Portable Eye Device May Aid Schizophrenia Diagnosis

Batya Swift Yasgur, MA, LSW

June 06, 2018

A portable device used by optometrists and ophthalmologists may aid in diagnosing schizophrenia, as well as help predict relapse, evaluate symptom severity, and assess treatment effectiveness, new research suggests.

Investigators used flash electroretinography (fERG), a technique used to examine retinal function, to compare retinal electrical activity in patients with schizophrenia vs a group of healthy persons who acted as a control comparator.

Results showed abnormalities in several aspects of retinal function in the patients with schizophrenia, including differences in cellular activation and cone response time.

"What's novel about our study is the use of the ERG device as a clinical tool," lead author Docia Demmin, a doctoral candidate in the Department of Psychology, Rutgers University, New Brunswick, New Jersey, told Medscape Medical News.

"Although it's not yet ready for routine clinical use, with additional research it could be appropriate for clinicians and psychiatrists to supplement their diagnostic determinations that may be a little more objective than interview-style questions aimed at getting at patients' experiences," Demmin said.

The study was published online in the May issue of the Journal of Abnormal Psychology.

Window to the Brain

fERG has "proven to be useful in identifying functional anomalies in neurological and psychiatric populations," write the investigators.

The technique "records electrical potentials generated by retinal cells in response to light stimuli," they explain. The study authors add that ERG recordings in photopic (light-adapted and rod-saturated) conditions indicate cone functioning, while data from scotopic (dark-adapted) conditions reflect rod functioning.

"We have long been interested in vision and eye functioning in schizophrenia and what the retina could potentially tell us about what's happening in the brain," said Demmin.

She noted that the retina is part of the central nervous system and shares the same neurotransmitters as the brain.

"Since neurotransmitter disruption or dysregulation is thought to be present in psychiatric disorders, including schizophrenia, looking at the retina can provide a window" into the brain, she explained.

A growing body of research into the use of fERG to examine the retina of patients with schizophrenia has demonstrated multiple anomalies in retinal cell functioning, suggesting trait-related as well as state-related changes.

These data point to photoreceptor activity, as reflected in the a-wave response as a state marker for schizophrenia, and bipolar cell activity, shown by b-wave response, as pertaining to trait or diathesis.

Replicate, Extend Past Research

The researchers set out not only to replicate previous studies but also to extend them by recording fERG data under both photopic and scotopic conditions not used before. They also included a flickering stimulus to isolate cone functioning.

In addition, they sought to study retinal ganglion activity via the photopic negative response (PhNR), a "potentially important variable for schizophrenia because abnormal activity in retinal ganglion cells has been assumed to exist in schizophrenia," they write.

Another objective "was to investigate the usefulness of ERG in schizophrenia diagnosis, since ERG was originally used medically by ophthalmologists to test for diabetic retinopathy or other eye conditions," Demmin said.

Its utility in psychiatry is that "it allows direct examination of the retina in ways one cannot otherwise do with a live brain," she added.

The researchers used the RETeval device (LKC Technologies), an instrument approved by the US Food and Drug Administration that does not require corneal contact or pupil dilation, to evaluate the retinas of 25 patients with schizophrenia. All were recruited from inpatient, partial hospitalization, and outpatient settings. Findings were compared with those from 25 healthy individuals who ranged in age from 18 to 60 years.

The investigators used several different conditions of light intensity, color, and flash duration.

Photopic testing was conducted using three conditions: condition P1, which used a 1-Hz repetition rate and no background luminance; P2, which was similar to conditions used in previous studies, although the researchers used a less intense background and a faster stimulus presentation rate to reduce testing time; and PPhNR, which used a red stimulus with a blue background, presented at 3.4 Hz to measure PhNR.

Scotopic tests S1 (2.8 Td·s [.25 Hz]), S2, (28 Td·s [.1 Hz]), and S3 280 Td·s (.05 Hz) utilized white flashes without a background light.

The Positive and Negative Syndrome Scale (PANSS) was used to assess patients' symptom severity, with scores based on a five-factor model comprising positive, negative, cognitive, excitement, and depression factors.

Significant Differences

Under photopic conditions, a-wave amplitude was reduced in the patients with schizophrenia relative to the control group across conditions, with conditions P1 and PPhNR remaining significant after false discovery rate (FDR) adjustment.

Likewise, b-wave amplitudes during photopic conditions showed significant differences between groups, with the schizophrenia group demonstrating reduced amplitudes in conditions P1 and P2.

Under scotopic conditions, the schizophrenia group demonstrated reduced a-wave amplitudes relative to the control group across all conditions, but the difference remained significant only for condition S3.

For b-wave amplitudes under scotopic conditions, post hoc comparisons revealed significantly reduced amplitudes in the schizophrenia group for conditions S2 and S3, with a trend-level difference between groups in all three scotopic conditions.

There were no differences between groups in a-wave implicit time under photopic conditions. However, the schizophrenia group demonstrated longer latencies in b-wave implicit time for condition P2.

Patients in the schizophrenia group demonstrated reduced amplitude on the flicker test, relative to the control participants, and attenuated negativity of the PhNR at 72 ms post stimulus.

The average pupil diameter at baseline was smaller in the schizophrenic group than in the control group. However, the degree of increase in pupil size in response to light stimulation did not differ between the groups.

"Promising" Device

The PANSS five-factor negative symptom dimension revealed "large, significant correlations" with a-wave amplitude during photopic conditions and b-wave amplitude during scotopic conditions, the researchers report. It also correlated with a-wave implicit time during scotopic conditions, although to a lesser extent.

Increased negative symptoms correlated with an attenuated minimum PhNR amplitude and PhNR amplitude when measured at 72 ms post stimulus.

Moreover, the PANSS excitement symptom dimension was significantly correlated with b-wave implicit time during condition S2.

After FDR correction, the two correlations that remained significant were negative symptoms and a-wave amplitude during photopic conditions (PPhNR) and excitement symptoms and b-wave implicit time during scotopic conditions (S2).

No significant correlations were found between medication (chlorpromazine) equivalent dosage photopic or scotopic fERG amplitudes, or implicit times.

The researchers summarize that the fERG device demonstrated "the utility of a flicker stimulus for isolating cone-related activity, and the use of the PhNR for isolating retinal ganglion cell activity," with results that were independent of medication effects.

"Our study confirmed findings of prior studies that showed abnormalities in retinal cell functioning in schizophrenia using EFG and also found new abnormalities," Demmin reported.

The device has "promising features" for use in patients with schizophrenia, such as the speed with which assessments can be conducted with the device, as well as its noninvasiveness — for example, "there is no need to dilate the pupil or touch the retina," she said.

Causal Role?

Commenting on the study for Medscape Medical News, Christopher von Bartheld, MD, professor, Department of Physiology and Cell Biology, and director, Center of Biomedical Research Excellence in Cell Biology, Reno School of Medicine, the University of Nevada, said he finds the "increasing evidence for visual abnormalities in schizophrenia extremely interesting because they point to deficiencies and abnormal visual experience that predate the development of schizophrenia symptoms by many years or even decades."

This suggests that "alterations of vision may have a causal role and are not only a sign of altered brain function once symptoms of schizophrenia become manifest," said Bartheld.

He expressed concern that the study "does not refer to downstream visual abnormalities, for example, of the visual cortex, as shown by Dorph-Petersen et al."

Additionally, "I am also missing reference to the profound effect of vision for schizophrenia," Bartheld said. For example, congenital blindness may confer protection against schizophrenia, as does perfect vision, "which seems to be the gray zone of early abnormal visual experiences that is a specific and very large risk factor."

Demmin noted that future studies should focus on utilizing fERG not only in schizophrenia but also in major depression and bipolar disorder "to fully make this into a solid diagnostic tool."

The study received no external funding. Docia Demmin, two of the remaining three study authors, and Dr von Bartheld have disclosed no relevant financial relationships. The remaining study author is employed by LKC Technologies.

J Abnorm Psychol. 2018;127:417-428. Abstract

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