Recovery Of Corneal Sensitivity Research Articles

Corneal anesthesia following application of 0.4% oxybuprocaine hydrochloride ophthalmic solution to normal feline eyes

To evaluate the loss and recovery of corneal sensitivity after instillation of 0.4% oxybuprocaine hydrochloride solution in the normal feline eye. Eighteen European shorthair cats free of ocular disease Baseline corneal touch threshold (CTT) readings were obtained bilaterally with a Cochet-Bonnet aesthesiometer prior to treatment. Subsequently, each cat received a single drop of 0.4% oxybuprocaine ophthalmic solution in the right eye and one drop of sterile 0.9% NaCl in the left eye to serve as control. The corneal touch threshold (CTT) of both eyes was then measured 1 min after drug administration and every 5 min for 60 min. The potential for ocular irritation following oxybuprocaine application was also evaluated. Baseline CTT readings were not significantly different (P > 0.05) between the control and oxybuprocaine-treated eyes with values of 1.75 ± 0.31 cm and 1.75 ± 0.30 cm, respectively. In control eyes, mean CTT did not significantly change (P > 0.05) during the study period. By contrast, after oxybuprocaine application mean CTT was significantly reduced from baseline (P < 0.05) for 45 min. Maximal corneal anesthesia, with a CTT value of 0, was achieved at 1 and 5 min in all treated eyes. A markedly reduced mean CTT of 0.14 ± 0.23 cm was still present at 20 min. Age and gender did not significantly affect corneal anesthesia. No clinically relevant ocular side effects occurred during the observation period. This is the first study that provides objective information on the depth and duration of corneal anesthesia following instillation of oxybuprocaine in healthy feline eyes.

Evaluation of standardized endodontic paper point tear test in New Zealand white rabbits and comparison between corneal sensitivity followed tear tests.

To evaluate endodontic paper point tear test (PPTT) in rabbits and compare changes in corneal touch threshold (CTT) induced by Schirmer tear test (STT) and PPTT. Normal corneal sensitivity recovery time after both tear tests was also measured. Also, mean PPTT and STT values were obtained. Tear production of 20 eyes, from 10 rabbits, was evaluated using STT and the PPTT. Central corneal touch threshold was measured by a Cochet-Bonnet esthesiometer before any tear test was performed (zero time), immediately after the test (1min), and consecutively at 6, 11, 16, and 26min. Tests were conducted on three consecutive days: Day 1 - control condition, no tear tests performed only the CTT; Day 2 - CTT before and after PPTT; and Day 3 - CTT before and after STT. CTT values were compared using repeated measures ANOVA. Corneal touch threshold was significantly increased for at least 16min after STT, indicating STT causes corneal discomfort. No difference was found between CTT following PPTT and controls, indicating PPTT caused minimal corneal discomfort. The mean (±SD) value for STT was 5.2±1.0mm/min and for PPTT was 13.8±1.5mm/min. The aqueous fraction of rabbit's tears can be successfully measured by PPTT. This report established reference values for PPTT in rabbits. Additionally, the absence of a significant difference in CTT after PPTT compared with controls shows that PPTT is well tolerated by rabbits. Considering the improved comfort (compared with STT), accuracy, and low cost, PPTT is a bona fide method of measuring aqueous tear production in rabbits.

Effect of Macrophage Migration Inhibitory Factor on Corneal Sensitivity after Laser In Situ Keratomileusis in Rabbit

PurposeTo investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery.MethodsNew Zealand white rabbits were used in this study. A hinged corneal flap (160-µm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer.ResultsExpression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 ± 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 ± 5.57 mm in the BSS treated group, 21.92 ± 2.44 mm in the MIF treated group, and 22.42 ± 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 ± 9.65, 35.00 ± 5.48, and 29.58 ± 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF.ConclusionsTopically administered MIF plays a significant role in the early recovery of corneal sensitivity after LASIK in the experimental animal model.

Long-term comparison of full-bed deep anterior lamellar keratoplasty and penetrating keratoplasty in treating keratoconus

To compare postoperative outcomes of full-bed deep anterior lamellar keratoplasty (DALK) with penetrating keratoplasty (PK) in treating keratoconus. Seventy-five eyes of 64 patients who received full-bed DALK and 52 eyes of 51 patients who received PK between June 2000 and August 2010 were included in this retrospective study. Full-bed DALK was performed using Yao's hooking-detaching technique. PK was performed using a standard technique. Intraoperative and postoperative complications, visual acuity, rejection, graft survival, endothelial cell density, corneal sensation recovery, and re-innervation were compared between the two groups. A best correct visual acuity of 0.5 or better was achieved in 90.7% of eyes after full-bed DALK and in 92.3% of eyes after PK (P=0.75). By the fifth postoperative year, graft endothelial cell loss reached 34.6% in the PK group vs. 13.9% in the full-bed DALK group (P<0.001). There were no statistical differences in corneal sensitivity recovery or corneal re-innervation between the groups (P>0.05). Intraoperative microperforation occurred in seven out of 75 (9.3%) eyes with a temporally postoperative double anterior chamber in two eyes in the full-bed DALK group. Postoperative complications in the PK vs. the full-bed DALK groups respectively were: rejection (7.7% vs. 0%, P=0.015), high intraocular pressure (IOP) (46.2% vs. 1.3%, P<0.001), secondary glaucoma (9.6% vs. 0%, P=0.006), complicated cataract (19.2% vs. 0%, P<0.001), and wound dehiscence (9.6% vs. 0%, P=0.006). Both full-bed DALK and PK can offer long-term satisfactory visual outcomes for keratoconus. Graft rejection, secondary glaucoma, complicated cataracts, and constant endothelial cell loss were observed in eyes only after PK.

Effect of Platelet-Rich Plasma in Nerve Regeneration After LASIK

To investigate the effect of topical eye application of platelet-rich plasma (E-PRP) on the recovery of corneal sensitivity after LASIK and the anatomical recovery of the sub-basal corneal plexus as studied by confocal microscopy. This was a randomized, consecutive, controlled, prospective and masked study on 108 myopic eyes receiving LASIK. The main variables of the study were the increase in corneal sensitivity (Cochet-Bonet aesthesiometer; Luneau, Paris, France) and the aspect of the sub-basal nerve plexus (confocal microscope). Additionally, a biomicroscopic study of the epithelial status of the cornea and a subjective questionnaire were completed. Each eye of each patient was assigned to one of two groups: 54 eyes treated with balanced saline solution and 54 fellow eyes receiving PRP drops for 3 months. No significant differences were detected when the corneal sensitivity thresholds were compared at any postoperative visit in both groups (P > .05 for all comparisons). Almost identical sub-basal fiber densities were estimated for both groups before LASIK (t test, P = .66). However, the type and severity of staining detected during the slit-lamp examinations at the first and third month postoperatively were significantly less evident in the E-PRP treatment group (Wilcoxon test, P < .05). PRP drops have beneficial effects for promoting epithelial status after LASIK but have no positive effect on recovery of corneal sensitivity, probably due to the limited bioavailability of growth factors in corneal stroma when the substance is topically administered.

Comparison of corneal sensitivity, tear function and corneal staining following laser in situ keratomileusis with two femtosecond laser platforms

PurposeTo evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers.MethodsIn a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer’s test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively.ResultsThere were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P > 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P < 0.05), 1 month (P < 0 .001), and 3 months (P < 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of −6.00 diopters (D) to −11.25 D as compared with eyes that had a relatively lower level of myopia of less than −6.00 D (P < 0.001). TBUT and Schirmer’s test values were significantly diminished at 1 week postoperatively (P < 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P < 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer’s test values, or corneal staining (P > 0.05).ConclusionThis study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications.

FK962 Promotes Neurite Elongation and Regeneration of Cultured Rat Trigeminal Ganglion Cells: Possible Involvement of GDNF

Amputation of the trigeminal nerve leads to decreased corneal sensitivity and dry eye. Our previous study showed that the drug FK962 (N-[1-acetylpiperidin-4-yl]-4-fluorobenzamide) induced neurite elongation from trigeminal ganglion (TG) cells and accelerated recovery of corneal sensitivity in a rabbit model of in situ keratomileusis (LASIK) surgery. However, the molecular pathways leading to FK962-induced neurite elongation and regeneration are not well defined. Thus, the purposes of the present experiments were to determine if FK962 induces elongation and regeneration of cultured rat TG cells and to investigate the mechanism of FK962-induced neurite elongation. Mixed TG cells were cultured with or without FK962, and immunocytochemistry was used to detect stimulation of neurite elongation. Neurite regeneration was also tested in an in vitro model of neuronal ablation. ELISA was used to detect glial cell line-derived neurotrophic factor (GDNF) and somatostatin (SST) release, and mRNA expression was measured by qPCR. Antibody neutralization was used to determine the mechanism for FK962-induced neurite elongation/regeneration. FK962 enhanced elongation and regeneration of neurites in TG neurons. GDNF treatment-induced neurite elongation and GDNF antibody significantly inhibited neurite elongation induced by GDNF and FK962. Nerve growth factor (NGF) treatment also induced neurite elongation, which was inhibited by NGF antibody, but NGF antibody did not inhibit FK962-induced neurite elongation. Our data suggested that FK962 stimulated induction of GDNF from TG cells. GDNF may be a part of the signaling pathway for FK962-induced neurite elongation/regeneration in rat TG neurons.

FK962 induces neurite elongation in cultured monkey trigeminal ganglion cells

LASIK refractive surgery is widely accepted for correcting myopia. Creation of the corneal flap in LASIK surgery can lead to dry eye due to amputation of corneal sensory nerves. Previous studies in the hippocampus showed that a substituted fluorobenzamide drug, FK962, caused release of neurotrophic peptides that stimulate and control nerve activity. Our studies in rabbits also showed that FK962 accelerated extension of neuronal processes and recovery of corneal sensitivity. The purposes of the present study were to 1) determine if FK962 induces spouting and elongation of neurites in cultured monkey trigeminal ganglion (TG) cells, and 2) investigate involvement of the neurotrophic peptide GDNF in FK‐induced neurite elongation. Dissociated, cultured TG cells, containing neuronal cells and Schwann cells, were cultured for 48 hours with or without FK962. Neuronal length and elongation were evaluated by staining with antibody for neurofilament specific to neurons. Culture with GDNF, or with antibody against GDNF, was used to determine the role of GDNF in neurite elongation. Our results showed that FK962, or GDNF alone, significantly induced neurite elongation. GDNF antibody significantly inhibited neurite elongation induced by FK962 or GDNF. Our data suggested that GDNF was a mediator of FK962‐induced neurite elongation. FK962 might be a candidate drug for treatment of complications after LASIK.Dr. Shearer receives consulting fees from, and Drs. Azuma and Nakajima are employees of, Senju Pharmaceutical Co. Ltd.

Topical FK962 Facilitates Axonal Regeneration and Recovery of Corneal Sensitivity After Flap Surgery in Rabbits

To test if the drug FK962 (N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide) facilitates axonal elongation and recovery of corneal sensitivity after creation of a corneal flap in rabbits. Animal study. Primary cultures of rabbit trigeminal ganglion cells were used to test if FK962 promoted nerve elongation in vitro. A 130 μm-thick×8.6 mm-diameter flap was created in rabbit corneas where topical 10(-6) M FK962 was administered 4 times daily. After treatment of 7 days, corneal mechanical sensitivity was measured using a Cochet-Bonnet esthesiometer. Whole-mount corneal sections were prepared, sensory nerve axons were stained with antibody for neurofilament, and axonal elongation from transected nerve termini were scored using standardized criteria. Ocular pharmacokinetics modeling was used to predict permeation of topical FK962 into cornea. FK962 accelerated sprouting and elongation of neurites in cultured neuronal cells from rabbit trigeminal ganglia. In the in vivo rabbit model, distal axons from transected nerve termini in corneas disappeared soon after flap surgery; but with time, axons regenerated and elongated. Topical application of 10(-6) M FK962 for 7 days significantly enhanced axonal elongation and increased corneal sensitivity. Increased corneal sensitivity was directly and significantly correlated with axonal elongation, suggesting functional enhancement of re-innervation by FK962. Results from a rabbit model of laser in situ keratomileusis (LASIK) surgery showed that topical FK962 facilitated corneal re-innervation leading to recovery of sensitivity. Results suggested that topical application of FK962 might decrease complications in patients after LASIK surgery.

Recovery of Corneal Sensitivity, Calcitonin Gene-Related Peptide–Positive Nerves, and Increased Wound Healing Induced by Pigment Epithelial–Derived Factor Plus Docosahexaenoic Acid After Experimental Surgery

To assess function of regenerated corneal nerves in correlation with epithelial wound healing after experimental nerve damage in rabbits treated with pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA). An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with βIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation. Eight weeks after surgery, calcitonin gene-related peptide-positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial-derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area. Pigment epithelial-derived factor plus DHA promotes regeneration of calcitonin gene-related peptide-positive corneal nerves, accelerating wound healing and return of corneal sensitivity. Pigment epithelial-derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.

Treatnent of myopia and astigmatism by sub-bowman keratomileusis

Objective To analysis the clinic effect of sub-bownan keratomileusis(SBK surgery)for myopia and sastigmatism. Methods Four hundred and sixty-eight eyes from two hundred tyirty four patients with myopia or astgmatism were treated with sub-bowman keratomileusis( SBK surgery). Among them man for 102 cases(204eyes) ,woman for 232 cases(464eyes). Age from 18 ～45 ,myopia from - 1.75DS ～- 11.75DS,astigmatism degree from -0.50DC ～ -4.75DC. All the patients have elaborate check before the SBK surgery, during the surgery ,we measured the thick of cornea flap,after the surgery, we investigated such conditions:the cure effect of cornea flap, the time of recovery of corneal sensitivity, the vision in day and at night, the dazzling and glare and the symptom of dry eye. Results After sub-bowman keratonileusis (SBK surgery), the time of recovery of corneal sensitivity is about three months, and it is about six months to cure the cornea flap with original comea, the symptom of dry eye is very light, so the patients neednot to use eye drops for a long time. And the vision is well. Conclusion Because the comeal base we cut is shallow during sub-bowwwman keratomileusis( SBK surgery), there is little complication after the SBK surgery.We can saw SBK surgery will become the regard of laser in keratectomy. Key words: Sub-bowman keratomileusis(SBK surgery) ; Ametropia; Clinical effect

Corneal nerve morphology and sensitivity changes after ultraviolet A/riboflavin treatment

Collagen crosslinking induced by riboflavin and ultraviolet A irradiation (UVAR) has recently been introduced as a clinical treatment to halt or reverse the progression of keratoconus. We investigated changes in corneal sensitivity and nerve morphology as part of a comprehensive safety evaluation of this treatment. Fifty-four New Zealand white rabbits were divided into three experimental groups: UVAR with deepithelialization, UVAR without deepithelialization, and deepithelialization alone. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer before treatment and 3, 7, 14, 30, 90, and 180 days after treatment. Corneal nerve morphology was evaluated using acetylcholinesterase histochemistry staining. We found that corneal sensitivity in the center of the treated area was significantly reduced 3 days after UVAR with deepithelialization treatment compared with the corneal sensitivity of the control eye but gradually recovered to normal levels at 90 days. Corneal sensitivity after deepithelialization treatment was significantly lower than control corneal sensitivity at 3 days but was significantly higher after 30 days of recovery compared with the corneal sensitivity after UVAR with deepithelialization. Corneal sensitivity after UVAR without deepithelialization treatment had significantly decreased at 7 days compared with control corneal sensitivity but was not significantly different from control values at other measurement times. In parallel with these functional alterations, corneal nerve degeneration was visible in the treatment area by 3 days; by 7 days there was a significant decrease in nerve density. Corneal nerve sprouts were identified from neighboring non-injured nerve fibers 7 days after treatment; by 90 days, excessively regenerating nerves were observed throughout the anterior stroma. The density of corneal nerve fibers appeared normal by 180 days. Ultraviolet A/riboflavin with deepithelialization treatment resulted in corneal nerve fiber damage and subsequent regeneration in the treatment area, simultaneously accompanied by the reduction and recovery of corneal sensitivity.

Corneal Sensitivity in Keratoconus after Penetrating and Deep Anterior Lamellar Keratoplasty

Purpose: To evaluate recovery of corneal sensitivity in the graft following penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. Materials and Methods: 113 eyes of 113 patients (39 females, 74 males) were examined. All eyes had undergone corneal grafting: 39 PK, 74 DALK. Corneal sensitivity tested using the Cochet-Bonnet esthesiometer was evaluated the day before and 3 days, 3, 6, 12 and 24 months after surgery. The corneal sensitivity recovery was associated with surgical techniques (PK or DALK), age and sex of recipient and donor, cadaver time and type of preservation of the cornea. Results: The average percentage of recovery of corneal sensitivity was 91% at 2 years. Surgical techniques and other qualitative and quantitative variables did not affect the statistically significant recovery of corneal sensitivity. Conclusions: In both surgical techniques, PK and DALK, we noticed a good recovery of corneal sensitivity in 2 years.

Prolonged corneal anaesthesia by proxymetacaine hydrochloride detected by a thermal cooling stimulus

To assess the duration, depth and recovery time of anaesthesia produced by 0.5% proxymetacaine hydrochloride (proparacaine), using a thermal cooling stimulus. Seventeen non-contact lens-wearing subjects were recruited (mean age=26+/-3.6 years, range=23-39; blue iris=8, brown iris=9). Central corneal sensitivity was measured in the right eye of each patient to establish a baseline, before 20microl of either 0.5% proxymetacaine hydrochloride (p) or 0.9% unpreserved saline (s) was instilled under four experimental conditions (right eye-left eye): p-p, p-s, s-p, s-s. Corneal sensitivity was re-measured at 2, 5, 10, 15, 20, 30, 45 and 60min post-instillation. The onset of anaesthesia was observed at 2min (Wilcoxon, p<0.001), with the maximum anaesthesia occurring at 15min (Wilcoxon, p<0.001). Recovery of corneal sensitivity to baseline levels did not occur by 60min (Wilcoxon, p<0.001). No difference in onset time, depth of anaesthesia, or recovery time was noted between the blue and brown iris subjects (Mann-Whitney, p>0.05). Although the anaesthetic effect of 0.5% proxymetacaine hydrochloride continues for more than 60min, this finding does not alter current clinical practice. The extended duration, however, is of relevance to studies that use corneal anaesthesia to investigate the role of corneal nerves in the blink mechanism.

Líquido amniótico tópico: uma potencial nova alternativa para doenças da superfície ocular

Amniotic fluid bathes the fetus during intrauterine life and is in permanent contact with the fetal ocular surface in this important period of development. It contains a series of growth factors that may have multiple effects on the wound healing process. These factors are thought to accelerate the recovery of corneal sensitivity and nerve regeneration after keratorefractive procedures, and also may control scar formation and balance the ocular surface after topical application. Hundreds of different proteins have been identified in the human amniotic fluid, and the role of each still not quite understood. The outcomes obtained so far with amniotic fluid application to ocular surface diseases suggest a promising therapy. Research is underway to identify the effects of specific factors of the amniotic fluid in ocular inflammation. The purpose of this review is to report the properties and current utilizations of amniotic fluid as well as to summarize the recent studies related to the use of this fluid for ocular surface diseases.

Cyclosporine 0.05% Ophthalmic Preparation to Aid Recovery From Loss of Corneal Sensitivity After LASIK

To determine whether cyclosporine (0.05%) can safely and effectively accelerate corneal nerve regeneration after LASIK, thereby facilitating faster recovery of corneal sensitivity. This prospective, randomized, single-center clinical study comprised 44 eyes of 22 patients scheduled to undergo bilateral LASIK. One eye was randomly assigned to receive cyclosporine drops twice daily for 3 months in addition to standard postoperative LASIK medication. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer in four areas outside and five areas inside the LASIK flap preoperatively and at 1 day, 1 week, 1 month, and 3 months postoperatively. Safety parameters of best spectacle-corrected visual acuity and the incidence of adverse events were also collected. For all four points outside the LASIK flap, normal corneal sensitivity was maintained throughout the study. In addition, no significant difference was found between the cyclosporine-treated eyes and the control eyes at these points. All points within the LASIK flap except the point closest to the hinge demonstrated profound corneal hypoesthesia at 1 day, 1 week, and 1 month postoperatively with no differences noted between the control and cyclosporine-treated eyes. These same points had statistically significantly greater corneal sensitivity in the cyclosporine group relative to the control group (P< or =.011) at 3 months postoperatively. Cyclosporine was shown to significantly improve corneal sensitivity at 3 months after LASIK, which suggests that topical cyclosporine promotes enhanced corneal nerve regeneration.

Subbasal Nerve Regeneration After Penetrating Keratoplasty

To evaluate subbasal nerve regeneration, corneal sensitivity, and tear film function after penetrating keratoplasty. Twenty keratoplasty patients were assessed before and 1, 3, 6, and 12 months after penetrating keratoplasty by using noncontact corneal esthesiometry, tear breakup time measurement, the phenol red thread test, and confocal microscopy. Ten healthy control subjects were also assessed by using these techniques on 1 occasion. Subbasal nerve images were analyzed by using customized software to evaluate nerve regeneration. Before surgery, the subbasal nerve plexus could be imaged only in 11 patients because of the existence of pathology. Significant deficits in nerve morphology were apparent in these patients compared with control subjects. No subbasal nerves were detected over the 12-month postoperative period. Central corneal sensitivity decreased significantly after surgery and returned to near normal levels after 12 months. Tear breakup time was significantly shorter at 3 and 12 months after keratoplasty. There were no significant differences in the phenol red thread test results before and after surgery. There is no direct association between subbasal nerve fiber regeneration, central corneal sensitivity, and tear film stability and volume. The apparent recovery of corneal sensitivity to normal levels 12 months postoperatively, in the absence of clinically observable subbasal nerves, may be a methodologic phenomenon related to the inability of current-generation confocal microscopes to image fine regenerating nerves that mediate corneal sensibility.

Recovery of corneal sensitivity in extremely high myopia after laser sub-epithelium keratomileusis

To evaluate the changes in corneal sensitivity following laser epithelial keratomileusis (LASEK) and epiploic laser in situ keratomileusis (Epi-LASIK) in treatment of extremely high myopia. Thirty-seven eyes of 37 patients underwent LASEK and Epi-LASIK to correct myopia, their equivalent sphere ranged from -9.50 DS to -12.50 DS, astigmatism < +/- 1.50 DC. Cornea sensitivity was measured with a Cochet-Bonnet esthesiometer at central part of the cornea. Treated eyes were divided into two groups by different operation methods: Epi-LASIK group and LASEK group. After the operation, each group was divided into two sub-groups according to the eyes with or without obvious epithelium edema. Obvious epithelium sheet edema happened in 6 eyes after LASEK and 3 eyes among them were due to broken epithelium sheets during the operation. By 2 weeks, 1, 2, 3 and 6 months after Epi-LASIK, corneal sensitivity recovered to 79.31%, 84.49%, 87.92%, 92.24% and 93.98% of preoperative level, respectively. Compare to the Epi-LASIK, cornea sensitivity after LASEK recovered to 69.64%, 78.57%, 83.21%, 85.70% and 87.86% of preoperative level, respectively. The recovery of corneal sensation in LASEK group was slower than that of Epi-LASIK group. The difference between these two groups was statistically significant at 2 weeks after the operation (P < 0.05). In LASEK group, there was a trend towards a great reduction in corneal sensitivity in epithelium edema eyes and the recovery was slower in these eyes. The difference of corneal sensitivity recovery between these two sub-groups was statistically significant (P < 0.05). The recovery of corneal sensitivity in extremely high myopia after Epi-LASIK is faster than that after LASEK, and reached to the platform stage by 3 months. The epithelium sheet edema after LASEK affects corneal sensitivity recovery.

PACAP Induces Neurite Outgrowth in Cultured Trigeminal Ganglion Cells and Recovery of Corneal Sensitivity After Flap Surgery in Rabbits

To evaluate the ability of pituitary adenylate cyclase-activating polypeptide (PACAP) to induce growth of neuronal processes in cultured trigeminal ganglion cells, and to accelerate neurite outgrowth and recovery of corneal sensitivity after creation of a corneal flap in a rabbit model of laser-assisted in situ keratomileusis (LASIK) surgery. Animal study. The cDNA of rabbit PACAP was sequenced, and the expression of PACAP receptors in the trigeminal ganglia from rabbits was quantified by quantitative real-time polymerase chain reaction. Trigeminal ganglion cells were isolated from rabbits and cultured for 48 hours with or without PACAP27 (bioactive N-terminal peptide from PACAP). Cells were stained with antibody against neurofilaments, and neurite outgrowth was quantified by cell counting. In the rabbit LASIK model, a corneal flap with a planned thickness of 130 microm and 8.5 mm diameter was created with a microkeratome. The rabbits then received eyedrops containing PACAP27 four times a day for eight weeks, and corneal sensitivity was measured. Neurite outgrowth was assessed by staining histologic sections of the flap area for cholinesterase. The deduced amino acid sequence of PACAP in rabbit was identical to that of human. PACAP receptor, PAC1, was highly expressed in trigeminal ganglia from newborn and adult rabbits. PACAP27 at 1 microM induced growth of neuronal processes in cultured primary trigeminal ganglion cells. In the LASIK model, extensions of neuronal processes from amputated nerve trunks in cornea were observed after administration of eyedrops containing 1 or 10 microM PACAP27. The 10 microM PACAP27 treatment also greatly accelerated recovery of corneal sensitivity. PACAP may be a candidate drug for ameliorating dry eye after LASIK surgery.

Recovery of corneal sensitivity after laser-assisted subepithelial keratectomy

To evaluate the recovery of corneal sensitivity after laser-assisted subepithelial keratectomy (LASEK) for myopia. Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China. In this prospective interventional case series, central corneal sensitivity (CCS) was measured using a Cochet-Bonnet esthesiometer (Luneau Ophthalmologie) in 85 eyes of 50 patients before and 2 weeks, 1 month, 3 months, and 6 months after LASEK for the treatment of myopia. For analysis, the eyes were divided into 2 groups-the low-moderate myopia group (spherical equivalent [SE] -1.0 to -6.0 diopters [D]) and the high myopia group (SE -6.0 to -16.0 D)-and the correlation between ablation depth and CCS was evaluated. In both groups, a significant decrease in CCS was present at 2 weeks and 1 month. In the low-moderate myopia group, the CCS recovered to preoperative values at 3 months. In the high myopia group, recovery of CCS was slower and preoperative values were reached only at the 6-month follow-up. Measured CCS was significantly correlated with the ablation depth used at the 3-month and 6-month examinations (r = -0.262 and r = -0.264, respectively; P<.05). Recovery of corneal sensitivity began 1 month after LASEK and was completed by 3 months in eyes treated for low-moderate myopia and at 6 months in eyes with high myopia. The depth of ablation during surgery affected the recovery of corneal sensitivity.