Central Corneal Sensation Research Articles

A New Method to Measure Ocular Surface Sensitivity: Repeatability and Reproducibility of the Liquid Jet Esthesiometer.

To assess the reliability of the liquid jet esthesiometer (LJA) for measurement of corneal sensitivity. Two separate studies were conducted to assess intrasession repeatability (study 1) and intersession reproducibility (study 2) of corneal sensitivity measured using the LJA. Thirty participants (13 female and 17 male participants, age 23±6 years) participated in study 1 and another 30 (18 female and 12 male participants, 35±10 years) participated in study 2. For study 1, mechanical sensation threshold of the central cornea was measured three times on the same day, with a 30-min break between repeats. For study 2, central corneal sensation threshold was measured on five different days by one of eight randomly assigned examiners. Corneal sensation thresholds obtained in studies 1 and 2 were 2.3±1.0 and 2.5±1.2 μL, respectively. No significant differences between repeated measurements were obtained in either study (P≥0.19). Thresholds were lower (i.e., corneal sensitivity was higher) in female than male participants (2.1±1.0 vs. 2.7±0.9 μL in male participants, P=0.02) but were not affected by contact lens wear. Clinical reliability of the LJA was good for intrasession repeatability (coefficient of repeatability ±1.6 μL, intraclass correlation coefficient 0.74, within-subject coefficient of variation (CVW) 24%) and moderate for intersession reproducibility (Coefficient of Reproducibility ±2.2 μL, CVW 32%). Measurement variability was independent of threshold level (P=0.84). The LJA offers good clinical repeatability and is a reliable tool to measure corneal sensitivity in different population groups, regardless of stimulus thresholds. Day-to-day fluctuations in corneal sensitivity probably account for the relatively lower reproducibility.

Corneal hypersensitivity to cold stimuli in symptomatic computer users.

Prolonged computer use may result in repeated stimulation of the ocular surface due to ocular dryness, potentially leading to alterations in its sensitivity. This study aimed to evaluate the relationship between ocular symptoms and corneal sensitivity to cold and mechanical stimuli in computer users. Fifty-two young (31 ± 6 years), frequent computer users, including symptomatic and asymptomatic users, participated in this study. Mechanical and cold sensation thresholds were determined at the central cornea of one randomly selected eye of each participant using the UNSW Liquid Jet Aesthesiometer. Ocular surface symptoms and digital eye strain were assessed using the Ocular Surface Disease Index, Ocular Comfort Index, Instant Ocular Symptom Survey, and Computer Vision Syndrome Questionnaire (CVS-Q). Associations between central corneal sensation thresholds and demographic variables, patterns of digital device use, and symptom scores were analyzed using Pearson (r) or Spearman (ρ) correlations and linear regression models. Age (ρ = 0.24), CVS-Q score (ρ = -0.33), CVS-Q dry eye score (ρ = -0.28), and mechanical sensation threshold (ρ = 0.63) were significantly associated with cold sensation threshold (p≤0.04). Conversely, there were no significant relationships with Ocular Surface Disease Index, Ocular Comfort Index, or Instant Ocular Symptom Survey or with other demographic variables (p≥0.34). In multiple linear regression models, age and mechanical sensation threshold were significant predictors of cold sensitivity (p=0.04 and p<0.001, respectively) (adjusted R2 = 0.459). There were no significant correlations between mechanical sensitivity and symptom scores (p≥0.09). Symptoms of digital eye strain, particularly those related to dry eye, were associated with higher corneal cold sensitivity. Corneal hypersensitivity to cold stimuli as a marker of ocular discomfort during computer use requires further investigation.

Co-existence of Neurotrophic Keratopathy in Eyes With Limbal Stem Cell Deficiency

PurposeTo investigate whether neurotrophic keratopathy is present in limbal stem cell deficiency (LSCD) by measuring corneal sensation and characterizing corneal subbasal nerve plexus. DesignProspective, cross-sectional “case-control” comparative study. MethodsForty-six eyes with LSCD and 14 normal eyes were recruited from 2019 to 2022. Corneal sensation was measured using a Cochet-Bonnet esthesiometer and subbasal nerve plexus was imaged using in vivo confocal microscopy (IVCM) at the central cornea and 4 limbal regions. Subbasal nerve density (SND, number of nerve/mm2), subbasal nerve length (SNL, total length of nerve/mm2) and subbasal nerve branch density (SNBD, number of branch/mm2) were quantified. LSCD was graded to stage 1, 2 and 3 using a previously established staging method` consisting of clinical scores, basal cell density, central corneal epithelial thickness and SNL. ResultsThe mean (±SD) cornea sensation in the central cornea and limbus were 29.2 ± 21.5 and 33.6 ± 15.1 mm in the LSCD group and 57.6 ± 5.8 and 54.3 ± 4.7 mm in the control group, respectively (all P < 0.001). In sectoral LSCD, the sensation in the affected regions (29.1 ± 17.6 mm) decreased significantly compared to the unaffected regions (41.4 ± 18.2 mm, P < 0.001). Central corneal SND, SNL and SNBD were reduced by 84.6%, 82.6%, and 89.2%, respectively in LSCD compared to the control (all P < 0.05). The central corneal sensation negatively correlated with the severity of LSCD (rho = -0.64, P < 0.0001) and positively correlated with SND, SNL, and SNBD (rho=0.63, 0.66, and 0.56, respectively; all P < 0.001). ConclusionsCorneal sensation was reduced in eyes with LSCD. The degree of corneal sensation reduction positively correlated with the severity of LSCD. This finding demonstrated the co-existence of neurotropic keratopathy in LSCD.

Clinical outcomes of corneal neurotization using sural nerve graft in neurotrophic keratopathy.

To evaluate the efficacy of corneal neurotisation using sural nerve graft coaptation of the contralateral supratrochlear nerve in unilateral neurotrophic keratopathy and corneal anesthesia. Corneal neuralization has emerged as a potential option in the treatment of neurotropic keratopathy, however not free from the predicament. We evaluated the long-term outcome of corneal neurotisation in the treatment of unresponsive unilateral neurotropic keratopathy using surgical variations to mimic and expedient the surgical procedure. A Prospective interventional study involving patients with unilateral neurotrophic keratopathy (NK) who did not respond to medical measures was conducted. The study parameters evaluated were best-corrected visual acuity improvement, ocular surface evaluation parameters [tear break-up time (TBUT), Schirmer's 1, and ocular surface staining scores (corneal and conjunctival staining)], central corneal sensation (Cochet Bonnet esthesiometer), sub-basal nerve fiber length (SBNFL), and sub-basal nerve fiber density (SBNFD) determined by central confocal microscopy at recruitment and during follow-up at 1-month, 3-month, 6-month, 9-month and 12-month respectively, following corneal neurotization. Eleven eyes of 11 patients with unilateral neurotrophic keratopathy (NK) who underwent corneal neurotisation were studied. The mean follow-up was 10.09±2.31months (range, 6-12). Mean best corrected visual acuity in log MAR at baseline, 1.35±0.52 improved significantly to 1.06±0.76 (P = 0.012) at 3 months and continued to 0.55±0.60 (P = 0.027) at 12 months. There was a significant reduction in NK grade severity and improvement in the ocular surface as early as 1 month, and central corneal sensations (P = 0.024) as soon as 3 months. Mean corneal SBNF improved from 3.12±1.84 mm/mm2 to 4.49±1.88 at 1 month (P = 0.008), 13.31±3.61 mm/mm2 (P = 0.028) at 12 months. Mean central corneal SBNFD evident at 6 months was 1.83±2.54no/mm2 (P = 0.018) and 4.90±3.12no/mm2 (P = 0.028) at 12 months. This study substantiates the routine practice of corneal neurotisation by simplifying the intricacies observed during the procedure.

Evaluation of Corneal Nerve Regeneration After Minimally Invasive Corneal Neurotization.

To evaluate the corneal nerve regeneration after minimally invasive corneal neurotization (MICN) and to further clarify the recovery patterns of sensory and trophic functions of the corneal nerves. A retrospective cohort study based in the Shanghai Ninth People's Hospital. Eighteen patients (18 eyes) who underwent MICN for neurotrophic keratopathy due to intracranial surgery was conducted to analyze their follow-up data at 6, 12, 18, and 24 months after surgery. At 12 months postoperatively, the growth of the central and peripheral corneal nerve fiber density (CNFD) was 11.47±8.56 and 14.73±8.08n/mm 2 with subsequent improvement slowing down, and the patient's corneal epithelium defect was healed ahead of the accomplishment of corneal nerve regeneration. The number of dendritic cells also reached its peak. At 18 months postoperatively, the recovery of central and peripheral corneal sensation was 37.22±23.06mm and 39.38±18.08mm with no subsequent improvement, and the growth of the central and peripheral corneal nerve branch density (CNBD) was 29.69±11.05 and 43.75±1.41n/mm 2 , with a positive and significant correlation between corneal sensation and CNBD (at central r =0.632, P <0.005; at peripheral r =0.645, P <0.005). At 24 months postoperatively, mean CNFD, CNBD, and corneal sensation recovered significantly compared with preoperative, but a few patients' corneal sensation recovered insignificantly with good CNFD recovery and poor CNBD recovery. After MICN, the trophic function of the corneal nerve recovers before the sensory function, and in particular, the recovery of sensation is based on the coexistence of the corneal nerve trunk and branches.

Clinical Outcomes of Minimally Invasive Corneal Neurotization After Cerebellopontine Angle Neurosurgical Procedures

PurposeTo report 12 patients with neurotrophic keratopathy due to the trigeminal nerve injury after intracranial tumor surgeries underwent minimally invasive corneal neurotization and evaluate the outcomes of corneal reinnervation.MethodsTwelve patients (12 eyes) with neurotrophic keratopathy caused by the trigeminal nerve injury after intracranial surgeries received minimally invasive corneal neurotization. All the preoperative central corneal sensation was under 5 mm, and minimally invasive corneal neurotization was performed over 6 months after the intracranial surgery. Follow-up was conducted 1 week and 1 month after the surgery and then every 3 months. Twelve healthy age-matched participants were enrolled as controls. The indicators included corneal sensation, best-corrected visual acuity, corneal nerve fiber length and branch density, diameter of nerve trunk, corneal ulcer lesion ratio, and sensation of the contralateral forehead.ResultsMean follow-up was 24.7 ± 7.1 months. Mean central corneal sensation rose from 0.4 ± 1.4 to 31.7 ± 21.8 mm. Corneal nerve fiber length improved from 9.56 ± 5.00 to 14.96 ± 4.65 mm/mm2 and corneal nerve branch density and diameter of nerve trunk both increased (p < .01 and p < .05, respectively). Corneal lesion ratio decreased from 0.17 ± 0.12 to 0.10 ± 0.10 (p < .01).ConclusionsMinimally invasive corneal neurotization promotes corneal reinnervation for patients with neurotrophic keratopathy induced by the trigeminal nerve injury after intracranial surgeries. The process of corneal reinnervation after minimally invasive corneal neurotization often lasts over 12 months, and it takes about 18 months to return to a higher level. Corneal sensation and corneal nerve fiber length are related to clinical outcomes such as corneal ulcer lesion and best-corrected visual acuity. The effect on the sensation of the contralateral side forehead is temporary, and most patients can restore normal forehead sensation of the contralateral side.

Corneal Neurotization: A Meta-analysis of Outcomes and Patient Selection Factors.

Corneal neurotization describes reinnervation of the anesthetic or severely hypoesthetic cornea with a healthy local nerve or graft. Preliminary evidence has shown corneal neurotization to improve corneal sensation, visual acuity, and ocular surface health. Factors that improve patient selection and lead to better neurotization outcomes have yet to be elucidated, limiting ability to optimize perioperative decision-making guidelines. A systematic review with meta-analysis was performed of the MEDLINE and Embase databases using variations of "corneal," "nerve transfer," "neurotization," and "neurotization." The primary outcomes of interest were corrected visual acuity, NK Mackie stage, and central corneal sensation. Regression analyses were performed to identify the effects of surgical technique, duration of denervation, patient age, and etiology of corneal pathology on neurotization outcomes. Seventeen studies were included. Corneal neurotization resulted in significant improvement in NK Mackie stage (0.84 vs 2.46, P < 0.001), visual acuity (logarithm of minimum angle of resolution scale: 0.98 vs 1.36, P < 0.001), and corneal sensation (44.5 vs 0.7, P < 0.001). Nerve grafting was associated with greater corneal sensation improvement than nerve transfer (47.7 ± 16.0 vs 35.4 ± 18.76, P = 0.03). Denervation duration was predictive of preneurotization visual acuity (logarithm of minimum angle of resolution scale; R2 = 0.25, P = 0.001), and older age (ß = 0.30, P = 0.03) and acquired etiology (ß = 0.30, P = 0.03) were predictive of improved visual acuity. Corneal neurotization provides significant clinical improvement in visual acuity, NK Mackie staging, and corneal sensation in patients who experience NK. Both nerve grafting and nerve transfer are likely to yield similar levels of benefit and ideally should be performed early to limit denervation time.

Clinical Features, Risk Factors, and Therapy of Epithelial Keratitis after Cataract Surgery.

Purpose The study aimed to assess the clinical characteristics, risk factors, and therapy of epithelial keratitis after cataract surgery. Methods Medical data of 89 consecutive patients who developed epithelial keratitis after cataract surgery, including 37 patients with diabetes mellitus (37 eyes) and 52 patients without diabetes mellitus (52 eyes), were retrospectively reviewed. The clinical characteristics, risk factors, and therapy in those patients were evaluated. Results The preoperative tear film function determined by the tear breakup time, meibomian gland atrophy score, and low tear meniscus height in diabetic patients was poorer than nondiabetic patients (P < 0.001). Of diabetic patients, 83.78% (31/37) had been diagnosed with meibomian gland dysfunction before cataract surgery and treated with topical nonsteroidal anti-inflammatory drugs after cataract surgery for 44.69 ± 10.51 days, compared to 42.31% (22/52) of nondiabetic patients receiving the topical nonsteroidal anti-inflammatory treatment for 33.35 ± 5.16 days (both P < 0.001). Epithelial lesions progressed within three to four days following cataract surgery in 59.46% (22/37) of diabetic patients, versus 30.77% (16/52) of the nondiabetic patients (P=0.025). Patients with combined meibomian gland dysfunction and epithelial defects accounted for 48.65% (18/37) in the diabetic group and 25.00% (13/52) in the nondiabetic group (P < 0.001). In vivo confocal microscopy showed absence of subbasal never fibers in eyes with epithelial defects, and central corneal sensation was also significantly depressed in those eyes, but there was no significant difference between the two groups (P=0.227). Corneal ulceration and herpes simplex keratitis were found in 2.70% (1/37) and 5.41% (2/37) of diabetic patients, respectively. Amniotic membrane transplantation was required in 32.43% (12/37) of patients in the diabetic group, and the proportion was higher than 1.92% (1/52) in the nondiabetic group (P < 0.001). Average healing time of the corneal epithelium in the diabetic group was 40.62 ± 20.0 days, much longer than 21.74 ± 6.94 days in the nondiabetic group (P=0.002). Conclusion Epithelial keratitis after cataract surgery in diabetic patients has the characteristics of rapid development, severe epithelial damage, and slow repair of the corneal epithelium. Amniotic membrane transplantation is a good choice for persistent epithelial defects associated with such epithelial keratitis. Attention should be paid to the tear film function and use of topical nonsteroidal anti-inflammatory drugs in patients undergoing cataract surgery.

Functional and Structural Changes Following Corneal Neurotisation in the Management of Neurotrophic Keratopathy: UK Single Centre Series.

ObjectiveTo report the functional and anatomical outcomes including structural changes in corneal nerve density and morphology using in vivo confocal microscopy (IVCM) after corneal neurotisation in patients with neurotrophic keratopathy (NK), using a sural nerve graft.Patients and MethodsProspective study of patients undergoing corneal neurotisation for NK. Functional outcomes were measured through visual acuity, slit-lamp examination of corneal and conjunctival staining, tear production (Schirmer’s 1 test), tear film break-up time, tear film meniscus height, quality and osmolarity, central corneal thickness and corneal sensation using Cochet–Bonnet esthesiometry. Structural outcomes were assessed from changes in corneal nerve density and morphology with IVCM. Subjective outcomes were assessed using VFQ-25 and latest telephonic consultation.ResultsBetween February 2016 and April 2018, 11 corneal neurotisations were performed on 11 patients (3 males, 8 females). Median age was 43 (range 25–62) years. Mean follow-up was 14.5 (range, 4–36) months. Snellen visual acuity improved in 6 patients, corneal and conjunctival staining decreased in 10, tear film breakup time increased in 9, tear meniscus height increased in 7, Schirmers test readings increased in 4, tear film osmolarity reduced in 8 and central corneal thickness increased in 10 patients. Corneal sensation improved in nine patients. Complete IVCM data were available in five cases and demonstrated an improvement of corneal nerve density and length at 12 months.ConclusionThis series confirms the fact that the outcomes of this technique are reproducible and that corneal neurotisation surgery helps restore trophic nerve function more consistently than touch-related sensation.

Evaluation of Clinical and Histological Outcomes of Adipose-Derived Mesenchymal Stem Cells in a Rabbit Corneal Alkali Burn Model.

To assess effects of adipose-derived mesenchymal stem cells (AMSCs) in corneal alkali injuries in an experimental animal model. Twenty white New Zealand rabbits were included in the study. The animal models were randomly divided into 2 groups. Rabbits in the AMSC group (n = 10) received an intrastromal, a subconjunctival injection, and topical instillation of 0.5 ml totally of phosphate-buffered saline (PBS) containing 2 × 106 AMSCs. In the control group (n = 10), rabbits received only 0.5 ml of PBS using the same methods. A masked investigator measured the corneal sensation, anterior chamber Inflammation (ACI), and conjunctival congestion. Additionally, a blind histological and immunohistochemical evaluation was made. In the AMSC group, the central corneal sensation was increased whereas ACI and conjunctival congestion were reduced compared to the control group in the 28 days of follow-up (p < 0.05). A statistically significant difference (p < 0.05) was noted between the two groups as recorded in the above parameters. Histological analysis showed that pathological vascularization was markedly reduced in the AMSC group which was consistent with the absence of factor VIII in the immunohistochemistry sections. There is a trend towards improved clinical outcomes including corneal sensation as well as acceleration in the restoration of normal corneal architecture in corneal alkali burns treated with AMSCs, results that support the need for further research in the field.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK.

To compare the short-term impacts of femtosecond lenticule extraction (FLEx) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) on ocular surface measures and tear inflammatory mediators. This prospective comparative nonrandomized clinical study comprised 75 eyes (75 patients). Totally 20 male and 15 female patients (age 21.62±3.25y) with 35 eyes underwent FLEx, and 26 male and 14 female patients (age 20.18±3.59y) with 40 eyes underwent FS-LASIK. Central corneal sensitivity, noninvasive tear breakup time, corneal fluorescein staining, Schirmer I test, tear meniscus height, and ocular surface disease index were evaluated in all patients. Tear concentrations of nerve growth factor (NGF), interleukin-1α (IL-1α), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and matrix metalloproteinase-9 (MMP-9) were assessed by multiplex antibody microarray. All measurements were performed preoperatively, and 1d, 1wk, and 1mo postoperatively. Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1wk after the procedure (P<0.01). NGF was significantly higher 1d and 1wk after surgery in the FS-LASIK group than in the FLEx group (P<0.01). By contrast, compared to those in the FLEx group, higher postoperative values and slower recovery of tear TGF-β1, IL-1α, and TNF-α concentrations were observed in the FS-LASIK group (P<0.01). Tear concentrations of NGF, TGF-β1, TNF-α, and IL-1α were correlated with ocular surface changes after FLEx or FS-LASIK surgery. There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK. NGF, TGF-β1, TNF-α, and IL-1α may contribute to the process of ocular surface recovery.

Corneal Neurotization: A Review of Pathophysiology and Outcomes.

The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization. A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms "corneal neurotization," "corneal neurotisation," "corneal reinnervation," and "neurotrophic keratopathy" was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed. A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6-10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0-17 years) as compared with adults (ages 18-82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011). Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation

AimTo report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory...

Abstract 13: Documentation Of Improved Ocular Surface Health After Corneal Neurotisation And Reinnervation Using Magnetoencephalography And Histology

PURPOSE: Corneal sensation is a component of reflexes that protect the eye from injury and corneal nerves contain neuromediators that are necessary for corneal epithelial maintenance and healing. Patients with absent corneal innervation develop neurotrophic keratopathy, which is characterized by persistent corneal ulcerations, scarring and vision loss. Corneal neurotisation improves corneal sensation, but it remains unknown whether neurotisation improves ocular surface health. Other than functional sensory data, there remains a paucity of evidence documenting corneal reinnervation after neurotisation. Here we describe our experience with corneal neurotisation, including data documenting ocular surface health, magnetoencephalography and histology of corneal explants after corneal transplantation. METHODS: Fifteen patients receiving corneal neurotisation were followed prospectively, documenting corneal sensation, ocular surface health, and visual acuity. Corneal sensation was determined using Cochet-Bonnet esthesiometry and visual acuity assessed using best spectacle corrected visual acuity (BSCVA). Magnetoencephalography (MEG) recordings were conducted in an adult patient prior to corneal neurotisation and 8 months afterward. Tactile stimuli were applied to the left and right forehead using an inflating plastic membrane tapped to the skin surface (approx. 200 stimuli at 0.8 pulses/second). The left and right corneas were also stimulated using air-puffs adjusted to the patient’s blink reflex threshold (0.6 pulses/second for 6 minutes). Source localization was carried out on the stimulus-locked averaged evoked responses (1 to 30 Hz) at 50 millisecond latency using an event-related beam-forming algorithm and superimposed on the patient’s structural (T1) MRI. Histological and immunohistochemical analysis was performed on corneal specimens from three patients undergoing corneal transplantation after neurotisation. Nerves were identified with neurofilament antibody clone 2F11 (Dako, Canada) using the DAKO Omnis platform. Neurotised corneas were compared to corneal samples obtained from six normal controls. In one patient, additional comparison was made to corneal tissue explanted from a corneal transplant prior to neurotisation. RESULTS: Median central corneal sensation improved from 0 mm pre-operatively (range, 0 to 10) to 60 mm (range, 0 to 60) post-operatively (p < .001). After neurotisation, patients experienced fewer episodes of persistent epithelial defects and there was no further vision loss in any patient undergoing corneal neurotisation with a median follow-up of 16.4 months (range, 1.5 - 43 months). Corneal transplantation to correct pre-existing corneal scarring was uncomplicated in three patients at a median of 30 months (range, 24 - 33), with improvement in visual acuity six months post-operatively. Histological examination of explanted corneal tissue confirmed the presence of neurofilament+ axon profiles in the cornea after neurotisation. Analysis of MEG data identified a clear absence of evoked response in the anaesthetic (right) cornea prior to neurotisation. Following neurotisation, an evoked response was detected in same (right) cornea, which was localized to the ipsilateral motor cortex, suggesting that the origin of the (right) corneal sensation after neurotisation was derived from the contralateral (left) forehead. CONCLUSION: Corneal neurotisation reinnervates the cornea using axons from the contralateral face, resulting in improved ocular surface health in addition to sensation. Corneal neurotisation permits successful corneal transplantation, giving visually impaired patients a new opportunity to regain their sight.

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

PurposeTo 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).MethodsSixty-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.ResultsThe 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.ConclusionsMultiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.

Corneal nerve structure and function after long-term wear of fluid-filled scleral lens.

The aim of this study was to determine whether long-term wear of a fluid-filled scleral lens alters basal tear production, corneal sensation, corneal nerve density, and corneal nerve morphology in 2 disease categories. Patients recruited from the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment program at the Weill Cornell Medical College were categorized into 2 groups: distorted corneas (DC) or ocular surface disease (OSD). We measured tear production, central corneal sensation, subbasal nerve density and tortuosity, and stromal nerve thickness before and after long-term wear of the prosthetic device used in PROSE treatment, defined as at least 60 days of wear for a minimum of 8 hours a day. Twenty patients were included in the study. After long-term wear of the prosthetic device, tear production decreased in patients with DC (21.2 ± 8.5 to 10.4 ± 4.6 mm; P < 0.0001) but did not change in patients with OSD (7.5 ± 5.2 to 8.7 ± 7.2 mm; P = 0.71). Corneal sensation increased in the DC group (45.6 ± 9.2 to 55.0 ± 5.6 mm; P < 0.05). There was no significant change in sensation in patients with OSD (45.0 ± 8.7 to 49.1 ± 14.8 mm; P = 0.37). Subbasal nerve density, subbasal nerve tortuosity, and stromal nerve thickness remained unchanged in both DC and OSD groups after long-term wear (P > 0.05). Patients with DC had significantly reduced basal tear production and increased corneal sensation after long-term wear of the scleral lens, but patients with OSD did not show any changes in tear production or corneal sensation.

Corneal nerve alterations after Descemet membrane endothelial keratoplasty: an in vivo confocal microscopy study.

Recent studies have identified diminishment of corneal nerves as another hallmark of Fuchs endothelial corneal dystrophy. This study aimed to analyze changes in corneal nerves after Descemet membrane endothelial keratoplasty (DMEK). Twenty-five patients were assessed for nerve alterations preoperatively and 1 week, 4 months, and 20 months after DMEK surgery. Morphology of the central subbasal nerve plexus was quantified by in vivo confocal microscopy. The total nerve length (481.2 ± 81.9 vs. 1536.0 ± 123.8 μm per frame, P < 0.0001), total nerve number (2.2 ± 0.3 vs. 7.2 ± 0.5 per frame, P < 0.0001), number of main nerve trunks (1.8 ± 0.2 vs. 3.5 ± 0.3 per frame, P < 0.0001), and number of nerve branches (0.5 ± 0.2 vs. 3.7 ± 0.4 per frame, P < 0.0001) were significantly decreased 1 week after DMEK compared with preoperative measurements. Ten months postoperatively, corneal nerves recovered to preoperative values. Central corneal sensation significantly reduced postoperatively (5.1 ± 1.0 vs. 6.0 ± 0.0, P = 0.001), but recovered during follow-up (10 months: 6.0 ± 0.0). DMEK diminishes the density and the function of subbasal corneal nerves early after transplantation. However, a complete recovery of corneal nerve density and function up to preoperative values occurs within 4 to 10 months.

Corneal nerve alterations in different stages of Fuchs' endothelial corneal dystrophy: an in vivo confocal microscopy study.

To analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs' endothelial corneal dystrophy (FECD). Thirty eyes with FECD underwent in vivo confocal microscopy using the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the central subbasal corneal nerve plexus (total nerve length, total nerve number, number of main nerve trunks, number of nerve branches) as well as esthesiometry (using the Cochet-Bonnet esthesiometer) of the central cornea to determine central corneal sensation as a measure of nerve function. Findings were correlated with an age-matched control group of 30 healthy individuals. Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal thickness were performed using Spearman correlation. Depending on slit-lamp examination, all 30 eyes were classified into FECD stage 1-4 (stage 1: six eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve length (ρ = -0.8, p < 0.001), total nerve number (ρ = -0.7, p < 0.001), number of main nerve trunks (ρ = -0.6, p < 0.001), and number of nerve branches (ρ = -0.7, p < 0.001) decreased significantly with increasing FECD stages. Comparing to the visual acuity, significant positive correlations were found for total nerve length (ρ = 0.5, p = 0.012), total nerve number (ρ = 0.5, p = 0.005), number of main nerve trunks (ρ = 0.4, p = 0.017), and number of nerve branches (ρ = 0.5, p = 0.009). With central corneal thickness, there were significant inverse correlations for total nerve length (ρ = -0.6, p = 0.001), total nerve number (ρ = -0.5, p = 0.012), number of main nerve trunks (ρ = -0.4, p = 0.015), and number of nerve branches (ρ = -0.4, p = 0.017). Central corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but mildly reduced in FECD stage 4 eyes. Increasing severity of Fuchs' endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the density, as well as mild diminishment of the function, of the subbasal corneal nerve plexus in late stage of the disease.

Comparison of Dry Eye and Corneal Sensitivity between Small Incision Lenticule Extraction and Femtosecond LASIK for Myopia

PurposeTo investigate the changes in dry eye symptoms and clinical signs and corneal sensitivity after small incision lenticule extraction (SMILE) and femtosecond LASIK (femto-LASIK).DesignProspective, non-randomized comparative study.MethodsThe study included a total of 71 eyes of 71 patients; the SMILE group comprised 38 eyes of 38 patients, and the femto-LASIK group comprised 33 eyes of 33 patients. Ocular Surface Disease Index (OSDI), Tear film breakup time (TBUT), the Schirmer test without anesthesia (S1T), corneal fluorescein staining, and central corneal sensation were evaluated before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery.ResultsOSDI scores in both groups were increased immediately and returned to preoperative level at 1 month after surgeries. The TBUT values in both groups were reduced after surgeries relative to their preoperative scores. Patients in SMILE group were less likely to have corneal staining compared with those in the femto-LASIK group ([odds ratio] OR = 0.50, 95% [confidence interval] CI 0.28 to 0.93, P = 0.03). Central corneal sensitivity was decreased at all postoperative time points in both groups. However, the central corneal sensation scores in the SMILE group were greater than that in the femto-LASIK group at all of the postoperative time points (all P<0.05).ConclusionsSMILE surgeries resulted in a short-term increase in dry eye symptoms, tear film instability, and loss of corneal sensitivity. Furthermore, SMILE surgeries have superiority over femto-LASIK in lower risk of postoperative corneal staining and less reduction of corneal sensation.

The Relationship between Subbasal Nerve Morphology and Corneal Sensation in Ocular Surface Disease

The purpose of this study was to evaluate the relationship between the in vivo confocal microscopic (IVCM) morphology of subbasal corneal nerves and corneal sensitivity in patients with ocular surface disease. Ten healthy volunteers (control group), 12 patients with dry eye (dry-eye group), and 14 patients treated with IOP-lowering topical medications (glaucoma group) were included. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. IVCM of the cornea was performed and the following subbasal corneal nerves parameters were analyzed: density, number, width, number of beadings, number of branching, tortuosity, and reflectivity. One eye of each subject was included in the study. Corneal sensitivity was significantly decreased in dry-eye and glaucoma patients compared with controls. The density and number of subbasal corneal nerves were also significantly decreased in dry eye and glaucoma patients compared with controls. There was no difference in terms of subbasal nerve width, number of beadings, tortuosity, reflectivity, and number of branching between the dry-eye, the glaucoma, and the control groups. In all subjects, corneal sensitivity correlated positively with the density and number of subbasal nerves; however, in the dry-eye group, corneal sensitivity correlated with the density and the number of nerves, whereas in the glaucoma group, corneal sensitivity correlated only with the tortuosity of subbasal nerves. The relationship between corneal sensation and subbasal nerve morphology, as evaluated with IVCM, depends on the pathophysiological mechanism of ocular surface disease.