Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy.

PURPOSE: To elucidate morphological determinants of rod and cone dysfunction in Sorsby fundus dystrophy (SFD), and to systematically compare visual function tests for interventional trials. DESIGN: Prospective cross-sectional study. METHODS: Patients with SFD (n = 16) and controls (n = 20) underwent visual function testing (best-corrected visual acuity [BCVA] and low luminance visual acuity [LLVA], contrast sensitivity, mesopic and dark-adapted (DA) fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related quality of life was evaluated. FCP and RMDA thresholds were analyzed using mixed models and structure-function correlation using machine learning (ML). Longitudinal data of 1 patient with high-dose vitamin A supplementation were available. RESULTS: Although photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20; 0.45] vs 0.20 LogMAR [0.03; 0.28], P < .05). Scotopic visual function exhibited a delayed rod-intercept time (21 minutes [12.15; 21] vs 4.05 minutes [3.22; 5.36], P < .001), and marked DA cyan mean sensitivity loss (-11.80 dB [-3.47; -19.85]), paralleled by a reduced vision-related quality of life. ML-based structure-function correlation allowed prediction of mesopic, DA cyan, and red sensitivity with high accuracy (cross-validated mean absolute error: 4.36, 7.77, and 5.31 dB, respectively), whereas RMDA could be slowed even in the absence of fundus alterations on multimodal imaging. After high-dose vitamin A supplementation, RMDA and DA thresholds improved markedly. CONCLUSIONS: Patients with SFD exhibit severely impaired scotopic visual function even in the absence of funduscopic alterations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in the early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake, as observed in one patient in our study, is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.

IMPAIRED DARK ADAPTATION ASSOCIATED WITH A DISEASED BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM.

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.

Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study).

BACKGROUND: Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). OBJECTIVE: To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. METHODS: This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. RESULTS: Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. CONCLUSION: The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.

Filtration of Short-Wavelength Light Provides Therapeutic Benefit in Retinitis Pigmentosa Caused by a Common Rhodopsin Mutation.

Purpose: The role of light exposure in accelerating retinitis pigmentosa (RP) remains controversial. Faster degeneration has however been observed in the inferior than superior retina in several forms ("sector" RP), including those caused by the rhodopsin P23H mutation, suggesting a modifying role of incident light exposure in such cases. Rearing of equivalent animal models in complete darkness has been shown to slow the degeneration. Here we investigate the use of red filters as a potential treatment strategy, with the hypothesis that minimizing retinal exposure to light <600 nm to which rods are maximally sensitive may provide therapeutic benefit. Methods: Knockin mice heterozygous for the P23H dominant rhodopsin mutation (RhoP23H/+) housed in red-tinted plastic cages were divided at weaning into either untinted or red-tinted cages. Subsequently, photoreceptor layer (PRL) thickness was measured by spectral-domain ocular coherence tomography, retinal function quantified by ERG, and cone morphology determined by immunohistochemical analysis (IHC) of retinal flatmounts. Results: Mice remaining in red-tinted cages had a significantly greater PRL thickness than those housed in untinted cages at all time points. Red housing also led to a highly significant rescue of retinal function as determined by both dark- and light-adapted ERG responses. IHC further revealed a dramatic benefit on cone morphology and number in the red- as compared with the clear-housed group. Conclusions: Limitation of short-wavelength light exposure significantly slows degeneration in the RhoP23H/+ mouse model. Red filters may represent a cost-effective and low-risk treatment for patients with rod-cone dystrophy in whom a sectoral phenotype is noted.