purpose. To determine the extent of interocular difference in visual acuity (VA) and the time to at least double the minimal angle of resolution (MAR) in a cohort of patients with Stargardt disease.

methods. One hundred fifty patients with Stargardt disease who were examined at least four times over a minimum period of 3 years were identified and their VA and age at each visit recorded. The maximum interocular difference of VA was determined by whether the MAR between the two eyes differed by less than a factor of 2 or by a factor of 2 or greater. Differences in maximum VA between the two eyes were also examined according to a Bland-Altman–type approach. One hundred thirty-one eyes from 76 patients were subjected to survival analysis to determine whether the time to at least double the MAR was dependent on age at baseline or starting VA.

results. Of the 150 patients, 48% had interocular MAR that differed maximally by a factor of less than 2. Thirty-five percent showed a maximum interocular difference in their Snellen VA of less than one line. The Bland-Altman– type analysis showed that maximum interocular acuity difference was dependent on the mean acuity of the two eyes. The hazard for at least doubling the MAR was related to baseline vision and patient age.

conclusions. This information has clinical significance for patient counseling and for monitoring possible benefits and patient selection in future treatment trials.

*ABCA4*gene.

^{ 1 }

^{ 2 }

^{ 3 }

^{ 4 }It is characterized by a loss of central vision and fundus changes that include the presence of yellowish-white fundus flecks and often an atrophic-appearing macular lesion that results in a central or a perifoveal scotoma.

^{ 5 }

^{ 6 }

^{ 7 }

^{ 8 }

^{ 9 }

^{ 10 }

^{ 11 }

^{ 8 }Fishman et al.,

^{ 12 }

^{ 13 }Aaberg,

^{ 14 }Stone et al.,

^{ 15 }and Oh et al.

^{ 16 }Most agree that a level of 20/200 to 20/400 in VA is often ultimately reached. It was found that the probability of maintaining a VA better than 20/40 decreases with age and that once VA drops to 20/40 or less, it often decreases more rapidly and stabilizes at, most frequently, 20/200.

^{ 17 }

^{ 18 }However, it was found that the younger the patients at the initial visit, the more rapidly they will reach 20/200 vision or worse.

^{ 18 }Rotenstreich et al.

^{ 18 }reported that the median number of years it took for the VA to decrease from 20/40 or better at baseline to 20/200 was dependent on patient age at the initial visit. In those who were first seen at age 20 or younger, the median time to reach a VA level of 20/200 or worse was 7 years. In contrast, it took 22 and 29 years for those who were initially seen at ages 21 to 40 and 41 to 60, respectively.

^{ 14 }who found 26% (15 of 56) of patients had a difference in VA between fellow eyes of two or more lines on a Snellen distance acuity chart on initial presentation. As the patients were monitored over 3 or more years, VA became more symmetrical between the two eyes.

^{ 19 }

^{ 20 }First, the absolute value of the interocular logMAR acuity difference was determined for each patient. These values were plotted as a function of the mean logMAR acuity of the two eyes for each patient.

*t*-test was used to compare the means of these variables. No statistical difference was detected in the two groups between the mean initial age (

*P*= 0.41), the mean age at maximum interocular difference (

*P*= 0.94), or the mean number of years of follow-up (

*P*= 0.49). The mean number of visits was statistically significantly different between the two groups (

*P*= 0.003). However, the actual mean difference was only 1.6 years.

*x*-axis. Each open circle represents a patient, and the symbols were jittered slightly along the

*x*-axis to avoid overlap (Fig. 1) . Data points for patients with the same acuity in each eye, or zero interocular acuity difference, fall on the

*x*-axis. The negatively sloped parallel lines passing through the data points show how interocular acuity differences could vary across different levels of acuity. The lines intersect the

*x*-axis in increments of Snellen acuity (e.g., 20/400, 20/200, 20/100). The extent of the line indicates the maximum possible interocular acuity difference for a fixed acuity value in one eye. For example, the right-most line represents all possible combinations of acuities for both eyes of patients in whom one or both eyes had acuities of 20/400. The intersection of this line and the

*x*-axis represents patients with acuities of 20/400 in each eye who, thus, have no difference in interocular acuity. Moving upward along this line, increasingly smaller values of logMAR acuity are found in the better eye. The intersection of this line and the positively sloped line indicates the maximum possible interocular difference for a patient with 20/400 acuity in the worse eye and 20/15 acuity in the better eye. The positively sloped line represents acuity values of approximately −0.125 logMAR (20/15) in the better eyes, a value that was not obtained from any patient in the sample. Thus, the triangular space defines all possible interocular acuity differences for all possible mean interocular acuity values, as measured with the Snellen chart.

*P*= 0.0002) for any doubling of the starting MAR and 0.864 (

*P*= 0.025) for any 5-year increase in starting age. That is, the hazard for at least doubling the MAR decreases with increasing age. For example, with a 5-year increase in age, the hazard of at least doubling the MAR is reduced by a factor of 0.864. Additionally, the hazard for at least a doubling the MAR becomes smaller as vision worsens. If the starting (baseline) MAR doubles (i.e., worsening of VA), the hazard of eventually doubling the MAR is reduced by a factor of 0.831. When both variables were included in a multivariate model, the corresponding hazard ratios were 0.730 (

*P*< 0.0001) for any doubling of the starting MAR and 0.739 (

*P*= 0.0001) for a 5-year difference in starting age.

^{ 21 }in 1982, the analysis would have been facilitated because these charts have a geometric progression of lines that is lacking in a Snellen chart. An ETDRS chart was not used primarily because none was available at the time VA was initially measured in a number of patients or because of its subsequent lack of application. Thus, we evaluated our data in an alternative manner using the MAR and its log equivalent as a criterion to assess VA.

^{ 18 }This finding was similar to the observation of Sunness et al.,

^{ 22 }who described the VA loss in 148 patients with geographic atrophy associated with age-related macular degeneration. They found that patients whose VA was better than 20/50 were at greater risk to lose three lines on an ETDRS chart than those with worse VA.

^{ 16 }reported that the VA loss in patients with Stargardt disease is dependent on the extent of fundus flecks in the posterior pole, whereas those with midperipheral flecks were less likely to maintain 20/200 or better VA compared with those whose disease was confined to the macula. In our retrospective study, we examined the maximum interocular difference and the factors associated with at least doubling of the MAR without considering the variability in fundus findings as a factor.

Interocular Difference | No. Patients | Age at Baseline (y) | Age at Maximum Difference (y) | No. Years Follow-up | No. Visits | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

Min | Max | Mean | SD | Min | Max | Mean | SD | Min | Max | Mean | SD | Min | Max | Mean | SD | ||||||||||||||

Less than factor of 2 | 72 | 6 | 60 | 26.1 | 13.7 | 8 | 65 | 29.4 | 15.4 | 3 | 42 | 14.3 | 8.1 | 4 | 16 | 6.3 | 2.7 | ||||||||||||

Factor of 2 or greater | 78 | 4 | 59 | 24.4 | 12.0 | 9 | 70 | 29.6 | 13.7 | 3 | 40 | 15.2 | 8.8 | 4 | 21 | 7.9 | 3.8 |

**Figure 1.**

**Figure 1.**

*ABCR*, in Stargardt disease. Am J Hum Genet. 1999;64(2)422–434. [CrossRef] [PubMed]