Optical coherence tomography and optical coherence tomography angiography findings in pseudoexfoliation syndrome and pseudoexfoliative glaucoma

Objective: The aim of this study is to comprehensively analyze the microvascular alterations in the retina and optic nerve of patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PEG) using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Additionally, the study evaluates the diagnostic performance of structural and microvascular parameters obtained from these imaging modalities in the early detection and differential diagnosis of glaucoma. Thus, it aims to identify imaging biomarkers that may facilitate earlier and more accurate detection of glaucomatous damage in PES and PEG cases. Materials and methods: This prospective, observational, cross-sectional comparative clinical study included a total of 196 eyes from 127 participants: 61 eyes of 46 patients with PES, 47 eyes of 37 patients with PEG, and 88 eyes of 44 healthy controls. All patients included in the study underwent a comprehensive ophthalmologic examination. This examination consisted of best-corrected visual acuity (BCVA) assessment in logMAR units, anterior segment evaluation with slit-lamp biomicroscopy, intraocular pressure (IOP) measurement using Goldmann applanation tonometry (GAT), and dilated fundus examination. Macular thickness, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness were measured using an SD-OCT device (Nidek Co Ltd). OCT-A imaging (RS-3000 Advance, Nidek Co Ltd) was used to assess macular superficial and deep capillary plexus (SCP and DCP) vessel densities (VD), foveal avascular zone (FAZ) parameters, and radial peripapillary capillary plexus vessel density (RPCP-VD). Results: Peripapillary RNFL thicknesses were significantly lowest in the PEG group and highest in the control group in all quadrants except the nasal quadrant (p<0.001). GCL thickness was also significantly lowest in PEG and highest in the control group (p<0.001). GEE and GLMM analyses identified inferior RNFL (I-RNFL), superior RNFL (S-RNFL), and inferior GCC (I-GCC) thicknesses as the strongest structural biomarkers. Except for the outer ring inferior quadrant, the inner ring superior quadrant and the central subfield, macular thickness values in all other quadrants were significantly lowest in the PEG group and highest in the control group (p<0.001). While no significant difference was observed between groups in FAZ area or perimeter (p=0.062 and p=0.051, respectively), the FAZ circularity index was significantly highest in the PEG group (p<0.001). Except for the inner ring superior quadrant, inner ring temporal quadrant, and the central region, superficial capillary plexus vessel density (SCP-VD) values were significantly lowest in the PEG group and highest in the control group (p<0.001). Mean DCP-VD and inner ring mean DCP-VD values were also significantly lowest 4 in PEG group and highest in controls (p<0.001). Peripapillary RPCP vessel densities in the superior and inferior quadrants were significantly lower in the PEG group and higher in the control group (p<0.001). Both the GEE and GLMM models demonstrated that age, BCVA, IOP, I-GCC, FAZ area, parafoveal superior SCP-VD, parafoveal inferior SCP-VD, S-RNFL, and I-RNFL were significantly associated with the presence of disease. Decreased values of I-GCC, SCP vessel densities (superior and inferior quadrant), and RNFL thicknesses were consistently associated with disease status in both models. IOP emerged as the primary risk factor increasing the likelihood of progression to PEG. Conversely, Parafovea I-MT, I-GCC, S-RNFL, and I-RNFL showed inverse correlations with disease in both models. Similarly, microvascular parameters including parafovea S-SCP VD, foveal SCP VD, and parafovea average-DCP VD demonstrated significant negative associations with disease severity. Sex and age were not statistically significant predictors in either model. Conclusions: According to the results of our study, the findings highlight the importance of utilizing both vascular and structural biomarkers together in clinical practice for the diagnosis of PES/PEG, for assessing the risk of progression, and for monitoring disease advancement. OCT and OCT-A examinations represent valuable tools that enable the clinical evaluation of structural and microvascular alterations in eyes with PES and PEG.