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

Figure 6.7 shows the three indices relating these segments to each other:

Anterior chamber VI. Axial length

VII. VitreousAnterior segment (cornea + anterior chamber + lens)

Cornea + anterior chamber VIII. Vitreous

The statistical study of these segments demonstrated that for indices VI and VIII, there is no significant difference between normal and glaucomatous eyes. However, the difference is highly significant in index VII. Table 6.2 shows the values of these indices.

Index VI Anterior chamber and Axial length

index VIII Cornea + anterior chamber Vitreous

are significantly different in both populations, because in most cases, eyes exposed to ocular hypertension increase their anteroposterior length harmoniously, i.e., both anterior chamber and vitreous length grow. In contrast, index VII is significantly lower in glaucomatous children, since it includes the lens, whose thickness is lower in eyes with congenital glaucoma.

Echometric Asymmetry in Bilateral

Congenital Glaucomas

Of a total of 60 cases studied, 20 were unilateral and 40 bilateral. In the latter, a manifest asymmetry was found in axial length as well as in each of the segments making up the transparent media. This asymmetry might be related to the difference in IOP usually found in the two eyes of the same patient. This finding markedly contrasts with the values obtained both in normal children (33 eyes) and in bilateral megalocorneas (ten eyes) where asymmetry is typical.

The Value of Echometry in the Follow-Up of Pure Congenital Glaucoma

Echometry is a very valuable method for the followup of congenital glaucomas after surgery. This was re-

ported for the first time by Buschmann and Bluth [4]. As shown in Fig. 6.8, we have found four different types of progression in pure congenital glaucomas:

a.The axial length stops growing with time, reaching the normal range band and, as the child grows, progressing further within the normal range; then it continues its growth normally. In most cases, this axial length behavior is consistent with IOP regulation up to 4 years of age. The functional results depend on the preoperative axial length. Those cases with axial lengths of 23–24 mm have good functional results, while in those over 25 mm, the results are generally less favorable (Fig. 6.8, solid line).

b.The axial length continues its growth through successive postoperative check-ups, going outside the normal range band. This type is generally associated with ocular hypertension that has not been resolved by surgery. In these cases, if IOP readings are normal, it will have to be measured under general anesthesia on different days at different times, in order to detect IOP peaks. It should be remembered that during the first 24 months of age, the normal IOP values should not exceed 7–14 mmHg (Fig. 6.8, hatched line).

c.In some cases, even though the IOP is regulated, the axial length remains stable for some time, but starts to grow between 2 and 4 years of age, and then becomes stable again. This phenomenon was reported

by M. Massin and B. Pellat (personal communication). The reason for this has not been elucidated, but the IOP in these cases should be monitored more frequently (Fig. 6.8, dashed line).

d.Some cases in which the eye continues to grow parallel to the normal range, while the IOP remains regulated, have a good prognosis (Fig. 6.8, double line).

Figure 6.8 illustrates the four types of progression. When echometry is performed at week 1 or 2 postoperatively, in most cases it yields slightly decreased axial length values compared with those found before surgery, but 2 or 3 months later, they have returned to their previous values. This phenomenon is more evident in myopic eyes with pure congenital glaucoma.

Every time an echometry is performed in the fol- low-up of a case of congenital glaucoma, an A and B echography of the eye and orbit must always be made, as illustrated by the following case history.

Examples

Case 1

A 4-month old girl, referred to us by another ophthalmologist with a presumed diagnosis of congenital glaucoma. The first measurements of intraocular pressure were:

The symptoms persisted (marked photophobia), without corneal edema, with normal diameter of both corneas, and with physiological excavation of the optic nerve. The only remarkable point was the pressure difference between the right eye (15 mmHg) and the left eye (9 mmHg). In the normal pressure curve corresponding to the age of this child (4 months), the maximum intraocular pressure should not exceed 12 mmHg. However, it is very difficult to indicate surgery in an eye with an intraocular pressure of 15 mmHg and a clear cornea. We were not sure whether or not to operate.

At 6 months of age, echometry was done. The length of the vitreous in the right eye was 14.55 mm and in the left eye was 12.66 mm. In successive echograms, it continued increasing its axial length. We operated, the growth stopped, and the ocular pressure equaled that of the other eye. This case shows the value of echometry in cases with uncertain diagnosis.

Case 2

A 3-month-old male child presented in October 1978 with symptoms of unilateral childhood congenital glaucoma, with a corneal diameter of 12 in the right eye and 12.5 in the left eye (pathological eye); the intraocular pressure under general anesthesia was 10 mmHg in the right eye and 29 mmHg in the left eye. The cornea of the left eye presented a 0.78-mm edema compared with 0.54 mm in the normal eye. The length of the vitreous and the axial length were significantly greater than in the healthy eye (see table below). We successfully performed a trabeculotomy in the affected eye. Two months later, in December 1978, he came back for a check-up and, as can be seen in the table below, the ocular pressure was 8 mmHg in the right eye and

8 mmHg in the left eye, and the corneal diameter had not changed. However, note the length of the vitreous body and the axial length of the healthy eye that had no symptoms; at that time, they were greater than those of the operated unhealthy eye. We took these data into account but, with no symptoms and no increased ocular pressure, with a normal optic nerve, we did not feel it was right to operate.

Two months later, in February 1979, when the child came for a check-up, everything was found to be perfectly under control in the operated eye, but the ocular pressure in the previously healthy eye (right eye) was 25 mmHg and the length of the vitreous body and the axial length, as well as being greater than those of the operated eye, were also greater than they had been in December. The cornea had also progressed from 12 mm to 13.5 mm. We immediately operated on the eye and, as can be seen in Fig. 6.9 and the measurements table for Case 1, the intraocular pressure dropped to normal values and the rapid, progressive increase in echom-

etry values stopped. In time, when the child reached 1.5 years of age, the dimensions were normal. For the family, the treatment was a complete success, but we know that the second eye, instead of being operated at 7 months, should have been done at 4 months.

Case 3

A male patient came to us at the age of 8 years. In each eye another colleague had done four surgeries for congenital glaucoma. The right eye had normal pressure and the optic nerve was normal, while the left eye presented phthisis bulbi.

One examination per year was done during the follow-up. When he was 12 years old, while doing the echography after the echometry, I found a mucocele invading the orbit after breaking through the orbit’s inner wall, extending as far as the ethmoidal and frontal sinus (Fig. 6.10).

Conclusions

Axial length enlargement in children with congenital glaucoma is not a recent discovery, since the word “buphthalmos” was coined by Ambroise Paré in 1561 for its resemblance to a bull’s eye.

The value of echometry for an accurate comparison of the growth of normal and glaucomatous eyes was stressed by Gernet and Hollwich [3] and the importance of the follow-up of congenital glaucomas was highlighted by Buschmann and Bluth [4]. Based on these studies, we [5, 6] have proposed echometry as

a vital method for the diagnosis and follow-up [7] of congenital glaucomas.

The study of axial length in children with congenital glaucoma is a very valuable parameter, and this has been widely confirmed since 1983. It is very useful in the diagnosis of congenital glaucoma cases in which the IOP is slightly above the normal range, or in the diagnosis of glaucoma in the fellow eye of children thought to have unilateral congenital glaucoma. IOP was considered the most important variable in the diagnosis of congenital glaucoma until this new application of echometry was found. The main difference between tonometry in adults and children is that it is impossible to perform diurnal pressure curves in children. The second difference lies in the fact that in some places it is necessary to measure IOP under general anesthesia. The literature around the world indicates that Penthrane cannot be used in some countries, or other types of anesthetic agents are used, though these give inaccurate values since they modify the blood pressure or they influence the central nervous system. In other places, intubation is used. Using the method we have introduced, with Penthrane, the values obtained are highly accurate.

Even if the IOP is measured according to our method, and the reading is accurate, we cannot monitor IOP for 24 h as we can in adults (diurnal pressure curve). The IOP varies greatly over the 24-h period, while the axial length growth in congenital glaucoma reflects only long-term variations (days, months, or years), as a result of IOP rises in distensible eyes. An IOP reading is true only for that particular moment, when it was measured, while axial length values yield information on what has happened in the course of the disease, for a longer period up to the moment of the measurement.

Moreover, IOP readings are influenced by different anesthetic agents, but not echometry. Echometry is therefore the first vital parameter for diagnosis, followed by IOP measurement and other clinical studies.

Echometry is also vital in the follow-up of the disease. In one of our cases, both the family and the ophthalmologist thought surgery had been successful because the child, who had come for consultation with 40 mmHg of IOP, had reduced it to 20 mmHg. Nevertheless, they were wrong, because the normal maximum IOP for a child aged 12 months is 14 mmHg. In cases like this one, since echometry shows that the eye has not stopped growing and that the axial length is growing further outside the normal range, the ophthalmologist will be aware of this and will prescribe medical therapy or reoperation; otherwise the eye will develop irreversible optic nerve, visual field, and macular function damage.

Some cases have very elevated IOP with no axial length growth, but these are late congenital glaucomas in which the IOP started to rise at 5 years of age, when the sclera has already lost its elasticity. Leydhecker [17], Ytterborg [18], and Dannheim [19] called attention to the variations of scleral rigidity in children of different ages.

Many other authors have confirmed our findings and added further data on the value of echometry in the diagnosis and follow-up of congenital glaucoma (B. Schwartz, personal communication; G. Quigley, personal communication).

References

1.Sampaolesi R (1969) La pression oculaire et le sinus camerulaire chez l’enfant normal et dans le glaucome congénital aux dessous de l’âge de 5 ans. Docum Ophthal 26:497–515

2.Sampaolesi R, Reca R, Carro A, Armando A (1976) Normaler Intraokularer Druck bei Kindern bis zu 5 Jahren mit und ohne Allgemeinnarkose. Seine Wichtigkeit für die Frühdiagnose des angeborenen Glaukoms. In: Glaukom Symposium Würzburg 1974, Enke, Stuttgart, pp 278–289

3.Gernet H, Hollwich F (1969) Oculometrie des kindlichen Glaukoms. Ver Zusammenkunft Dtsch Ophthalmol Ges 69:341–348

4.Buschmann W, Bluth K (1974) Ultrasonographic follow-up examination of congenital glaucoma. Graefes Arch Ophthalmol 192:313–319

5.Sampaolesi R (1980) Ocular echometry in the diagnosis of congenital glaucoma. In: Thijssen JM, Verbeek AM (eds) Doc Ophthalmol Proc Series, Vol. 29. Dr. W. Junk, The Hague, pp 177–189

6.Sampaolesi R, Carusso R (1982) Ocular echometry in the diagnosis of congenital glaucoma. Arch Ophthalmol 100:574–577

7.Sampaolesi R (1983) Ocular echometry and the diagnosis of congenital glaucoma and its evolution. In: Krieglstein GK, Leydhecker W (eds) Glaucoma update II. Springer, Berlin Heidelberg New York, pp 175–184

8.Reibaldi A (1982) Biometric ultrasound in the diagnosis and follow-up of congenital glaucoma. Glaucoma editorial. Ann of Ophthalmol pp 707–708

9.Tarkanen A, Uusitalo R, Mianowicz J (1983) Ultrasonographic biometry in congenital glaucoma. Acta Ophthalmol 61:618

10.Calixto N, Cronemberg Sobrinho A (1981) Glaucoma cortisônico. Etudo de 15 casos. Rev Bras Oftalmol 40:19–42

11.Carvalho CA, Betinjane AJ (1983) Variações da biometria ultrasonografica em olhos normais nos primeiros 50 meses de idade. Arq Bras Oftalmol 46:96–99

12.Fledelius HC (1990) Eye size of the premature infant around presumed term. In: Sampaolesi R (ed) Ultrasonography in ophthalmology, 12. Kluwer, Dordrecht, pp 165–172

13.Jansson F, Kock E (1962) Determination of the velocity of ultrasound in the human lens and vitreous. Acta Ophthalmol Kbh 39:899

14.François J, Goes F (1975) Oculometry of progressive myopia. In: François J, Goes F (eds) Ultrasonography in ophthalmology. Bibl Ophthalmol 83:277–282

15.Espildora Couso J, Vicuña R (1979) Alteraciones biométricas en el control tardío del ojo con glaucoma congénito operado. Glaucoma Symposium. The Panamerican Congress of Ophthalmology, Miami, 1979

16.Leydhecker W (1973) Glaukom. In: Ein Handbuch, 2. Springer, Berlin Heidelberg New York, pp 58–75

17.Ytterborg J (1960) On scleral rigidity. Oslo University Press, Oslo

18.Dannheim R (1968) Bericht über die 69. Zusammenkunft der DOG, p 248

For the ophthalmologist, just as for any medical doctor in any other clinical or surgical speciality, the advances in molecular biology, which include those in genetics, are difficult to understand because of the terminology used and the modern biological concepts involved.

These advances are one of the best examples of socalled translational research (translating basic research into clinical practice and vice-versa), for the practical management of these new concepts deriving from this research [1].

Our goal here is to give an easily understood account of the genetics of glaucoma and the diseases within glaucoma and the new therapies becoming available today.

Different statistics from a variety of countries show that today at least one in 50 newborns suffers from a significant congenital anomaly, one in 100 has a singlegene abnormality, and one in 200 a severe chromosome disorder.

What Is a Chromosome?

Chromosomes are organelles located in the nucleus of normal human cells with a set number of 46 (Fig. 7.1), 44 of which are autosomes and two sexual chromosomes (XX or XY). Chromosomes are structures composed of deoxyribonucleic acid that are arranged in the shape of a paired double helix, one of which comes from the father and the other from the mother.

They can be classified with hematological stains such as Giemsa according to the position of their cen-

tromeres, a primary construction within them. The centromere is the point where the identical double helixes of deoxyribonucleic acid (DNA) join – this makes it possible for the chromosomes to be classified as (Fig. 7.2):

1.Metacentric;

2.Submetacentric;

3.Acrocentric.

In metacentric chromosomes, the centromeres are in the middle (these are chromosomes 1, 3, 19, and 20).

In the submetacentrics, the centromere divides the chromosomes into a short arm (called p from the French petit) and a long one (called q as this is the next letter in the alphabet).

Acrocentric chromosomes are those that have very short arms and also, different from the former, have satellites (deoxyribonucleic acid sequences) joined to the centromere (these are chromosomes 13, 14, 15, 21, 22, and the sexual Y chromosome).

Chromosome abnormalities can thus be classified by modifications in their number and shape. On this basis, with each cell, for example the endothelial cell of the human trabecular meshwork, having 46 chromosomes with different shapes depending on the position of the centromere, and each chromosome being made up of various genes, it is logical to think that at least part of the etiology of a disorder can be detected in these structures.

Chromosome Abnormalities

Chromosome abnormalities are those in which their number, shape, or internal characteristics are altered. The internal characteristics are the number of genes, type of genes, dominant or recessive, change in location, and mutation leading to a change in function. These alterations give rise to serious anomalies in the phenotypical and functional characteristics to which these genes respond.

Chromosome abnormalities are seen in numerical or morphological alterations. Numerical alterations involve an increase or reduction in chromosomes.

The best example of an increase in chromosome quantity is the trisomies: one example is Down syndrome, in which the general anomalies manifest as a mental deficit, cardiac abnormalities, and short stature. Ophthalmological alterations are mongoloid palpebral fissure, cataract, myopia, nodules in the iris, hypoplasia of the peripheral iris, keratoconus, etc.

In other trisomies such as 13, or Patau syndrome, and 18, or Edward syndrome, there are multiple ocular abnormalities, but glaucoma is rarely found.

As mentioned above, the alterations in the number of chromosomes can manifest as a reduction in the normal number. One example of these numerical alterations is monosomy, where instead of two chromosomes there is only one.

Turner syndrome is an example of monosomy, in which the somatic manifestations are short stature, skeletal anomalies, prominent ears, and mental retardation.

In the anterior segment, its ocular manifestations include epicanthus, ptosis, blue sclera, microcornea, eccentric pupil, cataracts, posterior embryotoxon, and fundamentally all have glaucoma as well as nystagmus.

In the posterior segment, the retina will show tortuosity of the retinal blood vessels, pseudopapillitis, optic atrophy, Coats disease, retinitis pigmentosa, macular aplasia, and basically glaucoma, color blindness, and strabismus. As a result of these manifestations, nystagmus may appear.

A second very interesting example is cri-du-chat syndrome, another monosomy, like Coats disease. Its somatic manifestations are severe abnormalities of the intestines, microcephaly and mental retardation, short metacarpal bones, and micrognathia. Ocular manifestations are hypertelorism, epicanthal folds, coloboma of the eyelids, tear reduction, exotropia, cataracts, and tortuous retinal blood vessels, but glaucoma is very rare.

Another very important example of monosomy presenting with glaucoma is Degrouchy syndrome, which