Focal Lamina Cribrosa Defects Research Articles

Multimodal imaging of optic nerve head abnormalities in high myopia.

Highly myopic optic nerve head (ONH) abnormalities encompass a series of complications resulting from the stretching of papillary and peripapillary structures during significant axial elongation. The morphological changes in the ONH typically initiate with disk tilting or rotation, progressing to PHOMS and PPA. Tissue defects in each layer manifest as focal lamina cribrosa defects (FLDs), peripapillary intrachoroidal cavitations (PICCs), and acquired pits of the optic nerve (APON). Anterior vitreous/vascular traction and posterior scleral protrusion may lead to prelaminar schisis as well as paravascular cysts and holes, which can potentially develop into retinoschisis. Traditional color fundus photography (CFP) is often insufficient for visualizing most of these lesions, yet their description and quantification benefit significantly from the advancements in optical coherence tomography (OCT) and OCT angiography (OCTA), complemented by fundus autofluorescence (FAF), indocyanine green angiography (ICGA), and three-dimensional imaging. The effective diagnosis and classification of ONH abnormalities heavily rely on a comprehensive understanding of their multimodal imaging features, as outlined in this review. These findings provide valuable insights into optic neuropathy in high myopia, establishing a solid foundation for future endeavors in disease monitoring and treatment guidance.

Optic Disc Microvasculature Dropout in Pre-perimetric Glaucoma.

To investigate factors associated with optic disc microvasculature dropout (MvD-D) in pre-perimetric primary open-angle glaucoma (PPG) patients. 139 eyes of PPG patients were categorized according to the presence of MvD-D with optical coherence tomography angiography (OCTA). Factors including visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, focal lamina cribrosa (LC) defect, optic disc hemorrhage (DH), and parapapillary deep-layer microvasculature dropout (MvD-P) were compared between eyes with and without MvD-D. MvD-D was observed in 69 PPG eyes (49.6%). Compared with eyes without MvD-D, the ones with MvD-D had a significantly thinner RNFL in all areas except the nasal sector, worse VF MD, and a focal LC defect and MvD-P (P<0.05): male gender also was more highly prevalent. A considerable number of eyes with MvD-D lacked focal LC defect (62.3% (43/69)) or MvD-P (71.0% (49/69)), while a few eyes without MvD-D had focal LC defect (10.0% (7/70)) or MvD-P (2.9% (2/70)). In a multivariable logistic regression analysis, male gender (odds ratio [OR], 3.96; P<0.001), worse VF MD (OR, 1.44; P=0.019), thinner global RNFL (OR, 1.13; P<0.001), higher prevalence of focal LC defect (OR, 3.71; P=0.014) and MvD-P (OR, 7.85; P<0.001) were significantly associated with MvD-D. MvD-D was related to worse disease severity in PPG patients, and often was not accompanied by focal LC defect or MvD-P. This suggests that impaired optic disc circulation can be an early sign of glaucoma without noticeable changes in functional or structural features (i.e., VF, focal LC defect, MvD-P).

Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma

We investigated optic nerve head factors associated with initial parafoveal scotoma (IPFS) in primary open-angle glaucoma. Eighty (80) patients with an IPFS and 84 patients with an initial nasal step (INS) were compared. Central retinal vascular trunk (CRVT) deviation from the Bruch’s membrane opening (BMO) center was measured as a surrogate of lamina cribrosa (LC)/BMO offset, and its obliqueness was defined as the absolute value of angular deviation from the fovea-BMO axis. Proximity of retinal nerve fiber layer defect (RNFLD) was defined as the angular deviation of the inner RNFLD margin from the fovea-BMO axis. Microvasculature dropout (MvD) was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Factors associated with IPFS, as compared with INS, were assessed using logistic regression analyses and conditional inference tree analysis. The IPFS group had more oblique CRVT offset (P < 0.001), RNFLD closer to the fovea (P < 0.001), more MvD (P < 0.001), and more LC defects (P < 0.001) compared to the INS group. In logistic regression analyses, obliqueness of CRVT offset (P = 0.002), RNFLD proximity (P < 0.001), and MvD (P = 0.001) were significant factors influencing the presence of IPFS. Conditional inference tree analysis showed that RNFLD closer to the fovea (P < 0.001) in the upper level, more oblique CRVT offset (P = 0.013) and presence of MvD (P = 0.001) in the lower level were associated with the probability of having IPFS. IPFS was associated with closer RNFLD location to the fovea when assessed from the BMO. Oblique LC/BMO offset may not only mask RNFLD proximity to the fovea due to a deviated funduscopic disc appearance, but also potentiate IPFS via focal LC defect and MvD.

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature

PurposeTo describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments.MethodsRetrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO).ResultsTen eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 μm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results.ConclusionsMultimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

Characteristics of the Optic Nerve Head in Myopic Eyes Using Swept-Source Optical Coherence Tomography.

PurposeTo investigate the characteristics of the optic nerve head (ONH) in myopia using swept-source optical coherence tomography (SS-OCT).MethodsParticipants were divided into three groups according to the axial length (AL). The optic disc morphology, retinal nerve fiber layer (RNFL) thickness, and radial peripapillary capillary (RPC) vessel density (VD), optic disc tilt, rotation, Bruch's membrane opening distance (BMOD), border length (BL), border tissue angle, focal lamina cribrosa (LC) defects, β- and γ-zone peripapillary atrophy (PPA), microvasculature dropout (MvD), choroidal thickness (CT), and the choroidal vascularity index (CVI) were compared. Linear regression analysis evaluated relationships between spherical equivalent, AL, and ONH parameters.ResultsOne hundred five, 98, and 118 eyes were included in groups 1, 2, and 3, respectively. With AL increasing, the mean, superior and temporal CT, central mean and temporal, pericentral mean, inferior and nasal RPC VD, and temporal CVI decreased, whereas the mean and temporal RNFL thickness, optic disc, RIM and β-PPA area, presence and area of γ-PPA, BMOD and BL increased. Compared to other groups, group 3 depicted a larger cup area, more focal LC defect and total and juxtapapillary MvD; a lower central superior, inferior and nasal, pericentral superior, and temporal RPC VD. Group 1 demonstrated more tilted disc, larger inferior and nasal CT, mean, superior, inferior, and nasal CVI.ConclusionsMyopia eyes have larger ONH changes, PPAs, regional RNFL, and MvD, but smaller regional CTs, RPC VD, and CVIs. SS-OCT may be useful in detecting ONH variations during myopia.

Association between peripheral visual field defects and focal lamina cribrosa defects in highly myopic eyes.

We aimed to identify peripheral visual field (VF) defect pathogenesis in high myopia using optical coherence tomography (OCT) and microperimetry and to investigate the association between focal lamina cribrosa defects (fLCDs) and high myopia-specific peripheral visual field defects (HM-pVFDs). Retrospective case-control study. Thirty-five highly myopic patients (refractive error ≥ 8.0 D or axial length > 26.5mm) with an HM-pVFD, diagnosed using the V-4 isopter in Goldmann perimetry, and 35 age- and 35 sex-matched controls were studied. The optic nerve head (ONH) morphology was analyzed by use of OCT; retinal light sensitivities around the ONH were evaluated by use of microperimetry. The main outcome measures were best-corrected visual acuity (BCVA), axial length (AL), refractive error, intraocular pressure (IOP), the OCT findings, and the microperimetry findings. The BCVA, AL, IOP, and refractive error did not differ significantly between the patient and the control groups. Of the 35 eyes with an HM-pVFD, twenty-four had fLCDs detected by use of OCT, one showed no evidence of fLCDs, and ten had inadequate images due to excessive ONH tilting. Of the 35 control eyes, two had fLCDs, twenty-eight showed no evidence of fLCDs, and five had inadequate images. The peripapillary retinal light sensitivity was decreased in 29 of the 35 eyes with an HM-pVFD; no such decrease was noted in 30 of the 35 control eyes. Peripheral VF abnormality detection by use of microperimetry had 82.9% sensitivity and 85.7% specificity. Our findings indicate an important relationship between HM-pVFDs and fLCDs, suggesting fLCD involvement in peripheral VF abnormality pathogenesis in highly myopic patients. Furthermore, microperimetry is reproducible for evaluating HM-pVFDs.

Prevalence of focal lamina cribrosa defects in eyes with pachychoroid disease spectrum.

To determine the prevalence of focal lamina cribrosa (LC) defect among patients with pachychoroid disease spectrum (PDS) in the absence of peripapillary retinoschisis. This retrospective, cross-sectional study comprised of 180 patients with PDS, including polypoidal choroidal vasculopathy (PCV), central serous chorioretinopathy, and pachychoroidal neovasculopathy. Medical records and optic nerve head evaluations conducted using spectral-domain optical coherence tomography with enhanced depth imaging were reviewed. As a control group, 236 patients who underwent ophthalmologic evaluation for vitreous floaters, without obvious ocular disease, were also included. The mean age of the PDS group, which included 118 male patients (65.6%), was 57.4±11.1y. There was no significant difference between the two groups in age (P=0.710) or sex (P=0.248). Six patients (3.3%) in the PDS group and none in the control group showed focal LC defect (P=0.318). Among the six patients with focal LC defect in the PDS group, four eyes had PCV, one eye was the fellow eye of a PCV eye, and one eye had pachychoroidal neovasculopathy. Focal LC defect can be defected in patients with PDS in the absence of peripapillary retinoschisis. However, the prevalence of focal LC defect was not different significantly between PDS patients and those who did not have PDS.

Effects of Beta-zone Peripapillary Atrophy and Focal Lamina Cribrosa Defects on Peripapillary Vessel Parameters in Young Myopic Eyes.

The development of beta-zone peripapillary atrophy (β-PPA) and focal lamina cribrosa defect (FLD) was significantly associated with decreased peripapillary optical coherence tomography angiography (OCTA) vessel parameters in young myopic eyes. The purpose of this study was to investigate whether β-PPA and FLD affect peripapillary vessel density (VD) or perfusion density (PD) from OCTA in young myopic eyes. In a cross-sectional study, 330 eyes of 165 healthy volunteers with myopia were involved. Eyes underwent OCTA to measure peripapillary PD and VD. Eyes were grouped according to the presence of β-PPA or FLD: eyes without β-PPA or FLD (group A), eyes with β-PPA but without FLD (group B), and eyes with both β-PPA and FLD (group C). PD and VD were compared among 3 groups, and linear mixed-effect regression model was used to investigate the determinants of PD. β-PPA was found in 219 eyes (66.4%), and FLD was detected in 27 eyes (8.2%). The average VD and PD were greatest in group A (19.13±2.04 mm-1 and 0.375±0.038), followed by group B (18.34±2.26 mm-1 and 0.363±0.042) and group C (16.71±2.81 mm-1 and 0.330±0.052) (P<0.001). The linear mixed-effect model demonstrated that presence of FLD (P=0.001) or β-PPA (P<0.001), FLD count (P=0.004), and maximal β-PPA width (P<0.001) were significantly associated with average PD after controlling for multiple confounding factors. Development of β-PPA and FLD, which is closely related with axial elongation in myopic eyes, was significantly associated with reduced OCTA vessel parameters in young myopic eyes. OCTA may help to detect vascular changes and assess glaucoma risk in these eyes.

Intereye Comparison of Focal Lamina Cribrosa Defect in Normal-Tension Glaucoma Patients with Asymmetric Visual Field Loss

Introduction: To evaluate the association of focal lamina cribrosa (LC) defect with asymmetric visual field (VF) loss in normal-tension glaucoma (NTG) through intereye comparisons. Methods: Paired eyes were divided into better and worse eyes according to the mean deviation (MD), and ocular parameters were compared between them. Furthermore, patients in the asymmetric group were classified as subgroup A (one eye with LC defect and the fellow one without), subgroup B (both eyes without LC defect), and subgroup C (both eyes with LC defect). Generalized estimation equation approach was used to evaluate the association between ocular parameters and asymmetric VF. Results: A total of 140 eyes of 70 NTG patients were included in the asymmetric group. LC defects were more common in better eyes than that in worse eyes (27/70 [38.57%] vs. 10/70 [14.29%], p = 0.001), and all eyes with LC defect had myopia. Multivariate analysis revealed that the presence of LC defect was significantly associated with better eyes in the asymmetric group (odds ratio, 0.27; p = 0.001). For subgroup A, eyes with LC defects exhibited lower peak IOP (p = 0.011) and lower mean IOP (p = 0.018) than the fellow eyes without. In addition, longer AL (p = 0.025) and larger tilt ratio (p = 0.032) were found in eyes with LC defects. For subgroup B without LC defects, larger tilt ratio was shown to be a risk factor for VF loss (odds ratio, 6.13; p = 0.001). There was no significant difference of binocular parameters except for MD (p < 0.001) in subgroup C. Conclusions: LC defects in myopia were suggested to be associated with better eyes in NTG with asymmetric VF loss. However, in patients without LC defect, larger tilt ratio was a risk factor for VF defect. There might be different pathological mechanisms in asymmetric VF loss for different NTG subtypes.

Focal lamina cribrosa defects are not associated with steep lamina cribrosa curvature but with choroidal microvascular dropout

Focal lamina cribrosa (LC) defects have been found to play an important role in the development and progression of glaucomatous optic neuropathy. However, the mechanism of generation of focal LC defects is largely unknown. This cross-sectional study was performed to investigate LC curvature and the frequency of parapapillary choroidal microvascular dropout (MvD) in glaucomatous eyes with focal LC defects. This study was conducted by a retrospective review of patients with primary open-angle glaucoma (POAG) included in an ongoing prospective study being performed at the Seoul National University Bundang Hospital (Investigating Glaucoma Progression Study). A total of 118 eyes of 118 patients with POAG, 59 with and 59 without focal LC defects, with eyes matched by age, axial length, and severity of visual field (VF) damage were included. Posterior LC bowing was assessed by calculating LC curvature index (LCCI), as the inflection of a curve representing a section of the LC, on the optic nerve head images obtained by enhanced-depth-imaging (EDI) spectral-domain optical coherence tomography (OCT). MvD was detected by OCT angiography. LCCI and MvD frequency were compared between eyes with and without focal LC defects. Mean LCCI was significantly smaller than in eyes with than without focal LC defects (9.75 ± 1.29 vs. 11.25 ± 1.39, P < 0.001). MvD was significantly more frequent in eyes with than without focal LC defects (84.7% vs. 49.2%, P < 0.001). MvD in eyes with focal LC defects showed a strong topographic correlation with the focal LC defects. These findings suggest that focal LC defects may primarily result from vascular factors rather than from mechanical strain.

Characteristics of Focal Gamma Zone Parapapillary Atrophy.

PurposeThe purpose of this study was to investigate the characteristics of focal γ-zone parapapillary atrophy (focal γPPA) in patients with primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT).MethodsThree groups of POAG eyes (n = 214) were defined according to the circumferential extent of Bruch's membrane (BM) within the β-zone PPA, as follows: (1) no γPPA (intact BM; n = 81), (2) conventional γPPA (γPPA involving the fovea-BM-opening axis; n = 89), and (3) focal γPPA (γPPA not involving the fovea-BM-opening axis; n = 44). Clinical and ocular characteristics, including age, axial length (AXL), and focal lamina cribrosa (LC) defects were compared among the three groups.ResultsThe focal γPPA group was significantly older (60.6 ± 11.0 years) and had shorter AXL (24.10 ± 1.34 mm) than those of the conventional γPPA group (46.2 ± 13.8 years and 26.53 ± 1.61 mm, respectively; P < 0.001). These values of the focal γPPA group were similar to those of the no γPPA group (23.73 ± 0.97 mm for AXL and 64.0 ± 13.0 years for age). The focal γPPA group had a significantly higher prevalence of focal LC defects than did the other two groups (70.5% [31/44] for the focal γPPA group versus 46.1% [41/89] for the conventional γPPA group versus 37.0% [30/81] for the no γPPA group; P = 0.002).ConclusionsFocal γPPA was differentiated from conventional γPPA by older age and shorter AXL. Further, focal γPPA was frequently accompanied by focal LC defects. Longitudinal studies elucidating whether focal LC defects and focal γPPA share common pathogenesis are warranted.

Focal lamina cribrosa defects and significant peripapillary choroidal thinning in patients with unilateral branch retinal vein occlusion.

To investigate the prevalence of focal lamina cribrosa (LC) defects in patients with unilateral branch retinal vein occlusion (BRVO) and to compare ocular characteristics between eyes with and without focal LC defect and those eyes with normal-tension glaucoma (NTG). This retrospective, cross-sectional study included 121 patients. Thirty-nine patients had unilateral BRVO (BRVO group), 36 patients had NTG (NTG group), and 36 patients had vitreous floaters, but no other ocular diseases (control group). In addition to baseline characteristics such as age, sex, refractive errors, the ocular characteristics such as peripapillary choroidal thickness (PCT), retinal nerve fiber layer thickness, and subfoveal choroidal thickness were retrospectively analyzed. Focal LC defects were detected in 20 eyes of 14 patients (38.9%) in the BRVO group, 24 eyes of 15 patients (41.7%) in the NTG group, and none in the control group (P<0.001). In the BRVO-affected eyes, the mean PCT was 102.7±31.1 μm in the eyes with focal LC defects, and 163.1±70.1 μm in the eyes without LC defects (P = 0.009). In the BRVO-affected eyes, the mean PCT was 102.7±31.1 μm in the eyes with focal LC defects, and 163.1±70.1 μm in the eyes without LC defects (P = 0.009). In the NTG group, the mean PCT was 133.1±48.9 μm in the eyes with focal LC defects and 170.8±81.9 μm in those without (P = 0.042). The other baseline and ocular characteristics were not significantly different between the eyes with and without focal LC defects in both the BRVO group and the NTG group. About 40% of the patients with unilateral BRVO had focal LC defect in the BRVO-affected eyes and unaffected fellow eyes, similar prevalence to the patients with NTG. The mean PCT was significantly thinner in the eyes with focal LC defect than those without in the patients with BRVO and those with NTG, suggesting possible pathophysiologic correlation between these two diseases.

Spontaneous focal lamina cribrosa defect in glaucoma and its relationship with nonprogressive glaucomatous neuropathy

Objective: To investigate the relationship between the spontaneous focal lamina cribrosa (LC) defect and the progression of visual field defect (VFD) in primary open-angle glaucoma (POAG). Methods: Case-control study. The patients who were diagnosed as POAG with at least 5 visual field results had been collected from June 2018 to January 2019 at Beijing Tongren Hospital Affiliated to Capital Medical University. Serial imaging by swept source optical coherence tomography B-Scan of the optic discs were acquired at the end of the follow-up and LC defects status were reviewed. Intraocular pressure, mean defects of visual field, central corneal thickness and axis length were recorded in the follow-up duration. Eyes were classified as having either progressive or nonprogressive VFD, and associating factors were evaluated by χ(2) or Fisher's test, mixed-effect model analysis and multivariate Logistical regression analysis. Results: A total of 32 subjects (64 eyes) were enrolled in the study with mean age of (47±14) years, the group consisted of 17 males and 15 females. Fourty-five eyes showed nonprogressive VFD. LC defects were more common in eyes without (28/45) rather than with progressive VFD (5/19) (χ(2)=6.896, P=0.009). Eyes with nonprogressive VFD showed longer axis length[(26.82±1.34) mm vs. (25.79±1.44) mm; t=6.589, P=0.013] and wider LC defects diameter[211 (165-326) μm vs. 114 (106-156) μm; Z=4.797, P=0.042]. Multivariate Logistic regression analysis revealed that the presence of LC defect was significantly associated with nonprogressive VFD (odds ratio=0.217, P=0.012). There were 7 subjects with asymmetry VFD and the incedence of LC defects without progression (7/7) is higher than fellow eye with progression (1/7, P=0.002). There was only one patient with progressive VFD showed one LC defect with an smaller diameter (169 μm) than that in the contralateral eyes with stable VFD (269 μm). Conclusions: LC defects are more common in eyes with nonprogressive VFD. Spontaneous LC defects are associated with nonprogressive glaucomatous defects and could be a protective factor for POAG. (Chin J Ophthalmol, 2019, 55:338-346).

Association between focal lamina cribrosa defects and optic disc haemorrhage in glaucoma

Background/aimsTo explore the relationship between focal lamina defect (LD) size and optic disc haemorrhages (DH) in glaucomatous eyes.MethodsRadial B-scan images at 15° intervals obtained using enhanced depth imaging (EDI) spectral-domain...

Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology

To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.

Border Tissue Morphology Is Spatially Associated with Focal Lamina Cribrosa Defect and Deep-Layer Microvasculature Dropout in Open-Angle Glaucoma

To investigate the topographic relationship among focal lamina cribrosa (LC) defect, microvasculature dropout (MvD) and border tissue morphology in open angle glaucoma (OAG) eyes using spectral-domain (SD) optical coherence tomography (OCT) and OCT angiography. Cross-sectional study. One hundred twenty-six OAG eyes and 97 normal eyes were included. The maximum externally oblique border tissue (EOBT) length was measured by using enhanced depth imaging SD-OCT as well as focal LC defect size. Circumferential MvD width and height ratio were measured using OCT angiography. Significant correlations were found among the locations of focal LC defect, MvD and maximum EOBT length. The mean absolute locational difference was 29.1° (95% CI, -47.6 to 105.7) between focal LC defect and MvD, 10.0° (95% CI, -79.4 to 99.4) between focal LC defect and maximum EOBT length, and 10.6° (95% CI, -71.1 to 92.3) between MvD and maximum EOBT length. In multivariate logistic regression analysis, a worse VF defect was significantly associated with the presence of focal LC defects and MvDs (P < .002; P = .002, respectively). MvD circumferential width was associated with glaucoma severity (R = -0.66, P < .001), whereas focal LC defect size and MvD height ratio were associated with maximum EOBT length (R = 0.48, P < .001; R = 0.65, P < .001, respectively) and AL (R = 0.53, P < .001; R = 0.52, P < .001, respectively). There was a topographical correlation among the locations of focal LC defect, MvD and maximum border length. In addition, the presence of focal LC defect and MvD were also strongly associated with glaucoma severity. Thus, it is thought that focal LC defect and MvD may be biomarkers that reflect glaucoma severity especially at the location of maximum border tissue elongation.

Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma

Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] μm/y; difference, -0.43 [-0.76 to -0.09] μm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] μm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (β2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (β2, -0.05 [95% CI, -0.17 to 0.06], P = .36). These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

Parapapillary Deep-Layer Microvasculature Dropout and Visual Field Progression in Glaucoma

To evaluate the association between optical coherence tomography angiography (OCT-A)-derived parapapillary deep-layer microvasculature dropout and glaucomatous visual field (VF) progression. Retrospective, cohort study. A total of 138 eyes of 138 patients with primary open-angle glaucoma (mean follow-up, 5.5 years) and with ≥5 VFs prior to OCT-A imaging were included. VF progression was defined as either a Guided Progression Analysis-based "likely progression" event or a significant VF index (VFI) slope. Microvasculature dropout was defined as parapapillary deep-layer microvasculature dropout based on a qualitative analysis of OCT-A. Prevalence of dropout was compared between eyes with and without VF progression. Fifty-five eyes (39.9%) demonstrated VF progression. A higher proportion of eyes with dropout progressed than those without dropout (50/84 eyes [59.5%] vs 5/54 eyes [9.3%]; P < .001). In multivariable logistic regression analysis, mean and standard deviation intraocular pressure, optic disc hemorrhage, focal lamina cribrosa defect, and dropout were significantly associated with prior VF progression (P < .05). The VFI progression rate was significantly faster in eyes with dropout than in those without dropout (-2.23% ± 3.22%/year vs-0.05% ± 1.24%/year, respectively; P < .001), and the location of dropout and VF progression were spatially correlated. Eyes with parapapillary deep-layer microvasculature dropout detected by OCT-A had a significantly higher rate of VF progression than eyes without dropout. These findings implicate dropout as a structural parameter suggestive of past glaucomatous VF progression. Further prospective longitudinal studies are needed to elucidate the role of deep-layer microvasculature damage in thepathogenesis of glaucoma.

Optic disc microvasculature dropout in primary open-angle glaucoma measured with optical coherence tomography angiography.

PurposeTo evaluate microvasculature dropout in the optic disc (Mvd-D) using optical coherence tomography angiography (OCTA) and investigate factors associated with Mvd-D in primary open-angle glaucoma (POAG) eyes.MethodsOne hundred twenty-three eyes of 123 POAG patients were included from the Diagnostic Innovations in Glaucoma Study. The 3.0×3.0-mm optic nerve head OCTA scans were acquired using a spectral-domain OCT instrument. Images with whole-signal-mode were evaluated. Eyes were classified into 3 categories (Mvd-D, pseudo-Mvd-D, and no Mvd-D). Mvd-D and pseudo-Mvd-D had complete loss of OCTA signals on the temporal side of the optic disc on the en face projection image. They were distinguished base on the visualization of the anterior lamina cribrosa in the horizontal B-scans of that area. No Mvd-D was defined when no complete signal loss of OCTA signals was observed. Covariates including focal lamina cribrosa defects assessed by swept-source OCT and microvasculature dropout in the parapapillary region (Mvd-P) were analyzed.ResultsForty-two, 37, and 44 eyes were identified as having Mvd-D, pseudo-Mvd-D, and no Mvd-D, respectively. The eyes with Mvd-D showed significantly lower intraocular pressure, worse visual field mean deviation, larger cup-to-disc ratio, thinner circumpapillary retinal nerve fiber layer (cpRNFL), and lower circumpapillary vessel density within the RNFL than the eyes with pseudo-Mvd-D or the eyes without Mvd-D. Multivariable logistic regression analysis showed significant associations of Mvd-D with larger cup-to-disc ratio (OR, 1.08; P = 0.001), worse visual field mean deviation (OR, 1.09; P = 0.048), higher prevalence of focal lamina cribrosa defect (OR, 9.05; P = 0.002), and higher prevalence of Mvd-P (OR, 10.33; P <0.001).ConclusionsOCTA-derived Mvd-D was strongly associated with the presences of Mvd-P and focal lamina cribrosa defects, and these 3 findings were topographically associated with each other.

Position of Central Retinal Vascular Trunk and Preferential Location of Glaucomatous Damage in Myopic Normal-Tension Glaucoma

To investigate the spatial correlation between the central retinal vascular trunk and the preferential location of glaucomatous damage in myopic normal-tension glaucoma (NTG) eyes. Cross-sectional study. One hundred thirty-seven subjects with myopic NTG (137 eyes). The position of the vascular trunk was measured from the center of the Bruch membrane opening (BMO), which was delineated by optical coherence tomography imaging. The angular deviation was measured, with the horizontal nasal midline as 0° and the superior location as a positive value. The shift index was calculated as the distance of the vascular trunk from the BMO center relative to that of the BMO margin. The angular location of the midpoint of the retinal nerve fiber layer (RNFL) defect was measured from the BMO center. In cases with bi-hemispheric RNFL defects, the angular location was measured for the RNFL defect of larger width. For categorical analysis, hemispheric dominancy was determined if the RNFL defect in one hemisphere was larger than twofold that in the opposite hemisphere. In cases with no dominant hemisphere, the eye was classified as bi-equivalent involvement. The vascular trunk position within the BMO and the location of glaucomatous damage. The moderate- and severe-shift groups (shift index ≥ 0.5) were associated with younger age, longer axial length, smaller angular deviation, and lesser incidence of focal lamina cribrosa (LC) defect. A multiple regression analysis showed a significant correlation between the vascular trunk position and the RNFL defect location (P < 0.001). A logistic regression analysis revealed that the dominant RNFL defect occurred in the opposite hemisphere of the vascular trunk (P < 0.001), and bi-equivalent involvement in both hemispheres was associated with a larger shift index (P= 0.001). A conditional inference tree analysis showed that both the angular deviation (P < 0.001) and the extent of vascular trunk shift (P < 0.001) determined the RNFL defect location. In myopic NTG eyes, the vascular trunk is located in the direction opposite of the RNFL defect with reference to the BMO. Because the vascular trunk is embedded in the LC, this implies that LC shift during axial elongation is associated with greater vulnerability of myopic eyes to glaucomatous damage.