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.

Regression and wound healing after excimer laser PRK: a histopathological study on human corneas.

BACKGROUND: The results of excimer laser PRK are promising as more than 80% of eyes with up to -6.0 diopters of attempted correction have refractive results within 1.0 diopter of emmetropia. However, throughout the dioptric range some unexpected results have been observed with individual patients showing an aggressive wound healing response with excessive myopic regression and severe corneal haze. Unfortunately, only limited data are available about the cellular and extracellular responses in human corneas after PRK and this information is important to establish adequate postoperative pharmaceutical treatment. METHODS: We made a histopathological and immunohistochemical study on 20 human corneal samples from patients with severe corneal haze and myopic regression. The indirect immunofluorescence method was used for demonstration of collagen types I, III, IV laminin, chondroitin sulphate, dermatan sulphate, and keratin. RESULTS: All corneal specimens showed a hyperplastic epithelium. Histologically, most samples (16/20) showed mainly a loose lamination of extracellular material which could be identified as collagen type IV. The remaining four samples had newly synthesised collagen type III. CONCLUSIONS: Our histopathological results indicate that corneal wound healing after excimer laser PRK varies among individuals. In some people epithelial basement proteins, such as collagen type IV, are the main wound healing products, whereas in others mainly collagen type III is found postoperatively, which does not effect the synthesis of collagen type IV. This suggests the need for individually-tailored postoperative pharmaceutical treatment regimens.

Localization of the site of major resistance to fluid transport in Bruch's membrane.

PURPOSE: To determine the site of highest resistance to the movement of water across Bruch's membrane in humans. METHODS: A hydraulic conductivity chamber was designed that enabled us to measure flow across Bruch's membrane while ablating its subepithelial aspect using an excimer laser (193 nm). When resistance was lost, samples were fixed and processed for electron microscopy. RESULTS: Changes in the hydraulic conductivity of Bruch's membrane in response to the excimer-mediated sequential removal of tissue layers was studied in four control eyes of donors 26, 46, 61, and 76 years of age and in one eye of an 83-year-old donor with age-related macular degeneration. The number of laser pulses required to abolish the resistance in Bruch's membrane was found to be dependent on the age of the donor. The ablation rate was approximately 0.11 micron per pulse. Loss of resistance correlated with removal of layers internal to the layer of elastin. CONCLUSIONS: This study indicates that the inner collage-nous layer imparts the major resistance to fluid movement between the retinal pigment epithelium and the choroid. Aging changes in the ultrastructure of these compartments could be responsible for the decrease in hydraulic conductivity observed in early life in previous studies.

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.

The importance of the corneal epithelium in excimer-laser photorefractive keratectomy.

To evaluate the importance of the epithelium for postoperative regression we undertook excimer-laser photoreactive keratectomy (PRK) in six rabbits. After the epithelium had been removed mechanically, two rabbits underwent a -3.0 D procedure; two rabbits, a -6.0 D procedure; and two rabbits, a -9.0 D procedure. Refraction was monitored pre- and postoperatively using streak retinoscopy. Rabbits were killed at 3 weeks after PRK and the thickness of the corneal epithelium in the centre of the ablation zone and in an untreated area just outside the treatment zone was measured using light microscopy. At the time of killing, no stromal haze was visible on slit-lamp biomicroscopy. In all rabbits the thickness of the corneal epithelium over the untreated area was between 31.4 and 36.7 microns. In contrast, the thickness of the epithelium in the centre of the ablation zone in rabbits treated with a -3.0 D procedure was only slightly increased, and retinoscopy showed a change in refraction of around 3 D. All other rabbits showed a significant increase in epithelial thickness, whereas the amount of thickness correlated with the amount of myopic regression. One rabbit in the -6.0 D group showed an increase in epithelial thickness of 18.4 microns and a myopic regression of 1.5 D. In both rabbits in the -9.0 D group the amount of corneal tissue removed by the laser was nearly completely substituted by epithelial hyperplasia. Postoperative retinoscopy showed nearly the same refraction as had been obtained preoperatively. In summary, the postoperative control of epithelial thickness seems to be an important factor for the success of excimer-laser PRK and, in particular, for high degrees of myopia.

Treatment of band keratopathy by excimer laser phototherapeutic keratectomy: surgical techniques and long term follow up.

A series of 122 eyes with band keratopathy was treated by excimer laser phototherapeutic keratectomy (PTK), with a mean follow up of over 12.3 months (range 3 to 60 months). A single photoablation zone was used to remove the opacity over the visual axis in smooth surfaced band deposition. In eyes with reduced vision, an improvement was reported in 88% and in a series of 66 eyes mean Snellen visual acuity increased significantly (p < 0.05, t = 2.27). A reduction in glare was reported in 88% and in a series of 17 patients, visual contrast sensitivity (p < 0.01) and measurements of disability glare (p < 0.01) improved postoperatively. The mean hyperopic shift in 32 eyes at 6 months was 1.4 D (range 0-4.25 D). Multiple overlapping ablation zones, with mechanical debulking of large calcium plaques, were used to smooth the irregular corneal surface in eyes with rough bands. Ocular discomfort was improved in 95%. Band keratopathy recurred in nine eyes (8%) within 2 to 30 months (mean 12 months) of surgery, with silicone oil responsible in five eyes. Reablation was necessary in three eyes and performed successfully in all cases. Excimer laser PTK is a safe and effective outpatient treatment for band keratopathy.