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Visual acuity impairment in patients with retinitis pigmentosa at age 45 years or older
Visual Acuity Impairment in Patients with Retinitis Pigmentosa at Age 45 Years or Older Sandeep Grover, MD,1 Gerald A. Fishman, MD,1 Robert J. Anderson, PhD,2 Marcia S. V. Tozatti, MD,3 John R. Heckenlively, MD,4 Richard G. Weleber, MD,5 Albert O. Edwards, MD, PhD,6 Jeremiah Brown, Jr., MD7 Objective: To determine the severity of visual acuity impairment in patients, age 45 years or older, with either isolated or identifiable genetic subtypes of retinitis pigmentosa (RP) and Usher syndrome. Design: Multicenter, retrospective, cross-sectional analysis. Participants: Visual acuity data were obtained on 999 patients with different genetic subtypes of RP and Usher syndrome, age 45 years or older, from 4 major eye care centers in the United States. Intervention: The best-corrected visual acuity obtained on these patients from the eye with better vision on their most recent visit was used for the analysis. Main Outcome Measure: Best-corrected visual acuity was the main parameter analyzed for the study, and it was obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor). Results: The final analyses were done on 982 patients (17 patients with a sector form of RP were analyzed separately). Of the 982 patients, 506 (52%) had a visual acuity of 20/40 or better, and 678 (69%) had a visual acuity of 20/70 or better in at least one eye. There were 243 (25%) patients who had a visual acuity of 20/200 or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. The odds ratio for any patient having a visual acuity of 20/200 or worse in this population was 1.4 for each difference of 10 years of age. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye was 0.95 for a 10-year age difference. Conclusions: In this large population of patients with RP and Usher syndrome from four centers, it was rare for such patients to lose all vision in both eyes. One fourth of the patients had a visual acuity of 20/200 or worse in both eyes, and more than half of the population had a visual acuity of 20/40 or better in at least one eye. These data can be used to counsel such patients on the extent of potential visual acuity impairment from their disease. Ophthalmology 1999;106:1780 –1785 Retinitis pigmentosa (RP) includes a group of hereditary progressive retinal dystrophies typically characterized by
Originally received: October 26, 1998. Revision accepted: May 20, 1999. Manuscript no. 98709. 1 Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois. 2 Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois. 3 Department of Ophthalmology, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. 4 Jules Stein Eye Institute, Los Angeles, California. 5 Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon. 6 Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas. 7 Department of Ophthalmology, University of Iowa, Iowa City, Iowa. Presented in part at the Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, Florida, May 1998. Supported by a center grant from the Foundation Fighting Blindness, Baltimore, Maryland (GAF). Reprint requests to Gerald A. Fishman, MD, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612. E-mail:[email protected].
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night blindness, bone spicule-like pigmentary retinal changes, progressive loss of peripheral visual fields, and decreased or nondetectable responses on electroretinogram testing. The association of RP with congenital hearing loss is classified as Usher syndrome; type 1 is associated with severe sensorineural hearing loss with absent vestibular responses on caloric testing and unintelligible speech, and type 2 is associated with mild to moderate hearing loss with intact vestibular responses and intelligible speech. In the literature, RP is not infrequently cited as a “disease causing total blindness”1–3 or referred to as causing blindness,4 –7 not specifying whether it implies total or legal blindness. An earlier study showed that less than 0.5% of patients actually lost all vision in both eyes.8 This previous study included patients with RP seen by one of the authors (GAF) in all age groups. However, the number of patients with RP beyond middle age was not substantial enough to make a strong statement about the impairment of visual acuity in later life. Therefore, we collected and analyzed data from four centers in the United States obtained on patients with RP and Usher syndrome, age 45 years or older, in an attempt to assess the severity of their visual acuity impairment.
Grover et al 䡠 Visual Acuity in RP Table 1. Criteria for Exclusion Reason for Exclusion
Center 1
Center 2
Center 3
Center 4
Total
Glaucoma Keratopathy Refraction not done Diabetic retinopathy Dense cataract Retinal detachment Others*
12 4 — 1 — — —
3 2 — — 2 1 3
3 1 — — — — 1
— — 57 — — — —
18 7 57 1 2 1 4
Total
17
11
5
57
90
* Includes one patient each with mental retardation and cranial arteritis, and two patients from center 2 whose data are included in center 1.
Methods
center with the two extremes of visual acuity, those with 20/20 or better (n ⫽ 17) and those with 20/800 or worse (n ⫽ 10) because a proper refraction would not have significantly impacted on their visual acuity. There were two patients who were excluded from center 2 because data on these two patients were included from center 1. Data from 18 patients who had unilateral impairment of vision due to causes other than RP were included because our study analyzed data obtained from the better eye. Patients with dense cataracts in both eyes were excluded. However, patients with aphakia or pseudophakia were included in the study. We also did not include patients with Bardet-Biedl syndrome or cone-rod dystrophy. The data were obtained on a total of 999 patients with various genetic subtypes of RP (Table 2), including autosomal dominant (n ⫽ 182), autosomal recessive (n ⫽ 149), and X-linked recessive (n ⫽ 32). The criteria of classifying these patients into one of the genetic subtypes were defined earlier by one of the authors.9 Data on 90 patients who could not be classified readily into any of the genetic subtypes but for whom two other family members were known to be affected were also included as an indeterminate subtype. Also included were 16 patients with Usher syndrome type 1 and 48 patients with Usher syndrome type 2. Patients with RP who were known to be the only affected members in their families were included in the isolated subtype (n ⫽ 465). Seventeen patients from the entire dataset with a sector form of RP were analyzed separately because their visual prognosis is known to be more favorable than other RP subtypes.10,11
Visual acuities in patients with RP, age 45 years or older, obtained from four centers in the United States were evaluated to ascertain the severity of visual acuity impairment in this group of patients. The four centers were Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago (center 1); Jules Stein Eye Institute, Los Angeles (center 2); Casey Eye Institute, Oregon Health Sciences University, Portland (center 3); and Department of Ophthalmology, University of Iowa, Iowa City (center 4). The best-corrected visual acuities were obtained on both eyes from all patients. The visual acuities were obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor, Santa Barbara, CA) at one of the centers. Although there were instances when the visual acuities were different in the two eyes, the visual acuities correlated significantly between the two eyes (Spearman r ⫽ 0.81; P ⬍ 0.01). As in a previous study,8 visual acuity obtained in the eye with better acuity on the most recent visit of each patient was used for this study. All patients with RP seen at each center who fulfilled the entrance criteria were included in the analysis. Of the 1089 patients whose charts were initially reviewed, 90 patients were excluded from different centers (Table 1). Patients with glaucoma, diabetic retinopathy, keratopathy, and other ocular and medical conditions that could impact on the visual acuity of the patient were excluded (n ⫽ 31). From center 4, 57 patients were excluded because information on best-corrected visual acuity was not available. However, we did include patients from this
Table 2. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older in Various Genetic Subtypes from Different Centers: No. (%)* Mean Age (yrs)
Age Range (yrs)
Total
Center 1
Center 2
Center 3
Center 4
Males Females Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate Usher 1 syndrome Usher 2 syndrome
58 59 60 59 54 59 58 57 54
45–85 45–88 45–88 45–85 45–77 45–85 45–78 45–74 45–78
461 (47) 521 (53) 182 (19) 149 (15) 32 (3) 465 (47) 90 (9) 16 (2) 48 (5)
207 (47) 236 (53) 70 (16) 61 (14) 18 (4) 196 (44) 56 (13) 11 (2) 31 (7)
160 (44) 200 (56) 53 (15) 70 (19) 9 (2) 219 (61) 3 (1) 1 (⬍1) 5 (1)
72 (57) 54 (43) 43 (34) 15 (12) 5 (4) 26 (21) 24 (19) 4 (3) 9 (7)
22 (42) 31 (58) 16 (30) 3 (6) — 24 (45) 7 (13) — 3 (6)
Total
58
45–88
982
443 (45)
360 (37)
126 (13)
53 (5)
Sector
60
45–86
17
7
10
—
—
* All percentages are rounded off to the nearest whole number.
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Ophthalmology Volume 106, Number 9, September 1999 Table 3. Distribution of Patients with Retinitis Pigmentosa (RP) Age 45 Years or Older According to Genetic Subtype and Visual Acuity: No. (%)* Visual Acuity
Total† (n ⴝ 982)
AD (n ⴝ 182)
AR (n ⴝ 149)
XL (n ⴝ 32)
ISO (n ⴝ 465)
INDET (n ⴝ 90)
USH 1 (n ⴝ 16)
USH 2 (n ⴝ 48)
SECTOR (n ⴝ 17)
20/40 or better 20/70 or better Better than 20/200 20/200 or worse CF or worse
506 (52) 678 (69) 739 (75) 243 (25) 123 (12)
117 (64) 139 (76) 149 (82) 33 (18) 15 (8)
62 (42) 97 (65) 111 (74) 38 (26) 25 (17)
8 (25) 11 (34) 12 (38) 20 (62) 10 (31)
245 (53) 337 (72) 365 (78) 100 (22) 46 (10)
51 (57) 61 (68) 65 (72) 25 (28) 15 (17)
6 (38) 9 (56) 10 (62) 6 (38) 2 (12)
17 (35) 24 (50) 27 (56) 21 (44) 10 (21)
14 (82) 16 (94) 17 (100) — —
AD ⫽ autosomal dominant; AR ⫽ autosomal recessive; XL ⫽ X-linked recessive; ISO ⫽ isolated; INDET ⫽ indeterminate; USH 1 ⫽ Usher 1 syndrome; USH 2 ⫽ Usher 2 syndrome; CF ⫽ counting fingers. * All percentages are rounded off to the nearest whole number. † Does not include 17 patients with sector type of RP.
Excluding the patients with a sector form of RP (n ⫽ 17), the final analysis was done on 982 patients with RP. There were 461 men and 521 women in the study. The mean age of the patients was 58 years (range, 45 to 88 years). The mean ages and the age ranges of the patients in each genetic subtype are listed in Table 2. The population studied was comprised of 783 (80%) whites (mean age, 59 years; mean visual acuity, 20/100), 88 (9%) blacks (mean age, 57 years; mean visual acuity, 20/100), 50 (5%) Hispanics (mean age, 55 years; mean visual acuity, 20/90), and 61 (6%) others comprising additional different ethnic groups (mean age, 60 years; mean visual acuity, 20/60). Table 2 also shows the number of patients in each genetic subtype included from each of the four centers. The majority of the patients were from center 1 (443 patients) and center 2 (360 patients). Data from 126 patients and 53 patients were included from centers 3 and 4, respectively. There were 17 patients with a sector form of RP, 7 from center 1 and 10 from center 2. The percentages of each genetic subtype in this study, excluding the patients with Usher syndrome types 1 and 2, were very similar to those in our earlier study and also to the study by Boughman and Fishman.12 Therefore, our cohort of patients is likely representative of genetic subtypes of RP patients seen in the United States at various referral centers.
Results Analyzing the data from 982 patients with RP, age 45 years or older, regardless of genetic subtype, 506 (52%) patients had a visual acuity of 20/40 or better, 678 (69%) had a visual acuity of 20/70 or better, and 739 (75%) had a visual acuity of better than 20/200 in at least one eye (Table 3). Hence, 243 (25%) patients had
a visual acuity of 20/200 or worse in both eyes, out of which 123 (12%) patients had a visual acuity of count fingers or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. Assessing the impairment of visual acuity within the genetic subtypes, patients with autosomal dominant RP had better visual acuity than the rest of the subtypes, and patients with X-linked RP had the worst (Table 3). Sixty-four percent of patients with autosomal dominant RP had a visual acuity of 20/40 or better in at least one eye compared with 42% with autosomal recessive and 25% with X-linked recessive RP. The remaining subtypes and patients with Usher syndrome were in between the two extremes. Also, 18% of patients with autosomal dominant RP had a visual acuity of 20/200 or worse in both eyes compared with 26% with autosomal recessive and 62% with X-linked recessive RP. The mean age of patients with X-linked RP was 54 years, younger than most of the other subtypes by 3– 6 years. Of the five patients who had no light perception in both eyes, one had an autosomal dominant pattern of inheritance, two had an autosomal recessive pattern, and two were in the isolated subtype. A comparison between patients with Usher syndrome type 1 and type 2 did not show an appreciable difference. Six (38%) patients with Usher syndrome type 1 had a visual acuity of 20/40 or better in at least one eye compared with 17 (35%) patients with type 2. Conversely, 6 (38%) patients with type 1 had a visual acuity of 20/200 or worse in both eyes compared with 21 (44%) patients with type 2. The number of patients was too small for meaningful statistical comparisons. Patients with a sector form of RP were analyzed separately, and all patients (n ⫽ 17) had a visual acuity of better than 20/200 and 82% had a visual acuity of 20/40 or better in at least one eye (Table 3). The 982 patients with RP were classified into four arbitrary age groups, regardless of the genetic subtypes, and the severity of
Table 4. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older by Visual Acuity and Age: No. (%)* Visual Acuity
45–54 yrs
55–64 yrs
65–74 yrs
75ⴙ yrs
Total
20/40 or better 20/50–⬎20/200 20/200–⬎CF CF–NLP
250 (61) 80 (20) 43 (10) 37 (9)
148 (51) 72 (25) 39 (13) 32 (11)
88 (42) 54 (26) 32 (16) 34 (16)
20 (28) 27 (36) 6 (8) 20 (28)
506 (52) 233 (24) 120 (12) 123 (12)
410
291
208
73
982
Total
CF ⫽ counting fingers; NLP ⫽ no light perception. * All percentages are rounded off to the nearest whole number and are based on patients within each age subgroup.
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Grover et al 䡠 Visual Acuity in RP Table 5. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older with Visual Acuity 20/200 or Worse by Age Group and Genetic Subtype: No. (%) Age Group (yrs)
Total (n ⴝ 982)
AD (n ⴝ 182)
AR (n ⴝ 149)
XL (n ⴝ 32)
ISO (n ⴝ 465)
INDET (n ⴝ 90)
USH 1 (n ⴝ 16)
USH 2 (n ⴝ 48)
45–54 55–64 65–74 75⫹
80/410 (20) 71/291 (24) 66/208 (32) 26/73 (36)
10/68 (15)* 8/58 (14)* 10/40 (25) 5/16 (31)
11/58 (19)* 9/37 (24) 14/43 (33) 4/11 (36)
13/21 (61)* 4/8 (50) 2/2 (100) 1/1 (100)
26/191 (14)* 32/135 (24) 32/104 (31) 10/35 (29)
9/38 (24) 9/32 (28) 2/12 (17) 5/8 (62)
3/6 (50) 1/7 (14) 2/3 (67) —
8/28 (29) 8/14 (57)* 4/4 (100) 1/2 (50)
Total
243
33
38
20
100
25
6
21
AD ⫽ autosomal dominant; AR ⫽ autosomal recessive; XL ⫽ X-linked recessive; ISO ⫽ isolated; INDET ⫽ indeterminate; USH 1 ⫽ Usher 1 syndrome; USH 2 ⫽ Usher 2 syndrome. Note: All percentages (given in parentheses) are calculated by the number of patients with visual acuity 20/200 or worse out of their total number in each genetic subtype and age group. * Significant Bonferroni adjusted pairwise comparisons from logistic regression model within each age group [age group 45–54 yrs, XL vs. AD (P ⫽ 0.0001); XL vs. AR (P ⫽ 0.0005); XL vs. ISO (P ⫽ 0.0001). Age group 55– 64 years, AD vs. USH 2 (P ⫽ 0.0009)].
visual impairment was determined (Table 4). Of 410 patients in the age group 45–54 years, 250 (61%) had a visual acuity of 20/40 or better in at least one eye, and 80 (19%) patients were legally blind based on visual acuity criteria alone (visual acuity 20/200 or worse in both eyes). Even in an older population aged 75 or more years, of 73 patients, 20 (28%) had a visual acuity of 20/40 or better in at least one eye, and 26 (36%) had a visual acuity of 20/200 or worse in both eyes. One of the five patients who had no light perception in both eyes was in the age group 55– 64 years, whereas there were two each in age groups 65–74 years and more than 75 years. We also examined the distribution of patients who were legally blind by central acuity criteria, i.e., a visual acuity of 20/200 or worse in both eyes, within each age group and each genetic subtype (Table 5). Twenty-seven (11%) of the 243 patients who had a visual acuity of 20/200 or worse in both eyes were in the 75 years and older age group. In the 45–54 years age group, 10 (15%) of 68 patients with autosomal dominant RP had a visual acuity of 20/200 or worse in both eyes. This was in comparison to 13 (61%) of 21 with the X-linked type. The remaining subtypes were again between the autosomal dominant and X-linked recessive subtypes. A first logistic regression analysis performed within each of those four age groups modelled the probability of best visual acuity as a function of genetic subtype. Because of small sample sizes, only the autosomal dominant, autosomal recessive, indeterminate, and isolated subtypes were included in the model for the 65–74 years age group; only the autosomal dominant, autosomal recessive, indeterminate, isolated, and type 2 Usher syndrome subtypes were included in the model for patients 75 years or more. Pairwise comparisons among the genetic subtypes (with Bonferroni adjustments for multiple comparisons) revealed only four significant comparisons of the prevalence of best visual acuity of 20/200 or worse. For the 45–54 years age group, only the differences between X-linked recessive and autosomal dominant (P ⫽ 0.0001), X-linked recessive and autosomal recessive (P ⫽ 0.0005), and X-linked recessive and the isolated subtype (P ⫽ 0.0001) were statistically significant. In the 55– 64 years age group, only the difference between the autosomal dominant and the Usher syndrome type 2 (P ⫽ 0.0009) was statistically significant. The differences between any of the included genetic subtypes in the remainder of the age groups were not statistically significant. Combining the data from all centers and using only those patients in the autosomal recessive, autosomal dominant, isolated, and indeterminate groups, in which there were adequate numbers of patients, logistic regression models were obtained relating linear
age effects and group effects on the occurrence of visual acuity of 20/200 or worse. It was observed that the odds ratio for any patient having a visual acuity of 20/200 or worse in this mixed population of patients was 1.4 for each difference of 10 years of age. For example, the odds of a 60-year-old patient having a visual acuity of 20/200 or worse was 1.4 times that of a 50-year-old patient. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye for a 10-year age difference was 0.95. Again, for example, the odds of a 60-year-old patient having a visual acuity of 20/40 or better in at least one eye was 0.95 times that of a 50-year-old patient. Although these values were obtained from a cross-sectional study and thus do not reflect an observed change in visual acuity within individuals over time, they do suggest a slow progression of visual acuity loss. We compared the mean ages and the mean visual acuities of the patients who had been seen only once and those who had been followed for a duration of 5 years or more within each of the subtypes (Table 6). There was a notable similarity in the mean ages and the mean visual acuities between these two groups of patients. For this analysis, a best-corrected visual acuity of 2/800 on Feinbloom’s low vision chart was considered equivalent to count fingers. Hence, patients with visual acuity of count fingers were arbitrarily assigned a logMAR value of 2.6; hand motion, 2.7; light perception, 2.8; and no light perception, 2.9.
Discussion Although previous studies9,11,13–16 have addressed the issue of visual acuity impairment in patients with RP, the ophthalmic literature is replete with references to RP as a “blinding disease.”1–7 Sometimes it is difficult to interpret whether reference is being made to legal blindness by central visual acuity criteria, i.e., visual acuity no better than 20/200 in at least one eye, or total blindness, i.e., no light perception in both eyes. Our earlier study8 did show that total blindness among patients with RP was quite rare (⬍0.5%). Although the number of patients included in that study was substantial (n ⫽ 906), it included data on patients in all age groups and collected from only one center. Hence, the current multicenter analysis was done to obtain a better insight into the level of visual acuity impairment in patients
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Ophthalmology Volume 106, Number 9, September 1999 Table 6. Mean Ages and Mean Visual Acuities of Patients with Retinitis Pigmentosa, Age 45 Years or Older, Seen Once Compared with Those Seen for More Than 5 Years Mean Age* (yrs)
Mean Visual Acuity* (logMAR)
Genetic Subtype
1 Visit Only
ⱖ5 yrs
1 Visit Only
ⱖ5 yrs
% of Patients with 1 Visit Only†
Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate Usher 1 syndrome Usher 2 syndrome
61 (78) 59 (66) 57 (12) 59 (205) 59 (47) 56 (3) 52 (6)
59 (78) 60 (60) 52 (18) 60 (165) 55 (28) 56 (11) 54 (34)
0.6 (78) 0.9 (66) 1.9 (12) 0.6 (205) 0.7 (47) 1.0 (3) 1.1 (6)
0.5 (78) 0.8 (60) 1.1 (18) 0.7 (165) 0.6 (28) 0.9 (11) 1.1 (34)
43 44 38 44 52 19 12
Total
417
394
417
394
* Mean ages and mean visual acuities of patients with follow-up of 5 years or more duration were calculated from the data on their most recent visit. Numbers in parentheses indicate the actual number of patients. † Percentages are based on the number of patients with 1 visit only in each genetic subtype. Arbitrary scale for logMAR units: count fingers, 2.6; hand motion, 2.7; light perception, 2.8; no light perception, 2.9.
with RP in the age group 45 years or older. Because the data were collected on patients from four major referral eye care centers with a substantial number of patients with RP, the data represent patients from reasonably diverse geographic regions of the United States. Comparisons of visual acuity of 20/40 or better and 20/200 or worse between the initial study8 and the present study showed that the results were remarkably consistent. In the initial study, 489 (55%) of 889 patients with RP from one center in all age groups had a visual acuity of 20/40 or better in at least one eye compared with 506 (52%) of 982 patients in this multicenter study of patients aged 45 years or more. Similarly, 179 (20%) patients from the initial study had a visual acuity of 20/200 or worse in both eyes compared with 243 (25%) in this study. The percentages within each genetic subtype were also similar. More than half (52%) of this population of patients with RP had a visual acuity of 20/40 or better in at least one eye (Table 3). Pearlman13 similarly found that 52% of 167 patients with RP had a visual acuity of better than 20/50. Analyzing the percentages in the data reported by Berson et al14 on patients with autosomal dominant, autosomal recessive, and isolated RP, 90 (54%) patients in the 40⫹ years age group had a visual acuity of 20/40 or better. When we analyzed our data on these three subtypes of RP, we also found that 424 (54%) patients of 796 had visual acuity of 20/40 or better. In our population, 243 of 982 (25%) patients had a visual acuity of 20/200 or worse in both eyes. Therefore, not considering peripheral visual field limitations, about 25% of the patients were legally blind by central visual acuity criteria. Marmor11 analyzed visual acuity data on 91 RP patients, 71 of them with autosomal recessive RP, and reported that 50% of these patients had a visual acuity of 20/200 or worse by age 50 years. However, in our combined population of 149 patients, age 45 years or older, with autosomal recessive RP, only 26% had a visual acuity of 20/200 or worse (Table 3). Regarding total blindness, there were five patients who had no light perception in both eyes. There were two pa-
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tients each with autosomal recessive RP and the isolated subtype, whereas one patient had an autosomal dominant type of RP. Four of the five patients were in the age group 65 years and older and two of them in 75 years or older. This finding is in accord with our previous study, where we found only 1 of 906 patients who had lost all vision in both eyes. Marmor11 also did not report any patient with no light perception in both eyes in 91 patients. Another survey of visual impairment done in a referral eye hospital in India included 43 patients with RP, and none of them had no light perception in both eyes.17 As noted in our previous study8 and also in others,18,19 as a group patients with autosomal dominant RP showed better visual acuity than did those with other genetic subtypes (Table 3). Patients with X-linked RP had the worst visual acuity, and the remaining groups were in between the severity of these two subtypes. As has been reported, patients with a sector form of RP have the best visual prognosis and retain good visual acuity.8,10,11 Patients with type 1 and type 2 Usher syndrome did not show a difference in visual acuity impairment in this older age group of patients. This substantiates a trend observed in an earlier study on visual acuity impairment that showed that initially there was more visual acuity impairment in type 1 compared with type 2 Usher syndrome patients until about the middle of the fifth decade of life, after which the degree of the impairment was about the same between these two groups.20 Although RP has been cited as a “blinding disease,” with an implication for total loss of sight, there is no evidence in the literature to support this notion. Even in patients with X-linked RP, who overall have the worst visual prognosis, we found that none of the 32 patients with this genetic type of RP (mean age, 54 years) had no light perception in both eyes. Our previous study8 also showed that it was rare for patients with RP to lose all central vision in both eyes. However, it was theoretically possible that there could have been a bias, in that patients with either very good central vision or those with very poor central vision did not return
Grover et al 䡠 Visual Acuity in RP Table 7. Comparison of Mean Visual Acuities and Ages between Patients with Retinitis Pigmentosa Seen Only Once (Previous Study8) with Follow-up Data and Those Seen for a Duration of at Least 5 Years Mean Age (yrs)
with various genetic subtypes and Usher syndrome aged 45 years or older. The results of this study are of value for determining the ranges of visual impairment that can be encountered in RP patients of this age group.
Mean Visual Acuity (logMAR)
Genetic Subtype
1 Visit*
5-yr Follow-up†
1 Visit*
5-yr Follow-up†
Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate
52 (37) 55 (18) 34 (19) 47 (84) 51 (28)
47 (75) 47 (40) 34 (39) 46 (121) 39 (37)
0.4 (37) 0.8 (18) 1.3 (19) 0.6 (84) 0.8 (28)
0.4 (75) 0.7 (40) 0.9 (39) 0.6 (121) 0.6 (37)
* Consists of patients from the previous study8 who had been seen only once (n ⫽ 406) with their updated information on visual acuity and age. Numbers in parentheses are the actual number of patients. † Data obtained from Table 7 of previous study.8
for follow-up visits, and therefore the results might not accurately represent the overall RP population. This bias of ascertainment, if true, would also be applicable to the present study. Hence, we attempted to contact those patients from the previous study who had been to our center only once (n ⫽ 406 of a total population of 906 patients). Of those 406 patients, we obtained some information on 264 (65%) of them. Fourteen patients (3%) were deceased, 37 (9%) did not follow-up with any ophthalmologist after the initial consultation, and 18 (4%) were living outside the United States. Information on the most recent visual acuity could be obtained on 186 (46%) patients, 45 of whom had returned to our center since the last study was done. In the other 141 patients, the information on visual acuity was obtained from an ophthalmologist or optometrist. The majority of the patients who did not return to our center for subsequent follow-up did not do so either because of the geographic distance or because their health insurance carrier had changed. We compared the mean ages and the mean visual acuities of these patients with those of the patients from our earlier study that had been to our center for 5 years or more of follow-up (Table 7). We found the mean ages and visual acuities to be very similar. This does not support the argument that patients with very good or very poor visual acuities are less likely to return for follow-up examination. Since the mean ages and visual acuities of these patients who came to our center only once were similar to those of the patients who were followed for 5 years or more, we suspect that there is unlikely to be a significant bias of visual acuity results. Although a prospective study can obviate some of the potential difficulty encountered in a retrospective analysis, such an endeavor in a large population of RP patients with different genetic subtypes over an extended period of time would present a particularly arduous undertaking, necessitating appreciable collaborative resources and with uncertain success. This retrospective study analyzed the visual acuity impairment in probably the largest cohort of patients with RP
References 1. Bloome MA, Garcia CA. Manual of Retinal and Choroidal Dystrophies. New York: Appleton-Century-Crofts, 1982;43. 2. Stein HA, Slatt BJ, Stein RM. A Primer in Ophthalmology: A Textbook for Students. St. Louis: Mosby-Year Book, 1992; 142. 3. Sieving PA, Richards JE, Naarendorp F, et al. Dark-light: model for nightblindness from the human rhodopsin Gly-90Asp mutation. Proc Natl Acad Sci U S A 1995;92:880 – 4. 4. Denton MJ, Chen JD, Serravalle S, et al. Analysis of linkage relationships of X-linked retinitis pigmentosa with the following Xp loci: L1.28, OTC, 754, XJ-1.1, PERT 87, and C7. Hum Genet 1988;78:60 – 4. 5. Anandakrishnan I, Musarella MA. Genetic counseling in Xlinked retinitis pigmentosa. J Pediatr Ophthalmol Strabismus 1989;26:140 –5. 6. Jay B. Prevention of blindness from retinitis pigmentosa. Trans Ophthalmol Soc U K 1978;98:309 –12. 7. Friederich R. Eye disease in the Navajo Indians. Ann Ophthalmol 1982;14:38 – 40. 8. Grover S, Fishman GA, Alexander KR, et al. Visual acuity impairment in patients with retinitis pigmentosa. Ophthalmology 1996;103:1593– 600. 9. Fishman GA. Retinitis pigmentosa. Visual loss. Arch Ophthalmol 1978;96:1185– 8. 10. Farber MD, Fishman GA, Weiss RA. Autosomal dominantly inherited retinitis pigmentosa. Visual acuity loss by subtype. Arch Ophthalmol 1985;103:524 – 8. 11. Marmor MF. Visual loss in retinitis pigmentosa. Am J Ophthalmol 1980;89:692– 8. 12. Boughman JA, Fishman GA. A genetic analysis of retinitis pigmentosa. Br J Ophthalmol 1983;67:449 –54. 13. Pearlman JT. Mathematical models of retinitis pigmentosa: a study of the rate of progress in the different genetic forms. Trans Am Ophthalmol Soc 1979;77:643–56. 14. Berson EL, Sandberg MA, Rosner B, et al. Natural course of retinitis pigmentosa over a three-year interval. Am J Ophthalmol 1985;99:240 –51. 15. Madreperla SA, Palmer RW, Massof RW, Finkelstein D. Visual acuity loss in retinitis pigmentosa. Relationship to visual field loss. Arch Ophthalmol 1990;108:358 – 61. 16. Heckenlively JR, Yoser SL, Friedman HL, Oversier JJ. Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol 1988;105:504 –11. 17. Herse P, Gothwal VK. Survey of visual impairment in an Indian tertiary eye hospital. Indian J Ophthalmol 1997;45: 189 –93. 18. Krill AE. Retinitis pigmentosa: a review. Sight Saving Review 1972;42:21– 8. 19. Jay B. Hereditary aspects of pigmentary retinopathy. Trans Ophthalmol Soc U K 1972;92:173– 8. 20. Edwards A, Fishman GA, Anderson RJ, et al. Visual acuity and visual field impairment in Usher syndrome. Arch Ophthalmol 1998;116:165– 8.
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Originally received: October 26, 1998. Revision accepted: May 20, 1999. Manuscript no. 98709. 1 Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois. 2 Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois. 3 Department of Ophthalmology, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. 4 Jules Stein Eye Institute, Los Angeles, California. 5 Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon. 6 Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas. 7 Department of Ophthalmology, University of Iowa, Iowa City, Iowa. Presented in part at the Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, Florida, May 1998. Supported by a center grant from the Foundation Fighting Blindness, Baltimore, Maryland (GAF). Reprint requests to Gerald A. Fishman, MD, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612. E-mail:[email protected].
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night blindness, bone spicule-like pigmentary retinal changes, progressive loss of peripheral visual fields, and decreased or nondetectable responses on electroretinogram testing. The association of RP with congenital hearing loss is classified as Usher syndrome; type 1 is associated with severe sensorineural hearing loss with absent vestibular responses on caloric testing and unintelligible speech, and type 2 is associated with mild to moderate hearing loss with intact vestibular responses and intelligible speech. In the literature, RP is not infrequently cited as a “disease causing total blindness”1–3 or referred to as causing blindness,4 –7 not specifying whether it implies total or legal blindness. An earlier study showed that less than 0.5% of patients actually lost all vision in both eyes.8 This previous study included patients with RP seen by one of the authors (GAF) in all age groups. However, the number of patients with RP beyond middle age was not substantial enough to make a strong statement about the impairment of visual acuity in later life. Therefore, we collected and analyzed data from four centers in the United States obtained on patients with RP and Usher syndrome, age 45 years or older, in an attempt to assess the severity of their visual acuity impairment.
Grover et al 䡠 Visual Acuity in RP Table 1. Criteria for Exclusion Reason for Exclusion
Center 1
Center 2
Center 3
Center 4
Total
Glaucoma Keratopathy Refraction not done Diabetic retinopathy Dense cataract Retinal detachment Others*
12 4 — 1 — — —
3 2 — — 2 1 3
3 1 — — — — 1
— — 57 — — — —
18 7 57 1 2 1 4
Total
17
11
5
57
90
* Includes one patient each with mental retardation and cranial arteritis, and two patients from center 2 whose data are included in center 1.
Methods
center with the two extremes of visual acuity, those with 20/20 or better (n ⫽ 17) and those with 20/800 or worse (n ⫽ 10) because a proper refraction would not have significantly impacted on their visual acuity. There were two patients who were excluded from center 2 because data on these two patients were included from center 1. Data from 18 patients who had unilateral impairment of vision due to causes other than RP were included because our study analyzed data obtained from the better eye. Patients with dense cataracts in both eyes were excluded. However, patients with aphakia or pseudophakia were included in the study. We also did not include patients with Bardet-Biedl syndrome or cone-rod dystrophy. The data were obtained on a total of 999 patients with various genetic subtypes of RP (Table 2), including autosomal dominant (n ⫽ 182), autosomal recessive (n ⫽ 149), and X-linked recessive (n ⫽ 32). The criteria of classifying these patients into one of the genetic subtypes were defined earlier by one of the authors.9 Data on 90 patients who could not be classified readily into any of the genetic subtypes but for whom two other family members were known to be affected were also included as an indeterminate subtype. Also included were 16 patients with Usher syndrome type 1 and 48 patients with Usher syndrome type 2. Patients with RP who were known to be the only affected members in their families were included in the isolated subtype (n ⫽ 465). Seventeen patients from the entire dataset with a sector form of RP were analyzed separately because their visual prognosis is known to be more favorable than other RP subtypes.10,11
Visual acuities in patients with RP, age 45 years or older, obtained from four centers in the United States were evaluated to ascertain the severity of visual acuity impairment in this group of patients. The four centers were Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago (center 1); Jules Stein Eye Institute, Los Angeles (center 2); Casey Eye Institute, Oregon Health Sciences University, Portland (center 3); and Department of Ophthalmology, University of Iowa, Iowa City (center 4). The best-corrected visual acuities were obtained on both eyes from all patients. The visual acuities were obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor, Santa Barbara, CA) at one of the centers. Although there were instances when the visual acuities were different in the two eyes, the visual acuities correlated significantly between the two eyes (Spearman r ⫽ 0.81; P ⬍ 0.01). As in a previous study,8 visual acuity obtained in the eye with better acuity on the most recent visit of each patient was used for this study. All patients with RP seen at each center who fulfilled the entrance criteria were included in the analysis. Of the 1089 patients whose charts were initially reviewed, 90 patients were excluded from different centers (Table 1). Patients with glaucoma, diabetic retinopathy, keratopathy, and other ocular and medical conditions that could impact on the visual acuity of the patient were excluded (n ⫽ 31). From center 4, 57 patients were excluded because information on best-corrected visual acuity was not available. However, we did include patients from this
Table 2. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older in Various Genetic Subtypes from Different Centers: No. (%)* Mean Age (yrs)
Age Range (yrs)
Total
Center 1
Center 2
Center 3
Center 4
Males Females Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate Usher 1 syndrome Usher 2 syndrome
58 59 60 59 54 59 58 57 54
45–85 45–88 45–88 45–85 45–77 45–85 45–78 45–74 45–78
461 (47) 521 (53) 182 (19) 149 (15) 32 (3) 465 (47) 90 (9) 16 (2) 48 (5)
207 (47) 236 (53) 70 (16) 61 (14) 18 (4) 196 (44) 56 (13) 11 (2) 31 (7)
160 (44) 200 (56) 53 (15) 70 (19) 9 (2) 219 (61) 3 (1) 1 (⬍1) 5 (1)
72 (57) 54 (43) 43 (34) 15 (12) 5 (4) 26 (21) 24 (19) 4 (3) 9 (7)
22 (42) 31 (58) 16 (30) 3 (6) — 24 (45) 7 (13) — 3 (6)
Total
58
45–88
982
443 (45)
360 (37)
126 (13)
53 (5)
Sector
60
45–86
17
7
10
—
—
* All percentages are rounded off to the nearest whole number.
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Ophthalmology Volume 106, Number 9, September 1999 Table 3. Distribution of Patients with Retinitis Pigmentosa (RP) Age 45 Years or Older According to Genetic Subtype and Visual Acuity: No. (%)* Visual Acuity
Total† (n ⴝ 982)
AD (n ⴝ 182)
AR (n ⴝ 149)
XL (n ⴝ 32)
ISO (n ⴝ 465)
INDET (n ⴝ 90)
USH 1 (n ⴝ 16)
USH 2 (n ⴝ 48)
SECTOR (n ⴝ 17)
20/40 or better 20/70 or better Better than 20/200 20/200 or worse CF or worse
506 (52) 678 (69) 739 (75) 243 (25) 123 (12)
117 (64) 139 (76) 149 (82) 33 (18) 15 (8)
62 (42) 97 (65) 111 (74) 38 (26) 25 (17)
8 (25) 11 (34) 12 (38) 20 (62) 10 (31)
245 (53) 337 (72) 365 (78) 100 (22) 46 (10)
51 (57) 61 (68) 65 (72) 25 (28) 15 (17)
6 (38) 9 (56) 10 (62) 6 (38) 2 (12)
17 (35) 24 (50) 27 (56) 21 (44) 10 (21)
14 (82) 16 (94) 17 (100) — —
AD ⫽ autosomal dominant; AR ⫽ autosomal recessive; XL ⫽ X-linked recessive; ISO ⫽ isolated; INDET ⫽ indeterminate; USH 1 ⫽ Usher 1 syndrome; USH 2 ⫽ Usher 2 syndrome; CF ⫽ counting fingers. * All percentages are rounded off to the nearest whole number. † Does not include 17 patients with sector type of RP.
Excluding the patients with a sector form of RP (n ⫽ 17), the final analysis was done on 982 patients with RP. There were 461 men and 521 women in the study. The mean age of the patients was 58 years (range, 45 to 88 years). The mean ages and the age ranges of the patients in each genetic subtype are listed in Table 2. The population studied was comprised of 783 (80%) whites (mean age, 59 years; mean visual acuity, 20/100), 88 (9%) blacks (mean age, 57 years; mean visual acuity, 20/100), 50 (5%) Hispanics (mean age, 55 years; mean visual acuity, 20/90), and 61 (6%) others comprising additional different ethnic groups (mean age, 60 years; mean visual acuity, 20/60). Table 2 also shows the number of patients in each genetic subtype included from each of the four centers. The majority of the patients were from center 1 (443 patients) and center 2 (360 patients). Data from 126 patients and 53 patients were included from centers 3 and 4, respectively. There were 17 patients with a sector form of RP, 7 from center 1 and 10 from center 2. The percentages of each genetic subtype in this study, excluding the patients with Usher syndrome types 1 and 2, were very similar to those in our earlier study and also to the study by Boughman and Fishman.12 Therefore, our cohort of patients is likely representative of genetic subtypes of RP patients seen in the United States at various referral centers.
Results Analyzing the data from 982 patients with RP, age 45 years or older, regardless of genetic subtype, 506 (52%) patients had a visual acuity of 20/40 or better, 678 (69%) had a visual acuity of 20/70 or better, and 739 (75%) had a visual acuity of better than 20/200 in at least one eye (Table 3). Hence, 243 (25%) patients had
a visual acuity of 20/200 or worse in both eyes, out of which 123 (12%) patients had a visual acuity of count fingers or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. Assessing the impairment of visual acuity within the genetic subtypes, patients with autosomal dominant RP had better visual acuity than the rest of the subtypes, and patients with X-linked RP had the worst (Table 3). Sixty-four percent of patients with autosomal dominant RP had a visual acuity of 20/40 or better in at least one eye compared with 42% with autosomal recessive and 25% with X-linked recessive RP. The remaining subtypes and patients with Usher syndrome were in between the two extremes. Also, 18% of patients with autosomal dominant RP had a visual acuity of 20/200 or worse in both eyes compared with 26% with autosomal recessive and 62% with X-linked recessive RP. The mean age of patients with X-linked RP was 54 years, younger than most of the other subtypes by 3– 6 years. Of the five patients who had no light perception in both eyes, one had an autosomal dominant pattern of inheritance, two had an autosomal recessive pattern, and two were in the isolated subtype. A comparison between patients with Usher syndrome type 1 and type 2 did not show an appreciable difference. Six (38%) patients with Usher syndrome type 1 had a visual acuity of 20/40 or better in at least one eye compared with 17 (35%) patients with type 2. Conversely, 6 (38%) patients with type 1 had a visual acuity of 20/200 or worse in both eyes compared with 21 (44%) patients with type 2. The number of patients was too small for meaningful statistical comparisons. Patients with a sector form of RP were analyzed separately, and all patients (n ⫽ 17) had a visual acuity of better than 20/200 and 82% had a visual acuity of 20/40 or better in at least one eye (Table 3). The 982 patients with RP were classified into four arbitrary age groups, regardless of the genetic subtypes, and the severity of
Table 4. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older by Visual Acuity and Age: No. (%)* Visual Acuity
45–54 yrs
55–64 yrs
65–74 yrs
75ⴙ yrs
Total
20/40 or better 20/50–⬎20/200 20/200–⬎CF CF–NLP
250 (61) 80 (20) 43 (10) 37 (9)
148 (51) 72 (25) 39 (13) 32 (11)
88 (42) 54 (26) 32 (16) 34 (16)
20 (28) 27 (36) 6 (8) 20 (28)
506 (52) 233 (24) 120 (12) 123 (12)
410
291
208
73
982
Total
CF ⫽ counting fingers; NLP ⫽ no light perception. * All percentages are rounded off to the nearest whole number and are based on patients within each age subgroup.
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Grover et al 䡠 Visual Acuity in RP Table 5. Distribution of Patients with Retinitis Pigmentosa Age 45 Years or Older with Visual Acuity 20/200 or Worse by Age Group and Genetic Subtype: No. (%) Age Group (yrs)
Total (n ⴝ 982)
AD (n ⴝ 182)
AR (n ⴝ 149)
XL (n ⴝ 32)
ISO (n ⴝ 465)
INDET (n ⴝ 90)
USH 1 (n ⴝ 16)
USH 2 (n ⴝ 48)
45–54 55–64 65–74 75⫹
80/410 (20) 71/291 (24) 66/208 (32) 26/73 (36)
10/68 (15)* 8/58 (14)* 10/40 (25) 5/16 (31)
11/58 (19)* 9/37 (24) 14/43 (33) 4/11 (36)
13/21 (61)* 4/8 (50) 2/2 (100) 1/1 (100)
26/191 (14)* 32/135 (24) 32/104 (31) 10/35 (29)
9/38 (24) 9/32 (28) 2/12 (17) 5/8 (62)
3/6 (50) 1/7 (14) 2/3 (67) —
8/28 (29) 8/14 (57)* 4/4 (100) 1/2 (50)
Total
243
33
38
20
100
25
6
21
AD ⫽ autosomal dominant; AR ⫽ autosomal recessive; XL ⫽ X-linked recessive; ISO ⫽ isolated; INDET ⫽ indeterminate; USH 1 ⫽ Usher 1 syndrome; USH 2 ⫽ Usher 2 syndrome. Note: All percentages (given in parentheses) are calculated by the number of patients with visual acuity 20/200 or worse out of their total number in each genetic subtype and age group. * Significant Bonferroni adjusted pairwise comparisons from logistic regression model within each age group [age group 45–54 yrs, XL vs. AD (P ⫽ 0.0001); XL vs. AR (P ⫽ 0.0005); XL vs. ISO (P ⫽ 0.0001). Age group 55– 64 years, AD vs. USH 2 (P ⫽ 0.0009)].
visual impairment was determined (Table 4). Of 410 patients in the age group 45–54 years, 250 (61%) had a visual acuity of 20/40 or better in at least one eye, and 80 (19%) patients were legally blind based on visual acuity criteria alone (visual acuity 20/200 or worse in both eyes). Even in an older population aged 75 or more years, of 73 patients, 20 (28%) had a visual acuity of 20/40 or better in at least one eye, and 26 (36%) had a visual acuity of 20/200 or worse in both eyes. One of the five patients who had no light perception in both eyes was in the age group 55– 64 years, whereas there were two each in age groups 65–74 years and more than 75 years. We also examined the distribution of patients who were legally blind by central acuity criteria, i.e., a visual acuity of 20/200 or worse in both eyes, within each age group and each genetic subtype (Table 5). Twenty-seven (11%) of the 243 patients who had a visual acuity of 20/200 or worse in both eyes were in the 75 years and older age group. In the 45–54 years age group, 10 (15%) of 68 patients with autosomal dominant RP had a visual acuity of 20/200 or worse in both eyes. This was in comparison to 13 (61%) of 21 with the X-linked type. The remaining subtypes were again between the autosomal dominant and X-linked recessive subtypes. A first logistic regression analysis performed within each of those four age groups modelled the probability of best visual acuity as a function of genetic subtype. Because of small sample sizes, only the autosomal dominant, autosomal recessive, indeterminate, and isolated subtypes were included in the model for the 65–74 years age group; only the autosomal dominant, autosomal recessive, indeterminate, isolated, and type 2 Usher syndrome subtypes were included in the model for patients 75 years or more. Pairwise comparisons among the genetic subtypes (with Bonferroni adjustments for multiple comparisons) revealed only four significant comparisons of the prevalence of best visual acuity of 20/200 or worse. For the 45–54 years age group, only the differences between X-linked recessive and autosomal dominant (P ⫽ 0.0001), X-linked recessive and autosomal recessive (P ⫽ 0.0005), and X-linked recessive and the isolated subtype (P ⫽ 0.0001) were statistically significant. In the 55– 64 years age group, only the difference between the autosomal dominant and the Usher syndrome type 2 (P ⫽ 0.0009) was statistically significant. The differences between any of the included genetic subtypes in the remainder of the age groups were not statistically significant. Combining the data from all centers and using only those patients in the autosomal recessive, autosomal dominant, isolated, and indeterminate groups, in which there were adequate numbers of patients, logistic regression models were obtained relating linear
age effects and group effects on the occurrence of visual acuity of 20/200 or worse. It was observed that the odds ratio for any patient having a visual acuity of 20/200 or worse in this mixed population of patients was 1.4 for each difference of 10 years of age. For example, the odds of a 60-year-old patient having a visual acuity of 20/200 or worse was 1.4 times that of a 50-year-old patient. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye for a 10-year age difference was 0.95. Again, for example, the odds of a 60-year-old patient having a visual acuity of 20/40 or better in at least one eye was 0.95 times that of a 50-year-old patient. Although these values were obtained from a cross-sectional study and thus do not reflect an observed change in visual acuity within individuals over time, they do suggest a slow progression of visual acuity loss. We compared the mean ages and the mean visual acuities of the patients who had been seen only once and those who had been followed for a duration of 5 years or more within each of the subtypes (Table 6). There was a notable similarity in the mean ages and the mean visual acuities between these two groups of patients. For this analysis, a best-corrected visual acuity of 2/800 on Feinbloom’s low vision chart was considered equivalent to count fingers. Hence, patients with visual acuity of count fingers were arbitrarily assigned a logMAR value of 2.6; hand motion, 2.7; light perception, 2.8; and no light perception, 2.9.
Discussion Although previous studies9,11,13–16 have addressed the issue of visual acuity impairment in patients with RP, the ophthalmic literature is replete with references to RP as a “blinding disease.”1–7 Sometimes it is difficult to interpret whether reference is being made to legal blindness by central visual acuity criteria, i.e., visual acuity no better than 20/200 in at least one eye, or total blindness, i.e., no light perception in both eyes. Our earlier study8 did show that total blindness among patients with RP was quite rare (⬍0.5%). Although the number of patients included in that study was substantial (n ⫽ 906), it included data on patients in all age groups and collected from only one center. Hence, the current multicenter analysis was done to obtain a better insight into the level of visual acuity impairment in patients
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Ophthalmology Volume 106, Number 9, September 1999 Table 6. Mean Ages and Mean Visual Acuities of Patients with Retinitis Pigmentosa, Age 45 Years or Older, Seen Once Compared with Those Seen for More Than 5 Years Mean Age* (yrs)
Mean Visual Acuity* (logMAR)
Genetic Subtype
1 Visit Only
ⱖ5 yrs
1 Visit Only
ⱖ5 yrs
% of Patients with 1 Visit Only†
Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate Usher 1 syndrome Usher 2 syndrome
61 (78) 59 (66) 57 (12) 59 (205) 59 (47) 56 (3) 52 (6)
59 (78) 60 (60) 52 (18) 60 (165) 55 (28) 56 (11) 54 (34)
0.6 (78) 0.9 (66) 1.9 (12) 0.6 (205) 0.7 (47) 1.0 (3) 1.1 (6)
0.5 (78) 0.8 (60) 1.1 (18) 0.7 (165) 0.6 (28) 0.9 (11) 1.1 (34)
43 44 38 44 52 19 12
Total
417
394
417
394
* Mean ages and mean visual acuities of patients with follow-up of 5 years or more duration were calculated from the data on their most recent visit. Numbers in parentheses indicate the actual number of patients. † Percentages are based on the number of patients with 1 visit only in each genetic subtype. Arbitrary scale for logMAR units: count fingers, 2.6; hand motion, 2.7; light perception, 2.8; no light perception, 2.9.
with RP in the age group 45 years or older. Because the data were collected on patients from four major referral eye care centers with a substantial number of patients with RP, the data represent patients from reasonably diverse geographic regions of the United States. Comparisons of visual acuity of 20/40 or better and 20/200 or worse between the initial study8 and the present study showed that the results were remarkably consistent. In the initial study, 489 (55%) of 889 patients with RP from one center in all age groups had a visual acuity of 20/40 or better in at least one eye compared with 506 (52%) of 982 patients in this multicenter study of patients aged 45 years or more. Similarly, 179 (20%) patients from the initial study had a visual acuity of 20/200 or worse in both eyes compared with 243 (25%) in this study. The percentages within each genetic subtype were also similar. More than half (52%) of this population of patients with RP had a visual acuity of 20/40 or better in at least one eye (Table 3). Pearlman13 similarly found that 52% of 167 patients with RP had a visual acuity of better than 20/50. Analyzing the percentages in the data reported by Berson et al14 on patients with autosomal dominant, autosomal recessive, and isolated RP, 90 (54%) patients in the 40⫹ years age group had a visual acuity of 20/40 or better. When we analyzed our data on these three subtypes of RP, we also found that 424 (54%) patients of 796 had visual acuity of 20/40 or better. In our population, 243 of 982 (25%) patients had a visual acuity of 20/200 or worse in both eyes. Therefore, not considering peripheral visual field limitations, about 25% of the patients were legally blind by central visual acuity criteria. Marmor11 analyzed visual acuity data on 91 RP patients, 71 of them with autosomal recessive RP, and reported that 50% of these patients had a visual acuity of 20/200 or worse by age 50 years. However, in our combined population of 149 patients, age 45 years or older, with autosomal recessive RP, only 26% had a visual acuity of 20/200 or worse (Table 3). Regarding total blindness, there were five patients who had no light perception in both eyes. There were two pa-
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tients each with autosomal recessive RP and the isolated subtype, whereas one patient had an autosomal dominant type of RP. Four of the five patients were in the age group 65 years and older and two of them in 75 years or older. This finding is in accord with our previous study, where we found only 1 of 906 patients who had lost all vision in both eyes. Marmor11 also did not report any patient with no light perception in both eyes in 91 patients. Another survey of visual impairment done in a referral eye hospital in India included 43 patients with RP, and none of them had no light perception in both eyes.17 As noted in our previous study8 and also in others,18,19 as a group patients with autosomal dominant RP showed better visual acuity than did those with other genetic subtypes (Table 3). Patients with X-linked RP had the worst visual acuity, and the remaining groups were in between the severity of these two subtypes. As has been reported, patients with a sector form of RP have the best visual prognosis and retain good visual acuity.8,10,11 Patients with type 1 and type 2 Usher syndrome did not show a difference in visual acuity impairment in this older age group of patients. This substantiates a trend observed in an earlier study on visual acuity impairment that showed that initially there was more visual acuity impairment in type 1 compared with type 2 Usher syndrome patients until about the middle of the fifth decade of life, after which the degree of the impairment was about the same between these two groups.20 Although RP has been cited as a “blinding disease,” with an implication for total loss of sight, there is no evidence in the literature to support this notion. Even in patients with X-linked RP, who overall have the worst visual prognosis, we found that none of the 32 patients with this genetic type of RP (mean age, 54 years) had no light perception in both eyes. Our previous study8 also showed that it was rare for patients with RP to lose all central vision in both eyes. However, it was theoretically possible that there could have been a bias, in that patients with either very good central vision or those with very poor central vision did not return
Grover et al 䡠 Visual Acuity in RP Table 7. Comparison of Mean Visual Acuities and Ages between Patients with Retinitis Pigmentosa Seen Only Once (Previous Study8) with Follow-up Data and Those Seen for a Duration of at Least 5 Years Mean Age (yrs)
with various genetic subtypes and Usher syndrome aged 45 years or older. The results of this study are of value for determining the ranges of visual impairment that can be encountered in RP patients of this age group.
Mean Visual Acuity (logMAR)
Genetic Subtype
1 Visit*
5-yr Follow-up†
1 Visit*
5-yr Follow-up†
Autosomal dominant Autosomal recessive X-linked recessive Isolated Indeterminate
52 (37) 55 (18) 34 (19) 47 (84) 51 (28)
47 (75) 47 (40) 34 (39) 46 (121) 39 (37)
0.4 (37) 0.8 (18) 1.3 (19) 0.6 (84) 0.8 (28)
0.4 (75) 0.7 (40) 0.9 (39) 0.6 (121) 0.6 (37)
* Consists of patients from the previous study8 who had been seen only once (n ⫽ 406) with their updated information on visual acuity and age. Numbers in parentheses are the actual number of patients. † Data obtained from Table 7 of previous study.8
for follow-up visits, and therefore the results might not accurately represent the overall RP population. This bias of ascertainment, if true, would also be applicable to the present study. Hence, we attempted to contact those patients from the previous study who had been to our center only once (n ⫽ 406 of a total population of 906 patients). Of those 406 patients, we obtained some information on 264 (65%) of them. Fourteen patients (3%) were deceased, 37 (9%) did not follow-up with any ophthalmologist after the initial consultation, and 18 (4%) were living outside the United States. Information on the most recent visual acuity could be obtained on 186 (46%) patients, 45 of whom had returned to our center since the last study was done. In the other 141 patients, the information on visual acuity was obtained from an ophthalmologist or optometrist. The majority of the patients who did not return to our center for subsequent follow-up did not do so either because of the geographic distance or because their health insurance carrier had changed. We compared the mean ages and the mean visual acuities of these patients with those of the patients from our earlier study that had been to our center for 5 years or more of follow-up (Table 7). We found the mean ages and visual acuities to be very similar. This does not support the argument that patients with very good or very poor visual acuities are less likely to return for follow-up examination. Since the mean ages and visual acuities of these patients who came to our center only once were similar to those of the patients who were followed for 5 years or more, we suspect that there is unlikely to be a significant bias of visual acuity results. Although a prospective study can obviate some of the potential difficulty encountered in a retrospective analysis, such an endeavor in a large population of RP patients with different genetic subtypes over an extended period of time would present a particularly arduous undertaking, necessitating appreciable collaborative resources and with uncertain success. This retrospective study analyzed the visual acuity impairment in probably the largest cohort of patients with RP
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