Long-term effectiveness and safety of XEN45 in open-angle glaucoma patients.

BACKGROUND: To investigate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with phacoemulsification, in eyes with open-angle glaucoma (OAG). METHODS: Retrospective and single center study conducted on consecutive OAG patients who underwent a XEN45 implant between February-2017 and December-2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values. Surgical success was defined as an IOP-lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 13 mm Hg, without (Complete-success) or with (Qualified-success) antiglaucoma medications. RESULTS: A total of 158 eyes (34 (21.5%) eyes XEN-solo and 124 (78.5%) XEN + Phaco) were included. The median follow-up time was 28.5 months. In the overall study population, the mean preoperative IOP was significantly lowered from 19.4 ± 6.5 mm Hg to 12.4 ± 5.0 mm Hg. The mean preoperative (95% confidence interval) IOP was significantly lowered from 21.3 (19.3-23.2) mm Hg and 18.8 (17.7-20.0) mm Hg to 12.0 (10.4-13.6) mm Hg and 12.5 (11.6-13.5) mm Hg in the XEN-Solo and XEN + Phaco groups, respectively (p < 0.0001 each, respectively). The mean number of ocular-hypotensive medications was significantly reduced in the overall study sample (from 3.4 ± 0.9 to 0.9 ± 1.3, p < 0.0001), XEN-Solo (from 3.5 ± 1.1 to 0.6 ± 1.0, p < 0.0001, and XEN + Phaco (from 3.4 ± 1.1 to 0.9 ± 1.3, p < 0.0001) groups. Eighty-four (53.2%) eyes were categorized as success, with 49 (58.3%) classified as complete success. Eighty-one (51.3%) eyes underwent needling and 15 (9.5%) eyes required an additional surgical procedure. One (0.6%) eye had endophthalmitis. CONCLUSION: XEN implant, either alone or in combination with phacoemulsification significantly lowered IOP and reduced the need of ocular-hypotensive medication, while maintaining a good safety profile.

Hypotony Failure Criteria in Glaucoma Surgical Studies and Their Influence on Surgery Success.

PURPOSE: Review hypotony failure criteria used in glaucoma surgical outcome studies and evaluate their impact on success rates. DESIGN: Systematic literature review and application of hypotony failure criteria to 2 retrospective cohorts. PARTICIPANTS: A total of 934 eyes and 1765 eyes undergoing trabeculectomy and deep sclerectomy (DS) with a median follow-up of 41.4 and 45.4 months, respectively. METHODS: Literature-based hypotony failure criteria were applied to patient cohorts. Intraocular pressure (IOP)-related success was defined as follows: (A) IOP ≤ 21 mmHg with ≥ 20% IOP reduction; (B) IOP ≤ 18 mmHg with ≥ 20% reduction; (C) IOP ≤ 15 mmHg with ≥ 25% reduction; and (D) IOP ≤ 12 mmHg with ≥ 30% reduction. Failure was defined as IOP exceeding these criteria in 2 consecutive visits > 3 months after surgery, loss of light perception, additional IOP-lowering surgery, or hypotony. Cox regression estimated failure risk for different hypotony criteria, using no hypotony as a reference. Analyses were conducted for each criterion and hypotony type (i.e., numerical [IOP threshold], clinical [clinical manifestations], and mixed [combination of numerical or clinical criteria]). MAIN OUTCOME MEASURES: Hazard ratio (HR) for failure risk. RESULTS: Of 2503 studies found, 278 were eligible, with 99 studies (35.6%) lacking hypotony failure criteria. Numerical hypotony was predominant (157 studies [56.5%]). Few studies used clinical hypotony (3 isolated [1.1%]; 19 combined with low IOP [6.8%]). Forty-nine different criteria were found, with IOP < 6 mmHg, IOP < 6 mmHg on ≥ 2 consecutive visits after 3 months, and IOP < 5 mmHg being the most common (41 [14.7%], 38 [13.7%], and 13 [4.7%] studies, respectively). In both cohorts, numerical hypotony posed the highest risk of failure (HR, 1.51-1.21 for criteria A to D; P < 0.001), followed by mixed hypotony (HR, 1.41-1.20 for criteria A to D; P < 0.001), and clinical hypotony (HR, 1.12-1.04; P < 0.001). Failure risk varied greatly with various hypotony definitions, with the HR ranging from 1.02 to 10.79 for trabeculectomy and 1.00 to 8.36 for DS. CONCLUSIONS: Hypotony failure criteria are highly heterogenous in the glaucoma literature, with few studies focusing on clinical manifestations. Numerical hypotony yields higher failure rates than clinical hypotony and can underestimate glaucoma surgery success rates. Standardizing failure criteria with an emphasis on clinically relevant hypotony manifestations is needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk Factors for Failure in Glaucoma Patients Undergoing Microshunt Implantation.

PURPOSE: To evaluate risk factors for failure of Microshunt in glaucoma patients. DESIGN: Multicenter retrospective cohort study. METHODS: The study included 220 eyes from 220 consecutive glaucoma patients undergoing Microshunt implantation at six glaucoma units. Four intraocular pressure (IOP) success criteria were defined: (A) IOP ≤21 mm Hg with ≥20% IOP reduction; (B) IOP ≤18 mm Hg with ≥20% IOP reduction; (C) IOP ≤15 mm Hg with ≥25% IOP reduction; and (D) IOP ≤12 mm Hg with ≥30% IOP reduction from baseline. Kaplan-Meier analysis was used to estimate success rates according to the criteria above, and multivariable Cox models were used to identified risk factors for failure according to criterion A. RESULTS: Success rates varied based on different criteria, ranging from 43.3% to 62.5% (overall success for criteria D and A, respectively) and from 35.3% to 44.4% (complete success for criteria D and A, respectively) at 1-year follow-up. Higher intraoperative MMC concentration was associated with reduced risk of failure to maintain complete (0.4 vs 0.2 mg/mL: hazard ratio [HR] = 0.441, P < .001) and overall (0.4 vs 0.2 mg/mL: HR = 0.360, P = .004) success. For complete success, other risk factors for failure were pseudoexfoliation glaucoma/pigmentary glaucoma (HR = 1.641, P = .004), primary angle closure glaucoma (HR = 1.611, P < .001), and previous non-glaucomatous ocular surgeries (HR = 2.301, P = .002). For overall success, other risk factors for failure were lower preoperative IOP (for 1-mm Hg increase, HR = 0.934, P = .005), higher number of preoperative antiglaucoma agents (HR = 1.626, P < .001), and Microshunt combined with cataract surgery (HR = 1.526, P = .033). CONCLUSIONS: This study identified risk factors for Microshunt failure, highlighting the importance of high intraoperative MMC dose and careful patient selection to optimize surgical success.

Preserflo microshunt implant for the treatment of refractory uveitic glaucoma: 36-month outcomes.

OBJECTIVES: To determine 36-month efficacy and safety outcomes of the PRESERFLO Microshunt implant in the treatment of refractory uveitic glaucoma. METHODS: Consecutive patients with uncontrolled uveitic glaucoma despite maximum medical treatment received PRESERFLO Microshunt implant with mitomycin C (MMC) in a tertiary referral glaucoma practice. Efficacy and safety outcomes data were collected at month 6, 12, 24, and 36, postoperatively. The primary outcome was surgical success, defined as intraocular pressure (IOP) between 5 and 21 mmHg or > 20% reduction from baseline, and absence of criteria for surgical failure. Secondary outcomes were IOP, visual acuity (VA), use of glaucoma medical therapy, surgical complications, rate of reoperation for glaucoma. RESULTS: 21 eyes of 21 patients were included. The mean rate of success was 0.74 (95%CI 0.48-0.88), 0.68 (0.43-0.84), 0.47 (0.25-0.67), and 0.47 (0.25-0.67, at 6, 12, 24, and 36 months postoperatively, respectively. The mean IOP decreased by 30.7% (95% CI 13.7-47.7), 26.5% (95% CI 3.2-49.8), 33.5% (95% CI 21.8-45.3), and 30.1% (95% CI 7.2-52.9) from baseline at postoperative month 6, 12, 24, and 36, respectively (p < 0.001). The mean ± SD number of glaucoma medications decreased from 4.1 ± 0.9 to 0.9 ± 1.2 at the final follow up (p = 0.0005). No sight-threatening complications were reported by 36 months. CONCLUSIONS: Three-year results of the PRESERFLO Microshunt implant demonstrated favourable efficacy and safety profile in the treatment of refractory uveitic glaucoma.

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness Values Using Spectral-Domain and Swept-Source OCT.

Purpose: To compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC). Methods: Cross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves. Results: Both SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities. Conclusions: Thickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects. Translational Relevance: OCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients.

Combining Structural and Vascular Parameters to Discriminate Among Glaucoma Patients, Glaucoma Suspects, and Healthy Subjects.

Purpose: Compare the ability of peripapillary and macular structural parameters, vascular parameters, and their integration to discriminate among glaucoma, suspected glaucoma (GS), and healthy controls (HCs). Methods: In this study, 196 eyes of 119 patients with glaucoma (n = 81), patients with GS (n = 48), and HCs (n = 67) underwent optical coherence tomography (OCT) and OCT angiography to measure peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell-inner plexiform layer (mGCIPL) thicknesses, radial peripapillary capillary perfusion density (RPC-PD), and macular GCIPL perfusion density (GCIPL-PD). Parameters were integrated regionally with logistic regression and globally with machine learning algorithms. Diagnostic performances were evaluated with area under the receiver operating characteristic (AUROC) curves. Results: Patients with glaucoma had mild to moderate damage (median, -3.3 dB; interquartile range, -6.5 to -1.4). In discriminating between patients with glaucoma and the HCs, pRNFL thickness had higher AUROC curve values than RPC-PD for average (0.87 vs. 0.62; P < 0.001), superior (0.86 vs. 0.54; P < 0.001), inferior (0.90 vs. 0.71; P < 0.001), and temporal (0.65 vs. 0.51; P = 0.02) quadrants. mGCIPL thickness had higher AUROC curve values than GCIPL-PD for average (0.84 vs. 0.68; P < 0.001), superotemporal (0.76 vs. 0.65; P = 0.016), superior (0.72 vs. 0.57; P = 0.004), superonasal (0.70 vs. 0.56; P = 0.01), inferotemporal (0.90 vs. 0.72; P < 0.001), inferior (0.87 vs. 0.69; P < 0.001), and inferonasal (0.78 vs. 0.65, P = 0.012) sectors. All structural multisector indices had higher diagnostic ability than vascular ones (P < 0.001). Combined structural-vascular indices did not outperform structural indices. Similar results were found to discriminate glaucoma from GS. Conclusions: Combining structural and vascular parameters in a structural-vascular index does not improve diagnostic ability over structural parameters alone. Translational Relevance: OCT angiography does not add additional benefit to structural OCT in early to moderate glaucoma diagnosis.

Epidemiology of Corneal Neovascularization and Its Impact on Visual Acuity and Sensitivity: A 14-Year Retrospective Study.

Purpose: To quantify the severity and location of corneal neovascularization (cNV) and its impact on the visual acuity and corneal sensitivity in a cohort of the patients referred to a specialist cornea clinic and also to describe the etiology of cNV in the cohort. Methods: We retrospectively evaluated the charts of 13,493 subjects referred to the San Raffaele Cornea Unit between January 2004 and December 2018 to search for cNV diagnosis. The corneal neovascularization severity was measured in the quadrants (range: 1-4) and location was defined as superficial, deep, or both. Best spectacle corrected visual acuity (BSCVA) was measured in logMar. We used the multiple regression analysis to identify the independent predictors of logMAR, after adjusting for age, gender, keratoconus, herpes keratitis, penetrating keratoplasty, trauma, and cataract surgery. Results: Corneal neovascularization was diagnosed in 10.4% of the patients analyzed. The most prevalent etiology of cNV in our population was non-infectious corneal dystrophies/degenerations followed by herpes simplex virus infection. cNV affected OD, OS, or both eyes in 35.6, 40.2, and 24.2 of cases, respectively. Mean BSCVA (SD) was 0.59 (0.76), 0.74 (0.94), and 1.24 (1.08) in cNV one, two, and three or four of the quadrant groups. Superficial, deep, or mixed cNV occurred in 1,029, 348, and 205 eyes. Severe cNV (three or four of the quadrants) was a significant predictor of low visual acuity (p < 0.001) and reduced corneal sensitivity (p < 0.05). cNV location and its severity were associated (p < 0.05). In addition, corneal anesthesia was associated with lower BSCVA (p < 0.001). Conclusion: Severe and deep cNV are associated with the reduced visual acuity and corneal sensitivity. Our data strongly support the relevance of appropriate follow-up as cNV is a major risk factor for graft rejection.

The Use of Anterior-Segment Optical-Coherence Tomography for the Assessment of the Iridocorneal Angle and Its Alterations: Update and Current Evidence.

The introduction of anterior-segment optical-coherence tomography (AS-OCT) has led to improved assessments of the anatomy of the iridocorneal-angle and diagnoses of several mechanisms of angle closure which often result in raised intraocular pressure (IOP). Continuous advancements in AS-OCT technology and software, along with an extensive research in the field, have resulted in a wide range of possible parameters that may be used to diagnose and follow up on patients with this spectrum of diseases. However, the clinical relevance of such variables needs to be explored thoroughly. The aim of the present review is to summarize the current evidence supporting the use of AS-OCT for the diagnosis and follow-up of several iridocorneal-angle and anterior-chamber alterations, focusing on the advantages and downsides of this technology.

Treatment Outcomes Using the PAUL Glaucoma Implant to Control Intraocular Pressure in Eyes with Refractory Glaucoma.

PURPOSE: To investigate efficacy 1 year after implantation of a novel glaucoma tube shunt, the PAUL Glaucoma Implant (PGI; Advanced Ophthalmic Innovations, Singapore, Republic of Singapore), in the treatment of eyes with refractory glaucoma. DESIGN: Clinical trial. PARTICIPANTS: Glaucoma patients who are recalcitrant to maximum tolerated medical therapy and require tube shunt surgery. METHODS: Interventional cohort study involving consecutive PGIs implanted at 6 international centers between December 1, 2017, and December 1, 2018. All the participants were followed up for 1 year after surgery. MAIN OUTCOME MEASURES: The primary outcome measure was failure, defined prospectively as intraocular pressure (IOP) of more than 21 mmHg or less than 20% reduction from the preoperative baseline on 2 consecutive visits, 3 months or more after surgery; persistent late hypotony, defined as IOP of less than 6 mmHg on 2 consecutive visits after 3 months; additional glaucoma surgery; loss of light perception vision; or removal of the implant for any reason. RESULTS: Of 82 patients enrolled, 74 (74 eyes) completed 12 months of follow-up. The mean age ± standard deviation at enrollment was 62.3±14.7 years, 73.0% were men, and 36.5% had secondary glaucoma. One year after surgery, 4 patients (5.4%) fulfilled the surgical criteria for failure, 68.9% (51/74 eyes) were deemed complete successes, and 93.2% (69/74 eyes) were considered qualified successes. Compared with the medicated preoperative IOP (23.1±8.2 mmHg), the postoperative IOPs at 6 and 12 months were 13.8±4.0 mmHg and 13.2±3.3 mmHg, respectively (P < 0.001). The mean number of IOP-lowering drugs used before surgery and after 12 months of follow-up were 3.3±0.9 and 0.3±0.6, respectively (P < 0.001). Significant postoperative complications included self-limiting shallow anterior chamber (n = 11; 14.9%), hypotony requiring intervention (n = 7; 9.5%), tube shunt occlusion (n = 5; 6.8%), tube exposure (n = 3; 4.1%), and endophthalmitis with resultant loss of vision (n = 1; 1.4%). CONCLUSIONS: The PGI demonstrated comparable efficacy with other currently available implants, with almost three quarters of the enrolled patients with refractory glaucoma achieving complete surgical success after 1 year of follow-up.

Intravitreal Dexamethasone Implant as a Sustained Release Drug Delivery Device for the Treatment of Ocular Diseases: A Comprehensive Review of the Literature.

Drug delivery into the vitreous chamber remains a great challenge in the pharmaceutical industry due to the complex anatomy and physiology of the eye. Intravitreal injection is the mainstream route of drug administration to the posterior segment of the eye. The purpose of this review is to assess the current literature about the widening use of the intravitreal 0.7 mg dexamethasone (Dex) implant, and to provide a comprehensive collection of all the ocular disorders that benefit from Dex administration. Although anti-vascular endothelial growth-factors (VEGFs) have been largely indicated as a first-choice level, the Dex implant represents an important treatment option, especially in selected cases, such as vitrectomized eyes or patients in whom anti-VEGF failed or are contraindicated. In this article, the safety profile as well as the list of the possible complications related to intravitreal Dex injection are also discussed.

Separation and thickness measurements of superficial and deep slabs of the retinal nerve fiber layer in healthy and glaucomatous eyes.

Purpose: Describe a new method to analyze retinal nerve fiber layer (RNFL) thickness maps. Design: Cross-sectional study. Subjects: RNFL thickness maps of healthy and glaucomatous eyes. Methods: Optical coherence tomography (OCT) RNFL raster scans from 98 healthy and 50 glaucomatous eyes were analyzed. The RNFL thickness maps were separated into superficial (SNFL) and deep (DNFL) slabs through a partial thickness plane set at the modal thickness (mode). Association between mode and OCT signal strength (SS), age, axial length, and visual field mean deviation (VFMD) was tested (Pearson coefficient, r). Thicknesses of inferior and superior SNFL regions (i-,s-SNFL), and inferior, superior, nasal, and temporal DNFL regions (i-,s-,n-,t-DNFL) were calculated. The regions thicknesses were compared between healthy and glaucomatous eyes (t-test) and between glaucomatous eyes with early, moderate, and severe disease (ANOVA and linear regressions of thickness on VFMD). Diagnostic accuracy and correlation with VFMD of RNFL regions thicknesses were calculated as the area under the receiver operating characteristic curve (AUC) and Pearson r, respectively. P<0.05 was considered significant. Main outcome: Thickness of regions in SNFL and DNFL slabs. Results: The mode was not associated with SS, age, axial length, or VFMD, it circumscribed the thicker RNFL around the optic disc of healthy and glaucomatous eyes, and it was used to separate the SNFL and DNFL slabs of RNFL thickness maps. The thickness of the SNFL slab was less in glaucomatous eyes than in healthy eyes (P<0.001). S-SNFL and i-SNFL thicknesses (respectively) were 86.0±8.2µm and 87.3±9.6µm in healthy eyes vs. 66.1±9.1µm and 63.4±8.2µm in glaucomatous eyes (P<0.001 for both). The thickness of the DNFL slab was similar between groups (P=0.19). T-DNFL thickness was 37.0±5.3µm in healthy eyes vs. 33.9±5.0µm in glaucomatous eyes (P<0.001); thicknesses of all other DNFL regions were similar. The SNFL regions only thinned with progressively worse glaucoma severity, had excellent AUCs (AUC≥0.95, P<0.001), and correlated strongly with VFMD (r≥0.60, P<0.001). Conclusions: Glaucomatous RNFL thinning is predominantly detected within a slab with thickness greater than the mode. SNFL thickness has great AUC and correlation with VFMD in glaucomatous eyes. The usefulness for diagnosis and monitoring of glaucoma needs further study.

Optical Coherence Tomography Angiography in Neurodegenerative Disorders.

Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered an accessible 'window' to detect the microvascular damage occurring in the setting of neurodegenerative disorders. Optical coherence tomography angiography (OCT-A) is a non-invasive imaging modality providing depth resolved images of blood flow in the retina, choroid, and optic nerve. In this review, we summarize the current literature on the application of OCT-A in glaucoma and central nervous system conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Future directions aiming at evaluating whether OCT-A can be an additional biomarker for the early diagnosis and monitoring of neurodegenerative disorders are also discussed.

Long-term PERG monitoring of untreated and treated glaucoma suspects.

PURPOSE: To investigate long-term structural and functional progression of untreated and treated glaucoma suspects (UGS and TGS). METHODS: Retrospective analysis of serial steady-state pattern electroretinogram (PERG), mean retinal nerve fiber layer thickness (RNFLT), and standard automated perimetry mean deviation (SAP-MD) in UGS (N = 20) and TGS (N = 18). Outcome measures were the rates of change (linear regression slopes) of PERG amplitude, PERG phase, mean RNFLT, and SAP-MD over 9.8 ± 1.3 years (15.6 ± 4.2 visits). RESULTS: The number of patients with significant (P < 0.05) progression slopes for PERG amplitude, PERG phase, RNFLT, and SAP-MD was, respectively, UGS: 5, 0, 4, 2; TGS: 8, 2, 6, 5. In UGS, outcome measures were not correlated with each other. In TGS, both PERG amplitude and RNFLT were significantly (P < 0.05) correlated with SAP-MD (R ≥ 0.58), while PERG amplitude and RNFLT were not correlated with each other (R = 0.43, P = 0.064). The rate of change of SAP-MD was predicted (P < 0.05) by a linear combination of RNFLT slope and PERG amplitude slope. CONCLUSIONS: Results substantiate and extend previous results showing that steady-state PERG amplitude progressively decreased over time in a proportion of glaucoma suspects, with relatively steeper slope in TGS compared to UGS. RNFLT progression also had a steeper slope in TGS compared to UGS; however, progressions of PERG amplitude and RNFLT were not significantly correlated. Both PERG progression and RNFLT progression independently contribute to prediction of visual field progression.

Choroidal Vascularity Index: An In-Depth Analysis of This Novel Optical Coherence Tomography Parameter.

Remarkable improvements in optical coherence tomography (OCT) technology have resulted in highly sophisticated, noninvasive machines allowing detailed and advanced morphological evaluation of all retinal and choroidal layers. Postproduction semiautomated imaging analysis with dedicated public-domain software allows precise quantitative analysis of binarized OCT images. In this regard, the choroidal vascularity index (CVI) is emerging as a new imaging tool for the measurement and analysis of the choroidal vascular system by quantifying both luminal and stromal choroidal components. Numerous reports have been published so far regarding CVI and its potential applications in healthy eyes as well as in the evaluation and management of several chorioretinal diseases. Current literature suggests that CVI has a lesser variability and is influenced by fewer physiologic factors as compared to choroidal thickness. It can be considered a relatively stable parameter for evaluating the changes in the choroidal vasculature. In this review, the principles and the applications of this advanced imaging modality for studying and understanding the contributing role of choroid in retinal and optic nerve diseases are discussed. Potential advances that may allow the widespread adoption of this tool in the routine clinical practice are also presented.

Optical coherence tomography and optical coherence tomography angiography in glaucoma: diagnosis, progression, and correlation with functional tests.

The present review will summarize the most updated findings with regards to optical coherence tomography and optical coherence tomography angiography in glaucoma, highlighting their clinical use for detection and monitoring of the disease, and their correlation to functional tests (such as visual field) widely employed in the asset of modern glaucoma clinics.

Comparison of methods to quantify macular and peripapillary vessel density in optical coherence tomography angiography.

PURPOSE: To compare macular and peripapillary vessel density values calculated on optical coherence tomography angiography (OCT-A) images with different algorithms, elaborate conversion formula, and compare the ability to discriminate healthy from affected eyes. METHODS: Cross-sectional study of healthy subjects, patients with diabetic retinopathy, and glaucoma patients (44 eyes in each group). Vessel density in the macular superficial capillary plexus (SCP), deep capillary plexus (DCP), and the peripapillary radial capillary plexus (RCP) were calculated with seven previously published algorithms. Systemic differences, diagnostic properties, reliability, and agreement of the methods were investigated. RESULTS: Healthy eyes exhibited higher vessel density values in all plexuses compared to diseased eyes regardless of the algorithm used (p<0.01). The estimated vessel densities were significantly different at all the plexuses (p<0.0001) as a function of method used. Inter-method reliability and agreement was mostly poor to moderate. A conversion formula was available for every method, except for the conversion between multilevel and fixed at the DCP. Substantial systemic, non-constant biases were evident between many algorithms. No algorithm outperformed the others for discrimination of patients from healthy subjects in all the retinal plexuses, but the best performing algorithm varied with the selected plexus. CONCLUSIONS: Absolute vessel density values calculated with different algorithms are not directly interchangeable. Differences between healthy and affected eyes could be appreciated with all methods with different discriminatory abilities as a function of the plexus analyzed. Longitudinal monitoring of vessel density should be performed with the same algorithm. Studies adopting vessel density as an outcome measure should not rely on external normative databases.

Topographic Macular Microvascular Changes and Correlation With Visual Loss in Chronic Leber Hereditary Optic Neuropathy.

PURPOSE: To study the macular microvascular networks in patients affected by chronic Leber hereditary optic neuropathy (LHON) using optical coherence tomography angiography (OCTA), and to quantify these changes in different macular sectors. DESIGN: Prospective cross-sectional study. METHODS: Patients with a clinical and molecularly confirmed diagnosis of LHON (affected patients in the chronic stage) were enrolled from the neuro-ophthalmology clinic at the Doheny-UCLA. Patients and controls underwent a complete ophthalmologic evaluation, including imaging with OCTA. RESULTS: Twenty-nine eyes from 15 LHON patients (14 male) and 20 eyes from 20 healthy subjects (13 male) were included in the analysis. Mean age was 32.0 ± 14.2 years (range 16-49 years) in the LHON group and 34.2 ± 10.1 years (range 23-48 years) in the control group (P = .552). In the parafoveal region, the vessel length density was lower in LHON patients, at both the SCP (9.1% ± 0.5% and 9.3% ± 0.4%, P = .041) and DCP (9.4% ± 0.5% and 9.8% ± 0.3%, P = .008) levels. In the sectorial analysis, vascular changes remained significant only in the parafoveal nasal and inferior regions. Univariate linear regression analysis demonstrated that the strongest associations with visual acuity were with parafoveal SCP perfusion density (R2 = .276, P = .045) and parafoveal SCP vessel length density (R2 = .277, P = .044). CONCLUSIONS: LHON eyes have SCP and DCP changes that are mainly confined to the nasal and inferior parafoveal sectors that correspond to the papillomacular bundle. Furthermore, visual loss is associated with the SCP flow impairment, but not with the OCT-detectable structural damage.

Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker.

IMPORTANCE: The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. BACKGROUND: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. DESIGN: Prospective, cross-sectional, multicenter, observational study. PARTICIPANTS: Twenty-two LHON patients divided in four groups: unaffected mutation carriers (LHON-u); early sub-acute stage (LHON-e); late sub-acute stage (LHON-l); chronic stage (LHON-ch). METHODS: OCT-A scans centred on the optic disc were obtained by spectral domain OCT system. MAIN OUTCOME MEASURES: VD, retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were compared between groups. RESULTS: Significant VD changes were detected in every sector (P < 0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. CONCLUSIONS AND RELEVANCE: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology.