Blood Pressure and Glaucomatous Progression in a Large Clinical Population.

PURPOSE: To investigate the effect of systemic arterial blood pressure (BP) on rates of progressive structural damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 7501 eyes of 3976 subjects with glaucoma or suspected of glaucoma followed over time from the Duke Glaucoma Registry. METHODS: Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer (RNFL) loss from spectral-domain OCT (SD-OCT) over time. Models were adjusted for intraocular pressure (IOP), gender, race, diagnosis, central corneal thickness (CCT), follow-up time, and baseline disease severity. MAIN OUTCOME MEASURE: Effect of mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) on rates of RNFL loss over time. RESULTS: A total of 157 291 BP visits, 45 408 IOP visits, and 30 238 SD-OCT visits were included. Mean rate of RNFL change was -0.70 µm/year (95% confidence interval, -0.72 to -0.67 µm/year). In univariable models, MAP, SAP, and DAP during follow-up were not significantly associated with rates of RNFL loss. However, when adjusted for mean IOP during follow-up, each 10 mmHg reduction in mean MAP (-0.06 µm/year; P = 0.007) and mean DAP (-0.08 µm/year; P < 0.001) but not SAP (-0.01 µm/year; P = 0.355) was associated with significantly faster rates of RNFL thickness change over time. The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity, and corneal thickness. CONCLUSIONS: When adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic BP may be a significant factor in glaucoma progression.

Predicting Vision-Related Disability in Glaucoma.

PURPOSE: To present a new methodology for investigating predictive factors associated with development of vision-related disability in glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Two hundred thirty-six patients with glaucoma followed up for an average of 4.3±1.5 years. METHODS: Vision-related disability was assessed by the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at baseline and at the end of follow-up. A latent transition analysis model was used to categorize NEI VFQ-25 results and to estimate the probability of developing vision-related disability during follow-up. Patients were tested with standard automated perimetry (SAP) at 6-month intervals, and evaluation of rates of visual field change was performed using mean sensitivity (MS) of the integrated binocular visual field. Baseline disease severity, rate of visual field loss, and duration of follow-up were investigated as predictive factors for development of disability during follow-up. MAIN OUTCOME MEASURES: The relationship between baseline and rates of visual field deterioration and the probability of vision-related disability developing during follow-up. RESULTS: At baseline, 67 of 236 (28%) glaucoma patients were classified as disabled based on NEI VFQ-25 results, whereas 169 (72%) were classified as nondisabled. Patients classified as nondisabled at baseline had 14.2% probability of disability developing during follow-up. Rates of visual field loss as estimated by integrated binocular MS were almost 4 times faster for those in whom disability developed versus those in whom it did not (-0.78±1.00 dB/year vs. -0.20±0.47 dB/year, respectively; P < 0.001). In the multivariate model, each 1-dB lower baseline binocular MS was associated with 34% higher odds of disability developing over time (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.06-1.70; P = 0.013). In addition, each 0.5-dB/year faster rate of loss of binocular MS during follow-up was associated with a more than 3.5 times increase in the risk of disability developing (OR, 3.58; 95% CI, 1.56-8.23; P = 0.003). CONCLUSIONS: A new methodology for classification and analysis of change in patient-reported quality-of-life outcomes allowed construction of models for predicting vision-related disability in glaucoma.

The Impact of Location of Progressive Visual Field Loss on Longitudinal Changes in Quality of Life of Patients with Glaucoma.

PURPOSE: To evaluate the association between rates of progressive loss in different regions of the visual field and longitudinal changes in quality of life (QoL). DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study included 236 patients with glaucomatous visual field loss followed for an average of 4.3±1.5 years. METHODS: All subjects had the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) performed annually and standard automated perimetry (SAP) at 6-month intervals. Subjects were included if they had a minimum of 2 NEI VFQ-25 and 5 SAP tests during follow-up. Evaluation of rates of visual field change was performed using 4 different regions (central inferior, central superior, peripheral inferior, and peripheral superior) of the integrated binocular visual field. The association between change in NEI VFQ-25 Rasch-calibrated scores and change in different regions of the visual field was investigated with a joint multivariable longitudinal linear mixed model. MAIN OUTCOME MEASURES: The relationship between change in QoL scores and change of mean sensitivity in different regions of the visual field. RESULTS: There was a significant correlation between change in the NEI VFQ-25 Rasch scores during follow-up and change in different regions of the visual field. Each 1 decibel (dB)/year change in binocular mean sensitivity of the central inferior area was associated with a decline of 2.6 units/year in the NEI VFQ-25 scores (R(2) = 35%; P < 0.001). Corresponding associations with change in QoL scores for the peripheral inferior, central superior, and peripheral superior areas of the visual field had R(2) values of 30%, 24%, and 19%, respectively. The association for the central inferior visual field area was statistically significantly stronger than those of the central superior area (P = 0.011) and peripheral superior area (P = 0.001), but not the peripheral inferior area (P = 0.171). Greater declines in NEI VFQ-25 scores were also seen in patients who had worse visual field sensitivity at baseline. CONCLUSIONS: Progressive decline in sensitivity in the central inferior area of the visual field had the strongest association with longitudinal decline in QoL of patients with glaucoma.

Five-year treatment outcomes in the Ahmed Baerveldt comparison study.

PURPOSE: To compare the 5-year outcomes of the Ahmed FP7 Glaucoma Valve (AGV) (New World Medical, Cucamonga, CA) and the Baerveldt 101-350 Glaucoma Implant (BGI) (Abbott Medical Optics, Abbott Park, IL) for the treatment of refractory glaucoma. DESIGN: Multicenter, randomized, controlled clinical trial. PARTICIPANTS: A total of 276 patients, including 143 in the AGV group and 133 in the BGI group. METHODS: Patients aged 18 to 85 years with previous intraocular surgery or refractory glaucoma and intraocular pressure (IOP) of ≥18 mmHg in whom glaucoma drainage implant (GDI) surgery was planned were randomized to implantation of an AGV or a BGI. MAIN OUTCOME MEASURES: Surgical failure, IOP, visual acuity (VA), use of glaucoma medications, and complications. RESULTS: At 5 years, IOP (mean ± standard deviation [SD]) was 14.7±4.4 mmHg in the AGV group and 12.7±4.5 mmHg in the BGI group (P = 0.015). The number of glaucoma medications in use at 5 years (mean ± SD) was 2.2±1.4 in the AGV group and 1.8±1.5 in the BGI group (P = 0.28). The cumulative probability of failure during 5 years of follow-up was 44.7% in the AGV group and 39.4% in the BGI group (P = 0.65). The number of subjects failing because of inadequately controlled IOP or reoperation for glaucoma was 46 in the AGV group (80% of AGV failures) and 25 in the BGI group (53% of BGI failures; P = 0.003). Eleven eyes in the AGV group (20% of AGV failures) experienced persistent hypotony, explantation of implant, or loss of light perception compared with 22 eyes (47% of failures) in the BGI group. Change in logarithm of the minimum angle of resolution VA (mean ± SD) at 5 years was 0.42±0.99 in the AGV group and 0.43±0.84 in the BGI group (P = 0.97). CONCLUSIONS: Similar rates of surgical success were observed with both implants at 5 years. The BGI produced greater IOP reduction and a lower rate of glaucoma reoperation than the AGV, but the BGI was associated with twice as many failures because of safety issues.

Three-year treatment outcomes in the Ahmed Baerveldt comparison study.

PURPOSE: To compare 3-year outcomes and complications of the Ahmed FP7 Glaucoma Valve (AGV) (New World Medical, Cucamonga, CA) and the Baerveldt Glaucoma Implant (BGI) 101-350 (Abbott Medical Optics, Abbott Park, IL) for the treatment of refractory glaucoma. DESIGN: Multicenter, randomized, controlled clinical trial. PARTICIPANTS: A total of 276 patients: 143 in the AGV group and 133 in the BGI group. METHODS: Patients aged 18 to 85 years with refractory glaucoma and intraocular pressures (IOPs) ≥ 18 mmHg in whom an aqueous shunt was planned were randomized to an AGV or a BGI. MAIN OUTCOME MEASURES: The IOP, visual acuity (VA), supplemental medical therapy, complications, and failure (IOP >21 mmHg or not reduced by 20% from baseline, IOP <5 mmHg, reoperation for glaucoma or removal of implant, or loss of light perception vision). RESULTS: At 3 years, IOP (mean ± standard deviation) was 14.3 ± ± 4.7 mmHg (AGV group) and 13.1 ± 4.5 mmHg (BGI group) (P = 0.086) on 2.0 ± 1.4 and 1.5 ± 1.4 glaucoma medications, respectively (P = 0.020). The cumulative probabilities of failure were 31.3% (standard error [SE], 4.0%) (AGV) and 32.3% (4.2%) (BGI) (P = 0.99). Postoperative complications associated with reoperation or vision loss of >2 Snellen lines occurred in 24 patients (22%) (AGV) and 38 patients (36%) (BGI) (P = 0.035). The mean change in the logarithm of the minimum angle of resolution VA at 3 years was similar (AGV: 0.21 ± 0.88, BGI: 0.26 ± 0.74) in the 2 treatment groups at 3 years (P = 0.66). The cumulative proportion of patients (SE) undergoing reoperation for glaucoma before the 3-year postoperative time point was 14.5% (3.0%) in the AGV group compared with 7.6% (2.4%) in the BGI group (P = 0.053, log rank). The relative risk of reoperation for glaucoma in the AGV group was 2.1 times that of the BGI group (95% confidence interval, 1.0-4.8; P = 0.045, Cox proportional hazards regression). CONCLUSIONS: Implantation of the AGV was associated with the need for significantly greater adjunctive medication to achieve equal success relative to implantation of the BGI and resulted in a greater relative risk of reoperation for glaucoma. More subjects experienced serious postoperative complications in the BGI group than in the AGV group.

Mitomycin C 0.2 mg/ml versus Mitomycin C 0.4 mg/ml during the Implantation of an Ab Externo Polystyrene-isobutylene-styrene Microshunt: A Mega-analysis.

PURPOSE: To compare the effectiveness and adverse event profile of standalone polystyrene-isobutylene-styrene (SIBS) microshunt implantation with adjunct mitomycin C (MMC) 0.2 mg/ml and MMC 0.4 mg/ml. DESIGN: Mega-analysis using individual patient data from international prospective and retrospective clinical studies. PARTICIPANTS: Patients with glaucoma who underwent implantation of a SIBS microshunt with MMC as a standalone procedure. METHODS: A comparison of eyes that received MMC 0.2 mg/ml or 0.4 mg/ml. MAIN OUTCOMES MEASURES: Primary outcome was complete success defined as the proportion of eyes at 1 year with all of the following: (1) no 2 consecutive intraocular pressures (IOPs) > 17 mmHg; (2) no clinical hypotony; (3) ≥ 20% IOP reduction from baseline; and (4) no use of glaucoma medications. Secondary outcomes included IOP thresholds of 12 mmHg, 14 mm Hg, and 21 mmHg, median IOP, number of medications, risk factors for failure, interventions, adverse events, and reoperations. RESULTS: At 1 year, the complete success rate was significantly higher (71.3% vs. 50.46%; P < 0.001) and the median IOP was significantly lower (13.0 vs 14.2 mmHg; P < 0.05) in the MMC 0.4 mg/ml group. Mitomycin C 0.2 mg/ml was found to be a significant risk factor for failure (hazard ratio 1.75; 95% confidence interval 1.14-2.67). Needling and surgical revision occurred at a lower rate in the MMC 0.4 mg/ml group (7% vs 18.8%; P = 0.002 and 4.3% vs 13.7% P = 0.0087, respectively). Adverse events occurred at a similar frequency in both groups (26.6% MMC 0.2 mg/ml vs 29.6% MMC 0.4 mg/ml; P = 0.46), most of which were early and transient. CONCLUSION: Polystyrene-isobutylene-styrene microshunt implantation with MMC 0.4 mg/ml resulted in a higher success rate with greater IOP reduction compared with MMC 0.2 mg/ml. Higher MMC concentration was not associated with increased serious adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Trabeculectomy in Eyes With High Myopia.

PRCIS: Primary trabeculectomy was safe and effective at lowering intraocular pressure (IOP) in patients with primary open angle glaucoma and high myopia. PURPOSE: To investigate the efficacy and safety of trabeculectomy in patients with glaucoma and high myopia. PATIENT AND METHODS: Retrospective case-control study. Glaucomatous patients with high myopia undergoing primary trabeculectomy surgery with at least 1 year of follow-up were compared with an age-matched control group without high myopia undergoing the same procedure. Surgical success was defined as: IOP ≤ 15 mm Hg with (qualified) or without (complete) antiglaucoma medications and at least 20% reduction from baseline IOP at the end of 48 months of follow-up. RESULTS: We included a total of 90 eyes from 90 patients (45 eyes with high myopia and 45 controls). Within the 90 eyes, 70 eyes underwent trabeculectomy and 20 eyes underwent combined phacoemulsification and trabeculectomy. Although patients with high myopia had higher chances for failure (37% vs. 22%) compared with controls, the difference was not statistically significant ( P =0.067). In the multivariable analysis, patients of African descent ( P =0.043) and those with juvenile glaucoma ( P =0.001) had more chances of failure, even after adjusting for myopia. There was no statistically significant difference between complication rates in both groups. CONCLUSION: Trabeculectomy was effective in reducing IOP in patients with high myopia and glaucoma, without the additional risk of complications compared with a control group.

Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness for Diagnosing Early to Moderate Glaucoma.

PRCIS: In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes. PURPOSE: The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population. METHODS: A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >-12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter. RESULTS: Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91-0.96) and 0.93 (0.89-0.96), respectively; P =0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P =0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87-0.96) for RNFLT and 0.91 (0.86-0.95) for MRW ( P =0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P =0.230). CONCLUSIONS: MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.

24-2 SITA Standard versus 24-2 SITA Faster in Perimetry-Naive Normal Subjects.

PURPOSE: To compare the Swedish Interactive Thresholding Algorithm (SITA) Standard (SS) and SITA Faster (SFR) strategies in normal individuals undergoing standard automated perimetry (SAP) for the first time. DESIGN: Randomized, comparative, observational case series. PARTICIPANTS: Seventy-four perimetry-naive healthy individuals. METHODS: All individuals underwent SAP 24-2 testing with the Humphrey Field Analyzer III (model 850 Zeiss) using the SS and SFR strategies. One eye of each individual was tested. Test order between strategies was randomized, and an interval of 15 minutes was allowed between the tests. MAIN OUTCOME MEASURES: The following variables were compared: test time, foveal threshold, false-positive errors, number of unreliable tests, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and number of depressed points deviating at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total and pattern deviation probability maps. Specificity of the SS and SFR strategies were compared using Anderson's criteria for abnormal visual fields. RESULTS: The SFR tests were 60.4% shorter in time compared with SS (P < 0.001) and were associated with a significantly lower PSD (1.75 ± 0.80 decibel [dB] vs. 2.15 ± 1.25 dB; P = 0.016). There were no significant differences regarding the MD, VFI, foveal threshold, GHT, and number of points depressed at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total deviation and pattern deviation probability maps between SS and SFR. When all exams were analyzed and any of Anderson's criteria was applied, the specificity was 68% with SFR and 61% with SS (P = 0.250). The specificities observed with SFR and SS when only the first or second exams were analyzed were also similar (63% vs. 64% and 72% vs. 58%, respectively, P > 0.05). CONCLUSIONS: The SS and SFR were associated with similar specificities in perimetry-naive individuals. The SFR did not increase the number of depressed points in the total and pattern deviation probability maps. Ophthalmologists should be aware that both strategies are associated with disturbingly high false-positive rates in perimetry-naive individuals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

OCT detected optic nerve head remodeling in a young adult with early progressive myopia.

Purpose: To report a longitudinal OCT study of optic nerve head (ONH) neural canal remodeling in a young adult subject's eyes through the progression of early refractive myopia. Observations: Deep ONH changes early in the progression of myopia included enlargement of the Bruch's membrane opening, progressive temporal displacement of BMO relative to the anterior scleral canal opening, choroidal border tissue remodeling and exposure of the temporal scleral flange within the ONH neural canal of both eyes. Conclusions and Importance: Longitudinal OCT imaging of a young adult subject suggest that OCT is able to detect ONH neural canal remodeling early in the progression of refractive myopia that shares key features previously described only in more highly myopic eyes.

Gonioscopy-Assisted Transluminal Trabeculotomy for Glaucoma: 1-Year Outcomes and Success Predictors.

PRCIS: Our results suggest gonioscopy-assisted transluminal trabeculotomy (GATT) as an effective and safe option for the surgical management of open-angle glaucoma (OAG). Older age was the only risk factor for failure in our analysis. PURPOSE: To report 12-month clinical outcomes, safety profile and success predictors of GATT in patients with OAG. PATIENTS AND METHODS: A retrospective study of patients (18 y old and above) with medically uncontrolled OAG who underwent GATT as a solo procedure or combined with phacoemulsification (PHACO-GATT) between January 2018 and January 2020. Success at 12 months (primary outcome) was defined as intraocular pressure (IOP) <15 mm Hg, with an IOP reduction of at least 20%, OR a reduction of at least 2 glaucoma medications, compared with baseline. Secondary outcomes were success predictors and safety parameters. RESULTS: A total of 73 eyes (GATT=38; PHACO-GATT=35) from 58 patients with a mean age of 54.8±11.6 years were included. Overall, after 12 months of follow-up, the mean IOP was reduced from 24.9±8.5 to 12.1±2.1 mm Hg (P<0.001). The mean number of glaucoma medications was reduced from 3.5±0.7 to 1.2±1.2 (P<0.001). The success rate was 87% at 12 months, with no significant differences between GATT (85%) and PHACO-GATT (91%) eyes (P=0.330). Age was the only factor significantly associated with surgical success (hazard ratio=1.35; P=0.012; after adjusting for preoperative IOP and number of glaucoma medications). Patients older than 60 years had a significant greater chance of failure (hazard ratio=10.96; P=0.026) compared with those younger than 60 years. The most common postoperative complication was transient hyphema (39%; median duration, 5 d). No sight-threatening adverse event was documented. CONCLUSIONS: GATT was effective and safe at lowering IOP with or without cataract extraction in OAG. Patients 60 years or older had a higher risk of failure compared with those younger in age.

Treatment outcomes in the Ahmed Baerveldt Comparison Study after 1 year of follow-up.

PURPOSE: To determine the relative efficacy and complications of the Ahmed glaucoma valve (AGV) model FP7 (New World Medical, Ranchos Cucamonga, CA) and the Baerveldt glaucoma implant (BGI) model 101-350 (Abbott Medical Optics, Abbott Park, IL) in refractory glaucoma. DESIGN: Multicenter, randomized, controlled clinical trial. PARTICIPANTS: Two hundred seventy-six patients, including 143 in the AGV group and 133 in the BGI group. METHODS: Patients 18 to 85 years of age with refractory glaucoma having intraocular pressure (IOP) of 18 mmHg or more in whom an aqueous shunt was planned were randomized to undergo implantation of either an AGV or a BGI. MAIN OUTCOME MEASURES: The primary outcome was failure, defined as IOP >21 mmHg or not reduced by 20% from baseline, IOP ≤5 mmHg, reoperation for glaucoma or removal of implant, or loss of light perception vision. Secondary outcomes included mean IOP, visual acuity, use of supplemental medical therapy, and complications. RESULTS: Preoperative IOP (mean±standard deviation [SD]) was 31.2±11.2 mmHg in the AGV group and 31.8±12.5 mmHg in the BGI group (P = 0.71). At 1 year, mean±SD IOP was 15.4±5.5 mmHg in the AGV group and 13.2±6.8 mmHg in the BGI group (P = 0.007). The mean±SD number of glaucoma medications was 1.8±1.3 in the AGV group and 1.5±1.4 in the BGI group (P = 0.071). The cumulative probability of failure was 16.4% (standard error [SE], 3.1%) in the AGV group and 14.0% (SE, 3.1%) in the BGI group at 1 year (P = 0.52). More patients experienced early postoperative complications in the BGI group (n = 77; 58%) compared with the AGV group (n = 61; 43%; P = 0.016). Serious postoperative complications associated with reoperation, vision loss of ≥2 Snellen lines, or both occurred in 29 patients (20%) in the AGV group and in 45 patients (34%) in the BGI group (P = 0.014). CONCLUSIONS: Although the average IOP after 1 year was slightly higher in patients who received an AGV, there were fewer early and serious postoperative complications associated with the use of the AGV than the BGI.

Predicting Age From Optical Coherence Tomography Scans With Deep Learning.

Purpose: To assess whether age can be predicted from deep learning analysis of peripapillary spectral-domain optical coherence tomography (SD-OCT) B-scans and to determine the importance of specific retinal areas on the predictions. Methods: Deep learning (DL) convolutional neural networks were developed to predict chronological age in healthy subjects using peripapillary SD-OCT B-scan images. Models were built using the whole B-scan, as well as using specific regions through image ablation. Cross-validation was used for training and testing the model. Mean absolute error (MAE) and correlations between predicted and observed age were used to evaluate model performance. Results: A total of 7271 images from 542 eyes of 278 healthy subjects were included. DL predictions of age using the whole B-scan were strongly correlated with chronological age (MAE = 5.82 years; r = 0.860, P < 0.001). The model also accurately discriminated between the lowest and highest tertiles of age, with an area under the receiver operating characteristic curve of 0.962. In general, class activation maps tended to show a diffuse pattern of activation throughout the scan image. For specific structures of the B-scan, the layers with the strongest correlations with chronological age were the choroid and vitreous (both r = 0.736), whereas retinal nerve fiber layer had the lowest correlation (r = 0.492). Conclusions: A DL algorithm was able to accurately predict age from whole peripapillary SD-OCT B-scans. Translational Relevance: DL models applied to SD-OCT scans suggest that aging appears to affect several layers in the posterior eye segment.

Clear lens extraction in eyes with primary angle closure and primary angle-closure glaucoma.

The crystalline lens plays an important role in the pathophysiology of primary angle closure and primary angle-closure glaucoma. The aging process is associated with a progressive enlargement of the lens, resulting in greater iridolenticular and iridotrabecular contact, which exacerbates both pupillary block and appositional angle closure, irrespective of the cataract status of the lens. Cataract surgery has been shown to widen the angle and reduce intraocular pressure in eyes with primary angle closure or primary angle-closure glaucoma. Recently, clear lens phacoemulsification has been suggested as a treatment modality in such eyes. We review the literature on clear lens extraction in eyes with angle closure and discuss its efficacy, safety, and indications. Although it is evident that clear lens extraction is beneficial in eyes with primary angle closure and primary angle-closure glaucoma, it is technically challenging and should be performed by experienced surgeons who not only master the procedure but are also able to deal with potential complications. Since the follow-up of the reviewed studies is relatively short, long-term follow-up (>10 years) of patients who undergo this procedure is needed to evaluate the safety and confirm the early benefits reported.

The Effect of Age on Increasing Susceptibility to Retinal Nerve Fiber Layer Loss in Glaucoma.

Purpose: To determine whether aging modifies the effect of intraocular pressure (IOP) on progressive glaucomatous retinal nerve fiber layer (RNFL) thinning over time. Methods: This was a retrospective cohort study involving patients with glaucoma or suspected of having glaucoma who were followed over time from the Duke Glaucoma Registry. Rates of RNFL loss from spectral-domain optical coherence tomography (SD-OCT) were used to assess disease progression. Generalized estimating equations with robust sandwich variance estimators were used to investigate the effects of the interaction of age at baseline and mean IOP on rates of RNFL loss over time. Models were adjusted for gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. Results: The study included 85,475 IOP measurements and 60,026 SD-OCT tests of 14,739 eyes of 7814 patients. Eyes had a mean follow-up time of 3.5 ± 1.9 years. The average rate of change in RNFL thickness was -0.70 µm/year (95% confidence interval, -0.72 to -0.67). There was a significant interaction between age and mean IOP and the rate of RNFL loss (P = 0.001), with older eyes having significantly faster rates of RNFL loss than younger ones for the same level of IOP. The effect of IOP on rates of change was greater in the inferior and superior regions of the optic disc. Conclusions: Age is a significant modifier of the relationship between IOP and glaucomatous loss in RNFL thickness over time. Older patients may be more susceptible to glaucomatous progression than younger patients at the same level of IOP.

Can Psychologic Stress Elevate Intraocular Pressure in Healthy Individuals?

PURPOSE: To investigate if a stress event can influence intraocular pressure (IOP) in a group of healthy individuals. DESIGN: Case-control study. PARTICIPANTS: A total of 28 healthy subjects were included: 17 in the stress group and 11 in the control group. METHODS: The Trier Social Stress Test (TSST) is a tool to evaluate cortisol response to psychologic stimulation based on the stress induced by public speaking. All participants underwent a modified diurnal tension curve (DTC) 1 week before the TSST, with 3 IOP measurements performed between 8:00 am and 2:00 pm. We evaluated the response to the TSST measuring the levels of salivary cortisol, IOP, and heart rate before, immediately after, and 40 minutes after TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals. MAIN OUTCOME MEASURES: Changes in IOP (mmHg), salivary cortisol, heart rate, and STAI scores. RESULTS: At baseline, there were no significant differences between case and controls regarding age (52.2 ± 6.26 vs. 53.8 ± 8.4 years, P = 0.661), gender (52.94% male vs. 45.45% female, P = 0.669), and ethnicity. Salivary cortisol (6.8 nmol/l, P < 0.001) and heart rate (7.2 beats/min, P = 0.035) increased significantly after the TSST. We observed a mean IOP increase of 1.0 mmHg (right eye, P = 0.003) and 1.1 mmHg (left eye, P = 0.004) when comparing IOP measurements obtained during the DTC and immediately after TSST. In addition, 35% (6/17) of the subjects in the TSST group showed an IOP increase higher than 2 mmHg after the test compared with 18% (2/11) in the control group. The STAI state score significantly increased after the stress event compared with baseline (P = 0.026) and decreased from poststress to the recovery period (P = 0.006) in the TSST group. The control group did not show significant changes in IOP, heart rate, salivary cortisol levels, and STAI scores. CONCLUSIONS: Significant elevations of IOP, salivary cortisol, STAI scores, and heart rate occurred after inducing psychologic stress with TSST in a group of healthy individuals.

Human Versus Machine: Comparing a Deep Learning Algorithm to Human Gradings for Detecting Glaucoma on Fundus Photographs.

PURPOSE: To compare the diagnostic performance of human gradings vs predictions provided by a machine-to-machine (M2M) deep learning (DL) algorithm trained to quantify retinal nerve fiber layer (RNFL) damage on fundus photographs. DESIGN: Evaluation of a machine learning algorithm. METHODS: An M2M DL algorithm trained with RNFL thickness parameters from spectral-domain optical coherence tomography was applied to a subset of 490 fundus photos of 490 eyes of 370 subjects graded by 2 glaucoma specialists for the probability of glaucomatous optical neuropathy (GON), and estimates of cup-to-disc (C/D) ratios. Spearman correlations with standard automated perimetry (SAP) global indices were compared between the human gradings vs the M2M DL-predicted RNFL thickness values. The area under the receiver operating characteristic curves (AUC) and partial AUC for the region of clinically meaningful specificity (85%-100%) were used to compare the ability of each output to discriminate eyes with repeatable glaucomatous SAP defects vs eyes with normal fields. RESULTS: The M2M DL-predicted RNFL thickness had a significantly stronger absolute correlation with SAP mean deviation (rho=0.54) than the probability of GON given by human graders (rho=0.48; P < .001). The partial AUC for the M2M DL algorithm was significantly higher than that for the probability of GON by human graders (partial AUC = 0.529 vs 0.411, respectively; P = .016). CONCLUSION: An M2M DL algorithm performed as well as, if not better than, human graders at detecting eyes with repeatable glaucomatous visual field loss. This DL algorithm could potentially replace human graders in population screening efforts for glaucoma.

Evaluation of contrast sensitivity in patients with advanced glaucoma: comparison of two tests.

AIMS: To evaluate contrast sensitivity (CS) in patients with advanced glaucomatous visual field damage, and to compare two clinical CS tests. METHODS: This was a cross-sectional test-retest study. Twenty-eight patients with open-angle glaucoma, visual acuity (VA) better than 20/40 and visual field mean deviation (MD) worse than -15 dB were enrolled. Patients underwent VA, visual field and CS testing with the Pelli-Robson (PR) chart and the Freiburg Visual Acuity and Contrast Test (FrACT). Retest measurements were obtained within 1 week to 1 month. RESULTS: Median (IQR) age and MD were 61.5 (55.5 to 69.2) years and -27.7 (-29.7 to -22.7) dB, respectively. Median (IQR) VA was 0.08 logarithm minimum angle of resolution (0.02 to 0.16), corresponding to 20/25 (20/20 to 20/30). Median (IQR) CS was 1.35 (1.11 to 1.51) log units with the PR chart and 1.39 (1.24 to 1.64) log units with FrACT. VA explained less than 40% of the variance in CS (adjusted R2=0.36). CS estimates of both tests were closely related (rho=0.88, p=0.001), but CS was 0.09 log units higher with FrACT compared with the PR chart, and the 95% repeatability intervals (Bland-Altman) were 46% tighter with the PR chart. CONCLUSIONS: Despite near-normal VA, almost all patients showed moderate to profound deficits in CS. CS measurement provides additional information on central visual function in patients with advanced glaucoma.

Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review.

INTRODUCTION: Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to. AREAS COVERED: We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs. EXPERT OPINION: It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.