Relationship Between Foveal Cone Structure and Visual Acuity Measured With Adaptive Optics Scanning Laser Ophthalmoscopy in Retinal Degeneration

Abstract

PurposeTo evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations.MethodsAdaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an “E” optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity.ResultsETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5–0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02–0.7), and negatively correlated with ETDRS letters read (ρ = −0.64, 95% CI −0.8 to −0.2). AOSLO-VA remained ≥20/20 until cones decreased to 40.2% (CI 31.1–45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until cones were 42.0% (95% CI 36.5–46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = −0.79, 95% CI −0.9 to −0.4) and foveal sensitivity was ≥35 dB until cones were 43.1% (95% CI 39.3–46.6) below average.ConclusionsVA and foveal cone spacing were weakly correlated until cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal cone survival; cone spacing may be a more sensitive measure of cone loss.

Comparing Cone Structure and Function inRHO-andRPGR-Associated Retinitis Pigmentosa

“…In prior studies of patients with retinal degenerations, AOSLO-mediated acuity measures were not significantly better than ETDRS acuity in patients with retinal degenerations, perhaps because acuity was limited by reduced cone densities near the fovea. 41 Until AOMP becomes widely available, clinical microperimetry could be a useful tool to characterize macular function in RP patients, and may identify abnormal function in regions with relatively preserved outer retinal structure. However, if precise stimulus localization is required for disease assessment, AOMP can be useful to provide exact placement of stimuli on particular retinal areas on interest.…”

“…The PRL was identified with a recorded 10-second video of the patient observing a target created by modulating the scanning raster of the AOSLO as described previously. 40,41 The PRL in eyes with normal central vision is generally within approximately 0.10°of the location of maximum cone density. 42,43 Structure-Function Comparisons and Statistical Analysis.…”

Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium

“…72,92 Adaptive optics scanning laser ophthalmoscopy, that removes optical aberrations from retinal images to generate highresolution images of photoreceptors with single cell resolution, 93 is being used to monitor cones before significant loss of vision. [94][95][96][97] The discovery of socalled "dysflective cones" that appear to remain wired to native visual pathways [98][99][100] suggests that photoreceptors potentially amenable to rescue persist in the foveae in some IRDs beyond the stage of their loss of function.…”

Perspectives on Gene Therapy: Choroideremia Represents a Challenging Model for the Treatment of Other Inherited Retinal Degenerations

“…In moderately advanced disease, the ellipsoid zone (EZ) area reveals the extent of the remaining photoreceptors. Although VA may not yet begin to change, 18 , 19 conventional static perimetry, dark-adapted perimetry, and full-field stimulus threshold 20 measures are helpful. In later stages of disease, when the EZ area and VA provide limited data to discriminate change, full-field stimulus threshold, mobility tests, 1 , 21 , 22 and patient-reported outcomes 23 may reveal altered visual function.…”