América

As most cases of primary angle-closure present to Western ophthalmologists with dramatically raised lOP and florid symptoms of pain, reduced vision, and often nausea and vomiting, it is necessary to alleviate these. This is most effectively achieved by medical means, including acetazolamide, topical pilocarpine, beta-

blockers, alpha-agonists and occasionally intravenous mannitol. Iridotomy is now the standard treatment for angle-closure caused by pupil block, although it has evolved from surgical iridectomy. Surgical iridectomy was first described as a treatment for acute glaucoma by Graefe, although the pathophysiology of angle- closure was not well understood The underlying mechanism of angle-closure and the role of iridectomy were more fully elucidated by Curran in 1931^"^^. Laser iridoplasty (see section 1.7.7.3) is gaining popularity as a mode of managing symptomatic PAG. However, the definitive management of PAG relies on modifying the configuration of the drainage angle by either laser, surgical or medical means.

1.7.7.1 Laser peripheral iridotomy

Laser iridotomy is the technique of choice for managing PAG due to pupil-block. It is very difficult to confirm that any case of PAG does not have a pupil-block

component, and hence iridotomy is indicated in every case unless there is a compelling reason not to attempt this. It is widely agreed that laser PI is indicated in patients with any gonioscopic evidence of PAG (for example peripheral anterior synechiae or pigment smearing on the trabecular meshwork) and in eyes with occludable drainage angles and raised lOP.

Although the technique of iridotomy was developed using argon lasers, their use has largely been superseded by Nd-YAG lasers, which allow easier penetration of blue irises and use substantially less energy Pre-treatment with pilocarpine (2%) to stretch and thin the iris, and either apraclonidine (0.5%, topical) or

acetazolamide (500mg, PC) as prophylaxis against post-laser lOP spikes should be given. Apraclonidine has a theoretical advantage in that, as a vasoconstrictor, it may reduce bleeding from the iridotomy. The iridotomy should be sited in the superior quadrant, under the top lid where it cannot cause diplopia (but not at 12 o'clock where gas bubbles may obscure the view). To create an iridotomy without damaging lens or cornea, it is necessary to reach a compromise. The more

peripheral the location, the greater the separation between iris and lens, but the smaller the irido-corneal gap. In practice, the exact location is often dictated by the presence of a crypt where the iris is thinnest. In patients with a thick iris

stroma, gentle forward pressure with the Abraham’s contact lens will cause thinner areas to bulge forwards. Once a suitable thin area has been identified, the beam should be focused within the iris stroma and aimed away from the posterior pole. Usually 1-3 single pulses of around 1-2 mJ are sufficient in blue eyed patients. For persons with dark brown irises, 10-12 mJ is an appropriate power for the first few shots. Final perforation can usually be achieved with lower powers of 2-3 mJ. At higher powers, the patient should be warned that the laser shot may be felt. It has been calculated that an iridotomy should be at least 200pm in diameter to effectively prevent pupil-block

In patients with dark irises or a thick iris stroma, total YAG laser energy of 150 mJ may be needed. Often a plume of dispersed pigment may obscure a clear view of the iridotomy site, necessitating a second treatment session. Haemorrhage will sometime obscure a clear view, but this can be halted with slight forward pressure with the lens. The use of a sequential argon/Nd-YAG technique avoids these problems. Between 20 and 80 argon burns (700-1200 mW power, 0.1 s duration, 50pm spot size) will produce a "crater” in the iris stroma, which can then be easily perforated using Nd-YAG shots of 1-2 mJ. If charring of the iris begins to occur, the power and duration of the shots should be reduced Although perforation can usually be achieved at the first treatment session, use of the argon laser increases total laser energy by a factor of 10 to 100.

A topical steroid (such as prednisolone acetate 1%) should be used hourly on the day of treatment and four times daily for one week thereafter. Complications among a group of 200 patients treated with Nd-YAG laser included lOP rise (>10 mm Hg): 30%, haemorrhage: 20%, iritis: 11%, posterior synechiae: 7% and

corneal changes 4% Cataract is considered a potential long-term complication although one study found visual acuity was the same or improved in 85% of eyes at an average of 1.8 years after treatment. Cataract progression was responsible for eyes with decreased acuity; the rate of progression was the same as that in similarly-aged persons treated by surgical iridectomy

A detailed study of 140 eyes of 104 people with PAC in Japan treated by argon laser iridotomy found 67% of eyes (73/109) had a cupidisc ratio of >0.7 prior to treatment. The CDR enlarged in 28% (31) and remained unchanged in 59% (64); mean follow-up 1.7 and 2.7 years (in two groups). Visual field defects were minimal or absent in 81% (96/118), moderate in 16% (19/118) and advanced in 3% (3/118). The defects progressed in only 3 patients (all with initially mild changes). lOP < 21 mm Hg (with or without medication) after PI was achieved in 94%. lOP control was more likely to be successful if there were <180° PAS.

There was no significant change in the amount of PAS during the follow-up period. Loss of visual acuity by more than 3 lines occurred in 19%. It was stated that this was due to progression of lens opacities, although this was not quantified

1.7.7.2 Surgical iridectomy

Given current evidence, the sole indication for surgical iridectomy is probably the lack of access to a laser. A prospective, randomised comparison of laser

iridotomy and surgical iridectomy for symptomatic PAC in Europeans found control of lOP and post-operative visual acuity (VA) to be equivalent; 15/21 (70%) and

19/27 (72%) respectively had an lOP < 21 mm Hg after 3 years follow-up. Four patients with unsatisfactory medical control of lOP, and one with nerve damage and field loss were excluded from the study randomisation The risk of complications from intraocular surgery such as endophthalmitis does not seem justified, when a closed surgical technique is available.

1.7.7.3 Laser iridoplasty

If, after laser iridotomy, peripheral iris-crowding is believed to be a significant contributing factor in closure of the angle, argon laser iridoplasty or topical

pilocarpine should be considered. These are intended to draw the peripheral iris away from the face of the trabecular meshwork. Laser iridoplasty is usually

considered a temporizing measure and probably begins to lose its effect around 1- 2 years after treatment, although it may be repeated several times (Pitch &

Leibmann- personal communications 1997). Topical pilocarpine (1-2%) has a similar effect but has attendant complications of brow-ache, dimming of vision and accelerated formation of lens opacities.

Laser iridoplasty is now seen as an effective method of managing medically unresponsive primary angle-closure that would otherwise require surgical intervention. The aim is to apply low power contraction burns to the iris stroma either peripherally or at the sphincter. An Abraham’s lens (with a +66D section) should be used. The power setting is varied according to the colour and thickness of the iris (see Table 5). Starting at 100 mW, power is increased until stromal contraction is seen. If pigment is liberated, the power should be reduced. For iridoplasty, about ten burns are applied as peripherally as possible in each quadrant in areas which have been found to open with compression gonioscopy (or the inferior quadrant if this is not possible). The aim of sector pupilioplasty is to induce a localised constriction of the sphincter, causing peaking of the pupil and breaking the pupil block. Both techniques may be used together Once iridoplasty is successful, iridotomy should be performed without delay.

Table 5. The laser power parameters for laser iridoplasty and sector pupilioplasty

Iris colour Technique Spot size Duration Power

Light Iridoplasty 500 |im 0.5 s 200-1000 mW

Light Pupilioplasty 200 pm 0.5 s 200-500 mW

Dark Iridoplasty 100 pm 0.2 s 200-600 mW

Dark Pupilioplasty 50 pm 0.2 s 100-400 mW

(power should be increased according to the clarity of the cornea)

If corneal oedema obscures a clear view, topical glycerin may be used to

temporarily clear the cornea. Topical pilocarpine or an ag-agonist are appropriate as pre-medication. The possibility of a post-laser lOP spike should be

remembered. Topical steroids (prednisolone 1%,QID) should be used for 5-7 days.

1.7.7.4 Medical therapy

If satisfactory pressure control cannot be achieved with a PI alone, topical medical therapy should be used in a similar manner as for POAG. A target pressure should be set according to the degree of nerve damage and field loss. If the iris

contour has been satisfactorily changed by iridotomy (implying that pupil-block was the predominant mechanism), then a p-blocker would be an appropriate first choice. If the iris profile has not changed after the PI (suggesting peripheral iris crowding is the predominant mechanism), pilocarpine (1-2%) is a more

appropriate choice. An a-2 agonist is an appropriate second-line therapy. The prostaglandin analogue latanoprost has recently been touted as a method of medical management for RAC after laser PI. Although latanoprost is believed to reduce lOP by increasing aqueous outflow via the uveoscleral route (which would be compromised in angle-closure), a randomised, controlled trial found that latanoprost once daily achieved a significantly greater short-term lOP reduction than did timolol maleate twice daily Outcome of treatment by iridotomy and topical medication is summarised in Table 6.

Table 6. Long-term intraocular pressure control* in primary angle-closure by laser peripheral iridotomy and topical medication Location Eyes (Patients) Acute/fellow/ Chronic eyes Successful without Rx * Successful with Rx * Follow-up Design

Israel 53 (34) 20/15/18 15/15/0 16/15/? 2 years Case series

Baltimore (US) 98 (54) 28/20/50 50 total 21/20/46 Mean: 4.4 years Case series

Chicago (US) 19(16) 0/0/19 0 12 Mean: 1.3 years Case series

South Africa 78 (52) 0/0/78 7 40 Mean: 1.8 years Case series

Scotland 27 (27) 27/0/0 19 23 3 years Prospective RCT

* Success defined as lOP < 21 mm Hg RCT: Randomised, controlled trial

Source data: Israel Baltimore Chicago South Africa Scotland

1.7.7.5 T rabeculectomy

Trabeculectomy is indicated in cases of PAC with glaucomatous optic neuropathy that cannot be controlled by laser iridotomy and medication. There is often

concern that “malignant glaucoma” (cilio-lenticular block) may complicate

trabeculectomy in cases with primary angle-closure, although published data and anecdotal experience do not support this. One study in the UK of 309 eyes, found identical complication rates in the POAG and angle-closure groups. Shallow anterior chambers were seen in 22/126 POAG, 24/112 asymptomatic PAG and 8/71 symptomatic PAC (17%, 21% and 11% respectively). Surgery was most successful in achieving lOP control (< 21 mm Hg with medication; follow-up, 7 years) in symptomatic PAC (93%), then POAG (87%), with least success in asymptomatic PAC (80%)

1.7.7.6 Lens extraction

Because the position of the lens determines the iris profile, and therefore the angle configuration, lens extraction is a logical choice for surgical management of raised lOP in cases of PAC with visual impairment due to cataract. Extracapsular

cataract extraction was used in the management of PAC in 21 eyes of 20 patients (2 with raised lOP alone, 5 symptomatic and 14 asymptomatic). In 14 cases, lens extraction was performed in place of filtering surgery, where peripheral iridectomy or previous filtering surgery had failed. The mean lOP was reduced from 31 to 16 mm Hg after surgery. Seventy six percent (16/21 ) of eyes did not require further medication (follow-up: 6 to 42 months). It was noted that the lOP was reduced even if there were extensive previous PAS. In 6 patients with previous failed filtering surgery, lens extraction gave a median lOP reduction of 17.5 mm Hg (range 5 to 30).

A second study examining the lOP control achieved by cataract extraction in 17 patients (19 eyes- 9 symptomatic and 10 asymptomatic) found post-operative lOP < 22 mm Hg without medication was achieved in 68%. With medication, lOP was < 22 mm Hg in 94%. In 9 eyes with a CDR > 0.7, median lOP after surgery was 17.5 (range: 14 to 21) mm Hg, on a median of 0 medications (0 to 2). The authors of both studies concluded that combined cataract extraction and trabeculectomy may not be necessary in PACG.

1.7.7.7 Neuro-protection

It is believed that the primary pathological event in glaucomatous optic neuropathy is followed by a secondary neuro-degenerative process. This is probably

mediated by a neurotransmitter such as glutamate and free radicals that trigger apoptotic cell death. The possibility that some neuronal damage occurring after a period of elevated intraocular pressure may be prevented is attractive, and

particularly appropriate to the management of angle-closure. Blockade of the self- perpetuating neuro-chemical cascade by antagonists targeted on the N-methyl-D- aspartate (NMDA) glutamate receptor sub-group, using agents such as MK 801 has given promising experimental r e s u l t s T h e r e are no agents currently on the market with a proven neuro-protective capacity for glaucoma therapy.

1.7.7.8 Prognosis following treatment

A retrospective analysis of 57 Singaporeans with symptomatic PAC found that more than 24 hours delay in presentation or the need for a laser iridoplasty to achieve short-term pressure control were associated with worse pressure control after laser iridotomy (mean follow-up period, 20 months) Another retrospective study in South Africa of 52 asymptomatic patients (78 eyes) followed for a mean period of 22 months found lOP was controlled (< 21 mm Hg) without medication in 9%, and with medication in 51% of eyes. Trabeculectomy was required in 29% of eyes. The risk factors for needing trabeculectomy were: an lOP on presentation > 35 mm Hg, or > 3 quadrants of synechial angle-closure, or a cup:disc ratio of > 0.6. However, 36% of eyes with these risk factors were controlled by peripheral iridotomy with or without medication.

In light of these findings, the likelihood that a non-invasive procedure will control lOP and arrest progression of optic neuropathy probably justifies the use of laser PI as first line treatment in all but the most severe cases

1.7.7.9 Management of the asymptomatic narrow angle

In a multi-centre study of 129 asymptomatic patients with ACD < 2 mm or drainage angles that were potentially occludable, only 6% developed signs or symptoms consistent with PAC over a mean period of 2.7 years (maximum follow-up 6 years)

It would therefore appear that an individual’s risk of developing visually

threatening sequelae is low on a year-to-year basis. However, it is now accepted practice to perform a laser iridotomy on patients with early gonioscopic evidence of angle-closure reflecting the perceived (although unproven) high risk/benefit ratio for this procedure. This view is probably justified when one considers the potential for late-presentation or mis-diagnosis under non-ophthalmological care, and the low incidence of sight-threatening complications of laser iridotomy.

The management of an eye contra-lateral to one that had an episode of

symptomatic PAC is open to less conjecture. Follow-up of 200 such “fellow” eyes found 113 were managed by observation or with topical pilocarpine. Of this

number 51% (58 eyes) developed symptomatic PAG, half within a five year period. Twenty-six of the 58 were using topical pilocarpine In another study of 250 patients with PAC, 72 did not have prophylactic peripheral iridectomy. Forty-three developed PAC (33 symptomatic, 10 asymptomatic or unknown), 33 of these were affected within 6 years This is overwhelming evidence in favour of

prophylactic peripheral iridotomy by laser, or surgical iridectomy if no laser is available.