Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom

“…For hyper-AF, BEST1 exhibited the largest areas of hyper-AF, which can be attributed to the vitelliform lesion(s) that are characteristically observed in autosomal dominant and recessive forms of the disease 31–33 ( Figure 2.b ). For ring the presence of a macular ring typically corresponds to a demarcation between diseased and non-diseased retina, and is usually seen in RP and cone rod dystrophies, in keeping with our findings herein 3 ( Figure 2.c ). The lower vessel density observed in RP and LCA genes was also in keeping with the vessel attenuation commonly associated with these genes 34,35 ( Figure 2.d ).…”

“…However, there were some noteworthy exceptions for individual genes. In particular, BEST1 is associated with “yolk-like” regions of hyper-AF, typically within 2-3mm of the perifovea, which change over time through pre-vitelliform, vitelliform, pseudohypopyon, vitelliruptive stages and finally to the atrophic stage 3,33 . The highest hyper-AF signal would be associated with the vitelliform stage, progressively reducing in intensity to become a region of hypo-AF by the atrophic stage, which matches what we see as a decrease in foveal hyper-AF with age.…”

“…Some of these FAF signal changes are highly characteristic of specific IRDs and can indicate features such as areas of RPE atrophy or lipofuscin deposits. FAF is listed as a primary or secondary outcome in multiple clinical trials, and it has become a useful retinal biomarker for diagnostic and prognostication purposes in a wide variety of IRDs 3,7,8 .…”

“…Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders that affect the retina, and represent the leading cause of certifiable blindness among working-age adults in England and Wales and the second commonest cause in childhood 1 . This group of disorders can be caused by genetic mutations in any one of over 270 genes [2][3][4] .…”

“…FAF is listed as a primary or secondary outcome in multiple clinical trials, and it has become a useful retinal biomarker for diagnostic and prognostication purposes in a wide variety of IRDs 3,7,8 .…”