Diagnostic Power and Reproducibility of Objective Perimetry in Glaucoma.

PRCIS: An objective perimetry method provides four 30-2 style reports in 8 minutes. These comprise sensitivity and delay reports for both eyes. A combined report format shows comparable diagnostic power to two forms of automated perimetry. PURPOSE: To compare objective perimetry with two forms of standard automated perimetry (SAP) in glaucoma. METHODS: The study cohort contained 40 persons with glaucoma (PwG) and 94 normal control subjects. The PwG had both perimetric and pre-perimetric eyes. Multifocal pupillographic objective perimetry was performed with the objectiveField Analyser® (OFA®), which independently assesses the visual fields of both eyes concurrently. Its OFA30 test assessed the central ±30°, and the OFA15 test assessed the central ±15°, both providing 30-2 style reports. The OFA tests were repeated two weeks apart to assess test-retest variability (TRV). OFA was compared with Matrix and HFA-SITA fast 24-2 threshold testing. Diagnostic power was quantified as area under receiver operating characteristic curves (AUROC). Test durations, Mean Defects and Pattern Standard Deviations of the 4 tests were compared. RESULTS: At a median of 4.09±0.02 minutes/eye the OFA tests were quicker than SAP (all P≤0.0001), 2 minutes/eye if OFA per-region sensitivities and delays are considered separately. The %AUROCs for OFA, Matrix and HFA were not significantly different, averaging 93±3% (mean±SD) in perimetric eyes, and 73±6% in pre-perimetric eyes. For moderate to severe fields OFA TRV was less than published results for SAP. OFA30 mean defects were significantly correlated between repeats (r=0.91), and with OFA15 (r=0.93, both P<0.0001). CONCLUSIONS: OFA provides extra functional measures in the form of per-region delays, and between-eye asymmetries. Both the OFA wide-field and macular tests provided comparable diagnostic power to SAP and better TRV in damaged eyes.

Comparing 2-dimensional macular pigment optical density with objective and subjective perimetry and visual acuity in age-related macular degeneration.

PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). RESULTS: In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.

Objective perimetry identifies regional functional progression and recovery in mild Diabetic Macular Oedema.

PURPOSE: Retinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy. METHODS: Both eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions. RESULTS: In eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 µm to 234.2 ± 26.7 µm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 µm to 255.7 ± 20.6 µm (both p<0.05). Eyes that reduced in retinal thickness over time recovered to more normal OFA sensitivities and delays (all p<0.021). Matrix perimetry quantified fewer regions that changed significantly over the 27 months, mostly presenting in the central 8 degrees. CONCLUSIONS: Changes in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.

Prevalence and severity of diabetic retinopathy at first presentation to vitreoretinal services in Bhutan: a 3-year national study.

PURPOSE: To determine the prevalence and severity of diabetic retinopathy (DR) at first presentation among diabetic patients attending national vitreoretinal (VR) services in Bhutan STUDY DESIGN: Retrospective cross-sectional study METHODS: We included all diabetic patients in Bhutan who presented for retinal evaluation for the first time over a 3-year period (2013-2016). Data including demography, clinical details, diagnostic tests, and clinical staging of DR were analyzed. RESULTS: A total of 843 diabetic patients, aged 57.2 ± 12.0 (range 18-86) years, were enrolled. The majority were male (452, 53.6%; cumulative frequency [cf] 391, 46.4%; P = .14) and from urban settings (570, 67.6%; cf 273; 32.4%) and did not have modern schooling (555, 65.8%). Hypertension was the most common systemic comorbidity (501, 59.4%). The prevalence of DR was 42.7%, with mild nonproliferative DR (NPDR) being the most common type (187, 51.9%), followed by moderate NPDR (88, 24.4%) and proliferative DR (45, 12.5%). In addition, 120 patients had clinically significant macular edema (CSME), with a prevalence of 14.2%. Best-corrected visual acuity (BCVA) of 6/60 or worse occurred in 231 eyes (13.7%), and 41 patients (4.86%) had BCVA of 6/60 or worse bilaterally due to DR/CSME. A logistic regression model indicated that the major determinant of DR was the duration of diabetes, the odds rising by 1.27× with each year of disease (P < .0001). CONCLUSION: The prevalence of DR, including CSME, was high. Although a national DR screening program is established in Bhutan, there is a need to accelerate health education, community screening, and referral systems to reduce the prevalence of DR and CSME.

Rapid Objective Testing of Visual Function Matched to the ETDRS Grid and Its Diagnostic Power in Age-Related Macular Degeneration.

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade. Design: Evaluation of a diagnostic technology. Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure-function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA). Main Outcome Measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size. Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well. Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.

Cryotherapy versus Laser Does Not Influence Anatomic Success after Vitrectomy for Primary Rhegmatogenous Retinal Detachment Repair: Registry Analysis of 2413 Patients.

PURPOSE: To determine whether a difference exists between cryotherapy and endolaser photocoagulation retinopexy in terms of the rates of anatomic success after primary rhegmatogenous retinal detachment (RRD) repair with pars plana vitrectomy (PPV). DESIGN: Registry-based, nonrandomized, observational cohort study. SUBJECTS: Eyes with primary RRD in a binational retinal surgery registry that underwent repair with PPV and had a minimum of 3 months of follow-up. METHODS: Cases were recorded prospectively by participating surgeons, and the outcomes were recorded at 3 months. A generalized mixed model approach was used to compare the effect of retinopexy type on the outcomes. Variables known to be associated with retinal surgical success were considered as covariates for the final model. The eyes were divided into 2 groups: Cryo group (receiving cryotherapy as the only form of retinopexy) and Laser group (receiving endolaser as the only form of retinopexy). MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients with stable retinal reattachment without the need for further retinal detachment surgery, assessed 3 months after the surgery. Failure was defined as either retinal redetachment or foveal attachment with long-term silicone oil tamponade at the endpoint. The secondary outcome measured was visual acuity at 3 months compared with baseline measurements. RESULTS: A total of 2413 patients were included, and the overall single-procedure success rate was 85%. There was no statistically significant difference in surgical success between the adjusted proportion of successful reattachment for the Cryo group (87%) and that of successful reattachment for the Laser group (82%) (P = 0.84; odds ratio, 1.04; 95% confidence interval, 0.74-1.46). There was no difference in the mean change in the visual outcomes at 3 months between the groups (adjusted mean change of -0.48 logarithm of the minimum angle of resolution [logMAR] for the Cryo group vs. -0.50 logMAR for the Laser group, P = 0.82). CONCLUSIONS: The choice of cryotherapy versus endolaser retinopexy was observed to influence neither the anatomic success of PPV for RRD nor the visual acuity outcomes at 3 months after the surgery.

The clinical treatment of bacterial keratitis: A review of drop instillation regimes.

Bacterial keratitis (BK) presentations are often treated using the commercially available second-generation fluoroquinolones ciprofloxacin 0.3% and ofloxacin 0.3% as monotherapy. The guidelines available for instillation regimes are often not supported by data from clinical studies. This review examines the peer-reviewed clinical studies and compared treatment failure rates for ciprofloxacin 0.3% and ofloxacin 0.3% for BK in relation to Day-1 drop-regimes. From the statistical analysis, this review derived evidence-based clinically applicable minimum drop-regimes for the treatment of BK on Day-1. Lower numbers of drops of ciprofloxacin on Day-1 were significantly associated with increased treatment failure rates (p < 0.002). The derived minimum number of drops on Day for ciprofloxacin on Day-1 was 47 drops, and for ofloxacin 24 drops. The mean number of drops used in the clinical studies was significantly lower than the manufacturers' recommended Day-1 regimes for both ciprofloxacin (p = 0.0006) and ofloxacin (p = 0.048). From Day-3 to -6 of treatment the drop rates for ciprofloxacin relative to recommended rates were higher, and for ofloxacin lower (p = 0.014). The findings of this review were then compared with a representative sample of published guidelines and case studies to determine the validity of applying those drop-regimes in clinical practice. Although the manufacturers' suggested minimum drop-regimes on Day-1 were significantly different (120 drops ciprofloxacin, 34 drops ofloxacin, p < 0.0001), many of the published guidelines suggested the same drop-regime for both fluoroquinolones. The suggested drop numbers on Day-1 for ciprofloxacin in these guidelines and case studies were significantly less than those used in the clinical studies (p = 0.043). Increased treatment failure rates for ciprofloxacin are associated with lower drop numbers on Day-1. The Day-1 dosing rates for ciprofloxacin and ofloxacin should be considered separately, and the regimes suggested in published guidelines and case studies may need be re-considered in light of the findings of this review.

Clustered Volleys Stimulus Presentation for Multifocal Objective Perimetry.

PURPOSE: Multifocal pupillographic objective perimetry (mfPOP) is being developed as an alternative to subjective threshold perimetry for the management of visual and neurological disorders. Here, we evaluate, in normal subjects, differences in signal quality between the original mfPOP method of spatially sparse Continuous stimulus presentation and the new Clustered Volleys (CVs) method. We hypothesized that the CVs method would lead to increased signal-to-noise ratios (SNRs) over the original method due to the stabilization of gain within the pupillary system. METHODS: Data were collected from six separate studies where otherwise-identical pairs of mfPOP tests using either the original Continuous stimulus presentation method or the new CVs method were undertaken; 440 6-minute tests from 96 normal subjects of varying ages were included. Per-region SNRs were compared between the two methods. RESULTS: Mean SNRs for the CVs mfPOP variants were between 35% and 57% larger than the original Continuous mfPOP variants (P < 0.001 in five of six studies). Similarly, the goodness-of-fit measure (r2) demonstrated large and significant fold increases of between 2.3× and 3.4× over the original method (all P < 0.001). Significant improvements in SNRs were present in all of the 88 test regions (44/eye), ranging between 8.4% and 93.7%; mean SNRs were significantly larger in 98% of test subjects. CONCLUSIONS: The CVs mfPOP stimulus presentation method produced substantial increases in signal quality over the original method. This is likely due to the stabilization of pupillary gain during stimulus presentation. TRANSLATIONAL RELEVANCE: These improvements increase diagnostic accuracy and have enabled shorter, 80-second mfPOP tests to be developed.

An Objective Perimetry Study of Central Versus Peripheral Sensitivities and Delays in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to compare central versus peripheral retinal sensitivities and delays in neovascular age-related macular degeneration (nAMD) using US Food and Drug Administration (FDA)-cleared multifocal pupillographic objective perimetry (mfPOP). Methods: We recruited 18 patients with nAMD and commenced Pro re nata intravitreal anti- vascular endothelial growth factor (VEGF) injection. We compared macular (±15 degrees) and wide-field (±30 degrees) mfPOP variants. We examined temporal correlations between treated and untreated fellow eyes. We fitted linear models to selected treatment patterns, and compared the ability of central versus peripheral responses to predict the need for treatment. Results: Central sensitivity decreased by -2.23 ± 0.051 dB/month (P < 0.0002) in treated eyes, and -0.17 ± 0.07 dB/month (P = 0.033) in untreated eyes. Treated eyes showed quicker central responses by 13.08 ± 3.77 ms than untreated eyes (P = 0.001). Based on peripheral responses, we identified two eye-types. Among positive-eyes peripheral sensitivity increased by 9.88 ± 4.41 dB (P = 0.042) before treatment; delays increased by 3.49 ± 1.75 ms/month (P = 0.049). For negative-eyes peripheral delays were shorter a month before treatment by 9.38 ± 3.59 ms (P = 0.013). Correlations between treatment and peripheral sensitivities or delays peaked at 1 to 2 months post-treatment. Peripheral data significantly determined treatment frequency and final acuity (all P < 0.044). Conclusions: Peripheral macular function of treated and untreated eyes divided eyes into positive and negative groups. Those peripheral responses determined outcomes; changes preceding active disease by 1 to 3 months. Overall, mfPOP may provide potential biomarkers to assist nAMD management. Translational Relevance: Objective perimetry may identify the requirement for treatment in nAMD that accords with the decision of a skilled clinician based on optical coherence tomography (OCT) and clinical findings.

Comparing Objective Perimetry, Matrix Perimetry, and Regional Retinal Thickness in Mild Diabetic Macular Edema.

Purpose: To compare per-region macular sensitivity and delay from objective perimetry with Matrix perimetry and retinal thickness in mild diabetic macular edema (DMO). Methods: Thirty-three patients with type 2 diabetes (T2D) aged 59.2 ± 10.5 years participated in a longitudinal study. Macular thickness, sensitivities and delays from the objectiveFIELD Analyzer (OFA), and Matrix perimeter sensitivities were mapped onto a common spatial layout to compute per-region correlations between structure/function measures. A generalized linear mixed-effects logistic regression model determined which variables contributed to clinical diagnosis of DMO. Results: For OFA, the mean sensitivity differences compared with normal in patients with T2D were negative and the mean delay differences positive, indicating lowered sensitivities and prolonged delays, both increasing with diabetes duration. Shorter diabetes duration could produce either localized peripheral hypersensitivities or shorter delays. Functional change could occur when retinal thickness was stable. Peripheral macular thickness correlated with central and peripheral OFA sensitivity and delay, all P < 0.0012 in DMO and a median of P = 0.001 without DMO; this was not true for Matrix sensitivities. The logistic model determined that peripheral thickness, OFA sensitivity (P = 0.043), and time in the study (P = 0.001) contribute independently to the odds of DMO versus no DMO. Conclusions: Mean sensitivities decreased and mean delays increased with duration of diabetes. Peripheral macular thickness correlated significantly with central and peripheral macular OFA sensitivity and delay. Peripheral macular thickness and functional measures may provide sensitive prognostic data. Translational Relevance: Functional loss can precede structural change in DMO, so including such functional assessment for deciding on treatment may be beneficial.

Relationships between retinal structure and function and vision-related quality of life measures in advanced age-related macular degeneration.

PURPOSE: To evaluate the association between ophthalmic structure/function measures and five standardized quality of life (QoL) instruments, in patients with advanced age-related macular degeneration (AMD). METHODS: We examined 20 AMD patients (ages 66-93 years) recruited from the Canberra Hospital Ophthalmology Department. Visual function measures included low and high contrast visual acuity (LCVA and HCVA) and measures from 10-2 Matrix visual fields (VF). Optical coherence tomography (OCT) quantified central retinal thickness (CRT), average macular thickness (AT), and retinal nerve fibre layer thickness (RNFL). The QoL instruments were the macular degeneration-related quality of life (MacDQoL), the National Eye Institute Visual Functioning Questionnaire (VFQ), its two face-recognition questions (A6 and 11), and the Geriatric Depression Scale (GDS). Pearson correlations, Canonical Correlation Analysis (CCA), and cross-validated stepwise-regression were used to examine the relationships between structure/function measures and the QoL instruments. RESULTS: The selected models for the five instruments had R2 ranging from 0.65 ± 0.12 to 0.90 ± 0.05 (mean ± SD) and median F-statistics > 188. HCVA was strongly associated with all QoL except the GDS, for which CRT, AT and RNFL figured highly. RNFL was most important for MacDQoL, and 2nd for VFQ question-A6. Centrally weighted VF measures were rarely selected but global VF measures were common, especially for the overall NEI-VFQ questionnaire. CCA revealed that the structure/function measures and QoL instruments contained 2 statistically independent mechanisms. CONCLUSIONS: In patients with advanced AMD, CRT and HCVA were strong determinants of QoL instruments in AMD patients.

Correlation of Central Versus Peripheral Macular Structure-Function With Acuity in Age-Related Macular Degeneration.

Purpose: Patients with advanced age-related macular degeneration (AMD) may have preserved visual function despite significant retinal structural changes. We aimed to evaluate the relationships among retinal thickness, macular sensitivity, and visual acuity (VA) in advanced AMD. Methods: We examined 43 eyes of 22 patients with advanced AMD (ages 66-93 years), prospectively recruited from the Canberra Hospital Ophthalmology Department. Visual function was measured on participants with low and high contrast visual acuity (LCVA and HCVA) and 10-2 Matrix visual fields. Retinal structure was determined with spectral domain optical coherence tomography (OCT), and customized software mapped the 64 OCT macular thickness regions onto the 44 regions of the 10-2 test. Results: Median retinal thickness at each 10-2 region was near normal. Just 7 of 88 regions from the OCT analysis that were thicker than the median had sensitivity that declined significantly with increasing thickness (r = -0.698 ± 0.082, mean ± SD), whereas 17 of 88 thinner regions showed significantly decreasing sensitivity with decreasing thickness (r = 0.723 ± 0.078). The absolute value of deviations from median optical coherence tomography thickness (aOCT) outside the central eight degrees was significantly correlated with HCVA (r = -0.34, P = 0.047). Thickness in the central eight degrees was not. Similarly, matrix sensitivities inside the central eight degrees were significantly correlated with outer aOCT (r = -0.49, P = 0.002). Conclusions: Retinal thickness outside eight degrees were significantly associated with HCVA and macular sensitivity. These results suggest that outer macular thickness may be a useful prognostic indicator in AMD. Translational Relevance: Retinal structure at the borders of the macula may be a surrogate marker of vision and retinal thickness near fixation.

MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina.

INTRODUCTION: MicroRNAs (miRNAs) are small, non-coding RNA molecules that have powerful regulatory properties, with the ability to regulate multiple messenger RNAs (mRNAs) and biological pathways. MicroRNA-223-3p (miR-223) is known to be a critical regulator of the innate immune response, and its dysregulation is thought to play a role in inflammatory disease progression. Despite miR-223 upregulation in numerous neurodegenerative conditions, largely in cells of the myeloid lineage, the role of miR-223 in the retina is relatively unexplored. Here, we investigated miR-223 in the healthy retina and in response to retinal degeneration. METHODS: miR-223-null mice were investigated in control and photo-oxidative damage-induced degeneration conditions. Encapsulated miR-223 mimics were intravitreally and intravenously injected into C57BL/6J wild-type mice. Retinal functional responses were measured using electroretinography (ERG), while extracted retinas were investigated by retinal histology (TUNEL and immunohistochemistry) and molecular analysis (qPCR and FACS). RESULTS: Retinal function in miR-223-/- mice was adversely affected, indicating that miR-223 may be critical in regulating the retinal response. In degeneration, miR-223 was elevated in the retina, circulating serum, and retinal extracellular vesicles. Conversely, retinal microglia and macrophages displayed a downregulation of miR-223. Further, isolated CD11b+ inflammatory cells from the retinas and circulation of miR-223-null mice showed an upregulation of pro-inflammatory genes that are critically linked to retinal inflammation and progressive photoreceptor loss. Finally, both local and systemic delivery of miR-223 mimics improved retinal function in mice undergoing retinal degeneration. CONCLUSION: miR-223 is required for maintaining normal retinal function, as well as regulating inflammation in microglia and macrophages. Further investigations are required to determine the targets of miR-223 and their key biological pathways and interactions that are relevant to retinal diseases. Future studies should investigate whether sustained delivery of miR-223 into the retina is sufficient to target these pathways and protect the retina from progressive degeneration.

Intraocular Pressure Changes and Vascular Endothelial Growth Factor Inhibitor Use in Various Retinal Diseases: Long-Term Outcomes in Routine Clinical Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! PARTICIPANTS: Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up. METHODS: Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice. MAIN OUTCOME MEASURES: The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. RESULTS: We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P = 0.012] and 2.1 [95% CI, 1.1-3.8; P = 0.025], respectively). CONCLUSIONS: Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk.