Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

Finally, it is difficult to treat within the macula, especially when first using the instrument. This is because small movements will shift the placement of the lesion and that spot size is difficult to determine precisely. The BIOLP is therefore best suited for patients with peripheral disease.

The duration and power needed depends on multiple factors including the wavelength of the laser, the clarity of the media, and the pigmentationoftheretinalpigmentepithelium. It is best to use at least 200 msec burns, because slower burns can be observed as they occur and breaks in Bruch’s membrane may be prevented by stopping the treatment if the burns are becoming too intense. Lower power is needed with the argon BIOLP than with the infrared diode BIOLP if the media are clear. Conversely, in the presence of media opacity, the infrared diode BIOLP may need lower power than the argon BIOLP. Another note is that pigmented races need lower power and duration to achieve a white burn because the retinal pigment epithelium is more absorbent.

Availability of BIOLP Equipment

The latest versions are available as attachments to the argon laser, argon-krypton laser, frequency-doubled YAG laser, and infrared diode laser.

Anesthesia With BIOLP

Retinal burns with this instrument can be painful. Subconjunctival anesthesia should be used. Retrobulbar anesthesia is highly useful

to relieve pain but it has disadvantages. The patient cannot move the eye to the side of the lesion to facilitate visualization and treatment. When this happens, a cotton swab or other depressor can be used to move the eye or push the peripheral retina into view.

Adjusting the Aiming Beam

Once the eye is moved in the direction of the area requiring treatment, the aiming beam is adjusted so that it is in the middle of the retinal image. Power and duration are then titrated to achieve the burn required. If using a green wavelength, duration is set to 0.2 to 0.5 sec and power is increased as necessary. With the infrared diode laser, duration begins at 0.4 sec and power at 200 mW in a patient with well-pigmented retinal pigment epithelium. These change to 0.5 sec and 300 mW, respectively, in a patient with hypopigmented retinal pigment epithelium. The BIOLP delivery system has a greater potential of causing breaks in Bruch’s membrane than does the slit lamp because keeping a consistent burn size is difficult.

Precautions Using the BIOLP

Other people in the treatment room should wear safety goggles. Windows should be covered to avoid exposing people outside the room to stray laser light, and a sign mandating the use of safety goggles should be placed on the door.

Because the eyelashes may absorb the laser energy and burn, a lid speculum can be used to hold the eyelids open since there

Diabetic retinopathy is the most common form of retinal vascular disease, constituting the main cause of visual acuity loss in patients with less than 50 years of age in developed countries, and increasing in prevalence daily.(1-4) The following discussion will focus on the most common visually threatening complications of diabetic retinopathy, especially diabetic macular edema (DME), as the paradigm for retinal vascular disease, and subthreshold retinal photocoagulation (SRP) as a method of treatment.

Conventional Suprathreshold

Retinal Photocoagulation

The efficacy of retinal photocoagulation for the complications of diabetic retinopathy was established by the Diabetic Retinopathy Study (DRS, 1976), focusing on the treat-

ment of proliferative diabetic retinopathy (PDR); and the Early Treatment of Diabetic Retinopathy Study (ETDRS, 1985), focusing on the treatment of diabetic macular edema (DME) and the prevention of proliferative retinopathy. Despite major advances in the surgical and pharmacologic management of diabetic retinopathy in the decades since publication of these landmark studies, laser photocoagulation of the retina remains the mainstay of treatment, remarkably little changed in performance and conception. This chapter will examine how subthreshold retinal photocoagulation is effecting change in how photocoagulation for retinal vascular disease is performed, and understood, to the benefit of patients.

In the DRS and ETDRS, retinal photocoagulation was applied in a suprathreshold

fashion, using xenon arc (DRS) or argon laser (DRS and ETDRS) to produce grey to white retinal burns, leading to necrosis, inflammation, and finally fibrosis and atrophy (chorioretinal scarring) of the treated retina (Figure 1)(5). The thermal retinal destruction inherent to conventional threshold and suprathreshold laser photocoagulation is the single source of the many well-known adverse effects that may cause immediate or late postoperative visual loss. These inherent adverse effects place

significant limitations on treatment density, intensity, location, frequency, repeatability and thus utility and effectiveness. Due to the effectiveness of conventional suprathreshold photocoagulation these inherent adverse treatment effects have been considered necessary evils. The results of SRP suggest however, that the complications and inherent adverse effects of thermal retinal destruction, while evil, are in fact not necessary.

In the DRS and ETDRS, observations were made which set the stage for subthreshold retinal photocoagulation. In the DRS, complications of treatment were found higher with increasing treatment intensity; treatment efficacy was found to increase with higher treatment density; and the most common and practically achievable result of treatment for PDR was arrest and regression rather than complete disappearance of new vessels.(6–9) In the ETDRS, treatment risks and complications were also found to be higher with increasing treatment intensity, as well as proximity to the fovea; angiographic leakage was found to be a variable correlate rather than sine qua non of macular edema, with the risk of visual loss correlating more strongly with the location and extent of macular thickening than angiographic leakage (“clinically significant” DME, or CSME); that diffuse rather than focal angiographic leakage was associated with greater risk of disease progression and visual loss; and that angiographic leakage often persisted despite clinically effective treatment.(5,8,10,11) The relevance of each of these observations to use of subthreshold retinal photocoagulation in the management of diabetic retinopathy will be discussed.

Subthreshold Retinal

Photocoagulation (SRP)Defined

Traditionally, SRP is defined as retinal laser photocoagulation performed in such a way to produceaminimallyvisible,oracutelyinvisible treatment application endpoint.(12–14) Typically, avoidance of an acutely visible threshold

(partial thickness) or suprathreshold (fullthickness) retinal laser burn is accomplished by reducing retinal laser power density, or irradiance (power applied per unit of retinal surface area), and consequently thermal rise. By reducing the tissue temperature rise it is hoped that the many well-known sightthreatening complications and unavoidable side effects of conventional visible end-point retinal photocoagulation might be minimized or prevented while still achieving effective retinal photocoagulation.

A cause and effect relationship between creation of a visible retinal burn and treatment benefit has been generally presumed.(16) All traditional theories proposed to explain the effectiveness of laser photocoagulation for retinal vascular disease invoke creation of a chorioretinal scar as both fundamental and necessary. Remarkably, however, although the definite cause of all adverse treatment effects, chorioretinal scarring from thermal retinal destruction has never actually been proven necessary to produce the laser treatment benefits.

In the following discussion I coin a new taxonomy of SRP. This categorization will reflect the historical evolution of SRP from its roots in conventional suprathreshold photocoagulation, as well as critical practical, technical and clinical distinctions between different approaches often obscured by the single heading of “SRP”. In this new taxonomy I divide SRP into three categories, which I call “Classical”, “Clinical”, and “True” subthreshold retinal photocoagulation.

“Classical” Subthreshold

Retinal Photocoagulation

In the ETDRS treatment of CSME was performedusingsuprathresholdphotocoagulation directed at leaking macular microaneurysms, and/or placed in a grid pattern in areas of diffuse angiographic leakage associated with macular thickening. Confluent laser applications, and treatment near the fovea were avoided due to the risk of immediate treatment –associated visual loss. Direct thermal closure of angiographically leaking microaneurysms typically requires higher laser irradiances, increasing thermal retinal damage and scarring. Subsequently, it was learned that CSME could be effectively treated by grid photocoagulation alone, without direct treatment of microaneurysms. This lead to movement away from low-density, highintensity focal treatment to lower intensity grid treatment and the first attempts at SRP, which I term “classical” SRP.(17)

In classical SRP, the same continuous – wave (CW) laser used for suprathreshold retinal photocoagulation, argon green at first, later krypton red and diode infra-red lasers, was applied with reduced irradiance in a grid pattern (retinal burns separated by untreated intervals to avoid confluent retinal ablation) to the areas of macular thickening visible by contact lens biomicroscopy constituting CSME. The acute treatment endpoint sought is typically a barely visible burn, actually “threshold” rather than subthreshold, at the level of the outer retina and/or retinal pigment epithelium (RPE).(18) Morphologic inconsistency is defining

characteristic of “classical” SRP. With classical SRP, retinal laser lesions tend to vary widely within the treatment field from invisible to suprathreshold, with many more lesions apparent by postoperative fundus fluorescein angiography (FFA) than by biomicroscopy. (Figure 2) The reasons for this variability of burn intensity with classical SRP will be discussed below under “A model for understanding…”. Thus, while effective, “classical” SRP may reduce, but not eliminate, the risks of conventional suprathreshold retinal photocoagulation.

A

B

Figure 2: Macular appearance following “classical” subthreshold macular photocoagulation for diabetic macular edema. Note the subtle pigmentary disturbance seen clinically (A) and the obvious chorioretinal scarring demonstrated by FFA (B).

“Clinical” Subthreshold Retinal

Photocoagulation

Introduced in the early 1990’s the “micropulsed”(MP)laseremissionmodalityenhanced the ability to perform SRP.(19-23) Employing an infra-red 810nm solid-state diode laser to maximize absorption by melanin in the RPE and choroid and minimize absorption by neurosensory retina, laser energy could be fired in short microsecond bursts (micropulses) separated by irradiance-free millisecond intervals. Shortening of the pulse duration enhanced localization of laser effects to the target RPE. The “duty-cycle” (DC), or the ratio of the laser bursts over the repetition period within a pulse train (exposure envelope), could be adjusted from a very low ratio, such as 5% (5%, or 100us “laser on” followed by 95%, or 1900us “laser off”) to a very high ratio, such as 95% (1900us “laser on”, 100us “laser off”). As the DC

increases the MP laser effects approach the clinical characteristics of a conventional CW laser due to tissue heating. If the “off” interval of the micropulsed laser exceeds the thermal relaxation time of the absorbing chromophore (in this case, the RPE melanin), photocoagulation effects could theoretically be achieved without producing clinically significant tissue heating, thus precluding laser-induced thermal retinal damage.(14,15) Because of the much wider therapeutic window inherent in micropulsed vs. continuous wave photocoagulation (see below under “A model for understanding…”), SRP could be performed more reliably. The N -1/4 law, described by the Arrhenius curve, holds that the identical biologic effect can be produced by few high-energy laser applications or many low-energy laser applications. Thus, clinically subthermal subthreshold micropulsed retinal photocoagulation need not preclude clinically effective treatment (Figure 3).

Lead by Friberg, a number of investigators demonstrated both the effectiveness of clinical SRP for diabetic macular edema, and the predicted reduction in collateral thermal retinal injury over “classical” SRP. (19,24–30) However, despite employment of micropulse technology, these reports also continued to describe persistent limitations in both safety and effectiveness. These limitations define “clinical” SRP. While clinically effective, these investigatorscontinuedtoemployconventional grid laser application techniques, limiting the density of treatment and, therefore, potential treatment benefit. With regard to safety, all also continued to report a significant incidence of thermal retinal burns. However, unlike the retinal burns resulting from “classical” SRP, the lesions noted following “clinical” SRP were more likely acutely invisible, becoming increasingly apparent weeks and months following treatment, particularly by FFA.(31)

“True” Subthreshold Retinal

Photocoagulation

In an attempt to realize the full potential of MP SRP a new treatment paradigm was reported, novel in that, for the first time, complete avoidance of any thermal retinal injury was chosen as a treatment goal coequal with achievement of clinically effective retinal photocoagulation.(32-34) Successful implementation of theses goals defines “true” SRP.

Focusing on the treatment of DME, performance of true SRP in the treatment of DME was achieved by two fundamental changes in treatment conception: First, to reliably avoid creation of any inadvertent thermal retinal burns, a small retinal laser spot size (125 um),

to maximize heat dissipation was combined with very low micropulse duty cycle (5%), to minimize heat generation.

Practical elimination of the risk of thermal retinal injury by such “low intensity” micropulsed laser parameters allowed the second key change in treatment technique. Rather than applying low intensity photocoagulation focally or in a traditional low density grid of widely spaced applications, all areas of macular thickening due to DME up to the edge of the foveal avascular zone were treated confluently with contiguous laser applications, 360 degrees if indicated, even repeatedly with a single treatment session, to assure complete treatment coverage. The high density of laser application as well as potential proximity to the foveal center demanded absolutely consistent and reliable avoidance of any thermal retinal injury via “low – intensity” SRP. Thus, “true” SRP rests on these two necessary and complementary pillars of “high density” and “low intensity” micropulsed diode laser application.

Utilizing low intensity / high density micropulsed photocoagulation to perform true SRP (termed “SDM”, for “Subthreshold Diode Micropulse photocoagulation” by the authors), clinically effective treatment of DME and PDR were reported in pilot studies without any adverse treatment effects, or thermal retinal burns detectable by clinical biomicroscopy, FFA, or time-domain OCT. (32–34) Subsequent observations demonstrate the absence of any laser-induced retinal injury with SDM by indocyanine green fundus angiography, fundus auto fluorescence photography, and Fourier-domain OCT with postoperative follow up of as long as 10 years(35) (Figures 4-6).

The safety and effectiveness of SDM have been corroborated in subsequent studies of DME.(36,37) The results of the pilot study reporting SDM PRP effective for PDR await

confirmation.(34) From this point forward I will focus on SDM as epitomizing the goals and attributes of SRP for retinal vascular disease.