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Photocoagulation of Vascular Lesions of the Macula
P H O T O C O A G U L A T I O N O F V A S C U L A R LESIONS O F T H E M A C U L A GEORGE N . WISE, M . D . , CHARLES J. CAMPBELL, M . D . , PERCYVALDO F . WENDLER, M . D .
AND M . CATHERINE RITTLER, A.B.
New York Vascular diseases of the macula have become of great importance, in view of the increase in our aging population. In the past, therapy has often been unrewarding; however, recent advances in diagnostic techniques and therapeutic procedures hold the promise of treatment of many of these intractable syndromes. This is a report of the treatment by photocoagulation of a number of vascular diseases affecting primarily the macula. Fluorescein studies to detect the defects of Bruch's membrane are usually necessary before photocoagulation.
this sequence of events by sealing the initial defect in Bruch's membrane. Fluorescein appears to be ideally suited for detecting the break in Bruch's membrane. It is water-soluble, transported by serum, and will readily diffuse through those defects which permit the escape of serum itself. The dye is well tolerated by human subjects, with only rare side-reactions. The fluorescing quality is particularly valuable and indeed is essential for the detection of leaks. The fluorescence is stimulated by suitable filtered light, and the breaks in Bruch's membrane, represented by leak sites of the dye, have a bright luminous quality.
PATHOLOGIC PHYSIOLOGY
The detection of leak sites or defects in Bruch's membrane by the fluorescein test may sometimes be difficult. A leak, or positive fluorescein test, consists of a somewhat ill-defined fluorescing point or area, with increased brightness at the center and somewhat fuzzy edges. Perhaps the most important characteristic is the behavior of these fluorescing areas with time. They generally increase in brightness and size as the general choroidal fluorescence fades.
The recent investigations of Gass have demonstrated that many vascular syndromes of the macula result essentially from defects in Bruch's membrane. It is postulated that small defects in this membrane permit serum to escape from the choriocapillaris and serously elevate the retina. The pigment epithelium may also be serously elevated by the disease process, but in either case the basic defect lies in Bruch's membrane. Hemorrhages may also be associated with this pathologic process and the blood may be located beneath either the pigment epithelium or the retina. Perhaps as a consequence of hypoxia in the elevated retina, neovascularization, along with glial proliferation, may occur beneath the pigment epithelium, representing a final irreversible disciform type of lesion. The goal of treatment is to interrupt 1
From the Department of Ophthalmology, New York University School of Medicine (Drs. Wise and Wendler), and the Knapp Memorial Laboratory of Physiological Optics, College of Physicians and Surgeons, Columbia University, 635 West 165th Street 10032 (Dr. Campbell and Miss Rittler). This study was supported in part by U S P H S Grant NB-07130 of the National Institute of Neurological Disease and Blindness.
Not infrequently the fluorescein test may result in misleading or false data, particularly if, for unknown reasons, there is poor filling of the retinal vessels, as manifested by subnormal fluorescence after the dye injection. Of primary importance in unsatisfactory fluorescein tests are artifacts in the fundus. Areas of high reflectivity (exudates or medullated nerve fibers) may appear to be persistently bright ; however, their unchanging quality and true lack of fluorescence, should permit proper identification. A more subtle defect is the absence or reduced density of the pigment epithelium. This permits the normal choroidal fluorescence to be somewhat more prominent in that area. In this situation, however, generally there is not
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increased brightness of the fluorescing area in the center and the edges are usually not fuzzy; this fluorescing area fades with the fading of the general choroidal fluorescence and, during the course of time, does not increase in size. On the other hand, a true leak may be obscured by a superficial hemorrhage. These considerations indicate clearly that the interpretation of fluorescein data requires experience and meticulous attention to detail. The fluorescein data may be interpreted by either ophthalmoscopy or photography. The ophthalmoscopic techniques may employ either conventional direct ophthalmoscopy, indirect ophthalmoscopy, or slitlamp biomicroscopy with a contact lens. In all these situations it is essential that suitable filtering techniques be employed. Unfortunately, the characteristics of Bruch's membrane defects are often elusive, and the problem is even more difficult if there are many leak sites. As a consequence visual detection may not be adequate, particularly when the test is performed with treatment in mind. Effective therapy requires the detection of each leak site ; consequently fluorescein photography is usually necessary before treatment is undertaken. Photographs also permit serial comparison at different time-intervals after dye injection and hence provide quantitative evaluation of the potential leak sites. Furthermore, photographic evidence provides precise localization for coagulation therapy. LASER T H E R A P Y OF M A C U L A R LESIONS
Lesions of minimal intensity produced by the laser photocoagulator are characterized primarily by disturbances at the level of the pigment epithelium. • At the time of treatment, these lesions appear as ill-defined, extremely faint gray discs in which slight irregularities may be manifested as small central accumulations of pigment or as an irregular fine annulus of pigment at the edge of the lesion. The gray color disappears within a few days after treatment and a faint punctate pigment pattern results. Immediately 2
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453
after treatment, the principal effect noted histologically is an irregularity of the pigment epithelium. There is actual clumping of pigment cells in the more central area of the lesion. Slight subretinal exudate separates the retina from the pigment epithelium. No disturbance of the normal retinal architecture is apparent, and this is particularly true of the nerve fiber layer, which is significantly distant from the site of energy absorption. The subretinal exudate disappears within several days and there is evidence of slight pigment migration into the external layers of the retina. The retinal architecture, however, remains largely undisturbed in lesions of minimal intensity. Of particular importance to this investigation, there is no evidence of destruction in the nerve fiber layer in lesions of this intensity. 4
Laser photocoagulation appears to be a most suitable technique for the treatment of defects in Bruch's membrane. The energy is absorbed primarily at the level of the pigment epithelium. Little disturbance occurs to the retina itself, if lesions of minimal intensity are employed. In the instrumentation* used in this study, the laser beam may be focused sharply and located precisely on the retina, confining the energy to a sharply circumscribed region, with a high degree of localization. The technique of laser photocoagulation of central lesions is in general similar to that employed for peripheral pathology. The pupil must be dilated with a cycloplegic and the treatments are generally performed on an out-patient basis. Treatments may be performed within five degrees (one disc diameter) of the fovea with relative safety. Obviously the treatment of subfoveal leak sites will result in the destruction of central function and largely defeat the purpose of treatment. If the patient manifests uncertainty of fixation or if treatments are performed closer than five degrees to the fovea, a large retrobulbar injection is employed. * A O Instrument Company, Buffalo, New York.
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RESULTS
TABLE 1
Forty-three patients in three disease categories were treated. The findings are summarized in Table 1. Each group in itself merits definition and further comments may be of value in interpreting the data in the table. In this study, central serous retinopathy is defined as an elevation of the retina in the macular region by serum. It is due to escape of serum through the pigment epithelium from the choroidal circulation via a defect in Bruch's membrane. There may be multiple serous elevations in the general macular or posterior polar region. This disease may also be associated with blister-type elevation of the pigment epithelium.
SUMMARY OF RESULTS OF TREATMENT B Y LASER PHOTOCOAGULATION OF 43 PATIENTS WITH MACULAR VASCULAR PATHOLOGY
The indications for treatment of patients with central serous retinopathy can be defined with some precision. In general there should be a protracted course of the disease from its onset of at least three month's duration. Most patients included in this series had evidence of the disease for time-intervals varying between eight and 24 months. There may also be evidence, in addition to the extended time-interval, of progression of the disease with associated irreversible changes. In general this includes the occurrence of hemorrhages, exudates, or of subretinal organization or fibrosis. The fluorescein test always must be positive. Not infrequently, numerous leak sites are found again, confirming the importance of photography. The treatable area, that is, the leak site, must be located at least two degrees (one-third disc diameter) from the fovea. Table 2 shows the results of treatment of 22 patients with central serous retinopathy. Of these, 14 are classified as good results. In most cases the visual acuity is 20/20, the fluorescein test after treatment is negative, and there is no residual subretinal fluid. A moderate result, on the other hand, indicates a partial restoration of vision, generally between 20/25 and 20/50, and closure of the leak sites; there is no remaining subretinal fluid. In the results classified as poor there is
Central serous retinopathy (22) Disciform degeneration (14) Preretinal macular fibrosis (7)
Good
Moderate
Poor
14
3
5
3
4
7
1
5
1
generally a marked further reduction in visual acuity after treatment, ranging between 20/50 and 20/400. Frequently there is persistence of central subretinal fluid; the leak sites remain in spite of repeated photocoagulation, and, in two patients, the disease progressed to a disciform type of macular degeneration in which there was subretinal gliosis and organization, together with superficial retinal hemorrhages. These data indicate that great care must be taken in the selection of patients for treatment of central serous retinopathy. Disciform degeneration of the macula has been defined as a serous, exudative, hemorrhagic elevation of the retina, which may be associated with subretinal fibrosis and neovascularization. The primary pathology appears to be a defect in Bruch's membrane and an anoxemic vascular cycle. Indications for treatment of disciform degeneration of the macula are less well established than for the management of central serous retinopathy. In general, the diagnosis of disciform degeneration is ample reason for performing a fluorescein test. If widespread central destruction has occurred in the first eye as a consequence of disciform disease, the treatment may be carried out more vigorously and over a more extensive area if the second eye becomes involved. In general, it is believed that sharp focal leaks and leaks removed a significant distance from the macula respond more satisfactorily to this form of treatment. Older patients do not respond as well as those in younger age groups.
PHOTOCOAGULATION OF MACULA
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TABLE 2 CLINICAL DATA ON 22 PATIENTS WITH CENTRAL SEROUS RETINOPATHY
Duration of Disease Before Treatment Good 1 2 3 4 5 6 7
Visual Acuity After Before Treatment Treatment 20/30-2 20/40-1 20/20-3 20/30-2 20/25-2 20/200 20/15-1
20/20-2 20/20-3 20/20-3 20/20 20/15-2 20/50 20/15-1
20/50-2 20/25-2 20/20-2
20/40-2 20/20 20/15-3
Remarks
8 9 10
8 weeks 10 weeks 3 weeks
11
6 weeks
20/20
20/15-3
12
3 weeks
20/25-2
20/15-3
5 months 8 months
20/200 20/200
20/60-1 20/60
2nd eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment O.U.—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 3rd attack 1st eye involved—1 treatment 1st eye involved—1 treatment
20/40-2 20/7020/400-
20/40-2 20/5020/400
1st eye involved—2 treatments 1st eye involved—1 treatment O.U.—2 treatments
20/400 20/8020/70-1 20/2520/25-3
20/40020/400 20/40020/40020/40-
1st eye involved—1 treatment 2nd eye involved—2 treatments 1st eye involved—3 treatments 1st eye involved—1 treatment 1st eye involved—1 treatment
13 14 Moderate 15 16 17 Poor 18 19 20 21 22
4 5 2 ?20 3J 6 4
weeks months months years years months weeks
11 months 9 months ?19 years 3 4 5 3 4
months weeks months months months
The treatment is frequently difficult in this disease. On occasion hemorrhages and massive exudation make it extremely difficult or even impossible to produce a satisfactory reaction with the photocoagulator. The power values must be regulated carefully, but it must be realized that high-power values may be necessary to achieve the desired result in these abnormal conditions. Table 3 shows the results of treatment in 14 patients with the diagnosis of disciform degeneration. The results in three have been classified as good. In this disease a good result consists of improvement in visual acuity and a negative fluorescein test after treatment, with absence of serous elevation of the retina. For classification as a moderate result, the patient must have experienced improvement in visual acuity, the leak must be sealed, and no superficial hemorrhages remain. It does not necessarily mean that all
residual subretinal fluid has absorbed. A significant number of poor results have been obtained. In these patients the disciform process has progressed. The glial elevation remains, and widespread serous elevation of the retina is present. Extensive hemorrhages are found throughout the posterior pole. The fluorescein test in patients with poor results is generally positive over large areas at the posterior pole ; usually there is evidence that the original leak sites still leak, or new leaks have developed. Preretinal macular fibrosis is defined as a disease characterized initially by increased intraretinal edema, full veins, and altered highlights on ophthalmoscopic examination. Later there is ophthalmoscopic evidence of gliosis, striae, intraretinal cysts and serous elevation of the retina. It is suggested that this disease is the result of venous stasis, but it also has been proposed that it may be the
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TABLE 3 CLINICAL DATA ON 14 PATIENTS WITH DISCIFORM DEGENERATION
Duration of Disease Before Treatment Good 1 2 3 Moderate 4 5 6 7 Poor 8 9 10 11 12 13 14
4 months 4 months 8 months
Visual Acuity Before After Treatment Treatment
Remarks
20/30-2 20/400 20/15-2
20/25 20/70-2 20/15-2
1st eye involved—2 treatments 1st eye involved—1 treatment 2nd eye involved—2 treatments
3 10 6 7
months months weeks months
20/40020/40020/30-2 20/400
20/40020/400 20/30 20/80-2
2nd eye involved—1 treatment 1st eye involved—2 treatments 2nd eye involved—1 treatment 2nd eye involved—1 treatment
2 5 4 2 7 5 2
months months months months weeks weeks months
20/400 20/7020/40-2 20/40-3 20/50-2 20/50-2 20/40-
20/40020/200 20/60-2 20/40020/200 20/80-2 20/50-
1st eye involved—1 treatment 1st eye involved—2 treatments 2nd eye involved—1 treatment 1st eye involved—1 treatment 2nd eye involved—1 treatment 2nd eye involved—1 treatment 2nd eye involved—1 treatment
result of vitreous traction at the posterior pole. The fluorescein test in this disease is usually either negative or shows evidence of leaks from retinal veins. In no patients have leaks been defined through Bruch's membrane, and there is no evidence that this membrane is primarily involved. The rationale for laser photocoagulation of this disease differs from that in diseases in which the primary pathology is located in Bruch's membrane. The only leaks detected —those from retinal veins or capillaries— probably cannot be sealed by laser photocoagulation. In this study, treatment consisted of producing multiple, near-threshold, faint laser coagulations throughout the entire posterior pole of the eye, between the temporal vessels, including, in this series, the centrocecal region. Two, or even three, treatment sessions may be necessary to produce satisfactory reactions. Postoperatively, even after prolonged observation there is only the faintest evidence of a pigmentary reaction. The rationale for this form of therapy is the production of a closer association between the choroid and the retina. Hopefully, a firmer chorioretinal association will result in the restoration of some retinal function. Alternately, or perhaps additionally, the destruction of some retinal elements will re-
duce the stimulus to preretinal fibrosis. It is well known that viable retinal cells are necessary for fibrosis to progress. The criteria for treatment of patients of this disease category have not been fully established. Tentatively it would appear that a patient with 20/50 or less visual acuity should have photocoagulation, particularly if the disease has been present for an extended timeinterval. If the second eye is involved, treatment is performed earlier, and a patient with visual acuity of 20/30 or less would be treated shortly after onset of the disease. A total of seven patients with macular fibrosis were treated, as indicated in Table 4. A good result was obtained in only one patient (restoration of vision to 20/20 after a 17-month course of the disease). In this patient the second eye was involved and visual acuity had been reduced to 20/30. The postoperative follow-up interval in this patient is 30 months and the vision remains intact. A moderate result was obtained in five patients. In this situation an improvement in visual acuity occurred, although the final visual acuity in none of these patients was better than 20/25. In most of these, some slight remaining edema persisted at the posterior pole but was significantly reduced by the treatment. One patient in the entire series
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457
TABLE 4 CLINICAL DATA ON 7 PATIENTS WITH MACULAR FIBROSIS
Duration of Disease Before Treatment Good 1 Moderate 2 3 4 5 6 Poor 7
Visual Acuity After Before Treatment Treatment
Remarks
6 weeks
20/30+2
20/15-3
2nd eye involved—2 treatments
8 7 2 6
20/50-2 20/200 20/400 20/200
20/50-2 20/5020/200 20/200
8 months
20/15
20/15
2nd eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd eye involved—1 treatment subjective near vision improvement 1st eye involved—2 treatments
Many months
20/60-2
20/100 - 2
1st eye involved—1 treatment
months months years months
manifested poorer visual acuity after treatment than before treatment. This case is considered further in the discussion. Case histories are frequently of value in illustrating the application and the results obtained in this form of therapy. The first patient, aged 36 years, had a diagnosis of central serous retinopathy; five leak sites were found on fluorescein examination. Clinically there was a serous elevation of the macula without detachment of the pigment epithelium. The disease had been present for 21 months and the visual acuity was reduced to 20/40. Photocoagulation was performed at each leak site. On re-examination one month later, faint pigment was evident at the areas treated. The fluorescein test was repeated and found to be negative and on clinical examination there was no evidence of subretinal fluid centrally. The visual acuity was restored to 20/20. A second patient, aged 62 years, with the diagnosis of central serous retinopathy in his second eye, illustrates one of the less rewarding cases. This patient's first eye had developed a disciform type of macular degeneration some two years previously, with loss of central function. The disease in the second eye was characterized by a serous elevation of the retina centrally without involvement of the pigment epithelium. There was no deep glial proliferation and no deep exudation or hemorrhage. One small superficial hemorrhage was evident temporal to
the macula. The visual acuity was reduced to 20/80. On fluorescein examination a number of leaks were detected above the macula just inferior to the temporal vessel arcade. Photocoagulation was performed at the leak sites without complications. Six weeks after treatment the visual acuity was less than 20/400. At the treatment sites and in the macula there was a large glial elevation surrounded by extensive superficial retinal hemorrhages. The retina was also serously elevated over the gliosis. The fluorescein test showed extensive leaking at the treatment area but the leaks had become significantly larger, truly massive in size. Fluorescein was evident in the subretinal fluid throughout the entire posterior pole. It is apparent that photocoagulation in this patient was not of value and indeed may have accelerated the progression toward disciform degeneration. At this time it is not possible to differentiate early in the course of central serous retinopathy those patients who will respond satisfactorily to treatment and those in whom the disease is subject to progression. The third example is a patient, aged 71, years, with disciform degeneration of the macula. In this individual a large glial elevation was found temporal to the macula, associated with a relatively marked serous elevation of the retina which extended to the macula itself. Superficial hemorrhages were also evident in this area. The visual acuity was 20/400. On examination with intravenous
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AMERICAN JOURNAL OF OPHTHALMOLOGY
fluorescein three leaks were detected, slightly removed from the superior end of the temporal glial scar. Photocoagulation was performed to this area and resulted in the sealing of two leaks. On re-examination six weeks later, the fluorescein test showed one small remaining leak of the three original leaks. The treatment areas were all lightly pigmented, the extensive hemorrhages had largely disappeared, and the elevated glial plaque was much smaller in size. Only slight fluid persisted centrally. A second session of photocoagulation satisfactorily sealed the third persistent leak. At the time of treatment the corrected visual acuity was 20/30-2. Some eight weeks after the second session, visual acuity was 20/25-3. The treatment at the third leak site was by this time solidly pigmented and the intravenous fluorescein test was negative. No subretinal fluid was evident in the macula and there were no superficial hemorrhages. Persistent slight perifoveal cystic changes were present.
S E P T E M B E R , 1968
along with a significant number of patients in this and other disease categories, in the centrocecal area. After treatment the serous elevation of the retina was greatly decreased and there was some reduction in the preretinal fibrosis. The reduced visual acuity and the visual field defect appear to represent damage to the nerve-fiber layer of the retina. Although this type damage apparently occurred in only one patient in the entire series, it serves to emphasize the caution with which treatment in this area must be performed. When treatment is performed on serously elevated retina, particularly when associated with subretinal exudates and hemorrhages, substantially higher power values must be employed. The lesions produced by the laser photocoagulator at the time of treatment are often extremely difficult to detect. Therefore uncertainty may exist as to the exact energy required by the clinical problem. Treatment with higher-power values must be undertaken with careful consideration.
DISCUSSION
Some variability has been noted in the results obtained with the fluorescein test when it was performed on more than one occasion. Specifically, it has been found that leaks detected on one examination may not be present on reexamination a short time later but may be found still later on a third examination, suggesting that some leaks may be intermittent in nature and that it may be of value to repeat the fluorescein studies in some patients. The minimal intensity of the laser coagulations permits photocoagulation of relatively large areas with apparent safety. The centrocecal area and the peripapillary zones may be treated but extreme caution must be exercised to prevent damage to the nerve-fiber layer. In one patient, referred to previously with the diagnosis of preretinal macular fibrosis, the visual acuity was decreased after treatment. On perimetric examination a centrocecal visual field defect was found. Photocoagulation was performed in this patient,
CONCLUSIONS
A technique of study and treatment of patients with macular vascular diseases has been described. Although the results are not entirely rewarding they do show sufficient promise to suggest that this form of treatment merits further investigation. Meticulous clinical and fluorescein investigation preoperatively, and equally cautious therapy with the laser photocoagulator are required. Patients selected for this type of treatment must, in general, be those in whom there is definite evidence of irreversible progression of the disease process with a specific threat to central function. SUMMARY
The technique of fluorescein angiography permits critical evaluation of the retinal vascular system and the integrity of Bruch's membrane as a serum barrier. Laser photocoagulation allows the coagulating energy to be directed to the pigment epithelium of the
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P H O T O C O A G U L A T I O N OF M A C U L A
retina with great precision. These combined techniques have been employed in the treatment of selected vascular diseases of the macula, and results are shown in 43 patients. This form of therapy holds a measure of promise of effective control in some patients with these frequently intractable syndromes. 635 West 165th Street (10032) REFERENCES 1. Gass, J. D. M. : Pathogenesis of disciform detachment of the neuroepithelium. I. General concepts and classification. Am. J. Ophth. 63:573, 1967 ; II. Idiopathic central serous choroidopathy, p.
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EFFECTS
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587; III. Senile disciform macular degeneration, p. 617; IV. Fluorescein angiographic study of senile disciform macular degeneration, p. 645; V. Disciform macular degeneration secondary to focal choroiditis, p. 661 ; V I . Disciform detachment secondary to heredodegenerative, neoplastic and traumatic lesions of the choroid, p. 689. 2. Campbell, C. J., Koester, C. J., Curtice, V., Noyori, K. S. and Rittler, M. C. : Clinical studies in laser photocoagulation. Arch. Ophth. 74:57, 1965. 3. Campbell, C. J., Rittler, M . C , Noyori, K. S., Swope, C. H. and Koester, C. J. : The threshold of the retina to damage by laser energy. Arch. Ophth. 76:437, 1966. 4. Noyori, K. S., Campbell, C. J., Rittler, M. C. and Koester, C. J. : The characteristics of experimental laser coagulation of the retina. Arch. Ophth. 72:254, 1964.
PRODUCED BY EXPERIMENTAL LASERS
I. Q-SWITCHED RUBY LASER CHARLES J. CAMPBELL, M . D . M . CATHERINE RITTLER, A . B . New
York
AND C . HERMAS SWOPE, A . B . CHARLES J.
KOESTER,
PH.D.
Framingham, Massachusetts
The investigation of the ocular effects of Q-switched ruby lasers is important because it is a new source of light of very high power and because of the potential hazards associated with this type of laser. This report includes a description of the Q-switched laser photocoagulator and the experimental technique. The effects of maximum power levels of this radiation on the cornea, lens, iris, vitreous, and serously elevated retina have been explored, but particular attention has been directed toward the intact retina. A range of power values has been used, includFrom the Knapp Memorial Laboratory of Physiological Optics, Institute of Ophthalmology of Presbyterian Hospital, College of Physicians and Surgeons, Columbia University (Dr. Campbell and Miss Rittler) and American Optical Corporation, Research Division, Framingham, Massachusetts (Mr. Swope and Dr. Koester). This study was supported in part by U S P H S Grant NB-07130 of the National Institute of Neurological Diseases and Blindness of the National Institutes of Health, Bethesda, Maryland.
ing the energy necessary to produce a nearthreshold lesion. The characteristic appearance of these retinal lesions at various time intervals after treatment has been documented and related to the histologic findings. Previous investigators have reported on certain characteristics of the retinal lesions produced by Q-switched ruby lasers. Geeraets and associates noted that even in minimal lesions there was marked displacement forward of cells in the pigment epithelium. With higher energy values the displacement of the retina increased, as observed histologically. Minimal lesions were produced with 28.5 nanosecond exposures at an energy density of 0.07 joules/cm . Bergqvist and co-workers " studied retinal lesions of various sizes and noted different characteristics of lesions less than 0.1 mm compared with those found in lesions greater than 0.9 mm, the smaller lesions being craterlike and deeper. The larger le1
2
2
3
AND M . CATHERINE RITTLER, A.B.
New York Vascular diseases of the macula have become of great importance, in view of the increase in our aging population. In the past, therapy has often been unrewarding; however, recent advances in diagnostic techniques and therapeutic procedures hold the promise of treatment of many of these intractable syndromes. This is a report of the treatment by photocoagulation of a number of vascular diseases affecting primarily the macula. Fluorescein studies to detect the defects of Bruch's membrane are usually necessary before photocoagulation.
this sequence of events by sealing the initial defect in Bruch's membrane. Fluorescein appears to be ideally suited for detecting the break in Bruch's membrane. It is water-soluble, transported by serum, and will readily diffuse through those defects which permit the escape of serum itself. The dye is well tolerated by human subjects, with only rare side-reactions. The fluorescing quality is particularly valuable and indeed is essential for the detection of leaks. The fluorescence is stimulated by suitable filtered light, and the breaks in Bruch's membrane, represented by leak sites of the dye, have a bright luminous quality.
PATHOLOGIC PHYSIOLOGY
The detection of leak sites or defects in Bruch's membrane by the fluorescein test may sometimes be difficult. A leak, or positive fluorescein test, consists of a somewhat ill-defined fluorescing point or area, with increased brightness at the center and somewhat fuzzy edges. Perhaps the most important characteristic is the behavior of these fluorescing areas with time. They generally increase in brightness and size as the general choroidal fluorescence fades.
The recent investigations of Gass have demonstrated that many vascular syndromes of the macula result essentially from defects in Bruch's membrane. It is postulated that small defects in this membrane permit serum to escape from the choriocapillaris and serously elevate the retina. The pigment epithelium may also be serously elevated by the disease process, but in either case the basic defect lies in Bruch's membrane. Hemorrhages may also be associated with this pathologic process and the blood may be located beneath either the pigment epithelium or the retina. Perhaps as a consequence of hypoxia in the elevated retina, neovascularization, along with glial proliferation, may occur beneath the pigment epithelium, representing a final irreversible disciform type of lesion. The goal of treatment is to interrupt 1
From the Department of Ophthalmology, New York University School of Medicine (Drs. Wise and Wendler), and the Knapp Memorial Laboratory of Physiological Optics, College of Physicians and Surgeons, Columbia University, 635 West 165th Street 10032 (Dr. Campbell and Miss Rittler). This study was supported in part by U S P H S Grant NB-07130 of the National Institute of Neurological Disease and Blindness.
Not infrequently the fluorescein test may result in misleading or false data, particularly if, for unknown reasons, there is poor filling of the retinal vessels, as manifested by subnormal fluorescence after the dye injection. Of primary importance in unsatisfactory fluorescein tests are artifacts in the fundus. Areas of high reflectivity (exudates or medullated nerve fibers) may appear to be persistently bright ; however, their unchanging quality and true lack of fluorescence, should permit proper identification. A more subtle defect is the absence or reduced density of the pigment epithelium. This permits the normal choroidal fluorescence to be somewhat more prominent in that area. In this situation, however, generally there is not
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increased brightness of the fluorescing area in the center and the edges are usually not fuzzy; this fluorescing area fades with the fading of the general choroidal fluorescence and, during the course of time, does not increase in size. On the other hand, a true leak may be obscured by a superficial hemorrhage. These considerations indicate clearly that the interpretation of fluorescein data requires experience and meticulous attention to detail. The fluorescein data may be interpreted by either ophthalmoscopy or photography. The ophthalmoscopic techniques may employ either conventional direct ophthalmoscopy, indirect ophthalmoscopy, or slitlamp biomicroscopy with a contact lens. In all these situations it is essential that suitable filtering techniques be employed. Unfortunately, the characteristics of Bruch's membrane defects are often elusive, and the problem is even more difficult if there are many leak sites. As a consequence visual detection may not be adequate, particularly when the test is performed with treatment in mind. Effective therapy requires the detection of each leak site ; consequently fluorescein photography is usually necessary before treatment is undertaken. Photographs also permit serial comparison at different time-intervals after dye injection and hence provide quantitative evaluation of the potential leak sites. Furthermore, photographic evidence provides precise localization for coagulation therapy. LASER T H E R A P Y OF M A C U L A R LESIONS
Lesions of minimal intensity produced by the laser photocoagulator are characterized primarily by disturbances at the level of the pigment epithelium. • At the time of treatment, these lesions appear as ill-defined, extremely faint gray discs in which slight irregularities may be manifested as small central accumulations of pigment or as an irregular fine annulus of pigment at the edge of the lesion. The gray color disappears within a few days after treatment and a faint punctate pigment pattern results. Immediately 2
8
453
after treatment, the principal effect noted histologically is an irregularity of the pigment epithelium. There is actual clumping of pigment cells in the more central area of the lesion. Slight subretinal exudate separates the retina from the pigment epithelium. No disturbance of the normal retinal architecture is apparent, and this is particularly true of the nerve fiber layer, which is significantly distant from the site of energy absorption. The subretinal exudate disappears within several days and there is evidence of slight pigment migration into the external layers of the retina. The retinal architecture, however, remains largely undisturbed in lesions of minimal intensity. Of particular importance to this investigation, there is no evidence of destruction in the nerve fiber layer in lesions of this intensity. 4
Laser photocoagulation appears to be a most suitable technique for the treatment of defects in Bruch's membrane. The energy is absorbed primarily at the level of the pigment epithelium. Little disturbance occurs to the retina itself, if lesions of minimal intensity are employed. In the instrumentation* used in this study, the laser beam may be focused sharply and located precisely on the retina, confining the energy to a sharply circumscribed region, with a high degree of localization. The technique of laser photocoagulation of central lesions is in general similar to that employed for peripheral pathology. The pupil must be dilated with a cycloplegic and the treatments are generally performed on an out-patient basis. Treatments may be performed within five degrees (one disc diameter) of the fovea with relative safety. Obviously the treatment of subfoveal leak sites will result in the destruction of central function and largely defeat the purpose of treatment. If the patient manifests uncertainty of fixation or if treatments are performed closer than five degrees to the fovea, a large retrobulbar injection is employed. * A O Instrument Company, Buffalo, New York.
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RESULTS
TABLE 1
Forty-three patients in three disease categories were treated. The findings are summarized in Table 1. Each group in itself merits definition and further comments may be of value in interpreting the data in the table. In this study, central serous retinopathy is defined as an elevation of the retina in the macular region by serum. It is due to escape of serum through the pigment epithelium from the choroidal circulation via a defect in Bruch's membrane. There may be multiple serous elevations in the general macular or posterior polar region. This disease may also be associated with blister-type elevation of the pigment epithelium.
SUMMARY OF RESULTS OF TREATMENT B Y LASER PHOTOCOAGULATION OF 43 PATIENTS WITH MACULAR VASCULAR PATHOLOGY
The indications for treatment of patients with central serous retinopathy can be defined with some precision. In general there should be a protracted course of the disease from its onset of at least three month's duration. Most patients included in this series had evidence of the disease for time-intervals varying between eight and 24 months. There may also be evidence, in addition to the extended time-interval, of progression of the disease with associated irreversible changes. In general this includes the occurrence of hemorrhages, exudates, or of subretinal organization or fibrosis. The fluorescein test always must be positive. Not infrequently, numerous leak sites are found again, confirming the importance of photography. The treatable area, that is, the leak site, must be located at least two degrees (one-third disc diameter) from the fovea. Table 2 shows the results of treatment of 22 patients with central serous retinopathy. Of these, 14 are classified as good results. In most cases the visual acuity is 20/20, the fluorescein test after treatment is negative, and there is no residual subretinal fluid. A moderate result, on the other hand, indicates a partial restoration of vision, generally between 20/25 and 20/50, and closure of the leak sites; there is no remaining subretinal fluid. In the results classified as poor there is
Central serous retinopathy (22) Disciform degeneration (14) Preretinal macular fibrosis (7)
Good
Moderate
Poor
14
3
5
3
4
7
1
5
1
generally a marked further reduction in visual acuity after treatment, ranging between 20/50 and 20/400. Frequently there is persistence of central subretinal fluid; the leak sites remain in spite of repeated photocoagulation, and, in two patients, the disease progressed to a disciform type of macular degeneration in which there was subretinal gliosis and organization, together with superficial retinal hemorrhages. These data indicate that great care must be taken in the selection of patients for treatment of central serous retinopathy. Disciform degeneration of the macula has been defined as a serous, exudative, hemorrhagic elevation of the retina, which may be associated with subretinal fibrosis and neovascularization. The primary pathology appears to be a defect in Bruch's membrane and an anoxemic vascular cycle. Indications for treatment of disciform degeneration of the macula are less well established than for the management of central serous retinopathy. In general, the diagnosis of disciform degeneration is ample reason for performing a fluorescein test. If widespread central destruction has occurred in the first eye as a consequence of disciform disease, the treatment may be carried out more vigorously and over a more extensive area if the second eye becomes involved. In general, it is believed that sharp focal leaks and leaks removed a significant distance from the macula respond more satisfactorily to this form of treatment. Older patients do not respond as well as those in younger age groups.
PHOTOCOAGULATION OF MACULA
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TABLE 2 CLINICAL DATA ON 22 PATIENTS WITH CENTRAL SEROUS RETINOPATHY
Duration of Disease Before Treatment Good 1 2 3 4 5 6 7
Visual Acuity After Before Treatment Treatment 20/30-2 20/40-1 20/20-3 20/30-2 20/25-2 20/200 20/15-1
20/20-2 20/20-3 20/20-3 20/20 20/15-2 20/50 20/15-1
20/50-2 20/25-2 20/20-2
20/40-2 20/20 20/15-3
Remarks
8 9 10
8 weeks 10 weeks 3 weeks
11
6 weeks
20/20
20/15-3
12
3 weeks
20/25-2
20/15-3
5 months 8 months
20/200 20/200
20/60-1 20/60
2nd eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment O.U.—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 2nd attack 1st eye involved—1 treatment 3rd attack 1st eye involved—1 treatment 1st eye involved—1 treatment
20/40-2 20/7020/400-
20/40-2 20/5020/400
1st eye involved—2 treatments 1st eye involved—1 treatment O.U.—2 treatments
20/400 20/8020/70-1 20/2520/25-3
20/40020/400 20/40020/40020/40-
1st eye involved—1 treatment 2nd eye involved—2 treatments 1st eye involved—3 treatments 1st eye involved—1 treatment 1st eye involved—1 treatment
13 14 Moderate 15 16 17 Poor 18 19 20 21 22
4 5 2 ?20 3J 6 4
weeks months months years years months weeks
11 months 9 months ?19 years 3 4 5 3 4
months weeks months months months
The treatment is frequently difficult in this disease. On occasion hemorrhages and massive exudation make it extremely difficult or even impossible to produce a satisfactory reaction with the photocoagulator. The power values must be regulated carefully, but it must be realized that high-power values may be necessary to achieve the desired result in these abnormal conditions. Table 3 shows the results of treatment in 14 patients with the diagnosis of disciform degeneration. The results in three have been classified as good. In this disease a good result consists of improvement in visual acuity and a negative fluorescein test after treatment, with absence of serous elevation of the retina. For classification as a moderate result, the patient must have experienced improvement in visual acuity, the leak must be sealed, and no superficial hemorrhages remain. It does not necessarily mean that all
residual subretinal fluid has absorbed. A significant number of poor results have been obtained. In these patients the disciform process has progressed. The glial elevation remains, and widespread serous elevation of the retina is present. Extensive hemorrhages are found throughout the posterior pole. The fluorescein test in patients with poor results is generally positive over large areas at the posterior pole ; usually there is evidence that the original leak sites still leak, or new leaks have developed. Preretinal macular fibrosis is defined as a disease characterized initially by increased intraretinal edema, full veins, and altered highlights on ophthalmoscopic examination. Later there is ophthalmoscopic evidence of gliosis, striae, intraretinal cysts and serous elevation of the retina. It is suggested that this disease is the result of venous stasis, but it also has been proposed that it may be the
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TABLE 3 CLINICAL DATA ON 14 PATIENTS WITH DISCIFORM DEGENERATION
Duration of Disease Before Treatment Good 1 2 3 Moderate 4 5 6 7 Poor 8 9 10 11 12 13 14
4 months 4 months 8 months
Visual Acuity Before After Treatment Treatment
Remarks
20/30-2 20/400 20/15-2
20/25 20/70-2 20/15-2
1st eye involved—2 treatments 1st eye involved—1 treatment 2nd eye involved—2 treatments
3 10 6 7
months months weeks months
20/40020/40020/30-2 20/400
20/40020/400 20/30 20/80-2
2nd eye involved—1 treatment 1st eye involved—2 treatments 2nd eye involved—1 treatment 2nd eye involved—1 treatment
2 5 4 2 7 5 2
months months months months weeks weeks months
20/400 20/7020/40-2 20/40-3 20/50-2 20/50-2 20/40-
20/40020/200 20/60-2 20/40020/200 20/80-2 20/50-
1st eye involved—1 treatment 1st eye involved—2 treatments 2nd eye involved—1 treatment 1st eye involved—1 treatment 2nd eye involved—1 treatment 2nd eye involved—1 treatment 2nd eye involved—1 treatment
result of vitreous traction at the posterior pole. The fluorescein test in this disease is usually either negative or shows evidence of leaks from retinal veins. In no patients have leaks been defined through Bruch's membrane, and there is no evidence that this membrane is primarily involved. The rationale for laser photocoagulation of this disease differs from that in diseases in which the primary pathology is located in Bruch's membrane. The only leaks detected —those from retinal veins or capillaries— probably cannot be sealed by laser photocoagulation. In this study, treatment consisted of producing multiple, near-threshold, faint laser coagulations throughout the entire posterior pole of the eye, between the temporal vessels, including, in this series, the centrocecal region. Two, or even three, treatment sessions may be necessary to produce satisfactory reactions. Postoperatively, even after prolonged observation there is only the faintest evidence of a pigmentary reaction. The rationale for this form of therapy is the production of a closer association between the choroid and the retina. Hopefully, a firmer chorioretinal association will result in the restoration of some retinal function. Alternately, or perhaps additionally, the destruction of some retinal elements will re-
duce the stimulus to preretinal fibrosis. It is well known that viable retinal cells are necessary for fibrosis to progress. The criteria for treatment of patients of this disease category have not been fully established. Tentatively it would appear that a patient with 20/50 or less visual acuity should have photocoagulation, particularly if the disease has been present for an extended timeinterval. If the second eye is involved, treatment is performed earlier, and a patient with visual acuity of 20/30 or less would be treated shortly after onset of the disease. A total of seven patients with macular fibrosis were treated, as indicated in Table 4. A good result was obtained in only one patient (restoration of vision to 20/20 after a 17-month course of the disease). In this patient the second eye was involved and visual acuity had been reduced to 20/30. The postoperative follow-up interval in this patient is 30 months and the vision remains intact. A moderate result was obtained in five patients. In this situation an improvement in visual acuity occurred, although the final visual acuity in none of these patients was better than 20/25. In most of these, some slight remaining edema persisted at the posterior pole but was significantly reduced by the treatment. One patient in the entire series
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457
TABLE 4 CLINICAL DATA ON 7 PATIENTS WITH MACULAR FIBROSIS
Duration of Disease Before Treatment Good 1 Moderate 2 3 4 5 6 Poor 7
Visual Acuity After Before Treatment Treatment
Remarks
6 weeks
20/30+2
20/15-3
2nd eye involved—2 treatments
8 7 2 6
20/50-2 20/200 20/400 20/200
20/50-2 20/5020/200 20/200
8 months
20/15
20/15
2nd eye involved—1 treatment 1st eye involved—1 treatment 1st eye involved—1 treatment 2nd eye involved—1 treatment subjective near vision improvement 1st eye involved—2 treatments
Many months
20/60-2
20/100 - 2
1st eye involved—1 treatment
months months years months
manifested poorer visual acuity after treatment than before treatment. This case is considered further in the discussion. Case histories are frequently of value in illustrating the application and the results obtained in this form of therapy. The first patient, aged 36 years, had a diagnosis of central serous retinopathy; five leak sites were found on fluorescein examination. Clinically there was a serous elevation of the macula without detachment of the pigment epithelium. The disease had been present for 21 months and the visual acuity was reduced to 20/40. Photocoagulation was performed at each leak site. On re-examination one month later, faint pigment was evident at the areas treated. The fluorescein test was repeated and found to be negative and on clinical examination there was no evidence of subretinal fluid centrally. The visual acuity was restored to 20/20. A second patient, aged 62 years, with the diagnosis of central serous retinopathy in his second eye, illustrates one of the less rewarding cases. This patient's first eye had developed a disciform type of macular degeneration some two years previously, with loss of central function. The disease in the second eye was characterized by a serous elevation of the retina centrally without involvement of the pigment epithelium. There was no deep glial proliferation and no deep exudation or hemorrhage. One small superficial hemorrhage was evident temporal to
the macula. The visual acuity was reduced to 20/80. On fluorescein examination a number of leaks were detected above the macula just inferior to the temporal vessel arcade. Photocoagulation was performed at the leak sites without complications. Six weeks after treatment the visual acuity was less than 20/400. At the treatment sites and in the macula there was a large glial elevation surrounded by extensive superficial retinal hemorrhages. The retina was also serously elevated over the gliosis. The fluorescein test showed extensive leaking at the treatment area but the leaks had become significantly larger, truly massive in size. Fluorescein was evident in the subretinal fluid throughout the entire posterior pole. It is apparent that photocoagulation in this patient was not of value and indeed may have accelerated the progression toward disciform degeneration. At this time it is not possible to differentiate early in the course of central serous retinopathy those patients who will respond satisfactorily to treatment and those in whom the disease is subject to progression. The third example is a patient, aged 71, years, with disciform degeneration of the macula. In this individual a large glial elevation was found temporal to the macula, associated with a relatively marked serous elevation of the retina which extended to the macula itself. Superficial hemorrhages were also evident in this area. The visual acuity was 20/400. On examination with intravenous
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AMERICAN JOURNAL OF OPHTHALMOLOGY
fluorescein three leaks were detected, slightly removed from the superior end of the temporal glial scar. Photocoagulation was performed to this area and resulted in the sealing of two leaks. On re-examination six weeks later, the fluorescein test showed one small remaining leak of the three original leaks. The treatment areas were all lightly pigmented, the extensive hemorrhages had largely disappeared, and the elevated glial plaque was much smaller in size. Only slight fluid persisted centrally. A second session of photocoagulation satisfactorily sealed the third persistent leak. At the time of treatment the corrected visual acuity was 20/30-2. Some eight weeks after the second session, visual acuity was 20/25-3. The treatment at the third leak site was by this time solidly pigmented and the intravenous fluorescein test was negative. No subretinal fluid was evident in the macula and there were no superficial hemorrhages. Persistent slight perifoveal cystic changes were present.
S E P T E M B E R , 1968
along with a significant number of patients in this and other disease categories, in the centrocecal area. After treatment the serous elevation of the retina was greatly decreased and there was some reduction in the preretinal fibrosis. The reduced visual acuity and the visual field defect appear to represent damage to the nerve-fiber layer of the retina. Although this type damage apparently occurred in only one patient in the entire series, it serves to emphasize the caution with which treatment in this area must be performed. When treatment is performed on serously elevated retina, particularly when associated with subretinal exudates and hemorrhages, substantially higher power values must be employed. The lesions produced by the laser photocoagulator at the time of treatment are often extremely difficult to detect. Therefore uncertainty may exist as to the exact energy required by the clinical problem. Treatment with higher-power values must be undertaken with careful consideration.
DISCUSSION
Some variability has been noted in the results obtained with the fluorescein test when it was performed on more than one occasion. Specifically, it has been found that leaks detected on one examination may not be present on reexamination a short time later but may be found still later on a third examination, suggesting that some leaks may be intermittent in nature and that it may be of value to repeat the fluorescein studies in some patients. The minimal intensity of the laser coagulations permits photocoagulation of relatively large areas with apparent safety. The centrocecal area and the peripapillary zones may be treated but extreme caution must be exercised to prevent damage to the nerve-fiber layer. In one patient, referred to previously with the diagnosis of preretinal macular fibrosis, the visual acuity was decreased after treatment. On perimetric examination a centrocecal visual field defect was found. Photocoagulation was performed in this patient,
CONCLUSIONS
A technique of study and treatment of patients with macular vascular diseases has been described. Although the results are not entirely rewarding they do show sufficient promise to suggest that this form of treatment merits further investigation. Meticulous clinical and fluorescein investigation preoperatively, and equally cautious therapy with the laser photocoagulator are required. Patients selected for this type of treatment must, in general, be those in whom there is definite evidence of irreversible progression of the disease process with a specific threat to central function. SUMMARY
The technique of fluorescein angiography permits critical evaluation of the retinal vascular system and the integrity of Bruch's membrane as a serum barrier. Laser photocoagulation allows the coagulating energy to be directed to the pigment epithelium of the
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retina with great precision. These combined techniques have been employed in the treatment of selected vascular diseases of the macula, and results are shown in 43 patients. This form of therapy holds a measure of promise of effective control in some patients with these frequently intractable syndromes. 635 West 165th Street (10032) REFERENCES 1. Gass, J. D. M. : Pathogenesis of disciform detachment of the neuroepithelium. I. General concepts and classification. Am. J. Ophth. 63:573, 1967 ; II. Idiopathic central serous choroidopathy, p.
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EFFECTS
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587; III. Senile disciform macular degeneration, p. 617; IV. Fluorescein angiographic study of senile disciform macular degeneration, p. 645; V. Disciform macular degeneration secondary to focal choroiditis, p. 661 ; V I . Disciform detachment secondary to heredodegenerative, neoplastic and traumatic lesions of the choroid, p. 689. 2. Campbell, C. J., Koester, C. J., Curtice, V., Noyori, K. S. and Rittler, M. C. : Clinical studies in laser photocoagulation. Arch. Ophth. 74:57, 1965. 3. Campbell, C. J., Rittler, M . C , Noyori, K. S., Swope, C. H. and Koester, C. J. : The threshold of the retina to damage by laser energy. Arch. Ophth. 76:437, 1966. 4. Noyori, K. S., Campbell, C. J., Rittler, M. C. and Koester, C. J. : The characteristics of experimental laser coagulation of the retina. Arch. Ophth. 72:254, 1964.
PRODUCED BY EXPERIMENTAL LASERS
I. Q-SWITCHED RUBY LASER CHARLES J. CAMPBELL, M . D . M . CATHERINE RITTLER, A . B . New
York
AND C . HERMAS SWOPE, A . B . CHARLES J.
KOESTER,
PH.D.
Framingham, Massachusetts
The investigation of the ocular effects of Q-switched ruby lasers is important because it is a new source of light of very high power and because of the potential hazards associated with this type of laser. This report includes a description of the Q-switched laser photocoagulator and the experimental technique. The effects of maximum power levels of this radiation on the cornea, lens, iris, vitreous, and serously elevated retina have been explored, but particular attention has been directed toward the intact retina. A range of power values has been used, includFrom the Knapp Memorial Laboratory of Physiological Optics, Institute of Ophthalmology of Presbyterian Hospital, College of Physicians and Surgeons, Columbia University (Dr. Campbell and Miss Rittler) and American Optical Corporation, Research Division, Framingham, Massachusetts (Mr. Swope and Dr. Koester). This study was supported in part by U S P H S Grant NB-07130 of the National Institute of Neurological Diseases and Blindness of the National Institutes of Health, Bethesda, Maryland.
ing the energy necessary to produce a nearthreshold lesion. The characteristic appearance of these retinal lesions at various time intervals after treatment has been documented and related to the histologic findings. Previous investigators have reported on certain characteristics of the retinal lesions produced by Q-switched ruby lasers. Geeraets and associates noted that even in minimal lesions there was marked displacement forward of cells in the pigment epithelium. With higher energy values the displacement of the retina increased, as observed histologically. Minimal lesions were produced with 28.5 nanosecond exposures at an energy density of 0.07 joules/cm . Bergqvist and co-workers " studied retinal lesions of various sizes and noted different characteristics of lesions less than 0.1 mm compared with those found in lesions greater than 0.9 mm, the smaller lesions being craterlike and deeper. The larger le1
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