EBM review:ANGLE CLOSURE GLAUCOMA: A MECHANISTIC REVIEW MONISHA E. NONGPIURA, JUDY Y.F. KUA AND TIN AUNGA,B

CURRENT OPINION IN OPHTHALMOLOGY 2011,22:96–101

2011/3/17 R4 雷小蕾 /VS張雪麗

Risk factors for angle closure: recent findings

(1) Anatomical factors: (a) Anterior chamber – width, area and

volume. (b) Iris – thickness, area, and curvature. (c) Lens – lens vault.

(2) Altered physiology/ dynamic factors: (a) Iris – changes in volume with dilation. (b) Choroid – choroidal expansion/effusion

Altered physiology/dynamic factors

Iris volume changes with dilation

Recently, it was proposed that dynamic physiological factors also play a significant role in the pathogenesis of angle closure glaucoma

AS-OCT: pupil diameter greater in dark (a)

Iris cross-sectional area decreases with pupil dilation and its dynamic behavior is a risk factor in angle closure. Glaucoma 2009; 18:173–179. Quigley et al. evaluated changes in iris cross-sectional

area measured with AS-OCT in 65 glaucoma patients, including both open angle and angle closure, during physiological and pharmacological mydriasis.

4% loss in calculated iris volume per 1mm increase in pupil size, with peak loss complete in 5 s.

Glaucoma 2009; 18:173–179.

Anatomical risk factors such as axial length, refraction, gonioscopy and corneal curvature were not determinants of iris cross-sectional area or change in iris cross-sectional area with pupil dilation

angle closure: lost less iris volume compared with controls during dilation (P=0.008).

=> this dynamic behaviour is due to movements of extracellular fluid between the iris stroma and the anterior chamber.

Optical coherence tomography quantitative analysis of iris volume changes after pharmacologic mydriasis. Ophthalmology 2010; 117:3–10. the iris volume of fellow eyes of those with a

history of acute primary angle closure(APAC) and age and sex-matched controls, was directly measured using AS-OCT predilation and postdilation.

Prior to dilation, the iris volume were similar between fellow eyes and controls (P<0.1).

Thirty minutes post dilation, the mean iris volume in the fellow eyes increased (P<0.01), whereas those of the controls decreased (P<0.01).

Figure 2. Examples of 8 cross-sectional images of the iris at 0-, 45-, 90-,135-, 180-, 225-, 270-, and 315-degree meridians under illumination andafter pupil dilation (1% tropicamide) in (A, B) open-angle eyes and (C) fellow eyes. Iris volume changes from (A) 45.99 to 35.73 mm3 (23.3%), (B) 44.34 to 37.43 mm3 (16.6%), and (C) 44.39 to 50.19 mm3 (9.1%).Note that pupil dilation seems to be comparable in the 3 eyes; by contrast,the iris seems to be thicker in the fellow eye.

Ophthalmology 2010; 117:3–10.

biometric risk factors did not change significantly during mydriasis (P>0.1).

Significant predictors of a greater increase in iris volume postdilation included fellow eyes with a greater iris volume (P=0.008), brown eyes (P=0.01), and larger pupil diameter (P=0.02)

=>This dynamic iris behaviour may be a physiological adaptation to dilation to avoid blockage of the drainage angle.

Thus this inherent tendency to lose less or even gain volume during dilation, in eyes at risk of APAC, is possibly a contributing factor in the development of angle closure and may provide an alternative explanation for the higher incidence of angle closure among certain populations.

Choroidal expansion/effusion

The choroid: highly vascular structure with variable

thickness regulated by various parameters Choroidal effusion (or uveal or

ciliochoroidal effusion) :abnormal accumulation of fluid in the suprachoroidal space due to an imbalance of pressure differentials

Possible mechanisms of primary angle- closure and malignant glaucoma. J Glaucoma 2003; 12:167–180.

Quigley et al. : choroidal expansion is another mechanism for angle closure and may precede

and even precipitate APAC.

no trans-vitreous resistance: any choroidal expansion would be balanced by increasing aqueous outflow, without iris or lens movement.

vitreous has a limited capacity to transmit fluid: anterior movement of the compressed vitreous, iris and lens when trans-vitreous flow is restricted

In small eyes predisposed to angle closure, choroidal expansion leading to increased vitreous cavity pressure, may be a contributing cause

Uveal effusion in primary angleclosure glaucoma. Ophthalmology 2005; 112:413–419.

Sakai et al. :investigated the prevalence of choroidal effusion using UBM in 501 Japanese individuals with primary angle closure (PAC).

70 acute and fellow PAC eyes, and 431 chronic PAC

eyes.

choroidal effusion in acute PAC (58%) >chronic PAC (9%) > POAG (1.3%).

more frequent in acute PAC eyes than in fellow eyes (23%).

The ACD in phakic chronic PAC eyes with choroidal effusion was significantly shallower compared with eyes without effusion (P=0.019).

Within the acute PAC group though, there were no differences in the demographics and management profile between those with and without choroidal effusion.

Confirmation of uveal effusion in eyes with primary angle closure glaucoma: an ultrasound biomicroscopy study. Arch Ophthalmol 2008; 126:1647–1651.

In a Singaporean population, Kumar et al: the presence of choroidal effusion among 28 newly diagnosed PACG, 42 established PACG, and 12

APAC individuals.

Choroidal effusion: PACG (15.7%), APAC (25%), and newly diagnosed PACG patients prior to LPI (14.2%)

Two weeks after LPI, the effusion resolved in half of those with newly diagnosed PACG (7.1%).

The level of effusion : milder among PACG (all grade 1 effusion) vs APAC (grade 2 or 3).

In contrast to Sakai et al., they did not demonstrate a significant difference in ACD between those with and without effusion.

Grading of the uveal effusion

grade 0: none grade 1: slitlike

(supraciliary space less than half the ciliary body thickness)

grade 2: bandlike (supraciliary space greater than half the ciliary body thickness)

grade 3: obvious (supraciliary space greater than the ciliary body thickness).

grade 1

grade 3Confirmation of uveal effusion in eyes withprimary angle closure glaucoma: an ultrasound biomicroscopy study. ArchOphthalmol 2008; 126:1647–1651.

The presence of choroidal effusion in untreated eyes raises the question of whether it is a cause or effect of PACG/APAC.

effusion was more severe and more prevalent in APAC =>a significant role in the pathogenesis of APAC

a multilevel physiological trigger may initiate a sustained choroidal expansion, which in an anatomically predisposed eye, leads to APAC and PACG.

other investigators have failed to demonstrate significant changes in biometry (ACD, lens position, RLP) before and 2 weeks after LPI=> challenges the theory of anterior lens movement secondary to choroidal expansion as a possible mechanism for APAC.

Br J Ophthalmol 2005; 89:288–290.

In the future, use of UBM to detect effusion could potentially be important as a predictive test in anatomically predisposed eyes (smaller eyes, narrow angles), to identify those at higher risk of developing APAC or PACG

Conclusion The identification of several novel risk factors in

eyes with angle closure -> heterogeneous disease which can be caused by either one, or a combination of absolute or relative deviations in anatomical and/or physiological changes of both the anterior and posterior segment structures.

Evaluation of the different factors will assist population screening, help clinicians to identify the predominant mechanisms causing the angle to close, and aid in deciding the appropriate therapy.

early detection by effective screening and appropriate prophylaxis, angle closure glaucoma is a potentially preventable disease.

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