VISUAL LOSS IN RETINITIS PIGMENTOSA

MICHAEL F. MARMOR, M.D.

Stanford, California

Retinitis pigmentosa typically beginsin the equatorial retina, and progressesboth anteriorly and posteriorly until onlya tiny central island of visual field re­mains. Both cones and rods are involved,but damage to the rod system is mostprominent and the effects on central vi­sion are variable. Some patients maintaingood visual acuity throughout their lives,despite unrecordable electroretinogramsand 2- to 3-degree central fields. How­ever, others lose central vision at a youngage and are much more severely disa­bled.

The manner in which visual acuitychanges with age is important to patientswith this disease, but the course of visualloss in retinitis pigmentosa has neverbeen established. Surveys have shownthat roughly 50% of patients with retini­tis pigmentosa have visual acuity of 6/15(20/50) or worse and that the proportionof patients with poor visual acuity in­creases with age. 1-3 However, these dataare based upon the visual acuity at a singleexamination. Thus, they are influencedby the selection of patients seeking careand do not show whether the loss ofvision is gradual, step-wise, or abrupt.

I investigated the visual history of 91consecutive patients who have typicalretinitis pigmentosa, to determine whenand how fast central vision was affected.

From the Division of Ophthalmology, StanfordUniversity School of Medicine and the Ophthalmolo­gy Section, Veterans Administration Medical Center,Palo Alto, California. This study was supported inpart by National Eye Institute Grant EYOl678 and bythe National Institutes of Health Training GrantEYOOO51-1O.

Reprint requests to Michael F. Marmor, M.D.,Ophthalmology Section (1l2BI), Veterans Adminis­tration Medical Center, 3801 Miranda Ave., PaloAlto, CA 94304.

The results imply that visual loss is rapidand unpredictable.

SUBJECTS AND METHODS

The population studied comprised allpatients I saw in consultation and made adiagnosis of conventional retinitis pig­mentosa, from July 1973 through Sep­tember 1978. The diagnosis of retinitispigmentosa was confirmed by electro­physiologic recordings for most of thesepatients, but in some was made clinical­ly. Patients with mild variants of retinitispigmentosa such as sectorial disease ordelimited disease' were excluded, buttheir exclusion has little influence uponthese results because almost all of thesepatients maintain good visual acuity. Alsoexcluded were variants of retinitis pig­mentosa such as centroperipheral dis­ease, Laurence-Moon-Bied] syndrome orcone dystrophy, and patients in whom anacquired degeneration was suspected. Atotal of 91 patients with 179 nonambly­opic eyes fit the criteria. The probablemode of inheritance, determined byfamily history, was sporadic or recessivefor 140 eyes (71 patients: 46 male, 25female), dominant for 27 eyes (14 pa­tients: ten male, four female), and X­chromosome-linked for 12 eyes (six pa­tients: all male). Because of the smallnumber of eyes with dominant and X­chromosome-linked retinitis pigmentosa,most of the results are presented only forrecessive disease.

The visual history was investigated forevery patient whose corrected visualacuity, at the time of latest examinationby me, was 6/12 (20/40) or worse in eithereye. Hospital charts, physician's records,and optometry records were examined orreviewed by telephone, until a best

692 AMERICAN JOURNAL OF OPHTHALMOLOGY 89:692--698, 1980

VOL. 89, NO. 5 VISUAL LOSS IN RETINITIS PIGMENTOSA 693

corrected visual acuity of 6/9 (20/30) orbetter in both eyes could be shown oruntil no further information could belocated. No attempt was made to showany findings other than visual acuity,because the quality of past observationscould not be verified personally.

RESULTS

For each eye with recessive retinitispigmentosa, the latest visual acuity wasplotted against age (Fig. 1). The scatter ofpoints indicates that the relationship ofvisual acuity to age cannot be a simplemonotonic function. Instead of clusteringalong a diagonal between good vision inyouth and poor vision in old age, thepoints are concentrated in overlappingranges of good visual acuity (6/12 [20/40]or better) or poor visual acuity (6/60

[20/200] or worse). By my own examina­tion, all of these patients, regardless of vi­sual acuity, showed foveal abnormalitiesthat usually consisted of an absence offoveal reflexes and irregularity of the vi­treoretinal interface. Except for a few pa­tients with severe visual loss, who showedmarked pigmentary atrophy under thefovea, there was no obvious correlation be­tween visual acuity and foveal appearance.Only two patients in this series (bothwith recessive disease) had cataracts ofpossible visual significance, but both alsoshowed prominent foveal abnormality.

To determine the age and speed atwhich vision was lost, the previous visualhistory was investigated for the 116 eyesthat had a corrected visual acuity of 6/12(20/40) or worse. A total of 31 eyes couldnot be traced beyond 6/60 (20/200) visual

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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 asfollows: 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 MAY, 1980

acuity because old records or the patientcould not be located. Figure 2 is agraphic representation of the visual his­tory of the 59 eyes with recessive diseasefor which the visual acuity was traceableover a minimum change of three lines, orfive years of follow-up, or to an earliermeasurement of 6/12 (20/40) or better,There is a striking homogeneity in theslopes of the lines that represent visualchange. The prevailing slope is steep,and indicates that the median time for achange in visual acuity from 6/12 (20/40)to 6/60 (20/200) was approximately sixyears, and the change occurred in lessthan ten years for all but a few patients.Additionally, visual acuity was lost with arelatively even distribution over ages fiveto 60 years. Eyes with dominant andX-chromosome-linked disease lost visualacuity with a similar time course, butthere were too few cases to compare interms of age. Statistical analysis of thesedata was considered, but our consultant

believed that graphic presentation ofFigure 2 was more direct and accuratebecause eyes differed greatly in age atfirst or last examination, duration offollow-up, and frequency of follow-up.

Visual acuities were compared be­tween the eyes of patients with recessivedisease, to determine how often the lossof visual acuity was unilateral or bilateral.Only 21% of the patients showed adifference of more than two lines ofvisual acuity between the eyes, but many,of these individuals were young (withgood visual acuity), whereas others hadbeen legally blind in both eyes for years.Among cases for which a progressive lossof visual acuity could be historicallydocumented, approximately 40% showedsignificant asymmetry of vision for five ormore years.

The prevalence of visual loss in oculardisease has usually been calculated fromdata gathered at a single examination, amethod that depends greatly upon the

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Fig. 2 (Marmor). Visual history of eyes with recessive retinitis pigmentosa. Each line connects all recordedvisual acuities for one eye; only eyes that could be traced over five years or a three-line change in visualacuity are shown. Visual acuities of 6/9 (20/30) or better are not discriminated in this figure.

VOL. 89, NO. 5 VISUAL LOSS IN RETINITIS PIGMENTOSA 695

size and age distribution of the popula­tion being studied. These problems canbe minimized, and more accurate dataobtained from a small population, if thevisual acuity of each eye at different agesthroughout life is incorporated into thestatistics. Figures 3 and 4 show the resultof such an analysis from the present datafor recessive and dominant retinitis pig­mentosa. The current visual acuity ofeach eye was tabulated within the decadeof the patient's most recent examination,but the worst visual acuity within eachpreceding decade (obtained from thevisual history) was also tabulated. Thus,the youngest decade cumulated datafrom the entire sample. This method wasstraight-forward for individuals with acomplete visual history; once an eye was

noted to have good visual acuity (definedas 6/12 [20/40] or better for these plots) itwas presumed to have good visual acuityin younger age groups. However, a prob­lem developed for eyes that could not befully traced. Because the dates of visuallosswere unknown for these eyes, their vi­sual acuities were indeterminate in de­cades thatpreceded theirearliestexamina­tion. For presentation in histograms,these indeterminate visual acuities havebeen divided into two groups, dependingon 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 the140 eyes with recessive disease (Fig. 3)shows clearly that the percentage withgood visual acuity decreases steadily over

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Fig. 3 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with recessiveretinitis 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 eyeswhose earliest recorded visual acuity in an older age group was midrange or poor. The data were cumulatedfrom older to younger age groups to incorporate all available historical infonnation about each eye. Thenumber 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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Fig. 4 (Marmor). Prevalence of different levels of visual acuity, at different ages, for eyes with dominantretinitis pigmentosa.

the years, whereas the percentage withpoor visual acuity increases. The numberof eyes with middle-range visual acuityremains relatively small (about 10%)throughout the plot, which is consistentwith the impression from Figure 2 thatvisual acuity decreases rapidly at any agein retinitis pigmentosa and does notremain for any long period in the middlerange. The 27 eyes with dominant dis­ease (Fig. 4) showed a similar trend, anda somewhat larger percentage of eyeswith good visual acuity at any given age.

DISCUSSION

The data from recessive and sporadiccases of conventional retinitis pigmen­tosa show that the disease was unexpect­edly rapid in its effects on visual acuity.

Visual loss began at any age, and oncevisual acuity began to fail, it generallydropped to 6/60 (20/200) or below withina period of four to ten years (the medianis near six). There appeared to be fewcases 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 underestimatethe speed of visual loss; the visual historylines pass through all ofthe available visu­al acuity measurements for each eye, butif no examinations were recorded overa long period of time (for example, tenyears), then the line drawn between visualacuities at the beginning and end of thatperiod 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.

VOL. 89, NO.5 VISUAL LOSS IN RETINITIS PIGMENTOSA 697

Retinitis pigmentosa is not a homoge­neous disease. Different modes of inheri­tance have been accounted for in thisstudy, but there also may be unrecog­nized variants within each mode of inher­itance. Some of the differences in visualhistory, among individuals, may reflectsuch variants.

The present data suggest that theprogression of visual loss in dominantretinitis pigmentosa may be slightlyslower, and occur at a slightly older age,than in recessive disease. However, be­cause of the relatively small numbers ofcases, and the variability among individ­uals, that conclusion could tum out to beunfounded. The classic view3·5 has beenthat dominant disease is inherently mild­er, but one recent study" suggests thatthere is little distinction.

Prospective studies should ultimatelybe undertaken, but they are exceedinglydifficult with retinitis pigmentosa be­cause of the slow progression of thedisease. Although this was a retrospec­tive study in which information wasobtained from old record" and varioussources, visual acuity is a relativelystraight-forward measurement, and I didthe last examination of all patients toinsure that earlier measurements wereconsistent and that unrelated causes ofpoor visual acuity could be excluded.

The subjects of this report were allreferred for diagnosis or counseling;thus, asymptomatic individuals were un­likely to be included, as were individualswith long-standing poor vision for whomconsultation offered little benefit. Thisinherent bias of a referral population wasminimized by tracing the visual history,but could still influence the prevalencedata, especially at older ages.

Full visual histories were not obtaina­ble for all eyes with poor vision in thisstudy. The timing of visual loss was stilluncertain for at least one eye of 20 of thepatients, but there is no reason to expectthat these individuals, who either could

not be located or for whom no old re­cords could be obtained, showed any dif­ferent behavior than the individuals forwhom a visual history was traced. The re­gions of indeterminate visual acuity in theprevalence 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 pigmentepithelial atrophy were evident clinicallyin all of the present patients as well asin most patients with retinitis pigmentosaexamined by others.P However, thesechanges may be present while centralvisual acuity is still good. 7.9 It is difficult tojudge, therefore, whether a patient's lossof visual acuity results from primary dam­age to the photoreceptors or from a sec­ondary degenerative phenomenon such ascystoid macular edema. Clearly clinicaltests that are more subtle than Snellenvisual acuity are needed to evaluate andfollow up macular function in retinitis pig­mentosa. Both color vision" and contrastsensitivity'v '"may be abnormal in retinitispigmentosa while visual acuity is stillgood. However, these tests are not suffi­ciently refined, as yet, to monitor theearly stages of retinitis pigmentosa or topredict when visual loss is imminent.

The data presented in this report referto conventional cases of retinitis pigmen­tosa and not those with anatomically orfunctionally limited disease such as sec­torial retinitis pigmentosa or delimitedretinitis pigmentosa." Recognition of thelatter cases is important because theymay appear ophthalmoscopically similarto conventional retinitis pigmentosa, butthey have mild symptoms and a muchbetter visual prognosis. They are bestdistinguished by use of the electro­retinogram that characteristically showsmoderate amplitude and a normal coneb-wave implicit time."

698 AMERICAN JOURNAL OF OPHTHALMOLOGY MAY, 1980

The results of this study have impor­tant implications for patient counseling.Others have shown that most patientswith retinitis pigmentosa have signifi­cantly diminished visual acuity, and thatthe prevalence of good visual acuitydecreases with age. However, the preva­lence data in Figures 3 and 4 are the first,to the best of my knowledge, which havebeen calculated on the basis of previousas well as current information. Thesecumulative data show that more than60% (and possibly as many as 90%) ofpatients with recessive and dominantretinitis pigmentosa under the age of 20years have a visual acuity of 6/12 (20/40)or better; this percentage decreases to25% (or up to 35%) by the 50s. Thus, fewpatients with retinitis pigmentosa willhave 6/60 (20/200) or worse visual acuitybefore age 20 years, but by age 50 yearsat least 50% will be affected to thatdegree. Patients should be informed ofthese estimates to be aware not only ofpossible loss of vision, but of the hopefulaspects of the prognosis. For example,roughly 25% of patients with retinitispigmentosa retain good reading visionthroughout life, and the longer that goodvision is retained, the better the chancesof keeping it. Patients should also beaware that, in all hereditary groups ofretinitis pigmentosa, the midranges ofvisual acuity seem to be unstable andcarry a guarded prognosis. This latterobservation may be of some use inresearch, because patients with visualacuity between 6/15 (20/50) and 6/30(20/100) would be good subjects for theevaluation of new therapies, if secondaryfoveal changes can be ruled out as thecause of visual loss.

SUMMARY

I investigated the visual histories of 91consecutive patients with retinitis pig­mentosa to determine when, and howfast, visual acuity was affected by the

disease. The results from recessive casesshowed that visual loss may occur at anyage in retinitis pigmentosa, and typicallyprogresses from 6/12 (20/40) to 6/60(20/200) in about six years. At any giventime, most of the patients had either goodor poor visual acuity; intermediate levelsof visual acuity appeared to be unstable.Before age 20 years, 60 to 90% of the pa­tients had a visual acuity of6/12 (20/40)orbetter, and few had a visual acuity of6/60 (20/200) or worse. By age 50 years,25% of the patients still retained goodvisual acuity, but more than 50% had vi­sual acuity of 6/60 (20/200) or worse.

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1. Arakawa, T., Nishimura, M., Inomata, H.,Nabeshima, T., and Oshio, K.: Pigmentary retinaldystrophy, the statistical studies of 572 cases. FoliaOphthalmol. Jpn. 26:1036, 1975.

2. Pearlman, J. T., Axelrod, R. N., and Tom, A.:Frequency of central visual impairment in retinitispigmentosa. Arch. Ophthalmol. 95:894, 1977.

3. Fishman, G. A.: Retinitis pigmentosa. Visualloss. 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 mathematicalmodel of retinitis pigmentosa. In Tazawa, Y. (ed.):Proceedings of the XVI Symposium of the Inter­national Society for Clinical Electrophysiology ofVision. 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 inretinitis 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 tapetoretinaldegeneration. Doc. Ophthalmol. 13:41, 1977.

12. Arden, G. B., and Jacobson, J. J.: A simplegrating test for contrast sensitivity. Preliminaryresults indicate value in screening for glaucoma.Invest. Ophthalmol. Visual Sci. 17:23, 1978.

13. Marmor, M. F.: Contrast sensitivity. A subtletest for retinal disease. Ophthalmology 86:59, 1979.