Correlations between the Michigan Retinal Degeneration Questionnaire and visual function parameters in patients with retinitis pigmentosa.

PURPOSE: To validate the use of best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD; the difference between BCVA and LLVA), mean macular sensitivity and fixation stability as parameters of vision-related quality of life based on the novel Michigan Retinal Degeneration Questionnaire (MRDQ) in retinitis pigmentosa (RP) patients. METHODS: In this prospective cross sectional study, 30 patients with RP (47% female) were included with a median age of 41.0 years (interquartile range: 24.1-58.3 years). BCVA, LLVA and LLD were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Mesopic microperimetry was performed to measure mean macular sensitivity and fixation stability. Patients completed a Dutch translation of the MRDQ which results in an experienced disability (Θ-)score of seven domains. Spearman's rank correlation was used. RESULTS: BCVA correlated significantly to the MRDQ domain of central vision (r = 0.657; p < 0.001) and colour vision (r = 0.524; p = 0.003). Lower LLVA significantly correlated to higher experienced disability in the MRDQ domains for central vision (=0.550; p = 0.002) and contrast sensitivity (r = 0.502; p = 0.005). LLD was significantly correlated to the MRDQ domains of scotopic function (r = -0.484; p = 0.007) and mesopic peripheral function (r = -0.533; p = 0.002). Lower mean macular sensitivity was significantly associated with high experienced disability in all domains except for photosensitivity. CONCLUSIONS: The majority of the MRDQ domains is strongly associated with visual function parameters. These findings show that visual function measurements, especially LLVA, LLD and mean macular sensitivity on microperimetry, reflect vision-related quality of life and can be used as relevant outcome measures in clinical trials for RP.

Exploring the choroidal vascular labyrinth and its molecular and structural roles in health and disease.

The choroid is a key player in maintaining ocular homeostasis and plays a role in a variety of chorioretinal diseases, many of which are poorly understood. Recent advances in the field of single-cell RNA sequencing have yielded valuable insights into the properties of choroidal endothelial cells (CECs). Here, we review the role of the choroid in various physiological and pathophysiological mechanisms, focusing on the role of CECs. We also discuss new insights regarding the phenotypic properties of CECs, CEC subpopulations, and the value of measuring transcriptomics in primary CEC cultures derived from post-mortem eyes. In addition, we discuss key phenotypic, structural, and functional differences that distinguish CECs from other endothelial cells such as retinal vascular endothelial cells. Understanding the specific clinical and molecular properties of the choroid will shed new light on the pathogenesis of the broad clinical range of chorioretinal diseases such as age-related macular degeneration, central serous chorioretinopathy and other diseases within the pachychoroid spectrum, uveitis, and diabetic choroidopathy. Although our knowledge is still relatively limited with respect to the clinical features and molecular pathways that underlie these chorioretinal diseases, we summarise new approaches and discuss future directions for gaining new insights into these sight-threatening diseases and highlight new therapeutic strategies such as pluripotent stem cell‒based technologies and gene therapy.

Diagnosis and treatment of C3 glomerulopathy in a center of expertise.

C3 glomerulopathy is a rare renal disease that has been distinguished as a renal disease for about 10 years. It is caused by an excessive activation of the alternative complement pathway in the circulation, which leads to deposition of complement factor C3 in glomeruli. It is diagnosed based on clinical presentation, histological patterns in a kidney biopsy and tests of the complement pathways. It can closely resemble immune complexmediated glomerulonephritis and postinfectious glomerulonephritis. Renal failure develops in up to half of all patients within 10 years after presentation. A curative treatment is not available. Treatment relies on renoprotective measures, occasional immunosuppressive medication and experimental novel complement inhibitors. Because the disease is rare, its care and cure are concentrated in centers of expertise. Here we provide an overview of the state-ofthe-art diagnosis and treatment of C3 glomerulopathy in a center of expertise in the Netherlands.

[Fundus autofluorescence in patients with inherited retinal diseases : patterns of fluorescence at two different wavelengths]. / Fundusautofluoreszenz bei erblichen Netzhauterkrankungen : Fluoreszenzmuster in zwei verschiedenen Wellenlängenbereichen.

BACKGROUND: Fundus autofluorescence (FAF) may be excited and measured at different wavelengths. In the present study we compared short wavelength and near-infrared FAF patterns of retinal dystrophies. METHODS: We analysed both eyes of 108 patients with diverse retinal dystrophies. Besides colour fundus photographs, FAF images were obtained with the Heidelberg Retina Angiograph (HRA 2). Excitation wavelengths of 488 nm (blue; filter at 500 nm) and 787 nm (near-infrared; filter at 810 nm) were applied. For improvement of the signal-to-noise ratio a total of nine images were averaged, and the mean images (original grey values, not normalized) were analysed. RESULTS: Useful FAF images of both excitation wavelengths were achieved in all patients. We observed characteristic FAF patterns, which differed between excitation wavelengths depending on the disease. With time, FAF pattern changes and progression could be observed. CONCLUSION: FAF of both wavelengths provided additional information for phenotype description in retinal dystrophies. Other than short wavelength FAF, near-infrared FAF showed different pathological changes, which may be related to changes in RPE melanin. However, any conclusions may be limited by the still incomplete knowledge about the prognostic value of FAF in the diseases studied here.

Analysis of visual pigment by fundus autofluorescence.

This study investigated changes of short-wavelength fundus autofluorescence (SW-AF) by retinal bleaching effects. All measurements were performed with the Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done on a healthy eye after dark adaptation. Photopigment was bleached within the central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of this region was performed, and SW-AF of the surrounding, unbleached 25 degrees fundus region was subsequently studied by a wide-field lens. Next, another 30 degrees SW-AF image of the posterior pole was obtained after complete dark adaptation. Then an extra SW-AF examination was performed with 15 degrees temporal eccentricity, overlapping the original examination area. Finally, a successive image series was carried out on the dark-adapted eye to test for bleaching kinetics. The second and third experiments were also performed on eyes with macular dystrophies. Distinct regions of increased SW-AF were observed after strong illumination with the blue excitation light in all eyes studied. During light adaptation mean gray levels showed a saturation plateau after an initial steep increase. The resulting gray-value maps showed significant differences of pixel intensities between bleached and unbleached parts of the fundus. Two-dimensional density difference maps allowed analysis of visual pigment distribution and density in both healthy eyes and eyes with macular dystrophies. Our observations highlight the viability of objective, non-invasive evaluation of visual pigment in the healthy and diseased human retina by means of confocal fundus autofluorescence.