Genetic Analysis and Multimodal Retinal Imaging of Asymptomatic Fovea Plana Cases in the General Population (APOGEE)

Albinism is a genetic condition, resulting from mutations in at least 19 known genes responsible for the production of melanin in the skin, hair and eyes.

Ophthalmological manifestations are a constant feature of this disease. Albinism is believed to be responsible for 5% of visual impairments worldwide and all albino patients have some degree of fovea plana. In the milder forms, it is a slightly less marked foveolar depression with conservation of the normal diameter of the cones and, therefore, good visual function.

In addition to its known association with various ocular pathologies such as albinism, aniridia, nanophthalmia and retinopathy of prematurity, fovea plana was found in 3% of a population of normal children (without known ocular or systemic pathology) in a study conducted in 2014 to determine a pediatric normative basis for macular volume measured by optical coherence imaging (Stratus OCT).

More recently, a study carried out at the Hospital Foundation Adolphe de Rothschild showed that at least 35% of parents of albino children, who are totally asymptomatic, present with fovea plana in OCT. This frequency is higher than the 3% prevalence of fovea plana in asymptomatic subjects without a family history of albinism, suggesting a modulation of heterozygosity for a known gene for albinism.

The aim of this study is to verify, in patients with fortuitously discovered fovea plana (preoperative OCT for cataract surgery), with conservation of visual function and without known or manifest albinism, whether they are carriers of mutation in one of the genes referenced for albinism. This will also allow us to characterize these foveolar profiles in OCT according to the classification of Thomas et al., as well as in terms of retinal capillary density in OCT-Angiography, in order to know whether it is the same type of fovea plana or if the phenotype differs depending on the genetic damage.

Study Overview

• Status: Completed
• Conditions: Albinism; Fovea Plana
• Intervention / Treatment: Genetic: Genetic analysis; Procedure: Ophthalmologic exam

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amélie YAVCHITZ, MD; Phone Number: +33 (0)1 48 03 64 33; Email: ayavchitz@for.paris
• Study Contact Backup: Name: Raphaël LEJOYEUX, MD; Email: rlejoyeux@for.paris

Study Locations

• France
  • Paris, France, 75019
    • Hôpital Fondation A. de Rothschuld

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient over 18 years old;
• Diagnosis of fovea plana in one or both eyes, confirmed by two ophthalmologists blinded to each other from OCT-B imaging;

Exclusion Criteria:

• Known Albinism
• Known family history of albinism
• History of eye surgery other than cataract
• Alteration of macular visual function (loss of visual acuity independent of a disorder of the environments, central scotoma, metamorphopsies, etc.)
• Presence of another anomaly in OCT in addition to the fovea plana (epiretinal membrane, damage to the external retina, etc.)
• Syndromic fovea plana
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Genetic analysis

Genetic: Genetic analysis; Patient exome sequencing will be performed by Illumina technology on the NextSeq 550 sequencer. Briefly, the exons of the genes are selected by capture and are amplified by PCR simultaneously, in a single reaction, and then sequenced by Illumina technology. The analysis will only concern genes involved in albinism and in genetic pathologies associated with fovea plana.; Procedure: Ophthalmologic exam; Standard ophthalmologic assessment (measurement of visual acuity, measurement of intraocular pressure, slit lamp examination), OCT-B scan, OCT-Angiography, Adaptive optics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the results of genetic analysis for the various variants of known genes involved in albinism and in genetic pathologies associated with fovea plana	Genetic sampling carried out for the study. Patient exome sequencing. The analysis will only concern genes involved in albinism and in genetic pathologies associated with fovea plana	2 years

Collaborators and Investigators

• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild
• Investigators: Principal Investigator: Raphaël LEJOYEUX, MD, Hôpital Fondation A. de Rothschild

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Actual): November 2, 2023
• Study Completion (Actual): November 2, 2023

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: General population; Carriers
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Eye Diseases, Hereditary; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors; Pigmentation Disorders; Hypopigmentation; Albinism
• Other Study ID Numbers: RLX_2020_27

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No