Intravitreal bevacizumab in the treatment of peripapillary choroidal neovascular membrane secondary to idiopathic intracranial hypertension.

A 14 year-old Caucasian boy with idiopathic intracranial hypertension (IIH) presented with blurred vision in his left eye. Visual acuity was 20/20, right eye, and 20/80, left eye, and funduscopy revealed bilateral papilledema. In addition, there was peripapillary choroidal neovascular membrane (PPCNVM) in the left eye. Oral acetazolamide improved the symptoms and signs of IIH, but seven weeks later, acuity remained 20/80, left eye, with an increase in subretinal hemorrhage. Two weeks following an intravitreal injection of bevacizumab, visual acuity on the left had improved to 20/30 with resolution of subretinal hemorrhage and fibrosis of PPCNVM. After an additional 2 weeks, visual acuity improved to 20/20, and there has been no sign of recurrence over 3.5 years of follow-up.

Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted Müller stem cells into degenerating retina.

At present, there are severe limitations to the successful migration and integration of stem cells transplanted into the degenerated retina to restore visual function. This study investigated the potential role of chondroitin sulfate proteoglycans (CSPGs) and microglia in the migration of human Müller glia with neural stem cell characteristics following subretinal injection into the Lister hooded (LH) and Royal College of Surgeons (RCS) rat retinae. Neonate LH rat retina showed minimal baseline microglial accumulation (CD68-positive cells) that increased significantly 2 weeks after transplantation (p < .001), particularly in the ganglion cell layer (GCL) and inner plexiform layer. In contrast, nontransplanted 5-week-old RCS rat retina showed considerable baseline microglial accumulation in the outer nuclear layer (ONL) and photoreceptor outer segment debris zone (DZ) that further increased (p < .05) throughout the retina 2 weeks after transplantation. Marked deposition of the N-terminal fragment of CSPGs, as well as neurocan and versican, was observed in the DZ of 5-week-old RCS rat retinae, which contrasted with the limited expression of these proteins in the GCL of the adult and neonate LH rat retinae. Staining for CSPGs and CD68 revealed colocalization of these two molecules in cells infiltrating the ONL and DZ of the degenerating RCS rat retina. Enhanced immune suppression with oral prednisolone and intraperitoneal injections of indomethacin caused a reduction in the number of microglia but did not facilitate Müller stem cell migration. However, injection of cells with chondroitinase ABC combined with enhanced immune suppression caused a dramatic increase in the migration of Müller stem cells into all the retinal cell layers. These observations suggest that both microglia and CSPGs constitute a barrier for stem cell migration following transplantation into experimental models of retinal degeneration and that control of matrix deposition and the innate microglial response to neural retina degeneration may need to be addressed when translating cell-based therapies to treat human retinal disease.

Effects of Age-Related Macular Degeneration on Driving Performance.

Purpose: To explore differences in driving performance of older adults with age-related macular degeneration (AMD) and age-matched controls, and to identify the visual determinants of driving performance in this population. Methods: Participants included 33 older drivers with AMD (mean age [M] = 76.6 ± 6.1 years; better eye Age-Related Eye Disease Study grades: early [61%] and intermediate [39%]) and 50 age-matched controls (M = 74.6 ± 5.0 years). Visual tests included visual acuity, contrast sensitivity, visual fields, and motion sensitivity. On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist (masked to drivers' visual status). Outcome measures included driving safety ratings (scale of 1-10, where higher values represented safer driving), types of driving behavior errors, locations at which errors were made, and number of critical errors (CE) requiring an instructor intervention. Results: Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P = 0.012); safety ratings were associated with AMD severity (early: 5.5 versus intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence interval 1.47-6.36, P = 0.003) and exhibited more observation, lane keeping, and gap selection errors and made more errors at traffic light-controlled intersections (P < 0.05). Only motion sensitivity was significantly associated with driving safety in the AMD drivers (P = 0.005). Conclusions: Drivers with early and intermediate AMD can exhibit impairments in their driving performance, particularly during complex driving situations; motion sensitivity was most strongly associated with driving performance. These findings have important implications for assessing the driving ability of older drivers with visual impairment.

Identification of retinal breaks using subretinal trypan blue injection.

PURPOSE: To describe the use of subretinal trypan blue to identify retinal breaks during vitrectomy for rhegmatogenous retinal detachment (RD). DESIGN: Interventional case series. PARTICIPANTS: Five patients with RD in whom no retinal break could be identified by internal search with scleral indentation. METHODS: Trypan blue 0.15% was injected transretinally into the subretinal space using a 41-gauge cannula designed for macular translocation surgery. Perfluorocarbon heavy liquid was then injected into the vitreous cavity and the eye was rotated such that trypan blue was vented out of the break. The plume of trypan blue was used to identify retinal breaks, or in some cases staining of the break facilitated break detection. Subretinal fluid was then drained through the break or a drainage retinotomy and surgery was completed using standard techniques. MAIN OUTCOME MEASURE: Identification of previously unseen retinal breaks. RESULTS: This technique successfully identified a retinal break in 4 out of 5 patients. After absorption of the gas tamponade all retinas remained attached with a median visual acuity of 6/12. CONCLUSION: Failure to identify a retinal break during RD surgery is a well-recognized clinical challenge that may adversely affect outcome. In this setting, chromophore-assisted retinal break detection may be a useful surgical technique.

A study of retinal penetration of intravitreal tenecteplase in pigs.

PURPOSE: To determine the degree of retinal penetration of intravitreal tenecteplase in a porcine model. METHODS: Fluorescence-tagged tenecteplase (50 microg in 0.1 mL physiologic saline) was injected into the vitreous of the right and left eyes at 24 and 6 hours before death, respectively, in six nonvitrectomized pigs. Retinal penetration was assessed on frozen sections by epifluorescence microscopy and statistical analysis was performed. Frozen sections of two eyes without injection (control) were also assessed. RESULTS: Labeling of fluorescence-tagged tenecteplase was seen in all the layers of the retina at both time points with more intense signal at 24 hours after injection (P<0.05). CONCLUSIONS: Fluorescence-tagged tenecteplase can penetrate all the layers of the retina of porcine eyes after intravitreal injection. Intravitreal tenecteplase may be useful in the in the management of subretinal hemorrhage.

Retinal ischemia with neovascularization in cisplatin related retinal toxicity.

PURPOSE: To report a case of macular ischemia and retinal neovascularization in a patient who received cisplatin related chemotherapy. DESIGN: Interventional case report. METHODS: A patient with germ cell testicular tumor received polychemotherapy (bleomycin, etoposide, and cisplatin or BEP) for a recurrence of his tumor. Ten weeks after completion of treatment, he presented with loss of vision in his left eye. RESULTS: Fluorescein angiography revealed bilateral retinal ischemia and left retinal neovascularization. Panretinal laser photocoagulation was performed. Unfortunately, his vision did not improve. CONCLUSIONS: Like interferon, cisplatin related chemotherapy could cause considerable ocular morbidity. It can cause marked irreversible visual loss at therapeutic dose, and it is not well recognized. Retinal neovascularization related to cisplatin therapy has not been previously reported. Physicians should be aware and warn patients of the potential ophthalmic side effects of cisplatin related chemotherapy.

The cultivation of human retinal pigment epithelial cells on Bombyx mori silk fibroin.

We have presently evaluated membranes prepared from Bombyx mori silk fibroin (BMSF), for their potential use as a prosthetic Bruch's membrane and carrier substrate for human retinal pigment epithelial (RPE) cell transplantation. Porous BMSF membranes measuring 3 µm in thickness were prepared from aqueous solutions (3% w/v) containing poly(ethylene oxide) (0.09%). The permeability coefficient for membranes was between 3 and 9 × 10(-5) cm/s by using Allura red or 70 kDa FITC-dextran respectively. Average pore size (±sd) was 4.9 ± 2.3 µm and 2.9 ± 1.5 µm for upper and lower membrane surfaces respectively. Optimal attachment of ARPE-19 cells to BMSF membrane was achieved by pre-coating with vitronectin (1 µg/mL). ARPE-19 cultures maintained in low serum on BMSF membranes for approximately 8 weeks, developed a cobble-stoned morphology accompanied by a cortical distribution of F-actin and ZO-1. Similar results were obtained using primary cultures of human RPE cells, but cultures took noticeably longer to establish on BMSF compared with tissue culture plastic. These findings encourage further studies of BMSF as a substrate for RPE cell transplantation.

Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience.

BACKGROUND: The last major survey of adverse reactions to intravenous fluorescein angiography was performed more than 20 years ago. There have been two recent fatalities involving intravenous fluorescein in Australia. It is important to review the current incidence of adverse reactions and latest literature on the pathogenesis, prophylaxis and alternatives to intravenous fluorescein angiography. METHODS: A retrospective review of all adverse reactions to intravenous sodium fluorescein in patients undergoing fluorescein angiography between June 1998 and June 2004 was undertaken. The total number of fluorescein angiograms performed and the number of patients with adverse reactions were identified from the photographic department database and the fluorescein adverse reaction register at the Lions Eye Institute. RESULTS: A total of 11 898 fluorescein angiograms were performed during the study period. There were 132 adverse reactions recorded. The commonest adverse reactions were nausea and vomiting. There were no serious adverse reactions or deaths recorded. There was a statistically significant difference in the incidence of adverse reactions between sodium fluorescein used from two manufacturers. CONCLUSIONS: Fluorescein angiography is a relative safe procedure and comparable to other intravenous radiocontrast media angiography or investigation. The present results are consistent with previous studies. Prophylactic treatment, fluorescein desensitization or oral fluorescein angiography should be considered in high-risk patients. Safe guards should be in place to manage potential serious adverse reactions. Other imaging techniques, like optical coherence tomography, should be considered as an alternative in selected cases.