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These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis.Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8).Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole (p0.001). VEGF-A was significantly upregulated in individuals with exogenous endophthalmitis after cataract surgery (p = 0.001), vitrectomy (p = 0.024), and intravitreal injection (p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations (p0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 (p = 0.028).We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis.

Objective The purpose of this report is to develop a consensus for Canadian national guidelines specific to a tele-medicine approach to screening for diabetic retinopathy (DR) using evidence-based and clinical data. Methods Canadian Tele-Screening Grading Scales for DR and diabetic macular edema (DME) were created primarily based on severity grading scales outlined by the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDR) and the Scottish DR Grading Scheme 2007. Other grading scales used in international screening programs and the clinical expertise of the Canadian Retina Research Network members and retina specialists nationwide were also used in the creation of the guidelines. Results National Tele-Screening Guidelines for DR and DME with and without optical coherence tomography (OCT) images are proposed. These outline a diagnosis and management algorithm for patients presenting with different stages of DR and/or DME. General guidelines detailing the requirements for imaged retina fields, image quality, quality control, and follow-up care and the role of visual acuity, pupil dilation, OCT, ultra-wide-field imaging, and artificial intelligence are discussed. Conclusions Tele-retina screening can help to address the need for timely and effective screening for DR, whose prevalence continues to rise. A standardized and evidence-based national approach to DR tele-screening has been proposed, based on DR/DME grading using two 45° image fields or a single widefield or ultra-wide-field image, preferable use of OCT imaging, and a focus on local quality control measures.

Background Exogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti-inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against vascular endothelial growth factor (VEGF), has anti-inflammatory properties in experimental models of Gram-positive and Gram-negative inflammation. Methods BALB/c mice were subjected to lipopolysaccharide- (LPS) or peptidoglycan- (PGN) induced ocular inflammation and treated with IVT bevacizumab. Iris microvasculature was imaged 6 hours following irritant/treatment using intravital microscopy (IVM) before the mice were euthanized and the eyes were enucleated immediately post-mortem. Following enucleation, levels of VEGF and 23 cytokines and chemokines (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, TNF, KC, G-CSF, GM-CSF, Eotaxin, INF-γ, MCP-1, MIP-1α, MIP-1β, RANTES) were quantified using a multiplex assay. Results Levels of VEGF were significantly increased during the inflammatory response, triggered by either PGN or LPS. Both the adherence of leukocytes to the iris vascular endothelium and the levels of pro-inflammatory cytokines and chemokines were significantly increased following administration of either irritant. Treatment with bevacizumab decreased levels of leukocyte adherence in LPS-treated eyes, however, not in PGN-treated eyes. Conversely, bevacizumab treatment decreased levels of cytokines and chemokines (TNF, IL-6, MCP-1, MIP-1α, MIP-1β, RANTES, KC) in PGN-treated eyes, however, not in LPS-treated eyes. Conclusions Within a 6-hour window bevacizumab had anti-inflammatory actions that were distinct in both Gram-positive (PIU) and Gram-negative (EIU) models, respectively. Given our findings, this would suggest that bevacizumab may have utility as an adjunctive therapy to IVT antibiotics and vitrectomy in the management of exogenous endophthalmitis.

A 48-year-old man with a history of birdshot chorioretinitis presented with blurry vision, retro-bulbar pain and sinusitis. Though visual acuity was unaffected, he had left optic disc oedema and mild restriction of left eye abduction. His symptoms progressed quickly, with diplopia in primary gaze, epistaxis from his left nostril, and a left relative afferent pupillary defect (RAPD). On computed tomography, there was a mass in the nasal cavity that extended through the left cribriform plate and lamina papyracea and posteriorly into the optic canal.Pathological examination of biopsy specimens revealed sheets of undifferentiated cells with extensive areas of necrosis and islands of squamous differentiation. The tumour cells expressed monokeratin, p63, CD34, and p16. Molecular testing indicated rearrangement of the NUTM1 (15q14) locus and fusion of the NUTM1 and BRD4 (19p13.12) loci, confirming the diagnosis of NUT carcinoma of the sinonasal tract.This is the first reported case of NUT carcinoma in a patient with birdshot chorioretinitis. The onset of chorioretinitis may have been the earliest sign of the effects of the BRD4-NUTM1 fusion protein, resulting in expression of HLA-A29. There is evidence that bromodomain and extra terminal (BET) family proteins play a role in inflammatory marker expression. Keywords: NUT carcinoma, Orbit, Birdshot chorioretinitis, Epigenetics, Bromodomain and Extra Terminal (BET) proteins

Purpose The murine double minute (MDM)2 is a critical negative regulator of the p53 tumor suppressor, and MDM2 SNP309G is associated with a higher risk of proliferative vitreoretinopathy (PVR); in addition, the MDM2 T309G created using clustered regularly interspaced short palindromic repeats (CRISPR)/associated endonuclease (Cas)9 enhances normal rabbit vitreous-induced expression of MDM2 and survival of primary human retinal pigment epithelial (hRPE) cells in vitro. The goal of this study was to determine whether this MDM2 T309G contributes to the development of experimental PVR. Methods hRPE cells expressing MDM2 T309G or T309T only were treated with vitreous from human PVR donors (HV). The expression of MDM2 and p53 in the treated cells was examined by Western blot. The in vitro vitreous-induced cellular responses, such as contraction were assessed, and PVR was induced by intravitreal injection of the hRPE cells with MDM2 T309G or T309T only into rabbit eyes. Results Western blot analyses indicated that treatment of hRPE cells with HV led to a significant increase (1.7 ± 0.2-fold) in the expression of MDM2 and a significant decrease in p53 in the cells expressing MDM2 T309G compared with those with MDM2 T309T. In addition, HV promoted contraction of the hRPE cells expressing MDM2 T309G significantly more than those with MDM2 T309T only. Furthermore, MDM2 T309G in the hRPE cells enhanced the development of PVR in a rabbit model. Conclusions The MDM2 SNP309 in RPE cells enhances their potential of PVR pathogenesis.

Purpose Previous studies have shown that vitreous stimulates degradation of the tumor suppressor protein p53 and that knockdown of phosphatidylinositol 5-phosphate 4-kinases (PI5P4Kα and -β) abrogates proliferation of p53-deficient cells. The purpose of this study was to determine whether vitreous stimulated expression of PI5P4Kα and -β and whether suppression of PI5P4Kα and -β would inhibit vitreous-induced cellular responses and experimental proliferative vitreoretinopathy (PVR). Methods PI5P4Kα and -β encoded by PIP4K2A and 2B, respectively, in human ARPE-19 cells were knocked down by stably expressing short hairpin (sh)RNA directed at human PIP4K2A and -2B. In addition, we rescued expression of PI5P4Kα and -β by re-expressing mouse PIP4K2A and -2B in the PI5P4Kα and -β knocked-down ARPE-19 cells. Expression of PI5P4Kα and -β was determined by Western blot and immunofluorescence. The following cellular responses were monitored: cell proliferation, survival, migration, and contraction. Moreover, the cell potential of inducing PVR was examined in a rabbit model of PVR effected by intravitreal cell injection. Results We found that vitreous enhanced expression of PI5P4Kα and -β in RPE cells and that knocking down PI5P4Kα and -β abrogated vitreous-stimulated cell proliferation, survival, migration, and contraction. Re-expression of mouse PIP4Kα and -β in the human PI5P4Kα and -β knocked-down cells recovered the loss of vitreous-induced cell contraction. Importantly, suppression of PI5P4Kα and -β abrogated the pathogenesis of PVR induced by intravitreal cell injection in rabbits. Moreover, we revealed that expression of PI5P4Kα and -β was abundant in epiretinal membranes from PVR grade C patients. Conclusions The findings from this study indicate that PI5P4Kα and -β could be novel therapeutic targets for the treatment of PVR.

Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor α–mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis.

Proliferative vitreoretinopathy (PVR) is a complication that develops in 5% to 10% of patients who undergo surgery to correct a detached retina. The only treatment option for PVR is surgical intervention, which has a limited success rate that diminishes in patients with recurring PVR. Our recent studies revealed that antioxidants prevented intracellular signaling events that were essential for experimental PVR. The purpose of this study was to test whether N-acetyl-cysteine (NAC), an antioxidant used in a variety of clinical settings, was capable of protecting rabbits from PVR. Vitreous-driven activation of PDGFRalpha and cellular responses intrinsic to PVR (contraction of collagen gels and cell proliferation) were blocked by concentrations of NAC that were well below the maximum tolerated dose. Furthermore, intravitreal injection of NAC effectively protected rabbits from developing retinal detachment, which is the sight-robbing phase of PVR. Finally, these observations with an animal model appear relevant to clinical PVR because NAC prevented human PVR vitreous-induced contraction of primary RPE cells derived from a human PVR membrane. Our observations demonstrate that antioxidants significantly inhibited experimental PVR, and suggest that antioxidants have the potential to function as a PVR prophylactic in patients undergoing retinal surgery to repair a detached retina.

Previous investigators reported that epiretinal membranes isolated from patients with proliferative vitreoretinopathy (PVR) express various platelet-derived growth factor (PDGF) family members and PDGF receptors (PDGFRs) (Cui, J.Z., Chiu, A., Maberley, D., Ma, P., Samad, A., Matsubara, J.A., 2007. Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy. Eye 21, 200-208; Robbins, S.G., Mixon, R.N., Wilson, D.J., Hart, C.E., Robertson, J.E., Westra, I., Planck, S.R., Rosenbaum, J.T., 1994. Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases. Invest. Ophthalmol. Vis. Sci. 35(10), 3649-3663). Co-expression of ligand and receptor raises the possibility of an autocrine loop, which could be of importance in the pathogenesis of PVR. To begin to address this issue we determined whether the PDGFRs in epiretinal membranes isolated from PVR patient donors were activated. Indeed, immunohistochemical staining (using pan- and phospho-PDGFR antibodies) revealed that both PDGFR subunits were activated. Quantification of these data demonstrated that a greater percentage of cells expressed the PDGFR alpha subunit as compared with the beta subunit (44 +/- 13% versus 32 +/- 6.5%). Staining with phospho-PDGFR antibodies indicated that 36 +/- 10% of the PDGFR alpha subunits were activated, whereas only 16 +/- 5.5% of the PDGFR beta subunits were activated. Thus, a 2.25 fold greater percentage of the PDGFR alpha subunits was activated. Co-staining with diagnostic cell-type antibodies indicated that both retinal pigment epithelial and glial cells expressed activated PDGFR alpha subunits. These findings support the recent discovery that PDGF-C is the major vitreal isoform because PDGF-C is 3 times more likely to activate a PDGFR alpha subunit as compared with a PDGFR beta subunit. We conclude that PDGFRs are activated in epiretinal membranes of patients with PVR, and that the profile of active PDGFR subunits functionally supports the idea that PDGF-C is the predominant PDGF isoform present in the vitreous of patients with PVR. These findings identify PDGF-A, -AB and C as the best therapeutic targets within the PDGF family.

Most of the focus in choroidal and retinal angiogenesis centers on the regulation of endothelial function by soluble factors. Less well-understood, but nevertheless significant, is the regulation of endothelial cell function by its insoluble microenvironment, the extracellular matrix (ECM). Endothelial interaction with the ECM occurs primarily through cell surface receptors belonging to the integrin family that relay information from the ECM to the intracellular signaling machinery. The integrin family is composed of 24 heterodimeric type I transmembrane cell surface receptors containing an alpha and a beta subunit. To date, there are known to be 18 alpha and eight beta subunits [1]. Alpha subunits are designated 1–11, iib, v, D, E, L, M, and X. Beta subunits have designations of 1–8. The heterodimeric receptor is designated through identification of the corresponding alpha and beta subunits, e.g., αiibβ3 designates the platelet integrin. The ECM specificity of individual integrin family members covers a broad spectrum of selectivity as exemplified by the restricted specificity of the α5β1 integrin for only fibronectin and the promiscuous binding of the αvβ3 to a diverse set of ECM [2]. Even with this disparity in matrix selectivity, integrin family members can be categorized based on the subset of matrices recognized and cell type expression patterns. The four categories consist of integrins that preferentially bind collagen, laminin, or ECM containing an arg-gly-asp (RGD) tripeptide motif and integrins which are primarily leukocyte-specific receptors [1, 2]. The ability of a number of integrins to recognize the same primary matrix implies that there is potential overlap among family members. While there clearly can be some degree of functional compensation, as seen in the ability of the αvβ3 integrin to supplement fibronectin matrix assembly in the absence of α5β1 integrin [3], this functional compensation is incomplete, implying that each family member is likely to have a crucial functional role within a given biological process. The functional activity of integrin family members can be typically viewed as having a permissive role in providing adhesive function; however, in some cases, this role may be regulatory rather than permissive in nature, as in the case of the αvβ3 integrin, which is believed to modulate neovascular response [4]. Furthermore, the functional activity may also depend on the presence of other integrin family members, which may suppress function via a mechanism of transmodulation known as transdominance [5, 6]. It is clear that in order to gain a better understanding of how cell adhesion, and especially integrins, regulate a biological process, it is essential to understand the repertoire of integrins involved and their expression relative to disease progression. During neovascularization, several integrin family members have been implicated in regulating endothelial cell function, including α1β1, α2β1, α5β1, αvβ3, and αvβ5 [7]. In ocular neovascular membranes (POHS, idiopathic, choroidal neovascular [CNV], PVR, and PDR), integrin expression has been studied in only a few instances [8–10], with focus on either a subset of receptors [8, 9] or the examination of a broad range of integrin subunits in a small number of membranes [10]. To obtain a more comprehensive understanding of integrin family member expression in neovascular progression, we examined the expression of α1β1, α2β1, α5β1, αvβ3, and αvβ5 integrins in surgically removed subretinal membranes with an emphasis on identifying integrins expressed primarily on endothelial cells. In the present study, surgically removed human CNV membranes, for which the patient histories and disease progression are known, were characterized for integrin expression relative to the endothelial markers CD31 and VWF. Consistent with known neovascular responses, endothelial staining correlated well with patient histories, with endothelial staining in active and mid stage disease, but little or no staining of endothelial cells in tissues from late stage and fibrotic membranes. Integrin staining was primarily seen in early and mid stage where αvβ3, α1β1, α2 β1, and α5β1 staining colocalized with endothelial cells. No correlation between αvβ5 staining and endothelial cells was observed.

To compare the relative levels of connective tissue growth factor (CTGF), platelet-derived growth factor alpha (PDGF-AA), and hepatocyte growth factor (HGF) in glial and retinal pigment epithelial (RPE) cells of epiretinal membranes from proliferative vitreoretinopathy (PVR). A total of 37 PVR membranes, of various stages, underwent fluorescent immunohistochemisty and confocal laser scanning microscopy to localize CTGF, HGF, and PDGF-AA in RPE and glial cells. Numerous RPE, and relatively fewer glial cells, were found in all stages of PVR. CTGF immunoreactivity increased from early to late stage PVR and was principally expressed by RPE cells in early stage, and by glial cells in late stage PVR. HGF, expressed by both RPE and glial cells, was principally expressed in mid-stage PVR. PDGF-AA, expressed by both cell types, demonstrated a uniform level of staining throughout all stages of PVR. RPE and glial cells contribute to the expression of CTGF, HGF, and PDGF-AA during PVR, but with specific developmental patterns. PDGF-AA is expressed uniformly throughout all stages of PVR, while HGF expression peaks during mid stage, and CTGF expression is highest during late stage PVR. These results allow for the development of stage-specific therapeutics for PVR that may allow targeting of the early proliferative and/or the late tractional stages of PVR.

Background: The most widely used models of proliferative vitreoretinopathy (PVR) rely on injection of cells into the vitreous of animals. Using retinal pigment epithelial (RPE) cells from human PVR membranes may produce a more accurate model of human PVR. We performed a study to determine whether human RPE cells derived from a single epiretinal membrane (ERM) are capable of inducing the same disease in the rabbit eye, and whether the induced ERMs had cellular components similar to those of human PVR membranes. Methods: Cells were harvested from a human ERM obtained at surgery for PVR. RPE cells were cultured from the membrane and injected into the right eye of 24 New Zealand albino rabbits. The left eyes served as controls. The eyes were examined by indirect ophthalmoscopy over 4 weeks. The enucleated eyes were then examined by means of microscopy and histochemical analysis. Results: By day 7, PVR had developed in all but I of the 24 experimental eyes, with 8 progressing to localized tractional retinal detachment. By day 21, localized tractional retinal detachment had developed in 17 eyes; I eye progressed to extensive tractional retinal detachment by day 28. Immunostaining showed that mostly RPE cells, but also myofibroblasts, glial cells and collagen, were present in the newly formed rabbit PVR membranes. Interpretation: Human RPE cells cultured from a PVR membrane appear to be capable of inducing PVR in rabbits. The resultant ERMs are similar to those formed in human PVR and consist mainly of RPE cells.

Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor α, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non–PDGF-mediated activation of PDGF receptor α. These preclinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti–VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions.

Purpose To determine the frequency of anterior chamber contamination occurring during uncomplicated cataract surgery with intraocular lens implantation using phacoemulsification through a scleral tunnel incision. Methods In a prospective study, anterior chamber aspirates of one eye each of 103 consecutive ambulatory patients who underwent uncomplicated cataract surgery with lens implantation were cultured. The anterior chamber aspirate was withdrawn immediately upon the completion of surgery. Conjunctival cultures of the same eye were taken immediately before surgery, after the eye and periocular area had been prepared and draped. Multiple use topical medications used preoperatively on all patients were cultured at the end of the surgical day. Results Intraocular aspirates yielded positive cultures in five specimens (5%), four of which were identified as Staphylococcus epidermidis . Quantification disclosed colony counts ranging between 100 and 200 colony forming units per milliliter. Results of conjunctival cultures were positive in ten specimens (10%). Staphylococcus epidermidis was the most common isolate, identified in seven of the ten positive cultures. Positive intraocular and conjunctival culture results were not present concurrently in any patient. Microorganisms were recovered from the multiple use topical medications on nine of the 26 successive surgical days. Neisseria species was the most frequent isolate (7,44%), followed by S. epidermidis (5,31%). The frequency of contamination of the anterior chamber was independent of wound width (χ 2 = 0.869) and operative time (χ 2 = 4.77). Conclusion Bacterial contamination of the anterior chamber was detected in five (5%) of the patients. This reduced incidence of contamination compared with that of previous studies may be related to the preoperative preparation, the surgical technique, or both. Contamination of the multiple use topical medications and bulbar conjunctiva define possible sources of pathogens that may enter the anterior chamber. The absence of any clinical ocular infection in all patients attests to the small inoculum sizes, as well as the ability of the anterior chamber to clear small bacterial loads.

PURPOSE: The purpose of this study was to investigate the role of leptin in choroidal neovascularization. METHODS: We examined the localization of leptin by immunohistochemistry in nine choroidal neovascular membranes surgically excised from patients with age-related macular degeneration, idiopathic choroidal neovascularization, and ocular histoplasmosis. Controls included omission of primary antibody, use of an irrelevant primary antibody and leptin staining of posterior segment of four normal donor eyes. RESULTS: Leptin was present in eight membranes and appeared vesicular, within the cytoplasm. The more vascular membranes and those consisting of a larger number of retinal pigment epithelium cells were associated with greater leptin staining. Leptin was not seen in the posterior segment of the four normal eyes. CONCLUSION: We suggest that leptin plays an active role in choroidal neovascularization, although further experiments are necessary to establish a causal relationship.

Background: Neovascularization is a serious consequence of several eye diseases, including age-related macular degeneration. Neovascularization is under the control of proangiogenic factors, such as vascular endothelial growth factor and fibroblast growth factor. Recent work in our laboratory has focused on other, novel angiogenic factors, such as neuropilin-I, and their potential role in neovascularization. The purpose of this study was to investigate the role of neuropilin-1 in choroidal neovascularization (CNV). Methods: We examined the localization of neuropilin-1 by immunohistochemistry in nine choroidal neovascular membranes (CNVMs) surgically excised from four patients with age-related macular degeneration who had not undergone laser photocoagulation, four with idiopathic CNV and one with ocular histoplasmosis. We also stained the membranes for markers of endothelial and retinal pigment epithelial cells. Controls included omission of primary antibody, use of an irrelevant primary antibody, and neuropilin-1 staining of the posterior sclera, choroid and retina of four healthy donor eyes. Results: Neuropilin-1 was present in eight of the nine CNVMs. It was localized mainly to the plasma membrane. The more vascular membranes and those consisting of a larger number of retinal pigment epithelial cells were associated with greater neuropilin-1 staining. Neuropilin- I was not seen in the posterior segment of the four healthy eyes. Interpretation: Neuropilin-1 appears to play an active role in CNV. Further study is needed to establish a causal relation.

Nocardia is a gram-positive, weakly acid-fast, filamentous, soil-borne aerobic bacterium that has some morphological and staining features in common with fungi. 1,2 Endogenous intraocular nocardiosis is a rarely reported entity. 1,2 To our knowledge, the electron microscopic features of intraocular Nocardia have not been reported previously. Report of a Case. A 40-year-old black woman with severe renal disease was treated with a cadaveric renal transplant and immunosuppressive medications. Five months later she presented with fever, lethargy, and reduced vision. Funduscopic examination of the right eye disclosed a 4+ vitritis and a 6-mm-diameter well-circumscribed subretinal mass superonasally with an adjacent exudative retinal detachment. A chest radiograph revealed a right upper lobe cavitary lesion. Cranial computed tomography disclosed an occipital infarct, hydrocephalus, and multiple brain abscesses. Meningitis was diagnosed by lumber puncture. A biopsy specimen was taken of the cavitary lung lesion, which showed organisms consistent with Nocardia . She was treated with