Anatomy- versus Sensitivity-Based Loci Preselection in Detecting USH2A-Retinopathy Microperimetric Progression

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Usher syndrome type 2A (USH2A) is a genetic disorder causing progressive vision loss.
• Accurate monitoring of disease progression is crucial for managing USH2A-retinopathy.
• Current microperimetry methods may not fully capture the rate of visual field decline.

Purpose of the Study:

• To compare the progression rate of USH2A-retinopathy using different microperimetry metrics.
• To evaluate the efficacy of fundus autofluorescence coregistration and retinal sensitivity profiles in identifying disease progression.

Main Methods:

• A longitudinal study involving 17 patients with USH2A pathogenic variants.
• Microperimetry data analyzed using four metrics: mean macular sensitivity (MMS), edge of scotoma sensitivity (ESS), modified functional transitional point (mFTP), and hyperautofluorescent ring sensitivity (HRS).
• Comparison of trend-based (linear regression) and event-based (clinically significant change) progression rates.

Main Results:

• The modified functional transitional point (mFTP) showed a significantly faster trend-based progression rate (-1.53 dB/year) compared to MMS (-0.51 dB/year) and ESS (-1.11 dB/year).
• Hyperautofluorescent ring sensitivity (HRS) also demonstrated a rapid trend-based progression rate (-1.29 dB/year), comparable to mFTP.
• Event-based analysis revealed similar proportions of eyes with clinically significant visual field changes for ESS, mFTP, and HRS, while MMS showed a lower proportion.

Conclusions:

• Hyperautofluorescent ring sensitivity (HRS) and mFTP are superior metrics for assessing USH2A-retinopathy progression compared to MMS and ESS.
• mFTP offers an advantage by including patients without hyperautofluorescent rings.
• These findings support the use of mFTP and HRS for more sensitive monitoring of visual field changes in USH2A-retinopathy.