Table 1.

Molecular Genetic Profile of our DOA Cohort

Table 2.

Distribution of RNFL Indices for Our OPA1 Cohort

Table 3.

RNFL Thickness Data for OPA1 Patients and Normal Controls

Table 4.

Comparison of RNFL Thickness Between Pure DOA and DOA + Subgroups

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CME

Pattern of Retinal Ganglion Cell Loss in Dominant Optic Atrophy Due to OPA1 Mutations

Authors: Patrick Yu-Wai-Man, MRCOphth; Maura Bailie; Alaa Atawan; Patrick F. Chinnery, PhD, FRCPath; Philip G. Griffiths, FRCOphth
CME Released: 3/4/2011
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 3/4/2012

Start Activity

Target Audience and Goal Statement

This activity is intended for primary care clinicians, ophthalmologists, and other specialists who care for patients with DOA.

The goal of this activity is to review features of DOA and RGC loss in patients with the pure and syndromal forms of DOA.

Upon completion of this activity, participants will be able to:

Describe the clinical features of DOA
Identify extraocular features associated with DOA
Identify the peripapillary retinal nerve fibre layer (RNFL) quadrants most affected in patients with OPA1 mutations
Differentiate the pattern of RNFL thinning between patients with pure DOA and DOA+ phenotypes

Disclosures

As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author(s)

Patrick Yu-Wai-Man, MRCOphth

Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, United Kingdom; Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; Institute of Human Genetics, Newcastle University, United Kingdom

Disclosures

Disclosure: Patrick Yu-Wai-Man, MRCOphth, has disclosed no relevant financial relationships.

Maura Bailie

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

Disclosures

Disclosure: Maura Bailie has disclosed no relevant financial relationships.

Alaa Atawan

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

Disclosures

Disclosure: Alaa Atawan has disclosed no relevant financial relationships.

Patrick F. Chinnery, PhD, FRCPath

Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, United Kingdom; Institute of Human Genetics, Newcastle University, United Kingdom

Disclosures

Disclosure: Patrick F. Chinnery, PhD, FRCPath, has disclosed no relevant financial relationships.

Philip G. Griffiths, FRCOphth

Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, United Kingdom; Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

Disclosures

Disclosure: Philip G. Griffiths, FRCOphth, has disclosed no relevant financial relationships.

Editor(s)

A.J. Lotery, MD, FRCOphth

Editor-in-Chief, Eye

Disclosures

Disclosure: A.J. Lotery, MD, FRCOphth, has disclosed the following relevant financial relationships:
Received grants for clinical research from: Novartis Pharmaceuticals Corporation
Served as an advisor or consultant for: Alcon Laboratories, Inc.
Served as a speaker or member of a speakers bureau for: Bausch & Lomb Inc.

CME Author(s)

Désirée Lie, MD, MSEd

Clinical Professor; Director of Research and Faculty Development, Department of Family Medicine, University of California, Irvine at Orange

Disclosures

Disclosure: Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship:
Served as a nonproduct speaker for: "Topics in Health" for Merck Speaker Services

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosures

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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For Physicians

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Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Results

Peripapillary RNFL Profile Among Patients with OPA1 Mutations

The majority of eyes from patients with OPA1 mutations had an average RNFL thickness < 1% of the normal range (73/80, 91.3%), and this was also observed independently for the temporal (70/80, 87.5%), inferior (69/80, 86.3%), and superior (53/80, 66.3%) quadrants.

For the nasal quadrant, only 13/80 (16.2%) eyes had an RNFL thickness < 1%, compared with 44/80 (55.0%) eyes in the 5-95% range ( Table 2 ). There was a significant difference in the distribution of RNFL thickness between quadrants (Supplementary Table 1), except for the comparison between the temporal and inferior quadrants (P = 0.5868). To confirm these findings, peripapillary RNFL thickness in the OPA1 group (mean age = 42.7 years, standard deviation (SD) = 14.9 years, range = 7.0-69.0 years) was compared with the measurements obtained from an independent cohort of 15 age-matched normal controls (mean age = 40.3 years, SD = 12.3 years, range = 22.0-66.0 years, P = 0.5745). OPA1 patients had a statistically significant reduction in mean RNFL thickness for all measurement parameters (Supplementary Figure 2, Table 3 ), and the percentage decrease was greater in the temporal quadrant (59.0%), followed by the inferior (49.6%), superior (41.8%), and nasal (25.9%) quadrants.

Comparison of RNFL Thickness Between Pure DOA and DOA + Subgroups

There was no statistically significant difference in age between the pure DOA (mean = 40.1 years, SD = 15.7 years, range = 7.0-69.0 years, N= 26) and DOA + subgroups (mean = 47.6 years, SD =12.1 years, range = 21.0 = 64.0 years, N = 14, P = 0.1295) (Supplementary Figure 3A). Patients with DOA + features had significantly worse LogMAR visual acuities (mean = 1.26, SD = 0.85) compared with patients with pure DOA (mean = 0.76, SD = 0.54, P = 0.0018) (Supplementary Figure 3B). Except for the temporal quadrant, RNFL measurements were significantly thinner in the DOA + group (Figure 1, Table 4 ). There was a statistically significant inverse correlation between average RNFL thickness and LogMAR visual acuity (Figure 2), and this relationship was also significant for the inferior, superior, and nasal quadrants on subgroup analysis (Supplementary Table 2).

Figure 1.

Enlarge

Comparison of Average RNFL Thickness Between Patients with Pure DOA and DOA + Phenotypes.
***P-value = 0.0006.

Figure 2.

Enlarge

Correlation of Average RNFL Thickness with LogMAR Visual Acuity. Spearman's rank correlation coefficient = -0.6355, P< 0.0001.

« Back

Page 3 of 5

Discussion

CME Information

References

Table 1.

Table 2.

Table 3.

Table 4.

CME

Pattern of Retinal Ganglion Cell Loss in Dominant Optic Atrophy Due to OPA1 Mutations

Target Audience and Goal Statement

Disclosures

Author(s)

Patrick Yu-Wai-Man, MRCOphth

Maura Bailie

Alaa Atawan

Patrick F. Chinnery, PhD, FRCPath

Philip G. Griffiths, FRCOphth

Editor(s)

A.J. Lotery, MD, FRCOphth

CME Author(s)

Désirée Lie, MD, MSEd

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Pattern of Retinal Ganglion Cell Loss in Dominant Optic Atrophy Due to OPA1 Mutations: Results

Results

Peripapillary RNFL Profile Among Patients with OPA1 Mutations

Comparison of RNFL Thickness Between Pure DOA and DOA + Subgroups

Figure 1.

Figure 2.

Table of Contents

Table 1.

Table 2.

Table 3.

Table 4.

References

Faculty and Disclosures

Author(s)

Patrick Yu-Wai-Man, MRCOphth

Maura Bailie

Alaa Atawan

Patrick F. Chinnery, PhD, FRCPath

Philip G. Griffiths, FRCOphth

Editor(s)

A.J. Lotery, MD, FRCOphth

CME Author(s)

Désirée Lie, MD, MSEd

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

CME

Pattern of Retinal Ganglion Cell Loss in Dominant Optic Atrophy Due to OPA1 Mutations

Target Audience and Goal Statement

Disclosures

Author(s)

Patrick Yu-Wai-Man, MRCOphth

Maura Bailie

Alaa Atawan

Patrick F. Chinnery, PhD, FRCPath

Philip G. Griffiths, FRCOphth

Editor(s)

A.J. Lotery, MD, FRCOphth

CME Author(s)

Désirée Lie, MD, MSEd

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Pattern of Retinal Ganglion Cell Loss in Dominant Optic Atrophy Due to OPA1 Mutations: Results

Results

Peripapillary RNFL Profile Among Patients with OPA1 Mutations

Comparison of RNFL Thickness Between Pure DOA and DOA + Subgroups

Figure 1.

Figure 2.

Table of Contents