Recovery Of Corneal Sensitivity Research Articles

Novel bisdemethoxycurcumin@phytomicelle ophthalmic solution: In vitro formulation appraisal and in vivo prompting rapid corneal wound healing evaluations

A simple and novel phytochemical-based nano-ophthalmic solution was developed for the treatment of eye diseases. This nanoformulation was produced from the mixture of the phytochemicals glycyrrhizin and alpha-glycosyl hesperidin, which serve as the phytonanomaterials that solubilize bisdemethoxycurcumin (BDMC), a promising phytochemical with strong pharmacological activities but with poor water solubility. This novel nanoformulation is a clear solution named as BDMC@phytomicelle ophthalmic solution, which was formulated using a simple preparation process. The BDMC@phytomicelles were characterized by a BDMC encapsulation efficiency of 98.37% ± 2.26%, a small phytomicelle size of 4.06 ± 0.22 nm, and a small polydispersity index of 0.25 ± 0.04. With the optimization of the BDMC@phytomicelles, the apparent solubility of BDMC (i.e., the loading of BDMC in the phytomicelles) in the simulated lacrimal fluid was 3.19 ± 0.02 mg/ml. The BDMC@phytomicelle ophthalmic solution demonstrated a good storage stability. Moreover, it did not cause irritations in rabbit eyes, and it facilitated the excellent corneal permeation of BDMC in mice. The BDMC@phytomicelles demonstrated a marked effect on the in vivo induction of corneal wound healing both in healthy and denervated corneas, as seen in the induction of corneal epithelial wound healing, recovery of corneal sensitivity, and increase in corneal subbasal nerve fiber density. These strong pharmacological activities involve the inhibition of hmgb1 signaling and the induction of VIP signaling. Overall, the BDMC@phytomicelle ophthalmic solution is a novel and promising simple ocular nano-formulation of BDMC with significantly improved in vivo profiles.

How long does the recovery of corneal sensitivity in different corneal regions take after LASEK?

To determine the corneal sensitivity recovery period after laser-assisted sub-epithelial keratectomy (LASEK) refractive surgery and investigate the effects of ablation depth on it. In this study examinations were performed on 90 right eyes of 90 people (34 males and 56 females) with an age range of 20-35 and an average of 22.26±3.8 years old. A sensation of 5 corneal regions, including the center and 4 mid-peripheral regions, i.e., nasal, inferior, temporal, and superior, each at a distance of 2 mm from the center of the cornea were measured with a Cochet-Bonnet esthesiometer device in 3-time points including before LASEK, 1 and 3mo after the surgery, respectively. LASEK was performed on individuals with stabilized myopia of -1.00 to -7.00 diopters and astigmatism of less than 2.00 diopters. Furthermore, the individuals were divided into three groups regarding ablation depth. The highest level of corneal sensitivity before surgery was related to the center of the cornea (59.1±7.76), and the highest level of corneal sensitivity loss was also related to this region. The sensation of all measured corneal regions significantly reduced 1mo postoperatively and returned to their preoperative levels 3mo after surgery (mean of 5 corneal regions in levels of preoperation: 58.2±6.48, 1mo postoperation: 57.3±5.84, 3mo postoperation: 58.2±5.49; P<0.05). A significant relationship was found between ablation depth and corneal sensitivity changes in the center and temporal regions (P<0.05). Corneal sensitivity in myopia and low astigmatism decreases after LASEK and reaches the preoperative level within 3mo. The depth of ablation during surgery affected the recovery of corneal sensitivity.

Structural and functional alterations in corneal nerves after single-step transPRK.

To evaluate the relationship between structural and functional changes of corneal subbasal nerves after single-step transepithelial photorefractive keratectomy (TransPRK). Tianjin Medical University Eye Hospital. Prospective observational study. 51 eligible candidates who underwent TransPRK for moderate myopia were included. The regeneration of corneal subbasal nerves were evaluated by in vivo confocal microscopy (IVCM) prior to surgery and at 1 week and 1 month, 3 months, 6 months, and 12 months postoperatively. The corneal sensitivity was measured by Cochet-Bonnet esthesiometer. The number of complete and incomplete blinks were recorded by LipiView interferometer. A correlation analysis was performed between these variables. 51 eyes of 51 patients were enrolled in this study. IVCM revealed that the density and length of corneal nerve decreased immediately and did not return to preoperative levels by 12 months post-TransPRK ( P < .01). The mean corneal sensitivity was slightly lower compared with preoperative levels at 1 week postoperatively ( P = .001) and then increased to baseline preoperative level within 1 month postoperatively. Mean total blink frequency and the partial blink rates had no statistically significant change postoperatively ( P = .087). There was no direct correlation between postoperative recovery of corneal sensitivity, changes in blink frequency, and regeneration of subbasal corneal nerve. The significant and prolonged decrease in corneal subbasal nerve morphology was accompanied by only a slight and transient reduction in corneal sensitivity to mechanical stimuli within 1 month after TransPRK. The results demonstrated that the structural changes of subbasal nerves were not parallel to their functional changes after TransPRK.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

Tauopathy induces degeneration and impairs regeneration of sensory nerves in the cornea

The cornea is transparent and innervated by a dense collection of sensory nerves originating from the ocular branch of the trigeminal nerve. This study was designed to comprehensively analyze alterations of corneal sub-basal nerve plexus in a mouse model of tauopathy (P301L transgenic mice) to test the possibility of using corneal nerves as a biomarker for tauopathy. Corneal sensitivity, thickness and epithelial wound healing were measured non-invasively by aeshesiometer, optical coherence tomography and fluorescein staining, respectively. Tau, corneal nerves and immune cells were examined by immunohistochemistry or Western blot. At the early stage of tauopathy, although corneal sensitivity, thickness and nerve fiber density were not greatly altered, corneal nerve abnormalities were observed in the peripheral region of young P301L mice. With aging, the density of abnormal nerves increased, while corneal sensitivity, epithelial thickness, nerve fiber density and length decreased in middle-aged P301L mice compared with WT mice. After corneal epithelial injury in young mice, no difference in reepithelialization was observed between two groups of mice, however, the regeneration of corneal nerves in P301L mice lagged behind WT mice, which was reflected by delayed recovery of corneal sensitivity, decreased corneal nerve density and length and density of CD45+ dendriform cells in P301L mice. In conclusion, our data provide compelling evidence that corneal nerves were changed in a mouse model of tauopathy in an age-dependent manner. Moreover, tau overexpression impairs corneal nerve regeneration. These results suggest that cornea may serve as a promising ocular site for the early diagnosis of tauopathy.

Efficacy of rhNGF-loaded amniotic membrane transplantation for rabbit corneal epithelial and nerve regeneration.

To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane (rhNGF-AM) on corneal epithelial and nerve regeneration in rabbit model. Freshly prepared human amniotic membrane (AM) were immersed into PBS buffer containing 100 or 500 µg/mL rhNGF for 15, 30, and 60min at 4°C. The in vitro release kinetics of rhNGF was measured with ELISA. For in vivo evaluation, the AM were immersed with 500 µg/mL rhNGF for 30min. Fifty-seven rabbits were selected to establish corneal epithelial defect model. In addition to the 19 rabbits in control group, 38 rabbits received AM transplantation with or without rhNGF after the removal of central epithelium. Corneal epithelial defect area, sub-epithelial nerve fiber density, corneal sensitivity, rhNGF contents in resident AM and corneas were measured after the surgery. rhNGF was sustained release from the AM within 14d in vitro, with the positive correlation with initial immersion concentration. The immersion of AM in 500 µg/mL rhNGF for 30min achieved the most stable release within 14d. After transplantation in rabbit cornea, a high concentration of rhNGF in resident rhNGF-AM and cornea was maintained within 8d. Corneal epithelial healing, nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rhNGF-AM transplantation when compared to simple AM transplantation (all P<0.05). Simple immersion of AM achieves the sustained release of rhNGF, and promotes corneal epithelial wound healing and nerve regeneration, as well as the recovery of corneal sensitivity in rabbit.

The structural and functional corneal reinnervation mechanism at different regions after LASIK-an in vivo confocal microscopy study.

To determine the recovery of structural and functional corneal sensory nerves within the LASIK flap in order to provide insight to more proximal corneal reinnervation and symptoms post-LASIK. Twenty participants underwent femtosecond LASIK with a superior flap hinge. Ocular Comfort Index in Chinese (OCI-C), Cochet-Bonnet esthesiometry, and in vivo confocal microscopy were conducted before surgery and 1week, 1-, 3-, and 6-months post-LASIK to measure symptoms, corneal sensitivity, nerve fiberdensity, width, and the numberofinterconnections within the flap (central and mid-temporal regions), and next to the superior flap hinge. Linear mixed models were used to compare differences between corneal regions at each time point post-LASIK and changes over time post-LASIK. Spearman's correlation tests were used to examine the associations between variables post-LASIK. The least reduction in sensitivity (P < 0.03) and in nerve fiber density (P < 0.02) was found near the flap hinge compared to other regions, but no regional differences were found in nerve fiber width and interconnections. Nerve fiberdensity and the number of interconnections at all regions within the flap recovered over time (P < 0.02). The recovery of corneal sensitivity and nerve fiber width was only seen at the central and temporal regions (P < 0.04). No association was found between sensitivity and nerve parameters, but a higher OCI-C score was associated with a lower nerve fiber density near the hinge (r = - 0.43, P = 0.003) over time post-LASIK. Corneal sensitivity and density are preserved in the hinge, but this preservation of the corneal nerve damage does not affect the nerve morphology.

The effect of nerve growth factor on corneal nerve regeneration and dry eye after LASIK

Dry eye is the most common complication after refractive surgery, especially after laser in situ keratomileusis (LASIK), in which nerves may be cut when making the corneal flap. Nerve growth factor (NGF) has been demonstrated to stimulate corneal sensitivity and nerve regeneration and NGF has been suggested as a potential treatment for dry eye disease (DED). Hence, this study aimed to investigate the effect of NGF on corneal nerve regeneration, sensitivity and dry eye symptoms after LASIK, compared to hycosan and normal saline (NS) treatments. Thirty-eight New Zealand white rabbits that underwent LASIK procedures were randomly assigned to three groups. Each group underwent NGF, hycosan, and NS treatment. The nerve densities and the number of corneal sub-basal and superficial stromal nerves were measured with confocal microscopy, and the results were compared before surgery and at one month and three months postoperatively. Corneal sensitivity was assessed with an esthesiometer. The tear breakup time (TBUT) was recorded to check for signs of dry eye. The whole corneas of the experimental animals were excised at three months after the surgery for immunohistochemically analysis. After LASIK, treatment with NGF significantly accelerated the recovery of sub-basal and superficial stromal nerve densities and the numbers, compared to hycosan and NS treatments at one month and three months postoperatively (NGF vs. hycosan, P < 0.01 each; NGF vs. NS, P < 0.01 each). The recovery of corneal sensitivity was significantly enhanced in the NGF group compared to the hycosan or NS treatment groups after surgery (P < 0.05). Also, the TBUT data showed a statistically significant longer time in the NGF group at one month, and three months postoperatively (P < 0.05). Immunofluorescence analysis showed the nerve fiber quantity of the NGF group was larger than in the hycosan and NS groups. Taken together, the experimental results suggested that mNGF had an obvious effect on promoting corneal nerve repairing and the potential to improve dry eye in different periods following LASIK.

Corneal Sensitivity and Tear Function in Recurrent Corneal Erosion Syndrome.

PurposeTo determine the association of corneal sensitivity and tear functions on the prognosis of eyes after posttraumatic recurrent corneal erosion syndrome (RCES).MethodsPatients were enrolled retrospectively and had unilateral RCES and a history of ocular surface trauma. A corneal sensitivity test and tear function test (tear break-up time and Schirmer test) were performed at three time points (month 1 to month 3, month 3 to month 6, and month 6 to month 12). Depending on the number of recurrences during the follow-up, patients were divided into group A (n > 2) or group B (n = 2). A comparison between diseased and normal fellow eyes in each patient was performed.ResultsA total of 31 patients were enrolled and divided into group A (n = 14) and group B (n = 17). The mean age was 40.3 ± 12.2 years, whereas the mean follow-up was 28.0 ± 3.6 months. During the study period, corneal sensitivity, tear break-up time, and the Schirmer test results were all lower in diseased eyes than in normal fellow eyes in both groups. Compared to the first time point, recovery of corneal sensitivity and the Schirmer test values were observed in diseased eyes in group B at the second and third time points.ConclusionsPoor corneal sensitivity and tear function are associated with posttraumatic RCES. Recovery of corneal sensitivity and tear function may be associated with a reduction of recurrence in eyes with posttraumatic RCES.

Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

SUMMARYWe focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other’s effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.

Neuroprotective Effect of Citicoline Eye Drops on Corneal Sensitivity After LASIK.

To evaluate the accelerator role of a topically administered neuroprotective eye drop (citicoline) on the recovery of corneal sensitivity after laser in situ keratomileusis (LASIK). In this prospective, controlled study, 78 eyes of 78 patients (mean age: 26.8 ± 7.6 years) were enrolled in the study group and their eyes were treated with topical citicoline three times a day for 1 month postoperatively. Seventy-eight eyes of 78 patients (mean age: 26.1 ± 7.4 years) were randomly selected as the control group and their eyes were treated with lubricant hyaluronic acid (0.15%) eye drops three times a day for 1 month. Corneal sensitivity was assessed in both groups using a Cochet-Bonnet esthesiometer at baseline and 1, 2, 3, 4, 6, 8, and 12 weeks after the LASIK procedure. Corneal sensitivity at 1, 2, 3, 4, and 6 weeks after LASIK was significantly better in the citicoline group than the control group (P < .05 for all). Differences between the groups at 8 and 12 weeks after LASIK were not significant (P > .05). Topically administered citicoline eye drops had beneficial effects in the early recovery of corneal sensitivity during the first 6 weeks after LASIK, suggesting that citicoline may play a significant role in accelerating corneal reinnervation. [J Refract Surg. 2019;35(12):764-770.].

Comparison of Visual, Refractive and Ocular Surface Outcomes Between Small Incision Lenticule Extraction and Laser-Assisted In Situ Keratomileusis for Myopia and Myopic Astigmatism.

Laser-assisted in situ keratomileusis (LASIK) is the most commonly performed laser refractive surgical technique worldwide for the treatment of myopia and myopic astigmatism. In recent years, small incision lenticule extraction (SMILE) has emerged as a promising alternative to LASIK, requiring only a single femtosecond laser to create an intrastromal lenticule, which is then removed via a small incision. The technique obviates the need for a corneal flap. A number of published studies have compared the two techniques in terms of visual, refractive and ocular surface outcomes. This review compares the clinical outcomes between LASIK and SMILE in treating myopia and myopic astigmatism based on studies published in the last 5 years. Twenty-two studies were included, all of which were observational in nature. Results suggest that the two techniques have comparable visual outcomes in terms of safety, efficacy and predictability, although recovery in visual acuity may be slower in SMILE-treated than LASIK-treated eyes. SMILE is found to result in less severe postoperative dry eye symptoms and faster recovery of corneal sensitivity than LASIK. It is important to note, however, that the SMILE technique is limited by the lack of a cyclotorsion-compensation system and option for customized treatment profile. The heterogeneity of results in this review may be attributable to the use of different LASIK platforms in different studies. Few studies compared the outcomes regarding severity of myopia. Future prospective randomized controlled trials with a larger sample size and longer follow-up period will be highly beneficial for progress in this field.

Corneal Sub-Basal Nerve Changes in Patients with Herpetic Keratitis During Acute Phase and after 6 Months.

Background and objectives: The purpose of this study was to describe corneal sensitivity and the morphological changes of sub-basal corneal nerves using in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis-affected eyes, and to compare with both contralateral eyes and with the eyes of patients with a previous history of herpes labialis but no history of herpetic eye disease, and with healthy patients with no history of any HSV diseases, during the acute phase of the disease and after six months. Materials and Methods: A prospective clinical study included 269 patients. All of them underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM within the central 5 mm of the cornea. After six months, all the patients with herpetic eye disease underwent the same examination. Serology tests of the serum to detect HSV 1/2 IgG and IgM were performed. Results: HSV-affected eyes compared with contralateral eyes, herpes labialis and healthy control group eyes demonstrated a significant decrease in corneal sensitivity, corneal nerve fibre density, corneal nerve branch density, corneal nerve fibre length and corneal nerve total branch density (p < 0.05). During follow up after six months, corneal sensitivity and sub-basal nerve parameters had increased but did not reach the parameters of contralateral eyes (p < 0.05). Previous herpes labialis did not influence corneal sensitivity and was not a risk factor for herpetic eye disease. Conclusions: Corneal sensitivity and sub-basal nerve changes in HSV-affected eyes revealed a significant decrease compared with contralateral eyes, and with the eyes of patients with a previous history of herpes labialis, and of healthy controls. Following six months, corneal sensitivity and sub-basal nerve parameters increased; however, they did not reach the parameters of contralateral eyes and the eyes of healthy controls. The best recovery of corneal sensitivity was seen in patients with epithelial keratitis. Herpes labialis was not a risk factor for herpetic eye disease.

Recovery of Corneal Sensitivity and Increase in Nerve Density and Wound Healing in Diabetic Mice After PEDF Plus DHA Treatment.

Diabetic keratopathy decreases corneal sensation and tear secretion and delays wound healing after injury. In the current study, we tested the effect of treatment with pigment epithelium-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a mouse model of diabetes with or without corneal injury. The study was performed in streptozotocin-induced diabetic mice (C57BL/6). Ten weeks after streptozotocin injection, diabetic mice showed significant decreases of corneal sensitivity, tear production, and epithelial subbasal nerve density when compared with age-matched normal mice. After diabetic mice were wounded in the right eye and treated in both eyes with PEDF+DHA for 2 weeks, there was a significant increase in corneal epithelial nerve regeneration and substance P-positive nerve density in both wounded and unwounded eyes compared with vehicle-treated corneas. There also was elevated corneal sensitivity and tear production in the treated corneas compared with vehicle. In addition, PEDF+DHA accelerated corneal wound healing, selectively recruited type 2 macrophages, and prevented neutrophil infiltration in diabetic wounded corneas. These results suggest that topical treatment with PEDF+DHA promotes corneal nerve regeneration and wound healing in diabetic mice and could potentially be exploited as a therapeutic option for the treatment of diabetic keratopathy.

Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision.

To establish determining factors for fast corneal sensitivity (CS) recovery after pterygium excision. Thirty-two eyes of 14 males and 18 females with primary nasal pterygium were recruited. Differences in CS (in the 4 quadrants and the center using a Cochet-Bonnet esthesiometer), pterygium corneal area (PCA), tear osmolarity, tear break-up time, Schirmer test, and ocular symptoms were analyzed before and 1 month after lesion excision. The relationship between CS recovery (difference between the 2 time points; CS1 - CS0) and the other features was assessed. All the studied locations exhibited normal (6 cm) or near-normal mean CS at the 2 time points, except a tendency for moderate hypoesthesia in nasal CS0 (median 4.5; range: 1.5-6.0 cm). Point by point comparison revealed significant postoperative improvements in nasal location (P = 0.008; Wilcoxon signed-rank test) with normal values in 17 eyes (53%) and a median CS1 = 5.0 cm (2.5-5.5 cm) in 15 eyes with no complete recovery. No significant correlation was found between CS0 and the studied variables, and CS1 was only significantly correlated with PCA (rho: -0.441; P < 0.05). CS recovery also showed significant correlation with PCA (rho = -0.516; P < 0.01). CS recovery after pterygium excision showed important variability, and the only studied factor that seems to be determinant could be PCA. It would be advisable to operate when the lesion is relatively small, with lower surgical injury and faster and complete recovery, thus protecting ocular surface homeostasis.

FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells.

Corneal sensation, cell proliferation, and wound healing all depend on adequate corneal innervation. Disruption of corneal innervation can lead to dry eye and delayed wound healing. Our studies in rats and rabbits show that the substituted fluorobenzamide drug FK962 accelerates the extension of neuronal processes and recovery of corneal sensitivity. The purpose of the present study was 1) to determine whether FK962 induces sprouting and elongation of neurites in cultured monkey trigeminal ganglion cells, and 2) to investigate the involvement of the neurotrophic peptide GDNF in FK962-induced neurite elongation. Dissociated, cultured trigeminal ganglion cells, containing neuronal and Schwann cells were cultured for 48h with or without FK962. Neuronal elongation was evaluated by immunostaining with a neurofilament-specific antibody. Culture with or without GDNF, or with antibody against GDNF, was used to determine the role of GDNF in FK962-induced neurite elongation. FK962 or GDNF were found to significantly induce neurite elongation. The GDNF antibody significantly inhibited elongation induced by FK962. GDNF was found to be a mediator of FK962-induced neurite elongation in a relevant primate model. FK962 may be a candidate drug for treatment of neurotrophic disorders in the human cornea.

The PEDF Neuroprotective Domain Plus DHA Induces Corneal Nerve Regeneration After Experimental Surgery.

To compare a 44-mer pigment epithelial-derived factor (PEDF) peptide with neurotrophic activity, and a 34-mer PEDF with antiangiogenic properties in association with docosahexaenoic acid (DHA) in corneal nerve regeneration after experimental surgery. A corneal stromal dissection was performed in rabbits. Treatment groups received topical 44-mer, 34-mer, or full PEDF plus DHA. Corneal sensitivity and Schirmer's test were performed weekly. Rabbits were euthanized at 2 and 4 days and 8 weeks. Two- and 4-day samples were stained for neutrophils and CD11b+ cells. Corneal nerves were stained with βIII tubulin and calcitonin gene-related peptide (CGRP) antibodies in specimens collected at 8 weeks. Subepithelial nerve plexus density was calculated. A PEDF-receptor (PEDF-R) was analyzed in rabbit corneal epithelial cells (RCEC) by Western blot and immunofluorescence. Infiltration of CD11b+cells and neutrophils was reduced by treatment with 44-mer PEDF+DHA. A 3-fold increase in subepithelial corneal nerves and CGRP-positive nerves was found in the 44-mer PEDF+DHA-treated group compared with the 34-mer PEDF+DHA- and vehicle-treated groups. There was a 75% recovery of corneal sensitivity by week 7, and Schirmer's test reached control values in the 44-mer PEDF+DHA-treated corneas at 7 weeks. A PEDF-R protein with homology to calcium-independent phospholipase A2ς was expressed in RCEC. The 44-mer PEDF+DHA, but not the 34-mer PEDF+DHA, promotes functional regeneration of damaged corneal nerves. Forty four-mer PEDF, by activating a corneal epithelial receptor, in conjunction with DHA could be a novel therapeutic agent for the treatment of neurotrophic keratitis and dry eye that develops as a result of corneal nerve damage.

Recovery of corneal sensitivity after collagen crosslinking with and without epithelial debridement in eyes with keratoconus

To evaluate the changes in corneal sensitivity after corneal collagen crosslinking (CXL) with the epithelium off (epi-off) and with the epithelium on (epi-on) in eyes with keratoconus. Prospective interventional case series. Eye Clinic, A. Fiorini Hospital, Terracina (Latina), Rome, Italy. On the basis of the corneal pachymetry at the area of topographic steepening, eyes treated with CXL were divided in 2 groups: those with a corneal thickness of 400 μm or more (epi-off) and those with a corneal thickness of less than 400 μm (epi-on). Corneal sensitivity was measured using a contact esthesiometer (Cochet-Bonnet) before treatment and 1 and 7 days and 1, 3, 6, 9, and 12 months after treatment. The study evaluated 50 CXL-treated eyes in 50 patients (25 epi-on and 25 epi-off) from January 7, 2012, to December 15, 2012. In the epi-off group, corneal sensitivity was statistically significantly reduced for up to 3 months after CXL and gradually returned to normal levels. In the epi-on group, corneal sensitivity was statistically significantly reduced for up to 7 days but was not statistically significantly different from preoperative values at other measurement times. At 7 days, the corneal sensitivity was statistically significantly lower in the epi-off eyes than in the epi-on eyes. Epi-off and epi-on CXL both caused hypoesthesia, but corneal sensitivity subsequently recovered completely. The corneal hypoesthesia was more pronounced in eyes in which the epi-off technique was used, and the recovery time was shorter for eyes treated using epi-on CXL. No author has a financial or proprietary interest in any material or method mentioned.

Small Incision Lenticule Extraction (SMILE) in 2015

Following the early work by Sekundo et al. and Shah et al., small incision lenticule extraction (SMILE) using the VisuMax femtosecond laser (Carl Zeiss Meditec) has become increasingly popular. The accuracy of the lenticule dimensions has been verified using very-high-frequency digital ultrasound and optical coherence tomography. Visual and refractive outcomes and safety have been shown to be similar to LASIK. A number of studies have demonstrated a lower reduction and faster recovery of corneal sensitivity and subbasal nerve fiber density after SMILE than LASIK, as expected since the anterior stroma is disturbed only by the small incision. The potential biomechanical advantages of SMILE have been modeled based on the nonlinearity of tensile strength through the stroma. Extraction of an intact lenticule has also given rise to new applications such as cryopreservation of the lenticule for later reimplantation, and a new procedure, endokeratophakia, in which a myopic SMILE lenticule is implanted into a hyperopic patient.

Functional properties of nerves regenerating within bioengineered corneas

AbstractBioengineered substitutes for corneal extracellular matrix based on crosslinked collagen promote nerve regeneration. Electrophysiological recording of corneal nerves at different time points after implant showed no electrical activity inside the implant 1 day‐2 months after surgery. Active mechano‐ and polymodal nerve terminals showing increased spontaneous activity in absence of intended stimulation were recorded inside the implants at 3 months. At 8 months after the implant, active mechano‐ and polymodal nociceptors, and cold thermoreceptors with normal response to natural stimulation were recorded at the implant area. Spontaneous firing of nociceptive units was higher and spontaneous activity of cold thermoreceptive units was slightly lower than in intact eyes. Corneal nerves regenerate into collagen‐based materials, starting to be functional at 3 months post surgery. This is on the basis of the recovery of corneal sensitivity with time in transplanted corneas. The altered activity observed in regenerating corneal nerves is probably due to an increased expression of ion channels induced after nerve lesion, and may explain the presence of abnormal sensations experienced by patients after keratoplasty. (SAF2011‐22500 MINECO)