Pseudoinflammatory fundus dystrophy: a follow-up study

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  • Clinical Genetics 1990: 38: 21-32

    Pseudoinflammatory fundus dystrophy: a follow-up study

    ALDUR W. ERIKSSON, ERKKI A. SUVANTO, R. R. FRANTS AND HENRIK R. Fo~srus Institute of Human Genetics, Medical Faculty, Free University, Amsterdam, The Netherlands,

    *Eye Department, Satakunta Central Hospital, Pori, Finland, and 3Folkhalsan Institute of Genetics, Population Genetics Unit, Helsinki, Finland

    We have performed a reinvestigation of a family with a presumably autosomal recessive form of pseudoinflammatory dystrophy, which we have followed for 25 years. The symptoms in this family are subretinal haemorrhages appearing at age 13-40 years in the central fundus, resulting in glial cicatrication in the outer retinal layers, progressive myopia and profound choroidal atrophy in the advanced stages of the disease. During the follow-up study, a new affected subject was found in the younger generation, and two collateral cases, who had earlier been considered as probably affected subjects, were now considered to have other fundus affections. The new case is the daughter of an affected female. The possibilities of an autosomal dominant mode of inheritance or pseudodominance are discussed. Extended genealogical studies showed that the parents of all the affected subjects, with the exception of the new case, have their origin in an area which was isolated until recently and have several common ancestors within the last 8-10 generations. Recessive inheritance also logically explains the appearance of the disease in so few other members in the vertical line of the family. To this fundus dystrophy, the rule of Lenz seems to apply: If more or less the same phenotype can be caused by both a recessive and a dominant gene, the phenotype caused by the recessive gene is generally manifest- ed earlier and by more severe symptoms.

    Received 20 April, revised 17 October, acceptedfor publication 16 December 1989

    Key words: autosomal recessive; bilateral hemorrhagic degeneration; choroid; consanguinity; longitudinal study; progressive myopia; pseudoinflammatory fundus dystrophy; retina

    While studying X-chromosomal recessive retinoschisis in the province of Satakunta in southwestern Finland (Vainio-Mattila et al. 1969, Forsius & Eriksson 1980), we ran across an almost blind father being treated for choroiditis disseminata. The mother and three of the eight children of their family were also affected but, as we thought in the 1960s, by a different eye disorder, i.e. autosomal dominant pseudoinflammatory fundus dystrophy as described by Sorsby et al. (1949). However, after a longitudinal study lasting more than 20 years, we are

    now convinced that all 10 members of this nuclear family have a fundus dystrophy of the recessive type.

    The aim of this study is to demonstrate the importance of follow-up studies of rare ophthalmogenetic disorders with varying age of onset and varying progression.

    Follow-up Studies 1966-1 980

    In 1982 we published this family with pseu- doinflammatory dystrophy with autosomal recessive inheritance, which we had fol-

  • 22 E R I K S S O N ET A L .

    Table 1

    comparison of the two types of pseudoinflarnrnatory fundus dystrophy

    Type Sorsby Type Lavia (Finland)

    Age of manifestation Refraction error

    in the 4th and 5th decade normal distribution

    Visual acuity slowly lost Dark adaptation normal Peripheral retinal degeneration slight Colour vision seldom abnormalities Mode of inheritance autosomal dominant, McKusick


    ~~ ~~ ~~

    about 1WO years progressive myopia (up to -15

    rel. rapidly lost disturbed 1-4 log units strong often secondary dyschromatopsia autosomal recessive, McKusick 26442


    lowed for 16 years (Forsius et al. 1982). The symptoms of the fundus dystrophy in this family are subretinal haemorrhages in the central fundus, increasing myopia in the ac- tive phase of the disease, glial cicatrication of the outer retinal layers, and profound choroidal atrophy, particularly in the ad- vanced stages of the disease. Large numbers of deep hyaloid bodies in the retina can be seen to develop and again disappear in the same subjects. Fluorescein angiography demonstrated leakage through the pigment layer in the retinal tissue. The clinical pat- tern is similar to the autosomal dominant type of pseudoinflammatory dystrophy de- scribed by Sorsby et al. (1949) and later by others (for further references, see Hoskin et al. 1981 and Forsius et al. 1982). except that the disorder appeared earlier in this Finnish family, the members showed progressive myopia and the inheritance seemed to have an autosomal recessive mode (Table 1).

    A detailed ophthalmological description of the findings of the affected members of this family up to 1980 can be found in our earlier report. Only three of the eight children were affected when we first investi- gated them in the mid 1960s. Our first tenta- tive diagnosis was therefore pseudoinflam- matory dystrophy of Sorsby with an autoso- ma1 dominant inheritance (Fig. 1). Follow- up studies of probable infections (lues, tox- oplasmosis, histoplasmosis) causing central

    choroiditis were negative. We followed the sibs with photographs of the fundus and clinical investigations, and we found that all five sibs earlier declared healthy now had the same or very similar symptoms (see Cases IX, 48-55 in Fig. 2.).

    The parents both had large areas of de- generation in their retinas. The father had large pigmented scars all over the fundus resembling choroiditis disseminata, for which he had been treated earlier. During our longitudinal studies we could follow the changes of the fundus of the much younger wife from a stage with the typical glial scar in the macular area to more widespread de- generation throughout the fundus, thus coming closer to the clinical picture in her husband.


    Chroidlt is Pswdoinflmmtory 1 3 di rsminau ITbc?l 27 kndua dystrophy

    V I I I

    Fig. 1. Our diagnoses in 1966 of the family of the parents (V111,13 and V111,27 in Fig. 10) and their children. Only three of the eight children were affect- ed. The eyes of the father had been treated for dis- seminated choroiditis (tbc?). The much younger wife had reached this stage of fundus dystrophy 14 years later than her husband in 1966. At that time, all of 'he eight children were affected as well (cf. Fig. 2).

  • P S E U D 0 I N F L A M M A T 0 R Y FU N D U S D Y S T R 0 P H Y 23

    Follow-up Studies 1982-1989

    We have reinvestigated this family, focusing on those members who were of the age to acquire the disease and on those who had signs which could possibly develop into the specific dystrophy.

    Genealogical Studies Extended genealogical studies up to the 17th century showed that the parents and the grandparents of the eight children were re- lated in many different ways (Fig. 2). We concluded that if both parents were affected with the same autosomal recessive gene, all their children must get the disease, which they did eventually. The ancestors of the parents had not been known to have bad eye-sight. We could investigate nine of the sibs of the parents; the other had died by the time we performed our first studies in this family. Only one of the sibs (VIII, 23) of the affected parents was affected.

    Visual Acuity Fig. 3 shows the strong interindividual vari- ation in the progressive decrease of the vi- sus, but there are also considerable intrain- dividual differences. E.g. in child nr. 7 (in the pedigree, IX,54) the right eye was blind already at the age of 24 but the left eye still has normal visual acuity at the age of 35. Child nr. 8 (1x55) still has good visus in both his eyes at the age of 33. But child nr. 5 (IX,52) already had strongly decreased visual acuity in both his eyes a t the age of 15. The mother (VIII,27) was completely blind in both her eyes around the age of 60, but at about the same age. the father (VIII,13) still had visual acuity of 0.5 and 0.4 in his right and left eye, respectively.

    Refraction The myopia shows a tendency to increase progressively with age, particularly in the case of child 6 (IX,53) and the mother (VIII,27). On an average the decrease of

    26442 Pseudoinflammatory fundus dystrophy

    I1 1 .O -0 Investigated male, female 0610 Bad sight at the age of 10 t 60 I Consanguinity 0 - 9 ~ myopia




    V a Proband VI


    Died at the age of 60




    X I .m Fig. 2. Pedigree of the family with pseudoinflammatory dystrophy based on a follow-up study (1966-1989). Compared with our studies from 1980 (Forsius et al. 1982), a new affected subject, X,55, was noted. Two collateral cases, IX.21 and X,12, noted in 1980 as affected, have not progressed and are considered to have other fundus affections.

  • 24 E R I K S S O N ET A L .

    refraction starts later than the decrease of visual acuity (Fig. 4). There does not seem to be a good correlation between the de- crease of visual acuity and the decrease of refraction. E.g. child nr. 5 already had bad visus before the age of 20, but his refraction was still the best among the eight sibs, only 4 diopters of myopia, at the age of 36.

    The Nuclear Family Father. The father (VIII,13) of the eight af- fected children was examined ophthalmolo- gically for the first time at the age of 50, because he experienced a sudden decrease in the visual acuity of his left eye. At that time he had pigmented destructions and exudative areas in both fundi. At the age of 77 the visual acuity had decreased to counting fingers at 1 m in the right eye and at 30 cm in the left eye. Large atrophic retinochoroidal areas with pigmented scars all over the fundi, resembling choroiditis disseminata, were noted. The retinal arteries were attenuated (Fig. 5).

    Mother. The mother, who was 16 years younger (VIII,27), had a visual acuity that was even more decreased than her hus- bands (Fig. 3). The mothers status could not be explained as myopic macular de- generation ( -7 D in both eyes) because a myopic conus was totally missing and no other signs of attenuated myopic changes were noted. In the macular area in both eyes large scars with glial formation were seen (Fig. 6) and there were some small pigment- ed flecks in the periphery. At the age of 60 the visual acuity was counting fingers at 20-30 cm in both eyes. At the age of 68 her refraction was - 15 D and choroidal atrophy was total in both eyes.

    Grandchild TH. Female, born in 1963 (X,53) (former IV,6). Daughter of the oldest daugh- ter in the nuclear family. She was investi- gated in 1978 and nothing remarkable was found. Since then strong myopia has de- veloped and she uses contact lenses, -8.5 resp. - 8.0 D. She was investigated by us in

    7 7d 7s


    V.0c.a. for child n r . 7 V.oc.dx for child n r . 7 V.oc.sin for child n r . 7 MALE FEMALE

    age in years

    Fig. 3. Decrease of visual acuity in the affected parents (V111,13 and V11,27) and their affected children.

  • P S E U D O I N F L A M M A T 0 R Y FU N D U S D Y S T R O P H Y 25


    7=child nr.7

    1- -16

    I,, I 10 20 30 110 50 70

    age in years

    Fig. 4. Spherical equivalent of refractions in diopters of the affected parents (V111,13 and V111.27) and their children. Myopia increases from puberty onwards by an average of almost -0.5 D per year.

    1989. Visual acuity was 20125 with -9.0 D in both eyes. We also found a lightly pigmented eye fundus, and some small hya- loid bodies in the macular areas; A foveola reflex was seen. A few superficial small pig- ment flecks were noted in the periphery. With Goldmanns three-mirror contact lens, it could be seen that the pigment layer in the extreme periphery was absent. This sign has also been observed in youngsters who later developed pseudoinff ammatory fundus dystrophy, which is why we noted her as suspect for the disease.

    Child nr. 2. Female, born in 1944 (IX,49) (former 111,8). At the age of 15 her V~SUS, refraction and fovea were in both eyes. At the age of 20 the vision in her left

    Flg. 5. Fundus of the propositus V111.13, father of the family with the eight affected children at the age of 65: large atrophic retinochoroidal areas were ob- served all over the fundi.

    eye suddenly decreased to 0.1 but remained normal in the right eye (Fig. 3). At the age

  • 26 E R I K S S O N E T A L

    of 35, however, her visual acuity was only 0.1 in the right eye and counting fingers at 2.5 m and the myopia had progressed to - 6 D (Fig. 4). The scars caused by haemor- rhages and exudates had also increased in size (Fig. 7A and B). Her daughter is the next case.

    Grandchild R N . Female, born in 1964 (X,55) (former IV,8). In 1980 her vision was 25/20 without correction. The central areas in the fundi were normal. In the periphery above temporally in the fundus the pigment layer was uneven. In the right fundus below there were also ruptures in the pigment layer. No pigment at all covered the areas of the vor- ticous veins. We considered these changes to be within the normal range for a young fair child and did not note these findings as pathological (Forsius et al. 1982). In 1987, she had developed myopia of - 1.25 D in the right eye and -0.5 D with cyl. -0.5 DxO" in the left eye. When we saw her again in 1989 the visual acuity was finger counting 2-3 m with - 1.5 D in the right

    Fig. 6. The right eye of the mother of the family (pa- tient V111,27) at age 47. in the central area a large scar with glial formation was seen in the macula. There were some small pigment flecks in the per- iphery.

    eye. In the fundus there was a large glial scar in the macula surrounded by small haemorrhages and colloid bodies. The vis- ual acuity in the left eye was 20120 with a correction of - 1.0 D with cyl. -0.5 D x 180". The pigment layer in the macula was thin and very small pigmented rings with a light centre were observed. These looked like colloid bodies ophthalmosco-


    Fig. 7. A. Case IX,49, born In 1944. Central area of the fundus of the right eye of a 22-year-old female with normal visual acuity and fovea. Above the fovea but closer to the optic nerve head. a deep retinal haemorrhage as the first sign of retinal dystrophy is seen. 6. The same fundus as in A, but 13 years later (in 1979) after several exaverbations with haemor- rhaglc episodes. The retinal pigment layer of the central fundus is severely destroyed. Some pigment disturbances are seen also outside the central area.

  • P S E U D O I N F L A M M A T 0 R Y F U N D U S D Y S T R O P H Y 27

    pically but when seen with a biomicroscope through a contact lens their base was found to be flat. The pigment layer in the periph- ery was uneven, as if made up by microsco- pical spots. There was no doubt that this was a new typical case of pseudoinflamma- tory fundus dystrophy.

    Child nr. 3. Male born in 1946 (IX,50). At the age of 19 there were no pathological findings. When he was 32 years old his vi- sion was still ncjrmal but the refraction had decreased to - 6 D. Small nonspecific errors occurred in several pseudoisochromatic

    Fig. 8. A. Fun...


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