Changes in Corneal Subbasal Nerves after Punctal Occlusion in Dry Eye Disease.

PURPOSE: To evaluate corneal subbasal nerve plexus by in vivo confocal microscopy (IVCM) following punctal occlusion in patients with moderate to severe dry eye disease (DED). MATERIALS AND METHODS: Patients with grade 3 or 4 severity of DED based on Delphi Panel dry eye severity grading scheme were enrolled in the study. Permanent inferior punctal occlusion was performed. A comprehensive ophthalmic evaluation, including Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining, conjunctival Rose bengal staining, Schirmer's test, and corneal sensation by Cochet-Bonnet esthesiometry, were performed at baseline, and 1 and 3 months after punctal occlusion. Furthermore, density and number of corneal subbasal nerves were evaluated by IVCM. RESULTS: Forty-one eyes of 23 patients with a mean age of 46.3 ± 9.0 years were enrolled. Corneal fluorescein staining, Rose bengal staining, and TBUT significantly improved at 3 months following punctal occlusion (p < .015). Corneal esthesiometry significantly increased at both postoperative visits (p < .03), and OSDI scores improved only at 3-month follow-up (p < .005). Nerve density and total number significantly increased 3 months after punctal occlusion (p < .045). Baseline nerve density had significant correlations with TBUT, fluorescein staining, Rose bengal staining (p < .012), but not with esthesiometry, Schirmer scores, or OSDI scores (p > .329). CONCLUSIONS: Corneal subbasal nerve density and total number increased following punctal occlusion in patients with moderate to severe DED. These findings were associated with improvements in corneal sensation, and signs and symptoms of DED. This emphasizes the effect of punctal occlusion in regeneration of corneal subbasal nerve plexus.

Corneal nerves anatomy, function, injury and regeneration.

The cornea is a highly innervated tissue, exhibiting a complex nerve architecture, distribution, and structural organization. Significant contributions over the years have allowed us to come to the current understanding about the corneal nerves. Mechanical or chemical trauma, infections, surgical wounds, ocular or systemic comorbidities, can induce corneal neuroplastic changes. Consequently, a cascade of events involving the corneal wound healing, trophic functions, neural circuits, and the lacrimal products may interfere in the corneal homeostasis. Nerve physiology drew the attention of investigators due to the popularization of modern laser refractive surgery and the perception of the destructive potential of the excimer laser to the corneal nerve population. Nerve fiber loss can lead to symptoms that may impact the patient's quality of life, and impair the best-corrected vision, leading to patient and physician dissatisfaction. Therefore, there is a need to better understand preoperative signs of corneal nerve dysfunction, the postoperative mechanisms of nerve degeneration and recovery, aiming to achieve the most efficient way of treating nerve disorders related to diseases and refractive surgery.

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke.

OBJECTIVES: Corneal nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater corneal nerve damage in patients with recurrent ischemic stroke. METHODS: Corneal confocal microscopy (CCM) was used to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and corneal nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects. RESULTS: Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA1c, total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14). CONCLUSIONS: Corneal confocal microscopy identified greater corneal nerve fibre loss in patients with recurrent stroke compared to patients with first stroke, despite comparable risk factors. Longitudinal studies are required to determine the prognostic utility of corneal nerve fiber loss in identifying patients at risk of recurrent ischemic stroke.

Ocular manifestations of herpes simplex virus.

PURPOSE OF REVIEW: To review ocular manifestations and complications of herpes simplex virus (HSV) and discuss recent advancements in diagnostic and treatment strategy. RECENT FINDINGS: In-vivo confocal microscopy has expanded our understanding of corneal nerve degeneration, corneal dendritic cell activity, and changes in biomechanical properties in HSV keratitis. Although currently available only as a research tool, metagenomic deep sequencing has the potential to improve diagnostic accuracy beyond the well established PCR technology, especially in atypical cases. Development of an HSV vaccine has shown some encouraging results in a murine model. New treatment options for neurotrophic cornea offer promise, specifically cenegermin nerve growth factor. SUMMARY: Ocular herpes simplex infection and its complications continue to cause significant visual burden and decreased quality of life. Familiarity with its clinical features, wider adoption of viral PCR diagnostic technology, and recognition of the need for long-term maintenance medications for recurrent or chronic cases form the basis for effective management. Metagenomic deep sequencing, the development of a herpes vaccine, and cenegermin nerve growth factor offer promise as diagnostic, preventive, and therapeutic options, respectively.

Degeneration of Corneal Sensation and Innervation in Patients with Facial Paralysis: A Cross-Sectional Study Using in Vivo Confocal Microscopy.

Purpose: Facial paralysis (FP) leads to diverse periocular complications which threats visual acuity and affects corneal nerve functionally and morphologically. This study aims to summarize the clinical ophthalmic outcomes, corneal sensation, and morphological alterations of subbasal nerve and dendritic cells (DCs) in patients with facial paralysis.Methods: We performed a cross-sectional study of 48 consecutive patients with facial paralysis at one tertiary hospital. Forty-eight healthy participants were enrolled as controls. The images of corneal nerves and epithelial DCs were detected by in vivo confocal microscopy (IVCM). Each patient received thorough ophthalmic examination, tear film function tests, corneal fluorescence staining and Cochet-Bonnet esthesiometry test. Clinical and morphologic data were compared with controls.Results: Forty patients (83.3%) showed corneal injuries from punctate epithelial defects to corneal ulcers and scars. Visual impairment and eyelid malposition were observed. Corneal sensitivity remarkably decreased (25.1 ± 23.8 mm) in the affected eyes and was correlated to diminished subbasal nerve density (P = .019, r = 0.387). Numbers of corneal main nerve trunks and branches were significantly reduced (P < .0001) while DCs were increased (P < .0001) in patients with FP when compared with controls. Nerve fiber density showed inverse association with DC density (P = .019, r = -0.389).Conclusions: Ocular complications including corneal erosions, loss of corneal sensation, visual impairment and eyelid malposition have largely affected patients with facial paralysis. Morphological changes of diminished corneal subbasal nerve and increased DCs were detected by IVCM. Corneal epithelial defect, corneal opacity, corneal sensation, dendritic cell density are factors associated with corneal subbasal nerve density. Patients with FP are suggested to have complete ophthalmic evaluation and early instruction on ocular prevention.

Corneal nerves in health and disease.

The cornea is the most sensitive structure in the human body. Corneal nerves adapt to maintain transparency and contribute to corneal health by mediating tear secretion and protective reflexes and provide trophic support to epithelial and stromal cells. The nerves destined for the cornea travel from the trigeminal ganglion in a complex and coordinated manner to terminate between and within corneal epithelial cells with which they are intricately integrated in a relationship of mutual support involving neurotrophins and neuromediators. The nerve terminals/receptors carry sensory impulses generated by mechanical, pain, cold and chemical stimuli. Modern imaging modalities have revealed a range of structural abnormalities such as attrition of nerves in neurotrophic keratopathy and post-penetrating keratoplasty; hyper-regeneration in keratoconus; decrease of sub-basal plexus with increased stromal nerves in bullous keratopathy and changes such as thickening, tortuosity, coiling and looping in a host of conditions including post corneal surgery. Functionally, symptoms of hyperaesthesia, pain, hypoaesthesia and anaesthesia dominate. Morphology and function do not always correlate. Symptoms can dominate in the absence of any visible nerve pathology and vice-versa. Sensory and trophic functions too can be dissociated with pre-ganglionic lesions causing sensory loss despite preservation of the sub-basal nerve plexus and minimal neurotrophic keratopathy. Structural and/or functional nerve anomalies can be induced by corneal pathology and conversely, nerve pathology can drive inflammation and corneal pathology. Improvements in accuracy of assessing sensory function and imaging nerves in vivo will reveal more information on the cause and effect relationship between corneal nerves and corneal diseases.

Long-term corneal subbasal nerve plexus regeneration after laser in situ keratomileusis.

PURPOSE: To analyze the recovery of the subbasal nerve plexus in corneas treated with laser in situ keratomileusis (LASIK) at least 10 years prior compared with nonoperated corneas. SETTING: Clínica Novovisión, Madrid, Spain. DESIGN: Prospective nonrandomized observational study. METHODS: Eyes that had LASIK surgery at least 10 years before (LASIK group) were compared with nonoperated healthy eyes (control group). The subbasal nerve plexus morphology (main nerves density, nerve length, nerve branches density, grade of nerve tortuosity, and reflectivity) and the dendritic cell density from the confocal images obtained with the Heidelberg Retina Tomograph II were analyzed. RESULTS: The study comprised 47 eyes (27 eyes in the LASIK group and 20 eyes in the control group). The values were significantly lower in the LASIK group compared with the control group in main nerves density (9.15 nerves/mm2 ± 3.46 [SD] versus 11.75 ± 2.86 nerves/mm2; P = .009) and nerve branches density (2.96 ± 1.99 nerves/mm2 versus 5.35 ± 3.05 nerves/mm2; P = .002). No significant differences were found in nerve length, grade of nerve tortuosity, dendritic cell density, or subbasal nerve plexus reflectivity between the two groups. CONCLUSIONS: The outcomes suggested that the subbasal corneal nerve plexus did not completely recover its preoperative pattern at least 10 years after LASIK. Both main nerves density and nerve branches density continued to be significantly lower compared with virgin corneas after a mean 13-year follow-up, although other parameters of nerve morphology (nerve length, tortuosity, and reflectivity) returned to normal levels.

The effect of the duration of diabetes on dry eye and corneal nerves.

PURPOSE: To investigate the relationship between the duration of type 2 diabetes mellitus (DM) and the ocular surface, and to address the question of why some people with lengthy DM duration are asymptomatic, whereas some people with shorter DM duration have pain or discomfort in their eyes. METHODS: Eighty-seven eyes of 87 subjects with different durations of DM and 49 eyes of 49 subjects without DM underwent Schirmer I test, tear film break-up time, sodium fluorescein staining and tear meniscus height (TMH) measurement, and completed the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire. Corneal structure and function were assessed with in vivo confocal corneal microscopy and with a corneal sensitivity esthesiometer. Both corneal nerve fiber length and inferior whorl length (IWL) were assessed as indices for neural structure. Age and gender were matched between groups. HbA1c levels >7.8% and proliferative diabetic retinopathy were exclusion criteria. RESULTS: In the DM group, compared with the non-DM group, the SPEED score was significantly higher (p = 0.013), and corneal sensitivity and IWL were lower (p < 0.001). Schirmer I test, corneal sensitivity and IWL differed significantly between the group with DM duration >10 years and the non-DM (control) group (p = 0.021, p < 0.001, p < 0.001, respectively). Schirmer I test and IWL were significantly lower in the group with DM >10 years than in the group with DM ≤10 years (p = 0.023, p < 0.001, respectively). Corneal sensitivity was positively correlated with IWL regardless of diabetes status. CONCLUSIONS: The lower SPEED score and asymptomatic feeling in people with a longer DM duration may be explained by the decreased IWL and reduced sensitivity.

Corneal neurotization.

PURPOSE OF REVIEW: Neurotrophic keratopathy is a devastating corneal condition that can lead to ocular morbidity and blindness. Current medical and surgical treatments poorly tackle the essential problem of corneal aesthesia and hence fail to provide a permanent cure. Recent advances in corneal neurotization techniques have shown promise to restore corneal nerves in neurotrophic keratopathy. This article aims at reviewing the current surgical advances, along with the current thoughts and evidence available for corneal nerve regeneration. RECENT FINDINGS: Corneal neurotization was first introduced in 2009 by Terzis et al., but recently picked up more interest since 2014. Direct and indirect neurotization are being developed, and different nerves (sural nerve, great auricular nerve) have been explored for interposition between frontal nerve branches and the cornea. New endoscopic techniques are introduced for less invasive approaches. On the corneal front, confocal microscopy and esthesiometry studies have established that the regeneration of the corneal nerves is happening 6 months after the procedure. SUMMARY: Neurotization is a budding revolutionary technique that shows promise of cure for neurotrophic corneas, but at this stage, it is still reasonably invasive and still reserved for selected patients.

Update on corneal neurotisation.

Corneal neurotisation describes surgical restoration of nerve growth into the cornea to restore corneal sensation and trophic function. It represents an exciting and effective emerging treatment for neurotrophic keratopathy. Techniques described to date involve either direct nerve transfer or an interpositional nerve graft coapted to a healthy donor nerve. We review the experience to date with particular emphasis on a detailed review of techniques, outcomes and current thoughts.

Role of corneal nerves in ocular surface homeostasis and disease.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

Current understanding of meningeal and cerebral vascular function underlying migraine headache.

BACKGROUND: The exact mechanisms underlying the onset of a migraine attack are not completely understood. It is, however, now well accepted that the onset of the excruciating throbbing headache of migraine is mediated by the activation and increased mechanosensitivity (i.e. sensitization) of trigeminal nociceptive afferents that innervate the cranial meninges and their related large blood vessels. OBJECTIVES: To provide a critical summary of current understanding of the role that the cranial meninges, their associated vasculature, and immune cells play in meningeal nociception and the ensuing migraine headache. METHODS: We discuss the anatomy of the cranial meninges, their associated vasculature, innervation and immune cell population. We then debate the meningeal neurogenic inflammation hypothesis of migraine and its putative contribution to migraine pain. Finally, we provide insights into potential sources of meningeal inflammation and nociception beyond neurogenic inflammation, and their potential contribution to migraine headache.

Corneal nerve regeneration after herpes simplex keratitis: A longitudinal in vivo confocal microscopy study.

PURPOSE: To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, cross sectional. METHODS: This study included 16 patients with a history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was performed in all subjects at baseline and then after a mean follow-up of 37.3 ±â€¯1.7 months in the patient group. Corneal subbasal nerve density and corneal sensation were compared between groups at baseline and follow-up. RESULTS: At baseline, the mean subbasal nerve density was significantly lower in both affected eyes (1.4 ±â€¯0.6 mm/mm2) and contralateral unaffected eyes (6.4 ±â€¯0.7 mm/mm2) compared with the controls (14.1 ±â€¯1.6 mm/mm2; all P < .001). At the end of follow-up, the mean nerve density in affected eyes increased to 2.8 ±â€¯0.7 mm/mm2 (P = .006), with no significant change in contralateral unaffected eyes (6.5 ±â€¯1.0 mm/mm2, P = .72). However, both eyes had lower nerve density than controls (all P < .001). Corneal sensation was significantly lower in affected eyes (2.6 ±â€¯0.6 cm) than in the control group (6.0 ±â€¯0.0, P < .001) and showed no significant change at the end of follow-up (2.5 ±â€¯0.6 cm, P = .80). Corneal sensation in contralateral unaffected eyes was not different in comparison with controls at both baseline and follow up (all p > .05). CONCLUSIONS: Our results demonstrate that although corneal nerve regeneration occurs in patients with HSV keratitis, this change is not clinically significant and does not results in changes of corneal sensation. Therefore, these patients need to be followed closely for complications of neurotrophic keratopathy and might benefit from neuro-regenerative therapies.

Endoscopic Corneal Neurotization: Technique and Initial Experience.

PURPOSE: The authors describe a minimally invasive surgical technique to re-establish corneal sensibility in a patient with neurotrophic keratopathy with the supraorbital nerve harvested endoscopically. METHODS: Pedicled contralateral supraorbital nerve was harvested endoscopically through small eyelid crease and scalp incisions and transferred to the affected eye. RESULTS: Endoscopic corneal neurotization was successfully performed with restoration of corneal sensibility and corneal epithelial integrity. CONCLUSIONS: The use of an endoscope allows for a minimally invasive approach to successful corneal neurotization with the supraorbital nerve.

Impact of herpetic stromal immune keratitis in corneal biomechanics and innervation.

PURPOSE: To study corneal innervation in eyes with history of herpetic keratitis and its correlation with corneal sensitivity and biomechanical properties. METHODS: A total of 56 eyes were included, of which 16 had a history of unilateral immune stromal herpetic keratitis, 16 were their contralateral eyes, and 20 were healthy controls. Structural analysis of corneal nerve plexus was performed by confocal microscopy. Biomechanical properties were measured with the Ocular Response Analyzer. Corneal sensitivity was assessed by contact (Cochet-Bonnet) and non-contact (Belmonte) esthesiometry. RESULTS: The eyes with a history of herpetic keratitis had reduced sensitivity for mechanical stimuli when compared to healthy eyes (1441.88 ± 83 ml/min vs. 67.9 ± 7.86 ml/min). Nerve fiber density in the corneas with a history of herpetic disease was lower (4.13 ± 2.19 U/image) than in the contralateral eyes (7.44 ± 2.9 U/image, p value = 0.01) and than in healthy controls (10.35 ± 2.01, p value < 0.0001). The best structural and functional correlation was established between the total length of nerves per section and mechanic threshold assessed by Belmonte esthesiometer (Coef. -0.58 p value < 0.0001) and between total length of nerves and corneal resistance factor (CRF) (Coef. -0.64, p value < 0.0001). CONCLUSIONS: The corneal sensitivity impairment in eyes with immune stromal herpetic keratitis can be explained by the loss of nerve fibers. Biomechanical corneal properties are affected as well. Corneal hysteresis (CH) and CRF are lower for the eyes with a history of herpetic keratitis, and also for the contralateral eye when compared to healthy controls.

Neuroanatomical Structures in Human Extraocular Muscles and Their Potential Implication in the Development of Oculomotor Disorders.

The potential role of sensory feedback from human extraocular muscles has been subjected to considerable speculation in the ophthalmic literature. Extraocular muscles pull against a fairly even load and do not initiate a stretch reflex, even when the eyes are directed toward the boundaries of their respective field of action. These unique working conditions and physiological properties have led to the notion that the sensory signal arising from receptors in extraocular muscles differs from the conventional proprioceptive signal arising from their somatic counterparts. The interest in the receptors at the myotendinous junction of human extraocular muscles has been renewed due to their alleged role in the development of binocular vision and their potential implication in the etiology of binocular vision anomalies. The idea that extraocular muscles provide knowledge of eye position and whether this function can be affected by surgical intervention has initiated several clinical and neuroanatomical studies. Many of these studies support this concept and suggest that surgical procedures that impose only minimal interference with the proprioceptive signal will give a better postoperative result. However, other studies contradict this view because the afferent capacity of the receptors can be questioned and some uncertainties remain. The purpose of this study was to review the related literature and discuss the possible role of ocular proprioceptors in relation to binocular vision and the development of eye motility disorders. [J Pediatr Ophthalmol Strabismus. 2018;55(1):14-22.].

Efficacy of 2-Month Treatment With Cord Blood Serum Eye Drops in Ocular Surface Disease: An In Vivo Confocal Microscopy Study.

PURPOSE: To investigate the morphological changes of corneal epithelium and subbasal nerves by in vivo confocal microscopy in patients with ocular surface disease (OSD) treated with cord blood serum (CBS) eye drops. METHODS: Twenty patients with OSD (mean age 61.1 ± 12.6 years) were included in this prospective 1-arm study and treated with CBS eye drops for 2 months. Corneal sensitivity, Schirmer test score, breakup time, subjective symptoms [Ocular Surface Disease Index (OSDI) and Visual Analogue Scale (VAS)], and corneal staining were evaluated before (T0) and after (T1) treatment. In vivo confocal microscopy analyzed giant epithelial cells, subbasal nerve number and tortuosity, neuromas, beading, and dendritic cells (DCs) in the central cornea. RESULTS: OSDI, Visual Analogue Scale, and Oxford grading values significantly decreased at T1 versus T0 (respectively, 44.1 ± 18.9 vs. 74.2 ± 13.9; 3.7 ± 1.5 vs. 8.9 ± 0.9; and 2.4 ± 1.1 vs. 3.3 ± 1.3; P < 0.0001), whereas corneal sensitivity, Schirmer test score, and breakup time significantly increased (respectively, 49.5 ± 2.6 vs. 47.9 ± 2.9; 3.2 ± 2.0 vs. 2.4 ± 2.2; 4.6 ± 3.1 vs. 3.8 ± 2.1; P < 0.0001). Corneal nerve morphology improved at T1 versus T0 with a higher total nerve number (3.4 ± 1.6 vs. 2.5 ± 1.6 per frame) and lower tortuosity (3.0 ± 0.7 vs. 3.5 ± 0.6) (P < 0.01). The number of patients presenting with giant epithelial cells, beading, and neuromas decreased at T1. DC density did not change after treatment. The detection of neuromas and higher DC density at T0 were associated with greater OSDI reduction at T1 (P < 0.001). CONCLUSIONS: CBS eye drops significantly improved corneal nerve morphology and subjective symptoms in patients with severe OSD. The presence of neuromas and higher dendritic cell density at baseline were associated with greater reduction of discomfort symptoms after treatment.

Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study.

PURPOSE: To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE). METHODS: Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated. RESULTS: Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 µm/frame in the SSDE group, 2150 ± 1015 µm/frame in the NSDE group and 2725 ± 687 µm/frame in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of nerve fibers was decreased in the SSDE (P < 0.001) and the NSDE groups (P = 0.06), with increased nerve tortuosity and decreased reflectivity in both groups (both P < 0.05). The density of DCs was 71.65 ± 72.54 cells/mm2 in the SSDE group, 40.33 ± 31.63 cells/mm2 in the NSDE group and 27.53 ± 5.58 cells/mm2 in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of DCs was increased in the SSDE (P < 0.001) and the NSDE groups (P = 0.07). Significant correlations were found between the nerve density and DC density (r = -0.57, P < 0.001), between the nerve density and OSDI scores (r = -0.91, P < 0.001) and between the nerve reflectivity and OSDI scores (r = -0.75, P < 0.001). CONCLUSIONS: The corneas of eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.

Relationship of the Lateral Rectus Muscle, the Supraorbital Nerve, and Binocular Coordination with Episodic Tension-Type Headaches Frequently Associated with Visual Effort.

Objective: To study the relationship between tension-type headaches and the oculomotor system in terms of binocular coordination, mechanosensitivity of the supraorbital nerve, and myofascial trigger points in the lateral rectus muscle, assessing the influence of visual effort caused by using a computer at work. Design: Observational study with blind evaluation of the response variable. Methods: Two groups were compared: 19 subjects with tension-type headaches and 16 healthy subjects, both exposed to computer use at work. A blinded assessor conducted three tests: measurement of the supraorbital nerve pressure pain threshold using a pressure algometer, evaluation of myofascial trigger points of the lateral rectus using the verbal numerical scale, and assessment of binocular coordination in smooth pursuit eye movements using an innovative video-oculography system. Tests were performed before work began and four hours later, and subjects in the headache group were examined when they presented a headache score of less than or equal to 3 on the verbal numerical scale. Results: The headache group presented a greater sensitivity of the supraorbital nerve and greater local and referred pain of the lateral rectus ( P < 0.05). Visual effort caused a significant worsening of these variables in both groups. However, binocular coordination after visual effort was only significantly affected in the headache group ( P < 0.05), primarily in horizontal movements. Conclusions: The finding of a higher alteration of the sensitivity of the supraorbital nerve, the myofascial trigger points of the lateral rectus, binocular coordination, and the significant influence of visual effort in patients with tension-type headaches suggest a new clinical perspective for problems related to tension-type headaches.

Effect of corneal cross-linking on contact lens tolerance in keratoconus.

BACKGROUND: The aim was to investigate changes in corneal sensation and rigid gas-permeable (RGP) contact lens tolerance after corneal cross-linking (CXL) on patients with keratoconus. METHODS: Thirty eyes of 30 patients, who were RGP lens intolerant, were treated with CXL. The main outcome measures were corneal sensation evaluation by Cochet-Bonnet esthesiometry, sub-basal nerve fibre assessment by corneal in vivo confocal microscopy and RGP contact lens tolerance evaluation with the Likert scale and wearing time. All eyes were evaluated preoperatively and post-operatively at one, three and six months after CXL procedure. RESULTS: The mean age was 25.3 ± 6.2 years. Preoperatively, the maximum keratometry (Kmax) in study eyes was 56.89 ± 4.60 D. Six months after CXL, it reduced to 56.03 ± 4.85 D (p = 0.01). Preoperative mean corneal sensation was 0.44 ± 0.05 g/mm2 , (range: 0.40 to 0.55); it was significantly decreased at the first month and increased to preoperative values after six months. The sub-basal nerve plexus could not be visualised in 90 per cent of the patients by confocal microscopy at one month post-operatively. Gradual restoration of corneal innervation with almost similar preoperative levels at post-operative month six was noted. There were significant differences in Likert scores between preoperative and third and sixth months after CXL. Likert scale scores correlated significantly with corneal sensitivity. CONCLUSION: It can be concluded that increased RGP contact lens tolerance after CXL may be associated with the potential role of decreased corneal sensitivity and corneal flattening after CXL.