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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Purpose: To identify the presence of choroidal microvascular dropout (MvD) in nonarteritic anterior ischemic optic neuropathy (NAION) eyes and to characterize the topographical distribution for the mechanistic interpretation of MvD development. Methods: We performed optical coherence tomography angiography on 47 open-angle glaucoma (OAG) and 19 NAION eyes with ß-zone peripapillary atrophy (ßPPA). We recorded the presence of MvD and compared between the peripapillary topographical measures of MvD, retinal nerve fiber layer (RNFL) defect, and ßPPA in angular width and location. Results: MvD was present in both diseases, marginally more frequently in NAION eyes (19/19, 100.0%) than in OAG eyes (38/47, 80.6%, P = 0.050), without a discernable difference in appearance. NAION eyes also showed wider MvD and RNFL defects compared to OAG eyes (both P < 0.001). In topographical measurements, the distribution of MvD showed a strong correspondence to superimposition areas of ßPPA and RNFL defects, more distinctly than to RNFL defects (all P < 0.001). The outline of superimposition area also remarkably resembled the MvD area. Conclusions: MvD was present in both the OAG and NAION groups. The ßPPA-RNFL defect superimposition area topographically and morphologically matched MvD. Further investigations are needed to elucidate the role of RNFL defects in the pathogenesis of MvD and the clinical significance.

Methodology and Rationale for Ophthalmic Examinations in the Seventh and Eighth Korea National Health and Nutrition Examination Surveys (2017-2021).

This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.

Ahmed implant coated with poly(2-methacryloyloxyethyl phosphorylcholine) inhibits foreign body reactions in rabbit eyes.

PURPOSE: Wound healing after Ahmed glaucoma valve (AGV) implantation often entails fibrosis as a foreign body reaction to the silicone plate. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) forms an antifouling surface that inhibits fibrosis during wound healing. In this study, we aimed to compare the effects of the implantation of AGV coated with PMPC (wPMPC) versus AGV without PMPC (woPMPC) in rabbits. METHODS: Six New Zealand White rabbit does underwent AGV implantation in both eyes. For each rabbit, one eye was randomly selected for implantation of AGV wPMPC and a conventional AGV (woPMPC) was implanted in the contralateral eye. Gross conjunctival vascularity was compared between the two groups at the first, second, and fourth weeks after surgery. The eyes were enucleated in four weeks and subjected to staining with hematoxylin and eosin and Masson's trichrome stain. The fibrosis and inflammation status among the eye samples were compared by measuring the thickness of the fibrotic walls and counting the number of chronic inflammatory cells around the AGV. Counting of inflammatory cells and measuring fibrotic wall thickness were done in a blinded method to eliminate observer bias. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Gross and histological examinations revealed no toxic effects of PMPC. There were no apparent differences in overall conjunctival vascularity between the two groups at weeks 1, 2, and 4 after surgery. The average inflammatory cell counts were 14.3 ± 5.8 per slide and 27.3 ± 8.6 per slide in the wPMPC and woPMPC groups, respectively (p = 0.037). The average thicknesses of the fibrotic wall were 57.9 ± 11.3 µm and 81.5 ± 21.3 µm in the wPMPC and woPMPC groups, respectively (p = 0.025). CONCLUSION: Compared to the woPMPC group, the number of inflammatory cells and fibrosis were significantly decreased in the wPMPC group.

Association Between Chronic Renal Disease and the Risk of Glaucoma Development: A 12-year Nationwide Cohort Study.

Purpose: The purpose of this study was to present the results of our investigation into the risk of glaucoma development in patients with chronic renal disease (CRD). Methods: The present retrospective cohort study used the Korean National Health Insurance Service data, which consisted of 1,025,340 random subjects who were tracked from 2002 to 2013. Newly diagnosed glaucoma and CRD were included on the basis of the Korean Classification of Disease codes. The CRD group consisted of patients who received an initial CRD diagnosis between January 2003 and December 2007 as an index period (n = 3640). The control group (n = 17,971) was selected using 1:5 propensity-score matching using social and demographic factors, along with the year of enrollment. Each group subject was followed until 2013. We used multivariate Cox proportional hazard regression analysis to compare the risk of glaucoma development between the two groups. Results: Glaucoma consecutively developed in 4.3% in the CRD group and 2.8% in the control group (P < 0.0001). CRD increased the risk of glaucoma development (hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.34-1.98] after adjusting for age, sex, comorbidities, residence, household income, and the year of enrollment. In multivariate Cox regression analysis, patients with comorbidity of hypertension, diabetes mellitus, or aged ≥ 50 years showed a significantly higher risk of glaucoma development (all P < 0.008). Conclusions: A significant association between CRD and following development of glaucoma was revealed after adjusting the potential confounding factors.

Relationship between peripheral vasospasm and visual field progression rates in patients with normal-tension glaucoma with low-teen intraocular pressure.

PURPOSE: To investigate the association between peripheral vasospasm and the visual field (VF) progression rate in patients with normal-tension glaucoma (NTG) with low-teen intraocular pressure (IOP). METHODS: The finger temperature of 113 NTG patients was measured before and after exposure to ice water using a Temperature gun (cold pressor test). These patients had confirmed VF progression, despite a low-teen IOP during a follow-up period of >5 years. VF progression rates were calculated as the slope of the visual field index (VFI) and mean deviation (MD) over time. Demographic, systemic, and ocular factors and VF progression rates were compared, based on the cold pressor test results. A regression analysis was used to investigate the factors affecting VF progression rates. RESULTS: Mean age, initial IOP, mean IOP during the follow-up period, and initial VF MD were 57.1 years, 15.8 mmHg, 12.0 mmHg, and -5.2 dB, respectively. When patients were divided into two groups (less vasospasm and more vasospasm) according to changes in temperature after exposure to ice water, the VF progression rate was significantly faster in the group with more vasospasm. In a multiple regression analysis, older age, worse initial VF MD, and greater decrease in finger temperature after ice water exposure were significantly associated with faster VF progression rates. CONCLUSION: An excessive drop in finger temperature after exposure to ice water was significantly associated with faster VF progression in patients with low-teen NTG. This suggests that the blood flow in the optic nerve head may also be disturbed by peripheral vasospasm, accelerating glaucomatous damage regardless of IOP.

The Progression of Peripapillary Retinoschisis May Indicate the Progression of Glaucoma.

Purpose: To identify the temporal correlation between the increase in peripapillary retinoschisis (PPRS) and glaucoma progression during PPRS fluctuation. Methods: We performed a comparative clinical timeline analysis for PPRS and glaucomatous progression in eyes with PPRS. In particular, the interval between the increase in PPRS extent and glaucoma progression was analyzed. Temporal correlation was defined when the interval was less than one year between glaucoma progression and PPRS increase, including both de novo development and an increase in the amount of retinoschisis on serial optical coherence tomography. Results: We included 33 eyes of 30 patients, with an average follow-up period of 7.5 ± 3.0 years and a total of 253 glaucoma examinations. Glaucoma progression was observed in 21 of 33 eyes; 19 (90.5%) of the 21 eyes with glaucoma progression and 29 (74.4%) of the 39 episodes of PPRS increase showed temporal correlation. The de novo development of PPRS during the follow-up period over baseline PPRS was more frequently observed in the glaucoma progression group than in the no-progression group (P = 0.006). Conclusions: In glaucomatous eyes with PPRS, the increase in PPRS temporally correlated with glaucoma progression. Possible glaucoma progression may be considered around the time of increase and de novo development of PPRS.

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.