Multimodal Approach to Monitoring and Investigating Cone Structure and Function in an Inherited Macular Dystrophy

Published:April 20, 2015DOI:


      To examine a female subject, her father, and a brother harboring a missense mutation of the retinitis pigmentosa 1-like 1 (RP1L1) gene, over 2 years of follow-up.


      Observational case series.


      setting: Fondazione G.B. Bietti IRCCS, Rome, Italy. study population: RP1L1 family members and controls. main outcome measures: Images of the cone mosaic acquired with an adaptive optics retinal camera, spectral-domain optical coherence tomography (SD OCT), and full-field and multifocal electroretinography (mfERG).


      In the proband, best-corrected visual acuity (≤0.7 logMAR) was stable in both eyes during follow-up, though analysis of adaptive optics images showed decreased cone density in the central 9 degrees from the fovea with respect to controls (P < .05) and cone density loss in the parafoveal area (2 degrees; <12%–16%) during follow-up. Texture analysis of SD OCT images identified abnormalities of the ellipsoid zone in the central 7 degrees, while mfERG response amplitudes were reduced only in the central 5 degrees relative to controls. In the proband's father, who had 0.0 logMAR visual acuity, significant cone loss was found in the central 7 degrees from the fovea (P < .05); abnormal SD OCT and mfERG values with respect to controls were found in corresponding retinal areas. No defects in the cone structure and function were found in the proband's brother, who had 0.0 logMAR visual acuity.


      Occult macular dystrophy was diagnosed based on genetic and multimodal ophthalmic findings. The quantitative assessment of photoreceptor survival or loss, based on analysis of adaptive optics retinal images, was valuable to monitor disease progression at a cellular level.
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      Dr. Lucia Ziccardi graduated in Medicine and Surgery in 2002. She earned a specialized degree in Ophthalmology in 2006. Since 2007, she has been working at the Fondazione G.B. Bietti. In 2012, she achieved her PhD in “Neurobiology of neurodegenerative diseases and neural development” after working on the RS1-knock out mouse model of juvenile X-linked retinoschisis at the Section for Translation and Research in Retinal and Macular Degeneration at the US National Eye Institute.


      Dr. Marco Lombardo graduated in Medicine and Surgery in 1999. He was specialized in Ophthalmology in 2003 and earned his PhD in Biomedical and Computer Engineering in 2007. He has been working at Fondazione G.B. Bietti since January 2010. He is principal investigator in projects related to the clinical application of adaptive optics, the development of new treatment options for keratoconus and the design of novel regenerative therapies using corneal limbal stem cells.