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

In the areas corresponding to the bullous keratitis, a typical histologic image was obtained (Fig. 21.15).

The basement membrane of the epithelium persisted in some areas (Fig. 21.13b). In other areas, the basement membrane was destroyed (Fig. 21.13a).

Bowman Membrane

The Bowman membrane was preserved in the periphery, with a an abnormal area, thinning to fully disappear in the paracentral area (Fig. 21.15). Fig. 21.16, magnified, shows the transition zone to the point where Bowman membrane has fully disappeared.

Stroma

There is an increased number of keratocytes at the central area (Fig. 21.17). Figure 21.18 shows the area where there is an anterior synechia of the iris and where both tissues are difficult to identify.

Descemet Membrane and Endothelium

Figure 21.18 show the persistence of the Descemet membrane and endothelium at the corneal periphery, but then they disappear before the formation of the anterior synechia of the iris.

Fig. 21.18a,b Peters anomaly. Posterior corneal surface. a The left end corresponds to the area of the incision created with the trephine and at the right end there is iris tissue which continues in the corneal stroma. The Descemet membrane is absent. In the central part of the f igure, the corneal periphery, there are remnants of both Descemet membrane and endothelium,

which disappear up to the area of the iris synechia. b With ×4 magnification, disturbances of the Descemet membrane and endothelium. The Descemet membrane is very thin, reduced to one-third of its normal thickness and the endothelial nuclei show pyknosis

Pathogenesis

Von Hippel [20], described the picture as an inner corneal inflammatory ulcer.

Peters [18] believed it was a congenital defect of the Descemet membrane in the center of the cornea, which gave rise to a ring-shaped synechia of the iris at this level, as well as to peripheral athalamia and glaucoma.

Meisner [22], examining a similar case, but associated with congenital aphakia, stated it was a defect in the closure of the crystalline lens vesicle.

Appelmans et al. [23] described the absence of the normal structures of the chamber angle.

Reese and Ellsworth [28] considered it to be a syndrome due to an anterior chamber cleavage disorder.

Alkemade [6] made the distinction between primary and secondary Peters anomaly. The primary form (similar to the case we described above) is quite rare, a developmental defect of the cornea, of recessive heredity; the secondary form is a component that may accompany Rieger mesodermal dysgenesis of the cornea and iris.

Nakanishi et al. [29], with electron microscopy, demonstrated that both Bowman and Descemet membranes, even where they appear as normal at the periphery, are actually not so, and that the Descemet membrane is similar to one formed 3 days after a wound. These authors quoted reports by Hay and Ravel [30], which show that the epithelium is responsible for the embryogenesis of Bowman membrane. Nakanishi et al. [29] state that if this is so, Peters anomaly is an ectodermal disorder, and that the absence of Bowman membrane, as suggested by Alkemade, renders Reese and Ellsworth’s description embryologically incorrect, since the part of the cornea involved in Peters anomaly does not develop during anterior chamber formation.

As we can see, each author, on different grounds, supports a pathogenic mechanism. However, since our focus here is on glaucoma, we would like to recommend a paper by Atsushi et al. [31] covering the ultrastructure of sclerocornea.

Figure 21.19, reproduced from this paper, shows a central epithelium in the sclerocornea of eight to ten cell layers with absence of Bowman membrane; there are vessels in the stroma (stained in toluidine blue) and a thinned Descemet membrane (0.8–1.5 µm) one-tenth the thickness of a normal eye. Nath et al. [32] have also researched the same topic. There are similarities in the Bowman and Descemet membrane anomalies revealed by this preparation and Peters syndrome. In addition, in Peters syndrome and sclerocornea, there are general somatic disturbances, cardiac malformations, etc. Bowman membrane is generally absent in leukomas, unlike Descemet membrane, which is always present.

In my opinion, Axenfeld posterior embryotoxon, Rieger mesodermal dysgenesis, sclerocornea, and Peters syndrome are all anterior segment disorders with features in common as well as with distinct characteristics, some which clearly separate them: iris mesodermal dysgenesis, dominant hereditary pattern, Peters anomaly, and recessive heredity. They may be associated with glaucoma, but the case described in clinical history no. 2 should be kept in mind. In this case, mother and son had Rieger dysgenesis with a large malformation of the anterior segment: the child had severe glaucoma, whereas the mother was normal. In contrast, in clinical history no. 4, both mother and child had anterior segment anomalies and they both had glaucoma. Glaucoma in only present when aqueous humor outflow pathways are disturbed. This explains the case described by Appelmans [23], in which he found a fully anomalous chamber angle, or the case we described, where glaucoma was only secondary and with a normal chamber angle.

In my practice, I have seen minor forms of Peters anomalies, a forme fruste of Peters anomaly, with broad-based implantation synechiae corresponding to pericentral leukomas with a flat chamber angle and glaucoma. Leukomas are generally small, and when they are transparent, they reveal the synechiae of the iris with the posterior corneal defect (Fig. 21.20).

Aniridia

This was described for the first time in 1819 by Barrata [33]. However, the name coined for this entity is only valid in its clinical aspect since in most cases there is a rudimentary iris: irideremia [34]. This rudimentary stump is visible on gonioscopy, since it is behind the corneoscleral limbus, and sometimes is directly visible (Fig. 21.21). It is made up of a fragment of pigmentary epithelium covered by mesodermal tissue (Fig. 21.22).

The features of this malformation have been broadened and improved gradually, and, at present, the con-

dition is much more widely studied. The iris is not the only structure involved. Other ocular and extraocular structures are also anomalous. As a consequence of malformations at the chamber angle, it is associated with glaucoma in two-thirds of cases.

There are no difficulties in clinically diagnosing it and the pediatrician detects it upon the first examination of the newborn. When the eye is illuminated, the whole anterior segment appears in a reddish color.

The presence of aniridia stands out but not the symptoms of glaucoma. We have examined 32 eyes with aniridia.

Fig. 21.22a,b Aniridia. a Pathologic anatomy (personal observation). b The same image as a with ×2.5 magnification. The Schlemm canal is seen as a white slit, covered by a thickened trabecular meshwork in some sectors (left). Remnants of mesodermal tissue extend from the anterior surface of this stump

up to the trabecular meshwork, at the level of the middle of the Schlemm canal. The iris stump at the level of its insertion is dramatically thickened compared to the normal iris root, which is very thin and made up only of a deep mesenchymal layer

Heredity

This is a hereditary disease. The individual suffering from it transmits it in a dominant, regular fashion, even in the absence of a family history [12].

The rate in both genders is the same, so it is present in 50% of the descendants. Sometimes, it may appear in a healthy family by a mutation, when only one individual in the family has the disease, and it is extremely rare in other offspring. This may be useful knowledge for genetic counseling. The genealogic charts of Figs. 21.24 and 21.27 show these two modalities.

There is a genetic relationship between aniridia and iris coloboma. The presence of aniridia is more frequent in children born to parents with iris colobomas [35]. Aniridia, iris colobomas, iris holes, and circumpupillary aplasia are part of a genetic unit. It is the polyphenic effect of the gene. However, it should be remembered that, of this genetic unit, only aniridia is associated with macula aplasia: the other manifestations are not. In our case, the same patient had aniridia and choroidal coloboma (see clinical history No. 16).

Sex

Aniridia has no specific preference for either sex. The sex distribution shows no significance: X2 = 1.0 [36].

Frequency

According to Mollenbach [37], one case occurs per 100,000 births.

Clinical Picture

1.Aniridia is generally bilateral and it is accompanied with other ocular and general manifestations.

2.Usually, there is a marked visual acuity loss. This is due to macular aplasia, when present, to the refractive error (myopia or hyperopia) or to lens anomalies. Macular aplasia is clinically characterized by the absence of the central reflex and of the yellow color upon ophthalmoscopy with green light and causes amblyopia and nystagmus.

3.Glaucoma is present in two-thirds of cases with partially similar characteristics to those of congenital glaucoma. The chamber angle has a similar aspect to that of congenital glaucoma, since there is a good correlation between the filtering scleral trabecular meshwork surface and the intraocular pressure.

The thicker the pathological mesodermal layer covering it, the higher the intraocular pressure. In small

children, this tissue is lax and has broad meshes. In adolescents, it is denser, but maintains its characteristic appearance. Sometimes, it extends up to the spur, and in some cases, it reaches the Schlemm canal and even the Schwalbe line.

There are also cases of iris stumps folded against the scleral wall of the chamber angle and attached or forming a synechia with it. In these cases, the intraocular pressure is very high and there is corneal edema. Here we completely agree with the report by Chandler and Grant [38]. There is typical atrophy of the ciliary processes.

In glaucoma with aniridia, the reason for consultation is the aniridia and not the glaucoma. There is generally no corneal edema. There are no tears in the Descemet membrane, the corneal diameters are generally normal, and there is no photophobia. Patients should be examined regularly since, in many cases, ocular hypertension develops later.

Cornea

There is a pannus around the whole corneal circumference, with vessels coming into the center superficially and going deeper in the stroma. Sometimes the cornea is almost completely opacified. This corneal process is part of the same anomaly. Even with very dense opacities, patients maintain some visual acuity allowing them some autonomy.

Crystalline Lens

In three cases, I have found a colobomatous-type lens malformation that may mislead the ophthalmologist into thinking of a lens luxation. Figure 21.23a, b shows this clearly. It should be kept in mind that during adulthood, the lens becomes opacified generally near 40 years of age. Fifty percent of patients develop cataract. In some of them, the lens, whether opacified or not, luxates.

Funduscopy

Peripheral lipidic retinal degeneration appears on funduscopy.

Nystagmus

Nystagmus is almost constant and is a consequence of poor vision or of the myopia due to macular hypoplasia or aplasia. A lack of macular reflex and yellow pigment is common.

Fig. 21.23a,b Aniridia. a (Top) a schematic representation of the chamber angle where there is persistence of pathological mesodermal remnants. The crystalline lens is colobomatous. A quick examination of the patient may make the ophthalmologist think of a luxation, which is actually not present. The upper margin is acute and the lower one, blunt, as shown by the

optical section (pear-shaped). The lower zonula is less dense and sometimes it is even absent. a The lens with a cataract suggests a luxation, but this is not the case. b Section with a slit lamp, which shows a lens coloboma and the distended zonula at the bottom (pear-shaped crystalline lens)

Clinical History No. 11

This 18-year-old female was diagnosed with aniridia -(Fig. 21.24). She had an alcoholic father.

Visual acuity. Finger-counting and nystagmus in - both eyes.

- IOP. Right eye, 17 mmHg; left eye, 27 mmHg. Crystalline lens. As shown by Fig. 21.24, there is a cataract in the lens of the right eye while in the left eye the lens is transparent, though both seem to be luxated towards the top.

However, a thorough examination reveals a small, malformed, and colobomatous lens (Fig. 21.25). This lens has a normal equator and zonule in its upper half. There is a missing and round-shaped lower half. In the inferotemporal area, the zonular fibers are elongated and absent in the nasal sector. The lens of the left eye, even though it is transparent, has no evidence of an intracrystalline structure. There is pigment in its posterior surface and a small opacity in the anterior surface, which protrudes from the capsule like in a pyramidal

-cataract.

Right eye. (1) Upper chamber angle: the corneal profile line continues directly into that of the ciliary

processes. Between the two, there is an iris stump of apparently 0.5 mm; the pathological mesodermal remnants reach out to the Schwalbe line. (2) Temporal chamber angle: the pathological mesodermal remnants uncover the Schwalbe line. The ciliary processes are atrophic and dark, there is a crest of uveal tissue in front of the ciliary processes and then the iris stump. The pars plana shows a transparent cyst at 11 o’ clock and two further cysts at the end of the ciliary processes at 9 o’ clock. (3) Inferotemporal chamber angle: at 6 o’ clock there is a transparent and oval cyst in the pars plana. The iris is reduced to merely a small elevation. The retinal concretions seem to be calcareous. At the area of the ora serrata, there is a cystic degeneration. The pathological mesodermal remnants reach the Schwalbe line in their fullness. This eye appears to have no pressure because there is atrophy of the ciliary processes. (4) Nasal chamber angle: the scleral trabecular meshwork is free. The pathological mesodermal remnants reach the spur and the heads of the ciliary processes are all inclined in the same direction. In this area, the iris is barely a raised surface. The retinal concretions are on a whiter retina, are smaller, and greater in number. (5) Funduscopy: the optic disc is atro-

phic, and there is nasal vessel rejection. The macula has no reflexes (aplasia). At the center there is pigment on the pigmentary layer of up to three optic disc diameters. Then at the periphery, the pigment

-disappears and the choroid becomes visible.

Left eye. (1) Chamber angle: this is not a lens luxation but an atypical coloboma. The iris is identical to that of the right eye, but there is no anterior formation of ciliary processes. (2) Temporal chamber angle: this is the same as in the right eye; the peripheral retina, at the lower area is full of lipidic concretions, and there is a prominent Schwalbe line; the iris tissue extends up to it. The ciliary processes seem to be less atrophic. (3) Nasal chamber angle: the same as in the right eye. There are no cysts in the ciliary body. (4) Funduscopy: the retina is in the same condition as in the right eye.

Fig. 21.24 Genealogical tree of case no. 11

Clinical History No. 12

This 17-year-old female was the only family member of five siblings with the disease (Fig. 21.26).

Fig. 21.26 Genealogic tree of clinical history no. 12

This 36-year-old male was the only family member with aniridia in a family of five normal siblings and normal parents. He has one boy and one girl born to a normal wife. His daughter has aniridia. A daughter born from

-his wife’s previous marriage is normal (Fig. 21.27). - Visual acuity: finger-counting in both eyes.

- IOP: 27 mmHg in both eyes.

Crystalline lens: both eyes show an iris stump with a pigment ectropion. The pathological mesodermal remnants are very aplastic and reach up to the spur.

- In some parts, the Schwalbe line is protruded. Funduscopy: both eyes show peripheral lipidic retinal degeneration and disc cupping of 5/6. Temporal margin less than 1/3.

This is a 3-month-old female (daughter of case history no. 13) (see Fig. 21.27).

This child is a 3-month-year-old male whose genealogic tree is shown in Fig. 21.28.

This is a mutation in a healthy family. The couple is concerned about the likelihood of the presence of the disease in future children. Our genetic advice was that they could have more children, and indeed three healthy boys were born. The mother has a brother with Down syndrome and her father is an alcoholic.

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Preoperative pharmacotherapy generally fails and surgery is required. Surgical therapy is successful in 30% of cases, but the addition of pharmacotherapy is required in two-thirds of them. The procedure used is combined surgery: trabeculectomy and trabeculotomy, with, in most cases, added pharmacotherapy; Ocusert is found to be very effective.

In aniridia, the use of contact lenses preventing the passage of light, with the iris drawn inside them, improves photophobia and nystagmus [39].

Pathologic Anatomy

In cases associated with glaucoma, the gonioscopic findings are confirmed by the presence of pathologic mesodermal tissue obstructing the trabecular meshwork, which is positive for Gomori’s stain. Figure 21.29 evidences this.

These specimens are from a child who was operated, before he turned 1 year of age, by myself and Dr. Alezzandrini. When glaucoma appears so early in aniridia cases, which is rare, we believe it to be a different clinical form.

Etiopathogenesis

The first descriptions of the area of the chamber angle in aniridia cases can be traced back to Pagenstecher [40], De Benedetti [41], and Lembeck [42]. These authors describe eyes with congenital aniridia and glaucoma in which the chamber angle is occluded by the iris stump (Fig. 21.23). They describe this formation and also affirm that the Descemet membrane unfolds into two layers at the periphery, one going to the trabecular meshwork and the other to the iris. In 1962, Hogan and Zimmerman [43] confirmed these findings.

Rindgleisch [44] and Collins [45] describe eyes with aniridia not associated with glaucoma, in which this anomaly is not confirmed by histology.

Barkan [46] and Higgitt [47] described a displacement of these pathological mesodermal remnants that occurs with time and that cover the trabecular meshwork, thus giving rise to late glaucoma.