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Öğe Abnormal Dynamic Pupillometry Relates to Neurologic Disability and Retinal Axonal Loss in Patients With Multiple Sclerosis(Assoc Research Vision Ophthalmology Inc, 2021) Bitirgen, Gulfidan; Akpinar, Zehra; Turk, Huseyin B.; Malik, Rayaz A.Purpose: To assess alterations in quantitative dynamic pupil responses to light in relation to neurologic disability and retinal axonal loss in patients with multiple sclerosis (MS). Methods: Twenty-five patients with relapsing-remitting MS and 25 healthy subjects were included in this cross-sectional study. Pupillary responses were measured with an infrared dynamic pupillometry unit, and peripapillary retinal nerve fiber layer (RNFL) thickness was measured with spectral-domain optical coherence tomography. Neurologic disability was assessed by the Expanded Disability Status Scale (EDSS). Patients with a history of optic neuritis (ON) within 6 months were excluded. Only the right eyes were assessed, except in 11 patients with a history of unilateral ON in whom both eyes were further analyzed to evaluate the effect of previous ON. Results: The initial pupil diameter (P = 0.003) and pupil contraction amplitude (P = 0.027) were lower in patients with MS compared with healthy controls. Initial pupil diameter correlated with EDSS score (? = ?0.458; P = 0.021), and RNFL correlated with contraction latency (? = ?0.524; P = 0.007). There were no significant differences in any of the pupil parameters between eyes with and without a history of ON, and between the ON and fellow eyes of the 11 patients with previous unilateral ON. Conclusions: Dynamic pupillometry reveals significant alterations in pupillary light reflex responses associated with neurologic disability and retinal axonal loss, independent of previous ON. Translational Relevance: Dynamic pupillometry is a simple, noninvasive tool that may be useful in detecting autonomic dysfunction in patients with MS.Öğe Abnormal quantitative pupillary light responses following COVID-19(Springer, 2022) Bitirgen, Gulfidan; Korkmaz, Celalettin; Zamani, Adil; Iyisoy, Mehmet Sinan; Kerimoglu, Hurkan; Malik, Rayaz A.Purpose To characterize alterations in pupillary light reflex responses in subjects following coronavirus disease 2019 (COVID-19), especially those with long-COVID. Methods Thirty-five subjects with previous COVID-19 and 30 healthy control participants were enrolled in this cross-sectional comparative study. An infrared dynamic pupillometry system (MonPack One; Metrovision, France) was used to quantify pupillary light responses. The National Institute for Health and Care Excellence (NICE) long-COVID questionnaire was used to identify persisting symptoms at least 4 weeks after acute COVID-19. Results The median time after the diagnosis of acute COVID-19 was 4.0 (2.0-5.0) months. There was an increase in the latency of pupil contraction (P = 0.001) and a reduction in the duration of pupil contraction (P = 0.039) in post-COVID-19 subjects compared to healthy controls. No significant differences were observed in the initial pupil diameter, amplitude and velocity of pupil contraction or latency, velocity and duration of pupil dilation. Long-COVID was present in 25/35 (71%) subjects and their duration of pupil contraction was reduced compared to subjects without long-COVID (P = 0.009). The NICE long-COVID questionnaire total score (rho = - 0.507; P = 0.002) and neurological score (rho = - 0.412; P = 0.014) correlated with the duration of pupil contraction and the total score correlated with the latency of dilation (rho = - 0.352; P = 0.038). Conclusion Dynamic pupillometry reveals significant alterations in contractile pupillary light responses, indicative of parasympathetic dysfunction after COVID-19.Öğe Altered pupillary light responses are associated with the severity of autonomic symptoms in patients with Fabry disease(Nature Research, 2021) Bitirgen, Gulfidan; Turkmen, Kultigin; Zengin, Nazmi; Malik, Rayaz A.Symptoms of autonomic dysfunction are common in Fabry disease. In this study we aimed to evaluate alterations in the pupillary response to white light stimulation in patients with Fabry disease and their association with the severity of autonomic symptoms. Fourteen consecutive patients with Fabry disease and 14 healthy control participants were enrolled in this cross-sectional study. The Mainz Severity Score Index (MSSI) was used to measure the severity of Fabry disease and the Composite Autonomic Symptom Scale 31 (COMPASS 31) questionnaire was used to evaluate the severity of autonomic symptoms. The pupil light responses were assessed with an infrared dynamic pupillometry unit. There were significant reductions in the amplitude (P=0.048) and duration (P=0.048) of pupil contraction, and the latency of pupil dilation (P=0.048) in patients with Fabry disease compared to control subjects. The total weighted COMPASS 31 score correlated with MSSI (r=0.592; P=0.026) and the duration of pupil dilation (rho =0.561; P=0.037). The pupillomotor weighted sub-score of the COMPASS 31 correlated inversely with the duration of pupil contraction (r=-0.600; P=0.023) and latency of pupil dilation (rho=-0.541; P=0.046), and directly with the duration of pupil dilation (rho =0.877; P<0.001) and MSSI (r=0.533; P=0.049). In conclusion, abnormal pupillary function is demonstrated in patients with Fabry disease, which is associated with the severity of autonomic symptoms.Öğe Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections(Public Library Science, 2017) Bitirgen, Gulfidan; Belviranli, Selman; Malik, Rayaz A.; Kerimoglu, Hurkan; Satirtav, Gunhal; Zengin, NazmiPurpose To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD). Methods Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects. Results The mean number of ranibizumab injections per eye was 8.9 +/- 5.0 (range 3-20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P=0.237), and the eyes of healthy control subjects (P=0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters. Conclusions Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.Öğe Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections(Public Library Science, 2017) Bitirgen, Gulfidan; Belviranli, Selman; Malik, Rayaz A.; Kerimoglu, Hurkan; Satirtav, Gunhal; Zengin, NazmiPurpose To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD). Methods Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects. Results The mean number of ranibizumab injections per eye was 8.9 +/- 5.0 (range 3-20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P=0.237), and the eyes of healthy control subjects (P=0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters. Conclusions Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.Öğe Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease(Nature Publishing Group, 2018) Bitirgen, Gulfidan; Turkmen, Kultigin; Malik, Rayaz A.; Ozkagnici, Ahmet; Zengin, NazmiFabry disease is characterised by neuropathic pain and accelerated vascular disease. This study evaluates the utility of corneal confocal microscopy (CCM) to non-invasively quantify corneal nerve and endothelial cell morphology and dendritic cell (DC) density in relation to disease severity in subjects with Fabry disease. Seventeen consecutive participants with Fabry disease and 17 healthy control subjects were included in this cross-sectional study. Fabry disease severity was measured using the Mainz Severity Score Index (MSSI). Central corneal sensitivity was assessed with a contact corneal esthesiometer. There was a significant reduction in the corneal sensitivity (5.75 [5.25-6.00] vs. 6.00 [6.00-6.00] cm, P = 0.014), nerve fiber density (NFD) (26.4 +/- 10.1 vs. 33.7 +/- 7.9 fibers/mm(2), P = 0.025) and nerve fiber length (NFL) (15.9 +/- 3.4 vs. 19.5 +/- 4.4 mm/mm(2), P = 0.012) and an increase in DC density (38.3 [17.5-97.3] vs. 13.5 [0-29.4] cells/mm(2), P = 0.004) in subjects with Fabry disease compared to the healthy control subjects. The total MSSI score correlated with NFD (rho = -0.686; P = 0.006), NFL (rho = -0.692; P = 0.006), endothelial cell density (rho = -0.511; P = 0.036), endothelial cell area (rho = 0.514; P = 0.036) and alpha-galactosidase A enzyme activity (rho = -0.723; P = 0.008). This study demonstrates reduced corneal sensitivity, corneal nerve fiber damage and increased DCs in subjects with Fabry disease.Öğe Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID(Bmj Publishing Group, 2022) Bitirgen, Gulfidan; Korkmaz, Celalettin; Zamani, Adil; Ozkagnici, Ahmet; Zengin, Nazmi; Ponirakis, Georgios; Malik, Rayaz A.Background/Aims Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID. Methods Forty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density. Results The mean time after the diagnosis of COVID-19 was 3.7 +/- 1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (rho=-0.436; p=0.005, rho=-0.387; p=0.038, respectively) and CNFL (rho=-0.404; p=0.010, rho=-0.412; p=0.026, respectively). Conclusion Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.Öğe Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis(Springernature, 2023) Bitirgen, Gulfidan; Kucuk, Adem; Ergun, Mustafa Cagri; Satirtav, Gunhal; Malik, Rayaz A.Background/ObjectivesRheumatoid arthritis (RA) is a multisystem autoimmune disorder characterized by articular and extra-articular manifestations. Neuropathy is a poorly studied manifestation of RA. The aim of this study was to utilize the rapid non-invasive ophthalmic imaging technique of corneal confocal microscopy to identify whether there is evidence of small nerve fibre injury and immune cell activation in patients with RA.Subjects/MethodsFifty consecutive patients with RA and 35 healthy control participants were enrolled in this single-centre, cross-sectional study conducted at a university hospital. Disease activity was assessed with the 28-Joint Disease Activity Score and erythrocyte sedimentation rate (DAS28-ESR). Central corneal sensitivity was measured with a Cochet-Bonnet contact corneal esthesiometer. A laser scanning in vivo corneal confocal microscope was used to quantify corneal nerve fibre density (CNFD), nerve branch density (CNBD), nerve fibre length (CNFL), and Langerhans cell (LC) density.ResultsCorneal sensitivity (P = 0.01), CNFD (P = 0.02), CNBD (P < 0.001), and CNFL (P < 0.001) were lower, and mature (P = 0.001) and immature LC densities (P = 0.011) were higher in patients with RA compared to control subjects. CNFD (P = 0.016) and CNFL (P = 0.028) were significantly lower in patients with moderate to high (DAS28-ESR > 3.2) compared to mild (DAS28-ESR <= 3.2) disease activity. Furthermore, the DAS28-ESR score correlated with CNFD (r = -0.425; P = 0.002), CNBD (rho = -0.362; P = 0.010), CNFL (r = -0.464; P = 0.001), total LC density (rho = 0.362; P = 0.010) and immature LC density (rho = 0.343; P = 0.015).ConclusionsThis study demonstrates reduced corneal sensitivity, corneal nerve fibre loss and increased LCs which were associated with the severity of disease activity in patients with RA.Öğe Effects of panretinal laser photocoagulation on the corneal nerve plexus and retinal nerve fiber layer in retinal vein occlusion(Wichtig Publishing, 2017) Bitirgen, Gulfidan; Belviranli, Selman; Malik, Rayaz A.; Kerimoglu, Hurkan; Ozkagnici, AhmetPurpose: To determine the effects of panretinal photocoagulation (PRP) on corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with unilateral central retinal vein occlusion (CRVO) who had previously undergone PRP treatment. Methods: Sixty-four eyes of 32 patients (19 male, 13 female) with unilateral ischemic type CRVO who had undergone PRP treatment at least 6 months previously were included in this cross-sectional study. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the PRP-treated eyes were compared with those of the fellow unaffected eyes. Results: The mean age of patients was 63.5 +/- 10.7 years (range 45-85 years). The mean nerve fiber density (NFD), nerve branch density, and nerve fiber length (NFL) were significantly lower in PRP-treated eyes compared with fellow eyes (p<0.001 for all). Average peripapillary RNFL thickness was significantly lower in PRP-treated eyes than in fellow eyes (p = 0.007). The NFD and NFL showed a modest but significant positive correlation with average peripapillary RNFL thickness (r = 0.310, p = 0.013 and r = 0.272, p = 0.030, respectively). conclusions: Significant reductions in corneal SBNP parameters and average peripapillary RNFL thickness were observed in the eyes of patients receiving PRP for the treatment of ischemic CRVO.Öğe Evaluation of Contact Lens-Induced Changes in Keratoconic Corneas Using In Vivo Confocal Microscopy(Assoc Research Vision Ophthalmology Inc, 2013) Bitirgen, Gulfidan; Ozkagnici, Ahmet; Malik, Rayaz A.; Oltulu, RefikPURPOSE. To quantitatively analyze laser scanning in vivo confocal microscopy (IVCM) images of all corneal layers in contact lens-wearing and noncontact lens-wearing keratoconus patients. METHODS. The study population included rigid gas permeable (RGP) contact lens-wearing keratoconus patients (group 1; N = 29), keratoconus patients who did not wear contact lenses (group 2; N = 30), and subjects who neither had keratoconus nor wore contact lenses (group 3; N = 30), with groups 2 and 3 matched to group 1 by age and sex. The central cornea was examined with IVCM in all subjects. The mean duration of contact lens wear was 5.50 +/- 3.68 years (range, 2-15 years). RESULTS. Eyes with keratoconus showed significantly lower basal epithelial cell and anterior and posterior stromal keratocyte densities, as well as subbasal nerve fiber density, nerve branch density, and nerve fiber length compared with healthy control subjects. Furthermore, compared with group 2, group 1 had significantly lower basal epithelial cell density (4920 +/- 476 cells/mm(2) vs. 4503 +/- 461 cells/mm(2), P = 0.001) and anterior stromal keratocyte density (561 6 91 cells/mm2 vs. 464 6 55 cells/mm2, P < 0.001), but there was no significant difference for posterior stromal keratocyte density (P = 0.808), endothelial cell density (P = 0.699), or subbasal nerve fiber density (P = 0.142), nerve branch density (P = 0.614), and nerve fiber length (P = 0.850). CONCLUSIONS. Significant corneal microstructural abnormalities were observed in eyes with keratoconus. RGP contact lens wear was associated with a further reduction in the basal epithelial cell and anterior stromal keratocyte densities, but with no effect on posterior stromal keratocyte density, endothelial cell density, or corneal nerve morphology.Öğe In Vivo confocal Microscopic evaluation of corneal nerve Fibers and Dendritic cells in Patients With Behcet's Disease(Frontiers Media Sa, 2018) Bitirgen, Gulfidan; Kayitmazbatir, Emine Tinkir; Satirtav, Gunhal; Malik, Rayaz A.; Ozkagnici, AhmetCentral and peripheral nervous system involvement may occur during the course of Behcet's disease (BD). In vivo corneal confocal microscopy (CCM) can detect corneal small fiber damage and immune cell density. The aim of this study was to assess central corneal sensitivity, corneal subepithelial nerve plexus morphology and dendritic cell (DC) density in patients with BD. Forty-nine consecutive patients with BD and 30 healthy control subjects were included in this cross-sectional study conducted at a tertiary referral university hospital. Central corneal sensitivity was measured using the contact corneal esthesiometer (Cochet-Bonnet; Luneau, France). The laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (NFD), nerve branch density (NBD), nerve fiber length (NFL), and DC density. There was a significant reduction in NFD (P = 0.001) and NFL (P = 0.031) and an increase in DC density (P = 0.038) in patients with BD compared to healthy controls, whereas corneal sensitivity (P = 0.066) and NBD (P = 0.067) did not differ significantly. There was no difference in corneal sensitivity, corneal nerve parameters, or DC density between BD patients with [n = 18 (36.7%)] and without a previous history of uveitis (P > 0.05 for all). Disease duration [median (IQR), 6.5 (4.0-14.5) years] correlated with corneal sensitivity (rho = -0.463; P = 0.001) and NFD (rho = -0.304; P = 0.034) and corneal sensitivity correlated with NFD (rho = 0.411; P = 0.003) and NFL (rho = 0.295; P = 0.039) in patients with BD. CCM demonstrates corneal sub-basal nerve fiber loss and increased DC density, providing a non-invasive ophthalmic means to identify peripheral neuropathy and inflammation in patients with BD.Öğe In vivo corneal confocal microscopic analysis in patients with keratoconus(Ijo Press, 2015) Bitirgen, Gulfidan; Ozkagnici, Ahmet; Bozkurt, Banu; Malik, Rayaz A.AIM: To quantify corneal ultrastructure using laser scanning in vivo confocal microscopy (IVCM) in patients with keratoconus and control subjects. METHODS: Unscarred corneas of 78 keratoconic subjects without a history of contact lens use and 36 age-matched control subjects were evaluated with slit-lamp examination (SLE), corneal topography and laser scanning IVCM. One eye was randomly chosen for analysis. Anterior and posterior stromal keratocyte, endothelial cell and basal epithelial cell densities and sub-basal nerve structure were evaluated. RESULTS: IVCM qualitatively demonstrated enlarged basal epithelial cells, structural changes in sub -basal and stromal nerve fibers, abnormal stromal keratocytes and keratocyte nuclei, and pleomorphism and enlargement of endothelial cells. Compared with control subjects, significant reductions in basal epithelial cell density (5817 +/- 306 cells/mm(2) vs 4802 +/- 508 cells/mm(2), P<0.001), anterior stromal keratocyte density (800 +/- 111 cells/mm(2) vs 555 +/- 115 cells/mm(2), P<0.001), posterior stromal keratocyte density (333 +/- 34 cells/mm(2) vs 270 +/- 47 cells/mm(2), P<0.001), endothelial cell density (2875 +/- 223 cells/mm(2) vs 2686 +/- 265 cells/mm(2), P<0.001), sub-basal nerve fiber density (31.2 +/- 8.4 nerves/mm(2) vs 18.1 +/- 19.2 nerves/mm(2), P<0.001), sub -basal nerve fiber length (21.4 +/- 3.4 mm/mm(2) vs16.1 +/- 5.1 mm/mm(2), P<0.001), and sub-basal nerve branch density (median 50.0 (first quartile 31.2 - third quartile 68.7) nerve branches/mm(2) vs median 25.0 (first quartile 6.2 - third quartile 45.3) nerve branches/mm(2), P<0.001) were observed in patients with keratocon us. CONCLUSION: Significant microstructural abnormalities were identified in all corneal layers in the eyes of subjects with keratoconus using IVCM. This non invasive in vivo technique provides an important means to define and follow progress of microstructural changes in patients with keratoconus.Öğe Progressive Loss of Corneal and Retinal Nerve Fibers in Patients With Multiple Sclerosis: A 2-Year Follow-up Study(Assoc Research Vision Ophthalmology Inc, 2020) Bitirgen, Gulfidan; Akpinar, Zehra; Uca, Ali Ulvi; Ozkagnici, Ahmet; Petropoulos, Ioannis N.; Malik, Rayaz A.Purpose: To determine longitudinal alterations in corneal nerve fiber morphology, dendritic cell (DC) density, and retinal nerve fiber layer (RNFL) thickness over 2 years in patients with multiple sclerosis (MS). Methods: Thirty-one consecutive patients with relapsing-remitting MS (RRMS) underwent assessment of the Kurtzke Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS), corneal confocal microscopy to quantify corneal subbasal nerve morphology and DC density, and spectral-domain optical coherence tomography to quantify RNFL thickness at baseline and after 2 years. Results: There was a significant reduction in corneal nerve fiber area (CNFA) (P = 0.003), nerve fiber width (CNFW) (P = 0.005), and RNFL thickness (P = 0.004) with an increase in EDSS (P = 0.01) over 2 years. The change in corneal nerve fiber density (CNFD) correlated with the change in EDSS (rho = -0.468; P = 0.008), MSSS (rho = -0.442; P = 0.01), DC density (rho = -0.550; P = 0.001), and RNFL (rho = 0.472; P = 0.007). The change in corneal nerve fiber length (CNFL) correlated with the change in EDSS (rho = -0.445; P = 0.01) and MSSS (rho = -0.490; P = 0.005). Furthermore, there was a significant decrease in CNFL (P < 0.001), CNFA (P = 0.02), CNFW (P = 0.04), corneal total branch density (P = 0.01), and RNFL thickness (P = 0.02) and a significant increase in DC density (P = 0.04) in patients with worsening EDSS (n = 15). Conclusions: Corneal confocal microscopy can be used to detect progressive corneal nerve fiber loss that relates to a progression of disability in patients with RRMS. Translational Relevance: Corneal confocal microscopy acts as a sensitive imaging biomarker for progressive nerve degeneration in patients with MS.Öğe Use of Corneal Confocal Microscopy to Detect Corneal Nerve Loss and Increased Dendritic Cells in Patients With Multiple Sclerosis(Amer Medical Assoc, 2017) Bitirgen, Gulfidan; Akpinar, Zehra; Malik, Rayaz A.; Ozkagnici, AhmetIMPORTANCE Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies. OBJECTIVE To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS. DESIGN, SETTING, AND PARTICIPANTS This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017. Fifty-seven consecutive patients with relapsing-remittingMS and 30 healthy, age-matched control participants were enrolled in the study. Corneal subbasal nerve plexus measures and DC density were quantified in images acquired with the laser scanning in vivo corneal confocal microscope, and peripapillary RNFL thickness was measured with spectral-domain optical coherence tomography. MAIN OUTCOMES AND MEASURES Corneal nerve fiber density, nerve branch density, nerve fiber length, DC density, peripapillary RNFL thickness, and association with the severity of neurologic disability as assessed by the Kurtzke Expanded Disability Status Scale (score range, 0-10; higher scores indicate greater disability) and Multiple Sclerosis Severity Score (score range, 0.01-9.99; higher scores indicate greater severity). RESULTS Of the 57 participants with MS, 42 (74%) were female and the mean (SD) age was 35.4 (8.9) years; of the 30 healthy controls, 19 (63%) were female and the mean (SD) age was 34.8 (10.2) years. Corneal nerve fiber density (mean [SE] difference, -6.78 [2.14] fibers/mm(2); 95% CI, -11.04 to -2.52; P =.002), nerve branch density (mean [SE] difference, -17.94 [5.45] branches/mm(2); 95% CI, -28.77 to -7.10; P =.001), nerve fiber length (mean [SE] difference, -3.03 [0.89] mm/mm(2); 95% CI, -4.81 to -1.25; P =.001), and the mean peripapillary RNFL thickness (mean [SE] difference, -17.06 [3.14] mu m; 95% CI, -23.29 to -10.82; P <.001) were reduced in patients with MS compared with healthy controls. The DC density was increased (median [interquartile range], 27.7 [12.4-66.8] vs 17.3 [0-28.2] cells/mm(2); P =.03), independent of a patient's history of optic neuritis. Nerve fiber density and RNFL thickness showed inverse associations with the Expanded Disability Status Scale (rho = -0.295; P =.03 for nerve fiber density and rho = -0.374; P =.004 for RNFL thickness) and the Multiple Sclerosis Severity Score (R = -0.354; P =.007 for nerve fiber density and R = -0.283; P =.03 for RNFL thickness), whereas other study measures did not. CONCLUSIONS AND RELEVANCE These data suggest that corneal confocal microscopy demonstrates axonal loss and increased DC density in patients with MS. Additional longitudinal studies are needed to confirm the use of corneal confocal microscopy as an imaging biomarker in patients with MS.