MODULACIÓN FARMACOLÓGICA DEL EDEMA MACULAR CLÍNICAMENTE SIGNIFICATIVO, EN PACIENTES CON DIABETES TIPO 2 TRATADOS CON FOTOCOAGULACIÓN FOCAL

Abstract

Background: clinically significant macular edema (CSME) is a common cause of visual loss in patients with diabetic retinopathy. Photocoagulation is the standard treatment, which reduces the incidence of visual loss but improves best corrected visual acuity in few cases. Photocoagulation induces inflammation, which can increase macular thickness after treatment. Topical nonsteroidal anti-inflammatory therapy improves thickening resolution 3 weeks after photocoagulation, which could be caused by suppression of induced inflammation. Besides inflammation, other factors are involved in CSME pathophysiology that could be pharmacologically modulated, such as oxidative stress and local angiotensin. Identifying the amount in which they could be modulated could allow the design of therapeutic approaches to reduce resolution time, or improve vision. Local evaluation requires an experimental model, to correlate retinal angiotensin and oxidative stress changes with serum changes. Methods: Best corrected visual acuity and optical coherence tomography measured center point thickness (CPT) and macular volume were measured in eyes with CSME. The proportion of visual loss at the moment of diagnosis was identified; CPT and macular volume values were determined in eyes without retinopathy, and the expected value of CPT in eyes with CSME was estimated. Severity distribution of CSME was identified, as well as the evolution of CPT and macular volume 3 weeks after photocoagulation, in eyes with and without severe edema. The change in best corrected visual acuity was measured, and its correlation with anatomic changes was calculated. Using these reference values, eyes without severe edema were selected and assigned to 1 of 3 treatments during Virgilio Lima Gómez 20 1 week after photocoagulation: A (Ketorolac), B (Nepafenac) or C (placebo). The mans of CPT, macular volume and visual capacity were compared in each group 24, 48 and 168 hours after photocoagulation (Friedman); the change mean in each variable was compared between groups (Kruskall-Wallis). Simultaneously, a microsurgical technique was standardized to obtain isolated neuroretina, in an animal model of diabetes (rat). Results: 69.4%of the eyes had visual deficiency at the moment of diagnosis. CPT in eyes without retinopathy was lower than the international reference (156.6 ± 15.7 μm vs. 182 ± 23 μm). The expected value of CPT in eyes with CSME was 231.7 μm, within the rank internationally considered subclinical. 57.6 of the eyes had severe edema (52.1% in eyes with focal leakage). Three weeks after photocoagulation macular volume decreased significantly both in eyes with and without severe edema, and CPT increased significantly in eyes without severe edema. After treatment 32.9 of the eyes decreased their vision, 40.5% increased their vision and 26.6% did not change. Since the change of best corrected visual acuity was not significant, correlations with macular volume and CPT were low both in the sample and in eyes without severe edema. CPT did not change significantly in any treatment group; macular volume increased significantly in groups A and B, but not in group C. Best corrected visual acuity increased statistically, but not clinically, at 168 hours in group B. The standardized microsurgical technique leads to the complete isolation of the rat neurorretina, which allows biomarkers to be determined in this tissue, without the interference of those belonging to the choroid. Virgilio Lima Gómez 21 Discussion: eyes evaluated in the pharmacological intervention had mild or moderate edema, in order to detect in a better way the changes of CPT that arise after photocoagulation. The CPT value used to identify severe edema corresponded to the population of study, so its mean before and after photocoagulation was lower than those internationally reported. Anatomic outcome variables were used, because the correlation with the functional variable was low. Anti-inflammatory therapy was not efficient to treat the increase in CPT induced by photocoagulation, during the time of inflammatory activity. The standardization of the microsurgical technique allows the measurement of biomarkers in the retina, 20% of which is of vascular nature, without the involvement of the choroid, a mainly vascular tissue, as it could happen when eye homogenates are used. Conclusion: The effect of nonsteroidal anti-inflammatory therapy over CPT after photocoagulation could not be associated with the repression of induced inflammation. The characterization of CPT and macular volume changes three weeks after photocoagulation allows the identification of changes induced by pharmacologic interventions; the standardization of the technique for obtaining isolated retina from the rat is the required step for a valid comparison, between retinal and serum measurements.