Effect of collagenase inhibitors on corneal haze after PRK.

The aim of the study was to determine whether collagenase inhibitors reduce corneal haze after photorefractive keratectomy (PRK). Inhibition of the initial removal phase of healing may limit the subsequent repair and replacement phases responsible for haze and regression. Thirty rabbits received -6.00D 5 mm right PRK. They were randomized to five treatment groups: G. cysteine, G. ethylene diamine tetra-acetic acid (EDTA), G. ascorbate, Oc. tetracycline or no drops. Dichlorotriazinyl aminofluorescein (DTAF) was applied to the wound immediately after surgery in two rabbits of each group, to delineate newly-synthesized from original tissue. Corneal haze was assessed by a video-linked frame grabber with computerized grey scale analysis. Corneas were taken for histology at 1 or 3 months post-operatively. Corneal haze was not significantly different between the treatment groups and controls. The severity of the histological changes varied between individuals. Within the ablation zone the epithelium was on average 10% thicker (3--4 micro m) than outside, and in some rabbits there were irregularities of the epithelial--stromal junction. The new subepithelial tissue had a mean depth of 7.8 micro m, and the superficial stroma was disorganized to a mean depth of 49 micro m. No particular treatment demonstrated significant benefits over controls; but of the treatments used, cysteine tended to produce the best results. Eyes treated with EDTA fared worst in most respects. The collagenase inhibitors used did not improve the outcome of PRK in rabbits. It remains to be determined whether firstly, the new more potent agents would have an effect, and secondly, whether collagenase inhibitors are of benefit in humans.

Loss and recovery of corneal sensitivity following photorefractive keratectomy for myopia.

BACKGROUND: Photorefractive keratectomy affects corneal innervation in a new, and drastic, way. This inevitably results in a significant loss of corneal sensitivity. This paper investigates the pattern of sensitivity loss and recovery following PRK for low to moderate myopia. METHODS: Patients were recruited for two separate studies. Longitudinal Study: 10 patients, treated with a -6.00 D/6 mm PRK ablation, were examined over a 1-year period. Transverse Study: A comparison was made between 35 non-contact lens wearers, 80 contact lens wearers, and 60 patients who underwent five different PRK treatments, 1 year previously. Corneal sensitivity was assessed using the Non-Contact Corneal Aesthesiometer at four corneal locations: centrally, temporally, medially, inferiorly, on all patients. RESULTS: Longitudinal Study: Corneal sensitivity was significantly reduced at week 1, with a further significant reduction at week 2. A gradual recovery in sensitivity then followed to reach preoperative levels by 1 year. Transverse Study: There was no significant difference in corneal sensitivity found as a result of different PRK ablation depths. The depth of ablation was not a factor in corneal sensitivity recovery in low to moderate myopic corrections. Corneal sensitivity in the PRK treated eyes was significantly lower than in the control groups. CONCLUSION: The immediate loss of corneal sensitivity after surgery was due to the total removal of the corneal epithelial nerve supply and a substantial portion of the underlying stromal nerves. The further decrease at week 2 was probably due to the new epithelium acting as barrier to stimulation. The gradual recovery of corneal sensitivity was most likely caused by epithelial reinnervation within the ablation zone, but this was still below normal levels at 1 year after surgery. Corneal nerve function demonstrates a biphasic pattern of loss and recovery following the excimer laser correction of low to moderate myopia.

Keratocyte density and size in conscious humans by digital image analysis of confocal images.

PURPOSE: Confocal microscopy can give images of high magnification and resolution in undisturbed living tissue. It provides new information about the cellular structure of the cornea. Our aim was to measure the density, size and distribution of keratocytes. METHODS: Healthy cornea in four subjects was examined using tandem scanning confocal microscopy. Methods for digital analysis of images were developed. RESULTS: Keratocyte density in confocal cross-sections was greatest immediately under Bowman's membrane (maximum 800 cells/mm2) and decreased sharply towards posterior cornea (minimum 65 cells/mm2). Cross-sectional cell size ranged from 78 to 211 microns2, but did not correlate with depth in the tissue. CONCLUSIONS: Results are consistent with those of earlier work using histological and biochemical techniques in isolated tissue. The methods we have developed enable studies of ongoing processes in conscious humans and can be used to examine diseased tissue as well as the response to injury.

Effect of beam variables on corneal sensitivity after excimer laser photorefractive keratectomy.

AIM: To investigate changes in corneal touch sensitivity following excimer laser photorefractive keratectomy (PRK) using different beam configurations. METHODS: 20 subjects were given a unilateral -3.00 D correction with either a 5 mm (26 micrograms, n = 10) or 6 mm (42 micrograms, n = 10) beam diameter. Thirty subjects underwent a unilateral -6.00 D correction with 5 mm (62 micrograms, n = 10), 6 mm (78 micrograms, n = 10), or multizone (62 micrograms, n = 10) treatments. The multizone treatment was 6 mm in diameter with the depth of the 5 mm treatment. Corneal sensitivity was measured using a slit-lamp mounted Cochet-Bonnet aesthesiometer before and at 1, 3, 6, and 12 months after PRK. Stimulus locations included points lying within the ablated zone (central) and outside (peripheral). These were compared with the equivalent locations in control (untreated) eyes. RESULTS: There was a significant reduction in corneal sensitivity within the central (ablated) zone in all treatment groups after PRK. In most groups a return to full sensitivity was achieved by 6 months with the exception of the multizone treatment group which showed significant corneal hypoaesthesia at 12 months. Peripheral corneal sensitivity was also reduced in this group up to 3 months after the procedure. A comparison between the -3.00 D and -6.00 D treatment groups showed no significant difference. However, combining data from all treatment groups, a significant correlation was found between the interocular difference in central corneal sensitivity and postoperative haze at 3 and 6 months. CONCLUSIONS: For corrections up to -6.00 D ablation depth and treatment zone diameter do not appear to be clinically important determinants of corneal hypoaesthesia. In contrast, postoperative corneal haze appears to correlate with sensitivity loss.

Corneal optical aberrations induced by photorefractive keratectomy.

BACKGROUND: Photorefractive keratectomy causes marked alteration to anterior corneal topography, and is likely to induce major changes to the optical aberrations of the eye. METHODS: Six diopters (D) of myopia correction was attempted on one eye of 50 patients, randomly allocated to one of three different treatments: 5-mm or 6-mm single ablation zone, or a double ablation (multizone; -5.00 D correction over 4.6 mm and -1.00 D over 6 mm). Topographic data was used to estimate corneal aberration coefficients. These were compared for effect of ablation zone, before and 1 year after photorefractive keratectomy. The coefficients were used to derive modulation transfer functions for the anterior corneal surface. RESULTS: Corneal spherical aberrations and coma-like aberrations both increased significantly following photorefractive keratectomy (p < 0.001). The mean spherical aberration coefficient increased from 0.36 +/- 0.11 before, to 0.91 +/- 0.37 after treatment, while the mean coma-like aberration coefficient changed from 0.28 +/- 0.16 before, to 0.60 +/- 0.31 after treatment. Ablation zone form had a significant effect on spherical aberration (p = 0.030), but not for coma (p = 0.96). The spherical aberration coefficient increased least for the 6-mm ablation (by 0.38 +/- 0.17), compared with the 5-mm ablation (0.69 +/- 0.45) and the multizone (0.62 +/- 0.38). Corneal modulation transfer functions were reduced significantly following the photorefractive procedure. The effect was greatest for large pupil diameters and for spatial frequencies between 2 and 15 cycles per degree. CONCLUSIONS: Corneal modulation transfer function calculations suggest that a significant loss of visual performance should be anticipated following photorefractive keratectomy, the effect being greatest for large pupil diameters. Results for three ablation zones show that induced aberrations are least for the largest (6 mm) ablation zone.

A comparative study of the duration and efficacy of tetracaine 1% and bupivacaine 0.75% in controlling pain following photorefractive keratectomy (PRK).

OBJECTIVE: To evaluate if topical bupivacaine 0.75% provides better pain control after excimer laser over topical tetracaine 1% without affecting corneal wound healing, refractive outcome of visual function. DESIGN: A prospective, double-masked trial was conducted in which 38 patients were randomized to receive either tetracaine or bupivacaine every 30 minutes for 24 hours post-operatively. Pain was recorded over a four day period using a Visual Analogue Pain Scale. The rate of epithelial healing was assessed during digitized retro-illumination photography. Visual performance was recorded using best corrected Snellen acuity, objective measurements of haze, halo and glare over a six month period. RESULTS: Tetracaine afforded better pain control (p = 0.05). Full epithelial closure occurred in all patients within 72 hours and no statistically significant difference was recorded in any of the parameters measured. CONCLUSIONS: Contrary to our expectation, the longer acting anaesthetic, bupivacaine, was inferior to tetracaine. Limited and supervised use of topical anaesthetics is recommended in controlling pain following photorefractive keratectomy.

Confocal microscopy using oblique sections for measurement of corneal epithelial thickness in conscious humans.

PURPOSE: Thickness measurements by confocal microscopy in conscious human subjects may be liable to error as a result of instability of the eye or instrument. Our aim was to evaluate a technique which was expected to be less sensitive to such problems. METHOD: Thickness of corneal epithelium was determined from oblique confocal sections through cornea. A contact lens of known thickness worn by subjects was used to calibrate images. RESULTS: There were two layers in images which could have corresponded to the stromal/epithelial interface. The mean result in each subject ranged from 38 to 53 microm using the more superficial layer and 46 to 60 microm using the deeper one. The smaller values gave the distance between the epithelial surface and the sub-epithelial nerve plexus and thus seemed to correspond to epithelial thickness. CONCLUSIONS: Measurements of epithelial thickness by our new method are comparable with results of earlier studies.

An in vivo investigation of the structures responsible for corneal haze after photorefractive keratectomy and their effect on visual function.

PURPOSE: To make serial measurements of corneal haze and microscopic anatomy after photorefractive keratectomy (PRK) and compare the results with visual function measured at the same time points in the same single group of human subjects. METHODS: Ten patients underwent -6.00-diopter, 6-mm PRK. The patients were reviewed frequently for 12 months. Corneal haze was measured objectively in two ways: (1) an opacification index was determined from the variance in digitized retroillumination images; and (2) light reflected and scattered back from the cornea was assessed by gray-scale analysis of video slit images. In vivo confocal microscopy recorded the anatomic changes occurring in the cornea, and computer analysis of the images quantified the keratocytes and subepithelial deposit. Visual performance was assessed by Snellen visual acuity, contrast sensitivity, and glare-induced visual dysfunction. RESULTS: In the first week, epithelial irregularity resulted in a transient reduction in all aspects of visual function. In the first month, keratocyte disturbances reduced contrast sensitivity at high frequencies and produced glare. Over the next couple of months, the subepithelial deposit resulted in a more prolonged loss of contrast sensitivity at low frequencies and glare-induced visual dysfunction due to the scattering of light. In several patients, these visual defects persisted after 1 year. CONCLUSIONS: Epithelial and keratocyte disturbances only transiently affect visual function. The subepithelial deposit is more persistent and can have a lasting effect on visual performance. Therefore, attempts to improve the visual outcome of PRK must be aimed at controlling the synthesis of subepithelial material.

Biologic and environmental risk factors for regression after photorefractive keratectomy.

BACKGROUND/PURPOSE: After photorefractive keratectomy (PRK), the final refraction in the majority of patients is near the intended refraction. However, a significant proportion of patients show regression, which is commonly associated with corneal haze. This study aims to determine whether biologic and environmental factors influence the outcome of PRK. METHODS: One hundred patients prospectively underwent -3.00- or -6.00-diopter corrections. Three months after surgery, 100% of patients answered a questionnaire that recorded their biologic characteristics, medical and ocular history, and postoperative exposure to physical and chemical insults. Multivariable analysis identified those factors associated with regression. RESULTS: Multivariable analysis showed that the risk of regression was increased significantly in patients who underwent higher dioptric or smaller diameter treatments (P = 0.045) and in those who had had regression after treatment of the first eye (P = 0.019). There was no difference between the sexes, but regression was 13.5 times more likely in females who were taking oral contraceptives. Regression was increased in those exposed to solar radiation (odds ratio, 7.6; 95% confidence interval, 1.82-32.22) and sun beds (odds ratio, 2.4; 95% confidence interval, 0.64-9.39), and was significantly greater in patients with ocular-surface disorders (on univariable analysis only; P = 0.034). Regression was not associated with previous contact lens wear, swimming, cigarette smoking, or minor ocular trauma. CONCLUSION: The questionnaire identified biologic and environmental risk factors for regression. The biologic risk factors may be used preoperatively to counsel patients and, where necessary, advise them against surgery. The environmental risk factors are largely avoidable by modification of patient behavior.

Effect of ablation profile on wound healing and visual performance 1 year after excimer laser photorefractive keratectomy.

BACKGROUND: Early photorefractive keratectomy ablations were of limited diameter and depth to maintain the integrity of the globe and to minimise postoperative haze. This study evaluated the effects of deeper, larger diameter wounds on refractive stability and corneal haze, and investigated the effects of ablation profile on wound healing and visual performance. METHODS: One hundred patients undergoing -3.00D and -6.00D corrections were randomised to receive 5 mm, 6 mm, or multizone treatments. The multizone treatment was 6 mm in diameter, but only the depth of the 5 mm treatment. Outcome was measured by Snellen visual acuity, residual refractive error, objective techniques for haze and halos, pupil diameter, subjective night vision, and requirement for retreatment. RESULTS: Overall, the results of 6 mm treatments were superior to those of 5 mm and multizone treatments: they had a smaller hyperopic shift (p < 0.01), a more predictable (p < 0.001) and stable refractive outcome, less haze (p < 0.05), smaller halos (p < 0.05), fewer subjective night vision problems, and fewer patients required retreatment. CONCLUSIONS: Analysis of these data and a literature review of corneal wound healing demonstrated that the improved outcome associated with the 6 mm beam did not relate to the depth of ablation. The factor with greatest apparent influence on the development of haze and regression was the slope of the wound surface over the entire area of the ablation. Tapering the wound edge provided no additional benefit, and contributed to night vision problems. It is, therefore, recommended that small diameter or multizone treatments should not be used in low and moderate myopia.

Effects of ablation diameter, depth, and edge contour on the outcome of photorefractive keratectomy.

PURPOSE: To investigate the effects of the ablation diameter, depth, and edge contour on the outcome of excimer laser photorefractive keratectomy (PRK). METHODS: A prospective study was conducted in which 60 patients (60 eyes) were randomly allocated to 5.00-mm, 6.00-mm, or 5.00 to 6.00-mm multizone treatment groups. All eyes underwent a -6.00 diopter (D) correction using a Summit Omnimed excimer laser. RESULTS: In eyes treated with 6.00-mm diameter zones, the initial hyperopic shift was reduced, with significant differences at 1 and 4 weeks (p < 0.01). At 6 and 12 months, the refractive changes were closer to the intended correction with 6.00-mm diameters. The predictability of PRK was improved with 6.00-mm zones, with a significant reduction in variance of the refractive changes, at all stages postoperatively (p < 0.05 to p < 0.001). Objective measurements of haze were significantly less at 1, 3, and 6 months with 6.00-mm ablations (p < 0.05). There were no differences between the 5.00-mm and the 5.00- to 6.00-mm multizone groups. Computerized measurements of "night" halo were significantly smaller in the 6.00-mm treatment group at 1 week and 1 month (p < 0.05). At 12 months, two patients treated with 5.00-mm zones and three with the 5.00- to 6.00-mm multizone complained of severe night vision disturbances. No 6.00-mm eyes were similarly affected. CONCLUSIONS: Treatment with a 6.00-mm spherical ablation diameter produced less initial overcorrection, improved predictability, and was associated with a reduction in postoperative halos and night vision disturbances. Creating a superficial blend zone with a 5.00- to 6.00-mm multizone treatment had no beneficial effect on the outcome.

A prospective, randomized, double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy.

PURPOSE: To investigate the role of 1% tetracaine in controlling pain after photo-refractive keratectomy (PRK) and determining its effect, if any, on epithelial healing, refractive outcome, and visual performance. METHODS: In this study, 44 patients were randomized to receive either Gutt. 1% tetracaine or placebo after undergoing PRK. Drops were instilled at 30-minute intervals during waking hours for 24 hours postoperatively. In addition, all patients received two coproxamol (paracetamol + dextropropoxyphene) tablets every 6 hours for 2 days. Visual Analogue Pain Charts were used to record pain levels for 4 days after surgery. Serial digitized retro-illumination photography was used to assess rates of epithelial healing, and surface epithelial quality was monitored using topography. At fixed intervals over a 6-month period visual performance was assessed by measuring refractive outcome, best-corrected visual acuity, objective haze, halo, and glare. RESULTS: Patients in the tetracaine group had significantly less pain (P < 0.0001). Both groups demonstrated full epithelial closure within 72 hours. Similar numbers of patients in both groups at 1 week showed topographic irregularity that completely resolved by 1 month. No statistically significant difference was seen in any of the parameters monitoring visual performance. CONCLUSIONS: Tetracaine in conjunction with coproxamol is effective in reducing pain after PRK without adversely affecting corneal wound healing or visual performance.