Optical coherence tomography findings in paraneoplastic pseudovitelliform lesions in melanoma-associated retinopathy

Michael Javaheri1, Rahul N Khurana1, Rizwan A Bhatti1, Jennifer I Lim21Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA; 2Eye and Ear Infirmary, Department of Ophthalmology, University of Illinois, Chicago, IL, USAPurpose: To report an unusual case of paraneoplastic pseudovitelliform lesions associated with melanoma-associated retinopathy (MAR).Design: Observational case report.Methods: Retrospective review of the ophthalmic examination, fundus photography, fluorescein angiography, electroretinogram (ERG), and optical coherence tomography (OCT) of a patient with MAR.Results: A 65-year-old Caucasian man with a two-year history of metastatic melanoma was referred for evaluation of a six-month history of nyctalopia. Funduscopic examination in both eyes revealed multiple, creamy, yellow, pseudovitelliform lesions in the posterior pole, varying in size from 100–500 µm, at the level of the outer retinal/retinal pigment epithelium (RPE) junction, coalescing along the inferior portion, with overlying macular neurosensory detachments. OCT showed bilateral macular neurosensory detachments with multiple small areas of high refl ectivity at the level of the outer retinal/RPE junction. ERG demonstrated a selective loss of the b-wave and a normal a-wave under dark adapted, scotopic conditions.Conclusion: Clinicians should be aware of this atypical presentation of MAR that may include pseudovitelliform retinal findings.Keywords: cancer-associated retinopathy, melanoma-associated retinopathy, optical coherence tomography, paraneoplastic syndrome, paraneoplastic pseudovitelliform retinopath

MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene

Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB–NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB–NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1–ACTN1 and MYBL1–NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB–NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland

Conversion back to bevacizumab or ranibizumab for recurrent neovascular activity with aflibercept in age-related macular degeneration: a case series.

BackgroundNeovascular age-related macular degeneration often requires chronic therapy with anti-VEGF agents, and patients with recurrent disease are challenging to manage.MethodsThis retrospective case series evaluates patients who were switched from bevacizumab or ranibizumab to aflibercept and then back again because of recurrent fluid on optical coherence tomography (OCT) by reporting changes in OCT measurements over the course of medication changes.ResultsTwenty-one eyes in nineteen patients received an average of 20.7 bevacizumab and/or ranibizumab injections and then an average of 7.2 aflibercept injections before being switched back to bevacizumab or ranibizumab because of recurrent fluid on OCT. Median central macular thickness improved on transition from bevacizumab or ranibizumab (317 μm) to aflibercept (285 μm; p = 0.034), then worsened over the course of aflibercept treatment (296 μm; p = 0.080), but improved again with transition from aflibercept back to bevacizumab or ranibizumab (283 μm; p = 0.016). The total volume of subretinal fluid, intraretinal fluid, and pigment epithelial detachments also decreased on transition from bevacizumab or ranibizumab (2.56 mm3) to aflibercept (2.44 mm3; p = 0.080), then worsened over the course of aflibercept treatment (3.18 mm3; p = 0.019), and improved again on transition back to bevacizumab or ranibizumab (2.11 mm3; p = 0.016).ConclusionsWhile aflibercept appears initially effective, some patients develop recurrent fluid with aflibercept that improves with transition back to bevacizumab or ranibizumab. Rotating anti-VEGF agents may be beneficial with recurrent neovascular activity

Conversion back to bevacizumab or ranibizumab for recurrent neovascular activity with aflibercept in age-related macular degeneration: a case series.

BackgroundNeovascular age-related macular degeneration often requires chronic therapy with anti-VEGF agents, and patients with recurrent disease are challenging to manage.MethodsThis retrospective case series evaluates patients who were switched from bevacizumab or ranibizumab to aflibercept and then back again because of recurrent fluid on optical coherence tomography (OCT) by reporting changes in OCT measurements over the course of medication changes.ResultsTwenty-one eyes in nineteen patients received an average of 20.7 bevacizumab and/or ranibizumab injections and then an average of 7.2 aflibercept injections before being switched back to bevacizumab or ranibizumab because of recurrent fluid on OCT. Median central macular thickness improved on transition from bevacizumab or ranibizumab (317 μm) to aflibercept (285 μm; p = 0.034), then worsened over the course of aflibercept treatment (296 μm; p = 0.080), but improved again with transition from aflibercept back to bevacizumab or ranibizumab (283 μm; p = 0.016). The total volume of subretinal fluid, intraretinal fluid, and pigment epithelial detachments also decreased on transition from bevacizumab or ranibizumab (2.56 mm3) to aflibercept (2.44 mm3; p = 0.080), then worsened over the course of aflibercept treatment (3.18 mm3; p = 0.019), and improved again on transition back to bevacizumab or ranibizumab (2.11 mm3; p = 0.016).ConclusionsWhile aflibercept appears initially effective, some patients develop recurrent fluid with aflibercept that improves with transition back to bevacizumab or ranibizumab. Rotating anti-VEGF agents may be beneficial with recurrent neovascular activity

Surgical Management of Anterior Chamber Migration of a Dexamethasone Intravitreal Implant

Anterior chamber migration of the dexamethasone intravitreal implant (Ozurdex; Allergan, Irvine, CA) may lead to corneal edema and elevated intraocular pressure, warranting removal of the implant.A 59-year-old patient with a history of prior vitrectomy, a posterior chamber intraocular lens with a disrupted posterior capsule, and a large inferior peripheral iridectomy presented with decreased vision due to corneal edema following dexamethasone intravitreal implant injection. The authors describe their technique for implant removal, which uses standard vitreoretinal instrumentation, viscoelastic, a modified Sheets glide, and angled forceps in order to avoid fragmentation of the implant and limit iatrogenic morbidity.The implant was successfully explanted. Postoperatively, the patient experienced improvement in the corneal edema, and after Descemet's stripping endothelial keratoplasty achieved a final best corrected visual acuity of 20/60 at final 12-month follow-up.Patients with aphakic lens status, anterior chamber intraocular lens with a disrupted posterior capsule, posterior chamber intraocular lens and a ruptured capsule, prior vitrectomy, and large peripheral iridectomies may be susceptible to migration of dexamethasone intravitreal implants into the anterior chamber

Bartonella henselae infection presenting as a unilateral panuveitis simulating Vogt-Koyanagi-Harada syndrome

To report an unusual ocular manifestation of cat scratch disease. Observational case report. Review of the clinical, laboratory, photographic, and angiographic records of a patient with cat scratch disease. A 54-year-old woman presented with counting fingers visual acuity in the right eye associated with optic disk edema, diffuse choroidal thickening, and panuveitis. Fluorescein angiography showed disk leakage and hyperfluorescent spots with late leakage suggestive of Vogt-Koyanagi-Harada disease. She was diagnosed with cat scratch disease by serum antibody titers and clinical course. Ocular manifestations of cat scratch disease can include diffuse thickening of the choroid. Cat scratch disease may manifest with angiographic features suggestive of Vogt-Koyanagi-Harada disease

Histopathologic correlation of Aspergillus endophthalmitis following uncomplicated cataract surgery

A clinicopathologic correlation between two patients with acute-onset Aspergillus endophthalmitis undergoing enucleation is reported. These two patients presented with pain, redness, and decreased vision following uncomplicated cataract surgery. In both patients, vitreous aspiration and intravitreal injections were the initial treatment followed later by pars plana vitrectomy for clinical worsening. Despite repeated surgical and medical interventions, the clinical course of both patients was prolonged, unsuccessful, and resulted in enucleation for a blind painful eye. Histologic examination of the enucleated specimens showed that, in spite of prolonged local and systemic therapy, there was persistent diffuse infiltration of the anterior chamber and ciliary body by a filamentous mold