Glaucoma y Embarazo

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RESEARCH PAPER

Anti-glaucoma medication exposure in pregnancy:

an observational study and literature review

Clin Exp Optom 2010; 93: 6: 458–465 DOI:10.1111/j.1444-0938.2010.00526.x

M Reza Razeghinejad* MD

Mohammad Hosein Nowroozzadeh* MD

* Department of Ophthalmology, Shiraz

University of Medical Sciences, Shiraz,

Iran

E-mail: [email protected]

Background: There are limited data about the effects of anti-glaucoma drugs on preg

nancy. The purpose of this study was to observe pregnancies exposed to anti-glaucoma

medications.

Methods: Six pregnant glaucomatous patients referred to the glaucoma clinic after their

first trimesters were advised to continue their medications. In one patient who was on

oral acetazolamide, the drug was substituted with topical medications. In the last month

of pregnancy acetazolamide was started and all topical medications were stopped. The

control group comprised 24 individuals with no systemic disease or exposure to medica-

tions and with comparable age and gestational age on delivery. Pregnancy and delivery

complications, Apgar scores at one and five minutes, birth weight, congenital anomalies

and psychophysical development of children up to two years of age were evaluated.

Results: The mean age of the patients was 28.17 years with mean gestational age on

delivery of 38.80 weeks. Low birth weight was more common in the case group (p =

0.041). No other side-effects were observed. The one-minute Apgar scores were nine in

all newborns and improved to 10 at five minutes. The psychophysical development of allchildren was normal up to two years after birth.

Conclusions: Analysis of pregnancy outcome of six mothers taking topical glaucoma

medications showed no adverse effects apart from a small but statistically significant

increased risk of having low birth weight.

Submitted: 26 December 2009

Revised: 26 June 2010

Accepted for publication: 17 July 2010

Key words: anti-glaucoma medication, glaucoma, low birth weight, pregnancy

Glaucoma is rarely diagnosed in pregnant

women but occasionally, patients with

pre-existing glaucoma become pregnant.

Although it seems to be a relatively rare

clinical situation, a recent study revealed

that 26 per cent of consultant ophthal-

mologists in the United Kingdom had

first-hand experience in the management

of glaucoma during pregnancy.1 After

topical application of eye-drops, 80 per

cent of the volume drains through the

nasolacrimal duct and then is absorbed

systemically, bypassing hepatic metabo-

lism.2 This may explain the side-effects of

topical ophthalmic medications despite

the low topical dose.

Lipid-soluble, non-ionised, low molecu-

lar weight drugs readily cross the placenta

and enter the foetal circulation, where it

may be excreted into the amniotic fluid

from the foetal kidneys, skin or lungs. The

half-life of an administered drug may be

much longer in a foetus than in an adult

because of recirculation through the swal-

lowing and breathing movements and

re-excretion by the foetal kidneys.3 The

smaller blood volume and immature struc-

tures and metabolic system of the foetus

should be added to these mechanisms

Consequently, the plasma levels of mater-

nal ophthalmic medications may exceed

the therapeutic range in the foetus, which

may lead to an increased risk of adverse

C L I N I C A L A N D E X P E R I M E N T A L

OPTOMETRY

Clinical and Experimental Optometry 93.6 November 2010 © 2010 The Authors

458 Clinical and Experimental Optometry © 2010 Optometrists Association Australia



systemic effects.4 Therefore, when anti-

glaucoma medications are prescribed for

pregnant women, the clinicians must con-

sider the potential systemic effects not

only on the mother, but also on the devel-

oping foetus.5–9

Unfortunately, there is little definitive

information concerning the use of anti-

glaucoma medications in pregnant glau-

comatous patients. Further speculative

observation of patients who have used

glaucoma medications during pregnancy

seems necessary to help physicians pre-

scribe appropriate anti-glaucoma medica-

tions during pregnancy. Accordingly, this

study was conducted on pregnant patients

who received anti-glaucoma medications

to report the possible side-effects on their

delivery and foetuses.

METHODS

A prospective observational study was per-

formed on six pregnant women with glau-

coma who were exposed to anti-glaucoma

medications. They were referred to a uni-

versity affiliated glaucoma clinic between

September 2002 and July 2006. Informed

consent was obtained from the partici-

pants after giving them detailed informa-

tion and the study protocol was approvedby the Ethics Committee.

All of the patients came to our clinic

after their first trimester of pregnancy. In

all cases, the drugs used in the first trimes-

ter were the same as those used before

pregnancy. All patients underwent a com-

plete eye examination including visual

acuity, intraocular pressure (IOP) mea-

surement by a calibrated Goldmann appla-

nation tonometer, slitlamp biomicroscopy

and fundoscopy. The visual fields were

checked with SITA-strategy in all patients.

The participants had no co-morbid

disease and did not use any concomitant

medications. The patients were advised to

continue the same medications that they

were currently taking, except in one

patient whose oral acetazolamide was

replaced by topical anti-glaucoma medica-

tion. In the last month of pregnancy,

acetazolamide was started and all topical

medications stopped. The logic of this

strategy was rooted in the results of other

studies that revealed the relative safety

of acetazolamide in late pregnancy.10,11

Moreover, it has been reported that physi-

ologic changes during pregnancy (espe-

cially in late pregnancy) lead to a mild

decrease in the IOP compared to the pres-sure before pregnancy.12–18 This change

obviates using multiple classes of anti-

glaucoma medications to control IOP.

After delivery, the oral carbonic anhydrase

inhibitors were replaced by topical car-

bonic anhydrase inhibitors and latano-

prost in all patients. If the patient’s IOP

was not controlled using these medica-

tions, topical timolol was commenced

after the first post-partum month.

We followed patients throughout their

pregnancy and two years after delivery.

Pregnancy and delivery complications,

Apgar score at one and five minutes, birth

weight, congenital anomalies and psycho-

physical development of children up to

two years of age were evaluated as main

outcome measures. These data were

obtained according to the obstetrician

and paediatrician present at delivery and

during follow-up. To evaluate the rate of

low birth weight (less than 2,500 g),19

24 healthy mothers, without significant

exposure to any medications other than

multivitamins and iron supplements,served as controls. For each glaucomatous

patient, four healthy mothers of compa-

rable age (within three years) and gesta-

tional age on delivery (within one week)

were recruited.

Continuous variables were evaluated

using Mann-Whitney U test. Fisher’s exact

test was used to compare the rate of low

birth weight (LBW) between case and

control groups. A p value less than 0.05

was considered as statistically significant.

RESULTS

The case group included six pregnant

patients exposed to anti-glaucoma medica-

tions. The type of glaucoma, amount of

optic nerve damage, type of visual field

defect and prior surgery are shown in

Table 1. All but one patient had IOP con-

trolled during pregnancy and in none of

them the visual field showed progression.

In the case with uncontrolled IOP because

of advanced glaucoma and preservation of

a temporal island, checking the visual field

progression was not possible. The demo-

graphic data of patients and their

outcome of pregnancy are given in

Table 2. The mean age of the patients was28.17 4.79 years (range, 24 to 37 years).

Their mean gestational age on delivery

was 38.80 1.17 weeks (range, 37 to

40 weeks). The mean age of the control

group was 28.00 4.67 years (range, 22 to

40 years) with the mean gestational age on

delivery of 38.88 1.30 weeks (range, 36

to 41 weeks). There were no statistically

significant differences for age and gesta-

tional age on delivery between groups (p =

0.917 and p = 0.868, respectively). Three

neonates in the case group had a low birth

weight, while a low birth weight was found

in only two babies in the control group (p

= 0.041). All newborns with a low birth

weight in the case group had foetal expo-

sure to timolol, latanoprost and carbonic

anhydrase inhibitors and two of them were

exposed to brimonidine as well (Table 3).

In the case group, no abnormality

including congenital abnormalities other

than low birth weight was observed in the

newborns. No patient had systemic side-

effects, abortion or pre-term delivery. The

one-minute Apgar scores were nine in allnewborns and improved to 10 at five

minutes. The psychophysical development

of all children was normal up to two years

after birth.

DISCUSSION

Intraocular pressure usually decreases

during pregnancy. Pregnancy-related

physiological changes do not seem to

exacerbate the glaucoma.12–14 It could be

argued that optic nerve damage over a

conception period would be minimal such

that a mildly raised IOP could be tolerated

for the length of the pregnancy. There-

fore, observation alone can be the sole

management, if the disease is not progres-

sive or critical.20 Argon or selective laser

trabeculoplasty can be considered as a

first-line treatment to control glaucoma in

pregnant patients who are suitable candi-

dates for these modalities.

Anti-glaucoma medications in pregnancy Razeghinejad and Nowroozzadeh

© 2010 The Authors Clinical and Experimental Optometry 93.6 November 2010

Clinical and Experimental Optometry © 2010 Optometrists Association Australia 459



Case Diagnosis Visual acuity* IOP*† C/D* Visual field defect* Prior surgery

1 Weill-Marchesani syndrome (6/12; 1 mFC) (18; 20) (0.8; 0.95) (Inferior arcuate; pattern deviationreversal)

Trabeculectomy + MMC (OS)

2 Juvenile open angle glaucoma (HM; 6/6) (14; 17) (0.95; 0.35) (Pattern deviation reversal; normal) Trabeculectomy + MMC (OD)

3 Congential glaucoma (6/9; 6/7.5) (19; 20) (0.55; 0.45) (Paracentral scotoma, normal) Trabeculotomy (OU)4 Ir is naevus syndrome (6/6; 6/6) (22; 16) (0.6; 0.2) (Superior nasal step; normal) Trabeculectomy + MMC (OD)

5 Aphakic glaucoma(monocular OD)

6/15 21 0.5 Generalised suppression due tocorneal opacity

Lensectomy for congenitalcataract removal

6 Spherophakia(monocular OD)

1 mFC 25 0.9 Temporal island Laser iridotomy

* (OD; OS)† The values shown are median of IOP during follow-up in our clinicC/D = Cup/disc ratio; FC = finger count; HM = hand motion; IOP = intraocular pressure in mmHg; m = metre; MMC = mitomycin C; OD = right eye; OS= left eye; OU = both eyes

Table 1. Type of glaucoma, severity and prior surgeries in six pregnant patients

Case Age Anti-glaucoma medications Gestationalage on

delivery

Newborn’sweight

(grams)

Apgarscore

(at 1 min)

Baby’s physical andmental status within

2 years after birth*First trimester Second trimester &

first 2 months ofthird trimester

Last month

1 26 Timolol Timolol †Acetazolamide 40 2,300 9 NormalAcetazolamide Dorzolamide

Latanoprost

2 30 Timolol Timolol Acetazolamide 39 3,230 9 Normal

Latanoprost LatanoprostDorzolamide Dorzolamide

3 24 Timolol Timolol Acetazolamide 39 2,950 9 NormalLatanoprost LatanoprostDorzolamide Dorzolamide

4 37 Timolol Timolol Acetazolamide 40 3,400 9 NormalLatanoprost LatanoprostDorzolamide Dorzolamide

Brimonidine

5 27 Timolol Timolol Acetazolamide 38 2,450 9 NormalLatanoprost LatanoprostDorzolamide DorzolamideBrimonidine Brimonidine

6 25 Timolol Timolol Acetazolamide 37 2,200 9 NormalLatanoprost LatanoprostDorzolamide DorzolamideBrimonidine BrimonidineAcetazolamide Acetazolamide

* In all cases the drugs used in the first trimester were the same as the drugs used before pregnancy† The dosage was 1 g/day in all cases

Table 2. Mothers’ demographic data and their newborns’ outcomes






Medical management of glaucoma in

pregnancy is a controversial issue. There is

little literature demonstrating the terato-

genic effects of the commonly prescribed

anti-glaucoma medications and few

studies have specifically examined the

potential harms of the topically applied

anti-glaucoma medications.6–9,21

The US Food and Drug Administration

(FDA) classifies drugs into several catego-

ries of safety levels for use duringpregnancy.

1. Class A drugs have an established safety

record, with human testing data

proving safety.

2. Class B drugs have animal safety data

but no human data to confirm these

animal studies.

3. Class C drugs have either animal

studies with adverse effects or no

human or animal data.

4. Class D drugs have clear risks, although

use can be justified under certain

conditions.

5. Class X drugs are known to cause birth

defects and should never be used

during pregnancy.

Of the anti-glaucoma medications,

prostaglandin analogues (PGAs), beta-

blockers, carbonic anhydrase inhibitors

and cholinergic drugs are categorised as

class C. Brimonidine, an alpha2-agonist,

and non-specific adrenergic agonists are

considered as Class B.8,9

Although argon and selective laser tra-

beculoplasties,22 laser cyclophotocoagula-

tion23 and penetrating glaucoma surgery

are possible alternatives for medical glau-

coma therapy during pregnancy, they may

not be appropriate for the type or stage of

the disease. The patient may develop crises

of IOP elevation after each procedure or

may not reach the optimum IOP level,

mandating the use of glaucoma medica-

tions. There are also additional risks asso-ciated with glaucoma surgery for pregnant

patients, including those of the local or

general anaesthetics, the supine position-

ing and the post-operative medications.8,24

In this study, four categories of anti-

glaucoma medications were used by

patients: prostaglandin analogues, beta-

blockers, alpha2-agonists and carbonic

anhydrase inhibitors. No patient used

digital punctal pressure to decrease sys-

temic absorption until the time of referral

to the glaucoma clinic. We did not observe

any specific side-effects related to glau-

coma medications in the mothers or

babies. The only observed finding was a

low birth weight in three neonates, which

is compatible with the result of Ho, Hu

and Lin,25 who demonstrated that use of

anti-glaucoma drugs other than timolol

during pregnancy was associated with a

low birth weight. Because of foetal multi-

drug exposure and our small sample, we

cannot attribute this finding to any sub-

class of anti-glaucoma medications

Although Ho, Hu and Lin25 found no rela-

tionship between timolol use and a low

birth weight, it has been shown that the

beta-blocker atenolol, taken at the time of

conception and/or during the first trimes-ter of pregnancy (and not the second tri-

mester), was associated with a low birth

weight.26

In our study, all neonates with low birth

weights had foetal exposure to timolol and

carbonic anhydrase inhibitors in their first

trimester of pregnancy. Because timolol

can reach significant plasma levels when

applied topically,27 it may have been

responsible for this finding. Decreased

weight gain has been related to topica

carbonic anhydrase inhibitors in experi

mental studies28,29 and these agents may

also be regarded as another possible

contributing factor. Given that the major-

ity of our cases were not simple primary

glaucoma, the observed low birth weights

may be related to the mothers’ genetic

problems.

Prostaglandin analogues belong to

prostaglandin-F2 alpha analogues and they

are assumed to have oxytocic, luteolytic

and abortifacient activities in addition to

their IOP lowering effect.30 One fourth of

pregnant rabbits exposed to 80 times thehuman dose delivered no viable foetuses

at term but no adverse effects on the

embryo were reported when exposure was

up to 15 times the human dosage.31

Presently, there are debates regarding

the use of prostaglandin analogues in

pregnancy. Some experts have claimed

that prostaglandin analogues have insuffi-

cient active ingredients to induce adverse

effects on the foetus.32 Others believe that

the use of prostaglandins is generally

contra-indicated in pregnant women.8,32,33

In our study, five out of six patients used

latanoprost in their first trimester. All used

it in their second trimester and during

the first two months of the third trimester.

None of the patients developed pre

term or complicated pregnancies or con-

genital anomalies, corroborating the

results of an observational study stating no

complications in nine pregnant women

using latanoprost in their first trimester

of pregnancy.34 Altogether, becaus

Drug No. ofcases

Weeks ofexposure(Mean)

* Pregnancyoutcome

No. ofneonateswith LBW

Timolol 6 32 Normal 3

Latanoprost 6 30 Normal 3Brimonidine 3 28 Normal 2

Dorzolamide 6 30 Normal 3

Acetazolamide 6 6 Normal 3

* Including: maternal systemic side effects, abortion or pretermdelivery, major or minor congenital malformations, weight gain andpsychophysical development of childLBW = low birth weight

Table 3. Number of cases exposed to each anti-glaucoma

medication and duration of exposure






prostaglandin analogues increase uterine

contractility and, theoretically, can induce

premature labour, caution is advised in

using them late in the pregnancy.

Carbonic anhydrase inhibitors in the

systemic form with relatively high dosescan result in forelimb anomalies in rats,

mice and hamsters.35 Acetazolamide

administered to mice on day nine of

gestation at six to 70 times the human

dose has produced post-axial limb

malformations.36 Scott and associates37

demonstrated the carbonic anhydrase ter-

atogenesis in the embryonic rudiments of

structures susceptible to acetazolamide in

mice. The cellular or molecular basis for

teratogenicity has not been firmly estab-

lished. Interestingly, Ellison and Maren38

demonstrated evidence for potassium

depletion in rats treated with acetazola-

mide and concluded that replacement

therapy with potassium resulted in partial

to complete protection of developing

embryos.

No maternal or foetal complications

were reported in 12 pregnant women who

used oral acetazolamide (1 g/day) for

treatment of idiopathic intracranial hyper-

tension.10 On the other hand, there is a

case report of neonatal sacrococcygeal

teratoma in a mother using acetazolamideduring her early pregnancy.39 There are

two additional reports40,41 of renal tubular

acidosis, metabolic acidosis, hypocal-

caemia, and hypomagnesaemia in two

infants of glaucomatous mothers treated

with acetazolamide throughout their

pregnancies.

There are no reports of foetal complica-

tions following topical carbonic anhydrase

inhibitor use in pregnant women,

however, high doses of dorzolamide and

brinzolamide led to decreased weight gain

in the offspring of lactating rats.28,29 Aceta-

zolamide appears in breast milk at one-

third of the maternal plasma level,42 but

infant acetazolamide plasma levels from

nursing mothers on this drug have been

shown to be very low. Therefore, it is con-

sidered as a safe drug during breast-

feeding.11 Altogether, carbonic anhydrase

inhibitors at normal therapeutic doses

seem to be appropriate options for the

treatment of glaucoma in late pregnancy.

Beta-blockers affect the foetal heart rate

and are potentially harmful to the devel-

oping foetus.43–45 Beta-blockers, especially

atenolol, have been linked with foetal

growth retardation when given early in

pregnancy and continued for a longperiod.26,46–48 Therefore, it seems prudent

to avoid beta-blocker eye-drops during

pregnancy, especially in the first trime-

ster when the risk of teratogenesis is

highest.3,43

Timolol is 10 to 12 times more potent

than propranolol in blocking cardiac

chronotropic and inotropic effects.49

Because of the drug passage through the

nasolacrimal duct to the nose after topical

application, the possibility of systemic side-

effects are high,3,4,50,51 especially if timolol

is used in combination with systemic beta-

blockers.43 A review of the FDA and the

National Registry of Drug-Induced Ocular

Side Effects between 1978 and 1985

reported 450 cases of serious respiratory

and cardiovascular events and 32 reports

of death attributed to ophthalmic

timolol.52 Of particular relevance, there

are several case reports associating topical

timolol with impairment of respiratory

control in neonates.53,54

Among beta-blockers, at steady state,

the placental diffusion rate of the lipid-soluble timolol was three to four times

higher than that of the hydrophilic

atenolol and celiprolol.51 Therefore,

topical timolol may lead to significant

foetal exposure and adversely affect the

foetus. In one report, topical application

of timolol maleate in a 32-year-old preg-

nant woman with juvenile glaucoma con-

trolled the patient’s IOP without any side-

effects on either mother or child.55

Conversely, in another observation, a

21-week-old foetus of a 34-year-old woman

with glaucoma on timolol eye-drops (one

drop of 0.5% timolol in each eye daily)

showed bradycardia and arrhythmia,2 phe-

nomena observed in sheep as well.56 When

the timolol dose was halved, the foetal

heart rate partially normalised. After drug

discontinuation, the bradycardia disap-

peared within three days. Subsequently,

the baby was born with a cardiac con-

duction disorder.2 The authors claimed

that the conduction disorder may have

resulted from the alterations in cardiac

conduction induced by timolol in early

pregnancy.

Exposure to beta-blockers close to term

may induce beta2-mediated uterine

relaxation, neonatal bradycardia, mildhypotension and transient hypoglycae

mia.48,57 Timolol is concentrated in breast

milk to levels higher than in plasma.58–61

Because of the probable effects on delivery

and neonates, it is prudent to avoid beta-

blockers in late pregnancy and during

lactation.

A recent survey revealed that 45 pe

cent of consultant ophthalmologists in the

UK would use beta-blockers if they were to

use medical treatment in pregnancy,1

however, these medications may not be as

safe as is generally assumed. Beta-blockers

are the only class of anti-glaucoma medi-

cations demonstrated to cause adverse

reactions, if used any time during preg-

nancy. The recent advent of low-dose once

daily topical 0.1% timolol gel may provide

a safer option in pregnancy. A study com-

paring plasma timolol concentrations

using topical timolol alone or topical

timolol in combination with brimonidine

showed that maximum plasma timolol

concentration values were 20 per cent

lower in the combination treatment groupthan in the timolol group. The lower

timolol concentrations in the timolol/

brimonidine group was suggested to relate

to a slower absorption of timolol

explained by a difference in benzalko

nium concentrations.62 Conclusively

timolol 0.1% gel or timolol/brimonidine

combination may be a better option, if

physicians would like to use beta-blockers

during pregnancy. There are no pub

lished studies about use of other topical

beta-blockers, such as betaxolol and

levobunolol, in pregnant women.

Alpha2-agonist receptors are involved in

some vascular and hormonal responses

during foetal life. It has been shown that

basal prolactin levels were significantly

reduced by the selective alpha2-adrenergic

agonist,63 however, there are no similar

reports following topical application of

brimonidine.

Adrenergic drugs interfere with th

contraction of the uterus (by interfering






with the oxytocin pathway) and conse-

quently may delay labour and lead to

uterine hypotonia, which can prolong

post-partum bleeding.3 Brimonidine

readily penetrates the blood-brain barrier

and can cause central nervous systemdepression, including apnoea, if con-

sumed by infants and young children.58 It

is important to interrupt brimonidine

administration as soon as the child is deliv-

ered if the mother plans to breast-feed

because there is a possibility of its secre-

tion in the breast milk.64 Because milk pro-

duction starts in late pregnancy,19 it seems

rational to avoid this medication in this

period as well. In conclusion, although

brimonidine is considered as the safest

glaucoma medication during pregnancy

(according to FDA classification),8,9 its use

in late pregnancy may adversely affect

delivery, lactation and the foetus.

Apraclonidine belongs to the group C

of FDA classification. Perinatal and post-

natal studies in rats with mid- and high-

dose apraclonidine during gestation and

lactation demonstrated poor weight gain

and viability of offspring, although this

result was not statistically different from

the controls.65,66 Apraclonidine is not rec-

ommended as a long-term therapeutic

agent due to high incidence of localadverse reactions and tachyphylaxis.58

Overall, apraclonidine seems to be an

inappropriate option for treatment of

glaucoma during pregnancy.

Parasympathomimetics are in group C

of the FDA classification. These drugs

have shown teratogenic and adverse

foetal effects on animals.67,68 Because

echothiophate is a quaternary ammonium

compound, it may have more difficulty tra-

versing the placenta than pilocarpine, a

tertiary cholinergic amine that is a weak

base and traverses membranes well.3,69

These medications have significant local

adverse reactions.58 Therefore, parasym-

pathomimetics may not be good can-

didates for glaucoma therapy during

pregnancy.

As it is unlikely that controlled trials will

be performed on humans, we recommend

the following instructions on the basis of

current literature. These suggestions are

prepared based on both the FDA classifi-

cation and literature case observations,

which are not considered in preparing the

FDA classification. In the following sugges-

tions, it is important to point out that we

cannot use the terms such as ‘safe’ or ‘con-

traindicated’ for any of the recommenda-tions. Based on the animal studies and

case observations, herein, we just recom-

mend some rational instructions. The cli-

nicians may or may not follow these

recommendations. These suggestions may

be substantially modified in the future

based on the ongoing research.

Recently, the National Health and

Medical Research Council of Australia

(NHMRC) published draft guidelines for

glaucoma detection and management that

contain useful information about glau-

coma management during pregnancy.70

The Australian categorisation of risk of

drug use during pregnancy differs slightly

from that of the FDA classification. The

guidelines break the category B into three

subcategories with respect to the results of

animal studies. In that classification, beta-

blockers were placed in category C and all

other anti-glaucoma medications have

been placed in B subcategories, however,

they claimed that ‘the allocation of a B

category does not imply greater safety

than the C category’.The NHMRC suggested beta-blockers,

alpha2-agonists, cholinergics, carbonic

anhydrase inhibitors and prostaglandin

analogues, respectively, as the first to last

choices in pregnancy. Our suggestions

differ from NHMRC guidelines in that we

break pregnancy into its trimesters and

recommend distinct suggestions for each

trimester. In addition, we expand the

discussion toward more subtle issues

in prescribing each anti-glaucoma

medication. These suggestions could be

regarded as complementary to NHMRC

guidelines.

As a general recommendation, topical

forms of anti-glaucoma medications are

preferred, especially gel formulations (if

applicable), to reduce systemic side-

effects.71 Patients should be instructed to

use only one drop of medication on each

application, applying digital pressure over

the medial part of the lower eyelid or

gently closing the eyelids for one or

two minutes to minimise systemic drug

absorption.72,73

When two different subclasses of appro-

priate glaucoma medications have compa-

rable risks and benefits in a patient with

bilateral glaucoma, we could prescribetwo drugs from different subclasses, one

for each eye. This strategy would halve the

overall systemic level of each drug and

subsequently reduce the risk of foeta

complications. If the tailored regimen

contains timolol and brimonidine, the

timolol/brimonidine combination should

be encouraged because it is associated

with lower blood levels of drugs and, sub-

sequently, fewer side-effects.62 Use of

timolol in patients who are on systemic

beta-blockers for other reasons, such as

pre-eclampsia, should be avoided. Addi

tionally, carbonic anhydrase inhibitors

should be avoided in patients who suffer

from renal insufficiency, as in eclampsia.

Regarding the FDA safety level classifica-

tion, topical brimonidine may be the best

initial choice during pregnancy, however,

as brimonidine, timolol and prostaglan

din analogues, have possible adverse

effects on delivery, lactation, and the

neonate, it is prudent to replace these

medications in the last month of preg

nancy. Accordingly, carbonic anhydraseinhibitors may be the best choice in this

period.11

In the first trimester, brimonidine and

prostaglandin analogues seem to be safe.

It is wise to avoid beta-blockers and car-

bonic anhydrase inhibitors.

In the second and third trimesters, bri-

monidine can be used and topical car-

bonic anhydrase inhibitors, beta-blockers

and prostaglandin analogues should be

used with special caution. If beta-blockers

are used, regular monitoring of foeta

heart rate, rhythm and foetal growth is

necessary to detect any arrhythmia or

early signs of intrauterine growth retarda-

tion. To prevent the possible foetal or

neonatal hypokalaemia, acidosis and risk

of teratogenesis, while using carbonic

anhydrase inhibitors, monitoring the

plasma potassium level is recommended

while modifying the diet, if necessary

When prostaglandin analogues are used

attention should be directed toward






the signs and symptoms of premature

labour.

In the late third trimester and during

lactation, avoidance of brimonidine seems

a wise decision, as it penetrates the blood

brain barrier easily and can result in neo-natal central nervous system depression. If

beta-blocker usage is planned, the lower

concentration preparations are prefer-

able. Topical carbonic anhydrase inhibi-

tors seem to be a suitable option in this

period. If prostaglandin analogues are

started, the possibility of premature

labour should be kept in mind.

Theoretically, glaucoma medications

may damage the foetus or negatively affect

the outcome of the pregnancy, however,

according to the results of this study and

similar reports, they may not have substan-

tial clinical significance with routine

dosages. Therefore, most women with

glaucoma may be treated efficiently

during pregnancy.7 Once medication is

started, the patient should be monitored

frequently. The clinician must be mindful

of the possibility of adverse effects and be

prepared to alter or terminate treatment if

needed.

In this preliminary study, the sample

size was necessarily small and though the

prevalence of low birth weight was statisti-cally significant, we cannot conclude with

certainty that this finding was strictly

related to anti-glaucoma drugs.

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Corresponding author:

Dr Mohammad Hosein Nowroozzadeh

Poostchi Ophthalmology Research

Center

Poostchi Eye Clinic, Zand Street

Shiraz

IRAN

E-mail: [email protected]






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