Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab.

PurposeTo report the visual and anatomic outcomes in eyes with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) that were switched from either intravitreal bevacizumab or ranibizumab to intravitreal aflibercept.MethodsTwo-center retrospective chart review. Eyes with MO secondary to CRVO that received a minimum of three intravitreal injections of bevacizumab or ranibizumab and were switched to intravitreal aflibercept for persistent or recurrent MO not responding to either bevacizumab and/or ranibizumab.ResultsIn all 42 eyes of 42 patients were included in the study. The median visual acuity before the switch was 20/126, 1 month after the first injection of aflibercept 20/89 (P=0.0191), and at the end of the follow-up 20/100 (P=0.2724). The median CRT before the switch was 536 µm, 1 month after the first injection of aflibercept 293.5 µm (P=0.0038), and at the end of the follow-up 279 µm (P=0.0013 compared to before the switch). The median number of weeks between injections before the switch was 5.6 and after the switch was 7.6 (P<0.0001).ConclusionConverting eyes with refractory MO due to CRVO to aflibercept can result in stabilization of the vision, improved macular anatomy, and extension of the injection interval.

Adenocarcinoma of the esophagus presenting as choroidal metastasis.

Adenocarcinoma of the esophagus is an exceedingly rare cause of choroidal metastasis. We report the case of a 48-year-old Caucasian male with a 2-month history of decreased vision and dysphagia. Ophthalmologic examination revealed bilateral choroidal masses and an exudative retinal detachment in the left eye. Gastroduodenoscopy revealed a circumferential mass in the distal esophagus at 30 cm extending into and involving the gastroesophageal junction. Endoscopic biopsy disclosed an invasive, poorly differentiated adenocarcinoma. Systemic workup revealed widespread metastatic changes in the pericardium, liver, and left adrenal gland, and a right pleural effusion. The patient's condition rapidly deteriorated, and he passed away 40 days after initial presentation. To our knowledge, this represents the first case of choroidal metastasis as the initial manifestation of esophageal adenocarcinoma.

Retinal findings in patients with Alport Syndrome: expanding the clinical spectrum.

AIMS: To describe previously unreported retinal findings in patients with Alport Syndrome (AS), as well as review the range of ophthalmic manifestations. METHODS: Retrospective review of clinical records of patients with AS. RESULTS: Nine patients with AS were identified, of whom three had no eye findings, four showed classic features of AS, and two had new findings, bull's eye and vitelliform maculopathy. The genetic mutation responsible for the disease in the patient with vitelliform subretinal deposits was identified. CONCLUSIONS: Patients with AS can present with a variety of ophthalmic manifestations. Bull's eye maculopathy and vitelliform deposits can be features of AS. The mechanism of these new macular findings remains unknown. Possible pathophysiological overlap with other maculopathies including age-related macular degeneration is discussed.

Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates.

BACKGROUND: Drugs that simultaneously decrease platelet function and inflammation may improve the treatment of cardiovascular disorders. Here, we determined whether dipyridamole and aspirin, a combination therapy used to prevent recurrent stroke, regulates gene expression in platelet-monocyte inflammatory model systems. METHODS AND RESULTS: Human platelets and monocytes were pretreated with dipyridamole, aspirin, or both inhibitors. The cells were stimulated with thrombin or activated by adhesion to collagen, and gene expression was measured in the target monocytes. Thrombin-stimulated platelets increased monocyte chemotactic protein-1 (MCP-1) expression by monocytes. Dipyridamole but not aspirin attenuated nuclear translocation of NF-kappaB and blocked the synthesis of MCP-1 at the transcriptional level. Dipyridamole delayed maximal synthesis of interleukin-8 but did not alter cyclooxygenase-2 accumulation. Adherence to collagen and platelets also increased the expression of matrix metalloproteinase-9 (MMP-9) in monocytes, a response that was inhibited by dipyridamole. In this case, however, dipyridamole did not block transcription or distribution of MMP-9 mRNA to actively translating polysomes, indicating that it regulates the expression of MMP-9 protein at a postinitiation stage of translation. Dipyridamole also blocked MCP-1 and MMP-9 generated by lipopolysaccharide-treated monocytes, indicating that at least part of its inhibitory action is unrelated to its antiplatelet properties. CONCLUSIONS: These results indicate that dipyridamole has selective antiinflammatory properties that may contribute to its actions in the secondary prevention of stroke.

Differential translation of TOP mRNAs in rapamycin-treated human B lymphocytes.

TOP mRNAs (contain a 5' terminal oligopyrimidine tract) are differentially translated in rapamycin-treated human B lymphocytes. Following rapamycin treatment, ribosomal protein (rp) and translation elongation factor TOP mRNAs were translationally repressed, whereas hnRNP A1 TOP mRNA was not. Poly(A)-binding protein (Pabp1) TOP mRNA was translationally repressed under all conditions tested. To investigate the mechanism involved, chimeric mRNAs containing the hnRNP A1 5' untranslated region (UTR) linked to the human growth hormone (hGH) reporter were analyzed. Wild-type hnRNP A1 construct mRNA behaved similarly to endogenous hnRNP A1, whereas a single mutation (guanosine to cytidine) within the TOP element resulted in increased translational regulation. These results suggest that TOP mRNA translation can be modulated and that all TOP mRNAs are not translated with equal efficiency.

Bilateral central retinal vein occlusion in Eisenmenger syndrome.

PURPOSE: To report a case of bilateral central retinal vein occlusion in a patient with Eisenmenger syndrome. METHODS: Case report. A 60-year-old woman with Eisenmenger syndrome secondary to a congenital ventricular septal defect presented with a 2-week history of decreased vision in both eyes. RESULTS: Ophthalmic examination revealed bilateral central retinal vein occlusion. Laboratory findings included hematocrit of 50.3% and pO(2) of 52 mm Hg while on O(2) 5 L/min per nasal cannula, despite having undergone phlebotomy 2 weeks earlier. CONCLUSION: Chronic hypoxia caused by Eisenmenger syndrome may result in polycythemia with resultant hyperviscosity and bilateral central retinal vein occlusion.

Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay.

Candida endophthalmitis is a serious infection secondary to hematogenous dissemination or direct inoculation of the organisms following trauma or eye surgery. The diagnosis is based on the characteristic findings in the infected eye and on culture of vitreous samples. Unfortunately, the yield of vitreous cultures is limited. The use of a Candida albicans species-specific polymerase chain reaction (PCR) assay in the diagnosis of Candida endophthalmitis is reported herein. Four patients with suspected fungal endophthalmitis underwent vitrectomy for diagnostic and therapeutic purposes. In 2 of the 4, vitreous cultures were negative. However, characteristic PCR products were generated in all 4 patient specimens, enabling the rapid diagnosis of Candida endophthalmitis in all 4. Clinical response was observed in all cases. These results demonstrate the utility of PCR-mediated detection of C. albicans in vitreous samples.

Mechanisms of retinal arterial occlusive disease in African American and Caucasian patients.

BACKGROUND AND PURPOSE: The aim of our study was to evaluate the causes of retinal arterial occlusive disease in African American patients and to compare these etiologies with those observed in Caucasian patients with retinal ischemic symptoms. METHODS: We performed a retrospective analysis of a series of consecutive patients evaluated by both the ophthalmology department and the neurology/stroke clinic. Patients had a diagnosis of amaurosis fugax, branch retinal artery occlusion, central retinal artery occlusion, or intra-arterial retinal plaques. RESULTS: Twenty-nine African American patients and 17 Caucasian patients were evaluated. African American patients had a mean age of 61 years (range, 30 to 77 years) and Caucasian patients a mean age of 73 years (range, 56 to 94 years) (P=0.003). There was no statistically significant difference between the 2 groups with respect to visible emboli on funduscopy (P=0.462). After adjusting for age, there was also no difference between the 2 groups with regards to risk factors for arterial occlusive disease such as hypertension, coronary artery disease, hypercholesterolemia, tobacco use, and history of stroke or transient ischemic attacks. Caucasian patients had a 41% incidence (7/17) of high-grade ipsilateral internal carotid artery stenosis, measured by carotid duplex, compared with 3.4% incidence (1/29) in African American patients (P=0.002). CONCLUSIONS: There are racial differences in the causes of retinal arterial occlusion. African American patients have a low prevalence of moderate to severe extracranial carotid stenosis, and a high proportion of African American patients have cryptogenic retinal ischemia. In Caucasian patients there is a stronger association between extracranial carotid artery disease and retinal arterial occlusion.

Experimental neodymium:YAG laser damage to acrylic, poly(methyl methacrylate), and silicone intraocular lens materials.

PURPOSE: To compare neodymium:YAG (Nd:YAG) laser effects on acrylic, silicone, and poly(methyl methacrylate) (PMMA) intraocular lens (IOL) polymers. METHODS: Ten Nd:YAG laser exposures were produced in each of 6 implantation-quality acrylic (Alcon MA60BM), silicone (Staar AQ1016), and PMMA (Alcon MC60BM) IOLs under identical conditions. Each polymer type was irradiated at 6 power settings (0.3, 0.5, 1.0, 1.5, 2.0, and 3.0 mJ) and at 2 focal points (midpoint of lens optic and on the posterior surface to which a cellophane membrane was affixed). The linear extent of the damage was measured using light microscopy. Specimens exposed to 1.0 mJ were processed for scanning electron microscopy. RESULTS: The damage threshold (> or = 5 microns depth) was 0.3 mJ for silicone and 1.0 mJ for acrylic and PMMA IOLs. At the clinically relevant power levels, 1.0 to 2.0 mJ, the depth of damage in the acrylic polymer was 11.9 to 30.5 times less than the depth in the silicone polymer. Similarly, the depth of damage in the PMMA polymer was 5.4 to 52.6 times less than the depth in the silicone polymer. The morphologic pattern of damage in the silicone IOL showed a deep, irregularly configured trough with meandering tendrils. Acrylic IOL damage morphology consisted of an ameboid-shaped entry site without radiating fractures and mild posterior penetration. Poly(methyl methacrylate) IOL damage consisted of a shallow focal trough with radiating fractures. CONCLUSIONS: The silicone IOL polymer had the lowest threshold for laser-induced damage and greater linear extension of damage than the PMMA and acrylic IOL polymers. Poly(methyl methacrylate) and silicone polymers exhibited collateral damage or ejected particulates adjacent to the entry site, whereas the acrylic polymer showed a discrete locus of damage.

Extrusion of an anterior chamber intraocular lens complicated by Haemophilus endophthalmitis.

PURPOSE: To describe a case of late postoperative endophthalmitis in a patient who had undergone anterior chamber intraocular lens implantation 6 years previously. METHOD: Onset, course, and outcome of the patient's eye disease are presented. RESULTS: The patient was initially examined with erosion of the eyewall, extrusion of the lens haptic, and endophthalmitis. Intraocular cultures disclosed the pathogenic organism to be Haemophilus influenzae. CONCLUSION: Anterior chamber intraocular lens haptic extrusion can have grave consequences, including endophthalmitis and severe visual loss.

Familial Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss: a possible new genetic syndrome.

OBJECTIVE: To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss. METHODS: We performed a retrospective review of the medical charts and the ocular histopathological material of multiple members of a family. RESULTS: Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male half-sibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles. CONCLUSIONS: This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.

Central serous chorioretinopathy associated with inhaled or intranasal corticosteroids.

OBJECTIVE: The purpose of the study is to investigate the relationship between inhaled or intranasal adrenergic agonists and corticosteroids and the development of central serous chorioretinopathy (CSC). DESIGN: The medical records of three patients with CSC who were found to use inhaled adrenergic agents or corticosteroids or both were identified prospectively. A survey of members of the Retina, Macula, and Vitreous societies and the National Registry of Drug-Induced Ocular Side Effects identified three additional cases. RESULTS: Six patients with CSC were found to be chronic users of corticosteroid (four patients) or both beta adrenergic agonist and corticosteroid (two patients) metered dose inhalers or nasal sprays. In three cases, there was a close temporal correlation between the use of a corticosteroid nasal spray and the development of CSC. CONCLUSIONS: These findings suggest that, in patients who are susceptible, the periocular or systemic absorption of inhaled corticosteroids may be sufficient to produce CSC in humans, supporting previous hypotheses regarding the pathogenesis of the disorder. Further studies are needed to confirm this association and to determine whether inhaled adrenergic agents also contribute to the development of this disorder. Patients in whom CSC develops while using corticosteroid inhalers or nasal sprays should be alerted to the possible relationship between CSC and these agents.

Phacoemulsification for cataract following pars plana vitrectomy.

BACKGROUND AND OBJECTIVE: To determine if the technical aspects of phacoemulsification for removal of cataract following pars plana vitrectomy differ from those of phacoemulsification for removal of cataract in nonvitrectomized eyes. PATIENTS AND METHODS: Twenty-two eyes that had undergone prior vitrectomy were identified through a retrospective review of chart notes and operative records of 1039 consecutive cataract extractions performed by one surgeon. RESULTS: Complications of proliferative diabetic retinopathy was the most common indication for prior vitrectomy. The predominant lens change was nuclear sclerosis. Deep anterior chambers with large anterior to posterior excursions of the iris lens diaphragm with simultaneous fluctuation in pupil size occurred during phacoemulsification. The posterior capsule was flaccid and mobile during lens cortex removal. No posterior capsules ruptured. Postoperative visual acuity improved in 91% of the patients. CONCLUSIONS: Prior vitrectomy was associated with diabetes and nuclear sclerotic cataract. Phacoemulsification in this patient population was associated with inadequate pupillary mydriasis, superior conjunctival scarring, intraoperative anterior chamber depth, pupil size, and iris lens excursions that hindered phacoemulsification tip placement. Posterior capsules were excessively flaccid, prone to rapid anterior and posterior excursions, and may have plaques that are resistant to intraoperative removal.

Subretinal hemorrhages in proliferative diabetic retinopathy.

PURPOSE: To describe the clinical features of patients with advanced proliferative diabetic retinopathy who underwent vitrectomy and were found to have subretinal hemorrhages. METHODS: The authors conducted a retrospective study of 49 patients with complications of proliferative diabetic retinopathy requiring pars plana vitrectomy and demonstrating the presence of subretinal hemorrhage. Preoperative, intraoperative, and postoperative clinical characteristics were evaluated. Patients were observed for a minimum of 6 months. RESULTS: The location, size, and clearance of subretinal hemorrhages revealed wide variation. Forty-two patients had focal subretinal hemorrhages, and 14 patients within this group had submacular hemorrhages. A retinal break was observed in 15 patients (31%). Only one patient required drainage of the subretinal hemorrhage to achieve retinal reattachment. Vitreous surgery resulted in 59% of patients achieving a visual acuity > or = 5/200. Seventy-nine percent had stable or improved vision, whereas 20% had worse vision after surgery. CONCLUSION: Subretinal hemorrhages appear to be an uncommon feature associated with long-term, advanced proliferative diabetic retinopathy and portend a guarded visual prognosis. These hemorrhages may occur spontaneously in previously untreated eyes and are often unsuspected until observed at the time of vitreous surgery. In general, removal of subretinal hemorrhages was not necessary to achieve macular anatomic attachment, and most patients experienced improved visual function after surgery. Diabetic subretinal hemorrhages may indicate a retinal break, and, therefore, careful ophthalmic inspection should be performed in these patients.

Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears. METHODS: Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascular digest preparations to evaluate microvascular abnormalities. RESULTS: Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations. CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.

Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes.

PURPOSE: To determine whether vascular endothelial growth factor and basic fibroblast growth factor, which may be critical mitogens for neovascularization, are present together in human retinal and choroidal neovascular membranes. METHODS: Light microscopic immunocytochemistry using antibodies against vascular endothelial growth factor, basic fibroblast growth factor, and several cellular "marker" proteins on frozen sections from three choroidal neovascular membranes from patients with age-related macular degeneration, seven surgically excised epiretinal membranes from patients with proliferative diabetic retinopathy, and six epiretinal membranes from patients with nonischemic proliferative retinopathies. RESULTS: All three choroidal neovascular membranes and all seven epiretinal membranes stained positive for vascular endothelial growth factor. Two choroidal neovascular membranes and six of the epiretinal membranes were positive for basic fibroblast growth factor. The same cells were often positive for both antigens. None of the epiretinal membranes from patients with nonischemic proliferative retinopathies were positive for either growth factor. Many of the cells that demonstrated growth factors were glial cells, vascular endothelial cells, and retinal pigment epithelial cells. CONCLUSIONS: Colocalization of two growth factors in the same cells of ocular neovascular membranes suggests that more than one growth factor may contribute to pathologic angiogenesis. Growth factors in neovascular tissues are not localized exclusively in the vascular endothelium. Because expression of some growth factors is stimulated by hypoxia, their localization within choroidal neovascular membranes suggests that hypoxia may be an etiologic factor for choroidal as well as for retinal neovascularization.