Effect of prostaglandin analogs on macular microcirculation in patients with ocular hypertension and early glaucoma

To the Editor: Ocular hypertension (OHT) is defined by elevated intraocular pressure (IOP) without glaucomatous optic neuropathy. OHT may progress to primary open-angle glaucoma (POAG), which causes progressive optic neuropathy and vision loss. While IOP-lowering medications like prostaglandin analogs (PGAs) mitigate this risk, long-term use presents an economic burden and adverse effects. Previous studies have demonstrated the effectiveness of PGAs in lowering IOP and improving retinal blood perfusion and macular microcirculation.[1] However, the comparative responsiveness of OHT vs. POAG to PGAs remains unclarified. Optical coherence tomography angiography (OCTA) offers a non-invasive assessment of macular vascular density (mVD), a potential indicator of ganglion cell function and glaucoma progression.[2,3] Furthermore, mVD correlates with macular ganglion cell complex thickness and mean deviation (MD).[4,5] This study evaluated PGAs treatment efficacy in OHT and early POAG by using OCTA to examine changes in superficial macular vascular parameters. This prospective cohort study enrolled patients with newly diagnosed OHT or early POAG at West China Hospital of Sichuan University between February 2022 and January 2023. This study adhered to the Declaration of Helsinki and received approval from the Biomedical Ethics Review Committee of West China Hospital, Sichuan University (No. 2021-1761), and the Chinese Clinical Trial Registry (ChiCTR2300074942, http://www.chictr.org.cn). All participants provided written informed consent. Diagnostic criteria for OHT and POAG followed established Chinese expert consensus guidelines. Participants presented with abnormal IOP or cup-to-disc ratio detected during physical examination and were not using IOP-lowering medication at the time of enrollment. Inclusion criteria included open anterior chamber angles, elevated IOP, and the presence or absence of specific glaucomatous changes in the optic disc, retinal nerve fiber layer (RNFL), and visual field. Early POAG was defined as an absolute MD of less than 6 decibels (dB) on visual field testing. Participants also needed to use PGAs regularly and attend follow-up visits. Exclusion criteria included age under 18 years old, strabismus, refractive errors, best-corrected visual acuity of below 0.8, high myopia, abnormal axial length, media opacities, history of ocular surgery or trauma, other ocular or systemic diseases, prior use of certain medications (e.g., diuretics, glucocorticoids), inability to perform visual field testing, pregnancy/lactation, and PGA intolerance. Data collected at baseline and 6 months post-PGA treatment included demographic characteristics, central corneal thickness, IOP, vertical cup-to-disc ratio, RNFL thickness, macular vascular parameters obtained via OCTA (Cirrus 5000 HD-OCT with Angioplex™ system [Carl Zeiss Meditec, Dublin, CA, USA]), and visual field obtained via standard automatic perimetry. Both eyes of each participant were examined. The measurements of IOP, RNFL thickness, and macular vascular parameters were kept confidential (blinded). The eye with more pronounced abnormalities in either the IOP or cup-to-disc ratio was selected for analysis. The standard OCTA protocol was followed. The foveal avascular zone (FAZ) area reflected macular blood supply, and the circularity index reflected FAZ shape regularity. Vascular density represented perfused vessel length per unit area, while perfusion density represented the total area of perfused vessels per unit area. PGA choice was individualized; switching to a different PGA was allowed if the initial choice was insufficient for IOP lowering, and there were no pre-determined preferences or biases in the selection process. Statistical analysis used Pearson’s chi-squared test, Shapiro–Wilk test, Student’s t-test, paired t-test, Mann–Whitney U test, and Wilcoxon rank-sum test (α = 0.05). This study examined the impact of a 6-month medical treatment regimen on ocular parameters in newly diagnosed OHT and early POAG. Of the initial 37 OHT patients and 33 POAG patients; 22 OHT patients (8 using latanoprost, 5 using bimatoprost, 6 using travoprost, and 3 using tafluprost) and 18 POAG patients (6 using latanoprost, 4 using bimatoprost, 6 using travoprost, and 2 using tafluprost) completed follow-up, thus, there was no difference in PGA usage between groups (χ2 = 0.20, P = 0.978). Baseline characteristics are detailed in supplementary materials. Significant baseline differences existed between groups [Supplementary Tables 1 and 2, https://links.lww.com/CM9/C358]. The OHT group exhibited superior visual field function than POAG group shown by a higher MD (OHT: mean = −2.41 dB, POAG: mean = −3.67 dB, P = 0.002], lower pattern standard deviation (PSD) (OHT: mean = 1.75 dB, POAG: mean = 2.83 dB, P<0.001), smaller cup-to-disc ratio (OHT: mean = 0.43, POAG: mean = 0.61, P<0.001), and a thicker RNFL (OHT: mean = 93.34 μm, OAG: mean = 86.29 μm, P = 0.004). Furthermore, the OHT group also exhibited higher vascular density and perfusion density than the POAG group in the outer and overall macular regions (both P<0.05). Importantly, baseline IOP (P = 0.138) and central corneal thickness (P = 0.554) were comparable. Both groups showed statistically significant IOP reduction after 6 months of medication (OHT: Before, mean = 26.10 mmHg, After, mean = 18.61 mmHg, P<0.001; POAG: Before, mean = 24.60 mmHg, After, mean = 18.11 mmHg, P = 0.003). The OHT group also showed increased mVD and perfusion density across all macular regions (all P<0.05). FAZ circularity index increased in the OHT group compared with the POAG group (P = 0.010 vs.P = 0.279). No statistically significant changes occurred in cup-to-disc ratio, RNFL thickness, MD, or PSD in the OHT group (all P>0.05) [Supplementary Table 3, https://links.lww.com/CM9/C358]. The POAG group exhibited IOP reduction (P = 0.003) and MD improvement (P = 0.030). Similarly to the OHT group, the POAG group experienced increased macular vascular across all macular regions (all P<0.05). No other significant changes were observed in the POAG group [Supplementary Table 4, https://links.lww.com/CM9/C358]. The only notable difference in the changes of IOP and macular parameters between the groups in post-medication was a statistically significantly greater ratio change in the FAZ circularity index in the OHT group (P = 0.039). Crucially, this difference persisted even after controlling for the influence of age distribution using analysis of covariance. No other significant differences in macular parameter changes were observed [Supplementary Table 5 and Figure 1, https://links.lww.com/CM9/C358].Figure 1: Comparison of the ratio of IOP and macular parameters changes in post-medication between groups. Comparison of the ratio change before and after medication between OHT and early POAG groups in IOP (A), FAZ area (B), FAZ circularity index (C), macular vascular density (D), and macular perfusion density (E). FAZ: Foveal avascular zone; IOP: Intraocular pressure; OHT: Ocular hypertension; POAG: Primary open-angle glaucoma; * P<0.05.This study used OCTA to investigate the effects of PGAs on macular microcirculation in OHT and early POAG. OCTA offers superior retinal blood flow assessment, particularly in early or advanced glaucoma. A 6 mm × 6 mm macular area was analyzed, including FAZ parameters, especially the circularity index. Baseline central corneal thickness and IOP were similar between groups. However, the OHT group exhibited higher mVD and perfusion density, especially in the outer macula, correlating with MD and RNFL thickness, highlighting distinct pathophysiology of OHT and POAG. Six months of PGA treatment significantly reduced IOP in both groups by comparable magnitudes. Both groups showed improved mVD and perfusion density, but only the OHT group showed significant FAZ circularity index improvement, suggesting potential differences in FAZ vascular regulation. The limitations of this study include the small sample size, short follow-up, and use of a non-contact tonometer instead of a Goldmann tonometer, potentially introducing IOP measurement variability due to factors like central corneal thickness and eyeball wall stiffness. Despite these limitations, the study demonstrates the positive effects of PGAs on IOP and macular microcirculation in both OHT and early POAG, revealing subtle differences in responses, particularly regarding FAZ circularity, warranting further investigation. Funding This work was supported by grants from the Natural Science Foundation of China (No. 82070954), the Innovative Spark Grant of Sichuan University (No. 2018SCUH0062), 1·3·5 Project for Disciplines of Excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (No. 2021HXFH057), and the Key Project of the Science and Technology Department in Sichuan province (No. 2023YFS0309). Acknowledgments We thank all the subjects who participated in the study for their cooperation, as well as the glaucoma specialist team and the medical staff of the ophthalmology examination room for their technical support. Conflicts of interest None.