Estudio de los efectos del tratamiento con análogos de las prostaglandinas sobre las propiedades biomecánicas corneales

Résumé

BACKGROUND: Glaucomatous optic neuropathy (GON) is a multifactorial disease and a relevant cause of visual impairment and blindness worldwide. The evaluation of the intraocular pressure (IOP) is essential in glaucoma patients because it is the only risk factor that can be modified. At the current time, Goldmann applanation tonometry (GAT) is considered the gold standard for measuring IOP and the cornea plays an important role in this measurement. Several studies have suggested that corneal central thickness (CCT) and corneal biomechanical properties affect the accuracy of IOP measurement by GAT. It has also been reported that prostaglandin analogues (PGs), first line treatment of glaucoma and ocular hypertension (OHT), changes the CCT and may induce histological change of the corneal collagen and extracellular matrix. The Ocular Response Analyzer (ORA) and the Corvis ST are non-contact tonometers that allow IOP measurements and also provide an evaluation of the “in vivo” corneal biomechanical properties. The objective of the present study is to evaluate if chronic therapy PGs in primary open angle glaucoma (POAG) and OHT patients induces changes in the viscoelastic corneal properties and if these possible changes in the biomechanical properties induced by PGs therapy may make GAT unreliable in these eyes. MATERIAL AND METHODS: We included one trasversal study and two prospective studies (Prospective study A and Prospective study B). Also three intermediate analysis were included.The trasversal study included 390 consecutive patients with POAG or OHT with PGs treatment, who attended our outpatient glaucoma clinic. All subject were evaluated, in addition to a medical history and a complete ocular examination, using GAT, ultrasound pachymeter, Visual Field (VF) and ORA exploration. In the Prospective study A (a prospective, observational study) 68 eyes who were newly diagnosed with POAG or OHT were evaluated at baseline and after 6 months of treatment with PGs measured by GAT, ultrasound pachymeter, VF and ORA. In the Prospective study B (a prospective, observational study), we evaluated biomechanical corneal properties and IOP measured by GAT, Corvis ST and ORA in 67 eyes newly diagnosed of POAG or OHT, at baseline and month 3 and 6 from the beginning of PGs treatment. All patients of prospective studies were treatment-naïve. RESULTS: In the trasversal study we identified a significant and strong correlation between IOPg (Goldmann correlated intraocular pressure) and IOPcc (corneal compensated intraocular pressure) (p=0.0001, r2=0.9) and a weaker correlation between IOPg and IOP GAT (p=0.0001,r2=0.41) and between PIOg and Corneal Hysteresis (CH) (p=0.0006,r2=0.03). In the prospective studies we only found a statistically significant correlation of the VF mean deviation (MD) with the CH (p=0.003, r2=0.16) and the CCT (p=0.03, r2=0.08) in POAG patients.The IOPcc was significantly higher than GAT IOP in POAG (p=0.002), on the other hand we did not find any significant difference between both tonometers in OHT (p=0.5).We did not find any statistically significant difference between drug induced IOP decrease between GAT IOP and IOPcc, however IOP decrease measured by Corvis was significantly different (p= 0.0001).The CH increased significantly (p=0.0001), and this increase was correlated significantly with the basal CH (p=0.0001, r=0.64, r2=0.41). We identified a weak but significant relationship between the basal CH and the druginduced reduction of the GAT PIO (r2=0.06, p=0.01). Nevertheless, the increase in drug-induced CH was not correlated with the decrease in the GAT IOP. Finally, we found statistical significant changes after six months of treatment with PGs analogues at first time of corneal applanation (AT1) (p=0,03), second time of corneal applanation (AT2) (p=0,02), maximum amplitude deformity (DA) (p=0,0002), first corneal speed (AV1) (p=0,003), peak distance (PD) (p=0,03) and maximum radio of concavity (CCR) (p=0,03) measured by CST. The amount of the decrease in the IOP corvis (Δ IOP corvis) was correlated significantly with the AT1 (p=0.001, r2=0.98), AT2 (p=0.0001, r2=0.51) and the DA (p=0.001, r2=0.62). DISCUSSION: We found a stronger correlation between IOPg and IOPcc than between IOPg and IOP GAT in POAG or OHT patients with PGs treatment. In addition, we found that IOPcc was significantly higher than GAT IOP in newly diagnosed untreated POAG while we did not find any significant difference between both tonometers in OHT. These facts suggested that PIOg, measured by ORA, can not be considered equivalent to PIO TAG in this patients. We also found that CH and CCT are associated with the amount of VF damage in newly diagnosed treatment-naïve POAG eyes. We obtain that the IOP decrease induced by PGAs treatment, in patients with POAG or OHT, is different depending on the tonometer used. In addition to this, treatment with PGs increases CH and this increase was not correlated with the drug-induced drecrease in the GAT IOP, moreover eyes treated with PGs showed changes en several paramenters measured with Corvis ST, which suggested a direct effect of PGs on the viscoelastic corneal properties. CONCLUSIONS: The study of the glauocomatous patients cornea, by means of Corvis ST and ORA, shows that PGs treatment induces changes in biomechanical properties of the cornea. In these patients the IOPg, measured by ORA, can not be considered equivalent to IOP GAT and the measure of the IOP decrease induced by PGs is different depending on the tonometer used. Furthermore, the PGs produce changes in the CH and in some of the Corvis ST parameters that do not correlate significantly with the effect of the GAT IOP decrease after a 6 months treatment .These facts suggested a direct effect of PGs independent of the amount of the decrease in the GAT IOP induced by the therapy.