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

A Model for Understanding Invisible Endpoint Retinal Photocoagulation

In the absence of precedence for true SRP, the laser parameters employed and reported

in the pilot studies of SDM were selected intuitively and empirically. Despite these limitations, the goals of true SRP were achieved: effective retinal photocoagulation without any retinal damage. Remarkable good fortune, to be sure; but do these results also point

to a rational basis for understanding and optimizing invisible treatment endpoint retinal photocoagulation such as SDM other than the desired clinical effect?

In their pilot study of SDM for DME, Luttrull, Musch and Mainster suggested the American National Standards Institute (ANSI) “Maximum Permissible Exposure” (MPE) concept as a model for understanding true subthreshold, invisible endpoint, retinal photocoagulation such as SDM.(32) ANSI MPE standards are developed from a combination of theoretical and empirical data. The MPE represents the level of laser exposure associated with a 50% risk of a barely visible

(threshold) thermal retinal lesion. For CW laser photocoagulation, that level is approximately 10x MPE. For low DC micropulsed photocoagulation, the corresponding level is 100x MPE. The narrow therapeutic range, together with the heterogeneity of melanin distribution in the RPE, precludes true SRP with conventional CW lasers (“classical SRP”). Conversely, the wide therapeutic range of low DC micropulsed photocoagulation offers the unique opportunity of performing clinically effective (above 0x MPE) and simultaneously true (below 100x MPE) SRP (SDM). (Figure 7) But where in that range do the ideal SDM parameters lie?

As stated above, in the absence of precedent, critical laser parameters in the pilot study of SDM for DME were chosen intuitively and empirically, but found to be both safe and effective. (32) Subsequent calculations revealed that the SDM laser parameters in this study produced a laser exposure corresponding to 47x MPE, neatly dividing the interval between no expected biologic effect and a 50% threshold burn risk. In their parallel pilot study of SDM PRP for PDR, Luttrull, Musch, and Spink again reported laser parameters chosen without precedent.(34) In this study, retinal irradiance was reduced by use of larger retinal spot sizes and power limitations of the laser to an exposure level corresponding to just 18x MPE. Yet, despite this low level, clinically effective photocoagulation treatment was still observed. The findings of these two pilot studies begin to suggest an ideal therapeutic range for SDM.

Further insight can be gained by analysis of the “titration” approach typically employed in “clinical” SRP. In this approach, a visible suprathreshold micropulse retinal “test” burn is created, generally requiring at least 150 – 200x MPE. The laser power, duty cycle, and / or pulse duration are then reduced by 20 – 50% to produce acutely invisible retinal photocoagulation.Assuminga50%reductionin irradiance from the test burn level, treatment would then be performed at approximately 75 – 100x MPE. At 100x MPE, the risk of a threshold retinal burn from a MP laser is 50%. Thus, utilizing the “titration” technique to determine MP SRP treatment parameters, a high percentage of latent retinal burns are both predicted and observed. This observation may help further define the ideal SDM

exposure range as that below 75x MPE to minimize inadvertent retinal burns.

Thus, it appears that the ideal parameters for macular SDM may include the following: a small retinal spot size to maximize heat dissipation; a low-duty cycle to prevent heat build up by maximizing thermal relaxation between micropulses; and sufficient power and pulse train duration to achieve laser exposures of approximately 50x MPE. (Table 1, 2) At this level biologic effectiveness is predicted and observed, and inadvertent retinal burns are not. Remarkably, the empirically formulated micropulse laser parameters used to perform

TABLE 1

SDM for Diabetic Macular Edema: Suggested Laser Parameters

Table 1. Suggested SDM laser parameters for treatment of diabetic macular edema. 1. Employs a Mainster macular contact lens (magnification 1.05%) (Ocular Instruments) with 125 um aerial spot producing a 131um retinal spot. 2. All areas of macular thickening are treated confluently. A typical treatment session requires 300 – 1,000 SDM applications. 3. Use of macular spot sizes greater than 200 um and / or duty cycles of more than 10% significantly increase retinal burn risk, particularly in darker fundi.

SDM in the pilot study of DME treatment fortuitously approximate the ideal suggested by the ANSI MPE model. Correspondence between this calculable model and clinical findings may thus provide a reasonable basis for rational assessment of invisible endpoint retinal photocoagulation parameters in order to optimize treatment outcomes.

Subthreshold Retinal Photocoagulation and Current Concepts of Retinal Vascular Disease

The effectiveness of SDM calls into question all theories of retinal laser action that invoke as necessary the creation of chorioretinal scarring by thermal retinal destruction.(16) Instead, by exclusion SDM would appear to operate by laser - induced modulation of RPE cytokine production. This theory is consistent with

current understandings of the pathogenesis of retinal vascular disease, and is supported by clinical observations and laboratory stud-

ies.(32-39)

Clinically Significant vs. OCT DME

Current guidelines for treatment of DME were defined by the EDTRS, based on biomicroscopic findings and accounting for the risks of conventional suprathreshold macular photocoagulation. However, OCT now allows clinicians the ability to diagnose DME well below “clinically significant” macular thickening levels. The remarkable safety profile of SDM may make it uniquely suited to the treatment of OCT visible DME not meeting the ETDRS “clinically significant” threshold. As observed in the management of many other

disease states, such early treatment of DME may ultimately improve patient outcomes.

SDM: Clinical Observations

With ten years of clinical experience using SDM treatment as the exclusive laser modality for the treatment of retinal vascular disease, the author offers the following clinical observations:

•Due to the absence of retinal damage, SDM can be repeated as necessary over time to achieve the desired treatment effect, much like administration of a drug.

•Clinical improvement may continue slowly over a long period of time, thus retreatment is generally reserved for disease that fails to respond to initial treatment, or recurs.

•Serial OCT (for DME) and fundus photography (for PDR) are very helpful in monitoring treatment response (Figures 8 & 9). DME

DME may recur following SDM, as reported by Sivaprasad and associates.(28) Such recurrence is consistent with the proposed theory of action of SDM and permitted by the absence of treatment-induced chorioretinal scarring(28, 32 - 34, 40) (Figure 9). Recurrent DME following SDM may be successfully retreated without retinal injury.

• In patients with dark fundi, reduction in laser irradiance may be prudent to avoid inadvertent retinal burns. Although alterations in various laser parameters such as spot size, power, DC, and pulse envelope lead to

linear changes in exposure level, the clinical effects of such changes are not linear, but logarithmic in character due to tissue effects.

•Clinical experience demonstrates that, for treatment of DME, increasing retinal spot sizes to 200um or more, and / or DC beyond 5% may significantly increase retina burn risk even if total irradiance and exposure level in xMPE remains unchanged. (Figure 10)

•The 810nm diode laser wavelength penetrates media opacities such as nuclear sclerotic cataract, vitreous hemorrhage and intraretinal hemorrhage easily. Because it is