Lasers in diabetes

Introduction

Since the first direct evidence of retinal vascular abnormalities in diabetic patients was shown by Ashton in 1950,1 there have been continuing efforts to alleviate this visually debilitating condition. In 1952, Luft and coworkers2 carried out a hypophysectomy in the hope of ameliorating the vascular complications of diabetes, and, in 1959, photocoagulation for the treatment of diabetic retinopathy was first reported by Meyer-Schwickerath,3 who used a xenon arc photocoagulator to treat new vessels on the surface of the retina directly. During the 1970s, further treatments were developed (such as argon laser photocoagulation and pars plana vitrectomy) and their efficacy in preserving vision in patients with diabetic retinopathy examined in several landmark clinical trials which spanned the ensuing two decades. The Diabetic Retinopathy Study (DRS) of 1976, the first of such trials, showed that the rate of severe visual loss in high-risk proliferative diabetic retinopathy could be reduced by as much as 60% following the timely application of panretinal laser photocoagulation therapy.4 Subsequently, results from the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal laser photocoagulation treatment to the macula could substantially reduce the risk of visual acuity loss in patients with clinically significant diabetic macular edema.5

Diabetic retinopathy: classification

Diabetic retinopathy exists as a spectrum of findings ranging from mild to severe (Table 1). Diabetic retinopathy is broadly classified as nonproliferative diabetic retinopathy (NPDR), formerly known as

background diabetic retinopathy (BDR), and proliferative diabetic retinopathy (PDR). The retinal microvascular changes that occur in NPDR are limited to the confines of the retina, whereas PDR is characterized by the growth and extension of new vessels from the retina, beyond the internal limiting membrane, and out onto the posterior hyaloid surface.

The earliest funduscopic changes noted in diabetic retinopathy include retinal microaneurysms and dotblot hemorrhages. These are often most pronounced in the temporal macular region. Microaneurysms tend to cluster near zones of capillary nonperfusion, and their rate of formation appears to be an indication of the severity of diabetic retinopathy.6 Retinal hemorrhages are generally a reliable indicator of the severity of nonproliferative retinopathy. Acceleration of retinal capillary abnormalities eventually affects adjacent arterioles, resulting in arteriolar closure and discrete areas of capillary dropout or nonperfusion. Capillary closure with retinal ischemia leads to nerve-fiber layer infarcts (cotton wool spots), intraretinal microvascular abnormalities (IRMA), and venous beading. The DRS defined preproliferative diabetic retinopathy as any three of the following: nerve fiber layer infarcts, intraretinal microvascular abnormalities, venous beading, and at least moderately severe retinal hemorrhages and/or microaneurysmal formation.7 However, data from the ETDRS de-emphasized the significance of nerve fiber layer infarcts, finding that the severity of intraretinal microvascular abnormalities, hemorrhages and/or microaneurysms, and venous beading were the most important factors in predicting progression to proliferative retinopathy.8 Progressive capillary closure and retinal ischemia herald the development of proliferative retinopathy. Retinal neovascularization in diabetic retinopathy originates either from the op-

tic disc (NVD) or retinal surface elsewhere (NVE) and proliferates on the posterior cortical vitreous (Fig. 1).

New vessels proliferate along the posterior hyaloid surface and cause visual loss by either bleeding into the vitreous, or causing contraction of the

vitreous, thereby resulting in a tractional retinal detachment. Neovascularization can regress rarely spontaneously or following panretinal photocoagulation, forming residual, relatively avascular sheets of fibrovascular tissue along the posterior hyaloid surface.

The presence of microaneurysms are the earliest signs of diabetic retinopathy. They may be present at any stage of retinopathy from nonproliferative to proliferative. From these microaneurysms, leakage of fluid occurs within the retina resulting in edema. Macular edema is the most frequent cause of visual impairment in patients with diabetic retinopathy. The breakdown of the inner blood-retinal barrier can be associated with both nonproliferative and proliferative diabetic retinopathy. This excessive vascular permeability resulting in the leakage of fluid and plasma constituents, such as lipoproteins into the retina, leads to thickening of the retina. When thickening involves or threatens the center of the fovea, there is a higher risk of visual loss. In the ETDRS, the three-year risk of moderate visual loss (a doubling of the initial visual angle or a decrease of three lines or more on a logarithmic visual acuity chart) was 32%. The ETDRS classified macular edema as ‘clinically significant macular edema’ (CSME) if any

of the following features were present: (1) thickening of the retina at or within 500 µm of the center of the macula; (2) hard exudates at or within 500 µm of the center of the macula, if associated with thickening of the adjacent retina; or (3) a zone or zones of retinal thickening one disc area or larger, any part of which is within one disc diameter of the center of the macula (Fig. 2).

Epidemiology of diabetes and diabetic retinopathy

Diabetes mellitus affects approximately 17-18 million persons in the USA, and the majority (≈ 90%) of those patients have type 2 diabetes. According to the American Diabetes Association, of the roughly 17 million people who have diabetes, 5.9 million are unfortunately unaware that they have impaired glucose tolerance or definite diabetes. Diagnosed diabetes is most prevalent in the middle-aged and elderly

populations, affecting 6% of people aged 45-64 years and 18.4% of those aged 65 years or older, but only 1.5% of those aged 18-44 years.9,10

The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic patients in southern Wisconsin, provides the best data on the epidemiology of diabetic retinopathy and the risk factors associated with the development of diabetic retinopathy. According to the results of this study, retinopathy, either nonproliferative or proliferative, was seen in 13% of the patients whose age at diagnosis of diabetes was less than 30 years, had less than a five-year duration of diabetes, and were taking insulin at the time of the examination (presumably type 1). In contrast, up to 90% of patients with a 10-to-15-year duration of diabetes had some form of diabetic retinopathy. PDR is present in approximately 25% of patients with type

1diabetes and a 15-year duration of disease.11 For patients with an onset of diabetes at 30 years

of age or older (e.g., those with type 2 diabetes) and a duration of diabetes less than five years, 40% of insulin-requiring and 24% of non-insulin requiring diabetics have retinopathy.12 These rates increase to 84 and 53%, respectively, with an increased duration of diabetes of 15-19 years. PDR develops in 2% of patients with type 2 diabetes and a duration of less than five years, and in 25% of patients with a duration of 25 or more years.

For diabetic macular edema, again the best epidemiological data was obtained from the WESDR. It was found that the prevalence of macular edema did not vary as much by diabetes type. The prevalence of diabetic macular edema was approximately 18-20% in patients with either type 1 or type 2 diabetes, but increased significantly with the overall severity of diabetic retinopathy and duration of diabetes.13,14

The WESDR data discussed above suggested that the major factors associated with increased severity of retinopathy include patient age at diagnosis, increasing duration of diabetes, type 1 diabetes, and insulin-dependent diabetes. Other important factors include degree of metabolic control, blood pressure, elevated serum lipid levels, pregnancy and renal disease.

Laser therapy for proliferative diabetic retinopathy: historical background

The DRS was initiated in 1972 and completed in 1979, and provided important information concerning the understanding and treatment of proliferative diabetic retinopathy. This randomized, controlled, clinical trial determined the natural history of the disease without photocoagulation by following randomly selected control eyes, and confirmed the previously suggested beneficial treatment results with xenon arc and argon laser photocoagulation by examining a large number of patients at regular intervals for an extended time period. The DRS follow-up examinations were terminated in June 1979 after the study’s major goals had been achieved.19 In this study, panretinal photocoagulation was applied from around the disc and major arcades to or beyond the equator in one or several treatment sessions. The xenon technique used 400-800, 3° burns or 200-400, 4.5° burns. The argon blue-green technique used 0.1 second-, moderate-to-heavy-in- tensity retinal burns. The scatter pattern consisted of 800-1600, 500-µm burns, or 500-1000, 1000-µm burns with a spacing of about one burn width apart. Disc neovascularization or elevated neovascularization elsewhere was treated with scatter argon photocoagulation in an attempt to close the new vessels.

Flat neovascularization elsewhere was directly treated with either argon or xenon photocoagulation.

The DRS found that photocoagulation reduced the risk of severe visual loss (vision 20/80 or worse for two consecutive follow-up visits) by at least 50%.19 The overall risk of severe visual loss with proliferative diabetic retinopathy at the two-year follow-up examination was 16% in the control eyes compared to 6% in the treated eyes. With DRS high-risk characteristics, this risk increased to 26% in the control eyes and 11% in the treated eyes. However, when high-risk characteristics were absent, the risk of severe visual loss decreased to 7% of the control eyes and 3% of the treated eyes. In a separate study by Doft et al., the beneficial effect of panretinal photocoagulation persisted through 15 years of followup.21

Although argon and xenon photocoagulation were equally effective in preventing severe visual loss, argon emerged as the preferred treatment modality due to fewer harmful side-effects.19,23 Twenty-five percent of the xenon-treated eyes had visual field loss (Goldmann IV 4e test object) compared to 5% of eyes treated with argon photocoagulation, and 11% of the xenon-treated eyes experienced a permanent visual loss of two or more lines compared to 3% of the eyes treated with argon photocoagulation. Moreover, there was an increase in macular damage from vitreoretinal traction following xenon laser treatment.

Eyes receiving panretinal photocoagulation sometimes developed decreased vision, especially eyes with preexisting macular edema or in those eyes receiving heavy xenon panretinal photocoagulation. It was found that panretinal photocoagulation occasionally aggravated macular edema.24 Eyes treated with scatter argon photocoagulation (PRP) were approximately 60% more likely to lose two or more lines of visual acuity after photocoagulation than untreated eyes and xenon-treated eyes were approximately five times more likely to lose this much vision compared to untreated eyes within six weeks of photocoagulation. Therefore, the following recommendations were made to decrease photocoagula- tion-induced macular edema: (1) treat macular edema with focal photocoagulation prior to initiating panretinal photocoagulation; (2) avoid intense panretinal photocoagulation burns; and (3) divide panretinal photocoagulation into several treatment sessions.24

One arm of the ETDRS was designed to determine the best time to initiate panretinal photocoagulation in patients with diabetic retinopathy. The ETDRS concluded that scatter photocoagulation is not recommended for eyes with mild or moderate non-prolif- erative diabetic retinopathy, provided that careful follow-up can be maintained. The five-year rate of severe visual loss in this group was 1-3%. On the other hand, scatter photocoagulation should be considered when retinopathy is more severe and usually should not be delayed if the eye has reached the high-risk proliferative stage, as there was a 4- 7% risk of severe visual loss at five years.25 The

ETDRS data also failed to support the concept of staged scatter photocoagulation.25,26 The beneficial effects of panretinal photocoagulation were found to be independent of the wavelength used.22,27-36

Rubeosis iridis

Several reports have demonstrated that panretinal laser photocoagulation is effective in preventing the development of rubeosis and in causing the regression of pre-existing iris neovascularization.37-42 The best results are obtained when treatment is given prior to the development of neovascular glaucoma and extensive peripheral anterior synechia. A cyclodestructive and/or seton procedure may be required if panretinal laser photocoagulation fails to control rubeosis and neovascular glaucoma.

In 1983, Pavan et al.43 reported on the results of a prospective, randomized, controlled study that evaluated the benefit of panretinal photocoagulation for rubeosis iridis secondary to proliferative diabetic retinopathy. The rubeosis was documented using iris angiography before and five to seven weeks after panretinal photocoagulation. Panretinal photocoagulation was effective in causing the regression of severe rubeosis iridis (at least 0.5 x 0.5 millimeters in area), which improved in 11 (73%) of 15 treated eyes compared with two (18%) of 11 untreated eyes.

Laser guidelines

Panretinal photocoagulation

Panretinal photocoagulation is indicated for any eye with DRS high-risk characteristics, rubeosis iridis, or neovascular glaucoma. Photocoagulation of clinically significant macular edema should be considered before instituting scatter (panretinal) treatment. Scatter photocoagulation burns are placed from just within the vascular arcades to anterior to the equator. Tight (confluent) photocoagulation is applied directly to areas of flat peripheral neovascularization. The laser settings for scatter photocoagulation are given in Table 2.20 All wavelengths appear to be equally effective in inducing regression of proliferative disease. The red and diode wavelengths, however, are better able to penetrate cataracts or vitreous hemorrhage than the shorter wavelengths. The photocoagulation burns are placed approximately one burn width apart. The anterior edge of treatment should extend to or beyond the equator. The posterior edge of treatment includes an oval area that extends 500 µm nasal to the optic disc margin, along the temporal arcades, and two disc diameters temporal to the macular center. Use of a panfunduscopic contact lens, 3-mirror contact lens, or indirect ophthalmoscope laser delivery system is used for panretinal photocoagulation.

It should be kept in mind that treatment over retinal

hemorrhage, major retinal vessels, or chorioretinal scars should be avoided. Directly treating retinal hemorrhage can result in unnecessary inner retinal damage. When panretinal photocoagulation burns are placed over retinal vessels, vascular occlusion and rupture may potentially occur, albeit this is a rare complication. Overly intense burns can occur when photocoagulation burns are placed over pigmented chorioretinal scars, causing visual field loss.20 Treatment may extend within the vascular arcades within 3000 µm of the macular center for retinal neovascularization. Such localized scatter photocoagulation is performed with 200-µm burns when treating 5001500 µm from the center of the macula. Treatment should not extend closer than 500 µm from the macular center or disc margin. Care should be taken to avoid photocoagulating within the papillomacular bundle (Fig. 3).

Panretinal photocoagulation should be completed in several treatment sessions over a threeto sixweek period.21 Furthermore, dividing panretinal laser into multiple sessions decreases the risks of macular edema, exudative retinal detachment, choroidal detachment with secondary angle-closure glaucoma. The order in which the retina is treated is optional. The inferior retina is usually treated first, as vitreous hemorrhage, should it occur, tends to settle inferiorly, making it difficult to later photocoagulate this region. Although the DRS treatment protocol for scatter photocoagulation consisted of 800-1600, 500-µm burns, a complete treatment generally consists of approximately 1800-2200, 500-µm retinal burns. There are no postoperative physical restrictions following panretinal photocoagulation. Patients should be examined within four months of completing panretinal photocoagulation treatment.

The indications for additional treatment are multifactorial and must be individualized. Factors that favor additional photocoagulation include enlarging neovascularization, increasing activity of the neovascularization, e.g., the formation of tight vascular networks with a paucity of accompanying fibrous tissue, and in increase in the frequency or extent of vitreous hemorrhage if active neovascularization is present.20 Additional fill-in laser treatment may consist of scatter photocoagulation anterior to, poste-

b.

Fig. 3. a: ‘Full scatter’ panretinal photocoagulation therapy. Laser spots are spaced approximately one spot-width apart. The posterior margin of the treatment is about two disc diameters above, temporal, and below the center of the macula. b: Severe PDR prior to scatter photocoagulation (left), and 18 months following full scatter panretinal photocoagulation with additional ‘fill-in’ laser treatments (right). There is full regression of the neovascularization.

rior to, or between prior laser scars, as well as local photocoagulation to areas of flat peripheral retinal neovascualarization. For this, treatment consists of nearly confluent scatter photocoagulation applied directly to flat peripheral neovascularization using similar laser settings as that used for panretinal photocoagulation (vide supra).

Treatment of diabetic macular edema

Diabetic macular edema may be caused by either focal or diffuse leakage. Intraretinal edema results from leakage of fluid through damaged retinal endothelial cells. Focal retinal thickening is usually caused by leaking microaneurysms (Fig. 4). Diffuse retinal thickening is caused by a generalized breakdown of the inner blood-retinal barrier, i.e., leaking microaneurysms, intraretinal microvascular abnormalities, or short-capillary segments. In addition, a defective retinal pigment epithelial pump may also contribute to macular edema. Macular ische-mia is sometimes associated with macular edema and is a poor prognostic indicator for visual improvement with or without laser photocoagulation.44-47

Diabetic macular edema may be present at any level of retinopathy and is found in approximately

10% of all diabetic patients.13 As the severity of the retinopathy increases, the proportion of eyes with macular edema also increases ranging from 3% in eyes with mild nonproliferative diabetic retinopathy to 38% with moderate to severe non-prolifera- tive diabetic retinopathy and 71% with proliferative diabetic retinopathy.48 In clinic-based surveys, macular edema has been reported to be more frequent in older, adult-onset diabetic patients,49 whereas population studies demonstrate a higher prevalence of macular edema in juvenile-onset diabetics.13 This discrepancy may be explained by the fact that olderonset diabetic patients are almost ten times more common in the general population.

Photocoagulation treatment of diabetic macular edema with various wavelengths and treatment techniques has been used for a number of years with varying success.5,50-56 For example, Gupta et al.56 examined the efficacy of various wavelengths in the treatment of clinically significant macular edema. They compared argon green (514 nm), krypton red (647 nm), frequency-doubled Nd:YAG (532 nm), and diode (810 nm) for focal and/or grid laser photocoagulation treatment. Reduction or elimination of clinically significant macular edema was observed

in 93.3% of argon-treated eyes, 88.5% in krypton red group, 92.9% with frequency-doubled Nd:YAG, and 84.8% with diode laser. Although there was no statistically significant difference between the groups, frequency-doubled Nd:YAG treated eyes appeared to have the advantage of requiring fewer re-treat- ments. Nevertheless, all studies suggest a beneficial effect in either improving or stabilizing visual acuity with laser photocoagulation. Based on the available literature, particularly the ETDRS results, laser treatment should be considered for eyes with clinically significant macular edema.

Treatment guidelines

Treatment should be considered for all microaneurysm 500-3000 µm from the macular center, thought to be causing clinically significant macular edema. Treatment is initially optional for leaking microaneurysms within 500 µm of the macular center. If macular edema persists on follow-up examination and if vision is worse than 20/40 with a good perifoveal capillary network, focal treatment up to 300 µm from the center of the macula should be considered.20

Treatment settings for focal photocoagulation are given in Table 3. The desired endpoint of laser treatment of microaneurysms is a change in coloration (either whitening or blackening). Multiple treatments may be required for the same microaneurysm. For example, large microaneurysms (at least 40 µm in size) can usually be closed with several 50-75-µm burns. Although closure of smaller microaneurysms is often difficult or impossible, it may be facilitated by the following: (1) First place larger burns, i.e., 100-200 µm in size, over the microaneurysms. The induced outer retinal whitening prevents subsequent photocoagulation burns from penetrating into the retinal pigment epithelium. (2) Smaller (50-µm size) burns may then be able to close these microaneurysms. This technique may also be useful for fol- low-up treatment, as it avoids intense burns at the level of the retinal pigment epithelium caused by excessive uptake of laser energy from pigmented photocoagulation scars. Grid photocoagulation may also be used to treat clusters of small microaneurysms (vide infra). Small red spots seen clinically may be treated optionally if they are thought to be microaneurysms that do not fill on fundus fluorescein angiography. However, these should not be treated if they are thought to represent dot hemorrhages.

Areas of diffuse retinal thickening 500-3000 µm from the macular center thought to be causing clinically significant macular edema, should be treated using grid pattern photocoagulation. Grid photocoagulation should be applied to retinal avascular zones and clusters of small microaneurysms 500-3000 µm from the center of the macula that are associated with clinically significant macular edema. The laser setting for grid photocoagulation are given in Table 4. The grid spacing should be as close as one burn width apart. Photocoagulation should remain more than 500 µm from the disc margin. Treatment within the papillomacular bundle is allowed if it remains more than 500 µm from the center of the macula.

Photocoagulation is clearly beneficial for all types of clinically significant macular edema as defined by the ETDRS. However, treatment is most beneficial for eyes with more extensive macular thickening and greater degrees of central macular edema (Fig. 5).57 Immediate treatment must therefore be considered for retinal thickening at or within 500 µm of the macular center, as there is a significant risk of severe visual loss. For hard exudates at or within 500 µm of the macular center, if associated with thickening of the adjacent retina, treatment is less urgent if the visual acuity is normal. Laser is recommended if the risk of treatment causing visual loss appears small or if frequent follow-up examinations cannot be ensured. There is relatively low risk of visual loss from retinal thickening at least one disc area in extent, any part of which is within one disc diameter of the macular center. Although photocoagulation has been shown to be beneficial, it may be reasonable to follow these patients for progression before treating. This is particularly impor-

Table 3. Laser settings for focal photocoagulation for diabetic macular edema

(Adapted from Bloom and Brucker20 by courtesy of the publisher)

Table 4. Laser settings for focal/grid photocoagulation for diabetic macular edema

(Adapted from Bloom and Brucker20 by courtesy of the publisher)

tant when the majority of vascular leakage is close to the macular center, increasing the risk of foveal damage from laser burns.20

Patients should be examined three to four months after treatment, and considered for additional focal and/or grid photocoagulation if clinically significant macular edema is present. The decision of whether to retreat must be tempered, however, by other factors. For example, a patient with 20/25 vision and microaneurysms on the edge of the foveal avascular zone causing persistent clinically significant macular edema but who has shown an improvement in vision and a decrease in macular hard exudate and thickening following treatment can probably be followed initially without re-treatment.

Complications of laser treatment in diabetic retinopathy

Laser photocoagulation of the retina for the treatment of diabetic retinopathy has undergone significant advances and refinements since its initial application by Meyer-Schwickerath in 1959. Xenon arc light coagulation and ruby lasers have been replaced by argon, krypton, and dye, and diode lasers. The new lasers allow for smaller, more precise burns and diverse delivery systems. Photocoagulation is a minimally invasive treatment modality; nevertheless, complications are possible and diverse depending on the procedure employed.

Panretinal photocoagulation is a commonly performed and effective treatment for proliferative

a.

b.

c.

Fig. 5. a: Diffuse macular edema: retinal thickening and scattered hard exudates throughout the macula. b: Same eye four months after focal/grid laser photocoagulation. There is significantly less macular edema and exudate. However, typical circinate rings of hard exudate are still present, and repeat focal laser treatment was applied. c: Three months following the second focal laser treatment. There is residual exudate, but the edema has resolved.

diabetic retinopathy. The DRS suggests that photocoagulation for eyes at risk will reduce the risk of severe visual loss from PDR.19 Argon laser photocoagulation usually proceeds without complication, although reports of these are well-documented.58 Complications of PRP include damage to the cornea, iris, or lens;59-61 transient myopia and accommodative paresis;62 uveitis;63 pain; hemorrhage; vision loss; ciliochoroidal effusion/detachment;64 and el-

evated intraocular pressure with or without angleclosure.

The DRS Research Group demonstrated the beneficial effects PRP whereby between 800 and 1600, 500-µm argon laser burns were scattered throughout the peripheral retinal in a random pattern approximately one burn width apart. Since the results of that study were released, most retina specialists have noted that it is often necessary to treat patients who have proliferative retinopathy with increased numbers of photocoagulation burns in order to obtain neovascular tissue to regress, and have observed that in some patients with extensive disease it may become necessary to treat the entire peripheral retina. In addition, complications are usually noted to occur more frequently when PRP is performed during a single session versus multiple sessions.65 For example, Gentile et al.64 performed a prospective study using ultrasound biomicroscopy to determine the risk factors for ciliochoroidal effusion after PRP. They found that a threshold for the development of ciliochoroidal effusion after PRP exists and is dependent on three factors: (1) burn intensity, which is, in turn, dependent on the laser output parameters and the absorption qualities of the retina and choroid;

(2) burn size and number, which corresponds to the retinal surface area treated; and (3) axial length, which corresponds to the total retinal surface area and when combined with the retinal surface area treated, represents the percentage of the retinal surface area treated. The incidence of some degree of cilioretinal effusion after PRP is between 59% and 90%.66,67 These complications generally resolve within 14 days.

Moriarty et al.68 examined the breakdown of the blood-aqueous barrier using laser photometry after argon laser panretinal photocoagulation for proliferative diabetic retinopathy. These authors found a significant increase in aqueous flare at three, 24, and 48 hours following PRP with an argon green laser (2000 burns, 0.1-second exposure, 200-µm spot size). More pigmented irides underwent a greater breakdown of the blood-aqueous-barrier than the blue, paler irides and this is attributed to a possible increased absorption by iris pigment responsible for the increased thermal effects. In fact, there is also an increased absorption and scattering within the anterior segment of shorter wavelengths which increases with age as flavin pigments accumulate in the lens.69

With respect to laser treatment for diabetic macular edema, the ETDRS also showed that focal photocoagulation of clinically significant macular edema substantially reduces the risk of visual loss. Identification of the patient’s fixation point is important to avoid foveal burns. Treatment of diabetic macular edema can be challenging, particularly because the foveal reflex often is obscured by edema, blood or exudates. Fortunately, the adverse effects of photocoagulation for diabetic macular edema thus far have been rare. These complications include inadvertent

foveal photocoagulation, lipid precipitation in the fovea, subretinal or epiretinal fibrosis, increased foveal ischemia, choroidal or retinal hemorrhages or both, visual field defects/scotomas, expansion of laser scars, perforation of Bruch’s membrane, and choroidal neovascularization. Delivery of laser energy using small spot sizes, short durations, and high power has been proposed to increase the risk of perforation of Bruch’s membrane and development of choroidal neovascular membranes. It is important to keep in mind the treatment protocol of the ETDRS when treating patients for clinically significant macular edema. Excessive energy delivery should be avoided to any area in the macula, especially as the perifoveal area is approached.

Foveal burns can be avoided by finding the fixation point by projecting a fluorescein angiogram, and using akinesia if cooperation is poor. Scotomas are best avoided by not treating near the foveal avascular zone, using low energy, and avoiding the use of blue-green wavelengths.53 Enlargement of the burns over time can cause scotomas. However, this is more common in myopic eyes, and a 5% incidence has been described with a krypton grid.70 Precipitation of hard exudates, foveal migration, and subretinal fibrosis can occur in eyes with severe, chronic edema and with aggressive treatment as has been observed in eyes with macular edema secondary to branch vein occlusion.71 In these instances, treatment in multiple sessions is advised to allow gradual fluid resolution. Moreover, increase in macular edema can occur with aggressive treatment and concomitant panretinal photocoagulation. Therefore, treatment of macular edema prior to PRP reduces this risk.

Caution should be exercised in treating eyes with enlarged foveal avascular zones, because treatment can compromise the existing capillaries, leading to more ischemia. General recommendations to avoid complications include identifying the fixation point, treating with threshold laser burns sufficient to close microaneurysms, treating in multiple sessions if necessary, and avoiding treating directly over blood or fibrovascular tissue.

Conclusions

New laser modalities, expanding delivery systems, and novel applications of laser energy have vastly expanded our armamentarium for the treatment of diabetic eye disease in the 50 years since MeyerSchwickerath’s initial description of xenon arc light coagulation. The minimal invasiveness of laser treatment has significant appeal. Nevertheless, complications are possible, but many can be avoided with meticulous technique and experience.

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