Aging-associated changes of optical coherence tomography-measured ganglion cell-related retinal layer thickness and visual sensitivity in normal Japanese.

PURPOSE: To report aging-associated change rates in circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell-inner plexiform layer and complex thickness (MGCIPLT, MGCCT) in normal Japanese eyes and to compare the data in linear scaled visual field (VF) sensitivity of central 4 points of Humphrey Field Analyzer (HFA) 24-2 test (VF4TestPoints) to that in MGCIPLT in four 0.6-mm-diameter circles corresponding to the four central points of HFA 24-2 adjusted for retinal ganglion cell displacement (GCIPLT4TestPoints). STUDY DESIGN: Prospective observational study METHODS: HFA 24-2 tests and spectral-domain optical coherence tomography (SD-OCT) measurements of cpRNFLT, MGCIPLT, MGCCT and GCIPLT4TestPoints were performed every 3 months for 3 years in 73 eyes of 37 healthy Japanese with mean age of 50.4 years. The time changes of SD-OCT-measured parameters and VF4TestPoints were analyzed using a linear mixed model. RESULTS: The aging-associated change rates were -0.064 µm/year for MGCIPLT and and -0.095 for MGCCT (P=0.020 and 0.017), but could not be detected for cpRNFLT. They accelerated with aging at -0.009µm/year/year of age for MGCIPLT (P<0.001), at 0.011 for MGCCT (P<0.001) and at 0.013 for cpRNFLT(0.031). The aging-associated decline of -82.1 [1/Lambert]/year of VF4TestPoints corresponded to -0.095 µm/year of GCIPLT4TestPoints. CONCLUSION: We report that aging-associated change rates of cpRNFLT, MGCIPLT and MGCCT in normal Japanese eyes were found to be significantly accelerated along with aging. Relationship between VF sensitivity decline rates and SD-OCT measured GCIPLT decline rates during physiological aging in the corresponding parafoveal retinal areas are also documented.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.

PURPOSE: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. DESIGN: Prospective cross-sectional study. METHODS: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. RESULTS: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. CONCLUSIONS: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.

Differences in Factors Associated With Glaucoma Progression With Lower Normal Intraocular Pressure in Superior and Inferior Halves of the Optic Nerve Head.

Purpose: The purpose of this study was to investigate risk factors for progression in the superior and inferior hemi-visual fields (hemi-VFs) and the corresponding hemi-disc/retinas in eyes with normal tension glaucoma (NTG). Methods: A 5-year prospective follow-up of 90 patients with NTG with untreated intraocular pressure (IOP) consistently ≤ 15 mm Hg was conducted. The IOP and Humphrey Perimeter measurements and disc/retina stereo-photographs were taken every 3 and 6 months, respectively. Risk factors for progression in the superior and inferior hemi-VFs and in the superior and inferior hemi-disc/retinas were investigated. Results: The mean total deviation values decreased at -0.50 ± 0.76 and -0.13 ± 0.34 dB/year in the superior and inferior hemi-VFs, respectively (P < 0.001). In the superior hemi-VF, the risk factor for faster progression was greater long-term IOP fluctuation (P = 0.022). In the inferior hemi-VF, the risk factors were disc hemorrhage (DH), greater myopic refraction, body mass index (BMI), and vertical cup-to-disc ratio (v-C/D; P < 0.05). The progression probability was 47.7 ± 6.0 and 17.7 ± 4.7% at 5 years in the superior and inferior hemi-disc/retinas respectively (P < 0.001), and DH was a risk factor for progression in both (P = 0.001). Conclusions: In NTG eyes, greater BMI, myopia, and v-C/D are characteristic risk factors for faster progression in the superior half of the optic nerve head (ONH), whereas long-term IOP fluctuation is the significant risk factor in the inferior half of the ONH, whereas DH is a risk factor in both. Translational Relevance: Different risk factors were identified in superior and inferior hemifields in NTG eyes.

Association between Glaucoma Progression in Macular Ganglion Cell Complex and Disc Hemorrhage: Differences between Superior and Inferior Hemiretinas.

Disc hemorrhage (DH) is often associated with glaucoma progression. A vertically asymmetrical pattern is typical of glaucoma progression, but it remains unclear whether the association between DH and glaucoma progression differs between the superior and inferior hemiretinas. We compared the thickness changes of the macular ganglion cell complex (GCC) in the hemiretinas of normal-tension glaucoma patients with or without DH, as well as between hemiretinas positive and negative for DH, during five years. Both the superior and inferior hemiretinas in the DH-positive group had a more negative GCC thickness slope in association with more DH counts compared to those in the DH-negative group. Conversely, only the inferior hemiretina exhibited a significant relationship between GCC thickness slope and DH counts when hemiretinas positive and negative for DH in the DH-positive group were compared. In the superior hemifield, the slope of the total deviation changes in the DH-positive hemifield of the DH-positive group was more negative compared to that of the DH-negative group. The association between DH and glaucoma progression in the macular GCC may be stronger in the inferior hemiretina, suggesting that more attention should be paid to DH in the inferior disc area as a sign of glaucoma progression.

Glaucoma-Related Risk Factors for Endothelial Cell Loss and Graft Failure After Descemet's Stripping Automated Endothelial Keratoplasty.

PRCIS: Previous trabeculectomy and medical or surgical glaucoma treatment after Descemet's stripping automated endothelial keratoplasty (DSAEK) were significantly associated with endothelial cell loss and graft failure. The pupillary block was a significant risk factor for graft failure. PURPOSE: To evaluate the long-term risk factors associated with postoperative endothelial cell loss and graft failure after DSAEK in Japanese eyes, with special attention to glaucoma. PATIENTS AND METHODS: This retrospective study involved 117 eyes of 110 consecutive patients with bullous keratopathy who had undergone DSAEK. The patients were classified into 4 groups: (1) no glaucoma group (n = 23 eyes), (2) primary angle closure disease group (n = 32 eyes), (3) glaucoma group that had previously undergone trabeculectomy (n = 44 eyes) (glaucoma with bleb), and (4) glaucoma group that had not previously undergone trabeculectomy (n = 18 eyes) (glaucoma without bleb). RESULTS: The cumulative 5-year graft survival rate was 82.1%. The cumulative 5-year graft survival rate among the 4 groups is as follows: no glaucoma (73%), primary angle closure disease (100%), glaucoma with bleb (39%), and glaucoma without bleb (80%). Multivariate analysis revealed that additional glaucoma medication and glaucoma surgery after DSAEK were independent risk factors for endothelial cell loss. Conversely, glaucoma with blebs and pupillary block were independent risk factors for graft failure after DSAEK. CONCLUSION: Previous trabeculectomy and medical or surgical glaucoma treatment after DSAEK were significantly associated with endothelial cell loss and graft failure. Pupillary block was a significant risk factor for graft failure.

Charcot-Marie-Tooth Disease with a Novel Variant in Gap Junction Protein Beta 1 Presenting with Visual Field Defects.

Pathogenic variants in Gap Junction Protein Beta 1 (GJB1) cause X-linked Charcot-Marie-Tooth (CMT) disease type 1 (CMTX1), which is a common hereditary motor and sensory neuropathy. A 45-year-old man presented with progressive muscle weakness, atrophy, sensory disturbance of all limbs from childhood, and visual field defects in both eyes at 40 years old. A segregation analysis revealed a novel variant, c.173C>A (p.P58H), in the GJB1 gene. Patients with variants at codon 58 in GJB1 showed clinically varied phenotypes, ranging from demyelinating neuropathy to cerebellar ataxia. This patient may represent one of the various clinical phenotypes of GJB1 variants.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Trabeculectomy Tenon Advancement Technique May Reduce Bleb-Related Infections.

PRCIS: Trabeculectomy using the Tenon advancement technique with a fornix-based (FB) conjunctival flap showed avascular bleb formation less frequently and had a significantly lower risk of developing bleb-related infections than trabeculectomy with a limbus-based conjunctival flap. PURPOSE: To determine whether the Tenon advancement technique for trabeculectomy with a FB conjunctival flap is effective in preventing bleb-related infections. MATERIALS AND METHODS: This was a single-center, nonrandomized retrospective cohort study of 998 eyes from 854 patients with glaucoma who underwent trabeculectomy with mitomycin C. Trabeculectomy procedures were categorized into 3 groups: limbus-based (LB, 296 eyes), FB without Tenon advancement (FBTA-, 167 eyes), and FB with Tenon advancement (FBTA+, 535 eyes). The cumulative incidence of bleb-related infections and the rate of surgical success during the 5-year postoperative follow-up period were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards models. Intraocular pressure (IOP) reduction of <20% from baseline or additional glaucoma surgeries was deemed a surgical failure. Surgical success with or without IOP-lowering medications was evaluated according to different IOP criteria. RESULTS: Ten eyes developed bleb-related infections (8 eyes in the LB group and 1 eye in both the FBTA- and FBTA+ groups each). The cumulative probability of bleb-related infections in the LB, FBTA-, and FBTA+ groups was 4.8±1.7% (± standard error), 0.8±0.8%, and 0.3±0.3%, respectively. The FBTA+ group had a significantly lower risk of bleb-related infections than the LB group (hazard ratio, 0.06; 95% confidence interval, 0.01 to 0.39; P =0.009). The FBTA+ group did not have a higher risk of surgical failure. CONCLUSION: The Tenon advancement technique for trabeculectomy using an FB conjunctival flap may be effective in preventing bleb-related infections without compromising surgical success.

Ex-PRESS shunt combined with ab-interno peripheral iridectomy: A new surgical procedure for iridocorneal endothelial syndrome.

Purpose: Iridocorneal endothelial (ICE) syndrome may cause refractory glaucoma due to progressive synechial closure or membrane formation at the anterior chamber angle. Filtration surgeries are often required but are associated with a higher rate of surgical failure or complications than other types of glaucoma. Herein, we report a new and effective surgical procedure for glaucoma secondary to ICE syndrome: Ex-PRESS shunt combined with ab-interno peripheral iridectomy using a small-gauge vitreous cutter. Methods: Three patients with ICE syndrome who underwent surgery were included. Intraoperatively, an ab-interno peripheral iridectomy was performed using a small-gauge vitreous cutter through a corneal incision in the superior-nasal or superior-temporal quadrants to create space for the insertion of Ex-PRESS shunt free from the iris tissue. The shunt was inserted under the scleral flap. The first patient underwent combined cataract surgery, whereas patients 2 (pseudophakia) and 3 (phakia) underwent Ex-PRESS alone. Results: No intraoperative complications were observed. The intraocular pressure remained stable until the final postoperative visits at approximately 7, 4, and 1 year in Cases 1, 2, and 3, respectively. Case 2, with mild preoperative corneal edema due to graft failure in Descemet's stripping automated endothelial keratoplasty (DSAEK), underwent reDSAEK 6 months postoperatively. Conclusions and importance: Ex-PRESS shunt combined with ab-interno peripheral iridectomy using a small-gauge vitreous cutter may be a safe and effective surgical procedure in patients with ICE syndrome, regardless of the lens status.

Aldosterone as a Possible Contributor to Eye Diseases.

Aldosterone, an effector molecule of the renin-angiotensin-aldosterone system (RAAS), has been receiving more attention in the field of ophthalmology because of its possible role in the pathogenesis of various eye diseases or abnormalities; it may even become a target for their treatment. Primary aldosteronism, a typical model of a systemic aldosterone excess, may cause vision loss due to various ocular diseases, such as retinal vein occlusion, central serous chorioretinopathy, and, possibly glaucoma. RAAS components are present in various parts and types of cells present in the eye. Investigations of the local RAAS in various animal models of diabetic macular edema, retinal vein occlusion, retinopathy of prematurity, central serous chorioretinopathy, and glaucoma have found evidence that aldosterone or mineralocorticoid receptors may exacerbate the pathology of these disorders. Further studies are needed to elucidate whether the modulation of aldosterone or mineralocorticoid receptors is an effective treatment for preventing vision loss in patients with eye diseases.

Association of Ambulatory Blood Pressure and Other Factors With Intraocular Pressure-Related 24-Hour Contact Lens Sensor Profile in Untreated Glaucoma.

Purpose: To investigate the association of diurnal blood pressure (BP) and other factors with the intraocular pressure (IOP)-related 24-hour contact lens sensor (CLS) profile of patients with untreated glaucoma. Methods: The prospective study included 82 patients with untreated normal-tension glaucoma. CLS measurements and ambulatory BP monitoring were performed simultaneously for 24 hours. The association between the mean arterial pressure (MAP) and CLS profile was examined for the daytime and nocturnal periods using linear regression analysis. The associations between other factors and the CLS profile were also examined. Results: Multivariate analysis of data from 63 eligible patients showed that higher average MAPs were significantly associated with larger average nocturnal CLS values (ß coefficient = 0.273; P = 0.023); a larger increase in the last CLS value (ß coefficient = 0.366; P = 0.003); larger standard deviations (SDs) of CLS values for the daytime, nocturnal, and 24-hour periods (ß coefficient = 0.407, 0.293, and 0.375; P < 0.001, P = 0.032 and 0.002, respectively); and higher average ocular pulse frequencies for the daytime, nocturnal, and 24-hour periods (ß coefficient = 0.268, 0.380, and 0.403; P = 0.029, 0.002, and 0.001, respectively). Thicker subfoveal choroids and shorter axial length were significantly associated with larger SDs and larger average CLS values, respectively. Smaller anterior chamber volume and lower corneal hysteresis were associated with larger SDs or larger average ocular pulse amplitude. Conclusions: Ambulatory BP and several ocular parameters were significantly associated with various parameters of the 24-hour CLS profile. Translational Relevance: Ambulatory BP and ocular parameters may be modifiers of the 24-hour IOP-related profile of CLS.

Diurnal Variation of Corneal Hysteresis in Patients With Untreated Primary Open Angle Glaucoma and Normal Individuals.

PRCIS: Corneal hysteresis in both patients with untreated open angle glaucoma and normal individuals demonstrated significant diurnal variation independent of confounding factors and was higher in the nighttime than in the daytime. PURPOSE: To investigate diurnal variations in corneal hysteresis (CH) in patients with untreated primary open angle glaucoma (POAG) and normal individuals by using an ocular response analyzer. MATERIALS AND METHODS: This prospective study included 72 eyes of 53 patients with untreated POAG and 53 eyes of 47 normal individuals. Intraocular pressure (IOP) and CH were measured using Goldmann applanation tonometry (GAT) and ocular response analyzer, respectively, every 3 hours from 9:00 to 24:00. Mixed-effects models were used to determine factors associated with CH values and CH amplitude (maximum values minus minimum values) and to examine the diurnal variations in GAT IOP and CH in each group. Significant differences between time points were defined as significant variations. RESULTS: The diurnal average GAT IOP and CH in patients with POAG were significantly higher and lower than those in normal individuals ( P =0.001, 0.002). In the multivariate analysis, the larger central corneal thickness was associated with larger CH values in POAG and normal eyes (both P <0.001). A larger amplitude of GAT IOP was significantly associated with a larger CH amplitude in POAG and normal eyes ( P =0.010, 0.013). CH, in both groups, showed similar significant diurnal variation and was higher in the nighttime than in the daytime, even after adjusting for confounding factors, while IOP showed an antiphase pattern. CONCLUSION: CH in both untreated POAG patients and normal participants demonstrated similar diurnal variations, that is, higher at night, independent of confounding factors. These findings suggest that viscoelastic properties of the cornea may fluctuate diurnally independent of IOP.

Waveform changes of laser speckle flowgraphy in the temporal optic nerve head and peripapillary atrophy after trabeculectomy in open-angle glaucoma.

A prospective study was conducted on 33 eyes of 33 patients with open-angle glaucoma who underwent trabeculectomy to investigate hemodynamic changes in the temporal optic nerve head (ONH) and peripapillary atrophy (PPA) after trabeculectomy. Laser speckle flowgraphy of ONH and PPA was performed at baseline and at 1, 3, and 6 months postoperatively. The waveforms of the mean blur rate in the tissue area (MT) in the temporal ONH, ßPPA (with Bruch's membrane), and γPPA (without Bruch's membrane) were evaluated. Mean intra-ocular pressure (IOP) decreased from 19.1 ± 0.8 to 8.5-9.6 ± 0.7 mmHg at postoperative visits. The average MT in the ßPPA region increased significantly at all postoperative time points, whereas those in the ONH and γPPA regions remained unchanged. The blowout score (BOS) increased significantly, and the resistivity index decreased significantly at all time points in all regions, which was associated with decreased IOP. The current study showed two novel findings: MT increased after trabeculectomy only in ßPPA, where the choroid was present. IOP decrease-associated BOS increase occurred postoperatively in all regions, which indicates that IOP reduction may decrease vascular transmural pressure and contribute to stable blood flow uniformly, despite structural differences between the regions.

Comparing Surgical Outcomes in Neovascular Glaucoma between Tube and Trabeculectomy: A Multicenter Study.

OBJECTIVE: To compare the surgical outcomes between Baerveldt glaucoma implant (BGI) surgery and trabeculectomy with mitomycin C for patients with neovascular glaucoma (NVG). DESIGN: Retrospective clinical cohort study at 5 clinical centers in Japan. PARTICIPANTS: Patients treated with trabeculectomy or BGI for NVG between April 1, 2012, and December 31, 2019, at 5 clinical centers were recruited. METHODS: The inclusion criteria were age ≥ 20 years and having NVG. The exclusion criteria were eyes with no light perception vision and with previous tube-shunt surgery. If both eyes in the same patient satisfied the inclusion criteria, the eye that was treated first was investigated. We included 100 eyes undergoing BGI surgery and 204 eyes undergoing trabeculectomy. MAIN OUTCOME MEASURES: The primary outcome was surgical success or failure, with failure being defined according to 3 criteria: < 20% reduction of the preoperative intraocular pressure (IOP) or criterion A (IOP > 21 mmHg), criterion B (IOP > 17 mmHg), or criterion C (IOP > 14 mmHg). Cases of reoperation, a loss of light perception vision, or hypotony were also considered failures. RESULTS: The probability of success was significantly higher in patients undergoing BGI surgery than in those receiving trabeculectomy for criteria A (P < 0.01) and B (P = 0.01). Trabeculectomy was significantly associated with surgical failure in the multivariable analysis for criterion A (hazard ratio, 1.70) and criterion B (hazard ratio, 1.50). The overall incidence of postoperative complications was similar between the 2 groups. Reoperations for glaucoma were required significantly more frequently in the trabeculectomy group than in the BGI surgery group (20.1 % vs. 5.0%; P < 0.01). CONCLUSIONS: Baerveldt glaucoma implant surgery had a higher success rate compared with trabeculectomy in patients with NVG for a target IOP < 21 mmHg or < 17 mmHg. The rates of postoperative complications were similar between both surgical procedures. Additional glaucoma surgery was required more frequently after trabeculectomy than after BGI surgery.

Compromised Blood Flow in the Optic Nerve Head after Systemic Administration of Aldosterone in Rats: A Possible Rat Model of Retinal Ganglion Cell Loss.

PURPOSE: To investigate the optic nerve head (ONH) blood flow, retinal vessel diameters, and retinal ganglion cell (RGC) loss after systemic administration of aldosterone in rats. METHODS: Aldosterone (80 µg/kg/day) or vehicle was administered using an osmotic minipump in Brown Norway rats. The mean blur rate in the vessel (MV) and tissue (MT) regions and retinal vessel diameters in the ONH were measured by laser speckle flowgraphy before and 1, 2, and 4 weeks after administration of aldosterone or vehicle. Intraocular pressure (IOP), blood pressure, and heart rate were recorded. The retrogradely labeled RGCs were counted in the retinal flatmounts prepared 5 weeks after treatment. RESULTS: The MV and MT in the aldosterone group significantly decreased at 2 and 4 weeks (MV: 2 weeks, p = 0.001, 4 weeks, p < 0.001; MT: 2 weeks, p = 0.02, 4 weeks, p = 0.03). The artery and vein diameters significantly decreased at 1, 2, and 4 weeks in the aldosterone group (all p < 0.001). The MV, MT, and vessel diameters remained unchanged in the vehicle group. Other parameters did not change over time in either group. RGC counts were significantly lower in the aldosterone group than in the vehicle group (p < 0.001). CONCLUSIONS: ONH blood flow decreased following retinal vessel constriction without changes in IOP or blood pressure in a possible rat model of RGC loss by systemic administration of aldosterone.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

Relationship Between Changes in the Choroidal Structure and Blood Flow of the Macula After Trabeculectomy.

Purpose: To elucidate the relationship between changes in the choroidal structure and blood flow of the macula after trabeculectomy. Methods: A prospective study of 30 eyes of 30 patients with glaucoma who underwent trabeculectomy. Enhanced depth imaging optical coherence tomography with choroidal image binarization and laser speckle flowgraphy of the macula were performed at baseline and 1, 3, and 6 months postoperatively. Mixed-effects models with adjustment for confounders were used to analyze longitudinal changes in the mean choroidal thickness (mCT), mean choroidal vascular thickness (mCVT), mean choroidal interstitial thickness (mCIT), and mean blur rate (MBR). Results: The decrease in the intraocular pressure (IOP; 45%-51%) and axial length (0.5%-0.8%) and the increase in ocular perfusion pressure (OPP; 34%-38%), mCT (16%-19%), mCVT (16%-20%), mCIT (17%-20%), and MBR (22%-25%) were significant at each postoperative time point (all P < 0.001). In the multivariate analysis, the mCVT changes were positively correlated with the OPP and MBR changes (P = 0.04 and P < 0.001, respectively), whereas the mCIT changes were negatively correlated with IOP changes (P = 0.005). The MBR changes correlated significantly with changes in mCVT but not mCIT (P < 0.001 and P = 0.39, respectively). Conclusions: Thickness changes in the intraluminal and extraluminal parts of the choroid were closely associated with changes in blood flow and IOP, respectively, although both parts thickened comparably after IOP reduction by trabeculectomy. Translational Relevance: The choroid reacts to IOP reduction differently between the intraluminal and extraluminal areas, blood flow dependence in the vascular area, and IOP dependence in the stromal area.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Glaucoma-related central visual field deterioration after vitrectomy for epiretinal membrane: topographic characteristics and risk factors.

BACKGROUND/OBJECTIVES: To identify risk factors for glaucoma-related central visual field (VF) deterioration after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). SUBJECTS/METHODS: A prospective cohort study consisting of cases with or without glaucoma (33 eyes of 33 patients in each group) who underwent vitrectomy with ILM peeling for ERM. Humphrey 10-2 VFs and ganglion cell complex (GCC) thickness were measured at baseline and about 3, 6, and 12 months postoperatively. Longitudinal changes in VF indices and factors associated with their postoperative changes were investigated using mixed-effects models, as was sectorwise total deviation (TD) analysis using six sectors consisting of outer/inner arcuate and cecocentral sectors in each hemifield. RESULTS: VF mean deviation significantly deteriorated postoperatively only in the glaucoma group (P < 0.001). Older age, longer axial length, preoperative worse mean deviation, and thinner GCC were significant risk factors for postoperative deterioration (coefficient ± standard errors: -0.139 ± 0.067, -0.740 ± 0.241, 0.16 ± 0.07, 0.050 ± 0.020; P = 0.038, P = 0.002, P = 0.024, P = 0.012, respectively). Sectorwise analysis revealed that TD in the superior/inferior outer arcuate sectors significantly deteriorated only in the glaucoma group. Preoperative worse TD and thinner GCC were significant risk factors for deterioration in the superior outer arcuate sector (0.65 ± 0.11, 0.08 ± 0.03; P < 0.001, P = 0.042, respectively). CONCLUSIONS: Central VF deterioration, especially in the outer arcuate sectors, found to be glaucoma-related changes after vitrectomy with ILM peeling for ERM. Preoperative worse VF and thinner GCC were identified as risk factors for postoperative VF deterioration.