Efficacy and Safety of Rho Kinase Inhibitors vs. Beta-Blockers in Primary Open-Angle Glaucoma: A Systematic Review with Meta-Analysis.

Background: In order to support the positioning of Rho kinase inhibitors (Rhokis) in the European market for the treatment of glaucoma, scientific evidence comparing the efficacy and safety of Rhokis and beta-blockers (ß-ßs) in the treatment of open-angle glaucoma after 3 months was assembled through a systematic review and meta-analysis (meta-A) of randomized controlled trials (RCTs). Methods: Relevant articles were searched for on PubMed, EMBASE, and the Cochrane Library. Of the 251 articles found, three met all eligibility criteria. These three articles were assessed for risk of bias. Data were extracted and a random effects meta-A was performed. The studies' methods were homogeneous but there was great heterogeneity within the data (I2 = 92-93%; p < 0.001). Results: All studies had low risk of bias. The meta-A showed statistically better efficacy of ß-ßs, resulting in an intraocular pressure (IOP) reduction mean difference of 1.73 (1.19-2.27) at 8 a.m., 0.66 (0.19-1.15) at 10 a.m. and 0.49 mmHg (0.001-0.98) at 4 p.m., compared to Rhokis. This difference is not clinically significant as intra-operator variability of IOP measurements varies from ±2 to ±3 mmHg The adverse effects of Rhokis were essentially topical, whereas ß-ßs mainly caused systemic side effects. Conclusions: This Meta-A showed that Rhokis are clinically non-inferior to beta-blockers in reducing IOP. Rhokis have a better safety profile.

Understanding Posterior Staphyloma in Pathologic Myopia: Current Overview, New Input, and Perspectives.

Posterior staphyloma (PS) is considered the hallmark of pathologic myopia and is defined as an outpouching of a circumscribed portion of the eyeball with a radius of curvature smaller than that of the adjacent zone. Although more common in eyes with high myopia, it can affect those without it. The presence of PS is associated with a structurally and functionally worse course of high myopia that can lead to visual disability. Unfortunately, the pathogenesis of PS is unclear so far. Thus, due to the increasing prevalence of myopia which has been further exacerbated by the advent of COVID-19 lockdown, researchers are eager to elucidate the pathogenesis of pathologic myopia and that of its complications, especially PS, which will allow the development of preventive strategies. The aim of this work was to review the morphological characteristics of PS with emphasis on similarities with peripapillary staphyloma and to discuss the pathogenesis of PS considering recent suggestions about that of peripapillary staphyloma.

Peripapillary intrachoroidal cavitation at the crossroads of peripapillary myopic changes.

AIM: To analyze the prevalence of peripapillary intra-choroidal cavitation (PICC) in eyes with gamma peripapillary atrophy (γPPA), in eyes with peripapillary staphyloma (PPS) and in those combining γPPA and PPS and to analyze border tissue discontinuity in PICC. METHODS: This prospective cross-sectional non interventional study included highly myopic eyes. Non-highly myopic eyes were used as control. Radial and linear scans centered on the optic nerve head were performed using spectral-domain optical coherence tomography. Variables were analyzed along the twelve hourly optical coherence tomography sections in both eyes of each subject. RESULTS: A total of 667 eyes of 334 subjects were included: 229 (34.3%) highly myopic eyes and 438 (65.7%) non highly myopic eyes. The mean age of the highly myopic group was 48.99±17.81y. PICC was found in a total of 40 eyes and in 13.2% (29/220) of highly myopic eyes. PICC was found in 10.4% (40/386) of eyes with γPPA, in 20.5% (40/195) of eyes with PPS and in 22.7% (40/176) of those combining γPPA and PPS. All the eyes with PICC showed the co-existence of γPPA and PPS whereas none of the eyes presenting only one of these entities exhibited PICC. A border tissue discontinuity in the γPPA area was found in all eyes with PICC. CONCLUSION: We confirm the presence of a border tissue discontinuity in the γPPA area of all eyes with PICC. These findings suggest the involvement of mechanical factors in the pathogenesis of PICC which may contribute to PICC-related visual field defects.

Myopic (Peri)papillary Changes and Visual Field Defects.

Purpose: Myopic eyes combining gamma peripapillary atrophy and peripapillary staphyloma were sorted according to the presence of intrachoroidal cavitation (PICCs) or its absence (combinations). Visual field defects (VFDs) and factors discriminating these groups were analyzed. Methods: These groups were sorted by optical coherence tomography. VFDs were assessed using the Humphrey® Field Analyzer 3, SITA standard. Ovality index (OI) was the ratio between the shortest and longest diameters of the disc. The proportions of PICCs, lamina cribrosa defects (LCDs) and clusters in each Garway-Heath's sector (A-F) were analyzed. All variables were compared between PICCs and combinations. A multivariate logistic regression analysis was performed ultimately. Results: Of the 93 eyes, we obtained, 20 PICCs and 73 combinations. The prevalence of VFDs and LCDs in PICCs were 65% (13/20) and 30% (6/20), respectively. PICCs 85% (17/20) and LCDs 12% (11/93) predominated in sector B (inferotemporal) and clusters 9.7% (9/93) in the corresponding sector. The proportion of VFDs was significantly higher in PICCs than combinations (p < 0.001). In sector B, the proportion of LCDs was significantly higher in PICCs than combinations (p = 0.011). The mean OI was significantly lower (p < 0.001) in PICCs than combinations. Multivariate logistic regression analysis concluded that mean OI (p < 0.001) was the only statistically significant factor discriminating PICCs and combinations. Conclusion: Mean OI discriminating PICCs from combinations is further evidence of a gradation of structural changes between them. It could be related to the higher proportion of VFDs in PICCs. The predominant distribution of PICCs infero-temporally supports PICC as a cause of uncertainty in glaucoma diagnosis in high myopia. Furthermore, the highest proportion of PICCs and LCDs in this sector highlights its vulnerability to damage in myopic eyes and deserves further investigation as it is also primarily involved in glaucoma.

Peripapillary Intrachoroidal Cavitation.

Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of the retinal pigment epithelium, its intrachoroidal location was later revealed, justifying its current name. PICC is related to other myopic complications such as posterior staphyloma, but its pathogenesis is not clear to date. Although it has been considered a benign condition, most eyes with PICC show visual field defects, which leads to diagnostic uncertainty as these deficits resemble those seen in glaucoma. Furthermore, eyes with PICC may develop macular detachment with retinoschisis. Finally, misdiagnosis of PICC as a metastatic choroidal tumor may lead to unnecessary and anxiety-inducing investigations. Advances in optical coherence tomography (OCT) imaging have improved the visualization of ocular structures, contributing to the understanding of PICC. Recently, high optic nerve sheath traction forces during eye movements in highly myopic eyes have been suggested as promoters of PICC, renewing interest around this condition. However, a review of PICC is still lacking. Therefore, we aimed to provide a concise yet comprehensive overview of the current state of the art, focusing on OCT illustrations, pathophysiology and potential future perspectives based on the biomechanics of the optic nerve.

Visual field defects and retinal nerve fiber layer damage in buried optic disc drusen: a new insight.

AIM: To assess the association between buried optic disc drusen (BODD) location using spectral-domain optical coherence tomography (SD-OCT) and the location of associated visual field defects (VFD) using the Garway-Heath mapping. METHODS: This monocentric retrospective cross-sectional study was led at the authors' institution. Adult patients diagnosed with BODD who had complete records with a reliable Humphrey® 24-2 visual field, macular, and papillary OCT were enrolled. Fisher's exact test was used to measure the association between BODD location and VFD distribution according to Garway-Heath's mapping. RESULTS: Totally 20 eyes of 15 patients were included (60% females). The median age (interquartile range) was 63 (43)y and the median best corrected visual acuity (BCVA) was -0.08 (0.08) log MAR. BODD were mostly located in zones A, E, and F. The minimal rim width (MRW) was globally preserved. The retinal nerve fiber layer (RNFL) was predominantly altered in zones D, E, and F. There was a significant correlation between BODD location and that of RNFL alterations in zones D (P=0.03) and E (P=0.025); Moreover, the presence of BODD in the E zone was significantly related to damaged RNFL in the neighbouring sectors D and F (P=0.012; P=0.02 respectively). Sixty-three percent (12/19) of visual fields were abnormal and there was a significant match (Phi=0.7, P=0.009) between drusen location and VFD only in zone D. CONCLUSION: BODD do not only affect young patients and can be more harmful than usually expected, as we found VFD in 63% of cases. There is a correspondence between BODD location, RNFL damage, and VFD distributions. The presence of BODD induces the overestimation of MRW, thereby disrupting its sensitivity as an early indicator of ganglion fibers damage.

Analysis of Peripapillary Intrachoroidal Cavitation and Myopic Peripapillary Distortions in Polar Regions by Optical Coherence Tomography.

Purpose: To compare the peripapillary polar characteristics in eyes combining peripapillary staphyloma and gamma peripapillary atrophy according to whether peripapillary intrachoroidal cavitation (PICC) was present or absent (combination-group). Patients and methods: This prospective non-interventional cross-sectional study included 667 eyes of 334 subjects. From the polar peripapillary regions to the opening of Bruch's membrane, the following elements and their topographic relationships were analyzed using optical coherence tomography sections: configuration of the posterior curvature of the choroid, visibility of the subarachnoid space (SAS), and suprachoroidal detachment (SCD). Chi-squared and Fisher exact tests were used for statistical analysis. Results: The protrusion of the posterior choroidal wall, with anterior elevation on either side, observed in both groups progressed and transformed into a wedge-shaped deformity on the side of gamma peripapillary atrophy. This wedge configuration was significantly more frequent in PICC-group than in combination-group (p = 0.004 and p < 0.001) for the upper and lower poles, respectively. SAS was more frequently observed in PICC-group than in combination-group (p = 0.002 and p < 0.001) for the upper and lower poles, respectively. SCD was detected exclusively in PICC-group (p < 0.001, both poles). The wedge-shaped configuration and the SCD were aligned antero-posteriorly with the SAS. Conclusion: We confirmed that PICC is an SCD. We observed its constant alignment with the SAS. We suggest that the tensile forces of the optic nerve sheaths during adduction promote the collapse of the scleral flange onto the SAS, leading to PICC. Further studies are warranted to confirm this hypothesis.