Andrew C. Browning

Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study

pathophysiology in LHON. In this study, we reported that ganglion cell analysis could precisely detect the loss of retinal ganglion cell in a time-dependent manner during early phase of LHON when RNFL thickness had not decreased yet. We also raise the possibility that there might be many more patients>60 years of age with visual loss owing to LHON than we have supposed previously. It may be worth investigating mtDNA point mutations regardless of age if a patient presents with unknown visual acuity loss with central scotoma.

Syphilitic acute posterior placoid chorioretinitis in nonimmunocompromised patients

PurposeTo describe the clinical and angiographic features of three cases of secondary syphilis in immunocompetent patients, which presented as acute posterior placoid chorioretinitis (APPC) to the ophthalmologist.MethodsInterventional case series. The aetiology of the APPC was confirmed by serology to be secondary syphilis. Optical coherence tomography, electrophysiology, fundus fluorescein, and indocyanine green (ICG) angiography were performed at presentation and after resolution. Appropriate treatment for secondary syphilis was instituted in each patient.ResultsThe clinical features, fundus fluorescein and ICG angiography, multifocal electroretinography (mfERG), and optical coherence tomography findings of APPC are described. All three patients had a satisfactory resolution of the APPC with improvement in visual acuity.ConclusionsAPPC in secondary syphilis can occur even in immunocompetent patients. A high index of suspicion is required for early diagnosis of this condition resulting in a good visual outcome with adequate treatment. mfERG and optical coherence tomography are useful in the diagnosis and follow-up of these patients.

Visual outcome of malignant hypertension in young people

A retrospective review was carried out of patients under 16 years old with malignant hypertension, who had been referred to a teaching hospital ophthalmology department because of reduced visual acuity. Four patients (three girls, one boy) were seen between 1994 and 2000 with a mean age at presentation of 11.5 years (range 9–15). In the short term, visual acuity improved after control of blood pressure in all four patients. However, in the long term, two patients were registered blind one to two years after presentation, one because of a choroidal neovascular membrane developing at the macula, and the other because of progressive optic neuropathy. Both of these patients had a longer duration of symptoms before diagnosis, worse visual acuity, and higher blood pressure at presentation when compared with the patients who made a good visual recovery. These observations suggest that early diagnosis of malignant hypertension in children is essential in reducing the likelihood of permanent severe visual damage.

The effects of growth factors on the proliferation and in vitro angiogenesis of human macular inner choroidal endothelial cells

Aim: To investigate the effect of VEGF165, FGF2, IGF-1, PDGF-AA, PDGF-BB and IL-1β on the proliferation and angiogenic tube formation of human macular inner choroidal endothelial cells (ICEC). Methods: The proliferation of human macular ICECs after exposure to the aforementioned growth factors was determined by using both a WST-1 colorimetric assay and a cell-counting technique. The effect of growth factors on ICEC angiogenesis was assessed by sprout formation using a three-dimensional in vitro Matrigel duplex assay. Results: Using both the WST-1 assay and a cell-counting technique, VEGF165 and FGF2 both significantly increased human macular ICEC proliferation. The effect of equimolar concentrations of VEGF165 and FGF2 was additive. There was no significant effect for IGF-1, PDGF-AA, PDGF-BB or IL-1β on proliferation up to a growth factor concentration of 1000 pmol/l. The angiogenesis assay found a significant effect on sprout formation for VEGF165 and FGF-2. Again, the effect of equimolar concentrations of VEGF165 and FGF2 was additive. There was no significant effect for IGF-1, PDGF-AA, PDGF-BB or IL-1β on sprout formation at 1000 pmol/l. Conclusions: Both VEGF165 and FGF2 significantly increase human macular ICEC proliferation and sprout formation in an angiogenesis assay. When present together, their effect was additive. IGF-1, PDGF-AA, PDGF-BB and IL-1β did not have any significant effect on proliferation or sprout formation in vitro. These results suggest that targeting other growth factors such as FGF2, in addition to VEGF, may be beneficial in the treatment of neovascular age-related macular degeneration.

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration

Aim To analyse the benefit of intravitreal ranibizumab over 4 years for patients with neovascular age-related macular degeneration (AMD). Methods A retrospective case note review of all patients who started treatment between August 2007 and September 2009 in our unit, minimum follow-up 2 years, maximum 4 years. The main outcome measures were: numbers of patients with different levels of vision, changes in visual acuity, number of treatments and numbers remaining under follow-up. Results 1086 eyes of 1017 patients received treatment. Numbers of patients remaining under follow-up were 892/1017 (87.71%) at 12 months, 730/1017 (71.78%) at 24 months, 468/730 (64.11%) at 36 months and 110/217 (50.69%) at48 months. The main reasons for patients no longer being under follow-up were the consequences of old age or transfer of care. 50% of patients had 6/18 or better over 4 years. Patients received on average 5.79±2.53, 9.15±3.79, 11.22±4.92 and 13.7±7.84 injections by 12, 24, 36 and 48 months, respectively. Conclusions We suggest that the numbers of patients with a particular level of vision may best reflect the actual benefit of AMD treatment provided by a service. Long-term follow-up is required as only 72/730 (10%) had been discharged at 36 months, half of whom had good vision of greater than 60 letters. 83% and 65% of patients needed treatment in the third and fourth year. Follow-up may be for the rest of the patients’ life or at some point they may no longer be well enough to attend.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study

AimsTo evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis.MethodsPhase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24–78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least −6 dioptres.Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months.ResultsAt 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 μm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified.ConclusionsResults from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Clinical presentation, treatment, and outcomes in presumed intraocular tuberculosis: experience from Newcastle upon Tyne, UK

PurposeTo report the clinical manifestations and treatment outcomes of patients with presumed intraocular tuberculosis (TB) seen at the Newcastle Uveitis Service, Royal Victoria Infirmary, Newcastle upon Tyne, UK over a 10-year period.MethodsRetrospective review of case notes.ResultsA total of 21 patients were identified. Occlusive retinal vasculitis was the commonest ophthalmological presentation (12 patients). Eight patients (38%) were found to have underlying active systemic TB (four with mediastinal lymphadenopathy, three with pulmonary TB, one with cutaneous TB). Constitutional or respiratory symptoms, elevated inflammatory markers, and an abnormal chest radiograph were poor indicators of active TB. Two patients had inactive intrathoracic TB. Eleven patients had latent TB. Eighteen patients received anti-tuberculous treatment. Final visual acuity was better than or equal to initial visual acuity in 14 out of 16 patients who completed at least 6 months of standard anti-tuberculous treatment.ConclusionsMost patients with presumed intraocular TB have latent TB, but a significant minority has hitherto undetected active TB. Our series suggests that either proven or presumed intraocular TB occurs frequently in the absence of constitutional or respiratory symptoms, elevated inflammatory markers, or an abnormal chest radiograph. A minimum of 6 months standard anti-tuberculous treatment provides good visual outcomes in the majority of patients.

Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells.

Aim: To develop a method for the reliable isolation of adult human macular inner choroidal endothelial cells (ICECs) and to subsequently characterise them for their expression of a range of endothelial cell associated surface markers. Method: Human ICECs were isolated after manual dissection of maculas from fresh human posterior segments. Following enzyme digestion to form a single cell suspension, the ICECs were isolated using anti-CD31 coated Dynabeads. The isolated cells were grown in culture and examined for typical endothelial cell morphology, surface expression of vWf, CD 31, CD 105, VEGF receptors 1 and 2, and expression of E-selectin after stimulation with TNF-α. The cells were also examined for their ability to form fenestrations and capillary-like tubes in Matrigel. Results: The method enabled the rapid isolation of viable cells that demonstrated typical endothelial cobblestone morphology in culture. The cells stained positive for CD31, vWf, CD105, VEGF receptors 1 and 2, and E-selectin (after stimulation with TNF-α). The cells stained negative for α smooth muscle actin and fibroblast surface protein. The cells also developed fenestrations when cultured on fibronectin coated plates and formed capillary-like tubes structures when cultured on Matrigel. Conclusions: This technique isolates cells from the human macular inner choroid that display features consistent with vascular endothelial cells. These cells could subsequently be used to further the understanding of the pathophysiological mechanisms of diseases of the inner choroid, such as choroidal neovascularisation.

Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells

Background/Aims To investigate the difference between human umbilical vein endothelial cells (HUVEC) and human ocular microvascular endothelial cell (MVEC) gene expression, and to determine if these differences could improve the understanding of ocular angiogenic diseases. Methods The gene expression profiles of HUVEC and matched unpassaged human choroidal, retinal and iris endothelial cells were conducted using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Selected differences were confirmed by real time PCR. Functional cell proliferation assays were used to support microarray findings. Results HUVEC showed enrichment for probe sets involved in embryological development while ocular MVEC demonstrated enrichment for probe sets for MHC classes I and II, immune responses and cell signal transduction. Comparison of human retinal and choroidal endothelial cells demonstrated significant differences in the expression of probe sets encoding insulin-like growth factor 1 (IGF-1) signalling. Cell proliferation assays demonstrated the stimulatory role of IGF-1 on retinal endothelial cells compared with choroidal endothelial cells. Conclusions Gene expression profiling has demonstrated that HUVEC are probably not a suitable surrogate for the study of ocular angiogenic disorders. There are also significant differences in the gene expression of human retinal and choroidal endothelial cells, which may be important in the mechanism and treatment of choroidal and retinal neovascularisation.

Treatment of a choroidal neovascular membrane in a patient with late-onset retinal degeneration (L-ORD) with intravitreal Ranibizumab

Treatment of a choroidal neovascular membrane in a patient with late-onset retinal degeneration (L-ORD) with intravitreal Ranibizumab