| dc.description.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
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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.
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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. | |
