Prevalence of Retinitis Pigmentosa in Maine

PREVALENCE OF RETINITIS PIGMENTOSA IN MAINE CLAREANN

H. BUNKER, M.P.H.

Bar Harbor, Maine ELIOT

L. BERSON, M.D.

Boston, Massachusetts AND

WILLIAM

C. BROMLEY, M.D., ROBERT P. HAYES, B.A., AND THOMAS H. RODERICK, PH.D. Bar Harbor, Maine

Between 1976 and 1980, medical and social service sources were used to ascertain cases of retinitis pigmentosa in Maine (1980 population, 1,124,660). As of July 1, 1980, 241 clinically prevalent cases of retinitis pigmentosa were ascertained. Extensive pedigrees were collected for 185 of the subjects and medical records were obtained. One hundred fourteen cases were further evaluated by clinical examination including electroretinography. Adjusting for incorrect diagnosis (eight of 114,7%) and underascertainment (23 of 185, 12.5%), 'we estimated that prevalence of retinitis pigmentosa in Maine is 236 cases, 21 per 100,000 population or 1:4,756. Excluding Usher and Bardet-Biedl syndromes, the prevalence is 1:5,193. Estimated birth incidence of persons who will become affected with nonsyndrome retinitis pigmentosa is 1:3,544. Incidence of newly diagnosed cases per year is about six per 1,000,000 population. Among kindreds, 16 of 85 (19%) were autosomal dominant, 55 of 85 (65%) autosomal recessive or isolated cases, seven of 85 (8%) X-linked recessive, and seven of 85 (8%) not classified by mode of transmission. The name retinitis pigmentosa describes a group of hereditary, retinal pigmentary degenerations in which patients Accepted for publication Jan. 3, 1984. From the Center for Human Genetics, .Bar Harbor, Maine (Ms. Bunker, Mr. Hayes, and Drs. Bromley and Roderick); and the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (Dr. Berson). This study was supported in part by grants BH-77, 02CH-78, 07-CH-79, and 13-CH-80 from the Maine Bureau of Health; National Eye Institute Special Research Center Grant P50-EY02014; a grant from the National Retinitis Pigmentosa Foundation, Baltimore, Maryland; a grant from Maine Sight Conservation, Inc., and contributions from the Lions Clubs in Maine. Reprint requests to Thomas H. Roderick, Ph. D., Center for Human Genetics, .Bar Harbor, ME 04609.

report night blindness and loss of visual field, usually between the ages of 10 and 40 years. Affected patients, in the more advanced stages, characteristically show attenuated retinal vessels, and intraretinal pigment deposits distributed around the midperipheral fundus. They may show posterior subcapsular cataracts and macular degenerative changes. The rate of progression is variable. Some patients lose all useful vision by the age of 30 years and others retain central vision even beyond the age of 60 years. These disorders can be detected with certainty by the age of 6 years, if not at birth, even in an asymptomatic patient with a normalappearing fundus, with electroretinographic testing since affected patients

©AMERICAN JOURNAL OF OPHTHALMOLOGY 97:357--365, 1981l

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have electroretinograms that are reduced in amplitude with delayed timing. 1 Pedigrees with autosomal dominant, autosomal recessive, and X-linked recessive modes of transmission have been well documented. 2 Phenocopies of retinitis pigmentosa have been reported in association with infections or drugs. 3,4 Retinitis pigmentosa usually occurs without any known extraocular abnormalities but can be found as part of syndromes such as Bardet-Biedl syndrome or Usher's syndrome. In Bardet-Biedl syndrome, retinitis pigmentosa can be found in association with mental retardation, polydactyly, hypogonadism, and truncal obesity.! In Usher's syndrome, retinitis pigmentosa is found in association with vestibular ataxia and profound deafness from birth. Estimates of occurrence of retinitis pigmentosa range from a prevalence of one in 20,0004 to a worldwide incidence of one in 200. 3 Previous prevalence studies have been based on populations that may not be typical of white populations, that is, highly inbred populations.S? nonwhite populations.t or a voluntary registry"; in some cases, the population was not described.P't" No studies based on defined geographic populations have been reported from the United States. The purpose of the present study was to identify as many cases as possible in the state of Maine. This population could be geographically defined and was 99% white.P Extensive vital and public records, and the tendency for families to remain in a given region, provided an unusual opportunity to construct extensive pedigrees and thereby consider modes of transmission of retinitis pigmentosa in this population. SUBJECTS AND METHODS

The Maine Bureau of Health sent letters to all physicians and optometrists in Maine asking them to assist in ascertaining all Maine residents with retinitis pig-

MARCH, 1984

mentosa and to refer these persons and their families for diagnostic evaluation and genetic counseling. Presentations were made to annual professional meetings of ohthalmologists in Maine over a three-year period to encourage referrals. Also, the study staff contacted rehabilitation workers, public health nurses, school nurses, teachers in special programs for the blind, and teachers at the school for the deaf each year to aid in collecting data. Day-long public workshops on retinitis pigmentosa were presented in three regions of the state, each year, for health professionals and members of affected families. To preserve the confidentiality of the ascertainment process, only those families with referred members were contacted by the staff conducting this project. A home visit was conducted with each referred family at which time an extensive pedigree was constructed. Additional sources of information were contact with other family members, vital records, and other genealogical source materials. Families were classified as to origin by their reported country of origin or by the ethnic nature of the surname of the earliest known relevant ancestors. In making these determinations we knew of the many instances of anglicizing surnames, particularly French-Canadian names. Medical records were collected to confirm the diagnosis of retinitis pigmentosa. In families for whom there was no confirmation of diagnosis or for whom the mode ofinheritance was not clear, an effort was made to provide a complete diagnostic evaluation including electroretinograph y, dark-adaptation testing, visual field measurement, and detailed clinical examination. This evaluation was carried out at Massachusetts Eye and Ear Infirmary, Boston, by one of us (E.L.B.). In the case of isolated males, effort was made to provide the same evaluation to the mother or a daughter to determine whether or

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not she showed the carrier state of Xlinked recessive retinitis pigmentosa.P Diagnosis of retinitis pigmentosa associated with syndromes was, for the most part, based on medical records. Deceased affected patients and affected family members who were not residents in Maine were considered in pedigree analysis but were excluded from the count of prevalent cases. Deceased family members or others who could not be examined or for whom medical records could not be obtained were considered to be probably affected if night blindness and progressive loss of vision before the age of 40 years were reported, or were considered to be unaffected if they were visually asymptomatic after the age of 40 years. Ascertainment took place from 1976 to 1980. Prevalent cases were defined as those persons residing in Maine, on or about July 1, 1980, who were ascertained as being affected with retinitis pigmentosa. Only symptomatic cases were included; three asymptomatic cases identified by electroretinography were excluded from the count of prevalent cases, as it was not possible to perform electroretinography on all family members at risk. The mode of transmission was established for each affected person wherever possible. Autosomal dominant inheritance was defined as consecutive transmission of the disorder over three or more generations, where males and females were comparably affected. Probable autosomal dominant inheritance was defined as transmission over two consecutive generations, with comparably affected males and females, and no evidence of consanguinity. Autosomal recessive inheritance was the classification for kindreds with comparably affected male and female siblings, or two or more affected female siblings, born to unaffected parents. Probable autosomal recessive inheritance was the classification used when two or more affected male siblings

359

were born to normal consanguineous parents. Families were considered to show X-linked transmission if there was no evidence of male-to-male transmission and if symptomatic females showed less severity than males of comparable age and if the mother or a daughter of an affected male in the pedigree exhibited one or more characteristics of the Xlinked carrier state, that is, reduced electroretinographic responses. tapetal reflex, or bone spicule pigment. We considered a pedigree to manifest probable X-linked inheritance when women were reported to be much less severely affected than affected males of comparable age but where electroretinographic testing could not be carried out. Pedigrees with only one case were classified as isolated-case kindreds. Pedigrees in which there were more than one case, but the mode of inheritance could not be determined, were classified as "multiple cases, mode undetermined." Pedigrees were not available for 56 cases (54 nonsyndrome cases), which were ascertained but not referred; these were classified as ascertained only. RESULTS

As of July 1, 1980, 226 symptomatic cases of retinitis pigmentosa were ascertained in Maine. These included ten cases with Bardet-Biedl syndrome and nine cases with Usher's syndrome. Visual acuity in the cases ranged from 20/20 to minimal light perception. Visual fields ranged from full field to field so limited that it could not be measured. For 162 of these cases, extensive pedigrees were constructed and 23 additional affected patients were identified in Maine for a total of 185 prevalent cases in these families, and a total of 249 cases overall. We used the 23 of 185, or 12.5%, as an estimate of the percentage of cases missed by using our methods of ascertainment.

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Ocular examinations, including electroretinography, in 114 ascertained cases, disclosed that eight did not have retinitis pigmentosa. These patients had either retinoschisis, choroideremia, albipunctate dystrophy, congenital amaurosis of Leber, retinopathy subsequent to infection, or night blindness by history but no evidence of retinal malfunction. Therefore, we estimated an overascertainment of eight of 114 or about 7%. After adjusting for underascertainment and overascertainment we calculated the prevalence in Maine to be (0.93) (1.125) (226) or 236.5 cases. Given the Maine population of 1,124,660 the calculated prevalence rate is one in 4,756 residents or 21 per 100,000. When recognized syndromes were excluded (19 cases), prevalence was one in 5,193. One hundred sixty-eight patients were identified in 85 pedigrees with nonsyndrome retinitis pigmentosa. Table 1 shows the distribution of these cases and pedigrees by mode of transmission. Almost half (73 of 168, or 43%) of the cases appeared to have dominantly inherited retinitis pigmentosa, representing 19% (16 of 85) of the pedigrees. Probable autosomal recessive transmission was established in 20% (33 of 168) of the cases.

TABLE 1 DISTRIBUTION OF SYMPTOMATIC NONSYNDROME RETINITIS PIGMENTOSA CASES AND KlNDREDS BY MODE OF TRANSMISSION, MAINE, 1980

Kindreds"

Cases"

Mode of Transmission

%

No.

%

73 65 8 33 20 13

43

16 14 2 16 10 6

19

39 13 9 4

23 8

39 7 5 2

46 8

10 168

6 100

7 85

8 100

No.

Autosomal dominant Established Probable Autosomal recessive Established Probable Isolated case, mode undetermined X-linked recessive Established Probable Multiple case, mode undetermined Total

20

19

"Excludes 54 cases for which pedigrees were not obtained.

When isolated cases are combined with autosomal recessive cases, as many as 43% (72 of 168) of the cases and 65% (55 of 85) of the kindreds may be autosomal recessive. Of the families 8% were Xlinked recessive. Of the cases 8% were also X-linked. Table 2 shows that there was a slight but statistically nonsignificant

TABLE 2 DISTRIBUTION OF NONSYNDROME RETINITIS PIGMENTOSA CASES BY SEX AND MODE OF TRANSMISSION, MAINE, 1980

Males

Females

Unknown

Mode of Transmission•

No. of Cases

No.

%

No.

%

No.

%

Autosomal dominant Autosomal recessive Isolated cases X-linked recessive Multiple case, mode undetermined Cases ascertained only Total cases

73 33 39 13 10 54 222t

36 17 20 13 6 30 122

49 52 51 100 60 55 55

37 16 19 0 4 23 99

51 48 49 0 40 43 45

1 1

2 <1

"Established and probable modes of transmission combined. tExcluded from the total of 249 ascertained cases in these tables are the 19 syndrome cases, and the eight patients found not to have retinitis pigmentosa by clinical examination.

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TABLE 3 AGE DISTRIBUTION OF NONSYNDROME SYMPrOMATIC RETINITIS PIGMENTOSA CASES BY MODE OF TRANSMISSION, MAINE, 1980 Age in Years

Mode of Transmission

0-4 5-14 15-24 25-34 35-44 45-54 55--64 65-74 75--84 85+ Unknown Total

Autosomal dominant Autosomal recessive Isolated cases X-linked cases Multiple case, code undetermined Cases ascertained only Total cases

7 3

1 1

18 4 7 3

2

2

14

4 7 5

7 5 6 2

9 8

1 5

1 5 33

2 3 25

11

9

1 33

2

2

9

26

preponderance of males. After excluding X-linked cases, the distribution between males and females is virtually one-to-one. The age-specific distributions and prevalence rates per 100,000 for symptomatic retinitis pigmentosa are presented in Table 3 and the Figure, respectively. The rates rise with age as expected for a late-onset disorder. After the age of 40 years, the rates more or less level off since most cases are diagnosed by this age. Affected subjects resided irr all populated regions of the state. The distribution of families by country

z o

30

~
S 25

Total Nonsyndrome Cases

a. a.

o

g 20 o 0"

Q , 15

uv ur

Autosomal Re c e s srve and Isolated Cases

in


<> 10

'"

....

Z W ...J

~

w

/

5

/

"".. -.-

' .... :,... -;"', '......... " ........... ...... ............. .,····-"
/'

AutOS~:~le~Omlnanf

/.......

a: a.

........ o

10

20

30

40

50

60

70

AGE IN YEARS

Figure (Bunker and associates). Age-specific prevalence rates of symptomatic nonsyndrome retinitis pigmentosa in Maine, 1980.

5

2

2

6 1

5 1 1

1

3 6 28

2 6 22

1 6 14

1 2

2 2

19 23

73 33 39 13 10 54

222

of origin and by mode of transmission is presented in Table 4. About 67% (57 of 85) were of English or English-other background, 15% (13 of 85) FrenchCanadian, 7% (six of 85) English-French, and 11% (nine of 85) of other or of undetermined origin, including one family of Russian-Jewish origin. Overall the distribution of origin within each mode of inheritance is not strikingly different from the overall distribution of country of origin in all kindreds, taking into account the small number of kindreds. Thus, there was no evidence for clustering of cases within nationality groups, nor was there evidence of clustering in geographic regions. Pedigrees and medical records could not be obtained for 54 cases, which were ascertained only and were not referred. As shown in Table 5, when ascertained cases are classified on the basis of the limited information available, 54% of all cases may be autosomal recessive (including isolated cases). DISCUSSION

The estimated prevalence of nonsyndrome symptomatic cases of retinitis pigmentosa in the Maine population of 1,124,660 derived from the present study was one in 5,193. The prevalence in this population of predominantly English and

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MARCH, 1984

TABLE 4 DISTRIBUTION OF MODE OF TRANSMISSION BY COUNTRY ORIGIN OF KINDREDS WITH NON SYNDROME RETINITIS PIGMENTOSA, MAINE, 1980

Country of Origin

Mode of Transmission

Predominant English, Irish Scotch No. %

Autosomal dominant Autosomal recessive Isolated cases X-linked recessive Multiple case, mode undetermined Total kindreds

EnglishOther Country No. %

EnglishFrench No. %

Predominant FrenchCanadian No.

%

Other" No. %

Total No.

%

1 6

6 15

2 4

12 10

4 5 3

25

4

69 38 62 57

31 8

1 2 2 3t

6 12 5 43

16 16 39 7

100 100 100 100

4 49

58 58

1 8

14 9

6

7

1 13

14 15

1 9

11

14

7 85

100 100

11

6

24

"Includes undetermined. tOne nonwhite family.

French-Canadian background was similar to that found in geographically defined populations in Switzerland, one in 7,000,6 in Shanghai, China, one in 4,016,8 and in Israel, one in 4,500. 7 The distribution of kindreds by mode of transmission (Table 1) was similar to the distributions reported in Chicago by Fishman" and in England by Jay,15 but were clearly different from the findings in the inbred Swiss

population, where less than 9% of kindreds were autosomal dominant. The nearly equal numbers of affected males and females, aside from X-linked families, contrasts with an earlier suggestion" that even in non X-linked retinitis pigmentosa there is a male predominance and that heredity may even be sexcontrolled. It seems likely that deviations of the sex ratio from mendelian expecta-

TABLE 5 DISTRIBUTION OF CASES OF NONSYNDROME RETINITIS PIGMENTOSA BY MODE OF TRANSMISSION, MAINE, 1980, COMBINING CASES IN PEDIGREES AND CASES ASCERTAINED ONLY

Probable Mode of Transmission Autosomal dominant Autosomal recessive Isolated cases X-linked recessive Multiple case, mode undetermined Total cases

No. of Cases in Pedigrees

73

33

39 13 10 168

No. of Cases Ascertained Only

4· 2t 46* 0 2§

54

"Two mother-son pairs. tOne male-female sibling pair. :j:Forty-six cases with no mention of family history in ascertainment data. §One male-male sibling pair.

Total Cases

77

35

85 13 12 222

Percent of Cases 35

16 38 6 5 100

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tions are due to ascertainment biases. During the time of early studies women generally worked in the home and may have been less likely to have been ascertained than men who experienced difficulty in the workplace. On the other hand, Jay15 noted an ascertainment bias toward females in families ascertained through a genetics counseling clinic. The incidence of retinitis pigmentosa in Maine cannot be calculated from the prevalence of symptomatic cases over the entire population, since many asymptomatic cases exist in the population under the age of 35 years.'? Since most patients report night blindness by the age of 35 years, 17 one can estimate the incidence at birth of those who will develop symptoms of retinitis pigmentosa, from the prevalence of symptomatic cases in those aged 35 and more. This estimate must be made with the assumptions that persons with retinitis pigmentosa experience the same survival as the general population, that the population has been stable, and that the ascertainment probability for sympto-

363

matic cases is the same over younger and older age groups. Table 6 shows that the incidence rates estimated from symptomatic cases aged 35 to 75 years, based on the Maine population aged 35 to 74 years, or 425,296, are about one in 3,402 to one in 4,667 or 37% higher than the prevalence rates of symptomatic cases based on the entire population. Therefore, the birth incidence rate of persons who will develop symptoms of nonsyndrome retinitis pigmentosa is calculated to be 28.2 per 100,000 or one per 3,544 births. Based on the 1960 birth rate of about 23,000 in Maine, one would calculate an annual birth incidence of 6.5 cases per year. From the birth incidence of 9.64 per 100,000 (Table 6) of autosomal recessives and isolated cases combined, we estimate the frequency of carriers of recessive retinitis pigmentosa to be 0.0194 or about 2% of the population, based oil q2 = 9.64/100,000, heterozygote frequency = 2pq. This could be an overestimate if some of the isolated cases are not reces-

TABLE 6 PREVALENCE RATES AND ESTIMATED BIRTH INCIDENCE RATES OF NONSYNDROME RETINITIS PIGMENTOSA BY MODE OF TRANSMISSION, MAINE, 1980·

Prevalence Rates of Symptomatic Cases, All Ages Mode of Transmission

Birth Incidence Rates Estimated from Prevalence of Cases, Ages 35-74

Rate/ Ratio Estimate from Total Rate/ Ratio 100,000 Cases of Case: Estimated 100,000 Case: No. Population Population No. Unknown Age" No. Population Population

Autosomal dominant 73 Autosomal recessive and isolated 72 X-linked recessive 13 Total nonsyndrome cases 222 Total cases 241

6.49

1:15,406

32

1

33

7.76

1:12,888

6.40 1.16

1:15,620 1:86,512

40 8

1 0

41 8

9.64 1.88

1:10,373 1:53,162

1:5,066t 108 1:4,667* 113

12 12

120 125

28.22

1:3,544 1:3,402

19.74 21.43

29.39

"Maine population: total, all ages = 1,124,660; total, ages 35-74 = 425,296. tFor estimation purposes, one-half of cases of unknown age (see Table 3) are added to known number, age 35-74, to yield total estimated number of symptomatic cases, ages 35-74. iDiffer slightly from text (Results) because they are based on ascertained cases uncorrected for possible overascertainment and underascertainment.

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sive cases, but could be an underestimate if there is genetic heterogeneity of autosomal recessive retinitis pigmentosa. Incidence of newly diagnosed cases per calendar year may be calculated from age-specific prevalence rates using the method of Leske, Ederer, and Podgor." This method is appropriate for conditions that do not affect survival and are permanent after onset. In a stable population, when both disease and death are rare, then incidence is estimated by the slope of the smoothed graph of age-specific prevalence rates for the age period during which the majority of cases are diagnosed. We used linear regression to calculate the slope of age-specific prevalence rates, age 5 to 44 years (Table 7). From the slope we estimate annual incidence of total non syndrome cases to be 5.6 cases per 1,000,000 population. Thus, consistent with the annual birth incidence of 6.5 cases calculated

MARCH, 1984

above, the incidence rate of newly diagnosed cases is also about six per year in a population of 1,124,660. If similar rates prevail in the United States population, then one could estimate that in a population of 226 million, one could expect 6 times 226 or 1,356 newly diagnosed cases per year. There are different points in the progression of a disorder where estimates of incidence can be made. This estimate, based on the criterion of being newly diagnosed agrees well with another estimate based on a later criterion in the progression of the disorder, that of becoming legally blind. The 1983 Report of the National Advisory Eye Council" cites an estimate of 1,450 new cases of legal blindness per year in the United States caused by retinitis pigmentosa (based on unpublished model reporting area data of the National Society to Prevent Blindness). The estimates of prevalence and inci-

TABLE 7 ESTIMATED ANNUAL INCIDENCE OF NEWLY DIAGNOSED CASES OF NONSYNDROME RETINITIS PIGMENTOSA IN MAINE, BASED ON 1980 AGE-SPECIFIC PREVALENCE RATES 1980 Age-specific Prevalence Rates/l00,OOO

Age, Years

Maine Population

Age, Midpoint

Total Nonsyndrome

Autosomal Dominant

Autosomal Recessive and Isolated

Cases

Rate

Cases

Rate

Cases

0-4 78,653 2.5 2 5-14 178,309 10 14 205,769 20 15-24 33 178,684 30 26 25-34 35-44 122,630 40 33 112,049 45-54 50 25 107,695 60 28 .55-M 65-74 82,922 70 22 Correlation between age (midpoint) and prevalence rates, ages 5-44. Estimated annual incidence/loo,OOO (slope of linear regression line calculated for age (midpoint) and prevalence rate, ages 5 to 44 years.

2.54 7.85 16.04 14.55 26.91 22.31 26.00 26.53

0 7 18 9 11 7 9 5

0 3.93 8.75 5.04 8.97 6.25 8.36 6.03

2 3 11 11 11 11 10 8

Rate 2.54 1.68 5.35 6.16 8.97 9.82 9.29 9.65

Other Cases" Cases 0 4 4 6 11 7 9 9

Rate 0 2.24 1.94 3.36 8.97 6.25 8.37 10.85

0.91

0.57

0.97

0.85

0.557

0.114

0.227

0.216

*X-linked recessive, multiple case mode undetermined and cases ascertained only.

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dence of retinitis pigmentosa from the Maine Study provide a basis for planning medical, genetic, and social services. REFERENCES 1. Berson, E. L.: Retinitis pigmentosa and allied diseases. Applications of electroretinographic testing. Int. Ophthalmol. 4:7, 1981. 2. Bell, J.: Retinitis pigmentosa and allied diseases. In Pearson, K. (ed.): Treasury of Human Inheritance, vol. 2, pt. 1. Cambridge, Cambridge University Press, 1922. 3. Duke-Elder, S., and Dobree, J. H.: Diseases of the retina. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 10. St. Louis, C. V. Mosby, 1967, pp. 577-622. 4. Franeots, J.: Hereditary tapetoretinal degenerations. In Heredity in Ophthalmology. St. Louis, C. V. Mosby, 1961, pp. 441-455. 5. Campo, R. V., and Aaberg, T. M.: Ocular and systemic manifestations of the Bardet-Biedl syndrome. Am. J. Ophthalmol. 94:750, 1982. 6. Ammann, F., Klein, D., and Franceschetti, A.: Genetic and epidemiological investigations on pigmentary degeneration of the retina and allied disorders in Switzerland. J. Neurol. Sci. 2:183, 1965. 7. Merin, A., and Auerbach, E.: Retinitis pigmentosa. Surv. Ophthalmol. 20:303, 1976. 8. Hu, D.: Genetic aspects of retinitis pigmentosa in China. Am. J. Moo. Genet. 12:51, 1982. 9. Boughman, J. A., Conneally, P. M., and Nance, W. E.: Population genetic studies of retinitis pigmentosa. Am. J. Hum. Genet. 32:223, 1980.

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10. Wibaut, F.: De Betenkenis der Erfelijkheid Voor de Geneeskunde. Amsterdam, Strengholt, 1940, pp. 52 and 53. n. Hussels-Maumenee, I., Pierce, E. R., Bias, W. B., and Schleutermann, D. A.: Linkage studies of typical retinitis pigmentosa and common markers. Am. J. Hum. Genet. 27:505, 1975. 12. Bureau of the Census, U.S. Department of Commerce: Provisional estimates of social, economic and housing characteristics. 1980 census of population and housing. Table P-l. Publ. No. PHC8O-S1-1, 1982. 13. Berson, E. L., Rosen, J. B., and Simonoff, E. A.: Electroretinographic testing as an aid in detection of carriers of X-chromosome-linked retinitis pigmentosa. Am. J. Ophthalmol. 87:460, 1979. 14. Fishman, G. A.: Retinitis pigmentosa. Genetic percentages. Arch. Ophthalmol. 96:822, 1978. 15. Jay, M.: On the heredity of retinitis pigmentosa. Br. J. Ophthalmol. 66:405, 1982. 16. Fran~is, J. : Chorioretinal heredo-degeneration. Proc, R. Soc. Med. 54:1109, 1961. 17. Berson, E. L., Rosner, B., and Simonoff, E.: Risk factors for genetic typing and detection in retinitis pigmentosa, Am. J. Ophthalmol. 89:763, 1980. 18. Leske, M. C., Ederer, F., and Podgor, M.: Estimating incidence for age-specific prevalence in glaucoma. Am. J. Epidemiol. 113:606, 1981. 19. Vision Research: A National Plan 1983-1987. The 1983 Report of the National Advisory Eye Council. Vol. 1, NIH83-2469, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, p. 13, 1983.