Abstract: Diabetic retinopathy (DR) is a leading cause of visual loss worldwide. Disease severity is graded from mild non-proliferative DR to proliferative DR. Optical coherence tomography angiography (OCTA) has become widely accepted as a useful noninvasive technique that provides detailed imaging of the ocular vessels. It is also becoming an increasingly essential tool for both qualitative and quantitative assessment of DR, especially with the advent of wider imaging capabilities. Various angiographic features of DR, such as microaneurysms, intraretinal microvascular abnormalities, neovascularization, and nonperfusion have been comprehensively studied and described using OCTA. Different quantitative OCTA metrics have been introduced, such as vessel density, foveal avascular zone (FAZ) area, and area of nonperfusion. Current research has been focusing on the application of quantitative OCTA for the diagnosis of DR and treatment monitoring. The primary purpose of this article is to review the use of OCTA, including its challenges, in the diagnosis and management of DR.

Abstract: Diabetic retinopathy (DR) is the most common microvascular complication in patients with diabetes mellitus (DM), and remains the single greatest cause of blindness in working age adults around the world. In this article, we review the evolution of pharmacotherapies for both diabetic macular edema (DME) and DR such as anti-vascular endothelial growth factor inhibitors and various steroid formulations, as well as other emerging pharmacotherapies currently in late stage clinical testing for this disease.

Abstract: This submission will briefly review the anatomy and physiology of the optic nerve, and highlight various ischemic optic neuropathies including anterior ischemic optic neuropathies (non-arteritis and arteritic), diabetic papillopathy, posterior ischemic optic neuropathies, and ischemic optic neuropathies in the setting of hemodynamic compromise.

Abstract: Acute retinal arterial ischemia, which includes transient monocular vision loss (TMVL), branch retinal artery occlusion (BRAO), central retinal artery occlusion (CRAO) and ophthalmic artery occlusion (OAO), is most commonly the consequence of an embolic phenomenon from the ipsilateral carotid artery, heart or aortic arch, leading to partial or complete occlusion of the central retinal artery (CRA) or its branches. Acute retinal arterial ischemia is the ocular equivalent of acute cerebral ischemia and is an ophthalmic and medical emergency. Patients with acute retinal arterial ischemia are at a high risk of having further vascular events, such as subsequent strokes and myocardial infarctions (MIs). Therefore, prompt diagnosis and urgent referral to appropriate specialists and centers is necessary for further work-up (such as brain magnetic resonance imaging with diffusion weighted imaging, vascular imaging, and cardiac monitoring and imaging) and potential treatment of an urgent etiology (e.g., carotid dissection or critical carotid artery stenosis). Since there are no proven, effective treatments to improve visual outcome following permanent retinal arterial ischemia (central or branch retinal artery occlusion), treatment must focus on secondary prevention measures to decrease the likelihood of subsequent ischemic events.

Background: Pericytes are contractile cells that wrap along the walls of capillaries. In the brain, pericytes play a crucial role in the regulation of capillary diameter and vascular blood flow in response to metabolic demand. During ischemia, it has been suggested that pericytes may constrict capillaries, and that pericytes remain constricted after reperfusion thus resulting in impaired blood flow.

Methods: Here, we used a mouse model of retinal ischemia based on ligation of the central retinal artery to characterize the role of pericytes on capillary constriction. Ischemia was induced in transgenic mice carrying the NG2 promoter driving red fluorescent protein expression to selectively visualize pericytes (line NG2:DsRed).Changes in retinal capillary diameter at 1 hr after ischemia were measured ex vivo in whole-mounted retinas from ischemic and control eyes (n=4–6/group) using a stereological approach. Vessels and pericytes were three-dimensionally reconstructed using IMARIS (Bitplane). Furthermore, we used a novel and minimally invasive two-photon microscopy approach that allowed live imaging of microvasculature changes in the retina.

Results: Our data show a generalized reduction in capillary diameter in ischemic retinas relative to sham-operated controls in all vascular plexus (ischemia: 4.7±0.2 μm, control: 5.2±0.2 μm, student’s t-test, P<0.001). Analysis of the number of capillary constrictions at pericyte locations, visualized in NG2:DsRed mice, demonstrated a substantial increase in ischemic retinas relative to the physiological capillary diameter reductions observed in controls (ischemia: 1,038±277 constrictions at pericyte locations, control: 60±36 constrictions at pericyte locations, student’s t-test, P<0.01). Live imaging using two-photon microscopy confirmed robust capillary constriction at the level of pericytes on retinal capillaries during ischemia (n=6–8/group).

Conclusions: Collectively, our data demonstrate that ischemia promotes rapid pericyte constriction on retinal capillaries causing major microvascular dysfunction in this tissue. To identify the molecular mechanisms underlying the pathological response of pericytes during ischemia, we are currently carrying out experiments in mice and zebrafish to modulate signaling pathways involved in calcium dynamics leading to contractility in these cells.

Abstract: Pathological retinal neovascularization is the hallmark of primary blinding diseases across all age groups, yet surprisingly little is known about the causative factors. These diseases include diabetic retinopathy and retinopathy of prematurity where progressive decay of retinal vasculature yields zones of neural ischemia. These avascular zones and the hypoxic neurons and glia that reside in them are the source of pro-angiogenic factors that mediate destructive pre-retinal angiogenesis. Central neurons such as retinal ganglion cells (RGCs), which are directly apposed to degenerating vasculature in ischemic retinopathies, require stable metabolic supply for proper function. However, we unexpectedly found that RGCs are resilient to hypoxia/ischemia and a generally compromised metabolic supply and instead of degenerating, trigger protective mechanisms of cellular senescence. Paradoxically, while potentially favoring neuronal survival, the senescent state of RGCs is incompatible with vascular repair as they adopt a senescence-associated secretory phenotype (SASP) that provokes release of a secretome of inflammatory cytokines that drives paracrine senescence and further exacerbates pathological angiogenesis. The mechanisms that lead to retinal cellular senescence and dormancy as well as the therapeutic potential of targeting these pathways will be discussed.

Abstract: Successful management of a case of aggressive posterior retinopathy of prematurity (APROP) poorly responsive to laser therapy with intravitreal bevacizumab (IVB) is discussed. IVB is useful as rescue therapy in such cases, if given within the correct window period post laser therapy.

Abstract: To present spectral domain optical coherence tomography (OCT) findings during treatment in a case of acute isolated cilioretinal artery occlusion (CLRAO) reversed with intravenous systemic administration of mannitol and carbogen inhalation. Close monitoring with OCT thickness topographic map and cross section scans, every 12 hours, during treatment and till complete reversal of retinal nerve fiber layer edema. Fundus photography and fluorescein angiography (FFA) were used to illustrate occlusion and recanalization. After 72 hours of therapy, visual acuity improved from counting fingers (CF) to 7/10, Snellen’s chart. Consecutively OCT scans showed that the initial macular edema was gradually restored to typical 72 hours of treatment initiation. FFA performed after treatment confirmed recanalization of the cilioretinal artery. Early intervention with the combined intravenous administration of mannitol and carbogen inhalation can reverse acute onset loss of vision due to CLRAO. The reflectivity of retinal layers differs significantly regarding stages of acute CLRAO. In our case report increased reflectivity of the innermost layers of the retina was illustrated and a corresponding reduction in the outer retina and the retinal pigment epithelium and choriocapillaris layers. Macular thickness follow-up data recorded the course of intracellular edema to normal.

Abstract: Acute retinal necrosis (ARN) is a devastating syndrome characterized by panuveitis, retinal necrosis, and a high rate of retinal detachment that may result in poor visual outcomes if not promptly diagnosed and treated. ARN is most commonly caused by viruses within the herpesvirus family. Etiologies include varicella-zoster virus, herpes simplex virus, and cytomegalovirus, and may be promptly diagnosed by polymerase chain reaction testing of aqueous or vitreous fluid. The true incidence of ARN is not known due to its rarity; as a result, clinical treatment is often guided by retrospective case series, case reports, and expert opinion. Standard of care has evolved over time but currently includes a combination of systemic and intravitreal antiviral in conjunction with topical or oral steroids and surgical therapy as needed. Combination therapy may reduce the rate of severe vision loss and increase the rate of visual acuity gain, although further studies are needed in this area. In particular for patients with mild to moderate disease, combination therapy may reduce the rate of retinal detachment. Adjunctive therapies including oral corticosteroid and prophylactic laser barricade are incompletely studied, but corticosteroid in particular, may reduce inflammation, which also is involved in the severe disease pathogenesis observed in ARN. This review discusses the advances in diagnosis and treatment of ARN, including management with combination antiviral medication and surgical interventions.