Sai H. Chavala

Clinical images: Peripheral retinal neovascularization in the antiphospholipid antibody syndrome

motifs. Immunogenetics 1999;50:213–9. 44. Marsh SG, Parham P, Barber LD. The HLA FactsBook. San Diego (CA): Academic Press; 2000. 45. Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 1990;11:137–42. 46. Sobao Y, Tsuchiya N, Takiguchi M, Tokunaga K. Overlapping peptide-binding specificities of HLA–B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies. Arthritis Rheum 1999;42:175–81. 47. Yamaguchi A, Tsuchiya N, Mitsui H, Shiota M, Ogawa A, Tokunaga K, et al. Association of HLA–B39 with HLA– B27–negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients: evidence for a role of the peptide-anchoring B pocket. Arthritis Rheum 1995;38: 1672–7. 48. Colbert RA. The immunobiology of HLA-B27: variations on a theme. Curr Mol Med 2004;4:21–30. 49. Bowness P, Ridley A, Shaw J, Chan AT, Wong-Baeza I, Fleming M, et al. Th17 cells expressing KIR3DL2 and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol 2011;186:2672–80.

Embolic central retinal artery occlusion after subcutaneous auricular steroid injection.

A healthy 12-year-old boy had a subcutaneous triamcinolone acetonide steroid injection at the site of a keloid on his left earlobe in November, 2008, at a plastic surgery clinic. Within 5 min, he developed left-sided facial numbness, diaphoresis, dizziness, hypaesthesia of the left side of the mouth and tongue, left upper lid ptosis, and nearly complete vision loss in his left eye. Several hours later his systemic symptoms had resolved, he had regained partial vision in his left eye, and his right eye was asymptomatic. On examination by a retina specialist he was noted to have a visual acuity of 20/400 as well as multiple white steroid emboli in the retinal arteries of his left eye (fi gure). He also had diff use retinal whitening in the macula and other regions of the retina consistent with a central retinal artery occlusion (fi gure). 3 days later, his visual acuity improved to 20/150. This case represents a vision-threatening and potentially fatal complication of subcutaneous auricular steroid injection. Subcutaneous injections of dermal fi llers and corticosteroids are done in many specialties such as dermatology, otolaryngology, plastic surgery, and ophthalmology. Corticosteroid injections in the face, including the orbit, eyelids, nose, oral cavity, and maxilla, have been reported to cause ocular embolic events such as anterior segment ischaemia, branch and central retinal artery occlusions, and ophthalmic artery occlusions. Due to diff use anastomoses in the facial arterial system, facial injections can cause retrograde embolisation of the ophthalmic or central retinal arteries. This may cause severe, irreversible vision loss. For all injections within the face, good practice is to aspirate before injection and to inject as slowly as possible in order to limit forces that could propel emboli. Patients with visual problems after steroid injection should have immediate ophthal mological evaluation to allow intervention that might improve visual acuity. In embolic central retinal artery occlusion, ocular massage and reduction of intraocular pressure (by anterior chamber paracentesis and intraocular pressure lowering drugs) might help to mobilise emboli and restore ocular blood fl ow, although evidence that this could help is scarce.

Comparative Analysis of Circulating Endothelial Progenitor Cells in Age-Related Macular Degeneration Patients Using Automated Rare Cell Analysis (ARCA) and Fluorescence Activated Cell Sorting (FACS)

Background Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs), defined as CD34+VEGR2+ using traditional fluorescence activated cell sorting (FACS), are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA), a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. Methods We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and p<0.2 was considered indicative of a trend for this proof of concept study, while statistical significance was established at 0.05. Results We measured levels of CD34+VEGFR2+ EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17) using ARCA. Interestingly, CD34+VEGR2+ EPC analysis using FACS did not produce similar results (p = 0.94). Conclusions CD34+VEGR2+ may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample size were suggestive of a trend in ARMD using ARCA but not FACS. ARCA could be a helpful tool for developing a predictive test for ARMD phenotype conversion.

Ganciclovir-Resistant Cytomegalovirus (CMV) Retinitis in a Patient with Wild-Type CMV in Her Plasma

ABSTRACT A patient with systemic cytomegalovirus (CMV), including chorioretinitis, received localized and systemic ganciclovir, systemic cidofovir analog, and localized foscarnet. Mutations conferring ganciclovir and cidofovir resistance were detected in CMV from the aqueous fluid but not in CMV from plasma. Quantifying CMV from aqueous fluid was valuable for monitoring the clinical response and predicting resistance.

MDM2 inhibitors in the search for an optimized neovascular age-related macular degeneration treatment

Murine double minute-2 inhibitors offer a durable treatment for neovascular age-related macular degeneration by inducing apoptosis in pathologically proliferating cells, a similar effect as radiation therapy, but with potentially a more favorable side-effect profile since it does not induce DNA damage. Murine double minute-2 inhibitors may be complementary to current anti-VEGF treatments and potentially reduce the cumulative number of intravitreal injections.

Bilateral exudative retinal detachments in Sturge-Weber syndrome

An 11-year-old girl with a port-wine stain on both sides of her face (fi gure A, B) presented after reporting progressive diffi culty reading. Visual acuity in the right eye was 20/100 and in the left eye she could count fi ngers only. Fundus examination of the right eye showed an inferior retinal detachment with retinal pleats (fi gure C, arrow). A subretinal peripapillary lesion was also seen. Dilated examination of the left eye showed a bullous retinal detachment that could be seen through the pupil Lancet 2013; 382: 259

Induced Pluripotent Stem Cells: Generation, Characterization, and Differentiation—Methods and Protocols

Reprogramming fibroblasts into induced pluripotent stem cells (iPSC) remains a promising technique for cell replacement therapy. Diverse populations of somatic cells have been examined for their reprogramming potential. Recently, ocular ciliary body epithelial cells (CECs) have been reprogrammed with high reprogramming efficiency and single transcription factor reprogramming, making them an exciting candidate for cellular reprogramming strategies.

Ptosis, erythema, and rapidly decreasing vision.

A PREVIOUSLY HEALTHY 63-YEAR-OLD WHITE MAN PRESENTS TO THE EMERgency department with a swollen right eye and complete ptosis. Three weeks prior, the patient was evaluated for sinusitis by a local otolaryngologist. Cultures were performed on sinonasal aspirates and empirical ciprofloxacin and oral prednisone were initiated. The patient’s symptoms, however, worsened. Cultures revealed Enterobacter aerogenes. On the morning of presentation, a complete ptosis of the right eye had developed (FIGURE, A). Vital signs were stable, but visual acuity was 20/200 in the right eye and 20/25 in the left. Examination was remarkable for limited ocular motility (Figure, B; Video at http: //www.jama.com) and a right relative afferent pupillary defect (Figure, C). Within an hour, vision had deteriorated to light perception. Serum glucose level was measured at 690 mg/dL (38.3 mmol/L) without an anion gap, and hemoglobin A1c level was 8.9%. Maxillofacial computed tomography imaging revealed sinusitis and orbital stranding. The patient was transferred to our institution. On arrival he had lost light perception. An area of ocular adnexal tissue necrosis had developed. What Would You Do Next?

Peripheral retinal telangiectasia and ischemia in Takayasu's arteritis.

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Retinal arteriolar tortuosity and artery occlusion

A 56-year-old African-American man presented with 20/30 best-corrected visual acuity bilaterally. Fundoscopic examination, fundus photographs, and fl uorescein angiography showed signifi cant bilateral tortuosity of second and third order arterioles (fi gure). Other fi ndings in the left eye included an occluded superotemporal artery with arteriosclerosis and macular pigmentary changes. The tortuosity was believed to be most consistent with familial retinal arteriolar tortuosity (fRAT), a rare autosomal dominant disorder. However, the patient stated that he had no family history of ocular disease, and the only one of eight siblings accessible for examination did not demonstrate fRAT. Is olated tortuosity of the second and third order arterioles is pathognomonic for fRAT. Although a few associated systemic vascular abnormalities have been identifi ed, fRAT is considered to be an isolated retinal fi nding. Branch retinal artery occlusion has not been reported in fRAT, and this feature may be attributed to the patient’s other risk factors of cocaine use and signifi cant hypertension.