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Published on: July 19, 2019
Inner Plexiform Layer Microstructure Is Altered in Multiple Sclerosis
Maria Emfietzoglou1, Victor S M C Correa1, Gustavo Sakuno1
1Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States.
Investigative Ophthalmology & Visual Science
|June 2, 2026
Summary
Microstructural changes in the inner plexiform layer (IPL) are present in multiple sclerosis (MS) and can be detected using optical coherence tomography (OCT). These IPL alterations offer improved discrimination of MS compared to current retinal thickness metrics.
Area of Science:
- Ophthalmology
- Neuroscience
- Medical Imaging
Background:
- Optical coherence tomography (OCT) is crucial for assessing retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning in multiple sclerosis (MS).
- Standard OCT thickness metrics may not fully capture microstructural changes within the inner plexiform layer (IPL), a critical synaptic region.
- Investigating IPL microstructure offers potential for novel diagnostic markers in MS.
Purpose of the Study:
- To determine if inner plexiform layer (IPL) microstructure differs in individuals with multiple sclerosis (MS).
- To ascertain if observed IPL abnormalities in MS are independent of optic neuritis and general inner retinal thinning.
- To evaluate if IPL microstructure metrics enhance the diagnostic discrimination of MS beyond traditional RNFL and GCC thickness measurements.
Main Methods:
- A cross-sectional case-control study involving 49 MS patients (92 eyes) and 59 controls (109 eyes).
- Quantification of inner plexiform layer (IPL) reflectivity and sublayer patterns using optical coherence tomography (OCT).
- Statistical analysis employed mixed-effects models with adjustments for RNFL/GCC thickness and receiver operating characteristic (ROC) curve analysis for diagnostic discrimination.
Main Results:
- The percentage of IPL segments showing a distinct five-sublayer pattern was significantly lower in MS patients (-20 percentage points).
- MS eyes exhibited increased outer hyporeflective sublayer intensity and reduced contrast between the middle hyperreflective and outer hyporeflective sublayers.
- These IPL microstructural differences were evident even in MS eyes without optic neuritis and remained significant after adjusting for RNFL and GCC thickness. The IPL sublayer pattern effectively discriminated MS from controls (AUC=0.81).
Conclusions:
- Inner plexiform layer (IPL) microstructure is altered in multiple sclerosis (MS), independent of optic neuritis and inner retinal thinning.
- Quantitative OCT assessment of IPL microstructure provides valuable complementary structural information for MS.
- IPL microstructure analysis may serve as a sensitive biomarker for detecting MS-related retinal changes.
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