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Ophthalmol SciNovember 20250 citations

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

Charng Jason, Alonso-Caneiro David, Lamey Tina M, Thompson Jennifer A, Lim Jeremiah K H, Ong Elaine, McLaren Terri L, Chen Fred K


AI Summary

This study compared microperimetry progression methods in USH2A-retinopathy. Sensitivity-based (mFTP) and anatomy-based (HRS) point selections best detected progression, outperforming overall and scotoma-edge sensitivity. This improves monitoring for clinical trials.

Abstract

Purpose

To compare microperimetry progression rate in USH2A- retinopathy using prespecified points based on fundus autofluorescence coregistration with loci preselected based on retinal sensitivity profile.

Design

Cohort longitudinal study.

Subjects

Seventeen eyes from 17 patients with biallelic pathogenic variants in USH2A gene.

Methods

Microperimetry was recorded using 10-2 grid. The grid was partitioned into 68 2° × 2° nonoverlapping squares, representing the retinal coverage of each locus. Four metrics were defined at baseline: (1) mean macular sensitivity (MMS): average sensitivity of all loci; (2) edge of scotoma sensitivity (ESS): average sensitivity of all loci adjacent to a scotomatous loci at baseline; (3) modified Rate of Progression in USH2A -related Retinal Degeneration study-defined functional transitional point (mFTP): selection based on ranking of the proportion peripheral adjacent loci that showed ≥7 decibel (dB) decrease; and (4) hyperautofluorescent ring sensitivity (HRS): average sensitivity of stimulus squares which the hyperautofluorescent ring boundary transects into. Trend-based progression rates (gradient from linear regression) were compared between these metrics, and event-based analysis of the US Food and Drug Administration-defined clinically significant change in visual field (mean change of ≥7 dB across ≥5 prespecified loci).

Main outcome measures

Trend- and event-based measures in MMS, ESS, mFTP, and HRS.

Results

Seventeen patients (median age 37.0 years) had mean baseline values of 9.7 dB, 9.2 dB, 17.9 dB, and 13.1 dB for MMS, ESS, mFTP, and HRS, respectively. Using all longitudinal data (mean follow-up 4.0 years), trend analysis showed mFTP progression rate (-1.53 ± 1.37 dB/year) was significantly faster than MMS (-0.51 ± 0.63 dB/year) and ESS (-1.11 ± 1.23 dB/year) but similar to HRS (-1.29 ± 1.41 dB/year). Edge of scotoma sensitivity was more prone to floor effect and had lower baseline sensitivity than mFTP and HRS. In event-based analysis, the proportion of eyes that demonstrated clinically significant mean change was similar between ESS (2-year 36.4%, overall 45.5%), mFTP (2-year 33.3%, overall 43.8%), and HRS (2-year 28.5%, overall 42.9%) but noticeable less in MMS (2-year 13.3%, overall 12.5%).

Conclusions

Hyperautofluorescent ring sensitivity and mFTP showed comparable performance in both trend- and event-based analyses, superior to that of MMS and ESS. Additional advantage of mFTP is inclusion of patients without the autofluorescent ring.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Key Concepts5

In USH2A-retinopathy, the mFTP progression rate (-1.53 ± 1.37 dB/year) was significantly faster than MMS (-0.51 ± 0.63 dB/year) and ESS (-1.11 ± 1.23 dB/year) but similar to HRS (-1.29 ± 1.41 dB/year) in trend analysis using all longitudinal data (mean follow-up 4.0 years).

Comparative EffectivenessCohortCohort longitudinal studyn=17 eyes from 17 patients with biallel…Ch5Ch6

In USH2A-retinopathy, ESS was more prone to floor effect and had lower baseline sensitivity than mFTP and HRS, with mean baseline values of 9.7 dB for MMS, 9.2 dB for ESS, 17.9 dB for mFTP, and 13.1 dB for HRS.

DiagnosisCohortCohort longitudinal studyn=17 eyes from 17 patients with biallel…Ch5Ch6

In USH2A-retinopathy, the proportion of eyes demonstrating clinically significant mean change (≥7 dB across ≥5 prespecified loci) in event-based analysis was similar between ESS (2-year 36.4%, overall 45.5%), mFTP (2-year 33.3%, overall 43.8%), and HRS (2-year 28.5%, overall 42.9%) but noticeably less in MMS (2-year 13.3%, overall 12.5%).

Comparative EffectivenessCohortCohort longitudinal studyn=17 eyes from 17 patients with biallel…Ch5Ch6

Hyperautofluorescent ring sensitivity (HRS) and modified Rate of Progression in USH2A-related Retinal Degeneration study-defined functional transitional point (mFTP) showed comparable performance in both trend- and event-based analyses, superior to that of mean macular sensitivity (MMS) and edge of scotoma sensitivity (ESS) for detecting microperimetry progression in USH2A-retinopathy.

Comparative EffectivenessCohortCohort longitudinal studyn=17 eyes from 17 patients with biallel…Ch5Ch6

An additional advantage of mFTP (modified Rate of Progression in USH2A-related Retinal Degeneration study-defined functional transitional point) for detecting microperimetry progression in USH2A-retinopathy is the inclusion of patients without the autofluorescent ring.

DiagnosisCohortCohort longitudinal studyn=17 eyes from 17 patients with biallel…Ch5Ch6

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