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Visual Loss in Retinitis Pigmentosa
VISUAL LOSS IN RETINITIS PIGMENTOSA MICHAEL
F.
MARMOR, M.D.
Stanford, California
Retinitis pigmentosa typically begins The results imply that visual loss is rapid in the equatorial retina, and progresses and unpredictable. both anteriorly and posteriorly until only SUBJECTS AND METHODS a tiny central island of visual field remains. Both cones and rods are involved, The population studied comprised all but damage to the rod system is most patients I saw in consultation and made a prominent and the effects on central vi- diagnosis of conventional retinitis pigsion are variable. Some patients maintain mentosa, from July 1973 through Sepgood visual acuity throughout their lives, tember 1978. The diagnosis of retinitis despite unrecordable electroretinograms pigmentosa was confirmed by electroand 2- to 3-degree central fields. How- physiologic recordings for most of these ever, others lose central vision at a young patients, but in some was made clinicalage and are much more severely disa- ly. Patients with mild variants of retinitis bled. pigmentosa such as sectorial disease or The manner in which visual acuity delimited disease' were excluded, but changes with age is important to patients their exclusion has little influence upon with this disease, but the course of visual these results because almost all of these loss in retinitis pigmentosa has never patients maintain good visual acuity. Also been established. Surveys have shown excluded were variants of retinitis pigthat roughly 50% of patients with retini- mentosa such as centroperipheral distis pigmentosa have visual acuity of 6/15 ease, Laurence-Moon-Bied] syndrome or (20/50) or worse and that the proportion cone dystrophy, and patients in whom an of patients with poor visual acuity in- acquired degeneration was suspected. A creases with age. 1-3 However, these data total of 91 patients with 179 nonamblyare based upon the visual acuity at a single opic eyes fit the criteria. The probable examination. Thus, they are influenced mode of inheritance, determined by by the selection of patients seeking care family history, was sporadic or recessive and do not show whether the loss of for 140 eyes (71 patients: 46 male, 25 female), dominant for 27 eyes (14 pavision is gradual, step-wise, or abrupt. I investigated the visual history of 91 tients: ten male, four female), and Xconsecutive patients who have typical chromosome-linked for 12 eyes (six paretinitis pigmentosa, to determine when tients: all male). Because of the small and how fast central vision was affected. number of eyes with dominant and Xchromosome-linked retinitis pigmentosa, most of the results are presented only for From the Division of Ophthalmology, Stanford recessive disease. University School of Medicine and the OphthalmoloThe visual history was investigated for gy Section, Veterans Administration Medical Center, Palo Alto, California. This study was supported in every patient whose corrected visual part by National Eye Institute Grant EYOl678 and by the National Institutes of Health Training Grant acuity, at the time of latest examination by me, was 6/12 (20/40) or worse in either EYOOO51-1O. Reprint requests to Michael F. Marmor, M.D., eye. Hospital charts, physician's records, Ophthalmology Section (1l2BI), Veterans Administration Medical Center, 3801 Miranda Ave., Palo and optometry records were examined or reviewed by telephone, until a best Alto, CA 94304. 692
AMERICAN JOURNAL OF OPHTHALMOLOGY 89:692--698, 1980
VOL. 89, NO. 5
corrected visual acuity of 6/9 (20/30) or better in both eyes could be shown or until no further information could be located. No attempt was made to show any findings other than visual acuity, because the quality of past observations could not be verified personally.
[20/200] or worse). By my own examination, all of these patients, regardless of visual acuity, showed foveal abnormalities that usually consisted of an absence of foveal reflexes and irregularity of the vitreoretinal interface. Except for a few patients with severe visual loss, who showed marked pigmentary atrophy under the fovea, there was no obvious correlation between visual acuity and foveal appearance. Only two patients in this series (both with recessive disease) had cataracts of possible visual significance, but both also showed prominent foveal abnormality. To determine the age and speed at which vision was lost, the previous visual history was investigated for the 116 eyes that had a corrected visual acuity of 6/12 (20/40) or worse. A total of 31 eyes could not be traced beyond 6/60 (20/200) visual
RESULTS
For each eye with recessive retinitis pigmentosa, the latest visual acuity was plotted against age (Fig. 1). The scatter of points indicates that the relationship of visual acuity to age cannot be a simple monotonic function. Instead of clustering along a diagonal between good vision in youth and poor vision in old age, the points are concentrated in overlapping ranges of good visual acuity (6/12 [20/40] or better) or poor visual acuity (6/60
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Fig. 1 (Marmor). Visual acuity at latest examinarion vs age, for cases with probable recessive inheritance. Each point represents one eye. The divisions of visual acuity in this and the following illustration are as follows: 6/6 (20/20), 6/9 (20/30), 6/12 (20/40), 6/15 (20/50), 6/18 (20/60), 6/21 (20170), 6/24 (20/80), 6/30 (20/100), 6/60 (20/200), counting lingers, hand movements, and light perception.
694
AMERICAN JOURNAL OF OPHTHALMOLOGY
acuity because old records or the patient could not be located. Figure 2 is a graphic representation of the visual history of the 59 eyes with recessive disease for which the visual acuity was traceable over a minimum change of three lines, or five years of follow-up, or to an earlier measurement of 6/12 (20/40) or better, There is a striking homogeneity in the slopes of the lines that represent visual change. The prevailing slope is steep, and indicates that the median time for a change in visual acuity from 6/12 (20/40) to 6/60 (20/200) was approximately six years, and the change occurred in less than ten years for all but a few patients. Additionally, visual acuity was lost with a relatively even distribution over ages five to 60 years. Eyes with dominant and X-chromosome-linked disease lost visual acuity with a similar time course, but there were too few cases to compare in terms of age. Statistical analysis of these data was considered, but our consultant
MAY, 1980
believed that graphic presentation of Figure 2 was more direct and accurate because eyes differed greatly in age at first or last examination, duration of follow-up, and frequency of follow-up. Visual acuities were compared between the eyes of patients with recessive disease, to determine how often the loss of visual acuity was unilateral or bilateral. Only 21 % of the patients showed a difference of more than two lines of visual acuity between the eyes, but many ,of these individuals were young (with good visual acuity), whereas others had been legally blind in both eyes for years. Among cases for which a progressive loss of visual acuity could be historically documented, approximately 40% showed significant asymmetry of vision for five or more years. The prevalence of visual loss in ocular disease has usually been calculated from data gathered at a single examination, a method that depends greatly upon the
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AGE Fig. 2 (Marmor). Visual history of eyes with recessive retinitis pigmentosa. Each line connects all recorded visual acuities for one eye; only eyes that could be traced over five years or a three-line change in visual acuity are shown. Visual acuities of 6/9 (20/30) or better are not discriminated in this figure.
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VISUAL LOSS IN RETINITIS PIGMENTOSA
size and age distribution of the population being studied. These problems can be minimized, and more accurate data obtained from a small population, if the visual acuity of each eye at different ages throughout life is incorporated into the statistics. Figures 3 and 4 show the result of such an analysis from the present data for recessive and dominant retinitis pigmentosa. The current visual acuity of each eye was tabulated within the decade of the patient's most recent examination, but the worst visual acuity within each preceding decade (obtained from the visual history) was also tabulated. Thus, the youngest decade cumulated data from the entire sample. This method was straight-forward for individuals with a complete visual history; once an eye was
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noted to have good visual acuity (defined as 6/12 [20/40] or better for these plots) it was presumed to have good visual acuity in younger age groups. However, a problem developed for eyes that could not be fully traced. Because the dates of visual loss were unknown for these eyes, their visual acuities were indeterminate in decades that preceded theirearliest examination. For presentation in histograms, these indeterminate visual acuities have been divided into two groups, depending on whether the earliest known visual acuity was midrange (6/15 [20/50] to 6/30 [201100]) or poor (6/60 [20/200] or worse). The resulting frequency plot for the 140 eyes with recessive disease (Fig. 3) shows clearly that the percentage with good visual acuity decreases steadily over
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N~ )\}~.......................... : ?' n:jf~« 0-9 Fig. 3 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with recessive retinitis pigmentosa. Visual acuity is divided into three categories: good (6/12 [20/40] or better); midrange (6/15 [20/50] to 6/30 [20/100]); and poor (6160 [20/200] or worse). The indetenninate ranges represent eyes whose earliest recorded visual acuity in an older age group was midrange or poor. The data were cumulated from older to younger age groups to incorporate all available historical infonnation about each eye. The number of eyes in each category (N) is shown near the bottom of the histogram.
696
AMERICAN JOURNAL OF OPHTHALMOLOGY
MAY, 1980
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AGE Fig. 4 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with dominant retinitis pigmentosa.
the years, whereas the percentage with poor visual acuity increases. The number of eyes with middle-range visual acuity remains relatively small (about 10%) throughout the plot, which is consistent with the impression from Figure 2 that visual acuity decreases rapidly at any age in retinitis pigmentosa and does not remain for any long period in the middle range. The 27 eyes with dominant disease (Fig. 4) showed a similar trend, and a somewhat larger percentage of eyes with good visual acuity at any given age. DISCUSSION
The data from recessive and sporadic cases of conventional retinitis pigmentosa show that the disease was unexpectedly rapid in its effects on visual acuity.
Visual loss began at any age, and once visual acuity began to fail, it generally dropped to 6/60 (20/200) or below within a period of four to ten years (the median is near six). There appeared to be few cases in which midrange visual acuity (6/15 [20/50] to 6/30 [20/100]) was maintained for any period of time. Indeed, the data in Figure 2 may underestimate the speed of visual loss; the visual history lines pass through all ofthe available visual acuity measurements for each eye, but if no examinations were recorded over a long period of time (for example, ten years), then the line drawn between visual acuities at the beginning and end of that period may have a falsely shallow slope. In many patients the two eyes were affected simultaneously, but in 20 to 40% one eye was spared for live or more years.
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VISUAL LOSS IN RETINITIS PIGMENTOSA
Retinitis pigmentosa is not a homogeneous disease. Different modes of inheritance have been accounted for in this study, but there also may be unrecognized variants within each mode of inheritance. Some of the differences in visual history, among individuals, may reflect such variants. The present data suggest that the progression of visual loss in dominant retinitis pigmentosa may be slightly slower, and occur at a slightly older age, than in recessive disease. However, because of the relatively small numbers of cases, and the variability among individuals, that conclusion could tum out to be unfounded. The classic view3·5 has been that dominant disease is inherently milder, but one recent study" suggests that there is little distinction. Prospective studies should ultimately be undertaken, but they are exceedingly difficult with retinitis pigmentosa because of the slow progression of the disease. Although this was a retrospective study in which information was obtained from old record" and various sources, visual acuity is a relatively straight-forward measurement, and I did the last examination of all patients to insure that earlier measurements were consistent and that unrelated causes of poor visual acuity could be excluded. The subjects of this report were all referred for diagnosis or counseling; thus, asymptomatic individuals were unlikely to be included, as were individuals with long-standing poor vision for whom consultation offered little benefit. This inherent bias of a referral population was minimized by tracing the visual history, but could still influence the prevalence data, especially at older ages. Full visual histories were not obtainable for all eyes with poor vision in this study. The timing of visual loss was still uncertain for at least one eye of 20 of the patients, but there is no reason to expect that these individuals, who either could
697
not be located or for whom no old records could be obtained, showed any different behavior than the individuals for whom a visual history was traced. The regions of indeterminate visual acuity in the prevalence histograms show the magnitude of the uncertainty that must be accepted until better data become available. The cause of visual loss in retinitis pigmentosa has not been determined. Foveal pathologic findings such as absent reflexes, cystoid macular edema, or pigment epithelial atrophy were evident clinically in all of the present patients as well as in most patients with retinitis pigmentosa examined by others.P However, these changes may be present while central visual acuity is still good. 7.9 It is difficult to judge, therefore, whether a patient's loss of visual acuity results from primary damage to the photoreceptors or from a secondary degenerative phenomenon such as cystoid macular edema. Clearly clinical tests that are more subtle than Snellen visual acuity are needed to evaluate and follow up macular function in retinitis pigmentosa. Both color vision" and contrast sensitivity'v '" may be abnormal in retinitis pigmentosa while visual acuity is still good. However, these tests are not sufficiently refined, as yet, to monitor the early stages of retinitis pigmentosa or to predict when visual loss is imminent. The data presented in this report refer to conventional cases of retinitis pigmentosa and not those with anatomically or functionally limited disease such as sectorial retinitis pigmentosa or delimited retinitis pigmentosa." Recognition of the latter cases is important because they may appear ophthalmoscopically similar to conventional retinitis pigmentosa, but they have mild symptoms and a much better visual prognosis. They are best distinguished by use of the electroretinogram that characteristically shows moderate amplitude and a normal cone b-wave implicit time."
698
AMERICAN JOURNAL OF OPHTHALMOLOGY
The results of this study have important implications for patient counseling. Others have shown that most patients with retinitis pigmentosa have significantly diminished visual acuity, and that the prevalence of good visual acuity decreases with age. However, the prevalence data in Figures 3 and 4 are the first, to the best of my knowledge, which have been calculated on the basis of previous as well as current information. These cumulative data show that more than 60% (and possibly as many as 90%) of patients with recessive and dominant retinitis pigmentosa under the age of 20 years have a visual acuity of 6/12 (20/40) or better; this percentage decreases to 25% (or up to 35%) by the 50s. Thus, few patients with retinitis pigmentosa will have 6/60 (20/200) or worse visual acuity before age 20 years, but by age 50 years at least 50% will be affected to that degree. Patients should be informed of these estimates to be aware not only of possible loss of vision, but of the hopeful aspects of the prognosis. For example, roughly 25% of patients with retinitis pigmentosa retain good reading vision throughout life, and the longer that good vision is retained, the better the chances of keeping it. Patients should also be aware that, in all hereditary groups of retinitis pigmentosa, the midranges of visual acuity seem to be unstable and carry a guarded prognosis. This latter observation may be of some use in research, because patients with visual acuity between 6/15 (20/50) and 6/30 (20/100) would be good subjects for the evaluation of new therapies, if secondary foveal changes can be ruled out as the cause of visual loss. SUMMARY
I investigated the visual histories of 91 consecutive patients with retinitis pigmentosa to determine when, and how fast, visual acuity was affected by the
MAY, 1980
disease. The results from recessive cases showed that visual loss may occur at any age in retinitis pigmentosa, and typically progresses from 6/12 (20/40) to 6/60 (20/200) in about six years. At any given time, most of the patients had either good or poor visual acuity; intermediate levels of visual acuity appeared to be unstable. Before age 20 years, 60 to 90% of the patients had a visual acuity of6/12 (20/40) or better, and few had a visual acuity of 6/60 (20/200) or worse. By age 50 years, 25% of the patients still retained good visual acuity, but more than 50% had visual acuity of 6/60 (20/200) or worse. REFERENCES 1. Arakawa, T., Nishimura, M., Inomata, H., Nabeshima, T., and Oshio, K.: Pigmentary retinal dystrophy, the statistical studies of 572 cases. Folia Ophthalmol. Jpn. 26:1036, 1975. 2. Pearlman, J. T., Axelrod, R. N., and Tom, A.: Frequency of central visual impairment in retinitis pigmentosa. Arch. Ophthalmol. 95:894, 1977. 3. Fishman, G. A.: Retinitis pigmentosa. Visual loss. Arch. Ophthalmol. 96:1185, 1978. 4. Marmor, M. F.: The electroretinogram in retinitis pigmentosa. Arch. Ophthalmol. 97:1300, 1979. 5. Jay, B.: Hereditary aspects of pigmentary retinopathy. Trans. Ophthalmol. Soc. U.K. 92:173, 1972. 6. Pearlman, J. T., and Saxton, J.: A mathematical model of retinitis pigmentosa. In Tazawa, Y. (ed.): Proceedings of the XVI Symposium of the International Society for Clinical Electrophysiology of Vision. Tokyo, Japanese Journal of Opthalmology, 1979, pp. 307-314. 7. Francois, J., and Verriest, G.: Etude biometrique de la retinopathie pigmentaire. Ann. Oculistique 125:937, 1962. 8. Fishman, G. A., Maggiano, J. M., and Fishman, M.: Foveal lesions seen in retinitis pigmentosa. Arch. Ophthalmol. 95:1993, 1977. 9. Fetkenhour, C. L., Choromokos, E., Weinstein, J., and Shoch, D.: Cystoid macular edema in retinitis pigmentosa. Trans. Am. Acad. Ophthalmol. Otolaryngol, 83:515, 1977. 10. Franceschetti, A., Francois, J., and Babel, J.: Chorioretinal Heredodegenerations. Springfield, Charles C Thomas, 1974, pp. 163-198. 11. Wolkstein, M., Atkin, A., and Bodis-Wollner, I.: Grating acuity in two sisters with tapetoretinal degeneration. Doc. Ophthalmol. 13:41, 1977. 12. Arden, G. B., and Jacobson, J. J.: A simple grating test for contrast sensitivity. Preliminary results indicate value in screening for glaucoma. Invest. Ophthalmol. Visual Sci. 17:23, 1978. 13. Marmor, M. F.: Contrast sensitivity. A subtle test for retinal disease. Ophthalmology 86:59, 1979.
F.
MARMOR, M.D.
Stanford, California
Retinitis pigmentosa typically begins The results imply that visual loss is rapid in the equatorial retina, and progresses and unpredictable. both anteriorly and posteriorly until only SUBJECTS AND METHODS a tiny central island of visual field remains. Both cones and rods are involved, The population studied comprised all but damage to the rod system is most patients I saw in consultation and made a prominent and the effects on central vi- diagnosis of conventional retinitis pigsion are variable. Some patients maintain mentosa, from July 1973 through Sepgood visual acuity throughout their lives, tember 1978. The diagnosis of retinitis despite unrecordable electroretinograms pigmentosa was confirmed by electroand 2- to 3-degree central fields. How- physiologic recordings for most of these ever, others lose central vision at a young patients, but in some was made clinicalage and are much more severely disa- ly. Patients with mild variants of retinitis bled. pigmentosa such as sectorial disease or The manner in which visual acuity delimited disease' were excluded, but changes with age is important to patients their exclusion has little influence upon with this disease, but the course of visual these results because almost all of these loss in retinitis pigmentosa has never patients maintain good visual acuity. Also been established. Surveys have shown excluded were variants of retinitis pigthat roughly 50% of patients with retini- mentosa such as centroperipheral distis pigmentosa have visual acuity of 6/15 ease, Laurence-Moon-Bied] syndrome or (20/50) or worse and that the proportion cone dystrophy, and patients in whom an of patients with poor visual acuity in- acquired degeneration was suspected. A creases with age. 1-3 However, these data total of 91 patients with 179 nonamblyare based upon the visual acuity at a single opic eyes fit the criteria. The probable examination. Thus, they are influenced mode of inheritance, determined by by the selection of patients seeking care family history, was sporadic or recessive and do not show whether the loss of for 140 eyes (71 patients: 46 male, 25 female), dominant for 27 eyes (14 pavision is gradual, step-wise, or abrupt. I investigated the visual history of 91 tients: ten male, four female), and Xconsecutive patients who have typical chromosome-linked for 12 eyes (six paretinitis pigmentosa, to determine when tients: all male). Because of the small and how fast central vision was affected. number of eyes with dominant and Xchromosome-linked retinitis pigmentosa, most of the results are presented only for From the Division of Ophthalmology, Stanford recessive disease. University School of Medicine and the OphthalmoloThe visual history was investigated for gy Section, Veterans Administration Medical Center, Palo Alto, California. This study was supported in every patient whose corrected visual part by National Eye Institute Grant EYOl678 and by the National Institutes of Health Training Grant acuity, at the time of latest examination by me, was 6/12 (20/40) or worse in either EYOOO51-1O. Reprint requests to Michael F. Marmor, M.D., eye. Hospital charts, physician's records, Ophthalmology Section (1l2BI), Veterans Administration Medical Center, 3801 Miranda Ave., Palo and optometry records were examined or reviewed by telephone, until a best Alto, CA 94304. 692
AMERICAN JOURNAL OF OPHTHALMOLOGY 89:692--698, 1980
VOL. 89, NO. 5
corrected visual acuity of 6/9 (20/30) or better in both eyes could be shown or until no further information could be located. No attempt was made to show any findings other than visual acuity, because the quality of past observations could not be verified personally.
[20/200] or worse). By my own examination, all of these patients, regardless of visual acuity, showed foveal abnormalities that usually consisted of an absence of foveal reflexes and irregularity of the vitreoretinal interface. Except for a few patients with severe visual loss, who showed marked pigmentary atrophy under the fovea, there was no obvious correlation between visual acuity and foveal appearance. Only two patients in this series (both with recessive disease) had cataracts of possible visual significance, but both also showed prominent foveal abnormality. To determine the age and speed at which vision was lost, the previous visual history was investigated for the 116 eyes that had a corrected visual acuity of 6/12 (20/40) or worse. A total of 31 eyes could not be traced beyond 6/60 (20/200) visual
RESULTS
For each eye with recessive retinitis pigmentosa, the latest visual acuity was plotted against age (Fig. 1). The scatter of points indicates that the relationship of visual acuity to age cannot be a simple monotonic function. Instead of clustering along a diagonal between good vision in youth and poor vision in old age, the points are concentrated in overlapping ranges of good visual acuity (6/12 [20/40] or better) or poor visual acuity (6/60
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Fig. 1 (Marmor). Visual acuity at latest examinarion vs age, for cases with probable recessive inheritance. Each point represents one eye. The divisions of visual acuity in this and the following illustration are as follows: 6/6 (20/20), 6/9 (20/30), 6/12 (20/40), 6/15 (20/50), 6/18 (20/60), 6/21 (20170), 6/24 (20/80), 6/30 (20/100), 6/60 (20/200), counting lingers, hand movements, and light perception.
694
AMERICAN JOURNAL OF OPHTHALMOLOGY
acuity because old records or the patient could not be located. Figure 2 is a graphic representation of the visual history of the 59 eyes with recessive disease for which the visual acuity was traceable over a minimum change of three lines, or five years of follow-up, or to an earlier measurement of 6/12 (20/40) or better, There is a striking homogeneity in the slopes of the lines that represent visual change. The prevailing slope is steep, and indicates that the median time for a change in visual acuity from 6/12 (20/40) to 6/60 (20/200) was approximately six years, and the change occurred in less than ten years for all but a few patients. Additionally, visual acuity was lost with a relatively even distribution over ages five to 60 years. Eyes with dominant and X-chromosome-linked disease lost visual acuity with a similar time course, but there were too few cases to compare in terms of age. Statistical analysis of these data was considered, but our consultant
MAY, 1980
believed that graphic presentation of Figure 2 was more direct and accurate because eyes differed greatly in age at first or last examination, duration of follow-up, and frequency of follow-up. Visual acuities were compared between the eyes of patients with recessive disease, to determine how often the loss of visual acuity was unilateral or bilateral. Only 21 % of the patients showed a difference of more than two lines of visual acuity between the eyes, but many ,of these individuals were young (with good visual acuity), whereas others had been legally blind in both eyes for years. Among cases for which a progressive loss of visual acuity could be historically documented, approximately 40% showed significant asymmetry of vision for five or more years. The prevalence of visual loss in ocular disease has usually been calculated from data gathered at a single examination, a method that depends greatly upon the
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AGE Fig. 2 (Marmor). Visual history of eyes with recessive retinitis pigmentosa. Each line connects all recorded visual acuities for one eye; only eyes that could be traced over five years or a three-line change in visual acuity are shown. Visual acuities of 6/9 (20/30) or better are not discriminated in this figure.
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VISUAL LOSS IN RETINITIS PIGMENTOSA
size and age distribution of the population being studied. These problems can be minimized, and more accurate data obtained from a small population, if the visual acuity of each eye at different ages throughout life is incorporated into the statistics. Figures 3 and 4 show the result of such an analysis from the present data for recessive and dominant retinitis pigmentosa. The current visual acuity of each eye was tabulated within the decade of the patient's most recent examination, but the worst visual acuity within each preceding decade (obtained from the visual history) was also tabulated. Thus, the youngest decade cumulated data from the entire sample. This method was straight-forward for individuals with a complete visual history; once an eye was
80
~
noted to have good visual acuity (defined as 6/12 [20/40] or better for these plots) it was presumed to have good visual acuity in younger age groups. However, a problem developed for eyes that could not be fully traced. Because the dates of visual loss were unknown for these eyes, their visual acuities were indeterminate in decades that preceded theirearliest examination. For presentation in histograms, these indeterminate visual acuities have been divided into two groups, depending on whether the earliest known visual acuity was midrange (6/15 [20/50] to 6/30 [201100]) or poor (6/60 [20/200] or worse). The resulting frequency plot for the 140 eyes with recessive disease (Fig. 3) shows clearly that the percentage with good visual acuity decreases steadily over
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N~ )\}~.......................... : ?' n:jf~« 0-9 Fig. 3 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with recessive retinitis pigmentosa. Visual acuity is divided into three categories: good (6/12 [20/40] or better); midrange (6/15 [20/50] to 6/30 [20/100]); and poor (6160 [20/200] or worse). The indetenninate ranges represent eyes whose earliest recorded visual acuity in an older age group was midrange or poor. The data were cumulated from older to younger age groups to incorporate all available historical infonnation about each eye. The number of eyes in each category (N) is shown near the bottom of the histogram.
696
AMERICAN JOURNAL OF OPHTHALMOLOGY
MAY, 1980
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50-59
AGE Fig. 4 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with dominant retinitis pigmentosa.
the years, whereas the percentage with poor visual acuity increases. The number of eyes with middle-range visual acuity remains relatively small (about 10%) throughout the plot, which is consistent with the impression from Figure 2 that visual acuity decreases rapidly at any age in retinitis pigmentosa and does not remain for any long period in the middle range. The 27 eyes with dominant disease (Fig. 4) showed a similar trend, and a somewhat larger percentage of eyes with good visual acuity at any given age. DISCUSSION
The data from recessive and sporadic cases of conventional retinitis pigmentosa show that the disease was unexpectedly rapid in its effects on visual acuity.
Visual loss began at any age, and once visual acuity began to fail, it generally dropped to 6/60 (20/200) or below within a period of four to ten years (the median is near six). There appeared to be few cases in which midrange visual acuity (6/15 [20/50] to 6/30 [20/100]) was maintained for any period of time. Indeed, the data in Figure 2 may underestimate the speed of visual loss; the visual history lines pass through all ofthe available visual acuity measurements for each eye, but if no examinations were recorded over a long period of time (for example, ten years), then the line drawn between visual acuities at the beginning and end of that period may have a falsely shallow slope. In many patients the two eyes were affected simultaneously, but in 20 to 40% one eye was spared for live or more years.
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VISUAL LOSS IN RETINITIS PIGMENTOSA
Retinitis pigmentosa is not a homogeneous disease. Different modes of inheritance have been accounted for in this study, but there also may be unrecognized variants within each mode of inheritance. Some of the differences in visual history, among individuals, may reflect such variants. The present data suggest that the progression of visual loss in dominant retinitis pigmentosa may be slightly slower, and occur at a slightly older age, than in recessive disease. However, because of the relatively small numbers of cases, and the variability among individuals, that conclusion could tum out to be unfounded. The classic view3·5 has been that dominant disease is inherently milder, but one recent study" suggests that there is little distinction. Prospective studies should ultimately be undertaken, but they are exceedingly difficult with retinitis pigmentosa because of the slow progression of the disease. Although this was a retrospective study in which information was obtained from old record" and various sources, visual acuity is a relatively straight-forward measurement, and I did the last examination of all patients to insure that earlier measurements were consistent and that unrelated causes of poor visual acuity could be excluded. The subjects of this report were all referred for diagnosis or counseling; thus, asymptomatic individuals were unlikely to be included, as were individuals with long-standing poor vision for whom consultation offered little benefit. This inherent bias of a referral population was minimized by tracing the visual history, but could still influence the prevalence data, especially at older ages. Full visual histories were not obtainable for all eyes with poor vision in this study. The timing of visual loss was still uncertain for at least one eye of 20 of the patients, but there is no reason to expect that these individuals, who either could
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not be located or for whom no old records could be obtained, showed any different behavior than the individuals for whom a visual history was traced. The regions of indeterminate visual acuity in the prevalence histograms show the magnitude of the uncertainty that must be accepted until better data become available. The cause of visual loss in retinitis pigmentosa has not been determined. Foveal pathologic findings such as absent reflexes, cystoid macular edema, or pigment epithelial atrophy were evident clinically in all of the present patients as well as in most patients with retinitis pigmentosa examined by others.P However, these changes may be present while central visual acuity is still good. 7.9 It is difficult to judge, therefore, whether a patient's loss of visual acuity results from primary damage to the photoreceptors or from a secondary degenerative phenomenon such as cystoid macular edema. Clearly clinical tests that are more subtle than Snellen visual acuity are needed to evaluate and follow up macular function in retinitis pigmentosa. Both color vision" and contrast sensitivity'v '" may be abnormal in retinitis pigmentosa while visual acuity is still good. However, these tests are not sufficiently refined, as yet, to monitor the early stages of retinitis pigmentosa or to predict when visual loss is imminent. The data presented in this report refer to conventional cases of retinitis pigmentosa and not those with anatomically or functionally limited disease such as sectorial retinitis pigmentosa or delimited retinitis pigmentosa." Recognition of the latter cases is important because they may appear ophthalmoscopically similar to conventional retinitis pigmentosa, but they have mild symptoms and a much better visual prognosis. They are best distinguished by use of the electroretinogram that characteristically shows moderate amplitude and a normal cone b-wave implicit time."
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The results of this study have important implications for patient counseling. Others have shown that most patients with retinitis pigmentosa have significantly diminished visual acuity, and that the prevalence of good visual acuity decreases with age. However, the prevalence data in Figures 3 and 4 are the first, to the best of my knowledge, which have been calculated on the basis of previous as well as current information. These cumulative data show that more than 60% (and possibly as many as 90%) of patients with recessive and dominant retinitis pigmentosa under the age of 20 years have a visual acuity of 6/12 (20/40) or better; this percentage decreases to 25% (or up to 35%) by the 50s. Thus, few patients with retinitis pigmentosa will have 6/60 (20/200) or worse visual acuity before age 20 years, but by age 50 years at least 50% will be affected to that degree. Patients should be informed of these estimates to be aware not only of possible loss of vision, but of the hopeful aspects of the prognosis. For example, roughly 25% of patients with retinitis pigmentosa retain good reading vision throughout life, and the longer that good vision is retained, the better the chances of keeping it. Patients should also be aware that, in all hereditary groups of retinitis pigmentosa, the midranges of visual acuity seem to be unstable and carry a guarded prognosis. This latter observation may be of some use in research, because patients with visual acuity between 6/15 (20/50) and 6/30 (20/100) would be good subjects for the evaluation of new therapies, if secondary foveal changes can be ruled out as the cause of visual loss. SUMMARY
I investigated the visual histories of 91 consecutive patients with retinitis pigmentosa to determine when, and how fast, visual acuity was affected by the
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disease. The results from recessive cases showed that visual loss may occur at any age in retinitis pigmentosa, and typically progresses from 6/12 (20/40) to 6/60 (20/200) in about six years. At any given time, most of the patients had either good or poor visual acuity; intermediate levels of visual acuity appeared to be unstable. Before age 20 years, 60 to 90% of the patients had a visual acuity of6/12 (20/40) or better, and few had a visual acuity of 6/60 (20/200) or worse. By age 50 years, 25% of the patients still retained good visual acuity, but more than 50% had visual acuity of 6/60 (20/200) or worse. REFERENCES 1. Arakawa, T., Nishimura, M., Inomata, H., Nabeshima, T., and Oshio, K.: Pigmentary retinal dystrophy, the statistical studies of 572 cases. Folia Ophthalmol. Jpn. 26:1036, 1975. 2. Pearlman, J. T., Axelrod, R. N., and Tom, A.: Frequency of central visual impairment in retinitis pigmentosa. Arch. Ophthalmol. 95:894, 1977. 3. Fishman, G. A.: Retinitis pigmentosa. Visual loss. Arch. Ophthalmol. 96:1185, 1978. 4. Marmor, M. F.: The electroretinogram in retinitis pigmentosa. Arch. Ophthalmol. 97:1300, 1979. 5. Jay, B.: Hereditary aspects of pigmentary retinopathy. Trans. Ophthalmol. Soc. U.K. 92:173, 1972. 6. Pearlman, J. T., and Saxton, J.: A mathematical model of retinitis pigmentosa. In Tazawa, Y. (ed.): Proceedings of the XVI Symposium of the International Society for Clinical Electrophysiology of Vision. Tokyo, Japanese Journal of Opthalmology, 1979, pp. 307-314. 7. Francois, J., and Verriest, G.: Etude biometrique de la retinopathie pigmentaire. Ann. Oculistique 125:937, 1962. 8. Fishman, G. A., Maggiano, J. M., and Fishman, M.: Foveal lesions seen in retinitis pigmentosa. Arch. Ophthalmol. 95:1993, 1977. 9. Fetkenhour, C. L., Choromokos, E., Weinstein, J., and Shoch, D.: Cystoid macular edema in retinitis pigmentosa. Trans. Am. Acad. Ophthalmol. Otolaryngol, 83:515, 1977. 10. Franceschetti, A., Francois, J., and Babel, J.: Chorioretinal Heredodegenerations. Springfield, Charles C Thomas, 1974, pp. 163-198. 11. Wolkstein, M., Atkin, A., and Bodis-Wollner, I.: Grating acuity in two sisters with tapetoretinal degeneration. Doc. Ophthalmol. 13:41, 1977. 12. Arden, G. B., and Jacobson, J. J.: A simple grating test for contrast sensitivity. Preliminary results indicate value in screening for glaucoma. Invest. Ophthalmol. Visual Sci. 17:23, 1978. 13. Marmor, M. F.: Contrast sensitivity. A subtle test for retinal disease. Ophthalmology 86:59, 1979.