Krypton Red Laser Photocoagulation Research Articles

KRYPTON RED LASER PHOTOCOAGULATION OF THE OCULAR FUNDUS

The theoretical rationale, the histopathologic evidence, and the preliminary clinical studies related to krypton red laser (KRL) photocoagulation of the ocular fundus are reviewed. The authors report on their experience with currently available laser systems using this wavelength (647.1 nm) for photocoagulation of retinal vascular proliferative diseases and chorioretinal diseases associated with exudative manifestations. A histopathologic and clinical comparison of argon blue-green laser (ABGL), the pure argon green laser (AGL), and the krypton yellow laser (KYL), with reference to photocoagulation treatment of the ocular fundus is also discussed.

Growth factors in age-related macular degeneration: pathogenic and therapeutic implications.

To investigate the role of growth factors in choroidal neovascularization in humans with age-related macular degeneration (ARMD) and in rats with choroidal neovascularization produced by krypton laser photocoagulation. Autoradiography using 3H-thymidine in laser-treated rats. Light- and electron-microscopic immunocytochemistry using antibodies to several different growth factors and to the fibroblast growth factor (FGF) receptor. Tissues studied included the retinas of rats that had received krypton red laser photocoagulation, which induces formation of choroidal neovascularization 6-8 weeks after laser treatment, choroidal neovascular membranes (CNVMs) removed surgically from humans with ARMD and whole human eyes obtained postmortem with macular choroidal neovascular lesions from ARMD. Nuclei of retinal pigment epithelium (RPE) and choriocapillary cells in laser-treated rats were labeled with 3H-thymidine up to 80 days after photocoagulation, maximally at 2-7 days after laser treatment. At all intervals, RPE cells in treated areas immunolabeled for aFGF and bFGF. Labeling was strongest within lysosomes. RPE cells in untreated regions did not immunolabel for growth factors. RPE cells from CNVMs in the maculas of humans with ARMD also immunolabeled for aFGF and bFGF. Some choriocapillary endothelial cells in human CNVMs became labeled in a regular array along their anteluminal and luminal plasma membranes with anti-bFGF antibodies and, in a similar pattern, with antibodies to the FGF receptor. Finally, serial sections from some CNVMs in ARMD patients were immunostained alternately for bFGF and for vascular endothelial growth factor (VEGF). RPE cells and choriocapillary endothelial cells in these membranes immunostained for VEGF. Many immunostained for both bFGF and VEGF. In whole human eyes with macular CNVMs RPE cells in regions of normal retina did not immunostain for these growth factors. Several growth factors are not expressed at detectable levels by immunocytochemistry in normal RPE cells in rats or humans but do appear following photocoagulation or the development of CNVMs in ARMD. This suggests that these growth factors have a pathogenic role in choroidal neovascularization. Possibly, bFGF and VEGF act synergistically to accelerate neovascularization. The up-regulation of VEGF in CNVMs is of special interest because up-regulation of this growth factor in other systems appears to be stimulated by tissue hypoxia. Till now, hypoxia has not been considered a major pathogenic agent in the development of CNVMs in ARMD or other macular diseases.

Comparative effects of argon green and krypton red laser photocoagulation for patients with diabetic exudative maculopathy.

Focal treatment of diabetic macular oedema is usually done using a haemoglobin absorbing wave-length, such as argon green laser. This study aimed to compare photocoagulation with argon green (514 nm) and krypton red (647 nm), which is poorly absorbed by haemoglobin, in the focal treatment of patients with diabetic exudative maculopathy. A total of 151 eyes of 78 outpatients were assigned randomly to receive either argon green (n = 79) or krypton red (n = 72) laser treatment. Pretreatment and post-treatment ocular examinations included visual acuity, fundus biomicroscopic examination, and fluorescein angiography. A total of 141 eyes of 73 patients were available for evaluation after 1 year follow up. No statistically significant difference was found between the two treatment groups with respect to visual acuity results, resorption of hard exudates, and resolution of focal retinal oedema. Krypton red laser was effective in the treatment of diabetic exudative maculopathy. Our data suggest that differential absorption of the various wavelengths by haemoglobin within microaneurysms may not be an important factor for ultimate success of focal treatment.

The Influence of Treatment Extent on the Visual Acuity of Eyes Treated With Krypton Laser for Juxtafoveal Choroidal Neovascularization

To examine the direct relationship between the extent of treatment with krypton red laser photocoagulation and visual acuity loss in eyes with choroidal neovascularization secondary to ocular histoplasmosis or age-related macular degeneration. Photographic and visual acuity records from 129 eyes treated in the Ocular Histoplasmosis Study--Krypton Laser and 224 eyes treated in the Age-Related Macular Degeneration Study--Krypton Laser were reviewed. The proportion of eyes with severe visual acuity loss (6 or more lines of loss) was examined for subgroups of eyes based on the distance of the neovascular lesion from the center of the foveal avascular zone and on the extent of laser treatment to the lesion. Differences in the proportions with severe visual acuity loss were evaluated by longitudinal data analysis methods. Among eyes in the Ocular Histoplasmosis Study--Krypton Laser with lesions less than 200 microns from the center of the foveal avascular zone, only 5% of eyes with laser treatment that covered the foveal side and had a narrow (< or = 100 microns) border of treatment to adjacent uninvolved retina experienced severe visual acuity loss compared with approximately 25% of eyes with either some of the foveal side of the lesion left untreated or a wide border of treatment on the foveal side. Treatment extent had little influence on severe visual acuity loss in eyes in the Ocular Histoplasmosis Study--Krypton Laser with neovascular lesions 200 to 500 microns from the center of the foveal avascular zone or in eyes in the Age-Related Macular Degeneration Study--Krypton Laser with lesions in either distance category. Accurate, complete treatment of choroidal neovascularization close to the foveal center is required to provide the patient with the best chance of avoiding further severe visual acuity loss, especially in patients with ocular histoplasmosis. Even among experienced retinal specialists, the required accuracy of treatment is difficult to achieve.

Krypton Laser Photocoagulation for Neovascular Lesions of Age-Related Macular Degeneration

To the Editor. —The Macular Photocoagulation Study (MPS) Group recently reported the results of a randomized clinical trial comparing krypton red laser photocoagulation with no treatment for choroidal neovascular lesions involving the foveal avascular zone in patients with age-related macular degeneration. 1 Although a thorough review of the literature was not the purpose of the report, earlier work by Yassur et al 2 had bearing on the MPS results and should have been cited. Their results from a randomized trial involving 123 eyes with age-related macular degeneration and neovascular lesions involving the foveal avascular zone showed that 37 (67% ) of 55 untreated eyes had deterioration in visual acuity in comparison with only 22 (32% ) of 68 eyes treated with krypton laser. The MPS results for similar eyes showed that 98 (58% ) of 169 untreated eyes in comparison with 86 (49% ) of 174 treated eyes had severe visual loss (six or

Hereditary Hemorrhagic Macular Dystrophy

We treated two brothers who had a hemorrhagic macular lesion in one eye; a similar problem affected the fellow eye of both patients within eight months. Generalized fine granularity of the retinal pigment epithelium and peripheral iris transillumination defects were observed in both siblings. A study of the family suggested that the disorder was dominantly inherited and probably was Sorsby's pseudoinflammatory macular dystrophy. The macular lesions in one brother were treated by argon green laser photocoagulation and in the other brother by krypton red laser photocoagulation. Although the brother treated by krypton red laser photocoagulation attained better final visual function, additional differences in treatment methods also may have contributed to the final outcome.

Krypton Laser Photocoagulation for Neovascular Lesions of Age-Related Macular Degeneration

The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K.

Persistent and Recurrent Neovascularization After Krypton Laser Photocoagulation for Neovascular Lesions of Age-Related Macular Degeneration

The persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 247 eyes assigned to krypton red laser photocoagulation in the Age-Related Macular Degeneration Study-Krypton Laser were examined to describe the incidence, timing, visual impact, and potential risk factors for persistence and recurrence. Persistent neovascularization detected within 6 weeks of initial treatment was observed in 32% of treated eyes, and recurrent neovascularization was estimated by life-table methods to develop in an additional 47% over a 5-year period. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. The persistence rate among eyes having 10% or more of the foveal side of the neovascular membrane not covered by treatment was twice as high as in eyes having more extensive coverage. Patients having a fellow eye with a neovascular membrane or scar, a fellow eye with 20 or more drusen in the central macula, or a fellow eye with nongeographic atrophy at initial visit had more recurrences than patients without these characteristics. Ophthalmologists treating similar lesions may be able to reduce persistent neovascularization and the associated visual loss by covering the entire lesion with treatment.

Iatrogenic Choroidal Neovascularization After Krypton Red Laser Photocoagulation

A major cause for failure of krypton red laser photocoagulation in patients with exudative age-related macular degeneration has been the development of recurrent choroidal neovascularization adjacent to the previously treated areas. After reviewing the possible causes of recurrences, it is apparent that a certain number are iatrogenic, ie, induced by krypton red laser causing disruption and damage to the pigment epithelium-Bruch's membrane-choroidal complex. We describe three separate episodes in two patients of iatrogenic recurrent choroidal neovascularization after krypton red laser photocoagulation.

The Treatment of Serous Macular Detachment Secondary Choroidal Melanomas and Nevi

The authors successfully treated with laser photocoagulation five patients who had a serous macular detachment secondary to leakage from a pigmented choroidal tumor. Three patients had dye leakage on fluorescein angiography from a choroidal neovascular membrane. The subretinal fluid resolved in all three patients after the neovascular membrane was obliterated by either krypton red (2 patients) or argon green (1 patient) laser photocoagulation. The other two patients had prominent leakage from a localized choroidal neovascular membrane as well as mild diffuse leakage over the entire tumor. Focal argon laser treatment to the neovascular membrane alone did not cause permanent resolution of the subretinal fluid. The fluid did resolve, however, after the entire area of diffuse leakage was retreated with photocoagulation. In one of the patients who received both focal and confluent laser treatment, the choroidal tumor grew in a collar-button fashion through Bruch's membrane at the original site of focal treatment. This eye was enucleated, and results of histopathologic examination showed a choroidal melanoma.

Persistent and Recurrent Neovascularization After Krypton Laser Photocoagulation for Neovascular Lesions of Ocular Histoplasmosis

Persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 144 eyes assigned to krypton red laser photocoagulation in the Ocular Histoplasmosis Study-Krypton Laser were examined to describe persistence and recurrence in these patients. Persistent neovascularization was observed among 23% of treated patients and recurrent neovascularization was observed among an additional 8%. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. Patients with high blood pressure were more than 2.5 times as likely to have persistent neovascularization as patients without high blood pressure (95% confidence interval = 1.5, 4.8). Eyes in which the neovascular component of the complex was within 200 microns of the center of the foveal avascular zone were twice as likely to have persistent neovascularization (95% confidence interval = 1.2, 4.6). Eyes in which the treatment did not cover the neovascularization completely or did not meet the required level of intensity on the foveal side had a persistence rate approximately three times that of eyes in which the neovascularization was covered completely by intense, confluent burns (95% confidence interval = 1.7, 6.5). This last finding is of particular importance for ophthalmologists who treat similar patients.

RETINAL LASER PHOTOCOAGULATION

Three monkeys were treated with krypton red laser photocoagulation in a manner simulating treatment of a choroidal neovascular membrane. One eye of each monkey was treated by employing immediately the power level needed to produce a lesion judged biomicroscopically to be of sufficient intensity (Method A). The fellow eye was treated by starting with lower power levels and then gradually increasing to the level needed to produce a similar-appearing lesion (Method B). Parameters of spot size and treatment duration were kept constant. Animals were sacrificed three days, eight days, and four months after treatment. Both methods of treatments spared the overlying ganglion cell layer in all fundus locations, but Method A induced cell loss in the inner nuclear layer while Method B spared it. Since reaching the clinical endpoint for Method B required fewer spots at the highest power level, the number of spots at the highest power level is probably the most important factor in determining degree of inner retinal absorption. Since both methods of treatment resulted in satisfactory closure in the choriocapillaries, the histopathologic differences may not be clinically important.

Krypton Laser Photocoagulation for Neovascular Lesions of Ocular Histoplasmosis

The Ocular Histoplasmosis Study-Krypton Laser is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with ocular histoplasmosis that have either choroidal neovascularization 1 to 199 micron from the center of the foveal avascular zone (FAZ) or choroidal neovascularization 200 micron or further from the FAZ center with blood and pigment extending within 200 micron of the FAZ center. Patients were assigned to photocoagulation (n = 143) or to observation only (n = 145). Recruitment of patients with such lesions has been stopped because more untreated eyes than treated eyes had experienced severe visual acuity loss. At one year after randomization, 24.8% (31/125) of untreated eyes, in contrast with 6.6% (8/121) of treated eyes, had lost six or more lines of visual acuity; by three years after randomization, the corresponding values were 24.6% (15/61) and 4.6% (3/64). The superiority of treatment was evident at every point in time after six months. There were no subgroups in which there was convincing evidence that treatment was harmful. Follow-up of all patients continues to assess long-term results of treatment.

Krypton Red Laser Photocoagulation for Branch Retinal Vein Occlusion

Krypton red (647 nm) laser photocoagulation may offer distinct advantages in the treatment of branch retinal vein occlusion (BRVO), particularly in eyes with extensive intraretinal hemorrhage or in the presence of media opacities such as vitreous hemorrhage or cataract. Twenty-three eyes were followed for a minimum of 6 months (range, 6–38). Of 19 eyes treated for macular edema, 17 (89%) had complete resolution of their edema, one (5%) had reduction of its edema, and one (5%) was unchanged. Of five eyes treated for retinal neovascularization of the disc or retina, all eyes had complete elimination of neovascularization. The authors were unable to demonstrate any statistical correlation between final visual acuity and the following factors: duration of symptoms, cystoid macular edema (CME), degree of paramacular nonperfusion, and contiguous intraretinal hemorrhage extending into the foveal avascular zone (FAZ).

Review of Choroidal Osteoma: Successful Krypton Red Laser Photocoagulation of an Associated Subretinal Neovascular Membrane Involving the Fovea

Laser treatment of a subretinal neovascular membrane associated with a unilateral choroidal osteoma in a 28-year-old woman is described. To our knowledge, this is the first reported use of krypton red laser photocoagulation for the initial treatment of a subfoveal neovascular membrane in this setting. Early recognition of the membrane allowed treatment prior to involvement of the central fovea. Follow-up has shown obliteration of the membrane without recurrence and 20/20 vision. We emphasize recognition of this unusual tumor, self-monitoring with an Amsler grid, and early treatment of subretinal neovascularization in this high risk group of young patients.

Krypton and argon laser photocoagulation for central serous chorioretinopathy.

Based on medical records, the authors divided 86 eyes of 84 patients with central serous chorioretinopathy with serous detachment of the macula and retinal pigment epithelial leakage on fluorescein angiography into three groups: no laser treatment (45 eyes), argon laser treatment (26 eyes), and krypton laser treatment (15 eyes). One or more episodes of recurrence developed during the follow-up period in 10 untreated eyes (22%), 9 argon-treated eyes (35%), and 0 krypton-treated eyes. The difference in recurrence rate between argon- and krypton-treated eyes was statistically significant. The findings suggest that whenever laser treatment is indicated, krypton red laser photocoagulation may reduce the incidence of recurrence in eyes with central serous chorioretinopathy.

Recurrent Subretinal Neovascularization

To the Editor. —In a recent issue of theArchives, Wallow et al 1 reported a case of recurrent subretinal neovascularization originating from the retinal circulation following krypton laser photocoagulation. We have also observed this phenomenon clinically, 2 particularly originating from the venous side. We feel, however, that this form of recurrent subretinal neovascularization is most common following treatment with a hemoglobin-absorbing wavelength, such as argon blue-green or green laser. Argon laser photocoagulation commonly causes destruction and atrophy of the overlying retina. This procedure damages normal intraretinal structural barriers and displaces the retinal circulation into closer proximity to the choroidal circulation. Retinal-choroidal anastomoses and recurrent subretinal neovascularization originating from the retinal circulation are potential consequences. In our experience, this form of recurrent subretinal neovascularization following krypton red laser photocoagulation occurs under the following conditions: A very intense burn that extends to the overlying retina. In this case, the

Cell Proliferation After Laser Photocoagulation in Primate Retina

Argon blue-green laser and krypton red laser (KRL) photocoagulation were applied to primate retinas at intervals ranging from two to 23 days before the animals were killed. An injection of tritiated thymidine was given intravitreally three days before death. Argon blue-green laser photocoagulation induced cell proliferation in the retina and retinal pigment epithelium seven days after treatment, with quiescence at 23 days. Krypton red laser photocoagulation induced similar cell proliferation not only in the retina and retinal pigment epithelium but also around choroidal vessels and in the stroma of the choroid. Peak thymidine uptake occurred seven days after KRL treatment. There was less uptake at two and 11 days and no uptake at 23 days. Thymidine uptake in the retina and choroid also was detected with low levels of KRL treatment. True cell hyperplasia (cell division) occurred after laser treatment; only KRL treatment induced cellular reaction in the choroid.

Krypton red laser photocoagulation of peripapillary subretinal neovascular membranes

The visual outcome of 20 eyes of 20 patients with peripapillary subretinal neovascular membranes (SRNVM) treated with krypton red laser photocoagulation (KRLP) was studied. Complete obliteration of the SRNVM was achieved in all eyes in the study. In 18 of 20 patients, the visual acuity improved or remained the same during an average follow-up of 9.9 months. There were no treatment-related complications. The efficacy of KRLP in the management of patients with peripapillary SRNVM is discussed.

Krypton red laser photocoagulation in selected cases of central serous chorioretinopathy.

Krypton red laser photocoagulation was carried out in 15 eyes with chronic, uncomplicated monocular central serous chorioretinopathy. All patients had vocations requiring excellent binocular vision, and could not work effectively with their current visual acuity. Krypton red was selected as the most suitable photocoagulative source, given the nature of the disease, the tissue-selectiveness of krypton red laser on the retinal pigment epithelium, and the relative inability of the macular luteal pigment and capillary beds of the inner retinal layers to absorb the red wavelength. Visual acuity improved in all 15 eyes, and to at least 20/30 (6/9) in 12 eyes (80%). The visible effects of krypton red laser photocoagulation on the retinal pigment epithelium were minimal and, although nine eyes had had focal leaks within 100 microns of the foveal avascular zone and 12 eyes had been photocoagulated within the maculopapillar bundle, no adverse clinical effects were observed. In carefully selected cases, then, krypton red laser photocoagulation appears to be suitable and safe for the treatment of central serous chorioretinopathy in a tissue-specific manner.