Revista nº 814

López-Jiménez A, et al. | Choroidal thickness analysis in keratoconus patients 257 Actual Med. 2021; 106(814): 252- 259 (11), posterior scleritis (12) and sympathetic ophthalmia (13). It has also been linked to other inflammatory diseases with no ocular manifestations (14). KC is no longer considered a non-inflammatory disease (1) (15) (16), it has been associated with increased levels of pro- inflammatory cytokines (17) and cell adhesion molecules and metalloproteases (7). Oxidative stress has also been identified to play a role in the genesis of the disease (16) (18) (19). Consequently, we aimed to study the choroid of KC patients following this inflammation theory. Corneal stroma is composed of type I, III, V, VI and XII collagen fibers(16) (20). KC is related to connective tissue disorders (21) such as Ehler-Danlos syndrome (22), pseudoxanthoma elasticum, osteogenesis imperfecta (23) and mitral valve prolapse (24). Collagen type I is an important component of vascular vessels, so corneal alterations in KC eyes could be accompanied by structural changes in the choroid, which is a highly vascularized tissue. The most accepted hypothesis of the genesis of KC nowadays is the influence of certain environmental stimuli, which would act over structural alterations or predispositions of unknown origin (25). These predispositions may be based on different ethnic (26) (27), geographic (28) (29), climatic and or genetic factors (30) (31). Environmental stimuli that trigger KC disease include eye rubbing (32), contact lens wearing (6), rosacea, atopy (33) and UV light exposure (34). The progression of the disease could be the result of a complex interaction of all these mentioned factors with multiple genes with variable penetrance. Inflammation, cellular hypersensitivity and oxidative stress could initiate a vicious circle, expressing degrading enzymes (cathepsins) and metalloproteases, resulting in an imbalance between collagenolysis and collagenogenesis and decreased matrix regeneration leading to corneal ectasia. Gutiérrez-Bonet et al.(25), observed using SS-OCT thicker choroids in KC patients than in healthy patients (an average increase of 34%, p<0,05), being these differences lower in elder patients (>45 y.o, non- significant increase, p=0,37). Akkaya et al.(35) using EDI SD-OCT instead, reached similar results. On the contrary Yilmax et al.(36) did not find significant differences in the choroidal thickness of pediatric patients with KC versus age-related controls (mean age of 12 y.o). In a recent controlled, cross-sectional study, Pinheiro-Costa et al.(37) found significant thicker choroids in KC patients (mean difference of 67,55 μm), with a large sample size and relatively young patients (range 12-30 y.o). Akkaya et al. attributed higher subfoveal CT in KC eyes to ethnicity and age; the average age of his patients was very low (24,5 y.o; range 13-38 y.o). Margolis et al. (38) reported a decrease of 15,6 μm every decade of life, denoting the importance of age in CT measurement. Whereas Gutiérrez-Bonet et al. (25) highlighted that his results could not only be justified by collagen alteration but other factors like age, refraction, axial length, hematological causes, choroidal melanocitosis and pachychoroid-spectrum disorders. On the same line he found no significant differences above 45 y.o, possibly due to the progressive thinning of the choroid. Despite our original supposition, our thirteen CT values were lower in the KC group than in the healthy controls. CT in healthy controls was statistically thicker (310 μm) in T6 (3mm temporal to the fovea) than in the KC group (254 μm). These results disagree with those obtained by Akkaya et al (35), Gutiérrez-Bonet et al (25). and Joao et al (37). The higher CT values were found beneath the fovea in both groups, matching these three previous studies. 68% of the healthy eyes exceeded 300 μm of CT and 36% exceeded 400 µm in M. Both limits of CT are within normal CT range. Regarding these results and contrary to expectations, no evidence of thicker CT in KC patients was found in our study. Although T6 reached significant difference, in our opinion it alone cannot justify real differences. T6 is a very eccentric point, and real differences should be regarded in more locations and specially those closer to the fovea. When we analyzed topographic and keratometric variables in KC eyes, we do not find any correlation between them with subfoveal CT. There was neither correlation between the staging of KC, nor between the topographic location of the cone apex with subfoveal CT. The location of the cone in the KC group was similar to previous literature, being the inferior- temporal the most common location of the apex (58%) and the upper cones (3,5%) the least one. The main limitation of our study was the low sample size. CT was measured manually by the same explorer as in the three mentioned similar studies. All measurements were performed during the afternoon (between 12-15 am) to minimize the possible impact of circadian rhythms. The device used was EDI-OCT optical coherence tomography available at our center, which is considered comparable to Swept Source (SS) OCT in CT measurement (correlation coefficient 0.975) Only one random eye was included in the control group and in case of bilateral KC. In both groups, subjects with a refractive error of ± 2 D spherical equivalent were discarded. No other possible bias that could affect the choroidal vessels such as smoking habit or microvascular pathologies were discussed. In conclusion, KC is a complex disease whose exact etiology and development are still not fully understood. In this preliminary study we have not been able to validate a possible correlation between KC and CT. Further studies, with larger samples and comparable parameters, are therefore necessary to shed more light on this corneal ectasia. New generation non-invasive diagnostic methods of the retina and the choroid (SS- OCT and EDI-OCT) offer us a new pathway of research study the possible relationship between the structure of the choroid and corneal diseases. CONCLUSION

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