Ординатура / Офтальмология / Английские материалы / The Glaucomas Volume 1 Pediatric Glaucomas_Sampaolesi, Zarate_2009

Heredity

Congenital glaucoma has recessive heredity and late congenital glaucoma has dominant heredity, as does pigmentary glaucoma. The following paragraph from François [53] explains this clearly.

1.“The penetrance and expressivity of a gene may vary from 0 to 100%; it is known that gene penetrance of a gene expresses the frequency of its phenotypical manifestations, and the expressivity the degree of this manifestation.”

2.“A gene in heterozygotic state always determines a less severe clinical manifestation than a gene in homozygotic state. This explains why a recessive disorder is often less severe than a dominant disorder. Considering these two facts, it is easy to imagine that there is no fundamental difference between recessive and dominant or intermediate heredity. If the penetrance and the expressivity are nil or very weak, the heredity will be recessive; if they are strong, dominant, and if they are average, intermediate. Dominance and recessivity do not indicate opposing forms of heredity but only, as Cuendeti and Streiff said: ‘the opposite ends of the same unbroken chain, of variable modes of heredity but basically identical.’

In pigmentary glaucoma, one can also think of a phenomenon of gene linkage, i.e., a linking up of different genes in the same chromosome. In one chromosome, there may be a link between the glaucoma gene and the one that causes the pigment dispersion (Shaffer 1967 [54]).

Genetics

Anderson and Anderson et al. [55, 56] located the responsible gene in the telomeric extremity of the long arm of chromosome 7 (7q35-q369) and more recently found a second place in chromosome 18q.

Heredity: Clinical Cases

Family 1. A brother with typical pigmentary glaucoma, whose sister presented late-onset congenital glaucoma with all the signs in the chamber angle but without pigment. The mother was glaucomatous (Fig. 20.38).

Family 2. This family had of one generation of nine siblings, one of whom had died. We examined the remaining eight, calling them after diagnosing pigmentary glaucoma in patient no. 6 in the Table below, and we found pigmentary glaucoma also in a 42-year-old brother and late congenital glaucoma in a 49-year-old sister. The other five siblings were normal (Fig. 20.39). Of 15 descendants of the second generation, we checked only seven and found glaucoma in none of them, but we must point out that the eldest of them was only 25.

It is remarkable that in all the siblings the Schwalbe line was more prominent than normal. This prominence is not evident in the 360° of the angle but in particular zones.

Figure 20.39 and the table above show the various elements we studied in Family 2: refraction, depth of anterior chamber, shape of anterior chamber, ocular pressure, corneal diameter, transillumination, ring on the posterior face of the lens, chamber angle, and Krukenberg spindle. Pigmentary glaucomas occurred in two brothers; in one sister, there was late-onset congenital glaucoma. The three siblings with glaucoma are myopic, and the greater the myopia, the more severe the glaucoma; the rest of the siblings are emmetropic or hyperopic. The depth of the anterior chamber is significantly larger in the siblings with glaucoma. The three siblings with glaucoma have chamber angles typical of congenital glaucomas. The shape of the chamber is trapezoidal in the three siblings with glaucoma, planoconvex in four siblings, and concave-convex in the sister with the flattest chamber. We analyzed seven members of the second generation. From these it is interesting to point out that one of them, 9 years of age, has myopia of −6 D and a pressure of 18 mmHg in one measurement. Two brothers, one 25 and the other 13, have peripheral iris atrophy, which reveals the iris epithelial layer, as occurs in children, one of them with myopia of −3 D in both eyes.

Fig. 20.38 Genealogic tree corresponding to the patient in Family 1

Family 3. The patient is a male who attended for consultation and pigmentary glaucoma was diagnosed. His brother, who accompanied him, had his ocular pressure taken “just in case” and was found to have

34 mmHg in the right eye and 27 mmHg in the left. A sister is normotensive. The mother has late congenital glaucoma (Fig. 12.40).

Optic Nerve

The optic nerve was studied with direct ophthalmoscopy, retinography with double magnification and finally with HRT 1, 2, and 3, depending on the stage.

The study of normality and the five phases of glaucomatous alterations was made following our personal system (Chap. 18). There is always a good correlation between ocular pressure, optic nerve, and visual field. Because the majority of cases of pigmentary glaucoma have very high myopia, the evaluation is more difficult.

Fig. 20.42 Retinography with congenital dysversion of the optic disc

In some case it is possible to see an anomaly of the optic disc (dysversion of the disc). Figure 20.42 and 20.43 show a retinography with a congenital optic disc anomaly: dysversion of the optic disc, or situs inversus, a very pronounced glaucomatous excavation, papillary cone toward the inferior nasal region, partial albinism in the sector from the optic disc to the inferior nasal region (closing point of optic vesicle).

The staging of the visual field was made in accordance with the Brusini staging system, in six stages depending on the gravity. We should remember that the defects appear 4–5 years earlier with nonconventional perimetry (FDT) than with conventional perimetry (SAP).

Today we use the perimeter Octopus 101 program G2, the FDT, Matrix, and the Pulsar.

The defects prevail in a combination of diffuse defects and scotomatous effects.

We will provide examples later in the clinical histories.

Natural History

Pigmentary glaucoma is a progressive disease that requires medical or surgical management. In some cases, it becomes less severe and the pigment dispersion may regress and sometimes the intraocular pressure returns toward normal after treatment. This is why in some cases it is necessary to perform a differential diagnosis with low-tension glaucoma.

Robert Ritch [57] called the first (clinically irreversible) condition pigmentary glaucoma and the second pigment dispersion syndrome (clinically reversible).

Differential Diagnosis

Among the juvenile forms of glaucoma can be found congenital, late congenital, pigmentary, and simple glaucoma.

I.Congenital component of the chamber angle (peripheral depression of the iris at 6 o’ clock, persistence of pathological mesodermal remnants over the trabecular meshwork, prominent Schwalbe line,

peripheral atrophy of the iris, etc.); II. Deep chamber and myopia.

III.Pigmentary syndrome (trabecular ring, Krukenberg spindle, pigment rings on the posterior face of the lens);

In general, pigmentary glaucoma shows components I, II, and III. In late congenital glaucoma, components I and II are found. In simple glaucoma, in the young person, these elements are absent. Pigmentary glaucoma seems to be a special form of late congenital glaucoma.

There are cases of this pathology with great pigmentary dispersion that develop from the posterior of the iris around the pupil where there is also atrophy. Pseudoexfoliation and pigmentary glaucoma can also be found together, as we have seen in several cases.

Severe Uveitis

These cases of uveitis are so severe that they have lost pigment from the posterior face of the iris but never have the characteristic signs of pigmentary glaucoma.

Cysts of the Ciliary Body Band or of the Iris Periphery

In these cases, though there is pigmentary dispersion, there is no Krukenberg spindle or deposit of pigment on the crystalline lens as in pigmentary glaucoma. Pigmentary dispersion may also be found in the melanomas of the ciliary body or in melanomas of the angle, but with a very different picture.

Pigmentary Glaucoma and Glaucoma for Pseudoexfoliation

It is rare, but both pigmentary glaucoma and glaucoma for pseudoexfoliation (PEX) can coexist in a single eye, as we have seen in our practice. Figure 20.44 shows the features differentiating the two pathologies. On the right can be seen the chamber angle (Fig. 20.44a); peripheral atrophy of the pigment layer of the iris in a well-developed case (Fig. 20.44b); with dilated pupil, pigment rings in the rear face of the len (Fig. 20.44c). On the left is illustrated a case of exfoliative syndrome and glaucoma is schematized (Fig. 20.44a): the chamber angle shows fine pigment in the form of waves that cross the Schwalbe line toward the rear face of the cornea (Fig. 20.44b); atrophy of the pigment layer of the iris, peripupillary (Fig. 20.44b); with dilated pupil, typical image in the anterior face of the lens (Fig. 20.44c). Figure 20.44d and Fig. 20.44e illustrate pigment distribution in pigmentary glaucoma and exfoliative syndrome. Figure 20.44e shows the location of pigment in exfoliative syndrome and Fig. 20.44f, the location of pigment in pigmentary glaucoma. In Fig. 20.44d, the pigment joins the exfoliative material and, since it forms a larger mixture, it cannot pass through all the

trabecular meshwork and therefore remains at surface levels, not even reaching the juxtacanalicular tissue. In Fig. 20.44e, the granules of pigment come together in

larger quantities opposite the Schlemm canal, but they can pass through the trabecular meshwork and settle inside the Schlemm canal and in the external collectors.

Fig. 20.44a–e On the left, glaucoma in pseudoexfoliation, and on the right, pigmentary glaucoma. a, Chamber angle with pigment that passes the Schwalbe line and deposits on the posterior face of the cornea in the form of waves (the Sampaolesi line). On the right, chamber angle in pigmentary glaucoma shows dark pigmentation in the Schlemm canal and pathological mesodermal remnants. b The pigmentation of the pigment layer of the iris: on the left, peripupillary, and on the right, peripheral. c With dilated pupil in pseudoexfoliation, the typical

deposit on the anterior face of the lens in two circles. On the right, in the posterior surface of the lens, the deposit of pigment, in two circles at the place of the insertion of the posterior zonula. d The deposit of the exfoliative material of the pseudoexfoliation on the posterior face of the trabecular meshwork. e The deposit of pigment on the posterior face of the trabecular meshwork, inside the trabecular meshwork, inside the Schlemm canal and in the collector channels

Retinal Detachment

and Pigmentary Glaucoma

In a series of statistics [58–61], we have steadily increased the number of cases of pigmentary glaucoma to 107 and we reached the conclusion that the incidence of retinal detachment in pigmentary glaucoma is 12.6%, while in the normal population it is 0.0001% [58–61]. Some months earlier in France, Brachet and Chermet [62] wrote an article on the association between pigmentary glaucoma and retinal detachment.

Pigmentary glaucoma is accompanied by myopia between sph −1 and −27 D in 73.5% of cases. A careful examination shows that not only is posterior hyaloid detachment very common, with its consequent posterior vitreous detachment, but the anterior hyaloid also detaches from the Wieger capsulohyaloid ligament up to the ora serrata. This posterior vitreous detachment and anterior vitreous detachment mean that it remains suspended only by its base (Fig. 20.45). Sometimes this base of the vitreous detaches, especially in the upper region, and the pigment of the posterior chamber passes through the ora serrata, over the retina. These changes, added to the peripheral degeneration of the retina, often lead to retinal detachment, in general,

bags with tears in their rounded (metacystic) ends (Fig. 20.46).

In pigmentary glaucomas, a careful study of its peripheral retina is always essential, and if lesions are found, they must be treated. For this reason also, miotics are contraindicated because, in these conditions, they provoke retinal detachment. This occurred in two patients in whom we provoked retinal detachment with pilocarpine.

The first manifestation of pigmentary glaucoma may be that of glaucoma or of retinal detachment. In the latter case, the diagnosis of pigmentary glaucoma is missed and the patient as well as the doctor may continue to be unaware of it. If the retinal detachment department makes a gonioscopic examination as a matter of routine, these cases are detected as pigmentary glaucoma. Even though the ocular pressure is very low at that time, if the retina attaches, the ocular pressure gradually increases and reaches pathological levels. If the medication is not sufficient to regulate the ocular pressure and there are progressive visual field defects, it is preferable to make a trabeculotomy instead of a trabeculectomy, since this regulates ocular pressure at rather higher levels between 20 and 24 mmHg, better for an eye that has suffered retinal detachment.

This patient was a 49-year-old female who had been operated for retinal detachment in the left eye 10 years earlier. During a check-up, the ocular pressure was found to be high.

The postsurgical gonioscopic picture is very interesting because the pigment disappeared in the zone of the trabeculotomy. This case is the opposite of the previous ones, because the retinal detachment presented first and then the pigmentary glaucoma became evident (Fig. 20.47).

Blockage of the Chamber Angle

After a Pupillary Dilatation

During Examination

In a young, 39-year old patient with typical pigmentary glaucoma with all the characteristics present, on dilating the pupil a pupillary block occurred in that eye, which raised the intraocular pressure to 55 mmHg. The UBM (Fig. 20.48) gave a typical picture of pupillary block. A UBM should always be done in cases of pigmentary glaucoma because it gives an idea of the morphology of the anterior chamber.

In the past, we have treated patients using adrenergic antagonists and agonists, beta blockers, etc. Today we treat them directly with prostaglandins from the start. If this does not regulate the IOP we add other drugs. In our experience, miotics should never be used, and even less the strong miotics, in this type of glaucoma. The high frequency of retinal detachment must not be forgotten. We have produced a retinal detachment by applying miotics.

Surgery

Campbell [63] proposed using peripheral iridectomy for pigmentary glaucoma. More than ten authors with long experience have communicated that peripheral iridectomy does not work. Jampel [64] published a paper titled “Lack of effect of peripheral iridectomy in pigmentary dispersion syndrome,” just as Lehto did [65]. In our hands, the surgery that gives best results is trabeculectomy. In the series comprising 107 cases, the operation performed was trabeculectomy in most cases, and in eight patients, trabeculotomy: 79.1% of them without medication and 16.2% with medication regulated their pressure and stopped the development of their visual field defect. The daily pressure curve, visual field, and optic disc monitoring showed the defect to be regulated. In the cases in which the daily pressure curve was not regulated, the field continued to deteriorate. And when the IOP was not regulated with medication, they were reoperated.