OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

PURPOSE: To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). METHODS: We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. RESULTS: One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. CONCLUSION: Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

Contemporary Outcomes and Prognostic Factors of 23-Gauge Vitrectomy for Retained Lens Fragments After Phacoemulsification.

PURPOSE: To provide data on visual acuity (VA) outcomes and prognostic factors of microincision (23-gauge) vitrectomy surgery (MIVS) for retained lens fragments after complicated cataract surgery. DESIGN: Retrospective, interventional case series from 2012 to 2017. METHODS: Precataract surgery and intraoperative (vitrectomy) parameters, postvitrectomy complications, and best-corrected visual acuities (BCVAs) were identified. Vitrectomy was performed as early as corneal clarity permitted. Univariate and multivariate logistic regression were used to characterize factors associated with achieving VA better than 20/40, or worse than 20/200 at 6 months. RESULTS: This study included 291 consecutive eyes (291 patients). LogMAR BCVA improved from 0.73 ± 0.70 before cataract surgery to 0.46 ± 0.63 (P < .001) after vitrectomy. The previtrectomy VA was 1.43 ± 0.79. At 6 months, 183 (62.9%) and 45 patients (15.5%) achieved BCVAs better than 20/40 and worse than 20/200, respectively. Most frequent complications were de novo ocular hypertension (29 eyes, 10%) and transient cystoid macular edema (25 eyes, 8.6%). Postvitrectomy retinal detachment occurred in 9 eyes (3.1%). Final VA of 20/40 or better was independently associated only with better precataract surgery VA, age <75 years, absence of preexisting diabetic macular edema (DME) or postvitrectomy persistent cystoid macular edema (P < .05). Only poorer precataract surgery VA, delaying vitrectomy to later than 2 weeks, and final aphakic status were independently predictive of 20/200 or worse VA (P < .05). CONCLUSION: Contemporary VA outcomes of 23-gauge vitrectomy for retained lens fragments are comparable with that of prior predominantly non-MIVS cohorts, but fall short of benchmarks for uncomplicated cataract surgery. IOL type or timing of placement do not impact final VA.

REOPENING OF MACULAR HOLE AFTER INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To describe the clinical course and surgical outcome of a patient with full-thickness macular hole recurrence after aflibercept injections for wet age-related macular degeneration. METHODS: Case report with spectral domain optical coherence tomography retinal imaging. RESULTS: An 84-year-old patient, with a successfully closed full-thickness macular hole by vitrectomy and internal limiting membrane (ILM) peel 4 years ago in the right eye, developed neovascular age-related macular degeneration (AMD) of the same eye. After 6 intravitreal aflibercept injections, visual acuity was 20/50, with minimal subretinal fluid (SRF). Four days after the seventh aflibercept injection, visual acuity decreased to 20/200. Spectral domain optical coherence tomography demonstrated a reopened full-thickness macular hole of diameter 430 µm, associated with a reduction in pigment epithelial detachment height, increase in SRF, and an epiretinal membrane (ERM). A 23-gauge pars plana vitrectomy with indocyanine green-assisted removal of residual ILM and ERM, and sulfur hexafluoride (SF6) 20% tamponade was performed. At 1 month postoperatively, the full-thickness macular hole was successfully closed and visual acuity improved to 20/80. CONCLUSION: In wet AMD eyes with previously closed macular holes, hole reopening may occur as a rare complication of aflibercept therapy.

Retinal Nonperfusion Characteristics on Ultra-Widefield Angiography in Eyes With Severe Nonproliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy.

Importance: Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear. Objectives: To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE). Design, Setting, and Participants: This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom. Baseline images were obtained from 2 completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and December 31, 2015, and the CLARITY study recruited eyes with PDR between August 22, 2014, and November 20, 2015. Ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment were included. Main Outcomes and Measures: The total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion, and the area of peripheral retinal nonperfusion were measured. Results: A total of 92 patients (92 eyes) were included in the study: 59 in the PDR group (mean [SD] age, 42 [15] years; 20 female [33.9%]) and 33 in the NPDR group (mean [SD] age, 63 [10] years; 3 female [9.1%]). Forty eyes had NVE and 19 had NVD with or without NVE. We identified a retinal nonperfusion threshold of 118.3 disc areas (DA) with a specificity of 84.9% (95% CI, 68.1% to 94.9%) for PDR. The median area of retinal nonperfusion was 67.8 DA (95% CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (95% CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (95% CI, 42.2 to 97.7 DA; P < .001). No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (95% CI, -6.7 to 5.2 DA; P = .56). As for peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (95% CI, 48.4 to 94.9 DA; P < .001). Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (95% CI, 28.6 to 95.8 DA; P < .001) compared with eyes with only NVE. Conclusions and Relevance: These findings suggest eyes with at least 107.3 DA of nonperfusion are at risk of proliferative disease, and eyes with NVD have the largest area of retinal nonperfusion.

Disorganization of Retinal Inner Layers and Ellipsoid Zone Disruption Predict Visual Outcomes in Central Retinal Vein Occlusion.

PURPOSE: To assess the associations and predictive value of spectral-domain (SD) OCT inner and outer retinal structural parameters and visual acuity (VA) outcomes in macular edema (ME) secondary to central retinal vein occlusion (CRVO). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Eighty-four patients with ME secondary to CRVO receiving pro re nata anti-vascular endothelial growth factor (VEGF) therapy at 3 tertiary-level retina referral centers. METHODS: In all participants, VA, demographic and clinical parameters, and SD OCT images from baseline, 3 months, and 12 months were reviewed. Spectral-domain OCT-based morphologic features in the 1500-µm foveal zone were analyzed by masked graders for disorganization of the retinal inner layers (DRIL), ellipsoid zone (EZ) and external limiting membrane disruption, cone outer segment tip (COST) visibility, cysts, subretinal and intraretinal fluid, and epiretinal membranes. MAIN OUTCOME MEASURES: Spectral-domain OCT-based retinal structural parameters and VA outcomes. RESULTS: In multivariate analyses adjusting for baseline VA, worsening VA over 1 year was associated with 1-year increases in DRIL (point estimate, 0.06 per 100 µm; P < 0.001) and EZ disruption (0.07 per 100 µm; P = 0.023), but decreased COST visibility (-0.09 per 100 µm; P = 0.018). A 3-month increase in DRIL (0.05 per 100 µm; P = 0.003) and EZ disruption (0.10 per 100 µm; P < 0.001) were the only factors predicting VA worsening over 1 year, after controlling for baseline VA. A multivariate model including 3-month evolution in DRIL, EZ disruption, and VA accounted for 86.3% of variability in 1-year VA change. Absolute differences between predicted and actual 1-year VA were within 2 lines in 80.9%. When DRIL increased by 250 µm or more over 3 months, no eyes showed VA improvement of 1 line or more in 1 year. When EZ disruption decreased by 250 µm or more over 3 months, no eyes worsened by 1 line or more over 1 year. CONCLUSIONS: Early recovery over 3 months in both DRIL and EZ parameters are key drivers of 1-year VA outcomes. Predictive models incorporating 3-month changes in DRIL and EZ disruption support their usefulness as potential robust determinants of future VA.

One-year outcomes of ziv-aflibercept for macular edema in central retinal vein occlusion.

PURPOSE: To report the 12-month efficacy and safety outcomes of intravitreal ziv-aflibercept in macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Interventional case series documenting 12-month outcomes of intravitreal ziv-aflibercept (1.25 mg in 0.05 mL) in 6 patients with treatment-naive macular edema secondary to CRVO. All patients had comprehensive ophthalmic examination, spectral domain optical coherence tomography at baseline and all follow-up visits, and fluorescein. Retreatment decisions were based on recurrence or persistence of intraretinal or subretinal fluid, deterioration in visual acuity (VA), increase in central subfield thickness (CST) by ≥ 50 µm from the previous visit, or lowest recorded CST. RESULTS: Participants had (2 males, 4 females) an average age of 53.5 years. From baseline to 12 months, the mean logMAR VA improved from 0.86 (Snellen ≈ 20/145) to 0.33 (Snellen ≈ 20/40), central macular thickness decreased from 519 µm to 255 µm, and total macular volume decreased from 14.7 mm3 to 7.1 mm3. No eyes had uveitis, cataract progression, intraocular pressure (IOP) elevations, or systemic adverse events. CONCLUSIONS AND IMPORTANCE: Ziv-aflibercept achieves favorable intermediate-term functional and structural outcomes in macular edema secondary to CRVO. No safety concerns were raised. Low-cost ziv-aflibercept may thus be useful for CRVO in resource-poor countries. Further prospective studies in larger cohorts are needed further establish the efficacy and safety of this agent.

Quantitative Analysis of En Face Spectral-Domain Optical Coherence Tomography Imaging in Polypoidal Choroidal Vasculopathy.

BACKGROUND AND OBJECTIVE: Spectral-domain optical coherence tomography (SD-OCT) imaging can be used to visualize polypoidal choroidal vasculopathy (PCV) lesions in the en face plane. Here, the authors describe a novel lesion quantification technique and compare PCV lesion area measurements and morphology before and after anti-vascular endothelial growth factor (VEGF) treatment. PATIENTS AND METHODS: Volumetric SD-OCT scans in eyes with PCV before and after induction anti-VEGF therapy were retrospectively analyzed. En face SD-OCT images were generated and a pixel intensity thresholding process was used to quantify total lesion area. RESULTS: Thirteen eyes with PCV were analyzed. En face SD-OCT PCV lesion area quantification showed good intergrader reliability (intraclass correlation coefficient = 0.944). Total PCV lesion area was significantly reduced after anti-VEGF therapy (2.22 mm2 vs. 2.73 mm2; P = .02). The overall geographic pattern of the branching vascular network was typically preserved. CONCLUSION: PCV lesion area analysis using en face SD-OCT is a reproducible tool that can quantify treatment related changes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:126-133.].

Quantitative Changes in Pigment Epithelial Detachment Area and Volume Predict Retreatment in Polypoidal Choroidal Vasculopathy.

PURPOSE: To determine if changes in pigment epithelial detachment (PED) area and volume predict retreatment in polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective case-control study. METHODS: PCV patients on pro re nata (PRN) anti-vascular endothelial growth factor (VEGF) therapy with >1 year follow-up at an academic retina service were included. Monthly anti-VEGF injections were given until a dry macula was achieved, and treatment deferred. Retreatment indication was recurrence of intraretinal or subretinal fluid or new hemorrhage. PED area and volume changes between visits with a dry macula ("D") and immediate preceding visits ("D-1") were analyzed with an automated optical coherence tomography-based software. Univariate and multivariate analyses were conducted to determine associations between changes in PED parameters and retreatment need at immediate subsequent visits ("D+1"). RESULTS: Twenty-two PCV patients (mean age 69.6 years) were included. Of 46 visits D, 11 (23.9%) were followed by retreatment at D+1. An increase in PED area (>0.43 mm2) and volume (>0.0245 mm3) from D-1 to D was associated with 18.2 (95% CI, 3.7-125.6; P < .001) and 101.9 (95% CI, 9.5-14 308.0; P < .001) higher retreatment odds at D+1, respectively. These associations remained significant after multivariate analyses adjusting for baseline PED area or volume, greatest linear dimension, and type of anti-VEGF agent. CONCLUSION: In PCV on PRN anti-VEGF therapy, increases in PED area and volume at one visit, despite achievement of a dry macula, are associated with retreatment at the next visit. Retreatment criteria relying on intraretinal or subretinal fluid or new hemorrhages may be expanded to include PED changes. Studies are needed to determine if using PED parameters in treatment decisions reduces recurrences.

De novo ocular hypertension after Descemet stripping endothelial keratoplasty: comparative 3-year incidence, risk factors, and outcomes.

OBJECTIVE: To compare the 3-year incidence of de novo ocular hypertension (OHT) after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2-year outcomes after OHT development. METHODS: This was a review of the prospective Singapore Corneal Transplant Study at a single tertiary referral center. Consecutive DSAEKs and PKs for Fuchs' endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) in eyes without pre-existing glaucoma were analyzed. OHT incidence after DSAEK and PK were compared using Kaplan-Meier survival analysis, and OHT risk factors identified using Cox proportional regression. OHT was defined: intraocular pressure (IOP) ≥ 24 mmHg or ≥ 10 mmHg from baseline. Secondary outcomes 2 years after OHT development in DSAEK were rates of glaucoma medical therapy failure, IOP success, graft failure and rejection, and best-spectacle corrected visual acuity (BSCVA). RESULTS: There were 108 (96.4%) DSAEKs and 216 (96%) PKs. The 1-, 2- and 3-year de novo OHT incidence was not significantly different between DSAEK (36.1%, 47.2%, 47.2%, respectively) and PK (35.7%, 44.9%, 45.8%, respectively; P = 0.914). OHT incidence did not differ in subgroup analyses of multiple clinical variables (P > 0.1). OHT predictors after DSAEK were: fellow eye glaucoma (hazard ratio [HR] 3.20, P = 0.004), age <60 years (HR 2.41, P = 0.016), concurrent goniosynechiolysis (HR 3.29, P = 0.021), post-graft complications or procedures (HR 2.85, P = 0.006). Two years after OHT onset, 29.7% of DSAEKs failed glaucoma medical therapy requiring trabeculectomy. Complete and qualified IOP success was achieved in 23.5% and 76.5%, respectively. Graft failure developed in 9.8% and graft rejection in 5.9%. At 6 months, 1, and 2 years from OHT onset, 86.3%, 88.3%, and 92.1% achieved BSCVA 20/40, respectively. CONCLUSION: DSAEK and PK have comparable OHT risks. A significant 30% of DSAEK eyes with OHT require filtration surgery. Effective IOP control and good graft and visual outcomes are achieved with treatment.

Bilateral orbital subperiosteal hemorrhage following labor.

A 27-year-old woman presented with 13 days of bilateral periorbital swelling, discomfort, and visual loss, which developed immediately after labor. She had significant blood loss requiring blood transfusion. There was bilateral proptosis, left optic neuropathy, and a superior visual hemifield defect in the left eye. MRI of the orbits showed bilateral superior subperiosteal hematomas. She underwent bilateral orbitotomy and drainage of subperiosteal hematomas. Six months later, complete resolution of proptosis with normal ocular motility and visual acuity was observed; however, there was persistence of a left relative afferent pupillary defect with superior visual field loss. This case report highlights the need for a high index of diagnostic suspicion of subperiosteal hematoma arising in a nontraumatic setting, such as in the peripartum period, and consideration for emergent surgical management of optic neuropathy.