Ophthalmologie» / i9; 161 176 (1965) From (he Ophlhalmological Department of the Italian Hospital, Buenos Aires M egalocornea an d M osaic D ystrophy o f th e C ornea By E. MALBRAK, C. D’ALESSANDRO and J. VALENZUELA Ophthalinologica. Vol. 149, No. 3 (1965) 10 Downloaded by: Vanderbilt University Library 126.96.36.199 - 10/27/2017 6:48:52 PM Mosaic degeneration of the cornea, the name suggested by Valerio in 1939, was described lor the first time by Vogt in 1930 when he called it “crocodile shagreen” of the cornea. Although Weizenblatt in 1928 had already observed a degenerative disease of the cornea with similar characteristics in six cases, the Swiss author undoubtedly deserves the merit lor his description and identification of the disease as a nosological entity possessing ils own characteristics. Valerio, in 1939, described a juvenile form of the same de generation which he called “mosaic degeneration”. This lesion was found in the region of Bowman's membrane and in the more superficial layers of the parenchyma. In 1942 this same author mentioned that the father of his patient was suffering from a bilateral bandiform degeneration, which caused him to consider the disease as a genetically dominant one, the different manifesta tion depending on the time of evolution. In 1947, St reiff presented a further case and Mtiller in 1949 presented a case of post-traumatic keratitis with hypopyon. This is the first description of mosaic degeneration secondary to trau ma, and histopathological evidence of the disease. In 1953 More and Amidei in a new case, studied histopathologicallv, established the fact that the biomicroscopical aspect of ¡ulterior mosaic degeneration was combined with the histological characteristics of an incipient band keratopathy. The authors felt that mosaic degeneration should not be considered as a separate clinical entity, but as a stage in the degenerative process of the cornea, in which the lesions are not confined to Bowman’s mem brane alone, but also to the epithelium and superficial layers of the stroma, until the final stage of band degeneration is reached. 162 M albran, D 'Alessandro anil Valenzuela Kopsa and Marusic in 1958 found a family of six with five of the members suffering from mosaic degeneration of Bowman’s membrane. Despite the fact that in the second and third cases there was a traumatic history, the spontaneous appearance of the same disease in the other members of the family and in the two following generations made the authors feel that they were deal ing with a dominant type of hereditary degenerative disease such as described by Valerio. In 19(51 Holes Carenini described three further cases of mosaic degeneration of Bowman’s membrane, in three brothers suffering from megalocornea. This author accepts the heredofamilial character of corneal degeneration although, unlike Valerio, Kopsa and Marusic, he cannot show its dominating character as he only observed one generation. François, using Franceschetti and Form’s classification, places mosaic degeneration amongst the anterior limiting membrane de generations. Franceschefli and Forni in 1950. and Franceschetti in 1954. in their well-known classification, places mosaic degener ation amongst the degenerations of the anterior limiting mem brane in the same location as band dystrophy. A study of the literature shows that there is a series of different varieties of “crocodile shagreen” of the cornea described by Vogt. varieties which are difficult to relate one to each other. We will describe the clinical forms which we have had the opportunity of observing. A. Central dystrophies. 1) Senile or pre-senile forms: (Fig. 1), with no known here ditary antecedents. They are bilateral and symmetrical, and effect more specially the pupilar area, but also spread in a large part of the cornea and then gradually disappear as they approach the periphery. These opacities occur in Descemet s membrane (Fig. 2), the other parts of the cornea remaining unaffected. Although, as in other clinical forms, they are always large where the opacity is more dense, in this case the pupilar area, we wish to point out that amongst the cases of mosaic degeneration we have studied Downloaded by: Vanderbilt University Library 188.8.131.52 - 10/27/2017 6:48:52 PM Primary Mosaic Dystrophies Downloaded by: Vanderbilt University Library 184.108.40.206 - 10/27/2017 6:48:52 PM Megalocornea and Mosaic Dystrophy of the ('.ornea 164 Malbrnn. D'Mcssnnilrn and Vnlenzueln 2) Hereditary Form: Recessive, linked to the heterologous part of chromosome X and associated with familial megalocornea. We have found mosaic degeneration associated with megalocornea in four male members of the same family. In all of these patients there was bilateral and symmetrical opacity, which was central, with no change in vision, and both uniform and harmonic as re gards distribution, type and size. The mosaic in all patients was of medium size and in every way similar to that described by Vof/t and Valerio. What appeared more peculiar was that in some cases the dystrophy was found in the area of Bowman's (Fig. 3 and 4) membrane and in another in Descemet's membrane, and in two cases in both areas. The fact that we found this opacity in both the anterior and posterior limiting areas in the same family and also the two type in the same patient, makes us wonder as to how far classification in accordance with its location in the cornea is valid. Downloaded by: Vanderbilt University Library 220.127.116.11 - 10/27/2017 6:48:52 PM this type has the smallest units. We could perhaps call it “Venetian mosaic”, this being the name given to this small mosaic, to dif ferentiate it from the other types. We have found this mosaic in four cases only, there being no other changes and no known ante cedents. Megalocornea and Mosaic Dystrophy of the Cornea 165 1?. Senile or Pre-senile Peripheric Types: This form of mosaic opacity is often found associated with gerontoxon. This is more visible in the region of Descemet’s mem brane, although in the majority of cases the demarcating lines of the mosaic can also be seen near Bowman’s membrane. Like the senile arch, there is a lucid interval between the limbic area and that where the mosaics are slightly larger than the classical ones described. We never found that this clinical form of rhomhoidal mosaic opacity affected the pupilar area. It is bilateral, symme tric and harmonic in distribution, size and shape of the opacities and a common symptom in the daily examinations carried out on patients over 50 years of age. This is similar to the senile arch with plexiform type of dark lines described by Vogt. Secondary Mosaic Dystrophies We have not had the opportunity of studying, as yet, the traumatic form described by Mailer but we have seen a post-in flammatory type. This occured in a femal patient who presented, following several cyclitical episodes, a bandiform opacity of the right eye with secondary and incomplete degeneration of Bow man's membrane, where opacities, irregular in both shape and size, could be seen in the form of a mosaic. It would appear that the secondary forms observed by Müller and seen by us in this case are unilateral, irregular, disharmonic as regards size and shape, and the largest mosaics as yet described. These secondary forms of dystrophy appear to support those opinions that sustain there is a relationship between the early mo saic degeneration and the final stage of band keratopathy. Familial Mosaic Degeneration and Megalocornea Case I. This patient, the propositus of our study, A. M., is a 47-vear-old male, married, with two single daughters, 19 and 17 years old respectively, lie is the third child, second son, of a total of three females and two males from his mother’s second marriage. The antecedents of the mother show that she had five children by her first marriage also, three males and two females. Downloaded by: Vanderbilt University Library 18.104.22.168 - 10/27/2017 6:48:52 PM The following is a description of a family in which various of its male members were found to be suffering from mosaic degeneration associated with megalocornea. 1 66 M nib ran, D’Alessandro and Valenzuela one of which (Case 3) presents a similar picture. The youngest daughter of this first marriage had only one child (Case 4i who is now 31 years old and who is also suffering from a similar disease. The maternal grandfather of Case 1 had four children, only one of which was a female. According to reports he was operated for cataract and had noticeably large eyes, but no other data exists. The patient’s brother (Case 2) also has the same disease and is now blind. Examination: Cornea: both corneas have a diameter of 14 mm, inegalocornea, with radius betw'een 7.2 and 7.4 (Javal). In the region of Descemel’s membrane and occupying the pupilar area only, approximately 4 lo 5 mm. a greyish opacity could be seen made up of small polygonal figures separated by perfectly trans parent dark lines. These opacities are larger in the center and then become smaller and disappear into the normal cornea tit the pe riphery. Anterior Chamber: This is deeper than normal (4 mm between the endothelium and the border of the pupil). Gonioscopy: Wide “Arrondi” type angle with a large number of iridian trabeculae and with typical aspect of high pseudo-insertion of the iris, such as is seen in congenital glaucoma. Lens: Right eye, intumescent cataract. Left eye, nuclear cataract. Fundus oculi: No anomally of the retina of Ihe left eye can be seen. Vision: Right eye, good light projection. Left eye Vm. 1.0. P.: Goldman s aplanation tonometer shows both eyes to have 12 mm HG. Both eyes were operated by us for cataract with an interval of one year between operations. At the present time his vision is 20/20 and 20/30 with Sph - 9 Cyl. + 1 at 175° and Sph + 9 Cyl. -f 0.75 at 100°, in right and left eyes respectively. Summary: Megalocornea, incomplete congenital glaucoma, cataract and mosaic degeneration of Descemet’s membrane. Examination: Cornea: Both corneas show 15 mm. diameter. Corneal radii between 8.2 and 8.9 (Javal). Both eyes the same central greyish opacity as in Case 1, although in this case it in vades the region of Bowman’s membrane and apparently the par enchyma as well. Anterior Chamber: Deeper than normal in both eyes: 6 mm. Gonioscopy: “Arrondi” type wide angle in both eyes. High pseudo-insertion of the iris. Iris: There is marked atrophy of the mesodermic sheath in both eyes. The right eye also shows Downloaded by: Vanderbilt University Library 22.214.171.124 - 10/27/2017 6:48:52 PM Case 2. F. M., 48 years of age, bachelor. Elder brother of Case 1. Progressive loss of vision from youth. Lost the vision of his right eye suddenly and was operated for retinal detachment. The left eye was operated for cataract by another surgeon four years ago. Megalocornea and Mosaic Dystrophy of the Cornea 167 marked atrophy of the collarette, withe seclusion. The pupil of the left eye is free and round following surgical aphakia. Lens: Right eye, complete cataract with folds in the capsule, epithelial proliferation as seen in inveterate retinal detachment. Left eye, pale nerve with glyal proliferation at the centre. Vision: Right eye. poor light projection. Left eye. light perception. I.O.P. Aplanation tonometer shows right eye 10 mm HG and left eye 26 mm HG. Summary: Megalocornea (incomplete congenital glaucoma), mosaic degeneration of Bowman’s membrane. Cataract with cap sular-lenticular proliferation and probable detachment of the re tina of the right eye. Complete surgical aphakia and round pupil in the left eye. Case 3. A. I)., 55 years old, married man. Stepbrother of Cases 1 and 2 (mother's first marriage). Large eyes since childhood. Progressive diminution of vision, more marked in tire right eye, beginning some years ago. Fig. o Downloaded by: Vanderbilt University Library 126.96.36.199 - 10/27/2017 6:48:52 PM Examination: Cornea: Cornea of 18 mm in both eyes. Giant megalocornea (Fig. 5). Corneal radii between 8.5 and 8.7 mm. Grey ish opacities in the form of mosaic occupying the centre in an ex tension of from 6 to 7 mm leaving the periphery completely free. These opacities are located in the region of Bowman’s membrane I ISS Malbnm, D'Alessandro and Valenzuela and, as in (aise 2, the parenchyma appears to be compromised as does also Descemet's membrane, though this is not so noticeaisle as in Bowman’s membrane. Anterior Chamber: Unusually deep in both eyes, 6HI and (5 mm. Gonioseopy: In both eyes the picture is exactly similar to Case 2. Iris: Bilateral iridonesis. Ex treme atrophy of the anterior sheath. Lens: Bilateral phako donesis. Intumescent cataract in the right eye. Nuclear cataract in the left eye. Vision: Good light projection in the right eye, left eye 1/10. Both eyes were operated using enzymatic zonulolysis and peripherical iridectomy. Present visual acuity of 5/10 and 6/10 using spectacles. Summary: Megalocornea (incomplete congenital glaucoma), cataract, mosaic degeneration of Descemet’s and Bowman’s mem branes. Case i. K. L., 31-year-old male, married, with two sons aged four years and four months respectivilv. Only child of Ihe only sister of Case 3. Large eyes since childhood. Examination: Cornea: Corneal diameter of 15 mm in both eyes Imegalocornea). Corneal radii between 7.5 and 7.8. Mosaic opaci ties in the pupilar fields in the region of Bowman's and Descemet’s membranes. Bilateral Krukenberg’s spindle. Kayser’s ring in both eyes, similar to that of keraloconus which is more marked in the right eye. Anterior Chamber: Depth: right eye 4 'A mm, left eye 5 mm. Gonioseopy: Intense dark brown pigmentation of the scleral trabecula in both eyes, more specially the right eye. Scleral spur perfectly visible. The gonioscopical aspect is reminiscent of a pigmentary glaucoma. Iris: Atrophy of the mesodermie sheath. Lens: Normal. Fundus oculi, normal. 1.0.P.: Aplanation tonometer shows 12 mm IIG in both eyes. Vision: Right eye, 10/10 with Sph - 1.25 Cyl. - 1.75 at 10 . Left eye 10/10 with Sph - 1.75 Cvl. 0.75 at 170°. Summary: Megalocornea (incomplete congenital glaucoma). Anterior and posterior mosaic degeneration. Kayser’s ring. Atypi cal gerontoxon. Krukenberg’s spindle (pigmentary glaucoma?). The majority of familial megalocornea pedigrees are charac terized by the appearance of the recessive sex-linked form (Waardenburg 10(>1, François 1958).That is to say that heredity is pos- Downloaded by: Vanderbilt University Library 188.8.131.52 - 10/27/2017 6:48:52 PM Discussion Megalocornea and mosaic-like dystrophy Woman married twice Probably megalocornea and cataract 0 Carrier of both disorders in one X-chromosome D Megalocornea. Anterior and posterior mosaic dystrophy. Cataract B EB E Megalocornea. Anterior mosaic dystrophy. Cataract m Megalocornea. Posterior mosaic dystrophy. Cataract Megalocornea. Anterior and posterior mosaic dystrophy Abnormal Bowman’s reflex Propositus Fig. 6 169 a Downloaded by: Vanderbilt University Library 184.108.40.206 - 10/27/2017 6:48:52 PM Examined case Megalocornea and Mosaic Dystrophy of the Cornea Ophthalmologies, Vol. 149, No. 3 (1965) X Malbran, D'Alessandro and Valenzuela sible due to the responsible gene, with :i recessive characteristic, occupying the non-homologous part of chromosome X. Frieda in 1923, and Alaerts in 1949, mention in other pedi grees a sex-linked form with lielerozygole manifestation in the woman (intermediate heredity due to increased expressivity of the gene). In the majority of familial cases of megalocornca with heredity linked to chromosome X, the lens are enlarged and the cataract develops late in life. The association of cataract, subluxation of the lens and iridonesis is often found in familial megalocornea. If we accept the dual criterion of megalocornea and con genital glaucoma as separate entities, the genetic interpretation is not so difficult. But if the unicist theory is allowed, which consid ers megalocornea to be just an incomplete congenital glaucoma, a fact accepted by us in an earlier paper (Malbran and Dodds, 1960), the genetic interpretation is somewhat more complicated. The finding amongst brothers of megalocornea without glau coma, complete, early or late congenital glaucomas, Marfan’s syndrome, etc., apart from some indisputable morphological characteristics, makes it difficult to definitely separate these dis eases and makes the genetic study somewhat uncertain. As to heredity of crocodile degeneration, we have seen that in the cases described, emphasis is placed on the dominant character of the diseases and always referred to anterior mosaic degeneration or degeneration of Bowman’s membrane. As regards posterior mo saic degeneration, as stated by Waardenburg (1961), it is only considered a senile factor up to the present. Boles Carenini (1961), when describing his cases of megalo cornea and mosaic degeneration in three brothers out of a family of five brothers, states that this confirms its heredofamilial char acter, but as he did not study the parents he cannot confirm the dominant character. Probably even if it had been possible to per form this examination no data would have been obtained without a study of the previous generation. Specially if, as we believe, the coupling of the gene of mosaic degeneration to that of megalo cornea in the same chromosome is ruled by the recessive heredity linked to chromosome X, typical of megalocornea, and which was found by us in the family under discussion. The analysis of our pedigree (Fig. 6) shows the following: the first case in the family to be affected was the grandfather of the “propositus”. Although we have no precise data, we do know that Downloaded by: Vanderbilt University Library 220.127.116.11 - 10/27/2017 6:48:52 PM 170 171 he had large eyes (megalocornea) and that he was operated on for cataract. All the other cases suffering from megalocornea and mosaic degeneration in the third and fourth generation are males and have all been examined by us. Apart from the data given re garding the maternal grandfather, which allow one to suppose that he suffered from megalocornea at the very least, amongst the descendents of both marriages of the mother of the “propositus”, two males in each branch are affected; this being a clear demon stration that the carrier of the abnormal genes was this twice married woman. The fourth case, in the fourth generation, son of the second daughter of the first marriage, is another factor which shows that in this family ihe sons suffer from the disease which is transmitted by the genotypically affected women, who are phenotypically healthy. The foregoing proves that in this family megalocornea and mosaic degeneration are genetically manifested in recessive heredity form allied to the sex chromo some X. Horner’s law is applicable in the cases of the first and third generation, where the disease passed from the parents to the grandchildren without affecting the children. This type of here dity transmission is the one most often observed amongst the dif ferent pedigrees of megalocornea studied, but we think that this is the first family in which the hereditary character can be ascribed to mosaic degeneration of the cornea. This is probably the same type of heredity suffered by Boles-Carenini’s cases of megalocornea and mosaic degeneration of the cornea. In this pedi gree it is quite clear that both diseases, megalocornea and mosaic degeneration of the cornea are simultaneously transmitted and not independently, as this is the only case we have seen associated in the same patient and not inherited independently. We must accept the fact that there has been gene linkage of the pathologi cal genes of megalocornea and degeneration in mosaic, genes linked in coupling and both occupying the heterologous portion of one chromosome. This form of heredity, gene linkage, has, up to now, only been described in a form of myopia associated with hemeralopia and in a type of haemophilia linked to dyschromatopsia. On the other hand, as stated by François, the identification in the human of linkage or coupling requires the study of three successive generations. The intermediate sex linked heredity by which there are some phenotypical signs of the disease amongst the female carriers (intermediate phenotypia) should be discard- Downloaded by: Vanderbilt University Library 18.104.22.168 - 10/27/2017 6:48:52 PM Megalocornea and Mosaic Dystrophy of the Cornea Malbran, D’Alessandro and Valenzuela ed in the present family, at least insofar as referred to megalocornea, this latter disease being quite evident even by the non professional. However, mosaic degeneration of the cornea may have existed as it is only found by biomicroscopical examination because it does not alter the visual acuity. We carried out this latter examination on a woman who was, unquestionably, a car rier, the mother of Case 4 and found no signs of the two diseases under discussion. It now remains for us to discuss the semiological characteris tics as related to the genetic value in the pedigree we are present ing. Apart from the reasons we have mentioned regarding the familial character of the disease in our patients, we also find that they follow the fundamental rules of hereditary diseases: 1) Homochronicity: it begins at about the same age in the same family. 2) Homology and homotype: the same disease in all the affected members of the family. 3) Intrafamilial constancy in evolution. In agreement with the other semiological elements characterizing our cases, we found the following: Megalocomea: This malformation was naturally present since birth in the four cases, with some small morphological variations. Mosaic Degeneration: As a general rule the changes in the cor nea were much alike in all four cases as regards form, size, and surface occupied by the polygonal opacities. In respect to size we have the impression that, comparatively speaking, the youngest patient had a slightly smaller mosaic than the three older cases (1, 2, 3). We must stress one important detail, that is, we found that the area primarily affected (Bowman’s or Descemet’s mem branes) were different amongst the respective members of this family: i.e., a clear case of mosaic degeneration of Descemet’s membrane, as in case 1: mosaic degeneration of Bowman’s mem brane, case 2; and in cases 3 and 4 both Bowman’s and Descemet’s membranes were simultaneously affected. In our opinion these observations where the opacities are dis tributed in different layers in the same pedigree, are an impor tant aid towards the understanding of mosaic degeneration, show ing, as they do, that when both the superficial and deep layers are compromised this does not necessarily mean that two sepa rate entities are entailed. We cannot establish anything certain as regards homochronicity of mosaic degeneration with our patients. We found this change to be present in the three patients of the Downloaded by: Vanderbilt University Library 22.214.171.124 - 10/27/2017 6:48:52 PM 172 Megalocornea and Mosaic Dystrophy of the Cornea 173 third generation at 55, 48 and 47 years of age respectively, and in the fourth generation at 31 years of age. As regards visual acuity, we found that it is not affected to any great extent. The appear ance of a cataract in three of the patients over 40 years of age is frequent in cases of familial megalocornea, where lens opacity may show up as a late complication of the syndrome. There are no changes in the lens in the 31-year-old patient, case 3, up to the present. To conclude our findings on this pedigree, we wish to state that the clinical features of case 4 in respect to its similarity to pigmentary glaucoma, may be another contribution regarding the relationship between megalocornea, congenital glaucoma and pigmentary glaucoma, as was suggested by J. Malbran (1957), and commented on by us elsewhere (1960). Mosaic degeneration of the cornea is a change in this mem brane which can be caused by different etiologies: senile or he redity forms (primary dystrophies); inflammatory or traumatic forms (secondary dystrophies). As regards pedigree, there are pedigrees known which show the simultaneous appearance of mosaic degeneration and megalocornea in the same individual (Boles-Carcnini and the cases we present here). The character istic opacities of corneal dystrophy may appear in diverse loca tions in the affected cornea according to their distribution in the pupilar or limbic areas or in the region of Bowman’s or Descemet’s membranes, or else in both simultaneously. These opacities vary as to regularity, size or shape, and can be unilateral or bi lateral. Although there are some differences in the clinical forms discovered up to now, we may say that in the primary forms of mosaic degeneration, whether senile or hereditary, there is a cer tain regularity and symmetry (bilateralness) as regards distribu tion, form and size of the polygonal opacities. On the other hand, in mosaic degeneration secondary to traumatic or inflammatory processes, caused probably by identical pathogenies, the asym metry (unilateral in all the cases described up to now), the ir regularity of size and shape of the opacities, is very noticeable. These latter types, as the semiological and histopathological data mentioned would suggest, constitute a bond of union between this dystrophy and the so-called band keratopathy. As in the ma jority of cases, this type of opacity of the cornea does not alter Downloaded by: Vanderbilt University Library 126.96.36.199 - 10/27/2017 6:48:52 PM Conclusions 174 Malbran, D'Alessandro and Valenzuela visual acuity and ¡1 is probable that it has not been recognized more often, especially when associated with other types of ocular or general pathology. Up to the present time two forms of hereditary transmission have been proposed: dominating autosomic heredity and reces sive, linked to the heterologous part of chromosome X and asso ciated with megalocornea in the pedigree presented by us. If our conclusions as to the genetic order are correct, this form of hered ity is a further example of gene linkage and coupling in the same sexual chromosome of a determined pair. The unexpected find ing in one pedigree with intrafamilial constancy, and compromise of different corneal layers in different members of the family, with mixed forms in one patient, is one more element leading us to suppose that this dystrophy of the cornea is a form of reaction of the limiting membranes to noxae and that “crocodile” degener ation of Bowman’s or Descemet’s membranes described up to now cannot always be considered as a clinically separated entity. Summary Die mosaikahuliche Dystrophie der Cornea kann in verschiedener Tiefe des Stromas lokalisiert sein (Bowman’sche Zone, Descemet’sche Zone Oder beide beim gleichen Patienten). Downloaded by: Vanderbilt University Library 188.8.131.52 - 10/27/2017 6:48:52 PM The mosaic like corneal dystrophy can be located at different depths within the corneal stroma (Bowman’s zone, Descemet’s zone or both in the same patient). According to different clinical varieties of this ailment, the mosaic like opacities can be situated namely at the pupilar area or the peripheric zone of the cornea. This dystrophy is primary as the senile type as well as the hereditary type associated to me galocornea, or secondary as the post-traumatic or post-inflamma tory type which have histopathological features of the band shaped keratopathy. The authors present a family study on which the mosaic like dystrophy and megalocornea was present in four male members. The authors conclude that the inheritance was following the X sex linkage rules, and that both pathological genes were located and coupled (gene-linkage) on the heterologous part of the X Chromo some. Zusammenfassung Megalocornea and Mosaic Dystrophy of the Cornea 175 Entsprechend des unterschiedlichen klinischen Hildes dieses Leidens können die mosaikähnlichen Trübungen vorwiegend im Pupillarbereich oder in der Peripherie der Cornea liegen. Diese Dystrophie tritt einmal auf als seniler wie auch als erblicher Typ in Verbindung mit einer Megalocornea oder zum anderen als posttraumatischer oder entzündlicher Typ mit histopathologischen Bildern der bandförmigen Keralopathie. Die Verfasser untersuch ten eine Familie, in der die mosaikähnliche Hornhautdystrophie und die Megalocornea bei 4 männlichen Familienmitgliedern zu beobachten waren. Die Verfasser schließen daraus, daß die Ver erbung nach dem X-geschlechtsgebundenen Vererbungsmechanismus erfolgt und daß die beiden pathologischen Gene an den heterologen Teil des X-Chromosoms lokalisiert und gekoppelt sind (Gen-Koppelung). Résumé La dystrophie cornéenne en mosaïque peut être localisée à différentes profondeurs du stroma cornéen (membrane de Descemet, de Bowman ou dans les deux chez le même patient). Selon les différentes variétés cliniques de cette maladie, la dystrophie en mosaïque peut être située dans la zone pupillaire ou périphérique de la cornée. La forme primaire de type sénile aussi bien qu’héréditaire est associée à la mégalocornée. La secondaire est du type post-traumatique ou post-inflammatoire et a les carac tères histopathologiques de la kératopathie en bande. Les auteurs présentent l’étude d’une famille dans laquelle la dystrophie en mosaïque et la mégalocornée étaient présentes chez 4 hommes. Les auteurs en concluent que l’hérédité accompagne le chromosome X lié au sexe et que les gênes pathologiques étaient localisés et couplés (enchaînement des gênes) à la partie hétéro logue du chromosome X. Í. Alaerts, II.: Cited by Waardenburg, Franceschetti and Klein. 2. Berliner, M.: Biomicroscopie of the eye (Hocker, New York 1949). 3. Boles-Carenini, B.: Juvenile familial mosaic degeneration of the cornea associated with megalocornea. Brit. J. Ophthal. 45: 64-70 (1961). 4. Cremona, A.: Enfermedades heredodegenerativas de la cornea en su aspecto biomicroscópico. Actas VI Congreso Argentino de Oftalmología, p. 249-303. Abril 9 a 13, Mar del Plata, 1957. Downloaded by: Vanderbilt University Library 184.108.40.206 - 10/27/2017 6:48:52 PM References 176 Malbran, D’Alessandro and Valenzuela 5. Franceschetti, A.: Classification and treatment of hereditary dystrophies. Arch. Ophthal., Chicago 52: 1-12 (1954). 6. Franceschetti, A. and Forni, S.: The heredo familial degeneration of the cornea. Acta XVI Concilium Ophthalmologicum, London 193-244, 1950. 7. Franceschetti, A.; Dieterle, P. and Forni, S.: Cited by Waardenburg, Fran ceschetti and Klein. 8. François, J.: L’Heredité en Ophtalmologie, p.336 (Masson, Paris 1958). 9. François, J.: Citado por Cremona, A. 10. Friede, R.: Cited by Waardenburg, Franceschetti and Klein. 11. Kopsa, M. et Marusic, K.: Contribution a l’étude de la dégénérescence en mosaïque de la membrane de Bowman de la cornée. Ophthalmologica 136: 83-89 (1958). 12. Malbran, E. and Dodds, R.: Megalocornea and its relation to congenital glaucoma. Amer. J. Ophthal. 49: 908-921 (1960). 13. Malbran, J.: Le glaucome pigmentaire. Sa relation avec le glaucome con génital. Probl. act. Ophtal. I: 132 (1957). 14. Manzitti, E.: Sobre un caso de distrofia de la cornea en mosaico. Arch. Oftal. B. Aires 24: 314-317 (1949). 15. Moro, E. e Amidei, B.: Sui rapporti tra degenerazione corneale del tipo a pelle di coccodrillo de Vogt a cheratite a bandetella. G. ital. Oftal. 6': 444 (1953). 16. Muller, P.: Dégénérescence en mosaïque (Chagrin de crocodile de Vogt) de la membrane de Bowman à la suite d’une kératite traumatique avec hypopyon. Ann. Oculist. 187: 122 (1949). 17. Rillo Cabanne, G.: Megalocornea y enfermedad de Paget. Arch. Oftal. B. Aires 26; 272-284 (1954). 18. Streiff, E. B.: Lignes verticileuses vitréennes de la membrane de Bowman. Chagrin de la membrane de Descemet. Ophthalmologica 116: 125 (1958). 19. Valerio, M.: Due forme rare di degenerazione giovanile delle cornee. Boll. Ocul. 18: 659-670 (1939). 20. Valerio, M.: Di una nuova rara forma di distrofia corneale ereditaria. Arch. Ottal. 49: 76-93 (1942). 21. Vogt, A.: Lehrbuch und Atlas der Spaltlampenmikroskopie des lebenden Auges. Vol. 1, p. 120-142. Weinzenblatt: cited by Millier, P. (Springer, Berlin 1930). 22. Waardenburg, P. J.; Franceschetti, A. and Klein, D.: Genetics and Oph thalmology (Blackwell Scientific Publ. Ltd., Oxford 1961). Downloaded by: Vanderbilt University Library 220.127.116.11 - 10/27/2017 6:48:52 PM Authors’ address: Dr. E. Malbran, Dr. C. D’Alessandro and Dr. J. Valenzuela, Parera 94, Buenos Aires (Argentine).