Visual Acuity in Patients with Best Vitelliform Macular Dystrophy

Gerald A. Fishman, MD,z Wendy Baca, BA,l Kenneth R. Alexander, PhD,1 Deborah]. Derlacki, BA,l Andrew M. Glenn, FRCS, FCOphth,1 Marlos Viana, PhD1

,2

Purpose: Forty-seven patients with Best vitelliform macular dystrophy were eval­uated in a cross-sectional fashion for visual acuity loss with age.

Methods: The authors assessed only patients who had at least one eye with a recognizable phenotype of Best vitelliform macular dystrophy. Patients with absent foveal changes or with only minimal foveal pigment mottling and hypopigmentation in each eye were excluded.

Results: A significant difference was noted between the visual acuities of the two eyes of the patients (2 lines or greater in the majority [64%] of patients). Nevertheless, for both eyes a significant correlation was noted between patient age and visual acuity, with older patients tending to have worse visual acuities. In the eyes with the best visual acuity, the majority of patients younger than 40 years of age (76%) had a visual acuity of 20/40 or better. In patients older than 30 years of age, a substantial percentage (74%) had a visual acuity of 20/100 or worse in at least one eye.

Conclusion: The authors' findings indicate that although patients with Best vitel­liform macular dystrophy who show characteristic macular lesions may retain good visual acuity in at least one eye, an appreciable number can lose substantial visual acuity, at least monocularly. In this population, no patient older than 50 years of age fulfilled the visual acuity criterion of 20/40 in at least one eye, the requirement in most states for an unrestricted driver's license, and only 20% of patients older than 40 years of age fulfilled this visual acuity criterion. Ophthalmology 1993; 1 00: 1665-1670

Best vitelliform macular dystrophy is an autosomal dom­inantly inherited disorder with variable expressivity., ,2 In 1905, Bese described the first familial cases of this hered­itary macular degeneration, although, in 1883, Adams4

described " peculiar changes in the macula" when he pre-

sented a case report, which, in retrospect, was a patient with Best vitelliform dystrophy of the macula.

Originally received: February I, 1993. Revision accepted: March 29, 1993.

I Department of Ophthalmology and Visual Sciences, College of Med­icine, University of Illinois at Chicago, Chicago.

2 Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago.

Supported by core grant EYO 1792 and research grant EY0830 I from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, and by a center grant from the National RP Foundation Fighting Blindness, Baltimore, Maryland.

Reprint requests to Gerald A. Fishman, MD, UIC Eye Center, University of Illinois at Chicago, 1855 W. Taylor St, Chicago, IL 60612.

All patients with Best vitelli form macular dystrophy, regardless of age or stage of disease, have abnormal electro­oculogram (EOG) results. This finding was described in 1966 by Krill et al5 and Franc;:ois et al6 in separate pub­lications which indicated that the light-peak to dark-trough ratio of the EOG was abnormally low in such patients. Abnormal findings on an EOG are apparent, even in the absence of a clinically discernible retinal lesion. 7 The combination of severely abnormal results of an EOG with normal results of an electroretinogram is characteristic of Best vitelli form macular dystrophy.

Previous studies by Mohler and Fine2 and by Clemett8

of visual acuity impairment in patients with Best vitelli­form macular dystrophy have included those patients with absent or minimal and nonspecific macular lesions. Al­though the inclusion of such patients accurately accounts

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Ophthalmology Volume 100, Number 11, November 1993

for the spectrum of phenotypes within the disorder, it Table 1. Visual Acuity Data does not provide a realistic appraisal of the visual prog-nosis for those patients with characteristic macular lesions. Patient No./

Right Eye Left Eye In the current study, we assessed the visual acuity and Age (yrs)/ Visual Visual

stage of macular dystrophy in patients of various ages Sex Acuity Stage Acuity Stage with Best vitelliform macular dystrophy. All patients had

1/5/M 20/50 IIIb 20/100 IV a macular lesion in at least one eye that was consistent with recognizable phenotypes reported as occurring in this 2/6/M 20/40 II 20/60 II

type of macular dystrophy. No patient with absent foveal 3/6/M 20/40 IIIb 20/40 IIIb changes or with only minimal foveal pigment mottling 4/7/M 20/25 IIIe 20/25 IIIb and hypopigmentation in both eyes was included in the 5/8/F 20/15 IIIe 20/20 IV study, as the majority of these patients are documented 6/8/M 20/25 IIIe 20/25 IIIe to have a good visual prognosis.2

7/9/M 20/100 IV 20/50 IV 8/9/F 20/25 II 20/20 IIIe

Materials and Methods 9/1O/M 20/200 IV 20/20 IIIa lO/lO/M 20/20 IIIa 20/70 IIIa

We performed a cross-sectional study of the clinical re- 11/12/F 20/50 me 20/15 I

cords of 47 patients (23 families) with Best vitelliform 12/13/M 20/50 IV 20/20 IV

macular dystrophy seen by one of us (GAF). We used 13/14/M 20/20 II 20/40 IV

only data from patients on file for whom a diagnosis of 14/14/F 20/20 me 20/20 IIIe the disorder could be established unequivocally. To be 15/14/M 20/20 IIIa 20/20 IIIa included in this study, patients had to have an abnormally 16/16/M 20/70 I1Ie 20/40 IIIe low light-peak to dark-trough ratio on EOG testing, at 17/16/M 20/50 II 20/30 II least one eye with a vitelliform or other recognizable Best 18/17/M 20/20 I1Ie 20/20 IIIb macular lesion phenotype, and at least one other family 19/20/F 20/200 I1Id 20/70 IIIa member with the disorder. Table 1 shows data from the 20/25/F 20/100 I1Ie 20/30 I1Ie most recent visit of these patients, including age, sex, and 21/27/M 20/50 IIIe 20/50 IIIb the disease stage and visual acuity of each eye. Snellen visual acuity testing was performed in all patients except 22/29/F 20/30 IIIb 20/60 I1Ib

two in whom Feinbloom testing was performed. Ten ad- 23/30/M 20/20 IIIa 20/20 IIIa ditional patients from our files, with a mean age of 32.5 24/30/F 20/25 IIIe 20/25 IIIe years, were excluded from the study because each eye 25/31/M 20/100 IIIe 20/25 IV showed either no foveal lesion or nonspecific foveal 26/31/M 20/30 IV 20/200 IV changes. As anticipated, these patients had very good vi- 27/32/F 20/15 20/50 IV sual acuity, with the visual acuity in their best eye never 28/32/M 20/40 II 20/100 IV worse than 20/20 and that in their worst eye never worse 29/32/M 20/20 I1Ie 20/20 IIIe than 20/25. Another patient was excluded because she 30/32/F 20/40 IV 20/200 IV had a congenital anophthalmia of one eye. 31/33/M 20/40 IIIb 20/25 IV

Fundus photographs were staged according to a mod- 32/36/M 20/50 IIIe 20/50 IIIe ification of staging systems by Deutman 1 and Mohler and Fine.2 Our classification scheme was based solely on mac- 33/37/F 20/200 IIIb 20/200 I1Ib

ular appearance and included five major stages with sub- 34/38/F 20/200 IV 20/60 IV

divisions. Stage 0 was a normal macula with an EOG with 35/39/F 20/15 20/400 IV abnormal findings. Stage I was a mild degree of foveal 36/40/M 20/50 IIIe 20/50 I1Ie pigment mottling and nonspecific hypopigmentation, 37/42/M 20/200 IV 20/60 I1Ie usually accompanied by window defects on fluorescein 38/46/M 20/80 IIId 20/30 I1Id angiography. Stage II was a typical vitelliform lesion (egg 39/48/F 20/20 IV 20/200 IV yolk, "sunny side up" appearance). Stage IIIa marked the 4O/59/F 20/70 me 20/100 I1Ie beginning of resorption with a diluted, orange-tinge al- 41/61/F 20/200 IV 20/200 IIIe teration to the egg yolk-like lesion, giving a so-called 42/65/F CF IV 20/70 IV scrambled, or fried egg, appearance. Stage IIIb included 43/65/F 20/60 IV 20/100 IV partial resorption in which the residual material showed a pseudohypopyon appearance, occupying approximately 44/67/M 20/200 IV 20/100 IV

25% or more of the resorbing vitelliform cyst. In stage 45/68/M 20/200 IV 20/200 IV

IlIe, there was total resorption of, or only sparsely re- 46/70/M 5/200 IV 10/200 IV maining, yellowish material that was not layered in a 47/72/F 10/350 IIId 20/20 0 pseudohypopyon fashion. In some such patients, atrophy

CF = counting fingers. of the choriocapillaris also was apparent in stage IIId. In stage IV, the majority of vitelli form material was resorbed,

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Fishman et al . Best Vitelliform Macular Dystrophy

as in stage Ill. In addition, stage IV was characterized by a fibrotic-appearing scar, measuring approximately 0.5 disc diameter or more that could be associated with pig­ment clumping and/or neovascularization. The macular changes corresponding to the various stages are shown in Figure I.

Although we classified these phenotypes as stages, we do not wish to imply that Best vitelli form macular dys­trophy must evolve through all stages in all or even most patients. The stages do represent a spectrum of change that involves no macular lesion (stage 0), minimal macular pigment mottling and hypopigmentation (stage I), a classic vitelliform lesion (stage II), various stages of resorption of the vitelliform lesion (stages IlIa through IIId), and resorption plus fibrotic- or gliotic-appearing scar forma­tion with or without a neovascular membrane (stage IV).

Results

A significant difference was noted between the visual acu­ities of the two eyes of the patients with Best vitelliform macular dystrophy (t = 6.06, P < 0.0 I). The majority of patients (30/47 [64%]) had a visual acuity difference of two lines or greater between the two eyes (Table I). Only IS patients with Best vitelliform macular dystrophy (32%) had equal visual acuity in both eyes. A significant corre­lation was noted between patient age and visual acuity for both the right eye (r = 0.55, P < 0.01) and the left eye (r = 0.52, P < 0.0 I), with older patients tending to have the worst visual acuities.

Because visual acuities generally were unequal between the two eyes of the patients, we examined the relationship between best or worst visual acuity and patient age. Only eyes with stage II or greater lesions were considered in this evaluation. The data are summarized in Figure 2. The visual acuity categories in Figure 2 are based in part on the visual acuity criteria for restricted and unrestricted driver's licenses (see "Discussion" section).

In the eyes with worst visual acuity (Fig 2A), the ma­jority of patients 40 years of age and younger (23/36 [64%]) had visual acuities worse than 20/40. Of patients in this age group, 33% (12/36) had visual acuities worse than 20/ 70 and 19% (7/36) had visual acuities of 20/200 or worse. None of the patients older than 40 years had visual acuities better than 20/80 in their worst eye and 73% (8/11) had visual acuities of 20/200 or worse. In fact, 74% (17/23) of patients older than 30 years of age had a visual acuity of20/ 100 or worse in their worst eye. None of the patients older than 50 years had a visual acuity better than 20/ 100 in their worst eye.

In the eyes with best visual acuity (Fig 2B), the majority of patients younger than 40 years (25/33 [76%]) had visual acuities of20/40 or better. In fact, 75% (27 /36) of patients 50 years of age and younger still had a visual acuity of 20/40 or better in their best eye. The majority (6/10 [60%]) of patients older than 40 years of age had a visual acuity of 20/70 or better in their best eye, but only 20% (2/ I 0) had a visual acuity of 20/40 or better. Of the patients older than 50 years, 43% (3/7) had visual acuities of

20/70 or better, but none had a visual acuity of 20/40 or better.

In the 43 patients with stage II or greater lesions in each eye who had Best vitelliform macular dystrophy, a significant correlation was noted between the stage of dys­trophy in the two eyes (chi-square = 31.14; P < 0.01). (Patients with either stage 0 or I lesions were excluded from this analysis due to the low numbers of such pa­tients.) Of the 47 total patients with Best vitelliform mac­ular dystrophy, 70% (n = 33) had comparable lesions in the two eyes, and lesions were therefore classified into the same general stage bilaterally; 62% (29) of the patients had the same specific stage in both eyes.

The visual acuities, stages of the dystrophy, and patient ages are illustrated in Figure 3 for the eyes with the worst visual acuity (Fig 3A) and those with the best visual acuity (Fig 3B). Only eyes with stage II or greater lesions were included in these figures. An analysis of variance indicated a significant relationship between the stage of the dystro­phy and patient age for both the eye with the best visual acuity (F = 6.34; P < 0.01) and the eye with the worst visual acuity (F = 3.37; P < 0.05). (We note that statistical results based on eyes with best or worst visual acuity are only approximate, because the distribution of extreme values is known to be nonnormal.)

For the eyes with worst visual acuity, there was a sig­nificant relationship between visual acuity and stage of dystrophy after correction for age (F = 4.80; P < 0.05). However, there was no significant relationship between visual acuity and stage of dystrophy for the eyes with best visual acuity or for the right and left eyes considered sep­arately (F = 0.17, 1.24, and 2.44, respectively; P = not significant).

Discussion

Our results suggest that the visual prognosis for patients with Best vitelli form macular dystrophy who manifest characteristic macular lesions is not as optimistic as that for all patients with this type of dystrophy, including those with absent or minimal macular lesions. In our study, which specifically excluded analysis of eyes from patients with Best vitelliform macular dystrophy who have either stage 0 or stage I lesions, only 44% of eyes had a visual acuity of 20/40 or better. In contrast, Mohler and Fine2

reported that 77% of the patients' eyes in their study had visual acuities of 20/40 or better. However, in the study by Mohler and Fine, the prevalence of eyes with stage 0 or stage I lesions included in their analysis was 50%.

Our results are more similar to those of Clemett.8 In his study, the prevalence of eyes with stage 0 or stage I lesions was approximately 26%. This degree of prevalence is similar to that of our entire patient population, in which 21 % of eyes had either stage 0 or stage I lesions. Clemett reported that 43% (25/58) of eyes in his patient population had visual acuities of 20/60 or better. This percentage is similar to the 41% (37/90) of eyes with 20/60 or better visual acuity in our study that had a stage II or greater macular lesion.

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Ophthalmology Volume 100, Number 11, November 1993

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Fishman et al . Best Vite1liform Macular Dystrophy

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macular pathology" and noted that, overall, 61 % (54/89) had a visual acuity of 20/40 or better in their best eye. This is similar to 63% (27/43) of patients in our study with 20/40 or better visual acuity in their best eye who had a stage II or greater lesion.

We observed a high degree of symmetry between the two eyes ofthe patients with Best vitelli form macular dys­trophy in our study with regard to the stage of the dys­trophy. However, there was notable disparity between the visual acuities of the two eyes in the majority of these patients. Such findings were not noted by any of the pre­viously mentioned investigators.

The visual acuities of the patients with Best vitelliform macular dystrophy in our study were examined with ref­erence to the visual acuity criteria for driver's licenses. The majority of states (36/50 [72%]) have a visual acuity criterion of20/40 or better in the best eye as a requirement for obtaining an unrestricted driver's license.9 Thirty-nine states also have a visual acuity criterion for obtaining a restricted driver's license, although the criteria vary some­what from state to state.9 The most common visual acuity criterion for a restricted license is at least 20/70 in the better eye (16 states or 41 %), whereas the second most common criterion is 20/60 or better (8 states or 21 %). Together, these two criteria are used in 62% of the states that provide a restricted license.

For those patients in our study who were 40 years of age and younger, 76% (25/33) would have been able to meet the visual acuity criterion to obtain an unrestricted driver's license based on a visual acuity of 20/40 or better in their best eye. Only 3% of affected patients in this age category would have been unable to meet the visual acuity criterion of 20/70 of better in their best eye required for a restricted license. However, for those patients with Best vitelliform macular dystrophy older than 40 years of age, only 20% (2/10) would have met the visual acuity criterion for an unrestricted license. In this age group, 40% (4/10) would not have qualified for a restricted license based on a visual acuity criterion of 20/70 or better, and 60% (6/ 10) would not have qualified for a restricted license based on a visual acuity criterion of 20/60 or better. From our analysis of data from eight families reported by Bard and Cross, 10 we note that in their patients older than 45 years of age with visible macular pathology, only 29% (6/21) had a visual acuity of 20/40 or better and thus would qualify for an unrestricted license. In their study, 57% (10/21) of patients in this age group had a visual acuity of 20/70 or worse in their best eye compared with 67%

Figure 1. Fundus photographs represent various stages of macular lesions in Best vitelliform macular dystrophy. Top left, stage I, mild degree of foveal pigment mottling and nonspecific hypopigmentation. Top right, stage II, typical vitelliform or egg yolk lesion. Second row left, stage IlIa, scrambled or "fried egg" phase as vitelliform lesion becomes diffusely more amorphous and diluted in appearance. Second row right, stage IIIb, pseudohypopyon phase in which the yellow material in the vitelliform cyst develops a layered appearance. Third row left, stage lIIc, only a sparse amount of the yellowish vitelliform material remains. Third row right, stage IlId, similar to stage IlIe except that the choriocapillaris also is atrophic. Bottom, stage IV, both less and more extensive examples are depicted. Characteristic feature is a fibrotic-gliotic-appearing scar in addition to resorption of the vitelliform material.

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Ophthalmology Volume 100, Number 11, November 1993

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(6/9) of patients in our study who were older than 45 years of age. Thus, a majority of these patients in both studies would not have qualified for a restricted driver's license.

1670

These findings indicate that although at least one eye may retain reasonably good visual acuity in patients with Best vitelliform macular dystrophy and stage II or greater macular lesions, an appreciable number of such patients, after approximately 30 years of age, can lose substantial visual acuity in at least one eye. In our study, a notable number of patients older than 40 years of age no longer qualified for an unrestricted or even a restricted driver's license. A study involving a larger population of patients with Best vitelli form macular dystrophy older than 40 years of age will be necessary to more fully and conclu­sively validate our findings regarding visual prognosis in the fifth and sixth decades. Nevertheless, the studies avail­able to date consistently report that a notable reduction of vision in patients with Best vitelliform macular dystro­phy can occur in both eyes after approximately 50 years of age. These types of observations are valuable for patient counseling regarding the prognosis for visual limitations.

References

I. Deutman AF. The Hereditary Dystrophies of the Posterior Pole of the Eye. Assen: Van Gorcum, 1971;198-299.

2. Mohler CW, Fine SL. Long-term evaluation of patients with Best's vitelliform dystrophy. Ophthalmology 1981 ;88:688-92.

3. Best F. Ueber eine hereditare Maculaaffektion. Ztschr F Augenh 1905;13:199-212.

4. Adams JE. Case showing peculiar changes in the macula. Trans Ophthalmol Soc UK 1883;3:113-14.

5. Krill AE, Morse PA, Potts AM, Klien BA. Hereditary vi­tellirupti ve macular degeneration. Am J Ophthalmol 1966;6 1: 1405-15.

6. Fran<;ois J, DeRouck A, Fernandez-Sasso D. L'electro-ocu­lographie dans les degenerescences vitelli formes de la mac­ula. Bull Soc BeIge Ophtalmol 1966; 143:547-52.

7. Deutman AF. Electro-oculography in families with vitelli­form dystrophy of the fovea. Detection of the carrier state. Arch Ophthalmol 1969;81 :305-16.

8. Clemett R. Vitelliform dystrophy: long-term observations on New Zealand pedigrees. Aust N Z J Ophthalmol 1991; 19: 221-7.

9. Keltner JL, Johnson CA. Visual function , driving safety, and the elderly. Ophthalmology 1987;94: 1180-8.

10. Bard LA, Cross HE. Genetic counseling of families with Best macular dystrophy. Trans Am Acad Ophthalmol Oto­laryngol 1975;79:0P865-77.