2.1.3.1 Glaucoma associated with non-acquired ocular anomalies

• Axenfeld Rieger anomaly (Syndrome if systemic associations)

• Peters anomaly (Syndrome if systemic associations)

• Ectropion uveae

• Congenital iris hypoplasia

• Aniridia

• Persistent fetal vasculature/PFV (if glaucoma present before cataract surgery)

• Oculodermal melanocytosis (Nevus of Ota)

• Posterior polymorphous dystrophy

• Microphthalmos

• Microcornea

• Ectopia lentis

2.1.3.2 Glaucoma Associated with Non-acquired Systemic Disease or Syndrome

• Chromosomal disorders such as Trisomy 21 (Down syndrome)

• Connective tissue disorders

  • Marfan syndrome

  • Weill-Marchesani syndrome

  • Stickler syndrome

• Metabolic disorders

  • Homocysteinuria

  • Lowe syndrome

  • Mucopolysaccharidoses

• Phacomatoses

  • Neurofibromatosis (NF-1, NF-2)

  • Sturge-Weber syndrome

  • Klippel-Trenaunay-Weber syndrome

  • Rubinstein-Taybi

  • Congenital rubella

2.1.3.3 Glaucoma Associated with Acquired Condition

• Uveitis

• Trauma (hyphema, angle recession, ectopialentis)

• Steroid induced

• Tumors (benign/malignant, ocular/orbital)

• Retinopathy of Prematurity

2.1.3.4 Glaucoma Following Childhood Cataract Surgery

Secondary glaucoma is a frequent serious complication after cataract surgery in early infancy. The incidence may increase up to 50% if cataract surgery is performed before the 9^th month of life12, 13. This secondary glaucoma is difficult to treat and often needs long-tube drainage device surgery for long-term IOP control.

2.1.3.5 Treatment of secondary childhood glaucoma [I,D]

The management of these cases is particularly challenging.

Medical treatment is usually not effective nor practicable in long term. Medications, including oral CAIs can be used while decision is made on a surgical approach and in case of failed surgery while awaiting for further options.

Primary surgery: early goniotomy or trabeculotomy or filtration surgery may be indicated if these are unsuccessful. Repeat surgery is relatively frequent.

Treatment to be adapted to the primary anomaly, the mechanism of IOP elevation and the quality of life of the patient. These cases require highly specialized care.

2.2.2.1 Risk factors for the development of OAG (See FC V)

Initial evidence on potential risk factors for OAG has been provided by cross-sectional population-based studies. Firm conclusions on risk factors for the development of OAG can only be drawn by longitudinal population-based cohort studies27-30.

1. Age

   Cross-sectional population-based studies have consistently reported that the prevalence of OAG increases dramatically with age14-17,19-25,31. Longitudinal population-based studies have confirmed that older age is an important risk factor for OAG27-30. Two studies reported a 6% and 4% increased risk per year of age at baseline of developing OAG.

2. Intraocular pressure (IOP)

   Higher IOP has been consistently associated with the prevalence14-17,19-25,31 and incidence of OAG27,28,30,32. According to longitudinal data, the risk of developing OAG increases by 11-12% in Caucasians27,28, 10% in people of African origin32 and 18% in Latinos30 for each 1 mmHg increase in IOP. To date, IOP is the only modifiable risk factor for OAG.

3. Race/ethnicity

   The prevalence of glaucoma is several times higher in African-Americans and Afro-Caribbeans than in Caucasians18,33,34. In Latinos, it has been shown that the prevalence20-23 and incidence35 of OAG is higher than in Caucasians, but lower than in Afro-Caribbeans.

4. Family history of glaucoma

   Two studies studying different ethnic groups found that the risk of having OAG was 9.2-fold and 4 fold higher, respectively for individuals having a first-degree relative with confirmed OAG, compared with those who did not 36, 37. Also, self– reported family history of glaucoma has been associated with increased risk of developing OAG27,29.

5. Pseudoexfoliation

   Population-based studies which specifically assessed pseudoexfoliation and pseudoexfoliative glaucoma have consistently reported that pseudoexfoliation is associated with increased prevalence of OAG19,24,38-47. Based on longitudinal data, the presence of pseudoexfoliation is associated with an 11.2-fold increased risk of developing OAG27.

6. Central corneal thickness (CCT)

   In two population based studies, there was a 41% and 30% increased risk of developing OAG per 40 μm thinner CCT29,48.

7. Myopia

   Several cross-sectional population-based studies identified moderate to high myopia (greater than -3 diopters) as a factor associated with increased OAG prevalence47,49-55. A Dutch study showed that subjects with high myopia (greater than -4 D) had a 2.3-fold increased risk for developing OAG28. Latinos in California had a risk of OAG increased by 48% with each 1 mm increase in axial length30.

8. Ocular perfusion pressure

   The association of low ocular perfusion pressure with increased OAG prevalence has been a consistent finding in population-based studies20,31, 56-61. Recent evidence suggests that this association may depend on whether subjects are treated for systemic hypertension or not29,56,58,61-66.

   A phenotype characterized by vascular dysregulation has been described64. The Barbados Eye Study confirmed that low ocular perfusion pressure increases the risk for the development of OAG29.

   Because of our limited understanding of this complex variable and of its interaction with potential risk factors for glaucoma, the exact place of ocular perfusion pressure in glaucoma management remains unclear67-69.

9. Other factors

   There have been reports on other factors that may be associated with increased risk for OAG, such as diabetes, systemic blood pressure, migraine, Raynaud syndrome and obstructive sleep apnoea. However, data from the literature are inconsistent.

10. Risk factors by type of OAG

    In general, population-based studies analyses have not differentiated between types of OAG. A recent analysis which considered POAG and PEX glaucoma revealed that IOP was the only factor associated with both of them; vascular systemic diseases and their treatment were associated only with POAG47. This may suggest differences in pathogenesis between these two common types of OAG.

2.2.2.2 Risk factors and predictive factors for the conversion of ocular hypertension to POAG

The Ocular Hypertension Treatment Study (OHTS), and the European Glaucoma Prevention Study (EGPS)70 are two randomized controlled trials (RCTs) which evaluated the effect of IOP-lowering treatment on the conversion of ocular hypertension to POAG. The following risk factors and predictive factors were consistently reported in both the OHTS and the EGPS:

• Age (risk increased by 26% per decade)

• IOP (risk increased by 9% per 1 mmHg)

• Vertical and horizontal cup-to-disc ratio (risk increased by 19% per 0.1 larger)

• Pattern standard deviation (PSD) in the visual field (risk increased by 13% per 0.2 dB greater)

• CCT (2.04 fold increased risk per 40 μm thinner)

Based on the pooled OHTS–EGPS predictive model, a quantitative calculator was developed to estimate the 5-year risk for the conversion of ocular hypertension to POAG71. This tool is available to the clinician and may help to discuss frequency of visits and possible treatment.

However, limitations should also be considered. Because the calculator was based on the OHTS and EGPS data sets, results may not apply to individuals < 40 years old, individuals who have untreated IOPs < 22 mmHg or who are not of Caucasian or of African origin. Also, the calculator does not take into account other factors associated with increased risk for glaucoma, such as family history of glaucoma and pseudoexfoliation. In addition, life expectancy issues should be addressed.

2.2.2.3 Prognostic factors for progression of OAG

Factors associated with the progression of established OAG have been identified by large RCTs: Early Manifest Glaucoma Trial (EMGT)72, Advanced Glaucoma Intervention Study (AGIS)73, Collaborative Initial Glaucoma Treatment Study (CIGTS)74, Collaborative Normal Tension Glaucoma Study (CNTGS)75.

1. Age

   Older age is significantly associated with increased risk for the progression of OAG. In the EMGT, after a mean follow-up of 8 years, patients ≥ 68 years old had a 51% increased risk of progression compared to those who were younger72. In the AGIS the risk of progression increased by 30% with every 5 years increase in age73; in CIGTS the risk increased by 35% for every decade74. Also, in the untreated arm of the EMGT, progression was considerably faster in older than in younger patients76.

2. IOP

   Most of the above RCTs suggest a positive effect of IOP reduction on the onset or progression of glaucomatous damage. In the EMGT the risk of progression decreased by about 10% with each mmHg of IOP reduction from baseline to the first follow-up visit77. Conversely, the role of long term IOP fluctuation in glaucoma progression is still debated78-80. Also, the role of diurnal IOP fluctuation in glaucoma progression needs to be investigated more thoroughly in RCTs.

3. Pseudoexfoliation

   In the EMGT, the risk of progression increased by a 2.12-fold in those with pseudoexfoliation compared with those without pseudoexfoliation72. In addition, in the untreated arm of the EMGT, progression was considerably faster in eyes with pseudoexfoliation, despite similar baseline IOP values between the pseudoexfoliative and non pseudoexfoliative eyes76. Pseudoexfoliation has not been evaluated in the AGIS, CIGTS and CNTGS.

4. CCT

   In the EMGT, thinner CCT was a significant but weak prognostic factor for OAG and this association was observed only in patients with higher baseline IOP72. The role of CCT in glaucoma progression has not been evaluated in the AGIS, CIGTS and CNTGS.

5. Disc haemorrhages

   In the CNTGS the presence of optic disc haemorrhages was significantly associated with glaucoma progression80. Also, in the EMGT patients with disc haemorrhages had significantly shorter time to progression81. A systematic review (January 1950-January 2013) evaluating risk factors for glaucoma among routine diagnostic examination reported disc haemorrhage (LR, 12; 95% CI, 2.9-48) being highly suggestive of glaucoma, but the absence of a haemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98)82.

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2.2.3.1 Primary Open-Angle Glaucoma / High Pressure Glaucoma (POAG/HPG)

The relative risk for POAG rises continuously with the level of the intra-ocular pressure (IOP), and there is no evidence of a threshold IOP for the onset of the condition. It is presumed that risk factors other than IOP have a relatively greater importance if there is glaucomatous optic neuropathy at the lower (statistically ‘normal’) pressure levels. POAG has been arbitrarily subdivided into High Pressure and Normal-Pressure disease to reflect this, even though they may represent a spectrum of optic neuropathies variably sensitive to the IOP. See Ch. Introduction.

Etiology:

Unknown

Pathomechanism:

Unknown.

TIGR and Myoc mutations may be associated83, 84.

Features:

• Onset: from the young adult age onwards

• Signs and symptoms:

  • Asymptomatic until field loss advanced

  • Elevated IOP without treatment (diurnal tension curve)

• Optic nerve head: acquired characteristic glaucomatous damage and/or retinal nerve fiber layer changes (diffuse or localized defects) (See Ch. 1)

• Visual field: usually detectable glaucomatous defects corresponding to the optic disc damage may be present

• Gonioscopy: open anterior chamber angle (not occludable, no goniodysgenesis). (See Ch. 1).

Treatment:

Refer also to Introduction II and Ch. 3

A target pressure is to be identified for each case (See also Ch. 3.2 and FC IX-X) [I,D].

1. Medical treatment (See FC XI-XIII)

   1. Mono therapy

   2. Combination therapy as needed in selected patients

2. Laser trabeculoplasty (LTP)

3. Filtration Surgery with / without antimetabolites

4. Adjunctive medical therapy when needed

5. Insertion of aqueous long- tube drainage implants

6. Cyclodestructive procedures

Choice of primary therapeutic modality needs to be made on an individual patient basis [I,D].

Laser trabeculoplasty can be considered as primary treatment and as an alternative to additional medications [I,A].

2.2.3.2 Primary Open-Angle Glaucoma / Normal–Pressure Glaucoma (POAG/NPG)

Etiology:

Unknown

Pathomechanism:

Unknown.

Optineurin mutation has been found in families with NPG

Features:

• Onset: from the 35^th year onwards

• Signs and symptoms:

  • Normal IOP without treatment (diurnal curve or 24-hour phasing). Asymptomatic until field loss advanced

  • Optic nerve head damage typical of glaucoma

  • Disc haemorrhages

• Visual field defects typical of glaucoma; e.g. paracentral defects

• Gonioscopy: open anterior chamber angle (exclude intermittent angle-closure; See Ch. 2)

• No history or signs of other eye disease or steroid use.

• Consider central corneal thickness if findings do not match; CCT may be thinner than average (See Ch. 1.1).

Treatment:

Refer also to Chapter Introduction II, Ch. 3 and FC VI

There are few prospective clinical trials indicating clearly the advantages of treatment [I,A]. Target pressure: in most cases a peak IOP = 8 mm - 15 mm Hg on diurnal curve or a 30% IOP reduction from baseline (See Ch. 3.2) [I,D]

1. Medical therapy:

   1. Any drug singly or in combination which is effective and tolerated, whose IOP lowering effect is sufficient to reach a maintain the target IOP [I,D]

   2. Avoid medications with potential vasoconstrictive effects or with systemic hypotensive effects [II,D]

   3. Oral calcium channel blockers are being investigated in selected patients by some investigators.

2. Laser trabeculoplasty [I,D]

3. Glaucoma Surgery:

   In cases of progressive glaucomatous damage, in spite of maximal medical therapy or laser trabeculoplasty, or failure to reach target pressure [I,D]. Intensive postoperative care with bleb manipulation may be needed to maintain low IOPs [I,D]

Follow-up intervals, depending on the stage of disease and on the rate of progression, with examination of [II,D]:

• Optic disc

• Visual field

• IOP

• ONH and RNFL documentation

2.3.1.1 Secondary Open-Angle Glaucomas Caused By Ocular Disease

2.3.1.2 Open-angle glaucoma due to ocular trauma

Ocular trauma leads to glaucoma by several different mechanisms. The secondary traumatic glaucomas can be caused by both open-angle and angle-closure mechanisms. In order to identify and treat the causes of IOP elevation; careful evaluation of the ocular damage must be performed.

Etiology:

Blunt non-penetrating or penetrating trauma to the eye.

Pathogenic mechanisms:

Blunt non-penetrating trauma can lead to reduced trabecular outflow due to traumatic changes of the trabecular meshwork. Scarring and inflammation of the trabecular meshwork, obstruction by red blood cells and debris, angle recession, lens-induced glaucoma. Elevated IOP may occur a very long time after the trauma. Positive steroid response after anti-inflammatory treatment should also be considered. Penetrating injury may damage one or more intraocular structure leading to elevated IOP114.

Symptoms and signs:

Redness, pain, decreased vision with acute IOP elevation, or no symptoms with chronic IOP elevation. Acute or late IOP elevation (occurring months or even decades later) may follow blunt trauma.

Chemical burns, hyphaema, traumatic cataract, uveitis, angle recession, ruptured iris sphincter, iridodialysis can be present in various combinations.

Note: It is not recommended to perform gonioscopy in fresh ocular trauma to avoid compressing the eye. This examination can be delayed for several weeks.

Treatment [I,D]:

• Anti-inflammatory

• Topical and systemic IOP lowering medication

• Long-term IOP follow up in the presence of permanent anterior segment damage.

• Glaucoma surgery

2.3.2.1 Glaucoma due to corticosteroid treatment

Etiology:

Topical, intravitreal as well as high dose and long-term systemic corticosteroid therapy can induce acute or chronic IOP elevation115. The risk of IOP elevation depends on the chemical structure (strength) of the steroid, dose, frequency and duration of therapy, and route of administration. The risk factors for being steroid responder are: POAG, family history of glaucoma, diabetes, myopia, rheumatoid arthritis, children and elderly patients.

Pathogenic mechanism:

Corticosteroids induce changes in the trabecular extracellular matrix (glycoproteins) which lead to decreased outflow facility. A TIGR gene modification is present116.

Symptoms:

Pain and eye irritation are possible but not at all mandatory especially in acute IOP elevation.

Signs:

Elevated IOP usually develops 2 to 6 weeks after initiating therapy, but may occur at any time. Usually IOP elevation is slowly reversed after stopping the use of corticosteroid. Corneal oedema can be present. Prolonged IOP elevation can lead to typical glaucomatous optic nerve head changes and visual field damage.

Treatment [I,D]:

• Discontinuation of corticosteroid therapy is recommended; steroid-sparing therapy of underlying condition should be considered. If this is not possible, consider switching to weaker steroid (e.g. loteprednol, fluorometholone)

• Topical and systemic IOP lowering medication

• Laser trabeculoplasty

• Glaucoma surgery may be performed in intractable cases

2.3.2.2 Secondary open-angle glaucoma due to ocular surgery and laser

Ocular surgery can cause secondary open-angle glaucoma by some of the mechanisms discussed above: intraocular haemorrhage, inflammatory reaction, lens material, pigmentary loss from uveal tissue, or trauma117.

Pathogenic mechanism:

Open-angle glaucoma following ocular surgery or laser is a result of reduced trabecular outflow:

• IOP elevation after intraocular surgery is usually transient. The elevated IOP may be caused by: viscoelastic material, inflammatory debris, vitreous in the anterior chamber after cataract surgery, lens particles, intra-operative application of -chymotrypsin, and prostaglandin release.

• Acute onset secondar y IOP elevation af ter Nd:YAG laser i r idotomy, capsulotomy and laser trabeculoplasty. IOP elevation is usually transient, within the first 24 hours, most frequent in the first 4 hours after treatment.

• IOP elevation with open- angle following vitrectomy with sil icon oil implantation develops as a result of:

  • Migration of silicon oil into anterior chamber and obstruction of the trabecular meshwork (early post-op IOP increase) usually due to overfill of oil.

  • Migration of emulsified silicon oil into anterior chamber with obstruction of trabecular meshwork where oil particles are partially phagocytised by macrophages and accumulate in the trabecular meshwork especially in the upper quadrant and can induce trabeculitis (intermediate and late onset IOP increase). Prolonged contact of silicon oil with the trabecular meshwork may cause permanent structural changes. Risk factors for developing IOP elevation following vitrectomy with silicon oil implantation include pre-existing ocular hypertension or glaucoma, diabetes mellitus, and aphakia (closed angle type)118,119.

• Uveitis-glaucoma-hyphema (UGH) syndrome - IOP elevation associated with an anterior chamber intraocular lens due to induced iris root bleeding and anterior uveitis. Modern IOLs pose a significantly lower risk of inducing UGH syndrome.

Treatment [I,D]:

• Topical and systemic IOP lowering medication

• Anti-inflammatory treatment

• Removal of silicone oil may be considered in eyes with IOP elevation secondary to silicon oil emulsification. However current data suggest that removal of silicon oil is not effective in all cases and the risk of re-detachment increases. Trans-scleral cyclophotocoagulation and aqueous drainage devices seem to represent more effective options, although the latter are associated with the r isk of silicon oil escape into sub- conjuctival space. Endoscopic cyclophotocoagulation in eyes requiring silicon oil removal and antiglaucoma treatment seems to be effective option. Conventional filtration surgery is associated with poor prognosis.

• Removal of the intraocular lens may be needed in case of UGH syndrome

• Glaucoma surgery according to the specific condition.

2.3.3.1 Glaucoma caused by increased episcleral venous pressure

Etiology and pathogenic mechanism:

Episcleral, orbital or systemic diseases can cause the elevation of episcleral venous pressure with subsequent reduction of trabecular outflow and IOP elevation. The following disorders can be described:

• Episcleral and orbital causes: chemical burn or radiation damage of the episcleral veins, hemangioma in Sturge-Weber syndrome, Nevus of Ota, endocrine orbitopathy, orbital (retrobulbar) tumor, pseudotumor, orbital phlebitis, orbital or intracranial arteriovenous fistula

• Neurologic conditions: dural shunts, cavernous sinus thrombosis

• Other systemic causes: superior vena cava obstruction, jugular vein obstruction (radical neck dissection), pulmonary venous obstruction

• Idiopathic forms

Symptoms and signs:

IOP elevation can be acute with eye irritation and pain. Visual acuity can be decreased. Dilated, congested episcleral veins, chemosis, facial lymphedema, orbital bruit can be present. Vascular bruits are characteristic signs of A/V fistulae120

Treatment [I,D]:

• Treatment of the underlying disease

• Topical and systemic IOP lowering medication

• Glaucoma surgery

2.4.1.1 Natural History of PAC

PAC becomes more likely as the separation between the iris and TM decreases128. The risk of iridotrabecular contact in a “narrow” angle begins to increase once the iridotrabecular angle is ≤ 20°129. With angles of 20° or less, signs of previous angle-closure, such as PAS or iris pigment on the TM, should be carefully sought as signs of previous closure. Most angle- closure occurs asymptomatically. Although symptoms of pain, redness, blurring of vision or haloes may help identify people with significant angle-closure, the sensitivity and specificity of symptoms for identifying angle-closure are very poor. The most commonly identified sign which indicates that treatment is required is ITC. There is not a precise extent of gonioscopically evident ITC which will dictate the indication to treatment for all cases.

An international group of experts reached a consensus that 2 quadrants or more of ITC is an indication for prophylactic treatment130 [II,D].

Clearly, in established disease with high IOP, established PAS or glaucomatous optic neuropathy, any potential for angle-closure should be considered and treated on individual merits.

2.4.1.2 Staging of Primary Angle-closure123

1. Primary Angle-closure Suspect (PACS)

   Two or more quadrants of iridotrabecular contact (lTC), normal IOP, no PAS, no evidence of glaucomatous optic neuropathy (GON).

2. Primary Angle-closure (PAC)

   Iridotrabecular contact resulting in PAS and/or raised IOP. No evidence of GON.

3. Primary Angle-closure Glaucoma (PACG)

   Iridotrabecular contact causing GON; PAS and raised IOP may be absent at the time of initial examination.

2.4.1.3 Ocular Damage in Angle-closure

Primary angle-closure (PAC) may cause ocular tissue damage in many ways. Corneal endothelial cell loss occurs after symptomatic “acute” angle-closure. With very high IOP values the iris may suffer ischaemic damage to musculature causing iris whirling (distortion of radially orientated fibres) and/or a dilated, unresponsive pupil. The lens epithelium may suffer focal necrosis causing anterior sub-capsular or capsular opacity of the lens associated with focal epithelial infarct called “Glaukomflecken”. The trabecular meshwork can be damaged by the formation of PAS, or as the result of long- standing appositional closure. Optic neuropathy in angle-closure may manifest in at least 2 ways. After an “acute” symptomatic episode, the disc may become pale but flat, suggesting an anterior ischaemic optic neuropathy. Typical glaucomatous optic neuropathy manifests in with an excavated surface and a pattern of visual field loss indistinguishable from open-angle glaucoma. Angle-closure accounts for 50% of all glaucoma blindness worldwide, and is probably the most visually destructive form of glaucoma.

2.4.1.4 Outcome following treatment

In asymptomatic (“chronic”) angle-closure, a high presenting pressure (>35 mmHg), more than 6 clock hours of peripheral anterior synechiae and/or established glaucomatous optic neuropathy are signs that a case of angle-closure will not respond fully to a laser iridotomy131, and that a trabeculectomy may be needed to control pressure” [II,D].

2.4.1.5 Mechanisms of angle-closure

It is important to identify secondary causes of narrow or closed-angles, such as phakomorphic, uveitic and neovascular cases, as the management of these cases is initially directed at controlling the underlying disease. In isometropic eyes it is helpful to compare axial anterior chamber depths of the two eyes. Asymmetry of > 0.2 mm (3 standard deviations) is suggestive of a secondary pathological process. A-mode or ultrasound biomicroscopy may be helpful in measuring axial dimensions (Iength, AC depth and lens thickness) and defining anatomical relationships. In primary angle-closure these will be the same in each eye. Mechanisms responsible for angle- closure are described in terms of anatomical location of obstruction to aqueous flow, successively, at the pupil, the iris and ciliary body, the lens and behind the lens. This is also order of decreasing frequency of each mechanism. Two mechanisms may co-exist, especially levels I and II (i.e. pupil and iris/ciliary body). Often, one mechanism predominates.

1. Pupillary block mechanism

   Pupillary block is the predominant mechanism in around 75% of cases of primary angle-closure. Pupillary block is an exaggeration of a physiological phenomenon in which the flow of aqueous from the posterior chamber through the pupil to the anterior chamber is impeded causing the pressure in the posterior chamber to become higher than the pressure in the anterior chamber. As a result, the peripheral iris bows forward and comes into contact with the trabecular meshwork and/or peripheral cornea.

   In a minority of cases, this becomes a self-perpetuating cycle with obstruction of trabecular outflow leading to a rise in IOP up to 50-80 mmHg. When total trabecular obstruction occurs rapidly (within a few hours), it causes the symptoms and signs of acute angle-closure (AAC).

   The increased resistance to trans-pupillary aqueous flow is believed to result from co-activation of both sphincter and dilator muscles, causing the pupil margin to grip the anterior surface of the lens. This may occur in response to physiological stimuli, such as reading in poor light, or pharmacologically, such as with miotic therapy and concomitant dilator muscle stimulation by phenylephrine (the Mapstone provocation test)132. In most cases, the predisposition to pupil block is created by a narrow anterior segment and the age-related increase of lens volume (See Ch. 2.5.1 and 2.5.3).

   The prevalence of PAC is higher in elderly people women and in some races (especially East Asians). There is a weaker association with hypermetropia, exfoliation syndrome, diabetes and retinitis pigmentosa.

2. Anomalies at the level of the iris and/or ciliary body (“plateau iris configuration”)

   This group of anterior, non-pupil-block mechanisms are sometimes erroneously referred to under the umbrella term “plateau iris”. They are the result of variations in iris and ciliary body anatomy that brings the peripheral iris into contact with the trabecular meshwork. These include a thicker iris, a more anterior iris insertion and a more anterior ciliary body position. These anatomical factors predict failure of a laser iridotomy to open an appositionally closed angle133.

   Anteriorly positioned ciliary processes cause “typical” plateau iris configuration134. Plateau iris “syndrome” should be differentiated from plateau iris configuration. The “configuration” refers to a situation in which the iris plane is flat and the anterior chamber is not shallow axially. In most cases, the angle-closure glaucoma associated with the plateau iris configuration is cured by a peripheral iridectomy. “Plateau iris syndrome” refers to a post-laser condition in which a patent iridotomy has removed the relative pupillary block, but gonioscopically confirmed angle closure recurs without shallowing of the anterior chamber axially. Plateau iris syndrome is rare compared to the configuration, which itself is not common. It usually occurs in a younger age group than pupillary-block angle-closure. The treatment is laser iridoplasty or the long-term use of pilocarpine postoperatively as long as it is needed [II,D]. This syndrome must be considered in the differential diagnosis when the intraocular pressure rises unexpectedly following an adequate peripheral iridectomy procedure for angle-closure glaucoma135.

   Ideally, treatment should be instituted before synechial closure of the angle occurs [II,D]

3. Anomalies at the Level of the Lens

   The most widely recognised risk factor for primary angle-closure is a shallow anterior chamber. The anterior surface of the lens marks the depth of the anterior chamber, and as such, PAC patients typically have a thicker, more anteriorly positioned lens than people with wide open angles. Nuclear sclerotic cataract is a frequent finding in primary angle-closure. If a separate pathological or iatrogenic process causes the lens to suddenly increase in thickness (e.g. “classic” diabetic or post-traumatic cataract), become more anteriorly positioned (retinal gas or oil tamponade) or subluxate (Marfan syndrome or trauma), this may cause secondary angle-closure (See Ch. 2.5.1 and 2.5.3).

4. Anomalies posterior to the Lens (Aqueous misdirection syndrome)

   In rare cases, aqueous misdirection can complicate the management of primary angle-closure. This may occur following trabeculectomy, lens extraction, laser iridotomy and other surgical procedures. Forward movement of the lens iris diaphragm causes secondary angle-closure resulting in IOP elevation. These cases, typically have very small eyes (axial length <21 mm) and higher hypermetropic refraction (> +6D). It is believed that the ciliary processes come into contact with the lens equator, and/or a firm zonule/posterior capsule diaphragm, causing misdirection of aqueous into the vitreous135, 136. As a consequence, the lens/iris diaphragm is pushed forward and occludes the anterior chamber angle. After iridotomy or iridectomy, the use of miotics raises the IOP, whereas the use of cycloplegics reduces the IOP. This ‘inverse’ or ‘paradoxical’ reaction to parasympathomimetics should be tested only after iridotomy has been performed. Ultrasound biomicroscopy can demonstrate abnormal posterior chamber anatomy in these rare cases (See Ch. 2.5.3).

   Asymmetry of anterior chamber depth is a cardinal sign of secondary (types III and IV) angle-closure.

2.4.1.6 Demographic risk factors for Primary Angle-Closure135,138

• Older age

• Female

• Asian and Eskimoan Race

Family history if primary angle-closure: family screening is vital in these families as robust evidence now exists for significant increased risk of angle closure in family members of an affected patient: first degree relatives may have a 1 in 4 risk of a PAC disease requiring treatment139.

2.4.1.7 Descriptions of subtypes:

Primary angle-closure has previously been divided into 5 clinical subtypes according to mode of presentation. There is debate on whether this approach to classification is useful in determining the prognosis or optimal management.

• Primary Angle-Closure Suspect (PACS)

• Acute Angle-Closure (AAC)

• Intermittent Angle-Closure (IAC)

• Chronic Angle-Closure Glaucoma (CACG)

• Status Post-Acute Angle-closure Attack

2.4.1.7.4 Intermittent Angle-Closure (lAC)

Etiology:

Similar but milder clinical manifestations than AAC, it resolves spontaneously.

Pathomechanism: See above Ch. 2.4.1.5

Features:

Signs:

• May vary according to amount of iridotrabecular contact of chamber angle and mimic acute angle-closure in a mild form

• When not on miotics, pupil is round and reactive

• The optic disc rim may show atrophy with an afferent pupillary defect

Symptoms:

• Mild, intermittent symptoms of acute angle-closure type

Treatment:

Pupillary constriction, iridotomy, iridoplasty or lens extraction are to be considered according to the main mechanism determining angle occlusion [II,D]

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2.4.1.7.6 Status Post-Acute Angle-closure Attack

Etiology:

Previous episode of acute angle-closure attack

Pathomechanism: See Ch. 2.4.1.5

Features:

Signs:

• Patchy iris atrophy Iris torsion/spiralling posterior synechiae

• Pupil either poorly reactive or non-reactive

• “Glaukomflecken” of the anterior lens surface

• Peripheral anterior synechiae on gonioscopy

• Endothelial cell count can be decreased

Therapy:

Management according to angle, lens, IOP and disc/visual field. In case of cataract surgery, non dilatable pupil, low endothelial cell count and loose zonules are of concern.

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2.5.2.1 Neovascular glaucoma

The iridotrabecular fibrovascular membrane is induced by ocular microvascular disease with retinal ischemia; initially the neovascular membrane covers the angle, causing a secondary form of open angle glaucoma (See Ch 2.3 Secondary Open Angle Glaucoma)

Treatment [II,D]:

1. Topical atropine or equivalent

2. Topical steroid initially

3. Topical and systemic IOP lowering medication as needed

4. Retinal ablation with laser or cryotherapy

5. Cyclodestruction

6. Filtering procedure with antimetabolites

7. Aqueous drainage devices

8. Miotics are contraindicated

The intravitreal injection of anti-VEGF molecules has shown benefit for this indication [II,C] and is in widespread use.

2.5.2.2 Iridocorneal endothelial syndrome

Iridocorneal Endothelial (ICE) Syndrome, with progressive endothelial membrane formation and progressive iridotrabecular adhesion.

Peripheral anterior synechiae, due to prolonged primary angle-closure; this is theoretically a primary angle-closure.

Treatment [II,D]:

1. Topical and systemic IOP lowering medications as needed

2. Filtering procedure, with antimetabolite according to risk factors

3. Aqueous drainage device

2.5.2.3 Posterior polymorphous dystrophy

Treatment [II,D]:

1. Topical and systemic IOP lowering medication as needed

2. Filtering procedure, with antimetabolite according to risk factors

2.5.2.4 Epithelial and fibrous ingrowth after anterior segment surgery or penetrating trauma

Epithelial and fibrous ingrowth after anterior segment surgery or penetrating trauma Inflammatory membrane.

Treatment [II,D]:

1. Topical and systemic IOP lowering medication as needed

2. Excision, destruction of the immigrated tissue

3. Filtering procedure, with antimetabolite according to risk factors

4. Aqueous drainage device

5. Cyclodestruction

2.5.2.5 Inflammatory membrane

Treatment [II,D]:

1. Anti-inflammatory medications and cycloplegics

2. Topical and systemic IOP lowering medication as needed

3. Filtering procedure with antimetabolite

4. Aqueous drainage device

5. Cyclodestruction

2.5.2.6 Peripheral anterior synechiae after ALT and endothelial membrane covering the trabecular meshwork late after ALT

After argon laser trabeculoplasty (ALT), early and late peripheral anterior synechiae and endothelial membrane covering the trabecular meshwork

Treatment [II,D]:

1. Topical and systemic IOP lowering medication as needed

2. Filtering procedure

2.5.2.7 Aniridia

Treatment [II,D]:

1. Topical and systemic IOP lowering medication as needed

2. Trabeculotomy

3. Filtering procedure with antimetabolites

4. Aqueous drainage device

5. Cyclodestruction

2.5.3.1 Aqueous misdirection (also known as cilio-lenticular block, ciliary block or malignant glaucoma)

Etiology:

Angle-closure is caused by the ciliary body and iris rotating forward. Aqueous misdirection, or malignant glaucoma, is a rare type of secondary angle-closure glaucoma most commonly encountered after filtering surgery. The syndrome, also known as ciliary block glaucoma, can occur spontaneously or following any type of intraocular surgery.

Pathomechanism:

• The lens may be proportionally abnormally large or swollen, “phacomorphic glaucoma”

• Aqueous humour accumulates in the vitreous body (posterior aqueous humour misdirection) or behind and around the crystalline lens (perilenticular misdirection) or behind the iridocapsular diaphragm or posterior chamber intraocular lens (PCL) after extracapsular cataract surgery, with or without PCL implantation, “retrocapsular misdirection”

• Frequently precipitated by ocular surgery and flat anterior chamber

• Predisposition may be similar in both eyes particularly in small eyes

Treatment:

Medical treatment

1. Parasympatholytics (atropine, cyclopentolate) both initially and for long-term pupillary dilation and cycloplegia [I,C]

2. Aqueous production suppressants given orally and/or topically [I,D]

3. Hyperosmotics (Ch. 3.3.1.3) [I,D] Miotics are contraindicated!

Surgical treatment

1. A patent iridotomy must be present or, if not present, iridotomy should be performed [I,D]

2. YAG laser vitreolysis/capsulotomy, especially in aphakia, pseudophakia [II,C]

3. Anterior vitrectomy, especially in aphakia, pseudophakia [II,C]

4. Cyclo diode laser

5. In selected cases lens extraction [II,D]

2.5.3.2 Iris and ciliary body cysts, intraocular tumors

Treatment:

1. Tumour irradiation or excision

2. Filtering surgery

3. Cyclodestruction

2.5.3.3 Silicon oil or other tamponading fluids or gas implanted in the vitreous cavity138

Treatment:

1. Topical/systemic IOP lowering medications as needed

2. Silicon oil or gas aspiration

3. Filtering surgery

4. Drainage device

5. Cyclodestruction

2.5.3.4 Uveal effusion151,152

It is due to:

1. Inflammation as in scleritis, uveitis, HIV infection

2. Increased choroidal venous pressure as in nanophthalmos, scleral buckling, panretinal photocoagulation, central retinal vein occlusion, arterio-venous communication

3. Tumor

Treatment:

1. Anti-inflammatory medication (for 1)

2. Topical and systemic IOP lowering medication as needed (for 1,2 and 3)

3. Relaxation of scleral buckling; vitrectomy, sclerectomy in nanophthalmus (for Tumor excision or irradiation (for 3)

4. Cyclodestruction

2.5.3.5 Retinopathy of prematurity (stage V)

Features:

Signs and Symptoms:

• Variable discomfort, pain, redness, corneal oedema IOP ≥ 21 mmHg

• Axially shallow anterior chamber

Treatment:

1. Topical and systemic IOP lowering medications

2. Cyclodestruction

3. Filtering procedure with or without antimetabolite

4. Drainage devices

2.5.3.6 Congenital anomalies that can be associated with secondary glaucoma

These conditions are extremely variable in pathogenesis, clinical presentation and required management; an extensive discussion is outside the scope of this chapter.

Etiology:

Familial iris hypoplasia, anomalous superficial iris vessels, aniridia, Sturge-Weber syndrome, neurofibromatosis, Marfan’s syndrome, Pierre Robin syndrome, homocystinuria, goniodysgenesis, Lowe’s syndrome, microcornea, microspherophakia, rubella, broad thumb syndrome, persistent hyperplastic primary vitreous.

Pathomechanism:

Angle-closure is caused by pushing forward the ciliary body and iris. Increase of volume of the posterior segment of the eye.

Features:

Signs and Symptoms:

• IOP> 21 mmHg

• Pain, redness, corneal oedema

• Axially shallow anterior chamber

• Laser iridotomy and surgical iridectomy are not effective

Treatment:

Treatment to be adapted to the primary anomaly, the mechanism of IOP elevation and the quality of life of the patient.