Japan Glaucoma Society

Guidelines for GlaucomaJapan Glaucoma Society

Guidelines for GlaucomaJapan Glaucoma Society

Guidelines for GlaucomaJapan Glaucoma Society

Guidelines for GlaucomaJapan Glaucoma Society

Guidelines for Glaucoma

Japan Glaucoma Society

Guidelines for Glaucoma

Guidelines for Glaucoma

April 1, 2004

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Preface................................................................................................................................................................................................................................................... 1

Introduction..................................................................................................................................................................................................................................... 3

Flow-chartsⅠ. Examinations for glaucoma diagnosis.......................................................................................................................................................... 4Ⅱ. Classification of primary open-angle glaucoma (broad definition)............................................................................. 5Ⅲ. Classification of primary angle-closure glaucoma......................................................................................................................... 5Ⅳ. Automated static perimetry...................................................................................................................................................................................... 6Ⅴ. Treatment of primary open-angle glaucoma (broad definition): General principles................................ 7Ⅵ. Treatment of primary open-angle glaucoma (broad definition): Target intraocular pressure.......... 7Ⅶ. Treatment of primary open-angle glaucoma (broad definition): Medical treatment................................. 8Ⅷ. Treatment of primary angle-closure glaucoma................................................................................................................................... 8Ⅸ. Treatment of acute primary angle-closure glaucoma.................................................................................................................. 9

Section 1. Definition of Glaucoma.................................................................................................................................................................... 11

Section 2. Classification of GlaucomaⅠ. Primary glaucoma...............................................................................................................................................................................................................13

1. Primary open-angle glaucoma (broad definition)...................................................................................................................... 132. Primary angle-closure glaucoma..................................................................................................................................................................143. Mixed glaucoma............................................................................................................................................................................................................. 15

Ⅱ. Secondary glaucoma....................................................................................................................................................................................................... 151. Open angle mechanisms in secondary glaucoma.....................................................................................................................152. Angle closure mechanisms in secondary glaucoma...............................................................................................................16

Ⅲ. Developmental glaucoma..........................................................................................................................................................................................161. Early onset developmental glaucoma......................................................................................................................................................162. Late onset developmental glaucoma........................................................................................................................................................163. Developmental glaucoma with other congenital anomalies.........................................................................................16

Section 3. Examination of GlaucomaⅠ. History taking...........................................................................................................................................................................................................................19Ⅱ. Slit-lamp microscopy.......................................................................................................................................................................................................19Ⅲ. Tonometry....................................................................................................................................................................................................................................20Ⅳ. Gonioscopy................................................................................................................................................................................................................................21Ⅴ. Ophthalmoscopy..................................................................................................................................................................................................................22Ⅵ. Perimetry.......................................................................................................................................................................................................................................23

Table of Contents――――――――――――――――――――――――――――――――――――――――――――――――――――――――――――――――――

Section 4. Principles of Treatment for GlaucomaⅠ. Principles of glaucoma therapy............................................................................................................................................................................27Ⅱ. Current status of treatment........................................................................................................................................................................................27

1. Baseline data determination.............................................................................................................................................................................. 272. Target intraocular pressure.................................................................................................................................................................................. 273. Glaucoma and QOL.................................................................................................................................................................................................. 284. Compliance with glaucoma drug treatment.................................................................................................................................... 28

Ⅲ. Glaucoma treatment agents.................................................................................................................................................................................... 291. Classification of glaucoma treatment agents.................................................................................................................................. 292. Selection of drugs.......................................................................................................................................................................................................... 293. Treatment trials................................................................................................................................................................................................................. 294. Guidance in administration............................................................................................................................................................................... 295. Combined treatment.................................................................................................................................................................................................. 306. Glaucoma treatment agents.............................................................................................................................................................................. 30

Ⅳ. Laser surgery............................................................................................................................................................................................................................ 351. Laser iridotomy................................................................................................................................................................................................................ 352. Laser trabeculoplasty................................................................................................................................................................................................ 363. Laser gonioplasty (laser peripheral iridoplasty)........................................................................................................................... 374. Cyclophotocoagulation.......................................................................................................................................................................................... 375. Laser suturelysis.............................................................................................................................................................................................................. 38

Ⅴ. Invasive surgery.................................................................................................................................................................................................................... 381. Indications............................................................................................................................................................................................................................. 382. Surgical techniques..................................................................................................................................................................................................... 39

Section 5. Treatment for Each Type of GlaucomaⅠ. Primary glaucoma.............................................................................................................................................................................................................. 41

1. Primary open-angle glaucoma........................................................................................................................................................................ 412. Normal-tension glaucoma................................................................................................................................................................................... 423. Primary angle-closure glaucoma..................................................................................................................................................................424. Mixed glaucoma............................................................................................................................................................................................................. 445. Ocular hypertension.................................................................................................................................................................................................. 44

Ⅱ. Secondary glaucoma....................................................................................................................................................................................................... 451. Secondary open-angle glaucoma................................................................................................................................................................ 452. Secondary angle-closure glaucoma.......................................................................................................................................................... 46

Ⅲ. Developmental glaucoma......................................................................................................................................................................................... 471. Early onset developmental glaucoma..................................................................................................................................................... 472. Developmental glaucoma with other congenital anomalies........................................................................................ 48

Ⅳ. Secondary glaucomas in childhood............................................................................................................................................................... 48

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Preface

Glaucoma, found in approximately 5.8% of persons aged 40 and older, is a disease that cancause a severe impairment of visual function and leads to blindness if untreated. In today's agingsociety, glaucoma is the second-leading cause of acquired blindness, and the question of how toappropriately diagnose, treat, and manage the disease is of vital importance not only in maintain-ing patients' quality of life, but also in stemming the increasing burden on society imposed by thedisease.

Rather than as a single clinical entity, glaucoma should be understood as a syndrome, and inorder to diagnose, treat, and manage this illness, one must possess the expertise and discernmentneeded to consolidate intricate clinical findings, frequently over a lengthy disease course.

In light of this background, Japan Glaucoma Society has prepared the present guidelines as anaid to ophthalmologists in providing everyday medical care for glaucoma, including appropriatediagnosis and treatment.

In the present guidelines, we have attempted to systematically present the proper standards forcurrent glaucoma treatment. In preparing these guidelines, however, it has not been our intent toimpose limitations on physicians in diagnosing various clinical conditions. It is our hope that thepresent guidelines will serve as a reference for improving the level of care and reducing discrep-ancies among the various types of treatment provided. On the other hand, it would be improperto place excessive importance on these guidelines, as this would restrict the physician's flexibilityto introduce future progress in treatments by limiting his or her individual responses to various,clinical situations.

It is the hope of the authors that the present guidelines will contribute toward raising the stan-dard of glaucoma treatment in Japan.

September 2002

Yoshiaki Kitazawa, Chairman, Japan Glaucoma Society

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The Japan Glaucoma Society Guidelines for Glaucoma

Committee Members

Haruki Abe, MD, PhD, ChairYasuaki Kuwayama, MD, PhDMotohiro Shirakashi, MD, PhDShiroaki Shirato, MD, PhDHidenobu Tanihara, MD, PhDTetsuya Yamamoto, MD, PhD

Authors and assistant author of Japan Glaucoma Society

Guidelines for Glaucoma

Authors:Haruki Abe, MD, PhDYoshiaki Kitazawa, MD, PhDYasuaki Kuwayama, MD, PhDMotohiro Shirakashi, MD, PhDShiroaki Shirato, MD, PhDHidenobu Tanihara, MD, PhDTetsuya Yamamoto, MD, PhD

Assistant author:Kiyoshi Yaoeda, MD, PhD

Reviewed and approved by Japan Glaucoma Society Board of Trustees September 2002

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Glaucoma consistently ranks among the leading causes of blindness in Japan, and it is also anextremely serious illness from a social standpoint. According to a glaucoma survey conducted inseven areas of the country from 1988 to 1989, the prevalence of glaucoma was 3.56% of the pop-ulation above 40. Furthermore, a recent epidemiological survey of glaucoma conducted from2000 to 2002 (the Tajimi Study) showed that the prevalence of normal-tension glaucoma was3.60% of the population above age 40, which was approximately 11 times the prevalence of pri-mary open-angle glaucoma (0.32%). Accordingly, it was found that glaucoma is by no means arare disease in this country, with the percentage accounted for by normal-tension glaucoma beinghigher than expected. Moreover, as the rate of newly-discovered cases of glaucoma in the TajimiStudy was 89%, this clearly demonstrates that there are numerous latent cases of the disease inthis country that have not yet been treated.

Damage to the optic nerve and visual field caused by the two most prevalent forms of glauco-ma, namely primary open-angle glaucoma and normal-tension glaucoma, is essentially progres-sive and irreversible. In these types of glaucoma, as damage gradually progresses unnoticed bythe patient, early detection and treatment are of paramount importance in arresting or controllingthe progressive damage.

In recent years, progress in the diagnosis and treatment of glaucoma has been remarkable, withnumerous new diagnostic and therapeutic aids being introduced in the clinical setting, and thediagnosis and treatment of the disease has become multi-faceted. What has not changed, howev-er, is the difficulty of selecting appropriate diagnostic and therapeutic measures for the individualpatient, conducting early diagnosis and treatment, and ensuring long-term patient management inorder to improve both quality of life (QOL) and quality of vision. Moreover, even with a variety ofdiagnostic and therapeutic options at one's disposal, there is still a considerable number ofpatients in whom the progression of the disease cannot be arrested or slowed, and this remains amajor problem.

In particular, with recent technological innovations, increasing attention has been focused onmaintaining and increasing therapeutic standards, and there has been an increasingly pressingneed in recent years for glaucoma treatment guidelines in order to improve the quality of therapy.Moreover, guidelines are also needed in order to improve communication between patients andcaregivers, facilitate the selection of treatment options, provide relevant information to all partiesconcerned, and facilitate team medical care. From a social standpoint, moreover, it is necessary toreduce health care expenses by efficiently utilizing resources from the standpoint of globalizationof health care and medical economics.

Japan Glaucoma Society has therefore prepared the guidelines for glaucoma in light of thesecircumstances. In the guidelines, we first present flow-charts illustrating the main points of glauco-ma diagnosis and treatment, followed by explanations in five sections entitled "Definition ofGlaucoma," "Classification of Glaucoma", "Examination of Glaucoma", "Principles of Treatmentfor Glaucoma," and "Treatment for Each Type of Glaucoma" We hope that the present guidelineswill be widely applied and will prove useful as an aid in everyday glaucoma treatment.

Medical care is first and foremost at the discretion of the treating physician, and the physicianmust conduct the most appropriate diagnosis and treatment tailored to the individual patient.Japan Glaucoma Society assumes no responsibility for any legal problems arising in connec-tion with health care provided based on the present guidelines.

Introduction

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Ⅰ. Examinations for glaucoma diagnosis

Visual acuity and refraction tests

Slit-lamp microscopy

Tonometry

Gonioscopy

Ophthalmoscopy

Perimetry

Other tests

History taking

Comprehensive assessmentof test findings

Assessment of glaucomatous optic nerveand visual field damage

Type of glaucoma

Stage of glaucoma

Flow-charts

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Ⅱ. Classification of primary open-angle glaucoma (broad definition＊)

Anterior chamber angle

Normal

Ocular hypertension

Normal-tension glaucoma

Primary open-angle glaucoma

Normal-tension glaucoma(suspect)

Primary open-angle glaucoma(suspect)

Normal open angle

IOP= Intraocular pressure＊See Section 2; †See Section 3.

Normal ElevatedNormal ElevatedNormal Elevated

Optic nerveGlaucomatous damage

Visual fieldGlaucomatous damage

No Yes No Yes

IOP†� IOP†� IOP†�

Ⅲ. Classification of primary angle-closure glaucoma

Chronic typeAcute type

Mechanism of angle closure

Relative pupillary block Plateau iris

Plateau iris syndromePrimary angle-closure glaucomawith relative pupillary block

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Ⅳ. Automated static perimetry

Initial test

Threshold test Threshold test

Test reliability

Visual field assessment Visual field assessment

Retesting

Retesting

Test reliability

Screening test

During follow-up

＊Kinetic perimetry (Goldmann perimeter).†Perimetry using other perimeters.

Low

Normal Stable/improved

†�

＊�

Deteriorated

Normal

Low Normal

Abnormal

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V. Treatment of primary open-angle glaucoma (broad definition＊): General principles

Establish target IOP

Initiate treatment

Target IOP achieved

Continue treatment

Deterioration of optic nerve and/or visual field

Change treatment

Change target IOP

IOP= Intraocular pressure＊See Section 2.

No

YesNo

Yes

VI. Treatment of primary open-angle glaucoma (broad definition＊): Target intraocular pressure

IOP= Intraocular pressure＊See Section 2.

Low

Otherrisk factors

(－)

(＋)

IOP without treatment

High

Late

Stage of glaucoma

Early

Lower

Target IOP

Higher

Other risk factorsBaseline

IOP without treatmentStage of glaucoma

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IOP= Intraocular pressure＊See Section 2; †See Section 4.

No

No

Yes

Yes

VII. Treatment of primary open-angle glaucoma (broad definition＊): Medical treatment��

Initiate monotherapy

Target IOP achieved

Change monotherapy

Multi-drug therapy

Target IOP achieved

Change medication

Continue medical treatment Laser treatment and/or surgery†�

VIII. Treatment of primary angle-closure glaucoma

Mechanism of angle closure

Relative pupillary block

Laser iridotomy

Successful

Peripheral iridectomy

IOP control

Favorable Unfavorable

Follow-up Additional treatment to lower IOP(medical treatment and/or surgery)

Unsuccessful ornot possible

Plateau iris

MioticsLaser

gonioplasty

IOP= Intraocular pressure

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IX. Treatment of acute primary angle-closure glaucoma

Medical treatment

IOP control

Favorable

Follow-upAdditional treatment to lower IOP(medical treatment and/or surgery)

Unfavorable

Lowering IOP Opening chamber angle

Laser iridotomy

Successful Unsuccessful ornot possible

Peripheral iridectomy

Reducing inflammation

IOP= Intraocular pressure

Section 1 Definition of Glaucoma

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Glaucoma is a disease characterized by func-tional or structural anomalies of the eye in whichat least one characteristic change in the opticdisc or visual field is present and in which theprogression of optic nerve damage can ordinarilybe alleviated or halted by lowering intraocularpressure. This definition cannot necessarily beapplied unconditionally to all disease types.Please refer to the individual sections in questionfor definitions of individual disease types. Inthese guidelines, please refer to the individualsections in question for the definition of differentdisease types.

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Introduction

Glaucoma can be classified according to gonio-scopic findings and the presence or absence ofdiseases or conditions that may cause elevatedintraocular pressure. The disease can be classi-fied into primary glaucoma, in which no othercause of elevated intraocular pressure is present,secondary glaucoma, in which the elevation inintraocular pressure results from other ocular dis-eases, systemic diseases, or drug use, and devel-opmental glaucoma, in which the elevation inintraocular pressure results from developmentalanomalies in the anterior chamber angle. Primaryglaucoma is divided into primary open-angleglaucoma (broad definition) and primary angle-closure glaucoma. The former is a disease con-cept that encompasses both conventional prima-ry open-angle glaucoma and normal-tensionglaucoma.

In establishing treatment for glaucoma, classi-fication according to the mechanism of intraocu-lar pressure elevation is useful. It should be bornein mind that in secondary glaucoma, the mecha-nism of this elevation is not uniform, but dependson the subtype and disease stage.

In the present guidelines, we propose the glau-coma classification shown in Table 2-1 based onthe above considerations.

ⅠⅠ. Primary glaucoma

1. Primary open-angle glaucoma (broad defini-tion)Primary open-angle glaucoma (broad defini-

tion) is a disease concept including both conven-tional primary open-angle glaucoma (in the fol-lowing, this will denote the conventional conceptof primary open-angle glaucoma unless "broaddefinition" is specified) and normal-tension glau-coma. The risk of the development and progres-sion of primary open-angle glaucoma (broad def-inition) increases with increasing intraocularpressure. Moreover, there are differences in thevulnerability of the optic nerve to intraocularpressure, and because primary open-angle glau-coma and normal-tension glaucoma cannot bedistinguished based on specific intraocular pres-

sure values, the term primary open-angle glauco-ma (broad definition) has been developed as aconcept encompassing both disease types.Primary open-angle glaucoma (broad definition)can be conveniently subdivided in the clinicalsetting into an elevated intraocular pressuregroup (primary open-angle glaucoma) and a nor-mal intraocular pressure group (normal-tensionglaucoma). Primary open-angle glaucoma (broaddefinition) is characterized by chronic progres-sive optic neuropathy in which the optic disc andretinal nerve fiber layer show particular morpho-logical characteristics, i.e., thinning of the discrim and retinal nerve fiber layer defects. In prima-ry open-angle glaucoma (broad definition), otherabnormality and congenital anomalies that maycause elevation of the intraocular pressure areabsent and gonioscopy shows a normal openangle, although the presence of functional anom-alies of the anterior chamber angle cannot beruled out. This is accompanied by progressiveretinal ganglion cell loss and the correspondingvisual field defects.

In cases of discrepancies between optic nervefindings and perimetric findings, if the optic discis found to show pallor relative to the degree ofcupping, the visual field and optic nerve shouldbe retested, and brain imaging studies should beconducted in order to rule out intracranial dis-eases, etc. Moreover, among cases of primaryopen-angle glaucoma (broad definition), geneticaberrations such as TIGR/MYOC and optineurinanomalies may occur.

1) Primary open-angle glaucomaIn this subtype of primary open-angle glauco-

ma (broad definition), intraocular pressureexceeds the statistically determined normal rangeduring the progression of glaucomatous opticneuropathy, and abnormally elevated intraocularpressure is strongly suspected to play a role inthis optic neuropathy. As intraocular pressure isknown to be subject to diurnal and seasonal fluc-tuations, when intraocular pressure is only mea-sured a few times, there are many cases in whichabnormal intraocular pressure values are notdetected.

Section 2 Classification of Glaucoma

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2) Normal-tension glaucoma, normal-pressureglaucomaIn this subtype of primary open-angle glauco-

ma (broad definition), intraocular pressure con-stantly remains within the statistically determinednormal range during the development and pro-gression of glaucomatous optic neuropathy. How-ever, this does not necessarily mean that abnor-mal intraocular pressure does not play a role inthe development of optic neuropathy in normal-tension glaucoma. In many cases, as a possiblepathogenic factor, findings indicate that factorsindependent of intraocular pressure such as vas-cular factor may also play a role. As intraoc-ular pressure is known to be subject to diurnaland seasonal fluctuations, it is often quite difficultto establish that it is within the normal range, andrepeated tonometry including 24-hr phasing isnecessary in many cases.

3) Ocular hypertensionAlthough intraocular pressure shows similari-

ties to primary open-angle glaucoma, this sub-type lacks optic neuropathy and visual fieldanomalies. Some believe this subtype to be a pre-liminary stage of primary open-angle glaucoma,while others think it to be a type in which theresistance of the optic nerve to intraocular pres-sure is strong. Background factors such as familyhistory of glaucoma, vascular factors, age, race,corneal thickness and refraction are known to beassociated with the progression to glaucoma.Moreover, some researchers feel that intraocularpressure may be evaluated as falsely high be-cause of abnormal corneal thickness, at least insome patients.

2. Primary angle-closure glaucomaIn primary angle-closure glaucoma, elevated

intraocular pressure results from closure of theanterior chamber angle. Some researchers feelthat only patients with elevated intraocular pres-sure or changes in the optic nerve can be classi-fied as suffering from primary angle-closure glau-coma. In this disease type, however, as elevatedintraocular pressure or changes in the optic nerveresult from closure of the anterior chamber angle,in the present guidelines, we classify as primaryangle-closure glaucoma all cases with estab-

lished closure of the anterior chamber angle butwithout elevated intraocular pressure or opticnerve changes, including early-stage cases.

In primary angle-closure glaucoma, relativepupillary block and plateau iris mechanism arethe main angle-closure mechanisms. As the pri-mary mechanism of angle-closure is relativepupillary block in the majority of cases, primaryangle-closure glaucoma can ordinarily be de-fined as identical to primary angle-closure glau-coma with relative pupillary block. In this narrowdefinition of primary angle-closure glaucoma,however, the plateau iris mechanism frequentlyplays a role. Primary angle-closure glaucoma duesolely to the plateau iris mechanism is referred toas plateau iris syndrome.

1) Primary angle-closure glaucoma with relativepupillary blockPrimary angle-closure glaucoma with relative

pupillary block is subdivided into the acute typeand the chronic type.

In the acute type, extensive closure of the ante-rior chamber angle causes elevation of intraocu-lar pressure within a short period of time, result-ing in the clinical symptoms typical of so-calledglaucoma attacks. In the chronic type, as angleclosure occurs gradually or intermittently, eleva-tion of intraocular pressure is mild and gradual.Some researchers specify a subacute or intermit-tent category as an intermediate form betweenthe acute and chronic types.

(1) Acute primary angle-closure glaucomaThis disorder is characterized by acutely ele-

vated intraocular pressure, frequently reaching40-80 mm Hg, decreased visual acuity, and weak-ened or absent light reaction. On slit-lamp biomi-croscopy, findings include corneal edema, shal-low anterior chamber, moderate mydriasis, con-junctival hyperemia, and ciliary injection.Gonioscopy shows extensive angle closure.Ophthalmoscopic examination may show signssuch as papilledema, venous dilatation, and dischemorrhage, but the optic disc may also be nor-mal or show glaucomatous cupping. The felloweye shows a narrow anterior chamber angle.Subjective symptoms include decreased visualacuity, blurred vision, iridopsia, ocular pain,

15

headache, nausea, and vomiting. There are alsocases in which subjective symptoms are less pro-nounced and some of these symptoms are ab-sent.

(2) Chronic primary angle-closure glaucomaIn this subtype of primary angle-closure glau-

coma, subjects do not show and have no historyof the signs or symptoms of the acute type. Inaddition to a shallow anterior chamber and nar-row anterior chamber angle, the signs and symp-toms are similar to those seen in primary open-angle glaucoma. Intraocular pressure is not nec-essarily elevated.

2) Plateau iris syndromeThe mechanism in which, as a result of mor-

phological anomalies of the iris root, the anteriorchamber angle closes due to pupillary dilationwithout iris block is referred to as the plateau irismechanism. Cases in which angle closure occurspurely due to the plateau iris mechanism arereferred to as plateau iris syndrome, but suchcases are rare. Nevertheless, in primary angle-closure glaucoma, there are many cases in whichthere is a combination of the plateau iris mecha-nism and the pupillary block mechanism. In thelatter case, following laser iridotomy, despite flat-tening of the iris, the root of the iris takes on aspecific configuration, the plateau iris configura-tion, and partial angle closure is seen as a resultof pupillary dilation. Ultrasound biomicroscopyis useful in making the differential diagnosisbetween plateau iris syndrome and plateau irisconfiguration.

3. Mixed glaucomaCombined cases of primary open-angle glau-

coma and primary angle-closure glaucoma arereferred to as cases of mixed glaucoma.

In making a diagnosis of mixed glaucoma, thepossibility of chronic primary angle-closure glau-coma and primary open-angle glaucoma must beborne in mind in eyes with a narrow angle.

ⅡⅡ. Secondary glaucoma

Secondary glaucoma is glaucoma in whichelevated intraocular pressure is caused by otherocular diseases, systemic diseases, or drug use.Secondary glaucoma can be classified from sev-eral standpoints, including etiology, mechanismof intraocular pressure elevation, and means oftreatment. However, each of these classificationmethods has both advantages and drawbacks.For example, in classification according to etiolo-gy, it is difficult to express the concept that neo-vascular glaucoma begins as open-angle glauco-ma and then progresses while the mechanism ofintraocular pressure elevation changes, becomingangle-closure glaucoma.

In the present guidelines, we classify glauco-ma according to the mechanism of intraocularpressure elevation because it is very useful as anaid in determining the etiology and optimumtreatment method. Caution is required becausethere may be cases in which conditions havingthe same etiology show differing mechanisms ofintraocular pressure elevation, and the mecha-nism of intraocular pressure elevation may changeeven in the same eye. In diagnosing secondaryglaucoma, gonioscopic examination is essentialin order to confirm the mechanism of intraocularpressure elevation.

1. Open angle mechanisms in secondary glauco-ma

1) Characterized primarily by aqueous outflowresistance between the trabecular meshworkand anterior chamberAbnormal aqueous outflow resistance occurs

due to a fibrovascular membrane, the conjuncti-val epithelium, etc.

2) Characterized primarily by aqueous outflowresistance in the trabecular meshworkAbnormal aqueous outflow resistance results

from pseudoexfoliation material, inflammatorymaterial, macrophages, iris pigment, etc.

3) Characterized primarily by aqueous outflowresistance posterior to Schlemm's canalThese are cases resulting from increased epis-

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cleral venous pressure with accompanying eleva-tion of intraocular pressure and increased pres-sure in the superior vena cava.

4) Cases due to aqueous hypersecretion

2. Angle closure mechanisms in secondary glau-coma

1) Cases due to pupillary blockPupillary block is caused by factors such as

lens swelling, lens luxation, goniosynechiae, etc.

2) Cases due to anterior movement of intraocu-lar tissues or mass posterior to the lensCauses include anterior movement of the lens,

ciliary edema, etc.

3) Cases caused due to goniosynechiae withoutpupillary block or anterior movement ofintraocular tissues or mass posterior to thelensThese cases are unrelated to anterior chamber

depth, but are caused by peripheral anteriorsynechiae.

ⅢⅢ. Developmental glaucoma

Glaucoma resulting from malformation of theanterior chamber angle is treated in these guide-lines not as congenital glaucoma but as develop-mental glaucoma. Developmental glaucoma canbe easily understood when classified into earlyonset developmental glaucoma, in which mor-phological anomalies are limited to the anteriorchamber angle, late onset developmental glauco-ma, and developmental glaucoma accompanyingother congenital anomalies. Early onset develop-mental glaucoma is equivalent to the aforemen-tioned primary congenital glaucoma.

1. Early onset developmental glaucomaIn this disease type, congenital anomalies are

limited to the trabecular meshwork. Frequently,however, this is combined with mild hypoplasiaresulting from developmental anomalies of theiris.

2. Late onset developmental glaucomaThis type of glaucoma results from congenital

morphological anomalies of the anterior chamberangle, but as the extent of such morphologicalanomalies is slight, the age of onset is delayeduntil the teens or twenties.

3. Developmental glaucoma with other congeni-tal anomaliesThis category encompasses a wide variety of

conditions, including aniridia, Marfan syndrome,Axenfeld-Rieger syndrome, Peters’ anomaly,Sturge-Weber syndrome, and neurofibromatosis.

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Table 2-1. Classification of glaucoma

ⅠⅠ. Primary glaucoma

1. Primary open-angle glaucoma (broad defi-nition)

A. Primary open-angle glaucomaB. Normal-tension glaucoma, normal-pres-

sure glaucoma

2. Primary angle-closure glaucomaA. Primary angle-closure glaucomaB. Plateau iris syndrome

3. Mixed glaucoma

ⅡⅡ. Secondary glaucoma

1. Secondary open-angle glaucomaA. Secondary open-angle glaucoma charac-

terized primarily by aqueous outflowresistance between the trabecular mesh-work and anterior chamber (pretrabecu-lar form)Examples: Neovascular glaucoma, glau-

coma secondary to hetero-chromic iridocyclitis, glau-coma secondary to epithelialingrowth, etc.

B. Secondary open-angle glaucoma charac-terized primarily by aqueous outflowresistance in the trabecular meshwork(trabecular form)Examples: Steroid glaucoma, exfoliation

glaucoma, glaucoma accom-panying primary amyloidosis,glaucoma secondary to uveitis,lens-induced glaucoma, trau-matic glaucoma, glaucoma sec-ondary to vitreous surgery,ghost cell glaucoma, glaucomasecondary to cataract surgery,glaucoma secondary to corne-al transplantation, glaucomasecondary to foreign bodies inthe eye, glaucoma secondaryto intraocular tumors, Schwartzsyndrome, pigmentary glauco-

ma, pigment dispersion syn-drome, etc.

C. Secondary open-angle glaucoma charac-terized primarily by aqueous outflowresistance posterior to Schlemm's canal(posttrabecular form)Examples:Glaucoma accompanying ex-

ophthalmos, glaucoma accom-panying increased pressure inthe superior vena cava, etc.

D. Secondary open-angle glaucoma due toaqueous hypersecretion (hypersecretoryform)

2. Secondary angle-closure glaucomaA. Secondary angle-closure glaucoma with

pupillary block (posterior form withpupillary block)Examples: Glaucoma secondary to lens

bulging, glaucoma accompa-nying microphthalmia, glauco-ma secondary to posteriorsynechiae, glaucoma sec-ondary to lens subluxation,glaucoma secondary to epithe-lial ingrowth, etc.

B. Secondary angle-closure glaucoma dueto anterior movement of intraocular tis-sues posterior to the lens (posterior formwithout pupillary block)Examples: Malignant glaucoma, glauco-

ma secondary to retinal photo-coagulation, glaucoma sec-ondary to scleral bucklingsurgery, glaucoma secondaryto intraocular tumors, glauco-ma secondary to posterior scle-ritis/VKH disease, glaucomasecondary to central retinalvein occlusion, glaucoma sec-ondary to intraocular fillingmaterials, glaucoma secondaryto massive vitreous hemor-rhage, etc.

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thogranuloma, etc.C. Secondary angle-closure glaucoma dueto goniosynechiae without pupillary block or movement of the lens-iris dia-phragm (anterior form)Examples: Glaucoma secondary to flat or

shallow anterior chamber,glaucoma secondary to uveitis,glaucoma secondary to cor-neal transplantation, neovascu-lar glaucoma, ICE syndrome,glaucoma accompanying irido-dialysis, etc.

ⅢⅢ. Developmental glaucoma

1. Early onset developmental glaucoma2. Late onset developmental glaucoma3. Developmental glaucoma with other con-

genital anomaliesA. AniridiaB. Sturge-Weber syndromeC. Axenfeld-Rieger syndromeD. Peters’ anomalyE. Marfan syndromeF. Weill-Marchesani syndromeG. HomocystinuriaH. NeurofibromatosisI . Rubella syndromeJ . Pierre Robin syndromeK. Chromosomal aberrationsL. Persistent hyperplastic primary vitreousM. Congenital microcorneaN. Lowe syndromeO. Rubinstein-Taybi syndromeP. Hallermann-Streiff syndromeQ. Congenital ectropion uveaeR. Others

ⅣⅣ. Secondary glaucomas in childhood

Glaucoma secondary to retinopathy of pre-maturity, glaucoma secondary to retinoblas-toma, glaucoma secondary to juvenile xan-

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ⅠⅠ. History taking

The patient’s history is of fundamental impor-tance in the diagnosis and treatment of glauco-ma. In order to take into account the possibilityof secondary glaucoma, in addition to taking thehistory of ocular trauma, inflammation, surgery,infection, etc., it is important to determine thepatient’s history of systemic disease and medica-tion. It is also important to interview the patientconcerning subjective symptoms, with symptomssuch as blurred vision, iridopsia, ocular pain,headache, and hyperemia indicating a possiblehistory of acute glaucoma attacks. Moreover, it isimportant to ask about the patient's family histo-ry, and patients with a family history of glaucomain particular should be asked about visual func-tion damage in blood relatives. If informationfrom other physicians is available concerningdiagnosis and treatment with respect to theintraocular pressure, ocular fundus, or visualfield, such information should be used wheneverpossible.

1. Ocular painIn cases of markedly elevated intraocular pres-

sure due to acute glaucoma attacks, etc., thepatient will frequently experience sudden andsevere ocular pain. In general, the patient willexperience severe ocular pain when intraocularpressure rises markedly from a normal value to ahigh value. Ocular pain may also be caused byfactors such as irritation to the ciliary body result-ing from corneal epithelial damage or uveitis.

2. HeadacheIn acute glaucoma attacks, accompanying sud-

den elevation of intraocular pressure, the patientmay experience headache accompanied by nau-sea and vomiting, as well as symptoms such asreduced visual acuity, photophobia, and iridop-sia.

3. Blurred visionThe patient may experience blurred vision in

the event of secondary glaucoma resulting fromcorneal edema and uveitis accompanying amarked increase in intraocular pressure.

4. Visual field defectsIn the initial stage of glaucoma, even in cases

where abnormalities have been detected by visu-al field examination, the patient frequently hasno subjective symptoms of such abnormalities. Ifa patient complains of visual field abnormalities,this frequently means that optic nerve damage orvisual field damage has already progressed to aconsiderable degree.

5. CongestionCongestion is experienced not only in acute

glaucoma attacks, but also in various forms ofsecondary glaucoma such as glaucoma second-ary to uveitis, neovascular glaucoma, and pha-colytic glaucoma.

ⅡⅡ. Slit-lamp microscopy

Slit-lamp microscopy is of fundamental impor-tance in the diagnosis and treatment of glauco-ma. In this examination, the conjunctiva, anteriorchamber, iris, lens, etc., are observed, butgoniolenses or fundus lenses may also be used incombination in order to observe the anteriorchamber angle or ocular fundus.

1. CorneaCorneal edema is observed in cases of marked-

ly elevated intraocular pressure, such as acuteglaucoma attacks, but it is also seen in secondaryglaucoma accompanying corneal endothelialdysfunction, such as iridocorneal endothelial(ICE) syndrome, even though intraocular pressureis within the normal range. Following laser treat-ment (particularly laser iridotomy) or surgery, thecomplication of bullous keratopathy may occur,and this possibility should be borne in mind. Inearly onset developmental glaucoma, enlarge-ment of the eye ball (buphthalmos) accompany-ing elevated intraocular pressure may causebreaks in the Descemet’s membrane referred toas Haab's striae, which appear as meanderingraised lines on the corneal endothelium. In addi-tion, pigmentation on the posterior corneal sur-face and spindle-like pigmentation (Krukenbergspindle) may be observed in glaucoma resultingfrom uveitis and in pigmentary glaucoma or pig-

Section 3Examination of Glaucoma

20

ment dispersion syndrome, respectively.

2. Anterior chamberIn diagnosis of primary angle-closure glauco-

ma, screening for shallow anterior chamber byslit-lamp microscopy is a simple and useful pro-cedure. Japanese patients are known to show ahigher frequency of shallow anterior chamberthan Caucasians. In the van Herick method, thewidth of the anterior chamber angle is estimatedby comparing corneal thickness and peripheralanterior chamber depth.1) In plateau iris syn-drome, despite the fact that anterior chamberdepth is largely normal, as narrow angle andangle closure are observed, assessment of anteri-or chamber depth by slit-lamp microscopy is notsufficient to diagnose this condition, andgonioscopy is therefore necessary.

1) van Herick method1)

Taking the angle between the slit light beam ofthe slit-lamp microscope and the observation sys-tem as 60 degrees, the slit light beam is posi-tioned vertically with respect to the corneal lim-bus, and peripheral anterior chamber depth andcorneal thickness are compared in order to esti-mate the width of the anterior chamber angle.

Grade 1: Anterior chamber depth is less than1/4 of corneal thickness

Grade 2: Anterior chamber depth is 1/4 ofcorneal thickness

Grade 3: Anterior chamber depth is 1/4-1/2 ofcorneal thickness

Grade 4: Anterior chamber depth is ≥ cornealthickness

3. IrisUsually, the iris is flat or bulges slightly in an

anterior direction. In cases where the iris bulgesmarkedly in an anterior direction, the presence ofpupillary block is suspected. Abnormal findingsin the iris include anterior synechiae, posteriorsynechiae, neovascularization, atrophy, and nod-ules.

4. LensAbnormal lens findings associated with glau-

coma include abnormal size or shape of the lens

(lens swelling, spherophakia, etc.), abnormal lensposition (lens luxation, lens subluxation, etc.).Abnormalities of the ciliary zonule (congenitalanomalies, trauma, exfoliation glaucoma, etc.)may play a role in abnormal positioning of thelens. Abnormal lens position and increased lensthickness due to the progression of cataracts mayresult in angle closure. In the case of mature orhypermature cataracts, phacolytic glaucoma mayoccur with outflow of lens material. Observationof the anterior surface of the lens is also impor-tant. Following laser iridotomy and peripheral iri-dectomy, posterior synechiae may occur. In exfo-liation glaucoma, characteristic white depositsare observed on the anterior surface of the lensand the pupillary margin.

ⅢⅢ. Tonometry

1. Intraocular pressurePrevious studies in large numbers of subjects

have shown that the distribution of intraocularpressure is skewed towards higher values anddoes not show a normal distribution. In the nor-mal population, the average intraocular pressure(± standard deviation) is 15.5 (± 2.6) mm Hg andthe statistically determined upper limit value ofintraocular pressure is approximately 21 mmHg.However, these values are based on the results ofstudies conducted on Western subjects. Factorsassociated with intraocular pressures include age,gender, refraction, race, posture, exercise, andpalpebral and ocular movement. Moreover, avariety of drugs may affect intraocular pressure.There are diurnal fluctuations in intraocular pres-sure, with this pressure frequently being higher inthe morning, but the pattern varies among indi-viduals. Furthermore, intraocular pressure alsoshows seasonal variations, with pressure beinghigher in the winter and lower in the summer.

2. TonometersAs the Goldmann applanation tonometer is the

most clinically accurate device, this tonometer isused on a standard basis in the diagnosis andtreatment of glaucoma. The Goldmann applana-tion tonometer, unlike indentation tonometerssuch as the Schiötz tonometer, has the advantage

21

that measurement values are not affected by scle-ral rigidity. The Tono-Pen and the Perkins appla-nation tonometer are portable devices in whichintraocular pressure measurements can be con-ducted with the patient seated or supine. Non-contact tonometers involve simple measurementprocedures and should ordinarily be used onlyfor screening purposes. Intraocular pressure mea-surements are lower the thinner the cornea is,and this factor should be borne in mind in inter-preting intraocular pressure measurement valuestaken following laser surgery, such as photore-fractive keratectomy (PRK) and laser in situ ker-atomileusis (LASIK).

ⅣⅣ. Gonioscopy

1. Anterior chamber angleGonioscopy is indispensable in the diagnosis

and treatment of glaucoma. In eyes with angle-closure glaucoma or a narrow angle in particular,moderate pupillary dilation may induce an acuteglaucoma attack, so this should be borne in mindwhen using drugs that affect pupil diameter. Ingonioscopy, it is important to properly recognizethe various structures composing the anteriorchamber angle, such as Schwalbe's line, the tra-becular meshwork, the scleral spur, and the cil-iary body band. Angle neovascularization mayoccur in ischemic conditions such as proliferativediabetic retinopathy, retinal vein occlusion, andinternal carotid arterial occlusion. From a physio-logical standpoint, blood vessels may be ob-served in the angle, with these blood vessels fol-lowing a concentrical or radiating regular course.Pathological neovascularization involves anirregular curved course, with multiple bifurca-tions in many cases, and may also be accompa-nied by peripheral anterior synechiae. In the caseof active uveitis, nodules may also be observedin the form of inflammatory exudates in theangle, and this may also be accompanied byperipheral anterior synechiae.

1) Schwalbe's lineSchwalbe's line is located in an area equiva-

lent to the ending portion of the Descemet’smembrane and extends into the anterior

chamber.

2) Trabecular meshworkThe trabecular meshwork and Schlemm's

canal are located between Schwalbe's line andthe scleral spur. From the center of the trabecularmeshwork, the scleral spur side is equivalent tothe functional trabecular meshwork and isobserved as a pigmented band. In diseases suchas exfoliation glaucoma, pigmentary glaucoma,and pigment dispersion syndrome, a pronouncedpigmentation is frequently observed on the tra-becular meshwork. In exfoliation glaucoma inparticular, marked wavy pigmentations may beseen anterior to Schwalbe's line, and these arereferred to as Sampaolesi line.

3) Scleral spurThe scleral spur is observed as a white line

between the ciliary body band and the trabecularmeshwork. Iris processes are frequently seen onthe surface thereof. Gonioscopy of the eye withdevelopmental glaucoma reveals an anteriorinsertion of the iris directly into the trabecularmeshwork.

4) Ciliary body bandThe ciliary body band is equivalent to the ante-

rior surface of the ciliary body, and it is observedas a grayish-black band.

2. MethodsGonioscopy may be conducted either directly

or indirectly, and goniolenses can be classified aseither direct or indirect. An example of a directgoniolens is the Koeppe lens, and examples ofindirect goniolenses include the Goldmanngoniolens and the Zeiss 4-mirror goniolens.

3. Indentation gonioscopyIndentation gonioscopy is useful to differenti-

ate a simple narrow angle or reversible apposi-tional angle closure from irreversible synechialangle closure (peripheral anterior synechiae). In agoniolens used for indentation gonioscopy, thearea in contact with the cornea is small and flat.The anterior chamber angle is observed by lightlypressing against the center of the cornea andpressing down on the surface of the lens and iris.

22

In cases with a simple narrow angle or apposi-tional angle closure, this procedure widens theanterior chamber angle. However, in cases withsynechial angle closure, the angle is not widenedat the closure site. Indentation gonioscopy is use-ful in accurately determining the pathology ofangle-closure glaucoma.

4. Gonioscopic classifications1) Shaffer classification2)

Grade 0: Angle closure (angle, 0°), closurepresent

Grade 1: Extremely narrow angle (angle, 10°),closure probable

Grade 2: Moderately narrow angle (angle,20°), closure possible

Grade 3-4: Wide open angle (angle, 20-45°),closure impossible

2) Scheie classification3)

Grade 0 : All structures visibleGradeⅠ: Hard to see over iris root into recessGradeⅡ: Ciliary body band obscuredGradeⅢ: Posterior trabeculum obscuredGradeⅣ: Only Schwalbe’s line visible

5. Adjunctive diagnostic methodUltrasound biomicroscopy is a diagnostic

method that allows sectional observation of themicrostructure of the anterior ocular tissue,including the anterior chamber angle, and thistechnique has been reported to be useful in thediagnosis of glaucoma.

ⅤⅤ. Ophthalmoscopy

1. Optic disc and retinal nerve fiber layerIn diagnosing glaucoma, the detection of mor-

phological changes in the optic disc or retinalnerve fiber layer is extremely important.Although pathologic findings of the optic disc orretinal nerve fiber layer are related to the stage ofglaucoma, they are frequently detected prior todetection of visual field abnormalities. In normal-tension glaucoma in particular, the disease is fre-quently diagnosed when optic nerve damage isdetected. Stereoscopic evaluation of the opticdisc appearance is important: slit-lamp micros-

copy combined with a variety of auxiliary funduslenses is convenient and useful.

1) Cup-to-disc (C/D) ratioThe C/D ratio is 0.7 or greater in only 1-5% of

the population. In glaucomatous eyes, with pro-gressive optic nerve damage, the size of the opticdisc cup increases, and this increase occurs pre-dominantly in the vertical direction as comparedwith the horizontal direction. In normal subjects,the C/D ratio is frequently equivalent in botheyes, with asymmetry of the C/D ratio being lessthan 0.2 and greater than 0.2 in only 1% of thepopulation. Asymmetry between the C/D ratios inboth eyes of 0.2 or more should be regarded withsuspicion until glaucoma has been excluded.Since the C/D ratio is affected by the optic discsize and refraction of the eye, assessment thereofmust be carried out with caution. Additionalglaucomatous changes in the optic disc includesaucerization (shallow saucer-shaped expansionof the optic disc cup), notching (local thinning ofthe neural rim) and the laminar dot sign (expo-sure of the lamina cribrosa).

2) Location of retinal vessels on the optic discThe location of retinal vessels in relation to the

optic disc cup may have some diagnostic value.Nasalization of the vessels is thought to be a signof glaucomatous cupping.

3) Optic disc hemorrhageThe prevalence of optic disc hemorrhages is 0-

0.21% in normal subjects and 2.2- 4.1% in glau-coma patients. The prevalence of optic disc hem-orrhage is high especially in normal-tension glau-coma (up to approximately 40%). Optic dischemorrhages are usually found in the inferotem-poral sector of the optic disc, and it is frequentlyobserved prior to changes in the optic disc orretinal nerve fiber layer or progression of visualfield loss. Since optic disc hemorrhage is unusualin normal subjects, it is a significant finding, par-ticularly if it occurs repeatedly.

4) Peripapillary chorioretinal atrophyThe frequency and extent of peripapillary

chorioretinal atrophy are greater in glaucomatouseyes than in normal eyes. Ophthalmoscopically,

23

the more peripheral zone alpha is characterizedby irregular hypo- and hyper-pigmentation of theretinal pigment epithelium. Zone beta is locatedcloser to the optic disc border and is character-ized by visible sclera and large choroidal vessels.Zone beta has been repoted to be related to theseverity and progression of glaucoma.

5) Retinal nerve fiber layer defectsIn addition to changes in the optic disc, the

atrophy of ganglion cell axons can be observedin the peripapillary retinal nerve fiber layer inglaucomatous eyes. Glaucoma may producelocalized or diffuse defects of the retinal nervefiber layer, or a combination of both. Early local-ized defects are characterized by the presence ofslit or wedge-shaped defects in the nerve fiberlayer. Retinal nerve fiber layer abnormalitiesappear as darker areas, in which visibility of thenormal striation pattern is reduced or lost. In gen-eral, unlike diffuse defects, localized defects areeasier to detect because they are well outlined bysurrounding healthy nerve bundles. Althoughretinal nerve fiber layer defects are also seen inother neurological disorders as well as in normalindividuals, examination of the retinal nerve fiberlayer is useful in detecting early glaucomatousdamage.

2. Fundus photographyFundus photography is essential for the diag-

nosis and follow-up of glaucoma. It allows objec-tive recording of the optic disc and retinal nervefiber layer findings. Stereoscopic photography ispreferred. Simultaneous stereoscopic photogra-phy is particularly useful for three-dimensionalobservation of the optic disc.

3. Adjunctive diagnostic devicesDiagnostic devices such as the Heidelberg

Retina Tomograph (HRT), GDx Nerve FiberAnalyzer (GDx), Scanning Laser Ophthalmoscope(SLO), and Optical Coherence Tomograph (OCT)allow quantitative assessment of changes in theoptic disc or retinal nerve fibers, and have there-fore been reported to be useful in the diagnosis ofglaucoma.

ⅥⅥ. Perimetry

1. Visual fieldThe normal visual field has an elongated ellip-

tical shape, and with respect to the fixation point,it measures 60 degrees superiorly and nasally,70-75 degrees inferiorly, and 100-110 degreestemporally. The two means for measuring thevisual field are kinetic and static perimetry.Perimeters express the brightness of the target inunits of apostilbs (asb). 1 asb is equivalent to0.3183 candela/m2 (0.1 millilambert).

2. Goldmann perimeterThe Goldmann perimeter is in standard inter-

national use. Its background luminance is set at31.5 asb, and the distance between the target andthe test eye is 30 cm. Target sizes are 0 (1/16mm2), Ⅰ(1/4 mm2), Ⅱ(1 mm2), Ⅲ(4 mm2), Ⅳ(16mm2), and Ⅴ (64 mm2), and target brightnessranges from 1a (12.5 asb) to 4e (1,000 asb).Measurements are ordinarily conducted using thesettings of Ⅴ/4e,Ⅰ/4e,Ⅰ/3e,Ⅰ/2e, andⅠ/1e. Inkinetic perimetry using this perimeter, the techni-cian moves the target to plot several isopters.Experienced technicians can obtain quite accu-rate results using this method.

3. Automated static perimetryIn general, automated static perimetry is more

sensitive in detecting visual field abnormalities inthe early stages of glaucoma than kinetic perime-try using the Goldmann perimeter. The mostcommonly-used perimeters for this purpose arethe Humphrey and Octopus perimeters. In staticperimetry, sensitivity is expressed in decibels (1decibel (dB) = 0.1 log Unit). Although 0 decibelsis the brightest optical stimulus, this is not uni-form among different types of devices. For exam-ple, 0 decibels on the Humphrey perimeter indi-cates a different luminance from 0 decibels onthe Octopus perimeter, a discrepancy that mustbe borne in mind. Measurement results areaffected by factors such as blepharoptosis, refrac-tive error, media opacities, pupil size, and aging.Fixation loss rate, false-positive and false-nega-tive rates, and short-term fluctuation are usefulindices in evaluating the reliability of measure-ment results. The technician's degree of experi-

24

ence is also important, with first-time test resultsgenerally being less reliable than subsequent testresults. Test results are expressed using thresholdvalues, grayscale (graphic grayscale display ofthreshold values), total deviation (differencebetween the patient’s results and age-matchednormals), and pattern deviation (similar to thetotal deviation except that it is adjusted for anygeneralized depression in the overall field whichmight be caused by other factors such as lensopacities or miosis).

1) Humphrey perimeterThe central 24-2 or central 30-2 program is

ordinarily used. The background luminance is31.5 asb, stimulus time is 0.2 seconds, and stim-ulus intensity is 0-50 dB, with a maximum lumi-nance of 10,000 asb.(1) Reliability indices

i. Fixation loss rateCases in which there is a response with a tar-

get displayed in the blind spot are evaluated asfixation loss. If the fixation loss rate exceeds20%, reliability is assessed as low and XX is dis-played.

ii. False-positive rateCases in which there is a response even

though a target is not displayed are assessed asfalse-positive. If the false-positive rate exceeds33%, reliability is assessed as low and XX is dis-played.

iii. False-negative rateCases in which there is no response at sites

with a confirmed response even though a high-luminance target is displayed are assessed asfalse-negative. If the false-negative rate exceeds33%, reliability is assessed as low and XX is dis-played.

2) Octopus perimeterThe Octopus 1-2-3, 300 Series is an automatic

perimeter allowing visual field measurementwithin a central 30 degree-field, and it features acompact design using the direct projection sys-tem. The Octopus 101 is an automated projec-tion perimeter that allows static and kineticperimetry within the entire field. The standardmeasurement conditions are background illumi-nation of 31.4 asb (1-2-3, 300 Series, 101: kinetic

perimetry), 4 asb (101: static perimetry), stimulustime of 0.1 seconds, stimulus intensity of 0-40 dB(1-2-3, 300 Series), 0-47 dB (101), maximum illu-mination of 4,000 asb (1-2-3), 4,800 asb (300Series), and 1,000 asb (101). The programs usedfor glaucoma diagnosis are the G1X (1-2-3, 300Series) and the G2 (101).

3) New techniques for visual field measurementRecent newly-developed techniques for visual

field measurement include the Octopus dynamicstrategy, the TOP strategy, and the HumphreySITA program, which permit time-efficient visualfield measurements. Moreover, methods reportedto be effective in the diagnosis of glaucoma at theearliest stage include blue on yellow perimetry(SWAP), frequency doubling technology, andflicker perimetry.

4. Classifications of glaucomatous visual fielddefects

1) Kosaki classification (based on kineticGoldmann perimetry)4, 5)

StageⅠ: Earliest stage without any fieldchanges by kinetic Goldmann perimetry.a: Normal fieldb: Pathologic field detected only when a

more precise method is used.StageⅡ: Early stage with abnormal field for

isoptersⅠ-4,Ⅰ-3,Ⅰ-2, andⅠ-1, but withoutany abnormalities for an isopter Ⅴ-4.a: Normal for an isopterⅠ-4, but abnormal

for isoptersⅠ-3,Ⅰ-2, andⅠ-1.b: Abnormal for allⅠisopters.

Stage Ⅲ: Middle stage, with abnormal field foran isopter Ⅴ-4, but with field loss notexceeding 1/2 of the normal field for Ⅴ-4target (Ⅴ-4 field).a: Field loss (contraction) not exceeding

1/4 of Ⅴ-4 field.b: Field loss more than 1/4 but less than

1/2 of Ⅴ-4 field.Stage Ⅳ: Late stages, with field loss exceeding

1/2 of Ⅴ-4 field, but with preserved macu-lar field.

Stage Ⅴ: Very late stage.a: Macular field only.b: Without macular field, but with pre-

served field outside the macular field.

25

Stage Ⅵ: End stage with loss of Ⅴ-4 field.

2) Aulhorn classification (modified by Greve etal.)6)

Stage 0-1: Relative small glaucomatous visualfield defect (GVFD) with an intensity of 0.6log unit up to 1.0 log unit. With specialexamination methods and appropriate sta-tistical procedures, defects with an intensityof less than 0.6 log unit can be included inthis group.

Stage 1: Small GVFD with an intensity of morethan 1.0 log unit up to maximum lumi-nance. The size of stages 0-1 and 1 defectsshould not exceed the size of the blind spot.

Stage 2: Incomplete nerve fiber bundle defect(NFBD = arcuate defect) for maximumluminance.

Stage 3: Complete (from blind spot to nasalhorizontal meridian) NFBD for maximumluminance or incomplete (stage 2) NFBDwith nasal breakthrough.

Stage 4: Complete NFBD for maximum lumi-nance with nasal breakthrough involvingless than one quadrant.

Stage 5: Complete NFBD for maximum lumi-nance with nasal breakthrough involvingmore than one quadrant. Two stage 5 de-fects in the upper and lower half of the visu-al field form a central and temporal island.

Stage 6: Temporal island.

3) Criteria for glaucomatous visual filed defects(Humphrey perimetry)7)

Any of the following:1. The pattern deviation probability plot shows

a cluster of three or more nonedge pointsthat have sensitivities occurring in fewerthan 5% of the normal population (P< 5%),and one of the points has a sensitivity thatoccurs in fewer than 1% of the population(P< 1%);

2. The pattern standard deviation (or correctedpattern standard deviation) has a value thatoccurs in less than 5% of normal reliablefields (P< 5%); or

3. The glaucoma hemifield test indicates thatthe field is abnormal.

4) Classification of glaucomatous visual fielddefects (Humphrey perimetry)7)

An early defect meets all the following re-quirements:

1. The mean deviation is better than -6 dB;2. Fewer than 18 of the 76 points in a 30-2

pattern (25%) are defective in the total devi-ation probability plot at the 5% level;

3. Fewer than 10 points are defective at the1% level; and

4. No point in the central 5 degrees has a sen-sitivity less than 15 dB.

A moderate defect exceeds one or more of thecriteria required to keep it in the early defect cat-egory but does not meet the criterion to besevere.

A severe defect has any of the following:1. The mean deviation is worse than -12 dB;2. More than 37 (50%) of the points depressed

at the 5% level;3. More than 20 points depressed at the 1%

level;4. A point in the central 5 degrees with 0-dB

sensitivity; or5. Points closer than 5 degrees of fixation

under 15-dB sensitivity in both the upperand lower hemifields.

References

1) van Herick W, Shaffer RN, Schwarts A: Estimation ofwidth of angle of anterior chamber. Incidence andsignificance of the narrow angle. Am J Ophthalmol68: 626-629, 1969.

2) Hoskins HD Jr, Kass MA: Becker-Schaffer’s Diagnosisand Therapy of the Glaucomas. 6th edition, 106-116,Mosby, St Louis, 1989.

3) Scheie HG: Width and pigmentation of the angle ofthe anterior chamber. A system of grading bygonioscopy. Arch Ophthalmol 58: 510-512, 1957.

4) Kosaki H, Inoue Y: A new classification of stages ofchronic glaucomas. Nippon Ganka Gakkai Zasshi 76:1258-1267, 1972.

5) Kosaki H, Nakatani H, Tsukamoto H, Shimizu Y,Kinoshita S: Pattern of progression of visual fielddefects in glaucoma. Jpn J Clin Ophthalmol 32: 39-49, 1978.

6) Greve EL, Langerhorst CT, van den Berg TT-JP:Perimetry and other visual function tests in glaucoma.In: Cairns JE (ed): Glaucoma. Vol 1, 37-77, Grune &Stratton, London, 1986.

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7) Anderson DR, Patella VM: Automated StaticPerimetry. 2nd edition, 121-190, Mosby, St Louis,1999.

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ⅠⅠ. Principles of glaucoma therapy

1. The goal of therapy is to preserve the patient'svisual functionThe goal of glaucoma therapy at the present

time is to maintain the patient's visual function.Visual function damage severely impairs patients'quality of life (QOL). However, in providing treat-ment, one must not only bear in mind possibleadverse effects and complications of treatment,but also the social and economic implicationsimposed by hospital visits and/or hospitalizationand the damage to QOL caused by constantworry about losing eye sight.

2. The most reliable therapy is reduction ofintraocular pressureAt present, based on the evidence, the only

reliable therapy for glaucoma is to lower intraoc-ular pressure. Other therapeutic concepts are cur-rently being attempted that might prove effectivein the future. Enhancement of the optic nervehead blood flow and neuroprotective therapy ofganglion cells have attracted attention as newtherapeutic methods.

3. Causal therapy must be provided for all treat-able factors causing elevation of intraocularpressureIf it is possible to treat a causal factor in eleva-

tion of intraocular pressure, this factor must betreated in conjunction with therapy to lowerintraocular pressure. Types of causal therapyinclude peripheral iridotomy in types of glauco-ma in which pupillary block causes elevation ofintraocular pressure, such as primary angle-clo-sure glaucoma, antiinflammatory treatment inglaucoma with accompanying uveitis, retinalphotocoagulation in neovascular glaucoma, anddiscontinuation of steroid administration insteroid glaucoma.

4. Early detection is vitalAt present, once visual function has been lost

in glaucoma, there is no way to regain it. More-over, in the advanced stages of glaucoma, thedisease may continue to progress even whentreatment is provided. Accordingly, early detec-tion and treatment of glaucoma are of primaryimportance.

5. Achieving the maximum effect with the mini-mum required drugsThere are many antiglaucoma drugs available,

but the principle of drug treatment of the diseaselies in obtaining the maximum effect with theminimum required drugs and the minimum ad-verse effects. For this reason, the mechanism ofaction, adverse effects, and contraindications ofthe drugs used must be understood. In addition,the choice of therapy must take into account fac-tors such as QOL, treatment costs, and compli-ance.

6. Selecting among drugs, laser treatment, andsurgeryAs the therapeutic options in glaucoma include

drug treatment, laser treatment, and surgicaltreatment, an appropriate therapeutic modalitymust be selected based on the individual patientand the disease stage and type. Concomitant useof multiple drugs may increase adverse effectsand reduce compliance. Generally speaking,when three or more drugs are required to controlintraocular pressure, other therapeutic optionssuch as laser treatment or invasive surgery shouldbe considered.

ⅡⅡ. Current status of treatment

As glaucoma follows a chronic course in themajority of cases, the treatments discussed hereare used in primary open-angle glaucoma, nor-mal-tension glaucoma, primary angle-closureglaucoma following iridotomy, chronic sec-ondary glaucoma, etc.

1. Baseline data determinationPatient status prior to treatment is important as

a baseline. Unless treatment must be begun onan emergency basis, such as in late-stage cases, itis preferable to determine baseline data such asintraocular pressure, optic disc findings, andvisual field findings before beginning treatment.

2. Target intraocular pressureAlthough the final objective of glaucoma treat-

ment is the maintenance of visual function, inview of the fact that optic nerve damage is irre-

Section 4 Principles of Treatment for Glaucoma

28

versible and assessment of therapeutic effecttakes long periods due to the chronic course ofthe illness, it is rational to treat glaucoma by set-ting an intraocular pressure at which it is be-lieved that the progression of optic nerve damagecan be prevented (target intraocular pressure) (seeflow charts Ⅴ-Ⅶ).

1) Setting of target intraocular pressureAlthough it is difficult to accurately determine

in advance the intraocular pressure that can pre-vent further optic nerve damage, this target pres-sure can be set for each individual case takinginto account the factors listed in Table 4-1 (seeflow chart Ⅵ).

Table 4-1. Factors to be considered in settingtarget intraocular pressure

─────────────────────• Baseline intraocular pressure level

before treatment• Stage of glaucoma• Age/life expectancy of patient• Status of fellow eye• Family history• Other risk factors

─────────────────────As an example of target intraocular pressure

values, it has been proposed to set this pressureaccording to glaucoma stage at 19 mmHg orbelow for the early stage, 16 mmHg or below forthe moderate stage, and 14 mmHg or below forthe Iater stage1). In normal-tension glaucoma,however, it has been found that progression ofvisual field damage is significantly decreased bylowering intraocular pressure 30% from the ini-tial level at which disease progression is con-firmed2) 3), and the approach has been consideredof setting the target at 30% reduction of intraocu-lar pressure from the baseline level.

2) Re-evaluation of target intraocular pressureOne limitation on the method of treatment

according to a target intraocular pressure is thefact that the validity of the initially set value canonly be assessed after a certain period of time. Inother words, the target intraocular pressure canonly be confirmed to be appropriate when theprogression of optic nerve damage is halted. The

target intraocular pressure is not an absolutevalue; just as there are cases that progress evenwhen the target intraocular pressure has beenachieved, there are also cases that show no pro-gression even though this target has not beenachieved. Accordingly, the target intraocularpressure must periodically be reevaluated andrevised. For example, in cases where progressionof visual field damage is observed, the targetintraocular pressure must be revised downward.However, in reevaluating this target intraocularpressure, factors such as unfavorable complianceand diurnal fluctuations in pressure during thetreatment period must be excluded. Moreover, iftreatment is found to cause adverse effects orinfluence QOL, one must evaluate whether it isnecessary to maintain the target intraocular pres-sure. It is important to remember that the targetintraocular pressure is merely a therapeuticmeans rather than a therapeutic objective, and itwould be a mistake to overemphasize this targetpressure.

3. Glaucoma and QOLQOL is one of the most important factors for

the patient. Damage to visual function due toglaucoma has an enormous effect on QOL, butthere is the possibility that being diagnosed ashaving a chronic and potentially blinding dis-ease, even when properly diagnosed and ex-plained, may cause anxiety and fear in thepatient and his or her family. Moreover, QOLmay also be adversely affected by adverse effectsor economic and time burdens imposed by treat-ment.

In order to preserve the patient's QOL, wemust consider not only treatment of the disease,but the effect that diagnosis and treatment haveon the individual. The patient should be ques-tioned about his or her awareness of the currentsituation and course and what difficulties he orshe is experiencing in everyday life. If treatmentis impairing the patient's QOL, the physicianshould discuss the possibility of discontinuingtreatment with the patient.

4. Compliance with glaucoma drug treatmentGlaucoma is a progressive disease that follows

29

an extremely chronic course, requiring long-termadministration of eye drops and periodic obser-vation of the patient's course, and as there are nosymptoms in many cases, it is essential to securethe patient's cooperation in order to achieve ther-apeutic success.

Compliance in glaucoma drug treatment hasbeen reported to be far worse than physiciansbelieve. Poor compliance (Table 4-2) is an impor-tant factor in the progression of glaucomatousvisual field damage, and in selecting drugs forglaucoma treatment, compliance is therefore avital consideration.

Table 4-2. Poor compliance─────────────────────

• Forgetting to instill eye drops• Excessive use of eye drops (over-

dosage may cause systemic adverseeffects)

• Ineffective technique of self-adminis-tration

• Self-administration of non-prescribeddrug

• Improper timing of eye drops (fre-quently a problem when multipledrugs are prescribed or immediatelyafter the prescription is changed)

─────────────────────Moreover, the following are vital in improving

compliance: (1) providing thorough explanationsof the disease, treatment, and adverse effects; (2)keeping treatment to a minimum; (3) tailoringtreatment to the patient's lifestyle; and (4) provid-ing proper administration guidance.

ⅢⅢ. Glaucoma treatment agents

1. Classification of glaucoma treatment agents1) Adrenergic agonists

(1) Nonselective(2)α2-selective

2) Adrenergic antagonists(1)β-blockersi. Nonselectiveii.β1-selective

(2)αβ-blockers(3)α1-blockers

3) Parasympathomimetics

4) Prostaglandin analogues

5) Carbonic anhydrase inhibitors(1) Systemic(2) Topical

6) Hyperosmotics

2. Selection of drugsIn open-angle glaucomas such as primary

open-angle glaucoma and normal-tension glau-coma, β-blockers have an outstanding effect oflowering intraocular pressure and are favorablytolerated, and they have therefore been in usefor many years as the drug of first choice. Inrecent years, moreover, because of their power-ful intraocular pressure-lowering effect, pros-taglandin analogues have also been used as firstchoice drugs. However, in patients in whom theuse ofβ-blockers and prostaglandin analogues isunsuitable because of adverse effects, eye droppreparations such as carbonic anhydraseinhibitors,α1-blockers, nonselective adrenergicagonists, and parasympathomimetics have beenused as the drugs of choice.

3. Treatment trialsThere are individual differences in drug effect,

and intraocular pressure also varies both day-to-day and diurnally. Topical treatment should bestarted in one eye if possible, determining theintraocular ocular pressure lowering effect andadverse effects (one-eye trial), and then after theeffect has been confirmed, we should beginadministration in both eyes. In evaluatingβ-blockers, however, it should be borne in mindthat these drugs also exert a slight intraocularpressure-lowering effect in the untreated felloweye.

4. Guidance in administrationIn order to increase efficacy by improving

intraocular distribution, while minimizing ad-verse effects by reducing systemic distribution of

30

eye drops, and also in order to improve compli-ance, it is important to guide patients in the prop-er administration method as follows.

• Wash hands prior to administration.• Be careful not to allow the tip of the

eye drop bottle touch the eyelashes.• Administration should be conducted

one drop at a time.• After administration, gently close the

eye and compress the lacrimal sac.• Wipe away any excess solution from

eye drops that have overflowedaround the eye and wash off any eyedrops adhering to the hands.

• When multiple eye drop solutions areused, the administration intervalshould be 5 minutes or longer.

5. Combined treatmentWhen monotherapy with glaucoma treatment

agents does not produce a sufficient effect, theseagents may be combined with other drugs.Although combinations ofβ-adrenergic blockersand sympathomimetics or combinations ofprostaglandin analogues, which increase theuveoscleral outflow, and pilocarpine, whichdecreases uveoscleral outflow, appear to beunsuitable either from a pharmacological stand-point or from the mechanism of lowering intraoc-ular pressure, these combinations frequently doreduce intraocular pressure in actual use. Thecombined effect of such administration should beconfirmed in actual trial use according to thepoints listed in Table 4-3.

Table 4-3. Practical points for combined drugtherapy

─────────────────────• Drugs are to be added only when

necessary.• If the effect of a drug is insufficient or

tachyphylaxis occurs, one should firsttry switching to a different drug ratherthan adding a further drug.

• Drugs having the same pharmacologi-cal action should not be used in com-bination. For example, a combinationof twoβ-blockers or a combination of

carbonic anhydrase inhibitors in eyedrop and oral form should not beadministered.

• Even if eye drops are administeredmore frequently than prescribed inthe dosage regimen, this will notdecrease intraocular pressure, butwill increase adverse effects.

• In view of the intraocular pressure-lowering effect, adverse effects, andthe effect on compliance, if three ormore drugs are required in combina-tion, other therapeutic measures suchas laser surgery or incisional surgeryshould be considered as options.

─────────────────────

6. Glaucoma treatment agentsThe following is a summarized explanation of

the mechanism of action, dosage, contraindica-tions, adverse effects, etc., of various glaucomamedications.

As none of these drugs have been establishedas safe for use in children, they should be admin-istered to children only with extreme caution.These drugs should be administered to womenwho are pregnant or who may possibly be preg-nant only if the therapeutic benefits are assessedto outweigh the possible risks. As many drugshave been reported to be excreted in breast milk,they should not be given to nursing mothers, or ifsuch administration is absolutely necessary, nurs-ing should be discontinued.

1) Adrenergic agonists(1) NonselectiveGeneric name

EpinephrineDipivefrin

ActionIncreases aqueous outflow via Schlemm'scanalDecreases aqueous production

Dosage regimenDipivefrin 0.04%, 0.1%: 2 x dailyEpinephrine 1.25%: 2 x daily

Main adverse effectsAllergic conjunctivitis/blepharitis, conjunc-tival hyperemia, mydriasis, ocular pain, car-diopalmus, pigment deposition (conjuncti-

31

va, cornea, nasolacrimal ducts), ocularpemphigoid, macular edema, headache,sweating, tremor

Contraindications1. Patients with occludable angles (acute

angle-closure glaucoma attacks may occur)2. Patients with a history of hypersensitivity to

any ingredients of the drug

To be administered with caution in the followingcases:

1. Hypertension2. Arteriosclerosis3. Heart disease such as coronary failure or

heart failure4. Diabetes5. Hyperthyroidism

(2)αα2-selectiveUsed to prevent transient elevation of intraoc-

ular pressure following laser surgeryGeneric name

ApraclonidineAction

Decreases aqueous productionDosage regimen

Apraclonidine 1%: Instillation 1 hour beforeand immediately after laser surgery

Main adverse effectsConjunctival pallor, mydriasis, eyelid eleva-tion, thirst, dry feeling of the nose, and incontinuous use, allergic blepharoconjunc-tivitis

Contraindications1. Patients with a history of hypersensitivity to

this drug or clonidine2. Patients under treatment with monoamine

oxidase (MAO) inhibitorsTo be administered with caution in the followingcases:

1. Patients with severe cardiovascular disease2. Patients with unstable hypertension3. Patients with a history of vasovagal attacks

2) Adrenergic antagonists(1)ββ-blockersGeneric name

1. Nonselective

TimololCarteololBefunololLevobunolol

2. β1-selectiveBetaxolol

ActionDecreases aqueous production

Dosage regimenTimolol 0.25%, 0.5%: 2 x daily (Long-act-ing form:1 x daily)Carteolol: 1%, 2%: 2 x dailyBefunolol 0.25%, 0.5%, 1%: 2 x dailyLevobunolol 0.5%: 1-2 x dailyBetaxolol 0.5%: 2 x daily

Main adverse effectsOcular irritation symptoms, corneal epithelium

disorder, dry eye, allergic conjunctivitis, contactdermatitis, blepharoptosis, asthma attacks, brady-cardia, arrhythmia, palpitations, hypotension,heart failure, abnormal lipid metabolism,headache, depressionContraindications

Nonselective:1. Patients with bronchial asthma or a history

thereof, patients with bronchospasms orsevere chronic obstructive pulmonary dis-ease (may induce/aggravate asthma attacksdue to bronchial smooth muscle contractioncaused byβ-receptor blockade)

2. Patients with uncontrolled heart failure,sinus bradycardia, ventricular block (gradesⅡ, Ⅲ), or cardiogenic shock (these symp-toms may be aggravated due to a negativechronotropic/inotropic action resulting fromβ-receptor blockade)

3. Patients with a history of hypersensitivity toany ingredients of the drug

β1 selective:1. Patients with a history of hypersensitivity to

any ingredients of the drug2. Patients with uncontrolled heart failure

(symptoms may be aggravated)3. Women who are pregnant or who may pos-

sibly be pregnant (increased embryonic/fetalmortality has been reported in animal stud-ies)

To be administered with caution in the followingcases:

32

Nonselective:1. Right heart failure due to pulmonary hyper-

tension2. Congestive heart failure3. Diabetic ketoacidosis or metabolic acidosis4. Uncontrolled diabetesβ1 selective:1. Sinus bradycardia, ventricular block (gradesⅡ, Ⅲ), cardiogenic shock, congestive heartfailure

2. Uncontrolled diabetes3. Asthma, bronchospasms, or uncontrolled

obstructive pulmonary disease

(2) αα-ββ-blockersGeneric name

NipradilolAction

Decreases aqueous productionIncreases uveoscleral outflow

Dosage regimenNipradilol 0.25%: 2 x daily

Main adverse effectsSame asβ-blockers

Contraindications1. Patients with bronchial asthma, broncho-

spasms, or a history thereof, patients withsevere chronic obstructive pulmonarydisease (may induce/aggravate asthmaattacks due to bronchial smooth musclecontraction caused by β-receptor block-ade)

2. Patients with uncontrolled heart failure,sinus bradycardia, ventricular block (gradesⅡ, Ⅲ), or cardiogenic shock (these symp-toms may be aggravated due to a negativechronotropic/inotropic action resulting fromβ-receptor blockade)

3. Patients with a history of hypersensitivity toany ingredients of the drug

To be administered with caution in the followingcases:Same asβ-blockers

(3)αα1-blockersGeneric name

BunazosinAction

Increases uveoscleral aqueous outflow

Dosage regimenBunazosin 0.01%: 2 x daily

Main adverse effectsConjunctival hyperemia

ContraindicationsPatients with a history of hypersensitivity toany ingredients of the drug

3) Parasympathomimetics (cholinergic drugs)Generic name

PilocarpineCarbachol

ActionIncreases aqueous outflow via Schlemm'scanal

Dosage regimenPilocarpine 0.5-4%: 4 x dailyCarbachol 0.75%: 3-6 x daily

Main adverse effectsAphose due to miosis, deteriorated visual acu-

ity, accommodation disorders due to ciliary mus-cle contraction, myopia, browache, ciliary pain,conjunctival hyperemia, blepharitis, ocular pem-phigoid, retinal detachment, cataracts, diarrhea,nausea, vomiting, sweating, salivation, uterinemuscle contractionContraindications

Patients with iritis (possibility of iridial syn-echia due to pupillary contraction or aggravatedinflammation thereof)To be administered with caution in the followingcases:

1. Patients with bronchial asthma2. Patients at risk for retinal detachment3. In cases of malignant glaucoma, ciliary mus-

cle contraction may aggravate ciliary block4. In addition, in glaucoma due to lens sublux-

ation or intumescent cataracts, intraocularpressure may be increased, so caution isrequired

5. In the case of carbachol, as aggravation ofthe symptoms of acute heart failure, pepticulcers, gastrointestinal spasms, ileus, urinarytract obstruction, Parkinson's syndrome,and hyperthyroidism may occur, these drugsshould be administered with caution

4) Prostaglandin analoguesGeneric name

33

UnoprostoneLatanoprost

ActionIncreases uveoscleral aqueous outflow

Dosage regimenUnoprostone 0.12%: 2 x dailyLatanoprost 0.005%: 1 x daily

Main adverse effectsUnoprostone: Transient eye irritation symp-toms, corneal epithelium disorder, conjunc-tival hyperemia, and in rare cases, iridialpigment depositionLatanoprost: Conjunctival hyperemia, symp-toms of eye irritation, corneal epitheliumdisorder, blepharitis, iridial/palpebral pig-ment deposition, hypertrichosis of eye-lid/eyelashes, uveitis, cystoid macularedema (in aphakic eyes or eyes withimplanted intraocular lenses)

ContraindicationsUnoprostone: NoneLatanoprost: Patients with a history ofhypersensitivity to any of the ingredients ofthe drug

To be administered with caution in the followingcases:

Unoprostone: NoneLatanoprost:

1. Aphakic eyes or eyes with implanted intra-ocular lenses

2. Bronchial asthma or a history thereof3. Iritis, uveitis4. Patients with a possibility of latent herpes

virus infection5. Pregnant women, women in labor, nursing

mothers

5) Carbonic anhydrase inhibitors(1) Eye dropsGeneric name

DorzolamideAction

Decreases aqueous productionDosage regimen

Dorzolamide 0.5%, 1.0%: 3 x daily Main adverse effects

Ocular irritation symptoms, conjunctivalhyperemia, blurred vision immediately afterinstillation, allergic conjunctivitis, blephari-

tis, keratitisContraindications

1. Patients with a history of hypersensitivity toany ingredients of the drug

2. Patients with severe renal damageTo be administered with caution in the followingcases:

Patients with liver function disorders

(2) Oral and injection preparationsGeneric name

AcetazolamideAction

Decreases aqueous productionDosage regimen

Acetazolamide p.o.: Oral administration of250-1,000 mg dailyAcetazolamide injection: Intravenous orintramuscular injection of 250-1,000 mgdaily

Main adverse effectsTransient myopia, numbness of the extremities,

dysgeusia, metabolic acidosis, hypokalemia,hyperuricemia, anorexia, gastrointestinal disor-ders, nausea, vomiting, diarrhea, constipation,polyuria, urinary frequency, kidney/urinary tractstones, acute renal failure, fatigueability, systemicmalaise, drowsiness, dizziness, reduced libido,depression, mental confusion, aplastic anemia,hemolytic anemia, agranulocytosis, drug erup-tion, mucocutaneous ocular syndrome (Stevens-Johnson syndrome), toxic epidermal necrolysis(Lyell syndrome), shockContraindications

1. Should not be administered to the followingpatients:

A. Patients with a history of hypersensitivity tothe ingredients of the drug or sulfonamidepreparations

B. Patients with anuria or acute renal failure(adverse effects may be aggravated due todelayed drug excretion)

C. Patients with hyperchloremic acidosis,clearly decreased sodium/potassium in thebody fluids, adrenal insufficiency/Addison'sdisease (electrolyte abnormalities may beaggravated)

D. Patients under treatment with terfenadine orastemizole (QT prolongation or ventricular

34

arrhythmia may occur)2. Should not be administered for long periods

to the following patients:A. Patients with chronic angle-closure glauco-

ma (aggravation of glaucoma may be mask-ed)

To be administered with caution in the followingcases:

1. Patients with advanced liver cirrhosis2. Patients with severe coronary sclerosis or

cerebral arteriosclerosis3. Patients with severe renal damage4. Patients with liver disease/liver function dis-

orders5. Patients with severe hypercapnia requiring a

respirator, etc.6. Patients under treatment with digitalis

preparations, adrenocortical hormones, orACTH

7. Patients on a reduced-salt diet8. Elderly patients9. Infants

6) Hyperosmotics(1) MannitolGeneric name

D-mannitolAction

Decreases vitreous volumeDosage regimen

20% D-mannitol15% D-mannitol + 10% fructose15% D-mannitol + 5% D-sorbitolThe usual dose is intravenous drip infusionof 0.1-3.0 g, 5-15 mL/kg (however, dailydose of D-mannitol of up to 200 g)

Main adverse effectsHeadache, dizziness, thirst, nausea, diarrhea,

rigor, diuresis, urinary retention, hematuria, dehy-dration/electrolyte abnormalities, renal failure,angina pectoris, congestive heart failure, pul-monary edema, diabetic coma (preparations withadded fructose), rebound elevation of intraocularpressureContraindications

1. Patients with acute intracranial hematomas(in patients with suspected acute intracra-nial hematomas, if the drug is administeredwithout ruling out the presence of an

intracranial hematoma, in the event of tran-sient hemostasis due to intracranial pres-sure, bleeding may resume when intracra-nial pressure decreases, so the drug shouldnot be administered until the bleedingsource has been treated and the risk ofrenewed hemorrhage has been ruled out)

2. In the case of preparations with added fruc-tose, patients with hereditary fructose intol-erance (as such patients cannot metabolizefructose normally, hypoglycemia, etc., mayoccur, the risk of liver failure or kidney fail-ure)

To be administered with caution in the followingcases:

1. Dehydrated patients2. Patients with urinary retention or renal func-

tion disorders3. Patients with congestive heart failure4. Patients with diabetes insipidus5. Elderly patients

(2) GlycerinGeneric name

GlycerinAction

Decreases vitreous volumeDosage regimen

50% glycerin p.o. solution: 3 mL/kg is givenorally 1 - 2 x daily10% glycerin + 5% fructose (glycerol) :Intravenous drip infusion of 300-500 mLdaily

Main adverse effectsHeadache, dizziness, thirst, nausea, diarrhea,

rigor, diuresis, and for the intravenous prepara-tion, urinary retention, hematuria, dehydration/electrolyte abnormalities, renal failure, anginapectoris, congestive heart failure, pulmonaryedema, hyperosmolar nonketotic hyperglycemia,lactic acidosis, rebound elevation of intraocularpressureContraindications

Patients with congenital abnormalities of glyc-erin or fructose metabolism (severe hypo-glycemia may occur)To be administered with caution in the followingcases:

1. Diabetics

35

2. Patients with severe heart disease3. For the intravenous preparation, patients

with kidney disorders4. For the intravenous preparation, patients

with diabetes insipidus

(3) IsosorbideGeneric name

IsobideAction

Decreases vitreous volumeDosage regimen

70% isosorbide solution: 70-140 mL dailygiven in 2 - 3 divided oral administrations

Main adverse effectsNausea, vomiting, diarrhea

ContraindicationsPatients with acute intracranial hematomas (in

patients with suspected acute intracranialhematomas, if the drug is administered withoutruling out the presence of an intracranialhematoma, in the event of transient hemostasisdue to intracranial pressure, bleeding may re-sume when intracranial pressure decreases, sothe drug should not be administered until thebleeding source has been treated and the risk ofrenewed hemorrhage has been ruled out)To be administered with caution in the followingcases:

1. Dehydrated patients2. Patients with urinary retention or renal func-

tion disorders3. Patients with congestive heart failure

ⅣⅣ. Laser surgery

1. Laser iridotomy1) Purpose

To relieve pupillary block, equalize pressuredifferential between the anterior and posteriorchambers, and open the anterior chamber angle.

2) IndicationsThis procedure is the therapy of first choice in

primary or secondary angle-closure glaucomadue to pupillary block. It may also be performedin patients with suspected plateau iris syndromein order to eliminate the factor of pupillary block.

3) Preoperative preparation(1) In order to stretch/tighten the iris and facili-

tate perforation, 1~ 2 % pilocarpine isinstilled 1 hour before surgery.

(2) In order to prevent transient postoperativeelevation of intraocular pressure, apracloni-dine is instilled 1 hour before and immedi-ately after surgery.

(3) In the event of corneal edema, drugs suchas carbonic anhydrase inhibitors or hyper-osmotics are considered to make the corneatransparent prior to surgery.

(4) The operation is carried out under topicalanesthesia.

4) Contact lensContact lenses such as the Abraham or Wise

contact lens for iridotomy are used.

5) Technique/surgical siteA contact lens for iridotomy is used, and irra-

diation is conducted on the periphery of the irison the superior temporal and superior nasal sidescovered by the eyelid (in order to preventmonocular diplopia). However, a transparent siteon the cornea is selected, taking care to avoidareas of arcus senilis.

6) Laser settings(1) Nd-YAG laser iridotomy

1. As the plasma generation energy differsdepending on the unit used, the energymust be selected according to the modelused.

2. The beam is focused not on the surface ofthe iris, but on the parenchyma of the iris.

3. In order to prevent iridial hemorrhage, theplanned penetration site is pre-irradiatedusing an argon laser, etc.

(2)Thermocoagulation laser iridotomy using anargon laser, etc.1. StageⅠ(peripheral irradiation of the planned

perforation site in order to stretch the iris)Spot size: 200-500μmPower: 200 mWDuration: 0.2 seconds

2. StageⅡ(perforation irradiation)

36

Spot size: 50μmPower: 1,000 mWDuration: 0.02 seconds

As the pigment rises up from the irradiation sitein the form of oily smoke when perforation isachieved, further irradiation is carried out inorder to expand the perforation wound so that itwill be sufficiently large to relieve the pupillaryblock (100-200μm).

7) ComplicationsCorectopiaAnterior chamber hemorrhageCorneal opacityBullous keratopathyPostoperative iritisLocalized cataractsTransient postoperative elevation of intraoc-ular pressurePosterior synechiaReocclusion of penetration woundUnintended retinal irradiation

8) Postoperative management(1) Intraocular pressure is measured 1-3 hours

after surgery in order to determine whetheror not transient elevation has occurred.

(2) Carbonic anhydrase inhibitors or hyperos-motics are administered as needed.

(3) Postoperative inflammation will oftenresolve spontaneously even without admin-istration of adrenocortical steroids.

2. Laser trabeculoplasty1) Purpose

The trabecular meshwork is irradiated with alaser in order to improve aqueous outflow.

2) IndicationsPrimary open-angle glaucoma, exfoliation

glaucoma, pigmentary glaucoma, primary angle-closure glaucoma following laser iridotomy,mixed glaucoma, etc.

However, it is known to be difficult to normal-ize intraocular pressure in eyes in which thispressure is 25 mmHg or above. Rather than areplacement for invasive surgery, this procedureshould be considered an adjunct to drug therapy.Moreover, the intraocular pressure-lowering

effect of this procedure is known to recede overtime.

3) Preoperative preparation(1) In order to prevent transient postoperative

increases in intraocular pressure, apracloni-dine is given by instillation in the eye 1hour before and immediately after surgery.

(2) The procedure is carried out under topicalanesthesia.

4) Contact lensGoniolens for laser coagulation use

5) Technique/surgical siteAn argon laser, diode laser, etc., is used.

Approximately 25 applications are performed perquadrant at uniform intervals along 90º to 180º ofthe anterior chamber angle on the trabecular pig-ment band.

6) Laser settingsSpot size: 50μmPower: 400-800 mW (allows depigmenta-tion without the occurrence of small bub-bles)Duration: 0.1 seconds

7) ComplicationsPosterior chamber hemorrhagePeripheral anterior synechiaPostoperative iritisPostoperative elevation of intraocular pres-sure

8) Postoperative management(1) Intraocular pressure is measured 1-3 hours

after surgery in order to determine whethertransient elevation has occurred.

(2) Carbonic anhydrase inhibitors or hyperos-motics are administered as needed.

(3) Postoperative inflammation will oftenresolve spontaneously even without admin-istration of adrenocortical steroids.

9) OtherIn order to perform less invasive trabeculoplas-

ty, a dedicated half-wavelength (Nd-YAG) laserunit has been developed.

37

3. Laser gonioplasty (laser peripheral iridoplasty)1) Purpose

To contract the periphery of the iris by laserthermocoagulation in order to widen the anteriorchamber angle.

2) IndicationsPerformed in cases where laser iridotomy can-

not be carried out due to corneal opacity inangle-closure due to plateau iris syndrome orpupillary block, cases of primary open-angleglaucoma with a narrow anterior chamber angleas a preliminary step to laser trabeculoplasty, orin eyes following goniosynechiolysis in order toprevent postoperative recurrence of synechia.

However, this procedure is ineffective in sub-jects who have already developed peripheralanterior synechia. Moreover, in performing thisprocedure in glaucoma due to pupillary block,laser iridotomy should be performed at as early astage as possible.

3) Preoperative preparation(1) In order to prevent transient postoperative

elevation of intraocular pressure, apracloni-dine is instilled 1 hour before and immedi-ately after surgery.

(2) The operation is carried out under topicalanesthesia.

4) LensA goniolens or contact lens for iridotomy is

used.

5) Technique/surgical siteCoagulation is carried out with a width of 1-2

rows on the periphery of the iris over 180º or360º, with approximately 15 applications perquadrant.

6) Laser settingsSpot size: 200-500μmPower: 200-400 mWDuration: 0.2-0.5 seconds

7) ComplicationsTransient elevation of intraocular pressurePostoperative iritis

Corectopia

8) Postoperative management(1) Intraocular pressure is measured 1-3 hours

after surgery in order to determine whetheror not transient elevation has occurred.

(2) Carbonic anhydrase inhibitors or hyperos-motics are administered as needed.

(3) Postoperative inflammation will often re-solve spontaneously even without adminis-tration of adrenocortical steroids.

4. Cyclophotocoagulation1) Purpose

The ciliary body is destroyed with a laser inorder to inhibit aqueous production and therebyreduce intraocular pressure.

2) IndicationsIndicated in subjects in whom other glaucoma

surgery such as filtering surgery has been ineffec-tive or is not feasible.

As serious complications may occur, this pro-cedure is to be considered a last resort for reduc-ing intraocular pressure.

May be carried out using approaches such asthe transscleral, transpupillary, or transvitrealroute.

3) Preoperative preparationRetrobulbar anesthesia is carried out.

4) Technique/surgical site (transscleral diodelaser cyclophotocoagulation)A cyclophotocoagulation probe is placed 0.5-

2.0 mm from the limbus and the ciliary body iscoagulated, with 15-20 applications each timeover 180º-270º.

5) Laser settings (transscleral diode lasercyclophotocoagulation)

Power: 2000 mWDuration: 2 seconds

6) ComplicationsPainPersistent inflammationReduced visual acuity, loss of light senseSympathetic ophthalmia

38

Phthisis bulbi

7) Postoperative management(1) Antiinflammatory analgesics are adminis-

tered for pain relief.(2) Adrenocortical steroids are administered for

postoperative inflammation.(3) Although one-time irradiation frequently

causes elevation of intraocular pressure,multiple repeated irradiations will usuallybring about intraocular pressure control.

5. Laser suturelysis1) Purpose

To enhance filtration following trabeculectomy.

2) IndicationsCases in which it is assessed that aqueous fil-

tration via the scleral flap following trabeculecto-my is insufficient and it is assessed that filtrationwill not become excessive.

3) Preoperative preparation(1) During surgery, the scleral flap is sutured

with nylon thread.(2) Topical anesthesia is performed.

4) LensLens for laser suturelysis.

5) Technique/surgical siteThermocoagulation laser (use of a red laser is

preferred in order to prevent burning of the con-junctiva). Slight pressure is applied to the con-junctiva using the laser suturelysis lens, and thebeam is focused on the visualized suture thread.

6) Laser settingsSpot size: 50μmPower: 100-300 mWDuration: 0.1-0.2 seconds

7) ComplicationsConjunctival burning, perforationExcessive filtration

8) Postoperative managementIntraocular pressure and filtering bleb statusare to be confirmed.

ⅤⅤ. Invasive surgery

1. IndicationsGenerally speaking, invasive surgery is indi-

cated in cases in which sufficient reduction ofintraocular pressure cannot be achieved by othertherapeutic means such as drug therapy or lasertherapy, cases in which other appropriate meansof treatment cannot be used because of adverseeffects or poor-compliance, and cases in which itis thought that sufficient reduction of intraocularpressure cannot be achieved by other therapeuticmeans. The indication for surgery must be madefor each individual patient based on a compre-hensive assessment of disease type, disease stage,the patient's disease awareness, compliance, andthe patient's social background (Table 4-4).

Moreover, not only surgery, but all treatmentsmust be carried out after thoroughly explaining tothe patient the treatment method and incidentalsymptoms/complications associated therewithand then obtaining his or her consent.

Table 4-4. Items to be considered in determiningglaucoma surgery indication

─────────────────────• Glaucoma status

Disease stageDisease typeIntraocular pressureHistory of glaucoma surgery

• Nonsurgical treatment prognosisIntraocular pressure-lowering-effectAdverse effects, complicationsComplianceVisual function prognosis

• Prognosis for surgical therapyIntraocular pressure-lowering-effectSurgical complicationsVisual function prognosis

• Patient factorsSocial factors such as occupation andfamily environmentDisease awarenessAgeOphthalmic diseases other than glau-comaSystemic condition

─────────────────────

39

2. Surgical techniquesThe following is a summarized explanation of

various surgical techniques used in glaucoma. Inaddition to these, new techniques such as visco-canalostomy are being tried out in some cases,but the results for these new techniques have notyet been sufficiently studied. At the present time,the most widely used surgical technique for themajority of glaucoma types, beginning with pri-mary open-angle glaucoma is trabeculectomy.However, in selecting the surgical technique tobe used, one must first investigate factors such asthe mechanism of effect of the various tech-niques, long-term results, complications, and thedisease type, disease stage, and surgical history ofthe individual patient.

1) Filtering surgeryIn this surgery, a small hole is made in the

corneal limbus in order to create a new aqueousoutflow pathway between the anterior chamberand subconjunctival tissue. The most seriouscomplication is late infection of the filtering bleb.Patients undergoing filtering surgery such as tra-beculectomy should be given sufficient explana-tion concerning the risk of late infections.

(1) Full-thickness filtering surgeryIn this surgery, rather than preparing a scleral

flap, a direct aqueous outflow pathway from theanterior chamber is created underneath the con-junctiva. Compared to filtering surgery in which ascleral flap is prepared, such as trabeculectomy,it is difficult to control filtration volume, andcomplications such as a shallow anterior cham-ber are frequent, so this technique is currentlyindicated only in a few extremely refractorycases.

(2) TrabeculectomyIn this procedure, a scleral flap is prepared, the

limbal tissue is incised under the scleral flap, andthe scleral flap is then sutured in order to regulatefiltration volume. This is currently the most com-mon type of glaucoma surgery. In order to pre-vent scarring at the filtration site, antimetaboliteshave come to be used concomitantly, resulting ina marked improvement in trabeculectomy results.Moreover, the introduction of laser suturelysis has

made it possible to regulate intraocular pressureafter surgery, thus decreasing complications dueto excess filtration such as hypotony. Althoughre-surgery and other treatments are required insome cases, long-term intraocular pressure con-trol is achieved in most cases.

(3) Nonpenetrating trabeculectomyIn this technique, a portion of the tissue is

incised underneath the scleral flap to form anaqueous outflow pathway without penetration ofthe anterior chamber. Compared to trabeculecto-my, this procedure has been reported to showfew early postoperative complications and toshow high postoperative intraocular pressure.Long-term results of the procedure have not yetbeen sufficiently studied.

(4) Seton implant surgeryIn this procedure, an aqueous outflow pathway

is created between the anterior chamber and theoutside of the eye using a special implant. Thisprocedure is used in patients in whom trabecu-lectomy with concomitant administration ofantimetabolites has been unsuccessful, patientsshowing severe conjunctival scarring as a resultof previous surgeries, patients with little prospectof success in trabeculectomy, and patients inwhom filtering surgery is difficult from a techni-cal standpoint. The specialized implant is notapproved in Japan as a medical device.

2) Aqueous outflow pathway reconstructionsurgery

(1) TrabeculotomyIn this procedure, a trabeculotome is inserted

into Schlemm's canal under the scleral flap andis rotated to the anterior chamber in order toincise the trabecular meshwork from outside soas to promote aqueous outflow via Schlemm'scanal.

(2) GoniosynechiolysisIn this procedure, goniosynechia in eyes with

angle-closure glaucoma are lysed and aqueousoutflow via the physiological pathway is promot-ed in order to reduce intraocular pressure. Thisprocedure is more effective if carried out concur-rently with cataract surgery.

40

(3) GoniotomyUnder observation with a goniolens, a scalpel

inserted via the cornea is used to incise the ante-rior chamber angle from the anterior chamberside. This procedure is indicated in developmen-tal glaucoma.

3) Surgery to relieve pupillary block(1) Peripheral iridectomy

This procedure is conducted in glaucomascaused by pupillary block, such as primary angle-closure glaucoma, in order to equalize the pres-sure difference between the anterior and posteri-or chambers by incising the periphery of the iris.With the increasingly widespread use of laser iri-dotomy, invasive peripheral iridectomy hasbecome rare.

4) Cyclodestructive surgeryIn this procedure, the ciliary body is coagulat-

ed by means of a cryocoagulation device ordiathermy in order to reduce intraocular pressureby inhibiting aqueous production. This procedurehas become largely obsolete since laser unitscame into use for this purpose. Because the pro-cedure causes considerable pain and complica-tions such as phthisis bulbi, it is indicated only inrefractory cases where other treatments are inef-fective.

References

1) Iwata K: Primary open angle glaucoma and low ten-sion glaucoma. Pathogenesis and mechanism of opticnerve damage. Nippon Ganka Gakkai Zasshi 96:1501-1531, 1992.

2) Collaborative Norman-Tension Glaucoma StudyGroup: Comparison of glaucomatous progressionbetween untreated patients with normal-tension glau-coma and patients with therapeutically reducedintraocular pressures. Am J Ophthalmol 126: 487-497, 1998.

3) Collaborative Norman-Tension Glaucoma StudyGroup: The effectiveness of intraocular pressurereduction in the treatment of normal-tension glauco-ma. Am J Ophthalmol 126: 498-505, 1998.

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Introduction

For effective treatment of glaucoma, buildingtrust with patients is of prime importance in everyaspect of treatment (including decision on treat-ment plan, change, initiation, and follow-up).

Benefits and adverse reactions (complications)of each treatment should be carefully consideredin order to choose a method that provides bene-fits that outweigh the adverse effects on apatient's visual function, systemic condition, andquality of life. Follow-up intervals may be short-ened or extended depending on the individualpatient's intraocular pressure (IOP), and status ofthe optic nerve and visual field. They should notbe based on a standardized schedule. Follow-upexamination should include IOP measurement,visual field testing and optic nerve imaging.Optic nerve photography is also recommended.

ⅠⅠ. Primary glaucoma

1. Primary open-angle glaucomaThe target IOP is determined based on the indi-

vidual patient's disease stage and pathology (seeFlow Chart VI, Section 4). However, the targetIOP is merely a standard. Clinicians should notbe satisfied or neglect treatment once the targetIOP has been reached. Conversely, cliniciansshould avoid excessive treatment, worrying toomuch about IOP not reaching the target.

1) Medical treatment(1) Medical treatment is the first choice for pri-

mary open-angle glaucoma.(2) Medical treatment is initiated with topical

ocular hypotensives as monotherapy. Whenthe drug is ineffective, it is replaced byanother drug. If IOP is not satisfactorily con-trolled by monotherapy, multi-drug therapyis used.

(3) For confirmation of IOP-lowering effect, ifpossible, the IOP of the treated eye shouldbe compared to that of the fellow eye that isnot given the drug. Or, diurnal variations inIOP at baseline and during follow-up arecompared to determine stability of thera-peutic effect.

2) Laser trabeculoplasty(1) The advantage of laser trabeculoplasty is

that although it is an invasive procedure itcan be performed under topical anesthesiaon an outpatient basis.

(2) The IOP-lowering effect tends to diminishover time, and is maintained in only 10-30% of patients at 10 years postoperatively.

(3) Who will respond to this procedure andwho will not is unpredictable. In addition,the procedure may damage the trabeculartissue and reduce outflow facility over aprolonged period, and eventually elevateIOP. Therefore, laser trabeculoplasty shouldnot be performed as an alternative whenpatients are not candidates for invasivesurgery or refuse to undergo invasive sur-gery.

(4) When patients still maintain IOP higherthan 25 mm Hg despite medical treatment,it is difficult to lower it by laser trabeculo-plasty.

(5) Since some patients develop IOP elevationfollowing laser irradiation, they should bemonitored for IOP for several hours postop-eratively. If IOP is found elevated, measuresshould be taken to lower it depending onthe magnitude of elevation and status of theoptic nerve and visual field.

(6) Pre- and postoperative instillation of anα2

adrenergic agonist (apraclonidine) is effec-tive in preventing IOP elevation followinglaser irradiation. However, it does not com-pletely prevent IOP elevation, and IOPshould be monitored continuously.

3) Invasive surgery (with postoperative medica-tion if necessary)(1) Filtering surgery (trabeculectomy with or

without antimetabolites, nonpenetrating tra-beculectomy)

(2) Reconstruction of the aqueous outflowpathway (trabeculotomy, viscocanalostomy,etc.)

(3) Seton implant surgery

The most widely used surgical procedure atpresent is trabeculectomy. The IOP levelachieved by trabeculotomy is in the upper level

Section 5 Treatment for Each Type of Glaucoma

42

of 10 mm Hg, higher than that achieved by tra-beculectomy. Nevertheless, trabeculotomy isadvantageous because of fewer complicationsand no need of intraoperative antimetabolites.Results of nonpenetrating trabeculectomy andviscocanalostomy have not yet been fully investi-gated.

In filtering surgery, the formation of filteringblebs in the inferior region is associated with anextremely high risk of postoperative infection.Therefore, Seton surgery is frequently indicated inmany countries for patients whose upper opticalfield is unsuitable for filtering surgery. However,the Seton implant has not yet been approved inJapan as a medical device.

(4) Cyclodestructive surgeryThis procedure is rarely necessary for primary

open-angle glaucoma. It greatly affects the globestructure and functions. Whether this surgery isindicated should be carefully determined.

4) Follow-upFollow-up intervals may be shortened or

extended depending on the individual patient'sIOP and status of the optic nerve and visual field,and should not be based on a standardizedschedule. Even though the IOP is successfullycontrolled, IOP measurement and optic nerveexamination should be conducted monthly oronce every few months, and perimetry once ortwice a year. Also, fundus photography once ayear is useful for follow-up.

Patients who undergo filtering surgery shouldbe informed of potential risks of filtering blebinfection and instructed to consult their ophthal-mologist immediately in the event of any symp-tom that might indicate infection, such as hyper-emia, ocular or orbital pain, tearing, or blurredvision.

2. Normal-tension glaucomaIn a multicenter trial for normal-tension glau-

coma (NTG) conducted in the U.S., the progres-sion of visual field damage was significantly dif-ferent between patients who were not treated andpatients who were treated and achieved IOP

reduction of 30% or more from baseline. Thus,lowering IOP has been shown to be effectivetreatment. However, it is not clear whether anIOP reduction of 30% or more is necessary. Inthis trial, more than half of the patients under-went filtrating surgery to achieve this 30% reduc-tion. In addition, progression of postoperativecataract impaired visual function. The IOP-lower-ing effect on patients whose IOP is at the normalaverage level (15 mm Hg) or lower has not beenfully studied.

Treatment and follow-up are the same as in pri-mary open-angle glaucoma. However, laser tra-beculoplasty is less effective in NTG patients.

Improving optic nerve blood flow and protect-ing ganglion cells also may be effective treatmentfor NTG in addition to lowering IOP. Severalreports suggest that oral calcium antagonists areeffective, but no large-scale multicenter trial orrandomized clinical trial has been conducted todetermine a clear therapeutic effect.

3. Primary angle-closure glaucoma1) Primary angle-closure glaucoma with pupil-

lary blockWhether the disease is chronic or acute, reliev-

ing pupillary block by iridotomy or iridectomy isthe fundamental treatment and the first choice oftreatment. Hypotensive drugs are used to lowerIOP that remains elevated even after relief ofpupillary block (residual glaucoma), or to allevi-ate symptoms and signs of acute glaucomaattacks, as well as to facilitate laser iridotomy oriridectomy. Since this type of glaucoma is bilater-al, when one eye undergoes laser iridotomy oriridectomy for acute glaucoma attack or chronicangle-closure glaucoma, the fellow eye also isgiven the same procedure as a preventive mea-sure.

(1) Acute primary angle-closure glaucoma1. Medical treatmentA. Hyperosmotics

Hyperosmotics are the most effective drugs foralleviating severe elevation of IOP. Distributed inthe extracellular fluid, hyperosmotics elevateblood osmotic pressure and cause the aqueouscomponent of the intracellular fluid to migrate

43

into the extracellular fluid. In the eye, vitreousfluid migrates to choroidal capillaries, causing adecrease in vitreous volume, resulting in IOPreduction. Because the volume of vitreous isdecreased, the iris recedes, and the anteriorchamber is deepened, which is effective duringan acute attack of primary angle-closure glauco-ma.

Intravenously administered hyperosmotics arethe fastest-acting and most potent treatment inlowering IOP. However, a sudden systemicincrease in the volume of extracellular fluid mayincrease the volume of circulating plasma andplace a burden on the circulatory system; patientsprone to heart failure or pulmonary congestionmay develop pulmonary edema. Furthermore,the IOP-lowering effect of hyperosmotics is tem-porary, and repeated administration for achievinglong-term IOP reduction will only aggravate thepatient's systemic condition.

a. Intravenous administrationMannitol: 20% mannitol solution is intra-

venously administered at the dose of 1.0-3.0 g/kgfor 30-45 minutes. IOP reaches its lowest levelafter 60-90 minutes, and this effect persists for 4-6 hours. Since mannitol is excreted via the kid-neys, patients with impaired renal function maydevelop acute renal failure because increasedplasma osmolarity increases the volume of circu-lating plasma. Mannitol by its diuretic action mayaggravate dehydration in patients already dehy-drated due to vomiting during an attack of acuteglaucoma.

Glyceol: Glyceol 300-500 mL is intravenouslyadministered for 45-90 minutes. The lowest levelof IOP is reached 30-135 minutes after initiationof intravenous administration. The effect persistsfor approximately 5 hours. Caution is required inadministration to diabetic patients since Glyceolproduces glucose during its metabolic processand it has energy of 637 kcal per liter.

b. Oral administrationIsosorbide: 70-140 mL of a 70% solution is

administered daily in 2-3 divided doses.

Glycerin: 3 mL/kg of a 50% solution is admin-istered once or twice daily.

B. Miosis1% or 2% pilocarpine is instilled 2-3 times per

hour.

When the pupillary sphincter is ischemic dueto ocular hypertension and the light reflex isabsent (sphincter paralysis), frequent administra-tion of parasympathomimetics is ineffective. Itdoes not make the pupil constrict. On the con-trary, it displaces the ciliary body anteriorly andaggravates pupillary block. If a large volume ofmiotics is instilled, it can be absorbed systemical-ly through the nose and cause systemic adverseeffects. Therefore, topical administration ofpotent parasympathomimetics is not recommend-ed.

C. Decrease of aqueous productiona. Intravenous or oral administration of aceta-

zolamide 10 mg/kgb. Topical β-adrenergic blockersc. Topical α-β-adrenergic blockersd. Topical carbonic anhydrase inhibitors

D. Increase of aqueous outflowa. Topical prostaglandin analoguesb. Topical α1-adrenergic blockersc. Topical α-β-adrenergic blockers

2. Surgical treatmentA. Laser iridotomy

When laser iridotomy is performed, the corneamust be sufficiently clear. Laser irradiationthrough an opaque cornea involves a high risk ofbullous keratopathy. In patients with opaquecornea, laser irradiation should be avoidedwhenever possible, and surgical iridectomyshould be considered as an alternative. Bullouskeratopathy following laser iridotomy is commonin patients with cornea guttata, diabetic patients,patients with a history of acute attack of primaryangle-closure glaucoma, or patients whosecorneal endothelial cell count is already de-creased.

44

B. Surgical iridectomyWhile surgical iridectomy is advantageous in

patients with opaque cornea in whom laser irra-diation is difficult, it is associated with the riskspeculiar to intraocular surgery. In eyes with acuteattacks of primary angle-closure glaucoma in par-ticular, there is a risk of complications such asmalignant glaucoma and choroidal hemorrhage,and IOP must be sufficiently lowered prior tosurgery.

(2) Chronic primary angle-closure glaucomaAs is the case for acute primary angle-closure

glaucoma, alleviation of pupillary block is thefundamental treatment. Persistent ocular hyper-tension following pupillary block alleviation(residual glaucoma) is treated by medication,laser or surgery, the same as in primary open-angle glaucoma.

A. Medical treatmentThe following drugs may be used in combina-

tion as specified for primary open-angle glauco-ma.

a. Prostaglandin analoguesb. β-adrenergic blockersc. α-β-adrenergic blockersd. α1-adrenergic blockerse. Parasympathomimeticsf. Carbonic anhydrase inhibitors

B. Surgical treatmenta. Laser trabeculoplastyThis procedure can be performed in the area of

the chamber angle where the peripheral anteriorsynechiae are absent. The IOP-lowering effect israther weak. In eyes with narrow angle, peripher-al anterior synechia is likely to develop followingirradiation.

b. Reconstruction of aqueous outflow path-ways (goniosynechiolysis, trabeculotomy)

This procedure is indicated in patients withextensive peripheral anterior synechia (e.g.,involving over half of the anterior chamberangle). It has been reported that when combinedwith cataract extraction (plus intraocular lensesimplantation), this procedure produces an excel-lent IOP-lowering effect by preventing synechia

reformation.

c. TrabeculectomyThis procedure is used when medical treat-

ment has failed to achieve sufficient IOP control;when there is long-standing peripheral anteriorsynechia; when poor visibility of the anteriorchamber angle inhibits goniosynechiolysis; orwhen goniosynechiolysis or trabeculotomy isineffective. Patients with narrow anterior cham-ber angle are likely to develop complicationssuch as flat anterior chamber or malignant glau-coma.

2) Plateau iris syndrome(1) Medical treatment

Miotic drugs mechanically pull the peripheraliris toward the center, open the anterior chamberangle, and prevent the progression of angle clo-sure. When administration of miotics alone doesnot lower IOP sufficiently, other drugs are used todecrease aqueous production or increase aque-ous outflow, as is the case in chronic primaryangle-closure glaucoma following relief of pupil-lary block.

(2) Surgical treatmentLaser gonioplasty (laser peripheral iridoplasty)

shrinks the iris root to widen the distancebetween the iris root and the anterior chamberangle, although its long-term efficacy remainsunclear. Iridectomy or laser iridotomy is onlyeffective in plateau iris combined with pupillaryblock.

4. Mixed glaucomaA combination of primary open-angle glauco-

ma and primary angle-closure glaucoma is calledmixed glaucoma. However, it is difficult to strict-ly distinguish mixed glaucoma from chronic pri-mary angle-closure glaucoma or primary open-angle glaucoma occurring merely in eyes withnarrow angle. In treating mixed glaucoma, reliefof pupillary block is the primary consideration, asis the case for primary angle-closure glaucoma,after which treatment is given for primary open-angle glaucoma.

45

5. Ocular hypertensionOf patients with IOP above the statistically

determined normal upper limit without anom-alies of the optic nerve or visual field, only 1-2%progress to primary open-angle glaucoma annu-ally. In a multicenter trial conducted recently inthe U.S., patients with ocular hypertension of 24-32 mmHg were randomly assigned to a non-treatment group or a treatment group (treatedwith eye drops in order to reduce IOP to 24 mmHg or lower) and followed for 5 years. Theoccurrence of visual field damage or optic nervedamage was significantly lower in the treatmentgroup. However, the effect of treatment inpatients with IOP lower than 24 mmHg was notinvestigated. Accordingly, IOP slightly above thenormal upper limit alone does not justify treat-ment. Patients with repeatedly measured IOPs inthe upper 20s or with risk factors such as a familyhistory of glaucoma (see Section 2) should betreated with acceptable eye drops.

Patients with ocular hypertension are observedwithout treatment at an interval of one to severalmonths. For patients whose optic nerve and visu-al field are confirmed to be normal and withoutrisk factors for progression to primary open-angleglaucoma in the follow-up examination, IOPmeasurement, optic nerve examination andperimetry can be conducted at 1-2 year intervals.

ⅡⅡ. Secondary glaucomaTreatment of secondary glaucoma is primarily

directed to underlying diseases whenever possi-ble. Since treatment of secondary glaucomavaries widely depending on the underlying con-dition, the mechanism of IOP elevation involvedmust be determined for appropriate selection ofthe treatment. Secondary glaucomas are roughlysubdivided into open-angle glaucoma and angle-closure glaucoma. However, the distinctionbetween the mechanisms of open-angle andangle-closure glaucoma is not always clear,depending on the underlying condition and itspathology. Gonioscopy is essential in assessingthe mechanism of IOP elevation as well as indiagnosing the type of glaucoma.

The following are classifications of the princi-pal mechanisms of IOP elevation and theirunderlying diseases, as well as their typical treat-ments.

1. Secondary open-angle glaucoma1) Secondary open-angle glaucoma character-

ized primarily by aqueous outflow resistancebetween the trabecular meshwork and anteri-or chamber

Neovascular glaucoma, heterochromic iridocy-clitis, epithelial ingrowth, etc.

(1) Medical treatmentMedical treatment is performed as specifiedfor primary open-angle glaucoma. However,parasympathomimetics are often ineffectiveand may aggravate the condition by de-stroying the blood-aqueous barrier.

(2) Surgical treatmentTrabeculectomy(with or without antimetabo-lites) is performed. Laser trabeculoplasty isnot only ineffective but harmful.The efficacy of nonpenetrating trabeculecto-my or surgical reconstruction of aqueousoutflow pathways (trabeculotomy) has notbeen confirmed.Seton implant surgery and cyclodestructivesurgery are last resorts for lowering IOP. Inneovascular glaucoma, retinal coagulationshould be immediately performed by lasertherapy or cryotherapy.

2) Secondary open-angle glaucoma character-ized primarily by aqueous outflow resistancein the trabecular meshwork

Steroid glaucoma(1) Discontinuation of steroids(2) Topical and systemic administration of ocu-

lar hypotensives(3) Trabeculotomy, trabeculectomy (with or

without antimetabolites)Efficacy of laser trabeculoplasty has not been

confirmed. Seton implant surgery and cyclode-structive surgery are last resorts for reducing IOP.

Exfoliation glaucoma(1) Topical medication

46

(2) Laser trabeculoplasty often results in sub-stantial IOP reduction

(3) Trabeculectomy(withor without antimetabo-lites), trabeculotomySeton implant surgery and cyclodestructivesurgery are last resorts for reducing IOP.

Inflammatory diseases (Posner-Schlossman syn-drome, sarcoidosis, Behçet's disease, herpetickeratouveitis, bacterial/fungal endophthalmitis,etc.)

(1) Anti-inflammatory therapy(2) Topical medication(3) Trabeculectomy(with or without antimetabo-

lites)

Phacolytic glaucoma(1) Topical and systemic administration of ocu-

lar hypotensives(2) Extraction of causative lens or lens frac-

tions, instillation of anti-inflammatorydrugs, and in some cases, vitrectomy

(3) Trabeculectomy(with or without antimetabo-lites)

Schwartz syndrome(1) Topical and systemic administration of ocu-

lar hypotensives(2) Repositioning detachment surgery(3) Trabeculectomy(with or without antimetabo-

lites)Laser trabeculoplasty is ineffective. Efficacy of

trabeculotomy has not been confirmed. Setonimplant surgery and cyclodestructive surgery areused as last resorts.

Pigmentary glaucoma or pigment dispersion syn-drome

(1) Topical medicationMydriatics may cause pigment dispersion and

aggravate aqueous outflow.

(2) Laser trabeculoplastySince pigment deposition on the trabecular

meshwork is extensive, the laser power should belower than usual. IOP response fluctuates greatly.

(3) Trabeculectomy(with or without antimetabo-lites)

(4) Laser iridotomy, lens extractionIn cases of reverse pupillary block, these pro-

cedures may reduce pigment dispersion due tocontact between the iris and the lens and preventirreversible trabecular damage.

3) Secondary open-angle glaucoma character-ized primarily by aqueous outflow resistanceposterior to Schlemm's canal

Exophthalmos due to thyroid ophthalmopathy,elevated venous pressure due to carotid arteri-ovenous fistulae, etc.

(1) Treatment of underlying diseases(2) Administration of topical and systemic ocu-

lar hypotensives(3) Surgical treatment tailored to the individual

patient

2. Secondary angle-closure glaucoma1) Secondary angle-closure glaucoma with pu-

pillary block

Lens intumescence, microphthalmia, posteriorsynechia, lens dislocation, epithelial ingrowth,etc.

Treatment must be selected based on themechanisms causing pupillary block.

(1) Administration of topical and systemic ocu-lar hypotensives

(2) Laser iridotomy(3) Lens extraction, vitrectomy(4) Discontinuation of miotics in cases of

miotic-induced pupillary block

2) Secondary angle-closure glaucoma due toanterior movement of intraocular tissue pos-terior to the lens

Glaucoma due to anterior protrusion of the cil-iary body or shifting of the iris/lens (vitreousbody) diaphragm: malignant glaucoma, post-reti-nal photocoagulation, post-scleral buckling, pos-terior scleritis, Harada disease, central retinalvein occlusion, etc.

(1) Miotics are contraindicated, as they pro-mote anterior protrusion of the ciliary body

(2) Pupillary dilation and ciliary relaxation withatropine eye drops

47

(3) Systemic administration of hyperosmotics,and topical and systemic administration ofocular hypotensives

(4) Laser or surgical anterior hyaloidotomy andcapsulotomy in pseudophakic or aphakiceyes

(5) Vitrectomy combined with anterior hyaloid-otomy (in phakic eyes sometimes combinedwith lens extraction)

Glaucoma due to intraocular space-occupyinglesions: intraocular tumors, cysts, intraoculartamponade (gas, silicone, etc.), intraocular hem-orrhage (choroidal hemorrhage), etc.

(1) Topical and systemic administration of ocu-lar hypotensives

(2) Laser ablation of cyst or surgical cystectomy(3) Excision of intraocular tumor(4) Removal of tamponade materials(5) Removal of intraocular hemorrhage

3) Secondary angle-closure glaucoma due togoniosynechia without pupillary block ormovement of the lens-iris diaphragm (glauco-ma due to peripheral anterior synechia)

Persistent flat or shallow anterior chamber,inflammatory disease, post-corneal transplanta-tion, neovascular glaucoma, ICE syndrome, pos-terior polymorphous corneal dystrophy, iri-doschisis, etc.

(1) Medical treatment(2) Trabeculectomy(with or without antimetabo-

lites)

Seton implant surgery and cyclodestructivesurgery are last resorts to reduce IOP.

For peripheral anterior synechia due to persis-tent flat or shallow anterior chamber, lens extrac-tion and goniosynechiolysis might be effective insome cases.

(3) For neovascular glaucoma, retinal coagula-tion with laser or cryotherapy should beperformed whenever possible.

ⅢⅢ. Developmental glaucoma

1. Early onset developmental glaucomaSurgery is the first line of therapy for early-

onset developmental glaucoma for the followingreasons: 1) Since this type of glaucoma resultsfrom abnormal anatomical development of theanterior chamber angle, anatomical or surgicalcorrection is recommended. 2) Our experienceshows the effectiveness of surgery. 3) It is difficultto determine the effectiveness of medical therapyin infants and children because the procedure iscomplicated and may require anesthesia.Medical treatment is used as an auxiliary meansthe following types of surgery.

1) Surgical treatment(1) GoniotomyThis procedure is indicated in patients with

transparent cornea. In a single goniotomy proce-dure, an incision of 90-120 degrees can bemade. An additive effect is frequently seen withup to three repeated surgeries. The decision as towhether to perform goniotomy or trabeculotomyis based on the experience of the surgeon.

(2) TrabeculotomyAn advantage of this procedure is that unlike

goniotomy, surgery can be performed in caseswith hazy cornea. However, the conjunctival flapand scleral flap made for this procedure mayinhibit filtering surgery when it is necessary in thefuture. In eyes with megalocornea, it may be dif-ficult to identify Schlemm's canal in some casesand extensive surgical experience is required forperforming trabeculotomy.

(3) Filtering surgeryThis procedure is indicated in eyes for which

goniotomy or trabeculotomy is ineffective. Inpatients with early-onset developmental glauco-ma, the sclera is thin which makes it difficult toprepare a scleral flap, and anatomical anomaliesof the iris and ciliary body are common. Thedecision to perform this procedure must be madecarefully because in infants and children, filteringbleb formation may be difficult despite intraoper-ative use of antimetabolites. Even after filteringblebs are successfully formed, the patients may

48

be exposed to the risk of post-surgical infectionsfor the rest of their life because of the presence ofthe filtering bleb.

(4) Seton implant surgery

(5) Cyclodestructive surgery

2) Medical treatmentDrugs may be combined as specified for pri-

mary open-angle glaucoma. However, since ininfants and children, the dose of the drug admin-istered, even a topical drug, can be great inquantity with respect to body weight and bodysurface area, administration should begin withthe lowest possible dose. Clinicians must beaware that the safety and effectiveness of anydrug in infants and children have not been estab-lished.

2. Developmental glaucoma with other congeni-tal anomalies

Aniridia, Sturge-Weber syndrome, Axenfeld-Rieger syndrome, Peters, anomaly, persistenthyperplastic primary vitreous, Marfan syndrome,neurofibromatosis, rubella syndrome, congenitalmicrocornea, congenital exotropion uveae,Weill-Marchesani syndrome, homocystinuria,Pierre Robin syndrome, Lowe syndrome,Rubinstein-Taybi syndrome, Hallermann-Streiffsyndrome, etc.

Glaucoma is associated with the above dis-eases, although the probability of its incidencehas not been fully studied. Since the age of onsetvaries widely from birth to adulthood and mech-anisms of IOP elevation differ, treatment methodsare not uniform. As a rule, for infantile onset, thefirst-choice treatment is surgery as specified forearly-onset developmental glaucoma, while forlater pediatric onset, medical treatment is the firstchoice.

ⅣⅣ. Secondary glaucomas in childhood

Retinopathy of prematurity, retinoblastoma,juvenile xanthogranuloma, etc.

With incidence, onset, and IOP elevationmechanism varying widely in pediatric sec-ondary glaucoma, treatment methods are not uni-form.