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Glaucoma 3: Angle Closure and Secondary Glaucomas

4T in Autralia | 1CD + 1G in New Zealand | 8 December 2018



In glaucoma detection and management, it is important to recognise forms other than primary open angle  glaucoma(POAG). These would include angle closure glaucoma and various common and not-so-common secondary glaucomas. These conditions may afflict patients differing from the POAG demographic, such as younger patients, and may have a greater risk for visual disability.

Learning Outcomes

• Classes currently recognised for primary angle closure
• Epidemiology of angle closure glaucoma and societal burden of the disease
• Clinical characteristics of angle closure glaucoma and the therapeutic intervention for various types of the disease
• Clinical features and management of patients with exfoliative glaucoma
• Clinical features and management of patients with pigmentary glaucoma
• Clinical features and management of patients with neovascular and uveitic glaucoma.


Angle closure glaucoma is a heteronymous group of conditions. It is a severe type of glaucoma caused by the apposition of the iris to the trabecular meshwork, obstructing the outflow of aqueous, due to forces acting
at four successive anatomic levels: the iris (pupillary block), the ciliary body (plateau iris), the lens  (phacomorphic glaucoma), and vectors posterior to the lens (malignant glaucoma).

Historically, the term, ‘narrow angle glaucoma’ has been used to describe this condition. It is an antiquated and incorrect term to use. The presence of a narrow angle does not cause intraocular pressure (IOP) to elevate. The angle is either open or closed. It is more appropriate to discussangle closure glaucoma and abandon the term “Narrow angle glaucoma”.

Current terminology recognises four categories of primary angle closure; 1) primary angle closure suspect, 2) primary angle closure, 3) primary angle closure glaucoma, and 4) primary angle closure attack.

Primary angle closure suspects are very common and have the pigmented trabecular meshwork (TM) blocked by the iris for at least 1800, but there is no peripheral anterior synechiae (PAS) and the optic disc, retinal nerve fibre layer, and IOP are all normal. These are the patients encountered who have potentially occludable angles only. It is not clear if laser peripheral iridotomy (LPI) or observation is better for these patients.

Primary angle closure occurs when the pigmented TM is blocked by iris for at least 1800, and there is either PAS or elevated IOP (or both) as well. However, there is no disc damage or visual field loss. This condition is considered pathologic and LPI has historically been recommended.

Primary angle closure glaucoma occurs when the pigmented TM is blocked by iris for at least 1800, there is elevated IOP and often PAS and glaucomatous optic neuropathy and visual field loss also is present. In these cases, Laser peripheral iridotomy (LPI) is typically recommended and medical therapy may also be

Finally, there is the well known primary angle closure attack, where there is near complete apposition of iris to pigmented TM and the patient presents symptomatically with ocular redness, vision loss, nausea, emesis, halos around lights, corneal oedema, elevated IOP, inflammation, and a mid-dilated fixed pupil.

While any person can experience acute angle closure glaucoma (AACG), this condition is most common in patients of Asian descent.1-6 Patients are more likely to be older, hyperopic and female.2-8

The etiology of angle closure in young individuals differs from the older population and is typically associated with structural and developmental anomalies.9

Patients with acute angle closure glaucoma manifest the signs and symptoms of ocular and facial pain, unilateral blurring of vision, photopsia in the form of coloured haloes around lights, and occasionally nausea and vomiting. Acuity may be reduced significantly in the involved eye, often to 20/80 or worse.6,10,11 Acute angle closure glaucoma is frequently unilateral, but may be bilateral and, as a rule, should always be considered to have bilateral potential, though the timing of the fellow eye involvement may be different.2,3

The hallmark signs of AACG include significantly elevated IOP, virtually no visible anterior chamber angle structures upon gonioscopy, deep conjunctival and episcleral injection in a circumlimbal fashion, and a fixed, mid-dilated pupil. Biomicroscopically, there typically will be an oedematous or ‘steamy’ cornea and shallow anterior chamber. There may be a flat anterior chamber, or significant iris bombé, depending upon the mechanism of the angle closure.


Figure 1: Profound corneal oedema and inflammation from elevated IOP in acute angle closure glaucoma attack.

Applanation tonometry reveals IOP in the range of 30 to 60mmHg, occasionally higher in some cases.12-14 Gonioscopy, which may prove difficult because of microcystic corneal oedema, reveals no visible angle structures without indentation. There may be evidence of previous angle closure episodes in the form of peripheral anterior synechiae (PAS) in the involved or fellow eye as well as Glaukomflecken, which is  ecrotic
lens capsule resulting from acute IOP elevations.15,16

Figure 2: Glaukomflecken

Figure 3: Narrow Van Herick angles

Medication history is important in patients with AACG as the attack may be medically induced. Of particular
importance is the use of the sulfabased anti-epileptic medication Topiramate (Topamax; Ortho-McNeil Pharmaceutical, Raritan, NJ). Topiramate has been associated with the development of acute angle closure
glaucoma (unilateral and bilateral) and acquired myopia in patients previously not at risk for angle closure.6,17-21

Anatomically, patients with AACG have smaller eyes. It has been shown that these patients have axial lengths 5 per cent shorter, lenses that are 7 per cent thicker, anterior chambers that are 24 per cent shallower, and anterior chambers with 37 per cent less volume than other agematched individuals.22 It has been shown that eyes undergoing acute angle closure have greater iris thickness, contributingto a shallower anterior chamber.23,24 There is a high resistance to forward movement of aqueous through the irislens channel due to a tight apposition between the posterior iris and anterior lens capsule. This resistance is known as relative pupil block. Pupil block is a normal physiological phenomenon occurring in virtually every phakic person. In some cases, this resistance becomes pathological and results in AACG. In these individuals, there is an increased pressure differential between the anterior and posterior chambers with resultant angle closure. When this occurs, there is a marked bowing forward (convexity) of the iris, termed iris bombé.

Angle closure occurs when the peripheral iris physically opposes the pigmented TM and impedes aqueous outflow. Several mechanisms are possible. This may be simply due to genetic predisposition and anterior segment anatomy (primary pupil block), or from sources of secondary pupil block such as posterior synechiae, iris neovascularisation, aqueous misdirection syndrome, lenticular enlargement or displacement of the crystalline lens or IOL.1,25

Another mechanism, which may induce angle closure, involves an abnormal configuration of the iris, the so-called ‘plateau iris syndrome’. Patients with this presentation may boast a deep anterior chamber centrally; however, the iris demonstrates an unusual laxity, coming into close approximation with the angle peripherally. These patients may be prone to ‘angle crowding’ and subsequent closure during physiologic or
pharmacologic dilation.25

Expansion of the choroid appears to be a significant contributory factor for AACG in some cases.21,26-28 Ultrasound biomicroscopy has clearly demonstrated ciliochoroidal expansion as well as shallow choroidal effusions in patients undergoing angle closure attacks. This is associated with anterior rotation of the
ciliary body as well as forward movement of the iris and lens with subsequent shallowing of the anterior chamber and closure of the angle.6,21,26-29 Due to expansion of the choroid and ciliary body oedema (with possible choroidal effusion), there is a relaxation of the lens zonules with increased laxity and thickening of
the lens. Along with the angle closure glaucoma, there is refractive error shift with several diopters of acquired myopia. The clinical picture of choroidal expansioninduced AACG differs from that seen in primary pupil block in that there is a flat anterior chamber without iris bombé.

Choroidal expansion induced angle closure glaucoma has also been reported frequently due to administration of sulfabased medications such as sulfonamide, acetazolamide, topiramate and hydrochlorothiazide. Topiramate, which is used to manage chronic headache as well as induce weight loss, among other uses, has been strongly implicated in choroidal expansion induced bilateral angle closure glaucoma along with induced myopia.21,28 The theorised mechanism may be an inflammatory sulfa-allergic reaction.6

Figure 4: Optical coherence tomographic image of a flat anterior chamber and angle closure from ciliochoroidal expansion.

Properly managing any pupil block angle closure attack is to alter the physiologic mechanisms that cause the cornea to appose the trabecular meshwork.1 In primary pupil block, the tight apposition of the posterior iris to the anterior lens surface in the middilated state must be broken. This is done by lowering the IOP so that the iris can function normally and move from this mid-dilated, pupil-blocking state. This must be done quickly, as structural damage to the nerve fibre layer and trabecular meshwork, and functional damage to the visual field, can occur within a very short period of time.11,12,30

Choice of primary medication depends upon the pressure at presentation. As most miotics are ineffective at pressures over 40mmHg due to iris ischemia, aqueous suppressants such as topical beta-blockers, alpha-2 adrenergic agonists and carbonic anhydrase inhibitors should be used initially.30-32 While effective
for eyes with chronic angle closure, prostaglandin analogs are too slow to be effective in acute situations.33-37

Once the IOP is below 40mmHg, topical pilocarpine 1-2 per cent can be used to miose and reopen the angle. Higher concentrations of pilocarpine should be avoided as they can lead to uveal congestion and actually worsen the condition. Topical steroids such as prednisolone acetate 1 per cent can be used for the resultant inflammation. If the patient does not achieve significant reduction in IOP after 60 minutes, an oral carbonic anhydrase inhibitor (acetazolamide 2 x 250mg tablets) can be employed. A hyperosmotic agent such as three to five ounces of oral glycerin over ice may also assist in lowering the IOP and breaking the attack. It is safe to discontinue acute medical intervention when the IOP falls below 30mmHg and the angle
structures are again visible with gonioscopy. The patient should be maintained on the following medications until surgical therapy can be employed: pilocarpine 2 per cent and prednisolone acetate 1 per cent QID, a topical beta blocker and an alpha-2 adrenergic agonist BID.

The quintessential treatment for primary pupil block AACG is LPI.6,8,11,16,37-41 This should be performed as soon as safely possible. LPI will allow the aqueous fluid pressure to equilibrate between the posterior and anterior chamber. This will permit the iris to relax backward with dissipation of iris bombé allowing deepening of the anterior chamber opening of the angle, and aqueous access to trabecular drainage again. LPI should also be performed subsequently on any fellow eyes that are potentially occludable.42 Adjunctively, laser peripheral iridoplasty, an irido-retraction procedure, can be performed to physically pull the
iris taut and away from the trabecular meshwork. In fact, laser peripheral iridoplasty has been seen to be a safe, primary treatment for AACG.8,38,39 Incisional ocular surgery in the form of trabeculectomy, cataract extraction, cyclodestructive procedures, glaucoma implant and goniosynechialysis remain as options for cases unresponsive to medical and laser therapies.38,43-45 Trabeculectomy and goniosynechialysis are
often combined with cataract extraction.

In cases of AACG that are determined to be precipitated by a systemic medication, therapy is different. Often, discontinuation of the medication will resolve the attack. However, when the choroid contributes to angle closure glaucoma (which is often the mechanism of medicine-induced AACG), the use of a potent  cycloplegic agent such as atropine, as well as topical steroids, will allow for ciliary body relaxation and posterior rotation with resolution of the angle closure.6,17,21,26,27,29 Aqueous suppressants can be used concurrently, but miotics and oral carbonic anhydrase inhibitors should be avoided in these cases.

Following successful LPI, IOP may still be elevated secondary to damage to the trabecular meshwork caused by the prolonged or repeated iris-meshwork apposition.31 Persistent trabecular-iris contact or peripheral anterior synechia may block aqueous outflow, resulting in a progressive process in which Schlemm’s canal sustains endothelial damage with subsequent canal occlusion. Trabecular cell damage may also produce impairment of mitochondrial function and subsequent fusion of the trabecular beams.46 These changes may be the reason for residual glaucoma after laser iridotomy or cataract surgery. For this reason, long-term medical therapy may be necessary. Aqueous suppressants are a good choice and it appears that prostaglandin analogs also work especially well.31-34

The abrupt IOP elevation in AACG rapidly causes structural alterations. It has been shown with optical coherence tomography (OCT) that there is an increase in retinal nerve fibre layer (RNFL) thickness immediately after the acute attack, with subsequent atrophy months later.47-51 This can explain later-onset visual field and RNFL damage. The acute attack has been shown to cause disc pallor, RNFL atrophy and visual field loss, but not necessarily an increase in focal disc damage.51,52

Clinical Pearls

•    When managing patients in acute primary angle closure, remember that your goal is not to reduce the IOP, but to change the angle anatomy. Pressure reduction is merely part of the process.
•    The typical profile of an angle closure glaucoma patient is an older, hyperopic female. Asian descent increases the risk greatly.
•    There is popular thinking that for patients with primary acute angle closure that the best approach may be to medically break the attack if possible and quiet the eye and then schedule the patient for lens removal within the next month if they are stable, bypassing LPI altogether. However, this is not currently being widely performed.

While practitioners are well aware of the classic appearance of AACG, this condition represents only about 20 per cent of angle closure glaucoma. Much more common is primary chronic angle closure glaucoma (PCACG), representing 80 per cent of all angle closure cases. Patients with PCACG present  asymptomatically and are often discovered during routine eye examination. It is often mistaken for POAG if practitioners do not perform gonioscopy.

Biomicroscopically, there will be a shallow anterior chamber and narrow angles by Van Herick estimation method. However, the central chamber depth is typically deeper in PCACG than primary acute angle closure glaucoma. There will be characteristic glaucomatous damage to the retinal nerve fibre layer, optic disc and visual field. The distinguishing characteristic is the absence of gonioscopically visible anterior chamber angle structures. The angle may be appositionally closed and able to be opened upon manual pressure with a 4-mirror goniolens or the angle may be closed with broad areas of PAS. The superior and temporal quadrants of the anterior angle may be the earliest sites of synechial angle closure, with gradual extension to the nasal quadrant, until the angle closes in the inferior quadrant.53

Chronic angle closure denotes an angle with areas that are closed permanently with PAS. In angles that have closure without the formation of PAS, the term chronic appositional closure is often used. However, over time appositional closure will lead to PAS if unaddressed. In PCACG, the IOP may be initially normal, elevating asymptomatically as more of the angle becomes compromised. Peripheral anterior synechiae may occur after acute or subacute attacks of angle closure.

While in most cases, there is asymmetric closure (involving the superior angle first), there can also be an even, circumferential process that slowly progresses to symmetrical closure. This has been termed creeping angle closure and appears as an angle that becomes progressively more shallow over time.54 In
PCACG, pupillary block is not as strong a force as it is in acute primary angle closure. Thus, there is minimal iris bombé. There is more of a multi-mechanism with some degree of pupillary block as well as an anteriorly located lens and forward-rotated ciliary body that causes shallowing of the anterior chamber and an overall congestion of the angle leading to progressive synechial closure. Other features of PCACG that lead to angle
closure and subsequent PAS include a smaller corneal diameter, shorter axial length, shallower anterior chamber, swelling of ciliary process and anterior rotation of ciliary body.55,56

Primary angle closure, resulting from any degree of pupil block, is typically treated with LPI. However, while LPI can alter the anatomic status of the angle, a significant number of these patients will manifest residual angle closure after LPI from PAS.57 Additionally, there often will be elevated IOP despite a laser-induced open anterior chamber angle.58 This is due to damage to the trabecular meshwork from appositional and synechial closure. In PCACG eyes, the trabecular architecture has lost its regular arrangement, with fewer and narrower trabecular spaces and fusion of the trabecular beams in areas. In addition, there is evidence of loss of endothelial cells and reactive repair processes.59

Despite the presence of a patent LPI, most eyes with PCACG present with elevated IOP, optic disc and visual field damage, indicating that further treatment is required to control IOP, including possibly trabeculectomy and medical therapy.

Medical therapy that has been successful in lowering IOP in eyes with PCACG include beta blockers, miotics, alpha-2 adrenergic agonists, and prostaglandin analogs(PGAs).60,61 However, in recent years, it has come to light that PGAs are especially efficacious in eyes with PCACG that need IOP reduction both before and after LPI.62-65

Aung et al. noted that the IOP-reducing efficacy of latanoprost was not affected by the degree of angle  arrowing or extent of synechial angle closure.66 In a study of 14 eyes with PCACG and total occlusion of the angle by 360 degrees (evidenced by ultrasound biomicroscopy) secondary to PAS with no visible ciliary body face, once-daily dosing with latanoprost achieved a significant reduction in IOP.66 Medically speaking, it appears that PGAs are the most efficacious class of ocular hypotensive agents to use in PCACG.

Lens removal is now being seen as a primary treatment for chronic angle closure glaucoma and may become the preferred treatment. If cataract is present, then lens removal is a clear choice. However, if there is no cataract, then the choice is not as clear. Recently released results of The Effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) study, a prospective, randomised clinical trial, indicated that clear lens removal is a viable option. It compared the safety and effectiveness of LPI and medical therapy to clear lens extraction for patients with newly diagnosed chronic angle closure glaucoma. It involved the removal of clear lenses in eyes with PACG with IOP > 21mm or eyes with PAC (without glaucoma) and IOP > 30mm. Patients undergoing phacoemulsification lens extraction had far fewer IOP controlling meds than those undergoing LPI. Only one patient needed trabeculectomy after phacoemulsification whereas 24 patients in the LPI group needed trabeculectomy ultimately.67 It is becoming increasingly evident that the best surgical procedure for PCACG (and possibly for acute cases as well), is removal of the patient’s crystalline lens.

Another form of chronic angle closure that should be mentioned is plateau iris syndrome. This is a primary condition of any eye with a deep anterior chamber and narrow angle due to large last role of the iris, which is draped over forward displaced ciliary processes.

The angle remains either closed or potentially occludable following LPI. Plateau iris syndrome can only be diagnosed following laser peripheral iridotomy (LPI) performed either in prophylaxis of an occludable angle or as part of therapy for angle closure glaucoma. Despite the presence of a patent LPI, the angle remains occludable or actually closed. The ciliary processes provide structural support beneath the peripheral iris, preventing the iris root from falling away from the trabecular meshwork after iridotomy. An anatomical forward position of the ciliary processes keeps the peripheral iris root in apposition to the trabecular meshwork, consequently preventing the posterior repositioning of the iris following iridotomy, resulting in a persistent post-procedure narrow angle. The mechanism of glaucoma in plateau iris syndrome is primary angle closure without pupil block. A significant percentage of cases of chronic angle closure are actually plateau iris syndrome.

Lens removal typically does not resolve this situation. Miosis induced through pilocarpine use can improve the anatomic relationships, but rarely is a long-term solution. Argon laser iridoplasty has been seen as the most definitive treatment to pull the iris away from the trabecular meshwork.

A newer treatment for plateau iris syndrome is endoscopic cilioplasty. The goal is to change the architecture of the ciliary processes. Based on imaging studies, plateau iris patients have a narrow angle for the most  part because the ciliary processes are large and anteriorly displaced, so that they push the peripheral iris anteriorly. Cilioplasty aims to correct this situation by shrinking the ciliary processes and orienting them more posteriorly. Cilioplasty changes the architecture of the ciliary processes and widens the angle.


Exfoliative Glaucoma

Exfoliative glaucoma is a secondary glaucoma and considered the most commonly identified open angle glaucoma worldwide. Exfoliative glaucoma is predominantly a disease of the elderly and is rarely found in patients younger than 50 years. The highest prevalence rates have been found in patients over the age of 70 years.68-70

Patients present with a fine, flaky material on the anterior lens capsule at the pupillary margin. Over time, this will coalesce into the characteristic ‘bullseye’ pattern typically seen in exfoliation syndrome. There will be a central area on the lens capsule of exfoliative material, surrounded by a ‘clear’ area where the material has been eroded by the iris contracture, which itself is surrounded by a peripheral area of exfoliative material. This classic pattern is usually only observable when the patient’s pupil is dilated. Beyond the anterior lens surface, exfoliative material is most commonly seen accumulating at the pupillary margin. This may be visible in an undilated state. Pigment loss from the pupil margin with subsequent pigment granular  deposition on anterior chamber structures is a hallmark of the condition. This leads to increased transillumination of the iris at the pupillary margin, termed peripupillary transillumination defects. There may
be pigment granules on the corneal endothelium and iris surface. Within the angle there may be observable pigment, clear flaky material, or both.

Figure 5: Exfoliative material on the anterior lens surface.

Exfoliation involves the production and accumulation of an abnormal fibrillar extracellular material within the anterior chamber of the eye.71,72 The accumulated material consists of a fibrillar component and an amorphous component, though the exact chemical composition remains unclear. It appears that the  material represents abnormal basement membrane secreted by all structures within the anterior chamber and deposited on the anterior lens capsule, iris surface, and trabecular meshwork. Due to accumulation of material at the pupillary margin, there is increased lenticular apposition with the iris and subsequent erosion of iris pigment as the pupil dilates and constricts. This leads to increased iris transillumination and deposition of pigment granules on the endothelium, iris surface, and trabecular meshwork similar to pigment dispersion syndrome. The iris will also rub this material off the lens surface, with a mid-peripheral clear zone. As this is a condition that involves deposition of material on the anterior lens capsule, and not flaking-off of the lens capsule, lens removal is not curative.

The development of glaucoma typically occurs due to a build-up within the trabecular meshwork of pigment granules and exfoliative material. The primary cause of IOP elevation appears to be phagocytosis of accumulated pigment and material by the trabecular cells and Schlemm’s canal cells with subsequent degenerative changes of Schlemm’s canal and trabecular meshwork tissues. Thus, this is a secondary open angle glaucoma mechanism.

Genetic studies have identified a highly significant association between several polymorphisms in the lysyl oxidase-like 1 (LOXL1) gene in both exfoliation syndrome and exfoliative glaucoma, occurring in almost 100 per cent of exfoliative patients worldwide. LOXL1 is a pivotal cross-linking enzyme in extracellular matrix  metabolism and seems to be specifically required for elastic fibre formation and stabilisation. This suggests that LOXL1 enzyme function and expression are abnormal and thereby play a role in glaucoma development,
possibly due to abnormalities in the lamina cribrosa.73,74 There is evidence for an exfoliation-specific elastinopathy of the lamina cribrosa, resulting from a primary disturbance in LOXL1 regulation, possibly making exfoliative eyes more vulnerable to pressure-induced optic nerve damage and glaucoma  development and progression.73,74

Exfoliation syndrome without intraocular pressure rise requires periodic monitoring of the IOP, discs, nerve fibre layer, and visual fields due to possible later development of IOP elevation. Multiple IOP readings to establish a diurnal pressure curve is especially important as patients with exfoliation syndrome and exfoliative glaucoma demonstrate great variations in IOP. A significant number of exfoliative glaucoma patients demonstrate a peak IOP, at times outside normal office hours.

Exfoliative glaucoma is medically treated in the same manner as POAG. It must be remembered that exfoliative glaucoma can be a particularly aggressive form of open angle glaucoma. It appears that exfoliative eyes are more likely than eyes with POAG to show progressive disease, even at similarly treated IOP levels.

The clinician may use, if not systemically contraindicated, topical beta-blockers, topical carbonic anhydrase inhibitors, prostaglandin analogs, and alphaadrenergic agonists. However, the IOP in exfoliative glaucoma is typically higher than in POAG and is more difficult to temporise. Typically, a greater amount of medical therapy is needed to control patients with exfoliative glaucoma compared to POAG patients. Selective laser trabeculoplasty is a viable treatment option, often showing a greater effect than in eyes with POAG.75 Invasive procedures, such as trabeculectomy and drainage implant surgery, are viable management options.

Clinical Pearls

•    Pseudoexfoliative/ Exfoliative glaucoma is more severe than primary open angle glaucoma. More medications and surgery are needed to control exfoliative glaucoma than POAG. Pseudoexfoliative glaucoma is one of the worst chronic open angle glaucoma types to be encountered regularly in clinical practice.
•    Exfoliative material is easily missed without a dilated lens evaluation.
•    The transillumination defects in pigmentary glaucoma are mid-peripheral and are peri-pupillary in pseudoexfoliation syndrome.
•    Occasionally, patients with diagnosed ‘POAG’ develop peripupillary TIDs and eventually clinically visible exfoliative material. Thus, the patients likely always had exfoliative glaucoma. Always look for the development of pseudoexfoliative material in older, at risk patients.

Pigmentary Glaucoma

Pigmentary glaucoma (PG), a sequela of pigment dispersion syndrome, is asymptomatic. Patients with pigment dispersion syndrome and pigmentary glaucoma demonstrate liberation of iris pigment within the anterior chamber. Often, this is seen as diffuse accumulation or possibly a granular brown vertical band along the corneal endothelium known as a Krukenberg’s spindle. Pigment accumulation may also be evident on the lens and the surface of the iris.76,77

Figure 6: Mid-peripheral transillumination defects of the iris.

Dense pigmentation is seen gonioscopically, often covering the trabecular meshwork for 360 degrees. It is most prominent in the inferior quadrant due to gravity. When pigment accumulates on Schwalbe’s line, it is referred to as Sampaolesi’s line. The angle recess remains unchanged and open. Radial, spoke-like transillumination defects of the midperipheral iris are common.76,77

Figure 7: Dense trabecular meshwork pigmentation in pigmentary glaucoma. 

Pigment dispersion occurs as a result of the proximity between the posterior iris pigment epithelium and the zonular fibres of the lens. The abrasive nature of this physical contact leads to mechanical disruption of the iris surface and release of pigment granules into the posterior chamber, which follows the flow of the aqueous convection current into the anterior chamber angle.

Many patients with pigment dispersion syndrome and pigmentary glaucoma demonstrate a concave approach of the iris as it inserts into the anterior chamber angle, giving the iris a ‘backward bowed’ appearance on gonioscopy. This posterior bowing of the iris places the posterior iris into apposition with the lens zonules. As the iris responds to light, iridozonular friction results in pigment liberation from the posterior iris. Sometimes, the degree of pigment loss in the mid-peripheral areas produces visible transillumination defects corresponding to packets of iris zonular fibres. While the majority of these patients have a concave iris approach, others may have a flat or planar approach and the mechanisms are less clear.78,79

Interestingly, physical blockage of the trabecular meshwork by pigment granules is not the likely cause of the
pressure rise. Endothelial cells lining the trabecular beams of the trabecular meshwork quickly phagocytise small amounts of accumulated pigment preserving the normal architecture of the trabecular meshwork.  However, in chronic cases of pigment dispersion, greater amounts of pigment are more difficult for the cells to phagocytise. When this occurs, the endothelial cells that line the trabecular meshwork beams disintegrate. The resultant degeneration of the trabecular meshwork with the accumulation of debris, collapsed beams and loss of intratrabecular spaces is what produces the rise in IOP. The IOP rise in pigmentary glaucoma mostly occurs due to a breakdown of normal phagocytic activity of the endothelial cells
and subsequent loss of normal trabecular architecture and function.80,81

As pigment dispersion syndrome has no direct ramifications on ocular health or vision, other than potential future development of pigmentary glaucoma, these patients should be treated as glaucoma suspects.  Patients should be monitored for IOP spikes and optic nerve changes three to four times a year, with threshold visual fields, diagnostic imaging, and gonioscopy performed annually. One study noted the  conversion rate from pigment dispersion syndrome to pigmentary glaucoma to be 20 per cent, with the vast majority converting within 10 years from the diagnosis of pigment dispersion syndrome.82 However, patients with pigment dispersion syndrome who were followed for greater than 10 years without developing pigmentary glaucoma had a low risk of developing pigmentary glaucoma subsequently.82 Another study noted the risk of developing pigmentary glaucoma from pigment dispersion syndrome was 10 per cent at five years and 15 per cent at 15 years. Young, myopic men were more likely to convert to pigmentary glaucoma, and an IOP greater than 21mmHg at initial examination was associated with an increased risk of conversion.83

Medical treatment of pigmentary glaucoma involves reduction of IOP with aqueous suppressants. Prostaglandin medications have been seen to successfully lower IOP in eyes with pigment dispersion from pseudoexfoliative glaucoma. Thus, prostaglandin medications are a good therapeutic option for pigmentary glaucoma.

Patients with pigmentary glaucoma tend to respond well to argon laser trabeculoplasty, presumably due to the improved thermal effects on trabecular tightening, secondary to the increased meshwork pigmentation. There appears to be little published data regarding the efficacy of selective laser trabeculoplasty (SLT) in pigmentary glaucoma. However, since SLT works by creating inflammation where the immune system effectively cleans the spaces between the trabecular beams and since the mechanism of pigmentary glaucoma is secondary to trabecular beam damage, it would seem logical SLT would not be effective. In one series involving four patients, it was seen that a paradoxical post-SLT IOP elevation was a serious adverse
event.84 Trabeculectomy remains an option for patients with recalcitrant pigmentary glaucoma.

Clinical Pearls

•    There are many patients with pigment dispersion who do not develop glaucoma. However, be aware that there is a significant diurnal variation in IOP with PDS/PG and you must monitor PDS patients frequently.
•    Pigmentary glaucoma (and PDS) is different in African-American patients. There may not be transillumination defects or endothelial pigment. In fact, this is often overlooked as a cause of glaucoma in African-American patients.


Neovascular Glaucoma

Neovascular glaucoma (NVG) typically presents in patients with a chronically red, painful eye, which often  has significant vision loss. The majority of patients will have presenting acuity of less than 20/200.85 Further, there will be significant concurrent vascular disease such as diabetes, hypertension, carotid artery disease, or giant cell arteritis (GCA).86-88 There frequently is an antecedent history of a retinal vessel occlusion, carotid artery disease, chronic retinal detachment, or advanced diabetic retinopathy. In that patients typically have precipitating ischemic vascular disease, NVG is often found in older patients. Diabetes is the most common precipitating cause of NVG.89,90

There will be visible neovascularisation of the iris (NVI) and angle (NVA). Only rarely will NVA develop without NVI. The patient will typically have significant corneal oedema, anterior segment inflammation, anterior  chamber cell and flare reaction, and elevated IOP, often exceeding 60mmHg.88-90 Gonioscopically, there will be total or near-total angle closure with massive areas of PAS and neovascularisation of the angle. In early cases, microhyphema may be seen gonioscopically. Funduscopically, there will often be evidence of retinal vessel occlusion (either artery or vein), diabetic retinopathy, ocular ischemic syndrome, or another condition stimulating retinal ischemia.

In ischemic retinal disease, hypoxia induces vascular endothelial growth factor (VEGF), an angiogenic  peptide, which acts upon healthy endothelial cells of viable capillaries to stimulate the formation of a fragile new plexus of vessels (neovascularisation).91,92 In cases of extreme retinal hypoxia, there are essentially very few viable retinal capillaries available. Such is the case with ischemic central retinal vein occlusions. In that instance, VEGF is theorised to diffuse forward to the nearest area of viable capillaries, namely the  posterior iris. Neovascularisation buds off of the capillaries of the posterior iris, grow along the posterior iris, through the pupil, along the anterior surface of the iris, and then into the angle. Initially, invasion of the anterior chamber angle by a fibrovascular membrane obstructs aqueous outflow in an open-angle fashion. Once in the angle, the neovascularisation, along with attendant fibrovascular support membrane, acts to both physically block the angle as well as bridge the angle and physically pull the iris and cornea into apposition, thus blocking the trabecular meshwork. Peripheral anterior synechiae with permanent angle closure happens quickly. The pressure rise in NVG is from secondary angle closure without pupil block. Due to the extremely elevated intraocular pressure, there will be a modest amount of inflammation.

Neovascular glaucoma frequently results in a blind, painful eye. For this reason, prompt and aggressive therapy is mandated. This involves control of the intraocular pressure as well as management of the retinal ischemia as well as any precipitating conditions.

Upon first presentation, a topical cycloplegic such as atropine 1 per cent BID as well as a topical steroid such as prednisolone acetate 1 per cent (Pred Forte), QID should be prescribed. This will greatly add to patient comfort. Aqueous suppressants may be used in order to temporarily reduce IOP. Chronic medical therapy is not indicated for neovascular glaucoma. Aqueous suppressants will temporise IOP and lead to a false sense of security, as the neovascular process will continue with further angle closure.

Management of anterior segment neovascularisation and NVG involves eradication of the vessels. This is best accomplished with pan-retinal photocoagulation (PRP) to destroy ischemic retina, minimise oxygen demand of the eye, and reduce the amount of VEGF being released. PRP tends to be effective in causing regression and involution of anterior segment neovascularisation.

While PRP is the most definitive treatment for the neovascularisation causing NVG, the advent and use of antiangiogenic drugs has proven to be a valuable adjunct. Intravitreal bevacizumab (Avastin) has been demonstrated to cause prompt and thorough regression of anterior segment neovascularisation in NVG.93,94 Regression can be significant and occur within a period as short as one day following injection. Additionally, further formation of PAS can be halted. However, while superficial vessel formation can be  halted, deep stromal neovascularisation may be less affected. Additionally, neovascularisation can recur
following antiangiogenic injection if the causative factor is unaddressed. For that reason, antiangiogenic therapy should only be considered a valuable adjunct along with laser photoablation in the management of NVG.

Clinical Pearls

•    Definitive treatment of NVG typically will begin immediately with atropine, steroids, and aqueous suppressants. Following that, the patient will likely be treated with intravitreal anti-VEGF injection followed by PRP. Often, the patient will then undergo either trabeculectomy with mitomycin C or a tube implant procedure.
•    Medically treating neovascular glaucoma is like arranging deck chairs on the Titanic.
•    Treatment of the causative ischemic stimulus is necessary in every stage of NVG.
•    When examining a patient for early signs of anterior segment neovascularisation, look carefully at the pupil border. In early cases, NVI manifests not as blatant vessels, but a fine reddish hue around the pupil margin.

Uveitic Glaucoma

Patients with uveitic glaucoma typically fall into two categories; those that develop acute anterior uveitis replete with pain, photophobia, and lacrimation, and those experiencing lesser symptoms from chronic uveitis.95-97 Younger patients usually demonstrate greater amounts of inflammation with uveitic glaucoma
developing secondary to acute disease. Older patients frequently demonstrate lesser amounts of  inflammation with glaucoma developing more often from chronic disease, often with contributory long-term steroid use.95-97 The increased prevalence of glaucoma in chronic uveitis reflects the cumulative effects of inflammation and steroid use. In older patients, minimal amounts of inflammation may overcome a trabecular meshwork with declining function. In younger patients, severe inflammation is usually necessary to overcome a healthy, functional trabecular meshwork.

Biomicroscopically, there will be varying levels of inflammation, from few inflammatory cells and flare in chronic anterior uveitis (often in older patients) to plasmoid aqueous in acute disease in younger patients. Structural changes, such as posterior synechiae, secluded pupil with pupil block and iris bombé, angle closure, and PAS, are all possible findings. IOP elevation may be modest, not requiring intervention, or dramatic with possible rapid retinal nerve fibre layer (RNFL), optic disc, and visual field damage ensuing.

There are a plethora of possible pathophysiologic mechanisms accounting for the elevation of IOP in  patients with uveitis. Secondary IOP elevation occurs from abnormal aqueous humour dynamics precipitated by increased protein content and increased aqueous viscosity. This, combined with other factors, leads to a reduction in outflow through the trabecular meshwork.

Gonioscopy is crucial in determining the precise mechanism of uveitic glaucoma. In cases of extensive posterior synechiae, the pupil becomes secluded, leading to pupil block, iris bombé, and secondary angle closure, with PAS forming quickly. However, pupil block and iris bombé are not required for a patient with uveitis to develop synechial angle closure. Due to sticky inflammatory debris accumulation and fibrin membrane formation in the angle itself, PAS form and extend in a zippering, rapidly creeping fashion producing angle closure by creating an environment which allows the iris to be ‘stuck’ against the Schwalbe’s line of the cornea.

In yet another possible mechanism, the trabecular meshwork outflow can be impeded both by the accumulation of inflammatory cells as well as the inherent outflow infacility of proteinacious aqueous humour in patients with excessive flare. This glaucomatous mechanism is secondary open angle glaucoma. Flare is more of a factor in the development of IOP elevation than the amount of inflammatory cells as outflow facility is greatly reduced in patients with excessive amounts of aqueous protein, irrespective
of the number of inflammatory cells.98 This is due to increased viscosity of the aqueous humour. The source of the increased protein content found in the aqueous humour of patients with uveitis is from dilated vessels in the iris and ciliary body, as a result of the inflammatory cascade.

Accumulation of inflammatory cells can unquestionably impede aqueous humour outflow through the trabecular meshwork. However, the inflammatory cellular debris also leads to cellular depopulation of the trabecular meshwork. This is more significant than simple blockade of the trabecular meshwork by inflammatory cells. Though unsubstantiated by histological evaluation, there may be direct inflammation of the trabecular meshwork itself (trabeculitis), leading to a decreased ability to filter aqueous humour. This is suggested by conditions such as glaucomatocyclitic crisis, where the IOP may be dramatically elevated
despite minimally detectable anterior chamber inflammation.

Figure 8: Acute anterior uveitis and secondary glaucoma

Finally, corticosteroids may also contribute to the IOP rise in uveitic glaucoma. While a clinically significant steroid-induced rise in IOP may take several weeks, the response may be shorter in cases involving uveitis where abnormalities in the trabecular meshwork and alteration of aqueous humour composition and dynamics are already occurring. Control of inflammation is necessary to successfully manage uveitic  glaucoma. In acute anterior uveitis with heavy amounts of inflammation, loading doses of a potent steroid such as prednisolone acetate 1 per cent Q30 minutes for several hours, followed by hourly administration while awake until initial follow-up, is recommended. Follow-through dosing every two hours while awake is often necessary to overtake the initial event. Appropriate cycloplegia using atropine 1 per cent BID will serve to relieve pain and stabilise the normal blood vasculature, minimising leaking. In many cases, IOP elevation associated with acute anterior uveitis is self-limiting and will resolve as the uveitis resolves.99 Steroids should be considered to be the most important treatment for eyes with uveitic glaucoma.

Aqueous suppressants have been the mainstay of treatment of uveitis-related IOP rise. However, the efficacy of glaucoma medications may be variable and unpredictable in uveitic glaucoma. Topical beta blockers are a viable option, though they may have poor to no effect in uveitic glaucoma. Interestingly, topical carbonic anhydrase inhibitors have been seen to work especially well in lowering the IOP in uveitic glaucoma. An alpha-2 adrenergic agonist is also an acceptable option. Oral carbonic anhydrase inhibitors (acetazolamide and methazolamide) may also be considered. Miotics must be avoided as they increase vascular permeability and can worsen inflammation in anterior uveitis.99

Prostaglandin analogs (PGAs) have long been avoided due to the concern that they may potentiate  inflammation and possibly contribute to the formation of cystoid macular oedema. However, there is little evidence that PGAs disrupt the blood-aqueous barrier and only anecdotal evidence suggesting an increased risk of these rare findings. PGAs may be used in uveitic glaucoma when other topical treatments have not lowered IOP to the patient’s target range. They have been shown to be effective in IOP lowering without
increasing inflammation.100-102

Studies have highlighted the role of viruses, such as cytomegalovirus, herpes simplex virus, and more  recently Ebola virus, in the pathogenesis of uveitic glaucoma. Antiviral therapy may be beneficial in eyes with detectable viral DNA, those eyes with uveitis suspected of viral origin, and possibly those cases unresponsive to conventional therapy. Topical ganciclovir, as well as oral acyclovir, famciclovir, and valacyclovir, may be employed.103

In cases of uveitic glaucoma that cannot be controlled medically, surgery remains an option. Trabeculectomy
is a favoured procedure for patients with uncontrolled uveitic glaucoma. In order to have the greatest possibility for success, inflammation must be controlled as well as possible prior to surgery. However, trabeculectomy performed without adjunctive antimetabolites has a high failure rate due to the young age of many of the patients and the active inflammation that causes fibrosis and scarring of the sclerostomy site. For this reason, mitomycin C is frequently used intraoperatively to reduce fibrous proliferation and reduce scarring. Glaucoma drainage devices such as the Ahmed valve and Baerveldt implant are frequently used to enhance surgical success in patients with refractory uveitic glaucoma, especially in cases of previous trabeculectomy failure.

Clinical Pearls

•    In most cases of uveitic glaucoma, there will be a combination of factors causing pressure elevation.
•    Chronic low-grade inflammation is more likely to cause glaucoma and more likely to occur in older patients. In younger patients, greater degrees of inflammation (such as in acute anterior uveitis) is necessary to cause glaucoma.
•    There are a lot of secondary causes of glaucoma. It is too hard to memorise details for every possible situation. However, if you can tell whether the angle is open or closed, the rest will fall into place.


Joseph Sowka, OD, FAAO, Diplomate is a Professor of Optometry at Nova Southeastern University College of Optometry where he serves as Chief of The Advanced Care Service and Director of the Glaucoma Service at the College’s Eye Institute. He is also Chair of the Department of Optometric Sciences. He is the longest tenured faculty member at the College.

Dr. Sowka is a founding member of both the Optometric Glaucoma Society and Optometric Retina Society. He is also the Chair of the Neuro-Ophthalmic Disorders in Optometry Special Interest Group for the American Academy of Optometry. Dr. Sowka is a Glaucoma Diplomate of the American Academy of Optometry.

He is the lead author of the annual Handbook of Ocular Disease Management published by Review of Optometry. He is a partner and co-owner of Optometric Education Consultants.

1. Wang N, Wu H, Fan Z. Primary angle closure glaucoma in Chinese and Western populations. Chin Med J (Engl). 2002;115(11):1706-15.
2. Foster PJ.The epidemiology of primary angle closure and associated glaucomatous optic neuropathy. Semin Ophthalmol. 2002;17(2):50-8.
3. Xu L, Zhang L, Xia CR, et al. The prevalence and its effective factors of primary angle-closure glaucoma in defined populations of rural and urban in Beijing. Zhonghua Yan Ke Za Zhi. 2005;41(1):8-14.
4. Wojciechowski R, Congdon N, Anninger W, et al. Age, gender, biometry, refractive error, and the anterior
chamber angle among Alaskan Eskimos. Ophthalmology. 2003;110(2):365-75.
5. Congdon NG, Youlin Q, Quigley H, et al. Biometry and primary angle-closure glaucoma among Chinese,
white, and black populations. Ophthalmology. 1997;104(9):1489-95.
6. Congdon NG, Friedman DS. Angle-closure glaucoma: impact, etiology, diagnosis, and treatment. Curr Opin Ophthalmol. 2003;14(2):70-3.
7. Fuchs J, Holm K, Vilhelmsen K, et al. Hereditary high hypermetropia in the Faroe Islands. Ophthalmic Genet. 2005;26(1):9-15.
8. Huang S, Yu M, Qiu C, et al. The management of secondary glaucoma in nanophthalmic patients. Yan Ke Xue Bao. 2002;18(3):156-9.
9. Ritch R, Chang BM, Liebmann JM Angle closure in younger patients. Ophthalmology. 2003 Oct;110(10):1880-9.
10. Sowka JW. Pupil block glaucoma from traumatic vitreous prolapse in a patient with posterior chamber lens implantation. Optometry. 2002;73(11):685-93.
11. Wong JS, Chew PT, Alsagoff Z, et al Clinical course and outcome of primary acute angle-closure glaucoma in Singapore. Singapore Med J. 1997;38(1):16-8.
12. Lai JS, Tham CC, Chan JC, et al. Scanning laser polarimetry in patients with acute attack of primary angle closure. Jpn J Ophthalmol. 2003;47(6):543-7.
13. Lam DS, Chua JK, Tham CC, et al. Efficacy and safety of immediate anterior chamber paracentesis in the treatment of acute primary angle-closure glaucoma: a pilot study. Ophthalmology. 2002;109(1):64-70.
14. Aung T, Ang LP, Chan SP, et al. Acute primary angleclosure: long-term intraocular pressure outcome in Asian eyes. Am J Ophthalmol. 2001;131(1):7-12.
15. Choi JS, Kim YY.Relationship between the extent of peripheral anterior synechiae and the severity of visual field defects in primary angle-closure glaucoma. Korean J Ophthalmol. 2004;18(2):100-5.
16. Lim LS, Aung T, Husain R, et al. Acute primary angle closure: configuration of the drainage angle in the first year after laser peripheral iridotomy. Ophthalmology. 2004;111(8):1470-4.
17. Bhattacharyya KB, Basu S. Acute myopia induced by topiramate: report of a case and review of the literature. Neurol India. 2005;53(1):108-9.
18. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramateassociated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology. 2004;111(1):109-11.
19. Craig JE, Ong TJ, Louis DL, et al. Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma. Am J Ophthalmol. 2004;137(1):193-5.
20. Banta JT, Hoffman K, Budenz DL, et al. Presumed topiramate-induced bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001;132(1):112-4.
21. Chen TC, Chao CW, Sorkin JA. Topiramate induced myopic shift and angle closure glaucoma. Br J Ophthalmol 2003;87:648-9.
22. Friedman DS, Gazzard G, Foster P, et al.Ultrasonographic biomicroscopy, Scheimpflug photography,
and novel provocative tests in contralateral eyes of Chinese patients initially seen with acute angle closure. Arch Ophthalmol. 2003;121(5):633-42.
23. Wang BS, Narayanaswamy A, Amerasinghe N, et al.Increased iris thickness and association with primary angle closure glaucoma. Br J Ophthalmol. 2011;95(1):46-50.
24. Cronemberger S, Calixto N, de Andrade AO, Mérula RV. New considerations on pupillary block mechanism. Arq Bras Oftalmol. 2010;73(1):9-15.
25. Sellem E. Angle closure mechanisms of glaucoma. J Fr Ophtalmol. 2004 Jun;27(6 Pt 2):693-6.
26. Waheeb S, Feldman F, Velos P, et al. Ultrasound Biomicroscopic analysis of drug-induced bilateral angle
closure glaucoma associated with supraciliary choroidal effusion. Can J Ophthalmol 2003; 38:299-302.
27. Quigley HA, Friedman DS, Congdon NG. Possible mechanisms of primary angle closure and malignant
glaucoma. J Glaucoma 2003; 12:167-80.
28. Ikeda N, Ikeda T, Nagata, et al. Ciliochoroidal effusion syndrome induced by sulfa derivatives. Arch Ophthalmol 2002; 120:1775.
29. Sakai H, Morine-Shinjyo S, Shinzato M, et al.Uveal effusion in primary angle-closure glaucoma.
Ophthalmology. 2005;112(3):413-9.
30. Aung T, Husain R, Gazzard G, et al. Changes in retinal nerve fiber layer thickness after acute primary angle closure. Ophthalmology. 2004;111(8):1475-9.
31. Sihota R, Lakshmaiah NC, Walia KB, et al. The trabecular meshwork in acute and chronic angle closure
glaucoma. Indian J Ophthalmol. 2001;49(4):255-9.
32. Hoh ST, Aung T, Chew PT. Medical management of angle closure glaucoma. Semin Ophthalmol.
33. Kook MS, Cho HS, Yang SJ, et al. Efficacy of latanoprost in patients with chronic angle-closure glaucoma
and no visible ciliary-body face: a preliminary study. J Ocul Pharmacol Ther. 2005;21(1):75-84.
34. Aung T, Chan YH, Chew PT, et al. EXACT Study Group. Degree of angle closure and the intraocular  pressure lowering effect of latanoprost in subjects with chronic angle-closure glaucoma. Ophthalmology. 2005;112(2):267-71.
35. Chew PT, Hung PT, Aung T. Efficacy of latanoprost in reducing intraocular pressure in patients with primary angle-closure glaucoma. Surv Ophthalmol. 2002;47 Suppl 1:S125-8.
36. Hung PT, Hsieh JW, Chen YF, et al. Efficacy of latanoprost as an adjunct to medical therapy for residual
angle-closure glaucoma after iridectomy. J Ocul Pharmacol Ther. 2000;16(1):43-7.
37. Saw SM, Gazzard G, Friedman DS. Interventions for angle-closure glaucoma: an evidence-based update.
Ophthalmology. 2003;110(10):1869-78.
38. Renard JP, Giraud JM, Oubaaz A. Treatment of acute angle-closure glaucoma. J Fr Ophtalmol. 2004;27(6 Pt 2):701-5.
39. Lai JS, Tham CC, Chua JK, et al. Laser peripheral iridoplasty as initial treatment of acute attack of primary angle-closure: a long-term follow-up study. J Glaucoma. 2002;11(6):484-7.
40. Alsagoff Z, Aung T, Ang LP, et al. Long-term clinical course of primary angle-closure glaucoma in an Asian population. Ophthalmology. 2000;107(12):2300-4.
41. Choong YF, Irfan S, Menage MJ. Acute angle closure glaucoma: an evaluation of a protocol for acute treatment. Eye. 1999 ( Pt 5):613-6.
42. Stefanescu-Dima A. Preventive iridotomy--a prospective study. Oftalmologia. 2004;48(3):61-71.
43. Harasymowycz PJ, Papamatheakis DG, Ahmed I, et al. Phacoemulsification and goniosynechialysis in the management of unresponsive primary angle closure. J Glaucoma. 2005;14(3):186-9.
44. Lai JS, Tham CC, Lam DS.Incisional surgery for angle closure glaucoma. Semin Ophthalmol. 2002;17(2):92-9.
45. Wang JK, Lai PC.Unusual presentation of angle-closure glaucoma treated by phacoemulsification. J Cataract Refract Surg. 2004;30(6):1371-3.
46. Hamanaka T, Kasahara K, Takemura T. Histopathology of the Trabecular Meshwork and Schlemm’s Canal inPrimary Angle-Closure Glaucoma. Invest Ophthalmol Vis Sci. 2011;17;52(12):8849-61.
47. Mansoori T, Viswanath K, Balakrishna N. Quantification of Retinal Nerve Fiber Layer Thickness After
Unilateral Acute Primary Angle Closure in Asian Indian Eyes. J Glaucoma. 2011 Sep 22. [Epub ahead of print].
48. Tsai JC, Lin PW, Teng MC, Lai IC. Longitudinal changes in retinal nerve fiber layer thickness after acute primary angle closure measured with optical coherence tomography. Invest Ophthalmol Vis Sci. 2007;48(4):1659-64.
49. Fang AW, Qu J, Li LP, Ji BL. Measurement of retinal nerve fiber layer in primary acute angle closure glaucoma by optical coherence tomography. J Glaucoma. 2007;16(2):178-84.
50. Liu X, Li M, Zhong Y, et al. The damage patterns of retinal nerve fiber layer in acute and chronic intraocular
pressure elevation in primary angle closure glaucoma. Yan Ke Xue Bao. 2011;26(3):154-60.
51. Sng CC, See JS, Ngo CS, et al. Changes in retinal nerve fibre layer, optic nerve head morphology, and
visual field after acute primary angle closure. Eye (Lond). 2011;25(5):619-25. Epub 2011 Mar 25.
52. Chew SS, Vasudevan S, Patel HY, et al. Acute primary angle closure attack does not cause an increased cup-to-disc ratio. Ophthalmology. 2011;118(2):254-9.
53. Mok KH, Lee VW. Synechial angle closure pattern in Chinese chronic primary angle-closure glaucoma patients. J Glaucoma. 2001;10(5):427-8.
54. Lowe RF. Primary creeping angle closure glaucoma. Br J Ophthalmol 1964;48:544.
55. Wang T, Liu L, Li Z, et al. Studies of mechanism of primary angle closure glaucoma using ultrasound
biomicroscope. Zhonghua Yan Ke Za Zhi. 1998;34(5):365-8.
56. Marchini G, Chemello F, Berzaghi D, Zampieri A. New findings in the diagnosis and treatment of primary angleclosure glaucoma. Prog Brain Res. 2015;221:191-212.
57. He M, Friedman DS, Ge J, et al. Laser peripheral iridotomy in primary angle-closure suspects: biometric
and gonioscopic outcomes: the Liwan Eye Study. Ophthalmology. 2007;114(3):494-500.
58. Chen MJ, Cheng CY, Chou CK, et al. The long-term effect of Nd:YAG laser iridotomy on intraocular pressure in Taiwanese eyes with primary angle-closure glaucoma. J Chin Med Assoc. 2008;71(6):300-4.
59. Sihota R, Lakshmaiah NC, Walia KB, et al. The trabecular meshwork in acute and chronic angle closure
glaucoma. Indian J Ophthalmol. 2001;49(4):255-9.
60. Ruangvaravate N, Kitnarong N, Metheetrairut A, et al. Efficacy of brimonidine 0.2 per cent as adjunctive
therapy to beta-blockers: a comparative study between POAG and CACG in Asian eyes. J Med Assoc Thai.
61. Aung T, Wong HT, Yip CC, et al. Comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma: a preliminary study. Ophthalmology. 2000;107(6):1178-83.
62. How AC, Kumar RS, Chen YM, et al. A randomised crossover study comparing bimatoprost and latanoprost in subjects with primary angle closure glaucoma. Br J Ophthalmol. 2009;93(6):782-6.
63. Chen MJ, Chen YC, Chou CK, et al. Comparison of the effects of latanoprost and bimatoprost on intraocular pressure in chronic angle-closure glaucoma. J Ocul Pharmacol Ther. 2007;23(6):559-66.
64. Chen MJ, Chen YC, Chou CK, et al. Comparison of the effects of latanoprost and travoprost on intraocular pressure in chronic angle-closure glaucoma. J Ocul Pharmacol Ther. 2006;22(6):449-54.
65. Lou H, Zong Y, Ge YR, Cheng JW, Wei RL. Efficacy and tolerability of latanoprost compared with timolol in the treatment of patients with chronic angle-closure glaucoma. Curr Med Res Opin. 2014;30(7):1367-73.
66. Aung T, Chan YH, Chew PT; EXACT Study Group. Degree of angle closure and the intraocular pressure-lowering effect of latanoprost in subjects with chronic angle-closure glaucoma. Ophthalmology. 2005;112(2):267-71.
67. 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 angle-closure glaucoma (EAGLE):The Lancet. Volume 388, No. 10052, p1389–1397, 1 October 2016.
68. Jeng SM, Karger RA, Hodge DO, et al. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma
69. Puska PM. Unilateral exfoliation syndrome: conversion to bilateral exfoliation and to glaucoma: a prospective 10-year follow-up study. J Glaucoma. 2002;11(6):517-24.
70. Konstas AG, Hollo G, Astakhov YS, et al. Presentation and long-term follow-up of exfoliation glaucoma in
Greece, Spain, Russia, and Hungary. Eur J Ophthalmol. 2006;16(1):60-6.
71. Amari F, Umihira J, Nohara M, et al. Electron microscopic immunohistochemistry of ocular and extraocular pseudoexfoliative material. Exp Eye Res 1997;65:51-6.
72. Kubota T, Schlotzer-Schrehardt U, Inomata H, Naumann, GO. Immunoelectron microscopic localization
of the HNK-1 carbohydrate epitope in the anterior segment of Pseudoexfoliation and normal eyes. Curr Eye Res 1997;16(3):231-8.
73. Schlötzer-Schrehardt U, Hammer CM, Krysta AW, et al. LOXL1 deficiency in the lamina cribrosa as candidate susceptibility factor for a pseudoexfoliation-specific risk of glaucoma. Ophthalmology. 2012;119(9):1832-43.
74. Zenkel M, Schlötzer-Schrehardt U. Expression and regulation of LOXL1 and elastin-related genes in eyes with exfoliation syndrome. J Glaucoma. 2014;23(8 Suppl 1):S48-50.
75. Kara N, Altan C, Yuksel K, Tetikoglu M. Comparison of the efficacy and safety of selective laser trabeculoplasty in cases with primary open-angle glaucoma and pseudoexfoliative glaucoma. Kaohsiung J Med Sci. 2013;29(9):500-4.
76. Farrar SM, Shields MB. Current concepts in pigmentary glaucoma. Surv Ophthalmol 1993; 37(4):233-52.
77. Roberts DK, Miller E, Kim LS. Pigmentation of the posterior lens capsule central to Wieger’s ligament and the Scheie line: a possible indication of the pigment dispersion syndrome. Optom Vis Sci 1995; 72(10):756-62.
78. Campbell DG, Schertzer RM. Pathophysiology of pigment dispersion syndrome and pigmentary glaucoma. Curr Opin Ophthalmol 1995;6(2):96-101.
79. Potash SD, Tello C, Liebmann J, Ritch R. Ultrasound biomicroscopy in pigment dispersion syndrome.
Ophthalmology 1994;101(2q):332-9.
80. Sherwood M, Richardson TM. Evidence for in vivo phagocytosis by trabecular endothelial cells. Invest
Ophthalmol Vis Sci 1980;19(4 suppl):66.
81. Richardson TM, Hutchinson BT, grant WM. The outflow tract in pigmentary glaucoma: A light and electron
microcroscopy study. Arch Ophthalmol 1977;95:1015-25.
82. Mastropasqua L, Ciancaglini M, Carpineto P, et al. Early stadiation of pigmentary dispersion syndrome and long-term analysis of progression to pigmentary glaucoma. Ann Ophthalmol Glaucoma 1996; 28(5):301-7.
83. Siddiqui Y, Ten Hulzen RD, Cameron JD, et al.What is the risk of developing pigmentary glaucoma from pigment dispersion syndrome? Am J Ophthalmol.2003;135(6):794-9.
84. Harasymowycz PJ, Papamatheakis DG, Latina M, et al. Selective laser trabeculoplasty (SLT) complicated
by intraocular pressure elevation in eyes with heavily pigmented trabecular meshworks. Am J Ophthalmol.
85. Kuang TM, Liu CJ, Chou CK, et al. Clinical experience in the management of neovascular glaucoma. J Chin Med Assoc. 2004;67(3):131-5.
86. Hamanaka T, Akabane N, Yajima T, et al. Retinal ischemia and angle neovascularization in proliferative diabetic retinopathy. Am J Ophthalmol.2001;132(5):648-58.
87. Chen KJ, Chen SN, Kao LY, et al. Ocular ischemic syndrome. Chang Gung Med J. 2001;24(8):483-91.
88. Detry-Morel M. Neovascular glaucoma in the diabetic patient. Bull Soc Belge Ophtalmol. 1995;256:133-41.
89. Löffler KU. Neovascular glaucoma: aetiology, pathogenesis and treatment. Ophthalmologe.
90. Shazly TA, Latina MA. Neovascular glaucoma: etiology, diagnosis and prognosis. Semin Ophthalmol.
91. Hu DN, Ritch R, Liebmann J, et al. Vascular endothelial growth factor is increased in aqueous humor of
glaucomatous eyes. J Glaucoma. 2002;11(5):406-10.
92. Scholl S, Kirchhof J, Augustin AJ. Antivascular endothelial growth factors in anterior segment diseases.
Dev Ophthalmol. 2010;46:133-9.
93. Beutel J, Peters S, Lüke M, et al. Bevacizumab as adjuvant for neovascular glaucoma. Acta Ophthalmol.
94. Brouzas D, Charakidas A, Moschos M, et al. Bevacizumab (Avastin) for the management of anterior
chamber neovascularization and neovascular glaucoma. Clin Ophthalmol. 2009;3:685-8.
95. Herbert HM, Viswanathan A, Jackson H, et al. Risk factors for elevated intraocular pressure in uveitis.
J Glaucoma. 2004;13(2):96-9.
96. Kok H, Barton K. Uveitic glaucoma. Ophthalmol Clin North Am. 2002;15(3):375-87.
97. Sung VC, Barton K. Management of inflammatory glaucomas. Curr Opin Ophthalmol. 2004;15(2):136-40.
98. Ladas JG, Yu F, Loo R, et al. Relationship between aqueous humor protein level and outflow facility in patients with uveitis. Invest Ophthalmol Vis Sci. 2001;42(11):2584-8.Depending
99. Muñoz-Negrete FJ, Moreno-Montañés J, Hernández-Martínez P, Rebolleda G. Current Approach in the
Diagnosis and Management of Uveitic Glaucoma. Biomed Res Int. 2015;2015:742792.
100. Takeuchi M, Kanda T, Taguchi M, et al. Evaluation of Efficacy and Safety of Latanoprost/Timolol versus
Travoprost/Timolol Fixed Combinations for Ocular Hypertension Associated with Uveitis. Ocul Immunol
Inflamm. 2016 Jan 22:1-6.
101. Taylor SR, Gurbaxani A, Sallam A, Lightman S. Topical prostaglandin analogues and conjunctival
inflammation in uveitic glaucoma. Open Ophthalmol J. 2012;6:75-8.
102. Horsley MB, Chen TC. The use of prostaglandin analogs in the uveitic patient. Semin Ophthalmol.
103. Sng CC, Ang M, Barton K. Uveitis and glaucoma: new insights in the pathogenesis and treatment. Prog Brain Res. 2015;221:243-69.

' Patients with uveitic glaucoma typically fall into two categories; those that develop acute anterior uveitis replete with pain, photophobia, and lacrimation, and those experiencing lesser symptoms from chronic uveitis '