Ayala Pollack

Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis

The role of activated microglia (MG) in demyelinating neurodegenerative diseases such as multiple sclerosis is controversial. Here we show that high, but not low, levels of IFN-gamma (a cytokine associated with inflammatory autoimmune diseases) conferred on rodent MG a phenotype that impeded oligodendrogenesis from adult neural stem/progenitor cells. IL-4 reversed the impediment, attenuated TNF-alpha production, and overcame blockage of IGF-I production caused by IFN-gamma. In rodents with acute or chronic EAE, injection of IL-4-activated MG into the cerebrospinal fluid resulted in increased oligodendrogenesis in the spinal cord and improved clinical symptoms. The newly formed oligodendrocytes were spatially associated with MG expressing MHC class II proteins and IGF-I. These results point to what we believe to be a novel role for MG in oligodendrogenesis from the endogenous stem cell pool.

Age-related Macular Degeneration after Extracapsular Cataract Extraction with Intraocular Lens Implantation

PURPOSE To evaluate the course of age-related maculopathy after cataract surgery. METHODS Included were 47 patients with bilateral, symmetric, early age-related macular degeneration (AMD), documented by fluorescein angiography, who underwent extracapsular cataract extraction with intraocular lens implantation in one eye. The fellow eye served as the control. The patients were retrospectively reviewed or prospectively followed. RESULTS Wet AMD developed in nine eyes (19.1%) that were treated with surgery compared with two fellow eyes (4.3%). It was detected within 3 months of surgery in four (44.4%) of the nine affected eyes and within 6 to 12 months of surgery in four other eyes (44.4%). Progression to wet AMD occurred significantly more often in men than in women (P < 0.05). Soft drusen were found as a significant ocular risk factor (P < 0.05). The final visual outcome was poor in all eyes with such progression. CONCLUSIONS In this study, progression of AMD occurred more often in the surgical eyes compared with the fellow eyes. However, the reasons for the progression of AMD after cataract surgery are still uncertain. Further prospective studies are needed to investigate this observation.

Cystoid macular oedema following cataract extraction in patients with diabetes.

The course of cystoid macular oedema (CMO) following extracapsular cataract extraction with posterior chamber intraocular lens implantation was prospectively studied in 44 eyes of 44 consecutive diabetic patients without preoperative CMO. In 50% of eyes CMO was observed 6 weeks after surgery and in 25% was still present at 1 year. The preoperative presence of diabetic retinopathy significantly affected the postoperative onset and persistence of CMO. CMO occurred postoperatively in only 32% of eyes without pre-existing diabetic retinopathy and in 81% of eyes with pre-existing diabetic retinopathy (p < 0.05). CMO persisted at 1 year after surgery in only 7% of eyes without pre-existing diabetic retinopathy and in 56% of eyes in which diabetic retinopathy persisted (p < 0.01). Angiographic CMO (that is, detectable only on fluorescein angiography) was more common than clinical CMO (detectable on ophthalmoscopic examination as well) in eyes with no pre-existing diabetic retinopathy, whereas clinical CMO was seen more often than angiographic CMO when diabetic retinopathy was present preoperatively (p < 0.01). The course and final visual outcome of angiographic CMO were more favourable than in clinical CMO. Final visual acuity of at least 6/12 was achieved in 86% of eyes with angiographic CMO and in only 33% of eyes with clinical CMO. On the basis of the above findings we believe that cataract extraction should not be recommended for eyes with pre-existing diabetic retinopathy until the vision has deteriorated to at least 6/30-6/60.

Angiogenesis in pterygium: Morphometric and immunohistochemical study

Objective. To evaluate the role of angiogenesis in the pathogenesis of pterygium by comparing the expression of von-Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in pterygium, and in normal superior bulbar conjunctiva. Methods. 23 human samples from pterygium and the superior bulbar conjunctiva were stained using rabbit anti-vWF and anti-VEGF antibodies. The density of vWF and VEGF positive vessels, VEGF staining intensity and the number of VEGF positive stromal, epithelial and vascular endothelial cells were evaluated. Results. Pterygium specimens had higher average vWF and VEGF positive microvascular counts per high power field (P = 0.0012), higher average VEGF staining intensity scores in epithelial, stromal and endothelial cells (p < 0.0001) and higher VEGF positive cell counts (P < 0.0001) than normal conjuctiva. Conclusions. Over-expression of VEGF in pterygium tissue, together with the abundance of vWF-stained new vessels, may support previous suggestions that angiogenesis may play a role in the formation of pterygium.

The Course of Age-Related Macular Degeneration Following Bilateral Cataract Surgery

BACKGROUND AND OBJECTIVE Progression of age-related macular degeneration (AMD) following cataract surgery has been described. The aim of this study was to investigate whether an uneventful postoperative maculopathic course in one eye (the first eye) may predict a similar prognosis for the fellow eye (the second eye). PATIENTS AND METHODS Thirty-three patients with bilateral, similar, early AMD (defined by the presence of drusen and/or pigmentary abnormalities on fundal examinations and by the absence of late leakage as documented by fluorescein angiography) who had undergone unilateral cataract surgery, had had a stable postoperative maculopathic course following the first operation, and were scheduled for cataract surgery in the second eye were prospectively observed for at least 1 year after the second operation. The course of maculopathy of the second eye was compared with that of the first eye during the follow-up period of the second eye. RESULTS A total of 9 of the second eyes (27.2%) showed progression to wet AMD. Of these, 1 patient (3%) had progression in both eyes and 8 patients (24.2%) had progression in the second eye only. The conditions of 2 of the first operated on eyes (6.1%) deteriorated (P < .05). Hypertension (P < .05), soft drusen (P < .01), and Nd:YAG laser capsulotomy (P < .05) were risk factors for development of wet AMD. CONCLUSION In this study, 24.2% of the patients with early AMD who underwent bilateral cataract surgery and had an uneventful maculopathic course in the first eye had wet AMD in the second eye. Thus, patients with early AMD and soft drusen undergoing bilateral cataract surgery should be monitored for early detection of progression of maculopathy. Further prospective studies are needed to determine the course of maculopathy following cataract surgery.

The course of diabetic retinopathy following cataract surgery in eyes previously treated by laser photocoagulation

The course of diabetic retinopathy following extracapsular cataract extraction with posterior chamber lens implantation in eyes previously treated by laser photocoagulation for diabetic retinopathy was retrospectively studied in 33 eyes (33 patients). In 20 eyes (61%) there was no change in the retinal status postoperatively. In 13 (39%) there was postoperative progression of diabetic retinopathy compared with the fellow non-operated eye, in which progression occurred in nine eyes (27%). The severity of the preoperative status affected the incidence of progression. Four eyes (12%) developed complications of diabetic retinopathy--that is, rubeosis iridis and vitreous haemorrhage--which regressed after lasering. Cystoid macular oedema developed in 13 eyes (39%) and its incidence varied according to the postoperative course of diabetic retinopathy. The majority of the eyes showed a postoperative improvement in vision.

Comparison of trabeculectomy with mitomycin C with or without phacoemulsification and lens implantation

PURPOSE To compare the results of combined trabeculectomy with phacoemulsification and posterior chamber intraocular lens (IOL) implantation to those of trabeculectomy alone using mitomycin C (MMC) application intraoperatively in all cases. PATIENTS AND METHODS A retrospective comparative study of consecutive patients was conducted on two groups: 102 eyes of 90 patients studied in the combined procedure group, and 33 eyes of 30 patients in the trabeculectomy alone group. RESULTS Both groups showed a significant decrease in IOP. The combined group had a change from 21.5+/-5.8 mm HG preoperative to 14.73+/-3.44 mm HG postoperative, P=0.0001; the trabeculectomy group changed from 24.2+/-7.5 mm HG preoperative to 12.46+/-3.86 mm HG postoperative, P=0.0001. This represents a 31.5% reduction in IOP in the combined group versus a 48.5% reduction in the trabeculectomy alone group (P=0.0001). The follow-up time was longer in the trabeculectomy group (trabeculectomy group, 22.6+/-13.3 months; combined group, 14.2+/-8.0 months), P=0.0014. There were 97 eyes in the combined group (95%) and 32 eyes (97%) in the trabeculectomy group that had an IOP of less than 20 mm HG at the end of follow up. Postoperatively, the two groups showed similar significant reductions in the number of antiglaucomatous medications used (combined group, 0.82+/-1.0 compared with 2.65+/-0.84 preoperatively, P=0.0001; trabeculectomy group, 0.76+/-1.2 compared with 2.7+/-0.95 preoperatively, P=0.0001). There were no cases of bleb leakage in the combined group and two cases (6%) in the trabeculectomy group. CONCLUSION The reduction of IOP is significantly larger after trabeculectomy alone than after the combined procedure; however, the functional and anatomical results of the combined procedure of phacoemulsification, posterior chamber IOL implantation, and trabeculectomy with MMC application were as good as those of trabeculectomy alone with MMC.

Weekly Vaccination with Copaxone (Glatiramer Acetate) as a Potential Therapy for Dry Age-Related Macular Degeneration

Purpose: Drusen formation in age-related macular degeneration (AMD) shares some similarities with Alzheimers disease (AD), which is associated with amyloid deposits. Aggregated beta-amyloid induces microglia to become cytotoxic and block neurogenesis. Recent evidence showed that T cell-based vaccination with Copaxone in AD mice model resulted in modulation of microglia into neuroprotective phenotype and as a result in reduction of cognitive decline, elimination of plaque formation, and induction of neuronal survival and neurogenesis. The aim was to investigate whether the effect of Copaxone on drusen in dry AMD is similar to that on deposits of other age-related chronic neurodegenerative diseases such as Alzheimer disease (AD). Materials and Methods: Patients over 50 years of age with intermediate dry AMD in both eyes were randomized to receive Copaxone or sham injections and were weekly treated by subcutaneous injections of Copaxone (dose of 20 mg) or sham injections for 12 weeks. At baseline, 6-week, and 12-week visits, visual acuity, contrast sensitivity, fundus examination and photography, fluorescein angiography, and ocular coherent tomography were performed. Main outcome measure was a change in total drusen area (TDA) measured by Image-Pro software and presented in arbitrary units (AU). Results: Eight studied eyes of four treated patients showed a decrease in TDA from 48130 to 16205 AU at 12 weeks as compared to baseline. In contrast, four control eyes (two patients) demonstrated almost no change in TDA (from 32294 to 32781 AU). Conclusion: These preliminary results show that Copaxone reduces drusen area.

Development of exudative age-related macular degeneration after cataract surgery

The macular status of patients with findings consistent with early dry age-related macular degeneration (AMD) who underwent an extracapsular cataract extraction with intraocular lens implantation was evaluated by fundoscopy and fluorescent angiography pre-operatively and during the first post-operative year. Five patients who developed the exudative form of AMD, and who represent the problems arising when treating patients with AMD and cataract, are described. Patients who received laser photocoagulation responded with recurrent choroidal neovascularisation. We suggest that patients with signs of age-related changes scheduled for cataract surgery should undergo a thorough pre- and post-operative assessment of their retinal status.

An update on photodynamic therapy in age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible loss of central vision in people aged > 50 years in the western world. Until recently, the only proven treatment to reduce the risk of vision loss from its more severe neovascular form was laser photocoagulation, but this treatment was suitable for only 15% of cases. Photodynamic therapy (PDT) with verteporfin was recently proposed to be effective in reducing the risk of visual loss for an estimated 20 – 30% of neovascular AMD patients. This review covers AMD epidemiology, the mechanism of PDT, the 2-year results of the two major clinical studies of PDT with verteporfin, the cost-effectiveness of PDT and the current research status of other drugs for PDT in AMD.