Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis.

BACKGROUND/OBJECTIVES: Rheumatoid 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/METHODS: Fifty 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. RESULTS: Corneal 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 (ρ = -0.362; P = 0.010), CNFL (r = -0.464; P = 0.001), total LC density (ρ = 0.362; P = 0.010) and immature LC density (ρ = 0.343; P = 0.015). CONCLUSIONS: This 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.

Abnormal quantitative pupillary light responses following COVID-19.

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 (ρ = - 0.507; P = 0.002) and neurological score (ρ = - 0.412; P = 0.014) correlated with the duration of pupil contraction and the total score correlated with the latency of dilation (ρ = - 0.352; P = 0.038). CONCLUSION: Dynamic pupillometry reveals significant alterations in contractile pupillary light responses, indicative of parasympathetic dysfunction after COVID-19.

Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID.

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 (ρ=-0.436; p=0.005, ρ=-0.387; p=0.038, respectively) and CNFL (ρ=-0.404; p=0.010, ρ=-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.

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study.

Purpose: The purpose of this study was to evaluate the utility of corneal confocal microscopy (CCM) in identifying small nerve fiber damage and immune cell activation in patients with systemic lupus erythematosus (SLE). Methods: This cross-sectional comparative study included 39 consecutive patients with SLE and 30 healthy control participants. Central corneal sensitivity was assessed using a Cochet-Bonnet contact corneal esthesiometer and a laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (CNFD), nerve branch density (CNBD), nerve fiber length (CNFL), and Langerhans cell (LC) density. Results: Age was comparable among patients with SLE (33.7 ± 12.7) and controls (35.0 ± 13.7 years, P = 0.670) and the median duration of disease was 3.0 years (2.0-10.0 years). CNBD (P = 0.003) and CNFL (P = 0.019) were lower and mature LC density (P = 0.002) was higher, but corneal sensitivity (P = 0.178) and CNFD (P = 0.198) were comparable in patients with SLE compared with controls. The SELENA-SLEDAI score correlated with CNFD (ρ = -0.319, P = 0.048) and CNFL (ρ = -0.373, P = 0.019), and the total and immature LC densities correlated with CNBD (ρ = -0.319. P = 0.048, and ρ = -0.328, P = 0.041, respectively). Immature LC density was higher (P = 0.025), but corneal sensitivity and nerve fiber parameters were comparable between patients with (33%) and without neuropsychiatric symptoms and SLE. Conclusions: Corneal confocal microscopy identifies distal corneal nerve fiber loss and increased immune cell density in patients with SLE and corneal nerve loss was associated with disease activity. Translational Relevance: Corneal confocal microscopy may enable the detection of subclinical corneal nerve loss and immune cell activation in SLE.

Abnormal Dynamic Pupillometry Relates to Neurologic Disability and Retinal Axonal Loss in Patients With Multiple Sclerosis.

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 (ρ = -0.458; P = 0.021), and RNFL correlated with contraction latency (ρ = -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.

Altered pupillary light responses are associated with the severity of autonomic symptoms in patients with Fabry disease.

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 (ρ = 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 (ρ = - 0.541; P = 0.046), and directly with the duration of pupil dilation (ρ = 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.

Assessment of pupillary light reflex using dynamic pupillometry in laser-treated eyes with retinal vein occlusion.

PURPOSE: This study aims to evaluate the pupillary light reflex measured with dynamic pupillometry in patients who underwent retinal laser photocoagulation due to unilateral retinal vein occlusion (RVO). METHODS: A total of 48 patients with unilateral RVO were included in the study. Thirty-four patients had undergone retinal laser photocoagulation while the remaining 14 patients that did not undergo laser treatment were observed for control purposes. Of the laser-treated eyes, 14 eyes (41.2%) had central RVO (CRVO) and 20 eyes (58.8%) had branch RVO (BRVO). Among the 14 patients with RVO without laser treatment, nine eyes (64.3%) had CRVO and five eyes (35.7%) had BRVO. Pupillary light reflexes were assessed with dynamic pupillometry (MonPackOne®; Metrovision, France). The parameters of the eyes with RVO were compared with that of fellow healthy eyes. RESULTS: Mean patient age was 65.8 ± 10.4 years and median time after photocoagulation was 25.5 months. Eyes that received laser photocoagulation had lower pupil contraction amplitude (p = 0.037), prolonged contraction latency (p = 0.027), slower contraction velocity (p = 0.043), and slower dilation velocity (p < 0.001) compared to healthy fellow eyes. Subgroup analysis revealed that eyes with CRVO had lower contraction amplitude (p = 0.013) and slower dilation velocity (p = 0.003), and eyes with BRVO had slower dilation velocity (p = 0.003). Non-laser-treated eyes with RVO revealed no significant difference in any of the pupillary light reflex parameters compared to fellow eyes. CONCLUSION: Laser-treated eyes with RVO demonstrated changes in pupillary light reflex parameters including reduced contraction amplitude, prolonged contraction latency, and slower contraction and dilation velocities measured with dynamic pupillometry.

Traumatic hyphema in a patient with severe hemophilia A: Clinical features and management.

PURPOSE: To describe a case of traumatic hyphema in a patient with severe hemophilia A. CASE: We present a case of a 16-year-old boy with severe hemophilia A who presented to our ophthalmology department with total hyphema and elevated intraocular pressure 3 days after a history of blunt ocular trauma on his right eye. Due to the persistent intraocular pressure elevation and total hyphema despite medical intervention, an early anterior chamber washout was performed with the replacement of factor VIII preoperatively and postoperatively. Re-bleeding or any other complications were not experienced during surgery or postoperatively. At the first postoperative week, 20/20 visual acuity and a normal intraocular pressure without antiglaucoma medication was retained and remained stable during the 6-month follow-up. CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding.

Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology.

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.

Progressive Loss of Corneal and Retinal Nerve Fibers in Patients With Multiple Sclerosis: A 2-Year Follow-up Study.

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 (ρ = -0.468; P = 0.008), MSSS (ρ = -0.442; P = 0.01), DC density (ρ = -0.550; P = 0.001), and RNFL (ρ = 0.472; P = 0.007). The change in corneal nerve fiber length (CNFL) correlated with the change in EDSS (ρ = -0.445; P = 0.01) and MSSS (ρ = -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.

Analysis of Peripapillary Choroidal Thickness in Unilateral Amblyopia.

PURPOSE: To evaluate the peripapillary choroidal thickness (CT) in children with unilateral amblyopia using spectral-domain optical coherence tomography (SD-OCT). METHODS: One hundred and six eyes of 53 children with unilateral amblyopia and 20 eyes of 20 children with normal vision were involved in this study. Of the 53 children with unilateral amblyopia, 29 (54.7%) had hyperopic anisometropic amblyopia and 24 (45.3%) had strabismic amblyopia. Peripapillary CT was measured from 6 mm length radial B-scans at the optic nerve head using the enhanced depth imaging program of an SD-OCT (Heidelberg Engineering, Germany). Age, sex, refractive error, and best-corrected visual acuity were also recorded. RESULTS: The average peripapillary CT was greater in amblyopic eyes than in the fellow eyes of the children with amblyopia (P = 0.002), and control eyes (P < 0.001). There was no significant difference between the fellow eyes of children with amblyopia and the control eyes (P = 0.158). The average peripapillary CT was negatively correlated with axial length (AL) in amblyopic eyes (r = -0.381; P = 0.005) and fellow eyes (r = -0.392; P = 0.004) but not in control eyes (r = -0.232; P = 0.325). After adjustment for the possible effects of AL, the average peripapillary CT in amblyopic eyes was still greater than in fellow eyes (P = 0.014) and control eyes (P = 0.022). CONCLUSION: The peripapillary choroid of eyes with amblyopia was thicker than that of the fellow eyes and control eyes. No significant difference was observed between fellow eyes and control eyes.

Evaluation of Pupillary Light Reflex in Amblyopic Eyes Using Dynamic Pupillometry

Objectives: To evaluate the pupillary light reflex responses in patients with unilateral strabismic and anisometropic amblyopia using dynamic pupillometry. Materials and Methods: A total of 102 eyes of 51 patients with unilateral amblyopia were included in this cross-sectional study. Of the 51 patients, 37 (72.5%) had strabismic amblyopia and 14 (27.5%) had anisometropic amblyopia. All patients underwent complete ophthalmological examination, and pupillary light reflex responses were measured using a computerized dynamic pupillometry system (MonPack One; Metrovision, France). Initial pupil diameter; the amplitude, latency, duration, and velocity of pupil contraction; and the latency, duration, and velocity of pupil dilation were recorded. Results obtained from the patients' amblyopic and normal fellow eyes were compared using paired-samples t-test and Wilcoxon signed rank test. Results: The mean age of the patients was 11.9±6.0 years. Amblyopic eyes had longer contraction latency (p=0.009), shorter contraction duration (p=0.002), and higher dilation velocity (p=0.033) compared to fellow eyes, while other parameters did not show significant differences. In subgroup analysis, eyes with strabismic amblyopia had longer contraction latency (p=0.006) and shorter contraction duration (p=0.017), while eyes with anisometropic amblyopia had shorter contraction duration (p=0.030) when compared with fellow eyes. Conclusion: In this study, the objective records obtained by dynamic pupillometry showed that pupillary light reflex responses are affected in amblyopic eyes. This finding may shed light on unclear aspects of the pathophysiology of amblyopia.

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease.

Fabry 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/mm2, P = 0.025) and nerve fiber length (NFL) (15.9 ± 3.4 vs. 19.5 ± 4.4 mm/mm2, P = 0.012) and an increase in DC density (38.3 [17.5-97.3] vs. 13.5 [0-29.4] cells/mm2, P = 0.004) in subjects with Fabry disease compared to the healthy control subjects. The total MSSI score correlated with NFD (ρ = -0.686; P = 0.006), NFL (ρ = -0.692; P = 0.006), endothelial cell density (ρ = -0.511; P = 0.036), endothelial cell area (ρ = 0.514; P = 0.036) and α-galactosidase A enzyme activity (ρ = -0.723; P = 0.008). This study demonstrates reduced corneal sensitivity, corneal nerve fiber damage and increased DCs in subjects with Fabry disease.

In Vivo Confocal Microscopic Evaluation of Corneal Nerve Fibers and Dendritic Cells in Patients With Behçet's Disease.

Central and peripheral nervous system involvement may occur during the course of Behçet'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 (ρ = -0.463; P = 0.001) and NFD (ρ = -0.304; P = 0.034) and corneal sensitivity correlated with NFD (ρ = 0.411; P = 0.003) and NFL (ρ = 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.

Use of Corneal Confocal Microscopy to Detect Corneal Nerve Loss and Increased Dendritic Cells in Patients With Multiple Sclerosis.

Importance: 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-remitting MS 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/mm2; 95% CI, -11.04 to -2.52; P = .002), nerve branch density (mean [SE] difference, -17.94 [5.45] branches/mm2; 95% CI, -28.77 to -7.10; P = .001), nerve fiber length (mean [SE] difference, -3.03 [0.89] mm/mm2; 95% CI, -4.81 to -1.25; P = .001), and the mean peripapillary RNFL thickness (mean [SE] difference, -17.06 [3.14] µm; 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/mm2; 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 (ρ = -0.295; P = .03 for nerve fiber density and ρ = -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.

Unilateral Vision Loss without Ophthalmoplegia as a Rare Complication of Spinal Surgery.

Postoperative visual loss is an extremely rare complication of nonocular surgery. The most common causes are ischemic optic neuropathy, central retinal artery occlusion, and cerebral ischemia. Acute visual loss after spinal surgery is even rarer. The most important risk factors are long-lasting operations, massive bleedings, fluid overload, hypotension, hypothermia, coagulation disorders, direct trauma, embolism, long-term external ocular pressure, and anemia. Here, we present a case of a 54-year-old male who developed acute visual loss in his left eye after a lumbar instrumentation surgery and was diagnosed with retinal artery occlusion.

Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections.

PURPOSE: 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.

Effects of panretinal laser photocoagulation on the corneal nerve plexus and retinal nerve fiber layer in retinal vein occlusion.

PURPOSE: 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.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. RESULTS: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. CONCLUSIONS: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.