Συσχέτιση ευρημάτων blue on yellow περιμετρίας και μορφολογικών παραμέτρων του οπτικoύ νεύρου και των νευρικών ινών σε ύποπτους γλαυκωματικούς ασθενείς

Abstract

Introduction: The introduction of sophisticated instruments such as the Blue-on-Yellow (BoY) perimetry and the Heidelberg Retina Tomograph (HRT) has made the earlier diagnosis of glaucoma possible. Several studies have demonstrated that BoY perimetry global indices correlate well with certain stereometric HRT parameters. Objective: The objective of the study was to identify statistically significant differences in HRT stereometric parameters and/or BoY perimetry global indices among normal subjects, subjects suspected for glaucoma and patients with incipient glaucoma. In the cases of statistically significant differences the study also aimed to designate the cut-off values of each variable separating the suspects from the normals or the suspects from the patients, in order to predict beyond which values a normal subject is due to develop glaucoma. Patients and methods: The material of the study comprised 174 eyes of a cohort of 87 subjects, attending the Glaucoma Department of the “G. Gennimatas” General Hospital of Athens from January 2004 to February 2014. Their files were retrieved and the related data were evaluated and analyzed statistically. All subjects included in the study were reexamined every six months or at least annually according to a specific protocol that included HRT and BoY perimetry. Each subject was assigned to one of the following three study groups: Group 1: It is the group of ‘normal’ subjects who did not require treatment during the study, despite being suspected for glaucoma. They presented the following characteristics: IOP > 21 mm Hg, central corneal thickness < 520 nm and/or family history of glaucoma, lack of pathological findings in any visual field examinations or HRTs. Among the available data from multiple HRT and BoY perimetry examinations of subjects assigned to group 1 those registered on one randomly chosen examination were used for statistical analysis. Group 2: It is the group of subjects originally suspected for glaucoma who developed the disease during the study and required treatment. Although they initially presented the same 153 characteristics with those of group 1, posterior data from their files confirmed their developing glaucoma during follow-up, based on HRT (at least one specific zone outside the normal limits in Moorfields regression analysis at two consecutive examinations) and/or BoY perimetry findings (three adjacent but not edge points, except from those immediately above or below the nasal horizontal meridian, being < 5 dB, one of which < 10 dB). Among the available data from multiple HRT and BoY perimetry examinations of subjects assigned to group 2 those registered on their last normal examination (= before the diagnosis of glaucoma) were used for statistical analysis. Group 3: It is the group of patients with incipient glaucoma under treatment since the beginning of the study, exhibiting IOP > 22 mm Hg and repeatedly presenting pathological findings in HRT and repeatable BoY and W/W perimetry visual field abnormalities. Among the available data from multiple HRT and BoY perimetry examinations of subjects assigned to group 3 those registered on one randomly chosen examination posterior to the diagnosis of glaucoma were used for statistical analysis. First, representative values were calculated and the distribution normality of the investigated HRT parameters was checked. Then, the three study groups were compared by means of One-way ANOVA for normally distributed parameters and by means of KruskalWallis nonparametric ANOVA for non-normally distributed parameters. When statistically significant differences were encountered in the above, then pairwise comparisons of group means were performed, using Student’s t-tests for parametric and Mann-Whitney U test for nonparametric variables respectively. For the parameters, acting as classifiers of the subjects, ROC curves were designed and the respective areas under the curves (AUC) were calculated, along with confidence intervals and optimum cut-off values for 95% specificity. 154 Contingency analysis was performed for the p-values of the BoY perimetry global indices MD, SF, PSD and CPSD in the three study groups. Bivariate relationships were assessed with Cochran Mantel-Haenszel X2 statistics. For all the above analyses significance was determined at the 95% level (p-value <0.05). Results: From the 174 eyes of the 87 participants of the study 66 (37.9%) were assigned to group 1, 40 (23.0%) to group 2 and 68 (39.1%) to group 3. Statistical analysis established significant differences among the three study groups for the HRT parameters ‘cup shape measure’, ‘mean RNFL thickness’, ‘RNFL crosssectional area’ and ‘reference height’ (RH). Moreover, cup shape measure differed significantly (p < 0.0001) between groups 2 and 3 and between groups 2 and 1. ‘Mean RNFL thickness’ and ‘RNFL cross-sectional area’ differed significantly (p = 0.0149 and p = 0.006 respectively) between groups 1 and 3. RH was significantly (p < 0.0001) different between groups 1 and 3 and between groups 1 and 2. The RH value of 7.82 was found to be a positive estimator (p < 0.0001) between groups 1 and 3. In the related ROC analysis AUC was estimated at 0.742, demonstrating a relatively good discrimination ability between these groups with the optimum cut-off level for 95% specificity calculated at 0.38. Similarly, the RH value of 5.13 was a positive estimator (p < 0.0059) between groups 1 and 2. In the related ROC analysis AUC was estimated at 0.685, demonstrating a relatively not so good discrimination ability between these groups with the optimum cut-off level for 95% specificity calculated at 0.378. Cochran Mantel-Haenszel X2 test revealed statistically significant results for the index MD (p = 0.0024), distinguishing group 2 from groups 1 and 3: in groups 1 and 3 almost 35% of the subjects fell into the MD category 1 while in group 2 the respective percentage was 155 only 16.09%; moreover, in groups 1 and 3 4.6% of the subjects fell into the MD category 2, whereas in group 2 the respective percentage almost reached 7%. Conclusions: The conclusions of the study can be summarized in the following: The HRT stereometric parameter ‘reference height’ (RH) was significantly different among the three study groups and presented a good discrimination ability (AUC=0.742) between groups 1 and 3 and a satisfactory discrimination ability (AUC=0.685) between groups 1 and 2. The HRT stereometric parameter ‘cup shape measure’ was significantly different among the three study groups and distinguished group 2 from groups 1 and 3. The BoY perimetry global index ‘mean deviation’ (MD) was significantly different among the three study groups and distinguished group 2 from groups 1 and 3. These results may suggest the importance of the above variables for the early diagnosis and follow-up of glaucoma but need to be corroborated and interpreted through further longitudinal studies

Σκοπός: Σκοπός της μελέτης είναι η διερεύνηση στατιστικά σημαντικών διαφορών σε στερεομετρικές παραμέτρους του HRT ή/και σφαιρικούς δείκτες της ΒoΥ περιμετρίας ανάμεσα σε φυσιολογικά άτομα, ύποπτα για γλαύκωμα και ασθενείς με αρχόμενο γλαύκωμα. Ασθενείς και μέθοδοι: Το υλικό της μελέτης περιλαμβάνει 174 μάτια από πληθυσμό 87 ατόμων, παρακολουθούμενων στο Τμήμα Γλαυκώματος του Γ.Ν.Α. «Γ. Γεννηματάς» από τον Ιανουάριο του 2004 μέχρι και τον Φεβρουάριο του 2014. Κάθε συμμετέχων εντάχθηκε σε μια από τις ακόλουθες τρεις ομάδες:Ομάδα 1: Αποτελεί την ομάδα των «φυσιολογικών» ατόμων, που αν και θεωρούμενα ύποπτα για γλαύκωμα, δεν χρειάσθηκαν θεραπεία στην διάρκεια της μελέτης. Ομάδα 2: Αποτελεί την ομάδα των αρχικά υπόπτων ατόμων, που μετά από ποικίλο διάστημα παρακολούθησης ανέπτυξαν γλαύκωμα και χρειάσθηκαν θεραπεία. Ομάδα 3: Αποτελεί την ομάδα των ασθενών με διαγνωσμένο αρχόμενο γλαύκωμα, που τελούσαν υπό θεραπεία από την αρχή της μελέτης. Αποτελέσματα: Από τα 174 μάτια των 87 συμμετεχόντων στην μελέτη 66 (37.9%) ταξινομήθηκαν στην ομάδα 1, 40 (23%) στην ομάδα 2 και 68 (39.1%) στην ομάδα 3. Η στατιστική ανάλυση κατέδειξε σημαντικές διαφορές ανάμεσα στις τρεις ομάδες για τις παραμέτρους του HRT ‘cup shape measure’, ‘mean RNFL thickness’, ‘RNFL cross-sectional area’ και ‘reference height’ (RΗ). Ακόμη, βρέθηκε στατιστικά σημαντική διαφορά ως προς τον σφαιρικό δείκτη της ΒoΥ περιμετρίας MD Συμπεράσματα: Οι στερεομετρικές παράμετροι του HRT ‘reference height’ (RH) και ‘cup shape measure’ του HRT καθώς επίσης και ο σφαιρικός δείκτης της BoY περιμετρίας ‘mean deviation’ (MD) διαφοροποιούνται σε βαθμό στατιστικά σημαντικό ανάμεσα στις τρεις ομάδες της μελέτης