Detecting disease progression in mild, moderate and severe glaucoma.

PURPOSE OF REVIEW: The purpose of this review is to examine contemporary techniques for detecting the progression of glaucoma. We provide a general overview of detection principles and review evidence-based diagnostic strategies and specific considerations for detecting glaucomatous progression in patients with mild, moderate and severe disease. RECENT FINDINGS: Diagnostic techniques and technologies for glaucoma have dramatically evolved in recent years, affording clinicians an expansive toolkit with which to detect glaucoma progression. Each stage of glaucoma, however, presents unique diagnostic challenges. In mild disease, either structural or functional changes can develop first in disease progression. In moderate disease, structural or functional changes can occur either in tandem or in isolation. In severe disease, standard techniques may fail to detect further disease progression, but such detection can still be measured using other modalities. SUMMARY: Detecting disease progression is central to the management of glaucoma. Glaucomatous progression has both structural and functional elements, both of which must be carefully monitored at all disease stages to determine when interventions are warranted.

Automated Detection of Glaucoma With Interpretable Machine Learning Using Clinical Data and Multimodal Retinal Images.

PURPOSE: To develop a multimodal model to automate glaucoma detection DESIGN: Development of a machine-learning glaucoma detection model METHODS: We selected a study cohort from the UK Biobank data set with 1193 eyes of 863 healthy subjects and 1283 eyes of 771 subjects with glaucoma. We trained a multimodal model that combines multiple deep neural nets, trained on macular optical coherence tomography volumes and color fundus photographs, with demographic and clinical data. We performed an interpretability analysis to identify features the model relied on to detect glaucoma. We determined the importance of different features in detecting glaucoma using interpretable machine learning methods. We also evaluated the model on subjects who did not have a diagnosis of glaucoma on the day of imaging but were later diagnosed (progress-to-glaucoma [PTG]). RESULTS: Results show that a multimodal model that combines imaging with demographic and clinical features is highly accurate (area under the curve 0.97). Interpretation of this model highlights biological features known to be related to the disease, such as age, intraocular pressure, and optic disc morphology. Our model also points to previously unknown or disputed features, such as pulmonary function and retinal outer layers. Accurate prediction in PTG highlights variables that change with progression to glaucoma-age and pulmonary function. CONCLUSIONS: The accuracy of our model suggests distinct sources of information in each imaging modality and in the different clinical and demographic variables. Interpretable machine learning methods elucidate subject-level prediction and help uncover the factors that lead to accurate predictions, pointing to potential disease mechanisms or variables related to the disease.

Reduced Pulsatile Trabecular Meshwork Motion in Eyes With Primary Open Angle Glaucoma Using Phase-Sensitive Optical Coherence Tomography.

Purpose: The purpose of this study was to investigate the difference in pulsatile trabecular meshwork (TM) motion between normal and eyes with POAG using phase-sensitive optical coherence tomography (PhS-OCT). Methods: In this cross-sectional study, eight healthy subjects (16 eyes) and nine patients with POAG (18 eyes) were enrolled. A laboratory-based prototype PhS-OCT system was used to measure pulsatile TM motion. PhS-OCT images were analyzed to obtain parameters of pulsatile TM motion (i.e. maximum velocity [MV] and cumulative displacement [CDisp]). Outflow facility and ocular pulse amplitude were measured using pneumotonography. Detection sensitivity was compared among various parameters by calculating the area under the receiver operating characteristic curves (AUCs). Results: A pulsatile TM motion waveform synchronous with digital pulse was observed using PhS-OCT in both healthy and POAG eyes. The mean MV in eyes with glaucoma was significantly lower than healthy eyes (P < 0.001). The mean CDisp in POAG eyes was also significantly lower than healthy eyes (P < 0.001). CDisp showed a significant correlation (r = 0.46; P = 0.0088) with ocular pulse amplitude in the study. Compared with the outflow facility, both the MV and CDisp were found to have a better discrimination of glaucoma (P < 0.001 and P = 0.0074, respectively). Conclusions: Pulsatile TM motion was reduced in patients with POAG compared to healthy subjects. The underlying mechanism may be due to the altered tissue stiffness or other biomechanical properties of the TM in POAG eyes. Our evidence suggests that the measurement of pulsatile TM motion with PhS-OCT may help in characterizing outflow pathway abnormalities.

Laser Peripheral Iridotomy Curriculum: Lecture and Simulation Practical.

Introduction: Approximately 20 million people worldwide are affected by primary angle closure glaucoma, which is often treated with a laser peripheral iridotomy (LPI). In the United States, at least 60,000 to 80,000 LPIs are performed annually. However, complications can arise from improperly performed LPIs. While the Accreditation Council for Graduate Medical Education requires that all ophthalmology residents perform at least four primary LPIs prior to graduating, formal training is often lacking. In an effort to standardize LPI teaching, an LPI lecture curriculum and skills practice session were introduced. Methods: A lecture and wet-lab curriculum was developed at the University of Washington to formally teach first-year ophthalmology residents the indications and techniques for LPI. Pre- and postcurriculum knowledge was tested, and LPI performance was assessed by comparing pre- and postcurriculum total number of shots and time needed to successfully complete an LPI on a commercially available model eye. Results: The course was highly rated by 10 residents (all PGY 2), with an increase in pre- versus posttest scores, an improvement in LPI performance metrics, and an increase in pre- versus postcurriculum scores for the three survey questions regarding curriculum objectives. Discussion: This course improved learner knowledge and confidence in performing LPI. Test scores improved following the course, as did self-assessed confidence levels of the residents. Residents made a number of positive comments about the course. We plan to continue holding this training session every year at our institution.

Using Deep Learning to Automate Goldmann Applanation Tonometry Readings.

PURPOSE: To develop an objective and automated method for measuring intraocular pressure using deep learning and fixed-force Goldmann applanation tonometry (GAT) techniques. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Patients from an academic glaucoma practice. METHODS: Intraocular pressure was estimated by analyzing videos recorded using a standard slit-lamp microscope and fixed-force GAT. Video frames were labeled to identify the outline of the reference tonometer and the applanation mires. A deep learning model was trained to localize and segment the tonometer and mires. Intraocular pressure values were calculated from the deep learning-predicted tonometer and mire diameters using the Imbert-Fick formula. A separate test set was collected prospectively in which standard and automated GAT measurements were collected in random order by 2 independent masked observers to assess the deep learning model as well as interobserver variability. MAIN OUTCOME MEASURES: Intraocular pressure measurements between standard and automated methods were compared. RESULTS: Two hundred sixty-three eyes of 135 patients were included in the training and validation videos. For the test set, 50 eyes from 25 participants were included. Each eye was measured by 2 observers, resulting in 100 videos. Within the test set, the mean difference between automated and standard GAT results was -0.9 mmHg (95% limits of agreement [LoA], -5.4 to 3.6 mmHg). Mean difference between the 2 observers using standard GAT was 0.09 mmHg (LoA,-3.8 to 4.0 mmHg). Mean difference between the 2 observers using automated GAT videos was -0.3 mmHg (LoA, -4.1 to 3.5 mmHg). The coefficients of repeatability for automated and standard GAT were 3.8 and 3.9 mmHg, respectively. The bias for even-numbered measurements was reduced when using automated GAT. CONCLUSIONS: Preliminary measurements using deep learning to automate GAT demonstrate results comparable with those of standard GAT. Automated GAT has the potential to improve on our current GAT measurement standards significantly by reducing bias and improving repeatability. In addition, ocular pulse amplitudes could be observed using this technique.

Development and validation of a machine learning, smartphone-based tonometer.

BACKGROUND/AIMS: To compare intraocular pressure (IOP) measurements using a prototype smartphone tonometer with other tonometers used in clinical practice. METHODS: Patients from an academic glaucoma practice were recruited. The smartphone tonometer uses fixed force applanation and in conjunction with a machine-learning computer algorithm is able to calculate the IOP. IOP was also measured using Goldmann applanation tonometry (GAT) in all subjects. A subset of patients were also measured using ICare, pneumotonometry (upright and supine positions) and Tono-Pen (upright and supine positions) and the results were compared. RESULTS: 92 eyes of 81 subjects were successfully measured. The mean difference (in mm Hg) for IOP measurements of the smartphone tonometer versus other devices was +0.24 mm Hg for GAT, -1.39 mm Hg for ICare, -3.71 mm Hg for pneumotonometry and -1.30 mm Hg for Tono-Pen. The 95% limits of agreement for the smartphone tonometer versus other devices was -4.35 to 4.83 mm Hg for GAT, -6.48 to 3.70 mm Hg for ICare, -7.66 to -0.15 mm Hg for pneumotonometry and -5.72 to 3.12 mm Hg for Tono-Pen. Overall, the smartphone tonometer results correlated best with GAT (R2=0.67, p<0.001). Of the 92 videos, 90 (97.8%) were within ±5 mm Hg of GAT and 58 (63.0%) were within ±2 mm Hg of GAT. CONCLUSIONS: Preliminary IOP measurements using a prototype smartphone-based tonometer was grossly equivalent to the reference standard.

Effect of prior glaucoma surgery on intraocular pressure immediately after anti-vascular endothelial growth factor injection.

BACKGROUND: To characterize how prior incisional glaucoma surgery affects the intraocular pressure (IOP) elevation immediately following intravitreal anti-VEGF injections (IVI). METHODS: Single institution, experimental study. Patients with a history of incisional glaucoma surgery who were receiving anti-VEGF injections were recruited as well as control eyes. Pre- and post-injection IOP measurements were compared as well as time to recovery to within 5 and 10 mmHg of baseline IOP. RESULTS: Ten eyes with a history of glaucoma surgery and 29 control eyes receiving anti-VEGF injections were included. The most common indication for intravitreal anti-VEGF injection was proliferative diabetic retinopathy in both surgical and control eyes (50% vs 45%, p = 1.00). Post-injection IOP was significantly decreased compared to baseline IOP after anti-VEGF injection in surgical versus control eyes (26.5 ± 8.9 mmHg vs 44.2 ± 8.5 mmHg, respectively, p < 0.001). The mean change in IOP following intravitreal anti-VEGF injection was lower in surgical eyes (10.7 ± 6.6 mmHg vs 28.6 ± 8.3 mmHg, p < 0.001). The mean time for the IOP to return to within 10 mmHg of pre-injection IOP was less in surgical eyes (5.2 ± 4.1 min vs 13.3 ± 7.6 min, p = 0.002). CONCLUSIONS: Eyes with prior incisional glaucoma surgery demonstrated a significantly lower post-injection IOP elevation and a faster recovery to within 10 mmHg of their pre-injection IOP. Incisional glaucoma surgery may be considered for patients where the attenuation of post-injection IOP elevation is needed and other less invasive measures have failed.

Macular Vascular Microcirculation in Eyes With Open-angle Glaucoma Using Different Visual Field Severity Classification Systems.

PRECIS: We found significant differences in macular vascular microcirculation between normal and glaucomatous eyes using optical coherence tomography angiography (OCTA). Macular vascular microcirculation changes also showed significant correlations with visual field (VF) severity classification systems. PURPOSE: To correlate VF severity defined by different classification systems and macular vascular microcirculation in eyes with glaucoma using OCTA. PATIENTS AND METHODS: Twenty normal and 58 open-angle glaucoma (OAG) eyes were scanned using a swept-source OCTA (Plex Elite 9000) and macular vascular microcirculation was measured by calculating the overall blood flux index (BFI) and vessel area density (VAD) over the entire 6×6 mm area excluding the big retinal vessels. Glaucomatous eyes were staged into severity groups based on 4 VF severity classifications: Hodapp-Parrish-Anderson scale, Glaucoma Severity Staging system, ICD-10 glaucoma staging definitions, and VF mean deviation. Central 10-degree VF mean sensitivity (CMS) was calculated based on 24-2 VF. One-way analysis of variance was used to analyze the differences and correlation between macular vascular microcirculation and other clinical parameters. RESULTS: Glaucomatous eyes had significantly lower ganglion cell and inner plexiform layer BFI and VAD (P<0.0001) compared with normal eyes. In OAG patients, BFI and VAD were significantly higher in mild OAG compared with severe OAG with all VF disease severity classification systems (P<0.001). Glaucoma Severity Staging had the highest correlation with changes in macular vascular microcirculation metrics (r=0.734 for BFI; r=0.647 for VAD) and VF CMS had highest correlation with macular vascular microcirculation metrics (r=0.887 for BFI; r=0.903 for VAD). CONCLUSION: Macular vascular microcirculation metrics detected by OCTA correlate with disease severity in glaucomatous eyes. VF CMS, calculated from only 12 tested central 10-degree points, correlated best with macular OCTA.

Forecasting future Humphrey Visual Fields using deep learning.

PURPOSE: To determine if deep learning networks could be trained to forecast future 24-2 Humphrey Visual Fields (HVFs). METHODS: All data points from consecutive 24-2 HVFs from 1998 to 2018 were extracted from a university database. Ten-fold cross validation with a held out test set was used to develop the three main phases of model development: model architecture selection, dataset combination selection, and time-interval model training with transfer learning, to train a deep learning artificial neural network capable of generating a point-wise visual field prediction. The point-wise mean absolute error (PMAE) and difference in Mean Deviation (MD) between predicted and actual future HVF were calculated. RESULTS: More than 1.7 million perimetry points were extracted to the hundredth decibel from 32,443 24-2 HVFs. The best performing model with 20 million trainable parameters, CascadeNet-5, was selected. The overall point-wise PMAE for the test set was 2.47 dB (95% CI: 2.45 dB to 2.48 dB), and deep learning showed a statistically significant improvement over linear models. The 100 fully trained models successfully predicted future HVFs in glaucomatous eyes up to 5.5 years in the future with a correlation of 0.92 between the MD of predicted and actual future HVF and an average difference of 0.41 dB. CONCLUSIONS: Using unfiltered real-world datasets, deep learning networks show the ability to not only learn spatio-temporal HVF changes but also to generate predictions for future HVFs up to 5.5 years, given only a single HVF.

Optic Nerve Head Perfusion Before and After Intravitreal Antivascular Growth Factor Injections Using Optical Coherence Tomography-based Microangiography.

PURPOSE: To use optical coherence tomography angiography (OCTA) to evaluate the changes in optic nerve head perfusion following intravitreal antivascular endothelial growth factor injections. METHODS: Preinjection and postinjection intraocular pressure (IOP) and OCTA images were taken of both the injected and uninjected fellow eyes. RESULTS: Mean preinjection IOP was 16.6±4.7 mm Hg, which increased to a mean of 40.3±13.0 mm Hg (P<0.0001) during the first postinjection image and remained elevated at 36.1±11.5 mm Hg (P<0.0001) during the second postinjection image. Although no significant change was observed in flux, vessel area density, or normalized flux when comparing the OCTA preinjection and first postinjection images, a significant decrease at the second postinjection image was observed (P=0.03, 0.02, and 0.03, respectively). No significant change was observed in the uninjected fellow eye during the same time period (P=0.47, 0.37, and 0.38, respectively). CONCLUSIONS: Following an antivascular endothelial growth factor injection, mean IOP increased significantly and OCTA imaging of the optic nerve demonstrated a mild but significant decrease in optic nerve head perfusion parameters. Clinicians performing these injections should be aware of these findings and monitor the status of the optic nerve in patients undergoing injections.

Scheduled Postoperative Ripcord Removal in Baerveldt 350 Implants: A Prospective, Randomized Trial.

PURPOSE: Many surgeons remove the ripcord in the Baerveldt glaucoma drainage device to better control tube opening and intraocular pressure (IOP) lowering postoperatively. However, complications following Baerveldt implant surgery with or without ripcord removal are not well-characterized. We performed a prospective, randomized trial to test the hypothesis that scheduled ripcord removal decreases complications and final IOP. METHODS: Eighty-one patients were enrolled and randomized to scheduled ripcord removal at postoperative week 3 or to observation. They were followed for 6 months, and outcomes were compared between the 2 groups. RESULTS: Forty-four patients were randomized to scheduled ripcord removal and 37 to observation. The intervention group had a similar rate of total complications after ripcord removal (36% vs. 24%, P=0.24), a lower rate of tube fibrin obstruction (2.3% vs. 13.5%, P=0.05), and a larger decrease in the number of medications (1.3 vs. 0.49 fewer medications, P=0.01). The removal group's mean IOP decrease was 8.6 mm Hg and success rate was 59%, defined as 5 mm Hg

Optical coherence tomography angiography in glaucoma.

PURPOSE OF REVIEW: Optical coherence tomography angiography (OCTA) studies have demonstrated reduced microcirculation in the superficial optic nerve, peripapillary retina, and the macula of glaucoma patients. The scope of this review is to outline recent studies using OCTA in glaucoma and highlight how OCTA may help improve diagnosis and follow-up in glaucoma patients. RECENT FINDINGS: OCTA studies have provided evidence of vascular changes in the optic nerve head, peripapillary, and macula region in glaucoma in comparison to glaucoma suspects and normal eyes. Additionally, OCTA can detect longitudinal reduction of peripapillary and macula vessel density in glaucoma patients. It remains unclear whether the reduced microcirculation in glaucoma patients induces the neuronal damage or arises through reduced circulation requirements in damaged tissue. SUMMARY: OCTA is a novel imaging modality that has great potential to enhance our understanding of glaucoma and to improve our ability to detect and treat it.

Scleral Patch Graft With a Suture Reinforcement Technique in Surgical Management of Necrotizing Scleritis With Ectasia.

PURPOSE: To describe a technique for reducing and reinforcing scleral thinning in cases of necrotizing scleritis with ectasia. METHODS: Descriptive report of a surgical technique in 2 surgical cases with a video. RESULTS: Successful repair and reduction in uveal prolapse from scleral thinning in 2 cases of necrotizing scleritis with ectasia with a suturing technique using overlapping (weave) compressive suturing over a scleral patch. CONCLUSIONS: In cases of necrotizing scleritis with ectasia in which there is perforation or prolapsing uvea, this technique should be considered.

Resident-performed laser peripheral iridotomy in primary angle closure, primary angle closure suspects, and primary angle closure glaucoma.

PURPOSE: To investigate the power use and complication frequency of resident-performed laser peripheral iridotomy (LPI). METHODS: A retrospective analysis of 196 eyes from 103 patients who underwent neodymium: yttrium-aluminum-garnet laser iridotomy performed by resident physicians from January 1, 2010 through April 30, 2015 at a university-based county hospital was done. All patients were treated for primary angle closure, primary angle closure suspects, and primary angle closure glaucoma. Data were collected on pre- and post-laser intraocular pressure (IOP), ethnicity, laser parameters and complications. Mean power use and frequency of complications were evaluated. Complications included elevated post-laser IOP at 30-45 minutes (≥8 mmHg), hyphema, aborted procedures, and lasering non-iris structures. The number of repeated LPI procedures, was also recorded. RESULTS: Mean total power used for all residents was 78.2±68.7 mJ per eye. Power use by first-year trainees was significantly higher than second- and third-year trainees (103.5±75.5 mJ versus 73.7±73.8 mJ and 67.2±56.4 mJ, respectively, p=0.011). Complications included hyphema or microhyphema in 17.9% (35/196), IOP spikes in 5.1% (10/196), aborted procedures in 1.1% (3/196) and lasering non-iris structures in 0.5% (1/196). LPI was repeated in 22.4% of cases (44/196) with higher incidence of repeat LPI among non-Caucasian compared to the Caucasian subjects (p=0.02). Complication rates did not differ with increased training (p=0.16). CONCLUSION: Total power used for LPI decreased with increased resident training, while the complication rate did not differ significantly among resident classes. Complication rates were comparable to rates reported in the literature for attending-performed LPIs.

Cytokine biomarkers in tear film for primary open-angle glaucoma.

PURPOSE: To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG). METHODS: Patients without POAG and eye drop-naïve patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1ß, IL-2, IL-4, IL-6, IL-8, and TNFα). RESULTS: Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG. CONCLUSION: Proinflammatory cytokines were lower in eye drop-naïve newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG.

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss.

Importance: Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. Objective: To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Design, Setting, and Participants: Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Main Outcomes and Measures: Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Results: Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] µm; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] µm; 95% CI, -6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman ρ = 0.44; P = .045) and RNFL thickness (Spearman ρ = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Conclusions and Relevance: Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

VEGF as a Paracrine Regulator of Conventional Outflow Facility.

Purpose: Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility. Methods: We measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours of static culture or cyclic stretch. We used immunofluorescence microscopy to localize VEGF-A protein within the TM of mice. Results: VEGF-A164a increased C in enucleated mouse eyes. Cyclic stretch increased VEGF-A secretion by human TM cells, which corresponded to VEGF-A localization in the TM of mice. Blockade of VEGFR-2 decreased C, using either of the inhibitors SU5416 or Ki8751 or the inactive splice variant VEGF-A165b. VEGF-D increased C, which could be blocked by Ki8751. Conclusions: VEGF is a paracrine regulator of conventional outflow facility that is secreted by TM cells in response to mechanical stress. VEGF affects facility via VEGFR-2 likely at the level of SC endothelium. Disruption of VEGF signaling in the TM may explain why anti-VEGF therapy is associated with decreased outflow facility and sustained ocular hypertension.

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility. Methods: Patients with age-related macular degeneration who had received unilateral intravitreal anti-VEGF injections were recruited into two groups, those with ≤10 and those with ≥20 total anti-VEGF injections. Intraocular pressure and tonographic outflow facility of injected and uninjected fellow eyes were measured and compared between groups. Risk factors for development of reduced outflow facility also were assessed. Results: Outflow facility was 12% lower in the injected eyes of patients who received ≥20 anti-VEGF injections, compared to contralateral uninjected eyes (P = 0.02). In contrast, there was no facility reduction for patients with ≤10 anti-VEGF injections (P = 0.4). In patients with ocular hypertension in the uninjected eye (IOP > 21 mm Hg, n = 5), the outflow facility of injected eyes was on average 46% lower (P = 0.01) than in the uninjected fellow eyes. This was significantly greater than the difference observed in patients with IOP ≤ 21 mm Hg in the uninjected eye (P = 2 × 10-4). In patients with ocular hypertension in the injected eye (n = 6) the differences in facility and IOP between contralateral eyes were significantly greater than in patients with IOP ≤ 21 mm Hg in the injected eye (P = 2 × 10-4 and P = 7 × 10-4, respectively). Conclusions: Chronic anti-VEGF injections significantly reduce outflow facility in patients with AMD. The greatest facility reduction is observed in patients with baseline ocular hypertension. Ophthalmologists who administer anti-VEGF injections should be aware of these findings and monitor patients closely for changes in IOP or evidence of glaucoma, especially in those with pre-existing ocular hypertension.