Seven-year follow-up of LASIK for myopia.

PURPOSE: To assess the long-term refractive results, subjective parameters, and late sequelae of LASIK. METHODS: A retrospective follow-up study was conducted on 38 eyes of 21 patients (17 with bilateral treatment and 4 with unilateral treatment) who had LASIK surgery between 1999 and 2000. Laser ablations were done with an excimer laser (VISX STAR and STAR S2). Follow-up was 2 months, 2 years, and > 7 years postoperatively. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, indirect ophthalmoscopy, and wavefront analysis were measured at the last follow-up and a questionnaire was answered. RESULTS: Postoperatively, BSCVA < or = 0.0 (logMAR) was obtained in 91%, 100%, and 89% of eyes at 2 months, 2 years, and at last follow-up, respectively. Postoperative spherical equivalent refraction within +/- 0.50 diopters (D) was obtained in 75%, 63%, and 42% of eyes at 2 months, 2 years, and 7 to 8 years, respectively. At 2 months and 2 years, 83% of eyes were within +/- 1.00 D, which decreased to 42% at 7 to 8 years. Mean spherical equivalent refraction at 2 months was -0.41 D, at 2 years -0.57 D, and at 7 to 8 years continued to decrease to -1.38 D. Patient satisfaction was high--100% of patients would have LASIK again. CONCLUSIONS: LASIK outcomes tend to shift toward undercorrection over time. Postoperative ectasia was not noted 7 to 8 years after LASIK. All patients were satisfied with the postoperative results although emmetropia was not reached.

Photorefractive keratectomy retreatment after LASIK.

PURPOSE: To study the results of late photorefractive keratectomy (PRK) in corneas originally subjected to LASIK. METHODS: Seven eyes of seven patients who had LASIK for myopia were retreated with PRK at least 2 years after LASIK. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, and haze were evaluated before and after LASIK and after retreatment by PRK. RESULTS: Photorefractive keratectomy retreatment improved BSCVA in six (86%) of seven eyes, and one (14%) eye showed no changes. None of the eyes lost lines of BSCVA. Five of seven eyes developed mild haze, which disappeared before the last postoperative follow-up. CONCLUSIONS: Photorefractive keratectomy retreatment performed at least 2 years after LASIK can improve visual acuity. We hypothesize that LASIK-induced corneal nerve damage disturbs corneal wound healing by increasing the tendency for development of haze.

Phototherapeutic keratectomy for epithelial irregular astigmatism: an emphasis on map-dot-fingerprint degeneration.

PURPOSE: To study the changes in irregular astigmatism in patients with recurrent corneal erosion syndrome due to map-dot-fingerprint degeneration and to demonstrate that both symptomatic and asymptomatic map-dot-fingerprint degeneration/recurrent corneal erosion syndrome may be related to irregular astigmatism, which can effectively be corrected by phototherapeutic keratectomy (PTK) or standard spherical photorefractive keratectomy (PRK). METHODS: Eleven eyes with irregular astigmatism related to map-dot-fingerprint degeneration/recurrent corneal erosion syndrome with and without changes at the slit-lamp microscope were treated with PTK or spherical PRK, which was performed with a VISX S2 or S4 excimer laser. All eyes underwent videokeratography performed pre- and postoperatively using either the Tomey TMS-2N Topographic Modeling System or EyeSys Technologies Corneal Analysis System 2000. RESULTS: Mean pre- and postoperative best spectacle-corrected visual acuity (BSCVA) was -0.18 +/- 0.14 logMAR and 0.04 +/- 0.04 logMAR, respectively. This improvement in BSCVA was statistically significant. The mean gain in Snellen lines was 2.4 +/- 2.1. Preoperative corneal videokeratography showed irregular astigmatism with an elevation pattern that was corrected in all eyes despite the fact that no astigmatic photorefractive correction was performed. CONCLUSIONS: Following PTK, eyes with irregular astigmatism related to map-dot-fingerprint degeneration showed significant improvement in BSCVA and correction of irregular astigmatism as revealed by videokeratography. This study shows that irregular astigmatism can be exclusively of epithelial origin and in some eyes abnormal corneal epithelium may create optical aberrations. This possibility should be taken into account when, for example, wavefront-guided stromal photoablation procedures are being planned.

Improvement of visual acuity following refractive surgery for myopia and myopic anisometropia.

PURPOSE: To test the hypothesis that anisometropic adults without significant amblyopia suffer from mild visual impairment probably due to aniseikonia, which might be improved by corneal refractive surgery. METHODS: Fifty-seven patients presenting with myopic anisometropia > or = 3.25 diopters (D) and 174 myopic controls appropriate for refractive surgery were included. Photorefractive keratectomy (PRK) or LASIK was performed on 57 anisometropic eyes. As 43 of the 174 myopic control patients had bilateral surgery, PRK or LASIK was performed on 217 myopic control eyes. Best spectacle-corrected visual acuity (BSCVA), refraction, and refractive correction were measured preoperatively and at 1, 3, 5 to 7, 8 to 13, and 25 months following surgery. RESULTS: Preoperative mean spherical equivalent was -7.20 +/- 2.40 D for anisometropic patients and -6.40 +/- 1.90 D for myopic patients. At 8 to 13 months postoperatively, when 23 (40%) anisometropic eyes and 94 (43%) myopic eyes were examined, the mean spherical equivalent refractions were -0.80 +/- 1.60 D and -0.30 +/- 0.60 D, respectively. Preoperatively, the mean BSCVA on a logMAR scale was -0.0143 +/- 0.0572 (Snellen 0.98 +/- 0.12) in the anisometropic group and 0.0136 +/- 0.0361 (Snellen 1.04 +/- 0.09) in the control group (P = .001). Eight to 13 months postoperatively, these values were 0.0076 +/- 0.0659 (Snellen 1.03 +/- 0.15) and 0.0495 +/- 0.0692 (Snellen 1.13 +/- 0.18) and this difference remained statistically significant (P = .012). For the myopic patients, the improvement in BSCVA reached almost maximum at 3 months, and this improvement was found to be highly significant 3 months after surgery (P = .001). The improvement in BSCVA was significantly slower for anisometropic patients and became statistically significant only after 8 to 13 months postoperatively (P = .041). CONCLUSIONS: Anisometropia reduces visual acuity in the more myopic eye and can be at least partially reversed by refractive correction. The slower improvement in BSCVA for anisometropic patients suggests plastic changes in the visual cortex following refractive surgery.

Excimer laser refractive correction of myopia after episcleral buckling for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the long-term effects of excimer laser treatment for ametropia after surgical treatment of rhegmatogenous retinal detachment (RRD) with scleral buckles. SETTING: Helsinki University Eye Hospital, Helsinki, Finland. METHODS: Ten patients (10 eyes) who had 1 or more surgeries for RRD followed by refractive surgery for myopia were retrospectively enrolled in this study and were examined after excimer laser refractive surgery. Photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK) was performed using a Star S2 excimer laser system (Visx). The best spectacle-corrected visual acuity (BSCVA), refraction, degree of anisometropia, and topographical changes were evaluated before and after the surgeries. RESULTS: All patients were free of asthenopic symptoms after refractive surgery. At the end of the follow-up, a mean of 67 months +/- 14 (SD) after refractive surgery, 6 patients were within +/-1.0 diopter of the intended correction. Compared with previously reported cohorts of myopic patients, the achieved refraction in patients who previously had a scleral buckling procedure was worse. The postoperative refraction was stable, and corneal topography did not show induced scar formation, keratectasia, or irregular astigmatism. After refractive surgery, the BSCVA improved 1 Snellen line in 3 patients and 2 lines in 1 patient. One patient lost 1 Snellen line and another patient lost 2 lines. Four patients showed no changes. New retinal complications were not observed. CONCLUSIONS: In the long-term, PRK and LASIK were safe methods for the treatment of myopia in RRD patients after scleral buckling. The predictability of myopic LASIK/PRK may be worse than generally reported in myopic cohorts.

Airbag deployment-related eye injuries.

OBJECTIVE: We studied the correlation between airbag deployment and eye injuries using 2 different data sets. METHODS: The registry of the Finnish Road Accident (FRA) Investigation Teams was analyzed to study severe head- and eyewear-related injuries. All fatal passenger car or van accidents that occurred during the years 2009-2012 (4 years) were included (n = 734). Cases in which the driver's front airbag was deployed were subjected to analysis (n = 409). To determine the proportion of minor, potentially airbag-related eye injuries, the results were compared to the data for all new eye injury patients (n = 1,151) recorded at the Emergency Clinic of the Helsinki University Eye Hospital (HUEH) during one year, from May 1, 2011, to April 30, 2012. RESULTS: In the FRA data set, the unbelted drivers showed a significantly higher risk of death (odds ratio [OR] = 5.89, 95% confidence interval [CI], 3.33-10.9, P = 2.6E-12) or of sustaining head injuries (OR = 2.50, 95% CI, 1.59-3.97, P = 3.8E-5). Only 4 of the 1,151 HUEH patients were involved in a passenger car accident. In one of the crashes, the airbag operated, and the belted driver received 2 sutured eye lid wounds and showed conjunctival sugillation. No permanent eye injuries were recorded during the follow-up. The calculated annual airbag-related eye injury incidence was less than 1/1,000,000 people, 4/100,000 accidents, and 4/10,000 injured occupants. CONCLUSIONS: Airbag-related eye injuries occurred very rarely in car accidents in cases where the occupant survived and the restraint system was appropriately used. Spectacle use did not appear to increase the risk of eye injury in restrained occupants.

Interaction of purified tear lipocalin with lipid membranes.

PURPOSE: The principal lipid-interacting protein in human tears has been reported to be tear lipocalin (Tlc). Tlc has been suggested to scavenge harmful lipophilic substances from the corneal epithelium and to maintain the integrity of the anterior tear film lipid layer by binding and releasing lipid(s) that are accommodated within the protein. Although lipids can be extracted from Tlc, it is still unclear whether Tlc can actually bind to lipid membranes and accept membrane lipids and whether it possesses lipid transfer activity. The purpose of this study was to explore the interaction of Tlc with neutral, anionic, and cationic lipid membranes and to assess the potential of Tlc to facilitate the transfer of either polar or neutral lipids in a lipid transfer assay. METHODS: The binding of Tlc to lipid membranes was assessed by a monolayer technique and fluorescence spectroscopy. The polar lipid transfer activity of Tlc was assessed with a radiometric assay based on the transfer of (14)C-phosphatidylcholine (PC) from PC-liposomes to HDL(3). The neutral lipid transfer activity of Tlc was assayed by measuring the transfer of radioactive cholesteryl ester from LDL to HDL(3). RESULTS: Purified Tlc showed significant surface activity as evidenced by an increase in surface pressure at the air-buffer interface. Likewise, it interacted actively with neutral, anionic, and cationic lipid monolayers, as evidenced by an equal increase in surface pressure despite the surface charge. Enhanced quenching of the single tryptophan residue of Tlc by pyrene and I(-) anion suggested that different protein domains are involved in the interaction of Tlc with oppositely charged lipid membranes. Finally, radiometric assays revealed that Tlc does not possess any neutral or polar lipid transfer activity between lipid vesicles or/and lipoproteins. CONCLUSIONS: Tlc interacted with lipid membranes composed of neutral, cationic, or anionic membranes, which supports a role for Tlc in the maintenance of the tear film interfaces. Tlc did not show any neutral or polar lipid transfer activity whatsoever. The findings suggest that the notion of the role of Tlc as the major lipid-transferring protein in human tears should be revised.

Acinetobacter and Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis treated with antibiotics and phototherapeutic keratectomy.

PURPOSE: To report a method of treatment for through-the-flap multibacterial ulcerative keratitis after laser in situ keratomileusis (LASIK). METHODS: Bacterial ulcerative keratitis after LASIK was treated with topical and systemic antibiotics followed by flap lifting, cleaning, and phototherapeutic keratectomy (PTK). Follow-up examinations included in vivo confocal microscopy, corneal topography, and wavefront analysis. RESULTS: Rapid recovery of the ulcerative keratitis was observed after flap lifting and cleaning of the interface and PTK combined with topical and systemic antibiotics. Two years postoperatively, corneal topography showed a slight depression of the ulcer area and decentration of the photoablation. Wavefront analysis revealed an irregular scan with a pronounced coma-like aberration, which with a wavefront-guided custom test lens correction provided 20/16 visual acuity. CONCLUSIONS: Ulcerative bacterial keratitis is a possible sight-threatening complication of LASIK refractive surgery. Lifting and rinsing the flap combined with cleaning of the flap interface with PTK may be helpful in these conditions when regression of the ulcer does not occur with topical and oral antibiotic treatment.

Long-term corneal morphology after PRK by in vivo confocal microscopy.

PURPOSE: To examine human corneal morphology and nerve recovery 5 years after photorefractive keratectomy (PRK). METHODS: Fourteen eyes of 14 patients (ages, 27-53 years) who underwent 6-mm diameter PRK for low to moderate myopia (spherical equivalent [SE] -2.5 to -8.0 D) were examined once 5 years after surgery. Nine healthy individuals served as control subjects. Standard biomicroscopy, manifest refraction, and visual acuity tests were performed. The morphology of the corneas was examined by in vivo confocal microscope. Thicknesses of the epithelium and stroma, as well as the density of corneal opacity (haze) were obtained from digital image analysis of the confocal microscopy through-focusing (CMTF) scans. RESULTS: Confocal microscopy revealed increased reflectivity in the subepithelial extracellular matrix, keratocyte nuclei and processes in all patients. The mean objective haze estimate was 166.7 U (range, 50-390) in control corneas compared with a mean of 225.9 U (range, 125-430, P = 0.15) in the post-PRK corneas. The density of the subbasal nerve fiber bundles in post-PRK corneas (mean, n = 4.2; range, n = 1-7 per field of view) was not significantly lowered from that in control subjects (mean, n = 4.9; range, n = 3-6; P = 0.56). Bowman's layer was undetectable in all post-PRK corneas. Clinically, slit-lamp-observed trace of haze in four corneas correlated positively with the ablation depth (P = 0.016) and the thickness of the haze area (P = 0.006) in the confocal microscope. CONCLUSIONS: In vivo confocal microscopy demonstrates the presence of morphologic alterations even 5 years after PRK. However, these alterations are overcome by cellular and neural recovery and do not seem to interfere with visual performance.

Corneal innervation and morphology in primary Sjögren's syndrome.

PURPOSE: To analyze the in vivo morphology of the different corneal sublayers and corneal nerves in primary Sjögren's syndrome (SS). METHODS: Ten eyes of 10 patients with primary SS and 10 eyes of 10 sex- and age-matched control subjects were investigated. Diagnosis was based on American-European consensus criteria. In vivo confocal microscopy with through-focusing was used to investigate corneal morphology and to measure corneal sublayer thickness. RESULTS: Epithelial punctate staining with fluorescein was observed in 6 of 10 SS and none of 10 control corneas. In addition, Schirmer I test results were significantly lower in SS. Epithelial thickness did not differ between the SS and control groups. Confocal microscopy revealed patchy alterations or irregularities in surface epithelial cells in 6 of 10 SS corneas, whereas the basal epithelium appeared normal in all corneas. Average corneal thickness was lower in the SS group (515.9 +/- 22.0 micro m) than in the control (547.4 +/- 42.0 micro m; P = 0.050, t-test). Accordingly, the mean intraocular pressure was lower in the SS group (13.9 +/- 2.1 mm Hg) than in the control (16.7 +/- 2.9 mm Hg; P = 0.022). The subbasal nerve plexus and stromal nerve fiber bundles were present in all corneas. No difference was noted in nerve density. However, in 4 of 10 SS eyes, the subbasal nerve plexus showed structures resembling nerve sprouting, suggesting ongoing active neural growth. None of the control corneas exhibited such features. Signs of anterior keratocyte activation were observed in 5 of 10 SS corneas. CONCLUSIONS: In SS, the corneal surface epithelium was irregular and patchy. Anterior keratocytes frequently showed morphologic features of activation. The subbasal nerve fiber bundles revealed abnormal morphology, and the central corneal thickness was reduced by stromal thinning. The findings confirm epithelial, stromal, and neural abnormalities in the corneas of patients with SS.

Activation of matrix metalloproteinase-8 by membrane type 1-MMP and their expression in human tears after photorefractive keratectomy.

PURPOSE: Matrix metalloproteinases (MMPs) play a central role in the wound-healing process. The objective of this study was to identify and characterize the levels and molecular forms of human tear fluid collagenase-2 (MMP-8) and membrane type 1-MMP (MT1-MMP or MMP-14) in patients who had undergone excimer laser photorefractive keratectomy (PRK) and in healthy subjects. Whether MT1-MMP activates pro-MMP-8 was also determined. METHODS: Tear fluid samples were collected with scaled and blunted microcapillaries from healthy control subjects and, on the second postoperative day, from patients who had undergone PRK. Time and the volume collected were registered. Molecular forms and levels of pro and active MMP-8 and MT1-MMP in these samples were determined by Western immunoblot analysis, quantitated by computer scanning. The concentration of MMP-8 was also determined by immunofluorescence assay. The conversion of pure human polymorphonuclear neutrophil (PMN) pro-MMP-8 to the active form by the catalytic domain of MT1-MMP was studied by Western immunoblot analysis. RESULTS: The tear fluid flow was increased after PRK. Tear fluid flow-corrected excretion of MMP-8 was significantly higher in PRK-treated patients, as assessed by immunofluorescence assay and quantitative Western immunoblot analysis. The major MMP-8 species detected in tears of both PRK-treated patients and healthy control subjects represented latent and active 75- and 65-kDa highly glycosylated MMP-8 isoforms. The less-glycosylated 45- to 55-kDa MMP-8 isoform was not detectable. Tear fluid flow-corrected secretion of MT1-MMP was significantly higher in PRK-treated patients. Soluble 80-kDa MT1-MMP immunoreactivities were detected in tears of both healthy control subjects and PRK-treated patients, and may represent a complex captured by tissue inhibitor of metalloproteinase (TIMP)-2. Human PMN pro-MMP-8 was converted to the active form by MT1-MMP, and TIMP-2 prevented this activation. CONCLUSIONS: Corneal renewal eventually occurs at a high rate and is affected by the rate of corneal collagen and other matrix protein breakdown. Accordingly, tear fluid MMP-8 and MT1-MMP levels were shown to be constantly high in normal subjects. With PRK, a fast wound-healing process was associated with even higher MMP-8 and MT1-MMP levels and their activation. The results suggest a role for a MMP-8 and MT1-MMP network in the corneal wound-healing cascade. Furthermore, MT1-MMP (MMP-14) seems to activate pro-MMP-8.

Recovery of corneal sensitivity to mechanical and chemical stimulation after laser in situ keratomileusis.

PURPOSE: To evaluate the time course of changes in corneal sensitivity to mechanical and chemical stimuli produced by laser in situ keratomileusis (LASIK) in humans. METHODS: We performed a cross-sectional study of 17 LASIK-operated eyes (VisX S2, equipped with version 2.50-3.10 software) and 15 control eyes of 17 individuals to evaluate regeneration of corneal sensitivity after LASIK. Gas pulses of variable flow and compositions were applied to the cornea by a non-contact gas esthesiometer. Mechanical stimuli consisted of air puffs at flows from 0 to 200 ml/min. Chemical stimulation was made with gas pulses containing 0% to 80% CO2 in air at subthreshold flow. Mechanical and chemical thresholds and intensity-response curves for the evoked sensations were determined prior to surgery, and 7 to 9 days, 3 to 5 months, and 1.5 to 2.5 years after surgery. RESULTS: Corneal sensitivity to mechanical stimulation was enhanced 7 to 9 days after surgery but subsequently dropped markedly and remained significantly below control levels 3 to 5 months after LASIK. Sensitivity to both mechanical and chemical types of stimuli was close to normal 2 years postoperatively. CONCLUSIONS: Corneal sensitivity decreased immediately after LASIK but mechanical sensitivity showed a transient hyperesthesia 7 to 9 days afterward. Subsequently, a long-lasting and deep hypoesthesia to mechanical and chemical stimuli was observed. Gas esthesiometry revealed that disturbances of corneal sensation still exist at times when coarse mechanical sensitivity appeared to be normal.

Keratocyte activation and inflammation in diffuse lamellar keratitis after formation of an epithelial defect.

PURPOSE: To examine the inflammatory reaction in acute or late-onset post-laser in situ keratomileusis (LASIK) diffuse lamellar keratitis (DLK) associated with an epithelial defect. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: Six consecutive LASIK patients presented with stage 2 to 3 unilateral DLK 1 to 4 days after formation of an epithelial detachment (intraoperatively or up to 19 months postoperatively). Five corneas of 5 DLK patients, 1 eye twice, were examined by corneal in vivo confocal microscopy 1 to 8 days after the appearance of the epithelial defect. Confocal microscopy of conjunctival venules was performed in 2 of 6 DLK patients to quantify leukocyte rolling and extravasation. Corneas of 5 patients and conjunctival venules of 4 patients who had uneventful LASIK served as controls. RESULTS: Two of the 4 patients examined 0 to 1 day after the onset of DLK presented with small objects, presumably inflammatory cells (diameter 6.0 to 10.0 microm), in the LASIK flap interface. A third patient examined 1 day after the onset of DLK had larger objects (approximately 13.0 microm in diameter) in the interface. Three other cases (1 to 7 days after the onset of DLK) showed changes typical of keratocyte activation and altered extracellular matrix. All cases healed completely following treatment with steroids. Control LASIK subjects showed some keratocyte activation on day 5. CONCLUSIONS: Neither uneventful LASIK nor DLK induced an inflammatory reaction displaying leukocyte rolling in conjunctival venules or extravasation into the conjunctival stroma. Diffuse lamellar keratitis related to an epithelial defect does not always lead to the appearance of inflammatory cells in the flap interface. The corneal manifestations of epithelial defect-related DLK may originate from sterile epithelial-stromal or inflammatory cell-stromal cell interactions, leading to alteration of the keratocyte phenotype.

Late traumatic dislocation of laser in situ keratomileusis flaps.

We present 2 patients with late traumatic laser in situ keratomileusis flap dislocation 8 months and 17 months after surgery. One patient had a sharp trauma that caused a partial laceration and the second patient had a blunt trauma that caused a dislocation of the flap. The corneas were examined with slitlamp microscopy, computed corneal topography, and confocal microscopy. One flap was repositioned surgically; the other was treated conservatively with an eye patch. The final visual outcomes were good and illustrate the benefit of immediate attention and flap repositioning.

In vivo confocal microscopy of Fleck dystrophy and pre-Descemet's membrane corneal dystrophy.

PURPOSE: To assess the value of in vivo confocal microscopy (CM) in the diagnosis of Fleck dystrophy and pre-Descemet's membrane corneal dystrophy. METHODS: Case report of two patients. Standard slit-lamp and ophthalmic examination and in vivo CM were performed on both patients. The thickness of the cornea and the morphology of the corneal epithelium, stroma, endothelium, and subbasal nerves were evaluated by confocal microscopy. RESULTS: Biomicroscopy revealed bilateral, fine, dust-, and flour-like opacities in the corneal stroma for the Fleck dystrophy patient. In the pre-Descemet's membrane corneal dystrophy patient, biomicroscopy showed opacities larger than those in the first patient. Both patients were then examined by in vivo CM. Confocal microscopy of the Fleck dystrophy showed intracellular deposits throughout the stroma. In pre-Descemet's membrane corneal dystrophy, however, these and the extracellular deposits were observed immediately anterior to Descemet's membrane. The thicknesses of the corneas were 560 and 650 microm for Fleck and pre-Descemet's membrane corneal dystrophy, respectively. The surface epithelium, subbasal nerves, and endothelium showed normal morphology in both patients. CONCLUSION: In vivo CM is a valuable tool in diagnosing rare corneal dystrophies when the final diagnosis is difficult to obtain with conventional methods.

In vivo confocal microscopy after herpes keratitis.

PURPOSE: To describe the confocal microscopic findings, with special reference to corneal subbasal nerves, after herpes simplex virus (HSV) keratitis. METHODS: In this study, 16 HSV eyes and 14 contralateral eyes of 16 patients, diagnosed with unilateral HSV keratitis 1-12 months earlier by the presence of dendritic corneal ulceration or microbiologic confirmation, were examined by in vivo confocal microscopy for evaluation of corneal morphology. RESULTS: Herpes simplex virus eyes: In 2 eyes the surface epithelial cells appeared large, and no abnormalities were observed in the basal epithelial cells. In 2 eyes subbasal nerve fiber bundles were completely absent, in 3 eyes there was a reduced number of long nerve fiber bundles, and in 11 eyes the subbasal nerve plexus appeared normal. In 10 corneas, highly reflective dendritic structures were found at the level of the basal epithelial cells. Frequently these structures were found in the vicinity of stromal fibrosis. Areas with increased abnormal extracellular matrix were found in 11 eyes. Stromal nerves were not visualized in all corneas, but appeared normal when observed. Contralateral eyes: No abnormalities were observed in the epithelium. All corneas presented with a normal subbasal nerve plexus, but in 2 eyes dendritic particles were observed. Three corneas presented with activated keratocytes and increased amounts of abnormal extracellular matrix. CONCLUSIONS: When visualized by confocal microscopy, the subbasal nerve plexus appears relatively unaffected in cases with resolved HSV keratitis. Unidentified dendritic structures, presumably Langerhans cells, are frequently seen at the level of the basal epithelium in corneas with a history of herpetic disease.

Corneal innervation, corneal mechanical sensitivity, and tear fluid secretion after transscleral contact 670-nm diode laser cyclophotocoagulation.

PURPOSE: To examine the effect of 670-nm diode laser cyclophotocoagulation on corneal morphology, density of corneal subbasal nerves, corneal mechanical sensitivity, and the rate of tear fluid secretion in human eyes. PATIENTS AND METHODS: Transscleral contact cyclophotocoagulation was performed in 10 eyes of 10 consecutive patients on 180 degrees of the pars plicata of the ciliary body, using a 670-nm diode laser (power = 430 mW, application time = 10 seconds). In vivo confocal microscopy, with special attention to corneal morphology and the density of the subbasal nerves in the central and inferior perilimbal cornea, was performed preoperatively, and at 3 days and 1 month postoperatively. Corneal mechanical sensitivity was tested preoperatively, and at 3 days and 1 month postoperatively, using a Cochet-Bonnet esthesiometer. The rate of tear fluid secretion was measured preoperatively and 1 month postoperatively, using the Schirmer basic secretion tear test with topical anesthesia. RESULTS: After cyclophotocoagulation, in vivo confocal microscopy did not reveal any changes in any of the corneal layers or in the corneal subbasal nerves. After treatment, as compared with baseline (paired samples test, > 0.05), there was no statistically significant change in the mechanical sensitivity values in any part of the cornea or in the Schirmer basic secretion tear test result. CONCLUSION: The results of this preliminary study suggest that cyclophotocoagulation with the 670-nm diode laser does not impair corneal innervation.

Peripheral hypertrophic subepithelial corneal degeneration - clinical and histopathological features.

PURPOSE: To refine the diagnostic criteria for peripheral hypertrophic subepithelial corneal degeneration (PHSD) and characterize its clinical phenotype, histopathology and immunohistochemical features. METHODS: Diagnostic criteria were refined on the basis of literature data. Fourteen patients (13 women and one man; median age 52 years, range 33-66) were identified based on these criteria. Keratectomy specimens were evaluated via routine and immunohistochemical stainings. The main outcome measures were symptoms, clinical phenotype, immunological status and histopathologic results. RESULTS: We defined the diagnostic criteria of typical PHSD as elevated circumferential and perilimbal subepithelial fibrosis with focal superficial corneal neovascularization, which were supported by female sex (93%), bilaterality (86%), the centre being in the upper quadrants (81%) and irregular astigmatism of two dioptres or more. The typical symptoms were reduced vision (86%) and the symptoms of ocular surface disease (64%). Light microscopy showed fibrosis with abundant collagen deposition but no inflammation in all patients. An immunohistochemical analysis of nine patients showed uniform staining for vimentin in three distinct types of fibroblasts in variable proportions: keratocyte-like cells that were positive for CD34, myofibroblasts that were positive for smooth muscle actin (SMA) and fibroblasts that were negative for CD34 and SMA. Small numbers of CD68-positive macrophages were also found. CONCLUSIONS: Peripheral hypertrophic subepithelial degeneration is characteristic of middle-aged women, in whom it is typically a bilateral idiopathic degeneration of the cornea associated with ocular surface disease and reduced vision. The fibrotic lesions probably undergo remodelling, inducing changes in corneal contour. A smouldering low-grade inflammation favouring low TGF-ß1 concentrations is postulated as the primary pathological process leading to PHSD.

Peripheral hypertrophic subepithelial corneal degeneration: characterization, treatment and association with human leucocyte antigen genes.

PURPOSE: To evaluate the efficacy of keratectomy in treating irregular astigmatism caused by peripheral hypertrophic subepithelial corneal degeneration (PHSD) and to study the possible underlying immunological risk factors. MATERIALS AND METHODS: Patients (14 eyes) with diagnosed PHSD were treated with superficial keratectomy with or without the assistance of phototherapeutic keratectomy (VisX S4; VisX Inc., Santa Ana, CA, USA). Thirteen patients were subjected to analysis of human leucocyte antigen (HLA) genes, complement C4 gene numbers and total plasma immunoglobulin levels. Immunological risk factors between patients and a control group comprising 150 individuals were compared. RESULTS: The mean preoperative best spectacle corrected visual acuity (BCVA) improved from 0.16 ± 0.22 (LogMAR scale range 0-0.7) to 0.06 ± 0.13 (-0.1-0.4) (p < 0.01). The mean preoperative astigmatism decreased significantly from 3.8 ± 2.1 D (range 1.2-8.2) to 2.1 ± 1.4 (range 0.6-5.0, p = 0.02) based on corneal topography. The HLA-B*44 allele and the ancestral haplotype (AH) 8.1 were found significantly more often in PHSD patients than in controls (both p = 0.03). No differences in the C4 genes were found. CONCLUSIONS: Astigmatism secondary to PHSD can be effectively treated with keratectomy. Peeling of the fibrotic tissue reduced astigmatism and improved visual performance. We suggest that HLA-B*44 allele and AH 8.1 haplotype are immunological factors predisposing to the development of PHSD. The consequent disruption/alteration of the limbal barrier may lead to corneal peripheral fibrous formation inducing astigmatism.

Refractive surgery in anisometropic adult patients induce plastic changes in primary visual cortex.

PURPOSE: To prospectively study the effect of refractive surgery in the primary visual cortex of adult anisometropic and isometropic myopic patients. METHODS: Two anisometropic and two isometropic myopic patients were examined with multifocal functional magnetic resonance imaging technique (mffMRI) before refractive surgery and at 3, 6, 9 and 12 months postoperatively. Two controls without refractive surgery were also examined with mffMRI in the beginning and in the end of the study. Anisometropic patients had only their more myopic eye operated to correct the anisometropia. The myopic isometropic patients had their both eyes operated. RESULTS: Operated anisometropic eyes showed 65% reduced amount of active voxels in foveal data at 12 months postoperatively compared with the preoperative situation. In unoperated anisometropic eyes, the corresponding value was 86% and in myopic patients and controls 31% and 1%, respectively. To confirm this finding, the number of activated voxels representing the innermost ring of the stimulus was also calculated, and an exactly similar phenomenon was encountered in the anisometropic patients. Both anisometropic patients improved the best-spectacle-corrected visual acuity in the operated eye after refractive surgery. CONCLUSION: Our results suggest that plastic changes may take place in the primary visual cortex of anisometropic adult patients after refractive surgery.