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In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma

Published online by Cambridge University Press:  07 January 2022

Luca Agnifili*
Affiliation:
Ophthalmology Clinic, Department of Medicine and Ageing Science, University “G. D'Annunzio” of Chieti-Pescara, Chieti66100, Italy
Lorenza Brescia
Affiliation:
Ophthalmology Clinic, Department of Medicine and Ageing Science, University “G. D'Annunzio” of Chieti-Pescara, Chieti66100, Italy
Edoardo Villani
Affiliation:
Department of Clinical Sciences and Community Health, University of Milan & Eye Clinic San Giuseppe Hospital, IRCCS Multimedica, Milan20123, Italy
Giada D'Onofrio
Affiliation:
Ophthalmology Clinic, Department of Medicine and Ageing Science, University “G. D'Annunzio” of Chieti-Pescara, Chieti66100, Italy
Michele Figus
Affiliation:
Ophthalmology Unit, Department of Surgery, Medicine, Molecular and Emergency, University of Pisa, Pisa56124, Italy
Francesco Oddone
Affiliation:
IRCCS-Fondazione Bietti, Rome00198, Italy
Paolo Nucci
Affiliation:
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Rodolfo Mastropasqua
Affiliation:
Institute of Ophthalmology, University of Modena and Reggio Emilia, Modena41125, Italy
*
*Corresponding author: Luca Agnifili, E-mail: l.agnifili@unich.it
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Abstract

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of the Microscopy Society of America

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Footnotes

LA and LB equally contributed to this paper and share primary authorship.

References

Agnifili, L, Brescia, L, Oddone, F, Sacchi, M, D'Ugo, E, Di Marzio, G, Perna, F, Costagliola, C & Mastropasqua, R (2019). The ocular surface after successful glaucoma filtration surgery: A clinical, in vivo confocal microscopy, and immune-cytology study. Sci Rep 9(1), 11299.CrossRefGoogle Scholar
Agnifili, L, Fasanella, V, Costagliola, C, Ciabattoni, C, Mastropasqua, R, Frezzotti, P & Mastropasqua, L (2013). In vivo confocal microscopy of meibomian glands in glaucoma. Br J Ophthalmol 97(3), 343349.10.1136/bjophthalmol-2012-302597CrossRefGoogle ScholarPubMed
Agnifili, L, Mastropasqua, R, Fasanella, V, Brescia, L, Scatena, B, Oddone, F & Mastropasqua, L (2018). Meibomian gland features and conjunctival goblet cell density in glaucomatous patients controlled with prostaglandin/timolol fixed combinations: A case control, cross-sectional study. J Glaucoma 27(4), 364370.10.1097/IJG.0000000000000899CrossRefGoogle ScholarPubMed
Baghdasaryan, E, Tepelus, TC, Vickers, LA, Huang, P, Chopra, V, Sadda, SR & Lee, OL (2019). Assessment of corneal changes associated with topical antiglaucoma therapy using in vivo confocal microscopy. Ophthalmic Res 61(1), 5159.10.1159/000484632CrossRefGoogle ScholarPubMed
Baratz, KH, Nau, CB, Winter, EJ, McLaren, JW, Hodge, DO, Herman, DC & Bourne, WM (2006). Effects of glaucoma medications on corneal endothelium, keratocytes, and subbasal nerves among participants in the ocular hypertension treatment study. Cornea 25(9), 10461052.10.1097/01.ico.0000230499.07273.c5CrossRefGoogle ScholarPubMed
Bhattacharya, P, Edwards, K, Harkin, D & Schmid, KL (2020). Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: A review and meta-analysis. Br J Ophthalmol 104(12), 16331639.10.1136/bjophthalmol-2019-315231CrossRefGoogle ScholarPubMed
Bron, AJ, Evans, VE & Smith, JA (2003). Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 22(7), 640650.CrossRefGoogle ScholarPubMed
Cruzat, A, Qazi, Y & Hamrah, P (2017). In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf 15(1), 1547.CrossRefGoogle ScholarPubMed
Dell'Omo, R, Cifariello, F, De Turris, S, Romano, V, Di Renzo, F, Di Taranto, D, Coclite, G, Agnifili, L, Mastropasqua, L & Costagliola, C (2018). Confocal microscopy of corneal nerve plexus as an early marker of eye involvement in patients with type 2 diabetes. Diabetes Res Clin Pract 142, 393400.CrossRefGoogle ScholarPubMed
Ferdousi, M, Romanchuk, K, Mah, JK, Virtanen, H, Millar, C, Malik, RA & Pacaud, D (2019). Early corneal nerve fibre damage and increased Langerhans cell density in children with type 1 diabetes mellitus. Sci Rep 9(1), 8758.CrossRefGoogle ScholarPubMed
Fogagnolo, P, Dipinto, A, Vanzulli, E, Maggiolo, E, De Cilla’, S, Autelitano, A & Rossetti, L (2015). A 1-year randomized study of the clinical and confocal effects of tafluprost and latanoprost in newly diagnosed glaucoma patients. Adv Ther 32(4), 356369.CrossRefGoogle ScholarPubMed
Frezzotti, P, Fogagnolo, P, Haka, G, Motolese, I, Iester, M, Bagaglia, SA, Mittica, P, Menicacci, C, Rossetti, L & Motolese, E (2014). In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma. Acta Ophthalmol 92(2), e133e140.CrossRefGoogle ScholarPubMed
Giannaccare, G, Pellegrini, M, Sebastiani, S, Moscardelli, F, Versura, P & Campos, EC (2019). In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system. Graefes Arch Clin Exp Ophthalmol 257(3), 583589.10.1007/s00417-018-04225-7CrossRefGoogle ScholarPubMed
Hodapp, E, Parrish, RKII & Anderson, DR (1993). Clinical Decisions in Glaucoma. St Louis: The CV Mosby Co., 5261.Google Scholar
Kim, G, Singleton, JR, Mifflin, MD, Digre, KB, Porzio, MT & Gordon Smith, A (2013). Assessing the reproducibility of quantitative in vivo confocal microscopy of corneal nerves in different corneal locations. Cornea 32, 13311338.10.1097/ICO.0b013e31829dd7f8CrossRefGoogle ScholarPubMed
Kokot, J, Wylęgała, A, Wowra, B, Wójcik, Ł, Dobrowolski, D & Wylęgała, E (2018). Corneal confocal sub-basal nerve plexus evaluation: A review. Acta Ophthalmol 96(3), 232242.CrossRefGoogle ScholarPubMed
Labbé, A, Alalwani, H, Van Went, C, Brasnu, E, Georgescu, D & Baudouin, C (2012). The relationship between subbasal nerve morphology and corneal sensation in ocular surface disease. Invest Ophthalmol Vis Sci 53(8), 49264931.10.1167/iovs.11-8708CrossRefGoogle ScholarPubMed
Lagali, NS, Allgeier, S, Guimarães, P, Badian, RA, Ruggeri, A, Köhler, B & Rolandsson, O (2017). Reduced corneal nerve fiber density in type 2 diabetes by wide-area mosaic analysis. Investigative Opthalmology & Visual Science 58(14), 6318.10.1167/iovs.17-22257CrossRefGoogle ScholarPubMed
Martone, G, Frezzotti, P, Tosi, GM, Traversi, C, Mittica, V, Malandrini, A, Pichierri, P, Balestrazzi, A, Motolese, PA, Motolese, I & Motolese, E (2009). An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol 147(4), 725735.CrossRefGoogle Scholar
Mastropasqua, L, Agnifili, L, Mastropasqua, R, Fasanella, V, Nubile, M, Toto, L, Carpineto, P & Ciancaglini, M (2014). In vivo laser scanning confocal microscopy of the ocular surface in glaucoma. Microsc Microanal 20(3), 879894.10.1017/S1431927614000324CrossRefGoogle Scholar
Mastropasqua, R, Agnifili, L, Fasanella, V, Curcio, C, Brescia, L, Lanzini, M, Fresina, M, Mastropasqua, L & Marchini, G (2015). Corneoscleral limbus in glaucoma patients: In vivo confocal microscopy and immunocytological study. Invest Ophthalmol Vis Sci 56(3), 20502058.CrossRefGoogle ScholarPubMed
Mastropasqua, R, Agnifili, L, Fasanella, V, Lappa, A, Brescia, L, Lanzini, M, Oddone, F, Perri, P & Mastropasqua, L (2016). In vivo distribution of corneal epithelial dendritic cells in patients with glaucoma. Invest Ophthalmol Vis Sci 57(14), 59966002.CrossRefGoogle ScholarPubMed
Mastropasqua, R, Agnifili, L, Fasanella, V, Nubile, M, Gnama, AA, Falconio, G, Perri, P, Di Staso, S & Mariotti, C (2017). The conjunctiva-associated lymphoid tissue in chronic ocular surface diseases. Microsc Microanal 23(4), 697707.CrossRefGoogle ScholarPubMed
Patel, DV & McGhee, CN (2005). Mapping of the normal human corneal sub-basal nerve plexus by in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci 46(12), 44854488.CrossRefGoogle ScholarPubMed
Ranno, S, Fogagnolo, P, Rossetti, L, Orzalesi, N & Nucci, P (2011). Changes in corneal parameters at confocal microscopy in treated glaucoma patients. Clin Ophthalmol 5, 10371042.10.2147/OPTH.S22874CrossRefGoogle ScholarPubMed
Rossi, GCM, Scudeller, L, Lumini, C, Mirabile, AV, Picasso, E, Bettio, F, Pasinetti, GM & Bianchi, PE (2019). An in vivo confocal, prospective, masked, 36 months study on glaucoma patients medically treated with preservative-free or preserved monotherapy. Sci Rep 9(1), 4282.CrossRefGoogle ScholarPubMed
Roszkowska Licitra, C, Tumminello, G, Postorino, EI, Colonna, MR & Aragona, P (2021). Corneal nerves in diabetes. The role of in vivo corneal confocal microscopy in the assessment of peripheral small fiber neuropathy. Surv Ophthalmol 66(3), 493513.10.1016/j.survophthal.2020.09.003CrossRefGoogle Scholar
Shtein, RM & Callaghan, BC (2013). Corneal confocal microscopy as a measure of diabetic neuropathy. Diabetes 62(1), 2526.CrossRefGoogle ScholarPubMed
Stachs, O, Zhivov, A, Kraak, R, Hovakimyan, M, Wree, A & Guthoff, R (2010). Structural-functional correlations of corneal innervation after LASIK and penetrating keratoplasty. J Refract Surg 26(3), 159167.10.3928/1081597X-20100224-01CrossRefGoogle ScholarPubMed
Steger, B, Speicher, L, Philipp, W & Bechrakis, NE (2015). In vivo confocal microscopic characterization of the cornea in chronic graft-versus-host disease related severe dry eye disease. Br J Ophthalmol 99(2), 160165.10.1136/bjophthalmol-2014-305072CrossRefGoogle Scholar
Tavakoli, M, Quattrini, C, Abbott, C, Kallinikos, P, Marshall, A, Finnigan, J, Morgan, P, Efron, N, Boulton, AJM & Malik, RA (2010). Corneal confocal microscopy: A novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care 33(8), 17921797.CrossRefGoogle ScholarPubMed
Villani, E, Sacchi, M, Magnani, F, Nicodemo, A, Williams, SE, Rossi, A, Ratiglia, R, De Cillà, S & Nucci, P (2016). The ocular surface in medically controlled glaucoma: An in vivo confocal study. Invest Ophthalmol Vis Sci 57(3), 10031010.10.1167/iovs.15-17455CrossRefGoogle Scholar
Wolffsohn, JS, Arita, R, Chalmers, R, Djalilian, A, Dogru, M, Dumbleton, K, Gupta, PK, Karpecki, P, Lazreg, S, Pult, H, Sullivan, BD, Tomlinson, A, Tong, L, Villani, E, Yoon, KC, Jones, L & Craig, JP (2017). TFOS DEWS II diagnostic methodology report. Ocul Surf 15(3), 539574.CrossRefGoogle ScholarPubMed