Impaired Dark Adaptation Associated With a Diseased Bruch Membrane in Pseudoxanthoma Elasticum

Abstract

Purpose: To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. Methods: In this prospective case–control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. Results: Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. Conclusion: Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.

Low luminance visual acuity as a clinical measure and clinical trial outcome measure: a scoping review

“…However, the combined mean age for the healthy control subjects was 64 years. Hess et al 45 reported a mean LLD of 6.1 (±1.4) ETDRS letters in a younger sample (mean age 52.2, range 23–72). LLVA in healthy individuals declines with age, more than standard VA, thereby resulting in a larger LLD 14,17,72 .…”

“…In five studies, LLD has been shown to be a strong predictor of geographic atrophy progression and subsequent VA loss 10,38,39,41,43 . LLD is significantly reduced in patients with macular telangiectasia type 1, choroideremia and pseudoxanthoma elasticum when compared with healthy controls 44,45,50 . LLVA has been recommended as a clinical trial outcome measure for dry AMD, geographic atrophy and retinitis pigmentosa 25,37,75 .…”

“…However, most studies delivering useful insights into the impact of luminance levels on VA included only small participant numbers 5,8 . Similarly, in those studying rare diseases, large sample sizes are not feasible, but results can still be valuable 44,45,47,50 …”

A Reflectivity Measure to Quantify Bruch's Membrane Calcification in Patients with Pseudoxanthoma Elasticum Using Optical Coherence Tomography

“…Three studies in 35, 15, and 4 patients with PXE found reduced retinal function or dark adaptation, which supports this hypothesis. 43 – 45 However, one study did not find retinal dysfunction in seven patients with PXE. 46 Future research should compare retinal function with OCT reflectivity to further investigate the mechanism of lower photoreceptor reflectivity in patients with PXE.…”

Choroidale Neovaskularisation mit Visusminderung bei Pseudoxanthoma elasticum

“…Alternativ kann sicherlich auch eine IVOM-Therapie nach dem Treat-and-Extend-Schema erwogen werden. Es konnte gezeigt werden, dass durch die Kalzifizierung des elastischen Bindegewebes die Schwelle der Dunkeladaptation bei Patienten mit PXE signifikant erhöht ist, daher wird aufgrund möglicher positiver Effekte auch eine Nahrungsmittelergänzung mit Vitamin A diskutiert [10]. Zur Diagnostik und zum Nachweis der CNV beim PXE stehen neben dem OCT noch die Fluoreszenzangiografie (FAG) und OCT-Angiografie zur Verfügung.…”