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ot<br />

Sponsored by<br />

a<br />

Greg Heath BSc (Hons), MCOptom, DipClinOptom<br />

Ocular <strong>the</strong>rapeutic case studies<br />

Medical management of glaucoma<br />

The sine qua non of glaucoma management is to arrest optic nerve damage and, as<br />

such, prevent fur<strong>the</strong>r losses to <strong>the</strong> patient’s visual field. It is noteworthy that <strong>the</strong><br />

American Academy of Ophthalmology’s definition of open angle glaucoma – as a<br />

progressive neuropathy characterised by loss of ganglion cells – makes no<br />

reference to intraocular pressure (IOP). Notwithstanding, it is axiomatic that <strong>the</strong><br />

successful management of glaucomatous patients, whe<strong>the</strong>r medical or surgical, lies<br />

in <strong>the</strong> ability of <strong>the</strong> practitioner to lower <strong>the</strong> patient’s IOP.<br />

Topical anti-glaucoma agents are reserved for<br />

those patients who have glaucoma or ocular<br />

hypertension. The reasons for treating <strong>the</strong> latter<br />

group are twofold – first, to reduce <strong>the</strong> risk of<br />

acquiring central retinal vein occlusion, and<br />

second, topical hypotensive <strong>the</strong>rapy may delay or<br />

even prevent <strong>the</strong> onset of primary open angle<br />

glaucoma (POAG) in <strong>the</strong>se individuals. Evidence<br />

supporting <strong>the</strong> benefits to hypertensives came<br />

from <strong>the</strong> Ocular Hypertensive Treatment Study 1 ,<br />

conducted in <strong>the</strong> Washington School of Medicine.<br />

Of <strong>the</strong> 1,636 ocular hypertensives randomised to<br />

ei<strong>the</strong>r <strong>the</strong> treatment group or observation group,<br />

<strong>the</strong> cumulative probability of developing POAG in<br />

<strong>the</strong> treatment cohort was 4.4%, compared with<br />

9.5% in <strong>the</strong> observation cohort.<br />

Over <strong>the</strong> past decade, <strong>the</strong>re have been<br />

numerous additions to <strong>the</strong> ophthalmologist’s<br />

ocular hypotensive drugs cabinet. Indeed, <strong>the</strong><br />

addition of <strong>the</strong>se new agents to <strong>the</strong> treatment<br />

regimen has had a dramatic impact on <strong>the</strong><br />

overall management of glaucomatous patients.<br />

In <strong>the</strong>ir retrospective analysis of National Health<br />

stations in Scotland, Bateman et al 2 revealed a<br />

45.9% reduction in operation rates between<br />

1994 and 1999. By contrast, <strong>the</strong> number of<br />

patients treated via <strong>the</strong>ir topical counterparts<br />

had increased dramatically. The authors<br />

attributed this management swing to <strong>the</strong><br />

effectiveness of <strong>the</strong> new ocular hypotensive<br />

agents, namely <strong>the</strong> carbonic anhydrase inhibitors<br />

(CAIs), prostaglandin analogues and alpha2<br />

agonists.<br />

In keeping with <strong>the</strong> previous article in this<br />

CPD module (“Ocular <strong>the</strong>rapeutic case studies:<br />

glaucoma – when to operate?” OT 28/06/02),<br />

this article will focus on <strong>the</strong> most prevalent type<br />

of glaucoma – POAG. The medical <strong>the</strong>rapies<br />

currently available to combat this chronic<br />

malady, toge<strong>the</strong>r with <strong>the</strong>ir associated side<br />

effects, will be discussed.<br />

Therapeutic trials<br />

Since IOP varies diurnally, assessing <strong>the</strong><br />

patient’s control of <strong>the</strong>ir glaucoma through a<br />

single measurement is futile. It is for this reason<br />

that many practitioners (especially in <strong>the</strong> US)<br />

advocate a monocular <strong>the</strong>rapeutic trial prior to<br />

prescribing <strong>the</strong> drug in question. The usefulness<br />

of such a trial is illustrated in <strong>the</strong> following<br />

example.<br />

Patient GH presents to <strong>the</strong> glaucoma clinic<br />

with IOPs of 32mmHg in each eye. The<br />

practitioner prescribes his/her preferred topical<br />

hypotensive agent to <strong>the</strong> right eye only and<br />

re-examines <strong>the</strong> patient three weeks later. If, on<br />

<strong>the</strong> subsequent visit, <strong>the</strong> patient’s IOPs are now<br />

R 20mmHg and L 20mmHg, <strong>the</strong>n one can<br />

conclude that <strong>the</strong> drug has been ineffective<br />

(assuming that <strong>the</strong> patient adhered to <strong>the</strong><br />

prescriber’s instruction of instilling in <strong>the</strong> right<br />

eye only). However, if <strong>the</strong> readings are<br />

R 20mmHg and L 28mmHg on repeat<br />

examination, <strong>the</strong> effect of <strong>the</strong> drug is clear. One<br />

important caveat is that some drugs, such as<br />

beta-blockers, may lower <strong>the</strong> IOP in both eyes<br />

despite unilateral administration. That said,<br />

<strong>the</strong>se effects are usually asymmetric with <strong>the</strong><br />

administered eye exhibiting <strong>the</strong> greatest<br />

hypotensive effect.<br />

Therapeutic trials are also useful in<br />

evaluating <strong>the</strong> benefits of adding ano<strong>the</strong>r drug<br />

to <strong>the</strong> patient’s treatment regimen. They allow<br />

<strong>the</strong> practitioner to decide whe<strong>the</strong>r <strong>the</strong><br />

additional expense and potential for side effects<br />

is justified in each case.<br />

Table 1<br />

Main classes of ocular hypotensive drugs and <strong>the</strong>ir mechanisms<br />

DRUG<br />

Beta-blockers<br />

Miotics<br />

Adrenergics: Adrenaline and Dipivefrin<br />

alpha2 agonists<br />

Carbonic anhydrase inhibitors (CAIs)<br />

Prostaglandin analogues<br />

Hyperosmotic agents<br />

ACTION<br />

Decrease aqueous production<br />

Increase trabecular outflow by constricting longitudinal ciliary body<br />

muscle and opening trabecular meshwork<br />

Decrease aqueous production and increase outflow facility<br />

Decrease aqueous production<br />

Decrease aqueous production<br />

Increase uveoscleral outflow<br />

Increase osmolality of blood thus drawing aqueous from vitreous<br />

ABDO has awarded<br />

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2 CET credits (GD).<br />

The College of<br />

Optometrists has<br />

awarded this article 2<br />

CET credits. There are<br />

12 MCQs with a pass<br />

mark of 60%.<br />

Despite <strong>the</strong> effectiveness of such trials, <strong>the</strong><br />

major drawback is <strong>the</strong> time and number of<br />

hospital appointments required before a final<br />

treatment plan is established. In <strong>the</strong> UK, where<br />

<strong>the</strong> NHS doctors are beleaguered, such<br />

methodology may be impractical.<br />

Patient suitability<br />

Although medical <strong>the</strong>rapy is currently <strong>the</strong><br />

mainstay of treatment for glaucoma,<br />

practitioners should be aware that such<br />

stratagems are fraught with problems. The<br />

disadvantages of medical <strong>the</strong>rapy include:<br />

• IOP lowering effects less effective<br />

than surgery<br />

• Potential for serious side effects<br />

• Topical medications frequently overlooked as<br />

a cause of systemic side effects<br />

• Nuisance factor may interfere with <strong>the</strong><br />

patient’s quality of life<br />

• Costs of care are high in <strong>the</strong> long term<br />

• Compliance<br />

Poor compliance is an extremely important<br />

negative effect. Defaulting from medical <strong>the</strong>rapy<br />

can be a major factor in <strong>the</strong> progression of this<br />

insidious disease. Fur<strong>the</strong>rmore, poor compliance<br />

may occur for various reasons including age of<br />

patient, patient’s systemic status, occupation,<br />

lifestyle and <strong>the</strong>ir social situation. Thus, <strong>the</strong><br />

busier <strong>the</strong> patient’s lifestyle is, <strong>the</strong> less<br />

structured <strong>the</strong> environment and <strong>the</strong> more likely<br />

she/he is to disregard <strong>the</strong>ir treatment. Similarly,<br />

a patient with a co-existing chronic disease, e.g.<br />

rheumatoid arthritis, would lack <strong>the</strong> manual<br />

dexterity to instil <strong>the</strong> drugs. All of <strong>the</strong>se factors<br />

should be taken into account before a decision is<br />

made as to <strong>the</strong> best form of treatment for each<br />

individual.<br />

Medications<br />

Table 1 summarises <strong>the</strong> main classes of ocular<br />

hypotensive agents toge<strong>the</strong>r with <strong>the</strong>ir proposed<br />

mechanisms of action.<br />

Beta-blockers<br />

Since <strong>the</strong> introduction of Timolol in <strong>the</strong> late<br />

1970s, topical beta-blockers have remained <strong>the</strong><br />

quintessential drug in <strong>the</strong> management of<br />

26<br />

July 26, 2002 OT<br />


Module 4 Part 8<br />

glaucoma. Their popularity arose as a result of<br />

<strong>the</strong>ir potent hypotensive effects in most types of<br />

glaucoma, in addition to a relative dearth of<br />

associated ocular side effects exhibited by <strong>the</strong>ir<br />

topical counterparts (e.g. miosis, conjunctival<br />

hyperaemia). Notwithstanding <strong>the</strong>ir advantages,<br />

such agents have gained notoriety through <strong>the</strong>ir<br />

ability to induce potentially grave systemic side<br />

effects.<br />

Mechanism of action<br />

Beta-blockers reduce IOP by decreasing aqueous<br />

production. Their effects on uveoscleral outflow<br />

and episcleral venous pressure are negligible. In<br />

humans, <strong>the</strong>re are two main alpha-adrenoceptors<br />

– alpha1 and alpha2. While <strong>the</strong> former<br />

predominate in heart muscle, <strong>the</strong> latter reside in<br />

<strong>the</strong> bronchial musculature. Consequently,<br />

stimulation of alpha1 receptors would result in<br />

tachycardia (increased heart rate), whereas<br />

stimulation of alpha2 would result in bronchial<br />

dilatation.<br />

Most of <strong>the</strong> topical beta-blockers available<br />

are non-selective. In o<strong>the</strong>r words, <strong>the</strong>y block<br />

both types of receptor. The exception to this rule<br />

is Betaxolol, which is a relative cardioselective<br />

beta-blocker. However, it may still bind to its<br />

bronchial counterpart although <strong>the</strong> degree of<br />

potency is two orders of magnitude less than<br />

Timolol 3 .<br />

Drugs<br />

The various types of beta-blockers currently used<br />

in <strong>the</strong> treatment of glaucoma are listed in<br />

Table 2.<br />

Non-selective beta-blockers<br />

As mentioned earlier, Timolol has been <strong>the</strong><br />

anti-glaucoma drug par excellence for decades<br />

and, as such, has been considered <strong>the</strong> reference<br />

standard for IOP lowering efficacy. Probably <strong>the</strong><br />

major key to its success is its ability to lower IOP<br />

in up to 90% of prospective patients. It is<br />

available in two concentrations – 0.25% and<br />

0.5%. The lower concentration is suitable for<br />

patients possessing lightly pigmented irides,<br />

whereas <strong>the</strong> 0.5% is ideally suited for those with<br />

dark irides 4,5,6 .<br />

Despite boasting considerable reductions in<br />

IOP of up to 40% from baseline, Timolol’s<br />

efficacy diminishes over subsequent months in<br />

up to 20% of those individuals initially treated.<br />

Such a relative decline in efficiency has been<br />

coined ‘long-term drift’ by Steinert and<br />

co-workers 7 and <strong>the</strong>se effects should be borne in<br />

<strong>the</strong> practitioner’s mind when initiating betablocker<br />

mono<strong>the</strong>rapy.<br />

All topical beta-blockers share <strong>the</strong> same<br />

properties as Timolol with <strong>the</strong> exception of<br />

Carteolol, a non-selective beta-blocker exhibiting<br />

concomitant intrinsic sympathomimetic activity,<br />

and Betaxolol, a relatively selective beta-blocker.<br />

Owing to its intrinsic sympathomimetic<br />

activity, Carteolol may be more selective to <strong>the</strong><br />

eye and, as a consequence, <strong>the</strong> likelihood of<br />

inducing cardiopulmonary adverse effects would<br />

be considerably less than its non-selective<br />

counterparts 8 .<br />

www.optometry.co.uk<br />

DRUG<br />

Timolol<br />

Timoptic-Xe gel<br />

Levobunolol<br />

Carteolol<br />

Metipranolol<br />

Betaxolol<br />

Table 2<br />

Topical beta-blockers<br />


0.25%, 0.50%<br />

0.25%, 0.50%<br />

0.50%<br />

1%, 2%<br />

0.1%, 0.3%<br />

0.5%<br />

Betaxolol<br />

In keeping with most of <strong>the</strong> topical beta-blocker<br />

family, Betaxolol lacks intrinsic sympathomimetic<br />

activity. However, in contradistinction, it is more<br />

cardioselective. The corollary of this <strong>the</strong>rapeutic<br />

feature is that <strong>the</strong> drug is a better choice for<br />

patients with restrictive airways disease.<br />

However, <strong>the</strong>re is an important caveat since<br />

Betaxolol’s cardioselectivity is only relative and it<br />

may exacerbate pulmonary adverse effects in<br />

susceptible individuals.<br />

Although <strong>the</strong> IOP reductions achieved with<br />

twice daily administrations of Betaxolol are<br />

somewhat modest in comparison to Timolol, <strong>the</strong><br />

drug appears to be superior in retarding <strong>the</strong><br />

progression of visual field defects. Moreover,<br />

several investigators utilising doppler colour<br />

imaging of retinal blood vessels have shown an<br />

increase in retinal blood flow following topical<br />

administration of Betaxolol 9 . Such<br />

‘neuroprotective’ effects may explain, in part,<br />

<strong>the</strong> efficacious nature of Betaxolol in <strong>the</strong><br />

treatment of glaucoma despite relatively modest<br />

reductions in IOP.<br />

Side effects<br />

As illustrated in Table 3, beta-blockers have <strong>the</strong><br />

potential to produce a plethora of systemic side<br />

effects. The cardiovascular and bronchial adverse<br />

effects are <strong>the</strong> result of blockading <strong>the</strong> alpha1<br />

and alpha2 adrenoceptors respectively. Blockade<br />

of <strong>the</strong> former results in bradycardia and<br />

hypotension and, consequently, <strong>the</strong>y should not<br />

be given to patients suffering from heart block,<br />

sinus bradycardia or cardiac failure. Blockade of<br />

<strong>the</strong> alpha2 adrenoceptors can result in<br />

bronchospasm, which may prove fatal in patients<br />

suffering from asthma or chronic obstructive<br />

pulmonary disease.<br />

In a retrospective analysis of adverse<br />

reactions to topical Timolol between 1978 and<br />

1985, over 450 cases of serious respiratory and<br />

cardiovascular events were reported 10 . Tragically,<br />

<strong>the</strong> same study disclosed 32 deaths attributed to<br />

<strong>the</strong> topical administration of Timolol. This<br />

underscores <strong>the</strong> need for <strong>the</strong> prescribing<br />

practitioner to be fully conversant with <strong>the</strong>se<br />

unwanted sequelae, and it is prudent that<br />

she/he monitors <strong>the</strong> patient’s pulse prior to<br />

administration of beta-blocker <strong>the</strong>rapy even if<br />

<strong>the</strong> patient’s medical history appears<br />

unremarkable. Moreover, <strong>the</strong> practitioner should<br />

remain cognisant when acquiring a patient’s<br />

drug history since numerous oral medications<br />


Non<br />

Non<br />

Non<br />

Non<br />

Non<br />

Relative alpha1<br />

DOSAGE<br />

Od, bds<br />

Od<br />

Od, bds<br />

Od, bds<br />

Od, bds<br />

Bds<br />


Up to 24 hours<br />

Up to 24 hours<br />

Up to 24 hours<br />

Up to 24 hours<br />

Up to 24 hours<br />

Up to 12 hours<br />

may augment <strong>the</strong> beta-blockade. These drugs<br />

include Quinidine 11 , calcium channel blockers<br />

and Digitalis 12 .<br />

For those patients deemed suitable for<br />

topical beta-blocker <strong>the</strong>rapy, <strong>the</strong> practitioner<br />

can modify <strong>the</strong> prescription regimen in order to<br />

reduce <strong>the</strong> propensity of inducing systemic side<br />

effects. This could be achieved by ei<strong>the</strong>r<br />

prescribing <strong>the</strong> lowest effective dose possible<br />

and/or reducing <strong>the</strong> frequency of instillations,<br />

i.e. od instead of bds. Interestingly,<br />

beta-blockers are frequently prescribed bds. Yet,<br />

<strong>the</strong>re are numerous studies in <strong>the</strong> ophthalmic<br />

literature which support <strong>the</strong> hypotensive<br />

efficiency of a once daily regime 13,14,15 .<br />

Finally, a paucity of adverse effects should<br />

not entice <strong>the</strong> practitioner to relax his/her<br />

vigilance since systemic and local complications<br />

may only emerge years after initial<br />

treatment.<br />

Prostaglandin analogues<br />

Prostaglandins (PGs) are members of a family of<br />

substances known as <strong>the</strong> eicosonaoids. Although<br />

<strong>the</strong>re are several PG subtypes, low doses of PGF2α<br />

were found to induce significant ocular<br />

hypotensive effects in monkeys without altering<br />

<strong>the</strong>ir refractive status or pupil size.<br />

Owing to <strong>the</strong>ir superior safety record and<br />

potent hypotensive effects, <strong>the</strong> usage of PG<br />

analogues has become de rigeur in <strong>the</strong> medical<br />

management of <strong>the</strong> majority of glaucomas. The<br />

Table 3<br />

Main reported side effects<br />

of beta-blockers<br />


Cardiovascular:<br />

Bradycardia<br />

Hypotension<br />

Raynaud’s phenomenon<br />

Pulmonary:<br />

Asthma<br />

Bronchospasm<br />

Dyspnoea<br />

Neurological:<br />

Depression<br />

Confusion<br />

Impotence<br />

Insomnia<br />

Miscellaneous<br />

Diarrhoea and nausea,<br />

hypoglycaemia<br />

OCULAR<br />

Allergic<br />

blepharoconjunctivitis<br />

Dry eye<br />

Corneal anaes<strong>the</strong>sia<br />


ot<br />

DRUG<br />

Pilocarpine (1%, 2%, 3%, 4%)<br />

Carbachol (3%)<br />

Ecothiopate iodide (0.03%, 0.06%,<br />

0.125%, 0.25%)<br />

Physostigmine (Eserine) (0.25% -1.0%)<br />

Table 4<br />

Cholinergic agents<br />

two analogues currently available are<br />

Latanoprost 0.005% (XALATAN) and Travoprost<br />

0.004% (TRAVATAN). Both drugs bind to <strong>the</strong> PF<br />

receptor and possess <strong>the</strong> same mechanism of<br />

action – namely <strong>the</strong> augmentation of uveoscleral<br />

outflow.<br />

The efficiency of Latanoprost has been<br />

demonstrated in several multicentre, randomised<br />

controlled trials in <strong>the</strong> US, UK, Japan and<br />

Scandinavia 16,17,18 . These studies consistently<br />

revealed that a single dose of Latanoprost<br />

achieves between a 25-35% reduction in IOP<br />

from baseline readings. Fur<strong>the</strong>rmore, <strong>the</strong> timing<br />

of instillation is noteworthy with <strong>the</strong> majority of<br />

practitioners advocating evening administration,<br />

since <strong>the</strong> IOP-lowering effects usurp those<br />

achieved by Timolol maleate bds, when compared<br />

to morning applications alone 16 .<br />

Travoprost 0.004% was approved in March,<br />

2001 in <strong>the</strong> US. Used once daily, a 1.0-1.3mmHg<br />

greater reduction in IOP, compared with Timolol<br />

0.5% bds, was observed in 605 patients in phase<br />

III studies 19 . These findings were corroborated by<br />

Goldberg et al 20 , who revealed a 1.0-1.7mmHg<br />

enhanced reduction in IOP when comparing <strong>the</strong><br />

same drugs. In <strong>the</strong>ir randomised controlled trial<br />

comparing <strong>the</strong> efficiency of Travoprost,<br />

Latanoprost and Timolol, Netland et al 21<br />

disclosed <strong>the</strong> greatest reduction in IOP with <strong>the</strong><br />

former agent. Based on a criterion of a 30% or<br />

greater reduction in IOP from diurnal baseline,<br />

<strong>the</strong> overall responses to treatment for<br />

Travoprost, Latanoprost and Timolol were 54.7%,<br />

49,6% and 39.0% respectively.<br />

It is noteworthy that <strong>the</strong> same study<br />

demonstrated Travoprost’s superiority in lowering<br />

IOP levels in patients of African descent<br />

(2.4mmHg lower than Latanoprost and 4.6mmHg<br />

lower than Timolol). However, <strong>the</strong> a priori<br />

assumption that Travoprost should be employed<br />

as first line <strong>the</strong>rapy in such a population group<br />

requires validation from fur<strong>the</strong>r prospective<br />

studies.<br />

A novel anti-glaucoma agent which has<br />

recently been released in <strong>the</strong> UK is <strong>the</strong><br />

prostamide analogue, Bimatoprost 0.03%. Unlike<br />

<strong>the</strong> PG analogues, which are derived from<br />

arachidonic acid, Bimatoprost is derived from<br />

anandamide by <strong>the</strong> action of <strong>the</strong> enzyme<br />

cyclooxygenase 2 (COX 2). It reduces IOP by<br />

approximately 30% and is instilled once daily<br />

(preferably in <strong>the</strong> evening). When compared to<br />

Timolol 0.5% bds, <strong>the</strong> IOP decrease achieved<br />

following administration of Bimatoprost od is<br />

unrivalled 22 . Moreover, in <strong>the</strong> same study,<br />

Sherwood and Brandt demonstrated that in<br />

those eyes in which Bimatoprost had been<br />


Direct<br />

Direct<br />

Indirect<br />

Indirect<br />

DOSAGE<br />

Qds<br />

Tds<br />

0d, bds<br />

Qds<br />


4-8 hours<br />

6-12 hours<br />

12-24 hours<br />

4-6 hours<br />

instilled, <strong>the</strong>re was no significant diurnal<br />

variation in IOP reduction.<br />

Unlike Latanoprost and Travoprost,<br />

Bimatoprost does not bind to <strong>the</strong> PF receptors.<br />

Fur<strong>the</strong>rmore, <strong>the</strong> drug appears to not only<br />

enhance uveoscleral outflow, but promote<br />

outflow via <strong>the</strong> trabecular route 23 .<br />

Docosanoids<br />

Although <strong>the</strong>se drugs have been used clinically<br />

in Japan since 1994, <strong>the</strong>y only were approved in<br />

<strong>the</strong> US in August, 2000. Docosanoid compounds<br />

are derived from docosahexaenoic acid, which<br />

consists of a 22-carbon chemical backbone<br />

(cf, 20-carbon structure of arachidonic acid).<br />

Unlike PG analogues, <strong>the</strong> docosanoids do not<br />

bind to <strong>the</strong> PF receptor. The docosanoid<br />

prototype is Unoprostone isopropyl 0.15%<br />

(RESCULA).<br />

Even though <strong>the</strong> mechanism by which<br />

Unoprostone achieves its <strong>the</strong>rapeutic effects is<br />

known – via increasing outflow – <strong>the</strong> receptor to<br />

which <strong>the</strong> drug binds in order to achieve its<br />

effects remains elusive.<br />

Studies have shown Unoprostone to have an<br />

excellent safety profile. Notwithstanding, its use<br />

clinically as a form of mono<strong>the</strong>rapy is somewhat<br />

limited owing to <strong>the</strong> fact that its IOP-lowering<br />

effects are extremely modest. Indeed, in <strong>the</strong>ir<br />

randomised controlled trial comparing<br />

Latanoprost with Unoprostone, in patients with<br />

ei<strong>the</strong>r open angle glaucoma or ocular<br />

hypertension, <strong>the</strong> percentages of patients<br />

achieving a 30% reduction in IOP when treated<br />

with <strong>the</strong> drugs were 44% and 8% respectively 24 .<br />

However, it appears that Unoprostone may prove<br />

to be an effective adjunct to Latanoprost if <strong>the</strong><br />

IOPs remain greater than 22mmHg on <strong>the</strong> latter<br />

drug alone 25 .<br />

Side effects<br />

As mentioned earlier, <strong>the</strong> PG analogues have a<br />

very good safety record to date. However, one<br />

should execute a degree of caution since<br />

information is still being ga<strong>the</strong>red about <strong>the</strong><br />

safety of long-term treatment.<br />

In clinical trials, Latanoprost’s safety profile<br />

appeared promising with no systemic side effects<br />

reported 26 . Several ocular adverse effects, on <strong>the</strong><br />

o<strong>the</strong>r hand, have been noted. The most common<br />

ocular manifestations include hyperaemia 27 ,<br />

hypertrichosis 28 and an increase in both iris and<br />

eyelash pigmentation 26,28 .<br />

Although <strong>the</strong>se side effects are innocuous,<br />

<strong>the</strong>re have been some which are worthy of note,<br />

particularly cystoid macular oedema.<br />

Unfortunately, this maculopathy escaped <strong>the</strong><br />

safety net of clinical trials. Never<strong>the</strong>less, <strong>the</strong>re<br />

are numerous case reports suggesting that<br />

patients who have had a history of cataract<br />

surgery, cystoid macular oedema or uveitis are<br />

more susceptible 29-33 . In addition, a similar cohort<br />

is also at risk of acquiring uveitis following<br />

Latanoprost <strong>the</strong>rapy 33 . It <strong>the</strong>refore seems<br />

prudent to ei<strong>the</strong>r avoid <strong>the</strong>se drugs or use <strong>the</strong>m<br />

with extreme caution in any patient whose<br />

previous ocular history encompasses any of <strong>the</strong>se<br />

conditions.<br />

The adverse reactions of Travoprost are<br />

similar to Latanoprost.<br />

Cholinergic drugs<br />

Cholinergic drugs, or parasympathomimetics,<br />

remain <strong>the</strong> oldest effective treatment for<br />

glaucoma. However, with <strong>the</strong> exception of <strong>the</strong>ir<br />

possible use in closed angle glaucoma, <strong>the</strong>se<br />

agents have been superseded by <strong>the</strong> topical<br />

beta-blockers, CAIs, adrenergic agonists and PG<br />

analogues. This is due to <strong>the</strong>ir inherent,<br />

troublesome ocular adverse effects.<br />

Table 4 lists some of <strong>the</strong> various cholinergic<br />

agonists toge<strong>the</strong>r with <strong>the</strong>ir dosages and<br />

duration of effects.<br />

Acetylcholine (ACh) is a neurotransmitter<br />

released from vesicles in nerve terminals and<br />

rapidly hydrolysed by <strong>the</strong> enzyme<br />

acetylcholinesterase. This allows <strong>the</strong> receptor to<br />

repolarise and prepare for subsequent<br />

stimulation. Cholinergic drugs may exert <strong>the</strong>ir<br />

actions by ei<strong>the</strong>r stimulating <strong>the</strong> cholinergic<br />

receptors directly (agonists) or indirectly, by<br />

inhibiting <strong>the</strong> enzyme which breaks down ACh,<br />

acetylcholinesterase (cholinesterase inhibitors).<br />

Although <strong>the</strong> author has limited <strong>the</strong><br />

discussion to <strong>the</strong> management of POAG, <strong>the</strong> fact<br />

that pilocarpine, <strong>the</strong> most frequently prescribed<br />

drug of its class, is more commonly utilised in<br />

<strong>the</strong> initial management of angle-closure<br />

glaucoma warrants a brief overview of such<br />

management.<br />

As long as <strong>the</strong> IOP is not so elevated as to<br />

render <strong>the</strong> pupillary sphincter ischaemic,<br />

cholinergic agents may allow aqueous humour to<br />

communicate freely with <strong>the</strong> outflow channels by<br />

pulling <strong>the</strong> peripheral iris away from <strong>the</strong><br />

trabecular meshwork with a subsequent decrease<br />

in IOP. An important caveat to this mode of<br />

treatment is that pilocarpine has <strong>the</strong> capacity to<br />

precipitate angle-closure glaucoma, especially in<br />

eyes with shallow anterior chambers or<br />

spherophakia. The mechanisms underlying this<br />

unfortunate side effect are fur<strong>the</strong>r anterior<br />

chamber shallowing (due to forward movement<br />

of <strong>the</strong> iris-lens diaphragm) and an increase in<br />

<strong>the</strong> anteroposterior diameter of <strong>the</strong> lens (due to<br />

contraction of <strong>the</strong> ciliary muscle).<br />

In POAG, <strong>the</strong> parasympathomimetics decrease<br />

IOP by increasing <strong>the</strong> facility of outflow. The<br />

mechanism by which this is achieved is thought<br />

to be due to <strong>the</strong> stimulated contraction of <strong>the</strong><br />

longitudinal muscle of <strong>the</strong> ciliary body, <strong>the</strong>reby<br />

exerting traction on <strong>the</strong> scleral spur and<br />

trabecular meshwork. As a consequence, <strong>the</strong><br />

trabecular sheets become separated thus<br />

enhancing aqueous outflow.<br />

28<br />

July 26, 2002 OT<br />


Module 4 Part 8<br />

Sponsored by<br />

a<br />

Side effects<br />

a) Systemic<br />

The systemic side effects relate mainly to<br />

stimulation of <strong>the</strong> patient’s parasympa<strong>the</strong>tic<br />

system and include increased sweating and<br />

salivation, bradycardia, diarrhoea and<br />

anxiety. The most serious systemic<br />

complication is ‘scoline apnoea’ associated<br />

with ecothiopate iodide. Patients succumbing<br />

to this grave complication are unable to<br />

respire normally following termination of<br />

general anaes<strong>the</strong>sia. Owing to this and <strong>the</strong><br />

multitude of local adverse effects, this<br />

cholinesterase inhibitor is seldom used.<br />

b) Local<br />

To recapitulate, <strong>the</strong> local side effects negate<br />

<strong>the</strong> use of <strong>the</strong>se agents as first line <strong>the</strong>rapy<br />

against glaucoma. They include:<br />

• Miosis<br />

• Accommodative spasm<br />

• Iris cysts<br />

• Anterior subcapsular lens opacities<br />

• Angle-closure glaucoma<br />

• Retinal detachment<br />

• Increase in <strong>the</strong> permeability<br />

of <strong>the</strong> blood-aqueous barrier<br />

• Lacrimation<br />

All of <strong>the</strong> above ocular side effects are more<br />

pronounced with cholinesterase inhibitors. Since<br />

<strong>the</strong> permeability of <strong>the</strong> blood aqueous barrier is<br />

enhanced with <strong>the</strong>se drugs, <strong>the</strong>y should not<br />

under any circumstance be instilled in eyes<br />

suffering from glaucoma which has an<br />

inflammatory or neovascular aetiology.<br />

Carbonic anhydrase<br />

inhibitors (CAIs)<br />

Oral CAIs have been used to treat glaucoma for<br />

decades. Their serious side effects, such as<br />

metabolic acidosis and <strong>the</strong> potentially fatal<br />

haematological disorders (thrombocytopenia,<br />

agranulocytosis and aplastic anaemia), have<br />

resulted in <strong>the</strong> abrogation of such <strong>the</strong>rapy for<br />

<strong>the</strong> treatment of chronic glaucoma.<br />

There are many forms of <strong>the</strong> enzyme carbonic<br />

anhydrase (CA) distributed throughout <strong>the</strong><br />

human body and <strong>the</strong> eye is no exception. Indeed,<br />

CA is present in <strong>the</strong> corneal endo<strong>the</strong>lium,<br />

crystalline lens and in <strong>the</strong> non-pigmented ciliary<br />

epi<strong>the</strong>lium.<br />

The mechanism by which <strong>the</strong>se drugs achieve<br />

<strong>the</strong>ir hypotensive effects is to reduce <strong>the</strong><br />

formation of aqueous. This is achieved via<br />

<strong>the</strong>ir direct action on <strong>the</strong> ciliary epi<strong>the</strong>lial<br />

isoenzyme.<br />

The two topical CAIs available – Dorzolamide<br />

2% (TRUSOPT) and Brinzolamide 1% – are less<br />

effective than Timolol in reducing IOP and, as a<br />

consequence, are reserved as adjunctive, ra<strong>the</strong>r<br />

than first line <strong>the</strong>rapy 34 . The recommended<br />

mono<strong>the</strong>rapeutic dosage is tds, whereas a bds<br />

regimen is suggested when used concomitantly<br />

with o<strong>the</strong>r hypotensive agents. The agents which<br />

can be employed concurrently with <strong>the</strong> topical<br />

CAIs will be discussed later.<br />

www.optometry.co.uk<br />

Side effects<br />

Although <strong>the</strong>se drugs have not been associated<br />

with <strong>the</strong> serious systemic adverse effects<br />

observed in patients administering <strong>the</strong> oral<br />

counterpart, CNS effects have been recorded.<br />

These include taste perversion (especially with<br />

carbonated beverages) and nephrolithiasis 35 .<br />

The ocular side effects of <strong>the</strong>se drugs are<br />

numerous and may mitigate against <strong>the</strong>ir use in<br />

a significant number of patients. These include<br />

conjunctival hyperaemia, allergic reactions,<br />

blepharitis and a burning/stinging sensation<br />

upon instillation 36-38 . The latter complaint is <strong>the</strong><br />

most frequent ocular manifestation reported.<br />

Owing to <strong>the</strong> fact that CA exists in <strong>the</strong><br />

corneal endo<strong>the</strong>lium, concerns have been<br />

justifiably raised as to <strong>the</strong> implications which a<br />

topical CAI may have on corneal metabolism.<br />

Konowal and co workers 39 discovered that<br />

Dorzolamide can cause irreversible corneal<br />

oedema in glaucomatous patients with<br />

endo<strong>the</strong>lial compromise (e.g. subclinical Fuchs’<br />

dystrophy, post-surgical changes). Thus, it is<br />

incumbent on all practitioners to examine <strong>the</strong><br />

patient’s corneae carefully before a decision to<br />

prescribe <strong>the</strong>se agents is made.<br />

Adrenergic agonists<br />

Historically, adrenergic agonists have been used<br />

in <strong>the</strong> treatment of glaucoma and ocular<br />

hypertension since <strong>the</strong> early 20th century. The<br />

agonists currently available are – Adrenaline<br />

(Epinephrine) 0.5%, 1%, 2%, Dipivefrin<br />

(PROPINE) 0.1%, Apraclonidine (IOPIDINE) 0.5%,<br />

1%, and Brimonidine (ALPHAGAN-P, ALPHAGAN)<br />

0.15%, 0.2%.<br />

The adrenergic system consists of alpha1,<br />

alpha2, beta1 and beta2-r receptors. A decrease in<br />

aqueous production is mediated by <strong>the</strong><br />

beta-adrenergic system while an increase<br />

in outflow facility is mediated by <strong>the</strong><br />

alpha-adrenergic system. Intuitively, one would<br />

expect that non-selective adrenergic agonists,<br />

such as Adrenaline, would achieve <strong>the</strong>ir<br />

hypotensive effects through a combination of <strong>the</strong><br />

aforementioned mechanisms. Although <strong>the</strong> exact<br />

mechanism is disputed, <strong>the</strong> most widely accepted<br />

hypo<strong>the</strong>sis is that Adrenaline achieves its ocular<br />

hypotensive effects by increasing both<br />

conventional and unconventional outflows.<br />

Both Apraclonidine and Brimonidine are<br />

alpha2-agonists and lower IOP by decreasing<br />

aqueous formation. Interestingly, it appears that<br />

Brimonidine, which exhibits a higher degree of<br />

selectivity for <strong>the</strong> alpha2 receptor, also enhances<br />

uveoscleral outflow 40 .<br />

Since Brimonidine and Apraclonidine have<br />

supplanted both Adrenaline and its pro-drug,<br />

Dipivefrin, as <strong>the</strong> adrenergic agonist of choice in<br />

<strong>the</strong> treatment of glaucoma and ocular<br />

hypertension, <strong>the</strong> author will limit his discussion<br />

to <strong>the</strong> former two drug types.<br />

In view of <strong>the</strong> high allergy rate and<br />

tachyphylaxis associated with Apraclonidine, its<br />

use has been restricted to short-term <strong>the</strong>rapy<br />

such as post-laser trabeculoplasty and YAG laser<br />

iridotomy. The rationale behind instilling <strong>the</strong><br />

drug post-operatively is to reduce <strong>the</strong> risks of an<br />

acute rise in IOP. Brimonidine, on <strong>the</strong> o<strong>the</strong>r<br />

hand, has proved not only to be very efficacious<br />

as an adjunctive hypotensive agent (its effects<br />

are comparable to those achieved with Timolol)<br />

in long-term <strong>the</strong>rapy, but it also possesses both<br />

an excellent safety profile and intrinsic<br />

neuroprotective properties.<br />

In March 2001, <strong>the</strong> FDA approved a<br />

reformulated Brimonidine – Alphagan-P. The<br />

concentration of Brimonidine in Alphagan-P is<br />

slightly lower than <strong>the</strong> original (0.15%<br />

compared to 0.2%). Fur<strong>the</strong>rmore, whereas <strong>the</strong><br />

original formulation contains <strong>the</strong> preservative<br />

Benzalkonium chloride, <strong>the</strong> new formulation<br />

contains <strong>the</strong> proprietary preservative, Purite.<br />

The latter preservative is <strong>the</strong> same type used in<br />

<strong>the</strong> lubricant, Refresh tears.<br />

Both drugs appear equipotent in lowering<br />

IOP despite <strong>the</strong>ir disparate concentrations.<br />

Interestingly, <strong>the</strong> pH of <strong>the</strong> original lies between<br />

6.3 and 6.5 and is <strong>the</strong>refore relatively acidic. The<br />

pH range of Alphagan-P, on <strong>the</strong> o<strong>the</strong>r hand, is<br />

between 6.6 and 7.4. Thus, this solution errs<br />

more towards neutrality than its original<br />

counterpart. It is, <strong>the</strong>refore, reasonable to<br />

assume that <strong>the</strong> more neutral solution enhances<br />

bioavailability which, in turn, would allow <strong>the</strong><br />

drug to exert effects comparable to its more<br />

concentrated cousin.<br />

Drugs administered at a lower concentration<br />

have <strong>the</strong> obvious advantage of reducing <strong>the</strong><br />

likelihood of adverse effects. In addition, owing<br />

to <strong>the</strong> preservative used, a substantial reduction<br />

in <strong>the</strong> number of allergic reactions with<br />

Alphagan-P has been noted 41 .<br />

Side effects<br />

The side effects associated with Brimonidine are<br />

fairly unremarkable. The most common ocular<br />

manifestations include allergic conjunctivitis<br />

toge<strong>the</strong>r with a low rate of burning upon<br />

instillation. The systemic side effects are also<br />

innocuous and include drowsiness, headache,<br />

dry mouth and high levels of fatigue.<br />

Concomitant and<br />

combination <strong>the</strong>rapy<br />

Frequently, glaucoma patients with IOPs<br />

inadequately controlled with mono<strong>the</strong>rapy have<br />

to administer more than one type of ocular<br />

hypotensive drug. This section describes <strong>the</strong><br />

agents employed in clinical practice which work<br />

synergistically to provide an enhanced<br />

decrement in a patient’s IOP.<br />

The ocular hypotensive effects of <strong>the</strong> PG<br />

analogues may be augmented through <strong>the</strong><br />

concomitant use of numerous anti-glaucoma<br />

agents. In <strong>the</strong>ir retrospective analysis of 73 eyes<br />

of 73 patients with glaucoma and inadequate<br />

IOP control on Latanoprost alone, O’Connor et<br />

al 42 revealed that <strong>the</strong> greatest additional<br />

hypotensive effects were observed when <strong>the</strong><br />

patient received Dorzolamide bds (19.7%).<br />

Fur<strong>the</strong>r decrements in IOP were also<br />

observed with <strong>the</strong> concomitant use of betablockers<br />

and Brimonidine (12.3% and 9.5%<br />

respectively).<br />

The PG analogues may <strong>the</strong>mselves be added<br />


ot<br />

to any ocular hypotensive drug with <strong>the</strong><br />

exception of <strong>the</strong> cholinergic agonists, such as<br />

pilocarpine. Owing to <strong>the</strong> contraction of<br />

longitudinal muscle of <strong>the</strong> ciliary body, <strong>the</strong><br />

intercellular junctions on <strong>the</strong> body’s face tighten<br />

with <strong>the</strong> net effect of reducing uveoscleral<br />

outflow. Thus, mechanistically, <strong>the</strong>se agents<br />

antagonise <strong>the</strong> PG analogues whose <strong>the</strong>rapeutic<br />

mode of action is to increase uveoscleral<br />

outflow.<br />

To date, numerous studies have shown<br />

Brimonidine to be a very effective adjunctive<br />

agent. Indeed, when employed concurrently to<br />

beta-blockers, Brimonidine demonstrated<br />

significant additional decrements in IOP 43 .<br />

Moreover, <strong>the</strong>se effects appeared superior to<br />

those achieved when a topical CAI was<br />

administered concurrently to <strong>the</strong> same<br />

adrenergic antagonists. A recent randomised<br />

controlled trial comparing <strong>the</strong> efficacy of<br />

Brimonidine bds, and Latanoprost od, as<br />

adjunctive <strong>the</strong>rapy in <strong>the</strong> management of poorly<br />

controlled glaucomatous patients on<br />

beta-blocker mono<strong>the</strong>rapy, found no statistical<br />

difference in achieving <strong>the</strong> investigators’ target<br />

of a fur<strong>the</strong>r 15% reduction in IOP 44 .<br />

Fur<strong>the</strong>rmore, <strong>the</strong> authors were astute to point<br />

out that despite such <strong>the</strong>rapeutic parity, adverse<br />

effects associated with both types of drugs<br />

(watery eyes, cold hands and feet) were<br />

significantly higher following administration of<br />

Latanoprost.<br />

The fact that in one large scale study 45 ,<br />

Brimonidine induced a fur<strong>the</strong>r mean reduction<br />

in IOP of 20.3% when added to Latanoprost is<br />

testimony to its effectiveness as an adjunctive<br />

agent. An additional 18.9% reduction was<br />

observed when Brimonidine was introduced to a<br />

pre-existing concomitant regimen of<br />

Latanoprost and a non-selective<br />

beta-blocker.<br />

Interestingly, <strong>the</strong>re have been conflicting<br />

results regarding <strong>the</strong> additional <strong>the</strong>rapeutic<br />

efficacy when <strong>the</strong> docosanoid, Unoprostone<br />

isopropyl 0.12% is administered with<br />

Latanoprost 0.005%. The results collated by<br />

Stewart et al 25 seem to demonstrate a positive<br />

beneficial effect, whereas Aung et al 46 only<br />

noted such favourable results when Latanoprost<br />

was added to a pre-existing mono<strong>the</strong>rapeutic<br />

regimen of Unoprostone bds. When Unoprostone<br />

was introduced to eyes which were hi<strong>the</strong>rto<br />

treated with Latanoprost alone, no fur<strong>the</strong>r IOP<br />

lowering was observed. However, Saito and<br />

co-workers 47 found no net increase in<br />

hypotensive potency with <strong>the</strong> same combination<br />

irrespective of <strong>the</strong> prior mono<strong>the</strong>rapeutic<br />

regimen.<br />

Topical beta-blockers are an effective adjunct<br />

to <strong>the</strong> o<strong>the</strong>r hypotensive agents with <strong>the</strong><br />

exception of <strong>the</strong> sympathomimetics. However, as<br />

mentioned previously, <strong>the</strong>ir ability to sustain<br />

<strong>the</strong>ir IOP lowering effects may diminish with<br />

time in a significant proportion of patients.<br />

Thus, toge<strong>the</strong>r with <strong>the</strong> introduction of newer<br />

drugs with <strong>the</strong>ir superior safety profile, <strong>the</strong>ir<br />

future use as an adjunct may be somewhat<br />

limited.<br />

Combination drugs<br />

Combining two <strong>the</strong>rapeutic agents into one<br />

preparation has, potentially, many advantages.<br />

An enhanced ameliorative effect with a reduced<br />

dosage not only would reduce <strong>the</strong> risk of side<br />

effects but should also improve patient<br />

compliance.<br />

The Dorzolamide 2%/Timolol 0.5%<br />

(CAI/beta-blocker) combination (COSOPT)<br />

instilled bds appears to be similar in efficacy to<br />

<strong>the</strong> concomitant administration of <strong>the</strong><br />

components bds 48 . Ano<strong>the</strong>r study seemed to<br />

show <strong>the</strong> combination to be superior in lowering<br />

IOP compared with its individual components 49 .<br />

Ano<strong>the</strong>r combination agent containing<br />

Latanoprost 0.005% and Timolol 0.5% (Xalocam)<br />

instilled once daily has been shown to reduce<br />

IOP effectively in patients with ei<strong>the</strong>r ocular<br />

hypertension or glaucoma, but only<br />

demonstrated a modest degree of superiority<br />

over od dosing of Latanoprost alone<br />

(1-1.2mmHg) and Timolol bds alone (1.9mmHg) 50 .<br />

Case histories<br />

The previous article in this CPD module<br />

concentrated on case histories in which patients<br />

were ei<strong>the</strong>r unable to tolerate medical <strong>the</strong>rapy<br />

or where such <strong>the</strong>rapy failed to control <strong>the</strong>ir<br />

ocular malady. The following case histories, in<br />

general, illustrate <strong>the</strong> factors to be considered<br />

when deciding to initiate <strong>the</strong> appropriate<br />

medical <strong>the</strong>rapy.<br />

Case 1<br />

Patient details<br />

• Male, caucasian, aged 45 years<br />

• Occupation – long distance HGV driver<br />

• General health – good, no medication being<br />

taken, pulse regular, 60 beats/min<br />

• Diagnosis – POAG. Baseline IOPs –<br />

R 26mmHg, L 27mmHg<br />

• Previous ocular history – unremarkable<br />

Discussion<br />

As <strong>the</strong> patient’s general health was good and his<br />

pulse was regular, most of <strong>the</strong> topical<br />

hypotensive agents could be considered. In view<br />

of <strong>the</strong>ir effectiveness at lowering IOPs and low<br />

cost, beta-blockers prescribed od might be<br />

considered first. The only hypotensive agents<br />

which would be definitely contraindicated are<br />

<strong>the</strong> miotics, since <strong>the</strong> miosis associated with<br />

such agents would severely restrict his field of<br />

view and, as such, would be detrimental to his<br />

occupation.<br />

Case 2<br />

Patient details<br />

• Female, caucasian, aged 65 years<br />

• Occupation – retired<br />

• General health – good. No medication being<br />

taken. Pulse regular – 70 beats/min<br />

• Ocular history – unilateral POAG (R eye).<br />

Baseline IOPs – R 27mmHg, L 15mmHg.<br />

Also had early central, bilateral posterior<br />

subcapsular lens opacities<br />

Discussion<br />

Since this patient had unilateral glaucoma, a PG<br />

analogue would be a relative contraindication<br />

due to iris colour changes (a cosmetic concern)<br />

and <strong>the</strong> potential to induce unilateral<br />

hypertrichosis (again, a cosmetic concern).<br />

Miotics would also be contraindicated due to her<br />

pre-existing lens opacities.<br />

As with Case 1, beta-blockers would probably<br />

be <strong>the</strong> first drug of choice due to <strong>the</strong>ir<br />

effectiveness and low cost. The drug would be<br />

initially prescribed od and <strong>the</strong> patient<br />

reassessed approximately six to eight weeks<br />

later. (Note: such reassessment time-scale<br />

periods represent an ideal. However, <strong>the</strong> author<br />

is aware that this may be impractical in many<br />

glaucoma clinics owing to <strong>the</strong> overwhelming<br />

number of patients seen. Thus, <strong>the</strong> reassessment<br />

period may be longer, say three months.)<br />

Case 3<br />

Patient details<br />

• Male, caucasian, aged 50 years<br />

• Occupation – teacher<br />

• General health – ankylosing spondylitis<br />

(diagnosed five years). Taking Diclofenac<br />

Sodium. Asthmatic, taking Salbutamol and<br />

Fluticasone propionate<br />

• Ocular history – POAG. Baseline IOPs<br />

– R 25mmHg, L 26mmHg. Since he was<br />

diagnosed as suffering from ankylosing<br />

spondylitis, he developed three bouts of<br />

anterior uveitis in his right eye and two<br />

bouts in his left eye<br />

Discussion<br />

Due to <strong>the</strong> patient’s asthma, beta-blockers were<br />

contraindicated. Fur<strong>the</strong>rmore, <strong>the</strong> fact that he<br />

had a previous history of anterior uveitis<br />

associated with ankylosing spondylitis negated<br />

<strong>the</strong> use of PG analogues. The optimum<br />

mono<strong>the</strong>rapeutic drug of choice would be<br />

Brimonidine bds. Ideally, <strong>the</strong> lesser<br />

concentrated, purite form would be prescribed<br />

(if available) since it is associated with less local<br />

side effects.<br />

Case 4<br />

Patient details<br />

• Female, Asian, aged 65 years<br />

• Occupation – retired<br />

• General health – good. No medication being<br />

taken. Pulse regular – 68 beats/min<br />

• Ocular history – diagnosed bilateral POAG six<br />

months previously. Initial, baseline IOPs<br />

were R 32mmHg, L 30mmHg<br />

Discussion<br />

This patient was initially prescribed Timolol<br />

0.50% bds (due to dark irides and initial high<br />

IOPs). She was reassessed three months later.<br />

IOPs were R 24mmHg and L 23mmHg. In<br />

addition, visual fields were repeated and <strong>the</strong>re<br />

appeared to be a slight deterioration in both<br />

fields. The ophthalmologist added Latanoprost<br />

0.005% od, OU in <strong>the</strong> evening. The patient was<br />

30<br />

July 26, 2002 OT<br />


Module 4 Part 8<br />

Sponsored by<br />

a<br />

reviewed six weeks later and <strong>the</strong> IOPs recorded<br />

were R 19mmHg and L 17mmHg. Moreover, visual<br />

fields were repeated and <strong>the</strong>re was no overt<br />

difference from <strong>the</strong> plots recorded at her<br />

previous visit.<br />

Although o<strong>the</strong>r adjunctive agents could have<br />

been used, it is always prudent to add an agent<br />

which has <strong>the</strong> least dosage regimen (i.e. od) as<br />

<strong>the</strong> greater dosages correlate negatively with<br />

compliance. Since <strong>the</strong> PG analogues fit into this<br />

category, <strong>the</strong>y were <strong>the</strong> initial adjunct of choice<br />

for this patient.<br />

Case 5<br />

Patient details<br />

• Female, Afro-Caribbean, aged 70 years<br />

• Occupation – retired<br />

• General health – supraventricular tachycardia<br />

controlled with Quinidine.<br />

Hypercholesterolaemia controlled with<br />

Simvastatin<br />

• Ocular history – POAG OU. Initial baseline<br />

IOPs – R 27mmHg, L 29mmHg. Diagnosed<br />

with Fuchs’ dystrophy 10 years previously<br />

Discussion<br />

Due to her co-existing endo<strong>the</strong>lial changes,<br />

topical CAIs should not be employed in <strong>the</strong><br />

hypotensive regimen. In addition, topical<br />

beta-blockers were also contraindicated as<br />

Quinidine may enhance <strong>the</strong> beta-blockade.<br />

Since PG analogues remain <strong>the</strong> most effective<br />

mono<strong>the</strong>rapeutic hypotensive agent with <strong>the</strong><br />

simplest dosage regime, <strong>the</strong>y should be<br />

considered as <strong>the</strong> first line <strong>the</strong>rapy in this case.<br />

Moreover, since several studies have<br />

demonstrated Travoprost to possess greater<br />

hypotensive qualities in patients of<br />

Afro-Caribbean descent, it would seem<br />

reasonable to consider this agent first.<br />

Conclusion<br />

This article has outlined <strong>the</strong> agents which<br />

encompass <strong>the</strong> mainstay of glaucoma treatment<br />

to date. Owing to <strong>the</strong> chronicity of <strong>the</strong> disease<br />

and relative lack of symptoms, it is essential that<br />

<strong>the</strong> practitioner reinforces <strong>the</strong> importance of<br />

complying with <strong>the</strong> <strong>the</strong>rapy initiated. Finally, <strong>the</strong><br />

decision to prescribe a particular topical agent<br />

must not be made without prior knowledge of<br />

<strong>the</strong> patient’s medical status or level of<br />

independence.<br />

About <strong>the</strong> author<br />

Greg Heath is an optometrist working part-time<br />

in private practice. He is currently reading<br />

medicine at <strong>the</strong> Royal Free and University College<br />

London Medical School.<br />

Abbreviations<br />

Od – daily; bds – twice daily; tds – three times<br />

daily; qds – four times daily; OD – right eye; OS<br />

– left eye; OU – both eyes.<br />

References<br />

For a full set of references, please fax<br />

01252-816176 or email nicky@optometry.co.uk.<br />

www.optometry.co.uk<br />

Multiple choice questions<br />

Ocular <strong>the</strong>rapeutic case studies<br />

- Medical management of glaucoma<br />

Please note <strong>the</strong>re is only one correct answer<br />

1. Which one of <strong>the</strong> following agents lowers<br />

IOP by reducing aqueous production?<br />

a. Travoprost<br />

b. Pilocarpine<br />

c. Unoprostone<br />

d. Dorzolamide<br />

2. Which one of <strong>the</strong> following statements<br />

regarding pilocarpine is true?<br />

a. It is a sympathomimetic<br />

b. It is <strong>the</strong> mainstay of glaucoma treatment<br />

c. It can be used safely on all patients with<br />

narrow anterior chamber angles<br />

d. It can be employed in <strong>the</strong> treatment of both<br />

POAG and PCAG (closed angle glaucoma)<br />

3. Which one of <strong>the</strong> following statements<br />

concerning Betaxolol is true?<br />

a. It possesses intrinsic sympathomimetic<br />

activity<br />

b. It can be administered safely in all patients<br />

with chronic obstructive airways disease<br />

c. It may increase retinal blood flow<br />

d. It is usually prescribed od<br />

4. Which one of <strong>the</strong> following is ineffective<br />

when used as POAG mono<strong>the</strong>rapy?<br />

a. Brimonidine<br />

b. Unoprostone<br />

c. Latanoprost<br />

d. Timolol<br />

5. Which one of <strong>the</strong> following is not a potential<br />

side effect of PG analogues?<br />

a. Uveitis<br />

b. Cystoid macular oedema<br />

c. Trichiasis<br />

d. Conjunctival hyperaemia<br />

6. Which one of <strong>the</strong> following statements is<br />

true of medical <strong>the</strong>rapy for primary open<br />

angle glaucoma?<br />

a. It is associated with high long-term costs<br />

b. It is associated with no serious side effects<br />

c. It is <strong>the</strong> most efficacious method of<br />

lowering IOP<br />

d. It is less hassle than surgery for <strong>the</strong> patient<br />

7. For a patient who is a healthy 65-year old<br />

male with IOPs of R 15mmHg, L 25mmHg,<br />

which one of <strong>the</strong> following would be <strong>the</strong><br />

most likely initial <strong>the</strong>rapy?<br />

a. Timolol od, OU<br />

b. Latanoprost od, OD<br />

c. Dorzolamide tds, OU<br />

d. Levobunolol od, OS<br />

8. Which of <strong>the</strong> following are<br />

not suitable adjuncts?<br />

a. Timolol and Latanoprost<br />

b. Pilocarpine and Travoprost<br />

c. Dorzolamide and Levobunolol<br />

d. Brimonidine and Latanoprost<br />

9. A 60-year old healthy male pseudophake<br />

presents with IOPs of R 31mmHg,<br />

L 30mmHg. Which one of <strong>the</strong> following is<br />

<strong>the</strong> least likely to be prescribed?<br />

a. Timolol od<br />

b. Brimonidine bds<br />

c. Brinzolamide tds<br />

d. Travoprost od<br />

10. A patient is taking adjunctive <strong>the</strong>rapy for<br />

her POAG. Although her IOPs are well<br />

controlled, she complains of a dry mouth.<br />

Which one of <strong>the</strong> following drugs is <strong>the</strong><br />

most likely culprit?<br />

a. Levobunolol<br />

b. Pilocarpine<br />

c. Brimonidine<br />

d. Unoprostone<br />

11. Which of <strong>the</strong> following statements<br />

regarding beta-blockers is true?<br />

a. They are <strong>the</strong> most efficacious<br />

hypotensive agent<br />

b. They are <strong>the</strong> adjunctive agent<br />

of choice<br />

c. They can be administered safely<br />

in patients suffering from bradycardia<br />

d. They can be administered safely<br />

in patients with Fuchs’ dystrophy<br />

12. Which one of <strong>the</strong> following statements<br />

is true regarding POAG patients’<br />

compliance to medical <strong>the</strong>rapy?<br />

a. It is unrelated to <strong>the</strong> patient’s age<br />

b. It is influenced by <strong>the</strong> patient’s<br />

lifestyle<br />

c. It is unrelated to <strong>the</strong> patient’s systemic<br />

status<br />

d. It is unrelated to <strong>the</strong> patient’s<br />

occupation<br />

An answer return form is included in this issue. It should be completed and<br />

returned to: CPD Initiatives (c4082i), OT, Victoria House,<br />

178–180 Fleet Road, Fleet, Hampshire, GU51 4DA by September 4, 2002.<br />


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