Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss.

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma.

Estimating the Distribution of True Rates of Visual Field Progression in Glaucoma.

Purpose: The purpose of this study was to estimate the distribution of the true rates of progression (RoP) of visual field (VF) loss. Methods: We analyzed the progression of mean deviation over time in series of ≥ 10 tests from 3352 eyes (one per patient) from 5 glaucoma clinics, using a novel Bayesian hierarchical Linear Mixed Model (LMM); this modeled the random-effect distribution of RoPs as the sum of 2 independent processes following, respectively, a negative exponential distribution (the "true" distribution of RoPs) and a Gaussian distribution (the "noise"), resulting in a skewed exGaussian distribution. The exGaussian-LMM was compared to a standard Gaussian-LMM using the Watanabe-Akaike Information Criterion (WAIC). The random-effect distributions were compared to the empirical cumulative distribution function (eCDF) of linear regression RoPs using a Kolmogorov-Smirnov test. Results: The WAIC indicated a better fit with the exGaussian-LMM (estimate [standard error]: 192174.4 [721.2]) than with the Gaussian-LMM (192595 [697.4], with a difference of 157.2 [22.6]). There was a significant difference between the eCDF and the Gaussian-LMM distribution (P < 0.0001), but not with the exGaussian-LMM distribution (P = 0.108). The estimated mean (95% credible intervals, CIs) "true" RoP (-0.377, 95% CI = -0.396 to -0.359 dB/year) was more negative than the observed mean RoP (-0.283, 95% CI = -0.299 to -0.268 dB/year), indicating a bias likely due to learning in standard LMMs. Conclusions: The distribution of "true" RoPs can be estimated with an exGaussian-LMM, improving model accuracy. Translational Relevance: We used these results to develop a fast and accurate analytical approximation for sample-size calculations in clinical trials using standard LMMs, which was integrated in a freely available web application.

Choroidal hypertransmission width on optical coherence tomography: a prognostic biomarker in idiopathic macular hole surgery.

PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.

Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study.

PURPOSE: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Participants with ≥5 VFs (213 placebo, 217 treatment). METHODS: Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms. MAIN OUTCOME MEASURES: Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations. RESULTS: In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 µm thicker; P = 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression. CONCLUSIONS: No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hypotony Failure Criteria in Glaucoma Surgical Studies and Their Influence on Surgery Success.

PURPOSE: Review hypotony failure criteria used in glaucoma surgical outcome studies and evaluate their impact on success rates. DESIGN: Systematic literature review and application of hypotony failure criteria to 2 retrospective cohorts. PARTICIPANTS: A total of 934 eyes and 1765 eyes undergoing trabeculectomy and deep sclerectomy (DS) with a median follow-up of 41.4 and 45.4 months, respectively. METHODS: Literature-based hypotony failure criteria were applied to patient cohorts. Intraocular pressure (IOP)-related success was defined as follows: (A) IOP ≤ 21 mmHg with ≥ 20% IOP reduction; (B) IOP ≤ 18 mmHg with ≥ 20% reduction; (C) IOP ≤ 15 mmHg with ≥ 25% reduction; and (D) IOP ≤ 12 mmHg with ≥ 30% reduction. Failure was defined as IOP exceeding these criteria in 2 consecutive visits > 3 months after surgery, loss of light perception, additional IOP-lowering surgery, or hypotony. Cox regression estimated failure risk for different hypotony criteria, using no hypotony as a reference. Analyses were conducted for each criterion and hypotony type (i.e., numerical [IOP threshold], clinical [clinical manifestations], and mixed [combination of numerical or clinical criteria]). MAIN OUTCOME MEASURES: Hazard ratio (HR) for failure risk. RESULTS: Of 2503 studies found, 278 were eligible, with 99 studies (35.6%) lacking hypotony failure criteria. Numerical hypotony was predominant (157 studies [56.5%]). Few studies used clinical hypotony (3 isolated [1.1%]; 19 combined with low IOP [6.8%]). Forty-nine different criteria were found, with IOP < 6 mmHg, IOP < 6 mmHg on ≥ 2 consecutive visits after 3 months, and IOP < 5 mmHg being the most common (41 [14.7%], 38 [13.7%], and 13 [4.7%] studies, respectively). In both cohorts, numerical hypotony posed the highest risk of failure (HR, 1.51-1.21 for criteria A to D; P < 0.001), followed by mixed hypotony (HR, 1.41-1.20 for criteria A to D; P < 0.001), and clinical hypotony (HR, 1.12-1.04; P < 0.001). Failure risk varied greatly with various hypotony definitions, with the HR ranging from 1.02 to 10.79 for trabeculectomy and 1.00 to 8.36 for DS. CONCLUSIONS: Hypotony failure criteria are highly heterogenous in the glaucoma literature, with few studies focusing on clinical manifestations. Numerical hypotony yields higher failure rates than clinical hypotony and can underestimate glaucoma surgery success rates. Standardizing failure criteria with an emphasis on clinically relevant hypotony manifestations is needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk Factors for Failure in Glaucoma Patients Undergoing Microshunt Implantation.

PURPOSE: To evaluate risk factors for failure of Microshunt in glaucoma patients. DESIGN: Multicenter retrospective cohort study. METHODS: The study included 220 eyes from 220 consecutive glaucoma patients undergoing Microshunt implantation at six glaucoma units. Four intraocular pressure (IOP) success criteria were defined: (A) IOP ≤21 mm Hg with ≥20% IOP reduction; (B) IOP ≤18 mm Hg with ≥20% IOP reduction; (C) IOP ≤15 mm Hg with ≥25% IOP reduction; and (D) IOP ≤12 mm Hg with ≥30% IOP reduction from baseline. Kaplan-Meier analysis was used to estimate success rates according to the criteria above, and multivariable Cox models were used to identified risk factors for failure according to criterion A. RESULTS: Success rates varied based on different criteria, ranging from 43.3% to 62.5% (overall success for criteria D and A, respectively) and from 35.3% to 44.4% (complete success for criteria D and A, respectively) at 1-year follow-up. Higher intraoperative MMC concentration was associated with reduced risk of failure to maintain complete (0.4 vs 0.2 mg/mL: hazard ratio [HR] = 0.441, P < .001) and overall (0.4 vs 0.2 mg/mL: HR = 0.360, P = .004) success. For complete success, other risk factors for failure were pseudoexfoliation glaucoma/pigmentary glaucoma (HR = 1.641, P = .004), primary angle closure glaucoma (HR = 1.611, P < .001), and previous non-glaucomatous ocular surgeries (HR = 2.301, P = .002). For overall success, other risk factors for failure were lower preoperative IOP (for 1-mm Hg increase, HR = 0.934, P = .005), higher number of preoperative antiglaucoma agents (HR = 1.626, P < .001), and Microshunt combined with cataract surgery (HR = 1.526, P = .033). CONCLUSIONS: This study identified risk factors for Microshunt failure, highlighting the importance of high intraoperative MMC dose and careful patient selection to optimize surgical success.

Rate and associations of inner retinal thinning in eyes with retinal vein occlusion and regressed macular oedema.

PURPOSE: To investigate the associations between visual acuity (VA) and structural optical coherence tomography (OCT) features in retinal vein occlusion (RVO) eyes after cystoid macular oedema (CMO) regression and to assess whether inner retinal thinning is progressive. METHODS: Retrospective observational study of RVO eyes with regressed CMO for at least 6 months. OCT scans at CMO regression were analysed, and features were correlated with VA at that visit. The inner retinal thickness was longitudinally compared between RVO and unaffected fellow eyes (controls) with linear mixed models. The rate of inner retinal thinning was obtained as the interaction term between disease status and time. Associations between inner retinal thinning and clinical characteristics were explored. RESULTS: Thirty-six RVO eyes were followed for 34.2 ± 21.1 months after CMO regression. The presence of ellipsoid zone disruption (regression estimate[standard error(SE)] = 0.16[0.04] LogMAR vs. intact, p < 0.001) and lower inner retinal thickness (regression estimate[SE] = -0.25[0.12] LogMAR for 100-µm increase, p = 0.01) were associated with worse VA. The inner retinal thickness decreased faster in RVO than controls (rate of retinal thinning -0.27 ± 0.09 µm/month vs. -0.08 ± 0.11 µm/month, p = 0.01). Macular ischaemia was associated with a faster rate of retinal thinning (interaction term macular ischaemia*follow-up time, p = 0.04). CONCLUSION: Inner retinal and photoreceptors' layers integrity are associated with better visual acuity once CMO resolves. RVO eyes undergo progressive inner retinal thinning after CMO regression, faster in eyes with macular ischaemia.

Validating Trend-Based End Points for Neuroprotection Trials in Glaucoma.

Purpose: The purpose of this study was to evaluate the power of trend-based visual field (VF) progression end points against long-term development of event-based end points accepted by the US Food and Drug Administration (FDA). Methods: One eye from 3352 patients with ≥10 24-2 VFs (median = 11 years) follow-up were analyzed. Two FDA-compatible criteria were applied to these series to label "true-progressed" eyes: ≥5 locations changing from baseline by more than 7 dB (FDA-7) or by more than the expected test-retest variability (GPA-like) in 2 consecutive tests. Observed rates of progression (RoP) were used to simulate trial-like series (2 years) randomly assigned (1000 times) to a "placebo" or a "treatment" arm. We simulated neuroprotective "treatment" effects by changing the proportion of "true progressed" eyes in the two arms. Two trend-based methods for mean deviation (MD) were assessed: (1) linear mixed model (LMM), testing average difference in RoP between the two arms, and (2) time-to-progression (TTP), calculated by linear regression as time needed for MD to decline by predefined cutoffs from baseline. Power curves with 95% confidence intervals were calculated for trend and event-based methods on the simulated series. Results: The FDA-7 and GPA-like progression was achieved by 45% and 55% of the eyes in the clinical database. LMM and TTP had similar power, significantly superior to the event-based methods, none of which reached 80% power. All methods had a 5% false-positive rate. Conclusions: The trend-based methods can efficiently detect treatment effects defined by long-term FDA-compatible progression. Translational Relevance: The assessment of the power of trend-based methods to detect clinically relevant progression end points.

Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema.

INTRODUCTION: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). METHODS: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. RESULTS: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (ß = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (ß = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. CONCLUSION: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.

Laser goniopuncture after deep sclerectomy: incidence, long-term outcomes and risk factors for failure.

AIMS: To report the incidence, risk factors and long-term outcomes of laser goniopuncture (LGP) in patients with previous deep sclerectomy (DS). METHODS: Retrospective cohort study of 1765 eyes (1385 patients) undergoing DS with or without cataract surgery between 2001 and 2020 in two UK institutions. Kaplan-Meier was used to estimate LGP incidence. DS success after LGP was calculated for criteria A, B, and C defined as intraocular pressure (IOP) of ≤18, ≤15 and ≤12 mm Hg with 20%, 25% and 30% reduction, respectively. Cox regression was used to investigate factors associated with the risk of failure. RESULTS: LGP had an estimated incidence of 33.3% (30.9%-35.6%), 56.3% (53.5%-58.9%) and 62.8% (59.7%-65.6%) at 1, 3, 5 years, respectively. Mean (±SD) IOP significantly (p<0.001) decreased from 21.2 (±6.0) mm Hg pre-LGP to 13.8 (±5.2) mm Hg and 12.9 (±4.7) mm Hg at 3 and 5 years post-LGP, respectively. Success rates at 3 and 5 years were, respectively, 40.9% (37.5%-44.6%) and 33.7% (30.3%-37.6%) for criterion A; 27.1% (24.0%-30.5%) and 22.3% (19.3%-25.7%) for criterion B and 13.9% (11.6%-16.7%) and 11.6% (9.5%-14.3%) for criterion C. In all models, higher pre-LGP IOP (p<0.001) and higher pre-LGP medication number (p<0.001) were associated with increased failure, while male gender (p≤0.004), intraoperative mitomycin C (p≤0.031), longer interval between DS and LGP (p≤0.01) with reduced failure. CONCLUSION: Most patients undergoing DS will eventually require LGP. LGP is effective at rescuing eyes with a failing DS. This study identifies several factors associated with LGP outcomes, knowledge of which may help clinicians predict LGP success.

RISK FACTORS OF VISION LOSS AND MULTIPLE RECURRENCES IN MYOPIC MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the factors associated with maximum visual improvement (peak vision) gain and the risk factors of peak vision loss and multiple recurrences in myopic macular neovascularization undergoing antivascular endothelial growth factor therapy. METHODS: Retrospective study of 310 eyes with active myopic macular neovascularization and median follow-up of 3.5 years. We defined peak vision gain as the maximum best-corrected visual acuity value reached under treatment and peak vision loss as best-corrected visual acuity never scoring as peak vision. We used multiple-event Prentice, Williams, and Peterson models to compute recurrences' incidence and Cox regression to identify risk factors for peak vision gain, peak vision loss, and multiple recurrences. RESULTS: Eyes with worse baseline best-corrected visual acuity {hazard ratio (HR) = 2.59 (95% confidence interval [CI]: 1.63-4.11) for 0.1 logMAR increase, P < 0.001} had higher chance to achieve peak vision. Peak vision was lost in 162 eyes (52%). Older age (HR = 1.22 [95% CI: 1.02-1.43] for 10-year increase, P = 0.02) and recurrences (HR = 1.10 [95% CI: 1.01-1.22] for event, P = 0.04) predicted nonsustained peak vision. Older age (HR = 1.13 [95% CI: 1.04-1.27] for 10-year increase, P = 0.006), larger myopic macular neovascularization (HR = 1.06 [95% CI: 1.01-1.13] for 1-mm 2 increase, P = 0.04), and juxtafoveal location (HR = 1.88 [95% CI: 1.28-2.77] vs. extrafoveal, P = 0.001) predicted multiple recurrences. CONCLUSION: Myopic macular neovascularization eyes lose vision mainly because of multiple recurrences. Patients at risk for recurrences should undergo more attentive monitoring to avoid vision loss.

Short-term safety and efficacy of Preserflo™ Microshunt in glaucoma patients: a multicentre retrospective cohort study.

BACKGROUND/AIMS: To evaluate 1-year success rates and safety profile of Preserflo™ Microshunt in glaucoma patients. METHODS: Retrospective multicentre cohort study of 100 consecutive eyes (91 patients) from four tertiary-referral glaucoma centres. Four intraocular pressure (IOP) criteria were defined: A: IOP ≤ 21 mmHg+IOP reduction ≥20% from baseline; B: IOP ≤ 18 mmHg+IOP reduction ≥20%; C: IOP ≤ 15 mmHg+IOP reduction ≥25%; D: IOP≤12 mmHg+IOP reduction ≥30%. Success was defined as qualified or complete based on whether reached with or without medication. Primary outcome was success according to the above criteria. Secondary outcomes included: IOP, best-corrected visual acuity (BCVA), medication use, complications, postoperative interventions, and failure-associated factors. RESULTS: Qualified and complete success rates (95% CI) at 12 months were 74%(66-83%) and 58%(49-69%) for criterion A, 72%(63-82%) and 57%(48-68%) for B, 52%(43-63%) and 47%(38-58%) for C, 29%(21-40%) and 26%(19-36%) for D. Overall median (interquartile range (IQR)) preoperative IOP decreased from 21.5(19-28) mmHg to 13(11-16) mmHg at 12 months. BCVA was not significantly different up to 12 months (p = 0.79). Preoperative median (IQR) number of medications decreased from 3 (2-3) to 0 (0-1) at 12 months. Twelve eyes underwent needling, five surgical revision and one device removal due to corneal oedema. There were no hypotony-related complications. Non-Caucasian ethnicity was the only risk factor consistently associated with increased failure. CONCLUSIONS: Preserflo™ Microshunt is a viable surgical option in glaucoma patients, with reasonable short-term success rates, decreased medications use, excellent safety profile, smooth postoperative care, and rapid learning curve. Success rates for the most stringent IOP cutoffs were modest, indicating that it may not be the optimal surgery when very low target IOP is required.

Factors associated with the response to fluocinolone acetonide 0.19 mg in diabetic macular oedema evaluated as the area-under-the-curve.

OBJECTIVES: The area-under-the-curve (AUC) measures the average drug effect over time. We investigated the impact of baseline clinical and optical coherence tomography (OCT) factors on the response to fluocinolone acetonide (FAc) 0.19 mg implant in patients with diabetic macular oedema (DMO) as the AUC over 36 months. METHODS: Retrospective study of DMO eyes undergoing FAc with follow-up from 12 to 36 months. The AUC of the best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were calculated with the trapezoidal rule. Demographic and clinical data at the time of FAc administration were collected, and associations with BCVA and CMT changes were investigated with linear mixed models. RESULTS: Eighty-nine eyes of 63 patients were enroled; median follow-up was 26 months. Mean±standard deviation (SD) AUCBCVA and AUCCMT after FAc injection were 0.24 ± 0.17 LogMAR/month and 179.6 ± 54.3 µm/month, respectively. Worse baseline BCVA (ß = 0.30 LogMAR/month, p < 0.001), higher AUCCMT after FAc administration (ß = 0.08 LogMAR/month, p < 0.001), diagnosis of type 1 diabetes (ß = -0.04 LogMAR/month, p = 0.04), and absent ELM/EZ layers (ß = 0.06 LogMAR/month, p = 0.01) were associated with worse vision over time (higher AUCBCVA). Eyes with higher CMT at baseline (ß = 9.61 µm/month, p < 0.001) and those with tractional DMO (ß = 24.7 µm/month, p = 0.01) had worse anatomic outcomes (higher AUCCMT). The need for additional treatments after FAc was also associated with higher AUCCMT (ß = 33.9 µm/month, p = 0.001). CONCLUSION: Baseline better visual acuity, lower macular thickness, and photoreceptors' layers integrity are associated with better functional response to FAc in DMO. Eyes with severe DMO at the time of implant or tractional oedema have worse anatomic response. These findings might guide clinicians in a more informed decisional algorithm in treating DMO.

A Metascore of Multiple Imaging Methods to Measure Long-Term Glaucoma Structural Progression.

Purpose: To develop a structural metascore (SMS) that combines measurements from different devices and expresses them on a single scale to facilitate their long-term analysis. Methods: Three structural measurements (Heidelberg Retina Tomograph II [HRT] rim area, HD-Cirrus optical coherence tomography [OCT] average retinal nerve fiber layer [RNFL] thickness, Spectralis OCT RNFL global thickness) were normalized on a scale of 0 to 100 and converted to a reference value. The resultant metascores were plotted against time. SMS performance was evaluated to predict future values (internal validation), and correlations between the average grades assigned by three clinicians were compared with the SMS slopes (external validation). Results: The linear regression fit with the variance approach, and adjustment to a Spectralis equivalent was the best-performing approach; this was denominated metascore. Plots were created for 3416 eyes of 1824 patients. The average baseline age (± standard deviation) was 69.8 (±13.9), mean follow-up was 11.6 (±4.7) years, and mean number of structural scans per eye was 10.0 (±4.7). The mean numbers of scans per device were 3.8 (±2.5), 5.0 (±2.9), and 1.3 (±3.0) for HRT, Cirrus, and Spectralis, respectively. The metascore slopes' median was -0.3 (interquartile range 1.1). Correlations between the average grades assigned by the three clinicians and the metascore slopes were -0.51, -0.49, and -0.69 for the first (structural measurement printouts alone), second (metascore plots alone), and third (printouts + metascore plots) series of gradings, respectively. The average absolute predictive ability was 7.63/100 (whereas 100 = entire normalized scale). Conclusions: We report a method that converts Cirrus global RNFL and HRT global rim area normalized measurements to Spectralis global RNFL equivalent values to facilitate long-term structural follow-up. Translational Relevance: Because glaucoma changes usually occur slowly, patients are often examined with different instruments during their follow-up, a method that "unifies" structural measurements provided by different devices, which could assist patients' longitudinal structural follow-up.

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness Values Using Spectral-Domain and Swept-Source OCT.

Purpose: To compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC). Methods: Cross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves. Results: Both SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities. Conclusions: Thickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects. Translational Relevance: OCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients.

Long-term Incidence and Risk Factors of Macular Fibrosis, Macular Atrophy, and Macular Hole in Eyes with Myopic Neovascularization.

PURPOSE: To identify the risk factors associated with myopic macular neovascularization (mMNV)-related complications in patients treated with intravitreal anti-VEGF agents. DESIGN: Longitudinal cohort study. PARTICIPANTS: Myopic eyes (n = 313) with active mMNV and median (interquartile range) follow-up of 42 months (interquartile range, 18-68 months) after initiation of anti-VEGF treatment. METHODS: Data regarding patients' clinical and mMNV-related characteristics were collected at baseline. Subsequent OCT scans were inspected for mMNV-related complications. Best-measured visual acuity (BMVA) values were retrieved from each visit. MAIN OUTCOME MEASURES: Incidence rate and hazard ratio (HR, with 95% confidence interval [CI]) of risk factors for fibrosis and macular atrophy calculated with Kaplan-Meier curves and Cox regression models. Crude incidence of macular hole (MH). Longitudinal BMVA changes. RESULTS: Five-year incidence of fibrosis, atrophy, and MH were 34%, 26%, and 8%, respectively. The rate of fibrosis was 10.3 (95% CI, 8.25-12.6) per 100 person-years. Risk factors were subfoveal mMNV location (HR [95% CI] = 12.7 [2.70-56.7] vs. extrafoveal, P = 0.001) and intraretinal fluid at baseline (HR [95% CI] = 1.75 [1.05-2.98], P = 0.03). The rate of macular atrophy was 6.5 (95% CI, 5-8.3) per 100 person-years. Risk factors were diffuse (HR, 2.20 vs. tessellated fundus; 95% CI, 1.13-5.45; P = 0.02) or patchy chorioretinal atrophy (HR, 3.17 vs. tessellated fundus; 95% CI, 1.32-7.64; P = 0.01) at baseline and more numerous anti-VEGF injections before baseline (HR, 1.21; 95% CI, 1.06-1.38 for each treatment; P = 0.005). Eyes with fibrosis and macular atrophy had faster BMVA decay over follow-up. Twenty eyes (6%) developed MH. Two subtypes of MH were identified: "atrophic" and "tractional." CONCLUSIONS: Myopic MNV-related complications are common in the long term despite initially successful treatment and have detrimental effects on visual acuity. Insights into their incidence and risk factors may help for future treatments to mitigate sight-threatening outcomes.

ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE.

PURPOSE: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. METHODS: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. RESULTS: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- µ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. CONCLUSION: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.

CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS.

PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.