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We report a case of a 47-year-old female who experienced periorbital swelling while descending from a Himalayan mountain climb and was found to have bilateral superior ophthalmic vein thromboses (SOVT). Infectious, autoimmune, and hypercoagulability work-up were negative with no cavernous sinus involvement. Symptoms resolved upon initiation of anticoagulation and oral steroids. SOVT is a rare but serious condition and has a risk of extending into the cavernous sinus if not treated early. Although infection is the most common etiology, venous thrombosis can be precipitated under high altitude and low oxygen pressure environments. We present a case of superior ophthalmic vein thrombosis associated with high-altitude conditions.

Purpose To report the imaging findings of a single case of paracentral acute middle maculopathy associated with bilateral Purtscher-like retinopathy in the setting of recent viral illness. Methods Case report, multimodal imaging. Results A 21-year-old woman who awoke with sudden-onset bilateral finger count vision in the setting of a recent viral illness. Initial examination and imaging was consistent with a bilateral Purtscher-like retinopathy with evidence of paracentral acute middle maculopathy and ellipsoid zone thickening and hyperreflectivity on spectral domain optical coherence tomography (OCT). Baseline fluorescein angiography and OCT angiography revealed normal perfusion and flow, respectively. All laboratory investigation was negative for possible causative etiology. The patient was followed for 6 months with steady visual improvement to 20/20 in both eyes. En face OCT demonstrated near-complete restoration of the ellipsoid layer. The patient still noted bilateral scotomas which were mapped out on microperimetry and found to correlate to en face OCT findings. Conclusion Purtscher-like retinopathy in the setting of recent viral illness is a rare cause of vision loss that may be associated with the finding of paracentral acute middle maculopathy on spectral domain OCT. Despite poor presenting vision, in the presence of normal perfusion near total visual recovery is possible.

PurposeTo examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair.MethodsProspective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery.ResultsThe single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%).ConclusionThe management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.

To evaluate the safety and effects of oral eplerenone in chronic central serous chorioretinopathy.Prospective, randomized, double-blind, placebo-control study at a tertiary referral academic private practice. For a diagnosis of chronic central serous chorioretinopathy, patients must have had at least 3 months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on spectral-domain optical coherence tomography, and50% reduction in fluid thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone (25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once daily.Fifteen patients completed the study. Ten patients (15 eyes) were randomized into the eplerenone treatment arm, while the remaining 5 patients (6 eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of the minimal angle of resolution visual acuity improved from 0.394 (Snellen equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean logarithm of the minimal angle of resolution visual acuity slightly decreased from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With respect to anatomic changes, mean maximal subretinal fluid height in the eplerenone group improved from 139.3 μm at baseline to 51.8 μm (P = 0.02), mean subfoveal fluid height improved from 121.4 μm to 29.4 μm (P = 0.01), and mean central subfield thickness improved from 366.2 μm to 283.7 μm (P = 0.02). In comparison with the placebo group, mean maximal subretinal fluid height worsened from 135.9 μm to 172.3 μm (P = 0.32), mean subfoveal fluid height worsened from 92.1 μm to 134.0 μm (P = 0.54), and mean central subfield thickness worsened from 345.0 μm to 380.0 μm (P = 0.37). No patients in either group experienced serious adverse events to result in treatment discontinuation.These findings suggest that oral eplerenone therapy is safe and potentially effective in the treatment of chronic central serous chorioretinopathy with persistent subretinal fluid.

Purpose To quantify foveal avascular zone (FAZ) area and macular vascular density objectively using optical coherence tomography angiography (OCTA) and to examine correlations with visual acuity in eyes with diabetic retinopathy (DR) in the absence of diabetic macular edema. Design Retrospective observational case series. Participants Eighty-four eyes from 55 patients with DR and 34 control eyes from 27 age-matched healthy participants. Methods All eyes underwent OCTA (RTVue-XR Avanti; Optovue, Inc, Fremont, CA). Integrated automated algorithms were used to quantify FAZ area and macular vascular density. Main Outcome Measures FAZ area, vessel area density (VAD), vessel length density (VLD), and visual acuity. Results In each study eye, DR was classified as mild nonproliferative DR (NPDR; n = 32 [38%]), moderate-to-severe NPDR (n = 31 [37%]), or proliferative DR (n = 21 [25%]). Mean FAZ area was greater in diabetic eyes compared with control eyes both in the superficial (0.427 mm 2 vs. 0.275 mm 2 ; P 2 vs. 0.372 mm 2 ; P P P −1 vs. 21.55 mm −1 ; P −1 vs. 24.38 mm −1 ; P P P P P Conclusions Automated quantitative algorithms allow for objective assessment of retinal vascular changes in eyes with DR that are correlated to visual acuity. These methods may prove useful in monitoring disease progression and identifying parameters that affect visual function.

To describe the clinical features and management of six patients with ocular complications associated with direct oral anticoagulants (DOACs).The medical records of all adult patients known to be taking a DOAC and with an unusual bleeding event at a large tertiary referral center over a one-year period were reviewed. Patients with less than one-month follow-up were excluded. Data collection included relevant clinic notes, operative reports, surgical videos, and clinical images (fundus photography, optical coherence tomography, B-scan ultrasonography, and fluorescein angiography).Six eyes in six patients were identified with an unusual bleeding event associated with DOAC use. One patient was taking apixaban, two patients were taking dabigatran, and three patients were taking rivaroxaban. Two patients had large submacular hemorrhage (including one with vitreous hemorrhage breakthrough), three patients had vitreous hemorrhage, and one patient had recurrent hyphema. Presenting visual acuity ranged from 20/40 to light perception. Three individuals required therapeutic and/or diagnostic pars plana vitrectomy for vitreous hemorrhage. Final visual acuity ranged from 20/25 to count finger vision. The associated DOAC was permanently discontinued in two of the six cases. Follow-up was one to four months from onset of identified DOAC-related complication.DOAC use may be associated with ocular bleeding. Ophthalmologists should be aware of potential hemorrhagic complications and obtain consultation with primary providers regarding DOAC cessation guidelines.

To quantify density of macular vascular networks over regions of interest in healthy subjects using optical coherence tomography angiography (OCTA).Prospective cross-sectional study.Setting was the Retina and Oncology Services of Wills Eye Hospital. Subjects with no known systemic disease and without retinal pathology were included. OCTA was performed on a 3 × 3-mm region centered on the macula and en face angiograms of the superficial and deep vascular networks were acquired. Vascular density was calculated using an automated image thresholding method over regions of interest. Foveal and parafoveal vascular density were calculated. The differences between vascular networks, sexes, and fellow eyes and correlation between vascular density, signal strength, and age, as well as reproducibility of measurements, were evaluated.A total of 198 healthy eyes were imaged, from which 163 eyes of 122 subjects were included based on image quality criteria. In the parafoveal region, deep vascular density was significantly higher than the superficial (52% ± 2.4% vs 46% ± 2.2%; P.001), whereas the opposite was found in the foveal region (27% ± 5.2% vs 32% ± 3.2%; P.001). All vascular density measurements were statistically similar in fellow eyes and there was no sex difference (P.05). There was a negative correlation between vascular density and age that persisted upon adjusting for signal strength. Vascular density measurements were highly correlated between separate imaging sessions with intraclass correlation coefficients of over 0.85 for all assessments.Calculation of vascular density using OCTA is a reproducible and noninvasive method to quantitate individual networks within the macula. Understanding normal values and their correlations could affect clinical evaluation of the macula in healthy patients and disease states.

Aims To quantify the change in drusen volume over time and identify its prognostic value for individual risk assessment. Methods A prospective observational study over a minimum of 3 years and maximum of 5 years and follow-up examination every 3 months was conducted at the ophthalmology department of the Medical University of Vienna. 109 patients presenting early and intermediate age-related macular degeneration (AMD) were included, of which 30 patients concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were imaged every 3 months using spectral-domain and polarisation-sensitive optical coherence tomography (OCT). Drusen volume was measured using an automated algorithm. Data of a 6-month follow-up were segmented manually by expert graders. Results Gradings from 24 000 individual B-scans showed solid correlation between manual and automated segmentation with an initial mean drusen volume of 0.17 mm 3 . The increase in drusen volume was shown to be comparable among all eyes, and a model for long-term drusen volume development could be fitted as a cubic polynomial function and an R 2 =0.955. Spontaneous drusen regression was observed in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation and three geographic atrophy. Conclusions Drusen volume increase over time can be described by a cubic function. Spontaneous regression appears to precede conversion to advanced AMD. OCT might be a promising tool for predicting the individual risk of progression of AMD.

Loss to follow-up (LTFU) after anti-vascular endothelial growth factor (anti-VEGF) injections increases the risk of vision loss among patients with neovascular age-related macular degeneration (nAMD).To report rates of LTFU among patients with nAMD after anti-VEGF injections and to identify risk factors associated with LTFU in this population.This retrospective cohort study of data from 9007 patients who received anti-VEGF injections for treatment of nAMD was performed at an urban, private retina practice with multiple locations from April 1, 2012, to January 12, 2016.Rates of LTFU after anti-VEGF injections. Loss to follow-up was defined as receipt of 1 or more injections with no subsequent follow-up visit within 12 months.Among the 9007 patients (mean [SD] age, 81.2 [8.8] years; 5917 [65.7%] female; 7905 [87.8%] white), 2003 (22.2%) were LTFU. Odds of LTFU were greater among patients 81 to 85 years of age (odds ratio [OR], 1.58; 95% CI, 1.38-1.82; P .001), 86 to 90 years of age (OR, 2.29; 95% CI, 2.00-2.62; P .001), and more than 90 years of age (OR, 3.31; 95% CI, 2.83-3.86; P .001) compared with patients 80 years of age and younger. Odds of LTFU among African American patients (OR, 1.47; 95% CI, 1.00-2.16; P = .05), Asian patients (OR, 2.63; 95% CI, 1.71-4.03; P .001), patients of other race (OR, 3.07; 95% CI, 1.38-6.82; P = .006), and patients of unreported race (OR, 2.29; 95% CI, 1.96-2.68; P .001) were greater than odds of LTFU among white patients. Odds of LTFU were greater among patients with regional adjusted gross income of $50 000 or less (OR, 1.52; 95% CI, 1.30-1.79; P .001), $51 000 to $75 000 (OR, 1.35; 95% CI, 1.17-1.56; P .001), and $76 000 to $100 000 (OR, 1.28; 95% CI, 1.08-1.50; P = .004) compared with patients with incomes greater than $100 000. Odds of LTFU for patients living 21 to 30 miles (OR, 1.33; 95% CI, 1.05-1.69; P = .02) and more than 30 miles (OR, 1.55; 95% CI, 1.28-1.88; P .001) from clinic were greater compared with patients who lived 10 miles or less from the clinic. Odds of LTFU were greater among patients who received unilateral injections (OR, 1.44; 95% CI, 1.28-1.61; P .001) than among patients who received bilateral injections.We found a high rate of LTFU after anti-VEGF injections among patients with nAMD and identified multiple risk factors associated with LTFU among this population. Although our results may not be generalizable, data on LTFU in a clinical practice setting are needed to understand the scope of the problem so that interventions may be designed to improve outcomes.

BACKGROUND AND OBJECTIVE: This study evaluated the residual subfoveal fluid (SFF) immediately after rhegmatogenous retinal detachment (RRD) repair using intraoperative optical coherence tomography (iOCT). PATIENTS AND METHODS: This retrospective cohort study assessed fovea-involving RRD repaired by pars plana vitrectomy (PPV) using different drainage techniques. iOCT images were acquired through the fovea at the start of the case prior to initiating vitrectomy and then again immediately prior to introduction of tamponade. RESULTS: Ten eyes (32.3%) received perfluoro-n-octane (PFO), 12 (38.7%) underwent a posterior drainage retinotomy, and nine (29.0%) had drainage through the retinal break. There was no significant difference in the mean SFF thickness between eyes in either group ( P = .85). There was no significant association between SFF thickness on iOCT and functional or anatomic outcomes ( P > .05). CONCLUSION: There is no difference in the amount of residual SFF as measured on iOCT during RRD repair with pars plana vitrectomy using either direct drainage, drainage retinotomy, or PFO. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:497–503.]

To compare fluid detection of autosegmented en face to 12-line radial spectral domain optical coherence tomography scan patterns in neovascular age-related macular degeneration.Retrospective observational case series. Sixty-seven patients (94 eyes) with neovascular age-related macular degeneration underwent autosegmented en face optical coherence tomography (with associated 304-line raster scan) and 12-line radial scan patterns. Sensitivity and specificity of fluid detection for en face scan and 12-line radial scans were determined by combining radial and 304-line raster scans as a gold standard.Two hundred and fifty-eight en face and 12-line radial spectral domain optical coherence tomography scans were interpreted. Seventy-five scans (58.1%) had fluid, whereas 54 scans (41.9%) did not. En face scan pattern fluid detection sensitivity and specificity was 89.3% and 61.1%, respectively. Twelve-line radial scan pattern fluid detection sensitivity and specificity was 97.3% and 100%, respectively. The difference in fluid detection between scan patterns was statistically significant (P = 0.01). Decreased central macular thickness was associated with false-positive (P = 0.035) and false-negative (P = 0.01) fluid detection on en face scans.En face optical coherence tomography alone is not as sensitive or specific as the 12-line radial scan pattern in detecting fluid in neovascular age-related macular degeneration. En face scans should be corroborated with other optical coherence tomography protocols to guide clinical decision making.

PURPOSE To report a prospective, randomized comparative study assessing clinical outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy closure after 23-gauge pars plana vitrectomy. METHODS A single-masked, randomized, prospective study was undertaken with 49 eyes of 49 patients undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with either plain gut suture, PG910 (Vicryl) suture or a combination of the two. Assessment was based on both a postoperative pain scale and a standardized assessment of scleral inflammation at each suture site. RESULTS No wound leakage was noted postoperatively in any patient. Across all groups, scleral inflammation was significantly higher at the PG910 suture sites compared with the plain gut suture sites at both the 1-week (P = 0.04) and 1-month postoperative visits (P < 0.001). Patients with PG910 sutures reported greater pain at the 1-month postoperative visit than those with plain gut sutures (P = 0.018). CONCLUSION This prospective study suggests improved tolerability and reduced inflammation using plain gut suture compared with an 8-0 PG910 suture to close 23-gauge sclerotomies.

Immune cells utilize the IDO enzymatic conversion of trp to kyn to determine T-cell activation vs. anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here, we analyzed the difference between urine IDO levels in stable post-transplant vs. healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one-time urine samples, from 34 well children at general pediatric clinics, to the first-month post-transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first-month post-kidney transplant (median 16.6, range 3.9-44.0) vs. healthy children (median 9.2, range 3.51-17.0; p = 0.0057 by nonparametric Mann-Whitney test). Higher urine IDO levels even with stable transplant suggest a continuous ongoing low-grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies.

Objective: To assess the efficacy of surgical decompression

Background Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively. Methods We prospectively tested 217 blood and 167 urine serial samples, collected monthly for 12 months after transplantation from 29 consecutive children receiving a kidney transplant. The indoleamine 2,3-dioxygenase activity was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with AR, MIE, or stable group (no events) in the next 30 days. Results Using absolute cutoffs and allocating to samples to AR, MIE, or stable group, mean serum kyn/trp ratios were significantly elevated in the group that experienced AR (P=0.0007). Similarly, peripheral blood CD4-ATP levels were significantly lower in the group experiencing MIE (P=0.0351). Urine kyn/trp ratios and blood tacrolimus levels were not different between AR and stable groups. Within-subject analyses, accounting for repeated measures in subjects, also showed that, over time, serum kyn/trp ratios were higher before AR (P=0.031) and blood CD4-ATP levels were lower before MIE (P=0.008). Conclusions These results from our pilot discovery group suggest that a panel of biomarkers together can predict overimmunosuppression or underimmunosuppression. Further independent validation in a multicenter cohort is suggested.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42–0.95; P

BACKGROUND: We aimed to compare pain relief and safety of two doses of morphine in adult emergency department (ED) patients with acute limb trauma pain. METHODS: A total of 200 adult ED patients over 20 years of age requiring opioid analgesia were randomly allocated to two groups. Following a first dose of intravenous morphine sulfate at 0.10 mg/kg, a randomized double-blind placebo-controlled trial of intravenous morphine sulfate at 0.05 mg/kg versus the same amount of placebo was performed. Measurement of visual analogue scale pain intensity and assessment of adverse effects were performed at baseline (before morphine at 0.10 mg/kg), 30 minutes from baseline (just before study drug administration), and at 60 minutes from baseline (30 minutes after study drug). RESULTS: No significant difference was found between groups at 30 minutes from baseline. There was significant reduction in final pain after 1 hour in the 0.15 mg/kg compared to 0.10 mg/kg group (p

Purpose: To report a single case of paracentral acute middle maculopathy in association with retinal artery occlusion in the setting of ipsilateral facial cosmetic filler injection. Methods: Case report. Patient: A 35-year-old woman presenting with sudden vision loss to finger count vision immediately after left nasal fat pad cosmetic filler injection. Results: Dilated funduscopic examination revealed a swollen optic disc with multiple branch arterial occlusions with visible embolic material. Fluorescein angiography confirmed multiple branch arterial occlusions in addition to a focal choroidal infarction in the macula. Spectral-domain optical coherence tomography revealed middle retinal hyperreflectivity in the superotemporal macula consistent with paracentral acute middle maculopathy. En face optical coherence tomography demonstrated a superotemporal area of whitening at the level of the deep capillary plexus corresponding to the paracentral acute middle maculopathy lesion seen on spectral-domain optical coherence tomography. On twelve-month follow-up, final visual acuity was 20/100 due to optic neuropathy. Conclusion: Emboli from cosmetic facial filler injections may rarely result in ipsilateral arterial occlusions and now have a novel association with paracentral acute middle maculopathy likely due to deep capillary plexus feeder vessel occlusion.

To describe a surgical technique for fluorescein-assisted subretinal tissue plasminogen activator delivery during pars plana vitrectomy for submacular hemorrhage. Retrospective, interventional, consecutive case series. Six eyes of 6 patients were reviewed. Etiology of submacular hemorrhage was age-related macular degeneration in 2 eyes and polypoidal choroidal vasculopathy in 4 eyes. Twenty-three-gauge pars plana vitrectomy was performed and fluorescein-stained tissue plasminogen activator was injected in the subretinal space through a 41-gauge cannula in all eyes. Sulfur hexafluoride (SF6) gas (n = 5 eyes) or air (n = 1 eye) tamponade was instilled at the conclusion of surgery. Successful displacement of submacular hemorrhage was achieved in all eyes. Mean visual acuity improved from 20/693 preoperatively to 20/224 postoperatively (P = 0.14) at mean follow-up of 560 ± 464 days. No intraoperative or postoperative complications were encountered. Fluorescein-assisted subretinal delivery of tissue plasminogen activator was well tolerated and allowed for improved visualization of subretinal bleb formation during pars plana vitrectomy for submacular hemorrhage.

Purpose Optical coherence tomography angiography (OCTA) is a novel technology that uses motion contrast instead of dye to generate angiographic images. Using several modalities of OCTA, the authors describe and compare changes observed in branch retinal vein occlusion. Methods A case series of three patients with OCTA imaging. Results Despite presenting at different time frames, the authors found common imaging findings consisting of vascular hypoperfusion, increased tortuosity, and telangiectasia in all their cases. Furthermore, macular edema and intraretinal fluid were noted on the en-face angiograms. The extent of vascular and structural alterations could clearly be delineated in superficial and deep retinal networks. However, fine capillary alterations were better appreciated on smaller-size scans. Conclusion With the ability to noninvasively visualize vascular flow, OCTA could serve as a new diagnostic tool for current ophthalmic research and clinical practice. Such findings can help supplement other imaging modalities in establishing a diagnosis and monitoring disease progression over time. This would potentially be useful in regard to ischemic processes such as branch retinal vein occlusion and diseases affecting different layers of the retinal vasculature.

To measure the vascular density and foveal avascular zone (FAZ) area in the deep and superficial retinal vascular networks using optical coherence tomography angiography (OCTA) in patients with branch retinal vein occlusion (BRVO).Retrospective observational case series.Patients with unilateral BRVO involving the macula were enrolled. OCTA was performed on the BRVO and fellow eyes. Macular vascular density, FAZ area, and foveal thickness were measured in all eyes.Seventeen eyes of 17 patients met inclusion criteria. The mean overall vascular density measured in the entire scan was lower in BRVO eyes compared to fellow eyes in both the superficial (48.07% vs 52.60%, respectively; P.001) and deep (52.60% vs 57.67%, respectively; P.001) networks. In both networks, the density was lower in the affected BRVO sector compared to the unaffected sector in the same eye and in the fellow eye (P.001). In the deep network, the density was lower in the unaffected sector of the BRVO eye compared with the corresponding sector in the fellow eye (58.87% vs 61.65%, respectively; P = .04). A negative correlation was found between the logarithm of the minimal angle of resolution (logMAR) visual acuity and the overall density in superficial (r = -0.40, P = .02) and deep (r = -0.38, P = .03) networks. The mean FAZ area in BRVO eyes was significantly lower only at the level of the deep network when compared to the fellow eyes (0.519 mm(2) vs 0.410 mm(2), respectively; P = .02) and correlated positively with logMAR (r = 0.34, P = .04).In eyes with BRVO, quantitative OCTA measurements confirm decreased vascular density in both the superficial and deep vascular networks. Moreover, vascular density and FAZ area appear to correlate with visual function.

Purpose: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. Methods: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. Results: A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). Conclusions: En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV., LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, Macula Foundation, Inc.

More than 70% of Ewing tumors occur in the extremities and pelvis. This study identified factors influencing local control and functional outcomes after management with definitive radiotherapy (RT).A total of 75 patients with a localized Ewing tumor of the extremity or pelvis were treated with definitive RT at the University of Florida between 1970 and 2006 (lower extremity tumors in 30, pelvic tumors in 26, and upper extremity tumors in 19). RT was performed on a once-daily (40%) or twice-daily (60%) basis. The median dose was 55.2 Gy in 1.8-Gy daily fractions or 55.0 Gy in 1.2-Gy twice-daily fractions. The median observed follow-up was 4.7 years. Functional outcome was assessed using the Toronto Extremity Salvage Score.The 10-year actuarial overall survival, cause-specific survival, freedom from relapse, and local control rate was 48%, 48%, 42%, and 71%, respectively. Of the 72 patients, 3 required salvage amputation. Inferior cause-specific survival was associated with larger tumors (81% for tumors8 cm vs. 39% for tumors/=8 cm, p0.05). No patient characteristics or treatment variables were predictive of local failure. No fractures occurred in patients treated with hyperfractionation or with tumors of the distal extremities. Severe late complications were more frequently associated with use of8-MV photons and fields encompassing the entire bone or hemipelvis. A significantly better Toronto Extremity Salvage Score was associated with a late-effect biologically effective dose of91.7 Gy(3).Limb preservation was effectively achieved through definitive RT. Treating limited field sizes with hyperfractionated high-energy RT could minimize long-term complications and provides superior functional outcomes.

The taxanes are chemotherapeutic agents that may, in rare cases, cause cystoid macular edema without leakage on fluorescein angiography. Two patients with evidence of taxane-related macular edema presented and were evaluated using novel en face optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities. Although OCTA revealed no flow abnormalities in either patient, en face OCT revealed a striking bilateral symmetric cystic tessellation pattern. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:176–179.]

A 59-year-old patient with bilateral worsening diabetic macular edema received intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye only. On 1-month follow-up, there was noted bilateral improvement of visual acuity and diabetic macular edema on spectral-domain optical coherence tomography imaging, reflecting bilateral effect of unilateral treatment with aflibercept. [ Ophthalmic Surg Lasers Imaging Retina. 2016;47:474–476.]

Purpose To characterize the optical coherence tomography (OCT) angiography, en face OCT, and microperimetry features of paracentral acute middle maculopathy in both the acute phase and after resolution, and to propose a classification of distinct subtypes of this entity. Design Retrospective observational case series. Methods Clinical histories, high-resolution digital color imaging, spectral-domain OCT images, fluorescein angiography, OCT angiography images, and en face OCT images of 16 patients with paracentral acute middle maculopathy were evaluated. Microperimetry was available in 6 patients. Results The most common referring diagnoses were isolated branch retinal arterial occlusion (5/16), combined central retinal vein and cilioretinal artery occlusion (4/16), and isolated central retinal vein occlusion (4/16). All patients demonstrated hyperreflective plaque-like lesions at the level of the inner nuclear layer on spectral-domain OCT, with no fluorescein angiographic correlate. OCT angiography demonstrated variable areas of capillary dropout within the superficial and deep retinal capillary plexi in these areas. En face OCT highlighted confluent areas of middle retina hyperreflectivity corresponding to these lesions. Three distinct en face OCT patterns were observed: arteriolar, fern-like, and globular. Microperimetry demonstrated relative scotomas mapping to the area of middle retinal hyperreflectivity seen on en face OCT. Conclusions Paracentral acute middle maculopathy may be best evaluated with the use of en face OCT imaging, which corresponds to subjective and objective visual field defects. En face OCT appearance may be used to classify paracentral acute maculopathy into distinct subtypes.

Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF-β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial.To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF-β1 in renal allografts.Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF-β1 gene expression was assessed by Real Time PCR.The percentages of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF-β1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers.The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF-β1, it is likely to be implicated in chronic damages of allograft tissue.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease with variable clinical expression. Ethnic, racial and geographical factors have been associated with disease occurrence and expression. We intended to describe the clinical characteristics and assess the disease severity and treatment status in Iranian AS patients.A total of 320 AS patients were assessed for demographic variables, clinical manifestations, human leukocyte antigen (HLA) status, disease severity, functional capacities, quality of life and treatment status.A gender ratio of 3.8:1, an average age onset of 27 ± 7.3 and a mean diagnostic delay of 8 years were observed. Eleven percent had juvenile onset AS. Positive family history was higher than that observed in most other countries. Enthesitis was a very common finding involving more than two-thirds of our patients. Uveitis was the leading extra-articular manifestation. We found an HLA-B27 prevalence of 73% and four HLA-B27 subtypes. Disease activity was high and the functional status was poor as indicated by mean Bath AS Disease Activity, Functional and Metrology indices. Quality of life was considerably impaired in our patients. We found a low percentage of patients on biological medications and a relatively higher percentage on disease modifying anti-rheumatic drugs and corticosteroids.Our results demonstrate a broad characterization of Iranian AS patients providing a better understanding of this disease. A national multicenter registry would enable larger- scale prospective studies to be carried out further evaluating the disease burden on patients and society.

Inequalities in features and severity of ankylosing spondylitis (AS) have been noticed between men and women, suggesting a possible influence of gender on disease phenotypes. Comparing disease features and characterization of gender differences in clinical features and medications could help elucidate the potential influence of gender on the severity of AS in patients. This study aims to assess the influence of gender on disease patterns in Iranian patients with AS. Three hundred and twenty patients diagnosed with primary AS were assessed for demographic variables, clinical manifestations, HLA status, disease severity, functional capacities, quality of life, and treatment status. Sixty-seven women and 253 men were included corresponding to a male to female ratio of 3.78:1. Both groups were similar regarding ethnicity, positive family history, and juvenile onset AS. HLA-B27 was more frequent among males (78.3 vs. 55.2 %; p < 0.001). There was a higher proportion of female patients with overall enthesitis (p < 0.05). Extra-articular manifestations and treatment modalities presented similar frequencies in both genders. No difference in gender-associated diagnostic delays was observed. Female disease was at least as severe as male disease, and in some aspects, females presented with more severe disease. Despite a relatively similar disease profile, we observed a higher rate of enthesitis among women. Together with the equally high rate of disease activity indices in both genders, these findings indicate an overall longer delay to diagnosis in our country. Early detection and specialized care would be of great practical importance.

Importance There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections. Objective To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy. Design, Setting, and Participants An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. Interventions Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study. Main Outcomes and Measures Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures. Results Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μm at enrollment to 334.1 μm at the final visit ( P = .01). The mean maximum subretinal fluid height decreased from 126.6 μm at enrollment to 49.5 μm at the final visit ( P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μm at enrollment to 239.9 μm at the final visit ( P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit ( P = .60). Conclusions and Relevance These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

To evaluate the short-term functional and anatomic outcomes of patients with persistent diabetic macular edema (DME) who were converted from bevacizumab and/or ranibizumab to aflibercept.Retrospective, interventional, noncomparative, consecutive case series.Only eyes treated with at least 4 consecutive injections of ranibizumab/bevacizumab spaced 4-6 weeks apart prior to conversion and with at least 2 aflibercept injections afterward were considered for inclusion. Pertinent patient demographic, examination, and treatment data were extracted from clinical charts and tabulated for analysis.Fifty eyes of 37 patients were included. Eyes received a mean of 13.7 bevacizumab/ranibizumab injections prior to conversion, followed by 4.1 aflibercept injections over 4.6 months of subsequent follow-up. The mean logMAR visual acuity at the pre-switch visit was 0.60 ± 0.43 (Snellen equivalent, 20/80). This improved to 0.55 ± 0.48 (Snellen equivalent, 20/70) by the second visit after conversion, corresponding to a mean logMAR change of -0.05 ± 0.22 (P = .12). The average central macular thickness from the pre-switch spectral-domain optical coherence tomography scan was 459.2 ± 139.2 μm. This significantly improved to 348.7 ± 107.8 μm by the second visit following conversion, reflecting a mean decrease of 112 ± 141 μm (P .0001). The mean intraocular pressure (IOP) recorded at the pre-switch visit was 15.1 ± 3.3 mm Hg. At the second follow-up after converting to aflibercept, the IOP averaged 14.9 ± 3.2 mm Hg, with a mean decrease of 0.2 ± 3.0 mm Hg (P = .63).Conversion to aflibercept for persistent DME resulted in significant anatomic improvements. While trends towards improved visual acuity and reduction in IOP were observed, these were not statistically significant.

Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.

58-year-old woman residing in a rural area in southern Iran was admitted to the hospital with multiple nonhealing ulcers of 6 months’ duration on her right lower extremity. The lesions had started as small nonpruritic erythematous papules in the form of insect bites and developed graduallyoverthefollowingmonths,increasing in size and ulcerating into an open wound. The patient had no history of other symptoms, diseases, or use of medications. On physical examination the lesions consisted of 3 painless, nonpruritic, roughly circular ulcers with erythematous and indurated margins on the anterior aspect of the right shin and ankle (Figures 1-5), one of which was covered by a yellowish-brown crust (Figure 4). There was no lymphadenopathy. Routine laboratory test resultswerenormal.Askinbiopsywasobtained and sent for histopathological examination, whichconfirmedadiagnosisofcutaneousleishmaniasis with the presence of numerous leishmania bodies. The patient was treated with meglumine antimoniate (Glucantime). After cardiac consultation and assessment of renal function, Glucantime was administered at a dose of 20 mg/kg via 2 daily intramuscular injections for 20 days. Leishmania infections are characterized by a spectrum of clinical manifestations ranging from localized cutaneous leishmaniasis to disseminated visceral infection. The first sign of cutaneous infection is typically a small erythema developing after a variable prepatent period at the site of a sandfly bite. The erythema develops into a papule, then a nodule that progressively ulcerates over a period of 2 weeks to 6 months

Sarcoma associated with bone infarct is a rare condition sparsely reported in the literature. Sixty percent of cases arise about the knee and most are malignant fibrous histiocytomas. We report 15 patients; 12 of 15 presented with a tumor around the knee. Treatment was limb salvage in seven patients, amputation in six, and biopsy alone in two. For patients without metastatic disease at presentation, the 2-year disease-free survival rate was 63% (seven of 11). Two patients received chemotherapy and both were continuously disease-free at last followup. When we combined our 15 patients with the 52 previously reported in the literature, 38 of the 67 (57%) died of their disease at an average of 19.2 months after diagnosis; 21 patients (31%) were continuously disease-free for 24 months. Of 13 patients who received chemotherapy, eight (62%) were continuously disease-free at 24 months compared with 24% (13 of 54) of those who did not receive chemotherapy. Overall, prognosis for these patients is poor, but survival in patients without metastatic disease at diagnosis approaches that of other bone sarcomas. There is a trend suggesting adjuvant chemotherapy combined with appropriate surgery may improve patient outcomes.Level IV, therapeutic study.

Purpose To perform a review of the 40-year University of Florida experience treating spinal and paraspinal Ewing tumors. Patients and Methods A total of 27 patients were treated between 1965 and 2007. For local management, 21 patients were treated with radiotherapy (RT) alone and 6 with surgery plus RT. All patients with metastatic disease were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 17 years, and the most frequent subsite was the sacral spine ( n = 9). The median potential follow-up was 16 years. Results The 5-year actuarial overall survival, cause-specific survival, and local control rate was 62%, 62%, and 90%, respectively. For the nonmetastatic subset ( n = 22), the 5-year overall survival, cause-specific survival, and local control rate was 71%, 71%, and 89%, respectively. The local control rate was 84% for patients treated with RT alone vs. 100% for those treated with surgery plus RT. Patients who were >14 years old and those who were treated with intensive therapy demonstrated superior local control. Of 9 patients in our series with Frankel C or greater neurologic deficits at presentation, 7 experienced a full recovery with treatment. Of the 27 patients, 37% experienced Common Toxicity Criteria Grade 3 or greater toxicity, including 2 deaths from sepsis. Conclusion Aggressive management of spinal and paraspinal Ewing tumors with RT with or without surgery results in high toxicity but excellent local control and neurologic outcomes. Efforts should be focused on identifying disease amenable to combined modality local therapy and improving RT techniques.

This retrospective analysis describes our 35-year experience with respect to disease control and functional status.Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years.The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications.Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.

Purpose Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. Patients and Methods Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery ± RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). Results Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% ( p = 0.21), 73% vs. 47% ( p = 0.13), 73% vs. 40% ( p = 0.03), and 43% vs. 40% ( p = 0.52), respectively, for patients treated with surgery ± RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery ± RT group and 68% for the definitive RT group ( p = 0.03). The ranges of the TESS for surgery ± RT vs. RT alone were 70–100 (mean, 94) and 97–100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. Conclusions Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.

Chylous reflux is a manifestation of primary or secondary lymphatic obstruction. Primary lymphatic obstruction is defined as lymphangiectasia and incompetency of lymphatic valves without an underlying cause. Lymphangiectasia resulting from trauma, neoplasm, irradiation, or inflammation characterizes secondary lymphatic obstruction. Leakage of chyle into the uterus, vagina, bladder, or rectum can occur with either primary or secondary lymphatic obstruction. We report a patient with chylous vaginal discharge, a rare presentation of primary chylous reflux syndrome. CT-lymphangiography and magnetic resonance imaging clearly depicted this disorder. To our knowledge, only 20 cases of chylous vaginal discharge have been reported previously; chylous vaginal drainage occurred in the absence of chylous uterine reflux in only three. Although this is a rare anomaly, chylous reflux should be considered in a child with chronic vaginal discharge and lower extremity swelling.