Ординатура / Офтальмология / Английские материалы / Comprehensive Ophthalmology_Khurana_2007

4.Dilatation of pupil in patients with narrow anterior chamber angle may cause rise of IOP owing to a relative obstruction of the aqeuous drainage by the iris.

(B) General factors

1.Heredity. It influences IOP, possibly by multifactorial modes.

2.Age. The mean IOP increases after the age of 40 years, possibly due to reduced facility of aqueous outflow.

3.Sex. IOP is equal between the sexes in ages 2040 years. In older age groups increase in mean IOP with age is greater in females.

4.Diurnal variation of IOP. Usually, there is a tendency of higher IOP in the morning and lower in the evening (Fig. 9.7). This has been related to diurnal variation in the levels of plasma cortisol. Normal eyes have a smaller fluctuation (< 5 mm of Hg) than glaucomatous eyes (> 8 mm of Hg).

5.Postural variations. IOP increases when changing from the sitting to the supine position.

6.Blood pressure. As such it does not have longterm effect on IOP. However, prevalence of glaucoma is marginally more in hypertensives than the normotensives.

7.Osmotic pressure of blood. An increase in plasma osmolarity(asoccursafterintravenousmannitol,oral glycerol or in patients with uraemia) is associated with a fall in IOP, while a reduction in plasma osmolarity (as occurs with water drinking provocative tests) is associated with a rise in IOP.

8.General anaesthetics and many other drugs also influence IOP e.g., alcohol lowers IOP, tobacco smoking, caffeine and steroids may cause rise in IOP. In addition there are many antiglaucoma drugs which lower IOP.

GENERAL CONSIDERATIONS

DEFINITION AND CLASSIFICATION OF GLAUCOMA

Definition

Glaucoma is not a single disease process but a group of disorders characterized by a progressive optic neuropathy resulting in a characterstic appearance of the optic disc and a specific pattern of irreversible visual field defects that are associated frequently but

not invariably with raised intraocular pressure (IOP). Thus, IOP is the most common risk factor but not the only risk factor for development of glaucoma. Consequently the term ‘ocular hypertension’ is used for cases having constantly raised IOP without any associated glaucomatous damage. Conversely, the term normal or low tension glaucoma (NTG/LTG) is suggested for the typical cupping of the disc and/or visual field defects associated with a normal or low IOP.

Classification

Clinico-etiologically glaucoma may be classified as follows:

(A) Congenital and developmental glaucomas

1.Primary congenital glaucoma (without associated anomalies).

2.Developmental glaucoma (with associated

anomalies).

(B) Primary adult glaucomas

1.Primary open angle glaucomas (POAG)

2.Primary angle closure glaucoma (PACG)

3.Primary mixed mechanism glaucoma

(C) Secondary glaucomas

PATHOGENESIS OF GLAUCOMATOUS OCULAR DAMAGE

As mentioned in definition, all glaucomas (classified above and described later) are characterized by a progressive optic neuropathy. It has now been recognized that progressive optic neuropathy results from the death of retinal ganglion cells (RGCs) in a typical pattern which results in characteristic optic disc appearance and specific visual field defects.

Pathogenesis of retinal ganglion cell death

Retinal ganglion cell (RGC) death is initiated when some pathologic event blocks the transport of growth factors (neurotrophins) from the brain to the RGCs. The blockage of these neurotrophins initiate a damaging cascade, and the cell is unable to maintain its normal function. The RGCs losing their ability to maintain normal function undergo apoptosis and also trigger apoptosis of adjacent cells. Apoptosis is a genetically controlled cell suicide programme whereby irreversibaly damaged cells die, and are subsequently engulfed by neighbouring cells, without eliciting any inflammatory response.

Retinal ganglion cell death is, of course, associated with loss of retinal nerve fibres. As the loss of nerve fibres extends beyond the normal physiological overlap of functional zones. The characteristic optic disc changes and specific visual field defects become apparent over the time.

Etiological factors

Factors involved in the etiology of retinal ganglion cell death and thus in the etiology of glaucomatous optic neuropathy can be grouped as below:

A. Primary insults

1.Raised intraocular pressure (Mechanical theory). Raised intraocular pressure causes mechanical stretch on the lamina cribrosa leading to axonal deformation and ischaemia by altering capillary blood flow. As a result of this, neurotrophins (growth factors) are not able to reach the retinal ganglion cell bodies in sufficient amount needed for their survival.

2.Pressure independent factors (Vascular insufficiency theory). Factors affecting vascular perfusion of optic nerve head in the absence of raised IOP have been implicated in the glaucomatous optic neuropathy in patients with normal tension glaucoma (NTG). However, these may be the additional factors in cases of raised IOP as well. These factors include:

B. Secondary insults (Excitotoxicity theory)

Neuronal degeneration is believed to be driven by toxic factors such as glutamate (excitatory toxin), oxygen free radicals, or nitric oxide which are released when RGCs undergo death due to primary insults. In this way the secondary insult leads to continued damage mediated apoptosis, even after the primary insult has been controlled.

CONGENITAL / DEVELOPMENTAL

GLAUCOMAS

TERMINOLOGY

The congenital glaucomas are a group of diverse disorders in which abnormal high intraocular pressure results due to developmental abnormalities of the angle of anterior chamber obstructing the drainage of aqueous humour. Sometimes glaucoma may not occur until several years after birth; therefore, the term developmental glaucoma is preferred to describe such disorders.

Types

1. Primary developmental/congenital glaucoma.

flow. The retina and optic nerve share a peculiar mechanism of autoregulation of blood flow with rest of the central nervous system. Once the autoregulatory mechanisms are compromised, blood flow may not be adequate beyond some critical range of IOP (which may be raised or in normal range).

ii.Vasospasm is another mechanism affecting vascular perfusion of optic nerve head. This hypothesis gets credence from the convincing association between NTG and vasospastic disorders (migranous headache and Raynaud's phenomenon).

iii.Systemic hypotension particularly nocturnal dips in patients with night time administration of antihypertensive drugs has been implicated for low vascular perfusion of optic nerve head resulting in NTG.

iv.Other factors such as acute blood loss and abnormal coagulability profile have also been associated with NTG.

anomalies.

PRIMARY DEVELOPMENTAL/CONGENITAL GLAUCOMA

It refers to abnormally high IOP which results due to developmental anomaly of the angle of the anterior chamber, not associated with any other ocular or systemic anomaly. Depending upon the age of onset the developmental glaucomas are termed as follows:

1.True congenital glaucoma is labelled when IOP is raised during intrauterine life and child is born with ocular enlargement. It occurs in about 40 percent of cases.

2.Infantile glaucoma is labelled when the disease manifests prior to the child's third birthday. It occurs in about 50 percent of cases.

3.Juvenile glaucoma is labelled in the rest 10 percent of cases who develop pressure rise between 3-16 years of life.

When the disease manifests prior to age of 3 years, the eyeball enlarges and so the term‘buphthalmos’ (bull-like eyes) is used. As it results due to retention of aqueous humour (watery solution), the term ‘hydrophthalmos, has also been suggested.

Prevalence and genetic pattern

Most cases are sporadic. About 10 percent cases exhibit an autosomal recessive inheritance with incomplete peneterance.

Although sex linkage is not common in inheritance, over 65 percent of the patients are boys.

The disease is bilateral in 75 percent cases, though the involvement may be asymmetric.

The disease affects only 1 child in 10,000 births.

Pathogenesis

Maldevelopment of trabeculum including the iridotrabecular junction (trabeculodysgenesis) is responsible for impaired aqueous outflow resulting in raised IOP. In primary congenital glaucoma the trabeculodysgenesis is not associated with any other major ocular anomalies. Clinically, trabeculodysgenesis is characterized by absence of the angle recess with iris having a flat or concave direct insertion into the surface of trabeculum as follows:

Flat iris insertion is more common than the concave iris insertion. In it the iris inserts flatly and abruptly into the thickened trabeculum either at or anterior to scleral spur (more often) or posterior to scleral spur. It is often possible to visualize a portion of ciliary body and scleral spur.

Concave iris insertion is less common. In it the superficial iris tissue sweeps over the iridotrabecular junction and the trabeculum and thus obscures the scleral spur and ciliary body.

Clinical features

1.Photophobia, blepharospasm, lacrimation and eye rubbing often occur together. These are thought to be caused by irritation of corneal nerves, which occurs as a result of the elevated IOP. Photophobia is usually the initial sign, but is not enough by itself to arouse suspicion in most cases.

2.Corneal signs. Corneal signs include its oedema, enlargement and Descemet’s breaks.

i.Corneal oedema. It is frequently the first sign which arouses suspicion. At first it is epithelial, but later there is stromal involvement and permanent opacities may occur.

ii.Corneal enlargement. It occurs along with enlargement of globe-buphthalmos (Fig. 9.5), especially when the onset is before the age of 3 years. Normal infant cornea measures 10.5 mm. A diameter of more than 13 mm confirms enlargement. Prognosis is usually poor in infants with corneal diameter of more than 16 mm.

iii.Tears and breaks in Descemet’s membrane

(Haab’s striae). These occur because Descemet’s membrane is less elastic than the corneal stroma. Tears are usually peripheral and concentric with the limbus.

3.Sclera becomes thin and appears blue due to underlying uveal tissue.

4.Anterior chamber becomes deep.

5.Iris may show iridodonesis and atrophic patches in late stage.

6.Lens becomes flat due to stretching of zonules and may even subluxate.

7.Optic disc may show variable cupping and atrophy especially after third year.

8.IOP is raised which is neither marked nor acute.

9.Axial myopia may occur because of increase in axial length which may give rise to anisometropic amblyopia.

Examination (Evaluation)

A complete examination under general anaesthesia should be performed on each child suspected of having congenital glaucoma. The examination should include following:

Fig. 9.5. A child with congenital glaucoma.

1.Measurement of IOP with Schiotz or preferably hand held Perkin’s applanation tonometer since scleral rigidity is very low in children.

2.Measurement of corneal diameter by callipers.

3.Ophthalmoscopy to evalute optic disc.

4.Gonioscopic examination of angle of anterior chamber reveals trabeculodysgenesis with either flat or concave iris insertion as described in pathogenesis.

Differential diagnosis

It is to be considered for different presenting signs as follows:

1.Cloudy cornea. In unilateral cases the commonest cause is trauma with rupture of Descemet’s membrane (forceps injury). In bilateral cases causes may be trauma, mucopolysaccharidosis, interstitial keratitis and corneal endothelial dystrophy.

2.Large cornea due to buphthalmos should be differentiated from megalocornea.

3.Lacrimation in an infant is usually considered to be due to congenital nasolacrimal duct blockage and thus early diagnosis of congenital glaucoma may be missed.

4.Photophobia may be due to keratitis or uveitis.

5.Raised IOP in infants may also be associated with retinoblastoma, retinopathy of prematurity, persistent primary hyperplastic vitreous, traumatic glaucoma and secondary congenital glaucoma seen in rubella, aniridia and Sturge-Weber syndrome.

Treatment

Treatment of congenital glaucoma is primarily surgical. However, IOP must be lowered by use of hyperosmotic agents, acetazolamide and betablockers till surgery is taken up. Miotics are of no use in such cases.

Surgical procedures for congenital glaucoma

1. Goniotomy (Fig. 9.6). In this procedure a Barkan's goniotomy knife is passed through the limbus on the temporal side. Under gonioscopic control the knife is passed across the anterior chamber to the nasal part of the angle. An incision is made in the angle approximately midway between root of the iris and Schwalbe's ring through approximately 75°. The knife

Fig. 9.6. Technique of goniotomy : A, showing position of goniotomy knife in the angle under direct visualization; B, showing procedure of sweeping the knife in the angle.

is then withdrawn. Although the procedure may have to be repeated, the eventual success rate is about 85 percent.

2.Trabeculotomy. This is useful when corneal clouding prevents visualization of the angle or in cases where goniotomy has failed. In this, canal of Schlemm is exposed at about 12 O’clock position by a vertical scleral incision after making a conjunctival flap and partial thickness scleral flap. The lower prong of Harm’s trabeculotome is passed along the Schlemm’s canal on one side and the upper prong is used as a guide (Fig. 9.7). Then the trabeculotome is rotated so as to break the inner wall over one quarter of the canal. This is then repeated on the other side. The main difficulty in this operation is localization of the Schlemm's canal.

3.Combined trabeculotomy and trabeculectomy is now-a-days the preferred surgery with better results.

Fig. 9.7. Technique of trabeculotomy.

DEVELOPMENTAL GLAUCOMAS WITH ASSOCIATED ANOMALIES

A wide variety of systemic and/or ocular anomalies have an associated raised IOP, usually due to developmental defects of the anterior chamber angle. Some of the associations are as follows:

1.Glaucoma associated with iridocorneal dysgenesis. These include: posterior embryotoxon characterised by a prominent Schwalbe’s ring (Axenfeld anomaly), Rieger anomaly, Rieger syndrome, Peter’s anomaly and combined Rieger syndrome and Peter’s anomaly.

2.Glaucoma associated with aniridia (50% cases).

3.Glaucoma associated with ectopia lentis syndromes, which include Marfan’s syndrome, Weil-Marchesani syndrome and homocystinuria.

4.Glaucoma associated with phakomatosis is seen in Sturge-Weber syndrome ( 50% cases) and Von Recklinghausen’s neurofibromatosis (25% cases).

5.Miscellaneous conditions. Lowe’s syndrome (oculo-cerebro-renal syndrome), naevus of Ota, nanophthalmos, congenital ectropion uveae, congenital microcornea and rubella syndrome.

PRIMARY OPEN ANGLE GLAUCOMA AND RELATED CONDITIONS

PRIMARY OPEN ANGLE GLAUCOMA

As the name implies, it is a type of primary glaucoma, where there is no obvious systemic or ocular cause of rise in the intraocular pressure. It occurs in eyes with open angle of the anterior chamber. Primary open angle glaucoma (POAG) also known as chronic simple glaucoma of adult onset and is typically characterised by slowly progressive raised intraocular pressure (>21 mmHg recorded on at least a few occasions) associated with characteristic optic disc cupping and specific visual field defects.

ETIOPATHOGENESIS

Etiopathogenesis of POAG is not known exactly. Some of the known facts are as follows:

(A)Predisposing and risk factors. These include the following:

1. Heredity. POAG has a polygenic inheritance. The approximate risk of getting disease is 10% in the siblings, and 4% in the offspring of patients with POAG.

2. Age. The risk increases with increasing age. The POAG is more commonly seen in elderly between 5th and 7th decades.

3. Race. POAG is significantly more common, develops earlier and is more severe in black people than in white.

4. Myopes are more predisposed than the normals.

5. Diabetics have a higher prevalence of POAG than non-diabetics.

6. Cigarette smoking is also thought to increase its risk.

7. High blood pressure is not the cause of rise in IOP, however the prevalence of POAG is more in hypertensives than the normotensives.

8. Thyrotoxicosis is also not the cause of rise in IOP, but the prevalence of POAG is more in patients suffering from Graves’ ophthalmic disease than the normals.

(B)Pathogenesis of rise in IOP. It is certain that rise in IOP occurs due to decrease in the aqueous outflow facility due to increased resistance to aqueous

outflow caused by age-related thickening and sclerosis of the trabeculae and an absence of giant vacuoles in the cells lining the canal of Schlemm. However, the cause of these changes is uncertain.

(C) Corticosteroid responsiveness. Patients with POAG and their offspring and sibilings are more likely to respond to six weeks topical steroid therapy with a significant rise of IOP.

INCIDENCE OF POAG

It varies in different populations. In general, it affects about 1 in 100 of the general population (of either sex) above the age of 40 years. It forms about onethird cases of all glaucomas.

CLINICAL FEATURES

Symptoms

1.The disease is insidious and usually asymptomatic, until it has caused a significant loss of visual field. Therefore, periodic eye examination is required after middle age.

2.Patients may experience mild headache and eyeache.

3.Occasionally, an observant patient may notice a defect in the visual field.

4.Reading and close work often present increasing difficulties owing to accommodative failure due to constant pressure on the ciliary muscle and its nerve supply. Therefore, patients usually complain of frequent changes in presbyopic glasses.

5.Patients develop delayed dark adaptation, a disability which becomes increasingly disturbing in the later stages.

Signs

I. Anterior segment signs. Ocular examination including slit-lamp biomicroscopy may reveal normal anterior segment. In late stages pupil reflex becomes sluggish and cornea may show slight haze.

II. Intraocular pressure changes. In the initial stages the IOP may not be raised permanently, but there is an exaggeration of the normal diurnal variation. Therefore, repeated observations of IOP (every 3-4 hour), for 24 hours is required during this stage (Diurnal variation test). In most patients IOP falls during the evening, contrary to what happens in closed angle glaucoma. Patterns of diurnal variation of IOP are shown in Fig. 9.8. A variation in IOP of

over 5 mm Hg (Schiotz) is suspicious and over 8 mm of Hg is diagnostic of glaucoma. In later stages, IOP is permanently raised above 21 mm of Hg and ranges between 30 and 45 mm of Hg.

Fig. 9.8. Patterns of diurnal variations of IOP: A, normal slight morning rise; B, morning rise seen in 20% cases of POAG; C, afternoon rise seen in 25% cases of POAG;

D, biphasic variation seen in 55% cases of POAG.

III. Optic disc changes. Optic disc changes, usually observed on routine fundus examination, provide an important clue for suspecting POAG. These are typically progressive, asymmetric and present a variety of characteristic clinical patterns. It is essential, therefore, to record the appearance of the nerve head in such a way that will accurately reveal subtle glaucomatous changes over the course of follow-up evaluation.

Examination techniques. Careful assessment of disc changes can be made by direct ophthalmoscopy, slitlamp biomicroscopy using a + 90D lens, Hruby lens or Goldmann contact lens and indirect ophthalmoscopy.

The recording and documentation techniques include serial drawings, photography and photogrammetry. Confocal scanning laser topography (CSLT) i.e., Heidelberg retinal tomograph (HRT) is an accurate and sensitive method for this purpose. Other advanced imaging techniques include optical coherence tomography (OCT) and scanning laser polarimetry i.e., Nerve fibre analyser (NFA).

Glaucomatous changes in the optic disc can be described as early changes, advanced changes and glaucomatous optic atrophy. Figures 9.9A & B show normal disc configuration.

(a) Early glaucomatous changes (Figs. 9.9C&D) should be suspected to exist if fundus examination reveals one or more of the following signs:

1.Vertically oval cup due to selective loss of neural rim tissue in the inferior and superior poles.

2.Asymmetry of the cups. A difference of more than 0.2 between two eyes is significant.

3.Large cup i.e., 0.6 or more (normal cup size is 0.3 to 0.4) may occur due to concentric expansion.

4.Splinter haemorrhages present on or near the optic disc margin.

5.Pallor areas on the disc.

6.Atrophy of retinal nerve fibre layer which may be seen with red free light.

(b) Advanced glaucomatous changes in the optic disc (Figs. 9.10A&B):

1.Marked cupping (cup size 0.7 to 0.9), excavation may even reach the disc margin, the sides are steep and not shelving (c.f. deep physiological cup).

2.Thinning of neuroretinal rim which occurs in advanced cases is seen as a crescentric shadow adjacent to the disc margin.

3.Nasal shifting of retinal vessels which have the appearance of being broken off at the margin is an important sign (Bayonetting sign). When the edges overhang, the course of the vessels as they climb the sides of the cup is hidden.

4.Pulsations of the retinal arterioles may be seen at the disc margin (a pathognomic sign of glaucoma), when IOP is very high.

5.Lamellar dot sign the pores in the lamina cribrosa are slit-shaped and are visible up to the margin of the disc.

(c) Glaucomatous optic atrophy. As the damage progresses, all the neural tissue of the disc is destroyed and the optic nerve head appears white and deeply excavated (Figs. 9.10 C&D).

Pathophysiology of disc changes. Both mechanical and vascular factors play a role in the cupping of the disc.

Mechanical effect of raised IOP forces the lamina cribrosa backwards and squeezes the nerve fibres within its meshes to disturb axoplasmic flow.

Vascular factors contribute in ischaemic atrophy of the nerve fibres without corresponding increase of supporting glial tissue. As a result, large caverns or lacunae are formed (cavernous optic

atrophy).

IV. Visual field defects. Visual field defects usually run parallel to the changes at the optic nerve head and continue to progress if IOP is not controlled. These can be described as early and late field defects.

Anatomical basis of field defects. For better understanding of the actual field defects, it is mandatory to have a knowledge of their anatomical basis.

(A) Distribution of retinal nerve fibres (Fig. 9.11).

1.Fibres from nasal half of the retina come directly to the optic disc as superior and inferior radiating fibres (srf and irf).

2.Those from the macular area come horizontally as papillomacular bundle (pmb).

3.Fibres from the temporal retina arch above and below the macula and papillomacular bundle as superior and inferior arcuate fibres with a horizontal raphe in between (saf and iaf).

(B) Arrangement of nerve fibres within optic nerve head (Fig. 9.12): Those from the peripheral part of the retina lie deep in the retina but occupy the most peripheral (superficial) part of the optic disc. While fibres originating closer to the nerve head lie superficially in the retina and occupy a more central (deep) portion of the disc.

The arcuate nerve fibres occupy the superior and inferior temporal portions of optic nerve head and are most sensitive to glaucomatous damage; accounting for the early loss in the corresponding regions of the visual field. Macular fibres are most resistant to the glaucomatous damage and explain the retention of the central vision till end.

Progression of field defects. Visual field defects in glaucoma are initially observed in Bjerrum’s area (1025 degree from fixation) and correlate with optic disc changes. The natural history of the progressive glaucomatous field loss, more or less, takes the following sequence:

1.Isopter contraction. It refers to mild generalised constriction of central as well as peripheral field. It is the earliest visual field defect occurring in

glaucoma. However, it is of limited diagnostic value, as it may also occur in many other conditions.

2.Baring of blind spot. It is also considered to be an earlyglaucomatouschange,butisverynon-specific and thus of limited diagnostic value. Baring of the blind spot means exclusion of the blind spot from the central field due to inward curve of the outer boundaryof30°centralfield(Fig.9.13A).

Fig. 9.11. Distribution of retinal nerve fibres.

Fig. 9.12. Arrangement of nerve fibres within optic nerve head.

3.Small wing-shaped paracentral scotoma (Fig. 9.13B). It is the earliest clinically significant field defect. It may appear either below or above the blind spot in Bjerrum's area (an arcuate area extending above and below the blind spot to between 10o and 20o of fixation point).

4.Seidel’s scotoma.With the passage of time paracental scotoma joins the blind spot to form a sickle shaped scotoma known as Seidel’s scotoma (Fig. 9.13C).

5.Arcuate or Bjerrum’s scotoma. It is formed at a later stage by the extension of Seidel’s scotoma in an area either above or below the fixation point to reach the horizontal line (Fig. 9.13D). Damage to the adjacent fibres causes a peripheral breakthrough.

6.Ring or double arcuate scotoma. It develops when the two arcuate scotomas join together (Fig. 9.13E).

7.Roenne's central nasal step. It is created when the two arcuate scotomas run in different arcs and meet to form a sharp right-angled defect at the horizontal meridian (Fig. 9.13E).

Fig. 9.13. Field defects in POAG: A, baring of blind spot; B, superior paracentral scotoma; C, Seidel's scotoma; D, Bjerru-m's scotoma; E, double arcuate scotoma and Roenne's central nasal step.