MK-801 has neuroprotective and antiproliferative effects in retinal laser injury

PURPOSE: Treatment of the retina by laser photocoagulation often is complicated by an immediate side effect of visual impairment, caused by unavoidable, laser-induced destruction of healthy tissue adjacent to the lesion. A neuroprotective therapy that salvages this healthy tissue might enhance the benefit obtained from the treatment. This study was proposed to determine whether glutamate-receptor blockers can provide adjuvant neuroprotection during laser photocoagulation. The effect of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury was examined, in a rat model. METHODS: Argon laser lesions were created in the retinas of 36 DA rats, and were followed immediately by intraperitoneal injections of MK-801 (2 mg/kg) or saline. The animals were killed after 3, 20, or 60 days and the retinal lesions were evaluated histologically and morphometrically. RESULTS: Photoreceptor-cell loss was significantly less in MK-801-treated rats than in control animals. The proliferative membrane composed of retinal pigment epithelial cells and neovascular blood vessels, which was seen at the base of the lesion in control group retinas, was smaller in the MK-801-treated retinas. In rats treated with a higher dose of MK-801, the lesions showed almost no proliferative reaction. CONCLUSIONS: A potent noncompetitive NMDA-receptor blocker, MK-801 exhibits neuroprotective and antiproliferative properties in the retina. Glutamate-receptor blockers should be investigated further as potential adjuvant therapy in retinal photocoagulation treatments.     

Endolaser photocoagulation after vitrectomy on rabbit's eyes

Ophthalmoscopic and histopathologic studies of endolaser photocoagulation after vitrectomy were carried out on rabbit's eyes. The endoprobe was connected to the Coherent "Novus 2,000" argon laser system. Under appropriate application the grayish white retinal lesions produced by argon green and argon all wavelength endolaser photocoagulation were similar ophthalmoscopically at a treatment power of 80-100 mw and exposure duration of 0.2s. Histopathologically, the characteristic changes of the retinal lesions produced by argon all wave-length were more significant than that produced by argon green endolaser photocoagulation. Scattered retinal photocoagulation can be done when the opaque medium is cleared on the operating table.     

Acute retinal necrosis syndrome. Argon laser coagulation for prevention of rhegmatogenic retinal detachment

BACKGROUND: ARN syndrome follows severeintraocular infection by herpes viruses and primarily affects the peripheral retina. Following scar formation, despite antiviral treatment, rhegmatogenous retinal detachment occurs very often. Prophylactic argon laser photocoagulation has therefore been proposed. We report our experience. PATIENTS: We treated five patients presenting clinically with advanced unilateral ARN with acyclovir. All eyes received a prophylactic confluent double row of argon laser treatment (500 microns, 0.2 s, gray-white lesions) central to the affected area as soon as was possible, depending on the vitreous clouding. Four patients were treated with Aspirin. RESULTS: One of the five patients had a peripheral rhegmatogenous retinal detachment that was limited by the argon laser row. Another patient had a tractional detachment needing vitreoretinal surgery. Two eyes developed vitreal hemorrhage of unknown origin. CONCLUSION: A lower rate of rhegmatogenous retinal detachments than expected occurred post-laser treatment. Vitreal hemorrhage was more frequent than previously reported. The bleeding probably originated from anterior retinal neovascularization and may have been enhanced by Aspirin treatment. We recommend early prophylactic argon laser photocoagulation in all ARN patients in agreement with the results of previous studies.     

Diode laser thermokeratoplasty: application strategy and dosimetry

PURPOSE: To investigate suitable application parameters for efficient hyperopic correction by laser thermokeratoplasty (LTK) using mid-infrared laser diodes. SETTING: Medical Laser Center Lübeck, Lübeck, Germany. METHOD: A tunable continuous-wave laser diode in the spectral range between 1.845 and 1.871 microns was used. Transmitted by waveguides, the laser energy was used to induce coagulations on freshly enucleated porcine eyes to increase corneal curvature. The coagulations were equidistantly applied by a fiber-cornea contact and a noncontact focusing device that were adjusted on a ring concentric to the corneal apex. Different laser parameters and application geometries were evaluated. Refractive changes were measured by computer-assisted corneal topography before and after treatment. Polarization light microscopy and temperature calculations were used to analyze the coagulations. RESULTS: Because of the tunability of the laser diode, the influence of the corneal absorption coefficient (between 0.9 and 1.6 mm-1) on the refractive change could be measured. A laser power between 125 and 200 mW was adequate to achieve refractive changes up to 10.0 diopters. In the preferable focusing device, the refractive change increased almost logarithmically with the irradiation time up to 15 seconds. The number of coagulations on a fixed application ring showed no significant influence on refractive change; however, it showed an almost linear decrease with increasing ring diameter from 5.0 to 10.0 mm. Histological analysis revealed 3 stages of thermal damage. CONCLUSION: Diode LTK provided defined and uniform coagulations when using a well-adapted focusing device, resulting in sufficient refractive change. The results indicate that diode LTK is superior to pulsed holmium LTK.     

Diode laser for retinopathy of prematurity--early outcome

Diode laser treatment for retinopathy of prematurity was successful in 81% of 21 eyes with 'threshold' (zone 2, stage 3+) disease. This compares favourably with cryotherapy and argon laser photocoagulation. The retinal outcome and technique are discussed.     

Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat

AIMS: To investigate the longevity and reproducibility of choroidal neovascularisation (CNV) induced by krypton laser photocoagulation in the rat. The presence of cell adhesion molecules (CAMs) and vascular endothelial growth factor (VEGF) during the development of CNV was also studied. METHODS: 67 pigmented rats underwent retinal photocoagulation by krypton laser. The eyes were examined by either single or serial fluorescein angiography at 3 days, 1, 2-3, 4-5, 7-8, and 12 weeks post photocoagulation. The expression of CAMs (ICAM-1, E-selectin, and CD44) and VEGF post photocoagulation was studied by immunohistochemistry. RESULTS: CNV related fluorescein leakage appeared in 46.4% of 766 laser spots delivered to the 58 eyes that were tested at 2-3 weeks post treatment. The ratio of hyperfluorescent laser sites did not change significantly at 8 weeks post laser. The number of leaky spots was independent of the total number of lesions delivered to each eye (at 2-3 weeks post laser 10-15 spots/eye: 44% and 25-30 spots/eye: 49%; t = 0.7673; p = 0.3903). Nine eyes were followed by serial angiography between 2 and 12 weeks. The laser spots with fluorescein leakage at 2 weeks (51.5%) remained leaky at 12 weeks (51.5%). Histopathologically, macrophage accumulation peaked at 5 days and CNV was firstly observed at 1 week post photocoagulation. ICAM-1, E-selectin, CD44, and VEGF were maximally induced at 3-5 days post laser photocoagulation, and were localised to RPE, choroidal vascular endothelial, and inflammatory cells. VEGF was also detected in intravascular leucocytes at the sites of laser lesions. CONCLUSIONS: These studies demonstrated that krypton laser photocoagulation can be successfully used to produce lesions similar to those of human CNV. The response induced remained present for an extended period of time (12 weeks), thus offering a potential model to screen candidate CNV inhibitory agents. In addition, it is proposed that the expression of ICAM-1, E-selectin, CD44, and VEGF before new vessel formation might be linked to the initiation of CNV.     

A long-term course of experimentally produced choroidal neovascularization in the rat

We studied morphologically a long-term course of experimental choroidal neovascularization (ChNV) induced by krypton laser photocoagulation in the rat retina. Fifty-two weeks after photocoagulation, ChNV was enveloped completely by the retinal pigment epithelium. Vascular endothelial cells of ChNV were thin, with many fenestrations and wide lumen. The ChNV maintained the morphological characteristics of mature leaky capillaries similar to choriocapillaris. The lumen of the neovascularizations tended to be compressed by massive collagen fibers produced by the retinal pigmented epithelium. We found that experimental ChNV in the rat retina retains the characteristics of leaky capillaries for a long time unlike that in the monkey ChNV.     

Prevention of retinal detachment in Wagner-Stickler disease. Comparative study of different methods. Apropos of 22 cases

Prophylactic treatment in patients presenting Wagner-Stickler disease has not been yet well defined. We retrospectively studied twenty-two patients who had a retinal detachment on the first eye. Among the ten patients treated by peripheral confluent laser photocoagulation, five had a retinal detachment after a mean follow-up of fifteen months; with a 42% rate of spontaneous retinal detachment bilateralization, we can conclude that laser therapy has not been efficient. Four patients treated by focal or circular laser photocoagulation, cryotherapy or vitrectomy developed retinal detachment. Eight eyes treated by a preventive encircling scleral buckle did not develop retinal detachment, with a mean follow-up of twenty-one months. This follow-up is still too short, but greater than the mean bilateralization delay. Per and postoperative complications had no consequences.     

Experimental liver injury: serial splenoportography and post-mortem angiography by means of Schlesinger''s mass

Out of 222 eyes with diabetic retinopathy, observed during a period of 6-42 months after argon laser photocoagulation, 66 (30%) became worse. The most common complication was a fast increase of previous existing macular oedema due to extensive and heavy macular treatment. Another complication was an increase of the neovascularisation due to the inadequate treatment of avascular zones and heavy-leaking areas and to the growth of the neovascular tuft after the feeder vessel technique without previous peripheral ablation. Retinal and vitreal haemorrhages were frequent in this group. Fibrous tissue formation and vascular pseudopapillitis were less frequent complications. Large coagulations outside the macular area (peripheral ablation) are necessary to destroy the zones of borderline nutritional supply, which probably are closely related to the new vessel formation. The feeder vessel technique must not be used without a peripheral ablation although it may be of great help in destroying prepapillary or large neovascularisation.     

Silicone assisted, argon laser confinement of recurrent proliferative vitreoretinopathy related retinal detachment: a technique to allow silicone oil removal in problem eyes

AIMS/BACKGROUND: Recurrent peripheral retinal detachments may occur in eyes treated with vitrectomy and silicone oil for retinal detachments complicated by proliferative vitreoretinopathy (PVR). The aim of this study was to assess whether laser photocoagulation could be used in the presence of silicone oil to confine and stabilise recurrent PVR related peripheral retinal detachments enabling the timely removal of the oil. METHODS: 10 patients with recurrent peripheral retinal detachments after vitrectomy and silicone oil insertion were treated with posturing and subsequent focal argon laser to circumscribe the area of recurrent detachment. RESULTS: This technique alone was sufficient to limit the area of retinal detachment in seven of the cases. The remaining three cases required relieving retinotomies because of increasing retinal detachment despite the laser. In all 10 cases the silicone oil was later removed without progression of the detached areas. CONCLUSION: Silicone assisted argon laser 'confinement' can be effective in stabilising eyes with peripheral retinal detachments allowing the subsequent removal of silicone oil.     

Pilot study of anti-lipopolysaccharide human monoclonal antibody MAB-T88 in patients with gram-negative sepsis

8 cases of malignant choroidal melanoma were treated with argon and krypton laser photocoagulation of average 11 sessions and followed up an average 56 months. Clinical complete regression was observed in 5 cases (62.5%), in whom the tumors measured from 1.0mm x 1.2mm x 1.5mm to 6.0mm x 4.5mm x 2.5mm. The other 3 cases (37.5%) recurred, in whom the tumors measured from 4.0mm x 2.0mm x 3.5mm to 11.5mm x 12.5mm x 3.5mm. The complications of treatment included branch retinal vein occlusion, retinal neovascularization, vitreous hemorrhage, macular edema and optic atrophy. These results suggested that laser photocoagulation was useful in the treatment of small malignant choroidal melanomas.     

Automated perimetric changes following panretinal photocoagulation in diabetic retinopathy

Sixty eyes--30 with severe nonproliferative diabetic retinopathy (NPDR) and 30 with proliferative diabetic retinopathy (PDR)--underwent argon laser panretinal photocoagulation (PRP). Static perimetry (Humphrey automated visual field analyzer 630, Threshold Prog Central 30-1 and Peri 30/60-1) was done 1 day before and 6 weeks after the initial laser treatment. One day before treatment, the fields of the NPDR and PDR eyes differed mainly in the central field affection: the PDR eyes had more localized areas of markedly decreased retinal sensitivity and, therefore, a higher initial mean deviation value and higher corrected pattern standard deviation values. However, peripheral retinal sensitivity was equally depressed in the NPDR and PDR eyes. Six weeks after treatment, central retinal sensitivity had significantly improved in all of the eyes, although more so in the eyes with severe NPDR. This study suggests that static-perimetry-guided PRP is an effective treatment for diabetic retinopathy, especially severe NPDR.     

Multicenter clinical experience using an erbium:YAG laser for vitreoretinal surgery

PURPOSE: To evaluate the advantages, disadvantages, safety, complications, and surgical applicability of an erbium:YAG laser system for maneuvers in vitreoretinal surgery. METHODS: A prospective, consecutive trial of 68 eyes in 66 patients undergoing vitreoretinal surgery in which an erbium:YAG laser with graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and equipped with a flexible fiber optic and interchangeable 20-gauge intraocular fiber optic endoprobes was used to perform specific maneuvers, including transection, incision, and ablation of membranes, retinotomy, vessel coagulation, iridectomy, and lens tissue ablation. The patients were treated in five centers in contemporary vitreoretinal surgical settings for surgical indications, including proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and retinopathy of prematurity. RESULTS: One hundred seventy-four maneuvers were performed with an overall surgical efficacy rating of excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal membrane transection to a low of 25% for coagulation of blood vessels. Complications included retinal break or photocoagulative injury in 5% of epiretinal membrane incisions, minor bleeding from transected retinal vessels during 29% of retinotomies, and intraocular lens damage during two posterior capsulotomies. The most significant limitation was the cautious pace used during maneuvers near the retinal surface. CONCLUSION: The erbium:YAG laser is capable of versatile new approaches offering precise tissue cutting and ablation in vitreoretinal surgical maneuvers with a high degree of safety. The main limitation encountered was the slow speed of certain critical maneuvers near the retina.     

Intravitreal ganciclovir treatment in progressive outer retinal necrosis

PURPOSE: To report two patients with progressive outer retinal necrosis, which is presumed to be caused by the varicella-zoster virus in patients with acquired immunodeficiency syndrome (AIDS). METHOD: Case report. RESULTS: The patients were treated with intravenous foscarnet, 60 mg per kg of body weight three times per week, without response. Remission of retinal necrosis occurred with the commencement of intravitreal ganciclovir treatment, 400 mg two times per week. Laser photocoagulation was performed in both cases. Neither patient developed retinal detachment. CONCLUSIONS: Intravitreal ganciclovir treatment combined with systemic antiviral agent therapy in patients with progressive outer retinal necrosis may delay progress of the disease. Early photocoagulation may prevent the development of retinal detachment if retinal necrosis is controlled.     

Immunocytochemical study of retinal diode laser photocoagulation in the rat

AIM: To determine the nature of the cellular infiltrate, alterations in cell adhesion molecules, and MHC II antigen expression in the rat retina following diode laser retinal photocoagulation. METHOD: 20 normal Lister rats underwent diode laser photocoagulation of the retina. Frozen sections from eyes enucleated at 0, 1, 5, 13, and 33 days post laser were examined for T cells (R7.3), CD4 T cells (W3/25), activated CD4 T cells (OX-40), CD8 T cells (OX-8), B cells (OX-33), and macrophages (OX-42), MHC II antigen (OX-6), and E-Selectin-1, VCAM-1, and ICAM-1. RESULTS: Retinal diode laser photocoagulation stimulated a wound healing response in the outer retina and choroid. The cellular infiltrate included macrophages and activated CD4 T cells at 13 and 33 days post laser. Glial cells in the inner plexiform and inner nuclear layers expressed MHC II antigen at 24 hours only. ICAM-1 antigen was induced in RPE cells and in Muller cells in the inner retina at all time intervals post laser and intense staining for ICAM-1 was present around intraretinal migrated cells at 13 and 33 days post laser. VCAM-1 antigen expression was induced in the choroidal vascular endothelium and RPE at 13 and 33 days after laser as was E-Selectin-1 antigen expression which was also evident focally at the external limiting membrane in association with migrated cells adjacent to the burn. CONCLUSIONS: These results suggest that alterations in cell adhesion molecules may regulate the migration and activation of retinal pigment epithelium, macrophages and CD4 T cells at the outer blood-retinal barrier and choroid following diode laser photocoagulation of the normal Lister rat retina.     

Treatment of retinoblastoma with the transscleral diode laser

PURPOSE: To report a case of retinoblastoma successfully treated by contact transscleral photocoagulation with a diode laser. METHODS: In an 18-month-old girl, a small (6.6 x 4.3 x 3.2-mm) discrete retinoblastoma anterior to the superotemporal arcade in the right eye was treated with transscleral photocoagulation using a diode laser (810 nm) and a fiberoptic probe. RESULTS: The tumor regressed after photocoagulation, leaving a pigmented chorioretinal scar. There was no regrowth of the tumor 12 months after photocoagulation. CONCLUSION: Contact transscleral photocoagulation with a diode laser may be a viable new treatment for small retinoblastoma.     

The study on changes of macular light sensitivity before and after photocoagulation for diabetic macular edema

OBJECTIVE: The study was designed to determine whether laser photocoagulation could damage macular visual function in treatment of diabetic macular edema. METHODS: A prospective clinical trial was taken to determine the effects of argon green (514.5nm) laser photocoagulation on macular light sensitivity (MLS) by comparing the self MLS pairing data collected from a Humphrey automatic visual field analyzer before and after the procedure. Nineteen eyes of 15 patients with diabetic macular edema consistent with its diagnostic criteria were enrolled in this study, a follow-up period being 3 months. RESULTS: The mean MLS at the photocoagulation area, non-photocoagulation area, 5 degrees and 13 degrees eccentricity were significantly decreased within 1 week after the treatment, the drops of MLS were 1.85 dB, 1.05 dB, 0.99 dB, 1.66 dB respectively (P < 0.05). The mean reduction of MLS at the fovea within 1 week after the treatment has no statistical significance. The MLS gradually recovered at the 1st and 3rd month after photocoagulation, and the visual acuities in most of the cases were stable or increased. CONCLUSIONS: MLS is affected little by laser photocoagulation, and photocoagulation can reduce the risk of visual loss or increase visual acuity in an eye with diabetic macular edema.     

Photocoagulation in the prevention of retinal detachment in perforating injuries of the eye caused by warfare

Main indications for application of photocoagulation in the prevention of retinal detachment in penetrating eye war injuries were presented. Photocoagulation was performed when intrabulbar foreign body was present, before its extraction and in the cases of traumatic ruptures of sectorial traumatic tractional retinal detachment. Modified photocoagulation by argon laser, with linked spots in two rows was used since it was shown to be clinically the most suitable.     

Intralesional photocoagulation of periorbital hemangiomas

The purpose of this study was to examine the effects of intralesional bare fiber photocoagulation with the KTP and Nd:YAG lasers on periorbital hemangiomas of infancy. Initial reports by Apfelberg and Gregory suggest that intralesional laser therapy may have a role in the treatment of hemangiomas. Intralesional photocoagulation may be preferred to superficial laser treatment for several reasons. It may decrease cutaneous skin damage and more effectively reduce bulky, deep lesions. Twenty-three patients with periorbital hemangiomas were treated (KTP, n = 7; Nd:YAG, n = 16). An 18-g Angiocath was placed into the lesion to pass the fiber through. Laser energy was delivered by means of a 0.6-mm bare fiber at 10 to 15 J (KTP) or 7 J (Nd:YAG). Treatments were done under general anesthesia. Patients were followed closely for 1 month and then monthly to assess results and complications. Results are as follows: 61 percent demonstrated 50-percent or more reduction at 3 months; 22 percent demonstrated 50-percent or more reduction in 3 to 8 months, i.e., 83 percent of patients had 50-percent or more reduction within 8 months. To achieve these results, two patients required two treatments. The remaining 17 percent had 10- to 14-percent reduction at 1 to 3 months. Two of these patients had two treatments. A subgroup of patients had a very dramatic response. Thirty-five percent (8 of 23) had 50- to 90-percent reduction in 1 month. It is unclear why these patients responded so dramatically. We expected some ulceration during the healing phase. Seventeen percent developed ulceration. Complications were limited (4 percent) to one wound infection. Intralesional photocoagulation treatment with the KTP and Nd:YAG lasers is effective and safe for the treatment of periorbital hemangiomas in the majority of patients with minimal complications. Further study is necessary to identify factors that result in dramatic or limited responses.     

Breast cancer in older women

Successful laser treatment of haemangiomas requires selective photocoagulation of subsurface targeted blood vessels without thermal damage to the overlying epidermis. We present an in vivo experimental procedure, using a chicken comb animal model, and an infrared feedback system to deliver repetitive cryogen spurts (of the order of milliseconds) during continuous Nd:YAG laser irradiation. Gross and histologic observations show deep-tissue photocoagulation is achieved, while superficial structures are protected from thermal injury due to cryogen spray cooling. Experimental observation of epidermis protection in chicken comb animal models suggests selective photocoagulation of subsurface targeted blood vessels for successful treatment of haemangiomas can be achieved by repetitive applications of a cryogen spurt during continuous Nd:YAG laser irradiation.