CENTRAL RETINAL ARTERY OCCLUSION AS PRESENTATION OF BARTONELLA ENDOCARDITIS.

BACKGROUND/PURPOSE: To describe a rare ocular presentation of a systemic illness and the important lifesaving diagnosis made by a complete eye examination. METHODS: The patient was evaluated with a comprehensive ophthalmic examination and followed closely in the outpatient setting with optical coherence tomography, fluorescein angiography, and color fundus photos. RESULTS: A 66-year-old man presented with acute vision loss of the left eye. A complete eye examination revealed that he had a central retinal artery occlusion. Systemic workup revealed that he had a mitral valve vegetation and blood cultures grew Bartonella henselae. His kidney biopsy showed membranoproliferative glomerulonephritis, which is often seen with septic emboli. Furthermore, the patient lacked any ocular inflammatory signs. This constellation of findings was diagnostic for a thromboembolic etiology causing his central retinal artery occlusion. At follow-up, the optical coherence tomography demonstrated inner retinal hyperreflectivity and the fluorescein angiogram showed segmented flow and no neovascularization. On follow-up, the patient had a stable examination with light perception vision and completed antibiotic therapy for bartonella endocarditis. CONCLUSION: The detection of a fatal systemic illness was made promptly with a thorough ocular examination. We highlight the importance of a multidisciplinary approach in making a lifesaving diagnosis.

Fellow-Eye Retinal Detachment Risk as Stratified by Hyaloid Status on OCT.

PURPOSE: To evaluate the risk of a rhegmatogenous retinal detachment (RRD) in the fellow eye using posterior hyaloid status as determined by OCT at the time of initial RRD. DESIGN: Retrospective chart review. PARTICIPANTS: Patients with a diagnosis of RRD. METHODS: Posterior hyaloid status-presence or absence of a posterior vitreous detachment (PVD)-in both eyes at the time of initial RRD was determined by OCT imaging. Baseline characteristics, including lattice degeneration, refractive error, prior ocular laser procedures, lens status, and family history of RRD, were recorded. MAIN OUTCOME MEASURES: The main outcome measures were the development of fellow-eye RRD and the time to fellow-eye RRD. In addition, OCT imaging was used in those fellow eyes with a visible posterior hyaloid to document whether a PVD developed during follow-up and time to such an event. RESULTS: A total of 1049 patients with an RRD were followed up for an average of 5.7 ± 0.3 years. Overall, 153 patients (14.6%) received a diagnosis of bilateral sequential RRD during this follow-up period. OCT images were available for 582 fellow eyes; PVD was noted in 229 fellow eyes (39.3%), and an attached hyaloid was noted in 353 fellow eyes (60.7%). An RRD occurred in 7 fellow eyes (3.1%) with a PVD at presentation. Within the cohort of fellow eyes with an attached hyaloid, 28 eyes (7.9%) demonstrated an RRD during follow-up; however, when evaluating only those in which a PVD developed during follow-up, 23.7% of such eyes were found to have an RRD as well. At the time of PVD development in the fellow eye, an additional 21 eyes (17.8%) were noted to have a retinal tear that was treated without progression to RRD. CONCLUSIONS: OCT imaging of the fellow eye at the time of presentation with an RRD offers a significant amount of information regarding risk stratification for RRD in this eye. Patients noted to have a completely detached posterior hyaloid are at a significantly lower risk of RRD than those with a visible posterior hyaloid, who need to be monitored closely at the time of PVD development. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Silicone oil migration into the orbit.

PURPOSE: To report a case in of intravitreal silicone oil migration into the inferior orbit. Silicone oil tamponade is commonly used in retinal detachment repair and extrusion into the orbital tissues is very rare. METHODS: A 70-year-old male with a remote history of repair of a right ruptured globe and retinal detachment surgery presented with progressive right lower eyelid edema. There was a known history of intravitreal silicone oil instillation and removal. An elective right inferior orbitotomy with excisional biopsy was performed. RESULTS: Histopathology confirmed the presence of silicone oil intermixed with necrotic fat. The patient had excellent cosmetic and functional outcome. CONCLUSION: The presence of silicone oil within the orbital fat may be a result of increased intraocular pressure and extrusion through presumably water-tight sclerotomy sites.

Flat Electroretinography and Acute Visual Loss After Ocriplasmin Injection for Vitreomacular Adhesion Complicating Macular Schisis.

A 53-year-old woman with macular and diffuse retinoschisis complicated by presumed vitreomacular traction underwent unilateral intravitreal ocriplasmin injection. Within hours after injection, she noted a loss of vision and the perception of "negative" images in the treated eye. Electrophysiologic testing revealed flat waveforms, and optical coherence tomography (OCT) showed initial decreased central macular thickness at day 1, followed by massive increased macular thickness with subfoveal neurosensory retinal detachment at 1 week. Her central macular thickness on OCT slowly returned to baseline during a period of 1 month until development of a macula-off rhegmatogenous retinal detachment at 6 months after injection. The authors believe this unique case of vitreomacular adhesion and macular schisis complicated by post-injection visual loss and electroretinography changes may offer further insight into this unusual complication.

Human papilloma virus vaccine associated uveitis.

PURPOSE: To report a possible association between human papilloma virus (HPV) vaccination and uveitis. METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." MAIN OUTCOME MEASURES: Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. RESULTS: A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). DISCUSSION: According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

Analysis of the molecular biologic milieu of the vitreous in proliferative vitreoretinopathy.

PURPOSE: Previous investigations have explored molecular differences between proliferative vitreoretinopathy and primary retinal detachment. An exploration of a greater number of molecules might provide novel insight into the biology of this disorder and identify potential therapeutic targets. METHODS: Vitreous specimens were obtained from patients with epiretinal membranes or macular puckers (n = 15), patients with a primary retinal detachment without proliferative vitreoretinopathy (n = 15), and patients with retinal detachments and proliferative vitreoretinopathy (n = 15). A multiplex assay was performed to calculate the concentrations of 48 different cytokines and chemokines, and statistical analyses were performed to identify differences between the groups. RESULTS: Of the 48 molecules that were studied, we identified 10 that were statistically significantly different in cases of proliferative vitreoretinopathy, including interleukins 4, 5, 6, and 15; granulocyte-macrophage colony-stimulating factors; stem cell factor; stem cell growth factor; macrophage inflammatory protein 1α; and interferon γ-induced protein 10. CONCLUSION: Proliferative vitreoretinopathy represents a highly ordered molecular process that involves discrete changes in the concentrations of specific cytokines and chemokines. These molecules may represent novel therapeutic targets.

Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Infliximab stability after reconstitution, dilution, and storage under refrigeration.

PURPOSE: The purpose of this study was to investigate the stability of reconstituted infliximab solutions and determine whether infliximab is suitable for compounding for potential intravitreal use. METHODS: Infliximab was reconstituted, and the solution was aliquoted and stored refrigerated. On each day of testing, an aliquot was serially diluted to concentrations ranging from 50,000 pg/mL to 69 pg/mL. Each dilution was assayed by microsphere immunoassay daily for 5 days and weekly for a total of 6 weeks. The outcome measure was median fluorescence intensity measured by dual laser flow analysis of fluorochrome-labeled secondary antibodies to infliximab bound to tumor necrosis factor-alpha-coated microspheres. RESULTS: There was an increasing median fluorescence intensity for increasing infliximab concentration in a sigmoidal dose-response curve with a variable slope that was equivalent for each time point. Each respective concentration of infliximab showed nearly equivalent median fluorescence intensity for every time point over the 6-week period. CONCLUSION: The authors found that the immunoreactivity of 2 different concentrations of infliximab stored at 4 degrees C over a 6-week period remained stable. Infliximab is suitable for compounding and could be a cost-effective intravitreal medication for use in clinical practice if further study supports its safety and efficacy.

Adverse events after intravitreal infliximab (Remicade).

PURPOSE: To determine the tolerability of intravitreal infliximab (Remicade) in patients with refractory diabetic macular edema or choroidal neovascularization secondary to age-related macular degeneration. METHODS: This is a prospective, interventional, noncomparative, open-label, 12-week pilot study of intravitreal infliximab in four patients who failed conventional therapies. Two had diabetic macular edema and two had choroidal neovascularization secondary to age-related macular degeneration. All patients received 0.5 mg/0.05 mL intravitreal infliximab and were eligible for a second injection at 6 weeks if reinjection criteria were met. Outcome measures were best-corrected visual acuity using standard Early Treatment Diabetic Retinopathy Study refraction, central retinal thickness on optical coherence tomography, fluorescein angiography, standard electroretinography, and microperimetry. Patients were evaluated at Days 0 and 1 and Weeks 2, 6, and 12. Six months after study completion, all patients were tested for human antimouse and human antichimeric antibodies. RESULTS: At Week 12, visual acuity scores had declined in three patients. All patients had persistence of cystoid macular edema on optical coherence tomography, although two had a decrease in central retinal thickness. Three patients had an overall worsened appearance on angiography. On the final electroretinography, all patients had a decrease in maximal combined responses, from 7% to 24% from baseline, which may have been within expected variability of electroretinography data. To photopic flicker stimulus, three patients had slower latency of response, and all had decreased amplitudes. All patients declined on microperimetry. The first patient entered in the study met the criteria for a second injection because of improved standard electroretinography and microperimetry at Week 6. However, 2 weeks after the second injection, he developed panuveitis. Two other patients, after one injection only, had evidence of inflammation (vitritis or panuveitis) on examination at Week 6. Three patients developed systemic antibodies against infliximab (human antichimeric antibodies). CONCLUSION: Low-dose intravitreal infliximab was not well tolerated in this small group of patients and was both immunogenic and probably retinotoxic.

Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients.

BACKGROUND: Vitreous levels of unbound bevacizumab (Avastin) and unbound vascular endothelial growth factor (VEGF) were determined in two patients. Patient 1 underwent repair of an 8-day-old rhegmatogenous retinal detachment 4 weeks after a single intravitreal bevacizumab injection, and Patient 2 underwent vitreous biopsy for endophthalmitis 48 hours after a combined bevacizumab and triamcinolone injection. METHODS: The samples of vitreous fluid were analyzed for unbound bevacizumab and unbound VEGF levels using microsphere immunoassays targeted for bevacizumab and VEGF. RESULTS: In Patient 1, the unbound bevacizumab level was 0.16% of the loading dose (or 500,000 pg/mL) and the unbound VEGF concentration was <41 pg/mL 4 weeks after the bevacizumab injection. In Patient 2, the unbound bevacizumab level was 53% of the loading dose (or 166,000,000 pg/mL) at 48 hours, with an unbound VEGF level of <41 pg/mL. CONCLUSION: A single dose of intravitreal bevacizumab is likely to provide complete intravitreal VEGF blockade for a minimum of 4 weeks, with an intravitreal bevacizumab half-life of approximately 3 days.

Role of intravitreal triamcinolone acetonide in the treatment of postoperative endophthalmitis.

PURPOSE: To report the use of commercially available triamcinolone acetonide as adjunct treatment for acute-onset endophthalmitis after intraocular procedures. METHODS: Charts of 14 patients who received intravitreal triamcinolone in combination with intravitreal antibiotics for treatment of acute endophthalmitis were reviewed. Patients were included if they presented with pain, vision loss, and severe anterior chamber reaction or hypopyon. Visual acuities, intraocular pressures, anterior chamber reaction, and view of fundus details were recorded at baseline, 1 day, 1 week, 1 month, and 3 months to 5 months. RESULTS: Culture-positive results were found for 57% (8/14) of patients. Isolated species included Staphylococcus epidermidis, viridans streptococcus, group D Streptococcus (nonenterococcus), Propionibacterium acnes, and diphtheroid bacilli. Visual acuities improved an average of 7.5 Snellen lines. Preendophthalmitis level visual acuities were recovered in 78.6% patients (11/14), with 64% (9/14) of patients achieving visual acuity of 20/40 or better regardless of presenting vision. Resolution of anterior chamber reaction and view of fundus details were consistent with visual acuities. CONCLUSIONS: Intravitreal triamcinolone combined with intravitreal antibiotics appears to have a safety profile similar to current modalities with a favorable effect on visual recovery and function in the setting of acute postoperative endophthalmitis.

Vitreous penetration of topical moxifloxacin and gatifloxacin in humans.

PURPOSE: To determine the vitreous penetration of the new fourth-generation topical fluoroquinolones moxifloxacin 0.5% and gatifloxacin 0.3%. METHODS: A prospective randomized clinical trial comprising 12 eyes of 12 patients scheduled for pars plana vitrectomy between August 2003 and September 2003 was performed in a clinical practice. The patients were randomly assigned to receive topical moxifloxacin 0.5% (n = 6) or gatifloxacin 0.3% (n = 6). One half the patients in each antibiotic group received 1 drop every 15 minutes for a total of 3 doses starting 1 hour before surgery, and the other one half self-administered the antibiotic drop 4 times daily for 3 days before surgery and at 7 am on the day of surgery. Undiluted vitreous samples were obtained and analyzed using high-performance liquid chromatography. RESULTS: Either moxifloxacin 0.5% or gatifloxacin 0.3% was detected in the vitreous in all 12 patients in the study. There was no significant difference between the mean vitreous concentration of moxifloxacin 0.5% given over 1 hour preoperatively (0.012 +/- 0.011 microg/mL) and that given in the 3-day regimen (0.011 +/- 0.008 microg/mL) (P = 0.93). There was also no significant difference between the mean vitreous concentration of gatifloxacin 0.3% given over 1 hour preoperatively (0.001 +/- 0.0003 microg/mL) and that given over 3 days (0.008 +/- 0.006 microg/mL) (P = 0.11). Vitreous concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% in each eye were all lower than the 90% minimum inhibitory concentration for the commonest bacterial isolates causing endophthalmitis. With both dosing regimens, the mean vitreous concentration of moxifloxacin 0.5% was higher than that of gatifloxacin 0.3% administered at the same regimen, but this was not statistically significant. CONCLUSION: Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis.