H. Forsius

EXFOLIATION SYNDROME IN VARIOUS ETHNIC POPULATIONS

Abstract. This introductory lecture to the epidemiological session in the Workshop on the Exfoliation Syndrome (ES) gathers together figures for the prevalence of ES around the world. Prevalence figures from published reports are shown in the text separately for each country. Four ways of comparing the prevalences are used. 1) Prevalences in people over 60 years of age, 2) Percentages of glaucoma in persons with ES, 3) Percentages of ES in patients with glaucoma or ocular hypertension, with separate statistics for the proportion of capsular glaucoma in patients treated with laser trabeculoplasty (LTP), 4) Prevalence of ES in patients with cataract. The major differences in prevalence can partly be explained by the different techniques used in the investigations. Very few authors have studied people in different countries, which is the best way of obtaining comparable results. The author has personally studied Finns, Lapps, Eskimos in Greenland, Canada and Alaska, Icelanders, populations in Tunis, India and Peru and four populations in the USSR by the same technique. The prevalences vary from 0 % in Eskimos to 21 % in Finns over 60 years of age, and are at the same high level in Lapps, Finns, Russians in Novosibirsk and Icelanders, but significantly lower in all the others. The results support the opinion that ES is not uniformly distributed in all countries, and this is confirmed by many reports from different countries in this workshop.

Pseudoexfoliation of the lens capsule and liberation of iris pigment.

A total of 220 inmates of old peoples homes, all over 60 years of age, were examined for pseudoexfoliation of the lens capsule. The incidence recorded for the age group 60–69 years was 10%, 70–79 years 21.3% and 80–89 years 32.8%. The intraocular tension of the eyes with pseudo‐exfoliation averaged 17.5 mmHg, against an average of 15.4 mmHg in normal eyes. After mydriatics, pigmented floaters were seen in the aqueous humour of 61.5% of the normal eyes, and 83.3% of the eyes with pseudoexfoliation. In these latter eyes, moreover, the pigment liberation was distinctly more marked. The trabecular region of the affected eyes was more pigmented than that of the normal eyes. The mechanism by which pseudoexfoliation possibly affects pigment liberation and trabecular pigmentation is discussed.

Åland eye disease: no albino misrouting

Electrophysiological studies showed that a patient with Åland eye disease had no misrouting of the optic pathways which is always found in all forms of albinism as a consequence of the retinogeniculate anomaly. Also the spontaneous and optokinetic nystagmus did not resemble that of the large majority of human albinos. The marked asymmetry found in this patient seems to be typical for humans with a defective development of foveal binocular vision. These findings are in agreement with clinical, nystagmographic and EM findings that Åland eye disease is distinct from the Nettleship‐Falls type of X–linked ocular albinism. Furthermore, Åland eye disease is different from X‐chromosomal congenital stationary night blindness with myopia by the fact that the scotopic functions are only moderately affected and there is no restriction of the peripheral photopic visual fields. In addition, there is latent nystagmus of extraocular type that appears also in female carriers. There is no ophthalmoplegia, there is a progression of the myopia and the dyschromatopsia is of secondary type.

Forsius‐Eriksson syndrome: Its relation to the Nettleship‐Falls X‐linked ocular albinism

On the basis of clinical data, it had previously been proposed that the Forsius‐Eriksson syndrome is identical to Nettleship‐Falls X‐linked ocular albinism. We performed biopsies of clinically‐normal skin in patients with the Forsius‐Eriksson syndrome to look for the abnormal melanosomes characteristic of Nettleship‐Falls X‐linked ocular albinism. There were no abnormalities in the melanosomes of patients with Forsius‐Eriksson syndrome. Thus, this syndrome is distinct from the Nettleship‐Falls disorder.

Congenital cornea plana in Finland

Two different hereditary forms of congenital cornea plana are described: an autosomal dominant form with relatively mild symptoms, and an autosomal recessive form (CPCR) with more severe symptoms, such as decreased visual acuity, extreme hyperopia (total refraction usually 10 D or more), hazy limbus corneae, more or less pronounced opacities in the corneal parenchyma, and marked arcus senilis, often detectable at an early age.

Choroideremia: close linkage to DXYS1 and DXYS12 demonstrated by segregation analysis and historical-genealogical evidence.

Linkage studies using restriction fragment length polymorphisms were conducted in the X‐linked disorder, choroideremia, designated TCD for Progressive Tapeto‐Choroidal Dystrophy. Previously demonstrated close linkage with locus DXYS1 was confirmed (lod 11.44 at 0 recombination distance). In addition, locus DXYS12 was found to be closely linked with TCD (lod 3.31 at 0 recombination distance). The disease mainly occurs in three large kindreds in remote Northern Finland. While formal genealogical proof is lacking, all presently living (more than 80 affected males and 120 carrier females) probably originate from a common founder couple born in 1644 and 1646, twelve generations ago. All 36 patients and 48 carriers tested from the three kindreds had the same haplotype (TCD/DXYS1, llkb/DXYS12,1.6kb). Given that at least 105 female meioses transmitting TCD have occurred since 1650 in these kindreds, extremely close linkage between TCD, DXYS1 and DXYS12 is suggested. The above haplotype is a very useful diagnostic tool in these TCD families. We suggest that our historical‐genealogical approach to linkage analysis may be possible elsewhere in similar isolated populations.

The genetics of cornea plana congenita.

Cornea plana congenita is believed to occur in a mild autosomal dominant (CNA1) and a more severe autosomal recessive (CNA2) form. We recently assigned a CNA2 locus to a region on chromosome 12 by linkage analysis. In this study we compared these traits clinically and genetically. Using the horizontal corneal refraction value in diopters (D) as a parameter, a control population (n = 473) had a mean value of 43 center dot 4 (SD 1 center dot 5 D) for men and 43 center dot 7 (SD 1 center dot 6 D) for women, whereas in 51 subjects affected with CNA2 the mean value was 29 center dot 9 (SD 5 center dot 2 D) and in five subjects affected with CNA1 the mean value was 37 center dot 8 (SD 1 center dot 6 D). By linkage analysis in two CNA1 families the CNA2 locus could be conclusively excluded. These data suggest that at least two forms of hereditary cornea plana exist which are both clinically and genetically distinct.

SEASONAL VARIATIONS IN RETINAL DETACHMENT IN NORTHERN FINLAND AND NOVOSIBIRSK

Retinal detachments have a tendency to occur more commonly in spring and summer than in winter. Two new series are presented here, the first collected in Northern Finland at latitudes 64°–70° and the second from Novosibirsk, at a much lower latitude, 55°N, but with an equally long winter. A statistically significant seasonal variation is found in both. The highest incidence peak is seen in June in Oulu and in July in Novosibirsk, the difference between the prevalence curves was, however, not statistically significant. The Oulu series shows a statistically highly significant seasonal variation in low refractive errors but no seasonal difference in high myopia and aphakia.

Skewed secondary sex ratio in the offspring of carriers of the 214G > A mutation of the RS1 gene.

Carriers of X‐linked juvenile retinoschisis (RS) were previously suggested to give birth to an excess of boys. We determined the carrier status for the 214G > A mutation of the RS1 gene in 202 females belonging to a large RS founder pedigree. The secondary sex ratio (SSR) in the offspring of 149 carriers was 129.8 (z= 2.25), which differed significantly from that of the Finnish population (SSR 106) but not from that of 53 non‐carrier females belonging to the same pedigree (SSR 116.7; z= 0.51). Since possible causes for the skewed SSR include factors affecting fertilisation, implantation and embryonic death, we searched for expression of RS1 in various placental and uterine cells and found that, in addition to the retina, RS1 is expressed in the uterus. We hypothesize that the RS1 protein has a role in implantation or embryonic survival.

Pseudoinflammatory Fundus Dystrophy with Autosomal Recessive Inheritance

A family in southwest Finland with bilateral hemorrhagic degeneration of the retina and choroid was followed up for more than 16 years. The maculas showed subretinal hemorrhages, glial cicatrization of the outer retinal layers, and profound choroidal atrophy, particularly in the advanced stages of the disease. Fluorescein angiography demonstrated leakage through the pigment layer in the retinal tissue. The age of onset varied from the second to the fourth decade. The clinical pattern was similar to Sorsbys pseudoinflammatory dominant fundus dystrophy, except that the disorder appeared earlier in this Finnish family, the members of which show secondary dyschromatopsia, many deep hyaloid bodies in the retina, disturbed dark adaptation (1 to 4 log units), subnormal light-peak/dark-trough ratios, progressive myopia, and a mode of inheritance which is probably autosomal recessive. The affected parents are consanguineous in many ways and each of their eight children is affected.