Subset Of Eyes Research Articles

Censoring the Floor Effect in Long-Term Stargardt Disease Microperimetry Data Produces a Faster Rate of Decline

PURPOSETo evaluate progression rate estimation in long-term Stargardt disease microperimetry data by accounting for floor effect. DESIGNCohort study METHODSCross-sectional and longitudinal microperimetry data (Grid A: 18° diameter, Grid B: 6° diameter; MAIA microperimeter, dynamic range 0-36 dB) was extracted from patients with biallelic mutation in the ABCA4 gene. For each eye, mean sensitivity (MS) and responding point sensitivity (RPS) rates were extracted. Floor censored sensitivity (FCS) progression rate, which accounts for the floor effect at each locus by terminating calculation when scotoma was observed in 2 consecutive visits, was also calculated. In a subset of eyes with ≥1 scotomatous locus at baseline (Grid A), sensitivity progression of loci around the scotoma (edge of scotoma sensitivity, ESS) was examined against to other progression parameters. Paired t-test compared progression rate parameters across the same eyes. MAIN OUTCOME MEASURESMicroperimetry grid parameters at baseline and progression rates. RESULTSA total of 37 subjects with biallelic ABCA4 mutations and >2 years of longitudinal microperimetry data were included in the study. In Grid A, at baseline, the average MS and RPS were 16.5 ± 7.9 and 19.1 ± 5.7 dB, respectively. Similar MS (18.4 ± 7.6 dB) and RPS (20.0 ± 5.5 dB) values were found at baseline for Grid B. In Grid A, overall, MS, RPS and FCS progression rates were -0.57 ± 1.05, -0.74 ±1.24 and -1.26 ± 1.65 (all db/yr), respectively. FCS progression rate was significantly greater than the MS or RPS progression rates. Similar findings were observed in Grid B (MS -1.22 ± 1.42, RPS -1.44 ± 1.44, FCS -2.16 ± 2.24, all dB/yr), with paired t-test again demonstrated that FCS had a significantly faster rate of decline than MS or RPS. In patients with progression data in both grids, MS, RPS and FCS progression rates were significantly faster in the smaller Grid B. In 24 eyes with scotoma at baseline, fastest rate of decline was ESS combined with FCS compared to other progression parameters. CONCLUSIONSIncorporation of FCS can reduce confound of floor effect in perimetry analysis and can in turn detect a faster rate of decline.

The prophylactic value of TNF-α inhibitors against retinal cell apoptosis and optic nerve axon loss after corneal surgery or trauma.

Late secondary glaucoma is an often-severe complication after acute events like anterior segment surgery, trauma and infection. TNF-α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti-TNF-α antibodies are in animals very effective in protecting the retinal cells and the optic nerve-and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF-α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration. For drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub-set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified. Subconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50% axon loss as compared to 8% in the adalimumab treatment group. Subconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long-term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti-TNF-α biologics to reduce inflammation and future secondary glaucoma.

Progression of Early Glaucomatous Damage: Performance of Summary Statistics From Optical Coherence Tomography and Perimetry.

Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression. Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a "progressor" if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression. Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives. Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used. All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.

Outcome of Off-Label AREDS 2 Supplementation for the Treatment of Macular Degeneration in Non-Proliferative Idiopathic Type 2 Macular Telangiectasia.

PurposeTo evaluate if off-label Age-Related Eye Disease Study 2 (AREDS2) supplementation prevents visual and anatomical deterioration in non-proliferative Idiopathic Macular Telangiectasia Type 2 (IMT2).Patients and MethodsThis is a single-center retrospective, comparative study of 82 IMT2 eyes treated with AREDS2 from January 1st, 2013 to January 1st, 2018. The study analysis consisted of a non-comparative arm, which included all AREDS2 eyes, and a comparative arm (27 AREDS2 and 42 untreated eyes) that only included eyes with complete follow-up data. Eyes were evaluated at baseline, 12 and 24 months. Better/worse eye sub-analysis was performed in the comparative study arm. Primary outcomes were best corrected visual acuity (BCVA) and optical coherence tomography (OCT) anatomical characteristics including largest cavitation diameter, central macular thickness (CMT), and length of ellipsoid zone (EZ) loss at 24 months.ResultsIn the non-comparative arm, AREDS2 eyes showed stable BCVA (0.28 ± 0.18 logMAR at baseline vs 0.26 ± 0.19 logMAR at 24 months; p = 0.35) and OCT anatomical features after 24 months of supplementation. In the comparative arm, BCVA mean difference was greater for untreated eyes at 24 months (−0.09 ± 0.15 vs 0.03 ± 0.11 logMAR; p = <0.001). AREDS2 eyes had decreased cavitary diameter and EZ loss compared to untreated eyes at the study endpoint (p = 0.01 and p = 0.02, respectively). CMT remained stable for both cohorts throughout the study. For better/worse eye analysis, untreated eyes had worse BCVA at 24 months in both better and worse eyes (both p = 0.01). For anatomical outcomes, increases in both EZ loss (p = 0.04) and cavitary diameter (p = 0.001) among untreated eyes were only significant for eyes with worse baseline BCVA.ConclusionOur results suggest that off-label AREDS2 supplementation in non-proliferative IMT2 may prevent anatomical and visual deterioration in a subset of eyes.

Comparison and Repeatability of High Resolution and High Speed Scans from Spectralis Optical Coherence Tomography Angiography.

PurposeThe purpose of this study was to evaluate and compare the repeatability of optical coherence tomography angiography (OCTA) derived retinal vascular quantitative metrics using high resolution (HR) versus high speed (HS) acquisition modes.MethodsMacular 4.4 × 2.9-mm OCTA images from normal, healthy volunteers were captured using both HR (768 A-scans × 256 B-scans) and HS (384 A-scans × 256 B-scans) acquisition protocols. Vessel density and vessel length density of the superficial capillary plexus and deep capillary plexus, as well as choriocapillaris flow deficit were computed. In a subset of eyes, the OCTA scans were repeated twice 2 days later and the same metrics were recomputed to assess repeatability, using intraclass correlation coefficients and coefficient of variation (CV).ResultsComparison of measurements between HR and HS acquisitions in 41 healthy eyes showed statistically significant differences for all quantitative metrics (P < 0.01). However, no significant differences were observed among the three repeated scans (one on day 1 and two on day 3) obtained with each of the acquisition modes. The CVs ranged from 0.01 to 0.03 with the HR mode and 0.01 to 0.04 with the HS mode. The intraclass correlation coefficients (ICCs) among measurements were similar and high for both HR and HS modes, ranging from 0.844 to 0.949.ConclusionsHR and HS OCTA acquisition modes both yielded repeatable quantitative metrics for the retinal circulation and the choriocapillaris. However, despite a similar field, the HR and HS derived measurements differed significantly.Translational RelevanceTo establish OCTA imaging in clinical and research practice, standardized and repeatability image analysis are necessary.

Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in USH2A Retinopathy.

PurposeMicroperimetry is commonly used to assess retinal function. We perform cross-sectional and longitudinal analysis on microperimetry parameters in USH2A retinopathy and explore end points suitable for future clinical trials.MethodsMicroperimetry was performed using two grids, Grid 1 (18° diameter) and Grid 2 (6° diameter). In Grid 1, four parameters (number of nonscotomatous loci, mean sensitivity [MS], responding point sensitivity [RPS], and edge of scotoma sensitivity [ESS]) were analyzed. In Grid 2, number of nonscotomatous loci and MS were examined. Interocular symmetry was also examined. Longitudinal analysis was conducted in a subset of eyes.ResultsMicroperimetry could be performed in 16 of 21 patients. In Grid 1 (n = 15; average age, 35.6 years), average number of nonscotomatous loci, MS, RPS, and ESS were 46.6 loci, 10.0 dB, 14.7 and 9.6 dB, respectively. In Grid 2 (n = 13; average age, 37.4 years), 12 eyes had measurable sensitivity across the entire grid. Average MS was 23.8 dB. Interocular analysis revealed large 95% confidence intervals for all parameters. Longitudinally, Grid 1 (n = 12, average follow-up 2.6 years) ESS showed the fastest rate of decline (–1.84 dB/y) compared with MS (–0.34 dB/y) and RPS (–0.90 dB/y).ConclusionsOur data suggest that ESS may be more useful than MS and RPS in test grids that cover a large extent of the macula. We caution the use of contralateral eye as an internal control.Translational RelevanceESS may decrease the duration or sample size of treatment trials in USH2A retinopathy.

Quiescent Neovascular Age-Related Macular Degeneration After Endophthalmitis.

This article describes eyes that achieved extended remission of neovascular age-related macular degeneration (NVAMD) following acute endophthalmitis. Adults who presented to the Duke Eye Center with acute endophthalmitis over a 9-year period and had at least 3 months of follow-up were identified. A retrospective review of medical records was performed to collect clinical data including demographic information, examination findings, etiology, treatment, and outcomes. A total of 133 eyes of 130 patients with endophthalmitis were identified. Of these, 15 eyes of 14 patients (11.3%) were receiving intravitreal antivascular endothelial growth factor (anti-VEGF) injections for NVAMD. Six of these 15 eyes (40%) did not require an anti-VEGF injection after endophthalmitis for a mean of 36.2 months. Endophthalmitis was injection-related in 5 of 6 eyes (83%) and Baerveldt glaucoma drainage device-related in 1 of 6 eyes (17%). Two of the 6 (33%) had culture-proven infectious endophthalmitis, whereas 4 of 6 (67%) had culture-negative endophthalmitis. Five of 6 eyes have required no anti-VEGF therapy to date; the remaining eye restarted intravitreal aflibercept therapy 9.3 months after endophthalmitis. Acute endophthalmitis may be associated with reduced activity of choroidal neovascularization in a subset of eyes with NVAMD.

Myopia and anterior segment optical coherence tomography findings in laser-treated retinopathy of prematurity eyes

To evaluate structural features and visual outcomes in eyes with a prior history of laser treatment for retinopathy of prematurity (ROP). Laser-treated eyes for type 1 ROP, preterm monitored eyes, and full-term control eyes were included. LogMAR conversion of Snellen best-corrected visual acuity and spherical equivalent based on cycloplegic refraction were measured in children 5-15years of age. Anterior segment optical coherence tomography (OCT) was used to study structural features, including anterior chamber angle (ACA) in a subset of eyes. A total of 50 eyes of 50 patients were included (19 full-term eyes, 19 laser-treated type 1 ROP eyes, 12 preterm monitored eyes). Of these, 44 eyes had visual outcomes data, and 15 eyes had anterior segment data. There was no significant difference in sex or age at final examination between the three groups. There was no significant difference in gestational age between the laser-treated and preterm monitored groups. Compared with the full-term control group and the preterm monitored group, the laser-treated ROP group had narrower ACA and more myopic refractive error. There was a significant correlation between ACA and spherical equivalent. Laser treatment may affect angle configuration in ROP eyes. Anterior segment OCT is an easy and useful modality that could aid in screening for visually impairing conditions such as myopia and glaucoma in children with ROP.

A Deep Learning Approach for Automated Detection of Geographic Atrophy from Color Fundus Photographs

To assess the utility of deep learning in the detection of geographic atrophy (GA) from color fundus photographs and to explore potential utility in detecting central GA (CGA). A deep learning model was developed to detect the presence of GA in color fundus photographs, and 2 additional models were developed to detect CGA in different scenarios. A total of 59 812 color fundus photographs from longitudinal follow-up of 4582 participants in the Age-Related Eye Disease Study (AREDS) dataset. Gold standard labels were from human expert reading center graders using a standardized protocol. A deep learning model was trained to use color fundus photographs to predict GA presence from a population of eyes with no AMD to advanced AMD. A second model was trained to predict CGA presence from the same population. A third model was trained to predict CGA presence from the subset of eyes with GA. For training and testing, 5-fold cross-validation was used. For comparison with human clinician performance, model performance was compared with that of 88 retinal specialists. Area under the curve (AUC), accuracy, sensitivity, specificity, and precision. The deep learning models (GA detection, CGA detection from all eyes, and centrality detection from GA eyes) had AUCs of 0.933-0.976, 0.939-0.976, and 0.827-0.888, respectively. The GA detection model had accuracy, sensitivity, specificity, and precision of 0.965 (95% confidence interval [CI], 0.959-0.971), 0.692 (0.560-0.825), 0.978 (0.970-0.985), and 0.584 (0.491-0.676), respectively, compared with 0.975 (0.971-0.980), 0.588 (0.468-0.707), 0.982 (0.978-0.985), and 0.368 (0.230-0.505) for the retinal specialists. The CGA detection model had values of 0.966 (0.957-0.975), 0.763 (0.641-0.885), 0.971 (0.960-0.982), and 0.394 (0.341-0.448). The centrality detection model had values of 0.762 (0.725-0.799), 0.782 (0.618-0.945), 0.729 (0.543-0.916), and 0.799 (0.710-0.888). A deep learning model demonstrated high accuracy for the automated detection of GA. The AUC was noninferior to that of human retinal specialists. Deep learning approaches may also be applied to the identification of CGA. The code and pretrained models are publicly available at https://github.com/ncbi-nlp/DeepSeeNet.

Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy.

To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes. Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements. In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.

Mastering Lens Calculations: New Formulas and Comparisons

To provide a glimpse into some of the newer methods of performing IOL calculations and recent literature on which formulas and calculation strategies have been recommended for a certain subset of eyes. A literature review was performed to investigate all the relevant, recently published studies on the progress, comparisons, and recent advancements of IOL calculations. Based on this review, the appropriate history, evolution, progress, limitation, and recent advancements are analyzed and explained. A plethora of IOL formulas and calculation strategies have been developed to help surgeons achieve the most desired post-operative outcome for their patients. Modern IOL formulas, calculation strategies, and biometric devices perform well for average eyes; however, they remain less optimal for eyes with atypical biometric parameters. There is no single solution that has been deemed as the perfect formula which can simplify the process and consistently provide accurate results for all types of eyes. Over the years, a number of different formula optimization strategies have been devised for traditional IOL formulas and newer, more sophisticated IOL formulas with advanced mathematical algorithms have been developed. By addition of new input parameters and use of complex mathematics to better estimate post-operative lens position, these solutions may minimize refractive error. These methods may provide increasing improvement in both typical and atypical eyes in the years to come.

Outcomes of Pars Plana Vitrectomy for Epiretinal Membrane in Eyes With Coexisting Dry Age-related Macular Degeneration

There has been limited evidence on the benefits of pars plana vitrectomy with membrane peel (PPV-MP) for epiretinal membrane (ERM) in eyes with dry age-related macular degeneration (AMD). We sought to assess anatomic and functional outcomes of PPV-MP for ERM in this subset of eyes. A retrospective cohort study. Patients with dry AMD who underwent PPV-MP for ERM from January 1, 2010, to December 1,2016. Visual acuity (VA) and central foveal thickness (CFT) as measured on spectral-domain OCT were recorded and analyzed for the preoperative, 6-month, and final follow-up visits. The presence of cystoid macular edema (CME) and ellipsoid zone (EZ) integrity were recorded and compared with postoperative imaging. Conversion to neovascular AMD in eyes for which at least 2 years of follow-up were available, as confirmed by either OCT and/or fluorescein angiography and documentation of treatment with intravitreal antivascular endothelial growth factor, was recorded and compared between case eyes that underwent PPV-MP versus fellow control eyes. Postoperative VA. A total of 38 eyes from 38 patients met the study criteria. There was a significant improvement in the median (interquartile range, [IQR]) logarithm of the minimum angle of resolution [logMAR] VA from 0.60 (IQR 0.46-1.00) (20/80, Snellen equivalent) at the preoperative visit, to 0.48 (IQR 0.30-0.70) (20/60, Snellen equivalent) at the 6-month follow-up visit (P= 0.04), and to 0.48 (IQR 0.30-0.70) (20/60, Snellen equivalent) at the final visit (P= 0.01). There was a significant median decrease in CFT at the final visit (P < 0.001) compared with the preoperative CFT. Only eyes with either CME or an intact EZ showed significant improvement in median logMAR VA at the final visit compared with the preoperative visit (P= 0.01 and P= 0.004, respectively). In a subgroup analysis of eyes for which a minimum of 2 years of follow-up were available, 4 of 25 (16.0%) vitrectomized eyes and 1 of 25 (4.0%) fellow control eyes progressed to neovascular AMD (P= 0.16). PPV-MP appears to confer anatomic and functional improvement in eyes with ERM and coexisting dry AMD. Moreover, greater preoperative CFT, the presence of CME, and an intact EZ were predictors of VA improvement in these eyes.

Association Between Soluble CD14 in the Aqueous Humor and Hyperreflective Foci on Optical Coherence Tomography in Patients With Diabetic Macular Edema.

To investigate the associations between soluble CD14 (sCD14), a cytokine released by microglia and macrophages, and hyperreflective foci (HF) and various characteristics of spectral-domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME). Sixty-nine eyes from 51 patients with DME and 28 eyes from 28 control subjects were studied. sCD14 levels in the aqueous humor (AH) were measured using ELISA before bevacizumab injection (IVB), and the associations between sCD14 and visual acuity, the number of HF, retinal volume, and the DME pattern were assessed. sCD14 levels were higher in DME patients than in the control subjects (29.9 ± 41.6 pg/mL versus 8.1 ± 3.6 pg/mL, P < 0.001). sCD14 levels in diffuse edema were higher than those in focal edema (50.0 ± 65.3 pg/mL versus 19.8 ± 14.7 pg/mL, P = 0.039). The number of HF in the inner retina of patients with diffuse edema was significantly higher than that in patients with focal edema (4.4 ± 2.3 vs. 2.6 ± 2.1, P = 0.001), but no difference was found in the outer retina (5.8 ± 3.4 vs. 5.0 ± 3.9, P = 0.25). According to multivariate analyses, elevated sCD14 levels were associated with an increased inner nuclear layer volume and the total number of HF in all retinal layers on SD-OCT. Reduction of DME following IVB was correlated with reduction in the number of HF in a subset of eyes followed longitudinally in the study (n = 30). DME patients with diffuse edema exhibit higher sCD14 levels in the AH and more HF in the inner retina than patients with focal edema, indicating severe inflammation. The strong correlation between sCD14 and HF in the inner retina suggests that the HF observed on SD-OCT may be due to activated microglia in DME.

Recovery of Foveal Anatomy and Subfoveal Lucency after Pharmacologic and Surgical Macular Hole Closure in the Ocriplasmin Phase III Trials

To compare foveal anatomic features on OCT after macular hole (MH) closure, and their association with visual function, in the ocriplasmin phase III trials. Randomized clinical trial. One hundred fifty-three participants. Each participant had 1 eye with baseline MH randomized to single intravitreal injection of placebo or ocriplasmin. After enrollment in 1 of the 2 nonsurgical treatment groups, a subset of eyes were analyzed in a surgical treatment group that had pars plana vitrectomy (PPV) after placebo or ocriplasmin. Subfoveal lucency after MH closure was graded on time-domain OCT (TD-OCT) at all visits, and was compared with visual acuity (VA) and fluorescein angiography (FA) leakage at the final study visit. In a subset of visits with spectral-domain OCT (SD-OCT), subfoveal lucency, ellipsoid zone (EZ), and external limiting membrane (ELM) defects were graded and measured. Eyes in the placebo, ocriplasmin, and PPV groups with MH closure 1 month after treatment had subfoveal lucency in 5 of 5 (100%), 42 of 43 (98%), and 8 of 37 (22%) eyes, respectively; and eyes with MH closure 6 months after treatment had subfoveal lucency in 3 of 8 (38%), 30 of 44 (68%), and 11 of 60 (18%) eyes, respectively. Resolution of subfoveal lucency lagged behind EZ and ELM recovery in the ocriplasmin group, whereas it preceded EZ and ELM recovery in the PPV group. Subfoveal lucency base width increased after MH closure with ocriplasmin (+662±139 μm) but decreased after placebo (-255±154 μm) and PPV (-777±243 μm), when compared with pretreatment MH base width. Subfoveal lucency was not associated with FA leakage or VA outcomes in any treatment group. After MH closure with ocriplasmin, subfoveal lucency width was greater than pretreatment MH and persisted longer during follow-up compared with placebo or PPV. Subfoveal lucency was not a marker for visual function regardless of treatment group.

Newly Diagnosed Primary Open-Angle Glaucoma Randomized to 2 Trabecular Bypass Stents or Prostaglandin: Outcomes Through 36 Months.

PurposeTo examine outcomes through 36 months in phakic eyes with newly diagnosed primary open-angle glaucoma (POAG) naïve to therapy randomized to treatment with two trabecular micro-bypass stents or topical prostaglandin.MethodsSubjects with POAG naïve to therapy, with intraocular pressure (IOP) ≥21 and ≤40 mmHg, were randomized to implantation of two stents or travoprost. Additional medication was to be prescribed post-treatment for elevated IOP or glaucomatous optic nerve findings. Of 101 randomized subjects, 100 subjects were followed for 24 months and 73 subjects were followed for 36 months. Follow-up on all subjects is ongoing.ResultsIn this randomized cohort of 101 POAG subjects, 54 subjects underwent 2-stent surgery and 47 received topical travoprost. Mean pre-treatment IOP was 25.5 ± 2.5 mmHg in stent-treated eyes and 25.1 ± 4.6 mmHg in medication-treated eyes. By 3 years, mean IOP was 14.6 mmHg in stent eyes (with medication added in 6 eyes) and 15.3 mmHg in travoprost eyes (with a second medication added in 11 eyes). In the subset of eyes that did not require additional medical therapy, mean IOP was 14.5 mmHg and 15.7 mmHg in the respective groups. Ninety-one percent of stent eyes had 3-year IOP ≤18 mmHg without additional therapy (62% ≤ 15 mmHg) and 79% of travoprost eyes had 3-year IOP ≤18 mmHg (21% ≤ 15 mmHg). Safety was favorable in both groups.ConclusionsIn this prospective, randomized comparison of subjects with newly diagnosed POAG naïve to therapy, substantial IOP reduction with a favorable low complication rate was shown through 3 years after either 2 trabecular stents implanted as the sole procedure or topical travoprost therapy. These data suggest 2-stent implantation may be a viable initial treatment option comparable to topical prostaglandin in newly diagnosed POAG patients.Trial registration: ClinicalTrials.gov identifier, NCT01443988.FundingGlaukos Corporation, Laguna Hills, CA.Electronic supplementary materialThe online version of this article (doi:10.1007/s40123-016-0065-3) contains supplementary material, which is available to authorized users.

Comparative analysis of optical biometers

To evaluate the level of agreement, repeatability, and correlation of 2 optical biometers, the IOLMaster (based on partial coherence interferometry [PCI]) and Aladdin (based on optical low-coherence interferometry [OLCI]) in terms of axial length (AL), mean keratometry (K), anterior chamber depth (ACD), and corneal diameter. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. Prospective comparative case series. Each participant had biometry with both biometers. The level of agreement between thebiometers was calculated using the Bland-Altman method. Double-angle polar plots were used to display the astigmatism vectors. Internal consistency was computed with the Cronbach α coefficient of reliability, whereas the dispersion of probability distribution was assessed with the coefficient of variation (CoV). The intraoperator repeatability was analyzed using the intraclass correlation coefficient (ICC); the AL was evaluated in all eyes and the mean K and the ACD in a subset of eyes. The study comprised 215 eyes; the ICC for the mean K and ACD was calculated in a subset of 54 eyes. There was a statistically significant difference between the 2 biometers in all measurements (P<.05). The level of agreement was high with both methods. The ICC and internal consistency were excellent with both biometers; the CoVs were low. The OLCI biometer provided good agreement and repeatability compared with the PCI biometer, the current gold standard in ocular biometry. Further comparative studies are necessary to clearly define the role of the OLCI biometer in predicting postoperative refractive outcomes. Dr. Findl is a scientific advisor to Carl Zeiss Meditec AG. None of the other authors has a financial or proprietary interest in any material or method mentioned.

Dexamethasone Intravitreal Implant in the Treatment of Uveitic Macular Edema in the Perioperative Cataract Setting: A Case Series

To examine the efficacy of the dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc, Irvine, California, USA) in the control of uveitic macular edema in the perioperative setting of cataract surgery. Retrospective observational case series. setting: Clinical practice. A total of 17 eyes of 14 patients that received a DEX implant for cystoids macular edema (CME) associated with noninfectious uveitis who underwent subsequent phacoemulsification within 4months. Each patient was treated with a DEX 0.7mg intravitreal implant and underwent phacoemulsification with intraocular lens placement. Primary outcome measure was the change in central macular thickness (CMT) measured by optical coherence tomography (OCT), measured preoperatively and postoperatively. Seventeen eyes (14 patients) were included for analysis. There was no statistically significant change from preoperative CMT (mean 302μm) to postoperative CMT (307μm) on OCT. In the subset of eyes that underwent phacoemulsification within 4weeks of the DEX implant (8 eyes), the mean change in CMT was-47.0μm, compared to+51.1μm in those that received the DEX implant greater than 4weeks prior to phacoemulsification (P= .005). Intravitreal dexamethasone implant was shown to prevent the recurrence or worsening of macular edema in uveitic patients with a history of CME who underwent phacoemulsification. The mean CMT decreased in the subset of eyes that received the DEX implant within 4weeks prior to cataract surgery.

Aqueous Humor Outflow Physiology in NOS3 Knockout Mice.

To investigate the role of endothelial nitric oxide synthase (eNOS) on conventional outflow function using NOS3 knockout (KO) mice. Intraocular pressure was measured in both NOS3 KO and wild type (WT) by rebound tonometry. Outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. A subset of eyes was sectioned and stained for histology. Mock aqueous humor ± the nitric oxide (NO) donors nitroprusside dihydrate (SNP) or S-Nitroso-N-Acetyl-D,L-Penicillamine (SNAP) was perfused into enucleated eyes. SNP and SNAP was administered topically at 0, 1, 2, and 3 hours while the contralateral eyes served as vehicle controls. Intraocular pressure was measured in both eyes before and after the last drug treatment. Intraocular pressure was higher in KO mice (18.2 ± 0.7 mm Hg vs. 13.9 ± 0.5 mm Hg, mean ± SEM, n = 30, P < 0.05), and pressure-dependent conventional drainage was significantly lower (0.0058 ± 0.0005 μL/min/mm Hg, mean ± SEM, n = 21) compared with WT mice (0.0082 ± 0.0013 μL/min/mm Hg, n = 23, P < 0.05). No obvious morphological differences in iridiocorneal angle tissues were observed in hematoxylin and eosin (H&E)-stained sections. SNP and SNAP significantly increased pressure-dependent drainage in KO animals (n = 12, P < 0.05). In WT mice, SNP and SNAP caused a significant increase in pressure dependent drainage (n = 12, P < 0.05) to a similar degree as in KO mice. Topical application of SNP significantly reduced IOP in WT and KO mice (n = 12, P < 0.05), but SNAP did not change IOP significantly (n = 19). NOS3 KO mice have elevated IOP, which is likely the result of reduced pressure-dependent drainage. These findings are consistent with human data showing polymorphisms in the NOS3 gene associate with ocular hypertension and the development of glaucoma.

Cells at the vitreoretinal interface in small full-thickness macular holes.

To report on total number, distribution, and type of cells at the vitreomacular interface in small full-thickness macular holes. Internal limiting membrane specimens were removed from 20 consecutive patients with macular holes <250 μm at times when pharmacologic vitreolysis was not available. Specimens were flat mounted and investigated by phase contrast and interference microscopy and immunocytochemistry. Clinical data were documented including optical coherence tomography analysis using the caliper function. Thirteen antibodies were used for glial cells, hyalocytes, macrophages, retinal pigment epithelial cells, different types of collagen, alpha-smooth muscle actin, and proliferating cells. There was a positive correlation between macular hole size and cell density at the internal limiting membrane (Spearman's Rho: r = 0.519, P = 0.019). Mostly, single glial cells were found on the internal limiting membrane. In five patients, cell clusters were present. There was a strong immunoreactivity for glial cell markers. Immunoreactivity of hyalocyte markers, alpha-smooth muscle actin, and Ki-67 was found in cell clusters but otherwise sparse. Single cells of glial origin without signs of proliferation or contraction are present in eyes with small full-thickness macular holes. In some eyes, however, clusters of cells can be seen, capable of proliferation and exerting tangential traction. Our findings emphasize the need for better visualization of the vitreoretinal pathology by optical coherence tomography, especially to distinguish between single cells and cell clusters.

Outer Retinal Tubulation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)

To determine the prevalence of, risk factors for, and visual acuity (VA) correlations with outer retinal tubulation (ORT) seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) after anti-vascular endothelial growth factor (VEGF) therapy. Prospective cohort study within a randomized clinical trial. Patients with SD OCT images at weeks 56 and 104 in the Comparison of AMD Treatments Trials (CATT). Participants in the CATT were assigned randomly to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a monthly or pro re nata (PRN) injection-dosing regimen. A subset of eyes was imaged with SD OCT beginning at week 56. Cirrus 512×128 or Spectralis 20°×20° volume cube scan protocols were used to acquire SD OCT images. Two independent readers at the CATT OCT reading center graded scans, and a senior reader arbitrated discrepant grades. The prevalence of ORT, identified as tubular structures seen on at least 3 consecutive Cirrus B scans or 2 consecutive Spectralis B scans, was determined. The associations of patient-specific and ocular features at baseline and follow-up with ORT were evaluated by univariate and multivariate analyses. Outer retinal tubulations. Seven of 69 eyes (10.1%) at 56 weeks and 64 of 368 eyes (17.4%) at week 104 had ORTs. Absence of diabetes, poor VA, blocked fluorescence, geographic atrophy, greater lesion size, and presence of subretinal hyperreflective material at baseline were associated independently with greater risk of ORT at 104 weeks (P < 0.05). Neither drug nor dosing regimen were associated significantly with ORT. The mean VA of eyes with ORT at week 104 (58.5 Early Treatment Diabetic Retinopathy Study letters) was worse than the mean VA of eyes without ORT (68.8 letters; P < 0.0001). At 2 years after initiation of anti-VEGF therapy for neovascular AMD, ORTs are present in a substantial proportion of eyes. We identified baseline features that independently predict ORTs. It is important to identify ORTs because eyes with ORTs have worse VA outcomes than those without this finding.