Ординатура / Офтальмология / Английские материалы / Atlas of Glaucoma, Second Edition_Choplin, Lundy_2007

glaucomatous damage. The preferential loss of larger

has begun to identify genotypic susceptibility to

ganglion cells early in glaucoma may reflect the

glaucomatous cell death as a major factor in the

influence of this factor as well as others. Lamina

development of POAG. Not everybody with the

cribrosa pores are larger in the polar regions of the

abnormal gene will necessarily develop glaucoma,

optic nerve head (where the larger axons pass),

but having the gene may put one at higher risk.

with thinner septae between these pores than in

Understanding the environmental factors around

other areas of the nerve head. The repeated stress of

the ganglion cell will be important in better defin-

changing intraocular pressure (causing mechanical

ing how to address factors related to apoptosis.

deformation of the laminar plates) may lead to break-

down of the septae, loss of support for the axons,

Other potential factors

and axonal damage, as well as causing damaging

episodes of relative ischemia. The susceptibility of

Investigators have also sought to explore the link to

these large lamina cribrosa pores may thus also help

immune system function and the role of chronic

explain why larger diameter optic discs are more

infections as potential additional mechanisms for

prone to glaucomatous damage. Burgoyne and others

glaucoma. Intriguing evidence of heightened immune

have developed innovative measures to assess the

responses and potential autoimmune mechanisms

compliance and resistance of the lamina cribosa to

exist for subsets of patients with glaucoma. The

and fluctuations in intraocular pressure.

role played by infections, as with Helicobacter

pylori for gastric ulcers, remains to be proven in

Other optic nerve head characteristics

glaucoma.

Several risk factors in optic nerve head appearance

MAKING THE DIAGNOSIS OF POAG

that make glaucomatous progression more likely

have been reported. Not only are large optic discs

more likely to develop glaucoma, but those discs

As noted in the definition of POAG, four elements

with thinner neuroretinal rim areas are more likely

are needed to make the diagnosis: (1) the patient

to show progression of glaucomatous damage.

must be of adult age (with younger patients being

Also, optic discs with a larger beta zone of peripap-

defined as having juvenile-onset glaucoma, though

illary atrophy (the whitish area located immedi-

without necessarily any significant differences in

ately adjacent to the peripapillary scleral ring and

treatment philosophy); (2) the anterior chamber

characterized by visible underlying choroidal ves-

angles must be ‘open’ by gonioscopy (see Chapter 5);

sels and sclera) are more likely to show visual field

(3) there must be no known secondary cause for the

progression than discs with a smaller beta zone.

glaucoma (see Chapter 10); and (4) there must be optic

This larger beta zone is often associated with optic

nerve damage, manifested by either optic disc or

disc hemorrhage, another sign of glaucomatous

nerve fiber layer changes consistent with glaucoma

progression.

(see Chapter 6) or characteristic visual field abnor-

malities (see Chapter 8). It is important to note that,

Genetic analyses

of the patients who progressed to glaucoma in the

Ocular Hypertension Treatment Study, half of them

Two new areas of research may be of particular

progressed in terms of disc characteristics alone,

promise. First, the pursuit of localizing the gene(s)

while less than 10% were found to progress in

that are related to POAG proceeds apace. Several

terms of visual fields alone. To assist the clinician

genes that affect one’s susceptibility to glaucoma

in determining what changes are ‘characteristic of’ or

have already been identified. Mutations in the

‘consistent with’ POAG, the AAO provides illustra-

TIGR/myocilin gene are present in many cases of

tive examples of each. For visual fields, the definition

juvenile or early-onset POAG. Optineurin gene muta-

explicitly encompasses arcuate defects, nasal steps,

tions are present in some families with normal-tension

paracentral scotomata, or generalized depression.

glaucoma. Mutations in another gene, CYP1B1, have

For disc or retinal nerve fiber layer appearance, the

been linked to patients with congenital glaucoma,

AAO explicitly includes thinning or notching of

and many more genes possibly affecting glaucoma

the disc rim, progressive change over time, and nerve

continue to be studied. With the promise of molecular

fiber layer defects. For a full discussion and illus-

genetics, a greater grasp of the elements that cause

trations of these and other characteristics, please

POAG to develop may follow. Second, several inves-

refer to the chapters noted above.

tigators are now exploring the concept that apoptotic

As the sophistication of diagnosing POAG con-

mechanisms of preprogrammed cell death may under-

tinues to develop, new diagnostic guidelines may

lie a significant proportion of glaucomatous nerve

be proposed. Even with the PPP guidelines in place,

fiber and cell loss. Such cell death may either be

clinician subjectivity and variations in observation

triggered by or made more susceptible to certain

remain an issue when diagnosing the presence and

environmental conditions. Indeed, genetic analysis

severity of POAG. In the future, methods of diagnosis

following adequate lowering of intraocular pres-

Lowering of intraocular pressure

sure has been reported by several authors, particu-

Considering the definition of POAG, our current

larly in cases of early glaucoma among younger

patients. Figure 9.1 demonstrates a case of signifi-

ability to modulate the course of the disease is still

cant recovery of visual field following aggressive

relatively limited. At the present time, the only avail-

treatment of POAG. These illustrations are the

able treatment for POAG is to reduce the intraocular

preand postoperative fields of a patient with

pressure. Whether this functions to improve perfu-

advanced POAG who underwent a successful

sion or ocular blood flow or has a direct mechanical

trephination with postoperative intraocular pres-

benefit on the optic nerve, or both, is not clear. The

sures of between 6 and 8 mmHg. Thus, perhaps

evidence that lower intraocular pressure is more

our long-term goal of glaucoma treatment for the

effective in preventing visual field loss can be indi-

future should be to improve and restore significant

rectly seen in the results of the Moorfields Primary

amounts of visual functioning, as measured by a

Treatment Trial and the Scottish Glaucoma Trial,

variety of means.

in which initial trabeculectomy lowered intraocular

It is vital that treatment be tailored to the needs

pressure more than medicine did, and was also

of the individual patient in partnership with the

associated with less loss of field on follow-up.

physician. Issues including compliance with therapy,

Similarly, the lower intraocular pressure obtained

patient understanding of the disease, cost of treat-

with initial laser trabeculoplasty in the Glaucoma

ment, potential side-effects, and impact of therapy

Laser Trial was associated with less visual field

on the patient’s quality of life should be explicitly

loss than in the medication-first group.

incorporated into the patient’s care plan. It is not

Several recent clinical trials have directly shown

sufficient to limit discussions to intraocular pressure,

the importance of lowering intraocular pressure,

visual field, and optic nerve status; discussions

whether accomplished by medicines, laser, or surgery

about the implications of POAG and its care need

(Table 9.4). The Early Manifest Glaucoma Trial demon-

to be addressed with the patient.

strated that treating early glaucoma patients with

In looking at treatment from a ‘patient-centered’

medicine and argon laser trabeculoplasty reduced

perspective, we have significantly more information

their risk of progression by half compared to obser-

today on the impact of having glaucoma and glau-

vation. The Collaborative Initial Glaucoma Treatment

coma treatment. First, as shown in the Collaborative

Study reported that both medical and surgical treat-

Initial Glaucoma Treatment Study (CIGTS), patients

ments resulted in similar long-term reductions in

report significant amounts of emotional distress upon

visual field loss. In the Advanced Glaucoma

being informed of their diagnosis, including fears of

Intervention Study, patients with average intraocular

blindness. Second, from the Early Manifest Glaucoma

pressures of less than 14 mmHg had a lower rate of

Trial (EMGT), we know that patient self-reported

visual field progression than patients with higher

visual functioning, as measured by the NEI-VFQ

pressures. Further, those patients with intraocular

questionnaire, has a significant decrease when visual

pressures consistently under 18 mmHg were highly

field loss exceeds –4 dB of mean deviation loss or

unlikely to experience progression. Also, a comparison

at visual acuities of 20/100. Subsequent to that point,

of surgical sequences (performing either argon laser

visual functioning declines steadily as visual field

trabeculoplasty or trabeculectomy as the initial surgi-

worsens, as measured by patient self-report on the

cal procedure) showed that, while intraocular pres-

NEI-VFQ. Third, an unanswered question is the

sure was lowered by either sequence, black patients

extent to which issues not measured by the NEI-VFQ

tended to have better visual function outcomes from

or other questionnaires may be present in patients

argon laser trabeculoplasty first, while white patients

without any visual field loss. Indeed, patient ‘side-

tended to have better visual function outcomes from

effects’ and ‘symptoms’ were present at diagnosis

trabeculectomy first. Finally, in the Ocular Hyper-

with glaucoma in the CIGTS. Such issues are often

tension Treatment Study, lowering the intraocular

present and should be assessed at office visits, and

pressure in ocular hypertensive patients halved the

such effects were present in those who underwent

risk of progression to POAG. This study also high-

glaucoma surgery and those using medical therapy

lighted central corneal thickness as a powerful risk

in the CIGTS. Fourth, analysis from the Salisbury Eye

factor for the development of POAG in these patients.

Evaluation population-based study demonstrates

Once a diagnosis of POAG is made, the AAO PPP

that there is no ‘cutoff ’ or ‘inflection point’ in the

states that a ‘target pressure’ should be defined – i.e.

measured ability of patients to perform tasks such

the upper limit of what would be considered an

as reading, walking through a room, recognizing

‘acceptable’ pressure for that particular eye. This target

faces, or other important activities relative to visual

pressure is only an estimate and can be subject to

acuity, contrast sensitivity, or visual field. Therefore,

revision based on the patient’s clinical course. In

the choice of a ‘disability’ level is an arbitrary politi-

selecting the target pressure, it should be at least 20%

cal decision, not one based on patient ability to

lower than the baseline intraocular pressure range

function.

and should be set lower for those eyes that have

Follow-up and monitoring

use of medications, and general assessment of the

In order to determine whether the target pressure is

impact of the condition and treatment on daily living.

Each examination should include measurements of

appropriate, patients need periodic monitoring of

visual acuity and intraocular pressure in both eyes,

their optic nerve status, both directly through evalua-

as well as a slit-lamp examination. For periodic optic

tion of the disc and nerve fiber layer and indirectly

nerve evaluations, if the target intraocular pressure has

through the performance of periodic visual fields.

been achieved and no progression is noted, control

Detecting optic nerve head appearance change over

for longer than 6 months suggests that follow-up

time is complicated by the need for comparison with

disc evaluations every 6–18 months should be suf-

remote stereo disc photographs, which may not be

ficient. For more recent control ( 6 months), follow-

available in many instances. A national database of

up in 6–12 months is warranted. However, if the target

stereo disc photographs of glaucoma patients would

intraocular pressure needs to be reset because of pro-

perhaps be helpful in giving eye care providers a

gression at or below the initial target, follow-up disc

basis on which to compare present optic disc appear-

evaluation should occur in 2–6 months. For those

ances. If disc damage occurs at or below a target pres-

eyes in which the target has not yet been achieved,

sure, then the target pressure must be reset, again

follow-up should occur between 1 and 6 months

starting with at least an additional 20% reduction

(for progression) or 2 to 6 months (if no progression).

from the current intraocular pressure.

For interval visual fields, if the target intraocular

The interval between follow-up visits to the

pressure has been achieved and no progression is

physician is determined by attainment of the target

noted, control for longer than 6 months suggests

intraocular pressure (or failure to do so) and the

that follow-up every 6–24 months should be suffi-

presence or absence of disease progression. For

cient. For more recent control ( 6 months), follow-up

example, if the target intraocular pressure has been

in 6–24 months is warranted. However, if the target

achieved and no progression is noted, control for

intraocular pressure needs to be reset because of

longer than 6 months suggests that follow-up every

progression at or below the initial target, follow-up

3–12 months should be sufficient. For more recent

fields should occur in 3–12 months. For those eyes

control ( 6 months), follow-up in 1–6 months is

in which the target has not yet been achieved, follow-

warranted. However, if the target intraocular pres-

up should occur also between 3 and 12 months.

sure needs to be reset because of progression at or

The AAO makes clear that these are timing

below the initial target, follow-up should occur in

ranges that need to be adjusted to fit the needs of

1 week to 3 months. For those eyes in which the

each individual patient. Thus, for example, if

target has not yet been achieved, follow-up should

acceptable compliance is lacking, then physicians

occur between 1 day and 1 month (for progression)

need to adjust the treatment regimen to enhance

or 3 months (if no progression). These recommen-

the utility of the therapy for the patient. Similarly,

dations are summarized in Table 9.5.

if problems develop with certain medications,

During follow-up visits, the history should

switching patients to new medications will neces-

include interval ocular and systemic medical his-

sitate more frequent follow-up visits, just as if a new

tory, an inquiry into local or systemic problems

target pressure was set.

with medication, verification of the

appropriate

Progression of disease

Status

Duration of control

Recommended interval

Progressive optic nerve and/or

Not at target pressure

n/a

1 day to 1 month

visual field damage

No progression

Not at target pressure

n/a

1 day to 3 months

Progressive optic nerve and/or

Requires resetting target

n/a

1 week to 3 months

visual field damage at initial

target pressure; requires

resetting target

Progression documented at

New target recently

Less than 3 months

1 month to 3 months

prior visit

achieved

No progression

At target pressure

Less than 6 months

1 month to 6 months

No progression

At target pressure

More than 6 months

3 months to 12 months