PROSPECTIVE EVALUATION OF A SUSTAINED-RELEASE DEXAMETHASONE INTRAVITREAL IMPLANT FOR CYSTOID MACULAR EDEMA IN QUIESCENT UVEITIS.

PURPOSE: To investigate dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc) in the treatment of uveitic cystoid macular edema that had persisted in the absence of intraocular inflammation. METHODS: In this prospective interventional case series, 10 patients with uveitic cystoid macular edema and quiescent uveitis were treated with dexamethasone intravitreal implant at baseline and evaluated monthly for one year. Patients were retreated whenever cystoid macular edema recurred. The primary outcome measure was best-corrected visual acuity (BCVA) at day 90. RESULTS: At day 90, mean improvement from baseline BCVA was 14.4 letters (P = 0.0003), 70% of patients had a ≥10 letter BCVA improvement, 50% of patients had a ≥15 letter BCVA improvement, and the mean decrease from baseline central subfield retinal thickness was 140 µm (P = 0.008). Improvements were maintained through day 360 with retreatment as needed. At day 360, mean improvement in BCVA was 16.5 letters (P = 0.006) and the mean decrease in central subfield retinal thickness was 158 µm (P = 0.002). One patient experienced intraocular pressure >25 mmHg (managed with topical medication). Two phakic patients (2/8; 25%) had worsening of lens opacity requiring cataract extraction. CONCLUSION: Dexamethasone intravitreal implant may be an effective treatment for patients with persistent cystoid macular edema in quiescent uveitis.

THE ASSOCIATION OF EPIRETINAL MEMBRANE WITH MACULAR HOLE FORMATION AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To describe the clinical and optical coherence tomography findings associated with the development of full-thickness macular holes after rhegmatogenous retinal detachment (RRD) repair. METHODS: Retrospective, interventional case series. All patients who developed full-thickness macular holes after successful RRD repair from 3 clinical practices were reviewed. All cases of combined/simultaneous full-thickness macular hole and RRD were excluded. The main outcome measure was the presence of an epiretinal membrane at time of diagnosis of macular hole. RESULTS: Twenty-five full-thickness macular holes were diagnosed after successful retinal detachment repair. Surgical approach to RRD repair included pneumatic retinopexy (6, 24%), scleral buckle alone (5, 20%), pars plana vitrectomy only (8, 32%), and combined scleral buckle and pars plana vitrectomy (6, 24%). The preceding RRD involved the macula in 19 patients (76%) before the formation of the macular hole. The median time to full-thickness macular hole diagnosis after RRD repair was 63 days (range, 4-4,080 days). An epiretinal membrane was present in all 25 (100%) macular holes. Two macular holes (8%) spontaneously closed, whereas the other 23 (92%) were successfully closed with a single surgical procedure. Mean visual acuity improved by approximately 5 lines to 20/72 (range, 20/20 to counting fingers at 1 foot) from 20/240 (range, 20/30 to hand motions) after macular hole repair (P < 0.0001). CONCLUSION: Full-thickness macular hole formation can occur after all types of RRD repair and is associated with an epiretinal membrane. The epiretinal membrane may play a role in the pathogenesis of secondary macular hole formation after RRD repair.

Optic disk pit morphology and retinal detachment: optical coherence tomography with intraoperative correlation.

BACKGROUND: The pathogenesis of optic nerve head pits and associated retinal detachment, and the most effective surgical intervention when visual loss develops, remains unclear. METHODS: The morphology of the optic disk in patients with pits was investigated with optical coherence tomography. For those who underwent surgical treatment for pit-associated retinal detachment, the efficacy of treatment by vitrectomy and separation of the posterior hyaloid, with and without additional peeling of peripapillary tissue, was assessed. RESULTS: On optical coherence tomography imaging, 14 of 18 pits (78%) demonstrated a localized pit-like invagination, whereas 3 (17%) had disks with a generally excavated structure. For 16 of 18 pits (89%), there was evidence of condensed vitreous or glial tissue seen extending from the pit or inside the optic disk. Nine eyes with retinal detachment underwent vitrectomy, posterior hyaloid separation, and endolaser. The retinal detachment completely resolved in 6 of 6 cases where the surgeon additionally peeled the fibrous tissue from the pit and 2 of 3 cases where this was not performed. CONCLUSION: Spectral domain optical coherence tomography demonstrates the varying morphology of optic pit anatomy. Condensed vitreous strands or glial tissue in the optic nerve pit may also contribute to retinal detachment development.

Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

PURPOSE: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 µm and <125 µm] or ≥1 large drusen [≥125 µm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. INTERVENTION: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. MAIN OUTCOME MEASURES: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). RESULTS: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. CONCLUSIONS: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors.

PURPOSE: Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO). DESIGN: Multicenter, retrospective, nonconsecutive case series. SUBJECTS: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. METHODS: This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. MAIN OUTCOME MEASURES: Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course. RESULTS: Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks). CONCLUSIONS: Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.

Longer-term outcomes of a prospective study of intravitreal ranibizumab as a treatment for decreased visual acuity secondary to central retinal vein occlusion.

PURPOSE: To evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. METHODS: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. RESULTS: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 µm. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 µm (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 µm (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. CONCLUSION: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects.

Hemi-retinal vein occlusion in a young patient with COVID-19.

PURPOSE: To report a case of a hemi-retinal vein occlusion (HRVO) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBSERVATIONS: A 32-year-old healthy male presented with a paracentral scotoma, retinal hemorrhages, and dilated and tortuous retinal vessels inferiorly in the right eye. He was diagnosed with HRVO in the setting of recent SARS-CoV-2 infection. CONCLUSIONS AND IMPORTANCE: Venous thromboembolic complications and coagulation abnormalities have been widely reported in association with SARS-CoV-2 infection. We highlight this case to raise awareness that a retinal vein occlusion in an otherwise healthy, young patient may be a potential manifestation of the thromboinflammatory state associated with SARS-CoV-2 infection.

Surgical outcomes after massive subretinal hemorrhage secondary to age-related macular degeneration.

PURPOSE: Massive subretinal hemorrhage (SRH), defined as a thick submacular bleed that extends past the equator in at least two quadrants, is a rare sequela of age-related macular degeneration. This report describes outcomes after surgical intervention for massive SRH. METHODS: The study design is a retrospective interventional case series. Records of consecutive patients who underwent surgical intervention for massive SRH were reviewed. Outcomes included change from baseline in postoperative acuity at Months 1, 3, 6, 9, and 12 and postoperative complications. RESULTS: Fifteen consecutive eyes of 13 patients who underwent surgery for massive SRH were included. Procedures performed on initial surgery included subretinal instillation of 25 µg/0.1 mL tissue plasminogen activator (15 of 15), gas tamponade (12 of 15), oil tamponade (3 of 15), 180° or greater retinotomy (4 of 15), and/or cataract extraction (2 of 15). Patients were followed for a median of 20 months (range, 3-66 months). The median visual acuity at baseline and postoperative Month 1 was hand motions but improved to counting fingers at postoperative Months 3 (P = 0.04), 6 (P = 0.04), 9 (P = 0.04), and 12 (P = 0.10). Of the 15 eyes, 9 required at least 1 additional procedure for an indication of hyphema and/or vitreous hemorrhage (n = 6), retinal detachment (n = 2), glaucoma (n = 1), cataract (n = 1), and aphakia (n = 1). At the time of the onset of SRH, 5 of 13 patients were anticoagulated with warfarin (4 patients) or clopidogrel (1 patient), and 1 was diagnosed with a coagulopathy, factor XI deficiency. CONCLUSION: Massive SRH related to age-related macular degeneration has a grave prognosis. Risk factors may include anticoagulation and coagulopathy. Limitations of the study include its retrospective nature, small sample size, imprecision in acuity measurements below 20/400, and lack of a control group. In this series, surgical intervention was associated with a modest improvement in median visual acuity up to 1 year postoperatively.

The Value of Prior Response to Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration: A HARBOR Subanalysis.

PURPOSE: To evaluate disease activity-free intervals of patients with neovascular age-related macular degeneration (nAMD) in the pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) to determine whether duration of response to previous treatment with ranibizumab informs future disease activity and need for subsequent injections. DESIGN: Retrospective subgroup analysis of the phase 3 HARBOR study (clinicaltrials.gov identifier, NCT00891735). PARTICIPANTS: Patients from the ranibizumab 0.5 mg pro re nata arm of the phase 3 HARBOR clinical trial who received all 3 loading injections and missed no more than 1 study visit (N = 217). METHODS: A disease activity-free interval was defined as a consecutive period in months when treatment was not required because the patient did not meet protocol retreatment criteria. Percentage of disease activity-free eyes at the next 1 and 2 months after a first disease activity-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was evaluated. Additionally, duration that eyes remained untreated after disease activity-free intervals was evaluated by Kaplan-Meier estimates. MAIN OUTCOME MEASURES: Key outcome measures included duration of the first treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months achieved by each patient; mean number of additional months patients remained treatment free after a treatment-free interval; and percentage of eyes requiring treatment within 2 months after each treatment-free interval. RESULTS: Percentage of eyes requiring retreatment the month after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 60% (90/151), 33% (33/100), 26% (20/77), 36% (24/66), and 19% (9/48), respectively. Percentage of eyes requiring retreatment within 2 months after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 73% (109/149), 53% (53/100), 53% (40/75), 47% (30/64), and 43% (20/46), respectively. After treatment-free intervals of ≥2, ≥3, ≥4, ≥5, and ≥6 months, mean (standard error of the mean) additional time treatment free was 1.3 months (0.17 month), 2.4 months (0.33 month), 2.9 months (0.44 month), 3.2 months (0.50 month), and 4.0 months (0.60 month), respectively. CONCLUSIONS: Longer treatment-free intervals may indicate longer future disease-free intervals; however, this association varies. Thus, although longer intervals suggest greater likelihood of not needing retreatment within 1 to 2 months, regular assessment is warranted owing to the unpredictability of nAMD disease activity.

Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition.

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.

Alternating metabolic pathways in NGF-deprived sympathetic neurons affect caspase-independent death.

Mitochondrial release of cytochrome c in apoptotic cells activates caspases, which execute apoptotic cell death. However, the events themselves that culminate in caspase activation can have deleterious effects because caspase inhibitor-saved cells ultimately die in a caspase-independent manner. To determine what events may underlie this form of cell death, we examined bioenergetic changes in sympathetic neurons deprived of NGF in the presence of a broad-spectrum caspase inhibitor, boc-aspartyl-(OMe)-fluoromethylketone. Here, we report that NGF-deprived, boc-aspartyl-(OMe)-fluoromethylketone-saved neurons rely heavily on glycolysis for ATP generation and for survival. Second, the activity of F0F1 contributes to caspase-independent death, but has only a minor role in the maintenance of mitochondrial membrane potential, which is maintained primarily by electron transport. Third, permeability transition pore inhibition by cyclosporin A attenuates NGF deprivation-induced loss of mitochondrial proteins, suggesting that permeability transition pore opening may have a function in regulating the degradation of mitochondria after cytochrome c release. Identification of changes in caspase inhibitor-saved cells may provide the basis for rational strategies to augment the effectiveness of the therapeutic use of postmitochondrial interventions.

Treat and extend regimen with aflibercept for chronic central retinal vein occlusions: 2 year results of the NEWTON study.

BACKGROUND: To determine whether aflibercept (Eylea; Regeneron Pharmaceuticals, Inc., Tarrytown, NY) could continue to extend the macular edema free interval in patients on a treat and extend (TAE) with non-ischemic central retinal vein occlusions (CRVOs) previously treated with ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) or bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) in the second year. METHODS: Twenty patients with macular edema secondary to non-ischemic CRVOs previously treated with ranibizumab or bevacizumab were prospectively treated with intravitreal aflibercept injection (IAI) using a TAE dosing regimen. Injection frequencies were extended 2 weeks if there were no signs of disease activity on OCT or change in visual acuity. In the second year of the study, patients who have recurrences of macular edema could be re-challenged with a longer treatment interval under the following criterion: absence of any macular edema on three consecutive visits with the same treatment interval. RESULTS: Twenty patients had an average duration of a CRVO for 22 months (range 7-90) and averaged an anti-VEGF treatment every 42 days (range 28-60 days). The macular edema free interval increased from 38 to 75 days when switched to aflibercept (p = 0.000003) at month 24. There was an average increase of 37 days (median 34 days; range 0-91 days) in the macular edema free interval with aflibercept. At the month 24 visit, 50% (8/16) went > 12 weeks with a macular edema free interval between IAI. There was an improvement in vision (+ 8 ETDRS letters, p = 0.006) and decreased retinal thickness (158 µm, p = 0.00003) with aflibercept treatment at month 24. CONCLUSIONS: The 2-year results of the NEWTON study demonstrated the sustained benefits of a TAE dosing regimen with aflibercept in patients with chronic CRVOs. The visual acuity gains and anatomic improvements observed at year one were maintained through month 24 with less visits and treatments. This may help minimize the treatment burden in patients with recurrent macular edema secondary to non-ischemic CRVO.Trial Registration ClinicalTrials.gov, NCT01870427, Registered June 6, 2013, https://clinicaltrials.gov/ct2/show/NCT01870427?cond=NEWTON&rank=1.Presented at the RETICON 2017: The Retina Congress with Live Surgery, Chennai, India-April 2017.

Ultrastructural correlation of spectral-domain optical coherence tomographic findings in vitreomacular traction syndrome.

PURPOSE: To examine the ultrastructural correlates of spectral-domain optical coherence tomography (SD-OCT) findings in patients with vitreomacular traction (VMT). DESIGN: Observational case series. METHODS: Retrospective analysis of six eyes of consecutive patients who underwent vitrectomy surgery for VMT was performed in this single-center, noncomparative study. One patient had a concurrent macular hole. Preoperative assessment included SD-OCT examination with 3-dimensional image reconstruction. During surgery the vitreous cone was dissected from the vitreous body using scissors, then removed from the surface of the retina with a combination of sharp dissection and peeling, and subsequently submitted for histologic and transmission electron microscopic processing. RESULTS: SD-OCT showed prominent vitreal-foveal adhesion in all six eyes. Each eye had an epiretinal membrane (ERM) under the detached perifoveal posterior vitreous detachment. In all eyes this ERM appeared to course up the cone of attached vitreous and along the back surface of the posterior vitreous face. Ultrastructural analysis showed fibrocellular proliferations in the vitreous specimens in all six cases, which included retinal pigment epithelium (RPE) cells (five eyes), fibrocytes (four eyes), and macrophages (three eyes). CONCLUSIONS: The adhesion between the vitreous and fovea in vitreomacular traction syndrome is accompanied by fibrocellular proliferation along the exposed surfaces of the inner retina and the posterior surface of the vitreous. This fibrocellular proliferation may augment the adhesion between the vitreous and fovea, and may account for the prominent OCT signal seen along the posterior surface of the vitreous in these cases.

Predictors of anti-VEGF-associated retinal pigment epithelial tear using FA and OCT analysis.

PURPOSE: To identify fluorescein angiography and optical coherence tomography (OCT) predictors for retinal pigment epithelial (RPE) tear in eyes with pigment epithelium detachment (PED) associated with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) modulating therapy. DESIGN: Retrospective comparative case series. METHODS: In a single institutional center, 60 consecutive patients with PED and neovascular age-related macular degeneration treated with VEGF modulating therapy (either pegaptanib, bevacizumab, or ranibizumab) for more than a 27-month period were included in the study. Fluorescein angiography (FA) and OCT imaging was performed before and after anti-VEGF therapy. Formal statistical analysis comparing the tear group to the nontear group was performed to identify high-risk features for RPE tear. RESULTS: RPE tear rate for eyes with vascularized PED receiving anti-VEGF therapy was 17% (10/60). There were highly statistically significant differences in the median PED size on fluorescein angiography (greatest linear diameter) (3.2 mm versus 1.8 mm, respectively; P < 0.001) and in the median maximum PED height on OCT (394 mum versus 149 mum, respectively; P = 0.001) between the tear group and nontear group. There was also a significant difference in terms of the presence of subretinal fluid on OCT between the two groups (87.5% versus 39%, respectively; P = 0.019). CONCLUSION: Large PED basal diameter and vertical height are correlated with an increased risk of developing an RPE tear after anti-VEGF therapy. Patients with large vascularized PED by fluorescein angiography and/or OCT analysis should be alerted of the risk for vision loss due to RPE tear after anti-VEGF therapy.

Aflibercept for Previously Treated Macular Edema Associated with Central Retinal Vein Occlusions: 1-Year Results of the NEWTON Study.

PURPOSE: To determine whether aflibercept (Eylea; Regeneron Pharmaceuticals, Tarrytown, NY) can extend the macular edema-free interval in patients with nonischemic central retinal vein occlusions (CRVOs) previously treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech, South San Francisco, CA). DESIGN: Prospective, single-arm, interventional study. PARTICIPANTS: Twenty patients with chronic nonischemic CRVOs. METHODS: Patients with nonischemic CRVOs previously treated with ranibizumab or bevacizumab were switched to aflibercept. The inclusion criteria included treatment for ≥6 months with ≥3 initial loading doses and evidence of recurrence of edema when treatment with either ranibizumab or bevacizumab extended beyond 4 weeks. Intravitreal aflibercept was administered with a treat-and-extend dosing regimen. Injection frequencies were extended 2 weeks if there were no signs of disease activity on OCT or change in visual acuity. MAIN OUTCOME MEASURES: Macular edema-free interval at week 52. RESULTS: Twenty patients had an average duration of a CRVO for 22 months (range, 7-90 months) and averaged an anti-vascular endothelial growth factor (anti-VEGF) treatment every 42 days (range, 28-60 days). These patients received a mean of 15 treatments (range, 5-47 treatments) of ranibizumab or bevacizumab for macular edema secondary to nonischemic CRVO. Among the 17 patients who completed 1 year of follow-up, 94% had a greater macular edema-free interval with aflibercept treatment. The macular edema-free interval increased from 5.4 weeks to 9.1 weeks when treatment was switched to aflibercept (P = 0.000003). There was an average increase of 26 days (range, 0-63 days) in the macular edema free interval with aflibercept. There was an improvement in vision (+6 Early Treatment Diabetic Retinopathy Study letters, P = 0.02) and decreased retinal thickness (152 µm, P = 0.0002) with aflibercept treatment. CONCLUSIONS: In patients previously treated with ranibizumab or bevacizumab for macular edema due to nonischemic CRVO, aflibercept increased the macular edema free interval. This may help minimize the treatment burden in patients with recurrent macular edema secondary to nonischemic CRVO.

Abducens nerve ocular neuromyotonia following non-sellar or parasellar tumors.

Ocular neuromyotonia is an uncommon disorder resulting from episodic involuntary discharge of ocular motor nerves producing sustained contraction of their respective ocular muscles. Ocular neuromyotonia manifests in brief spells of diplopia occurring spontaneously or after eccentric gaze holding. In most cases, ocular neuromyotonia follows months or years after radiotherapy to the sellar and parasellar region and involves the oculomotor nerve. We report two unusual cases of abducens nerve ocular neuromyotonia that followed radiation therapy of tumors in areas other than the sellar or parasellar region.

Incidence of Presumed Silicone Oil Droplets in the Vitreous Cavity After Intravitreal Bevacizumab Injection With Insulin Syringes.

Importance: Intravitreal bevacizumab is a frequently used antivascular endothelial growth factor medication in the United States, but its off-label use is associated with risks associated with the compounding preparation. Objective: To determine the incidence of presumed silicone oil droplets after intravitreal bevacizumab was prepared in insulin syringes by a compounding pharmacy. Design, Setting, and Participants: A retrospective review was conducted of 60 patients who experienced intravitreal silicone oil droplets in the eye after intravitreal bevacizumab injections from a single specialist practice from October 1, 2015, to November 30, 2016. Bevacizumab, 1.25 mg/0.05 mL, was delivered in insulin syringes with a 31-gauge needle. Main Outcomes and Measures: Small, round clear spheres in vitreous on dilated biomicroscopic retinal examination. Results: Over a 14-month period involving 6632 intravitreal bevacizumab injections, 60 cases (35 [58%] women) of intravitreal silicone droplets were identified. Mean [SD] age of the patients was 80 [12] years; the population comprised 48 white, 9 Asian, and 3 Hispanic patients. The incidence of silicone oil droplet injections was 0.03% (1 of 3230) from October 2015 to April 2016 and 1.7% (59 of 3402) from May to November 2016 (Fisher exact test, P < .001; odds ratio [OR], 57; 95% CI, 9.8-2260). From May to November 2016, nonpriming the syringe before the intravitreal injection had a higher risk of intravitreal silicone oil droplets compared with priming the syringe (6.4% [47 of 739] vs 0.5% [12 of 2627]; Fisher exact test, P < .001; OR, 15.1; 95% CI, 7.9-33.4). Among the 60 cases, 41 patients (68%) were symptomatic, and the main symptom was floaters with spots of light. Among the patients with floaters, 36 (88%) improved over time (range, 2-8 months) despite the silicone droplets still being present on ophthalmoscopic examination. Conclusions and Relevance: An increase in intravitreal silicone oil associated with bevacizumab prepared with insulin syringes was documented. Priming the syringe before injection was associated with a lower frequency of this complication. These findings suggest that physicians should counsel their patients on the risk of floaters with intravitreal bevacizumab preloaded in insulin syringes.

Inflammation in retinal vein occlusion.

Retinal vein occlusion is a common, vision-threatening vascular disorder. The role of inflammation in the pathogenesis and clinical consequences of retinal vein occlusion is a topic of growing interest. It has long been recognized that systemic inflammatory disorders, such as autoimmune disease, are a significant risk factor for this condition. A number of more recent laboratory and clinical studies have begun to elucidate the role inflammation may play in the molecular pathways responsible for the vision-impairing consequences of retinal vein occlusion, such as macular edema. This improved understanding of the role of inflammation in retinal vein occlusion has allowed the development of new treatments for the disorder, with additional therapeutic targets and strategies to be identified as our understanding of the topic increases.

Effects of intravitreal anti-vascular endothelial growth factor treatment on retinal vasculature in retinal vein occlusion as determined by ultra wide-field fluorescein angiography.

PURPOSE: To investigate both peripheral and central retinal vascular changes after intravitreal anti-vascular endothelial growth factor (VEGF) therapy in the setting of acute retinal vein occlusion (RVO). METHODS: Two patients with macular edema, one secondary to central RVO (CRVO) and one secondary to branch RVO (BRVO), underwent ultra wide-field (200°) photography and fluorescein angiography before and after a single intravitreal injection of an anti-VEGF agent. The patient with CRVO received an intravitreal injection of ranibizumab (0.5 mg/0.05 mL). The patient with BRVO received an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). The eye with CRVO was reevaluated with ultra wide-field photography and fluorescein angiography at 7 days and 35 days after treatment. The eye with BRVO was reevaluated with ultra wide-field photography and fluorescein angiography at 30 days after treatment. Photographs and fluorescein angiographic results were analyzed for posttreatment changes in arteriovenous transit time, vessel caliber, vessel leakage, peripheral capillary nonperfusion, retinal hemorrhages, and nerve fiber layer infarcts. RESULTS: In both eyes, there were no changes detected in the arteriovenous transit time or peripheral capillary nonperfusion after anti-VEGF therapy. A reduction in intraretinal hemorrhages and nerve fiber layer infarcts was observed at 7 days and 35 days after treatment in the patient with CRVO and at 30 days after treatment in the patient with BRVO. A decrease in vessel caliber was observed at 7 days after treatment in the patient with CRVO and at 30 days after treatment in the patient with BRVO. In the patient with CRVO, an increase in vessel caliber with a recurrence of vascular leakage was noted at the visit on Day 35. CONCLUSION: Anti-VEGF therapy in the setting of RVO may initially decrease vessel caliber, retinal hemorrhages, and nerve fiber layer infarcts but does not appear to affect arteriovenous transit time or areas of peripheral capillary nonperfusion after a single treatment. The beneficial effects of anti-VEGF therapy in RVO appear transient, and multiple injections may be required for control of macular edema. Ultra wide-field angiography can be a useful tool in monitoring the treatment of RVO.