Study Details Alternative End Points for Stargardt Treatment Trials

Microperimetric mean sensitivity and deep scotoma points may be useful end points for clinical trials investigating emerging treatments for Stargardt disease, according to a study published in JAMA Ophthalmology.

Stargardt disease is an inherited disorder of the retina that typically causes vision problems during childhood and adolescence, according to the National Eye Institute. Stargardt disease type 1 (STGD1) can lead to atrophic-appearing macular lesions and variable loss of best-corrected visual acuity (BCVA).

Although BCVA is the most commonly used functional end point in clinical trials for various retinal diseases, one recent study found that due to the slow rate of BCVA loss, the measure is only likely to be a sensitive outcome measure in certain STGD1 subgroups, authors explain.

In comparison, “fundus-controlled (micro)perimetry allows precise functional analysis of the macula by displaying stimuli in preplanned retinal areas.”

In a multicenter prospective cohort study, investigators assessed longitudinal changes in microperimetric sensitivity during a 12-month period and the association between the changes and different parameters in patients with STGD1.

Overall, 200 patients (359 eyes) were recruited from tertiary referral centers between October 2013 and February 2017. Average patient age was 33 years and 43.5% of the population were male. All participants underwent 3 study visits 6 months apart where a microperimeter was used to test sensitivity at 68 test locations (MP-1 test).

“The standard test pattern had the central 4 points at 1.7° from the anatomical fovea, which were grouped as foveal; the 12 perifoveal points were at a distance of 3.5° to 4.7° from the center of the grid and were grouped as the inner ring; and the remainder of the test locations 5.6° to 10.1° from the center were the outer ring,” researchers said.

Each retinal location’s sensitivity was determined by adjusting light intensity until the dimmest visible stimulus was found for all 68 locations. Sensitivity was determined on a scale of 0 to 20 dB. In addition, “test locations with a sensitivity of 0 dB (seen or not seen) were defined as deep scotomas, and test locations with a sensitivity of more than 0 dB but less than 12 dB were defined as relative scotomas.”

Data revealed that between the baseline exam and 12-month follow-up:

• Mean (SD) yearly change in macular sensitivity (MS) was −0.68 (2.04) dB (95% CI, −0.89 to −0.47 dB&#894; P&thinsp;<&thinsp;.001)
• Deep scotoma points increased by a mean (SD) of 1.56 (5.74) points per year
• Points with sensitivity of 12 dB or higher decreased in sensitivity by a mean (SD) of −3.01 (9.84) dB (95% CI, −4.03 to −1.99 dB&#894; P&thinsp;<&thinsp;.001)
• Mean (SD) yearly change in MS was not significantly different between the eyes with a grading of good or fair pattern placement at both visits (−0.67 [2.1] dB) and the eyes with a poor pattern placement during at least 1 visit (−0.64 [2.2] dB) (P&thinsp;=&thinsp;.91)

Limitations of the study include the relatively small sample size, along with unmeasured potentially confounding variables that may have affected functional variability, such as time of day or season.

“Simple microperimetric measures, such as overall MS or the count of normal, relative, or deep scotomatous points, may detect functional changes during a study period of 12 months,” authors conclude. “Potentially, microperimetry may detect changes in early stages of STGD1 before structural changes can be detected.”

Reference:

Schönbach EM, Strauss RW, Muñoz B, et al. Longitudinal microperimetric changes of macular sensitivity in Stargardt disease after 12 months. JAMA Ophthalmol. Published online May 28, 2020. doi:10.1001/jamaophthalmol.2020.1735