Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes.

PURPOSE: To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results. METHODS: Baseline corneal SPs were measured using Corvis ST (Oculus Optikgeräte GmbH). Participants were followed up every 6 months with clinical examination, HVF testing, and OCT. The baseline SP at first applanation (SP-A1) and highest concavity predicted the prospective outcome measures. MAIN OUTCOME MEASURES: Structural progression was measured by the OCT rate of thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL). Functional progression was assessed by permutation analysis of pointwise linear regression criteria on HVF testing. RESULTS: Stiffness parameters correlated positively with central corneal thickness (CCT), which was adjusted for in all analyses. A higher SP-A1, suggestive of a stiffer cornea, was associated with a faster rate of RNFL thinning (P < 0.001), synergistic with thinner CCT (P = 0.004) over a mean follow-up of 4.2 years. Eyes with higher SP-A1 and thinner CCT (thin and stiff corneas) showed accelerated RNFL thinning by 0.72 µm/year relative to eyes with lower SP-A1 and thicker CCT (95% confidence interval [CI], 0.17-1.28; P = 0.011) and were at 2.9-fold higher likelihood of fast RNFL progression of more than 1 µm/year (95% CI, 1.4-6.1; P = 0.006). Consistent results also were observed with GCIPL thinning. Furthermore, a higher SP-A1 was associated with a greater risk of visual field progression (P = 0.002), synergistic with thinner CCT (P = 0.010). Eyes with higher SP-A1 and thinner CCT were at 3.7-fold greater risk of visual field progression relative to eyes with thicker CCT and lower SP-A1 (95% CI, 1.3-10.5; P = 0.014). CONCLUSIONS: Glaucoma suspect eyes with higher corneal SPs and lower CCT, suggestive of thin and stiff corneas, are at greater risk of progression. Corneal SPs seem to act synergistically with CCT as risk factors for glaucoma progression.

Effect of phacoemulsification cataract surgery on intraocular pressure in early glaucoma: A prospective multi-site study.

IMPORTANCE: Cataract and primary open-angle glaucoma (POAG) commonly co-exist, and cataract surgery is thought to reduce intraocular pressure (IOP), the major modifiable risk factor of POAG. BACKGROUND: Previous studies exploring the effect of cataract surgery on IOP are limited by retrospective design, lack of a control group, medication use and washout and loss to follow up. DESIGN: Prospective, multicentre, matched case-control Australian study. PARTICIPANTS: 171 eyes of 108 POAG patients who underwent cataract surgery, matched to 171 control eyes. METHODS: Serial longitudinal IOP measurements were compared before and after cataract surgery, and relative to the controls. A mixed-effect model was used for the longitudinal data. MAIN OUTCOME MEASURES: Change in IOP. RESULTS: The mean follow-up time was 4.8 (1.4) years. Cataract surgery reduced mean IOP by 2.22 mmHg (95% confidence interval: 1.93-2.52 mmHg, P < .001) with 59 eyes (34%) achieving at least 3 mmHg reduction. Compared to matched controls, the mean reduction in IOP was 1.75 mmHg (95% confidence interval 1.15-2.33 mmHg; P < .001). Higher preoperative IOP and being on fewer topical glaucoma medications preoperatively were strongly predictive of a larger IOP reduction in a multivariable model. Anterior chamber depth was not associated with IOP reduction. Eyes with preoperative IOP ≥24 mmHg had a mean IOP reduction of 4.03 mmHg with 81% experiencing at least 3 mmHg reduction. Sub-analysis of medication naïve and pseudoexfoliation patients showed similar results. CONCLUSIONS AND RELEVANCE: Cataract surgery has a confirmed effect in reducing IOP in a "real world" setting of early glaucoma patients.

Performance of iPad-based threshold perimetry in glaucoma and controls.

IMPORTANCE: Independent validation of iPad visual field testing software Melbourne Rapid Fields (MRF). BACKGROUND: To examine the functionality of MRF and compare its performance with Humphrey SITA 24-2 (HVF). DESIGN: Prospective, cross-sectional validation study. PARICIPANTS: Sixty glaucomas mean deviation (MD:-5.08±5.22); 17 pre-perimetric, 43 HVF field defects and 25 controls. METHODS: The MRF was compared with HVF for scotoma detection, global indices, regional mean threshold values and sensitivity/specificity. Long-term test-retest variability was assessed after 6 months. MAIN OUTCOME MEASURES: Linear regression and Bland Altman analyses of global indices sensitivity/specificity using (ROC) curves, intraclass correlations. RESULTS: Using a cluster definition of three points at <1% or two at 0.5% to define a scotoma on HVF, MRF detected 39/54 abnormal hemifields with a similar threshold-based criteria. Global indices were highly correlated between MRF and HVF: MD r2 = 0.80, PSD r2 = 0.77, VFI r2 = 0.85 (all P < 0.0001). For manifest glaucoma patients, correlations of regional mean thresholds ranged from r2 = 0.45-0.78, despite differing array of tested points between devices. ROC analysis of global indices showed reasonable sensitivity/specificity with (AUC) values of MD:0.89, (PSD:0.85) and (VFI:0.88). MRF retest variability was low with (ICC) values at 0.95 (MD and VFI), 0.94 (PSD). However, individual test point variability for mid-range thresholds was higher. CONCLUSIONS AND RELEVANCE: MRF perimetry, despite using a completely different test paradigm, shows good performance characteristics compared to HVF for detection of defects, correlation of global indices and regional mean threshold values. Reproducibility for individual points may limit application for monitoring change over time, and fixation monitoring needs improvement.

Use baseline axial length measurements in myopic patients to predict the control of myopia with and without atropine 0.01.

PURPOSE: Identifying axial length growth rate as an indicator of fast progression before initiating atropine 0.01% for myopia progression in children. METHOD: From baseline, axial length growth over six months was measured prospectively. Subjects were then initiated on atropine 0.01% if axial length growth was greater than 0.1mm per 6 months (fast progressors), axial length and spherical equivalent change measurements recorded every six months. The rate of change was compared to the baseline pre-treatment rate. If axial length change was below the threshold, subjects received monitoring only. RESULTS: 73 subjects were identified as fast progressors and commenced atropine 0.01%, (mean baseline refraction of OD -2.9±1.6, OS -2.9±1.8 and a mean baseline axial length OD 24.62 ± 1.00 mm, OS 24.53 ± 0.99 mm). At six months, the mean paired difference of axial length growth rate was significantly reduced by 50% of baseline (all 73 subjects, p<0.05). 53 subjects followed to 12 months, and 12 to 24 months maintained a reduced growth rate. Change in mean spherical equivalent was significantly reduced compared to pre-treatment refractive error (mean paired difference p<0.05) and at each subsequent visit. 91 children were slow progressors and remained untreated. Their axial length growth rate did not change significantly out to 24 months. Spherical equivalent changed less than -0.5D annually in this group. CONCLUSION: Identifying fast progressors before treatment initiation demonstrated a strong treatment effect with atropine 0.01% reducing their individual rate of myopia progression by 50%. Another large group of myopic children, slow progressors, continued without medical intervention. A baseline axial length growth rate is proposed as a guideline to identify fast progressors who are more likely to benefit from atropine 0.01%.

The impact of continuous positive airway pressure treatment on retinal vascular changes in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) was recently shown to be associated with quantifiable retinal vascular changes, which correlate with disease severity. This follow-up study examines the response of retinal vascular changes in patients with OSA receiving continuous positive airway pressure (CPAP) treatment. METHODS: This prospective cohort study recruited adult patients undergoing diagnostic polysomnography at a tertiary sleep clinic in Sydney, Australia, stratified into 4 groups by the apnea-hypopnea index; control patients and patients with mild, moderate, and severe OSA. At baseline and follow-up approximately 24 months later, static retinal vascular calibers were derived from fundus photographs, and dynamic vascular pulsation amplitudes were measured on video fundoscopy. A proportion of patients started CPAP therapy after baseline assessment. RESULTS: Seventy-nine patients participated in this follow-up study: 9 control patients and 18 patients with mild OSA, 21 patients with moderate OSA, and 31 patients with severe OSA. Twenty-five patients started CPAP after baseline. In the severe group, patients not on treatment showed progressive narrowing of retinal arteries from baseline, whereas those on CPAP showed a slight improvement (mean, 171.3-165.1 and 171.2-174.0 µm, respectively; P = .012). Arterio-venous ratio was also significantly reduced in the nontreatment group compared to the treatment group in those with severe OSA (0.836-0.821 and 0.837-0.855, respectively; P = .031). CPAP did not seem to have a significant impact on venous caliber or vascular pulsatility. CONCLUSIONS: This study shows that patients with severe untreated OSA demonstrate progressive retinal arterial narrowing, whereas CPAP treatment may be protective.

A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry.

PURPOSE: Intraocular pressure (IOP) elevations may occur in early morning or outside office hours and can be missed during routine in-clinic IOP measurements. Such fluctuations or peaks likely contribute to glaucoma progression. We sought to investigate the relationship between an IOP polygenic risk score (PRS) and short-term IOP profile. DESIGN: Cross-sectional study. PARTICIPANTS: Four hundred seventy-three eyes from 239 participants with suspected or established primary open-angle glaucoma sampled from 4 outpatient clinics in Australia between August 2016 and December 2019. METHODS: Participants underwent Icare HOME (Icare Oy, Vanda, Finland) tonometer measurements to record IOP 4 times daily for 5 days. Unreliable measurements were excluded. A minimum of 2 days with at least 3 reliable measurements were required. We used a validated IOP PRS derived from 146 IOP-associated variants in a linear regression model adjusted for central corneal thickness and age. MAIN OUTCOME MEASURES: Highest recorded early morning IOP and mean IOP within and outside office hours. Early morning IOP spikes were defined by a higher early morning IOP than the maximum in-office hours IOP. RESULTS: Reliable measurements were obtained from 334 eyes of 176 participants (mean age, 64 ± 9 years). Eyes in the highest IOP PRS quintile showed an early morning IOP increase of 4.3 mmHg (95% confidence interval [CI], 1.4-7.3; P = 0.005) and mean increase in IOP outside office hours of 2.7 mmHg (95% CI, 0.61-4.7; P = 0.013) than the lowest quintile, which were significant independently after accounting for a recent in-clinic IOP measured by Goldmann applanation tonometry. Eyes in the highest PRS quintile were 5.4-fold more likely to show early morning IOP spikes than the lowest quintile (odds ratio 95% CI, 1.3-23.6; P = 0.023). CONCLUSIONS: A validated IOP PRS was associated with higher early morning IOP and mean IOP outside office hours. These findings support a role for genetic risk prediction of susceptibility to elevated IOP that may not be apparent during in-clinic hours, requiring more detailed clinical phenotyping using home tonometry, the results of which may guide additional interventions to improve IOP control.