A refractive and histopathologic study of excimer laser keratectomy in primates.

Using a 193-nm excimer laser, we produced wide-area, refractive keratectomies on 18 cynomolgus monkey corneas and followed them up for up to 18 months. All corneas developed some subepithelial haze by one month. Electron microscopy disclosed epithelial thickening, absence of Bowman's layer, and subepithelial activated fibroblasts surrounded by disorganized collagen. By six months, the haze faded to a variable degree, the epithelium regained normal thickness, and the collagen was more organized. Persistent corneal haze at 12 months in some corneas correlated with electronlucent spaces in the subepithelial zone. Corneas were 90 microns thinner centrally two weeks after myopic ablation, but returned to preoperative thickness by six months. Myopic flattening and hyperopic steepening of 6 diopters were targeted, and over 7 diopters of each were achieved initially. Regression of induced curvature stabilized over several months. At 18 months, 4.4 diopters of myopic flattening and 5.2 diopters of hyperopic steepening remained.

Experimental corneal studies with the excimer laser.

The excimer laser is potentially capable of achieving wide area central corneal reprofiling because of its extreme precision and limited penetration into adjacent tissues. A beam modifying system designed for this application is described. Initial clinical studies in monkeys and in ten human patients with blind eyes were performed. Long-term clinical data and interim histologic analyses are available from these studies. The results indicate that following ablation with an ultraviolet laser in both humans and primates, the ablated tissue shows a normal healing reaction resulting in a mild to moderate stromal interface haze. The effects of this healing on best corrected vision must be elucidated through additional research. Some loss of refractive effect was seen early in the healing process with apparent stabilization.

Human excimer laser keratectomy. Short-term histopathology.

The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in the initial three of 10 human eyes has been described with the clinical appearance and short-term (less than 14 days) histopathologic evaluation of these three eyes. The process of laser superficial keratectomy has proved one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations of corneal wound healing following laser ablation as well as the nature and long-term stability of the corneal excisions or induced refractive corrections are needed. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analysed.

Human excimer laser lamellar keratectomy. A clinical study.

The first ten blind human eyes in the United States to receive excimer laser (ArFl 193 nm) lamellar keratectomy (reprofiling) are presented. Seven of these patients were followed 6 to 12 months after ablation. All eyes are grossly clear in the region of ablation. Results of slit-lamp examination of all flattened ablated areas show mild superficial haze at the epithelial/stromal interface. This haze might not interfere significantly with vision in patients 7 to 10. Serial pachymetry and keratometry measurements, refraction, and digital keratoscopy show a progressive filling in of the excavated area by approximately two thirds but a loss of initial diopteric correction of only one third. Histopathologic analysis was obtained for four eyes. Transmission electron microscopy of three eyes enucleated 3 to 12 days after ablation shows 40-microns ablation depths through Bowman's layer and superficial stroma with minimal adjacent tissue damage and no inflammatory cells. The epithelium is increased in thickness by 50%, and firmly attached to the underlying stroma. A 4-month postablation specimen shows keratocyte activation with increased protein synthesis (presumed collagen and ground substance).

Excimer laser instrumentation and technique for human corneal surgery.

The design and development of the instrumentation utilized during the clinical and histopathologic evaluations of the first human eyes treated by argon fluoride excimer laser radiation are described. The laser, optical, alignment, measurement, and control subsystems required for this research were constructed to create a laser beam that has an axially symmetric energy distribution, can be calibrated and measured, can be aligned with the target tissue, and can be manipulated to excise surface tissue. The use of this excimer laser system has demonstrated that a nonuniform superficial lamellar keratectomy can be produced to excise areas of opacified, scarred, or abnormal cornea or to create a new anterior corneal curvature in attempts to correct refractive errors.

Human excimer laser corneal surgery: preliminary report.

The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in ten human eyes has been described with the histopathological evaluation of four eyes and the longer gross appearance of six eyes at intervals extending to 10 months post-excimer laser treatment. The process of laser superficial keratectomy has proved to be one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations need to be undertaken on the corneal wound healing process following laser ablation as well as the nature, and long-term stability of the corneal excisions or induced refractive corrections. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques, and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analyzed.

Clinical applications of the organic dye laser.

Clinical research utilizing the yellow, orange and red wavelengths of the dye laser (Rhodamine 6G and MD-631) indicates that the liquid organic dye laser may have considerable applications in ocular photodynamic and photocoagulation therapy. The effectiveness of the dye laser as a photodynamic (photoradiation) and photocoagulation source is due to the large numbers of wavelengths of relatively high output power that can be produced in the visible spectrum. Therefore, a target tissue can be selectively destroyed with minimal laser energy necessarily transmitted through the refractive media. The dye laser, as a photoradiation or photocoagulation system, should prove valuable in the therapy of ocular disease.

Clinical photocoagulation with the organic dye laser. A preliminary communication.

Clinical research utilizing the yellow, orange, and red wavelengths of the liquid organic dye laser has demonstrated that this laser may be successfully used for photocoagulation of certain ophthalmic defects. The advantage of the dye laser as a photocoagulation source is its capability to produce monochromatic wavelengths at relatively high output powers through a large range of the visible spectrum. Therefore, a target tissue can be coagulated with minimal transmittal of laser energy through the ocular media, by the selection of a wavelength that would be most highly absorbed by that tissue. The dye laser, as a system that permits transspectral photocoagulation, should prove valuable in the treatment of ocular disease.

Trans-spectral organic dye laser photocoagulation.

Clinical research utilizing the yellow, orange, and red wavelengths of the dye laser (Rhodamine 6G and MD-631) appears to have considerable promise and may demonstrate that the liquid organic dye laser is the laser of choice for photocoagulation of many types of ocular defects. The effectiveness of the dye laser as a photocoagulation source is due to the trans-spectral availability of relatively high output power wavelengths. Therefore, a target tissue can be selectively coagulated with minimal laser energy transmitted through the refractive media and minimal damage to nearby normal tissues. The dye laser, as a photocoagulation system, should prove valuable in the therapy of many ocular diseases.

Carbon dioxide laser trabeculostomy for the treatment of neovascular glaucoma.

During the past 24 months, 23 cases of advanced neovascular glaucoma, unresponsive to medical therapy, have been treated by a trabeculostomy procedure using a carbon dioxide laser. This procedure entails surgical entry into the anterior chamber from beneath either a conjunctival or scleral flap in such a way as to completely cauterize any neovascular tissue in the corneoscleral angle and to permit adequate drainage of the aqueous in fluid from the anterior chamber to the periocular space. The average intraocular pressure prior to carbon dioxide laser trabeculostomy was 54 mmHg and these pressures were lowered below 18 mmHg in over 70% of the cases followed for longer than six months postlaser therapy. Treatment was considered a failure in 16% of the cases where the intraocular pressure was not lowered substantially. Fourteen percent of the treated eyes sustained a pressure decrease to within the 26-35 mmHg range. Carbon dioxide laser trabeculostomy provides a new method of lowering the intraocular pressure in severe cases of neovascular glaucoma without the hazard of intraocular hemorrhage common with other filtration procedures or the ciliary destruction present with the cyclocautery operations. The indications, surgical technique, and complications will be discussed.

Carbon dioxide laser trabeculostomy for the treatment of neovascular glaucoma.

During the past 18 months, 23 cases of advanced neovascular glaucoma, unresponsive to medical therapy, have been treated by a trabeculostomy procedure using a carbon dioxide laser. This procedure entails surgical entry into the anterior chamber from beneath either a conjunctival or a scleral flap in such a way as to completely cauterize any neovascular tissue in the iridocorneal angle and to permit adequate drainage of the aqueous fluid from the anterior chamber to the periocular space. The average intraocular pressure, prior to carbon dioxide laser trabeculostomy was 54 mm Hg and these pressures were lowered below 18 mm Hg in over 57% of the cases followed for longer than six months post-laser therapy. Treatment was considered a failure in 26% of the cases where the intraocular pressure was not lowered substantially, and 17% of the treated eyes sustained a pressure decrease to within the 25 to 35 mm Hg range. Carbon dioxide laser trabeculostomy or trabeculo-sclerostomy provides a new method of lowering the intraocular pressure in severe cases of neovascular glaucoma without the hazard of intraocular hemorrhage, common with other filtration procedures. These procedures have proved satisfactory in alleviating the high pressures of neovascular glaucoma in a relatively large proportion of the patients treated. If the eye is grossly hyperemic and irritated because of the high intraocular pressure and the deteriorated condition of the eye, it is suggested that the carbon dioxide laser trabeculostomy procedure with a scleral flap be performed with an implanted seton as the procedure of choice. If the eye is relatively quiet and has some visual reserve but an exceedingly high and intractable intraocular pressure, it is advisable to use either the carbon dioxide laser trabeculostomy procedure or the carbon dioxide laser trabeculo-sclerostomy operation as described. These procedures are being further refined, but the results of this investigation suggest that these procedures can be utilized judiciously, and should prove useful, particularly in those eyes with advanced neovascular glaucoma with useful vision still remaining.

Diabetic retinopathy: update on therapeutic advances.

It is clear that real advances have occurred in the therapy of diabetic retinopathy. However, this complication of diabetes can and does lead to blindness in the older patient. The present treatment modalities offer a means of maintaining or, in some patients, improving the visual performance of the patient. Laser photocoagulation and vitrectomy are the major new therapies. The future will hopefully give us a better understanding of the cause of diabetic retinopathy so that it may be prevented and cured. However, in the interim, all patients with diabetes mellitus should be urged to see on ophthalmologist yearly in order to obtain the best available therapy.

Diabetic retinopathy.

The only methods of treatment for severe diabetic retinopathy that have been proved effective by controlled clinical trials are photocoagulation and pituitary ablation. It must be noted that photocoagulation and pituitary ablation impede but do not cure diabetic retinopathy. Pars plana vitrectomy can be highly effective for removing blood from the vitreous of the eye, allowing better vision, particularly if the retina has been shown to be functional by electrophysiologic testing and ultrasonography. In addition, vitrectomy allows the ophthalmologist to visualize, evaluate, and treat the diabetic retina by photocoagulation or other methods. Attempts at better regulation of blood sugar have reduced the development of microangiopathy in experimental animals and recently in man. The benefits of rigorous regulation of the blood sugar has been noted in a policy statement by the American Diabetes Association. The development of a practical, beneficial pancreas has been undertaken, and may be required in order to reap the full benefits of rigorous blood sugar control. It has been recommended that all patients be evaluated by an ophthalmologist as soon as they have been found to have diabetes, that all diabetics be examined ophthalmologically on an annual basis, and that patients with significant retinopathy be seen at 6 month or shorter intervals by their ophthalmologist. The evaluation and treatment of diabetic retinopathy has progressed enormously during the past decade. It is hoped that the cause of diabetic microangiopathy and retinopathy will be discovered in the near future so that treatment will ultimately cure rather than control the process of diabetic retinopathy.