Abstract
Purpose.:
To describe anterior segment optical coherence tomography (AS-OCT) parameters in phacomorphic angle closure eyes, mature cataract eyes, and their fellow eyes, and identify those parameters that could be used to differentiate phacomorphic angle closure eyes from those with mature cataract and no phacomorphic angle closure.
Methods.:
In this cross-sectional study, a total of 33 phacomorphic angle closure subjects and 34 control patients with unilateral mature cataracts were enrolled. All patients underwent AS-OCT imaging and A-scan biometry of both eyes. Anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness, iris curvature, lens vault (LV), and angle parameters, including angle opening distance (AOD750) and trabecular-iris space area (TISA750), were measured in qualified images using customized software and compared among eyes with phacomorphic angle closure, mature cataract eyes, and their fellow eyes.
Results.:
There was no significant difference in axial length among the four groups. Phacomorphic angle closure had the smallest angle (AOD750, TISA750) and anterior chamber parameters (ACD, ACA, anterior chamber width) and the greatest LV among the groups. This pattern was similar when comparing fellow eyes of mature cataract patients and fellow eyes of phacomorphic angle closure. Anterior chamber area less than 18.62 mm2, ACD less than 2.60 mm, LV greater than 532.0 μm, and AOD750 less than 0.218 mm had the highest odds ratios (ORs) for distinguishing fellow eyes of phacomorphic angle closure versus fellow eyes of mature cataracts, with OR values of 9.90, 8.31, 7.91, and 7.91, respectively. Logistic regression showed that ACA less than 18.62 was the major parameter associated with fellow eyes of phacomorphic angle closure (OR = 10.96, P < 0.001).
Conclusions.:
Anterior chamber depth, ACA, AOD750, and LV are powerful indicators in differentiating phacomorphic angle closure eyes from those with mature cataract and their fellow eyes.
Acute phacomorphic angle closure results from an increase in anteroposterior diameter of a swollen, mature cataract.
1 It is an important disease to potentially screen in populations of lower socioeconomic status with inadequate access to health care. A considerable number of cataract extractions in developing countries are for phacomorphic angle closures, with reported rates of approximately 4% of all cataract surgeries in India.
2,3
Formerly known as phacomorphic glaucoma, phacomorphic angle closure is a more appropriate name for this disease, as optic neuropathy is preventable, if the disease is recognized and treated early. This condition occurs in the setting of a thick lens, which causes acute closure of the drainage angle, leading to rapid and substantial elevation of IOP.
4,5 When the lens swells, angle closure with pupillary block occurs in the acute phase; in the late phase, it can occur even without pupillary block as a result of forward movement of the peripheral iris.
6,7 However, not all patients with mature cataract inevitably develop phacomorphic angle closure. It is important to identify which of the patients with mature cataract are at increased risk of phacomorphic glaucoma.
Although several ocular risk factors have been identified for angle closure disease, such as Chinese ethnicity, short axial length, shallow anterior chamber, and a thick and anteriorly positioned lens,
8–12 the literature about phacomorphic angle closure is sparse. Lee and associates
13 recently evaluated axial length (AL) and anterior chamber depth (ACD) by A-scan ultrasonography in phacomorphic patients and compared them with a control group; they found that eyes with phacomorphic glaucoma had statistically shorter axial lengths compared with their age- and sex-matched control counterparts.
With the advent of anterior segment optical coherence tomography (AS-OCT), researchers can capture a cross section of the entire anterior segment in a single image to assess angle, iris, and lens more precisely. This device allows users to quantify angle width and measure anterior chamber parameters, including novel factors such as lens vault (LV), anterior chamber width (ACW), and anterior chamber area (ACA), thus helping researchers to further understand the pathogenesis of anterior segment disease.
9,14–17
In this study, eyes with phacomorphic angle closure, mature cataracts, and their fellow eyes were evaluated. We used AS-OCT and A-scan biometry to measure ocular biometric parameters, including lens characteristics and the new parameter LV. We investigated angle, iris, anterior segment, and lens parameters as risk factors for development of phacomorphic angle closure in eyes with mature cataracts.
In this cross-sectional study, we enrolled consecutive patients who presented with unilateral phacomorphic angle closure or mature cataracts to the emergency department and the comprehensive eye clinic of Farabi Eye Hospital, Tehran, Iran, and obtained images before any therapeutic procedures. The protocol for the project was approved by the institutional review board of Tehran University of Medical Sciences, Tehran, Iran. All patients gave written, informed consent to participate in this research protocol. The research was conducted in compliance with the Declaration of Helsinki. Inclusion criteria were patients with unilateral mature cataract or phacomorphic angle closure in one eye, and broken attack with medication.
The mature cataract group consisted of eyes with mature cataracts without phacomorphic angle closure. A mature cataract was defined as a crystalline lens that was completely opaque with no view of the fundus.
Phacomorphic angle closure was defined by the presence of an intumescent cataract and the following criteria: (1) at least two of the symptoms of an acute episode of IOP rise, which are ocular pain or headache, nausea and/or vomiting, decreased vision, and rainbow-colored halos around lights; (2) IOP at presentation of at least 30 mm Hg by Goldmann applanation tonometry; (3) examination findings such as conjunctival injection, corneal epithelial edema, fixed mid-dilated pupil, and shallow anterior chamber; and (4) closed anterior chamber angles in at least three quadrants on gonioscopic examination.
Exclusion criteria were inability to perform testing; preexisting glaucoma; history of intermittent angle closure, trauma, uveitis, surgery; or any kind of laser or intraocular surgery (eg, laser peripheral iridotomy) in the affected or contralateral eye. Eyes that met the criteria were classified into four groups: (1) phacomorphic angle closure (28 eyes), (2) fellow eye of primary angle closure (26 eyes), (3) mature cataract (32 eyes), and (4) fellow eye of mature cataract (27 eyes).
Patients with phacomorphic angle closure received intravenous mannitol (20%), oral acetazolamide, and topical timolol (0.5%) eyedrops were administered to all patients to reduce IOP and corneal edema. Timolol twice daily and acetazolamide 250 mg four times daily were continued for the patient to maintain IOP control. Eyes whose attack could not be broken, defined as reduction of IOP and improvement of corneal clarity, with these medications were excluded from the study and treated with further therapy. Miotic, mydriatic, and cycloplegic medications were not used for any of the patients.
Detailed slit-lamp examination of the anterior segment was done and IOP was measured with Goldmann applanation tonometry. Gonioscopy was performed using a Zeiss-style 4-mirror gonioscopic lens (model OPDSG; Ocular Instruments, Inc., Bellevue, WA, USA) in a dark room. Shaffer method was used for grading of the angles. Narrow angle was defined in eyes when at least 180° of the posterior pigmented trabecular meshwork was not visible on gonioscopy in the primary position of gaze without indentation. Posterior pole funduscopy was performed using a 90-diopter lens. B-scan ultrasonography was used to evaluate posterior segments when funduscopy was impossible. A-scan biometry (Echoscan, model U3300; Nidek, Tokyo, Japan) was used to measure AL and lens thickness for all the patients.
Statistical analysis was performed using SPSS software version 17 (SPSS, Inc., Chicago, IL, USA). Assuming SD = 0.9 mm for AL, we needed 30 cases for detecting a difference of 0.66 mm between groups with a power of 80%. The mean and SD were calculated for the continuous anterior segment variables. Continuous variables were analyzed using ANOVA. Bonferroni correction was applied for multiple testing of continuous variables. The anterior segment parameters were compared between fellow eyes of mature cataracts and fellow eyes of phacomorphic angle closures. Linear mixed-effects regression was used for controlling anterior segment measurements for age, sex, and pupil diameter (PD). The area under the receiver operating characteristic curve (AROC) was used to reveal the parameters that are best qualified to identify the fellow eye of phacomorphic angle closures. Dichotomization was performed after determining best cutoff based on Youden's index for these variables. Sensitivity, specificity, and odds ratio (OR) were determined for each variable.
To determine the most important variable that was associated with fellow eyes of phacomorphic angle closure, we used a backward logistic regression model, including the most significant variable at each iteration and dichotomized variable. A P less than 0.05 was considered significant.
Although there are several articles evaluating eyes with primary angle closure glaucoma, the pathogenesis of phacomorphic angle closure is not well understood. To our knowledge, this is the first study to describe the anterior segment parameters of phacomorphic angle closure. In this study using AS-OCT, we identified the parameters that could be used to differentiate phacomorphic angle closure eyes from those with mature cataract and no phacomorphic angle closure. We found that fellow eyes of phacomorphic angle closure patients have shallower anterior segments, greater LV, and narrower angles. Anterior chamber area less than 18.62 mm was considered the single most significant parameter associated with phacomorphic angle closure.
During the phacomorphic angle closure attack, changes in the anterior chamber dimensions and lens thickness of the involved eye occur, making these parameters unreliable as risk factors to study for the development of phacomorphic glaucoma. To overcome this problem, assuming similarity of dimensions in most of the fellow eyes, we measured the contralateral anterior chamber parameters of the eye with phacomorphic angle closure and compared them with the contralateral eyes of mature cataract eye.
In the literature, phacomorphic angle closure is described as a condition that is seen in eyes with deep or shallow chamber.
26 Although studies found that the fellow eyes of patients with acute angle closure have a mean ACD that was 0.63 mm shallower than in healthy controls,
27 a study on phacomorphic angle closure did not find any statistically significant association between the contralateral anterior chamber depths of mature cataracts and phacomorphic angle closure cases.
28 In our patients, fellow eyes of phacomorphic angle closure were 0.46 mm shallower than fellow of mature eyes. Eyes with ACD less than 2.6 mm had an OR of 7.9 to develop phacomorphic angle closure as compared with eyes that have mature cataracts. In agreement with this finding, the ACA was less in fellow eyes of phacomorphic angle closure subjects. It was the single most important risk factor statistically for developing phacomorphic angle closure in mature cataract eyes, accounting for one-third of the variance in phacomorphic angle closure occurrence when the cataract becomes mature. In fact, a smaller anterior segment of the eye predisposes the eye to develop an acute angle closure attack when the cataract matures. In contrast to the other studies about primary angle closure,
22 we did not find any difference in ACW between the two groups.
As the main pathology in phacomorphic angle closure seems to be the intumescent cataract rather than the angle configuration, as in primary angle closures, it has been reported to occur in previously open-angle eyes.
29 However, only one-fourth of our contralateral eyes of phacomorphic angle closure had open angles. Quantitatively, we found that fellow eyes of phacomorphic angle closures had narrower angles, with a mean AOD750 of 200 μm smaller than fellow eyes of mature cataracts.
Lens vault is an important anatomic risk factor and was previously regarded as among the strongest predictors of primary angle closure glaucoma.
17,30 The greater the LV, the more the iris is pushed anteriorly, leading to a crowded angle. In our study, the fellow eyes of matures and phacomorphic angle closures had similar nuclear opacity and thickness. However LV was greater in fellow eyes of phacomorphic angle closure. Although after becoming a mature cataract, lens thickness and position may change, our study suggests that anterior protrusion of the lens might have a prominent role in development of phacomorphic angle closure.
For phacomorphic angle closure, Lee et al.
13 first demonstrated that eyes with AL of 23.2 mm or less were 4.3 times as likely to develop phacomorphic glaucoma compared with eyes with AL greater than 23.7 mm. However, we did not find any significant difference among our four groups. We suggest that the anterior segment dimensions of the eye might play a more important role in the development of angle closure
Eyes with thicker iris or a prominent iris roll also have been associated with narrower angles. Wang et al.
20 reported that increased iris thickness was associated with narrower angles. Lee et al.
26 compared iris thickness in different races and demonstrated that racial groups that historically showed higher prevalence of primary angle closure glaucoma possess thicker irides. However, other studies have not shown a significant difference in iris thickness between angle closure and healthy controls.
15 Similarly, our patients with phacomorphic angle closure did not have a thicker iris. Differences in race also may contribute to the dissimilarity of our results.
The results of our study should be interpreted with its limitations in mind. Because patients were of Iranian descent, it is unclear whether similar associations would be seen in other racial groups. Another limitation of this study was that the imaging in the phacomorphic group was performed after the resolution of an acute episode, so these results may not directly demonstrate anterior chamber parameters of eyes before an acute attack. Moreover, one may say some of mature cataract eyes may develop phacomorphic angle closure in the near future and should be classified in the angle closure group. To address this question, mature cataract eyes might need to be assessed and followed prospectively for phacomorphic angle closure, which would not be ethically feasible. We admit that due to the cross-sectional nature of our study, we cannot assign causal relationships for the determinants of phacomorphic angle closure. Finally, we were not able to accurately assess the lens thickness measurements for phacomorphic angle closure eyes, and thus we could not evaluate the role of lens thickness in these eyes.
In summary, we have assessed anterior segment parameters of eyes prone to phacomorphic angle closure in comparison with eyes that are at risk but have not developed angle closure. In our study ACD, ACA, LV, and angle opening distance were significant indicators for having phacomorphic angle closure. Smaller ACA was considered the single most significant parameter associated with phacomorphic angle closure.
The authors did not receive any financial support from any public or private sources. The authors have no financial or proprietary interest in a product, method, or material described herein.
Disclosure: M. Mansouri, None; F. Ramezani, None; S. Moghimi, None; A. Tabatabaie, None; F. Abdi, None; M. He, None; S.C. Lin, None