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Purpose To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography (OCT) imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). Methods Case report and review of the relevant literature. Patients Single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services. Results A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disc drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-wide field OCT. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis nor clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. Conclusion Here we present a patient with nanophthalmos, optic disc drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield OCT, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP-associated nanophthalmos.

Purpose To describe central serous chorioretinopathy (CSCR) cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases. Methods Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging and biometry of four eyes of three patients were assessed. A literature review was conducted. Results The three patients had peripheral choroidal detachment and inferior bullous retinal detachment associated with CSCR features detected using multimodal imaging, including fluorescein and indocyanine green angiography. The choroid was thick in the three patients, and uveal effusion occurred after steroid treatment in all cases. Subretinal fluid drainage and deep sclerectomy with flaps of 4x4 mm in both inferior quadrants were performed in 3 eyes of 2 patients with good outcomes. One patient was treated with photodynamic therapy. All three patients developed a typical leopard-spot pigmentary pattern in the fundus. Conclusion A severe presentation of highly exudative CSCR may occur in rare cases with a peripheral choroidal detachment mimicking uveal effusion syndrome. These severe cases highlighted the role of choroidal thickening and hyperpermeability, choroidal vein dilation and possible scleral thickening in both entities.

Objective This study aimed to analyze our outcomes of primary premaxillary ostectomy and setback combined with lip adhesion as the first stage in repair of the bilateral cleft lip with fly-away premaxilla. Methods This retrospective study included all patients who required primary premaxillary setback by a single surgeon to achieve successful lip repair between 2011 and 2017 at a tertiary children's hospital. All patients had bilateral cleft lip and complete cleft palate with significant premaxillary protrusion. All patients either had failed presurgical orthodontic manipulation or were thought to be poor candidates because of the rigidity of the premaxilla on clinical examination. Patient data were obtained from review of medical records and photographs. Surgical technique is described. Results Eleven patients with bilateral cleft lip, all of whom also had complete cleft palate, underwent primary premaxillary setback and lip adhesion at an average age of 8.2 months. The mean follow-up was 1.9 years (range, 139 days to 4.5 years). All patients subsequently completed formal lip repair, of which 10 have undergone palatoplasty. Serial photography documented stable premaxillary position and successful lip repair within the follow-up time frame. No patient had postoperative premaxillary instability or vascular compromise. One patient had dehiscence of the lip adhesion requiring reoperation. Conclusions Primary premaxillary ostectomy and setback allows for successful staged formal lip repair in patients with bilateral cleft lip and palate who have failed presurgical infant orthopedics. Further research is required regarding long-term follow-up with respect to midfacial growth.

To describe a novel optical coherence tomography (OCT) finding in a case of macular serous retinal detachment (SRD) after pars plana vitrectomy (PPV) and panretinal photocoagulation (PRP).Retrospective case report.A 52-year-old Hispanic male presented with dense vitreous hemorrhage secondary to proliferative diabetic retinopathy in his right eye, for which PPV with endolaser was performed.His post-operative course was complicated by significantly decreased vision and a macular SRD that was characterized on OCT by a reticular network of hyperreflective bands in the subretinal space. Fluid and hyperreflective material in the subretinal space resolved by post-operative week (POW) 6 with standard post-operative eye drops. However, persistent ellipsoid zone disruption was seen up to POW 20.Extensive subretinal bands can be seen after PRP. This novel finding can pose diagnostic and management challenges, but may resolve with conservative medical management.

Purpose To report a case of Stickler type IV with familial exudative vitreoretinopathy (FEVR) phenotype. Material and methods Retrospective case report. Results A 24-year-old female presented with right eye exotropia and decreased vision. She had no facial or typical retinal features of Stickler syndrome, but complained of right-sided hearing loss and right-sided neck pain. Examination of the right eye showed a chronic combined exudative and traction retinal detachment (E-TRD) with temporal retinal dragging associated with far temporal retinal exudations and fibrovascular proliferations. The left eye had an attached retina with large areas of peripheral temporal retinal non-perfusion on fluorescein angiography, sharply demarcated by end circulation vascular pruning and mild peripheral vascular leakage, consistent with familial exudative vitreoretinopathy (FEVR) phenotype. Genetic analysis identified two heterozygous c.1052C>A and c.1349A>G variants in COL9A1, but did not disclose any mutation in genes classically associated with FEVR. Conclusion FEVR-like retinal vascular features can be the presenting sign in patients with Stickler syndrome type IV.

Purpose To describe two cases of catastrophic, bilateral retinal vascular occlusion following intravitreal (IVT) bevacizumab injection. Methods Case series. Main outcome measures included clinical and fluorescein angiography (FA) findings. Results Case 1 - A 65-year-old woman with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST) syndrome developed acute, severe, bilateral visual loss two weeks following bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and FA revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2 - An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left then right eye approximately three weeks following IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. FA showed diffuse venous leakage. Extensive testing revealed an elevated anti-nuclear antibody and mildly elevated anti-cardiolipin antibody. Conclusion Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion following treatment with IVT bevacizumab. The moderate to severe intraocular inflammation in both cases, and the contralateral involvement following unilateral IVT injection in Case 2, suggest a possible delayed immune-mediated mechanism.

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,1 and serology analysis indicated sterol 27-hydroxylase deficiency,2 confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.2

Purpose To describe a case of AA amyloidosis which produced an orbital inflammatory response with a novel presentation. Methods Case report. Results A 24 year-old Caucasian female with a history of intravenous (IV) heroin use was hospitalized for tricuspid valve endocarditis and methicillin resistant Staphylococcus aureus bacteremia, as well as acute renal failure. She received hemodialysis and IV daptomycin and had negative blood cultures for 3 weeks, when she developed sudden bilateral orbital swelling and blurred vision. Visual acuity was 20/200 in the right eye (OD) and 20/400 in the left eye (OS). Examination revealed proptosis, conjunctival chemosis and desiccation, optic disc swelling, creamy choroidal infiltrates and inferiorly located exudative retinal detachments in both eyes (OU). Multimodal imaging demonstrated thickening of the sclera, choroid and choriocapillaris as well as outer retinal disruption, subretinal fluid and deposits of hyperfluorescent debris within the choriocapillaris, outer retina and vitreous. Oral prednisone at 60 mg per day resolved the choroidal infiltrates and exudative detachments. Persistent nephrotic syndrome called for a renal biopsy, which demonstrated AA amyloidosis. Conclusion - Orbital and choroidal AA amyloidosis can induce a local inflammatory response manifesting as orbital swelling, papillitis, posterior scleritis, choroiditis and exudative retinal detachment, which responds to steroid therapy. The underlying pathology is likely a reactive inflammation and vaso-occlusive process involving the choriocapillaris and orbital vasculature to the presence of amyloid fibrils.

To show surgical results of the intraoperative 3D fluorescein angiography-guided pars plana vitrectomy for branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.The NGENUITY 3D visualization system was used for the digital-assisted vitrectomy. Three-dimensional fluorescein angiography-guided pars plana vitrectomy was performed in three patients with branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.In all eyes, the scatter retinal photocoagulations for a nonperfusion area, depicted as hypofluorescein, and the segmentation and delamination of the perivascular fibrovascular proliferative membrane, depicted as hyperfluorescein, could be safely performed on the same screen while implementing intraoperative 3D fluorescein angiography.Three-dimensional fluorescein angiography-guided pars plana vitrectomy, a novel approach that fully uses the advantages of digital-assisted vitrectomy, can be one of the useful techniques for the treatment of branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.

To characterize the progression of structural and functional changes in the retinas of a small cohort of unrelated patients with early late-onset retinal degeneration and evaluate these changes as potential biomarkers for future treatment trials.Best-corrected visual acuity, contrast sensitivity, Goldman visual fields, retinal sensitivity measurement by mesopic microperimetry, extent of ellipsoid zone disruption using spectral domain optical coherence tomography, and fundus autofluorescence imaging were performed at each biennial visit.Three unrelated patients with molecularly confirmed late-onset retinal degeneration (S163R mutation in C1QTNF5 ) were prospectively followed for 4 years.The patient's ages were 44, 54, and 62 at baseline. Over the 4-year follow-up period, one patient demonstrated a significant reduction in best-corrected visual acuity (6 Early Treatment of Diabetic Retinopathy Study letters), whereas two patients suffered a significant reduction in contrast sensitivity. Early in the disease, there was a close relationship between ellipsoid zone disruption and a loss in retinal sensitivity. Later in the course of the disease, there were areas outside the zones of ellipsoid zone disruption that also suffered progressive loss of retinal sensitivity, suggesting that ellipsoid zone loss was not the only factor responsible for the loss of retinal sensitivity. Changes in fundus autofluorescence and Goldman visual field loss were not closely related to changes in ellipsoid zone disruption or retinal sensitivity loss.This study has found that the monitoring of the progression of ellipsoid zone disruption and changes in mesopic microperimetry may be useful biomarkers in future clinical trials in patients with late-onset retinal degeneration.

Xiao, F, Yang, Y, Xiao, L, Xia, Z, Wang, L, Yang, K, and Wang, S. Reduction of T cells and hsa-miR150-5p in female canoeing athletes: Preliminary evidence between exercise training and immune. J Strength Cond Res 36(11): e106-e113, 2022-This article aims to reveal the alteration of immune profile in teenage canoeing athletes, by which applies a clue for regulation of exercise on human immune. Thirty-one teenagers of female canoeing athletes and age-matched subjects participated in this research. Peripheral leukocytes' microRNAs (miRNAs) were analyzed using Agilent human microRNA 2.0 and gene software. The miRNA candidates were quantified by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The percentages of various lymphocytes were tested using flow cytometry. There were 6 miRNAs (hsa-miR150-5p, 31-5p, 3659, 4419a, 650, and 8485) lower in canoeing athletes, and the reduction of miR-150 was identified by RT-qPCR ( p = 0.021). Canoeing athletes had lower percent of CD3 + T cells than the subjects with no exercise training had ( p0.001), but the ratio of CD4 + to CD8 + and the percent of CD4 + T cells and CD8 + T cells showed no significant difference between these 2 groups. T cells and hsa-miR150-5p are sensitive to the long-time heavy exercise training, and the exercise for winning competition regulates the immune system by inhibiting T cells and hsa-miR150-5p.

PURPOSE To describe four eyes of three patients with presumed acute fovealitis to expand the clinical variants of this recently described disorder. METHOD The patients underwent a comprehensive ophthalmic examination, including multimodal imaging and electrophysiological tests. RESULTS Three female patients aged from 18 to 24 years presented sudden central visual disturbances in one or both eyes. The visual acuity ranged from 20/25 to 20/70 in the affected eyes. All of them showed a subtle yellowish lesion in the foveola. Fundus autofluorescence and fluorescein angiography were unremarkable. Optical coherence tomography disclosed focal disarrangement of the outer retinal layers restricted to the fovea and hyperrefective lesions above the external limiting membrane. Multifocal electroretinography responses were attenuated. The electrooculogram response was normal. All patients recovered normal visual acuity and the outer retinal layers. CONCLUSION Attenuated multifocal electroretinography foveal response and normal electrooculogram are newly described clinical findings in patients with acute fovealitis.

To report a case of a pituitary macroadenoma that presented with bilateral intraretinal hyporeflective spaces located primarily in the inner nuclear layer on the macular SD-optical coherence tomography.Case report.Based on the findings of a macular SD-optical coherence tomography, a 53-year-old man was considered as having cystoid macular edema secondary to a retinovascular condition. He was treated with intravitreal vascular endothelial growth factor inhibitors and corticosteroids with no improvement. Confrontation visual fields suggested a bitemporal defect. MRI confirmed the presence of a nonsecreting pituitary macroadenoma compressing the optic chiasm.Not all intraretinal hyporeflective spaces in the optical coherence tomography are secondary to a retinal vascular condition. Hyporeflective spaces in the inner nuclear layer on optical coherence tomography imaging that do not leak on fluorescein angiography may be secondary to optic atrophy from chiasmal compression.

PURPOSE Adams-Oliver syndrome is a rare, inherited disorder of embryologic development that affects multiple systems. Ocular manifestations have been poorly characterized due to the low prevalence and high mortality of the disease when it is associated with internal organ and/or ophthalmic manifestations. We present a case of Adams-Oliver syndrome in a 13-year-old patient whose multimodal retinal imaging findings helped direct management. METHODS Case report reviewing medical records and imaging. PATIENTS Single patient. RESULTS Visual acuity upon presentation was 20/40 in each eye. Ultra-widefield fluorescein angiography revealed peripheral non-perfusion with terminal vascular bulbs, as well as leakage from a temporal fibrovascular complex in the left eye. Fundus autofluorescence imaging showed hyperautofluorescence associated with optic disc drusen and the fibrovascular complex. Treatment with targeted laser photocoagulation was associated with regression of the neovascularization. CONCLUSIONS Retinal manifestations of Adams-Oliver syndrome as observed with ultra-widefield fundus imaging may resemble those of familial exudative vitreoretinopathy and retinopathy of prematurity. Treatment of avascular retina with panretinal photocoagulation can be considered.

To describe a case of choroidal nevus with intralesional cavitations detected with enhanced depth imaging optical coherence tomography and to show its changes during an 8-year follow-up.A case report.A 55-year-old male patient was found to have a pigmented lesion at the posterior pole of his right eye, just temporal to the fovea. A complete multiimaging examination was obtained and showed a lesion of about 4 mm of diameter with a small amount of subretinal fluid and chronic changes in the retina overlying the lesion. Based on clinical examination, a diagnosis of choroidal nevus was made, but interestingly the enhanced depth imaging optical coherence tomography revealed the presence of intralesional cavitations. Close follow-up with no intervention was planned, and over 8 years of observation, the lesion remained stable in size, with a gradual increase of the central necrosis.Benign pigmented choroidal lesions can show internal cavitations likely secondary to internal necrosis. This feature does not represent a sign of malignancy of the lesion. Enhanced depth imaging optical coherence tomography is a feasible imaging tool for the visualization of the internal cavitations and to follow their evolution over time.

Melanoma-associated retinopathy responds poorly to currently-available therapies, with continued chronic decline in visual function being the norm, despite treatment. The purpose of this report is to describe the excellent response of a patient with melanoma-associated retinopathy to a triple therapy regimen of rituximab, intravenous immunoglobulin, and intravitreal corticosteroids.Single interventional case report describing management of melanoma-associated retinopathy and the patient's response to this treatment. Retinal function was monitored by serial visual acuity, fundus exams, Goldmann visual fields, and electroretinography.A 65-year old man presented with new onset photopsia, decrease visual acuity and nyctalopia in both eyes in the setting of recently-diagnosed Stage IIIB melanoma, initially treated with wide local excision and adjuvant interferon. He was diagnosed with melanoma-associated retinopathy that initially worsened during his course of interferon for treatment of the melanoma. We initiated triple therapy with rituximab, intravenous immunoglobulin, and intravitreal corticosteroids, and this resulted in full return of electroretinography function and resumption of 20/20 visual acuity in both eyes.This is the first reported case of the utility of triple therapy with rituximab, intravenous immunoglobulin, and intravitreal steroids for successful management of melanoma-associated retinopathy as demonstrated by improvement in acuity, symptoms, visual fields, and electroretinography.

Purpose To describe a patient with a history of pre-B cell acute lymphoblastic leukemia (pre-B ALL) in remission, who developed recurrent alternating intraocular pre-B ALL manifesting with pseudohypopyon, uveal mass, and serous retinal detachment. In multiple instances this constellation of ocular findings preceded systemic leukemia recurrence. Method Case report. Results A 29-year old man with history of pre-B cell acute lymphoblastic leukemia, in remission following a hematopoietic stem cell transplant, presented with pseudo-hypopyon, uveal lesions, and serous retinal detachment of the right eye. Comprehensive workup for infectious and inflammatory etiologies was unremarkable, and a bone marrow biopsy revealed systemic recurrence of leukemia. One year later, while again in remission, the patient developed a pseudo-hypopyon, uveal mass, and serous retinal detachment of the other eye. Repeat bone marrow biopsy showed impending leukemia relapse, which occurred 1 month later. Orbital radiation resulted in complete ocular resolution. Conclusions The constellation of pseudohypopyon, serous retinal detachment, and uveal mass (pseudo-panuveitis) should be recognized as a harbinger for systemic pre-B ALL recurrence.

Purpose To report a case of bilateral sequential, CRVO in a man with newly diagnosed hemoglobin C trait. Methods A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. Results The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal anti-angiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal anti-angiogenic therapy. Conclusion This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

Purpose To report a case of symptomatic multiple retinal emboli during a carotid doppler ultrasonography (CDU) procedure. Material and methods Case report documented with clinical records, fundus photography (FP), optical coherence tomography angiography (OCT-A) of the retina and computed tomography angiography (CT-A) of the supra-aortic vessels. Results A 60-year-old male patient, presented to the emergency department with sudden vision loss in the left eye (LE) and pain in the left upper eyelid noticed during a CDU procedure. On the LE, the best corrected visual acuity (BCVA) was 20/200 and fundus observation revealed retinal arteriolar attenuation, retinal whitening with cherry point and multiple intra-arterial emboli in all arcades of the central retinal artery. CT-A of the supra-aortic vessels revealed an absence of filling throughout the cervical, petrous and cavernous segment of the left internal carotid artery, resuming only in the ophthalmic segment and an important stenosis of the left external carotid artery. He had no indication to be submitted to left carotid endarterectomy and began ocular massage and oral anticoagulant. 4 months later, ptosis was no longer present, BCVA improved to 20/20 with a residual scotoma and emboli disappeared on FP. Conclusion Embolic occlusion of retinal arteries may be an extremely rare but serious complication associated with CDU and patients and clinicians should be aware of it.

Purpose To report a novel case of dark without pressure in a patient with a choroidal osteoma. To our knowledge this association has not been previously reported. Methods Observational case report. Review of clinical examination and multi-modal imaging findings in a patient with a choroidal osteoma and dark without pressure. Results A 21-year-old African American female with no significant past medical history presented with a large, unilateral, juxtapapillary, subretinal, orange-colored, ovoid shaped lesion with macular involvement. An overlying area of mottled pigmentary changes, fibrosis, and atrophy were present. Adjacent to and surrounding the osteoma was an annular band of hyperpigmented mid-peripheral retina with a sharply demarcated scalloped border that abruptly changed to normal-appearing peripheral retina. Multi-modal imaging including wide-field fluorescein angiography, optical coherence tomography, and ophthalmic B-scan were performed. The funduscopic and imaging findings were consistent with a diagnosis of choroidal osteoma and dark without pressure. Conclusion The examination and imaging findings in this patient suggest a unique association between two relatively uncommon lesions, choroidal osteoma and dark without pressure. Though these two lesions may simply be coinciding in the same eye, there may be an association with space- occupying lesions causing a change in photoreceptor structure.

To report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after intravitreal injection in a patient with a history of fellow-eye NAION.Observational case report.An 82-year-old woman with a history of fellow eye NAION developed an inferior visual field defect 1 day after an intravitreal aflibercept injection for neovascular age-related macular degeneration. She was found to have optic disk edema and an inferior altitudinal defect, consistent with NAION. The mechanism may have involved compromised perfusion to the optic nerve head related to elevated intraocular pressure or vasoconstriction because of antivascular endothelial growth factor activity.Nonarteritic anterior ischemic optic neuropathy is a rare complication of intravitreal injection and may be related to postinjection elevation in intraocular pressure. Monitoring of intraocular pressure postinjection with low-threshold for preinjection aqueous suppression or postinjection anterior chamber paracentesis for persistently elevated intraocular pressure is recommended in patients with a history of NAION.

PURPOSE To examine the three-dimensional foveal cone photoreceptor structure in a patient who had suffered laser pointer induced retinal injury. METHODS Patient underwent standard fundus photography and clinical spectral domain optical coherence tomography (SD-OCT) imaging. High-resolution imaging was performed using an Adaptive Optics-OCT-Scanning Laser Ophthalmoscope (AO-OCT-SLO). RESULTS AO imaging revealed loss of inner and outer segments of cone photoreceptors while the anterior retinal layers appeared healthy. Analysis of cone topology showed an increase in Voronoi domain area and a less regular hexagonal packing structure closer to the lesion site. CONCLUSION Exposure to laser pointer radiation, however brief, can result in damage to the retina. Here, repeated imaging nine months later showed a decrease in the size of the lesions (ranging from 3.7 to 23.9%) compared to the first time point. However, the longer-term prognosis is likely permanent scarring.

We report the case of a 27-year-old monocular woman with a history of sickle cell disease who received intra-arterial tissue plasminogen activator (tPA) after presenting with acute painless vision loss secondary to incomplete central retinal artery occlusion presenting as paracentral acute middle maculopathy in her left eye.Ultrawidefield fundus photography, ultrawidefield fluorescein angiography, en face optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were obtained and reviewed, followed by cerebral angiography and infusion of intra-arterial tissue plasminogen activator.A patient with a history of sickle cell disease presented with a new onset of a dense central scotoma, and the visual acuity diminished to 20 of 200 from baseline 20 of 20 in her left eye. Fluorescein angiogram was nondiagnostic. Optical coherence tomography revealed perifoveal hyper-reflective bands in the inner nuclear layer in a pattern characteristic of paracentral acute middle maculopathy. The patient received intra-arterial tissue plasminogen activator through her left ophthalmic artery shortly after presentation, resulting in a gradual restoration of the visual acuity to 20 of 20 in the three months after the procedure.This is the first report describing the use of intra-arterial tissue plasminogen activator to treat incomplete central retinal artery occlusion presenting as a paracentral acute middle maculopathy lesion in a patient with sickle cell disease.

Lower airway sampling is important in the assessment of lower respiratory tract infection in children with cancer or posthematopoietic stem cell transplant and can be done via bronchoalveolar lavage (BAL). Clinicians can struggle with balancing the benefits of BAL against the risks. This study aimed to define the diagnostic and clinical utility of BAL in this population.A single-center retrospective review of BAL performed in children with cancer or posthematopoietic stem cell transplant. Data extracted included demographics, BAL method and results and antimicrobial treatment. Variables significantly associated with diagnostic yield, diagnostic impact (confirmation or exclusion of infection), and clinical impact (any change in antimicrobial or nonantimicrobial therapy) were assessed in both univariate and multivariate analysis.Seventy-three BAL episodes were included. In 26 (35.6%) episodes, a pathogen was identified on BAL. Forty-nine (67%) BAL episodes had a diagnostic impact and 15 (21%) had a clinical impact. Late BAL (gt;72 hours) compared with early BAL (odds ratio 3.27; 95% CI: 1.03-10.86), and flexible bronchoscopy compared with nonbronchoscopic lavage (odds ratio 6.10; 95% CI: 1.90-24.0), were more likely to have a diagnostic impact on multivariate analysis. No associations were found for clinical impact.One-third of BAL episodes identified a pathogen, two-thirds had a diagnostic impact, and almost a quarter of episodes impacted antimicrobial prescribing. The method and timing of BAL may be important, with flexible bronchoscopy 6-fold more likely and late BAL 3-fold more likely to have a diagnostic impact.

Purpose To present a surgical technique and case presentation of internal chandelier-assisted macular buckling for myopic foveoschisis. Methods Review of patient clinical features, visual-acuity and optical coherence tomography (OCT) results following internal chandelier-assisted macular buckling for myopic foveoschisis. Results A 48-year-old highly myopic female (axial length 29.85mm) underwent internal chandelier-assisted macular buckling for myopic foveoschisis with macular detachment. The best-corrected visual acuity improved from 20/150 to 20/40. Post-operative OCT confirmed central buckle positioning and demonstrated resolved foveoschisis and macular detachment. There were no complications. Conclusions Internal chandelier-assisted macular buckling is a valuable tool to optimize buckle position and patient outcomes.

To report a case of nonleaking cystoid macular edema (CME) associated with pentosan polysulfate sodium (PPS)-induced pigmentary maculopathy.Multimodal imaging, including optical coherence tomography, fundus photography, autofluorescence, and fluorescein angiography, was used to substantiate our diagnosis, further characterize the cystoid macular edema showed by our patient and to monitor the response to treatment.A 59-year-old woman was referred for decreased visual acuity and bilateral macular edema. She had been treated for interstitial cystitis with PPS for 10 years. Multimodal imaging showed the characteristic features of PPS-induced pigmentary maculopathy. Moreover, fluorescein angiogram showed nonleaking cystoid macular edema in both eyes. She was treated successfully with intravitreal injections of bevacizumab.To our knowledge, this report is the first to demonstrate that PPS-associated cystoid macular edema can be nonleaking on fluorescein angiography and responds well to intravitreal anti-vascular endothelial growth factor injections.

To describe the case of a 12-year-old woman with vitreoretinal manifestations of Type 3 Gaucher disease.A retrospective case report including multimodal imaging and histologic examination of the vitreous.A 12-year-old woman with a history of Gaucher disease Type 3 was referred to the ophthalmology service for evaluation of vitreous deposits in both eyes. Funduscopic examination was notable for white vitreous opacities in both eyes. Ultra-widefield fluorescein angiography demonstrated areas of blockage associated with the deposits and focal areas of leakage. Optical coherence tomography angiography showed shadow artifact without intrinsic flow at these sites. Three years after presentation, she developed a right hemorrhagic posterior vitreous detachment, requiring pars plana vitrectomy with scleral buckle. A vitreous sample was sent to pathology, which demonstrated Gaucher cells.Gaucher disease is a rare metabolic condition caused by an autosomal recessive deficiency of glucocerebrosidase. To the best of our knowledge, this is the first report of hemorrhagic posterior vitreous detachment in Type 3 Gaucher disease, including ultra-widefield imaging, optical coherence tomography angiography, and histopathology.

Purpose To describe a novel clinical and imaging finding in patients with tubercular posterior uveitis. Methods A retrospective review of 3 cases presented at a tertiary referral eye centre in North India between June 2016 to March 2019 was performed. All the patients had received an initial diagnosis of non-infective etiologies (sympathetic ophthalmia, necrotizing scleritis and lymphoma). Fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF), and enhanced-depth imaging optical coherence tomography (EDI-OCT) were reviewed. Results Three patients (all Asian Indian females: aged 18, 49 and 52 years) diagnosed with panuveitis were investigated for various etiologies based on the initial clinical suspicion. During the course of therapy, all the patients developed peripheral yellow sub-retinal pigment epithelim (RPE) deposits (YSRPE) which appeared hypo-autofluorescent on FAF, and initially hypofluorescent with late hyperfluorescence on FA. The patients were subjected to detailed systemic evaluation and laboratory tests. All the patients showed acid fast bacilli on invasive tissue biopsies. After initiation of anti-tubercular therapy, the lesions resolved in all eyes. Conclusions YSRPE deposits represent a novel and important diagnostic sign of tubercular posterior uveitis.

To describe a potential case of pentosan polysulfate maculopathy that seemed to manifest nearly 3 years after drug cessation.Complete ophthalmic examination, including multimodal fundus imaging, electroretinography, automated perimetry, and molecular testing, was performed.A 44-year-old woman with a 435 g cumulative exposure to pentosan polysulfate sodium presented 38 months after drug cessation with 6 months of worsening metamorphopsia and prolonged dark adaptation. Fundus examination and multimodal fundus imaging demonstrated characteristic features of pentosan polysulfate maculopathy, and molecular testing was unremarkable. By contrast, color fundus photographs of the same patient acquired at an outside facility 25 months before did not display features consistent with pentosan polysulfate sodium maculopathy.This case suggests that new-onset clinically detectable pentosan polysulfate maculopathy may develop years after drug cessation. If corroborated, this finding has important ramifications for pentosan polysulfate sodium dosing and surveillance guidelines.

To report a sporadic case of a familial adenomatous polyposis (FAP) discovered in a patient with bilateral retinal pigment epithelial lesions.Case report.A 30-year-old Asian woman presented for evaluation of bilateral pigmented lesions at the level of the retinal pigment epithelium. She had no personal or family history of colonic polyps or colon cancer. Colonoscopy revealed innumerable adenomatous polyps and genetic testing revealed a mutation in the adenomatous polyposis coli gene consistent with FAP. She subsequently underwent prophylactic total colectomy.The pigmented retinal pigment epithelium lesions of FAP have a characteristic appearance and it is vital for the retinal specialist to be familiar with them. De novo mutations in the APC gene are responsible for 20% to 30% of FAP cases. In the presence of the characteristic retinal pigment epithelium lesions, it is important to send the patient for work up of FAP even in the absence of family history of FAP.

OBJECTIVE To evaluate S1 transsacral (TS) corridors on reformatted and non-reformatted computed tomography (CT) images to determine which most reliably identifies narrow corridors. DESIGN Retrospective cohort. SETTING Level 1 trauma center. PATIENTS 245 patients with operative pelvic ring injuries. INTERVENTION CT scan review. MAIN OUTCOME MEASUREMENTS Preoperative CT scans were evaluated to determine the width of the S1 TS corridor on standard axial non-reformatted (ANR), axial reformatted (AR), and coronal reformatted (CR) images. Sensitivity and specificity of each format to detect a narrow corridor (

Purpose To evaluate the utility of extending the limbus-to-cannula distance to 6.0 mm during pars plana vitrectomy (PPV) for highly myopic eyes. Methods Four eyes with axial lengths exceeding 31.0 mm, that underwent 25-gauge PPV were retrospectively evaluated. Assuming that cannulas were inserted 3.5 and 6.0 mm from the corneal limbus, the distance from the cannula to the fovea (CF distance) was preoperatively evaluated using anterior segmental optical coherence tomography. Surgical complications were also investigated. Results The CF distance was shortened by 1.22±0.05 mm and 1.22±0.09 mm on the temporal and nasal sides, respectively, by inserting the cannula at 3.5 to 6.0 mm from the corneal limbus. As per the preoperatively measured CF distance, one of the cannulas was inserted 6.0 mm from the corneal limbus in 3 eyes. Their cannulas were confirmed to be inserted at the pars plana, and no surgical complications associated with this technique were observed. Conclusion Extending the limbus-to-cannula distance to 6.0 mm during PPV could be one of the options to reach the posterior pole in highly myopic eyes. A preoperatively measured CF distance can be a clinical criterion in determining the cannula position.

OBJECTIVES To determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) carrier augmentation in managing critical-sized bone defect (CSBD) with induced membrane technique (IMT). DESIGN Retrospective comparative study. SETTING Academic level I trauma center.Patients/Participants: The study included 14 patients who underwent rhBMP-2 with HA carrier (rhBMP-2/HA) augmentation in IMT for managing CSBD (BMP group). Moreover, 14 patients who underwent IMT without rhBMP-2 augmentation were matched by propensity score analysis (non-BMP group). INTERVENTION IMT with or without rhBMP-2/HA augmentation. MAIN OUTCOME MEASUREMENT Changes in quality and quantity measurements of grafted bone to regenerated bone using serial computed tomography. RESULTS In the BMP and non-BMP groups, the changes in densities from grafted bone to regenerated bone were +379.63 Hounsfield unit (HU) and +248.55 HU (P = 0.034), changes in dense bone percentage were +37.52% and +23.31% (P = 0.027), corticalization rates under the plate were 79.70% and 39.30% (P = 0.007), changes in volume were -20.77% and -23.35% (P = 0.812), union rates were 85.71% and 78.57% (P = 0.622), numbers of patients requiring additional procedures were 4 and 3 (P = 0.663), and time to union were 316.3 and 585.45 days (P = 0.040), respectively. CONCLUSIONS RhBMP-2/HA augmentation increases the density of regenerated bone, enhances corticalization under the plate, and shortens the time to union while managing CSBD with IMT.

PURPOSE Evaluation of intra-operative aphakic axial eye length (AL) measurements using swept source optical coherence tomography. SETTING Hanusch Hospital, Vienna, Austria. DESIGN Prospective single-center study. METHODS Patients scheduled for cataract surgery were measured using swept-source optical coherence tomography (ss-OCT, IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany) to assess the axial eye length. Intra-operatively, swept source optical coherence tomography (ss-OCT) measurements were performed with a prototype device (IOLMaster 700 connected to an OPMI Lumera 700 microscope, CZM) at the beginning of cataract surgery furthermore of the aphakic eye and 2 months after surgery. RESULTS Of the 59 eyes of 59 patients, the phakic median AL pre-operatively (pre-OP) and intra operatively (intra-OP) were 23.61 mm ± 0.96 (SD) and 23.51 mm ± 0.96 (SD). Absolute median difference was 0.028 ± 0.02 (SD) (p=0.049). Median phakic AL intra-OP versus 2 months post operatively (post-OP) was 23.51 mm ± 0.97 (SD) vs 23.49 mm ± 0.95 (SD). Absolute median difference was 0.049 ± 0.04 (SD) (p=0.000).Median AL intra-OP aphakic versus vs 2 months post-Op pseudophakic were 23.42 mm ± 0.97 (SD) versus 23.42 mm ± 0.97 (SD). Absolute median difference was 0.038 ± 0.04 (SD) (p=0.379). CONCLUSIONS Intra-OP swept source OCT technology of the phakic and aphakic eye shows excellent comparability to pre- and post-operative measurements. This technique allows axial eye length measurements with high precision in cases where pre-op biometric measurements are not possible.

Purpose To examine the long-term efficacy and safety of myopic implantable collamer lens (ICL) implantation in active duty US military personnel. Setting Hospital practice. Design Retrospective longitudinal observational study. Methods 1485 patients (median age: 25, Inter-quartile range: 22, 29) underwent ICL surgery. Patients received a preoperative exam including uncorrected visual acuity (UDVA), intraocular pressure (IOP), manifest refraction measuring best corrected visual acuity (CDVA), corneal topography and tomography, qualitative grading of perceived ectatic risk, ophthalmic biometry, and baseline endothelial cell counts (ECC). Outcome measures included UDVA, IOP, vault size, manifest refraction, CDVA, and ECC. Long-term follow-up data ware drawn from the US Military medical record system. Results A total of 3105 eyes were evaluated. Patients received ICLs either due to abnormal topography 68% (2111 eyes) or due to high myopia 32% (994 eyes). Nearly 80% (94 eyes) of eyes maintained UDVA of 20/25 or better up to 8 years postoperatively. The rate of achieving the desired refractive correction was 97% (503 eyes) at 1 year and 90% (81 eyes) at 8 years. Stability of these outcomes were also shown by minimal change in manifest refraction. Documented mean ECC loss was 22% at post-operative year 5. The overall rate of adverse events was 1.2% (36 eyes) including visually significant cataract formation, glaucoma, retinal detachment, and traumatic incision opening. A removal/replacement rate of 4.5% (135 eyes) was observed. Conclusions ICL implantation was found to be effective and safe. Vault sizes decreased over time suggesting an increased risk of cataract formation after seven years. Further study is necessary to assess long-term clinical significance of ECC decline.

Trazodone (TZD) is a tetracyclic serotonin antagonist and reuptake inhibitor that is used as a second-generation phenylpiperazine antidepressant. However, the plasma concentrations of TZD have shown individual variations in clinical practice. Quantification of TZD plasma concentrations may be an effective and valuable method to balance the clinical efficacy and adverse reactions. This study aimed to establish a novel liquid chromatography coupled with mass spectrometry (LC-MS) assay for measuring TZD concentrations in human plasma for therapeutic drug monitoring (TDM).After protein precipitation with acetonitrile, LC-MS quantification of TZD was performed in the multiple reaction monitoring mode with chromatographic separation using a mobile phase of MeOH and 0.1% formic acid in water. This method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect, and stability according to United states food and drug administration guidelines.This method showed good selectivity because no interfering peaks were observed in the plasma samples during the 2-minute run time. The range of the calibration curve was 1-3000 ng/mL. The detection and quantification limits were 0.3 and 1 ng/mL, respectively. The intraday and interday accuracies were 96.5%-103.4%, with precision relative SD% values of5%, except for the limit of quality. The mean TZD recovery from human plasma was 95.4%-104.5%. Finally, this method was successfully applied to TDM in 20 patients. The TZD plasma concentrations of the patients ranged between 21.5 and 2267.3 ng/mL.A novel analytical method was established to measure TZD by LC-MS coupled with an automatic 2-dimensional liquid chromatograph mass spectrometer coupler 9500 (LC-MS/MS-Mate 9500), which is superior to the ordinary LC-MS system in separation, transport, anti-interference, sensitivity, and quantitative analysis stability.

PurposeTo compare axial length (AL) measurements in long eyes by two swept-source optical coherence tomography (SS-OCT) biometers, one based on the group refractive index (IOLMaster 700, Zeiss) and the other based on sum of segments (Argos, Movu), and compare these measurements to previously published methods to optimize AL.SettingI.R.C.C.S. - G.B. Bietti Foundation, Rome, ItalyDesignProspective case seriesMethodsAL was measured with both optical biometers in myopic patients (AL > 24.00 mm) and compared to the values obtained with Wang-Koch adjustment, polynomial equations for the Holladay 1 and 2 formulas and Cooke modified AL (CMAL).ResultsIn 102 eyes of 55 subjects, a statistically significant difference (p

Student-run free clinics (SRFCs) act as primary care providers that bring health care to populations in need and are an important source of undergraduate medical education (UME), guiding trainees through the art of history taking and physical examination. However, they are also social justice and advocacy initiatives-addressing disparity in access to care and educating medical trainees with firsthand exposure to socioeconomic determinants of health and language and medical illiteracy barriers. The authors present an examination of the impact of SRFCs, supported by academic literature, in their 3 roles as medical care providers, as a component of medical education, and as advocacy organizations. Based on the evidence of that literature and decades of direct SRFC leadership experience, the authors make the case that SRFCs deserve a prominent role in the discussion of how UME institutions contribute to correcting health care disparities and to serving social justice reform.

PURPOSE To assess agreement of measurements by two swept source optical coherence tomography (SS-OCT) biometers and to evaluate the prediction error (PE) in intraocular lens (IOL) power calculation with seven formulas. SETTING Tertiary public eye hospital. DESIGN Consecutive observational. METHODS Axial length (AL), keratometry (K), anterior chamber depth (ACD), lens thickness (LT), and corneal diameter (CD) were measured with IOL Master 700 (Biometer A) and Anterion (Biometer B). Agreement was quantified by the limits of agreement (LoAs) and concordance correlation coefficient (CCC). The PE, the median absolute error (MedAE), and the mean absolute error (MAE) of the Barrett Universal II (BUII), EVO 2.0, Haigis, Hoffer Q, Holladay 1, Kane, and SRK/T formulas was inverstigated after constant optimization. RESULTS In 78 eyes from 78 patients, excellent agreement was obtained for AL (CCC >0.99), very good agreement for K, ACD, and LT (CCC >0.95), and strong agreement for CD (CCC>0.72). An additive offset of 0.07 mm was measured for ACD and LT whose mean values were higher with Biometer B (p

Purpose To create an equation for predicting the trabecular iris angle (TIA) and to verify its accuracy after implantable collamer lens (ICL) implantation. Setting Nagoya Eye Clinic, Nagoya, Japan. Design Retrospective evaluation of a screening approach. Methods The subjects included 174 eyes (174 patients) that underwent ICL implantation. Patients were randomly assigned to the prediction equation group (116 eyes) or verification group (58 eyes). Anterior segment optical coherence tomography (AS-OCT; CASIA2 TOMEY) was performed before and 3 months after ICL surgery. For the prediction group, a prediction equation was created with the preoperative AS-OCT parameters and ICL size as independent variables and the postoperative anterior chamber depth (ACD) as dependent variables. Then, by applying the predicted post-ACD and preoperative AS-OCT parameters as independent variables and TIA after ICL surgery as the dependent variable, a prediction equation was created to predict the postoperative TIA (post-TIA) after ICL surgery. Each prediction equation was created using stepwise multiple regression analysis, and its accuracy was verified by a Bland-Altman plot in the verification group. Results The explanatory variables (standardized partial regression coefficient) selected in the post-TIA prediction equation were post-ACD (0.629), TIA750 (0.563), iris curvature (0.353), pupil diameter (-0.281), iris area (-0.249), and trabecular iris space area 250 (-0.171) (R2 = 0.646). There were no clinically significant systematic errors between measured and predictive post-TIA values in the verification group. The average absolute prediction error was 3.43° ± 2.22°. Conclusions Post-TIA can be accurately predicted from the predicted post-ACD and other preoperative AS-OCT parameters.

The concept of significant polyps and early colorectal cancer encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. The assessment and management of these lesions is contentious and increasingly important due to the significant risk of over- or undertreatment.Following the recommendations of the Significant Polyps and Early Colorectal Cancer National Program, we implemented a dedicated multidisciplinary team meeting and analyzed the influence on patient outcomes.This was a retrospective study using a prospectively collected database of patients discussed at the dedicated multidisciplinary team meeting.This study was conducted in a single tertiary-care center.Consecutive patients with significant polyps and early colorectal cancer were identified either through the Bowel Cancer Screening Program or colonoscopy for symptomatic patients.Proportions of patients who had organ preservation, and secondary treatment and recurrence rate served as outcome measures.Overall, 135 patients discussed at the dedicated multidisciplinary team meeting were included, with a median age of 71 years. Median size of the lesions was 25 mm, and 39% were in the rectum. Patients were discussed either after the lesion was removed during the initial colonoscopy (n = 38), of whom 16 (42%) had unexpected cancer, or had no initial treatment with subsequent case review (n = 97). Of these 97 patients, 46 underwent endoscopic excision (26% cancer), 20 trans-anal excision (10% cancer), 23 primary surgical resection (35% cancer), and 8 had no treatment. In 104 (82%) patients, organ preservation was achieved. Secondary surgery was required in 7 of 104 (6.7%) patients after local excision due to radical treatment of high-risk T1 lesions, local recurrence, or patients' decisions. The cumulative hazard estimates for recurrence after a median follow-up of 18.5 months was less than 10% for both benign and malignant lesions.This study was limited by its relatively small sample size and single-center setting.A dedicated multidisciplinary team meeting improved the management of significant polyps and early colorectal cancer, safely refining organ preservation for patients, with low recurrence rates. See Video Abstract at http://links.lww.com/DCR/B826.ANTECEDENTES:El concepto de pólipos complejos y cáncer colorrectal temprano abarca engloba pólipos avanzados que no es posible la reseccion endoscopica rutinaria, o aquellos en los que no se puede excluir malignidad. La evaluación y el manejo de estas lesiones es controversial y cada vez más importante debido al riesgo significativo de ser tratadas o no.OBJETIVO:Siguiendo las recomendaciones del Programa Nacional de Pólipos Complejos y Cáncer Colorrectal Temprano, implementamos reuniónes del equipo multidisciplinario especializado y analizamos el impacto en los resultados de los pacientes.DISEÑO:Estudio retrospectivo sobre una base de datos recopilada prospectivamente de los pacientes discutidos en la reunión del equipo multidisciplinario especializado.AJUSTE:Este estudio se realizó en un centro de atención terciaria.PACIENTES:Pacientes consecutivos con pólipos complejos y cáncer colorrectal temprano identificado a través del Programa de detección de cáncer intestinal o colonoscopia para pacientes sintomáticos.PRINCIPALES MEDIDAS DE RESULTADO:Proporción de pacientes que tuvieron preservación de órganos, tratamiento secundario y tasa de recurrencia.RESULTADOS:En total, se incluyeron 135 pacientes discutidos en la reunión del equipo multidisciplinario especializado dedicada, con una media de edad de 71 años. El tamaño medio de las lesiones fue de 25 mm y el 39% estaban en el recto. Se discutio de los pacientes después de que se resecara la lesión durante la colonoscopia inicial [n = 38, de los cuales 16 (42%) tenían un cáncer imprevisto] o no recibieron tratamiento de inicio, con revisión posterior del caso (n = 97). De estos, 46/97 fueron sometidos a resección endoscópica (26% cáncer), 20/97 resección transanal (10% cáncer), 23/97 resección quirúrgica primaria (35% cáncer) y 8/97 no recibieron tratamiento. En 104 (82%) pacientes, se logró la preservación de órgano. Cirugía secundaria fue requeria en 7/104 (6,7%) pacientes después de la resección local debido a tratamiento radical de lesiones T1 de alto riesgo, recidiva local o decisión del paciente. Las estimaciones de riesgo acumulativo de recurrencia después de una media de seguimiento de 18,5 meses fue inferior al 10% tanto para las lesiones benignas como para las malignas.LIMITACIONES:Tamaño de muestra relativamente pequeño y entorno de un solo centro.CONCLUSIONES:La Reunion del equipo multidisciplinario especializado mejoró el manejo de los pólipos complejos y cáncer colorrectal temprano, refinando de manera segura la preservación de órganos para los pacientes, con bajas tasas de recurrencia. Consulte Video Resumen en http://links.lww.com/DCR/B826. (Traducción- Dr. Francisco M. Abarca-Rendon).

Management of enterocutaneous fistulas in Crohn's disease is challenging. Most patients still need intestinal resection in the biologic era.The aim of this study was to evaluate the efficacy of endoscopic treatment for enterocutaneous fistulas.This is a retrospective study of medical records.This study was conducted in a single institution.All consecutive patients with Crohn's disease with an enterocutaneous fistula who underwent endoscopic fistula closure with the use of an over-the-scope clip or a hemostatic clip were included.The main outcome measured was the clinical success 3 months after the procedure, which was defined as the complete closure of all fistulas at physical examination and complete cessation of the drainage from the external opening, without surgery.Eight patients (men, 25%; median age 45 years [interquartile range, 33-51]) were followed. Fistulas were localized at the ileocolonic or colocolonic anastomosis in 7 patients and at the stomach in 1 patient. Seven patients were treated with an over-the-scope clip, and one was treated with a hemostatic clip. Technical success was achieved in all cases. Clinical success at 3 months was achieved in 75% of cases (6/8 patients). After a median 16-month (interquartile range, 13-23) follow-up, 3 of 8 (37.5%) patients had enterocutaneous fistula closure and 2 of 8 (25%) needed intestinal resection. No complications were observed.The retrospective nature, the small sample size of the study, and the heterogeneity of the population limit the interpretation of the results.Endoscopic treatment of enterocutaneous fistulas is feasible with a short-term effectiveness. Additional studies are needed to confirm these results. See Video Abstract at http://links.lww.com/DCR/B614.ANTECEDENTES:Es desafiante el manejo de las fístulas enterocutáneas en enfermedad de Crohn. En la era biológica, la mayoría de los pacientes todavía requieren de resección intestinal.OBJETIVO:Evaluar la eficacia por tratamiento endoscópico de fístulas enterocutáneas.ENTORNO CLINICO:Estudio retrospectivo de registros médicos.AJUSTE:Realizado en una sola institución.PACIENTES:Se incluyeron todos los pacientes consecutivos con fístula enterocutánea en enfermedad de Crohn, sometidos a cierre endoscópico de la fístula con clip sobre el endoscopio o clip hemostático.PRINCIPALES MEDIDAS DE VALORACION:El éxito clínico a los 3 meses después del procedimiento. Definido al examen físico, como el cierre completo de todas las fístulas y cese completo del drenaje por la abertura externa, sin cirugía.RESULTADOS:Se estudiaron a ocho pacientes (hombres, 25%, mediana de edad de 45 años (rango intercuartílico, 33-51)). En 7 pacientes, las fístulas se localizaron en la anastomosis ileocolónica o colocolónica y un paciente, en el estómago. Siete pacientes fueron tratados con clip sobre el endoscopio y uno con clip hemostático. Se logró éxito técnico en todos los casos. Se logró éxito clínico a los 3 meses en 75% de los casos (6/8 pacientes). Después de una mediana de 16 meses (rango intercuartílico, 13-23), de seguimiento 3/8 (37,5%) pacientes presentaron cierre de fístulas enterocutáneas y 2/8 (25%) requirieron resección intestinal. No se observaron complicaciones.LIMITACIONES:Estudio retrospectivo, pequeño tamaño de la muestra y heterogeneidad de la población, limitaron la interpretación de los resultados.CONCLUSIONES:Es posible el tratamiento endoscópico de fístulas enterocutáneas con efectividad a corto plazo. Se requieren nuevos estudios para confirmar estos resultados. Consulte Video Resumen en http://links.lww.com/DCR/B614. (Traducción-Dr. Fidel Ruiz Healy).

Cyclosporine is an essential component of many immunosuppressive regimens. However, its pharmacokinetic and pharmacodynamic (PKPD) modeling has not been widely investigated. This study aims to develop a time-dissociated PKPD model of cyclosporine in renal transplant patients.Medical records of renal transplant patients at Penang General Hospital were retrospectively analyzed. A time-dissociated PKPD model with covariate effects was developed using NONMEM to evaluate renal graft function response, quantified as estimated glomerular filtration rate (eGFR), toward the cyclosporine cumulative exposure (area under the concentration-time curve). The final model was integrated into a tool to predict the potential outcome. Individual eGFR predictions were evaluated based on the clinical response recorded as acute rejection/nephrotoxicity events.A total of 1256 eGFR readings with 2473 drug concentrations were obtained from 107 renal transplant patients receiving cyclosporine. An Emax drug effect with a linear drug toxicity model best described the data. The baseline renal graft level (E0), maximum effect (Emax), area under the concentration-time curve achieving 50% of the maximum effect, and nephrotoxicity slope were estimated as 12.9 mL·min-1·1.73 m-2, 50.7 mL·min-1·1.73 m-2, 1740 ng·h·mL-1, and 0.00033, respectively. The hemoglobin level was identified as a significant covariate affecting the E0. The model discerned acute rejection from nephrotoxicity in 19/24 cases.A time-dissociated PKPD model successfully described a large number of observations and was used to develop an online tool to predict renal graft response. This may help discern early rejection from nephrotoxicity, especially for patients unwilling to undergo a biopsy or those waiting for biopsy results.

Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) is widely used to guide therapy, avoid toxicity, and assess patient compliance. Commercial immunologic quantification methods are common practice; however, as they are only applicable to one specific drug and prone to cross-reacting metabolites, their practical applicability is limited. In this article, the authors proposed a high-performance liquid chromatography method using ultraviolet detection (HPLC-UV) for simultaneous quantification of 11 ASMs and active metabolites (carbamazepine, felbamate, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, zonisamide, carbamazepine-10,11-epoxide, and licarbazepine) in serum.Chromatographic separation was performed on a Phenomenex Luna PFP(2) (3-µm particle size; 150 × 4.6 mm i.d.) analytical column. The mobile phase comprised phosphate buffer (20 mM; pH 3), acetonitrile (ACN), and methanol using gradient elution. Analyses were conducted at 35°C and a 1.3-mL/min flow rate. The detection wavelength for all analytes was 210 nm. The samples were prepared by protein precipitation using ACN.The HPLC-UV method was validated according to the FDA guidelines and applied to measure patient samples in TDM. Calibration curves showed excellent linearity (r20.99) and covered the entire reference range for each analyte. Intraday and interday imprecisions and inaccuracies were10% for all samples. Extensive stability testing showed no significant degradation (15%), and interference measurements additionally ensured clinical applicability. Furthermore, the sensitivity was comparable with that of previously published HPLC methods using mass spectrometry.The authors developed an HPLC-UV method for the simultaneous quantification of 11 ASMs in the human serum and demonstrated its practical applicability in TDM. The method requires only standard laboratory equipment and simple sample preparation, making TDM available in less specialized laboratories.

BACKGROUND Guanfacine, a selective α2A-adrenoreceptor agonist, is a second-line medication for treating children and adolescents with attention-deficit/hyperkinetic disorder (ADHD). The dosage administered as milligram per body weight to balance the potential benefits and risks of treatment. Therapeutic drug monitoring (TDM) is useful for identifying a patient's therapeutic window to optimize individual drug dosing and reduce the risk of adverse drug reactions. However, in children and adolescents, intravenous sample collection is especially stressful and thus remains a primary challenge, restricting the use of TDM. Therefore, evaluating alternative specimens to facilitate TDM is a worthwhile task. The aim of this study was to assess the feasibility of using oral fluid for TDM of guanfacine in children and adolescents. METHODS Herein, nine patients (median age 8.1 years; 6 boys, 3 girls) undergoing treatment with guanfacine were included. Simultaneously collected oral fluid and serum samples were deproteinized using methanol containing a stable isotope-labeled internal standard prior to the determination of guanfacine by liquid chromatography-tandem mass spectrometry. Pearson's correlation and paired t-test were used for statistical analysis. RESULTS The mean serum guanfacine concentration was three times higher than that detected in oral fluid (7.47 ng/mL vs. 2.36 ng/mL; t (8) = 5.94; P < 0.001). A strong positive linear correlation (r = 0.758, P = 0.018) was identified between oral fluid and serum concentrations. A strong but non-significant negative correlation (r = -0.574, P = 0.106) was detected between the oral fluid pH and oral fluid-to-serum concentration ratio. CONCLUSIONS The strong correlation between oral fluid and serum concentration and the probable small effect of oral fluid pH on oral fluid-to-serum concentration ratio supports guanfacine as a suitable candidate for TDM in oral fluid.

Background Separation gels are often used in collection tubes, but adsorption of drugs onto the gel may cause falsely low concentrations in therapeutic drug monitoring. In this study, the stability of apixaban, edoxaban, rivaroxaban, flecainide, amiodarone, and desethylamiodarone was assessed in tubes, with and without gel separators. Methods Drug-free blood was spiked and stored for up to 7 d in non-gel tubes and gel tubes from two manufacturers (Vacuette and Vacutainer). The samples were analyzed in triplicates using ultra high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results At ambient temperature conditions, the serum concentrations of apixaban, edoxaban, and rivaroxaban in a tube with acrylic-based gel had already decreased at baseline, while it took 6 h to observe the same result in a tube with olefin-based gel. At 4 °C, the reduction in serum concentration was considerably slower. For flecainide, the gel tube concentrations were stable at ambient temperature for 3 d, but decreased after 7 d in acrylic-based gel tubes. Amiodarone and desethylamiodarone stored in gel tubes at 4 °C showed decrease in concentrations after 24 h and 6 h, respectively. Conclusion Acrylic-based gel tubes should not be used for any of the tested drugs. Although olefin-based gel tubes may be used for anticoagulants and flecainide, it is advisable to prefer non-gel tubes as a general precaution.

To investigate, by means of spectral domain optical coherence tomography, retinal reflectivity changes as an early biomarker anticipating radiation-induced macular edema (ME) in patients treated by iodine-125 (I-125) brachytherapy.Thirty patients planned for I-125 brachytherapy because of uveal melanoma were prospectively included and followed every 4 months for five years. Reflectivity alterations, namely hyperreflective retinal foci, were characterized and counted by two independent masked examiners by means of spectral domain optical coherence tomography imaging. Hyperreflective retinal foci were defined as discrete intraretinal reflectivity changes ≤30 µm, with reflectivity similar to nerve fiber layer and without back shadowing.Macular edema occurred in 17 patients (24.2 ±15.1 months) (group 1) after irradiation. Thirteen patients showed no signs of ME at the 5-year follow-up (group 2). The number of hyperreflective retinal foci was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (P0.0001). In group 1, hyperreflective retinal foci at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P = 0.0002, r2=0.6129). The intergrader agreement was almost perfect (intraclass correlation coefficient = 0.80).Hyperreflective retinal foci may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy.

As men age, the prostate continues to grow on average 2.5% per year. While the variable growth rate of the total prostate gland is recognized, the growth rate of different prostate zones remains largely unclear. We evaluated the growth patterns of the prostate zones and identified clinical parameters contributing to the zonal growth rates.Prostate magnetic resonance imaging (MRI) data and clinical information were obtained retrospectively on 156 patients who had at least 3 prostate MRIs between 2003 and 2018. Different prostate zonal volumes were measured and analyzed. The outcome was analyzed using linear regression.We observed that prostate growth rates vary depending on body mass index (BMI), transition zone index (TZI), the prostate zone and 5-alpha reductase inhibitor (5ARI) use. The peripheral zone volume growth rates increased with age and peaked at 60-70 years of age (p=0.047), while the transition zone volume demonstrates continuous growth without a peak through all ages. BMI and TZI are associated with the growth rate of the peripheral zone (p=0.026, p0.001, respectively) but not the transition zone growth rate. 5ARI use is significantly associated with the reduction in the transition zone growth rate (p=0.033), not the peripheral zone. In addition, patients with TZI greater than 60% had the most significant reduction in the transition zone growth rate while taking 5ARI (p0.001).Transition and peripheral zones of the prostate grow at variable rates. BMI and TZI affect peripheral zone growth rate, while 5ARI use reduces the transition zone growth rate.

BACKGROUND Therapeutic drug monitoring (TDM) is necessary for immunosuppressive therapy with tacrolimus and everolimus after kidney transplantation. Several studies have suggested that the concentrations of immunosuppressive agents in allografts may better reflect clinical outcomes than whole blood concentrations. This study aimed to develop a method for the simultaneous quantification of tacrolimus and everolimus concentrations in clinical biopsy samples and investigate their correlation with histopathological findings in kidney transplant recipients. METHODS Fourteen biopsy samples were obtained from kidney transplant recipients at 3 months after transplantation. Kidney allograft concentrations (Ctissue) of tacrolimus and everolimus were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the corresponding whole blood trough concentrations (C0) were obtained from clinical records. RESULTS The developed method was validated over a concentration range of 0.02[FIGURE DASH]2.0 ng/mL for tacrolimus and 0.04[FIGURE DASH]4.0 ng/mL for everolimus in kidney tissue homogenate. The Ctissue of tacrolimus and everolimus in kidney biopsies ranged from 21.0 to 86.7 pg/mg tissue and 33.5 to 105.0 pg/mg tissue, respectively. Dose-adjusted Ctissue of tacrolimus and everolimus was significantly correlated with the dose-adjusted C0 (P < 0.0001 and P = 0.0479, respectively). No significant association was observed between the Ctissue of tacrolimus and everolimus and the histopathologic outcomes at 3 months after transplantation. CONCLUSIONS This method could support further investigation of the clinical relevance of tacrolimus and everolimus allograft concentrations after kidney transplantation.

BACKGROUND: The recommended infliximab (IFX) dose in (pediatric) rheumatology practice is 3-6 mg/kg every 4-8 weeks. Higher dosage regimens (>10 mg/kg) of IFX are effective and safe. To optimize IFX treatment in patients with juvenile idiopathic arthritis (JIA), therapeutic drug monitoring might be beneficial. To support routine therapeutic drug monitoring of IFX and regimen optimization for patients with JIA, in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. As soon as the optimal therapeutic drug ranges are known, PK model-based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for patients with JIA. METHODS: Data including IFX trough concentrations and anti-IFX antibodies of 27 pediatric patients with JIA on IFX maintenance treatment were retrieved from electronic charts. Three population PK models from the literature were validated for the authors' data set using the nonlinear mixed-effects modeling program NONMEM. A novel population PK model was developed based on the study data. RESULTS: A total of 65 blood samples obtained after a median of 32 days after the last IFX infusion (interquartile range 28-42) were analyzed. The 3 published models underpredicted the observed trough concentrations. A newly developed one-compartment model best described the data corresponding to IFX serum concentration over time in patients with JIA. CONCLUSIONS: This study shows a novel PK model for IFX in patients with JIA. The data show that different PK models are needed for different age categories (children or adults) and different diseases.