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PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P

Background: To determine the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema. Methods: Prospective, interventional cohort study at two clinical sites. Sixteen eyes of ten subjects with diabetic macular edema underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia, SC, USA) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1. The primary outcome of the study was feasibility of image transfer and performing navigated laser photocoagulation for subjects with diabetic macular edema between two distant clinics. Secondary measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by spectral-domain optical coherence tomography at 3 months after treatment. Results: The teleretinal treatment plan was able to be successfully completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ± 0.1, which remained stable (0.45 ± 0.1) 3 months after treatment (p = 0.060). The CRT improved from 290.1 ± 37.6 μm at baseline to 270.8 ± 27.7 μm 3 months after treatment (p = 0.005). All eyes demonstrated improvement in the area of retinal edema after laser photocoagulation, and no eyes demonstrated visual acuity loss 3 months after treatment. Conclusion: This study introduces the concept of retinal telephotocoagulation for diabetic macular edema, and demonstrates the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance.

Purpose To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. Design Eighteen-month, multicenter, randomized, controlled clinical trial. Participants Sixty patients with treatment-naive neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. Methods Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. Main Outcome Measures Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. Results The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm 2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm 2 , respectively ( P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann–Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development ( P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively). Conclusions Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA.

Purpose To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naive neovascular age-related macular degeneration (AMD) patients. Design Phase IIIb, multicenter, randomized, controlled clinical trial. Participants Sixty patients with treatment-naive neovascular AMD randomized 1:2 to monthly or TREX management. Methods Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol. Main Outcome Measures Mean ETDRS BCVA change from baseline. Results At baseline, mean age was 77 years (range, 59–96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 μm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively ( P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7–13) in the monthly and TREX cohorts, respectively ( P Conclusions The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing.

Vision loss associated with the idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome most commonly occurs from macular edema or complications related to neovascularization. The authors present a case of advanced IRVAN associated with a massive exudative response characterized by peripheral retinal telangiectasias, exudative retinal detachment, and macular edema with lipid maculopathy. The patient was managed successfully with visual acuity from hand motion to 20/150 using a combination of local corticosteroids, intravitreal bevacizumab, panretinal photocoagulation, and eventually pars plana vitrectomy for progressive vitreomacular traction. VEGF- and non-VEGF-mediated mechanisms appear to be involved in the pathogenesis of IRVAN given the efficacy of combination therapy. [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:599–602.]

Purpose: To report the macular hole closure rate and visual outcomes of patients with residual triamcinolone acetonide in the fovea after macular hole repair. Methods: We reviewed the medical records of consecutive patients who underwent macular hole surgery at our institution between 2005 and 2008. Only patients with visible triamcinolone in the fovea in the first postoperative month were included. Results: Six patients with Stage III or IV macular holes were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Triamcinolone acetonide was used to visualize the vitreous in every patient, and diluted indocyanine green was used to stain the internal limiting membrane in five patients. The median preoperative best-corrected visual acuity was 20/200, which improved to a median of 20/40 at the last follow-up. Five patients eventually developed retinal pigment epithelial alterations. Anatomic hole closure was achieved in every patient. The mean follow-up was 23 months (range, 3-36 months). Conclusion: Residual triamcinolone sequestered in the fovea after macular hole surgery did not affect hole closure or prevent improvement in visual acuity. It is unclear whether the retinal pigment epithelial alterations in our patients represent toxicity or are unrelated to the triamcinolone exposure.

Purpose Assessment of visual outcome of pediatric eyes that underwent cataract extraction with primary intraocular lens (IOL) implantation at a single center. Methods A retrospective review of charts of 510 consecutive pediatric patients that underwent cataract extraction was performed. Exclusion criteria were traumatic cataract, secondary IOL implantation, retinopathy of prematurity, severe developmental delay, age less than 4 years at last follow-up, and follow-up less than 6 months. In bilateral cases, only right eye data were included. Results One hundred thirty-nine eyes met inclusion criteria. Median age at surgery was 5.12 years (range, 0.03-16.92); median age at last follow-up was 9.05 years, and median follow-up was 3.65 years. Sixty-six of 139 (47.5%) patients had unilateral cataracts compared with 73/139 (52.5%) bilateral cases. The median visual acuity of all eyes was 20/30, with median visual acuity of unilateral and bilateral cases being 20/40 and 20/25, respectively. Older patients achieved better visual acuity (unilateral cases: p = 0.003; bilateral cases: p = 0.07). Eyes with a greater interocular axial length difference achieved poorer visual acuity. Forty-five patients had a final visual acuity worse than 20/40. Of these, 34 (76%) had a diagnosis of amblyopia as the sole cause. Nineteen of 139 (13.7%) eyes had final visual acuity worse than 20/200. Eighteen patients required strabismus surgery, and 22 required additional intraocular surgery. Conclusions Better visual acuity was associated with bilateral cataract, older age at surgery, and normal interocular axial length difference. Amblyopia was the major cause of residual visual deficit.

Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and towhat extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated myocardial fibroblasts from MI and non-MI (remote) regions at 7 days post-MI (n = 35) and from the free wall and septum of unoperated control C57BL/6 mice (n = 14). Proliferation was increased 182 ′ 28% in MI, but not in remote, fibroblasts compared with unoperated controls (P = 0.01). Migration decreased 61 ′ 8%, adhesion to laminin decreased 79 ′ 8%, adhesion to collagen IV increased 196 ′ 27%, and collagen synthesis increased 169 ′ 24% in fibroblasts isolated from the MI region (all P < 0.05). Migration, adhesion, and collagen synthesis changes were similar in remote fibroblasts, and the phenotypic differences were maintained through passage four. Transforming growth factor β1 (TGFpl) is a bioactive molecule that has been shown to affect fibroblast function. Stimulation of unoperated control fibroblasts with 10 ng/ml TGFβ 1 increased proliferation 137 ′ 7% (P = 0.03 vs. unstimulated), increased adhesion to collagen IV 149 ′ 6% (P < 0.01), and increased collagen I levels 187 ′ 10% (P = 0.01). TGFpl may, therefore, explain some of the changes in post-MI fibroblast phenotype. These data demonstrate for the first time region specific alterations in post-MI fibroblast biology that are maintained in vitro. Additionally, our model provides a novel in vitro template for examining the cellular mechanisms of wound healing and scar formation post-MI.

Objective To test the hypothesis that couples with sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI) values >27% would not achieve pregnancy with assisted reproductive techniques (ART) and to investigate how DFI and high DNA stainability (HDS), as measured by the SCSA, affect fertilization, cleavage, implantation, and pregnancy rates in IVF cycles. Design Prospective clinical study. Setting Academic human reproduction laboratory. Patient(s) One hundred couples undergoing IVF with conventional insemination or intracytoplasmic sperm injection. Intervention(s) Testing with SCSA was performed by SCSA Diagnostics (Brookings, South Dakota) on a semen aliquot taken from ejaculate used for ART. Main Outcome Measure(s) Relating total DFI and HDS to conventional semen parameters and cycle-specific outcomes after ART. Result(s) Nine of nineteen couples achieved clinical pregnancy when DFI was ≥27%, and 2 of 22 couples achieved clinical pregnancy when DFI was ≤9%. One of nine couples achieved clinical pregnancy with HDS >17%. The DFI was negatively correlated with sperm density ( r = −0.23, P r = −0.55, P r = −0.37, P Conclusion(s) Sperm chromatin structure assay failed to identify elevated DFI thresholds for negative pregnancy outcome after ART. Patients with low DFI (≤9%) were least likely to become pregnant, which is also contradictory to SCSA marketing, which states that DFIs of ≤15% have excellent fertility potential. Patients with HDS ≥17% had low pregnancy rates, indicating decreased fertility potential, which deserves further investigation. Larger studies are necessary to confirm that low DFI is associated with decreased fertility and, if proved, might redefine the use of the SCSA in evaluating infertility.

The bis(aryl)diacetylenes 1,4-bis(3-quinolyl)-1,3-butadiyne (1), 1,4-bis(4-isoquinolyl)-1,3-butadiyne (2), and 1,4-bis(3-pyridyl)-1,3-butadiyne (3) form strongly halogen bonded complexes with organ...

BACKGROUND: Adverse events after uterine artery embolization, including hysterectomy and premature ovarian failure, are concerning for women who desire future fertility. CASE: A 39-year-old woman underwent emergency hysterectomy after uterine artery embolization embolic microspheres found within the ovarian arterial vasculature. CONCLUSION: Uterine artery embolization for the treatment of uterine fibroids has been associated with loss of ovarian function in up to 14% of patients. This case report demonstrates that embolic microspheres injected into the uterine artery can unintentionally migrate through anastomotic channels into the ovarian arterial vasculature and potentially compromise ovarian blood flow. Hypoxic tissue injury may be the mechanism of premature ovarian failure observed after uterine artery embolization. Understanding the etiology of premature ovarian failure after uterine artery embolization might allow better patient selection.

An 82-year-old man with hypothyroidism had vertical diplopia and swelling around his left eye. Visual acuity was 20/20 OD and 20/50 OS. There was moderate blepharoptosis and edema of the left eyelids and superior scleral show of the right eye. The left eye showed 4 mm of proptosis, motility restriction, afferent pupillary defect, and normal optic disc. Orbital MRI revealed enlargement of the left superior and medial rectus muscles without tendinous involvement. These findings were initially suggestive of thyroid orbitopathy. Thyroid function tests were normal. Coronal MRI showed additional superior oblique enlargement and involvement of the levator superioris palpebrae muscle, which are both suggestive of a non-thyroid pathology. Muscle biopsy revealed large B-cell lymphoma. The patient was treated with chemotherapy, immunotherapy, and radiotherapy, with complete tumor control. Orbital lymphoma can simulate thyroid orbitopathy, even in patients with classic "thyroid-like" symptoms and imaging.

Objective To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy. Methods Retrospective review of 4 patients with a diagnosis of unilateral acute idiopathic maculopathy. Clinical characteristics (age, symptoms, Snellen visual acuity, and funduscopic features) and images from spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed. Results The median (range) age at presentation was 31 (27-52) years. The median (range) interval between symptom onset and presentation was 4 (1-20) weeks. Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive coxsackievirus titers (50%). The median (range) visual acuity at initial examination was 20/400 (20/70 to 1/400), which improved to 20/30 (20/20 to 20/60) at final follow-up. The median (range) follow-up time was 8 (8-13) weeks. Early in the disease course, the central macula developed irregular, circular areas of white-gray discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. Fluorescein angiography demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. Spectral-domain optical coherence tomography showed a partially reversible disruption of the outer photoreceptor layer. Fundus autofluorescence initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. Indocyanine green angiography showed “moth-eaten”–appearing choroidal vasculature, suggestive of choroidal inflammation. Conclusions The imaging characteristics highlight the structural changes during the active and resolution phases of unilateral acute idiopathic maculopathy. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.

Purpose To report the outcomes after cataract extraction in eyes previously treated for retinoblastoma. Methods We reviewed the medical records of consecutive patients treated with cataract extraction at our institution for radiation-induced cataract following retinoblastoma treatment between 1992 and 2007. Results Twelve eyes of 11 patients were included. The median age at diagnosis of retinoblastoma was 7.4 months. The median quiescent interval before cataract surgery was 34.6 months (range, 17-240 months). All patients underwent limbal-based extracapsular cataract extraction with scleral-tunnel wound construction. Anterior vitrectomy and posterior capsulotomy were performed in 7 eyes; an intraocular lens was placed in 10 eyes. A laser capsulotomy was subsequently performed in 5 eyes. No postoperative complications occurred. One patient underwent a pars plana vitrectomy for vitreous hemorrhage and proliferative retinopathy 5 years after cataract extraction. The median follow-up after surgery was 6.0 years (range, 1.1-12.3 years). Final visual acuity was between 20/20 and 20/60 in 6 eyes, between 20/70 and 20/200 in 2 eyes, and worse than 20/200 in 4 eyes. No intraocular tumor recurrences or metastases occurred. Two patients developed secondary rhabdomyosarcomas; 1 patient succumbed to the disease. Conclusions Limbal-based cataract extraction in our series was not associated with tumor recurrence or metastasis. The optimal quiescent interval is not known; however, no tumor recurrences occurred in our series when a minimum 17-month quiescent period was achieved. Visual improvement was noted in every patient, although several patients only experienced modest gains.