Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion
Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Ophthalmology Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666914522001038 |
| _version_ | 1811154311829258240 |
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| author | Matthew Gillings, MD Andrew Mastro, MD Xunzhi Zhang Kelly Kiser, MD Jane Gu Chao Xing, PhD Danielle M. Robertson, OD, PhD W. Matthew Petroll, PhD V. Vinod Mootha, MD |
| author_facet | Matthew Gillings, MD Andrew Mastro, MD Xunzhi Zhang Kelly Kiser, MD Jane Gu Chao Xing, PhD Danielle M. Robertson, OD, PhD W. Matthew Petroll, PhD V. Vinod Mootha, MD |
| author_sort | Matthew Gillings, MD |
| collection | DOAJ |
| description | Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE−) and to assess the correlation of these parameters with disease severity. Design: Cross-sectional, single-center study. Participants: Fifty-two eyes of 29 subjects with a modified Krachmer grade of FECD severity from 1 to 6 were included in the study. Fifteen of the 29 subjects carried an expanded TCF4 allele length of ≥ 40 cytosine-thymine-guanine repeats (RE+). Main Outcomes Measures: In vivo confocal microscopy assessments of corneal nerve fiber length (CNFL), corneal nerve branch density, corneal nerve fiber density (CNFD), and anterior corneal stromal backscatter (haze); Scheimpflug tomography densitometry measurements of haze in anterior, central, and posterior corneal layers. Results: Using confocal microscopy, we detected a negative correlation between FECD severity and both CNFL and CNFD in the eyes of RE+ subjects (Spearman ρ = −0.45, P = 0.029 and ρ = −0.62, P = 0.0015, respectively) but not in the eyes of RE− subjects. Additionally, CNFD negatively correlated with the repeat length of the expanded allele in the RE+ subjects (Spearman ρ = −0.42, P = 0.038). We found a positive correlation between anterior stromal backscatter and severity in both the RE+ and RE− groups (ρ = 0.60, P = 0.0023 and ρ = 0.44, P = 0.024, respectively). The anterior, central, and posterior Scheimpflug densitometry measurements also positively correlated with severity in both the RE+ and RE− groups (P = 5.5 × 10−5, 2.5 × 10−4, and 2.9 × 10−4, respectively, after adjusting for the expansion status in a pooled analysis. However, for patients with severe FECD (Krachmer grades 5 and 6), the posterior densitometry measurements were higher in the RE+ group than in the RE− group (P < 0.05). Conclusions: Loss of corneal nerves in FECD supports the classification of the TCF4 trinucleotide repeat expansion disorder as a neurodegenerative disease. Haze in the anterior, central, and posterior cornea correlate with severity, irrespective of the genotype. Quantitative assessments of corneal nerves and corneal haze may be useful to gauge and monitor FECD disease severity in RE+ patients. |
| first_indexed | 2024-04-10T04:14:44Z |
| format | Article |
| id | doaj.art-39d71abdce6640558ab4c049e6052c14 |
| institution | Directory Open Access Journal |
| issn | 2666-9145 |
| language | English |
| last_indexed | 2024-04-10T04:14:44Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj.art-39d71abdce6640558ab4c049e6052c142023-03-12T04:22:25ZengElsevierOphthalmology Science2666-91452023-03-0131100214Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat ExpansionMatthew Gillings, MD0Andrew Mastro, MD1Xunzhi Zhang2Kelly Kiser, MD3Jane Gu4Chao Xing, PhD5Danielle M. Robertson, OD, PhD6W. Matthew Petroll, PhD7V. Vinod Mootha, MD8Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TexasDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TexasEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TexasDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TexasDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TexasEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TexasDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TexasDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas; Correspondence: W. Matthew Petroll, PhD, 5323 Harry Hines Blvd, Dallas, TX 75390–9057.Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas; V. Vinod Mootha, MD, 5323 Harry Hines Blvd, Dallas, TX 75390–9057.Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE−) and to assess the correlation of these parameters with disease severity. Design: Cross-sectional, single-center study. Participants: Fifty-two eyes of 29 subjects with a modified Krachmer grade of FECD severity from 1 to 6 were included in the study. Fifteen of the 29 subjects carried an expanded TCF4 allele length of ≥ 40 cytosine-thymine-guanine repeats (RE+). Main Outcomes Measures: In vivo confocal microscopy assessments of corneal nerve fiber length (CNFL), corneal nerve branch density, corneal nerve fiber density (CNFD), and anterior corneal stromal backscatter (haze); Scheimpflug tomography densitometry measurements of haze in anterior, central, and posterior corneal layers. Results: Using confocal microscopy, we detected a negative correlation between FECD severity and both CNFL and CNFD in the eyes of RE+ subjects (Spearman ρ = −0.45, P = 0.029 and ρ = −0.62, P = 0.0015, respectively) but not in the eyes of RE− subjects. Additionally, CNFD negatively correlated with the repeat length of the expanded allele in the RE+ subjects (Spearman ρ = −0.42, P = 0.038). We found a positive correlation between anterior stromal backscatter and severity in both the RE+ and RE− groups (ρ = 0.60, P = 0.0023 and ρ = 0.44, P = 0.024, respectively). The anterior, central, and posterior Scheimpflug densitometry measurements also positively correlated with severity in both the RE+ and RE− groups (P = 5.5 × 10−5, 2.5 × 10−4, and 2.9 × 10−4, respectively, after adjusting for the expansion status in a pooled analysis. However, for patients with severe FECD (Krachmer grades 5 and 6), the posterior densitometry measurements were higher in the RE+ group than in the RE− group (P < 0.05). Conclusions: Loss of corneal nerves in FECD supports the classification of the TCF4 trinucleotide repeat expansion disorder as a neurodegenerative disease. Haze in the anterior, central, and posterior cornea correlate with severity, irrespective of the genotype. Quantitative assessments of corneal nerves and corneal haze may be useful to gauge and monitor FECD disease severity in RE+ patients.http://www.sciencedirect.com/science/article/pii/S2666914522001038ConfocalCorneaFuchs’ endothelial corneal dystrophyImagingScheimpflug |
| spellingShingle | Matthew Gillings, MD Andrew Mastro, MD Xunzhi Zhang Kelly Kiser, MD Jane Gu Chao Xing, PhD Danielle M. Robertson, OD, PhD W. Matthew Petroll, PhD V. Vinod Mootha, MD Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion Ophthalmology Science Confocal Cornea Fuchs’ endothelial corneal dystrophy Imaging Scheimpflug |
| title | Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion |
| title_full | Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion |
| title_fullStr | Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion |
| title_full_unstemmed | Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion |
| title_short | Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs’ Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion |
| title_sort | loss of corneal nerves and corneal haze in patients with fuchs endothelial corneal dystrophy with the transcription factor 4 gene trinucleotide repeat expansion |
| topic | Confocal Cornea Fuchs’ endothelial corneal dystrophy Imaging Scheimpflug |
| url | http://www.sciencedirect.com/science/article/pii/S2666914522001038 |
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