Ab interno trabeculectomy revision with 5-flourouracil for failed trabeculectomy in advanced glaucoma: 3-year outcomes.

OBJECTIVE: To describe the 3-year outcomes of patients who underwent ab interno trabeculectomy revision with a translimbal sclerostomy spatula augmented with 5-flourouracil. DESIGN: Retrospective cohort study. PARTICIPANTS: In this single-centre study, inclusion criteria included patients who were 18 years of age or older with advanced glaucoma who had undergone ab interno trabeculectomy revision with 5-flourouracil due to subconjunctival fibrosis and above-target intraocular pressure (IOP). Patients were required to have a minimum follow-up of 3 years. METHODS: The primary outcome measure was IOP. Secondary outcome measures included number of topical IOP-lowering medications, best-corrected distance visual acuity, visual field mean deviation, and postoperative complications. RESULTS: Forty-one eyes of 41 patients met the criteria for inclusion. Survival analysis demonstrated success defined by criterion A (IOP <15 mm Hg and >20% reduction) in 44% of eyes without medication (complete success) and 71% of eyes with or without medication (qualified success) at 3-year follow-up. Complete and qualified successes defined by criterion B (IOP <12 mm Hg and >20% reduction) were achieved by 31% and 44% of eyes, respectively. Early complications included transient hypotony in 26 eyes (63%) and transient hyphema in 3 eyes (7.3%). No persistent complications were reported within the 3-year study period. CONCLUSION: Ab interno trabeculectomy revision can be an effective technique for achieving a low target IOP in patients with advanced glaucoma in up to 3-year follow-up.

Variability of scan quality and perfusion density in longitudinal optical coherence tomography angiography imaging.

BACKGROUND/AIMS: Optical coherence tomography angiography (OCT-A) images are subject to variability, but the extent to which learning impacts OCT-A measurements is unknown. We determined whether there is a learning effect in glaucoma patients and healthy controls imaged with OCT-A. METHODS: Ninety-one open-angle glaucoma patients and 54 healthy controls were imaged every 4 months over a period of approximately 1 year in this longitudinal cohort study. We analysed 15°×15° scans, centred on the fovea, in one eye of each participant. Two-dimensional projection images for the superficial, intermediate and deep vascular plexuses were exported and binarised after which perfusion density was calculated. Linear mixed-effects models were used to investigate the association between perfusion density and follow-up time. RESULTS: The mean (SD) age of glaucoma patients and healthy controls was 67.3 (8.1) years and 62.1 (9.0) years, respectively. There was a significant correlation between perfusion density and scan quality in both glaucoma patients (r=0.50 (95% CI 0.42 to 0.58); p<0.05) and healthy controls (r=0.41 (95% CI 0.29 to 0.52); p<0.05). An increase in perfusion density occurred over time and persisted, even after adjustment for scan quality (1.75% per year (95% CI 1.14 to 2.37), p<0.01). CONCLUSIONS: Perfusion density measurements are subject to increasing experience of either the operator or participant, or a combination of both. These findings have implications for the interpretation of longitudinal measurements with OCT-A.

Non-arteritic anterior ischemic and glaucomatous optic neuropathy: Implications for neuroretinal rim remodeling with disease severity.

PURPOSE: Post-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies. METHODS: We compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness. RESULTS: MRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups. CONCLUSIONS: The neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON.

Efficacy and safety of ab interno trabeculectomy revision with 5-fluorouracil in advanced glaucoma due to subconjunctival fibrosis.

OBJECTIVE: To describe the outcomes of patients who underwent a single ab interno trabeculectomy revision augmented with 5-fluorouracil. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients who had undergone ab interno trabeculectomy revision at a single tertiary care centre during the 5-year study period. All patients had advanced glaucomatous optic neuropathy, and all treated ages and glaucoma subtypes were included. METHODS: Outcome measures included surgical success, number of topical intraocular pressure (IOP)-lowering drops, best-corrected visual acuity, visual field mean deviation, and postoperative complications. Success at 12 months was defined using 2 criteria: criterion A (IOP <15 mm Hg and >20% reduction) and criterion B (IOP <12 mm Hg and >20% reduction). Each success criterion was subdivided into patients who achieved success without topical IOP-lowering drops (complete success) or with topical therapy (qualified success). RESULTS: This study included 46 eyes of 46 patients. Of these, 34 patients were followed for 12 months or more to assess surgical success. Success defined by criterion A was achieved by 68% of these 34 patients (53% complete, 15% qualified). Success defined by criterion B was achieved by 47% of these patients (38% complete, 9% qualified). Early hypotony was noted in 68% of eyes but was not associated with negative visual acuity or visual field outcomes. CONCLUSIONS: An IOP of <12 mm Hg and a >20% IOP reduction were achieved by 47% of patients overall (with or without topical therapy) at 12 months of follow-up. Transient early postoperative hypotony should be expected following ab interno revision trabeculectomy.

Elucidating macular structure-function correlations in glaucoma.

Correlation between structural data from optical coherence tomography and functional data from the visual field may be suboptimal because of poor mapping of OCT measurement locations to VF stimuli. We tested the hypothesis that stronger structure-function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3° × 3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2° × 2°) OCT grid was mapped to each of the 68 locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed. Vector maps showing the maximum correlation between each VF unit and OCT pixel was generated. CMA yielded significantly higher structure-function correlations compared to LMA. Only 20% of the vectors with CMA and < 5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of structural damage more likely impact correlations compared to precise mapping of VF stimuli.

Rates of Visual Field Change in Patients With Glaucoma and Healthy Individuals: Findings From a Median 25-Year Follow-up.

Importance: Estimating the rate of glaucomatous visual field change provides practical assessment of disease progression and has implications for management decisions. Objective: To assess the rates of visual field change in patients receiving treatment for glaucoma compared with healthy individuals over an extensive follow-up period and to quantify the impact of important covariates for these rates. Design, Setting, and Participants: This prospective longitudinal cohort study was conducted in a hospital-based setting from January 1991 to February 2020. The study included 40 patients receiving treatment for open-angle glaucoma and 29 healthy participants. One eye of each participant was randomly selected as the study eye. Exposures: Patients with glaucoma and healthy participants received testing with standard automated perimetry every 6 months. Individual rates of mean sensitivity change were computed using ordinary least-squares regression analysis, and linear mixed-effects modeling was used to estimate the mean rates of mean sensitivity change in the 2 groups and the impact of baseline mean sensitivity, baseline age, and follow-up intraocular pressure for rate estimates. Main Outcomes and Measures: Rate of mean sensitivity change in patients with glaucoma and healthy participants. Results: A total of 40 patients with glaucoma (median age, 53.07 years [IQR, 48.34-57.97 years]; 21 men [52%]) and 29 healthy participants (median age, 48.80 years [IQR, 40.40-59.07 years], 17 women [59%]) were followed up for a median of 25.65 years (IQR, 22.49-27.02 years) and 19.56 years (IQR, 16.19-26.21 years), respectively. Most participants (65 individuals [94%]) self-identified as White, with the exception of 2 patients with glaucoma (1 self-identified as Black and 1 as South Asian) and 2 healthy participants (both self-identified as South Asian). The mean follow-up intraocular pressure of patients with glaucoma (median, 15.83 mm Hg [IQR, 13.05-17.33 mm Hg]) was similar to that of healthy participants (median, 14.94 mm Hg [IQR, 13.28-16.01 mm Hg]; P = .25). In an ordinary least-squares regression analysis, 31 patients (78%) with glaucoma had rates of mean sensitivity change within the range of healthy participants (ie, between -0.20 dB/y and 0.15 dB/y). Linear mixed-effects modeling revealed that the mean (SE) rate of mean sensitivity change in healthy participants was 0.003 (0.033) dB/y (95% CI, -0.062 to 0.068; P = .93). In comparison, patients with glaucoma had a mean (SE) rate of mean sensitivity change that was -0.032 (0.052) dB/y faster, but this difference was not statistically significant (95% CI, -0.134 to 0.070; P = .53). Among covariates, only baseline mean sensitivity was associated with the rate of mean sensitivity change (mean [SE], 0.021 [0.010] dB/y/dB; 95% CI, 0.002-0.041; P = .03). Conclusions and Relevance: The results of this cohort study suggest that over a median follow-up of more than 25 years, the rate of visual field change in patients receiving treatment for glaucoma was comparable to that of healthy individuals. These findings could guide practitioners in making management decisions.

Impact of Glaucoma Severity on Rates of Neuroretinal Rim, Retinal Nerve Fiber Layer, and Macular Ganglion Cell Layer Thickness Change.

PURPOSE: To determine the impact of glaucoma severity on rates of change of minimum rim width (MRW), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness. DESIGN: Prospective, cohort study. METHODS: Glaucoma patients and healthy subjects had optical coherence tomography scans at 6-month intervals. Individual rates of change for MRW, RNFL, and GCL thickness were estimated with ordinary least-squares regression. Linear mixed-effect models were used to estimate the rate of change of each parameter and evaluate the impact of glaucoma severity (expressed by visual field mean deviation, MD) and age on these rates. RESULTS: A total of 132 glaucoma patients and 57 healthy subjects were followed for a median of 4.3 years and 3.7 years, respectively. Healthy subjects had a statistically significant deterioration in MRW (-1.66 µm/year), RNFL (-0.46 µm/year), and GCL thickness (-0.22 µm/year). While glaucoma patients had a faster rate of change in each parameter compared with healthy subjects, only GCL thickness showed a statistically significant group difference (mean difference: -0.17 µm/year; P = .03). Older baseline age was associated with faster GCL thickness change (-0.07 µm/year; P = .03), but not other parameters. Baseline MD had no impact on the subsequent rates of change in any of the parameters. CONCLUSIONS: The rates of MRW, RNFL, and GCL thickness change were not significantly influenced by glaucoma severity at baseline; however, GCL thickness was able to statistically contrast the rate of change between healthy subjects and glaucoma patients throughout the disease spectrum.

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.

Value of 10-2 Visual Field Testing in Glaucoma Patients with Early 24-2 Visual Field Loss.

PURPOSE: To determine whether the 10-2 test of the Humphrey Field Analyzer detected a higher proportion of abnormal visual fields compared with the 24-2 test in the central 10° of patients with early glaucomatous visual field damage. DESIGN: Prospective observational study. PARTICIPANTS: Patients with open-angle glaucoma and healthy control participants. METHODS: All participants underwent a 24-2 and 10-2 test. Only the 12 central test locations of the 24-2 test were included to analyze equivalent visual field areas. The performance of the 2 tests was compared across 4 pointwise criteria: total deviation (TD) and pattern deviation (PD) analyses at the 5% and 2% levels. Analyses also were conducted for 2 pairs of follow-up tests, each performed 4 months apart. MAIN OUTCOME MEASURES: (1) Area under the receiver operating characteristic curve (AUC), (2) sensitivity at identically matched specificity for the 4 criteria, (3) overlap (entire field and by quadrant) of abnormal visual fields with both tests, and (4) repeatability of the findings in 2 subsequent follow-up tests. RESULTS: One eye each of 97 glaucoma patients (median mean deviation, -2.31 dB) and 65 control participants were included in the study. The AUCs for the 24-2 and 10-2 tests were not significantly different for any of the 4 criteria and ranged from 0.88 to 0.93 and from 0.91 to 0.94, respectively. At matched specificity, the sensitivity of the 24-2 test was significantly higher for all criteria except for PD analysis at 5%. In patients with an abnormal field with either test, the overlap varied from 60% to 86% depending on the criterion, whereas by quadrant, concordance ranged from 70% to 87%. Over the follow-up, the repeatability of test results (both 24-2 and 10-2 abnormal, either abnormal, or both normal) was achieved in 55% to 70% of patients. CONCLUSIONS: In this study of glaucoma patients with early damage with the 24-2 test, there was little evidence that adding the 10-2 test revealed additional undetected defects in the central visual field. It may be more prudent to reserve 10-2 testing for following up selected patients with higher risk of central visual field progression.

Discrepancy in Loss of Macular Perfusion Density and Ganglion Cell Layer Thickness in Early Glaucoma.

PURPOSE: To identify characteristics of patients with early open-angle glaucoma exhibiting greater macular perfusion density (PD) loss compared with macular ganglion cell layer (GCL) thickness loss. DESIGN: Cross-sectional study. METHODS: Optical coherence tomography (OCT) imaging of the optic nerve head and macula was conducted in patients and healthy control subjects. Minimum rim width, retinal nerve fiber layer and GCL thickness, and PD from OCT angiography were derived. Only high-quality images were included. For direct comparison, raw PD and GCL thickness values in patients were converted to relative age-corrected loss values based on data from controls. Demographic and ocular variables related to greater PD loss compared with GCL thickness loss were identified with multivariate logistic regression. RESULTS: Data from 89 patients (median mean deviation with the 24-2 and 10-2 tests, Humphrey Field Analyzer: -1.96 dB and -1.49 dB, respectively) and 54 controls were analyzed. Sixty-three (71%) patients had relatively more GCL thickness loss, whereas 26 (29%) had relatively more PD loss. More PD loss was associated with lower OCT and OCT-angiography signal strength (odds ratio [95% confidence interval], 0.64 [0.40, 0.96] and 0.60 [0.38, 0.86], per dB, respectively), thicker retinal nerve fiber layer thickness (1.08 [1.01, 1.16] per µm), and female sex (6.57 [1.25, 48.79]). CONCLUSION: Less than one-third of patients with early glaucoma had more loss of perfusion compared with conventional structural loss in the macula. Even within a range of high-quality images, lower signal strength may be at least partially responsible for apparent perfusion loss.

Asymmetry analysis of macular optical coherence tomography angiography in patients with glaucoma and healthy subjects.

BACKGROUND/AIMS: Quantitative analysis of optical coherence tomography angiography (OCT-A) images requires a reproducible approach that accounts for sectoral loss. The objective of this study was to determine whether an index that accounts for both global (perfusion density, PD) and asymmetric loss of perfusion, rather than PD alone, more reliably measures loss of perfusion in patients with glaucoma. METHODS: We analysed macular OCT-A scans of 95 glaucoma patients and 59 control subjects. Two-dimensional projection images corresponding to the superficial vascular plexus were exported and analyses performed to calculate global PD and image asymmetry. An unsigned perfusion asymmetry index (PAI) that included PD and asymmetry (with 1:1 wt) was calculated. Perfusion density and PAI were compared with 10-2 visual field mean deviation and ganglion cell layer (GCL) thickness. RESULTS: Median (IQR) visual field mean deviation was -1.73 (-3.76, 0.30) dB for the glaucoma group and 0.67 (0.16, 1.18) dB for the control group. The strength of the correlation with mean deviation was stronger for PAI (r=0.47), compared with PD (r=0.35), whereas with GCL thickness they were comparable (r=0.45 and 0.43, respectively). Compared with controls, mean PD was 12% lower in patients with glaucoma (0.27 vs 0.30), while PAI was 17% lower (0.40 vs 0.48). However, diagnostic accuracy of either PD or PAI was worse than GCL thickness. CONCLUSIONS: While PAI yielded better correlation with mean deviation and GCL thickness, and a slightly improved separation between patients with glaucoma and healthy controls, diagnostic accuracy was inferior compared with GCL thickness.

Evaluating selective laser trabeculoplasty versus argon laser trabeculoplasty in pseudoexfoliation glaucoma patients.

OBJECTIVE: Laser trabeculoplasty effectively reduces intraocular pressure (IOP) in primary open angle glaucoma, with argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) showing equivalent outcomes. However, it is unclear which laser modality is more effective in pseudoexfoliation (PXE) glaucoma. This study aims to compare the effectiveness of ALT and SLT in PXE glaucoma. DESIGN: Retrospective cohort study. METHODS: A chart review evaluating patients diagnosed with PXE glaucoma and treated with laser trabeculoplasty from 2005-2015. Patients with previous glaucoma surgery, other forms of secondary glaucoma, ocular surgery within six months of initial trabeculoplasty or lacking preoperative IOP measurements were excluded. Post-laser measurements were recorded until 24 months after initial intervention. Follow-up data was censored if the patient underwent a subsequent trabeculoplasty different from initial laser treatment. RESULTS: We included 84 patients in the ALT group and 123 in the SLT group. The mean (SD) baseline IOP values were 22.7 (±5.6) and 21.6 (±4.8) respectively (p = 0.11), while number of medications were 2.0 (±1.0) and 1.8 (±1.3) for ALT and SLT groups respectively (p = 0.36). The mean IOP reduction for the ALT group at 6, 12 and 24 months were 5.2 (±6.1), 5.4 (±6.9), and 4.9(±7.7) respectively. The corresponding values for the SLT group were 3.4 (±5.2), 3.8 (±4.6), and 4.6 (±6.5). Comparison of both lasers at each time point revealed no significant differences (p > 0.05) in IOP reduction or reduction of glaucoma medication. CONCLUSIONS: Our study showed equivalent efficacy between ALT and SLT in patients with PXE glaucoma.

The optimal trabeculectomy: patient and procedure.

Guarded external fistulization procedures remain important surgical options for patients who are experiencing progressive vision loss caused by glaucoma. The progenitor procedure, the trabeculectomy, has undergone continuous modifications over the past 40 or more years, rendering the surgery safer and the outcomes more predictable. Studies are cumulating to show that very low intraocular pressures can both reduce glaucomatous vision loss and positively change the rate of progression. Optimal patient selection and patient preparation, as well as some guiding procedural principles, are described in this review.

Rates of glaucomatous visual field change in a large clinical population.

PURPOSE: To determine the rate of glaucomatous visual field change in routine clinical care. METHODS: Mean deviation (MD) rate was computed in one randomly selected eye of all glaucoma patients and suspects with ≥5 examinations in a tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed in tertile groups by the number of examinations, baseline age, and MD. The MD rates were compared to the Canadian Glaucoma Study (CGS), a prospective study with IOP interventions mandated by visual field progression, by pairwise matching of patients by baseline MD. RESULTS: There were 2324 patients with median (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, -0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was 17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of fast and catastrophic progressors, with each tertile of increasing age. Worse MD rate was associated with lower follow-up IOP. Neither MD rate nor the number of fast and catastrophic progressors was significantly different in clinical care patients matched to CGS patients. CONCLUSIONS: Most patients under routine glaucoma care demonstrate slow rates of visual field progression. The MD rate in the current study was similar to an interventional prospective study, but considerably less negative compared to published studies with similar design.