Citation Information :
Ciociola EC, Patel K, Blahnik T, Ghosh A, Klifto MR, Fleischman D. A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease. J Curr Glaucoma Pract 2023; 17 (3):126-133.
Aim: To investigate the limitations of diagnosing glaucoma in patients with coexistent neurodegenerative disease (NDD) by collecting information on demographics, examination findings, optical coherence tomography (OCT), and visual field (VF) tests.
Materials and methods: Retrospective cohort study of patients with primary open-angle glaucoma and coexistent dementia, multiple sclerosis (MS), Parkinson's disease (PD), or cerebrovascular accident (CVA) from 2014 to 2020. We included patients with a minimum of 3 years of follow-up. Demographics, ophthalmic exam, OCT, and VF findings were reported and compared across NDD groups using the Chi-squared and analysis of variance tests.
Results: We included 199 patients with glaucoma and coexistent NDD, including dementia (51.3%), CVA (11.2%), PD (18.1%), and MS (19.6%). Cupping, neuroretinal rim thinning, pallor, and peripapillary atrophy of the optic nerve were most frequently observed. There was a high number of missing values from OCT to VF tests, and zero patients had a complete OCT or VF test. Additionally, 67.8 and 77.4% of patients received <1 OCT and VF/year, respectively. Retinal nerve fiber layer (RNFL) thinning was observed most frequently in the superior (33.2% OD and 30.7% OS) and inferior (25.6% OD and 30.2% OS) quadrants, with the most significant thinning seen in CVA patients compared to other NDDs (p < 0.05). Glaucoma hemifield tests (GHTs) were abnormal in 23.1% OD and 22.6% OS, and the average mean deviation was −7.43 [standard deviation (SD) 8.23] OD and −8.79 (SD 7.99) OS.
Conclusion: The OCT and VF tests are frequently unavailable and may be confounded in patients with coexistent glaucoma and NDDs, complicating glaucoma diagnosis and management.
Clinical significance: Diagnosing and managing glaucoma in patients with coexistent NDD is difficult, given the lack of available and reliable OCT and VF testing data. Providers may be forced to rely on intraocular pressure (IOP) and other imperfect measures.
Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA 2014;311(18):1901–1911. DOI: 10.1001/jama.2014.3192
Kwon YH, Fingert JH, Kuehn MH, et al. Primary open-angle glaucoma. N Engl J Med 2009;360(11):1113–1124. DOI: 10.1056/NEJMra0804630
Gedde SJ, Vinod K, Wright MM, et al. Primary open-angle glaucoma preferred practice pattern®. Ophthalmology 2021;128(1):P71–P150. DOI: 10.1016/j.ophtha.2020.10.022
Doustar J, Torbati T, Black KL, et al. Optical coherence tomography in Alzheimer's disease and other neurodegenerative diseases. Front Neurol 2017;8:701. DOI: 10.3389/fneur.2017.00701
Hinton DR, Sadun AA, Blanks JC, et al. Optic-nerve degeneration in Alzheimer's disease. N Engl J Med 1986;315(8):485–487. DOI: 10.1056/nejm198608213150804
Blanks JC, Hinton DR, Sadun AA, et al. Retinal ganglion cell degeneration in Alzheimer's disease. Brain Res 1989;501(2):364–372. DOI: 10.1016/0006-8993(89)90653-7
Bock M, Brandt AU, Dörr J, et al. Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 2010;112(8):647–652. DOI: 10.1016/j.clineuro.2010.04.014
Grudziecka Pyrek M, Selmaj K. Optical coherence tomography assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis. Front Neurol 2022;13:953188. DOI: 10.3389/fneur.2022.953188
Aykan U, Akdemir MO, Yildirim O, et al. Screening for patients with mild Alzheimer disease using frequency doubling technology perimetry. Neuroophthalmology 2013;37(6):239–246. DOI: 10.3109/01658107.2013.830627
Risacher SL, Wudunn D, Pepin SM, et al. Visual contrast sensitivity in Alzheimer's disease, mild cognitive impairment, and older adults with cognitive complaints. Neurobiol Aging 2013;34(4):1133–1144. DOI: 10.1016/j.neurobiolaging.2012.08.007
Coppola G, Di Renzo A, Ziccardi L, et al. Optical coherence tomography in Alzheimer's disease: a meta-analysis. PLoS One 2015;10(8):e0134750. DOI: 10.1371/journal.pone.0134750
den Haan J, Verbraak FD, Visser PJ, et al. Retinal thickness in Alzheimer's disease: a systematic review and meta-analysis. Alzheimers Dement (Amst) 2017;6:162–170. DOI: 10.1016/j.dadm.2016.12.014
Cunha LP, Almeida AL, Costa-Cunha LV, et al. The role of optical coherence tomography in Alzheimer's disease. Int J Retina Vitreous 2016;2:24. DOI: 10.1186/s40942-016-0049-4
Ferrari L, Huang SC, Magnani G, et al. Optical coherence tomography reveals retinal neuroaxonal thinning in frontotemporal dementia as in Alzheimer's disease. J Alzheimers Dis 2017;56(3):1101–1107. DOI: 10.3233/jad-160886
Trebbastoni A, D'Antonio F, Bruscolini A, et al. Retinal nerve fibre layer thickness changes in Alzheimer's disease: results from a 12-month prospective case series. Neurosci Lett 2016;629:165–170. DOi: 10.1016/j.neulet.2016.07.006
Calabresi PA, Balcer LJ, Frohman EM. Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology. Brain 2010;133(Pt 6):1575–1577. DOI: 10.1093/brain/awq133
Parisi V, Manni G, Spadaro M, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999;40(11):2520–2527.
Parisi V. Correlation between morphological and functional retinal impairment in patients affected by ocular hypertension, glaucoma, demyelinating optic neuritis and Alzheimer's disease. Semin Ophthalmol 2003;18(2):50–57. DOI: 10.1076/soph.18.104.22.16855
Trip SA, Miller DH. Imaging in multiple sclerosis. J Neurol Neurosurg Psychiatry 2005;76(Suppl 3):iii11–iii18. DOI: 10.1136/jnnp.2005.073213
Klistorner A, Garrick R, Barnett MH, et al. Axonal loss in non-optic neuritis eyes of patients with multiple sclerosis linked to delayed visual evoked potential. Neurology 2013;80(3):242–245. DOI: 10.1212/WNL.0b013e31827deb39
Henderson AP, Trip SA, Schlottmann PG, et al. An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 2008;131(Pt 1):277–287. DOI: 10.1093/brain/awm285
Fisher JB, Jacobs DA, Markowitz CE, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006;113(2):324–332. DOI: 10.1016/j.ophtha.2005.10.040
Satue M, Garcia-Martin E, Fuertes I, et al. Use of Fourier-domain OCT to detect retinal nerve fiber layer degeneration in Parkinson's disease patients. Eye (Lond) 2013;27(4):507–514. DOI: 10.1038/eye.2013.4
Moreno-Ramos T, Benito-León J, Villarejo A, et al. Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. J Alzheimers Dis 2013;34(3):659–664. DOI: 10.3233/jad-121975
Moschos MM, Tagaris G, Markopoulos I, et al. Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. Eur J Ophthalmol 2011;21(1):24–29. DOI: 10.5301/ejo.2010.1318
Inzelberg R, Ramirez JA, Nisipeanu P, et al. Retinal nerve fiber layer thinning in Parkinson disease. Vision Res 2004;44(24):2793–2797. DOI: 10.1016/j.visres.2004.06.009
Hajee ME, March WF, Lazzaro DR, et al. Inner retinal layer thinning in Parkinson disease. Arch Ophthalmol 2009;127(6):737–741. DOI: 10.1001/archophthalmol.2009.106
Satue M, Rodrigo MJ, Obis J, et al. Evaluation of progressive visual dysfunction and retinal degeneration in patients with Parkinson's disease. Invest Ophthalmol Vis Sci 2017;58(2):1151–1157. DOI: 10.1167/iovs.16-20460
Ye C, Kwapong WR, Tao W, et al. Characterization of macular structural and microvascular changes in thalamic infarction patients: a swept-source optical coherence tomography-angiography study. Brain Sci 2022;12(5):518. DOI: 10.3390/brainsci12050518
Rashid AS, Rashid D, Yang G, et al. Homonymous visual field defect and retinal thinning after occipital stroke. Brain Behav 2021;11(10):e2345. DOI: 10.1002/brb3.2345
Lee JI, Boerker L, Gemerzki L, et al. Retinal changes after posterior cerebral artery infarctions display different patterns of the nasal und temporal sector in a case series. Front Neurol 2020;11:508. DOI: 10.3389/fneur.2020.00508
Gunes A, Inal EE, Demirci S, et al. Changes in retinal nerve fiber layer thickness in patients with cerebral infarction: evidence of transneuronal retrograde degeneration. Acta Neurol Belg 2016;116(4):461–466. DOI: 10.1007/s13760-015-0592-z
Cesareo M, Martucci A, Ciuffoletti E, et al. Association between Alzheimer's disease and glaucoma: a study based on heidelberg retinal tomography and frequency doubling technology perimetry. Front Neurosci 2015;9:479. DOI: 10.3389/fnins.2015.00479
Tsironi EE, Dastiridou A, Katsanos A, et al. Perimetric and retinal nerve fiber layer findings in patients with Parkinson's disease. BMC Ophthalmol 2012;12:54. DOI: 10.1186/1471-2415-12-54
Yenice O, Onal S, Midi I, Ozcan E, et al. Visual field analysis in patients with Parkinson's disease. Parkinsonism Relat Disord 2008;14(3):193–198. DOI: 10.1016/j.parkreldis.2007.07.018
Kitsos G, Detorakis ET, Papakonstantinou S, et al. Perimetric and peri-papillary nerve fibre layer thickness findings in multiple sclerosis. Eur J Neurol 2011;18(5):719–725. DOI: 10.1111/j.1468-1331.2010.03256.x
Corallo G, Cicinelli S, Papadia M, et al. Conventional perimetry, short-wavelength automated perimetry, frequency-doubling technology, and visual evoked potentials in the assessment of patients with multiple sclerosis. Eur J Ophthalmol 2005;15(6):730–738. DOI: 10.1177/112067210501500612
Lee YJ, Lee SC, Wy SY, et al. Ocular manifestations, visual field pattern, and visual field test performance in traumatic brain injury and stroke. J Ophthalmol 2022;2022:1703806. DOI: 10.1155/2022/1703806
Estiasari R, Diwyacitta A, Sidik M, et al. Evaluation of retinal structure and optic nerve function changes in multiple sclerosis: longitudinal study with 1-year follow-up. Neurol Res Int 2021;2021:5573839. DOI: 10.1155/2021/5573839
Pilat A, McLean RJ, Proudlock FA, et al. In vivo morphology of the optic nerve and retina in patients with Parkinson's disease. Invest Ophthalmol Vis Sci. Aug 1 2016;57(10):4420–4427. DOI: 10.1167/iovs.16-20020
Tsai CS, Ritch R, Schwartz B, et al. Optic nerve head and nerve fiber layer in Alzheimer's disease. Arch Ophthalmol 1991;109(2):199–204. DOI: 10.1001/archopht.1991.01080020045040