Estudio de la coroides mediante tomografía de coherencia óptica swept source en sujetos sanos y pacientes diabéticos tipo 2
- Autores: Francisco de Asís Bartol Puyal
- Directores de la Tesis: Pilar Calvo Perez (dir. tes.), Antonio Ferreras Amez (dir. tes.)
- Lectura: En la Universidad de Zaragoza ( España ) en 2020
- Idioma: español
- Programa de doctorado: Programa de Doctorado en Medicina por la Universidad de Zaragoza
- Materias:
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- Resumen
Type 2 diabetes (T2D) is a disease with a multisystemic affection, which can be classified into macro and microangiopathy. The former include ischemic cardiopathy, cerebrovascular accident and peripheral artery disease. The latter comprise nephropathy, peripheral polyneuropathy and diabetic retinopathy (DR). Based on the international classification, DR is divided into five steps: no DR, mild, moderate, severe and proliferative diabetic retinopathy (PDR). Mild, moderate and severe are classified as non-proliferative DR (NPDR). Another additional retinal manifestation is diabetic macular oedema (DME), which usually implies a poorer visual acuity (VA). DME is reversible if correctly treated in time.
Optical coherence tomography (OCT) has been found very useful for detecting DME, as well as for measuring retinal thickness (RT). The development of swept-source optical coherence tomography (SS-OCT) and the enhanced depth-imaging (EDI) technology have enabled deep and accurate analyses of the choroid.3 The previous version of OCT was the spectral-domain OCT (SD-OCT) and it had lower axial resolution compared to SS-OCT, showing inaccurate segmentation of the choroid, unless the EDI mode was enabled. The choroid is mainly made up of blood vessels and it carries blood supply to the external retinal layers. For the last years, the choroid has been thoroughly evaluated and its thickness has been related to multiple physiological conditions, and ocular and systemic diseases. Most studies agree that CT is reduced in T2D eyes. Nevertheless, it still remains unclear how DME affects CT. Moreover, it has been suggested that the choroid may follow an irregular pattern, but no further research has been conducted so far assessing its precise topography and how it varies with different conditions and diseases.
The main subject of the four articles making up this doctoral thesis was the study of the choroid and its topography with SS-OCT in healthy and T2D patients. The purposes were the following: to assess the intrasession repeatability of choroidal thickness (CT) measurements with SS-OCT in healthy individuals and in T2D patients with DR, to compare CT between healthy subjects and T2D patients with different stages of DR, with and without DME, to determine and compare the topographic features of CT between T2D patients and age-matched healthy controls, to evaluate the relationship between macular CT and HbA1c levels and duration of diabetes, and to compare CT in the macular region between young healthy, aged healthy and T2D individuals.
A cross-sectional study was performed at the Miguel Servet University Hospital in Zaragoza (Spain) between November 2015 and November 2017, with different study groups enrolled. Inclusion criteria for the first group were T2D patients between 55 and 75 years old, with an AL ≤ 26mm, < 6 D of myopia and < 2 D of cylinder. In case of DME, a minimum central RT of 300 μm was required. Inclusion criteria for the second group were the same but without the presence of T2D. Inclusion criteria for the third study group included young healthy volunteers between 18 and 35 years old with an AL ≤ 26 mm, < 6 D of myopia and < 2 D of cylinder. For all of them, exclusion criteria were: any ocular pathology, previous ophthalmological treatment or surgery, amblyopia, a race different from Caucasian, pregnancy or puerperium, endocrine or neurological disease, cancer history, systemic treatment with corticosteroids, immunosuppressive drugs, biologic therapies and previous treatment with potentially toxic drugs to the retina and/or optic nerve.
All OCT scans were acquired through dilated pupils at the same day time and by the same experienced technician. Two types of captures were performed: a horizontal 12-mm line and a macular 6x6 mm cube. In the horizontal line scan, 11 manual measurements of CT were obtained. In the macular cube, CT were obtained both in the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and in a grid of 30x30 little cubes, from which two-dimension (2D) and three-dimension (3D) representations were generated and a new choroidal division was established for CT comparisons.
Below is a summary of the four articles: 1. Abadía B, Calvo P, Bartol-Puyal F, Verdes G, Suñén I, Ferreras, A. Repeatability of choroidal thickness measurements assessed with swept-source optical coherence tomography in healthy and diabetic individuals. Retina. 2019 Apr;39(4):786-793.
This was a cross-sectional study including 50 eyes of 33 healthy subjects and 60 eyes of 43 T2D patients, and whose purpose was to assess the intrasession repeatability of CT measurements obtained using SS-OCT in T2D patients and in healthy controls. Among the diabetic group, 7 patients had no DR, 13 had mild, 32 had moderate, 5 had severe, and 3 proliferative DR. Half of the T2D patients had DME. Repeatability was analysed after measuring CT in three different scans which had been consecutively obtained in a single session and automatically delineated by the internal software. Over a horizontal 12-mm line, 11 locations with 500-μm intervals were measured with the caliper by the same operator.
Mean age was 68.02±8.80 years old in the healthy group, and 66.28±7.80 years old in the T2D group (p=0.28). Mean subfoveal CT in healthy subjects and in T2D patients was 222.97±79.90 μm and 192.67±74.30 μm, respectively (p=0.013). The intraclass correlation coefficient (ICC), the coefficient of variation (COV) and the test-retest variability were calculated. All ICC were higher than 0.95 and 0.99, respectively. COV were less than 4.4% and 1.8%, respectively. The test-retest variability ranged from 0.76 μm to 11.12 μm, and from 0.64 μm to 6.29 μm, respectively. No significant differences were found in the intrasession repeatability of any choroidal measurement between healthy subjects and T2D patients.
In conclusion, SS-OCT provided excellent intrasession repeatability of CT measurements in healthy and T2D patients.
2. Abadia B, Suñen I, Calvo P, Bartol F, Verdes G, Ferreras A. Choroidal thickness measured using swept-source optical coherence tomography is reduced in patients with type 2 diabetes. PLoS One. 2018 Feb 2;13(2):e0191977.
This was a cross-sectional study comprising 157 eyes of 94 T2D patients and 71 eyes of 38 healthy subjects. Its objective was to compare CT between T2D patients and age-matched healthy controls.
Among the 157 T2D eyes, 48 had DME. 49 eyes had no DR, 27 had mild NPDR, 60 had moderate NPDR, 14 had severe NPDR and 7 PDR. On every SS-OCT image, 11 CT measurements were manually performed. One was subfoveal, five nasal and five temporal, with 500-μm intervals between them. Besides comparing CT between the three study groups, a correlation analysis was performed between diabetes duration, glycosylated haemoglobin (HbA1c) levels and CT. A masking was performed so that the operator could not identify whose patient was that slab.
Mean age was 67.60±8.10 years and there were no differences in age, AL or blood pressure between groups (p>0.05). Mean diabetes duration was 16.6±9.5 years, while mean HbA1c was 7.7±1.3%. Overall, the choroid was significantly thinner in T2D patients. Individuals with DME had reduced choroidal thickness in all measurements, except at 2000 and 2500-μm nasal positions, compared to healthy controls. There was a moderate correlation between CT and HbA1c levels in DME patients (r=0.342, p=0.017 in subfoveal position). Diabetes duration did not correlate significantly with CT. In both groups, the choroid revealed a similar pattern: it was the thickest at the subfoveal position, followed by temporal and nasal. These results were similar to other studies.10–12 In conclusion, SS-OCT measurements revealed that the choroid was significantly thinner in T2D patients, moderate NPDR patients, and DME patients than in healthy individuals.
3. Abadia B, Bartol-Puyal F, Calvo P, Verdes G, Isanta C, Pablo L. Mapping choroidal thickness in patients with type 2 diabetes. Can J Ophthalmol. 2019 Aug 9. pii: S0008-4182(19)30344-8 This was a cross-sectional study whose objective was to determine and compare topographic features of CT between T2D patients and aged-matched healthy controls based on SS-OCT. 66 eyes of 33 healthy individuals and 192 eyes of 96 T2D patients were enrolled. 36 eyes had no DR, 26 had mild NPDR, 25 had moderate NPDR, 5 had severe NPDR and 4 had PDR. None of them had DME.
A macular 6x6 mm cube was scanned with SS-OCT and choroid was automatically segmented and its thickness automatically measured. The scanned area was divided into different zones based on CT, and equivalent zones were compared between groups. In addition, 3D maps were created to represent the choroid.
There were no differences in age or AL (p>0.05). Mean age was 66.83±7.31 years old in the healthy group, and 67.94±7.93 years old in the T2D group. Overall, CT was significantly thinner in T2D patients (p<0.05). Outside the fovea, the mean CT was thicker in the superior hemiretina and decreased inferiorly, temporally and nasally, with minimum thickness in the most distant points.
These results were similar to those stating that CT is thinner in diabetes mellitus (DM) patients, but it was the first time that it was displayed in exhaustive 3D maps originated from data obtained from SS-OCT with automatic segmentation and measurements.
In conclusion, CT follows an ellipsoid pattern in both nondiabetic and diabetic eyes, with diffuse thinning in the latter. Understanding these differences is important for future studies aimed at explaining the pathophysiology and relationship between choroid and DR.
4. Bartol-Puyal F, Isanta C, Ruiz-Moreno Ó, Abadía B, Calvo P, Pablo L. Distribution of Choroidal Thinning in High Myopia, Diabetes Mellitus, and Aging: A Swept-Source OCT Study. J Ophthalmol. 2019 Aug 15;2019:3567813.
This was a cross-sectional study comparing the macular choroidal thinning between young healthy, aged healthy, young high myopic, and aged T2D patients using the ETDRS grid and 3D maps. The first study group comprised 102 eyes of 51 young healthy subjects, the second included 60 eyes of 30 aged healthy subjects, the third was composed of 110 eyes of 55 T2D patients, and the fourth consisted of 24 eyes of 12 young high myopic patients.
CT values were obtained in grids of 30x30 cubes of 200x200 μm every cube, which were automatically provided by the OCT, and 3D maps were created to represent CT. This was also obtained in every ETDRS grid sector. Mean age was 27.31±3.95, 66.41±7.54, 27.69±3.89, and 66.48±7.59 years in the four groups, respectively. CT was not shown to be uniform, as superior and central zones were thicker in all groups. All ETDRS sectors were always thicker (p<0.05) in young healthy individuals than in the others. It was found that the choroidal sector which got thinner was the inferior in case of age (103.28 μm decrease), the inferior-nasal in high myopia (86.19 μm decrease), and the temporal in T2D (55.57 μm decrease).
Young healthy subjects’ choroid was used as a reference and divided into different zones according to the mean CT in every macular cube. Five nasal and five temporal zones were delimited. Comparisons of CT between equivalent zones revealed that choroid got thinner in those regions where it was thicker in healthy subjects.
Choroidal 3D representations showed different patterns: a ‘mountain range’ pattern in young healthy individuals, a ‘mountain peak’ in aged healthy individuals, an ‘inverted gorge’ pattern in young high myopic patients, and a ‘gathered hills’ pattern in aged T2D patients. Some authors had tried to make topographic descriptions or choroidal maps but it was the first time that such an in-depth map has been created. Furthermore, it was the first time that different topographic patterns have been defined.
In conclusion, not all choroidal regions are affected in a similar way, as it depends on the pathology. For a better understanding and a more exhaustive analysis, 3D maps are a useful tool. Further studies should be performed to explain the pathophysiology of these different choroidal patterns.
