OCCULT MACULAR DYSTROPHY WITH MUTATIONS IN THE RP1L1 AND KCNV2 GENES.

PURPOSE: To report a case of occult macular dystrophy associated with mutations in the RP1L1 and KCNV2 genes. METHODS: Case report. Multimodal retinal imaging and the results of genetic testing are described. RESULTS: A 27-year-old Chinese man presented with complaints of decreased central vision and normal retinal examination. Color fundus photography and fundus autofluorescence were unremarkable. Spectral-domain optical coherence tomography did reveal central ellipsoid loss in each eye. Genetic testing confirmed mutations in the RP1L1 and KCNV2 genes. CONCLUSION: The presence of central ellipsoid loss with spectral-domain optical coherence tomography should be evaluated for genetic disorders such as RP1L1 and KCNV2 mutations.

Prostaglandin-induced cystoid macular edema following routine cataract extraction.

To our knowledge, we are reporting the first case of a 59-year-old man who developed recurrent CME with three separate trials of three different prostaglandin class drugs following uncomplicated phacoemulsification with intraocular lens implantation. Despite multiple reports of individual prostaglandin (PG) analogues being suggested as the cause of CME, there are no recommendations regarding withholding these medications in the perioperative period. Our patient first developed CME OD 4-months post uncomplicated cataract extraction. XALATAN (Latanoprost) had been restarted after surgery and discontinued at onset of CME. While off XALATAN (Latanoprost), the patient's CME resolved, but his IOP rose. The patient was started on LUMIGAN (Bimatoprost) to control the IOP, but within weeks his CME recurred. The patient's CME was again treated and his IOP remained acceptable, but then progressively increased. TRAVATAN (Travoprost) was attempted, but he presented with a third round of CME. Definitive conclusions about causal relationships cannot be made without well-designed, prospective clinical trials addressing this issue.

Coarctation of the aorta presenting as spontaneous subarachnoid haemorrhage in the absence of cerebral aneurysm: a report of a rare clinical entity.

Subarachnoid haemorrhage (SAH) is a common neurologic event characterised by bleeding into the space immediately surrounding the brain. In non-traumatic SAH, the predominant cause is aneurysmal rupture of the cerebral vasculature. A significant number occur in the absence of vascular anomalies. This report describes a case of a 35-year-old male who presented with a subarachnoid haemorrhage in the absence of intracranial aneurysm. Subsequent workup demonstrated severe proximal hypertension due to congenital aortic coarctation as the cause of this event. This case demonstrates the importance of considering congenital abnormalities when evaluating patients with cerebrovascular events in the absence of common aetiologies.

Thrombin-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells.

Thrombin is a procoagulant inflammatory agonist that can disrupt the endothelium-lumen barrier in the lung by causing contraction of endothelial cells and promote pulmonary cell proliferation. Both contraction and proliferation require increases in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)). In this study, we compared the effect of thrombin on Ca(2+) signaling in human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells. Thrombin increased the [Ca(2+)](cyt) in both cell types; however, the transient response was significantly higher and recovered quicker in the PASMC, suggesting different mechanisms may contribute to thrombin-mediated increases in [Ca(2+)](cyt) in these cell types. Depletion of intracellular stores with cyclopiazonic acid (CPA) in the absence of extracellular Ca(2+) induced calcium transients representative of those observed in response to thrombin in both cell types. Interestingly, CPA pretreatment significantly attenuated thrombin-induced Ca(2+) release in PASMC; this attenuation was not apparent in PAEC, indicating that a PAEC-specific mechanism was targeted by thrombin. Treatment with a combination of CPA, caffeine, and ryanodine also failed to abolish the thrombin-induced Ca(2+) transient in PAEC. Notably, thrombin-induced receptor-mediated calcium influx was still observed in PASMC after CPA pretreatment in the presence of extracellular Ca(2+). Ca(2+) oscillations were triggered by thrombin in PASMC resulting from a balance of extracellular Ca(2+) influx and Ca(2+) reuptake by the sarcoplasmic reticulum. The data show that thrombin induces increases in intracellular calcium in PASMC and PAEC with a distinct CPA-, caffeine-, and ryanodine-insensitive release existing only in PAEC. Furthermore, a dynamic balance between Ca(2+) influx, intracellular Ca(2+) release, and reuptake underlie the Ca(2+) transients evoked by thrombin in some PASMC. Understanding of such mechanisms will provide an important insight into thrombin-mediated vascular injury during hypertension.

Molecular biology of chronic thromboembolic pulmonary hypertension.

Recent efforts have seen major advances in elucidating the mechanisms underlying pulmonary arterial hypertension. However, chronic thromboembolic pulmonary hypertension (CTEPH) often has been excluded from these studies. Consequently, whereas the clinical, radiographic, and hemodynamic characteristics of CTEPH have been well described, there remains a deficit in our understanding of the cellular, molecular, and genetic mechanisms underlying CTEPH. Furthermore, although prior venous thromboembolism may act as the inciting event, it is still unclear what predisposes some patients to develop CTEPH. CTEPH has two major pathogenic components. The first is the primary obstruction of central pulmonary arteries by accumulation of thrombotic material. The second is characterized by severe pulmonary vascular remodeling, similar to that seen in idiopathic pulmonary arterial hypertension. Other articles in this series describe the pathological, surgical, and therapeutic aspects of CTEPH. Here, we review the potential molecular and cellular mechanisms that may contribute to the pathogenesis of CTEPH.