Therapies for DME and Rationale for Combination Therapy
Therapies for DME and Rationale for Combination Therapy
Laser photocoagulation was the recommended treatment for DMO for several years. The exact mechanisms of action of laser photocoagulation in reducing oedema in DMO are unknown. Plausible mechanisms include destruction of high-oxygen consuming photoreceptors, increased oxygenation of the retina through diffusion from the choroid, restoration of new retinal pigment epithelium (RPE) barrier, production of cytokines including transforming growth factor-β and pigment epithelium-derived factor from the stimulated RPE as discussed in the review by Bhagat et al. In the early treatment diabetic retinopathy study (ETDRS), DMO eyes treated with laser had lower rates of visual loss compared with control group (12% vs 24% at 3 years). This benefit was only noticeable in eyes with clinically significant DMO. In eyes with diffuse DMO, response to grid laser photocoagulation was of limited benefit, with only 15% showing a visual improvement, 24% developing visual deterioration, and 61% unchanged. The average best corrected visual acuity (BCVA) change in laser-treated eyes in the diabetic retinopathy clinical research network (DRCRnet) and RESTORE (ranibizumab monotherapy or combined with laser vs laser monotherapy for DMO) studies were +2.7 to +3.2 letters at 12 months, and the fovea remained thickened in a large proportion of the laser-treated eyes. Although effective in some cases of DMO, ETDRS protocol photocoagulation may require placement of burns close to the centre of the macula. Over time, laser burns may develop into areas of progressive RPE and neuroretinal atrophy that become larger than the original laser spot size and encroach upon fixation, or subretinal membranes may occur. Photocoagulation for DMO may be associated with loss of central vision, central scotomas, and decreased colour vision. In an attempt to reduce these adverse effects, many retinal specialists now treat with burns that are lighter and less intense than originally specified in the ETDRS (modified-ETDRS technique). In the alternative approach of mild macular grid laser, mild, widely spaced burns are applied throughout the macula, avoiding the foveal region. By design, some burns could be placed in clinically normal retina if the entire retina was not abnormally thickened, including areas within the macula that are relatively distant from the area of thickening. As such, laser photocoagulation is not advised in eyes where the leakage is close to the fovea and when the oedema is centre involving.
Subthreshold laser photocoagulation has recently been suggested as a better alternative in the treatment of DMO as the collateral damage to the retina-choroid complex is limited. That is because subthreshold laser does not destroy the RPE on account of the much shorter duration. The role of subthreshold laser therapy in DMO has yet to be widely taken up, and requires further evaluation.
Laser Photocoagulation
Laser photocoagulation was the recommended treatment for DMO for several years. The exact mechanisms of action of laser photocoagulation in reducing oedema in DMO are unknown. Plausible mechanisms include destruction of high-oxygen consuming photoreceptors, increased oxygenation of the retina through diffusion from the choroid, restoration of new retinal pigment epithelium (RPE) barrier, production of cytokines including transforming growth factor-β and pigment epithelium-derived factor from the stimulated RPE as discussed in the review by Bhagat et al. In the early treatment diabetic retinopathy study (ETDRS), DMO eyes treated with laser had lower rates of visual loss compared with control group (12% vs 24% at 3 years). This benefit was only noticeable in eyes with clinically significant DMO. In eyes with diffuse DMO, response to grid laser photocoagulation was of limited benefit, with only 15% showing a visual improvement, 24% developing visual deterioration, and 61% unchanged. The average best corrected visual acuity (BCVA) change in laser-treated eyes in the diabetic retinopathy clinical research network (DRCRnet) and RESTORE (ranibizumab monotherapy or combined with laser vs laser monotherapy for DMO) studies were +2.7 to +3.2 letters at 12 months, and the fovea remained thickened in a large proportion of the laser-treated eyes. Although effective in some cases of DMO, ETDRS protocol photocoagulation may require placement of burns close to the centre of the macula. Over time, laser burns may develop into areas of progressive RPE and neuroretinal atrophy that become larger than the original laser spot size and encroach upon fixation, or subretinal membranes may occur. Photocoagulation for DMO may be associated with loss of central vision, central scotomas, and decreased colour vision. In an attempt to reduce these adverse effects, many retinal specialists now treat with burns that are lighter and less intense than originally specified in the ETDRS (modified-ETDRS technique). In the alternative approach of mild macular grid laser, mild, widely spaced burns are applied throughout the macula, avoiding the foveal region. By design, some burns could be placed in clinically normal retina if the entire retina was not abnormally thickened, including areas within the macula that are relatively distant from the area of thickening. As such, laser photocoagulation is not advised in eyes where the leakage is close to the fovea and when the oedema is centre involving.
Subthreshold laser photocoagulation has recently been suggested as a better alternative in the treatment of DMO as the collateral damage to the retina-choroid complex is limited. That is because subthreshold laser does not destroy the RPE on account of the much shorter duration. The role of subthreshold laser therapy in DMO has yet to be widely taken up, and requires further evaluation.