Primary Angle-Closure Glaucoma
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In the past, variable and sometimes conflicting terminology has been used to describe different forms of angle-closure glaucoma. The problem arose from the fact that terminology was developed prior to the advent of indentation gonioscopy and laser iridotomy, when the mechanisms of angle-closure glaucoma were poorly understood. [1, 2]
In the era of surgical iridectomy, an attack of acute angle-closure glaucoma (AACG) could arise in an eye that had developed peripheral anterior synechiae (PAS) because of gradual angle closure prior to the development of the attack. Conversely, a prolonged acute attack or a series of subacute attacks could lead to progressive PAS formation. Patients undergoing surgical iridectomy were dilated routinely after surgery, and shallow anterior chambers were not uncommon. Patients undergoing surgical iridectomy for AACG who were dilated postoperatively and had shallow anterior chambers not infrequently formed PAS. [3, 4] Prolonged apposition or repeated subacute attacks lead to gradual PAS formation. These usually begin in the superior angle, which is narrower than the inferior angle, as pinpoint synechiae, reaching to the midtrabecular meshwork and gradually expanding in width. [5]
Primary angle-closure suspect (PACS) was defined as nonvisibility of the filtering trabecular meshwork for 180° or more in the absence of PAS with normal intraocular pressure (IOP). Primary angle closure (PAC) can be further classified as synechial or appositional. Primary (appositional) angle closure refers to an eye with raised IOP (>21 mm Hg) associated with obstructed filtering trabecular meshwork of more than 180° in the absence of PAS, disc damage, or field changes. On the other hand, primary (synechial) angle closure (PAC) refers to an eye in which portions of the anterior chamber angle are closed permanently by PAS with more than 180° of iridotrabecular contact with or without raised IOP. The term primary angle-closure glaucoma (PACG) is used to denote PAC eyes with glaucomatous optic nerve damage or visual field loss. [6]
Eyes with progressive PAS formation eventually may develop AACG when pupillary block results in closure of the remaining portions of the angle unaffected by PAS. However, many patients develop gradual angle closure, elevated IOP, and glaucomatous damage in the absence of symptoms. The presentation is similar to that of PACG, with progression of glaucomatous cupping and visual field loss. [7]
PAS also may form during an acute attack, remaining after iridotomy has opened the unaffected portions of the angle. These PAS are usually high and broad. When first observed at this stage, it is impossible to determine whether the PAS formed before or during the attack, or at both times.
In eyes with darker irides, a second mechanism of progressive angle closure is more common. The closure is circumferential and begins in the deepest portion of the angle. Closure occurs more evenly in all quadrants, so that the angle progressively becomes shallower. The appearance over time is of a progressively more anterior iris insertion. Lowe has termed this creeping angle closure. [8] The PAS gradually creep up the ciliary face to the scleral spur and then to the trabecular meshwork.
Combined mechanism glaucoma
Combined mechanism glaucoma refers to situations in which both open-angle and angle-closure components are present. Most commonly, angle-closure glaucoma is treated successfully with iridotomy, eliminating all appositional closure, and IOP still remains elevated, with or without the presence of PAS of any extent.
Conversely, an eye with open-angle glaucoma may later develop angle closure, either because of the natural development of pupillary block or because of exacerbation by miotic therapy.
Exfoliation syndrome commonly predisposes to combined mechanism glaucoma. [9] In this case, open-angle glaucoma can develop independently years after iridotomy for angle closure, with progressive blockage of the trabecular network. In all of these cases, the residual open-angle component is treated as open-angle glaucoma.
Mixed mechanism glaucoma
This term often is used interchangeably with combined mechanism glaucoma, but should not be, because it creates additional confusion. It is better to reserve this term to describe an eye with angle closure due to more than one contributory mechanism. When pupillary block is eliminated by iridotomy and the angle opens to a greater degree than before the iridotomy, an appositional closure remains on the basis of plateau iris, phacomorphic glaucoma, or malignant glaucoma, a mixed mechanism may be present.
Plateau iris
Plateau iris refers to an anatomic configuration in which the iris root angulates forward and then centrally. [10, 11, 12] The iris root often is short and inserted anteriorly on the ciliary face, so that the angle is shallow and narrow, with a sharp drop-off of the peripheral iris at the inner aspect of the angle. The iris surface is relatively flat and the anterior chamber is not unusually shallow.
When appositional angle closure develops in the presence of a patent iridotomy or iridectomy, either spontaneously or after pupillary dilation, in an eye with this anatomic configuration, plateau iris syndrome is present. [13] Some patients may develop AACG. The risk of postoperative pupillary dilation after iridectomy or iridotomy frequently is realized.
Until recently, plateau iris syndrome was considered rare. Two subtypes have been differentiated. In the complete syndrome, which is rare, IOP rises when the angle closes with pupillary dilation. In the incomplete syndrome, IOP does not rise. The differentiating factor is the height of the plateau with respect to the angle structures. If the angle closes to the upper meshwork or Schwalbe line, IOP rises because aqueous outflow is blocked completely, whereas, if the angle closes partially, leaving the upper portion of the filtering meshwork open, aqueous humor can still exit the eye. This condition is far more common, and its detection is important; these patients can develop PAS up to years after a successful iridotomy produces what appears as a well-positioned angle.
Plateau iris occurs because large and/or anteriorly positioned ciliary processes hold the peripheral iris up against the trabecular meshwork. [14, 15] Iris cysts also may cause a situation equivalent to plateau iris. When dynamic gonioscopy is performed in such an eye, the ciliary processes prevent posterior movement of the peripheral iris. As a result, a sinuous configuration results (ie, double hump sign), in which the iris follows the curvature of the lens, reaches its deepest point at the lens equator, and then rises again over the ciliary processes before dropping peripherally. Much more force is needed during gonioscopy to open the angle than in pupillary block because the ciliary processes must be displaced, and the angle does not open as widely. In a morphometric study of the ciliary sulcus, Orgul et al proposed that the displacement of the pars plicata from the peripheral iris to the iris root during embryogenesis may be incomplete in eyes of shorter axial length. [16]
Patients with plateau iris tend to be female, younger (30s-50s), and less hyperopic than those with relative pupillary block. They often have a family history of angle-closure glaucoma. Except in the rare younger patients (20s-30s), some element of pupillary block also is present. If plateau iris was not diagnosed before iridotomy and IOP is elevated postlaser, careful gonioscopy should be performed. If the angle is open, secondary damage to the trabecular meshwork or pigment liberation with dilation are the most likely causes. If the angle is closed, the differential diagnosis, besides plateau iris, should include malignant glaucoma, in which the anterior chamber is extremely shallow; PAS, which can be ruled out by dynamic gonioscopy; or incomplete iridectomy.
Miotic-induced angle-closure glaucoma
Prolonged miotic treatment in eyes with open-angle glaucoma and narrow angles may lead to pupillary block and angle-closure glaucoma. [17] PACG has been seen to develop after several years of miotic therapy in eyes that initially had wide-open angles. In some eyes, zonular relaxation occurs more readily than in other eyes, so that anterior lens movement and an increase in axial lens thickness may facilitate pupillary block and angle closure.
In other eyes, little change in the lens occurs, but progressively increasing pressure in the posterior chamber gradually pushes the peripheral iris against the trabecular meshwork. It is believed that eyes with exfoliation syndrome are particularly prone to develop miotic-induced angle closure. In these eyes, the iris is thicker and stiffer than normal because of deposition of exfoliation material within the stroma. In addition, zonular weakness allows the lens to move forward, leading to pupillary block.
Less commonly, miotic therapy can have a pronounced effect on lens position and trigger malignant glaucoma. [18, 19, 20] Unequal anterior chamber depths, a progressive increase in myopia, or progressive shallowing of the anterior chamber are clues to the correct diagnosis.
Worldwide
The worldwide prevalence of PACG among persons aged 40 years and older was estimated to be 0.69% in 2010, as compared to 1.96% for primary open-angle glaucoma (POAG), with China having the highest prevalence of PACG, at 1.26%. The number of people with PACG in the world was estimated to be over 15 million in 2010 (compared with >44 million for POAG), with 47.5% of these patients in China. By 2020, the number of patients with PACG in the world may increase to over 21 million. [21]
Europe and United States
The current evidence-based estimate of PACG prevalence in European-derived populations is suggested to be 130,000 people in the United Kingdom, 1.60 million people in Europe, and 581,000 people in the United States. Accounting for aging population structures, cases are predicted to increase by 19% in the United Kingdom, 9% in Europe, and 18% in the United States within the next decade. [22]
Asia
The overall pooled prevalence of PACG among adult Asians was 0.75%. Ethnicity-specific pooled prevalence estimates were 0.97% in the Middle East group, 0.66% in the Southeast Asia group, 0.46% in the India group, 1.10% in the China group, and 1.19% in the Japan group. [23]
Mortality/Morbidity
If IOP is not controlled, glaucomatous optic neuropathy and visual field loss may progress.
The prevalence of PACG appears to be highest among Chinese (1.26% among those ≥40 years), according to a review of worldwide statistics. The prevalence of PACG in whites of European ancestry is around 0.25%. The prevalence of PACG appears to be lowest among Africans and people of Middle Eastern ancestry (0.16%). [21]
Among the subtypes of angle closure, creeping angle closure is uncommon in whites, but it is much more prevalent in Asians, in whom it ranks high as a cause of blindness. Black patients with angle closure also tend to have this form.
Patients with PACG and plateau iris tend to be female.
Patients with PACG tend to be elderly, often with coexisting cataract or at least lens thickening.
Patients with plateau iris tend to be in their fourth to sixth decade of age.
The prognosis is favorable with control of the IOP. [24]
Factors associated with disease progression in PACG eyes include large IOP fluctuations [25] and a thin central corneal thickness. [26]
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Clement Chee-yung Tham, BM, BCh, MA, FRCS(Glasg) SH Ho Professor of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong; Honorary Chief-of-Service, Hong Kong Eye Hospital; Secretary General, Asia-Pacific Academy of Ophthalmology
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Consultancy: Alcon Laboratories Inc; Allergan, Inc; Bausch & Lomb; IOPtima Ltd.; Merck & Co Inc; Pfrizer Inc; Santen Pharmaceutical Co Ltd; Sensimed;C-MER Eye Care Holdings Ltd<br/>Serve(d) as a speaker or a member of a speakers bureau for: Lectures Fees: Alcon Laboratories Inc; Merck & Co Inc, Pfizer Inc; Santen Pharmaceutical Co, Ltd.<br/>Received research grant from: Aeon Astron Corporation; Alcon Laboratories Inc; AMO Asia Ltd; Icare Finland; Pfizer Inc; Santen Pharmaceutical Co Ltd; Sensimed; <br/>Travel Support for: Alcon Laboratories Inc; Allergan Inc; Merck & Co Inc; Pfizer Inc; Santen Pharmaceutical Co Ltd.
Robert Ritch, MD Shelley and Steven Einhorn Distinguished Chair in Ophthalmology, Chief of Glaucoma Service, Surgeon Director, Professor, Department of Ophthalmology, New York Eye and Ear Infirmary, New York Medical College
Robert Ritch, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Ophthalmological Society, Chinese American Medical Society, International College of Surgeons, New York Academy of Medicine, New York Academy of Sciences
Disclosure: Received none from Sensimed for board membership; Received none from iSonic Medical for board membership; Received consulting fee from Aeon Astron for consulting; Received honoraria from Pfizer for speaking and teaching; Received honoraria from Allergan for speaking and teaching; Received honoraria from Ministry of Health of Kuwait for speaking and teaching; Received honoraria from Aeon Astron for speaking and teaching; Received royalty from Ocular Instruments for other.
Noel C Y Chan, MBChB, FRCSEd, FCOphth(HK), FHKAM(Ophth) Physician Specialist, Hong Kong Eye Hospital; Honorary Clinical Assistant Professor, Department of Ophthalmology and Visual Sciences, Honorary Clinical Assistant Professor, Clinical Skills Learning Center, The Chinese University of Hong Kong, China
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Martin B Wax, MD Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Research and Development, Head, Ophthalmology Discovery Research and Preclinical Sciences, Alcon Laboratories, Inc
Martin B Wax, MD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, Society for Neuroscience
Disclosure: Nothing to disclose.
Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
Andrew I Rabinowitz, MD Director of Glaucoma Service, Barnet Dulaney Perkins Eye Center
Andrew I Rabinowitz, MD is a member of the following medical societies: Aerospace Medical Association, American Academy of Ophthalmology, American Society for Laser Medicine and Surgery, American Academy of Ophthalmology, American Medical Association
Disclosure: Nothing to disclose.
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