Purpose To determine the rate of progression and optimal follow up time in patients with advanced stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral domain optical coherence tomography. Design Retrospective analysis of progression rate. Methods Longitudinal imaging follow up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. Results Significant progression was observed in >75% of patients during the 2 year mean follow up. The mean annual progression rates of ellipsoid zone line, and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45° (4.9%), 0.51° (4.1%), and 0.42° (4.0%), respectively. The e llipsoid zone line width, and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5% and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. Conclusions Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1 year intervals should be adequate to efficiently detect progression.

SummaryHigh‐temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age‐related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key. We assess the high‐risk genotype at 10q26 by proteomic comparison of protein levels of RPE cells with and without the mutation. We show HTRA1 protein level is increased in high‐risk RPE cells along with several extracellular matrix proteins, including known HTRA1 cleavage targets LTBP‐1 and clusterin. In addition, two novel targets of HTRA1 have been identified: EFEMP1, an extracellular matrix protein mutated in Doyne honeycomb retinal dystrophy, a genetic eye disease similar to AMD, and thrombospondin 1 (TSP1), an inhibitor of angiogenesis. Our data support the role of RPE extracellular deposition with potential effects in compromised barrier to neovascularization in exudative AMD.

No abstract

Various factors are thought to cause the development and progression of disease in macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Some of the deleterious processes include oxidative stress, hypoxia, metabolic derangement, genetics, and vasculopathy. In this review, we present a unified theory for the pathophysiology of several retinopathies based on the unique and intense metabolism of rod photoreceptors.

No abstract