Primary angle-closure glaucoma

Historical review and classifications

The Hippocratic aphorisms include two mentions of blindness, one of which may refer to glaucoma: ‘When headache develops in cases of ophthalmia and accompanies it for a long time, there is a risk of blindness.’1 Gradually the different causes of blindness were separated, with the most important distinction between cataract (which was treatable by couching) and glaucoma (which was not).Thirteenth century Syrian Salah-ad-din-ibin Yusuf al-kahal bi Hamah described a condition that he called ‘migraine of the eye’ or ‘headache of the pupil’: possibly a description of acute angle-closure glaucoma, with painful hemicrania and dilation of the pupil.1

Itinerant British oculist Richard Banister published a clear description of end-stage or absolute glaucoma in which he observed that the eye was hard to palpation.2 Further descriptions of congestive glaucoma and the firmness of the eye were published by Platner, Guthrie, Beer, and Demours.2 Demours also reported halo vision in glaucoma.2

In 1853, von Arlt ascribed the cause of glaucoma to the struggle for a livelihood, grief, weeping, vexation, eyestrain, and a damp dwelling.3 Most other scientists in the eighteenth and nineteenth centuries viewed glaucoma as a disease of the vitreous humor that was associated with iritis and arthritis. Following the development of the ophthalmoscope in 1851 by von Helmholtz, Jacobson, Jaeger, von Graefe, and Weber disproved this theory by noting glaucomatous cupping in eyes with clear vitreous bodies.2 The lack of vitreous involvement in glaucomatous eyes was confirmed histopathologically by Mackenzie and Muller.2

Another important step in our understanding of glaucoma came from studies by Leber,Weber, and Knies of the aqueous humor circulation in animal and human eyes.2 The association between shallow anterior chambers and acute attacks of angle-closure glaucoma became clear in the late nineteenth century.4,5 It was during this time that von Graefe,5 in one of the landmark papers of ophthalmology, proposed iridectomy as a treatment for glaucoma. In the 1920s, Curran,6 Banziger,7 and Raeder8 independently put forth theories regarding the mechanism of pupillary block and further proposed that peripheral iridectomy cured angle-closure glaucoma by relieving this block. The efficacy of peripheral iridectomy as a treatment for glaucoma was confirmed by many physicians, including Gifford,9 O’Connor,10 Elschnig,11 Barkan,12 and Chandler.13 With the development of gonioscopy by Trantas, Salzmann, Koeppe, and Troncoso, the mechanism of angle closure was confirmed; and glaucoma was classified in modern terms by Barkan according to the state of the angle.14 Rosengren’s prescient biometric studies of the anterior segments in the ‘primary glaucomas’

distinguished the symptomatic angle-closure eyes from the asymptomatic open-angle eyes.15 This classification system was clinically elaborated by Sugar,16 and later adopted by the American Academy of Ophthalmology in 1949.17

Today glaucoma continues to be classified into open-angle and angle-closure forms (see Ch. 1). In open-angle glaucoma, there is increased resistance to aqueous humor outflow through the trabecular meshwork–Schlemm’s canal–episcleral venous system by a variety of mechanisms which do not involve visible obstruction by the iris. In the angle-closure glaucomas there is increased resistance to outflow because of damage to, or obstruction of, the trabecular meshwork by the peripheral iris, preventing the aqueous humor from reaching the outflow channels.

Classifications of angle-closure disease

Historically the angle-closure glaucoma nomenclature has been confusing: conditions were sometimes classified by the time course of the disease, sometimes by the effects of the angle closure, and sometimes by the presumptive pathophysiology of the angle closure. For example, angle-closure glaucoma has been described by the adjective pairs congestive/non-congestive and compensated/uncompensated.These terms have been abandoned because they lack specificity. The congestion and corneal decompensation are usually a function of the rapidity with which the pressure rises, or reflect underlying causal phenomena such as uveitis.

Similarly the terms acute, subacute, and chronic have often been used to reflect the time course and/or presence of symptoms. Abrupt and total angle closure is acute; recurrent and self-limiting episodes of closure with elevated intraocular pressure (IOP) are subacute; and asymptomatic elevated IOP or peripheral anterior synechiae is chronic. Although these and similar temporal terms (e.g., ‘latent’ and ‘imminent’) have long had currency, even appearing in an elaborate contemporary classification of European and Inuit angleclosure disease based on high-resolution anterior segment imaging and clinical presentations,18 this complex scheme is problematic for two reasons. First, it is cumbersome for epidemiologic assessment, and often requires guesswork by the clinician – which makes standardization of diagnoses difficult. Second, these terms add little or no value to clinical strategies for patient care. Such terms explicitly presume correlated clinical signs and symptoms in the presentations of angle-closure glaucoma, with the time course of the patient’s disease retroactively designated by the clinican.Yet in one assessment of worldwide primary angle-closure glaucoma, four-fifths of patients presented entirely without symptoms.19 We concur with newer diagnostic definitions that discard older time-based terms, because they neither shed light on the natural history of disease progression,

nor contribute to stage-specific management interventions for the disease.20

In large part due to the recent appreciation of the magnitude of glaucoma blindness in the world, a disproportionate part of which occurs in Asians with primary angle-closure disease,21,22 consensus meetings among world glaucoma experts were held under the auspices of the Association of International Glaucoma Societies (AIGS) in 2006 to elaborate consistent and clinically applicable sets of definitions for angle-closure glaucoma disease (see Appendix).23 Based on over a decade’s attempts to develop a simplified, clinically relevant clas- sification,24–27 this terminology has been endorsed by the American Academy of Ophthalmology, the International Society of Geography and Epidemiology of Ophthalmology (ISGEO), and the Southeast Asia Glaucoma Interest Group. Comparable schemes are now being used in numerous studies throughout the world:28 in Japan,29 Thailand,30 India,31–34 Mongolia,35 and among various Chinese populations.36–38

This uniformity of approach has two major merits. Epidemiologically, it greatly facilitates meaningful comparison among population studies, which further helps elucidate risk factors relevant to angle closure, determining clinical markers for progression of disease, distinguishing differential responses and complications of interventions, and discovering clues as to underlying pathogenic mechanisms. And for the individual patient, this scheme of the natural history of primary angle closure addresses both the prognosis for progression, and the stage-appropriate need for treatment.

Twenty-first century consensus classification

The new classification of primary angle-closure (PAC) disease relies on three simple categories: IOP measurement, gonioscopy, and disc and visual field evaluation. In other words, the presenting patient’s clinical examination alone determines the staging of the disease, regardless of the presence, absence, or reliability of symptom history, alleged duration, intermittency of problems, etc.

1.Primary angle closure SUSPECT (PAC suspect): greater than 270° of irido-trabecular contact plus absence of peripheral anterior synechiae (PAS) plus normal IOP, disc, and visual field. In other words, the suspect eye has normal IOPs, optic nerves and visual fields, i.e., no signs of clinical glaucoma, but whose angle before indentation gonioscopy is graded as a Shaffer grade 2 or less, without PAS on compression. The angle is at risk.

2.Primary angle CLOSURE (PAC): greater than 270° of irido-trabecular contact with either elevated IOP and/or PAS plus normal disc and visual field examinations. In other words, angle closure demonstrates irido-trabecular contact in 75% of the angle, with either PAS or elevated IOPs, but without disc and visual field changes. The angle is abnormal in structure (PAS) or function (elevated IOP).

3.Primary angle-closure GLAUCOMA (PACG): greater than 270° of irido-trabecular contact plus elevated IOP plus optic nerve and visual field damage. In other words, angleclosure glaucoma manifests the criteria of closure above, plus demonstrable disc and/or visual field changes. The angle is abnormal in structure and function, with optic neuropathy.

It is important, of course, not to exclude all temporal information in this scheme: acute PACG remains a specific observable presentation category of the disease, requiring immediate recognition and intervention.

Clarifications and commentary

Mastery of indentation (compression) gonioscopy with such devices as the Posner or Zeiss 4-0 mirror goniolens (see Chs 5 and 7) is the indispensable skill required to apply this classification. Since narrow angles are not particularly common – an estimated 2–6% of Caucasian eyes have suspiciously narrow angles (Shaffer

grade 2 or less), and 0.6–1.1% have critically narrow angles (grade 1 or less)39,40 gonioscopic subtleties can only be learned by its

routine practice in the clinic on every new patient, young or old. Irido-trabecular contact needs to be identified as present or absent, and then discriminated as either appositional (by indenting and revealing angle structures) or synechial, while documenting the latter’s extent (in terms of degrees or total clock hours). The use of a goniolens larger than the corneal diameter (e.g., Goldmann or Koeppe lenses) may allow better resolution of angle structures,41but successful indentation to view deeper into the angle is usually not possible.

Consistent and competent gonisocopy technique is required, such as conducting all examinations in a dark room, using a small, 1-mm slit-lamp beam away from the pupil, identifying the most anterior point of iris–angle contact, and avoiding inadvertent compression.42 It is helpful to characterize PAS as to their height (e.g., ‘to Schwalbe’s line’), regularity (e.g., ‘symmetric, tented PAS’ or ‘broad, shaggy PAS’) and circumferential extent (e.g., ‘from 3 to 6 o’clock’). Indirect estimations of angle embarrassment, such as the van Herick method,39 or tangential pen-light examination, are not by themselves sufficient for screening; slit-lamp gonioscopy is indis-

pensable, and preferably with indentation assessment (Figs. 15-1 and 15-2).43,44

The quintessential finding for a PAC suspect is that of iridotrabecular contact, a concept with greater specificity than ‘anatomically narrow angle’ or ‘occludable angle’ (although the latter term is still used in ICD-9-CM coding). A ‘narrow angle’ without contact, sometimes characterized as ‘occludable’, can imply for the clinician a predictive risk for closure which is not, in fact, substantiated by rigorous epidemiologically-derived criteria. The decision to proceed with iridotomy or surveillance requires a variety of factors to be considered: the patient’s access to care, whether the lens may soon require cataract surgery for visual reasons, the status of the fellow eye, the patient’s age and ethnicity, etc.

In the absence of iris–trabecular touch, it is imperative to estimate the angle depth.Though there are a variety of useful schemes to visually quantify the angle configuration (see Ch. 7), the Shaffer

assessment of 20° or less of an irido-trabecular angle appears to be a robust and inclusive benchmark.25,26 It is also crucial to empha-

size that gonioscopy in any PAC suspect needs to be repeated on a regular and recurrent basis as part of standard ophthalmic care.

Controversy remains regarding the extent of irido-trabecular contact in the definitions used to distinguish between ‘suspect’ and ‘closure’. At issue are the earliest effects and interplay of the two mechanisms, frequently co-existent, that are responsible for damage to the angle structures: (1) intermittent appositional abutment of iris to trabeculum, which can histologically manifest as degenera-

tion of meshwork tissue even in sites remote from PAS;45 and (2) PAS, whose extent correlates with levels of IOP elevation.46,47

The implications of precisely defining ‘suspect’ and ‘closure’ have real-world impact of great import, highlighting the eminent practicality of this classification and its flexibility for refinement over time. A ‘looser’ definition (e.g., 180° or less of touch) than the current criterion of 270° of irido-trabecular contact could classify

(A)

(B)

Fig. 15-2  Slit-lamp examination of the peripheral anterior chamber. (A) If the distance between the iris surface and the corneal endothelium is equal to the corneal thickness, the angles are likely to be deep. (B) Conversely, if the distance is less than one-fourth of the corneal thickness, the angles are likely to be narrow.

(Modified from van Herick W, Shaffer RN, Schwartz A: Am J Ophthalmol 68:626, 1969. Published with permission from The American Journal of Ophthalmology. Copyright by the Ophthalmic Publishing Company.)

up to 50% more eyes as diseased, requiring monitoring for PAS

or immediate treatment of elevated IOPs; epidemiologically speaking, this could pose an enormous burden.20,34 Another aspect of

this controversy is that using visible light – as is inherent in clinical gonioscopy – may be minimizing our perception of irido-trabecular contact, by unavoidably constricting the pupil and thus opening the angle to some degree. Hence our current instrumentation for clinically detecting the disease is underestimating the likelihood or extent of repetitive appositional iris–trabecular contact, which can cause chronic, cumulative trabecular damage.

There are those, however, who argue for the advantage of a lower threshold for characterizing PAC: by requiring less than 270° of irido-trabecular contact, detection is made more inclusive and attentive to early signs of angle embarrassment. In effect, this view prefers that the clinician be pre-emptive, and categorically assert that a patient does not have any stigmata of angle closure rather than, as is now done, tolerate findings that there is angle closure already underway. Earlier detection, so this line of thinking goes, might lead to earlier iridotomy treatment before the momentum of progressive disease occurs.48

But since we do not precisely know which eyes will progress to actual glaucoma despite early manifestations of narrow angles with or without trabecular dysfunction, the oft-assumed benign nature of laser iridotomy needs to be reconsidered. The first considera-

tion is that laser iridotomy therapy may, to some small extent, affect the lens and predispose to cataract formation.49–51 With the shunt-

ing of aqueous through a peripheral patent iridotomy, instead of its normal physiologic pathway through the pupil, there may be an adverse impact on overall lenticular metabolism.52 Moreover, focal tissue alterations have been seen following laser treatment. Small focal lenticular changes below the anterior capsule following yttrium-aluminum-garnet (YAG) iridotomy may predispose to long-term cataractous visual changes.53 Similarly, in marginally healthy corneas, the focal corneal endothelial loss sometimes seen following argon laser iridotomy may predispose to long-term focal or diffuse corneal decompensation.54–67

Yet another consideration is that a patent iridotomy is not necessarily effective in eliminating irido-trabecular touch,68 with one