Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders: Long-Term Follow-up of 21 Cases

Erin A. Boese, Nieraj Jain, Jia Yali, Catie L. Schlechter, Cary Harding, Simon S. Gao, Rachel C. Patel, David Huang, Richard Weleber, Melanie Gillingham, Mark Pennesi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders. Design Retrospective case series. Participants Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD). Methods Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings. Results Participants were followed up for a median of 5.6 years (range 0.3–20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients. Conclusions Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

Original languageEnglish (US)
Pages (from-to)2183-2195
Number of pages13
JournalOphthalmology
Volume123
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Mitochondrial Trifunctional Protein
3-Hydroxyacyl-CoA Dehydrogenase
Optical Coherence Tomography
Multimodal Imaging
Electroretinography
Outcome Assessment (Health Care)
Visual Fields
Visual Acuity
Vertebrate Photoreceptor Cells
Nutritionists
Trifunctional Protein Deficiency With Myopathy And Neuropathy
Myopia

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders : Long-Term Follow-up of 21 Cases. / Boese, Erin A.; Jain, Nieraj; Yali, Jia; Schlechter, Catie L.; Harding, Cary; Gao, Simon S.; Patel, Rachel C.; Huang, David; Weleber, Richard; Gillingham, Melanie; Pennesi, Mark.

In: Ophthalmology, Vol. 123, No. 10, 01.10.2016, p. 2183-2195.

Research output: Contribution to journalArticle

@article{7488c941f051438b974ad719dc67f7f2,
title = "Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders: Long-Term Follow-up of 21 Cases",
abstract = "Purpose To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders. Design Retrospective case series. Participants Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD). Methods Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings. Results Participants were followed up for a median of 5.6 years (range 0.3–20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients. Conclusions Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.",
author = "Boese, {Erin A.} and Nieraj Jain and Jia Yali and Schlechter, {Catie L.} and Cary Harding and Gao, {Simon S.} and Patel, {Rachel C.} and David Huang and Richard Weleber and Melanie Gillingham and Mark Pennesi",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.ophtha.2016.06.048",
language = "English (US)",
volume = "123",
pages = "2183--2195",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders

T2 - Long-Term Follow-up of 21 Cases

AU - Boese, Erin A.

AU - Jain, Nieraj

AU - Yali, Jia

AU - Schlechter, Catie L.

AU - Harding, Cary

AU - Gao, Simon S.

AU - Patel, Rachel C.

AU - Huang, David

AU - Weleber, Richard

AU - Gillingham, Melanie

AU - Pennesi, Mark

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Purpose To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders. Design Retrospective case series. Participants Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD). Methods Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings. Results Participants were followed up for a median of 5.6 years (range 0.3–20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients. Conclusions Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

AB - Purpose To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders. Design Retrospective case series. Participants Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD). Methods Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings. Results Participants were followed up for a median of 5.6 years (range 0.3–20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients. Conclusions Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

UR - http://www.scopus.com/inward/record.url?scp=84991104782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991104782&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2016.06.048

DO - 10.1016/j.ophtha.2016.06.048

M3 - Article

C2 - 27491397

AN - SCOPUS:84991104782

VL - 123

SP - 2183

EP - 2195

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 10

ER -