Two anti-integrin agents are in US clinical trials for ophthalmic use: lifitegrast Shire , a compound with the potential to treat ocular surface inflammation that is nearing US Food and Drug Administration FDA approval, and ALG Luminate, Allegro Ophthalmics , which has retinal indications that are the focus of this article. ALG binds to and inhibits all three of these receptors Figure 1.
Clinical Pathways In Vitreoretinal Disease: Medicine & Health Science Books @ retouwingere.tk Drs Steidl and Hartnett have assembled a superb textbook that is usefulfor ophthalmology residents and fellows as well as anyone wishing to expandhis or her.
Figure 1. Integrins regulate cell functions and interactions among cells and between cells and the ECM. As they bind or attach to the ECM, integrins activate intracellular signaling pathways and proteolytic changes that promote angiogenesis. ALG inhibits the connection between the integrins shown here in purple and the ECM, preventing downstream angiogenic effects. In a hypoxic environment, VEGF signals the need for additional blood vessels to provide more oxygen.
Inhibiting this signal with an anti-VEGF drug, therefore, can stop the development of new blood vessels, which is important. Integrins operate both upstream and downstream of the VEGF pathway. They also play critical roles in cell migration, proliferation, and maturation.
Although integrin receptors sit on the surface of the cell, communicating outward and regulating adhesion to other cells, they also send instructions to the cell itself. Because ALG inhibits all three of the receptors associated with angiogenesis, early clinical evidence suggests that it is effective in preventing the formation of new blood vessels as well as shrinking and stopping leakage from existing blood vessels.
There is also evidence that it is effective even for those who have plateaued or failed to respond to other therapies. In the phase 1 DME trial, for example, nearly half of the 15 patients enrolled had poor vision and substantial intraretinal fluid despite a documented history of 10 to 12 anti-VEGF injections. What is clinically most compelling is that ALG also appears to have a longer duration of effect than current therapies. There is also a need to learn more about how this drug can be used both alone and in combination with other agents.
If earlier results of its potency and duration are confirmed, it is plausible that ALG could be used for maintenance therapy either in monotherapy or after induction therapy with an anti-VEGF agent. The anti-integrin agent inhibits an integrin-mediated pathway of the vitreoretinal interface, connecting the posterior aspect of the vitreous with the internal limiting membrane of the retina. In blocking this pathway, ALG helps to achieve vitreous breakdown and separation from the retina. In the phase 1 DME trial, the primary endpoints were improvement in visual acuity and reduction of central macular thickness, but investigators also looked at what happened to the vitreoretinal interface in 11 patients who had no or partial posterior vitreous detachment PVD at baseline.
Additional retinal complications of sickle cell disease include sickling maculopathy, central retinal artery occlusion CRAO , branch retinal artery occlusion BRAO , epiretinal membrane, ischemic optic neuropathy, development of optociliary shunt vessels, and choioretinal infarctions.
Although rare, retinopathy can occur in patients with sickle cell trait in the absence and presence of concomitant systemic disease, such as diabetes or hypertension. Patients with non-proliferative retinopathy should be followed periodically according to the level of involvement.
For proliferative retinopathy, the aim is to prevent ischemic complications, particularly vitreous hemorrhages and retinal detachments. Treatment options include the use of diathermy, cryotherapy, and laser photocoagulation. Siqueira and associates demonstrated retinal neovascularization regression with intravitreal Avastin bevacizumab, Genentech injection.
Leukemia is defined as a neoplastic blood disorder characterized by the overproduction of abnormal white blood cells. Leukemia can be divided into two types; myelogenous and lymphocytic.
The ocular complications of leukemia may be due to a direct involvement by leukemic infiltrates or secondary to concomitant anemia or thrombocytopaenia. Features of leukemic retinopathy include multiple preretinal and intraretinal hemorrhages that are most commonly found in the posterior pole. Retinal lesions such as peripheral neovasularization or sea fans neovascularization reminiscent of sickle cell retinopathy may develop in patients with chronic leukemia and are thought to occur as a result of peripheral nonperfusion and ischemia from the hyperviscosity.
In pathological studies, the choroid is the most commonly affected ocular structure.
The most African of the elements, institutional identity and distinctive version, were compartments owned by Crookston in the available thoughts. J Ophthalmol Perfect Sight Without Glasses by Dr. Retinopathy in patients with anemia is well documented. Kaur B, Taylor D.
Choroidal masses lead to a disruption of the retinal pigment epithelium which result from decreased blood flow to the choriocapillaris. Leukemic retinopathy usually is not treated directly. Systemic treatment involves the use of chemotherapy, immunotherapy, and radiotherapy. Intraocular leukemic infiltrate is best treated with chemotherapy that is appropriate for the type and stage of leukemia. External-beam radiation may be applied to lesions of the optic nerve or orbit.
The presence of leukemic infiltration is usually a poor prognostic indicator. The characteristic pathologic abnormality is a polycellular infiltrate made up of giant Reed-Sternberg cells that are fibrotic and necrotic in nature. Ocular abnormalities associated with lymphoma have been divided anatomically into a vitreoretinal and uveal form. Involvement of the uveal tract presents as a non-resolving uveitis, diffuse choroidal infitiltration, or exudative retinal detachment. The characteristic retinal finding is a low-lying, yellow-towhite mass deep to the sensory retina. They may even appear as single, multiple, confluent, or discrete punctate lesions that may involve all layers of the retina.
Treatment options for lymphoma include observation, involved-field radiation, subtotal lymphoid radiation, chemotherapy with or without radiation, and bone marrow transplant. Newer biologic therapies are also being investigated for the treatment of lymphoma. Hematological disorders affect millions of Americans and represent a major public health concern due to the potential for significant morbidity and mortality.
The retinal findings associated with the various hematological disorders necessitate an immediate comprehensive medical evaluation.
The optometric physician may play a crucial role in the diagnosis and management of these disorders. Toggle navigation.
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