Effect of connective tissue growth factor gene editing using adeno-associated virus-mediated CRISPR-Cas9 on rabbit glaucoma filtering surgery outcomes.

Suppressing excessive wound healing responses is critical to ensure surgical success in glaucoma filtration surgery (GFS). Currently used adjunctive materials can lead to side effects due to the nonselectivity in cell inhibition and may require repeated applications. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system may become a compelling opportunity in glaucoma surgery due to its high selectivity and permanent effect. Connective tissue growth factor (CTGF) is one of the most potent stimulators of tissue fibrosis in the eye. Therefore, we tested the effect of CTGF suppression using the CRISPR-Cas9 system on GFS fibrosis. We used an adeno-associated virus (AAV)-CRISPR-Cas9 system and confirmed successful CTGF suppression was achieved in fibroblasts in vitro through western blot analysis and deep sequencing. In the in vivo intereye-comparison rabbit GFS model, CRISPR-CTGF-treated eyes showed significantly better survival of the surgery site, less subconjunctival fibrosis, limited collagen deposition, and reduced cellularity than untreated eyes. Our results suggest a new possibility of CRISPR-Cas9-mediated CTGF suppression to improve human GFS outcomes.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

Membrane-tube-type glaucoma shunt device for refractory glaucoma surgery.

PURPOSE: To evaluate the safety and efficacy of a novel membrane-tube (MT)-type glaucoma shunt device for refractory glaucoma surgery. The device consists of an expanded polytetrafluoroethylene membranous reservoir, as well as a silicone tube (300-µm external and 200-µm internal diameter) with an intraluminal stent. We named the device "Finetube MT". METHODS: The Finetube MT was implanted into 44 glaucomatous eyes that had insufficient intraocular pressure (IOP) control despite medical treatment or previous trabeculectomy. The membranous reservoir was placed underneath the Tenon's capsule, with each end located below the recti muscles; the tube was placed in the anterior chamber through a partial-thickness scleral track. We investigated the baseline and post-operative IOP values, the number of IOP-lowering medications used, and complications. RESULTS: The mean age of the subjects was 51.6 ± 17.2 years, and the mean follow-up duration was 22.5 ± 12.0 months. One year after the surgery, the mean IOP had decreased from 32.8 ± 12.2 mmHg to 16.9 ± 6.4 mmHg (48.5 % reduction; p < 0.01), and the mean number of IOP-lowering medications used had decreased from 2.5 ± 0.8 to 1.1 ± 0.9 (p < 0.01). We considered the surgery as a success when the IOP was between 6 and 21 mmHg, and had been reduced by ≥ 20 % from baseline; by this standard, the success rate was 92.4 % after 1 year, and 85.0 % after 3 years. Neither postoperative ocular hypotony-related complications nor tube exposure occurred in any case. CONCLUSIONS: The Finetube MT showed promising surgical outcomes as a treatment for refractory glaucoma, with minimal risk of postoperative ocular hypotony or tube-related complications.

Optical coherence tomography measurements in compressive optic neuropathy associated with dysthyroid orbitopathy.

BACKGROUND: The purpose of the study was to assess the influence of optic nerve compression on the peripapillary retinal nerve fiber layer (RNFL) thickness in eyes with acute and chronic dysthyroid optic neuropathy (DON). METHODS: Patients with DON and healthy control subjects underwent peripapillary optical coherence tomography (OCT) scanning with the Cirrus HD-OCT. Patients were classified as acute (within 6 months from the onset of DON) versus chronic (6 months or more from the onset of DON) DON. The thickness of peripapillary RNFL was compared between eyes with acute and chronic DON and control eyes. Baseline factors associated with visual acuity at the last visit were also analyzed. RESULTS: The mean temporal peripapillary RNFL thickness was thinnest in chronic DON at 66 ± 12 µm compared to 76 ± 8 µm in eyes with acute DON and 73 ± 12 µm in control eyes (p = 0.014). In a multivariable analysis, patients with greater inferior peripapillary RNFL thickness and younger age tended to have better visual acuity at the last visit (p = 0.034, odds ratio [OR] = 1.038 and p = 0.007, OR = 0.912, respectively). CONCLUSIONS: Our data revealed a notable difference in temporal peripapillary RNFL thickness in eyes with chronic DON compared to eyes with acute DON and control eyes. We also found a significant association between inferior peripapillary RNFL thickness and visual acuity at the last visit. Thicker inferior peripapillary RNFL thickness was associated with better visual outcome. Further studies with large sample sizes using a prospective design should more clearly reveal the time aspect of the association between the onset of DON and the changes in peripapillary RNFL, and their clinical significance.

Novel membrane-tube type glaucoma shunt device for glaucoma surgery.

BACKGROUND: The background of this study is to introduce the surgical technique and outcomes of a novel membrane-tube (MT) type glaucoma shunt device (MicroMT), which was developed to achieve safer and more predictable intraocular pressure (IOP) control compared with conventional trabeculectomy. DESIGN: This is a retrospective, non-comparative, interventional case series study. PARTICIPANTS: The MicroMT was implanted in 43 glaucomatous eyes with insufficient IOP control despite medical treatment. METHODS: The MicroMT consists of an expanded polytetrafluoroethylene membrane and a silicone tube with an intraluminal stent, which allows aqueous drainage from the anterior chamber to the lamellar scleral flap. The intraluminal stent prevents excessive aqueous drainage and allows additional IOP reduction through retraction or removal of the stent. MAIN OUTCOME MEASURES: The main outcome measures of this study are IOP changes and complications. RESULTS: The mean (SD) IOP decreased from a preoperative value of 22.5 (6.9) mmHg to 11.1 (3.6) mmHg 3 years after the operation (50.7% reduction from baseline; P < 0.01). Intraluminal stent removal 4 weeks after the operation induced an additional 40.2% IOP reduction (P < 0.01). When success was defined as an IOP between 6 and 21 mmHg, and an IOP reduction of ≥20% from baseline, the success rate was 89.5% at 3 years after the operation. No postoperative ocular hypotony (IOP <6 mmHg) or tube-related complications occurred. CONCLUSIONS: MicroMT implantation is a novel therapy that may reduce IOP safely and effectively, with no apparent risk of postoperative ocular hypotony. Glaucoma surgery using this device may be a good alternative to conventional glaucoma surgery.

Long-term outcomes of argon laser photocoagulation in small size cyclodialysis cleft.

BACKGROUND: To evaluate the long-term outcomes of Argon laser photocoagulation compared to surgical direct cyclopexy in small-size cyclodialysis cleft patients. METHODS: This is a retrospective study. Small-size cyclodialysis cleft patients who underwent Argon laser photocoagulation and surgical direct cyclopexy were reviewed. The mean follow-up period were 82.4 (range, 61 - 145) months and 99.9 (range, 62 - 184) months in both groups. The comparison of best corrected visual acuity (BCVA), intraocular pressure (IOP), postoperative peak IOP and time to normalization of IOP before and after the treatment. RESULTS: The causes of all included 15 cyclodialysis cleft cases were blunt trauma. seven patients underwent Argon laser photocoagulation and eight patients underwent surgical direct cyclopexy. The mean age of included patients was not significantly different (p = 0.38). Preoperatively, the mean logMAR BCVA (standard deviation, SD) was 0.7 (0.2) and 1.1 (0.9) and mean IOP was 4.4 (2.4) mmHg and 3.0 (1.5) mmHg in Argon laser group and surgical direct cyclopexy group (p = 0.24 and p = 0.18, respectively). The extension of cyclodialysis and duration of cyclodialysis cleft were not significantly different between the two groups (p = 0.08 and p = 0.24, respectively). The mean follow-up period were 82.4 (range, 61 - 145) months and 99.9 (range, 62 - 184) months in both groups (p = 0.41). Postoperatively, the mean logMAR BCVA was 0.0 (0.1) and 0.2 (0.3) and mean IOP was 14.5 (3.1) mmHg and 16.8 (2.5) mmHg (p = 0.15 and p = 0.16, respectively). Postoperative peak IOP and time to normalization of IOP were not different between the two groups (p = 0.75 and p = 0.91, respectively). DISCUSSION: It is necessary to use invasive treatment such as cryotherapy or surgical direct cyclopexy in cyclodialysis cleft with hypotonic maculopathy. In the present study, Argon laser photocoagulation showed good prognosis in a small-size cyclodialysis cleft below 1.5 clock-hours. Considering possible complications and cost of surgical direct cyclopexy, Argon laser can be more beneficial than surgical direct cyclopexy in small-size cyclodialysis cleft below 1.5 clock-hours. CONCLUSIONS: The clinical ourcome of Argon laser photocoagulation seems to be as good as surgical direct cyclopexy in small-size cyclodialysis cleft below 1.5 clock-hours.

Differential protein expression and metabolite profiling in glaucoma: Insights from a multi-omics analysis.

Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi-omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, n = 5), exfoliation glaucoma (XFG, n = 4), primary open-angle glaucoma (POAG, n = 11), and cataracts (control group, n = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data-independent acquisition and data-dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L-phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L-phenylalanine or C3, APOD, and L-valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma.

Different glaucoma progression rates by age groups in young myopic glaucoma patients.

We aimed to investigate the age-related glaucoma progression rates in myopic normal tension glaucoma (NTG). In this long-term retrospective cohort (7.2 ± 3.5 years), we grouped patients based on their age at initial presentation: group A (age < 30 years, 60 eyes), group B (30 ≤ age < 40, 66 eyes), and group C (40 ≤ age < 50 years, 63 eyes). We used a linear mixed-effects model to estimate retinal nerve fiber layer (RNFL) defect width enlargement rates. Group A showed a significantly faster rate of RNFL defect progression (3.01 ± 1.74°/year) than those of groups B and C (2.05 ± 1.55°/year and 2.06 ± 1.29°/year, P = 0.004 and 0.002). The difference was more marked when calculated for the first 10 years of follow-up in group A, B, and C (3.95 ± 2.70°/year, 2.39 ± 1.64°/year, and 1.98 ± 1.31°/year), and between the periods of age < 30 years, 30 ≤ age < 40 years, and 40 ≤ age < 50 years within group A. This is the first evidence of rapid glaucoma progression in the young adulthood and stabilization in older age in myopic NTG. Clinicians should consider the potentially aggressive course of glaucoma, especially in younger patients with myopic NTG, in contrast to the general slow progression in adulthood.

Longitudinal changes in optic disc cupping from the baseline in chiasmal lesion optic neuropathy and glaucoma.

We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P < 0.001); the minimum residual neuroretinal rim width showed a more pronounced difference (29.7 ± 8.2% vs 7.1 ± 3.9%, P < 0.001). The changes distributed predominantly towards the nasal direction in chON, contrasting the changes to the arcuate fibers in glaucoma. In conclusion, our results provide the first longitudinal evidence of true pathological cupping in chONcompared to photographically disease-free baseline. The marked difference in the residual minimum rim width reaffirms the importance of rim obliteration in the differential diagnosis between the two diseases.

Factors affecting near vision after monofocal intraocular lens implantation.

PURPOSE: To identify factors that influence near vision after monofocal intraocular lens (IOL) implantation for distance vision. METHODS: A retrospective review was conducted of patients who underwent cataract surgery with monofocal IOL implantation from October 2009 to April 2010 at Samsung Medical Center. Eyes were classified as having good (⩾ J4) or poor (< J4) near vision. Factors analyzed included age, sex, intraocular lens (IOL) movement, axial length, pupil size, degree and type of astigmatism, IOL type, total aberration, and higher-order aberrations. Binary logistic regression and odds ratios with 95% confidence intervals were determined. RESULTS: This retrospective study involved 84 eyes of 84 patients. Thirty-four eyes were classified as having good near vision and 50 eyes as having poor near vision. All groups had a postoperative uncorrected visual acuity greater than 0.2 logMAR (Snellen 20/32) and a refractive error within ± 0.5 diopter of spherical equivalent. Pupil size and axial length were inversely associated with good near vision (P = .034 and .039, respectively). A pupil size smaller than 2.6 mm and an axial length less than 23.0 mm resulted in better near vision than larger measurements after monofocal IOL implantation for distant target. CONCLUSIONS: Among the factors analyzed, small pupil size and short axial length predicted good near vision after phacoemulsification and monofocal IOL implantation.

Ancillary PanoMap OCT shows the progression of glaucomatous papillomacular bundle defect with disc haemorrhage on the fovea-disc axis.

BACKGROUND/AIMS: To identify the spatial relationship between disc haemorrhage (DH) on the fovea-disc axis and retinal nerve fibre layer (RNFL) defect in the papillomacular bundle (PMB) using ancillary PanoMap optical coherence tomography (OCT). METHODS: We investigated the presence and progression of spatially corresponding PMB defects in glaucomatous eyes with temporally located DH on the fovea-disc axis (FoDi-DH). We identified PMB defects using ancillary PanoMap OCT with guided progression analysis, in addition to red-free photographs. RESULTS: We studied 36 eyes of 35 glaucoma patients with FoDi-DH, pre-existing PMB defects were observed in 18 eyes (50.0%) at the time and location of the initial FoDi-DH occurrence, 14 (38.9%) of which progressed during the follow-up period. New development of PMB defects occurred in 15 (41.7%) of 18 eyes without pre-existing PMB defects. Overall, FoDi-DH was associated with PMB defects in 33 (91.7%) eyes at locations spatially overlapping the PMB defect. Red-free photography and OCT were complementary in detecting PMB defects and progression. Among 47 cases, 20 were concordant, while 10 and 17 were detected only in photography and OCT, respectively. The central visual field defect increased significantly throughout the follow-up period (p=0.006). CONCLUSION: Most FoDi-DH cases were related to the presence and progression of glaucomatous PMB defects at locations spatially overlapping the defect. OCT helped clarify changes in PMB defects detected by red-free photograph and the detection of photo-negative PMB defects as well. Similar to inferotemporal and superotemporal-direction DH, temporal DH on the PMB may be an indicator of ongoing RNFL damage that deserves close attention.

Deep Optic Nerve Head Morphology in Tilted Disc Syndrome and Its Clinical Implication on Visual Damage.

Purpose: To study deep optic nerve head (ONH) morphology in tilted disc syndrome (TDS) and identify factors associated with retinal nerve fiber layer (RNFL) defect. Methods: In patients with TDS, we evaluated the optic disc shape using the Bruch's membrane opening (BMO)-anterior scleral canal opening (ASCO) offset and measured the border tissue (BT) length, depth, and angle in the direction of the tilt, using radial ONH optical coherence tomography (OCT). We compared the parameters between the TDS groups with and without RNFL defects. Results: Twenty-one eyes had no glaucomatous RNFL defect, and 38 eyes had a glaucomatous RNFL defect. The group with RNFL defects had a higher baseline IOP, larger tilt axis of BMO-ASCO optic disc margin (76.4° ± 14.5° vs. 87.9° ± 15.4°, P = 0.012), larger BMO-lamina cribrosa insertion (LCI) angle (25.6° ± 9.3° vs. 43.6° ± 15.2°, P < 0.001), and more lamina cribrosa (LC) defects (4.3% vs. 30.6%, P = 0.028) than without RNFL defects. The tilt axis and BMO-LCI angle were significant factors after adjusting for baseline IOP and LC defect. The BMO-LCI angle had excellent diagnostic power for glaucomatous RNFL defect in TDS, similar to the visual field mean deviation. Conclusions: OCT-based large deep ONH BT angle and tilt axis were factors associated with the presence of RNFL defects in TDS. The results suggest a mechanism of RNFL defect associated with structural ONH deformation. Further investigations are warranted to understand the role of ONH structures in a general population with and without optic disc tilt.

Filtering Bleb Size in the Early Postoperative Period Affects the Long-term Surgical Outcome after Trabeculectomy.

PURPOSE: To investigate whether postoperative filtering bleb size affects the surgical outcome after trabeculectomy. METHODS: In this study, we retrospectively reviewed 145 medically uncontrolled glaucoma patients with intraocular pressure (IOP) values >21 mmHg before surgery and data from ≥2 years of follow-up. Postoperative IOP, filtering bleb size including extent and height, and other clinical factors were measured after trabeculectomy. We divided bleb extent into quadrants and bleb height by 0.5 intervals of corneal thickness. The main outcome measure was surgical success. We confirmed complete success when the IOP was ≤21 mmHg and decreased by >20% from baseline without medication or additional procedures. Qualified success used the same criteria but allowed for medication or additional procedures. Cases with reoperation or two consecutive IOP measurements <6 mmHg were considered failures. RESULTS: A total of 145 eyes of 145 patients was included. The average observation period was 30.8 ± 10.9 months. During multivariate Cox regression analysis, a larger extent of filtering bleb revealed significantly low hazard ratios in both complete and surgical success (0.509 and 0.494, respectively); however, there was no significant relationship between bleb height and surgical outcome. CONCLUSIONS: The extent of the filtering bleb was associated with surgical outcomes of trabeculectomy in glaucoma patients.

Association between atrial fibrillation and the risk of glaucoma development: a 12-year Nationwide cohort study.

OBJECTIVE: To investigate the risk of glaucoma development in patients with atrial fibrillation (A-fib) using Korean National Health Insurance Service data. METHODS: The present study used a National Sample Cohort consisting of approximately one million random subjects who were tracked from 2002 to 2013 (12 years). Newly diagnosed glaucoma and A-fib were included based on the Korean Classification of Disease codes. The A-fib group consisted of patients who received an initial A-fib diagnosis between January 2003 and December 2007 as an index period (n = 8765). The control group (n = 43,352) was selected using a 1:5 propensity-score matching for social and demographic factors. Each subject was followed up until 2013. Multivariate Cox proportional hazard regression analysis was performed to compare the risk of glaucoma development between the A-fib group and the control group. RESULTS: The rate of glaucoma development was 3.54% in the A-fib group and 2.96% in the control group (P < 0.0001). A-fib increased the risk of glaucoma development [hazard ratio = 1.31; 95% confidence interval (CI): 1.15 to 1.48] after adjusting for age, sex, comorbidities, residence, household income, and year of enrollment. In multivariable Cox regression analysis, patients with comorbidity of diabetes mellitus and chronic renal failure and those aged ≥50 years showed significantly higher risk of glaucoma development (all P < 0.001). CONCLUSIONS: A-fib was significantly associated with the development of glaucoma after adjusting for potential confounding factors. Physicians may need to monitor patients with A-fib carefully for possible glaucoma development.

Peripapillary Vascular Density in Compressive Optic Neuropathy and Normal-Tension Glaucoma: A Severity-Controlled Comparison.

Purpose: To investigate the differences in peripapillary vessel density (VD) between compressive optic neuropathy (CON) and normal-tension glaucoma (NTG). Methods: We compared patients with chronic CON and NTG, particularly after strictly controlling the mean extent of macular damage by the area of the ganglion cell-inner plexiform layer (GCIPL) loss in optical coherence tomography (OCT). We compared retinal nerve fiber layer (RNFL) and GCIPL thickness from OCT and peripapillary and macular VD from OCT angiography (OCTA) between the CON and NTG groups. Results: From the initial 184 patients with CON and 443 patients with OAG, we included 41 patients with CON (57 eyes) and 64 patients with NTG (75 eyes) with a comparable extent of macular GCIPL thinning. Under similar mean macular involvement, the peripapillary VD was significantly lower in the CON group than in the NTG group after considering the effects of age, spherical equivalent, visual field sensitivity, peripapillary RNFL (pRNFL) thickness, GCIPL thickness, and image quality scores (P < 0.001). Marked loss of VD in the temporal and nasal sectors in CON was notable, attributing to the significantly lower peripapillary VD compared to NTG. Conclusions: Patients with CON had a significantly lower peripapillary VD than those with NTG under similar mean degrees of pRNFL thickness and GCIPL damage. Our results reveal the potential utility of OCTA VD besides OCT pRNFL thickness, in relation to different topographic patterns of pRNFL loss, and possible differences in the pathogenesis of microvascular compromise between CON and NTG.

Fibroblastic low-grade malignant peripheral nerve sheath tumor in the orbit.

Malignant peripheral nerve-sheath tumors (MPNSTs) are rare, poorly defined spindle cell sarcomas, and they are accompanied by heterologous elements in some cases. Among them, a fibroblastic element is one of the rarest and has been mentioned in some organs in several publications, but not in the orbit. The authors report a case of fibroblastic low-grade MPNSTs in the orbit. The mass was removed surgically, and the patient has been under close observation without evidence of disease recurrence for 2 years.

Parapapillary deep-layer microvasculature dropout is only found near the retinal nerve fibre layer defect location in open-angle glaucoma.

PURPOSE: We aimed to investigate the topographic correspondence between deep-layer microvasculature dropout (MvD) and retinal nerve fibre layer (RNFL) defects in eyes with open-angle glaucoma (OAG) using spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCT-A). METHODS: Microvasculature dropout width and location were determined using OCT-A, RNFL thickness, RNFL defect width and location were revealed using SD-OCT. The association between MvD and RNFL widths and that between the location of the MvD and RNFL defects were investigated. In addition, patients with OAG were divided into two groups: the RNFL defect in one hemiretina (RNFLD-HR) group (n = 24 eyes) and the RNFL defects in both hemiretinas (RNFLD-BR) group (n = 25 eyes). The presence, width and location of MvDs were compared between the two groups. RESULTS: Forty-nine eyes were included. In 24 RNFLD-HR eyes, all MvDs were found in the inferior area, corresponding with the location of the RNFL defect. Meanwhile, in 25 RNFLD-BR eyes, 18 MvDs (72%) were found in the inferior hemiretina, two (8%) were found in the superior hemiretina, and five (20%) were found in both hemiretinas. In RNFLD-BR eyes, the average RNFL thickness was thinner in a location with MvD than a location without MvD. CONCLUSION: Considering that MvD is only observed at the location of the RNFL defect in RNFLD-HR eyes and is usually found in the location of more severe RNFL defects in RNFLD-BR eyes, MvD seems to be a sign that accompanies glaucomatous damage in OAG eyes.

Topographic Relationships among Deep Optic Nerve Head Parameters in Patients with Primary Open-Angle Glaucoma.

PURPOSE: To investigate the topographic relationships among the deep optic nerve head (ONH) parameters representing myopic axial elongation or changes in the lamina cribrosa (LC) in patients with primary open-angle glaucoma (POAG). METHODS: Among patients with POAG who visited the clinic between January 2015 and March 2017, the following deep ONH parameters were measured using spectral-domain optical coherence tomography (SD-OCT): externally oblique border tissue (EOBT) length, ONH tilt angle, optic canal (OC) obliqueness, and anterior LC insertion depth (ALID). In addition, the angular locations of the maximal value of each parameter were measured. We analyzed the correlations between the parameters, correlations with axial length (AL), and the spatial correspondence with glaucomatous ONH damage. RESULTS: A total of 100 eyes with POAG were included in the analysis. The EOBT length, ONH tilt angle, and OC obliqueness were correlated with each other and with AL, whereas ALID showed less correlation with the other parameters and AL. The angular location where the three AL-related parameters had maximum values was also correlated with the predominant region of the glaucomatous ONH damage, while the angular location of the deepest ALID showed less correlation. CONCLUSIONS: Among the deep ONH parameters, the AL-related parameters EOBT length, ONH tilt angle, and OC obliqueness showed strong spatial correspondence with glaucomatous ONH damage, whereas the LC-related parameter ALID was less correlated with both AL and the region with glaucomatous ONH damage. Further studies are needed to determine how these differences affect glaucomatous ONH change.

Border tissue morphology is associated with the pattern of visual field progression in open-angle glaucoma.

The etiology of open-angle glaucoma (OAG) is yet unclear. This study investigated possible risk factors, such as the morphology of the border tissue that affect the pattern of visual field (VF) progression in eyes with OAG. 166 eyes of 166 OAG patients with an externally oblique border tissue (EOBT) at least in one direction were included. EOBT was obtained by analyzing enhanced depth imaging spectral-domain optical coherence tomography images. A pointwise linear regression was used to determine VF progression by measuring the deterioration rate of each point in the VF. The odds ratio of VF progression for each risk factor was estimated using logistic regression analysis. Seventy (42.2%) eyes showed VF deterioration. In multivariate analysis, longer follow-up period, higher baseline intraocular pressure (IOP), lower mean ocular perfusion pressure (MOPP), and smaller angular location of the longest EOBT were associated with VF progression (all p values were below 0.05). In the multivariate analysis, the location of the longest EOBT was significantly associated with inferior (p = 0.002) and central (p = 0.017) VF progression. In conclusion, VF progression pattern in OAG eyes is associated with the location of the longest EOBT as well as other known risk factors.

Border tissue morphology is associated with macular ganglion cell thickness in open-angle glaucoma.

Externally oblique border tissue (EOBT) configuration is topographically associated with glaucomatous damage in the optic nerve head. We investigated the relationship between the EOBT characteristics and macular retinal ganglion cell (RGC) thickness in patients with open-angle glaucoma (OAG). A total of 149 eyes with OAG that had an EOBT observed on optical coherence tomography exams were included. After determining the maximum EOBT length and angular location of the maximal EOBT length, we analyzed their correlation with macular ganglion cell inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. The macular GCIPL and pRNFL thickness were compared based on the angular location of the longest EOBT, and their association was assessed using multivariable regression analysis. Maximum EOBT length was significantly correlated with macular GCIPL thickness, but not with pRNFL thickness. Macular GCIPL was thinnest in eyes with EOBT located in a temporal direction to the optic disc. Longer maximum EOBT and temporally elongated EOBT were independently associated with a thinner macular GCIPL in the multivariable regression analysis. These suggest that temporal elongation of the EOBT may increase the stress and strain on the RGCs derived from the macula and make RGCs more susceptible to glaucoma-inducing damage.