Subfoveal Lucency after Treatment of Vitreomacular Traction without Macular Hole in the Phase 3 Trials of Ocriplasmin Vitreolysis.

PURPOSE: To describe the clinical impact of subfoveal lucency (SFL) seen on OCT before and after treatment of vitreomacular traction (VMT) or symptomatic vitreomacular adhesion (VMA) without macular hole (MH) in the prospective phase 3 trials of ocriplasmin vitreolysis. DESIGN: Randomized double-blind placebo-controlled multicenter study. PARTICIPANTS: Four hundred ninety-nine eyes with VMT or VMA without MH. METHODS: Eyes were randomized to either a single intravitreal injection of ocriplasmin or placebo treatment and were followed up for 6 months. MAIN OUTCOME MEASURES: Eyes were analyzed for presence, dimensions, and course of SFL on OCT, release of VMT, and their effect on visual acuity (VA). RESULTS: Among eyes without baseline SFL, new SFL was more frequent after ocriplasmin than placebo at week 1 (23.1% vs. 6.54%; P = 0.0002) and week 2 (19.7% vs. 3.85%; P = 0.0001), but was similar in frequency by week 4 (8.37% vs. 7.69%; P = 0.83). Six-month VA for eyes demonstrating SFL after ocriplasmin during the first 2 weeks was comparable with those without SFL at any point in the study (P = 0.12). In placebo-treated eyes but not ocriplasmin-treated eyes, SFL was associated with worse VA at all visits. The increase in SFL width from baseline to week 2 was significantly greater with ocriplasmin than placebo (P = 0.029). Among ocriplasmin-treated eyes at month 6, those with SFL and VMT release had better VA than those with SFL and persistent adhesion (P = 0.037) and similar VA to those with persistent adhesion without SFL (P = 0.17). In the placebo group, those with baseline SFL showed low rates of spontaneous VMT release at month 6 compared with those without baseline SFL (3/21 eyes vs. 33/99 eyes; P = 0.045). CONCLUSIONS: Compared with placebo, SFL occurred more frequently only in the initial weeks after treatment with ocriplasmin. When SFL developed after ocriplasmin administration, VA was not impacted at the 6-month visit. Persistent SFL in ocriplasmin-treated eyes at month 6 was associated with poorer vision if VMT had not released. Eyes with SFL at baseline had low rates of spontaneous VMT release and may need treatment.

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

PURPOSE: To compare foveal anatomic features on OCT after macular hole (MH) closure, and their association with visual function, in the ocriplasmin phase III trials. DESIGN: Randomized clinical trial. PARTICIPANTS: One hundred fifty-three participants. METHODS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

PURPOSE: To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational study. PARTICIPANTS: Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. METHODS: High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. MAIN OUTCOME MEASURES: Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). RESULTS: Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. CONCLUSIONS: Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years. These quantitative SD OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials.

A Comparative Study of Rebound Tonometry With Tonopen and Goldmann Applanation Tonometry Following Vitreoretinal Surgery.

PURPOSE: To investigate agreement in intraocular pressure (IOP) measurements among Icare rebound tonometry, Tonopen tonometry, and Goldmann applanation tonometry following vitreoretinal surgery. DESIGN: Reliability analysis of tonometers. METHODS: Fifty-eyes of 50 adults undergoing vitreoretinal surgery were enrolled. IOP was measured on first postoperative day using Icare (Tiolat, Helsinki, Finland), followed by Tonopen (Reichert, Depew, New York, USA) and Goldmann (Haag-Streit USA, Mason, Ohio, USA) in randomized order. Intraclass correlation coefficients (ICC) and Bland-Altman plots were calculated for all subcategories. RESULTS: Icare successfully measured IOP in all eyes, while Goldmann was unmeasurable in 6 eyes (12%) and Tonopen in 1 eye (2%). Mean IOP by Icare, Tonopen, and Goldmann was 15.9 ± 8.9, 16.9 ± 6.2, and 16.0 ± 7.3 mm Hg, respectively (P = .76). Type of intraocular tamponade, status of lens, status of cornea, gauge of instrumentation, and history of prior vitrectomy did not result in significant differences among the 3 tonometers. ICC was excellent (>0.75) in all subgroups, except at IOP <10 and ≥ 23 mm Hg (based on Icare). In eyes with IOP <10 mm Hg, Icare underestimated IOP (mm Hg; P = .01) compared to Goldmann (2.0 ± 2.1) and Tonopen (3.5 ± 2.4), whereas at IOP ≥ 23 mm Hg Icare was overestimated (P = .01) compared to Goldmann (3.77 ± 3.49) and Tonopen (4.97 ± 3.33). Overall, differences in IOP were ≤ 3 mm Hg in 58% of eyes for Icare-Tonopen, 72% for Tonopen-Goldmann, and 62% for Icare-Goldmann. CONCLUSION: IOP measurements using Icare rebound tonometry, Tonopen, and Goldmann tonometry are in excellent agreement following vitreoretinal surgery. However, Icare overestimates at IOP ≥ 23 and underestimates at IOP <10 mm Hg.

Outer retinal tubulation in the comparison of age-related macular degeneration treatments trials (CATT).

PURPOSE: 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. DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: Patients with SD OCT images at weeks 56 and 104 in the Comparison of AMD Treatments Trials (CATT). METHODS: 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. MAIN OUTCOME MEASURES: Outer retinal tubulations. RESULTS: 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). CONCLUSION: 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.

Comparison of optical coherence tomography assessments in the comparison of age-related macular degeneration treatments trials.

OBJECTIVE: To determine agreement between spectral-domain (SD) and time-domain (TD) optical coherence tomography (OCT) image assessments by certified readers in eyes treated for neovascular age-related macular degeneration (AMD). DESIGN: Cross-sectional study within the Comparison of AMD Treatments Trials (CATT). PARTICIPANTS: During year 2 of CATT, 1213 pairs of SD OCT and TD OCT scans were compared from a subset of 384 eyes. METHODS: Masked readers independently graded OCT scans for presence of intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid and performed manual measurements of retinal, SRF, and subretinal tissue complex thicknesses at the foveal center. MAIN OUTCOME MEASURES: Presence of fluid was evaluated with percent agreement, κ coefficients with 95% confidence intervals (CIs), and McNemar tests. Thickness measurements were evaluated with mean difference (Δ) ±95% limits of agreement and intraclass correlation coefficients (ICCs) with 95% CIs. RESULTS: Between SD OCT and TD OCT, agreement on presence of any fluid was 82% (κ = 0.46; 95% CI, 0.40-0.52), with 5% more SD OCT scans demonstrating fluid (P<0.001). Agreement on presence of SRF was 87% and sub-RPE fluid was 80%, with more SD OCT scans demonstrating fluid (both P < 0.001). Agreement on IRF was 73% (κ = 0.47; 95% CI, 0.42-0.52), with 6% more TD OCT scans demonstrating fluid (P < 0.001). Between SD OCT and TD OCT, mean thickness of the retina was Δ = 5±67 µm, SRF was Δ = 1.5±35 µm, and subretinal tissue complex was Δ = 5±86 µm. Thickness measurements were reproducible for retina (ICC = 0.84; 95% CI, 0.83-0.86), SRF (ICC = 0.88; 95% CI, 0.86-0.89), and subretinal tissue complex (ICC = 0.91; 95% CI, 0.89-0.92), with ≤25-µm difference in these measurements in 71%, 94%, and 61% of paired scans, respectively. CONCLUSIONS: Agreement on fluid presence and manual thickness measurements between paired scans from each OCT modality was moderate, providing a reasonable basis to compare CATT results with future SD OCT-based trials. Fluid was detected 5% more frequently with SD OCT, which may increase frequency of fluid-based treatment. Lower-resolution and artifactual interpretation of dark areas as cystoid edema may explain the greater frequency of IRF detected with TD OCT.

Spectral domain optical coherence tomography characterization of pediatric epiretinal membranes.

PURPOSE: To compare the macular morphology of pediatric versus adult eyes with epiretinal membrane (ERM) using spectral domain optical coherence tomography and identify characteristics associated with postoperative visual acuity. METHODS: This retrospective study analyzed spectral domain optical coherence tomography from pediatric subjects and a randomly selected cohort of adult subjects with ERM. Morphologic retinal and ERM features were graded by two masked spectral domain optical coherence tomography readers and compared with a postoperative change in visual acuity. RESULTS: Pediatric ERMs (age, 0.3-16.5 years) were more confluently attached to the retina than adult ERMs (age, 40-88 years; P = 0.009) and had less fibrillary appearance of the inner retina when separation was present (P = 0.044). Pediatric ERMs were associated with more vessel dragging (P = 0.019) and less external limiting membrane (P = 0.001) and inner segment band visibility (P = 0.010), with a trend toward foveal sparing by ERM (P = 0.051) and "taco" retinal folds (P = 0.052) compared with adult eyes. Visual acuity improvement was associated with intact (P = 0.048) and smooth (P = 0.055, trend) inner segment band in children and with smooth inner segment band (P = 0.083, trend) and visible external limiting membrane (P = 0.098, trend) in adults. CONCLUSION: We identified morphologic differences between pediatric and adult ERM on spectral domain optical coherence tomography. Similar to adults, photoreceptor integrity with pediatric ERM seems to predict better visual acuity changes after surgical ERM removal.

Lateral and axial measurement differences between spectral-domain optical coherence tomography systems.

We assessed the reproducibility of lateral and axial measurements performed with spectral-domain optical coherence tomography (SDOCT) instruments from a single manufacturer and across several manufacturers. One human retina phantom was imaged on two instruments each from four SDOCT platforms: Zeiss Cirrus, Heidelberg Spectralis, Bioptigen SDOIS, and hand-held Bioptigen Envisu. Built-in software calipers were used to perform manual measurements of a fixed lateral width (LW), central foveal thickness (CFT), and parafoveal thickness (PFT) 1 mm from foveal center. Inter- and intraplatform reproducibilities were assessed with analysis of variance and Tukey-Kramer tests. The range of measurements between platforms was 5171 to 5290 µm for mean LW (p<0.001), 162 to 196 µm for mean CFT (p<0.001), and 267 to 316 µm for mean PFT (p<0.001). All SDOCT platforms had significant differences between each other for all measurements, except LW between Bioptigen SDOIS and Envisu (p=0.27). Intraplatform differences were significantly smaller than interplatform differences for LW (p=0.020), CFT (p=0.045), and PFT (p=0.004). Conversion factors were generated for lateral and axial scaling between SDOCT platforms. Lateral and axial manual measurements have greater variance across different SDOCT platforms than between instruments from the same platform. Conversion factors for measurements from different platforms can produce normalized values for patient care and clinical studies.

Quantitative classification of eyes with and without intermediate age-related macular degeneration using optical coherence tomography.

OBJECTIVE: To define quantitative indicators for the presence of intermediate age-related macular degeneration (AMD) via spectral-domain optical coherence tomography (SD-OCT) imaging of older adults. DESIGN: Evaluation of diagnostic test and technology. PARTICIPANTS AND CONTROLS: One eye from 115 elderly subjects without AMD and 269 subjects with intermediate AMD from the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. METHODS: We semiautomatically delineated the retinal pigment epithelium (RPE) and RPE drusen complex (RPEDC, the axial distance from the apex of the drusen and RPE layer to Bruch's membrane) and total retina (TR, the axial distance between the inner limiting and Bruch's membranes) boundaries. We registered and averaged the thickness maps from control subjects to generate a map of "normal" non-AMD thickness. We considered RPEDC thicknesses larger or smaller than 3 standard deviations from the mean as abnormal, indicating drusen or geographic atrophy (GA), respectively. We measured TR volumes, RPEDC volumes, and abnormal RPEDC thickening and thinning volumes for each subject. By using different combinations of these 4 disease indicators, we designed 5 automated classifiers for the presence of AMD on the basis of the generalized linear model regression framework. We trained and evaluated the performance of these classifiers using the leave-one-out method. MAIN OUTCOME MEASURES: The range and topographic distribution of the RPEDC and TR thicknesses in a 5-mm diameter cylinder centered at the fovea. RESULTS: The most efficient method for separating AMD and control eyes required all 4 disease indicators. The area under the curve (AUC) of the receiver operating characteristic (ROC) for this classifier was >0.99. Overall neurosensory retinal thickening in eyes with AMD versus control eyes in our study contrasts with previous smaller studies. CONCLUSIONS: We identified and validated efficient biometrics to distinguish AMD from normal eyes by analyzing the topographic distribution of normal and abnormal RPEDC thicknesses across a large atlas of eyes. We created an online atlas to share the 38 400 SD-OCT images in this study, their corresponding segmentations, and quantitative measurements.

Progression of intermediate age-related macular degeneration with proliferation and inner retinal migration of hyperreflective foci.

PURPOSE: Drusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression. DESIGN: Prospective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. PARTICIPANTS: Patients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits. METHODS: The number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis. MAIN OUTCOME MEASURES: The mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye. RESULTS: In 299 study eyes, the 2-year increase in the number of HF (P<0.001) and the AxD (P<0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P<0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P<0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P<0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95). CONCLUSIONS: Proliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Assessment of retinal morphology with spectral and time domain OCT in the phase III trials of enzymatic vitreolysis.

PURPOSE: To determine the relative ability of time domain (TD)-optical coherence tomography (OCT) compared with spectral domain (SD)-OCT to assess vitreoretinal interface abnormalities and pharmacologic treatment of symptomatic vitreomacular adhesion (VMA)/traction (VMT) with or without full-thickness macular hole (FTMH), and the reproducibility of trained readers' evaluation of these images in an interventional phase III program of ocriplasmin. METHODS: Eyes from the MIVI-TRUST program with concurrent SD-OCT and TD-OCT at baseline and day 28 were included. Pairwise intermodality agreement frequency and interreader reproducibility were calculated for baseline OCT features and the study endpoints of VMA resolution and FTMH closure. RESULTS: A total 186 eyes (186 patients) met the inclusion criteria for this study. There was excellent agreement between TD-OCT and SD-OCT for the reader-determined presence or absence of VMA (96.7%), FTMH (97.1%), and all other baseline parameters except epiretinal membrane (84.3%), which was detected at a significantly greater rate with SD-OCT than TD-OCT (44.6% vs. 35.3%, P < 0.001). There was excellent agreement for the study endpoints of VMA resolution (95.4%) and FTMH closure (100%) at day 28. Interreader reproducibility was similar but consistently greater with SD-OCT than TD-OCT to detect baseline VMA (kappa 0.6 vs. 0.52); FTMH (kappa 0.9 vs. 0.78); and epiretinal membrane (kappa 0.65 vs. 0.45). CONCLUSIONS: Readers using SD-OCT or TD-OCT have similar ability to assess vitreoretinal interface abnormalities and outcomes of enzymatic vitreolysis. SD-OCT may be superior for formal clinical trial grading due to greater interreader reproducibility and, therefore, decreased need for arbitration of discrepant values. (ClinicalTrials.gov numbers,NCT00781859, NCT00798317.).

Characterization of vitreoretinal interface disorders using OCT in the interventional phase 3 trials of ocriplasmin.

PURPOSE: We determined the reproducibility of a novel optical coherence tomography (OCT) protocol designed to evaluate formally vitreoretinal interface abnormalities on scans obtained during two phase 3 studies of intravitreal ocriplasmin to treat symptomatic vitreomacular adhesion with or without macular hole. METHODS: Certified technicians obtained time-domain OCT scans that included a macular thickness map (MTM), Fast MTM, and three high resolution linear scans: one 10 mm horizontal and one 10 mm vertical through the optic nerve head (ONH), and one 10 mm 5-degree-offset through the ONH and fovea. Reading Center teams graded all 3695 scans from 652 study eyes for pre-established quantitative and morphologic features. Grading reproducibility at baseline and follow-up visits was tested for presence of vitreomacular adhesion (VMA), width of vitreous adhesion (focal <1500 µm versus broad >1500 µm), presence and minimum width of full thickness macular hole (FTMH), and presence of epiretinal membrane (ERM). RESULTS: Team grading reproducibility for VMA (kappa 0.91, 95% confidence interval [CI] 0.81-1.00), broad versus focal width of vitreous adhesion (kappa 0.87, 95% CI 0.78-0.95), FTMH (kappa 0.87, 95% CI 0.78-0.95), and ERM (kappa 0.87, 95% CI 0.78-0.95) was high. Percent agreement was 97%, 92%, 95%, and 82% for VMA, vitreous adhesion width, FTMH, and ERM, respectively. For repeated measurements of FTMH width, the intraclass correlation was 0.89 (95% CI 0.85-0.93), and the mean paired difference between grading team measurements was 34.4 µm (95% limits of agreement -149.5-218.2 µm). CONCLUSIONS: Quantitative and morphologic vitreoretinal interface features were assessed reproducibly using a newly developed OCT scan acquisition and grading protocol. This protocol will be useful to evaluate OCT endpoints in future clinical trials, and can facilitate identification of vitreoretinal interface pathology during care of individual patients. (ClinicalTrials.gov number, NCT00781859 and NCT00798317.).

Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD.

PURPOSE: Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD. METHODS: A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators. RESULTS: Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001). CONCLUSIONS: A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

Macular hole surgery prognostic success rates based on macular hole size.

BACKGROUND AND OBJECTIVE: To evaluate the correlation between macular hole (MH) surgery outcomes and preoperative factors believed to affect surgical success rates. PATIENTS AND METHODS: A retrospective, consecutive case series was designed to evaluate the correlation between anatomic success and preoperative factors: MH duration prior to surgery, visual acuity (VA), and MH diameter measured by optical coherence tomography (OCT) at the base and the narrowest midpoint. RESULTS: A total of 153 eyes were enrolled. There was no significant difference in mean duration prior to surgery for MH success and failure (P = .13). Mean preoperative VA was significantly better for MH success than failure (P = .03). Mean mid-hole diameter (P < .001) and mean base-hole diameter (P < .001) were significantly less for MH success than failure. Failure rate was 0% among eyes with mid-hole diameter less than 500 microns and 14.9% with mid-hole 500 microns or greater (P < .001). Failure rate was 0% among eyes with base-hole diameter less than 500 microns, 1.4% with base-hole 500 to 999 microns, and 19.1% with base-hole of 1,000 microns or greater (P = .001). CONCLUSION: Preoperative VA, mid-hole diameter, and base-hole diameter are correlated with anatomic success in MH surgery. An excellent surgical prognosis exists for MHs with mid-hole diameter less than 500 microns and base-hole less than 1,000 microns.

Effect of successful and partly successful filtering surgery on the velocity of glaucomatous visual field progression.

PURPOSE: We sought to determine whether filtering surgery, even when only partially successful, delays or slows visual field (VF) progression. METHODS: The records of all patients seen in a glaucoma referral practice from 1999 to 2009 were reviewed. Group A comprised eyes with ≥ 5 VFs before surgery and group B comprised eyes with ≥ 5 VFs after surgery. Eyes in group B were further divided into those requiring postoperative topical ocular hypotensive therapy (group B-2) and those that did not (group B-1). Automated pointwise linear regression was used to determine global rates (dB/y) of change and progression endpoints. A progression endpoint was determined when 2 or more adjacent test locations in the same hemifield showed a threshold sensitivity decline at a rate of ≥ 1.0 dB/year with P < 0.01. RESULTS: A total of 206 treated eyes (206 patients; mean age, 63.8 ± 13.0 y; 11.3 ± 3.1 VFs; 6.4 ± 1.8 y follow-up) were included. Mean global VF progression rates in group A (-0.86 ± 0.8 dB/y) were faster than those in group B (-0.49 ± 0.9 dB/y, P < 0.01). Group A also had a greater risk of reaching a progression endpoint compared with group B (odds ratio = 2.41, P < 0.01). Groups B-1 and B-2 had different follow-up intraocular pressure means (12.7 ± 3.7 vs. 15.5 ± 2.7 mm Hg, respectively; P < 0.01) and peaks (19.4 ± 5.2 vs. 21.2 ± 4.2 mm Hg; P = 0.08). The velocity of VF progression was similar for groups B-1 and B-2 (-0.40 ± 0.6 vs. -0.58 ± 1.1 dB/y; P = 0.22) and there was no significant difference between the 2 groups regarding the risk of reaching a progression endpoint (odds ratio = 0.83, P = 0.62). CONCLUSIONS: Filtering surgery reduces the rate of disease progression and this effect persists even if adjunctive glaucoma medical therapy is required.

Diffuse retinal capillary leakage in coats disease.

PURPOSE: Coats disease is a rare condition characterized by retinal vascular telangiectasia, aneurysms, and leakage from these abnormal blood vessels. We report the phenomenon and treatment of Coats disease with diffuse hyperpermeability from angiographically normal retinal capillaries. METHODS: This case series describes two patients with Coats disease, diagnosed based on fundus photography and fluorescein angiography. The first patient was treated with intravitreal bevacizumab and limited laser photocoagulation. The second patient was treated only with limited photocoagulation. RESULTS: The diffuse exudation from normal retinal capillaries resolved with treatment of the focal primary vascular Coats lesions. CONCLUSION: Vasculopathies such as Coats disease may produce diffuse hyperpermeability of otherwise normal capillaries in the fundus. Limiting treatment only to the primary Coats lesions is a minimally invasive strategy that preserves normal capillaries.

An in vivo morphologic comparison of retinal neovascularization in sickle cell and diabetic retinopathy.

PURPOSE: To analyze the in vivo morphology of the sea fan in proliferative sickle cell retinopathy and compare it with the neovascularization in proliferative diabetic retinopathy. METHODS: Brief case report of spectral-domain optical coherence tomography imaging of a sea fan in a patient with sickle cell anemia and newly diagnosed proliferative sickle cell retinopathy, and morphologic comparison with spectral-domain optical coherence tomography imaging of a neovascular membrane in a diabetic patient with proliferative diabetic retinopathy. RESULTS: Spectral-domain optical coherence tomography imaging revealed that the sea fan is a thicker caliber preretinal fibrovascular membrane involving primarily the retinal nerve fiber and ganglion cell layers. The diabetic membrane has more vitreous adhesions, and it is more closely intertwined with the retina, involving all the retinal layers down to the outer plexiform layer. CONCLUSION: Spectral-domain optical coherence tomography imaging identified important in vivo morphologic differences between neovascularization in proliferative sickle cell retinopathy and proliferative diabetic retinopathy. These differences were consistent with previous histological studies and may explain the increased risk of tractional retinal detachment in patients with diabetes.

Glaucoma surgery decreases the rates of localized and global visual field progression.

PURPOSE: Incisional glaucoma surgical procedures produce greater intraocular pressure (IOP) reduction and less IOP variability than medical treatment. We sought to determine the efficacy of glaucoma surgery in decreasing localized and global rates of visual field (VF) progression. DESIGN: Retrospective, interventional case series. METHODS: Subjects in the New York Glaucoma Progression Study with glaucomatous optic neuropathy, repeatable VF loss, and 10 or more Swedish interactive threshold algorithm standard VF examinations were assessed for eligibility. Patients who underwent successful glaucoma surgery (not requiring further surgical intervention and IOP < 18 mm Hg) in either eye and who were followed up for at least 2 years before and after surgery were enrolled. Automated pointwise linear regression analysis was used to calculate global and localized rates of progression before and after surgery. Eyes with other ocular conditions likely to affect the VF and an insufficient number of VF to create a slope before and after surgery were excluded. Comparisons were performed within the same eyes before and after surgery (Student paired t test). RESULTS: We enrolled 28 eyes of 28 patients (mean age, 61.2 +/- 14.5 years). The mean number +/- standard deviation of VF was 13.4 +/- 2.3, spanning 7.1 +/- 1.2 years (range, 4 to 9 years). Mean IOP +/- standard deviation decreased from 19.0 +/- 3.9 mm Hg before surgery to 11.3 +/- 3.7 mm Hg after surgery (40% reduction; P < .01). Mean global progression rates decreased from -1.48 +/- 1.4 dB/year before surgery to -0.43 +/- 0.8 dB/year after surgery (70% reduction; P = .01). Twelve eyes (42.8%) had at least 1 significantly progressing point before surgery, whereas only 2 (7.1%) had at least 1 progressing point after surgery. Each 1 mm Hg of IOP reduction after surgery resulted in a 0.1 dB/year decrease in the global rate of progression. CONCLUSIONS: Successful IOP reduction after glaucoma surgery greatly reduces both the number of progressing points and the localized and general rates of VF progression.