Jorge G. Arroyo

Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

A matched study of primary scleral buckle placement during repair of posterior segment open globe injuries

Aims: To compare the visual and anatomical outcomes of patients who underwent primary scleral buckle (SB) placement during posterior segment open globe repair with matched control patients who did not undergo primary SB placement. Methods: Patients who underwent open globe repair alone or with SB placement at Duke University Eye Center (November 1994–September 1997) and the Massachusetts Eye and Ear Infirmary (July 1993–July 1997) were identified. 19 open globe patients who received primary SB placement were matched with control patients who did not receive a primary SB based on three important prognostic factors: (1) visual grade; (2) zone of injury; and (3) mechanism of injury. The outcomes of interest were: (1) visual outcome; (2) anatomical outcome; (3) subsequent retinal detachment (RD); and (4) number of subsequent surgeries. Results: Baseline characteristics between the groups were similar. Patients who received primary SB placement had a better final visual grade (p = 0.02), logMAR vision (p = 0.007), and anatomical grade (p = 0.01) compared with control patients. Primary SB patients had an average final vision of 20/270, whereas control patients had an average final vision of hand movement. Primary SB placement also resulted in fewer subsequent RDs (26% versus 53%), but this difference did not reach statistical significance (p = 0.10). There were no complications associated with primary SB placement. Conclusion: Primary SB placement during posterior segment open globe repair may decrease the risk of subsequent RD and improve final visual and anatomical outcome.

A role for excitatory amino acids in diabetic eye disease

Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

Primary scleral buckling in Open-globe Injury involving the posterior segment

PURPOSE To determine whether scleral buckle placement at the time of primary repair of open-globe injury of the posterior segment is beneficial. DESIGN Retrospective, comparative, nonrandomized interventional study. PARTICIPANTS One hundred twenty-five open-globe injuries treated at the Duke University Medical Center from June 1980 to May 1997. METHODS Open-globe injuries were classified with the Open-globe Injury Classification. Eyes that had zone 2 and 3 injuries that had a primary buckle placed were compared with those that did not. MAIN OUTCOME MEASURES Subsequent retinal detachment, visual outcome, and need for subsequent scleral buckling. RESULTS The rate of retinal detachment and the visual outcome were similar in the two groups. More than half of those who did not have a primary buckle placed had subsequent scleral buckling surgery. CONCLUSIONS Many open-globe injuries of the posterior segment require eventual scleral buckle. There may be a role for placement of a scleral buckle at the time of primary repair.

Postoperative Complications of Scleral Buckling Surgery

The postoperative course of scleral buckling surgery can witness a host of untoward events, which may undo the anatomical success of retinal reattachment. Diligent preoperative identification of all retinal breaks and meticulous intraoperative technique will enhance the likelihood of a tranquil postoperative course.

Morphologic differences in epiretinal membranes on ocular coherence tomography as a predictive factor for surgical outcome.

Purpose: To evaluate whether morphologic differences in idiopathic epiretinal membranes seen on optical coherence tomography may help predict surgical outcomes. Methods: Seventy-five eyes of 74 patients who underwent primary pars plana vitrectomy with membrane peeling were retrospectively reviewed. Outcome measures included visual acuity, macular contour on optical coherence tomography, central macular thickness, and reoperation rate. Results: According to the preoperative macular contour, 75 eyes were categorized into 4 types: 42 eyes were included in the diffuse (DIF) type, 12 in the cystoid macular edema (CME) type, 14 in the pseudolamellar hole (PLH) type, and 7 in the vitreomacular traction (VMT) type. Surgical procedure significantly improved vision in all types except for the PLH type (DIF, P < 0.0001; CME, P = 0.0378; PLH, P = 0.838; and VMT, P = 0.0273). There was a significant relationship between pre- and postoperative macular contour. All preoperative VMT showed normal contour on postoperative optical coherence tomography but had the highest reoperation rate. Conclusion: Surgical intervention for the PLH-type epiretinal membrane was not associated with the visual improvement seen in other epiretinal membrane types, and the VMT type had the highest reoperation rate. Future studies should evaluate the potential benefit of internal limiting membrane peeling with or without short-term gas tamponade in these cases.

Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens

Although some behavioral effects of cocaine are hypothesized to be due to blockade of dopamine uptake in nucleus accumbens, it has been reported that in nucleus accumbens there are no specific cocaine binding sites and that cocaine is a weak inhibitor of dopamine uptake. [3H]GBR 12935 and an unlabelled analog, GBR 12909, are ligands that bind with great affinity and specificity to a site on dopamine uptake complex in striatum. We therefore investigated the interaction of these GBR compounds with the dopamine uptake complex in nucleus accumbens. We found specific high affinity [3H]GBR 12935 binding and a significant correlation between displacement of [3H]GBR 12935 binding by a series of compounds in striatum and nucleus accumbens. GBR 12909 inhibited dopamine uptake with equal potency in nucleus accumbens and striatum. Thus, there appear to be some aspects of the dopamine uptake complex in nucleus accumbens and striatum that are similar.

Minocycline Inhibition of Photoreceptor Degeneration

OBJECTIVE To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD). METHODS Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling. RESULTS Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD. CONCLUSIONS Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD. CLINICAL RELEVANCE Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia.

PURPOSE To characterize the angiogenic and inflammatory vitreous biomarker profiles in a spectrum of ischemic retinopathies, including neovascular glaucoma. METHODS This institutional review board-approved study retrospectively analyzed 80 undiluted vitreous samples obtained during pars vitrectomy. The specimens were frozen (-80°C) and sent for concentration analysis of 34 proteins by Bio-Plex Pro assays. Specimens were divided into four groups: patients undergoing epiretinal membrane (ERM) peeling and/or macular hole (MH) surgery with no history of diabetes (non-DM group), patients undergoing ERM peeling, and/or MH surgery with a history of diabetes (DM group), patients with proliferative diabetic retinopathy (PDR group), and patients with neovascular glaucoma (NVG group). Parametric and nonparametric analyses of demographics and cytokine levels were performed using SPSS. RESULTS There were no significant differences in demographics among cohorts. Numerous proteins were significantly elevated between non-DM and DM (G-CSF, sCD40L, Endoglin, IL-6, placental growth factor [PlGF], VEGF-D), DM and PDR (leptin, IL-8, PlGF, VEGF-A), and PDR and NVG (G-CSF, leptin, TIE-2, sCD40L, EGF, HB-EGF, IL-6, IL-8, PlGF, TNF-α). Only PlGF was significantly elevated between each successive cohort. The most potent drivers of NVG were PlGF, VEGF-A, IL-6, and IL-8. CONCLUSIONS While the role of angioproliferative growth factors is well documented in ischemic retinopathy, our study delineates the importance of inflammatory and previously underreported angiogenic proteins. It also demonstrates a significant incremental increase in certain factors with increasing levels of ischemia. Both of these findings may guide the development of future therapies for ischemic retinopathies.

Pseudophakic cystoid macular edema.

In 1953, Irvine described a syndrome of vitreous changes after cataract extraction associated in some cases with ‘‘macular degeneration.’’ This degeneration, he speculated, was likely due to vitreous traction on the macula, and he described an association with an ‘‘irritation’’ of the eye. Gass et al in 1966 described cystoid macular changes seen clinically and a pattern of fluorescein leakage observed in some patients weeks or months after cataract surgery. All of these characteristics describe the entity now well known as pseudophakic cystoid macular edema (CME). Though still far from complete, our understanding of this syndrome and our strategies for managing it have certainly grown over the intervening years. At the same time, as patient expectations for visual acuity outcomes after cataract extraction continue to rise, particularly with the use of ‘‘premium’’ intraocular lenses (IOLs), the level of tolerance for a decline in vision due to this surgical complication continues to decline. Though the precise mechanistic details underlying pseudophakic CME remain to be elucidated, 2 primary hypothetical components have been implicated in its pathogenesis. The first of these is ocular inflammation, as alluded to by Irvine’s classical description of an ‘‘irritated’’ eye. This hypothesis has been supported by several points of evidence. In a comparative study of patients with bilateral cataract