Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases.

Massive retinal gliosis, a nonneoplastic retinal glial proliferation, was first described in detail over 25 years ago, before the era of immunohistochemistry, in a series of 38 cases-to which can be added 30 case reports or small series (no more than 3 cases) subsequently. We analyze a new series of 3 nontumoral intraretinal glioses and 15 cases of tumoral retinal gliosis, not all of which, strictly speaking, were massive. The data from this series are compared with the findings in previously published cases. Included are 2 cases of massive retinal gliosis diagnosed from evisceration specimens. In reviewing all published and current cases, we were able to establish 3 subgroups of retinal tumoral glioses rather than a single "massive" category: focal nodular gliosis, submassive gliosis, and massive gliosis. Among 43 reported cases, including the present series, but excluding the previous large series of 38 cases in which substantial clinical data were omitted, there were 19 men and 24 women. Their mean and median ages were 36.2 years and 36 years, respectively, with a range of 2 to 79 years. All lesions were composed of mitotically quiet, compact spindled fibrous astrocytes devoid of an Alcian blue-positive myxoid matrix. The most common associated ocular conditions were phthisis bulbi and congenital diseases or malformations. Histopathologically, all 3 tumoral categories were accompanied by progressively more extensive fibrous and osseous metaplasia of the pigment epithelium, the latter forming a clinically and diagnostically useful, almost continuous, outer rim of eggshell calcification in the submassive and massive categories that should be detectable with appropriate imaging studies. In decreasing order of frequency, microcysts and macrocysts, vascular sclerosis, exudates, calcospherites, and Rosenthal fibers were observed among the proliferating fibrous astrocytes. Immunohistochemistry was positive for glial fibrillary acidic protein in all cases and nestin in most (an intermediate cytoplasmic filament typically restricted to embryonic and reparative neural tissue). The nonneoplastic nature of all categories of gliosis was confirmed by absent TP53 (tumor suppressor gene) dysregulation, Ki-67 negativity, and intact p16 expression (the protein product of the p16 tumor suppressor gene) in the overwhelming majority of cases. These findings indicate an intrinsic attempt to regulate and maintain a low level of glial cell proliferation that becomes unsuccessful as the disease evolves. The categories of tumoral proliferation appeared to constitute a spectrum. We conclude that focal nodular tumors encompass lesions previously called retinal vasoproliferative lesions, which display the same histopathologic and immunohistochemical findings as 3 major categories of retinal gliosis characterized herein.

Anti-vascular endothelial growth factor (anti-VEGF) drugs - ranibizumab, aflibercept, and off-label bevacizumab - are vital to the treatment of common retinal diseases, including exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema (ME) associated with retinal vein occlusion (RVO). Given the high prevalence of AMD and retinal vascular diseases, anti-VEGF agents represent a large cost burden to the United States (US) healthcare system. Although ranibizumab and aflibercept are 30-fold more expensive per injection than bevacizumab, the two more costly medications are commonly used in the US, even though all three have been shown to be effective and safe for treatment of these retinal diseases. We investigated the availability and content of professional ophthalmic guidelines on cost consideration in the selection of anti-VEGF agents. We found that current professional guidelines were limited in availability and lacked specific guidance on cost-based anti-VEGF drug selection. This represents a missed opportunity to encourage the practice of value-based medicine. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

PURPOSE: Anterior ischemic optic neuropathy (AION) is the most common cause of non-glaucomatous optic nerve head (ONH) injury among older adults. AION results from a sudden ischemic insult to the proximal portion of the optic nerve, typically leading to visual impairment. Here, we present an experimental model of photodynamically induced ONH injury that can be used to study neuroprotective modalities. METHODS: Intraperitoneal injection of mesoporphyrin IX was followed by photodynamic treatment of the ONH in one eye of Brown-Norway rats; the fellow eye received the reverse sequence as a sham control. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and visual evoked potential (VEP) recordings were performed at different time points following laser treatment. Immunohistochemistry was used to monitor apoptotic cell death (TUNEL) and macrophage infiltration (CD68). Cytokine levels were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: FA showed early hyperfluorescence and late leakage of the ONH, while SD-OCT revealed optic nerve edema. No leakage or other abnormalities were detected in control eyes. VEPs were significantly reduced in amplitude and showed prolonged responses compared to sham eyes. The number of apoptotic retinal ganglion cells was elevated one day after laser treatment (13.77 ± 4.49, p < 0.01) and peaked on day 7 (57.22 ± 11.34, p < 0.01). ONH macrophage infiltration also peaked on day 7 (101.8 ± 9.8, p < 0.05). ELISAs performed showed upregulation of macrophage chemoattractant protein-1 and macrophage inflammatory protein-2 on days 3 and 1, respectively. CONCLUSIONS: Photodynamic treatment of the ONH after administration of mesoporphyrin IX leads to macroscopic, histologic, and physiologic evidence of ONH injury. Given the long half-life of mesoporphyrin IX and the ease of intraperitoneal injections, this new model of photodynamically induced ONH injury may be a useful tool for studying optic nerve injury and possible neuroprotective treatments.

BACKGROUND: Endothelial cells (EC) grown on collagen particles inhibit intimal hyperplasia in animal models when applied perivascularly, and this effect appears to be, at least in part, the result of EC-derived soluble factors that suppress local vascular inflammation. To elucidate the molecular basis of the therapeutic effects of EC grown on collagen particles, the anti-inflammatory activity of conditioned medium from these cells was characterized. METHODS: Human aortic EC (HAEC) and, for chromatin immunoprecipitation assays, human umbilical vein EC (HUVEC) were treated with tumor necrosis factor alpha (TNFα) in the presence of conditioned medium generated by HAEC grown on collagen particles (ECPCM), and the anti-inflammatory effects were evaluated by analysing the expression of the inflammation-related adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The therapeutic activity of ECPCM was studied using the mouse strain JR5558, which develops spontaneous choroidal neovascularisation (CNV) lesions driven by local inflammation. RESULTS: ECPCM significantly suppressed TNFα-induced expression of E-selectin and VCAM-1. ECPCM did not affect the mRNA stability of the two genes, but suppressed TNFα-induced binding of the p65 subunit of NF-kB transcription factor to E-selectin and VCAM-1 promoters. In vivo, systemic ECPCM treatment significantly reduced the CNV area and the recruitment of activated macrophages to the lesions. Characterization of the molecule responsible for the anti-inflammatory activity in ECPCM indicates that it is unlikely to be a protein and that it is not any of the better characterized EC-derived anti-inflammatory molecules. CONCLUSIONS: Medium conditioned by HAEC grown on collagen particles exhibits significant anti-inflammatory activity via inhibition of genes that mediate inflammatory responses in EC.

PURPOSE: Horizontal peripheral prisms for hemianopia provide field expansion above and below the horizontal meridian; however, there is a vertical gap leaving the central area (important for driving) without expansion. In the oblique design, tilting the bases of both prism segments toward the horizontal meridian moves the field expansion area vertically and centrally (closing the central gap) while the prisms remain in the peripheral location. However, tilting the prisms results also in a reduction of the lateral field expansion. Higher prism powers are needed to counter this effect. METHODS: We developed, implemented, and tested a series of designs aimed at increasing the prism power to reduce the central gap while maintaining wide lateral expansion. The designs included inserting the peripheral prisms into carrier lenses that included yoked prism in the opposite direction, combination of two Fresnel segments attached at the base and angled to each other (bi-part prisms), and creating Fresnel prism-like segments from nonparallel periscopic mirror pairs (reflective prisms). RESULTS: A modest increase in lateral power was achieved with yoked-prism carriers. Bi-part combination of 36Δ Fresnel segments provided high power with some reduction in image quality. Fresnel reflective prism segments have potential for high power with superior optical quality but may be limited in field extent or by interruptions of the expanded field. Extended apical scotomas, even with unilateral fitting, may limit the utility of very high power prisms. The high-power bi-part and reflective prisms enable a wider effective eye scanning range (more than 15 degrees) into the blind hemifield. CONCLUSIONS: Conventional prisms of powers higher than the available 57Δ are limited by the binocular impact of a wider apical scotoma and a reduced effective eye scanning range to the blind side. The various designs that we developed may overcome these limitations and find use in various other field expansion applications.

Mutations in NOTCH 3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a neurological disorder characterized by stroke, and vascular cognitive impairment and dementia. Loss of vascular smooth muscle cells (VSMC) and accumulation of granular osmiophilic material (GOM) deposits are hallmarks of CADASIL. There are no therapies for CADASIL and experimental endpoints to examine the preclinical efficacy of potential drugs are lacking. This study aims to use a mouse carrying the C455R mutation in Notch 3 to identify biomarkers associated with CADASIL. Mass spectrometry and antibody arrays were used to explore the aorta and blood proteomes of CADASIL mice, ELISA assays were utilized for biomarker validation, a ligand-dependent assay was applied to examine the relationship between Notch signaling and biomarker expression, and retinal histology was performed for quantification of VSMC loss in arteries. Two-hundred day-old mice with the C455R CADASIL mutation in Notch 3 mice display robust VSMC loss in retinal arteries and had increased plasma levels of collagen18α1/endostatin (col18α1) and high-temperature requirement A serine peptidase 1 (HTRA1) and reduced levels of Notch 3 extracellular domain (N3ECD), compared to control wild type mice. Measurements of plasma endostatin, HTRA1 and N3ECD, along with VSMC quantification in retinal arteries, may serve as surrogate endpoints for assessing efficacy in preclinical therapeutic studies of CADASIL using mice.

Mucous membrane pemphigoid is a systemic disorder that primarily affects mucous membranes. When localized to the conjunctiva, it is known as ocular cicatricial pemphigoid, a potentially blinding disease. Ocular cicatricial pemphigoid is an indication for systemic immunosuppressive treatment to achieve adequate remission. Immunosuppressive agents are selected with a "stepladder" approach, commencing with medications having the fewest side effects. We provide an update of the literature on immunomodulatory agents since 2011 as additional treatment modalities have been explored in the last 4 years.