Ophthalmology. Glaucoma最新文献

Purpose: Glaucoma is a leading cause of irreversible blindness. While polygenic risk scores (PRSs) have shown promise for patient risk stratification, their consistency and reliability across diverse populations remain insufficiently characterized. This study aimed to determine whether published glaucoma PRSs demonstrate consistent population-level performance and individual-level risk assignment in 2 large, multiethnic cohorts.

Design: A cross-sectional study.

Participants: A total of 243 300 individuals (7190 open-angle glaucoma [OAG] cases; 236 110 controls) from the All of Us (AoU) Research Program and 30 306 individuals (1899 cases; 28 407 controls) from the Mass General Brigham (MGB) biobank were included. Participants were aged ≥35 years with available genotype and electronic health record phenotype data.

Methods: We evaluated the performance of 11 published glaucoma PRSs in the Polygenic Score Catalog using logistic regression models. The agreement of PRSs in risk classification was evaluated using Pearson correlation and Jaccard index.

Main outcome measures: Associations between cataloged PRSs and OAG and agreement of PRSs in risk classification.

Results: Higher PRSs were all significantly associated with higher odds of OAG; odds ratios (ORs) (per standard deviation) ranged from 1.17 to 1.41 (AoU) and 1.17 to 1.57 (MGB). In AoU, associations were strongest in individuals of European ancestry (ORs 1.22-1.55) and attenuated in African (1.08-1.21) and admixed American (1.09-1.33) ancestries. Despite consistent population-level performance, individual risk concordance across PRSs was low: median Pearson r = 0.42 (interquartile range, 0.35-0.50) and median Jaccard index = 0.16 (interquartile range, 0.13-0.19) for high-risk classification. This discordance persisted across cases, controls, ancestries, and both cohorts.

Conclusions: Our results demonstrate that while PRSs predict glaucoma risk at the cohort level, their instability at the individual level limits stand-alone clinical application. Polygenic risk scores should therefore be considered adjuncts to established glaucoma risk factors. Future work should prioritize developing tools to assess individual PRS reliability and standardizing analytic methods to improve comparability and clinical applicability.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To evaluate the reliability and concordance of visual field (VF) assessments conducted unsupervised at home using the web-browser-based Melbourne Rapid Fields (MRF) online perimetry system, in comparison with conventional supervised clinic-based Humphrey Field Analyzer Swedish Interactive Threshold Algorithm (SITA)-Faster (HFA-SFr) testing.

Design: Prospective observational comparison study.

Subjects/participants: Fifty-three glaucoma patients.

Methods: Fifty-three patients with glaucoma with prior experience using MRF platform were recruited. Participants completed bilateral 24-2 white-on-white automated perimetry tests at home using the MRF online system on their own personal computers. Humphrey Field Analyzer SITA-Faster results from the most recent clinic visits served as the comparator. Data from the first 3 months of home monitoring were analyzed in this study. Test-retest variability and agreement between MRF and HFA-SFr were analyzed using Bland-Altman plots and intraclass correlation coefficients (ICCs). Regional analysis was conducted using Garway-Heath structurally defined zones.

Main outcome measures: Mean deviation (MD), pattern deviation/pattern standard deviation (PD/PSD), test-retest variability, agreement between home-based MRF and clinic-based HFA-SFr, and regional visual field variability.

Results: Participants comprised 19 preperimetric, 23 early, 6 moderate, and 5 advanced glaucoma cases. Visual field testing with MRF performed at home showed strong correlation for mean deviation (MD) values with HFA-SFr (ICC = 0.905) and moderate correlation for pattern deviation (PD)/pattern standard deviation (ICC = 0.685). Test-retest for MRF also showed strong correlation for MD (ICC = 0.983) and PD/pattern standard deviation (ICC = 0.947). Test-retest variability between MRF tests found a bias of -0.18 dB and 95% limits of agreement of (-2.97, 2.62 dB) for MD, and a bias of +0.21 dB and 95% limits of agreement of (-2.29, 2.68 dB) for PD. Zone-specific analysis showed that the temporal zone has a higher degree of test-retest variability compared with other zones.

Conclusions: Melbourne Rapid Fields online perimetry is a reliable and clinically valid tool for monitoring VF at home in glaucoma cases. Future study of a larger sample size and a more diverse cohort is required to assess its potential for teleophthalmology management of glaucoma and earlier detection of disease progression.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To assess glaucoma prevalence and its determinants in an aged population.

Design: Population-based cohort study.

Participants: The population-based Ural Very Old Study was performed in a rural area and urban region of Bashkortostan/Russia and consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85+ years.

Methods: The study participants underwent a structured interview and a detailed ocular and systemic examination. The presence and degree of glaucoma were assessed on conventional color fundus photographs, red-free fundus images, and OCT images.

Main outcome measures: Prevalence and associations of glaucoma.

Results: Among 961 individuals with available fundus images, glaucomatous optic neuropathy was detected in 116 of 840 right eyes (13.8%; 95% confidence interval [CI]: 11.3-16.3) and 122 of 841 left eyes (14.5%; 95% CI: 12.0-17.0), with overall 148 participants (15.4%) having glaucoma. Out of 111 right and 116 left eyes with glaucoma and measurement of best-corrected visual acuity (BCVA), 18 (16%) and 20 (17%) eyes were blind, respectively (BCVA: <3/60), and 61 (55%) and 63 (54%) eyes had moderate-to-severe vision impairment (MSVI), respectively (BCVA: <6/18 and ≥3/60). In 24 of 38 glaucomatous blind eyes (63%) and 50 of the 124 glaucomatous eyes (40.3%) with MSVI, vision loss was caused by glaucoma. The ratio of open-angle glaucoma to angle-closure glaucoma was 71% to 29%. The prevalence of angle-closure glaucoma was markedly higher in phakic glaucomatous eyes (62/113; 54.9%) than in pseudophakic glaucomatous eyes (6/125; 4.8%). Best-corrected visual acuity did not differ (P = 0.56) between open-angle glaucoma and angle-closure glaucoma. Among 148 participants with glaucoma, 54 (36.5%) individuals were under therapy. Intraocular pressure (IOP) was ≤21 mmHg in 83% of glaucomatous eyes without antiglaucomatous therapy. Higher prevalence (and severity) of glaucoma correlated with longer axial length (odds ratio [OR]: 1.43; 95% CI: 1.14-1.78; P = 0.002), higher IOP (OR: 1.14; 95% CI: 1.07-1.22; P < 0.001), higher prevalence of pseudoexfoliation (OR: 1.39; 95% CI: 1.17-1.65; P < 0.001), and older age (OR: 1.15; 95% CI: 1.04-1.27; P = 0.008).

Conclusions: In this population-based recruited multiethnic cohort aged 85+ years, the prevalence factors of glaucoma-related blindness and MSVI were relatively high, and the majority of glaucomatous eyes were untreated and had single IOP readings of ≤21 mmHg. As in younger cohorts, higher glaucoma prevalence was associated with longer axial length, in addition to higher IOP and older age.

Financial disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose: The prevalence of glaucoma increases with age and as life expectancy rises, the number of glaucoma patients in their 10th decade of life will increase. Here we aimed to assess the usefulness of glaucoma diagnostic testing in the very old and identify ways to improve testing reliability.

Design: Cohort study.

Subjects: Patients aged 90-99 years who were seen in our university-based glaucoma division between February 1, 2020, and May 10, 2023.

Methods: All Swedish Interactive Testing Algorithm-Standard 24-2 visual fields (VFs) performed by subjects were collected. Reliability indices and summary metrics were recorded.

Main outcome measures: Rate of reliable VF tests among individuals aged 90 years or older at the time of the test. The main criterion for a reliable field was a false-positive (FP) rate <15%. The effect of age, gender, and time of testing on FP, false-negative (FN), fixation losses (FLs), and test duration were also evaluated.

Results: A total of 3951 VF tests were collected from 289 patients (530 eyes) who met the inclusion criteria. The mean age at the time of the most recent VF was 92.8 ± 2.3 years. One hundred six (7.5%) of the VFs were unreliable based on the FP<15% criteria. Testing after age 90 increased the rate of FP, FN, and FL (all P < 0.001) compared to tests performed at a younger age. In addition, among VF performed by nonagenarians, tests performed in the afternoon were associated with statistically significant higher rates of FP (P < 0.01). A higher FP was also found among the eyes tested first. Testing in the afternoon was also associated with significantly increased FN rates (P < 0.05).

Conclusions: In the very old, reliable perimetry can be obtained. Reliability deteriorates with age and testing should be performed in the morning to maximize performance.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective: Pigment dispersion syndrome (PDS) is a known risk factor for glaucoma, with at least 1 in 10 patients with PDS developing glaucoma. There are no standardized clinical tools to stratify the risk of glaucoma onset or progression in the context of PDS. This study investigated whether multitrait polygenic risk scores (PRSs) built from variants collectively associated with open-angle glaucoma, intraocular pressure (IOP), and vertical cup:disc ratio (VCDR) could stratify individuals with PDS for their risk of glaucoma development.

Design: Cross-sectional study of 2 independent PDS cohorts: the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG, n = 264), and the Glaucoma Services at the University of Iowa Carver College of Medicine (n = 203).

Participants: Participants of European ancestry with PDS were classified as PDS-Glaucoma (n = 288), PDS-Glaucoma Suspect (n = 110), or PDS-No Glaucoma (n = 69).

Methods: Previously published and validated PRS for open-angle glaucoma, IOP, and VCDR were expressed as a percentile or quintile of an ancestrally matched normal population. Multivariable logistic and linear regressions and survival analyses were performed.

Main outcome measures: Odds of pigmentary glaucoma and odds of clinically relevant outcomes.

Results: Participants from ANZRAG with PDS in the top quintile of an open-angle glaucoma-PRS had greater odds of glaucoma diagnosis compared with the bottom quintile (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 1.57-21.28; P = 0.011). This observation was replicated among participants with PDS from the University of Iowa (adjusted OR, 4.07; 95% CI, 1.24-13.85; P = 0.021). Among those with PDS-Glaucoma across both cohorts combined, participants in the top quintile of glaucoma-PRS compared with the bottom quintile were diagnosed 8 years earlier (95% CI, 5.17-10.41; P < 0.001), recorded a maximum IOP 8 mmHg higher (95% CI, 2.89-11.95; P = 0.001), were at greater risk of escalation to incisional surgery (adjusted OR, 1.37; 95% CI, 1.03-1.87; P = 0.038), and were at greater risk of additional incisional surgeries to the same eye (adjusted OR, 1.27; 95% CI, 1.08-1.52; P = 0.006). A PRS for IOP also differentiated pigmentary glaucoma status; a PRS for VCDR did not.

Conclusions: A multitrait PRS for open-angle glaucoma stratifies risk of glaucoma onset and disease severity among individuals with PDS.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: Little is known about how medication adherence is related to longitudinal structural and functional losses. Here, we investigate the associations between medication adherence with mean intraocular pressure (IOP) measurements, explore whether adherence predicts rates of change in mean deviation (MD) and retinal nerve fiber layer thickness (RNFLT), and identify factors associated with worse adherence using a large sample of glaucoma and glaucoma suspect eyes.

Design: A retrospective longitudinal cohort study.

Participants: Adults with glaucoma or glaucoma suspect status in at least 1 eye, defined by ICD code H40. All eyes had a minimum of five visual field or OCT tests over time.

Methods: Proportion of days covered (PDC), defined as the proportion of days a patient has access to their medication over a given period using pharmacy refill data, was used to assess adherence. Multivariable linear mixed-effects models were used to investigate the relationship between PDC with mean IOP and rates of change in both MD and RNFLT. Similar models were employed to examine predictors of PDC.

Main outcome measures: Mean IOP, rates of change in MD, and RNFLT.

Results: A total of 13 670 eyes from 8163 patients were included with a median (interquartile range) PDC of 60 (40.9-77.5). Below the 60% adherence threshold (median), each 10% decrease in PDC was associated with higher mean IOP (β = 0.82 mmHg, P < 0.001), while the association showed a smaller effect size above the median (β = 0.37 mmHg, P < 0.001). Proportion of days covered was associated with -0.03 units/year faster rates of MD and RNFLT loss (P < 0.01). Predictors of worse PDC included female gender (β = -1.22%, P = 0.02; vs. males), Black race (β = -5.04%, P < 0.001; vs. White), worse baseline MD (β = -0.23%, P = 0.01; per 5 decibel decrease), lower baseline RNFLT (β = -0.17%, P = 0.03; per 10 μm thinner), using two eye drops (β = -6.37%, P < 0.001; vs. 1), and unilateral drop use (β = -8.85%, P < 0.001; vs. bilateral).

Conclusions: Lower adherence was associated with higher IOP, with a stronger effect seen at PDC values below the median, and accelerated glaucomatous damage, including faster rates of MD deterioration and increased RNFLT loss. Lower adherence was associated with female gender, Black race, greater baseline damage, greater number of drops, and unilateral drop use.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To evaluate the effectiveness of transscleral diode laser cyclophotocoagulation in a population of patients with refractory glaucoma, comparing the results between the slow-coagulation continuous-wave cyclophotocoagulation (SC-CPC) and micropulse laser treatment (MP-LT) techniques.

Design: Prospective 2-center randomized clinical trial.

Subjects: Sixty eyes from 60 patients with medically uncontrolled glaucoma under maximum therapy and no prior cyclodestructive procedures.

Methods: Patients were enrolled at 2 centers and randomly assigned to laser treatment with SC-CPC or MP-LT. The technique was standardized (1250 mW, 4 s/spot, 20 spots for SC-CPC; 2000 mW, 90 s/quadrant, 31.3% duty-cycle for MP-LT; the 3- and 9-o'clock meridians were spared in both groups). Success was defined as postoperative intraocular pressure (IOP) between 6 and 18 mmHg and ≥20% reduction, without the need for additional glaucoma surgery or clinically significant visual acuity loss, including loss of light perception.

Main outcome measures: Treatment success over 18 months. The secondary outcome measures included postoperative IOP, number of IOP-lowering medications, need for retreatments, postoperative complications, and visual acuity throughout follow-up.

Results: Treatment success was achieved in 70.0% of SC-CPC eyes and 30.0% of MP-LT eyes (log-rank test, P = 0.001), with a lower cumulative failure probability in the SC-CPC group (33.4% vs. 70.4%). At the last visit, the mean IOP was significantly lower in the SC-CPC group compared to the MP-LT group (18.4 ± 12.9 mmHg vs. 22.5 ± 9.3 mmHg; P = 0.005), with a greater percentage reduction from baseline (23.1% vs. 11.5%; P = 0.020). The SC-CPC group required fewer IOP-lowering medications at final follow-up (2.1 ± 1.1 vs. 2.7 ± 1.1; P = 0.020). Repeated treatments and additional surgeries were more frequent in the MP-LT group.

Conclusions: Slow-coagulation continuous-wave cyclophotocoagulation demonstrated superior IOP control and lower surgical failure rates compared to MP-LT. These findings support SC-CPC as a more effective option for refractory glaucoma.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To compare 10-2 visual field (VF) test results obtained with the Swedish Interactive Threshold Algorithm (SITA) Standard and those obtained with a family of variational Bayes linear regression (VBLR) VF algorithms-VBLR-VF (standard program), VBLR-VF Fast, and VBLR-VF Fast+-in patients with glaucoma.

Design: Multicenter prospective observational cohort study.

Participants: One eye from each of 133 patients with glaucoma.

Methods: Among the 133 patients, 43 underwent VBLR-VF and the SITA-Standard, 45 underwent VBLR-VF Fast and the SITA-Standard, and 45 underwent VBLR-VF Fast+ and the SITA-Standard, all of which were performed with the 10-2 test program on the same day. Each test pair was repeated within 6 months in reverse order.

Main outcome measures: The mean deviation (MD), pattern standard deviation (PSD), pointwise VF sensitivity, test-retest repeatability (root mean square error [RMSE]), and test duration were compared between the SITA-Standard and each VBLR-VF algorithm.

Results: There was no significant difference in MD between the SITA-Standard and VBLR-VF. In contrast, the MD values obtained with VBLR-VF Fast and Fast+ were significantly greater than those obtained with the SITA-Standard by 0.61 to 0.81 dB (P < 0.01). Pattern standard deviation with the VBLR-VF method was 0.62 dB greater than that with the SITA-Standard in the second test (P < 0.01), whereas there was no significant difference in the first test. No significant differences in PSD were detected between VBLR-VF Fast or Fast+ and the SITA-Standard. The pointwise VF sensitivities with VBLR-VF were 0.8 to 0.9 dB lower than those with the SITA-Standard (P < 0.01), whereas 0.2 dB higher values were observed with VBLR-VF Fast and Fast+ (P < 0.05). The RMSE did not significantly differ between any of the VBLR-VF algorithms and the SITA-Standard. Test durations with VBLR-VF, VBLR-VF Fast, and VBLR-VF Fast+ at the first visit were significantly shorter than those with the SITA-Standard by 12.2%, 37.8%, and 46.3%, respectively, and were further reduced at the second visit by 10.5%, 26.0%, and 26.3%, respectively (all P < 0.01).

Conclusions: All the VBLR-VF algorithms substantially reduced the test duration while maintaining repeatability. Significant or nonsignificant minor differences in 10-2 VF sensitivity were observed between the SITA-Standard and the VBLR-VF algorithms.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To examine the effect of 24-hour ambulatory blood pressure (BP) measurements on the rates of change in central and peripheral visual field (VF) loss in eyes with glaucoma and suspected glaucoma.

Design: Prospective cohort study.

Participants: One hundred twenty-four eyes of 63 subjects with glaucoma or suspect of glaucoma at baseline.

Methods: Participants underwent 24-hour ambulatory BP measurement acquired at the baseline visit and 24-2C standard automated perimetry (SAP) every 4 months for up to 48 months. The rates of change in mean sensitivity (MS) were calculated with linear mixed models and used to investigate the effect of BP on the rates of VF loss in the central (≤10°, 26 points) and peripheral (>10°, 36 points) regions separately. Models were adjusted for age, gender, race, intraocular pressure during follow-up, baseline glaucoma severity, and central corneal thickness.

Main outcome measures: Effect of 24-hour BP values on the rates of future central and peripheral VF loss.

Results: Eyes had an average of 7.7 ± 2.2 SAP tests over 27.4 ± 6.4 months of follow-up. The median rate in global mean deviation change was 0.23 dB/year (range -1.00 to 0.94 dB/year). Each 10 mmHg lower in 24-hour average systolic BP (SBP) and diurnal mean arterial pressure (MAP) were associated with -0.119 dB/year (P = 0.021) and -0.162 dB/year (P = 0.018) faster rates of MS loss in the central region, respectively, after adjusting for confounding factors. Lower diurnal MAP was also significantly associated (P = 0.003) with faster progression in the peripheral VF. Eyes of subjects within the lowest tertile of average 24-hour SBP (range 100-116 mmHg) had significantly faster rates of central VF loss than the highest tertile (range 125-168 mmHg; difference between tertiles 0.06 dB/year faster; P = 0.045), but not faster peripheral loss (P = 0.101).

Conclusions: Lower baseline 24-hour ambulatory BP measurements were significantly associated with faster rates of SAP progression in the central and peripheral regions. Subjects with the lowest values of average 24-hour SBP demonstrated significantly faster rates of central VF loss and may be used as a predictor for severe glaucomatous progression.

Financial disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.