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Optical coherence tomography indices of structural retinal pathology in schizophrenia

Published online by Cambridge University Press:  13 December 2017

Steven M. Silverstein ,
Danielle Paterno ,
Lindsay Cherneski  and
Stuart Green
Steven M. Silverstein*
Affiliation:
Rutgers – University Behavioral Health Care, Piscataway, NJ, USA Department of Psychiatry, Rutgers – Robert Wood Johnson Medical School, Piscataway, NJ, USA
Danielle Paterno
Affiliation:
Rutgers – University Behavioral Health Care, Piscataway, NJ, USA
Lindsay Cherneski
Affiliation:
Rutgers – University Behavioral Health Care, Piscataway, NJ, USA
Stuart Green
Affiliation:
Department of Ophthalmology, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA NJ Retina, New Brunswick, NJ, USA
*
Author for correspondence: Steven M. Silverstein, Ph.D., E-mail: [email protected]
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Abstract

Background

Prior optical coherence tomography (OCT) studies of schizophrenia have identified thinning of retinal layers. However, findings have varied across reports, and most studies have had serious methodological limitations. To address unresolved issues, we determined whether: (1) retinal thinning in schizophrenia occurs independently of comorbid medical conditions that affect the retina; (2) thinning is independent of antipsychotic medication dose; (3) optic nerve parameters are abnormal in schizophrenia; and (4) OCT indices are related to visual and cognitive impairments common in schizophrenia.

Methods

A total of 32 people with schizophrenia and 32 matched controls participated. Spectral domain OCT generated data on retinal nerve fiber layer (RNFL), macula, and ganglion cell-inner plexiform layer (GCL-IPL) thickness, in addition to cup volume and the cup-to-disc ratio at the optic nerve head. Subjects with schizophrenia also completed measures of symptoms, visual processing, and IQ.

Results

The groups did not differ on RNFL, macula, or GCL-IPL thickness. However, thinning of these layers was related to the presence of diabetes or hypertension across the sample as a whole. The schizophrenia group demonstrated enlarged cup volume and an enlarged cup-to-disc ratio in both eyes, which were unrelated to medical comorbidity, but were related to increased cognitive symptoms.

Conclusions

Past reports of retinal thinning may be artifacts of medical comorbidity that is over-represented in schizophrenia, or other confounds. However, optic nerve head abnormalities may hold promise as biomarkers of central nervous system abnormality, including cognitive decline, in schizophrenia.

Keywords

Schizophreniaretinaoptic nervevisionoptical coherence tomography (OCT)perceptiondiabeteshypertension
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 12 , September 2018 , pp. 2023 - 2033
Copyright
Copyright © Cambridge University Press 2017 

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References

Ascaso, FJ, Cabezon, L, Quintanilla, MA, Gutierrez-Galve, L, Lopez-Anton, R, Cristobal, JA et al. (2010) Retinal nerve fiber layer thickness measured by optical coherence tomography in patients with schizophrenia: a short report. European Journal of Psychiatry 4, 227–335.Google Scholar
Ascaso, FJ, Rodriguez-Jimenez, R, Cabezon, L, Lopez-Anton, R, Santabarbara, J, De La Camara, C et al. (2015) Retinal nerve fiber layer and macular thickness in patients with schizophrenia: influence of recent illness episodes. Psychiatry Research 229, 230–236.Google Scholar
Budenz, DL (2008). Symmetry between the right and left eyes of the normal retinal nerve fiber layer measured with optical coherence tomography (an AOS thesis). Transactions of the American Ophthalmological Society 106, 252–275.Google Scholar
Butler, PD, Silverstein, SM and Dakin, SC (2008) Visual perception and its impairment in schizophrenia. Biological Psychiatry 64, 40–47.Google Scholar
Cabezon, L, Ascaso, F, Ramiro, P, Quintanilla, M, Gutierrez, L, Lobo, A et al. (2012) Optical coherence tomography: a window into the brain of schizophrenic patients. Acta Ophthalmologica 90.Google Scholar
Celik, M, Kalenderoglu, A, Sevgi Karadag, A, Bekir Egilmez, O, Han-Almis, B and Simsek, A (2016) Decreases in ganglion cell layer and inner plexiform layer volumes correlate better with disease severity in schizophrenia patients than retinal nerve fiber layer thickness: findings from spectral optic coherence tomography. European Psychiatry 32, 9–15.Google Scholar
Chen, MF, Chui, TY, Alhadeff, P, Rosen, RB, Ritch, R, Dubra, A et al. (2015) Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma. Investigative Ophthalmology and Visual Science 56, 674–681.Google Scholar
Chu, EM, Kolappan, M, Barnes, TR, Joyce, EM and Ron, MA (2012) A window into the brain: an in vivo study of the retina in schizophrenia using optical coherence tomography. Psychiatry Research 203, 89–94.Google Scholar
Curtis, CE, Iacono, WG and Beiser, M (1999) Relationship between nailfold plexus visibility and clinical, neuropsychological, and brain structural measures in schizophrenia. Biological Psychiatry 46, 102–109.Google Scholar
Deveau, J, Lovcik, G and Seitz, AR (2014) Broad-based visual benefits from training with an integrated perceptual-learning video game. Vision Research 99, 134–140.Google Scholar
Dinkin, M (2017) Trans-synaptic retrograde degeneration in the human visual system: slow, silent, and real. Current Neurology and Neuroscience Reports 17, 16.Google Scholar
Dorph-Petersen, KA, Caric, D, Saghafi, R, Zhang, W, Sampson, AR and Lewis, DA (2009) Volume and neuron number of the lateral geniculate nucleus in schizophrenia and mood disorders. Acta Neuropathologica 117, 369–384.Google Scholar
Dorph-Petersen, KA, Pierri, JN, Wu, Q, Sampson, AR and Lewis, DA (2007) Primary visual cortex volume and total neuron number are reduced in schizophrenia. Journal of Comparative Neurology 501, 290–301.Google Scholar
Duman, R, Duman, R, Sabaner, MC and Cetinkaya, E (2017) Effect of smoking on the thickness of retinal layers in healthy smokers. Cutaneous and Ocular Toxicology 36, 366–369.Google Scholar
Farmer, AE, Mcguffin, P and Spitznagel, EL (1983) Heterogeneity in schizophrenia: a cluster-analytic approach. Psychiatry Research 8, 1–12.Google Scholar
Ferrari, L, Huang, SC, Magnani, G, Ambrosi, A, Comi, G and Leocani, L (2017) Optical coherence tomography reveals retinal neuroaxonal thinning in frontotemporal dementia as in Alzheimer's disease. Journal of Alzheimer's Disease 56, 1101–1107.Google Scholar
First, M, Spitzer, R, Gibbon, M and Williams, JBW (2002) Structured Clinical Iinterview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P), New York, NY: New York State Psychiatric Institute.Google Scholar
Fusar-Poli, P, Smieskova, R, Kempton, MJ, Ho, BC, Andreasen, NC and Borgwardt, S (2013) Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neuroscience & Biobehavioral Reviews 37, 1680–1691.Google Scholar
Gardner, DM, Murphy, AL, O'Donnell, H, Centorrino, F and Baldessarini, RJ (2010) International consensus study of antipsychotic dosing. American Journal of Psychiatry 167, 686–693.Google Scholar
Geyman, LS, Garg, RA, Suwan, Y, Trivedi, V, Krawitz, BD, Mo, S et al. (2017) Peripapillary perfused capillary density in primary open-angle glaucoma across disease stage: an optical coherence tomography angiography study. British Journal of Ophthalmology 101, 1261–1268.Google Scholar
Ghazi, NG, Dibernardo, C, Ying, H, Mori, K and Gehlbach, PL (2006) Optical coherence tomography of peripheral retinal lesions in enucleated human eye specimens with histologic correlation. American Journal of Ophthalmology 141, 740–742.Google Scholar
Ghilardi, MF, Chung, E, Bodis-Wollner, I, Dvorzniak, M, Glover, A and Onofrj, M (1988) Systemic 1-methyl,4-phenyl,1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates. Life Sciences 43, 255–262.Google Scholar
Gordon-Lipkin, E, Chodkowski, B, Reich, DS, Smith, SA, Pulicken, M, Balcer, LJ et al. (2007) Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 69, 1603–1609.Google Scholar
Guimaraes, J and Sa, MJ (2012) Cognitive dysfunction in multiple sclerosis. Frontiers in Neurology 3, 74.Google Scholar
Harwerth, RS and Wheat, JL (2008) Modeling the effects of aging on retinal ganglion cell density and nerve fiber layer thickness. Graefes Archive for Clinical and Experimental Ophthalmology 246, 305–314.Google Scholar
Harwerth, RS, Wheat, JL and Rangaswamy, NV (2008) Age-related losses of retinal ganglion cells and axons. Investigative Ophthalmology and Visual Science 49, 4437–4443.Google Scholar
Ho, BC, Andreasen, NC, Ziebell, S, Pierson, R and Magnotta, V (2011) Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry 68, 128–137.Google Scholar
Inzelberg, R, Ramirez, JA, Nisipeanu, P and Ophir, A (2004) Retinal nerve fiber layer thinning in Parkinson disease. Vision Research 44, 2793–2797.Google Scholar
Iseri, PK, Altinas, O, Tokay, T and Yuksel, N (2006) Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. Journal of Neuro-Ophthalmology 26, 18–24.Google Scholar
Jaeger, J, Berns, SM and Czobor, P (2003) The multidimensional scale of independent functioning: a new instrument for measuring functional disability in psychiatric populations. Schizophrenia Bulletin 29, 153–168.Google Scholar
Jahshan, C, Wolf, M, Karbi, Y, Shamir, E and Rassovsky, Y (2017) Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia. Psychiatry Research 253, 38–42.Google Scholar
Jindal, V (2015) Interconnection between brain and retinal neurodegenerations. Molecular Neurobiology 51, 885–892.Google Scholar
Kay, SR, Fiszbein, A and Opler, LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Knight, OJ, Chang, RT, Feuer, WJ and Budenz, DL (2009) Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology 116, 1271–1277.Google Scholar
Lalor, EC, De Sanctis, P, Krakowski, MI and Foxe, JJ (2012) Visual sensory processing deficits in schizophrenia: is there anything to the magnocellular account? Schizophrenia Research 139, 246–252.Google Scholar
Lee, JY, Ahn, J, Kim, TW and Jeon, BS (2014) Optical coherence tomography in Parkinson's disease: is the retina a biomarker? Journal of Parkinson's Disease 4, 197–204.Google Scholar
Lee, WW, Tajunisah, I, Sharmilla, K, Peyman, M and Subrayan, V (2013) Retinal nerve fiber layer structure abnormalities in schizophrenia and its relationship to disease state: evidence from optical coherence tomography. Investigative Ophthalmology and Visual Science 54, 7785–7792.Google Scholar
Liao, CH, Chang, CS, Wei, WC, Chang, SN, Liao, CC, Lane, HY et al. (2011) Schizophrenia patients at higher risk of diabetes, hypertension and hyperlipidemia: a population-based study. Schizophrenia Research 126, 110–116.Google Scholar
Lindenmayer, JP, Bernstein-Hyman, R and Grochowski, S (1994 a). Five-factor model of schizophrenia. Initial validation. Journal of Nervous and Mental Disease 182, 631–638.Google Scholar
Lindenmayer, JP, Bernstein-Hyman, R and Grochowski, S (1994 b). A new five factor model of schizophrenia. Psychiatric Quarterly 65, 299–322.Google Scholar
Liu, D, Zhang, L, Li, Z, Zhang, X, Wu, Y, Yang, H et al. (2015) Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease. BMC Neurology 15, 14.Google Scholar
London, A, Benhar, I and Schwartz, M (2013) The retina as a window to the brain-from eye research to CNS disorders. Nature Reviews: Neurology 9, 44–53.Google Scholar
Meier, MH, Shalev, I, Moffitt, TE, Kapur, S, Keefe, RS, Wong, TY et al. (2013) Microvascular abnormality in schizophrenia as shown by retinal imaging. American Journal of Psychiatry 170, 1451–1459.Google Scholar
Mitelman, SA and Buchsbaum, MS (2007) Very poor outcome schizophrenia: clinical and neuroimaging aspects. International Review of Psychiatry 19, 345–357.Google Scholar
Mo, S, Phillips, E, Krawitz, BD, Garg, R, Salim, S, Geyman, LS et al. (2017) Visualization of radial peripapillary capillaries using optical coherence tomography angiography: the effect of image averaging. PLoS ONE 12, e0169385.Google Scholar
Moises, HW, Wollschlager, D and Binder, H (2015) Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder. Translational Psychiatry 5, e616.Google Scholar
Najjar, S, Pahlajani, S, De Sanctis, V, Stern, JNH, Najjar, A and Chong, D (2017) Neurovascular unit dysfunction and blood-brain barrier hyperpermeability contribute to schizophrenia neurobiology: a theoretical integration of clinical and experimental evidence. Frontiers in Psychiatry 8, 83.Google Scholar
Nasrallah, HA, Meyer, JM, Goff, DC, Mcevoy, JP, Davis, SM, Stroup, TS et al. (2006) Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: data from the CATIE schizophrenia trial sample at baseline. Schizophrenia Research 86, 15–22.Google Scholar
Ong, YT, Hilal, S, Cheung, CY, Venketasubramanian, N, Niessen, WJ, Vrooman, H et al. (2015) Retinal neurodegeneration on optical coherence tomography and cerebral atrophy. Neuroscience Letters 584, 12–16.Google Scholar
Onitsuka, T, Mccarley, RW, Kuroki, N, Dickey, CC, Kubicki, M, Demeo, SS et al. (2007) Occipital lobe gray matter volume in male patients with chronic schizophrenia: a quantitative MRI study. Schizophrenia Research 92, 197–206.Google Scholar
Patel, PJ, Foster, PJ, Grossi, CM, Keane, PA, Ko, F, Lotery, A et al. (2016) Spectral-Domain optical coherence tomography imaging in 67 321 adults: associations with macular thickness in the UK biobank study. Ophthalmology 123, 829–840.Google Scholar
Petracca, M, Cordano, C, Cellerino, M, Button, J, Krieger, S, Vancea, R et al. (2017) Retinal degeneration in primary-progressive multiple sclerosis: a role for cortical lesions? Multiple Sclerosis 23, 43–50.Google Scholar
Petzold, A (2015) Meta-analysis of optical coherence tomography in multiple sclerosis. In Calabrese, PA, Balcer, LJ and Frohman, EM (eds). Optical Coherence Tomography in Neurologic Diseases. Cambridge, UK: Cambridge University Press.Google Scholar
Pulicken, M, Gordon-Lipkin, E, Balcer, LJ, Frohman, E, Cutter, G and Calabresi, PA (2007) Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 69, 2085–2092.Google Scholar
Saidha, S, Syc, SB, Ibrahim, MA, Eckstein, C, Warner, CV, Farrell, SK et al. (2011) Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain 134, 518–533.Google Scholar
Satue, M, Seral, M, Otin, S, Alarcia, R, Herrero, R, Bambo, MP et al. (2014) Retinal thinning and correlation with functional disability in patients with Parkinson's disease. British Journal of Ophthalmology 98, 350–355.Google Scholar
Schonfeldt-Lecuona, C, Kregel, T, Schmidt, A, Pinkhardt, EH, Lauda, F, Kassubek, J et al. (2016) From imaging the brain to imaging the retina: optical coherence tomography (OCT) in schizophrenia. Schizophrenia Bulletin 42, 9–14.Google Scholar
Scripsema, NK, Garcia, PM, Bavier, RD, Chui, TY, Krawitz, BD, Mo, S et al. (2016) Optical coherence tomography angiography analysis of perfused peripapillary capillaries in primary open-angle glaucoma and normal-tension glaucoma. Investigative Ophthalmology and Visual Science 57, OCT611–OCT620.Google Scholar
Selemon, LD and Begovic, A (2007) Stereologic analysis of the lateral geniculate nucleus of the thalamus in normal and schizophrenic subjects. Psychiatry Research 151, 1–10.Google Scholar
Sham, PC, Castle, DJ, Wessely, S, Farmer, AE and Murray, RM (1996) Further exploration of a latent class typology of schizophrenia. Schizophrenia Research 20, 105–115.Google Scholar
Silverstein, SM (2016) Visual perception disturbances in schizophrenia: a unified model. Nebraska Symposium on Motivation 63, 77–132.Google Scholar
Silverstein, SM, All, SD, Kasi, R, Berten, S, Essex, B, Lathrop, KL et al. (2010) Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI. Psychological Medicine 40, 1159–1169.Google Scholar
Silverstein, SM, Keane, BP, Barch, DM, Carter, CS, Gold, JM, Kovacs, I et al. (2012) Optimization and validation of a visual integration test for schizophrenia research. Schizophrenia Bulletin 38, 125–134.Google Scholar
Silverstein, SM, Keane, BP, Wang, Y, Mikkilineni, D, Paterno, D, Papathomas, TV et al. (2013) Effects of short-term inpatient treatment on sensitivity to a size contrast illusion in first-episode psychosis and multiple-episode schizophrenia. Frontiers in Psychology 4, 466.Google Scholar
Silverstein, SM and Rosen, R (2015) Schizophrenia and the eye. Schizophrenia Research: Cognition 2, 46–55.Google Scholar
Souza, VB, Moura Filho, FJ, Souza, FG, Pereira Filho, SA, Coelho, SS, Furtado, FA et al. (2008) Intraocular pressure in schizophrenic patients treated with psychiatric medications. Arquivos Brasileiros de Oftalmologia 71, 660–664.Google Scholar
Syc, SB, Warner, CV, Saidha, S, Farrell, SK, Conger, A, Bisker, ER et al. (2011) Cup to disc ratio by optical coherence tomography is abnormal in multiple sclerosis. Journal of the Neurological Sciences 302, 19–24.Google Scholar
Tohid, H, Faizan, M and Faizan, U (2015) Alterations of the occipital lobe in schizophrenia. Neurosciences (Riyadh, Saudi Arabia) 20, 213–224.Google Scholar
Toledo, J, Sepulcre, J, Salinas-Alaman, A, Garcia-Layana, A, Murie-Fernandez, M, Bejarano, B et al. (2008) Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Multiple Sclerosis 14, 906–912.Google Scholar
Tsai, CS, Ritch, R, Schwartz, B, Lee, SS, Miller, NR, Chi, T et al. (1991) Optic nerve head and nerve fiber layer in alzheimer's disease. Archives of Ophthalmology 109, 199–204.Google Scholar
Vajzovic, L, Hendrickson, AE, O'Connell, RV, Clark, LA, Tran-Viet, D, Possin, D et al. (2012) Maturation of the human fovea: correlation of spectral-domain optical coherence tomography findings with histology. American Journal of Ophthalmology 154, 779–789.Google Scholar
Vizzeri, G, Weinreb, RN, Gonzalez-Garcia, AO, Bowd, C, Medeiros, FA, Sample, PA et al. (2009) Agreement between spectral-domain and time-domain OCT for measuring RNFL thickness. British Journal of Ophthalmology 93, 775–781.Google Scholar
Wadhwani, M, Bali, SJ, Satyapal, R, Angmo, D, Sharma, R, Pandey, V et al. (2015) Test-retest variability of retinal nerve fiber layer thickness and macular ganglion cell-inner plexiform layer thickness measurements using spectral-domain optical coherence tomography. Journal of Glaucoma 24, e109–e115.Google Scholar
Warner, CV, Syc, SB, Stankiewicz, AM, Hiremath, G, Farrell, SK, Crainiceanu, CM et al. (2011) The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials. PLoS ONE 6, e22947.Google Scholar
Wechsler, D (2011) Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-II), San Antonio, Texas: NCS Pearson.Google Scholar
Wickham, H, Walsh, C, Asherson, P, Gill, M, Owen, MJ, Mcguffin, P et al. (2002) Familiality of clinical characteristics in schizophrenia. Journal of Psychiatric Research 36, 325–329.Google Scholar
Wickham, H, Walsh, C, Asherson, P, Taylor, C, Sigmundson, T, Gill, M et al. (2001) Familiality of symptom dimensions in schizophrenia. Schizophrenia Research 47, 223–232.Google Scholar
Yilmaz, U, Kucuk, E, Ulgen, A, Ozkose, A, Demircan, S, Ulusoy, DM et al. (2016) Retinal nerve fiber layer and macular thickness measurement in patients with schizophrenia. European Journal of Ophthalmology 26, 375–378.Google Scholar
Yu, JG, Feng, YF, Xiang, Y, Huang, JH, Savini, G, Parisi, V et al. (2014) Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS ONE 9, e85718.Google Scholar