Spatial differences in corneal electroretinogram potentials measured in rat with a contact lens electrode array

PURPOSE: It has been known for several decades that the magnitude of the corneal electroretinogram (ERG) varies with position on the eye surface, especially in the presence of focal or asymmetric stimuli or retinal lesions. However, this phenomenon has not been well-characterized using simultaneous measurements at multiple locations on the cornea. This work provides the first characterization of spatial differences in the ERG across the rat cornea. METHODS: A contact lens electrode array was employed to record ERG potentials at 25 corneal locations simultaneously following brief full-field flash stimuli in normally sighted Long-Evans rats. These multi-electrode electroretinogram (meERG) responses were analyzed for spatial differences in a-wave and b-wave amplitudes and implicit times. RESULTS: Spatially distinct ERG potentials could be recorded reliably. Comparing relative amplitudes across the corneal locations suggested a slight non-uniform distribution when using full-field, near-saturating stimuli. Amplitudes of a- and b-waves were approximately 3 % lower in the inferior quadrant than in the superior quadrant of the cornea. CONCLUSIONS: The present results comprise the start of the first normative meERG database for rat eyes and provide a basis for comparison of results from eyes with functional deficit. Robust measures of spatial differences in corneal potentials will also support optimization and validation of computational source models of the ERG. To fully utilize the information contained in the meERG data, a detailed understanding of the roles of the many determinants of local corneal potentials will eventually be required

Molecular Diagnostic Testing by eyeGENE: Analysis of Patients With Hereditary Retinal Dystrophy Phenotypes Involving Central Vision LossMolecular Diagnostic Testing by eyeGENE

PurposeTo analyze the genetic test results of probands referred to eyeGENE with a diagnosis of hereditary maculopathy.MethodsPatients with Best macular dystrophy (BMD), Doyne honeycomb retinal dystrophy (DHRD), Sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5, and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4, and the c.2513G>A p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool PolyPhen.ResultsAmong the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, and 54 CRD; six had both PD and BMD, and one had no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients with VUS, one was diagnosed with both BMD and PD. A novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients, PRPH2 variants in 14 PD patients, ABCA4 variants in four PD patients, and p.Arg838His GUCY2D mutation in six patients diagnosed with dominant CRD; one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD.ConclusionsOf the 213 samples, 55 patients (26%) had known causative mutations, and 13 (6%) patients had a VUS that was possibly pathogenic. Overall, selective screening for mutations in BEST1, PRPH2, and ABCA4 would likely yield the highest success rate in identifying the genetic basis for macular dystrophy phenotypes. Because of the overlap in phenotypes between BMD and PD, it would be beneficial to screen genes associated with both diseases

Molecular Diagnostic Testing by eyeGENE: Analysis of Patients With Hereditary Retinal Dystrophy Phenotypes Involving Central Vision Loss

PURPOSE. To analyze the genetic test results of probands referred to eyeGENE with a diagnosis of hereditary maculopathy. METHODS. Patients with Best macular dystrophy (BMD), Doyne honeycomb retinal dystrophy (DHRD), Sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5, and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4, and the c.2513G>A p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool PolyPhen. RESULTS. Among the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, and 54 CRD; six had both PD and BMD, and one had no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients with VUS, one was diagnosed with both BMD and PD. A novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients, PRPH2 variants in 14 PD patients, ABCA4 variants in four PD patients, and p.Arg838His GUCY2D mutation in six patients diagnosed with dominant CRD; one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD. CONCLUSIONS. Of the 213 samples, 55 patients (26%) had known causative mutations, and 13 (6%) patients had a VUS that was possibly pathogenic. Overall, selective screening for mutations in BEST1, PRPH2, and ABCA4 would likely yield the highest success rate in identifying the genetic basis for macular dystrophy phenotypes. Because of the overlap in phenotypes between BMD and PD, it would be beneficial to screen genes associated with both diseases