMARr0.3; mild visual impairment 0.3 < logMARr0.6; moderate/severe visual impairment logMAR > 0.6 ACD indicates anterior chamber depth.
In the multiple linear regression analysis of the associations with LV, the variables that were entered in regression model included age, sex, VA, spherical equivalent, ACD, and AL. The value of the Durbin-Watson estimate was 2.06, which indicates fulfilment of independent assumption of the variables in the model. No significant association was found between LV and VA (P = 0.35), or between LV and spherical equivalent (P = 0.06) in eyes with angle closure (Table 2). Figures 2 and 3 are the scatter plots depicting the bivariate correlation between LV and VA (coefficient of determination (r2) = 0.006), and LV and spherical equivalent (r2 = 0.13), respectively. There was poor correlation between LV and IOP (r2 = 0.008), and also between LV and the number of quadrants of PAS (r2 = 0.06).
DISCUSSION Laser peripheral iridotomy (LPI) is the established first-line treatment for angle closure as it eliminates pupillary block. However, LPI does not open up the angle in all cases, and evidence of progression of PACG in the presence of a patent iridotomy has been reported.13,14 Plausible reasons for the persistence of iridotrabecular contact have been attributed to mechanisms other than pupillary block, such as plateau iris syndrome, a lens-related element or the presence of PAS.
FIGURE 2. Scatter plot showing the bivariate correlation between visual acuity and lens vault in the study population. The coefficient of determination (r2) between the variables for all subjects is 0.006; for open angle is 0.003, and for angle closure it is 0.014.
Although LT can be biometrically determined and was initially studied as a possible contributory factor, the data suggesting an association between LT and angle closure remains inconsistent.2,15,16 In contrast, we and others have shown that LV, which represents the magnitude of the lens anterior to the plane of the anterior chamber angles (ie, anterior to the level of the scleral spurs), is independently associated with angle closure.4,17 LV has also been shown to have a greater ability to differentiate eyes with angle closure (AUC, 0.94 to 0.96) compared with LT (AUC, 0.61 to 0.75) or ACD (AUC, 0.75 to 0.90).4,17,18 In light of the importance and strong association of LV with angle closure supported both by epidemiological evidence and our understanding of the mechanism of pupil block, we believe that this aspect of the lens may need to be considered in the management of the disease. With advancing age, there is both an increase in thickness as well as a more anteriorly placed lens19,20; which in predisposed eyes would worsen angle crowding. This nonpupillary block component may be recalcitrant to an iridotomy and only relieved by subsequent lens extraction. Some have even
TABLE 2. Multiple Linear Regression for Associations With Lens Vault (mm) in Eyes With Angle Closure (N = 295) (R2 = 0.31)
Measures Visual acuity (logMAR) Spherical equivalent (D) Axial length (mm) Anterior chamber depth (mm)
B
95% CI of B
P
Tolerance
VIF
33.2 11.5 24.5 430
67.7 to 134.2 23.3 to 0.3 148.9 to 0.09 517 to 343
0.35 0.06 0.05 < 0.001
0.83 0.74 0.72 0.89
1.21 1.34 1.39 1.13
B = regression estimate. R = a measurement of the correlation between the observed value of the lens vault and the predicted value based on the regression model. VIF indicates variance inflation factor.
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J Glaucoma
Volume 25, Number 3, March 2016
Impact of Lens Vault on Visual Acuity and Refractive Error
FIGURE 3. Scatter plot showing the bivariate correlation between spherical equivalent and lens vault in the study population. The coefficient of determination (r2) between the variables for all subjects is 0.13; for open angle is 0.094, and for angle closure it is 0.00014.
While it may be tempting to speculate that lens extraction is preferable to LPI throughout the angle-closure spectrum in the presence of borderline visually significant cataracts, realistically this scenario depends on each individual case. An assessment of LV may be useful in the education of patients and to guide in the decision-making process. Of note, this study showed that increasing LV in angle-closure eyes is not associated with either a myopic shift in refraction or a decrease in VA. This permits the ASOCT to be more useful from a mechanistic view rather than a simple interpretation of whether the angles are open or closed. An estimation of the LV if available is useful as it better defines the role of the lens directly in relation to the anterior chamber angles. An added advantage is the ability to visualize the relative positions of the anterior segment structures from a single ASOCT image. One of the limitations of our study was the high proportion of undetectable scleral spurs in ASOCT images. Improvements in ASOCT resolution and fully automated image analysis techniques should reduce this. Secondly, we did not have data on the cataract grades of the subjects. Availability of such data would enhance our understanding of the effect of cataractogenesis on LV and VA. In summary, this study suggests that there is a significant population of angle-closure individuals with a large LV but good VA. The clinical relevance of LV may lie in aiding decision making in those for whom LPI or phacoemulsification may be equally acceptable treatment options. Lens extraction should be a consideration in those cases with large LV in the absence of visually significant cataract.
explained the IOP-lowering effect of phacoemulsification in such eyes to be more than just a relief of the anatomic situation.6,7,21,22 As greater LV carries a higher risk of angle closure, it follows therefore that lens removal in patients with greater LV is likely to reduce this risk significantly. In this study we examined a large community-based population group and found no association between the degree of LV and extent of visual impairment in subjects with angle closure. In eyes with a large LV, even if visually asymptomatic, lens extraction may be of benefit as the lens-related aspect could be refractory to an iridotomy. In addition to a relief of the anatomic situation, phacoemulsification of the lens in angle closure eyes is known to have an IOP-lowering effect believed to occur due to better access for the outflow of aqueous through the trabecular meshwork.6,7,21,22 However, we do not advocate primary lens extraction in all angle-closure eyes with a large LV. In those eyes with persistent angle closure and/or progression of disease despite a patent iridotomy and a large LV, lens extraction can be considered even in the presence of good VA. In the absence of visually significant cataract, whether to extract the lens in cases of PACG, is currently being investigated by the randomized-controlled EAGLE study8 with particular reference to quality-of-life metrics. Many elderly PACG patients will develop cataracts in the near future and will require surgery. This includes both those with naturally ageing cataract and in some cases from the effect of conventional glaucoma treatment.23–25 Naturally, it can also improve the visual function in patients with hypermetropia (found in the majority of PACG patients), by correcting this refractive error. Although admirable, the remit of the EAGLE study8 does not address the whole spectrum of angle closure and mainly concerns quality of life rather than long-term glaucoma control.
1. Tomlinson A, Leighton DA. Ocular dimensions in the heredity of angle-closure glaucoma. Br J Ophthalmol. 1973;57:475–486. 2. Lowe RF. Aetiology of the anatomical basis for primary angleclosure glaucoma: biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol. 1970;54:161–169. 3. Markowitz SN, Morin JD. The ratio of lens thickness to axial length for biometric standardization in angle-closure glaucoma. Am J Ophthalmol. 1985;99:400–402. 4. Nongpiur ME, He MG, Amerasinghe N, et al. Lens vault, thickness and position in Chinese subjects with angle closure. Ophthalmology. 2011;118:474–479. 5. Fotedar R, Mitchell P, Burlutsky G, et al. Relationship of 10year change in refraction to nuclear cataract and axial length findings from an older population. Ophthalmology. 2008;115: 1273–1278. 6. Tham CC, Leung DY, Kwong YY, et al. Effects of phacoemulsification versus combined phaco-trabeculectomy on drainage angle status in primary angle closure glaucoma (PACG). J Glaucoma. 2010;19:119–123. 7. Shin HC, Subrayan V, Tajunisah I. Changes in anterior chamber depth and intraocular pressure after phacoemulsification in eyes with occludable angles. J Cataract Refract Surg. 2010;36:1289–1295. 8. Azuara-Blanco A, Burr JM, Cochran C, et al. Effectiveness in Angle-closure Glaucoma of Lens Extraction (EAGLE) Study Group. The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angleclosure glaucoma (EAGLE): study protocol for a randomized controlled trial. Trials. 2011;12:133. 9. Lavanya R, Foster PJ, Sakata LM, et al. Screening for narrow angles in the Singapore population: evaluation of new noncontact screening methods. Ophthalmology. 2008;115: 1720–1727. 10. Console JW, Sakata LM, Aung T, et al. Quantitative analysis of anterior segment optical coherence tomography images: the
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11. 12.
13. 14. 15. 16. 17.
Zhongshan Angle Assessment Program. Br J Ophthalmol. 2008;92:1612–1616. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996;103:357–364. Dimitrov PN, Mukesh BN, McCarty CA, et al. Five-year incidence of bilateral cause-specific visual impairment in the Melbourne Visual Impairment Project. Invest Ophthalmol Vis Sci. 2003;44:5075–5081. Nolan WP, Foster PJ, Devereux JG, et al. YAG laser iridotomy treatment for primary angle closure in East Asian eyes. Br J Ophthalmol. 2000;84:1255–1259. Thomas R, Arun T, Muliyil J, et al. Outcome of laser peripheral iridotomy in chronic primary angle closure glaucoma. Ophthalmic Surg Lasers. 1999;30:547–553. Salmon JF, Swanevelder SA, Donald MA. The dimensions of eyes with chronic angle-closure glaucoma. J Glaucoma. 1994;3: 237–243. Sihota R, Ghate D, Mohan S, et al. Study of biometric parameters in family members of primary angle closure glaucoma patients. Eye. 2008;22:521–527. Ozaki M, Nongpiur ME, Aung T, et al. Increased lens vault as a risk factor for angle closure: confirmation in a Japanese population. Graefes Arch Clin Exp Ophthalmol. 2012;250: 1863–1868.
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18. Lee RY, Huang G, Cui QN, et al. Association of lens vault with narrow angles among different ethnic groups. Curr Eye Res. 2012;37:486–491. 19. Lowe RF. Anterior lens displacement with age. Br J Ophthalmol. 1970;54:117–121. 20. Koretz JF, Neider MW, Kaufman PL, et al. Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment. Exp Eye Res. 1987;44:307–318. 21. Tham CC, Kwong YY, Leung DY, et al. Phacoemulsification versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract. Ophthalmology. 2008;115:2167–2173. 22. Husain R, Gazzard G, Aung T, et al. Initial management of acute primary angle closure: a randomized trial comparing phacoemulsification with laser peripheral iridotomy. Ophthalmology. 2012;119:2274–2281. 23. Lim LS, Husain R, Gazzard G, et al. Cataract progression after prophylactic laser peripheral iridotomy: potential implications for the prevention of glaucoma blindness. Ophthalmology. 2005;112:1355–1359. 24. Vesti E. Development of cataract after trabeculectomy. Acta Ophthalmol (Copenh). 1993;71:777–781. 25. Dreyer EB, Chaturvedi N, Zurakowski D. Effect of mitomycin C and fluorouracil-supplemented trabeculectomies on the anterior segment. Arch Ophthalmol. 1995;113:578–580.
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The Impact of Lens Vault on Visual Acuity and Refractive Error: Implications for Management of Primary Angle-closure Glaucoma Monisha E. Nongpiur, MD,*w Shweta Singhal, PhD,* Stephen Stewart, MA, MBBS,z Hla M. Htoon, PhD,*w Arun K. Narayanaswamy, DO, DNB, MMED,*w Tien Y. Wong, FRCS, PhD,*wy Shamira A. Perera, BSc (Hons), FRCOphth,* and Tin Aung, FRCS, PhD*wy
Purpose: To investigate the relationship between lens vault (LV), visual acuity (VA), and refraction. Methods: This was a cross-sectional study of 2047 subjects aged 50 years and older recruited from a community polyclinic. Anterior segment optical coherence tomography was performed, and customized software was used to measure LV. VA was measured using a logarithm of minimum angle of resolution chart (logMAR chart; Lighthouse Inc.), and was classified as normal (logMAR < 0.3), mild impairment (0.3 < logMAR < 0.6), and moderate/severe impairment (logMAR > 0.6). Refraction was measured with an autorefractor machine and spherical equivalent was defined as sphere plus half cylinder. Angle closure was defined as posterior trabecular meshwork not visible for Z2 quadrants on nonindentation gonioscopy. Results: Complete data were available for 1372 subjects including 295 (21.5%) with angle closure. Angle-closure subjects were significantly older (P < 0.001), with shorter axial length (P < 0.001), shallower anterior chamber depth (P < 0.001), and greater LV (P < 0.001). There was no significant difference in VA (P = 0.12) compared with those without angle closure. After adjusting for age, sex, axial length, anterior chamber depth, and spherical equivalent, there was no significant association between LV and VA (P = 0.35) or between LV and spherical equivalent (P = 0.06). Conclusions: The magnitude of LV was not associated with VA or spherical equivalent. Lens extraction may be a consideration in eyes with angle closure with large LV in the absence of visually significant cataract. Key Words: lens vault, visual acuity, angle closure
(J Glaucoma 2016;25:e236–e240)
T
he lens plays an important role in the pathogenesis of primary angle-closure glaucoma (PACG).1–3 In addition to the thickness and position of the lens, another parameter, found to be associated with angle closure is the Received for publication July 1, 2014; accepted March 25, 2015. From the *Singapore National Eye Centre, Singapore Eye Research Institute; wDuke-NUS Graduate Medical School; yYong Loo Lin School of Medicine, National University of Singapore, Singapore; and zUniversity College London Medical School, London, UK. M.E.N. and S.S. are joint first authors. Supported by grants from National Medical Research Council, Singapore. Disclosure: The authors declare no conflict of interest. Reprints: Tin Aung, FRCS, PhD, Singapore National Eye Center, Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000264
lens vault (LV).4 The LV, imaged by anterior segment optical coherence tomography (ASOCT), is a surrogate measurement of the amount of lens that is located anterior to the plane of the anterior chamber angles. An increase in LV may worsen angle crowding in an already predisposed eye by instigating a more pronounced iris bowing through relative pupil block, and in more severe cases may also directly push the peripheral iris towards the angles.4 LV has been found to distinguish eyes with angle closure from those with open angles better than biometric parameters such as anterior chamber depth (ACD), axial length (AL), lens thickness (LT), and lens position.4 LV is the ASOCT risk factor for angle closure that is most analogous to the lens component. Although an increased LV may either represent an aged lens, an intumescent lens or subluxed lens, the targeted removal of this component converges to a lens extraction. With age, the compaction of crystallins during cataractogenesis may lead to an increase in refractive index and a yellowing of the lens itself. This is often accompanied by an increase in LT and a myopic shift related to the development of nuclear cataract.5 Studies have shown that for cases of visually significant cataract and PACG, cataract extraction results in deepening of the anterior chamber and widening of the angles, and in some cases, may lower intraocular pressure (IOP) and reduce the likelihood of progression.6,7 However, there is a lack of consensus on the role of lens extraction in eyes with PACG or primary angle closure with good visual acuity (VA). An ongoing multicentered randomized-controlled trial, the effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) is currently investigating whether early lens extraction in PACG improves patient-reported outcomes and costeffectiveness compared with standard care.8 The relationship of LV with VA or refractive error is not known, particularly in eyes with angle closure. Whereas good VA may naturally preclude cataract surgery, an increased LV may support the decision to proceed with cataract surgery even with a VA that was considered “normal” for surgical intervention. The aim of this study was to investigate the relationship between LV, VA, and refraction in subjects with angle closure.
METHODS Approval for the study was granted by the Singapore Eye Research Institute institutional review board. This study was conducted in accordance with the Declaration of
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J Glaucoma
Volume 25, Number 3, March 2016
Helsinki, and written informed consent was obtained from all subjects before enrollment. Subjects aged 50 years and older were recruited from a government-run polyclinic that provides primary health care services for residents living in the area around the clinic. Details of the study have been described previously.9 Recruited subjects did not have any ophthalmic complaints and individuals with a history of glaucoma, previous intraocular surgery, previous laser treatment, or penetrating eye injury were excluded. All subjects underwent a detailed eye examination that included an assessment of VA using a logarithm of minimum angle of resolution chart (logMAR chart; Lighthouse Inc., Long Island, NY), slit-lamp examination (model BQ 900; Haag-Streit, Bern, Switzerland), stereoscopic optic disc examination with a 78-D lens (Volk Optical Inc., Mentor, OH), and measurement of IOP with a Goldmann applanation tonometer (Haag-Streit, Koniz, Switzerland). AL and ACD were measured by IOLMaster (Carl Zeiss, Jena, Germany). Refraction was measured with an autorefractor machine (Topcon Auto K KR7100D; Topcon Corp., Tokyo, Japan). Spherical equivalent was defined as sphere plus half cylinder. Static nonindentation and dynamic indentation gonioscopy were performed using the Goldmann 2-mirror lens and Sussman 4-mirror lens, respectively. The drainage angles were assessed under the lowest level of ambient illumination that permitted a view of the angle, and high magnification ( 16). An eye was considered to have angle closure if the posterior pigmented trabecular meshwork was not visible for at least 180 degrees on nonindentation gonioscopy with the eye in the primary position. Slight tilting of the gonioscopy lens was permitted in the presence of convex iris profile. Each of the 2 mirrors of the Goldmann 2-mirror lens was inclined at an angle of 62 degrees towards the front surface. Indentation gonioscopy with a Sussman 4-mirror lens was used to establish the presence or absence of peripheral anterior synechiae (PAS).
Impact of Lens Vault on Visual Acuity and Refractive Error
FIGURE 1. Anterior segment optical coherence tomography images illustrating the measurement of lens vault as determined by the Zhongshan Angle Assessment Program.
Classification of Visual Impairment For all subjects, their logMAR VA was classified as normal vision/minimal visual impairment (logMARr0.3), mild visual impairment (0.3 < logMARr0.6), moderate/ severe (logMAR > 0.6) visual impairment. These classes are based on similar stratification used in previous studies.11,12
Statistical Analysis Statistical analyses were performed with IBM SPSS Statistics for Windows (version 21.0., Armonk, NY: IBM Corp). We examined the relationship between VA and LV, and that between spherical equivalent and LV. A multiple linear regression model was constructed with LV as the dependent variable with age, sex, VA, spherical equivalent, AL, and ACD as independent variables. The independence of variables in the linear regression model was assessed by the Durbin-Watson estimate. Variance inflation factor and tolerance were calculated to test potential multicollinearity among the independent variables. R2 (coefficient of multiple determination) was evaluated to examine the adequacy of the multiple linear regression model. A P-value of 21 mm Hg. None of the subjects had corresponding glaucomatous optic neuropathy. Table 1 shows the distribution of the various parameters among eyes with angle closure and those without angle closure. Angle-closure eyes were seen more often in older patients (P < 0.001) and had significantly shorter AL (P < 0.001), smaller ACD (P < 0.001), and greater LV (P < 0.001) but no significant differences were noted in the VA among the 2 groups (P = 0.12). The majority of subjects had normal VA/mild visual impairment (86.3% to 86.8%) in both the groups.
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J Glaucoma
Volume 25, Number 3, March 2016
TABLE 1. Demographic and Clinical Data of the Study Subjects
Measures Age (SD) (y) Women [n (%)] Race (Chinese) [n (%)] Visual acuity [mean (SD)] (logMAR) Axial length [mean (SD)] (mm) Spherical equivalent [mean (SD)] (D) ACD [mean (SD)] (mm) Lens vault (SD) (mm) Visual acuity [n (%)] Normal vision/mild visual impairment Moderate/severe visual impairment
No Angle Closure (n = 1077) 61.8 559 949 0.37
(7.4) (51.9) (88.1) (0.22)
Angle Closure (n = 295) 64.6 193 284 0.39
P
(7.4) < 0.001 (65.4) < 0.001 (96.3) < 0.001 (0.20) 0.12
24.15 (1.37)
23.07 (0.88) < 0.001
+ 0.37 (2.78)
+ 2.04 (1.78) < 0.001
3.20 (0.33)
2.69 (0.22) < 0.001
388 (252)
775 (188)
929 (86.3)
256 (86.8)
147 (13.7)
39 (13.2)
< 0.001 0.41
Normal vision = logMARr0.3; mild visual impairment 0.3 < logMARr0.6; moderate/severe visual impairment logMAR > 0.6 ACD indicates anterior chamber depth.
In the multiple linear regression analysis of the associations with LV, the variables that were entered in regression model included age, sex, VA, spherical equivalent, ACD, and AL. The value of the Durbin-Watson estimate was 2.06, which indicates fulfilment of independent assumption of the variables in the model. No significant association was found between LV and VA (P = 0.35), or between LV and spherical equivalent (P = 0.06) in eyes with angle closure (Table 2). Figures 2 and 3 are the scatter plots depicting the bivariate correlation between LV and VA (coefficient of determination (r2) = 0.006), and LV and spherical equivalent (r2 = 0.13), respectively. There was poor correlation between LV and IOP (r2 = 0.008), and also between LV and the number of quadrants of PAS (r2 = 0.06).
DISCUSSION Laser peripheral iridotomy (LPI) is the established first-line treatment for angle closure as it eliminates pupillary block. However, LPI does not open up the angle in all cases, and evidence of progression of PACG in the presence of a patent iridotomy has been reported.13,14 Plausible reasons for the persistence of iridotrabecular contact have been attributed to mechanisms other than pupillary block, such as plateau iris syndrome, a lens-related element or the presence of PAS.
FIGURE 2. Scatter plot showing the bivariate correlation between visual acuity and lens vault in the study population. The coefficient of determination (r2) between the variables for all subjects is 0.006; for open angle is 0.003, and for angle closure it is 0.014.
Although LT can be biometrically determined and was initially studied as a possible contributory factor, the data suggesting an association between LT and angle closure remains inconsistent.2,15,16 In contrast, we and others have shown that LV, which represents the magnitude of the lens anterior to the plane of the anterior chamber angles (ie, anterior to the level of the scleral spurs), is independently associated with angle closure.4,17 LV has also been shown to have a greater ability to differentiate eyes with angle closure (AUC, 0.94 to 0.96) compared with LT (AUC, 0.61 to 0.75) or ACD (AUC, 0.75 to 0.90).4,17,18 In light of the importance and strong association of LV with angle closure supported both by epidemiological evidence and our understanding of the mechanism of pupil block, we believe that this aspect of the lens may need to be considered in the management of the disease. With advancing age, there is both an increase in thickness as well as a more anteriorly placed lens19,20; which in predisposed eyes would worsen angle crowding. This nonpupillary block component may be recalcitrant to an iridotomy and only relieved by subsequent lens extraction. Some have even
TABLE 2. Multiple Linear Regression for Associations With Lens Vault (mm) in Eyes With Angle Closure (N = 295) (R2 = 0.31)
Measures Visual acuity (logMAR) Spherical equivalent (D) Axial length (mm) Anterior chamber depth (mm)
B
95% CI of B
P
Tolerance
VIF
33.2 11.5 24.5 430
67.7 to 134.2 23.3 to 0.3 148.9 to 0.09 517 to 343
0.35 0.06 0.05 < 0.001
0.83 0.74 0.72 0.89
1.21 1.34 1.39 1.13
B = regression estimate. R = a measurement of the correlation between the observed value of the lens vault and the predicted value based on the regression model. VIF indicates variance inflation factor.
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J Glaucoma
Volume 25, Number 3, March 2016
Impact of Lens Vault on Visual Acuity and Refractive Error
FIGURE 3. Scatter plot showing the bivariate correlation between spherical equivalent and lens vault in the study population. The coefficient of determination (r2) between the variables for all subjects is 0.13; for open angle is 0.094, and for angle closure it is 0.00014.
While it may be tempting to speculate that lens extraction is preferable to LPI throughout the angle-closure spectrum in the presence of borderline visually significant cataracts, realistically this scenario depends on each individual case. An assessment of LV may be useful in the education of patients and to guide in the decision-making process. Of note, this study showed that increasing LV in angle-closure eyes is not associated with either a myopic shift in refraction or a decrease in VA. This permits the ASOCT to be more useful from a mechanistic view rather than a simple interpretation of whether the angles are open or closed. An estimation of the LV if available is useful as it better defines the role of the lens directly in relation to the anterior chamber angles. An added advantage is the ability to visualize the relative positions of the anterior segment structures from a single ASOCT image. One of the limitations of our study was the high proportion of undetectable scleral spurs in ASOCT images. Improvements in ASOCT resolution and fully automated image analysis techniques should reduce this. Secondly, we did not have data on the cataract grades of the subjects. Availability of such data would enhance our understanding of the effect of cataractogenesis on LV and VA. In summary, this study suggests that there is a significant population of angle-closure individuals with a large LV but good VA. The clinical relevance of LV may lie in aiding decision making in those for whom LPI or phacoemulsification may be equally acceptable treatment options. Lens extraction should be a consideration in those cases with large LV in the absence of visually significant cataract.
explained the IOP-lowering effect of phacoemulsification in such eyes to be more than just a relief of the anatomic situation.6,7,21,22 As greater LV carries a higher risk of angle closure, it follows therefore that lens removal in patients with greater LV is likely to reduce this risk significantly. In this study we examined a large community-based population group and found no association between the degree of LV and extent of visual impairment in subjects with angle closure. In eyes with a large LV, even if visually asymptomatic, lens extraction may be of benefit as the lens-related aspect could be refractory to an iridotomy. In addition to a relief of the anatomic situation, phacoemulsification of the lens in angle closure eyes is known to have an IOP-lowering effect believed to occur due to better access for the outflow of aqueous through the trabecular meshwork.6,7,21,22 However, we do not advocate primary lens extraction in all angle-closure eyes with a large LV. In those eyes with persistent angle closure and/or progression of disease despite a patent iridotomy and a large LV, lens extraction can be considered even in the presence of good VA. In the absence of visually significant cataract, whether to extract the lens in cases of PACG, is currently being investigated by the randomized-controlled EAGLE study8 with particular reference to quality-of-life metrics. Many elderly PACG patients will develop cataracts in the near future and will require surgery. This includes both those with naturally ageing cataract and in some cases from the effect of conventional glaucoma treatment.23–25 Naturally, it can also improve the visual function in patients with hypermetropia (found in the majority of PACG patients), by correcting this refractive error. Although admirable, the remit of the EAGLE study8 does not address the whole spectrum of angle closure and mainly concerns quality of life rather than long-term glaucoma control.
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