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

lacetic) is found in the urine, which has given rise to various tests to detect this substance, the most com-

-mon of which are:

The ferric chloride test, which gives a bluish green - color.

The Fishberg test: a drop of urine on a developed - photographic plate, dark brown in color.

The Momers and Katsch test: the urine alkalinized with ammonia takes on a red color when drops of hydrogen peroxide are added; it later turns brown.

For more details on the varieties of the clinical picture, consult the complete work of Dr. R.H. Cambiaso [11].

The following clinical history is particularly interesting because it shows the possible consequences of the infiltration of homogentisic acid on the tissues: spontaneous lens luxation and secondarily ocular hypertension [12].

Clinical Case No. 2

Endogenous Ochronosis (Alkaptonuria)

Clinical case no. 2, aged 63, was a male who consulted for pain and reduced sight in the right eye in February 1966. Ocular hypertension was found and it was treated with miotics. In April he returned with the same problem and the examination gave this result:

and external rectus muscles. There are also deposits below in the sclera, in the tendon insertion region of the internal and external recti, but these are bluish-black in color, as well as in the limbus at 3 and 9 o’ clock, in the form of small yellowish-brown drops. These accumulations are subepithelial. Greater magnification shows that beside each drop there are smaller drops that look like oil (Fig. 23.5).

The chamber angle is open but narrow.

The right eye showed edematous cornea. The anterior chamber was irregular in depth, flatter in the lower part. Dilating the pupil of the right eye showed the luxation of the lens upward and forward, letting a tongue of vitreous penetrate through the lower part of the pupil. The Berger space was also positive, as was the Wieger capsulohyaloid ligament.

At the height of the insertion of the external rectus, the dark color of the deposits of ochronotic pigment can be seen. Immediately after this region, toward the cornea, the deposits typical in conjunctiva can be seen, some of them in the form of complete rings and others in half-rings. In the cornea, next to the limbus, deposits of the same substance can be clearly seen as yellowbrown drops.

Biomicroscopy showed small brown or ochre-colored deposits in the deep planes of the conjunctiva of both eyes, in the form of commas and rings that move when the conjunctiva is moved at the insertion of the internal

X-rays of the dorsolumbar spine showed generalized osteoporosis with calcification of the intervertebral ligaments. There were multiple discopathies with ossification. Rhizomelic spondylitis (Betcherev disease) was diagnosed. The hips showed slight signs of bilateral arthrosis and ossification of the muscle tendon insertions in the iliacs.

Progression and Treatment

The progressive results (Fig. 23.6) show the first IOP measurement at 75 mmHg for the right eye and 16 mmHg for the left eye, with visual acuity 20/200 for the right eye and 20/20 for the left eye. The patient returned 1 month later, on May 10, 1966, and the IOP was still high: 62 mmHg. With miotics and Diamox treatment, it only decreased to 55 mmHg, so glycerol was tried orally, and on May 12 the IOP was checked

three times at 5:30, 7:30, and 10:30 to find the best time for performing surgery. On May 13, the lens was extracted, after administering glycerol, using cryoextractor. During surgery, a piece of conjunctiva was removed for a biopsy. The postoperative period was normal and, 1 year later, on June 12, 1967, the IOP was normal in both eyes – 16 mmHg in the right eye and 18 mmHg in the left eye – and visual acuity has increased in the right eye from 20/200 to 20/40 using a contact lens.

Anatomopathological

Examination of the Biopsy

-Macroscopy. The material sent was a grey-col- ored piece measuring 4×3×1 mm and was fixed in

-formol.

Microscopy (after paraffin embedding and staining with hematoxylin-eosin). The conjunctival stroma contained accumulations of homogeneous yellow- ish-brown material, varied in shape, some shaped like commas. There was extensive degeneration of the collagen fibers of the stroma, with abundant formation of hyaline-looking material. The epithelium of the conjunctiva was absent in some areas of the section, but the rest was normal (Fig. 23.7).

Seitz [13], made the first histopathological description of a biopsy of conjunctiva obtained from a patient with ochronosis. Since then, the work of Rodenhäuser [14], Rones [15], Allen et al. [16], and Ashton et al. [17] have confirmed and broadened Seitz’s observations. The conjunctival biopsies described by Seitz and Rodenhäuser are practically identical to ours: degeneration, homogenization and fragmentation of the elastic and collagen fibers, with deposit of hyaline material similar to that seen in pingueculae, as well as the presence of yellowish-brown ochronotic pigment, without definite structure or form (comma, ring, etc.).

The nature of ochronotic pigment, although it is not finally clarified, is probably the same as melanin. This is confirmed by studies made with the electron microscope by Cooper and Moran [18], as well as the special stains used by Rones (depigmentation, stains for melanin, iron, and fats) and Allen (Fontana, Nile blue sulphate, Variant 1, Variant 2, Masson’s trichromic, periodic acid-Schiff, cresyl violet, Mallory’s aniline blue).

According to Allen, the ochronotic pigment should be thought of as unleashing a process of destruction, either by altering the physical properties of the tissues with the consequent reduction of their resistance, or by directly producing their necrosis. In the sclera, Ashton has described degeneration of the elastic fibers, elastotic degeneration of the collagen fibers, and disappearance of the tissue cells. Duke Elder’s [19] opinion on this is similar to that of Allen and Ashton.

As yet there is no satisfactory explanation to justify the preference of the ochronotic pigment for the region of the interpalpebral opening. Anderson considers it may stem from the influence of the light easing the enzymatic activity of the tyrosinase.

Analyzing the ocular manifestations of the case we have just presented, this spontaneous lens luxation in a disease stemming from a metabolism error, similar to other clinical pictures or syndromes that also have lens luxation and metabolism error.

In conclusion, it is remarkable that:

1.In homocystinuria there is an error in the metabolism of methionine, as the cystathionine-synthetase does not act to change it into cysteine with the appearance of homocysteine in urine. In the first and the second of the histological preparations of Henkind and Ashton, a thickened basal membrane of the ciliary epithelium with marked atrophy of the unpigmented epithelium can be seen, which leads to a degeneration of the zonula with lens luxation and iridodonesis. The hyaline layer covering the atrophic epithelium is typical of this disorder. The electron microscope shows atrophy of the unpigmented epithelial layer, thickening of the basal membrane, the zonula with its granular appearance, and the normal pigment layer. The deficiency of the zonula stems from the alterations in the development of the ciliary epithelial cells that contain cysteine and are responsible for the formation of these fibers (Table 23.1).

2.In Marfan disease, hydroxyproline appears in the urine [20], and there are modifications in the mucoproteins and in the electrophoretic picture of the proteins, and lens luxation. In Marchesani disease, it is still not known whether there is a metabolism error.

3.In alkaptonuria, there are alterations in the uvea and in the ciliary body. Allen et al. described deposits of alkapton (Fig. 23.8).

For these reasons, we believe that the degeneration of the fibers of the zonula is possible in endogenous ochronosis and that this opens the way to the spontaneous luxation of the lens and secondarily to ocular hypertension.

Summary

In alkaptonuria and endogenous ochronosis, glaucoma is caused by a luxation of the lens from alterations in zonula at its insertion in the ciliary body where cysteine accumulates. It is actually secondary glaucoma, and its treatment consists in extracting the luxated lens, thus curing the glaucoma.

References

Fig. 23.8 Deposits of alkapton at the level of the ciliary body at the height of the source of the zonular fibers. This may explain the reason for the lens luxation. Courtesy of Allen O’ Malley and Straatsma

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Increased excretion of hydroxyproline in Marfan’s syndrome. Lancet 2:994

The congenital mesodermal dystrophies are systemic diseases and essentially consist of Marfan syndrome (arachnodactyly and dolichostenomelia) and Marchesani syndrome (spherophakia and brachymorphia). Both diseases, as well as their somatic manifestations, affect the eyeball. The basic manifestation is seen in alterations in the position and shape of the lens which, added to other ocular malformations can, secondarily, produce glaucomas. It is transmitted by autosomal dominant inheritance. There are great differences in gene penetrance and expressivity [1].

Marfan Syndrome

General Manifestations

The main symptom of Marfan syndrome is ectopia of the lens: 78% of the syndromes show this luxation or subluxation of the lens [3]. This problem was first described by Borger [4]. In most cases, the lens luxates upward and outward, but it can also do so toward the interior of the eye, and in these cases is accompanied by retinal detachment, or toward the anterior segment, accompanied by acute glaucoma. The eye may also present axial myopia. At other times, the myopia is caused by anterior luxation of the lens or by spherophakia.

At times there is spherophakia and microphakia [5–7]. These basic ocular manifestations may occur with coloboma of the lens [5]; coloboma of the iris [8, 9]; miosis, poor reaction to atropine, and aplasia of the pupil dilator [10–12]; aniridia [13]; pupillary membrane [14–16]; megalocornea [17]; buphthalmia [18]; coloboma of the optic nerve [19]; heterochromia iridis; and sometimes tapetoretinal degeneration [20, 21]. Marfan syndrome may also be found with Lobstein– van der Hoeve syndrome [22], blue sclerotics, bone fragility, and lung alterations.

Glaucoma

Marfan syndrome [2] is characterized by a lanky appearance (dolichomorphism) and long limbs (dolichostenomelia), particularly long-boned hands and feet. The third phalanx and the metacarpals in the hands are overlong. This, added to the retraction of the flexor tendons, creates a spider-like aspect, which is why it has been called arachnodactyly, or spider fingers. The thorax is pigeon-shaped, and there is kyphoscoliosis and dolichocephaly. These patients also present muscular hypotonia resulting from wastage of the muscles. The tendons are hyperextensible. This looseness of the ligaments favors luxations (congenital hip luxation). These are accompanied by heart and large blood vessel problems: interauricular and interventricular communication and dissecting aortic aneurysm. Marfan syndrome, then, is a malformation deriving from problems in embryo development of the mesoderm with localized manifestations in the bone and muscle system and in the elastic conjunctive tissues.

In some cases, glaucoma may be caused by the luxation of the lens to the anterior chamber, i.e., phacogenic glaucoma that is cured by extracting the lens, and in others by the presence of alterations to the chamber angle, with marked persistence of congenital mesodermal remains. The chamber angle in Marfan syndrome is very similar to that of congenital glaucoma, with very thick pathological mesodermal remnants. Reeh and Lehman [23] present the pathological anatomy of the chamber angle. They show how the superficial mesodermal layer of the iris continues at the angle with the outer wall, an iris lacking crypts, without collarette, and an endothelial membrane that covers the anterior surface of the iris. Other authors such as Burian and Allen [24] and Wachtel [25] describe alterations in the shape and size of the Schlemm canal.

Marchesani Syndrome

-General manifestations. Marchesani syndrome [26] is marked by brachymorphia. As opposed to Marfan syndrome, here the patient has a short stature, with a well-developed muscular system, good adipose panicle, and a pyknic constitution. Brachymorphia can be seen, as in Marfan syndrome, in the hands and feet, which are brachycephalous. Weill [8] was the first to describe ectopia of the lens in a 42-year- old patient who presented these clinical features (small hands and fat fingers). Heredity may be dom-

-inant or recessive, depending on the case.

Ocular Manifestations. The basic manifestation is seen in the alteration of the shape of the lens:

spherophakia, spherical lens, sometimes accompanied by microphakia. There may be luxation of the lens. There are some alterations of the chamber angle seen in the persistence of pathological mesodermal remnants with similar features to those of congenital glaucoma or late congenital glaucoma. The shape of the lens predisposes to high myopia, its luxation to phacogenic glaucoma, and the alteration of the angle to a late congenital type glaucoma.

Duke Estrada [27] presented a patient with glaucoma: in one eye the ocular hypertonia was secondary to an anterior luxation of the lens with pupillary blockage, while in the other eye, without lens luxation, there was marked ocular hypertension. The therapy in the first eye was extraction of the lens and in the second eye was goniotomy. The author describes the persistence of pathological mesodermal remnants in the chamber angle, extending beyond Schwalbe’s line.

N.Calixto(personalcommunication)haskindlyprovided Fig. 24.4, where a microphakic and spherophakic lens can be seen.

The glaucoma may occur through two mechanisms, either from pupillary block, by spherophakic lens (in-

verse glaucoma because the ocular pressure diminishes with mydriatics), or through lens luxation. However, Calixto has shown that despite extracting the lens, ocular hypertension persists.

Even though the lens has an ectodermic origin, the alterations it undergoes in these two syndromes stem from alterations of the ciliary muscle, which is generally very hypotrophic.

The clinical histories above on Marfan syndrome and the following two on Marchesani syndrome show how difficult it is to attribute glaucoma to the deep alterations of the anterior segment and the existence of lens luxation.

A Case of Marchesani Syndrome

Without Glaucoma

Clinical history No. 2 involves a 42-year-old male with a very deep anterior chamber in both eyes.

In the iris, atrophy of the peripupillary pigmentary layer can be seen, and in its ciliary zone there is peripheral iridodonesis, seen with transillumination. Both eyes have microphakic and spherophakic lenses. Varying the size of the pupil with eyedrops does not alter the IOP. The daily pressure curve is normal in both eyes. The chamber angle on both the right and left sides shows persistence of pathological mesodermal tissue with a picture similar to that of congenital glaucoma in children. The shape of the anterior chamber is trapezoidal.

A Case of Marchesani Syndrome with Glaucoma

Clinical history No. 3 involves a 35-year-old male. In 1956, he was seen for glaucoma in the left eye, with pain and colored halos. In 1962, he experienced temporary hemiplegia because of congenital arterial problems (thrombosis of the right brachiocephalic trunk, with no radial and carotid pulse and basilar trunk aneurysm). In 1966, a colleague operated the left eye for glaucoma. Today he shows the following features.

In the right eye, gonioscopy shows wide open angle, pigmented Schlemm canal. There is atrophy of the superficial and deep mesenchymal layer that reveals the epithelial pigmentary layer in triangular zones with an appearance identical to that of the chamber angle of the newborn child. The pathological mesodermal remnants are dysplastic and reveal the upper half of the ciliary body band, whitish in color, where the greater arterial circle of the iris runs and is visible at times. There is peripheral iridodonesis and deep atrophy of the iris pigmentary layer that enables the equatorial edge of the lens to be seen by transillumination. The diagnosis of microspherophakia can therefore be made. The atrophy of the pigmentary layer shows in two zones, one peripheral and one central next to the frill of the iris. The iris parenchyma is atrophic from the frill of the iris to the periphery. The left eye shows a similar picture in the anterior segment, plus a total iridodonesis from the complete luxation of the lens (Fig. 24.2).

A year and a half later, the patient returned because the lens in this eye had luxated. The extraction was made with cryo with no complications.

One year later, the patient returned with ocular hypertension of 28 mmHg in the right eye and surprisingly with the retina attached, with no surgery and a visual acuity of 20/30. The visual field can be seen in Fig. 24.3. The pressure was regulated with medication.

N.Calixto(personalcommunication)haskindlyprovided Fig. 24.4, where a microphakic and spherophakic lens can be seen.